Prevalence, characteristics and prognostic impact of aortic valve disease in patients with heart failure and reduced, mildly reduced, and preserved ejection fraction: An analysis of the ESC Heart Failure Long-Term Registry.
European journal of heart failure
AIMS:To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]). METHODS AND RESULTS:Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23-1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07-1.74) but not AR (adjusted HR 1.13, 95% CI 0.96-1.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category. CONCLUSIONS:In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category.
10.1002/ejhf.2908
Pulmonary hypertension with a precapillary component in heart failure with preserved ejection fraction.
Heart (British Cardiac Society)
OBJECTIVES:Heart failure with preserved ejection fraction (HFpEF) is often complicated by pulmonary hypertension (PH), which is mainly characterised by postcapillary PH and occasionally accompanied by a precapillary component of PH. Haemodynamic changes in worsening heart failure (HF) can modify the characteristics of PH. However, the clinical features of PH after HF treatment in HFpEF remain unclear. We investigated the prevalence and clinical significance of the precapillary component of PH after HF treatment in HFpEF, using data from the Prospective Multicentre Observational Study of Patients with HFpEF (PURSUIT-HFpEF). METHODS:From the PURSUIT-HFpEF registry, 219 patients hospitalised with acute HF who underwent right heart catheterisation after initial HF treatment were divided into four groups according to the 2015 and 2018 PH definitions: non-PH, isolated postcapillary pulmonary hypertension (Ipc-PH), precapillary PH and combined postcapillary and precapillary pulmonary hypertension (Cpc-PH). The latter two were combined as PH with the precapillary component. RESULTS:Using the 2015 definition, we found that the prevalence of PH after HF treatment was 27% (Ipc-PH: 20%, precapillary PH: 3%, Cpc-PH: 4%). Applying the 2018 definition resulted in a doubled frequency of precapillary PH (6%). PH with a precapillary component according to the 2015 definition was associated with poor clinical outcomes and characterised by small left ventricular dimension and high early diastolic mitral inflow velocity/early diastolic mitral annular tissue velocity. CONCLUSION:After initial HF treatment, 7% of hospitalised patients with HFpEF had precapillary component of PH according to the 2015 definition. Echocardiographic parameters of the left ventricle can contribute to the risk stratification of patients with HFpEF with a precapillary component of PH.
10.1136/heartjnl-2022-321565
Biventricular cardiac power reserve in heart failure with preserved ejection fraction.
European journal of heart failure
AIMS:Cardiac and extracardiac abnormalities play important roles in heart failure with preserved ejection fraction (HFpEF). Biventricular cardiac power output (BCPO) quantifies the total rate of hydraulic work performed by both ventricles, suggesting that it may help to identify patients with HFpEF and more severe cardiac impairments to better individualize treatment. METHODS AND RESULTS:Patients with HFpEF (n = 398) underwent comprehensive echocardiography and invasive cardiopulmonary exercise testing. Patients were categorized as low BCPO reserve (n = 199, < median of 1.57 W) or preserved BCPO reserve (n = 199). As compared to those with preserved BCPO reserve, those with low reserve were older and leaner, with more atrial fibrillation, higher N-terminal pro-B-type natriuretic peptide levels, worse renal function, more impaired left ventricular (LV) global longitudinal strain, worse LV diastolic function and right ventricular longitudinal function. Cardiac filling pressures and pulmonary artery pressures at rest were higher in low BCPO reserve, but central pressures were similar during exercise to those with preserved BCPO reserve. Exertional systemic and pulmonary vascular resistances were higher and exercise capacity was more impaired in those with low BCPO reserve. Reduced BCPO reserve was associated with increased risk for the composite endpoint of heart failure hospitalization or death over 2.9 (interquartile range 0.9-4.5) years of follow-up (hazard ratio 2.77, 95% confidence interval 1.73-4.42, p < 0.0001). CONCLUSIONS:Inability to enhance BCPO during exercise is associated with more advanced HFpEF, increased systemic and pulmonary vascular resistance, reduced exercise capacity and increased adverse events in patients with HFpEF. Novel therapies that enhance biventricular reserve merit further investigation for patients with this phenotype.
10.1002/ejhf.2867
Effectiveness of adding a defibrillator with cardiac resynchronization therapy in heart failure according to the modified Model for End-stage Liver Disease-Albumin score.
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
Current guidelines lack clear recommendations between the implantation of cardiac resynchronization therapy (CRT) with defibrillator (CRT-D) and CRT with pacemaker (CRT-P). We hypothesized that modified model for end-stage liver disease score including albumin (MELD-Albumin score), could be used to select patients who may not benefit from CRT-D. We consecutively included patients with CRT-P or CRT-D implantation between 2010 and 2022. The primary endpoint was the composite of all-cause mortality or worsening heart failure. We performed multivariable-adjusted Cox proportional hazard regression. We assessed the interaction between the MELD-Albumin score and the effect of adding a defibrillator with CRT.A total of 752 patients were included in this study, with 291 implanted CRT-P. During a median follow-up of 880 days, 205 patients reached the primary endpoint. MELD-Albumin score was significantly associated with the primary endpoint in the CRT-D group [HR 1.16 (1.09-1.24); P < 0.001] but not in the CRT-P group [HR 1.03 (0.95-1.12); P = 0.49]. There was a significant interaction between the MELD-Albumin score and the effect of CRTD (P = 0.013). The optimal cut-off value of the MELD-Albumin score was 12. For patients with MELD-Albumin ≥ 12, CRT-D was associated with a higher occurrence of the primary endpoint [HR 1.99 (1.10-3.58); P = 0.02], whereas not in patients with MELD-Albumin < 12 [HR 1.19 (0.83-1.70); P = 0.35). Our findings suggest that CRT-D is associated with an excess risk of composite clinical endpoints in HF patients with higher MELD-Albumin score.
10.1093/europace/euad232
Relationship between remnant cholesterol and risk of heart failure in participants with diabetes mellitus.
European heart journal. Quality of care & clinical outcomes
BACKGROUND:Evidence about the association between calculated remnant cholesterol (RC) and risk of heart failure (HF) in participants with diabetes mellitus (DM) remains sparse and limited. METHODS:We included a total of 22 230 participants with DM from the UK Biobank for analyses. Participants were categorized into three groups based on their baseline RC measures: low (with a mean RC of 0.41 mmol/L), moderate (0.66 mmol/L), and high (1.04 mmol/L). Cox proportional hazards models were used to evaluate the relationship between RC groups and HF risk. We performed discordance analysis to evaluate whether RC was associated with HF risk independently of low-density lipoprotein cholesterol (LDL-C). RESULTS:During a mean follow-up period of 11.5 years, there were a total of 2232 HF events observed. The moderate RC group was significantly related with a 15% increased risk of HF when compared with low RC group (hazard ratio [HR] = 1.15, 95% confidence interval [CI]: 1.01-1.32), while the high RC group with a 23% higher HF risk (HR = 1.23, 95% CI: 1.05-1.43). There was significant relationship between RC as a continuous measure and the increased HF risk (P < 0.01). The association between RC and risk of HF was stronger in participants with HbA1c level ≥ 53 mmol/mol when compared with HbA1c < 53 mmol/mol (P for interaction = 0.02). Results from discordance analyses showed that RC was significantly related to HF risk independent of LDL-C measures. CONCLUSIONS:Elevated RC was significantly associated with risk of HF in patients with DM. Moreover, RC was significantly related to HF risk independent of LDL-C measures. These findings may highlight the importance of RC management to HF risk in patients with DM.
10.1093/ehjqcco/qcad030
Body composition and short-term mortality in patients critically ill with acute-on-chronic liver failure.
JHEP reports : innovation in hepatology
Background & Aims:Body composition is sex dependent and associated with an increased mortality risk in patients with cirrhosis. We evaluated whether it was also associated with short-term mortality in patients critically ill with acute-on-chronic liver failure (ACLF). Patients and methods:We retrospectively included all patients with cirrhosis and ACLF hospitalised in the intensive care unit (ICU) of Lausanne University Hospital between 2010 and 2019 for whom an abdominal computed tomography (CT) scan performed ±7 days from admission was available. Patients from the ICU of Paul Brousse University Hospital admitted between 2017 and 2020 served as an external cohort. All body composition parameters at the third lumbar vertebral level (L3) were quantified using a deep learning-based method. Results:In total, 192 patients from Lausanne were included. Median age was 62 years and 28-day survival rate was 58.2%. In males, variables independently associated with 28-day mortality on days 1 and 3 were Chronic Liver Failure Consortium (CLIF-C) ACLF-lactate and sarcopenia. In females, CLIF-C ACLF-lactate on days 1 and 3 was the only predictor of 28-day survival. We derived two scores combining sarcopenia and the CLIF-C ACLF-lactate score on days 1 and 3, with area under the receiver operating characteristic outperforming the CLIF-C ACLF-lactate score alone in male but not in female patients. Comparable results were found in the external cohort of 58 patients and supported the sex specificity of the performance of the model. Patients with sarcopenia had increased risks of invasive fungal infection and renal replacement therapy. Conclusion:Sarcopenia was associated with 28-day mortality in male but not in female patients critically ill with ACLF. Although screening for sarcopenia could impact the management of male patients, further studies are needed in female cohorts to investigate whether other body composition parameters are associated with outcomes. Impact and implications:Body composition, easily assessed by CT, is altered in patients with cirrhosis and associated with outcome; it has never been investigated in patients critically ill with ACLF. The results of the present study, underlining the benefit of sarcopenia evaluation to improve prognosis prediction in males critically ill with ACLF, are of importance for physicians managing such patients to optimise the decision-making process toward continued treatment, liver transplantation, or limitation of care. In a wider sense, besides the number and course of organ failures, the results recall the weight of the general condition of males with ACLF at admission to ICU. In females critically ill with ACLF, in analyses limited by the sample size, none of the body composition parameters was associated with short-term mortality independently of organ failures; this suggests that the number and course of organ failures are the main determinant of mortality in these patients.
10.1016/j.jhepr.2023.100758
Alveolar Dead Space Is Augmented During Exercise in Patients With Heart Failure With Preserved Ejection Fraction.
Chest
BACKGROUND:Patients with heart failure with preserved ejection fraction (HFpEF) exhibit many cardiopulmonary abnormalities that could result in V˙/Q˙ mismatch, manifesting as an increase in alveolar dead space (VD) during exercise. Therefore, we tested the hypothesis that VD would increase during exercise to a greater extent in patients with HFpEF compared with control participants. RESEARCH QUESTION:Do patients with HFpEF develop VD during exercise? STUDY DESIGN AND METHODS:Twenty-three patients with HFpEF and 12 control participants were studied. Gas exchange (ventilation [V˙], oxygen uptake [V˙o], and CO elimination [V˙co]) and arterial blood gases were analyzed at rest, twenty watts (20W), and peak exercise. Ventilatory efficiency (evaluated as the V˙/V˙co slope) also was measured from rest to 20W in patients with HFpEF. The physiologic dead space (VD) to tidal volume (VT) ratio (VD/VT) was calculated using the Enghoff modification of the Bohr equation. VD was calculated as: (VD / VT × VT) - anatomic dead space. Data were analyzed between groups (patients with HFpEF vs control participants) across conditions (rest, 20W, and peak exercise) using a two-way repeated measures analysis of variance and relationships were analyzed using Pearson correlation coefficient. RESULTS:VD increased from rest (0.12 ± 0.07 L/breath) to 20W (0.22 ± 0.08 L/breath) in patients with HFpEF (P < .01), whereas VD did not change from rest (0.01 ± 0.06 L/breath) to 20W (0.06 ± 0.13 L/breath) in control participants (P = .19). Thereafter, VD increased from 20W to peak exercise in patients with HFpEF (0.37 ± 0.16 L/breath; P < .01 vs 20W) and control participants (0.19 ± 0.17 L/breath; P = .03 vs 20W). VD was greater in patients with HFpEF compared with control participants at rest, 20W, and peak exercise (main effect for group, P < .01). Moreover, the increase in VD correlated with the V˙/V˙co slope (r = 0.69; P < .01), which was correlated with peak V˙o (r = 0.46; P < .01) in patients with HFpEF. INTERPRETATION:These data suggest that the increase in V˙/Q˙ mismatch may be explained by increases in VD and that increases in VD worsens ventilatory efficiency, which seems to be a key contributor to exercise intolerance in patients with HFpEF.
10.1016/j.chest.2022.06.016
Association of Dental Diseases and Oral Hygiene Care With the Risk of Heart Failure in Patients With Type 2 Diabetes: A Nationwide Cohort Study.
Journal of the American Heart Association
Background To evaluate the association of dental diseases and oral hygiene care with incidence of heart failure (HF) among patients with type 2 diabetes. Methods and Results This study included 173 927 patients with type 2 diabetes aged ≥40 years, who underwent Korean National Health Insurance Service health examinations in 2008 and were followed up until the end of 2017. Hazard ratios (HRs) and 95% CIs for HF were estimated using multivariable Cox proportional hazards regression analysis. During a median follow-up of 9.3 years, 1.94% of participants developed HF. An increased number of missing teeth was associated with a higher risk of HF (<0.001). HRs of HF increased among individuals with ≥15 missing teeth (HR, 1.37 [95% CI, 1.14-1.64]) compared with those without missing teeth. Decreased risk of HF was observed in individuals with ≥1 time/year of professional dental cleaning (HR, 0.93 [95% CI, 0.87-0.99]) and in those with ≥2 times/d of toothbrushing (HR, 0.90 [95% CI, 0.82-0.98]) compared with those without these practices. While combined presence of missing teeth and periodontal disease (=0.004) or dental caries (=0.007) increased HF risk, combined oral hygiene care was associated with further HF risk reduction (=0.024). Better oral hygiene care was associated with decreased HF risk, even as the number of missing teeth increased (<0.001). Conclusions Among patients with type 2 diabetes, dental diseases and oral hygiene care are important determinants of HF development. Dental disease management and good oral care may prevent HF in patients with type 2 diabetes.
10.1161/JAHA.122.029207
Prognostic importance of glycemic variability on left ventricular reverse remodeling after the first episode of ST-segment elevation myocardial infarction.
Cardiovascular diabetology
BACKGROUND:This study aimed to investigate the effect of glycemic variability (GV), determined using a continuous glucose monitoring system (CGMS), on left ventricular reverse remodeling (LVRR) after ST-segment elevation myocardial infarction (STEMI). METHODS:A total of 201 consecutive patients with STEMI who underwent reperfusion therapy within 12 h of onset were enrolled. GV was measured using a CGMS and determined as the mean amplitude of glycemic excursion (MAGE). Left ventricular volumetric parameters were measured using cardiac magnetic resonance imaging (CMRI). LVRR was defined as an absolute decrease in the LV end-systolic volume index of > 10% from 1 week to 7 months after admission. Associations were also examined between GV and LVRR and between LVRR and the incidence of major adverse cardiovascular events (MACE; cardiovascular death, acute coronary syndrome recurrence, non-fatal stroke, and heart failure hospitalization). RESULTS:The prevalence of LVRR was 28% (n = 57). The MAGE was independent predictor of LVRR (odds ratio [OR] 0.98, p = 0.002). Twenty patients experienced MACE during the follow-up period (median, 65 months). The incidence of MACE was lower in patients with LVRR than in those without (2% vs. 13%, p = 0.016). CONCLUSION:Low GV, determined using a CGMS, was significantly associated with LVRR, which might lead to a good prognosis. Further studies are needed to validate the importance of GV in LVRR in patients with STEMI.
10.1186/s12933-023-01931-3
An innovative model for predicting coronary heart disease using triglyceride-glucose index: a machine learning-based cohort study.
Cardiovascular diabetology
BACKGROUND:Various predictive models have been developed for predicting the incidence of coronary heart disease (CHD), but none of them has had optimal predictive value. Although these models consider diabetes as an important CHD risk factor, they do not consider insulin resistance or triglyceride (TG). The unsatisfactory performance of these prediction models may be attributed to the ignoring of these factors despite their proven effects on CHD. We decided to modify standard CHD predictive models through machine learning to determine whether the triglyceride-glucose index (TyG-index, a logarithmized combination of fasting blood sugar (FBS) and TG that demonstrates insulin resistance) functions better than diabetes as a CHD predictor. METHODS:Two-thousand participants of a community-based Iranian population, aged 20-74 years, were investigated with a mean follow-up of 9.9 years (range: 7.6-12.2). The association between the TyG-index and CHD was investigated using multivariate Cox proportional hazard models. By selecting common components of previously validated CHD risk scores, we developed machine learning models for predicting CHD. The TyG-index was substituted for diabetes in CHD prediction models. All components of machine learning models were explained in terms of how they affect CHD prediction. CHD-predicting TyG-index cut-off points were calculated. RESULTS:The incidence of CHD was 14.5%. Compared to the lowest quartile of the TyG-index, the fourth quartile had a fully adjusted hazard ratio of 2.32 (confidence interval [CI] 1.16-4.68, p-trend 0.04). A TyG-index > 8.42 had the highest negative predictive value for CHD. The TyG-index-based support vector machine (SVM) performed significantly better than diabetes-based SVM for predicting CHD. The TyG-index was not only more important than diabetes in predicting CHD; it was the most important factor after age in machine learning models. CONCLUSION:We recommend using the TyG-index in clinical practice and predictive models to identify individuals at risk of developing CHD and to aid in its prevention.
10.1186/s12933-023-01939-9
Right ventricular myocardial work for the prediction of early right heart failure and long-term mortality after left ventricular assist device implant.
European heart journal. Cardiovascular Imaging
AIMS:Right heart failure (RHF) after left ventricular assist device (LVAD) implant is burdened by high morbidity and mortality rates and should be prevented by appropriate patient selection. Adequate right ventricular function is of paramount importance but its assessment is complex and cannot disregard afterload. Myocardial work (MW) is a non-invasive Speckle Tracking Echocardiography-derived method to estimate pressure-volume loops. The aim of this study was to evaluate the performance of right ventricular myocardial work to predict RHF and long-term mortality after LVAD implant. METHODS AND RESULTS:Consecutive patients from May 2017 to February 2022 undergoing LVAD implant were retrospectively reviewed. Patients without a useful echocardiographic exam prior to LVAD implant were excluded. MW analysis was performed. The primary endpoints were early RHF (<30 days from LVAD implant) and death at latest available follow-up. We included 23 patients (mean age 64 ± 8 years, 91% men). Median follow-up was 339 days (IQR: 30-1143). Early RHF occurred in six patients (26%). A lower right ventricular global work efficiency [RVGWE, OR 0.86, 95% confidence intervals (CI) 0.76-0.97, P = 0.014] was associated with the occurrence of early RHF. Among MW indices, the performance for early RHF prediction was greatest for RVGWE [area under the curve (AUC) 0.92] and a cut-off of 77% had a 100% sensitivity and 82% specificity. At long-term follow-up, death occurred in 4 of 14 patients (28.6%) in the RVGWE > 77% group and in 6 of 9 patients (66.7%) in the RVGWE < 77% group (HR 0.25, 95% CI 0.07-0.90, P = 0.033). CONCLUSION:RVGWE was a predictor of early RHF after LVAD implant and brought prognostic value in terms of long-term mortality.
10.1093/ehjci/jead193
Association of insulin use with LV remodeling and clinical outcomes in diabetic patients with heart failure and reduced ejection fraction: assessed by cardiac MRI.
Cardiovascular diabetology
BACKGROUND:Insulin is commonly used in type 2 diabetes mellitus (T2DM) to achieve glycemic control. However, recent evidence showed that insulin use is associated with poor outcomes in the context of heart failure (HF). Since heart failure with reduced ejection fraction (HFrEF) accounts for approximately 50% of cases in the general HF population, we aimed to evaluate the effect of insulin treatment on left ventricular (LV) remodeling and contractility abnormalities in a HFrEF cohort and assess whether insulin was a predictor of adverse outcomes in this entity. METHODS:A total of 377 HFrEF patients who underwent cardiac MRI were included and divided according to diabetes status and the need for insulin treatment. LV structural and functional indices, as well as systolic strains, were measured. The determinants of impaired myocardial strains were assessed using linear regression analysis. The associated endpoints were determined using a multivariable Cox proportional hazards model. RESULTS:T2DM patients on insulin displayed a higher indexed LV end-diastolic volume and LV mass than those with T2DM not on insulin or those without T2DM, despite similar LV ejection fractions, accompanied by a higher three-dimensional spherical index (P < 0.01). Worse longitudinal and circumferential peak systolic strain was shown to occur in T2DM patients on insulin (P < 0.01). Insulin treatment was independently associated with impaired magnitudes of systolic strain. The median follow-up duration was 32.4 months (IQR, 15.6-43.2 months). Insulin treatment remained consistently associated with poor outcomes after adjustment for established confounders, with an adjusted hazard ratio of 3.11; (95% CI, 1.45-6.87; P = 0.009) in the overall cohort and 2.16 (95% CI, 1.08-4.59; P = 0.030) in the diabetes cohort. CONCLUSIONS:Insulin may further lead to adverse LV remodeling and contractile dysfunction in the context of HFrEF with T2DM. Considerable care should be taken when treating HFrEF patients with insulin.
10.1186/s12933-023-01944-y
Phenotyping heart failure by echocardiography: imaging of ventricular function and haemodynamics at rest and exercise.
European heart journal. Cardiovascular Imaging
Traditionally, congestive heart failure (HF) was phenotyped by echocardiography or other imaging techniques according to left ventricular (LV) ejection fraction (LVEF). The more recent echocardiographic modality speckle tracking strain is complementary to LVEF, as it is more sensitive to diagnose mild systolic dysfunction. Furthermore, when LV systolic dysfunction is associated with a small, hypertrophic ventricle, EF is often normal or supernormal, whereas LV global longitudinal strain can reveal reduced contractility. In addition, segmental strain patterns may be used to identify specific cardiomyopathies, which in some cases can be treated with patient-specific medicine. In HF with preserved EF (HFpEF), a diagnostic hallmark is elevated LV filling pressure, which can be diagnosed with good accuracy by applying a set of echocardiographic parameters. Patients with HFpEF often have normal filling pressure at rest, and a non-invasive or invasive diastolic stress test may be used to identify abnormal elevation of filling pressure during exercise. The novel parameter LV work index, which incorporates afterload, is a promising tool for quantification of LV contractile function and efficiency. Another novel modality is shear wave imaging for diagnosing stiff ventricles, but clinical utility remains to be determined. In conclusion, echocardiographic imaging of cardiac function should include LV strain as a supplementary method to LVEF. Echocardiographic parameters can identify elevated LV filling pressure with good accuracy and may be applied in the diagnostic workup of patients suspected of HFpEF.
10.1093/ehjci/jead196
Incident Heart Failure Risk Reclassification With Race-Independent Estimated Glomerular Filtration Rate: A National Heart, Lung, and Blood Institute Pooled Cohorts Analysis.
Journal of cardiac failure
BACKGROUND:This study compared the predictive value of the race-independent creatinine- and cystatin C-based estimated glomerular filtration rate (eGFR) and the race-dependent creatinine-based eGFR (eGFR) for incident heart failure (HF). METHODS:This study combined the participant-level data from ARIC (Atherosclerosis Risk in Communities) (visit 4) and MESA (Multi-Ethnic Study of Atherosclerosis) (visit 1) to calculate eGFR and eGFR. The primary outcome of the study was adjudicated incident HF over a follow-up period of 10 years. Multivariable Cox models were used to assess the risk of incident HF with the quartiles of eGFR and eGFR. RESULTS:Among 15,615 individuals (median age: 62 [57-68] years; 55.0% females; 23.9% Black), the median eGFR and eGFR were 91.4 (79.4, 102.0) mL/min/1.73m and 84.7 (72.0, 94.7) mL/min/1.73m, respectively. Compared with the fourth quartile of eGFR, the hazard ratio for incident HF was 1.02 (95% CI:0.80-1.30) in the third quartile, 1.02 (95% CI:0.80-1.30) in the second quartile, and 1.47 (95% CI:1.16-1.86) in the first quartile. Compared with the 4th quartile of the eGFR the risk of incident HF was similar in the 3rd (HR:0.90 [95% CI:0.73-1.12]), 2nd (HR: 0.96 [95% CI:0.77-1.20]), and 1st (HR:1.15 [95% CI:0.93-1.44]) quartiles. C-statistics were similar for the multivariable-adjusted Cox models for incident HF using eGFR (0.80 [0.79-0.81]) and eGFR (0.80 [0.79-0.82]). CONCLUSION:The eGFR and eGFR had comparable predictive values for incident HF.
10.1016/j.cardfail.2023.07.009
Two-Year Changes in Diabetic Kidney Disease Phenotype and the Risk of Heart Failure: A Nationwide Population-Based Study in Korea.
Diabetes & metabolism journal
BACKGRUOUND:Diabetic kidney disease (DKD) is a risk factor for hospitalization for heart failure (HHF). DKD could be classified into four phenotypes by estimated glomerular filtration rate (eGFR, normal vs. low) and proteinuria (PU, negative vs. positive). Also, the phenotype often changes dynamically. This study examined HHF risk according to the DKD phenotype changes across 2-year assessments. METHODS:The study included 1,343,116 patients with type 2 diabetes mellitus (T2DM) from the Korean National Health Insurance Service database after excluding a very high-risk phenotype (eGFR <30 mL/min/1.73 m2) at baseline, who underwent two cycles of medical checkups between 2009 and 2014. From the baseline and 2-year eGFR and PU results, participants were divided into 10 DKD phenotypic change categories. RESULTS:During an average of 6.5 years of follow-up, 7,874 subjects developed HHF. The cumulative incidence of HHF from index date was highest in the eGFRlowPU- phenotype, followed by eGFRnorPU+ and eGFRnorPU-. Changes in DKD phenotype differently affect HHF risk. When the persistent eGFRnorPU- category was the reference, hazard ratios for HHF were 3.10 (95% confidence interval [CI], 2.73 to 3.52) in persistent eGFRnorPU+ and 1.86 (95% CI, 1.73 to 1.99) in persistent eGFRlowPU-. Among altered phenotypes, the category converted to eGFRlowPU+ showed the highest risk. In the normal eGFR category at the second examination, those who converted from PU- to PU+ showed a higher risk of HHF than those who converted from PU+ to PU-. CONCLUSION:Changes in DKD phenotype, particularly with the presence of PU, are more likely to reflect the risk of HHF, compared with DKD phenotype based on a single time point in patients with T2DM.
10.4093/dmj.2022.0096
Controlling nutritional status score predicts 2-year outcomes in elderly patients admitted for acute heart failure.
Internal and emergency medicine
BACKGROUND:Heart failure (HF) is a major cause of death among the elderly. Its prevalence increases dramatically with age. The prevalence of malnourished subjects is high in hospitalized elderly patients. We aimed to investigate the prognostic role of malnutrition, assessed by controlling nutritional status (CONUT) score, on adverse clinical outcomes in the elderly admitted for acute HF. METHODS:We enrolled 293 patients (mean age 84 years; 48% men) consecutively admitted for acute HF to the Internal Medicine or Geriatrics Divisions at the 'IRCCS Sacro Cuore-Don Calabria' Hospital of Negrar (Verona, Italy) from 2013 to 2015. We predicted the risk of all-cause death, re-hospitalizations for HF and non-HF causes, and the composite of all-cause death or hospitalizations over 2-year follow-up. Patients were divided into four groups according to CONUT score: normal-CONUT (0-1; n = 30); mild-CONUT (2-3; n = 56); moderate-CONUT (4-7; n = 171); and severe-CONUT (≥ 8; n = 36). RESULTS:Higher CONUT scores were associated with older age and lower entry blood pressures. No difference in hemodynamics was noted at the discharge. Kaplan-Meier curves showed a significant association between worsening CONUT scores and risk of all-cause death (p < 0.01), re-hospitalizations (p < 0.01), or both (p < 0.001). Cox regression analysis revealed these significant associations persisted after adjustment for age, sex, pre-existing cardiovascular disease, diabetes, chronic kidney disease, heart rate, systolic blood pressure, and plasma brain natriuretic peptide levels at discharge (all-cause mortality HR = 1.29 (1.00-1.66), p = 0.049; hospitalization for HF HR = 1.36 (1.03-1.81), p = 0.033; hospitalization for non-HF HR = 1.38 (1.03-1.86), p = 0.034; composite outcome HR = 1.33 (1.07-1.64), p = 0.01). CONCLUSIONS:Malnutrition, assessed by the CONUT score, is common among elderly patients admitted for acute HF and is strongly related to increased long-term risk of all-cause death and re-hospitalizations.
10.1007/s11739-023-03230-x
Patient mortality following new-onset heart failure stratified by cancer type and status.
European journal of heart failure
AIM:Expected 1-year survival is essential to risk stratification of patients with heart failure (HF); however, little is known about the 1-year prognosis of patients with HF and cancer. Thus, the objective was to investigate the 1-year prognosis following new-onset HF stratified by cancer status in patients with breast, gastrointestinal, or lung cancer. METHODS AND RESULTS:All Danish patients with new-onset HF from 2000 to 2018 were included. Cancer status was categorized as history of cancer (no cancer-related contact within 5 years of HF diagnosis), non-active cancer (curative intended procedure administered) and active cancer. Standardized 1-year all-cause mortality was reported using G-computation. Age-stratified 1-year all-cause mortality was estimated using the Kaplan-Meier estimator. In total, 193 359 patients with HF were included, 7.3% had either a breast, gastrointestinal, or lung cancer diagnosis. Patients with cancer were older and more comorbid than patients without cancer. Standardized 1-year all-cause mortality (95% confidence intervals) was 24.6% (23.0-26.2%), 27.1% (25.5-28.6%), and 29.9% (25.9-34.0%) for history of breast, gastrointestinal and lung cancer, respectively, which was comparable to patients with non-active cancers. For active breast, gastrointestinal and lung cancer, standardized 1-year all-cause mortality was 36.2% (33.8-38.6%), 49.0% (47.2-50.9%), and 61.6% (59.7-63.5%), respectively. One-year all-cause mortality increased incrementally with age, except for active lung cancer. CONCLUSION:Standardized 1-year all-cause mortality was comparable for patients with history of cancer and non-active cancer regardless of cancer type, but varied comprehensively for active cancers. Prognostic impact of age was limited for active lung cancer. Thus, granular stratification of cancer is necessary for optimized management of new-onset HF.
10.1002/ejhf.2984
Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction: The CAMEO-DAPA Trial.
Circulation
BACKGROUND:Sodium-glucose cotransporter-2 inhibitors reduce risk of hospitalization for heart failure in patients who have heart failure with preserved ejection fraction (HFpEF), but the hemodynamic mechanisms underlying these benefits remain unclear. This study sought to determine whether treatment with dapagliflozin affects pulmonary capillary wedge pressure (PCWP) at rest and during exercise in patients with HFpEF. METHODS:This was a single-center, double-blinded, randomized, placebo-controlled trial testing the effects of 10 mg of dapagliflozin once daily in patients with HFpEF. Patients with New York Heart Association class II or III heart failure, ejection fraction ≥50%, and elevated PCWP during exercise were recruited. Cardiac hemodynamics were measured at rest and during exercise using high-fidelity micromanometers at baseline and after 24 weeks of treatment. The primary end point was a change from baseline in rest and peak exercise PCWPs that incorporated both measurements, and was compared using a mixed-model likelihood ratio test. Key secondary end points included body weight and directly measured blood and plasma volumes. Expired gas analysis was performed evaluate oxygen transport in tandem with arterial lactate sampling. RESULTS:Among 38 patients completing baseline assessments (median age 68 years; 66% women; 71% obese), 37 completed the trial. Treatment with dapagliflozin resulted in reduction in the primary end point of change in PCWP at rest and during exercise at 24 weeks relative to treatment with placebo (likelihood ratio test for overall changes in PCWP; <0.001), with lower PCWP at rest (estimated treatment difference [ETD], -3.5 mm Hg [95% CI, -6.6 to -0.4]; =0.029) and maximal exercise (ETD, -5.7 mm Hg [95% CI, -10.8 to -0.7]; =0.027). Body weight was reduced with dapagliflozin (ETD, -3.5 kg [95% CI, -5.9 to -1.1]; =0.006), as was plasma volume (ETD, -285 mL [95% CI, -510 to -60]; =0.014), but there was no significant effect on red blood cell volume. There were no differences in oxygen consumption at 20-W or peak exercise, but dapagliflozin decreased arterial lactate at 20 W (-0.70 ± 0.77 versus 0.37 ± 1.29 mM; =0.006). CONCLUSIONS:In patients with HFpEF, treatment with dapagliflozin reduces resting and exercise PCWP, along with the favorable effects on plasma volume and body weight. These findings provide new insight into the hemodynamic mechanisms of benefit with sodium-glucose cotransporter-2 inhibitors in HFpEF. REGISTRATION:URL: https://www. CLINICALTRIALS:gov; Unique identifier: NCT04730947.
10.1161/CIRCULATIONAHA.123.065134
Microvascular Burden and Incident Heart Failure Among Middle-Aged and Older Adults With Type 1 or Type 2 Diabetes.
Diabetes care
OBJECTIVE:To examine the association between microvascular disease (MVD) and risk of heart failure (HF) among individuals with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS:We included 1,713 and 28,624 participants with T1DM and T2DM, respectively, from the UK Biobank who were free of HF during enrollment. MVD burden reflected by the presence of retinopathy, peripheral neuropathy, and chronic kidney disease (CKD) at baseline was prospectively evaluated for the association with incidence of HF. Hazard ratios (HRs) and 95% CIs of HF were estimated by Cox regression models adjusted for multiple traditional risk factors. RESULTS:There were 145 and 2,515 incident cases of HF recorded among participants with T1DM and T2DM, respectively, during a median follow-up of 11.5 years. The association between the number of MVD and HF was stronger among participants with T1DM than among those with T2DM (P for interaction <0.001). Compared with participants with no MVD, those with all three MVD had an adjusted HR (95% CI) of 11.37 (5.62, 22.99) in T1DM and 3.66 (2.74, 4.88) in T2DM. In T1DM, HRs (CIs) were 2.69 (1.75, 4.14) for retinopathy, 2.11 (1.38, 3.23) for peripheral neuropathy, and 2.21 (1.53, 3.18) for CKD. The corresponding estimates in T2DM were 1.24 (1.13, 1.36), 1.63 (1.36, 1.96), and 1.73 (1.59, 1.89), respectively. CONCLUSIONS:While a heavier burden of MVD was associated with excess risk of HF both in T1DM and T2DM, the association was evidently more pronounced in T1DM.
10.2337/dc22-0177
Association of Social Isolation and Loneliness With Incident Heart Failure in a Population-Based Cohort Study.
JACC. Heart failure
BACKGROUND:Social isolation and loneliness have emerged as important risk factors for cardiovascular diseases, particularly during the coronavirus disease pandemic. However, it is unclear whether social isolation and loneliness had independent and joint associations with incident heart failure (HF). OBJECTIVES:This study sought to examine the association of social isolation, loneliness, and their combination with incident HF. METHODS:The UK Biobank study is a population-based cohort study. Social isolation and loneliness were assessed using self-reported questionnaires. HF cases were identified by linking hospital records and death registries. The weighted polygenic risk score associated with HF was calculated. RESULTS:Among the 464,773 participants (mean age: 56.5 ± 8.1 years, 45.3% male), 12,898 incident HF cases were documented during a median follow-up of 12.3 years. Social isolation (most vs least: adjusted HR: 1.17; 95% CI:1.11-1.23) and loneliness (yes vs no: adjusted HR: 1.19; 95% CI: 1.11-1.27) were significantly associated with an increased risk of incident HF. The association between an elevated risk of HF and social isolation was modified by loneliness (P = 0.034). A gradient of association between social isolation and the risk of incident HF was found only among individuals without loneliness (P < 0.001), but not among those with loneliness (P = 0.829). These associations were independent of the genetic risk of HF. CONCLUSIONS:Social isolation and loneliness were independently associated with a higher likelihood of incident HF regardless of genetic risk. The association between social isolation and incident HF was potentially modified by loneliness status.
10.1016/j.jchf.2022.11.028
Incremental diagnostic value of post-exercise lung congestion in heart failure with preserved ejection fraction.
European heart journal. Cardiovascular Imaging
AIMS:Lung ultrasound (LUS) may unmask occult heart failure with preserved ejection fraction (HFpEF) by demonstrating an increase in extravascular lung water (EVLW) during exercise. Here, we sought to examine the dynamic changes in ultrasound B-lines during exercise to identify the optimal timeframe for HFpEF diagnosis. METHODS AND RESULTS:Patients with HFpEF (n = 134) and those without HF (controls, n = 121) underwent a combination of exercise stress echocardiography and LUS with simultaneous expired gas analysis to identify exercise EVLW. Exercise EVLW was defined by B-lines that were newly developed or increased during exercise. The E/e' ratio peaked during maximal exercise and immediately decreased during the recovery period in patients with HFpEF. Exercise EVLW was most prominent during the recovery period in patients with HFpEF, while its prevalence did not increase from peak exercise to the recovery period in controls. Exercise EVLW was associated with a higher E/e' ratio and pulmonary artery pressure, lower right ventricular systolic function, and elevated minute ventilation to carbon dioxide production (VE vs. VCO2) slope during peak exercise. Increases in B-lines from rest to the recovery period provided an incremental diagnostic value to identify HFpEF over the H2FPEF score and resting left atrial reservoir strain. CONCLUSION:Exercise EVLW was most prominent early during the recovery period; this may be the optimal timeframe for imaging ultrasound B-lines. Exercise stress echocardiography with assessments of recovery EVLW may enhance the diagnosis of HFpEF.
10.1093/ehjci/jead007
Unfavourable outcomes in patients with heart failure with higher preserved left ventricular ejection fraction.
European heart journal. Cardiovascular Imaging
AIMS:Newly introduced drugs for heart failure (HF) have been reported to improve the prognosis of HF with preserved ejection fraction (HFpEF) in the lower range of left ventricular ejection fraction (LVEF). We hypothesized that a higher LVEF is related to an unfavourable prognosis in patients with HFpEF. METHODS AND RESULTS:We tested this hypothesis by analysing the data from a prospective multicentre cohort study in 255 patients admitted to the hospital due to decompensated HF (LVEF > 40% at discharge). The primary endpoint of this study was a composite outcome of all-cause death and readmission due to HF, and the secondary endpoint was readmission due to HF. LVEF and the mitral E/e' ratio were measured using echocardiography. In multicovariate parametric survival time analysis, LVEF [hazard ratio (HR) = 1.046 per 1% increase, P = 0.001], concurrent atrial fibrillation (AF) (HR = 3.203, P < 0.001), and E/e' (HR = 1.083 per 1.0 increase, P < 0.001) were significantly correlated with the primary endpoint. In addition to these covariates, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use was significantly correlated with the secondary endpoint (HR = 0.451, P = 0.008). Diagnostic performance plot analysis demonstrated that the discrimination threshold value for LVEF that could identify patients prone to reaching the primary endpoint was ≥57.2%. The prevalence of AF or E/e' ratio did not differ significantly between patients with LVEF ≥ 58% and with 40% < LVEF < 58%. CONCLUSION:A higher LVEF is independently related to poor prognosis in patients with HFpEF, in addition to concurrent AF and an elevated E/e' ratio. ACEI/ARB use, in contrast, was associated with improved prognosis, especially with regard to readmission due to HF. CLINICAL TRIAL REGISTRATION:https://www.umin.ac.jp/ctr/index.htm. UNIQUE IDENTIFIER:UMIN000017725.
10.1093/ehjci/jeac240
A streamlined, machine learning-derived approach to risk-stratification in heart failure patients with secondary tricuspid regurgitation.
European heart journal. Cardiovascular Imaging
AIMS:Secondary tricuspid regurgitation (sTR) is the most frequent valvular heart disease and has a significant impact on mortality. A high burden of comorbidities often worsens the already dismal prognosis of sTR, while tricuspid interventions remain underused and initiated too late. The aim was to examine the most powerful predictors of all-cause mortality in moderate and severe sTR using machine learning techniques and to provide a streamlined approach to risk-stratification using readily available clinical, echocardiographic and laboratory parameters. METHODS AND RESULTS:This large-scale, long-term observational study included 3359 moderate and 1509 severe sTR patients encompassing the entire heart failure spectrum (preserved, mid-range and reduced ejection fraction). A random survival forest was applied to investigate the most important predictors and group patients according to their number of adverse features.The identified predictors and thresholds, that were associated with significantly worse mortality were lower glomerular filtration rate (<60 mL/min/1.73m2), higher NT-proBNP, increased high sensitivity C-reactive protein, serum albumin < 40 g/L and hemoglobin < 13 g/dL. Additionally, grouping patients according to the number of adverse features yielded important prognostic information, as patients with 4 or 5 adverse features had a fourfold risk increase in moderate sTR [4.81(3.56-6.50) HR 95%CI, P < 0.001] and fivefold risk increase in severe sTR [5.33 (3.28-8.66) HR 95%CI, P < 0.001]. CONCLUSION:This study presents a streamlined, machine learning-derived and internally validated approach to risk-stratification in patients with moderate and severe sTR, that adds important prognostic information to aid clinical-decision-making.
10.1093/ehjci/jead009
A higher probability of subsequent stroke and ischemic heart disease in migraine patients: a longitudinal follow-up study in Korea.
The journal of headache and pain
BACKGROUND:Whether migraine is related to the risk of cardiovascular diseases (CVDs) remains unclear. Therefore, we conducted a longitudinal follow-up study to address the association between migraine and the development of CVDs in Korea. METHODS:Using data from the national health screening cohort, we included 45,246 patients diagnosed with migraine between 2002 and 2019 and age-, sex-, income-, and residential region-matched nonmigraine participants at a ratio of 1:4. Participants with previous CVDs were excluded. Cox proportional hazards regression models were used to estimate the hazard ratios of three CVDs, stroke, ischemic heart disease, and heart failure, in patients with migraine after adjusting for potential cardiovascular risk factors. RESULTS:The incidence rate differences of stroke, ischemic heart disease, and heart failure among patients with migraine were 2.61, 1.69, and 0.11, respectively. The probability of developing stroke and ischemic heart disease in patients with migraine was significantly higher than that in controls after controlling for multiple confounders (adjusted hazard ratio [HR] = 1.35, 95% confidence interval [CI] = 1.31-1.39 and adjusted HR = 1.31, 95% CI = 1.26-1.35, respectively). However, when compared with the patients without migraine, patients with migraine did not have an increased HR of developing heart failure (adjusted HR = 1.01, 95% CI = 0.95-1.08). The overall migraine group, as well as groups stratified by migraine subtypes with and without aura, each showed a significantly higher probability of subsequent stroke and ischemic heart disease than the control group. CONCLUSIONS:Our longitudinal follow-up study demonstrated a significant association between the presence of migraine and the development of stroke and ischemic heart disease in Korea, even after adjusting for cardiovascular risk factors.
10.1186/s10194-023-01632-y
New Classification for the Combined Assessment of the Fractional Excretion of Urea Nitrogen and Estimated Plasma Volume Status in Acute Heart Failure.
Journal of the American Heart Association
Background The fractional excretion of urea nitrogen (FEUN) has been used as a renal blood flow index related to cardiac output, and the estimated plasma volume status (ePVS) as a body fluid volume index. However, the usefulness of their combination in acute decompensated heart failure (HF) management is unclear. We investigated the effect of 4 hemodynamic categories according to the high and low FEUN and ePVS values at discharge on the long-term prognosis of patients with acute decompensated HF. Methods and Results Between April 2011 and December 2018, we retrospectively identified 466 patients with acute decompensated HF with FEUN and ePVS values at discharge. Primary end point was postdischarge all-cause death. Secondary end points were (1) the composite of all-cause death and HF readmission, and (2) HF readmission in a time-to-event analysis. The patients were divided into 4 groups according to the high/low FEUN (≥35%, <35%) and ePVS (>5.5%, ≤5.5%) values at discharge: high-FEUN/low-ePVS, high-FEUN/high-ePVS, low-FEUN/low-ePVS, and low-FEUN/high-ePVS groups. During a median follow-up period of 28.1 months, there were 173 all-cause deaths (37.1%), 83 cardiovascular deaths (17.8%), and 121 HF readmissions (26.0%). The Kaplan-Meier curve analysis showed that the high-FEUN/low-ePVS group had a better prognosis than the other groups (log-rank test, <0.001). In the multivariable Cox regression analysis, the low-FEUN/high-ePVS group had a higher mortality than the high-FEUN/low-ePVS group (hazard ratio, 2.92 [95% CIs, 1.73-4.92; <0.001]). Conclusions The new classification of the 4 hemodynamic profiles using the FEUN and ePVS values may play an important role in improving outcomes in patients with stable acute decompensated HF.
10.1161/JAHA.122.025596
Combination of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as a Novel Predictor of Cardiac Death in Patients With Acute Decompensated Heart Failure With Preserved Left Ventricular Ejection Fraction: A Multicenter Study.
Journal of the American Heart Association
Background Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel inflammation markers. Their combined usefulness for estimating the prognosis of patients with heart failure with preserved ejection fraction (HFpEF) admitted for acute decompensated heart failure remains elusive. Methods and Results We investigated 1026 patients registered in the Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction. Both NLR and PLR values were measured at the time of admission. Comorbidity burden was defined as the number of occurrences of 8 common comorbidities of HFpEF. The primary end point was cardiac death. The patients were stratified into 3 groups based on the optimal cut-off values of NLR and PLR on the receiver operating characteristic curve analysis for predicting cardiac death (low NLR and PLR, either high NLR or PLR, and both high NLR and PLR). After a median follow-up of 429 days, 195 patients died, with 85 of these deaths attributed to cardiac causes. An increased comorbidity burden was significantly associated with a higher proportion of patients with high NLR (>4.5) or PLR (>193), or both. High NLR and PLR values were independently associated with cardiac death, and a combination of both values was the strongest predictor (hazard ratio, 2.66 [95% CI, 1.51%-4.70%], =0.0008). A significant difference was found in the rate of cardiac death among the 3 groups stratified by NLR and PLR values. Conclusions The combination of NLR and PLR is useful for the prediction of postdischarge cardiac death in patients with acute HFpEF. Registration URL: ClinicalTrials.gov; Unique identifier: UMIN000021831.
10.1161/JAHA.122.026326
Positive Airway Pressure Therapy Adherence and Health Care Resource Use in Patients With Obstructive Sleep Apnea and Heart Failure With Preserved Ejection Fraction.
Journal of the American Heart Association
Background Obstructive sleep apnea (OSA) is common in heart failure with preserved ejection fraction (HFpEF). However, current evidence is equivocal regarding the potential benefits of treating OSA with positive airway pressure (PAP) therapy in HFpEF. This study assessed the association between adherence to PAP therapy and health care resource use in patients with OSA and HFpEF. Methods and Results Administrative insurance claims data linked with objective PAP therapy usage data from patients with OSA and HFpEF were used to determine associations between PAP adherence and a composite outcome including hospitalizations and emergency room visits. One-year PAP adherence was based on an adapted US Medicare definition. Propensity score methods were used to create groups with similar characteristics across PAP adherence levels. The study cohort included 4237 patients (54.0% female, mean age 64.1 years); 40% were considered adherent to PAP therapy (30% intermediate adherent, 30% nonadherent). In the matched cohort, PAP-adherent patients had fewer health care resource use visits than nonadherent patients, a 57% decrease in hospitalizations, and a 36% decrease in emergency room visits versus the year before PAP initiation. Total health care costs were lower in adherent patients than nonadherent patients ($12 732 versus $15 610, <0.001). Outcomes for intermediately adherent patients were most similar to those for nonadherent patients. Conclusions Treating OSA with PAP therapy in patients with HFpEF was associated with a reduction in health care resource use. These data highlight the importance of managing concomitant OSA in patients with HFpEF, and the need for strategies to enhance PAP adherence in this population.
10.1161/JAHA.122.028733
Impact of Complete Revascularization on Development of Heart Failure in Patients With Acute Coronary Syndrome and Multivessel Disease: A Subanalysis of the CORALYS Registry.
Journal of the American Heart Association
Background The impact of complete revascularization (CR) on the development of heart failure (HF) in patients with acute coronary syndrome and multivessel coronary artery disease undergoing percutaneous coronary intervention remains to be elucidated. Methods and Results Consecutive patients with acute coronary syndrome with multivessel coronary artery disease from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of first hospitalization for HF or cardiovascular death was the primary end point. Patients were stratified according to completeness of coronary revascularization. Of 14 699 patients in the CORALYS registry, 5054 presented with multivessel disease. One thousand four hundred seventy-three (29.2%) underwent CR, while 3581 (70.8%) did not. Over 5 years follow-up, CR was associated with a reduced incidence of the primary end point (adjusted hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]), first HF hospitalization (adjusted HR, 0.67 [95% CI, 0.49-0.90]) along with all-cause death and cardiovascular death alone (adjusted HR, 0.74 [95% CI, 0.56-0.97] and HR, 0.56 [95% CI, 0.38-0.84], respectively). The results were consistent in the propensity-score matching population and in inverse probability treatment weighting analysis. The benefit of CR was consistent across acute coronary syndrome presentations (HR, 0.59 [95% CI, 0.39-0.89] for ST-segment elevation myocardial infarction and HR, 0.71 [95% CI, 0.50-0.99] for non-ST-elevation acute coronary syndrome) and in patients with left ventricular ejection fraction >40% (HR, 0.52 [95% CI, 0.37-0.72]), while no benefit was observed in patients with left ventricular ejection fraction ≤40% (HR, 0.77 [95% CI, 0.37-1.10], for interaction 0.04). Conclusions CR after acute coronary syndrome reduced the risk of first hospitalization for HF and cardiovascular death, as well as first HF hospitalization, and cardiovascular and overall death both in patients with ST-segment elevation myocardial infarction and non-ST-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04895176.
10.1161/JAHA.122.028475
Haemodynamic gain index and heart failure incidence- Prognostic and preventive value.
European journal of preventive cardiology
AIMS:Heart failure (HF) is a non-curable, life-threatening condition, characterized by impaired haemodynamic function and poor survival. This study aimed to assess the association between haemodynamic gain index (HGI) and HF incidence in men. METHODS AND RESULTS:Exposure was HGI, [(HRpeak*SBPpeak) - (HRrest*SBPrest)]/(HRrest*SBPrest) measured from treadmill exercise testing in 5539 men aged 59 ± 11.5 years who were free from HF at baseline. The outcome was the incidence of HF. Cox hazard models adjusted for established risk factors were analysed for the association between HGI and HF. During 14.3 ± 6 years of follow-up, 297 cases of HF occurred (average annual incidence rate 3.7 events per 1000 person-years) and average HGI was 1.6 ± 0.7 bpm/mmHg. In a continuous model, every one unit higher in HGI was associated with a 44% [hazard ratio 0.56, 95% confidence interval (0.45-0.69), P < 0.001] lower risk of HF incidence. In a categorical model, compared with those in quartile-4 (HGI > 2.0), those in quartile-3 (HGI 1.51-2.0), quartile-2 (HGI 1.05-1.5), and quartile-1 (HGI < 1.05) exhibited 70%, 220%, and 280% higher risks for developing HF, respectively (P trend < 0.001). CONCLUSION:HGI was found to be a strong predictor of HF incidence in men, supporting its prognostic value. Higher HGI was independently associated with lower risk of HF incidence, while low HGI could serve as a prognostic risk factor for HF. Integrating HGI in the screening and early detection paradigm and referring individuals with low HGI to exercise rehabilitation could potentially enhance public health and prevention strategies against HF.
10.1093/eurjpc/zwad236
Epicardial Fat Volume, Cardiac Function, and Incident Heart Failure: The Rotterdam Study.
Journal of the American Heart Association
Background Larger epicardial fat volume (EFV) has been associated with increased risks of cardiovascular disease and atrial fibrillation. Yet, evidence on the association of EFV with cardiac function and incident heart failure (HF) remains scarce. Methods and Results We included 2103 participants (mean age, 68 years; 54.4% women) from the prospective population-based RS (Rotterdam Study) with computed tomography-based EFV and repeated echocardiography-based assessment of left ventricular (LV) systolic and diastolic function. Linear mixed effects and Cox-proportional hazard regression models, adjusted for cardiovascular risk factors, were used to assess the associations of EFV with repeated measurements of echocardiographic parameters and with incident HF. During a median follow-up of 9.7 years, 124 HF events occurred (incidence rate, 6.37 per 1000 person-years). For LV systolic function, 1-SD larger EFV was associated with 0.76 (95% CI, 0.54-0.98) mm larger LV end-diastolic dimension, 0.66 (95% CI, 0.47-0.85) mm larger LV end-systolic dimension, and 0.56% (95% CI, -0.86% to -0.27%) lower LV ejection fraction. Interactions between EFV and time were small. For LV diastolic function, 1-SD larger EFV was associated with 1.02 (95% CI, 0.78-1.27) mm larger left atrial diameter. Larger EFV was also associated with incident HF (hazard ratio per 1-SD increase in EFV, 1.34 [95% CI, 1.07-1.68] per 1-SD larger EFV). Conclusions We report an independent association between EFV with new-onset HF in the general population. EFV seems to exert its influence on HF through different pathways contributing to deteriorations in systolic function and larger left atrial size in part, likely through mechanical restraint and hypertrophy.
10.1161/JAHA.122.026197
Impact of Empagliflozin in Heart Failure With Reduced Ejection Fraction in Patients With Ischemic Versus Nonischemic Cause.
Journal of the American Heart Association
Background Outcomes and treatment effects of therapy may vary according to the cause of heart failure (HF). Methods and Results In this post hoc analysis of the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) trial, the effect of empagliflozin on cardiovascular and renal outcomes was assessed according to the cause of HF. The cause of HF was investigator reported and stratified as ischemic or nonischemic. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs. Of the 3730 patients enrolled, 1929 (51.7%) had ischemic cause. In the placebo arm, patients with ischemic cause of HF did not have a significantly higher risk of cardiovascular mortality (HR, 1.21 [95% CI, 0.90-1.63]) and hospitalization for HF (HR, 0.90 [95% CI, 0.72-1.12]) compared with nonischemic cause. Empagliflozin compared with placebo significantly reduced the risk of cardiovascular death or hospitalization for HF in patients with ischemic and nonischemic cause (HR, 0.82 [95% CI, 0.68-0.99] for ischemic and HR, 0.67 [95% CI, 0.55-0.82] for nonischemic cause; interaction=0.15). The benefit of empagliflozin on HF hospitalization, the renal composite end point, estimated glomerular filtration slope changes, and health status scores were also consistent in both groups without treatment by cause modification. Conclusions Empagliflozin offers cardiovascular and renal benefits in patients with heart failure with reduced ejection fraction regardless of the cause of HF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.
10.1161/JAHA.122.027652
Short-term prognosis of changes in plasma potassium following an episode of hyperkalaemia in patients with chronic heart failure.
European journal of internal medicine
BACKGROUND/AIM:There is an increasing prevalence of chronic heart failure (HF). It is well known that patients with HF and disturbances in the potassium level have an increased mortality risk. The aim of this study was to investigate the prognosis of a second plasma-potassium measurement after an episode with hyperkalaemia on short-term mortality in patients with chronic HF. METHODS AND RESULTS:From Danish national registers, 2,339 patients with chronic HF and hyperkalaemia (>4.6 mmol/L) at first potassium measurement within 14-365 days from concomitant treatment were identified. To be included, a second measurement was required within 6-30 days subsequent to the first measurement and the 60-day mortality was observed. Based on the second measurement, the patients were divided into five groups: <3.5 mmol/L (n = 257), 3.5-4.0 mmol/L (n = 709), 4.1-4.6 mmol/L (n = 1,204, reference), 4.7-5.0 mmol/L (n = 89) and >5.0 mmol/L (n = 80). To assess all-cause and cardiovascular mortality, we used the Cox regression model. The multivariable analysis showed that patients with potassium concentrations <3.5 mmol/L (hazard ratio (HR): 3.03; 95% CI: 2.49-3.70) and 3.5-4.0 mmol/L (HR: 1.81; 95% CI: 1.54-2.14) had a worse prognosis compared to the reference. We observed similar results when calculating the risk of cardiovascular mortality. A restricted cubic spline curve showed a U-shaped relationship between plasma-potassium and all-cause mortality. CONCLUSION:Patients with chronic HF and hyperkalaemia who became hypokalaemic after 6-30 days were associated with a higher 60-day all-cause and cardiovascular mortality compared to the reference. This also applied for patients with low normal potassium concentrations (3.5-4.0 mmol/L).
10.1016/j.ejim.2023.07.031
Sodium-glucose cotransporter 2 inhibitor use in early-phase acute coronary syndrome with severe heart failure.
European heart journal. Cardiovascular pharmacotherapy
AIMS:Sodium-glucose cotransporter 2 inhibitor (SGLT2i) improves clinical outcomes in patients with heart failure (HF), but has limited evidence of SGLT2i use in early-phase acute coronary syndrome (ACS). We determined association of early SGLT2i use compared with either non-SGLT2i or dipeptidyl peptidase 4 inhibitor (DPP4i) use in hospitalized patients with ACS. METHODS AND RESULTS:This retrospective cohort study that used the Japanese nationwide administrative claims database included patients hospitalized with ACS aged ≥20 years between April 2014 and March 2021. The primary outcome was a composite of all-cause mortality or HF/ACS rehospitalization. Using 1:1 propensity score matching, the association with outcomes of the early SGLT2i use (≤14 days after admission) compared with non-SGLT2i or DPP4i use was determined according to the HF treatment. Among 388 185 patients included 115 612 and 272 573 with and without severe HF, respectively. Compared to non-SGLT2i users, the SGLT2i users had a lower hazard ratio (HR) with the primary outcome [HR: 0.83, 95% confidence interval (CI): 0.76-0.91; P < 0.001] in the severe HF group; however, there was no significant difference in the non-severe HF group (HR: 0.92, 95% CI: 0.82-1.03; P = 0.16). SGLT2i use showed a lower risk of the outcome in patients with severe HF and diabetes compared with DPP4i use (HR: 0.83, 95% CI: 0.69-1.00; P = 0.049). CONCLUSION:SGLT2i use in patients with early-phase ACS showed a lower risk of primary outcome in patients with severe HF, but the effect was not apparent in patients without severe HF.
10.1093/ehjcvp/pvad035
Medications for specific phenotypes of heart failure with preserved ejection fraction classified by a machine learning-based clustering model.
Heart (British Cardiac Society)
OBJECTIVE:Our previously established machine learning-based clustering model classified heart failure with preserved ejection fraction (HFpEF) into four distinct phenotypes. Given the heterogeneous pathophysiology of HFpEF, specific medications may have favourable effects in specific phenotypes of HFpEF. We aimed to assess effectiveness of medications on clinical outcomes of the four phenotypes using a real-world HFpEF registry dataset. METHODS:This study is a posthoc analysis of the PURSUIT-HFpEF registry, a prospective, multicentre, observational study. We evaluated the clinical effectiveness of the following four types of postdischarge medication in the four different phenotypes: angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB), beta blockers, mineralocorticoid-receptor antagonists (MRA) and statins. The primary endpoint of this study was a composite of all-cause death and heart failure hospitalisation. RESULTS:Of 1231 patients, 1100 (83 (IQR 77, 87) years, 604 females) were eligible for analysis. Median follow-up duration was 734 (398, 1108) days. The primary endpoint occurred in 528 patients (48.0%). Cox proportional hazard models with inverse-probability-of-treatment weighting showed the following significant effectiveness of medication on the primary endpoint: MRA for phenotype 2 (weighted HR (wHR) 0.40, 95% CI 0.21 to 0.75, p=0.005); ACEi or ARB for phenotype 3 (wHR 0.66 0.48 to 0.92, p=0.014) and statin therapy for phenotype 3 (wHR 0.43 (0.21 to 0.88), p=0.020). No other medications had significant treatment effects in the four phenotypes. CONCLUSIONS:Machine learning-based clustering may have the potential to identify populations in which specific medications may be effective. This study suggests the effectiveness of MRA, ACEi or ARB and statin for specific phenotypes of HFpEF. TRIAL REGISTRATION NUMBER:UMIN000021831.
10.1136/heartjnl-2022-322181
Comparative Outcomes of a Transthyretin Amyloid Cardiomyopathy Cohort Versus Patients With Heart Failure With Preserved Ejection Fraction Enrolled in the TOPCAT Trial.
Journal of the American Heart Association
Background Transthyretin cardiac amyloidosis (ATTR-CM), found in 6% to 15% of cohorts with heart failure with preserved ejection fraction, has long been considered a rare disease with poor prognosis. New treatments have made it one of the few directly treatable causes of heart failure. This study sought to determine whether patients with ATTR-CM, particularly those treated with tafamidis, have comparable survival to an unselected cohort with heart failure with preserved ejection fraction. Methods and Results We compared the clinical characteristics and outcomes between a single-center cohort of patients with ATTR-CM (n=114) and patients with heart failure with preserved ejection fraction enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial (n=1761, excluding Russia and Georgia). The primary outcome was a composite of all-cause death, heart failure hospitalization, myocardial infarction, and stroke. Subgroup analysis of patients with ATTR-CM treated with tafamidis was also performed. Patients with ATTR-CM had higher rates of the primary composite outcome compared with patients enrolled in the TOPCAT trial (hazard ratio [HR], 1.44 [95% CI, 1.09-1.91]; =0.01), with similar rates of all-cause death (HR, 1.43 [95% CI, 0.99-2.06]; =0.06) but higher rates of heart failure hospitalizations (HR, 1.62 [95% CI, 1.15-2.28]; <0.01). Compared with patients enrolled in TOPCAT, patients with ATTR-CM treated with tafamidis had similar rates of the primary composite outcome (HR, 1.30 [95% CI, 0.86-1.96]; =0.21) and all-cause death (HR, 1.10 [95% CI, 0.57-2.14]; =0.78) but higher rates of heart failure hospitalizations (HR, 1.96 [95% CI, 1.27-3.02]; <0.01). Conclusions Patients with ATTR-CM treated with tafamidis have similar rates of all-cause death compared with patients with heart failure with preserved ejection fraction, with higher rates of heart failure hospitalizations.
10.1161/JAHA.123.029705
Individual and joint associations of anxiety disorder and depression with cardiovascular disease: A UK Biobank prospective cohort study.
European psychiatry : the journal of the Association of European Psychiatrists
BACKGROUND:Growing evidence suggests that individuals with anxiety disorder have an elevated risk of cardiovascular disease (CVD) but few studies have assessed this association independently of or jointly with depression. METHODS:We conducted a prospective cohort study using UK Biobank. Diagnoses of anxiety disorder, depression, and CVDs were ascertained through linked hospital admission and mortality data. Individual and joint associations between anxiety disorder and depression and CVD overall, as well as each of myocardial infarction, stroke/transient ischemic attack, and heart failure, were analyzed using Cox proportional hazard models and interaction tests. RESULTS:Among the 431,973 participants, the risk of CVD was higher among those who had been diagnosed with anxiety disorder only (hazard ratio [HR] 1.72; 95% confidence interval [CI] 1.32-2.24), depression only (HR 2.07; 95% CI 1.79-2.40), and both conditions (HR 2.89; 95% CI 2.03-4.11) compared to those without these conditions, respectively. There was very little evidence of multiplicative or additive interaction. Results were similar for myocardial infarction, stroke/transient ischemic attack, and heart failure. CONCLUSIONS:Having anxiety is associated with the same magnitude of increased risk of CVD among people who do not have depression and those who do. Anxiety disorder should be considered for inclusion in CVD risk prediction and stratification, in addition to depression.
10.1192/j.eurpsy.2023.2425
Coexistence of Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Kidney Disease Is a More Potent Risk Factor for Ischemic Heart Disease.
Journal of the American Heart Association
Background Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as fatty liver with overweight/obesity, type 2 diabetes, or metabolic abnormalities, is a newly proposed disease. However, it remains unclear whether the coexistence of MAFLD and chronic kidney disease (CKD) is a more potent risk factor for ischemic heart disease (IHD). Methods and Results We investigated the risk of the combination of MAFLD and CKD for development of IHD during a 10-year follow-up period in 28 990 Japanese subjects who received annual health examinations. After exclusion of subjects without data for abdominal ultrasonography or with the presence of IHD at baseline, a total of 14 141 subjects (men/women: 9195/4946; mean age, 48 years) were recruited. During the 10-year period (mean, 6.9 years), 479 subjects (men/women, 397/82) had new onset of IHD. Kaplan-Meier survival curves showed significant differences in rates of the cumulative incidence of IHD in subjects with and those without MAFLD (n=4581) and CKD (n=990; stages 1/2/3/4-5, 198/398/375/19). Multivariable Cox proportional hazard model analyses showed that coexistence of MAFLD and CKD, but not MAFLD or CKD alone, was an independent predictor for development of IHD after adjustment for age, sex, current smoking habit, family history of IHD, overweight/obesity, diabetes, hypertension, and dyslipidemia (hazard ratio, 1.51 [95% CI, 1.02-2.22]). The addition of the combination of MAFLD and CKD to traditional risk factors for IHD significantly improved the discriminatory capability. Conclusions The coexistence of MAFLD and CKD predicts new onset of IHD better than does MAFLD or CKD alone.
10.1161/JAHA.123.030269
Individual Assessment of Perioperative Brain Growth Trajectories in Infants With Congenital Heart Disease: Correlation With Clinical and Surgical Risk Factors.
Journal of the American Heart Association
Background Infants with congenital heart disease (CHD) are at risk of neurodevelopmental impairments, which may be associated with impaired brain growth. We characterized how perioperative brain growth in infants with CHD deviates from typical trajectories and assessed the relationship between individualized perioperative brain growth and clinical risk factors. Methods and Results A total of 36 infants with CHD underwent preoperative and postoperative brain magnetic resonance imaging. Regional brain volumes were extracted. Normative volumetric development curves were generated using data from 219 healthy infants. scores, representing the degree of positive or negative deviation from the normative mean for age and sex, were calculated for regional brain volumes from each infant with CHD before and after surgery. The degree of -score change was correlated with clinical risk factors. Perioperative growth was impaired across the brain, and it was associated with longer postoperative intensive care stay (false discovery rate <0.05). Higher preoperative creatinine levels were associated with impaired brainstem, caudate nuclei, and right thalamus growth (all false discovery rate =0.033). Older postnatal age at surgery was associated with impaired brainstem and right lentiform growth (both false discovery rate =0.042). Longer cardiopulmonary bypass duration was associated with impaired brainstem and right caudate growth (false discovery rate <0.027). Conclusions Infants with CHD can have impaired brain growth in the immediate postoperative period, the degree of which associates with postoperative intensive care duration. Brainstem growth appears particularly vulnerable to perioperative clinical course, whereas impaired deep gray matter growth was associated with multiple clinical risk factors, possibly reflecting vulnerability of these regions to short- and long-term hypoxic injury.
10.1161/JAHA.122.028565
Association of Depressive Symptom Trajectory With Physical Activity Collected by mHealth Devices in the Electronic Framingham Heart Study: Cohort Study.
JMIR mental health
BACKGROUND:Few studies have examined the association between depressive symptom trajectories and physical activity collected by mobile health (mHealth) devices. OBJECTIVE:We aimed to investigate if antecedent depressive symptom trajectories predict subsequent physical activity among participants in the electronic Framingham Heart Study (eFHS). METHODS:We performed group-based multi-trajectory modeling to construct depressive symptom trajectory groups using both depressive symptoms (Center for Epidemiological Studies-Depression [CES-D] scores) and antidepressant medication use in eFHS participants who attended 3 Framingham Heart Study research exams over 14 years. At the third exam, eFHS participants were instructed to use a smartphone app for submitting physical activity index (PAI) surveys. In addition, they were provided with a study smartwatch to track their daily step counts. We performed linear mixed models to examine the association between depressive symptom trajectories and physical activity including app-based PAI and smartwatch-collected step counts over a 1-year follow-up adjusting for age, sex, wear hour, BMI, smoking status, and other health variables. RESULTS:We identified 3 depressive symptom trajectory groups from 722 eFHS participants (mean age 53, SD 8.5 years; n=432, 60% women). The low symptom group (n=570; mean follow-up 287, SD 109 days) consisted of participants with consistently low CES-D scores, and a small proportion reported antidepressant use. The moderate symptom group (n=71; mean follow-up 280, SD 118 days) included participants with intermediate CES-D scores, who showed the highest and increasing likelihood of reporting antidepressant use across 3 exams. The high symptom group (n=81; mean follow-up 252, SD 116 days) comprised participants with the highest CES-D scores, and the proportion of antidepressant use fell between the other 2 groups. Compared to the low symptom group, the high symptom group had decreased PAI (mean difference -1.09, 95% CI -2.16 to -0.01) and the moderate symptom group walked fewer daily steps (823 fewer, 95% CI -1421 to -226) during the 1-year follow-up. CONCLUSIONS:Antecedent depressive symptoms or antidepressant medication use was associated with lower subsequent physical activity collected by mHealth devices in eFHS. Future investigation of interventions to improve mood including via mHealth technologies to help promote people's daily physical activity is needed.
10.2196/44529
Association of Longitudinal B-Type Natriuretic Peptide Monitoring With Kidney Failure in Patients With CKD: A Cohort Study.
American journal of kidney diseases : the official journal of the National Kidney Foundation
RATIONALE & OBJECTIVE:Both hypervolemia and hypovolemia are associated with chronic kidney disease (CKD) progression. Although longitudinal monitoring of B-type natriuretic peptide (BNP) may aid physicians' decision making about the optimization of volume status, its clinical benefit remains uncertain in CKD. This study assessed the association between BNP monitoring and the risk of incident kidney replacement therapy (KRT). STUDY DESIGN:Retrospective cohort study. SETTING & PARTICIPANTS:A total of 2,998 outpatients with stages 3-5 of nondialyzed CKD referred to the department of nephrology at an academic hospital. EXPOSURE:BNP monitoring. OUTCOME:KRT, acute kidney injury (AKI), and heart failure hospitalization. ANALYTICAL APPROACH:Marginal structural models, which create a balanced pseudo population at each time point, were applied to account for potential time-dependent confounders. Inverse probability weighted pooled logistic regression models were employed to estimate hazard ratios. RESULTS:At baseline, the median age and estimated glomerular filtration rate were 66 years and 38.1mL/min/1.73m, respectively. During the follow-up period (median, 5.9 [IQR, 2.8-9.9] years), 449 patients required KRT, 765 had AKI, and 236 were hospitalized for heart failure. After adjustment for time-updated clinical characteristics and physician-specific practice styles, BNP monitoring was associated with lower risks of KRT (HR, 0.44 [95% CI, 0.21-0.92]), AKI (HR, 0.36 [95% CI, 0.18-0.72]), and heart failure hospitalization (HR, 0.37 [95% CI, 0.14-0.95]). The association between BNP monitoring and KRT was attenuated after additional adjustment for AKI or heart failure hospitalization as a time-varying covariate. LIMITATIONS:Residual confounding by measured and unmeasured variables or indications for BNP measurements. CONCLUSIONS:BNP monitoring was associated with a lower risk of KRT among patients with CKD that did not require dialysis. This association is potentially mediated through a reduced risk of AKI or heart failure hospitalization. PLAIN-LANGUAGE SUMMARY:Both volume overload and volume depletion are deleterious to kidney function. B-type natriuretic peptide (BNP) is a biomarker that reflects volume status not only in heart failure but also in nondialysis chronic kidney disease (CKD). Although longitudinal BNP monitoring may aid physicians' decision making about the optimization of volume status, its clinical benefit remains uncertain in CKD. In this cohort study analyzing 2,998 patients with nondialyzed CKD, BNP monitoring was associated with a lower risk of kidney replacement therapy, acute kidney injury, and heart failure hospitalization over the follow-up period. The association with kidney replacement therapy may be mediated through a reduced risk of acute kidney injury or heart failure hospitalization. BNP monitoring may aid physicians in optimal fluid management, potentially conferring better kidney outcomes.
10.1053/j.ajkd.2023.05.003
Association of sodium-glucose cotransporter 2 inhibitors with post-discharge outcomes in patients with acute heart failure with type 2 diabetes: a cohort study.
Cardiovascular diabetology
BACKGROUND:Given the cumulative evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on chronic heart failure, demand is emerging for further information on their effects in patients who are hospitalized for acute heart failure. However, there is still limited evidence about the class effect of SGLT2is on acute heart failure. We investigated whether initiating treatment with SGLT2is after an episode of acute heart failure reduces the risks of post-discharge heart failure readmission or cardiovascular mortality among patients with type 2 diabetes. METHODS:A retrospective cohort study was conducted in a cohort of patients with type 2 diabetes who hospitalized for heart failure, using Korean Health Insurance Review & Assessment database (2015-2020). The exposure was defined as initiation of SGLT2is during hospitalization or at discharge. We assessed hazards of post-discharge heart failure readmission and cardiovascular death at 1-year, and 30-, 60-, and 90-day from the date of discharge in the SGLT2is users and non-users. Cox proportional hazards models with propensity score-based inverse probability of treatment weighting were used to estimate hazard ratios and 95% confidence intervals. RESULTS:Among 56,343 patients with type 2 diabetes hospitalized for heart failure, 29,290 patients were included in the study cohort (mean [SD] age, 74.1 [10.8] years; 56.1% women); 818 patients (2.8%) were prescribed SGLT2is during index hospitalization or at discharge. Patients with a prescription for SGLT2i vs. those without prescription had lower rates of heart failure readmission or cardiovascular death at 1 year (22.4% vs. 25.3%; adjusted hazard ratio, 0.90 [95% confidence interval, 0.87-0.93]), and also at 30 days (7.0% vs. 7.7%%; 0.74 [0.69-0.79]). CONCLUSIONS:Among patients with type 2 diabetes, initiating SGLT2i treatment after an episode of acute heart failure was significantly associated with a reduced combined risk of heart failure readmission and cardiovascular mortality in a nationwide cohort reflecting routine clinical practice.
10.1186/s12933-023-01896-3
Effects of finerenone in people with chronic kidney disease and type 2 diabetes are independent of HbA1c at baseline, HbA1c variability, diabetes duration and insulin use at baseline.
Diabetes, obesity & metabolism
AIM:To evaluate the effect of finerenone by baseline HbA1c, HbA1c variability, diabetes duration and baseline insulin use on cardiorenal outcomes and diabetes progression. MATERIALS AND METHODS:Composite efficacy outcomes included cardiovascular (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure), kidney (kidney failure, sustained ≥ 57% estimated glomerular filtration rate decline or renal death) and diabetes progression (new insulin initiation, increase in antidiabetic medication, 1.0% increase in HbA1c from baseline, new diabetic ketoacidosis diagnosis or uncontrolled diabetes). RESULTS:In 13 026 participants, risk reductions in the cardiovascular and kidney composite outcomes with finerenone versus placebo were consistent across HbA1c quartiles (P interaction .52 and .09, respectively), HbA1c variability (P interaction .48 and .10), diabetes duration (P interaction .12 and .75) and insulin use (P interaction .16 and .52). HbA1c variability in the first year of treatment was associated with a higher risk of cardiovascular and kidney events (hazard ratio [HR] 1.20; 95% confidence interval [CI] 1.07-1.35; P = .0016 and HR 1.36; 95% CI 1.21-1.52; P < .0001, respectively). There was no effect on diabetes progression with finerenone or placebo (HR 1.00; 95% CI 0.95-1.04). Finerenone was well-tolerated across subgroups; discontinuation and hospitalization because of hyperkalaemia were low. CONCLUSIONS:Finerenone efficacy was not modified by baseline HbA1c, HbA1c variability, diabetes duration or baseline insulin use. Greater HbA1c variability appeared to be associated with an increased risk of cardiorenal outcomes.
10.1111/dom.14999
Diastolic delta best predicts paravalvular regurgitation after transcatheter aortic valve replacement as assessed by cardiac magnetic resonance: the APPOSE trial.
European heart journal. Cardiovascular Imaging
AIMS:Paravalvular regurgitation (PVR) is a common complication after transcatheter aortic valve replacement (TAVR) that poses an increased risk of rehospitalization for heart failure and mortality. The aim of this study was to assess the accuracy of haemodynamic indices to predict relevant PVR. METHODS AND RESULTS:In this prospective single-centre clinical trial, four haemodynamic indices of PVR measured during TAVR were assessed for their correlation with gold standard cardiac magnetic resonance (CMR)-derived regurgitant fraction (CMR-RF) at 1 month follow-up: diastolic delta (DD), heart rate-adjusted diastolic delta (HR-DD), aortic regurgitation index (ARI), and aortic regurgitation index ratio (ARI ratio). These haemodynamic indices were analysed for their ability to predict relevant PVR (defined as CMR-RF > 20%) using receiver operating characteristic (ROC) curves with corresponding area under the ROC curves (AUCs). A total of 77 patients were included and had CMR performed 41 ± 14 days after TAVR. Mean CMR-RF was 12.4 ± 9.3%. Fifteen (19.5%) patients had CMR-RF > 20%. DD had the best correlation with CMR-RF and the highest AUC to predict relevant PVR (0.82; 95% CI, 0.72-0.92), followed by HR-DD (AUC 0.78; 95% CI, 0.67-0.89), ARI (AUC 0.78; 95% CI, 0.66-0.89), and ARI ratio (AUC 0.65; 95% CI, 0.49-0.81). The optimal cut-off value for DD was 32 mmHg, with sensitivity of 69% and specificity of 77% in predicting relevant PVR. CONCLUSION:DD measured during TAVR best predicts relevant PVR. Correction for heart rate (HR-DD) or systolic blood pressure (ARI, ARI ratio) did not improve this predictive value.
10.1093/ehjci/jead033
The value of NLR versus MLR in the short-term prognostic assessment of HBV-related acute-on-chronic liver failure.
International immunopharmacology
BACKGROUND:Systemic inflammation is associated with the development and progression of hepatitis B-associated acute-on-chronic liver failure (HBV-ACLF). The neutrophil-to-lymphocyte ratio (NLR) has been reported to be a prognostic biomarker in patients with HBV-ACLF. However, the role of the monocyte-to-lymphocyte ratio (MLR) as a prognostic inflammatory biomarker in multiple diseases is rarely mentioned in HBV-ACLF. METHODS:We included a total of 347 patients with HBV-ACLF who met the definition of the Chinese Guidelines for the Diagnosis and Treatment of Liver Failure (2018 edition). Among them, 275 cases were included retrospectively, and 72 cases were collected prospectively. Clinical characteristics and laboratory examination data were collected from medical records within 24 h after diagnosis to calculate MLR and NLR levels, and lymphocyte subpopulation counts were collected in prospectively included patients. RESULTS:Of the 347 patients with HBV-ACLF, 128 patients in the non-surviving group had a mean age of 48.87 ± 12.89 years; 219 patients in the survival group had a mean age of 44.80 ± 11.80 years and a combined 90-day mortality rate of 36.9%. The median MLR was higher in the non-survivors than in the survivors (0.690 vs 0.497, P < 0.001). MLR values were significantly associated with 90-day mortality in HBV-ACLF (OR 6.738; 95% CI 3.188-14.240, P < 0.001). The AUC for the predictive power of the combined MLR and NLR analysis for HBV-ACLF was 0.694, and the calculated MLR threshold was 4.495. In addition, in the analysis of peripheral blood lymphocyte subsets in HBV-ACLF, a significant decrease in the number of circulating lymphocytes was found in HBV-ACLF patients in the non-surviving group (P < 0.001), with a predominant decrease in the number of CD8 + T cells and no significant difference in the number of CD4 + T cells, B cells or NK cells. CONCLUSION:Increased MLR values are associated with 90-day mortality in patients with HBV-ACLF, and the MLR may serve as a potential prognostic indicator for patients with HBV-ACLF. Decreased CD8 + T-cell counts may be associated with poor survival in patients with HBV-ACLF.
10.1016/j.intimp.2023.110489
Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes.
Circulation
SGLT2 (sodium-glucose cotransporter 2) inhibitors interfere with the reabsorption of glucose and sodium in the early proximal renal tubule, but the magnitude and duration of any ensuing natriuretic or diuretic effect are the result of an interplay between the degree of upregulation of SGLT2 and sodium-hydrogen exchanger 3, the extent to which downstream compensatory tubular mechanisms are activated, and (potentially) the volume set point in individual patients. A comprehensive review and synthesis of available studies reveals several renal response patterns with substantial variation across studies and clinical settings. However, the common observation is an absence of a large acute or chronic diuresis or natriuresis with these agents, either when given alone or combined with other diuretics. This limited response results from the fact that renal compensation to these drugs is rapid and nearly complete within a few days or weeks, preventing progressive volume losses. Nevertheless, the finding that fractional excretion of glucose and lithium (the latter being a marker of proximal sodium reabsorption) persists during long-term treatment with SGLT2 inhibitors indicates that pharmacological tolerance to the effects of these drugs at the level of the proximal tubule does not meaningfully occur. This persistent proximal tubular effect of SGLT2 inhibitors can be hypothesized to produce a durable improvement in the internal set point for volume homeostasis, which may become clinically important during times of fluid expansion. However, it is difficult to know whether a treatment-related change in the volume set point actually occurs or contributes to the effect of these drugs to reduce the risk of major heart failure events. SGLT2 inhibitors exert cardioprotective effects by a direct effect on cardiomyocytes that is independent of the presence of or binding to SGLT2 or the actions of these drugs on the proximal renal tubule. Nevertheless, changes in the volume set point mediated by SGLT2 inhibitors might potentially act cooperatively with the direct favorable molecular and cellular effects of these drugs on cardiomyocytes to mediate their benefits on the development and clinical course of heart failure.
10.1161/CIRCULATIONAHA.123.064346
Lipoprotein(a), family history of cardiovascular disease, and incidence of heart failure.
Journal of lipid research
Lipoprotein(a) (Lp(a)) is a largely genetically determined biomarker for cardiovascular disease (CVD), while its potential interplay with family history (FHx) of CVD, a measure of both genetic and environmental exposures, remains unclear. We examined the associations of Lp(a) in terms of circulating concentration or polygenetic risk score (PRS), and FHx of CVD with risk of incident heart failure (HF). Included were 299,158 adults from the UK Biobank without known HF and CVD at baseline. Hazards ratios (HRs) and 95% Cls were estimated by Cox regression models adjusted for traditional risk factors defined by the Atherosclerosis Risk in Communities study HF risk score. During the 11.8-year follow-up, 5,502 incidents of HF occurred. Higher levels of circulating Lp(a), Lp(a) PRS, and positive FHx of CVD were associated with higher risks of HF. Compared with individuals who had lower circulating Lp(a) and no FHx, HRs (95% CIs) of HF were 1.36 (1.25, 1.49), 1.31 (1.19, 1.43), and 1.42 (1.22, 1.67) for those with higher Lp(a) and a positive history of CVD for all family members, parents, and siblings, respectively; similar results were observed by using Lp(a) PRS. The risk estimates for HF associated with elevated Lp(a) and positive FHx were attenuated after excluding those with incident myocardial infarction (MI) during follow-up. Lp(a) and FHx of CVD were independent risk factors for incident HF, and the highest risk of HF was observed among individuals with both risk factors. The association may be partly mediated by myocardial infarction.
10.1016/j.jlr.2023.100398
A network medicine approach to study comorbidities in heart failure with preserved ejection fraction.
BMC medicine
BACKGROUND:Comorbidities are expected to impact the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). However, comorbidity profiles are usually reduced to a few comorbid disorders. Systems medicine approaches can model phenome-wide comorbidity profiles to improve our understanding of HFpEF and infer associated genetic profiles. METHODS:We retrospectively explored 569 comorbidities in 29,047 HF patients, including 8062 HFpEF and 6585 HF with reduced ejection fraction (HFrEF) patients from a German university hospital. We assessed differences in comorbidity profiles between HF subtypes via multiple correspondence analysis. Then, we used machine learning classifiers to identify distinctive comorbidity profiles of HFpEF and HFrEF patients. Moreover, we built a comorbidity network (HFnet) to identify the main disease clusters that summarized the phenome-wide comorbidity. Lastly, we predicted novel gene candidates for HFpEF by linking the HFnet to a multilayer gene network, integrating multiple databases. To corroborate HFpEF candidate genes, we collected transcriptomic data in a murine HFpEF model. We compared predicted genes with the murine disease signature as well as with the literature. RESULTS:We found a high degree of variance between the comorbidity profiles of HFpEF and HFrEF, while each was more similar to HFmrEF. The comorbidities present in HFpEF patients were more diverse than those in HFrEF and included neoplastic, osteologic and rheumatoid disorders. Disease communities in the HFnet captured important comorbidity concepts of HF patients which could be assigned to HF subtypes, age groups, and sex. Based on the HFpEF comorbidity profile, we predicted and recovered gene candidates, including genes involved in fibrosis (COL3A1, LOX, SMAD9, PTHL), hypertrophy (GATA5, MYH7), oxidative stress (NOS1, GSST1, XDH), and endoplasmic reticulum stress (ATF6). Finally, predicted genes were significantly overrepresented in the murine transcriptomic disease signature providing additional plausibility for their relevance. CONCLUSIONS:We applied systems medicine concepts to analyze comorbidity profiles in a HF patient cohort. We were able to identify disease clusters that helped to characterize HF patients. We derived a distinct comorbidity profile for HFpEF, which was leveraged to suggest novel candidate genes via network propagation. The identification of distinctive comorbidity profiles and candidate genes from routine clinical data provides insights that may be leveraged to improve diagnosis and identify treatment targets for HFpEF patients.
10.1186/s12916-023-02922-7
Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure.
JAMA cardiology
Importance:Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear. Objective:To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes. Design, Setting, and Participants:This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023. Exposure:LTL. Main Outcomes and Measures:Cardiovascular imaging traits and HF. Results:Of 40 459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P = 1.8 × 10-6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume. Conclusions and Relevance:In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.
10.1001/jamacardio.2023.2167
Knowledge about self-efficacy and outcomes in patients with heart failure and reduced ejection fraction.
European journal of heart failure
AIM:Although education in self-management is thought to be an important aspect of the care of patients with heart failure, little is known about whether self-rated knowledge of self-management is associated with outcomes. The aim of this study was to assess the relationship between patient-reported knowledge of self-management and clinical outcomes in patients with heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS:Using individual patient data from three recent clinical trials enrolling participants with HFrEF, we examined patient characteristics and clinical outcomes according to responses to the 'self-efficacy' questions of the Kansas City Cardiomyopathy Questionnaire. One question quantifies patients' understanding of how to prevent heart failure exacerbations ('prevention' question) and the other how to manage complications when they arise ('response' question). Self-reported answers from patients were pragmatically divided into: poor (do not understand at all, do not understand very well, somewhat understand), fair (mostly understand), and good (completely understand). Cox-proportional hazard models were used to evaluate time-to-first occurrence of each endpoint, and negative binomial regression analysis was performed to compare the composite of total (first and repeat) heart failure hospitalizations and cardiovascular death across the above-defined groups. Of patients (n = 17 629) completing the 'prevention' question, 4197 (23.8%), 6897 (39.1%), and 6535 (37.1%) patients had poor, fair, and good self-rated knowledge, respectively. Of those completing the 'response' question (n = 17 637), 4033 (22.9%), 5463 (31.0%), and 8141 (46.2%) patients had poor, fair, and good self-rated knowledge, respectively. For both questions, patients with 'poor' knowledge were older, more often female, and had a worse heart failure profile but similar treatment. The rates (95% confidence interval) per 100 person-years for the primary composite outcome for 'poor', 'moderate' and 'good' self-rated knowledge in answer to the 'prevention' question were 12.83 (12.11-13.60), 12.08 (11.53-12.65) and 11.55 (11.00-12.12), respectively, and for the 'response' question were 12.88 (12.13-13.67), 12.22 (11.60-12.86) and 11.56 (11.07-12.07), respectively. The lower event rates in patients with 'good' self-rate knowledge were accounted for by lower rates of cardiovascular (and all-cause) death and not hospitalization for worsening heart failure. CONCLUSIONS:Poor patient-reported 'self-efficacy' may be associated with higher rates of mortality. Evaluation of knowledge of 'self-efficacy' may provide prognostic information and a guide to which patients may benefit from further education about self-management.
10.1002/ejhf.2944
Examination of potentially modifiable dementia risk factors across the adult life course: The Framingham Heart Study.
Alzheimer's & dementia : the journal of the Alzheimer's Association
INTRODUCTION:We examined for associations between potentially modifiable risk factors across the adult life course and incident dementia. METHODS:Participants from the Framingham Heart Study were included (n = 4015). Potential modifiable risk factors included education, alcohol intake, smoking, body mass index (BMI), physical activity, social network, diabetes, and hypertension. Cox models were used to examine associations between each factor and incident dementia, stratified by early adult life (33-44 years), midlife (45-65 years), and late life (66-80 years). RESULTS:Increased dementia risk was associated with diabetes (hazard ratio [HR] = 1.62; 95% confidence interval [CI] = 1.07-2.46) and physical inactivity (HR = 1.57; 95% CI = 1.12-2.20) in midlife, and with obesity (HR = 1.76; 95% CI = 1.08-2.87) in late life. Having multiple potential modifiable risk factors in midlife and late life was associated with greater risk. DISCUSSION:Potentially modifiable risk factors individually have limited impact on dementia risk in this population across the adult life course, although in combination they may have a synergistic effect. HIGHLIGHTS:Diabetes and physical inactivity in midlife is associated with increased dementia risk. Obesity in late life is associated with increased dementia risk. Having more potentially modifiable risk factors in midlife and late life is associated with greater dementia risk.
10.1002/alz.12940
A meta-analysis of GFR slope as a surrogate endpoint for kidney failure.
Nature medicine
Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min per 1.73 m or kidney failure with replacement therapy). We used a Bayesian mixed-effects meta-regression model to relate treatment effects on GFR slope with those on the clinical endpoint across all studies and by disease groups (diabetes, glomerular diseases, CKD or cardiovascular diseases). Treatment effects on the clinical endpoint were strongly associated with treatment effects on total slope (median coefficient of determination (R) = 0.97 (95% Bayesian credible interval (BCI) 0.82-1.00)) and moderately associated with those on chronic slope (R = 0.55 (95% BCI 0.25-0.77)). There was no evidence of heterogeneity across disease. Our results support the use of total slope as a primary endpoint for clinical trials of CKD progression.
10.1038/s41591-023-02418-0
C-Reactive Protein and Risk of Incident Heart Failure in Patients With Cardiovascular Disease.
Journal of the American College of Cardiology
BACKGROUND:Patients with established cardiovascular disease (CVD) are at high risk of incident heart failure (HF), which may in part reflect the impact of systemic inflammation. OBJECTIVES:The goal of this study was to determine the association between C-reactive protein (CRP) and incident HF in patients with established CVD. METHODS:Patients from the prospective UCC-SMART (Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease) cohort with established CVD, but without prevalent HF were included (n = 8,089). Incident HF was defined as a first hospitalization for HF. The association between baseline CRP and incident HF was assessed using Cox proportional hazards models adjusted for established risk factors (ie, age, sex, myocardial infarction, smoking, diabetes mellitus, body mass index, blood pressure, cholesterol, and kidney function). RESULTS:During a median follow-up of 9.7 years (IQR 5.4-14.1 years), 810 incident HF cases were observed (incidence rate 1.01/100 person-years). Higher CRP was independently associated with an increased risk of incident HF: HR per 1 mg/L: 1.10 (95% CI: 1.07-1.13), and for last vs first CRP quartile: 2.22 (95% CI: 1.76-2.79). The association was significant for both HF with reduced (HR: 1.09; 95% CI: 1.04-1.14) and preserved ejection fraction (HR: 1.12; 95% CI: 1.07-1.18) (P for difference = 0.137). Additional adjustment for medication use and interim myocardial infarction did not attenuate the association, and the association remained consistent beyond 15 years after the CRP measurement. CONCLUSIONS:In patients with established CVD, CRP is an independent risk marker of incident HF. These data support ongoing trial efforts to assess whether anti-inflammatory agents can reduce the burden of HF.
10.1016/j.jacc.2023.05.035
The impact of the stress hyperglycemia ratio on mortality and rehospitalization rate in patients with acute decompensated heart failure and diabetes.
Cardiovascular diabetology
BACKGROUND:The relationship between stress hyperglycemia and long-term prognosis in acute decompensated heart failure (ADHF) patients is unknown. This study investigated the associations of stress hyperglycemia with mortality and rehospitalization rates among ADHF patients with diabetes. METHODS:We consecutively enrolled 1904 ADHF patients. Among them, 780 were with diabetes. Stress hyperglycemia was estimated using the stress hyperglycemia ratio (SHR), which was calculated by the following formula: SHR = admission blood glucose/[(28.7 × HbA1c%) - 46.7]. All diabetic ADHF subjects were divided into quintiles according to the SHR. The primary endpoint was all-cause death at the 3-year follow-up. The secondary endpoints were cardiovascular (CV) death and heart failure (HF) rehospitalization at the 3-year follow-up. A Cox proportional hazards model and restricted cubic spline analysis were used to elucidate the relationship between the SHR and the endpoints in diabetic ADHF patients. Further analyses were performed to examine the relationships between SHR and the outcomes in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). RESULTS:A total of 169 all-cause deaths were recorded during a median follow-up of 3.24 years. Restricted cubic spline analysis suggested a U-shaped association between the SHR and the mortality and rehospitalization rates. Kaplan-Meier survival analysis showed the lowest mortality in the 2nd quintile (P = 0.0028). Patients categorized in the highest range (5th quintile) of SHR, compared to those in the 2nd quintile, exhibited the greatest susceptibility to all-cause death (with a hazard ratio [HR] of 2.76 and a 95% confidence interval [CI] of 1.63-4.68), CV death (HR 2.81 [95% CI 1.66-4.75]) and the highest rate of HF rehospitalization (HR 1.54 [95% CI 1.03-2.32]). Similarly, patients in the lowest range (1st quintile) of SHR also exhibited significantly increased risks of all-cause death (HR 2.33, 95% CI 1.35-4.02) and CV death (HR 2.32, 95% CI 1.35-4.00). Further analyses indicated that the U-shape association between the SHR and mortality remained significant in both HFpEF and HFrEF patients. CONCLUSION:Both elevated and reduced SHRs indicate an unfavorable long-term prognosis in patients with ADHF and diabetes.
10.1186/s12933-023-01908-2
Association Between Wearable Device Measured Activity and Patient-Reported Outcomes for Heart Failure.
JACC. Heart failure
BACKGROUND:Wearable devices are increasingly used in research and clinical care though the relevance of their data in the context of validated outcomes remains unknown. OBJECTIVES:The purpose of this study was to characterize the relationship between smartwatch activity and patient-centered outcomes in patients with heart failure. METHODS:CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) was a randomized-controlled clinical trial that enrolled participants with heart failure and a compatible smartphone. Participants were provided a Fitbit Versa 2 and completed serial Kansas City Cardiomyopathy Questionnaires (KCCQs) through a smartphone application. We evaluated the relationship between daily step count and floors climbed and KCCQ total symptom (TS) and physical limitation (PL) scores at baseline and their respective changes between 2 and 12 weeks using linear regression models, with restricted cubic splines for nonlinear associations. RESULTS:In total, 425 patients were included: 44.5% women, 40.9% with reduced ejection fraction. Baseline daily step count increased across categories of KCCQ-TS scores (2,437.6 ± 1,419.5 steps/d for scores 0 to 24 vs 4,870.9 ± 3,171.3 steps/d for scores 75 to 100; P < 0.001) with similar results for KCCQ-PL scores. This relationship remained significant for KCCQ-TS and KCCQ-PL scores after multivariable adjustment. Importantly, changes in daily step count were significantly associated with nonlinear changes in KCCQ-TS (P = 0.004) and KCCQ-PL (P = 0.003) scores. Floors climbed was associated with baseline KCCQ scores alone. CONCLUSIONS:Daily step count was nonlinearly associated with health status at baseline and over time in patients with heart failure. These results may inform interpretation of wearable device data in clinical and research contexts. (A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure [CHIEF-HF]; NCT04252287).
10.1016/j.jchf.2023.05.033
Plasma angiopoietin-2 and its association with heart failure in patients with atrial fibrillation.
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
AIMS:Several biomarkers are associated with clinical outcomes in patients with atrial fibrillation (AF), but a causal relationship has not been established. This study aimed to evaluate angiopoietin-2, a novel candidate biomarker of endothelial inflammation and vascular remodelling, in patients with AF. METHODS AND RESULTS:Angiopoietin-2 was measured in plasma obtained from patients with AF treated with aspirin monotherapy (exploration cohort, n = 2987) or with oral anticoagulation (validation cohort, n = 13 079). Regression models were built to assess the associations between angiopoietin-2, clinical characteristics, and outcomes. In both cohorts, plasma angiopoietin-2 was independently associated with AF on the baseline electrocardiogram and persistent/permanent AF, age, history of heart failure, female sex, tobacco use/smoking, body mass index, renal dysfunction, diabetes, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Angiopoietin-2 was independently associated with subsequent hospitalization for heart failure after adjusting for age, creatinine, and clinical characteristics in the exploration cohort [c-index 0.79, 95% confidence interval (CI) 0.75-0.82; third vs. first quartile, hazard ratio (HR) 1.74, 95% CI 1.26-2.41] and in the validation cohort (c-index 0.76, 95% CI 0.74-0.78; HR 1.58, 95% CI 1.37-1.82). In both cohorts, the association persisted when also adjusting for NT-proBNP (P ≤ 0.001). In full multivariable models also adjusted for NT-proBNP, angiopoietin-2 did not show statistically significant associations with ischaemic stroke, cardiovascular and all-cause death, or major bleeding that were consistent across the two cohorts. CONCLUSIONS:In patients with AF, plasma levels of angiopoietin-2 were independently associated with subsequent hospitalization for heart failure and provided incremental prognostic value to clinical risk factors and NT-proBNP.
10.1093/europace/euad200
Regional contributions to impaired myocardial mechanical function in heart failure with preserved ejection fraction.
European heart journal. Cardiovascular Imaging
AIMS:Hypertensive heart disease (HHD) is recognized as a key clinical precursor to heart failure with preserved ejection fraction (HFPEF). However, pathophysiological transition from HHD to HFPEF is not well understood. We sought determine whether regional differences in impaired myocardial function may underlie the greater mechanical dysfunction seen in HFPEF compared to HHD. METHODS AND RESULTS:We used standardized echocardiography to assess regional myocardial deformation in a cohort of n = 327 adults with preserved left ventricular (LV) ejection fraction (≥45%), including: n = 129 with HFPEF, n = 158 with HHD and no heart failure, and n = 40 normotensive controls. From detailed measurements of LV systolic strain performed in multiple views, we derived and then compared regional measures of basal, mid-ventricular, and apical longitudinal strains. In models adjusting for clinical covariates, basal and mid-ventricular LV myocardial deformation was more impaired in HHD than in controls (P ≤ 0.003), whereas apical deformation was more impaired in HFPEF than in HHD (P = 0.005). In multivariable-adjusted analyses, only apical strain remained independently associated with HFPEF vs. HHD status [odds ratio 1.18 (1.02-1.37), P = 0.030 per 1% decrease in apical strain]. Compared to other regional strains, apical longitudinal strain optimally differentiated HFPEF from HHD (area under the receiver operating curve: apical longitudinal strain = 0.67; mid-ventricular longitudinal strain = 0.59; basal longitudinal strain = 0.60). CONCLUSION:We found that while apical mechanical function is preserved in HHD, it was impaired in HFPEF and may contribute to the transition from an asymptomatic heart disease to a symptomatic heart disease.
10.1093/ehjci/jead062
Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction.
JACC. Heart failure
BACKGROUND:Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). OBJECTIVES:This study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. METHODS:Study investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. RESULTS:Among 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. CONCLUSIONS:In HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden. (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure [REDUCE LAP-HF II]; NCT03088033).
10.1016/j.jchf.2023.05.024
Association of healthy sleep pattern with risk of recurrent cardiovascular events among patients with coronary heart disease.
European heart journal. Quality of care & clinical outcomes
AIMS:To examine the association of a healthy sleep pattern with the risk of recurrent cardiovascular events among patients with coronary heart disease (CHD). METHODS AND RESULTS:This prospective cohort study included 21 193 individuals with CHD from the UK Biobank. A healthy sleep score was generated based on a combination of chronotype, sleep duration, insomnia, and excessive daytime sleepiness. Cox proportional hazards regression models were applied to estimate the associations between healthy sleep score and recurrent cardiovascular events. During a median of 11.1 years of follow up, we documented 3771 recurrent cardiovascular events, including 1634 heart failure cases and 704 stroke cases. After multivariable adjustment, including lifestyle factors, medical history, and CHD duration, sleep 7-8 h/day, never/rarely insomnia, and no frequent daytime sleepiness were each significantly associated with a 12-22% lower risk of heart failure. In addition, compared with participants who had a healthy sleep score of 0-1, the multivariable-adjusted HR (95% CI) for participants with a healthy sleep score of 4 was 0.86 (0.75, 0.99) for recurrent cardiovascular events, 0.71 (0.57, 0.89) for heart failure, and 0.72 (0.51, 1.03) for stroke. CONCLUSIONS:Adherence to a healthy sleep pattern was significantly associated with a lower risk of recurrent cardiovascular events among patients with CHD, especially for heart failure. These findings indicate that healthy sleep behaviours could be beneficial in the prevention of cardiovascular event recurrence.
10.1093/ehjqcco/qcad043
Relationship Between In-Hospital Adverse Events and Hospital Performance on 30-Day All-cause Mortality and Readmission for Patients With Heart Failure.
Circulation. Cardiovascular quality and outcomes
BACKGROUND:Hospitals with high mortality and readmission rates for patients with heart failure (HF) might also perform poorly in other quality concepts. We sought to evaluate the association between hospital performance on mortality and readmission with hospital performance rates of safety adverse events. METHODS:This cross-sectional study linked the 2009 to 2019 patient-level adverse events data from the Medicare Patient Safety Monitoring System, a randomly selected medical records-abstracted patient safety database, to the 2005 to 2016 hospital-level HF-specific 30-day all-cause mortality and readmissions data from the United States Centers for Medicare & Medicaid Services. Hospitals were classified to one of 3 performance categories based on their risk-standardized 30-day all-cause mortality and readmission rates: better (both in <25th percentile), worse (both >75th percentile), and average (otherwise). Our main outcome was the occurrence (yes/no) of one or more adverse events during hospitalization. A mixed-effect model was fit to assess the relationship between a patient's risk of having adverse events and hospital performance categories, adjusted for patient and hospital characteristics. RESULTS:The study included 39 597 patients with HF from 3108 hospitals, of which 252 hospitals (8.1%) and 215 (6.9%) were in the better and worse categories, respectively. The rate of patients with one or more adverse events during a hospitalization was 12.5% (95% CI, 12.1-12.8). Compared with patients admitted to better hospitals, patients admitted to worse hospitals had a higher risk of one or more hospital-acquired adverse events (adjusted risk ratio, 1.24 [95% CI, 1.06-1.44]). CONCLUSIONS:Patients admitted with HF to hospitals with high 30-day all-cause mortality and readmission rates had a higher risk of in-hospital adverse events. There may be common quality issues among these 3 measure concepts in these hospitals that produce poor performance for patients with HF.
10.1161/CIRCOUTCOMES.122.009573
Inferior vena cava diameter is associated with prognosis in patients with chronic heart failure independent of tricuspid regurgitation velocity.
Clinical research in cardiology : official journal of the German Cardiac Society
AIMS:A high, Doppler-derived, tricuspid regurgitation velocity (TRV) indicates pulmonary hypertension, which may contribute to right ventricular dysfunction and worsening tricuspid regurgitation leading to systemic venous congestion, reflected by an increase in inferior vena cava (IVC) diameter. We hypothesized that venous congestion rather than pulmonary hypertension would be more strongly associated with prognosis. METHODS AND RESULTS:895 patients with chronic heart failure (CHF) (median (25th and 75th centile) age 75 (67-81) years, 69% men, LVEF 44 (34-55)% and NT-proBNP 1133 (423-2465) pg/ml) were enrolled. Compared to patients with normal IVC (< 21 mm) and TRV (≤ 2.8 m/s; n = 504, 56%), those with high TRV but normal IVC (n = 85, 9%) were older, more likely to be women and to have LVEF ≥ 50%, whilst those with dilated IVC but normal TRV (n = 142, 16%) had more signs of congestion and higher NT-proBNP. Patients (n = 164, 19%) with both dilated IVC and high TRV had the most signs of congestion and the highest NT-proBNP. During follow-up of 860 (435-1121) days, 239 patients died. Compared to those with both normal IVC and TRV (reference), patients with high TRV but normal IVC did not have a significantly increased mortality (HR: 1.41; CI: 0.87-2.29; P = 0.16). Risk was higher for patients with a dilated IVC but normal TRV (HR: 2.51; CI: 1.80-3.51; P < 0.001) or both a dilated IVC and elevated TRV (HR: 3.27; CI: 2.40-4.46; P < 0.001). CONCLUSION:Amongst ambulatory patients with CHF, a dilated IVC is more closely associated with an adverse prognosis than an elevated TRV.
10.1007/s00392-023-02178-4
Rationale and design of ENDEAVOR: A sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction.
European journal of heart failure
AIMS:Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity-induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b-3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF. METHODS:In phase 2b, approximately 660 patients with heart failure and ejection fraction >40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6-min walk distance (6MWD) of 30-400 m with a <50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ-TSS. The sample size provides 85% power to detect placebo-adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ-TSS at overall two-sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo. CONCLUSION:ENDEAVOR is the first phase 2b-3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF.
10.1002/ejhf.2977
Which congestion presentation pattern on the physical findings is associated with future adverse events? A cluster analysis in the multicenter acute heart failure registry.
Clinical research in cardiology : official journal of the German Cardiac Society
BACKGROUND:Clinical congestion is the most frequent reason for hospital admission in patients with acute heart failure (AHF). However, few studies have investigated the patterns and prognostic implication of the physical congestion using unbiased and robust statistical methods. METHODS:A hierarchical agglomerative clustering analysis was performed in the multicenter Japanese AHF registry (N = 3151) with the distance calculated by Jaccard's distance for jugular vein distention (JVD), leg edema, S3, crackles, and orthopnea. The primary outcome was a composite of cardiac death and heart failure readmission within 1-year. RESULTS:At the time of admission, the median number of prevalent congestive signs was 2. We identified three phenogroups: 'no physical congestions' (N = 251); 'congestion without JVD' (N = 1415); and 'congestion with JVD' (N = 1495). Patients in 'no physical congestion' were the youngest (median 75 [62, 83] years) with the lowest systolic blood pressure (122 [106, 142] mmHg). Patients in 'congestion without JVD', and 'congestion with JVD' were similar in terms of age (77 [67, 84] vs. 78 [69, 84] years) and systolic blood pressure (138 [118, 160] vs. 137 [118, 158] mmHg). While 30-day mortality was similar (4.0%, 3.7%, and 4.3% in 'no physical congestion,' 'congestion without JVD,' and 'congestion with JVD', respectively), the patients in 'congestion with JVD' were at the highest risk for the primary outcome (adjusted hazard ratio 1.79, 95% CI 1.26-2.55 when 'no physical congestion' was a reference). CONCLUSIONS:Our clustering analysis demonstrated that congestion signs, particularly JVD, allowed identification of AHF phenogroups with distinct clinical characteristics and long-term outcomes.
10.1007/s00392-023-02201-8
Prediction of worsening heart failure in hypertrophic cardiomyopathy using plasma proteomics.
Heart (British Cardiac Society)
OBJECTIVE:Heart failure (HF) is one of the most common and lifestyle-limiting complications of hypertrophic cardiomyopathy (HCM). Prediction of worsening HF using clinical measures alone remains limited. Moreover, the mechanisms by which patients with HCM develop worsening HF have not been elucidated. Therefore, the aim of this study was to develop a plasma proteomics-based model to predict worsening HF among patients with HCM and to identify signalling pathways that are differentially regulated in those who subsequently develop worsening HF. METHODS:In this multi-centre, prospective cohort study of 389 patients with HCM, plasma proteomics profiling of 4986 proteins was performed at enrolment. A proteomics-based random forest model was developed to predict worsening HF using data from one institution (training set, n=268). This model was externally validated in patients from a different institution (test set, n=121). Pathway analysis of proteins significantly dysregulated in patients who subsequently developed worsening HF compared with those who did not was executed, using a false discovery rate (FDR) threshold of <0.001. RESULTS:Using the 11-protein proteomics-based model derived from the training set, the area under the receiver-operating characteristic curve to predict worsening HF was 0.87 (95% CI: 0.76 to 0.98) in the test set. Pathway analysis revealed that the Ras-MAPK pathway (FDR<0.00001) and related pathways were dysregulated in patients who subsequently developed worsening HF. CONCLUSIONS:The present study with comprehensive plasma proteomics profiling demonstrated a high accuracy to predict worsening HF in patients with HCM and identified the Ras-MAPK and related signalling pathways as potential underlying mechanisms.
10.1136/heartjnl-2023-322644
Simple and safe digitoxin dosing in heart failure based on data from the DIGIT-HF trial.
Clinical research in cardiology : official journal of the German Cardiac Society
BACKGROUND:The present study aimed to develop a simple dosing score when starting the cardiac glycoside digitoxin in heart failure with reduced ejection fraction (HFrEF) employing first data from the randomized, double-blinded DIGIT-HF trial. METHODS AND RESULTS:In DIGIT-HF, digitoxin was started with a dose of 0.07 mg once daily (o.d.) in all patients. For score derivation, 317 patients were analyzed who had been randomized to digitoxin. In these patients, after scheduled determination of serum levels at study week 6, the digitoxin dose had remained unchanged or had been reduced to 0.05 mg o.d. (97% of patients) to achieve serum concentrations within a predefined range (10.5-23.6 nmol/l). In logistic regression analyses, sex, age, body mass index (BMI), and estimated glomerular filtration rate (eGFR) were associated with need for dose reduction and, therefore, selected for further developing the dosing score. Optimal cut-points were derived from ROC curve analyses. Finally, female sex, age ≥ 75 years, eGFR < 50 ml/min/1.73 m, and BMI < 27 kg/m each were assigned one point for the digitoxin dosing score. A score of ≥ 1 indicated the need for dose reduction with sensitivity/specificity of 81.6%/49.7%, respectively. Accuracy was confirmed in a validation data set including 64 patients randomized to digitoxin yielding sensitivity/specificity of 87.5%/37.5%, respectively. CONCLUSION:In patients with HFrEF, treatment with digitoxin should be started at 0.05 mg o.d. in subjects with either female sex, eGFR < 50 ml/min/1.73m, BMI < 27 kg/m, or age ≥ 75 years. In any other patient, digitoxin may be safely started at 0.07 mg o.d.
10.1007/s00392-023-02199-z
Co-Occurrence of Social Risk Factors and Associated Outcomes in Patients With Heart Failure.
Journal of the American Heart Association
Background Among patients with heart failure (HF), social risk factors (SRFs) are associated with poor outcomes. However, less is known about how co-occurrence of SRFs affect all-cause health care utilization for patients with HF. The objective was to address this gap using a novel approach to classify co-occurrence of SRFs. Methods and Results This was a cohort study of residents living in an 11-county region of southeast Minnesota, aged ≥18 years with a first-ever diagnosis for HF between January 2013 and June 2017. SRFs, including education, health literacy, social isolation, and race and ethnicity, were obtained via surveys. Area-deprivation index and rural-urban commuting area codes were determined from patient addresses. Associations between SRFs and outcomes (emergency department visits and hospitalizations) were assessed using Andersen-Gill models. Latent class analysis was used to identify subgroups of SRFs; associations with outcomes were examined. A total of 3142 patients with HF (mean age, 73.4 years; 45% women) had SRF data available. The SRFs with the strongest association with hospitalizations were education, social isolation, and area-deprivation index. We identified 4 groups using latent class analysis, with group 3, characterized by more SRFs, at increased risk of emergency department visits (hazard ratio [HR], 1.33 [95% CI, 1.23-1.45]) and hospitalizations (HR, 1.42 [95% CI, 1.28-1.58]). Conclusions Low educational attainment, high social isolation, and high area-deprivation index had the strongest associations. We identified meaningful subgroups with respect to SRFs, and these subgroups were associated with outcomes. These findings suggest that it is possible to apply latent class analysis to better understand the co-occurrence of SRFs among patients with HF.
10.1161/JAHA.122.028734
Long-Term Outcomes of Early Coronary Artery Disease Testing After New-Onset Heart Failure.
Circulation. Heart failure
BACKGROUND:Coronary artery disease (CAD) testing remains underutilized in patients with newly diagnosed heart failure (HF). The longitudinal clinical impact of early CAD testing has not been well-characterized. We investigated changes in clinical management and long-term outcomes after early CAD evaluation in patients with incident HF. METHODS:We identified Medicare patients with incident HF from 2006 to 2018. The exposure variable was early CAD testing within 1 month of initial HF diagnosis. Covariate-adjusted rates of cardiovascular interventions after testing, including CAD-related management, were modeled using mixed-effects regression with clinician as a random intercept. We assessed mortality and hospitalization outcomes using landmark analyses with inverse probability-weighted Cox proportional hazards models. Falsification end points and mediation analysis were employed for bias assessment. RESULTS:Among 309 559 patients with new-onset HF without prior CAD, 15.7% underwent early CAD testing. Patients who underwent prompt CAD evaluation had higher adjusted rates of subsequent antiplatelet/statin prescriptions and revascularization, guideline-directed therapy for HF, and stroke prophylaxis for atrial fibrillation/flutter than controls. In weighted Cox models, 1-month CAD testing was associated with significantly reduced all-cause mortality (hazard ratio, 0.93 [95% CI, 0.91-0.96]). Mediation analyses indicated that ≈70% of this association was explained by CAD management, largely from new statin prescriptions. Falsification end points (outpatient diagnoses of urinary tract infection and hospitalizations for hip/vertebral fracture) were nonsignificant. CONCLUSIONS:Early CAD testing after incident HF was associated with a modest mortality benefit, driven mostly by subsequent statin therapy. Further investigation on clinician barriers to testing and treating high-risk patients may improve adherence to guideline-recommended cardiovascular interventions.
10.1161/CIRCHEARTFAILURE.122.010426
Sex Differences in the Effectiveness of Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Sacubitril-Valsartan for the Treatment of Heart Failure.
Journal of the American Heart Association
Background PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) suggested a potential benefit of sacubitril-valsartan in women with preserved ejection fraction. Among patients with heart failure previously treated with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), we studied whether effectiveness of treatment with sacubitril-valsartan compared with ACEI/ARB monotherapy differed between men and women for both preserved and reduced ejection fraction. Methods and Results Data were derived from the Truven Health MarketScan Databases between January 1, 2011, and December 31, 2018. We included patients with a primary diagnosis of heart failure on treatment with ACEIs, ARBs, or sacubitril-valsartan on the basis of the first prescription after diagnosis. A total of 7181 patients treated with sacubitril-valsartan, 25 408 patients using an ACEI, and 16 177 patients treated with ARBs were included. A total of 790 readmissions or deaths occurred among 7181 patients in the sacubitril-valsartan group and 11 901 events in 41 585 patients treated with an ACEI/ARB. Adjusted for covariates, the hazard ratio (HR) for treatment with sacubitril-valsartan compared with an ACEI or ARB was 0.74 (95% CI, 0.68-0.80). The protective effect of sacubitril-valsartan was evident for men and women (women: HR, 0.75 [95% CI, 0.66-0.86]; <0.01; men: HR, 0.71 [95% CI, 0.64-0.79]; <0.01; 0.03). A protective effect for both sexes was seen only among those with systolic dysfunction. Conclusions Treatment with sacubitril-valsartan is more effective at reducing death and admission to the hospital for heart failure compared with ACEIs/ARBs similarly among men and women with systolic dysfunction; sex differences in the effectiveness of sacubitril-valsartan in diastolic dysfunction requires further investigation.
10.1161/JAHA.122.028865
Association of Tricuspid Regurgitation With Outcome in Acute Heart Failure.
Circulation. Cardiovascular imaging
BACKGROUND:Tricuspid regurgitation (TR) is common in chronic heart failure (HF) and is associated with negative prognosis. However, evidence on prognostic implications of TR in acute HF is lacking. We sought to investigate the association between TR and mortality and the interaction with pulmonary hypertension (PH) in patients admitted for acute HF. METHODS:We enrolled 1176 consecutive patients with a primary diagnosis of acute HF and with available noninvasive estimation of TR and pulmonary arterial systolic pressure. RESULTS:Moderate-severe TR was present in 352 patients (29.9%) and was associated with older age and more comorbidities. The prevalence of PH (ie, pulmonary arterial systolic pressure >40 mm Hg), right ventricular dysfunction, and mitral regurgitation was higher in moderate-severe TR. At 1 year, 184 (15.6%) patients died. Moderate-severe TR was associated with higher 1-year mortality risk after adjustment for other echocardiographic parameters (pulmonary arterial systolic pressure, left ventricle ejection fraction, right ventricular dysfunction, mitral regurgitation, left and right atrial indexed volumes; hazard ratio, 1.718; =0.009), and the association with outcome was maintained when clinical variables (eg, natriuretic peptides, serum creatinine and urea, systolic blood pressure, atrial fibrillation) were added to the multivariable model (hazard ratio, 1.761; =0.024). The association between moderate-severe TR and outcome was consistent in patients with versus without PH, with versus without right ventricular dysfunction, and with versus without left ventricle ejection fraction <50%. Patients with coexistent moderate-severe TR and PH had 3-fold higher 1-year mortality risk compared with patients with no TR or PH (hazard ratio, 3.024; <0.001). CONCLUSIONS:In patients hospitalized for acute HF, the severity of TR is associated with 1-year survival, regardless of the presence of PH. The coexistence of moderate-severe TR and estimated PH was associated with a further increase in mortality risk. Our data must be interpreted in the context of potential underestimation of pulmonary arterial systolic pressure in patients with severe TR.
10.1161/CIRCIMAGING.122.014988
Machine Learning for Mortality Prediction in Patients With Heart Failure With Mildly Reduced Ejection Fraction.
Journal of the American Heart Association
Background Machine-learning-based prediction models (MLBPMs) have shown satisfactory performance in predicting clinical outcomes in patients with heart failure with reduced and preserved ejection fraction. However, their usefulness has yet to be fully elucidated in patients with heart failure with mildly reduced ejection fraction. This pilot study aims to evaluate the prediction performance of MLBPMs in a heart failure with mildly reduced ejection fraction cohort with long-term follow-up data. Methods and Results A total of 424 patients with heart failure with mildly reduced ejection fraction were enrolled in our study. The primary outcome was all-cause mortality. Two feature selection strategies were introduced for MLBPM development. The "All-in" (67 features) strategy was based on feature correlation, multicollinearity, and clinical significance. The other strategy was the CoxBoost algorithm with 10-fold cross-validation (17 features), which was based on the selection result of the "All-in" strategy. Six MLBPMs with 5-fold cross-validation based on the "All-in" and the CoxBoost algorithm with 10-fold cross-validation strategy were developed by the eXtreme Gradient Boosting, random forest, and support vector machine algorithms. The logistic regression model with 14 benchmark predictors was used as a reference model. During a median follow-up of 1008 (750, 1937) days, 121 patients met the primary outcome. Overall, MLBPMs outperformed the logistic model. The "All-in" eXtreme Gradient Boosting model had the best performance, with an accuracy of 85.4% and a precision of 70.3%. The area under the receiver-operating characteristic curve was 0.916 (95% CI, 0.887-0.945). The Brier score was 0.12. Conclusions The MLBPMs could significantly improve outcome prediction in patients with heart failure with mildly reduced ejection fraction, which would further optimize the management of these patients.
10.1161/JAHA.122.029124
Predicting Stroke in Heart Failure and Preserved Ejection Fraction Without Atrial Fibrillation.
Circulation. Heart failure
BACKGROUND:The rate of stroke in patients with heart failure (HF) and preserved ejection fraction but without atrial fibrillation (AF), is uncertain as is whether it is possible to reliably predict the risk of stroke in these patients. METHODS:We validated a previously developed simple risk model for stroke among patients enrolled in the I-Preserve trial (Irbesartan in Heart Failure With Preserved Systolic Function) and PARAGON-HF trial (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction). The risk model consisted of 3 variables: history of previous stroke, insulin-treated diabetes, and plasma N-terminal pro-B-type natriuretic peptide level. RESULTS:Of the 8924 patients included in the pooled trial dataset, 5126 patients did not have AF at baseline. Among patients without AF, 190 (3.7%) experienced a stroke over a median follow-up of 3.6 years (rate 10.5 per 1000 patient-years). The risk for stroke increased with increasing risk score: second tertile hazard ratio, 1.78 (95% CI, 1.17-2.71); third tertile hazard ratio, 3.03 (95% CI, 2.06-4.47), with the first tertile as reference. For patients in the third tertile, the occurrence rate of stroke was 17.7 per 1000 patient-years, similar to that in patients with AF not receiving anticoagulation (20.7 per 1000 patient-years), and those with AF who were receiving anticoagulation (14.5 per 1000 patient-years). Model discrimination was good with a C index of 0.81 (0.68-0.91) and a simple score could be created from the model. CONCLUSIONS:A simple risk model can detect a subset of HF and preserved ejection fraction patients without AF who have a higher risk for stroke. The balance of risk-to-benefit in these individuals may justify the use of prophylactic anticoagulation, but this hypothesis needs to be prospectively evaluated. REGISTRATION:URL: https://www. CLINICALTRIALS:gov; Unique identifiers: NCT00095238 and NCT01920711.
10.1161/CIRCHEARTFAILURE.122.010377
Predicting emergency department visits and hospitalizations for patients with heart failure in home healthcare using a time series risk model.
Journal of the American Medical Informatics Association : JAMIA
OBJECTIVES:Little is known about proactive risk assessment concerning emergency department (ED) visits and hospitalizations in patients with heart failure (HF) who receive home healthcare (HHC) services. This study developed a time series risk model for predicting ED visits and hospitalizations in patients with HF using longitudinal electronic health record data. We also explored which data sources yield the best-performing models over various time windows. MATERIALS AND METHODS:We used data collected from 9362 patients from a large HHC agency. We iteratively developed risk models using both structured (eg, standard assessment tools, vital signs, visit characteristics) and unstructured data (eg, clinical notes). Seven specific sets of variables included: (1) the Outcome and Assessment Information Set, (2) vital signs, (3) visit characteristics, (4) rule-based natural language processing-derived variables, (5) term frequency-inverse document frequency variables, (6) Bio-Clinical Bidirectional Encoder Representations from Transformers variables, and (7) topic modeling. Risk models were developed for 18 time windows (1-15, 30, 45, and 60 days) before an ED visit or hospitalization. Risk prediction performances were compared using recall, precision, accuracy, F1, and area under the receiver operating curve (AUC). RESULTS:The best-performing model was built using a combination of all 7 sets of variables and the time window of 4 days before an ED visit or hospitalization (AUC = 0.89 and F1 = 0.69). DISCUSSION AND CONCLUSION:This prediction model suggests that HHC clinicians can identify patients with HF at risk for visiting the ED or hospitalization within 4 days before the event, allowing for earlier targeted interventions.
10.1093/jamia/ocad129
Hyperuricemia and gout increased the risk of long-term mortality in patients with heart failure: insights from the National Health and Nutrition Examination Survey.
Journal of translational medicine
BACKGROUND:The prevalence of hyperuricemia, gout, and heart failure (HF) is on the rise, and these conditions often share similar risk factors. The present study aimed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality. METHODS:The data on nonpregnant participants aged ≥ 20 years with or without hyperuricemia, gout, and HF from the National Health and Nutrition Examination Survey 2001-2018 and 2007-2018 were included in this study. The binary logistic regression, Kaplan-Meier curve, Cox proportional-hazards model, and restricted cubic spline analysis were employed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality. RESULTS:Of 204,179,060 and 223,702,171 weighted eligible participants, 40,044,228 (19.6%) and 9,158,600 (4.1%) had hyperuricemia and gout, respectively. Older age, diabetes, stroke, and coronary artery disease were the risk factors for HF among patients with hyperuricemia and gout. The median survival time was 7.00 years and 6.25 years and the 5-year survival rate was 59.9% and 55.9% for patients with HF and hyperuricemia and those with HF and gout, respectively. Patients with hyperuricemia or gout were 2.46 and 2.35 times more likely to have HF and 1.37 and 1.45 times more likely to experience all-cause mortality compared with those who did not exhibit these conditions. The restricted cubic spline showed a nonlinear correlation between uric acid levels and HF and a J-shaped correlation between uric acid levels and all-cause mortality. CONCLUSIONS:Ambulatory patients with hyperuricemia or gout were more likely to have HF compared with those without hyperuricemia or gout. Patients with HF with hyperuricemia or gout were more likely to experience all-cause mortality in the long-term follow-up.
10.1186/s12967-023-04307-z
Impact of type 2 diabetes on life expectancy and role of kidney disease among inpatients with heart failure in Switzerland: an ambispective cohort study.
Cardiovascular diabetology
BACKGROUND:Type 2 diabetes (T2D) is expected to worsen the prognosis of inpatients with heart failure (HF) but the evidence from observational studies is inconsistent. We aimed to compare mortality outcomes and life expectancy among inpatients with HF with or without T2D and explored whether chronic kidney disease (CKD) influenced these associations. METHODS:We collected hospital and civil registry records of consecutive inpatients from a tertiary hospital in Switzerland with a diagnosis of HF from the year 2015 to 2019. We evaluated the association of T2D with mortality risk using Cox regression and adjusted for confounders. RESULTS:Our final cohort consisted of 10,532 patients with HF of whom 27% had T2D. The median age (interquartile range [IQR]) was 75 [68 to 82] and 78 [68 to 86] for the diabetes and non-diabetes groups, respectively. Over a median follow-up [IQR] of 4.5 years [3.3 to 5.6], 5,347 (51%) of patients died. T2D patients had higher risk of all-cause mortality (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.14 to 1.29). Compared to control (i.e. no T2D nor CKD), average life expectancy (95% CI) among T2D patients, CKD, or both was shorter by 5.4 months (95% CI 1.1 to 9.7), 9.0 months (95% CI 8.4 to 9.6), or 14.8 months (95% CI 12.4 to 17.2), respectively. No difference by sex or ejection fraction category was observed. CONCLUSIONS:T2D is associated with a significantly higher risk of all-cause mortality and shorter life expectancy compared to those without among middle-aged and elderly inpatients with HF; presence of CKD may further increase these risks.
10.1186/s12933-023-01903-7
Association between serum albumin and outcomes in heart failure and secondary mitral regurgitation: the COAPT trial.
European journal of heart failure
AIMS:Low serum albumin levels are associated with poor prognosis in numerous chronic disease states but the relationship between albumin and outcomes in patients with heart failure (HF) and secondary mitral regurgitation (SMR) has not been described. METHODS AND RESULTS:The randomized COAPT trial evaluated the safety and effectiveness of transcatheter edge-to-edge repair (TEER) with the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone in patients with symptomatic HF and moderate-to-severe or severe SMR. Baseline serum albumin levels were measured at enrolment. Among 614 patients enrolled in COAPT, 559 (91.0%) had available baseline serum albumin levels (median 4.0 g/dl, interquartile range 3.7-4.2 g/dl). Patients with albumin <4.0 g/dl compared with ≥4.0 g/dl were older and more likely to have ischaemic cardiomyopathy and a hospitalization within the year prior to enrolment. After multivariable adjustment, patients with albumin <4.0 g/dl had higher 4-year rates of all-cause death (63.7% vs. 47.6%; adjusted hazard ratio 1.34, 95% confidence interval 1.02-1.74; p = 0.032), but there were no significant differences in HF hospitalizations (HFH) or all-cause hospitalizations according to baseline serum albumin level. The relative effectiveness of TEER plus GDMT versus GDMT alone was consistent in patients with low and high albumin levels (p = 0.19 and 0.35 for death and HFH, respectively). CONCLUSION:Low baseline serum albumin levels were independently associated with reduced 4-year survival in patients with HF and severe SMR enrolled in the COAPT trial, but not with HFH. Patients treated with TEER derived similarly robust reductions in both death and HFH regardless of baseline albumin level.
10.1002/ejhf.2809
Improved long-term survival with tafamidis treatment in patients with transthyretin amyloid cardiomyopathy and severe heart failure symptoms.
European journal of heart failure
AIM:The value of disease-modifying therapies (such as tafamidis) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and severe heart failure symptoms has been debated. This study assessed long-term all-cause survival in patients with New York Heart Association (NYHA) class III symptoms in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) long-term extension (LTE) study. METHODS AND RESULTS:At the baseline of ATTR-ACT, 55/176 (31.3%) patients receiving tafamidis 80 mg and 63/177 (35.6%) receiving placebo had NYHA class III symptoms. After 30 months of treatment, patients could join an ongoing LTE study to receive open-label tafamidis. In an interim analysis of the LTE study (August 2021), all-cause mortality was lower among patients with NYHA class III symptoms who received continuous tafamidis in ATTR-ACT and the LTE study (hazard ratio 0.64; 95% confidence interval 0.41-0.99; median follow-up: 60 months), as compared with those who received placebo in ATTR-ACT and tafamidis in the LTE study (median follow-up: 56 months). Similar findings were observed in patients with NYHA class I/II symptoms at baseline (0.50; 0.35-0.73; tafamidis 80 mg n = 121; placebo n = 114; median follow-up of 61 and 60 months, respectively). CONCLUSION:We observed reduced all-cause mortality with continuous tafamidis treatment compared with delayed tafamidis treatment (placebo then tafamidis) in patients with NYHA class III symptoms at baseline over a median follow-up of ∼5 years. These findings demonstrate the value of tafamidis treatment in patients with ATTR-CM and severe heart failure symptoms, and emphasize the importance of early treatment. CLINICAL TRIAL REGISTRATIONS:ClinicalTrials.gov NCT01994889 and NCT02791230.
10.1002/ejhf.2974
Insight into different phenotypic presentations of heart failure with preserved ejection fraction.
Progress in cardiovascular diseases
Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for half of all HF diagnoses, and its prevalence is increasing at an alarming rate. Lately, it has been recognized as a clinical syndrome due to diverse underlying etiology and pathophysiological mechanisms. The classic echocardiographic features of HFpEF have been well described as preserved ejection fraction (≥50%), left ventricular hypertrophy, and left atrial enlargement. However, echocardiography can play a key role in identifying the principal underlying mechanism responsible for HFpEF in the individual patient. The recognition of different phenotypic presentations of HFpEF (infiltrative, metabolic, genetic, and inflammatory) can assist the clinician in tailoring the appropriate management, and offer prognostic information. The goal of this review is to highlight several key phenotypes of HFpEF and illustrate the classic clinical scenario and echocardiographic features of each phenotype with real patient cases.
10.1016/j.pcad.2023.07.003
Classification of Heart Failure Events by Severity: Insights From the VICTORIA Trial.
Journal of cardiac failure
BACKGROUND:Hospitalization due to heart failure (HFH) is a major source of morbidity, consumes significant economic resources and is a key endpoint in HF clinical trials. HFH events vary in severity and implications, but they are typically considered equivalent when analyzing clinical trial outcomes. OBJECTIVES:We aimed to evaluate the frequency and severity of HF events, assess treatment effects and describe differences in outcomes by type of HF event in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction). METHODS:VICTORIA compared vericiguat with placebo in patients with HF with reduced ejection fraction (< 45%) and a recent worsening HF event. All HFHs were prospectively adjudicated by an independent clinical events committee (CEC) whose members were blinded to treatment assignment. We evaluated the frequency and clinical impact of HF events by severity, categorized by highest intensity of HF treatment (urgent outpatient visit or hospitalization treated with oral diuretics, intravenous diuretics, intravenous vasodilators, intravenous inotropes, or mechanical support) and treatment effect by event categories. RESULTS:In VICTORIA, 2948 HF events occurred in 5050 enrolled patients. Overall total CEC HF events for vericiguat vs placebo were 43.9 vs 49.1 events/100 patient-years (P = 0.01). Hospitalization for intravenous diuretics was the most common type of HFH event (54%). HF event types differed markedly in their clinical implications for both in-hospital and post-discharge events. We observed no difference in the distribution of HF events between randomized treatment groups (P = 0.78). CONCLUSION:HF events in large global trials vary significantly in severity and clinical implications, which may have implications for more nuanced trial design and interpretation. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov (NCT02861534).
10.1016/j.cardfail.2023.04.015
Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure: A Randomized, Placebo-Controlled, Double-Blind Study.
Journal of cardiac failure
BACKGROUND:Evidence for modulating the sodium chloride (NaCl) intake of patients hospitalized with acute heart failure (AHF) is inconclusive. Salt restriction may not benefit; hypertonic saline may aid diuresis. OBJECTIVE:To compare the safety and efficacy of oral NaCl during intravenous (IV) diuretic therapy in renal function and weight. METHODS:Seventy hospitalized patients with AHF who were being treated with IV furosemide infusion consented to receive, randomly, 2 grams of oral NaCl or placebo 3 times a day in a double-blind manner during diuresis. Treatment efficacy (bivariate primary endpoints of change in serum creatinine levels and change in weight) was measured at 96 hours, and adverse safety events were tracked for 90 days. RESULTS:Sixty-five patients (34 NaCl, 31 placebo) were included for analysis after 5 withdrew. A median of 13 grams of NaCl was given compared to placebo. At 96 hours, there was no significant difference between treatment groups with respect to the primary endpoint (P = 0.33); however, the trial was underpowered, and there was greater than expected standard deviation in weight change. The mean change in creatinine levels and weight was 0.15 ± 0.44 mg/dL and 4.6 ± 4.2 kg in the placebo group compared with 0.04 ± 0.40 mg/dL and 4.0 ± 4.3 kg in the NaCl group (P = 0.30 and 0.57, respectively). Across efficacy and safety endpoints, we observed no significant difference between the 2 groups other than changes in serum sodium levels (-2.6 ± 2.7 in the placebo group and -0.3 ± 3.3 mEq/L in the NaCl group; P < 0.001) and in serum blood urea nitrogen levels (11 ± 15 in the placebo group; 3.1 ± 13 mEq/L in the NaCl group; P = 0.025). CONCLUSIONS:In this single-center study, liberal vs restrictive oral sodium chloride intake strategies did not impact the safety and efficacy of intravenous diuretic therapy in patients with AHF. (ClinicalTrials.gov registration NCT04334668.).
10.1016/j.cardfail.2023.03.018
Safety, usability, and performance of a wireless left atrial pressure monitoring system in patients with heart failure: the VECTOR-HF trial.
European journal of heart failure
AIMS:In heart failure (HF), implantable haemodynamic monitoring devices have been shown to optimize therapy, anticipating clinical decompensation and preventing hospitalization. Direct left-sided haemodynamic sensors offer theoretical benefits beyond pulmonary artery pressure monitoring systems. We evaluated the safety, usability, and performance of a novel left atrial pressure (LAP) monitoring system in HF patients. METHODS AND RESULTS:The VECTOR-HF study (NCT03775161) was a first-in-human, prospective, multicentre, single-arm, clinical trial enrolling 30 patients with HF. The device consisted of an interatrial positioned leadless sensor, able to transmit LAP data wirelessly. After 3 months, a right heart catheterization was performed to correlate mean pulmonary capillary wedge pressure (PCWP) with simultaneous mean LAP obtained from the device. Remote LAP measurements were then used to guide patient management. The miniaturized device was successfully implanted in all 30 patients, without acute major adverse cardiac and neurological events (MACNE). At 3 months, freedom from short-term MACNE was 97%. Agreement between sensor-calculated LAP and PCWP was consistent, with a mean difference of -0.22 ± 4.92 mmHg, the correlation coefficient and the Lin's concordance correlation coefficient values were equal to 0.79 (p < 0.0001) and 0.776 (95% confidence interval 0.582-0.886), respectively. Preliminary experience with V-LAP-based HF management was associated with significant improvements in New York Heart Association (NYHA) functional class (32% of patients reached NYHA class II at 6 months, p < 0.005; 60% of patients at 12 months, p < 0.005) and 6-min walk test distance (from 244.59 ± 119.59 m at baseline to 311.78 ± 129.88 m after 6 months, p < 0.05, and 343.95 ± 146.15 m after 12 months, p < 0.05). CONCLUSION:The V-LAP™ monitoring system proved to be generally safe and provided a good correlation with invasive PCWP. Initial evidence also suggests possible improvement in HF clinical symptoms.
10.1002/ejhf.2869
Prognostic benefit of early diagnosis with exercise stress testing in heart failure with preserved ejection fraction.
European journal of preventive cardiology
BACKGROUND:Delayed diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) can lead to poor clinical outcomes. Exercise stress testing, especially exercise stress echocardiography, plays a primary role in the early detection of HFpEF among dyspnoeic patients, but its prognostic significance is unknown, as is whether initiation of guideline-directed therapy could improve clinical outcomes in such early-stage HFpEF. METHODS AND RESULTS:Ergometry exercise stress echocardiography was performed in 368 patients with exertional dyspnoea. Heart failure with preserved ejection fraction was diagnosed by a total score of HFA-PEFF algorithm Step 2 (resting assessments) and Step 3 (exercise testing) ≥ 5 or elevated pulmonary capillary wedge pressure at rest or during exercise. The primary endpoint comprised all-cause mortality and worsening HF events. Heart failure with preserved ejection fraction was diagnosed in 182 patients, while 186 had non-cardiac dyspnoea (controls). Patients diagnosed with HFpEF had a seven-fold increased risk of composite events than that of controls [hazard ratio (HR) 7.52; 95% confidential interval (CI), 2.24-25.2; P = 0.001]. Patients with an HFA-PEFF Step 2 < 5 points but had an HFA-PEFF ≥ 5 after exercise stress testing (Steps 2-3) had a higher risk of composite events than controls. Guideline-recommended therapies were initiated in 90 patients diagnosed with HFpEF after index exercise testing. Patients with early treatment experienced lower rates of composite outcomes than those without (HR 0.33; 95% CI, 0.12-0.91; P = 0.03). CONCLUSION:Identification of HFpEF by exercise stress testing may allow risk stratification in dyspnoeic patients. Furthermore, initiation of guideline-directed therapy may be associated with improved clinical outcomes in patients with early-stage HFpEF. LAY SUMMARY:Delayed diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) can lead to poor clinical outcomes. Exercise stress testing, especially exercise stress echocardiography, plays a primary role in the early identification of HFpEF among dyspnoeic patients, but its prognostic significance is unknown, as is whether initiation of guideline-directed therapy could improve clinical outcomes in such early-stage HFpEF. In the current study, ergometry exercise stress echocardiography was performed in 368 patients with exertional dyspnoea. Heart failure with preserved ejection fraction was diagnosed by the established algorithm consisting of Step 2 (resting assessments) and Step 3 (exercise echocardiography or exercise right heart catheterization). The primary endpoint comprised all-cause mortality and worsening HF events. Heart failure with preserved ejection fraction was diagnosed in 182 patients and non-cardiac dyspnoea (controls) in 186 patients. Patients newly diagnosed with HFpEF had a seven-fold increased risk of composite events than that of controls. Guideline-recommended therapies were initiated in 90 patients newly diagnosed with HFpEF after index exercise testing. Patients with early treatment experienced lower rates of composite outcomes than those without. In conclusion, identification of HFpEF by exercise stress testing may allow risk stratification in patients with chronic exertional dyspnoea. Furthermore, initiation of guideline-directed therapy may be associated with improved clinical outcomes in patients with early-stage HFpEF.
10.1093/eurjpc/zwad127
Disproportionate exercise-induced pulmonary hypertension in relation to cardiac output in heart failure with preserved ejection fraction: a non-invasive echocardiographic study.
European journal of heart failure
AIMS:Pulmonary hypertension (PH) and pulmonary vascular remodelling are common in patients with heart failure with preserved ejection fraction (HFpEF). Many patients with HFpEF demonstrate an abnormal pulmonary haemodynamic response to exercise that is not identifiable at rest. This can be estimated non-invasively by the mean pulmonary artery pressure-cardiac output relationship (mPAP/CO slope). We sought to characterize the pathophysiology of disproportionate exercise-induced PH in relation to CO (DEi-PH) and its prognostic impact in patients with HFpEF. METHODS AND RESULTS:A total of 345 patients (166 HFpEF and 179 controls) underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. DEi-PH was defined as the mPAP/CO slope >5.2 mmHg/L/min (median value). At rest, there were no differences in right ventricular (RV) function and severity of PH between HFpEF patients with and without DEi-PH. Compared with controls (n = 179) and HFpEF without DEi-PH (n = 83), HFpEF with DEi-PH (n = 83) demonstrated worse exercise capacity (lower peak oxygen consumption), depressed RV systolic function, impaired RV-pulmonary artery coupling, limitation in CO augmentation, more right-sided congestion, and worse ventilatory efficiency (higher minute ventilation vs. carbon dioxide volume) during peak exercise. Kaplan-Meier analyses showed that HFpEF patients with DEi-PH had higher rates of composite outcomes of all-cause mortality or heart failure events than those without (log-rank p = 0.0002). CONCLUSION:Patients with HFpEF and DEi-PH demonstrated distinct pathophysiologic features that become apparent only during exercise. These data suggest that DEi-PH is a pathophysiologic phenotype of HFpEF and reinforce the importance of exercise stress echocardiography for detailed characterization of HFpEF.
10.1002/ejhf.2821
Serial assessment of biomarkers and heart failure outcomes in patients with atrial fibrillation.
European journal of heart failure
AIMS:Cardiac functional and structural remodelling in patients with atrial fibrillation (AF) contributes to development of heart failure (HF) as their major cardiovascular comorbidity. Circulating biomarkers may reflect these cardiac alterations. METHODS AND RESULTS:ENGAGE AF-TIMI 48 was a randomized trial of edoxaban versus warfarin in 21 105 patients with AF. We performed a nested biomarker study, analysing high-sensitivity troponin T (hsTnT, n = 8705), N-terminal pro-B-type natriuretic peptide (NT-proBNP, n = 8765), and growth differentiation factor-15 (GDF-15, n = 8705) at baseline and 12 months. Of the biomarker cohort, 5207 had a history of HF, among whom 3996 had known ejection fraction (EF): 926 with reduced EF (HFrEF; ≤40%), 1043 with mildly reduced EF (HFmrEF; 40-49%), and 2027 with preserved EF (HFpEF; ≥50%). Elevated baseline hsTnT, NT-proBNP, and GDF-15 were associated with higher risk of hospitalization for HF (HHF) or HF death overall and in subpopulations defined by HF history and EF (p < 0.001 for each). These associations of outcome with each biomarker were consistent regardless of a history of HF or EF (p-interaction >0.05 for each). Patients who had an increase in or had persistently elevated values in any of the three biomarkers over 12 months were at higher risk for HHF or HF death in the overall population (p < 0.001 for each biomarker and category). CONCLUSION:Serial measurement of hsTnT, NT-proBNP, and GDF-15 revealed that higher baseline values, and increasing or persistently elevated values over 1 year are associated with higher risk of HF outcomes in patients with AF regardless of HF history or HF phenotype based on EF. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov unique identifier NCT00781391.
10.1002/ejhf.2844
Left atrial enlargement is associated with pulmonary vascular disease in heart failure with preserved ejection fraction.
European journal of heart failure
AIMS:Elevated left atrial (LA) pressure is a pathophysiologic hallmark of heart failure with preserved ejection fraction (HFpEF). Chronically elevated LA pressure leads to LA enlargement, which may impair LA function and increase pulmonary pressures. We sought to evaluate the relationship between LA volume and pulmonary arterial haemodynamics in patients with HFpEF. METHODS AND RESULTS:Data from 85 patients (aged 69 ± 8 years) who underwent exercise right heart catheterization and echocardiography were retrospectively analysed. All had symptoms of heart failure, left ventricular ejection fraction ≥50% and haemodynamic features of HFpEF. Patients were divided into LA volume index-based tertiles (≤34 ml/m , >34 to ≤45 ml/m , >45 ml/m ). A subgroup analysis was performed in patients with recorded LA global reservoir strain (n = 60), with reduced strain defined as ≤24%. Age, sex, body surface area and left ventricular ejection fraction were similar between volume groups. LA volume was associated with blunted increases in cardiac output with exercise (p <0.001), higher resting mean pulmonary artery pressure (p = 0.003), with similar wedge pressure (p = 1). Pulmonary vascular resistance (PVR) increased with increasing LA volume (p <0.001). Larger LA volumes featured reduced LA strain (p <0.001), with reduced strain associated with reduced PVR-compliance time (0.34 [0.28-0.40] vs. 0.38 [0.33-0.43], p = 0.03). CONCLUSION:Increasing LA volume may be associated with more advanced pulmonary vascular disease in HFpEF, featuring higher PVR and pulmonary pressures. Reduced LA function, worse at increasing LA volumes, is associated with a disrupted PVR-compliance relationship, further augmenting impaired pulmonary haemodynamics.
10.1002/ejhf.2805
The Influence of Body Mass Index on Clinical Interpretation of Established and Novel Biomarkers in Acute Heart Failure.
Journal of cardiac failure
BACKGROUND:Body mass index (BMI) is a known confounder for natriuretic peptides, but its influence on other biomarkers is less well described. We investigated whether BMI interacts with biomarkers' association with prognosis in patients with acute heart failure (AHF). METHODS AND RESULTS:B-type natriuretic peptide (BNP), high-sensitivity cardiac troponin I (hs-cTnI), galectin-3, serum neutrophil gelatinase-associated lipocalin (sNGAL), and urine NGAL were measured serially in patients with AHF during hospitalization in the AKINESIS (Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic Heart Failure) study. Cox regression analysis was used to determine the association of biomarkers and their interaction with BMI for 30-day, 90-day and 1-year composite outcomes of death or HF readmission. Among 866 patients, 21.2%, 29.7% and 46.8% had normal (18.5-24.9 kg/m), overweight (25-29.9 kg/m) or obese (≥ 30 kg/m) BMIs on admission, respectively. Admission values of BNP and hs-cTnI were negatively associated with BMI, whereas galectin-3 and sNGAL were positively associated with BMI. Admission BNP and hs-cTnI levels were associated with the composite outcome within 30 days, 90 days and 1 year. Only BNP had a significant interaction with BMI. When BNP was analyzed by BMI category, its association with the composite outcome attenuated at higher BMIs and was no longer significant in obese individuals. Findings were similar when evaluated by the last-measured biomarkers and BMIs. CONCLUSIONS:In patients with AHF, only BNP had a significant interaction with BMI for the outcomes, with its association attenuating as BMI increased; hs-cTnI was prognostic, regardless of BMI.
10.1016/j.cardfail.2023.03.029
Parameters associated with improvement of systolic function in patients with heart failure.
Heart (British Cardiac Society)
AIMS:Identifying clinical and echocardiographic parameters associated with improvement in systolic function in outpatients with heart failure with reduced ejection fraction (HFrEF) could lead to more targeted treatment improving systolic function and outcome. METHODS:In a retrospective cohort study, echocardiographic examinations from the first and final visit of 686 patients with HFrEF at the heart failure clinic at Gentofte Hospital were retrieved and analysed. Parameters associated with left ventricular ejection fraction (LVEF) improvement and survival according to LVEF improvement were assessed using linear regression and Cox regression, respectively. Beta-coefficients (β-coef) are standardised. Strain values are absolute. RESULTS:While undergoing heart failure treatment, 559 (81.5%) patients improved systolic function ( Δ LVEF >0%), with 100 (14.6%) being super responders defined by LVEF improvement >20%. After multivariable adjustment, LVEF improvement was significantly associated with a less impaired global longitudinal strain (β-coef 0.25, p<0.001), higher tricuspid annular plane systolic excursion (β-coef 0.09, p=0.018), smaller left ventricular internal dimension in diastole (β-coef -0.15, p=0.011), lower E-wave/A-wave ratio (β-coef -0.13, p=0.003), higher heart rate (β-coef 0.18, p<0.001) and absence of ischaemic cardiomyopathy (β-coef -0.11, p=0.010) and diabetes (β-coef -0.081, p=0.033) at baseline. Mortality incidence rates differed with LVEF improvement ( Δ LVEF <0% vs Δ LVEF >0%, 8.3 vs 4.3 per 100 person years, p=0.012). Greater improvement in LVEF was associated with significantly lower mortality risk (tertile 1 vs tertile 3, HR 3.23, 95% CI 1.39 to 7.51, p=0.006). CONCLUSION:In this outpatient HFrEF cohort, most patients improved systolic function. Heart failure aetiology, comorbidities and echocardiographic measures of heart structure and function were significantly, independently associated with future LVEF improvement. Greater LVEF improvement was significantly associated with lower mortality.
10.1136/heartjnl-2023-322371
Individual Trajectories of Health Status During the First Year of Discharge From Hospitalization for Heart Failure and Their Associations With Death in the Following Years.
Journal of the American Heart Association
Background Improving health status is one of the major goals in the management of heart failure (HF). However, little is known about the long-term individual trajectories of health status in patients with acute HF after discharge. Methods and Results We enrolled 2328 patients hospitalized for HF from 51 hospitals prospectively and measured their health status via the Kansas City Cardiomyopathy Questionnaire-12 at admission and 1, 6, and 12 months after discharge, respectively. The median age of the patients included was 66 years, and 63.3% were men. Six patterns of Kansas City Cardiomyopathy Questionnaire-12 trajectories were identified by a latent class trajectory model: persistently good (34.0%), rapidly improving (35.5%), slowly improving (10.4%), moderately regressing (7.4%), severely regressing (7.5%), and persistently poor (5.3%). Advanced age, decompensated chronic HF, HF with mildly reduced ejection fraction, HF with preserved ejection fraction, depression symptoms, cognitive impairment, and each additional HF rehospitalization within 1 year of discharge were associated with unfavorable health status (moderately regressing, severely regressing, and persistently poor) (<0.05). Compared with the pattern of persistently good, slowly improving (hazard ratio [HR], 1.50 [95% CI, 1.06-2.12]), moderately regressing (HR, 1.92 [1.43-2.58]), severely regressing (HR, 2.26 [1.54-3.31]), and persistently poor (HR, 2.34 [1.55-3.53]) were associated with increased risks of all-cause death. Conclusions One-fifth of 1-year survivors after hospitalization for HF experienced unfavorable health status trajectories and had a substantially increased risk of death during the following years. Our findings help inform the understanding of disease progression from a patient perception perspective and its relationship with long-term survival. Registration URL: https://www.clinicaltrials.gov; unique identifier: NCT02878811.
10.1161/JAHA.122.028782
Association between the triglyceride-glucose index and the risk of mortality among patients with chronic heart failure: results from a retrospective cohort study in China.
Cardiovascular diabetology
BACKGROUND:The triglyceride-glucose (TyG) index has been demonstrated to be a reliable surrogate marker of insulin resistance (IR) and an effective predictive index of cardiovascular (CV) disease risk. However, its long-term prognostic value in patients with chronic heart failure (CHF) remains uncertain. METHODS:A total of 6697 consecutive patients with CHF were enrolled in this study. Patients were divided into tertiles according to their TyG index. The incidence of primary outcomes, including all-cause death and CV death, was recorded. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. RESULTS:During a median follow-up of 3.9 years, a total of 2158 (32.2%) all-cause deaths and 1305 (19.5%) CV deaths were documented. The incidence of primary events from the lowest to the highest TyG index tertiles were 50.61, 64.64, and 92.25 per 1000 person-years for all-cause death and 29.05, 39.40, and 57.21 per 1000 person-years for CV death. The multivariate Cox hazards regression analysis revealed hazard ratios for all-cause and CV deaths of 1.84 (95% CI 1.61-2.10; P for trend < 0.001) and 1.94 (95% CI 1.63-2.30; P for trend < 0.001) when the highest and lowest TyG index tertiles were compared. In addition, the predictive ability of the TyG index against all-cause death was more prominent among patients with metabolic syndrome and those with heart failure with preserved ejection fraction phenotype (both P for interaction < 0.05). Furthermore, adding the TyG index to the established model for all-cause death improved the C‑statistic value (0.710 for the established model vs. 0.723 for the established model + TyG index, P < 0.01), the integrated discrimination improvement value (0.011, P < 0.01), the net reclassification improvement value (0.273, P < 0.01), and the clinical net benefit (probability range, 0.07-0.36). CONCLUSIONS:The TyG index was significantly associated with the risk of mortality, suggesting that it may be a reliable and valuable predictor for risk stratification and an effective prognostic indicator in patients with CHF.
10.1186/s12933-023-01895-4
Incidence, Predictors, and Outcomes Associated With Worsening Renal Function in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.
Journal of the American Heart Association
Background The incidence and implications of worsening renal function (WRF) after mitral valve transcatheter edge-to-edge repair (TEER) in patients with heart failure (HF) are unknown. Therefore, the aim of this study was to determine the proportion of patients with HF and secondary mitral regurgitation who develop persistent WRF within 30 days following TEER, and whether this development portends a worse prognosis. Methods and Results In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, 614 patients with HF and severe secondary mitral regurgitation were randomized to TEER with the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone. WRF was defined as serum creatinine increase ≥1.5× or ≥0.3 mg/dL from baseline persisting to day 30 or requiring renal replacement therapy. All-cause death and HF hospitalization rates between 30 days and 2 years were compared in patients with and without WRF. WRF at 30 days was present in 11.3% of patients (9.7% in the TEER plus GDMT group and 13.1% in the GDMT alone group; =0.23). WRF was associated with all-cause death (hazard ratio [HR], 1.98 [95% CI, 1.3-3.03]; =0.001) but not HF hospitalization (HR, 1.47 [ 95% CI, 0.97-2.24]; =0.07) between 30 days and 2 years. Compared with GDMT alone, TEER reduced both death and HF hospitalization consistently in patients with and without WRF (=0.53 and 0.57, respectively). Conclusions Among patients with HF and severe secondary mitral regurgitation, the incidence of WRF at 30 days was not increased after TEER compared with GDMT alone. WRF was associated with greater 2-year mortality but did not attenuate the treatment benefits of TEER in reducing death and HF hospitalization compared with GDMT alone. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.
10.1161/JAHA.123.029504
Prognostic Stratification of Clinically Stable Patients with Heart Failure by Echocardiographic Pressure/Volume Loop Model.
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
BACKGROUND:Pressure/volume (P/V) loops provide useful information on left ventricular performance and prognosis in patients with heart failure (HF) but do not lend themselves to routine clinical practice. The authors developed a noninvasive method to compute individualized P/V loops to predict adverse clinical outcomes in patients with stable HF, which the authors believe can be used clinically. METHODS:A derivation cohort (n = 443 patients) was used to develop an echocardiography P/V loop model, using brachial arterial pressure and trans-thoracic two-dimensional Doppler echocardiographic data. Each patient's P/V loop was depicted as an irregular pentagon, and a centroid was derived for each loop. The centroid distance (CD) from a reference centroid (derived from 101 healthy control subjects) was computed. This model was prospectively applied to 435 patients who constituted the validation cohort. The study end point was a composite of cardiac death or hospitalization for HF among study patients. RESULTS:In the derivation cohort, CD was threefold greater among patients who experienced adverse events than those who did not. During a follow-up period of 30 months (15-45 months), event rates were 35% (72 of 206 patients) and 12% (29 of 237 patients P < .001), respectively, among patients with CD > 33 mL/mm Hg and those with CD ≤33 mL/mm Hg (prognostic cutoff derived by receiver operating characteristic analysis). Multivariate Cox analysis identified CD as an independent predictor of adverse outcome (hazard ratio, 1.61; 95% CI, 1.03-2.50) independently of left ventricular end-diastolic volume, pulmonary capillary wedge pressure, and left ventricular ejection fraction. These conclusions were confirmed in the validation cohort. CONCLUSIONS:The authors propose a method to create a noninvasive P/V loop and its centroid. These data provide useful pathophysiologic and prognostic information in patients with HF.
10.1016/j.echo.2023.02.006
Major cardiovascular events and subsequent risk of kidney failure with replacement therapy: a CKD Prognosis Consortium study.
European heart journal
AIMS:Chronic kidney disease (CKD) increases risk of cardiovascular disease (CVD). Less is known about how CVD associates with future risk of kidney failure with replacement therapy (KFRT). METHODS AND RESULTS:The study included 25 903 761 individuals from the CKD Prognosis Consortium with known baseline estimated glomerular filtration rate (eGFR) and evaluated the impact of prevalent and incident coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) events as time-varying exposures on KFRT outcomes. Mean age was 53 (standard deviation 17) years and mean eGFR was 89 mL/min/1.73 m2, 15% had diabetes and 8.4% had urinary albumin-to-creatinine ratio (ACR) available (median 13 mg/g); 9.5% had prevalent CHD, 3.2% prior stroke, 3.3% HF, and 4.4% prior AF. During follow-up, there were 269 142 CHD, 311 021 stroke, 712 556 HF, and 605 596 AF incident events and 101 044 (0.4%) patients experienced KFRT. Both prevalent and incident CVD were associated with subsequent KFRT with adjusted hazard ratios (HRs) of 3.1 [95% confidence interval (CI): 2.9-3.3], 2.0 (1.9-2.1), 4.5 (4.2-4.9), 2.8 (2.7-3.1) after incident CHD, stroke, HF and AF, respectively. HRs were highest in first 3 months post-CVD incidence declining to baseline after 3 years. Incident HF hospitalizations showed the strongest association with KFRT [HR 46 (95% CI: 43-50) within 3 months] after adjustment for other CVD subtype incidence. CONCLUSION:Incident CVD events strongly and independently associate with future KFRT risk, most notably after HF, then CHD, stroke, and AF. Optimal strategies for addressing the dramatic risk of KFRT following CVD events are needed.
10.1093/eurheartj/ehac825
Utility of the Kidney Failure Risk Equation and Estimated GFR for Estimating Time to Kidney Failure in Advanced CKD.
American journal of kidney diseases : the official journal of the National Kidney Foundation
RATIONALE & OBJECTIVE:The Kidney Failure Risk Equation (KFRE) predicts the 2-year risk of kidney failure for patients with chronic kidney disease (CKD). Translating KFRE-predicted risk or estimated glomerular filtration rate (eGFR) into time to kidney failure could inform decision making for patients approaching kidney failure. STUDY DESIGN:Retrospective cohort. SETTING & PARTICIPANTS:CKD Outcomes and Practice Patterns Study (CKDOPPS) cohort of patients with an eGFR<60mL/min/1.73m from 34 US nephrology practices (2013-2021). EXPOSURE:2-year KFRE risk or eGFR. OUTCOME:Kidney failure defined as initiation of dialysis or kidney transplantation. ANALYTICAL APPROACH:Accelerated failure time (Weibull) models used to estimate the median, 25th, and 75th percentile times to kidney failure starting from KFRE values of 20%, 40%, and 50%, and from eGFR values of 20, 15, and 10mL/min/1.73m. We examined variability in time to kidney failure by age, sex, race, diabetes status, albuminuria, and blood pressure. RESULTS:Overall, 1,641 participants were included (mean age 69±13 years; median eGFR of 28mL/min/1.73m [IQR 20-37mL/min/1.73 m]). Over a median follow-up period of 19 months (IQR, 12-30 months), 268 participants developed kidney failure, and 180 died before reaching kidney failure. The median estimated time to kidney failure was widely variable across patient characteristics from an eGFR of 20mL/min/1.73m and was shorter for younger age, male sex, Black (versus non-Black), diabetes (vs no diabetes), higher albuminuria, and higher blood pressure. Estimated times to kidney failure were comparably less variable across these characteristics for KFRE thresholds and eGFR of 15 or 10mL/min/1.73m. LIMITATIONS:Inability to account for competing risks when estimating time to kidney failure. CONCLUSIONS:Among those with eGFR<15mL/min/1.73m or KFRE risk>40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Our results demonstrate that estimating time to kidney failure in advanced CKD can inform clinical decisions and patient counseling on prognosis, regardless of whether estimates are based on eGFR or the KFRE. PLAIN-LANGUAGE SUMMARY:Clinicians often talk to patients with advanced chronic kidney disease about the level of kidney function expressed as the estimated glomerular filtration rate (eGFR) and about the risk of developing kidney failure, which can be estimated using the Kidney Failure Risk Equation (KFRE). In a cohort of patients with advanced chronic kidney disease, we examined how eGFR and KFRE risk predictions corresponded to the time patients had until reaching kidney failure. Among those with eGFR<15mL/min/1.73m or KFRE risk > 40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Estimating time to kidney failure in advanced CKD using either eGFR or KFRE can inform clinical decisions and patient counseling on prognosis.
10.1053/j.ajkd.2023.03.014
Reducing Pulmonary Capillary Wedge Pressure During Exercise Exacerbates Exertional Dyspnea in Patients With Heart Failure With Preserved Ejection Fraction: Implications for V˙/Q˙ Mismatch.
Chest
BACKGROUND:The primary cause of dyspnea on exertion in heart failure with preserved ejection fraction (HFpEF) is presumed to be the marked rise in pulmonary capillary wedge pressure during exercise; however, this hypothesis has never been tested directly. Therefore, we evaluated invasive exercise hemodynamics and dyspnea on exertion in patients with HFpEF before and after acute nitroglycerin (NTG) treatment to lower pulmonary capillary wedge pressure. RESEARCH QUESTION:Does reducing pulmonary capillary wedge pressure during exercise with NTG improve dyspnea on exertion in HFpEF? STUDY DESIGN AND METHODS:Thirty patients with HFpEF performed two invasive 6-min constant-load cycling tests (20 W): one with placebo (PLC) and one with NTG. Ratings of perceived breathlessness (0-10 scale), pulmonary capillary wedge pressure (right side of heart catheter), and arterial blood gases (radial artery catheter) were measured. Measurements of V˙/Q˙ matching, including alveolar dead space (Vd; Enghoff modification of the Bohr equation) and the alveolar-arterial Po difference (A-aDO; alveolar gas equation), were also derived. The ventilation (V˙e)/CO elimination (V˙co) slope was also calculated as the slope of the V˙e and V˙co relationship, which reflects ventilatory efficiency. RESULTS:Ratings of perceived breathlessness increased (PLC: 3.43 ± 1.94 vs NTG: 4.03 ± 2.18; P = .009) despite a clear decrease in pulmonary capillary wedge pressure at 20 W (PLC: 19.7 ± 8.2 vs NTG: 15.9 ± 7.4 mm Hg; P < .001). Moreover, Vd (PLC: 0.28 ± 0.07 vs NTG: 0.31 ± 0.08 L/breath; P = .01), A-aDO (PLC: 19.6 ± 6.7 vs NTG: 21.1 ± 6.7; P = .04), and V˙e/V˙co slope (PLC: 37.6 ± 5.7 vs NTG: 40.2 ± 6.5; P < .001) all increased at 20 W after a decrease in pulmonary capillary wedge pressure. INTERPRETATION:These findings have important clinical implications and indicate that lowering pulmonary capillary wedge pressure does not decrease dyspnea on exertion in patients with HFpEF; rather, lowering pulmonary capillary wedge pressure exacerbates dyspnea on exertion, increases V˙/Q˙ mismatch, and worsens ventilatory efficiency during exercise in these patients. This study provides compelling evidence that high pulmonary capillary wedge pressure is likely a secondary phenomenon rather than a primary cause of dyspnea on exertion in patients with HFpEF, and a new therapeutic paradigm is needed to improve symptoms of dyspnea on exertion in these patients.
10.1016/j.chest.2023.04.003
Non-Alcoholic Fatty Liver Disease (NAFLD) and risk of new-onset heart failure: a retrospective analysis of 173,966 patients.
Clinical research in cardiology : official journal of the German Cardiac Society
BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) represents the leading cause of chronic liver disease. Its high mortality and morbidity are mainly caused by non-hepatic comorbidities and their clinical complications. Accumulating evidence suggests an association between NAFLD and heart failure (HF), but large-scale data analyses from Germany are scarce. METHODS:Using the Disease Analyzer database (IQVIA), this analysis retrospectively evaluated two cohorts of outpatients with and without NAFLD with respect to the cumulative incidence of HF as the primary outcome between January 2005 and December 2020. Cohorts were propensity score matched for sex, age, index year, yearly consultation frequency, and known risk factors for HF. RESULTS:A total of 173,966 patients were included in the analysis. Within 10 years of the index date, 13.2% vs. 10.0% of patients with and without NAFLD were newly diagnosed with HF (p < 0.001). This finding was supported by univariate Cox regression analysis in which NAFLD was found to be significantly associated with subsequent HF (Hazard Ratio (HR) 1.34, 95% Confidence Interval (CI) 1.28-1.39, p < 0.001). The association between NAFLD and HF was observed across all analysed age groups and as comparable between both men (HR 1.30, 95% CI 1.23-1.38; p < 0.001) and women (HR: 1.37, 95% CI 1.29-1.45; p < 0.001). CONCLUSION:NAFLD is significantly associated with an increased cumulative incidence of HF, which, given its rapidly increasing global prevalence, could be crucial to further reduce its high mortality and morbidity. We recommend risk stratification within a multidisciplinary approach for NAFLD patients, including systematic prevention or early detection strategies for HF.
10.1007/s00392-023-02250-z
Association of Carbohydrate Antigen 125 on the Response to Dapagliflozin in Patients With Heart Failure.
Journal of the American College of Cardiology
BACKGROUND:Elevated circulating carbohydrate antigen 125 (CA125) is a marker of congestion and a predictor of outcomes in acute heart failure (HF). Less is known about CA125 in chronic ambulatory HF with reduced ejection fraction. OBJECTIVES:This study examined the association between baseline CA125 (and changes in CA125) and outcomes in patients with HF with reduced ejection fraction in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; NCT03036124) trial and its relationship with the effect of dapagliflozin. METHODS:The primary outcome was a composite of a first episode of worsening HF or cardiovascular death. CA125 was measured at baseline and 12 months following randomization. RESULTS:Median baseline CA125 was 13.04 U/mL (IQR: 8.78-21.13 U/mL) in 3,123 of 4,774 patients with available data. Compared with CA125 ≤35 U/mL (upper limit of normal), patients with CA125 >35 U/mL were at a higher risk of the primary outcome (adjusted HR: 1.59; 95% CI: 1.29-1.96). The adjusted risks of the primary outcome relative to quartile 1 (Q1) (≤8.78 U/mL) were as follow: Q2, 8.79-13.04 U/mL (HR: 0.94; 95% CI: 0.71-1.24); Q3, 13.05-21.13 U/mL (HR: 1.22; 95% CI: 0.94-1.59); Q4, ≥21.14 U/mL (HR: 1.63; 95% CI: 1.28-2.09). The beneficial effect of dapagliflozin compared with placebo on the primary outcome was consistent whether CA125 was analyzed in quartiles (interaction P = 0.13) or as a continuous variable (interaction P = 0.75). The placebo-corrected relative change in CA125 at 12 months was -5.2% (95% CI: -10.6% to 0.5%; P = 0.07). CONCLUSIONS:In DAPA-HF, elevated CA125 levels were an independent predictor of the risk of worsening HF or cardiovascular death. Dapagliflozin reduced the risk of worsening HF or cardiovascular death regardless of baseline CA125.
10.1016/j.jacc.2023.05.011
Sacubitril/valsartan in heart failure with mildly reduced or preserved ejection fraction: a pre-specified participant-level pooled analysis of PARAGLIDE-HF and PARAGON-HF.
European heart journal
AIMS:The PARAGLIDE-HF trial demonstrated reductions in natriuretic peptides with sacubitril/valsartan compared with valsartan in patients with heart failure (HF) with mildly reduced or preserved ejection fraction who had a recent worsening HF event, but was not adequately powered to examine clinical outcomes. PARAGON-HF included a subset of PARAGLIDE-HF-like patients who were recently hospitalized for HF. Participant-level data from PARAGLIDE-HF and PARAGON-HF were pooled to better estimate the efficacy and safety of sacubitril/valsartan in reducing cardiovascular and renal events in HF with mildly reduced or preserved ejection fraction. METHODS AND RESULTS:Both PARAGLIDE-HF and PARAGON-HF were multicentre, double-blind, randomized, active-controlled trials of sacubitril/valsartan vs. valsartan in patients with HF with mildly reduced or preserved left ventricular ejection fraction (LVEF >40% in PARAGLIDE-HF and ≥45% in PARAGON-HF). In the pre-specified primary analysis, we pooled participants in PARAGLIDE-HF (all of whom were enrolled during or within 30 days of a worsening HF event) with a 'PARAGLIDE-like' subset of PARAGON-HF (those hospitalized for HF within 30 days). We also pooled the entire PARAGLIDE-HF and PARAGON-HF populations for a broader context. The primary endpoint for this analysis was the composite of total worsening HF events (including first and recurrent HF hospitalizations and urgent visits) and cardiovascular death. The secondary endpoint was the pre-specified renal composite endpoint for both studies (≥50% decline in estimated glomerular filtration rate from baseline, end-stage renal disease, or renal death). Compared with valsartan, sacubitril/valsartan significantly reduced total worsening HF events and cardiovascular death in both the primary pooled analysis of participants with recent worsening HF [n = 1088; rate ratio (RR) 0.78; 95% confidence interval (CI) 0.61-0.99; P = 0.042] and in the pooled analysis of all participants (n = 5262; RR 0.86; 95% CI: 0.75-0.98; P = 0.027). In the pooled analysis of all participants, first nominal statistical significance was reached by Day 9 after randomization, and treatment benefits were larger in those with LVEF ≤60% (RR 0.78; 95% CI 0.66-0.91) compared with those with LVEF >60% (RR 1.09; 95% CI 0.86-1.40; Pinteraction = 0.021). Sacubitril/valsartan was also associated with lower rates of the renal composite endpoint in the primary pooled analysis [hazard ratio (HR) 0.67; 95% CI 0.43-1.05; P = 0.080] and the pooled analysis of all participants (HR 0.60; 95% CI 0.44-0.83; P = 0.002). CONCLUSION:In pooled analyses of PARAGLIDE-HF and PARAGON-HF, sacubitril/valsartan reduced cardiovascular and renal events among patients with HF with mildly reduced or preserved ejection fraction. These data provide support for use of sacubitril/valsartan in patients with HF with mildly reduced or preserved ejection fraction, particularly among those with an LVEF below normal, regardless of care setting.
10.1093/eurheartj/ehad344
Declining risk of heart failure hospitalization following first acute myocardial infarction in Scotland between 1991-2016.
European journal of heart failure
AIM:Mortality from acute myocardial infarction (AMI) has declined, increasing the pool of survivors at risk of later development of heart failure (HF). However, coronary reperfusion limits infarct size and secondary prevention therapies have improved. In light of these competing influences, we examined long-term trends in the risk of HF hospitalization (HFH) following a first AMI occurring in Scotland over 25 years. METHODS AND RESULTS:All patients in Scotland discharged alive after a first AMI between 1991 and 2015 were followed until a first HFH or death until the end of 2016 (minimum follow-up 1 year, maximum 26 years). A total of 175 672 people with no prior history of HF were discharged alive after a first AMI during the period of study. A total of 21 445 (12.2%) patients had a first HFH during a median follow-up of 6.7 years. Incidence of HFH (per 1000 person-years) at 1 year following discharge from a first AMI decreased from 59.3 (95% confidence interval [CI] 54.2-64.7) in 1991 to 31.3 (95% CI 27.3-35.8) in 2015, with consistent trends seen for HF occurring within 5 and 10 years. Accounting for the competing risk of death, the adjusted risk of HFH at 1 year after discharge decreased by 53% (95% CI 45-60%), with similar decreases at 5 and 10 years. CONCLUSION:The incidence of HFH following AMI in Scotland has decreased since 1991. These trends suggest that better treatment of AMI and secondary prevention are having an impact on the risk of HF at a population level.
10.1002/ejhf.2965
Effect of onset of type 2 diabetes on risks of cardiovascular disease and heart failure among new Zealanders with impaired glucose tolerance over 25 years: tapered-matched landmark analysis.
Cardiovascular diabetology
BACKGROUND:This study aimed to examine the association between the incident onset of T2DM and 5- and 10-year risks of CVD and HF in people with IGT identified in primary care in South and West Auckland, New Zealand (NZ) between 1994 and 2019. METHODS:We compared CVD and HF risks in patients with IGT and with/without T2D newly diagnosed within the exposure window (1-5 years). Tapered matching and landmark analysis (to account for immortal bias) were used to control for potential effects of known confounders. RESULTS:Among 26,794 patients enrolled with IGT, 845 had T2D newly diagnosed within 5 years from enrolment (landmark date) and 15,452 did not have T2D diagnosed. Patients progressing to T2D (vs. those not progressing) had a similar 5-year risk for CVD (hazard ratio 1.19; 95% CI 0.61-2.32) but significantly higher 10-year risk of CVD (2.45(1.40-4.29)), 5-year risk of HF (1.94(1.20-3.12)) and 10-year risk of HF (2.84(1.83-4.39). The association between the onset of T2D and risk of 10-year risk of CVD, 5-year and 10-year risk of HF was more likely among men, the socioeconomically deprived, those currently smoking, patients with higher metabolic measures and/or those with lower renal function. Patients of NZ European ethnicity had a lower 10-year risk of CVD. CONCLUSIONS:The study suggests that the diagnosis of T2D mediates the risk of CVD and HF in people with IGT. The development of risk scores to identify and better manage individuals with IGT at high risk of T2D is warranted.
10.1186/s12933-023-01871-y
Comparison of the effects of gemigliptin versus glimepiride on cardiac function in patients with type 2 diabetes uncontrolled with metformin: The gemi-heart study.
Diabetes, obesity & metabolism
AIM:To investigate the effects of gemigliptin on cardiac function and compare the effects of gemigliptin and glimepiride in patients with type 2 diabetes (T2D). MATERIALS AND METHODS:Sixty T2D patients being treated with metformin were assigned to a gemigliptin group (50 mg daily) or a glimepiride group (2 mg daily) for 24 weeks. The preadjudicated extension period was up to 52 weeks. Glucose metabolism variables and cardiac biomarkers were measured. Echocardiography was used to evaluate cardiac functions. RESULTS:The HbA1c levels decreased significantly from 8.1% ± 0.6% to 6.8% ± 0.6% in the gemigliptin group and from 8.1% ± 0.6% to 7.0% ± 0.7% in the glimepiride group, without a between-group difference. Gemigliptin reduced insulin resistance, high sensitivity C-reactive protein and low-density lipoprotein cholesterol levels, and blood pressure, and increased adiponectin level compared with glimepiride therapy. Gemigliptin induced favourable changes in body composition. Left ventricular end-diastolic volume decreased in the gemigliptin group but increased in the glimepiride group, with a borderline between-group difference. Cardiac biomarkers did not change significantly in either group. At 52 weeks, the HbA1c levels in both groups increased slightly; 7.3% ± 0.8% in the gemigliptin group versus 7.7% ± 1.3% in the glimepiride group, without a between-group difference. CONCLUSIONS:Gemigliptin had a comparable glucose-lowering efficacy without deleterious effects on cardiac functions or on biomarkers reflective of myocardial injury or heart failure during the 24-week observation period. However, larger, longer-term studies are needed to confirm these findings.
10.1111/dom.15095
Quantitative Blood Volume Analysis and Hemodynamic Measures of Vascular Compliance in Patients With Worsening Heart Failure.
Journal of cardiac failure
BACKGROUND:The role of blood volume (BV) expansion vs a change in vascular compliance in worsening heart failure (HF) remains under debate. We aimed to assess the relationship between BV and resting and stress hemodynamics in worsening HF and to further elucidate the significance of BV in cardiac decompensation. METHODS AND RESULTS:Patients with worsening HF underwent radiolabeled indicator-dilution BV analysis and cardiac catheterization. Intravascular volumes and resting/stress hemodynamics were recorded. Provocative stress maneuvers included change in systolic blood pressure (ΔSBP) from lying to standing and Valsalva and intracardiac pressure changes with leg raise. Correlation between BV and invasive hemodynamics were assessed by linear regression. Of 27 patients with worsening HF, patients' characteristics included mean age 61 ± 12 years, 70% male, 19% Black, and mean ejection fraction 29% ± 15%. Of the patients, 13 (48%) had hypervolemia as measured by total BV, which weakly correlated with ΔSBP by position (R = 0.009) and Valsalva (R = 0.003) and with right atrial (R = 0.049) and pulmonary capillary wedge (R = 0.047) pressure changes during leg raise. CONCLUSIONS:In patients with worsening HF, BV mildly correlated with intracardiac pressures at rest. Provocative maneuvers intended to test vascular compliance did not correlate with BV, indicating that compliance may serve as a stand-alone metric in HF.
10.1016/j.cardfail.2022.04.004
Left Ventricular Physiology and Ventricular-Vascular Interactions in Young Patients After Heart Transplantation.
Journal of the American Heart Association
Background In patients after heart transplantation, systemic arterial hypertension and enhanced central aortic stiffness contribute to increased ventricular afterload, which might lead to graft dysfunction. The aim of our study was to characterize systemic arterial elastance and its impact on left ventricular function and ventriculo-arterial coupling in a cohort of children, adolescents, and young adults after heart transplantation using invasive conductance catheter technique. Methods and Results Thirty patients who had heart transplants (age, 20.0±6.5 years, 7 female) underwent invasive cardiac catheterization including pressure-volume loop analysis. Load-independent parameters of systolic (ventricular elastance [Ees]) and diastolic (ventricular compliance) function as well as systemic arterial elastance (Ea, end-systolic pressure/stroke volume) and ventriculo-arterial coupling (Ea/Ees) were assessed at baseline level and during dobutamine infusion (10 μg/kg/min). Ees showed an appropriate increase under inotropic stimulation from 0.43 (0.11-2.52) to 1.00 (0.20-5.10) mm Hg/mL/m (<0.0001), whereas ventricular compliance remained rather unchanged (0.16±0.10 mm Hg/mL/m to 0.12±0.07 mm Hg/mL/m; =0.10). Ventriculo-arterial coupling Ea/Ees was abnormal at rest and did not improve significantly under dobutamine (1.7 [0.6-6.7] to 1.3 [0.5-4.9], =0.70) due to a simultaneous rise in Ea from 0.71 (0.37-2.82) to 1.10 (0.52-4.03) mm Hg/mL/m (<0.0001). Both Ees and ventricular compliance were significantly associated with Ea at baseline and under dobutamine infusion. Conclusions Patients who underwent heart transplantation show impaired ventriculo-arterial coupling at rest and under inotropic stimulation despite preserved left ventricular contractile reserve. An abnormal response in vascular function resulting in increased afterload seems to represent an important factor that may play a role for the development of late graft failure.
10.1161/JAHA.122.028766
Association Between Electrocardiographic Age and Cardiovascular Events in Community Settings: The Framingham Heart Study.
Circulation. Cardiovascular quality and outcomes
BACKGROUND:Deep neural networks have been used to estimate age from ECGs, the electrocardiographic age (ECG-age), which predicts adverse outcomes. However, this prediction ability has been restricted to clinical settings or relatively short periods. We hypothesized that ECG-age is associated with death and cardiovascular outcomes in the long-standing community-based FHS (Framingham Heart Study). METHODS:We tested the association of ECG-age with chronological age in the FHS cohorts in ECGs from 1986 to 2021. We calculated the gap between chronological and ECG-age (Δage) and classified individuals as having normal, accelerated, or decelerated aging, if Δage was within, higher, or lower than the mean absolute error of the model, respectively. We assessed the associations of Δage, accelerated and decelerated aging with death or cardiovascular outcomes (atrial fibrillation, myocardial infarction, and heart failure) using Cox proportional hazards models adjusted for age, sex, and clinical factors. RESULTS:The study population included 9877 FHS participants (mean age, 55±13 years; 54.9% women) with 34 948 ECGs. ECG-age was correlated to chronological age (r=0.81; mean absolute error, 9±7 years). After 17±8 years of follow-up, every 10-year increase of Δage was associated with 18% increase in all-cause mortality (hazard ratio [HR], 1.18 [95% CI, 1.12-1.23]), 23% increase in atrial fibrillation risk (HR, 1.23 [95% CI, 1.17-1.29]), 14% increase in myocardial infarction risk (HR, 1.14 [95% CI, 1.05-1.23]), and 40% increase in heart failure risk (HR, 1.40 [95% CI, 1.30-1.52]), in multivariable models. In addition, accelerated aging was associated with a 28% increase in all-cause mortality (HR, 1.28 [95% CI, 1.14-1.45]), whereas decelerated aging was associated with a 16% decrease (HR, 0.84 [95% CI, 0.74-0.95]). CONCLUSIONS:ECG-age was highly correlated with chronological age in FHS. The difference between ECG-age and chronological age was associated with death, myocardial infarction, atrial fibrillation, and heart failure. Given the wide availability and low cost of ECG, ECG-age could be a scalable biomarker of cardiovascular risk.
10.1161/CIRCOUTCOMES.122.009821
Prevalence and prognostic impact of chronic kidney disease and anaemia across ACC/AHA precursor and symptomatic heart failure stages.
Clinical research in cardiology : official journal of the German Cardiac Society
BACKGROUND:The importance of chronic kidney disease (CKD) and anaemia has not been comprehensively studied in asymptomatic patients at risk for heart failure (HF) versus those with symptomatic HF. We analysed the prevalence, characteristics and prognostic impact of both conditions across American College of Cardiology/American Heart Association (ACC/AHA) precursor and HF stages A-D. METHODS AND RESULTS:2496 participants from three non-pharmacological German Competence Network HF studies were categorized by ACC/AHA stage; stage C patients were subdivided into C1 and C2 (corresponding to NYHA classes I/II and III, respectively). Overall, patient distribution was 8.1%/35.3%/32.9% and 23.7% in ACC/AHA stages A/B/C1 and C2/D, respectively. These subgroups were stratified by the absence ( - ) or presence ( +) of CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m) and anaemia (haemoglobin in women/men < 12/ < 13 g/dL). The primary outcome was all-cause mortality at 5-year follow-up. Prevalence increased across stages A/B/C1 and C2/D (CKD: 22.3%/23.6%/31.6%/54.7%; anaemia: 3.0%/7.9%/21.7%/33.2%, respectively), with concordant decreases in median eGFR and haemoglobin (all p < 0.001). Across all stages, hazard ratios [95% confidence intervals] for all-cause mortality were 2.1 [1.8-2.6] for CKD + , 1.7 [1.4-2.0] for anaemia, and 3.6 [2.9-4.6] for CKD + /anaemia + (all p < 0.001). Population attributable fractions (PAFs) for 5-year mortality related to CKD and/or anaemia were similar across stages A/B, C1 and C2/D (up to 33.4%, 30.8% and 34.7%, respectively). CONCLUSIONS:Prevalence and severity of CKD and anaemia increased across ACC/AHA stages. Both conditions were individually and additively associated with increased 5-year mortality risk, with similar PAFs in asymptomatic patients and those with symptomatic HF.
10.1007/s00392-022-02027-w
Time to clinical benefit of eplerenone among patients with heart failure and reduced ejection fraction: A subgroups analysis from the EMPHASIS-HF trial.
European journal of heart failure
AIM:Eplerenone reduces the risk of cardiovascular death or first hospitalization for heart failure (HF) in patients with HF and a reduced ejection fraction (HFrEF), but it is still frequently underused in routine practice. We evaluated the time course of benefits of eplerenone after its initiation in HFrEF patients from the EMPHASIS-HF trial. METHODS AND RESULTS:The EMPHASIS-HF trial was a double-blind randomized clinical trial assessing the effect of eplerenone in patients (n = 2737, mean age 68.6 ± 7.6 years, 22.3% women) with HFrEF and mild symptoms. The time trajectories for the effect of eplerenone versus placebo on the primary composite endpoint (cardiovascular death or first hospitalization for HF) were investigated using Cox proportional hazards models with truncated data at each day post-randomization. A significant reduction in the primary composite endpoint was observed 26 days after randomization (hazard ratio 0.58; 95% confidence interval, 0.34-1.00, p = 0.049). Eplerenone was first associated with a significant reduction in the primary endpoint in 35 days or less in most subgroups, including patients with HF history ≥18 months (day 24), estimated glomerular filtration rate <60 ml/min (day 12), ischaemic HF aetiology (day 28), age ≥65 years (day 28), narrow QRS (day 30), higher MAGGIC score (day 35), lower potassium (day 30), left ventricular ejection fraction ≥30% (day 28) or already treated with beta-blockers (day 25). CONCLUSIONS:Eplerenone provides statistically significant and clinically meaningful benefits shortly after treatment initiation in most patients, irrespective of clinical profile. This result reinforces the need for an early initiation of eplerenone in HFrEF, as part of rapidly instituting guideline-directed medical therapy.
10.1002/ejhf.2952
Global longitudinal strain predicts clinical outcomes in patients with heart failure with preserved ejection fraction.
European journal of heart failure
AIMS:Patients with heart failure with preserved ejection fraction (HFpEF) are at high risk for hospitalization and mortality and many of these patients experience a deterioration in left ventricular ejection fraction (LVEF) over time. Global longitudinal strain (GLS) is a sensitive marker of myocardial dysfunction that could help predict risk for future events in this population. We assessed whether GLS can predict adverse clinical outcomes and future deterioration in LVEF in patients with HFpEF. METHODS AND RESULTS:In this retrospective cohort study, patients with HFpEF were divided into groups according to abnormal GLS (>-15.8%) or normal GLS (<-15.8%).The primary outcomes were: a composite of cardiovascular mortality or heart failure hospitalization and deterioration in LVEF to <40%. Among the 311 patients with HFpEF, 128 patients (41%) had normal GLS and 183 patients (59%) had abnormal GLS. After a median follow-up of 4.6 years, the composite outcome occurred more commonly in patients with abnormal GLS compared to patients with normal GLS (62% vs. 44%; hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.3-2.4, p < 0.001). Patients with abnormal GLS were also more likely to experience a deterioration in LVEF (19% vs. 10%; HR 2.2, 95% CI 1.2-4.3, p = 0.018). When assessed as a continuous variable, each 1% increase in GLS was associated with 10% increased odds for the composite outcome and 13% increased odds for deterioration in LVEF. CONCLUSION:In patients with HFpEF, abnormal GLS is common and is a strong predictor for clinical events and future deterioration in LVEF.
10.1002/ejhf.2947
Clinical Characteristics and Outcomes in Patients With Heart Failure: Are There Thresholds and Inflection Points in Left Ventricular Ejection Fraction and Thresholds Justifying a Clinical Classification?
Circulation
BACKGROUND:Recent guidelines proposed a classification for heart failure (HF) on the basis of left ventricular ejection fraction (LVEF), although it remains unclear whether the divisions chosen were biologically rational. Using patients spanning the full range of LVEF, we examined whether there was evidence of LVEF thresholds in patient characteristics or inflection points in clinical outcomes. METHODS:Using patient-level information, we created a merged dataset of 33 699 participants who had been enrolled in 6 randomized controlled HF trials including patients with reduced and preserved ejection fraction. The relationship between the incidence of all-cause death (and specific causes of death) and HF hospitalization, and LVEF, was evaluated using Poisson regression models. RESULTS:As LVEF increased, age, the proportion of women, body mass index, systolic blood pressure, and prevalence of atrial fibrillation and diabetes increased, whereas ischemic pathogenesis, estimated glomerular filtration rate, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) decreased. As LVEF increased >50%, age and the proportion of women continued to increase, and ischemic pathogenesis and NT-proBNP decreased, but other characteristics did not change meaningfully. The incidence of most clinical outcomes (except noncardiovascular death) decreased as LVEF increased, with a LVEF inflection point of around 50% for all-cause death and cardiovascular death, around 40% for pump failure death, and around 35% for HF hospitalization. Higher than those thresholds, there was little further decline in the incidence rate. There was no evidence of a J-shaped relationship between LVEF and death; no evidence of worse outcomes in patients with high-normal ("supranormal") LVEF. Similarly, in a subset of patients with echocardiographic data, there were no structural differences in patients with a high-normal LVEF suggestive of amyloidosis, and NT-proBNP levels were consistent with this conclusion. CONCLUSIONS:In patients with HF, there was a LVEF threshold of around 40% to 50% where the pattern of patient characteristics changed, and event rates began to increase compared with higher LVEF values. Our findings provide evidence to support current upper LVEF thresholds defining HF with mildly reduced ejection fraction on the basis of prognosis. REGISTRATION:URL: https://www. CLINICALTRIALS:gov; Unique identifiers: NCT00634309, NCT00634400, NCT00634712, NCT00095238, NCT01035255, NCT00094302, NCT00853658, and NCT01920711.
10.1161/CIRCULATIONAHA.122.063642
Rapid kidney function decline and increased risk of heart failure in patients with type 2 diabetes: findings from the ACCORD cohort : Rapid kidney function decline and heart failure in T2D.
Cardiovascular diabetology
BACKGROUND:Impaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D, independent of baseline kidney function, albuminuria, and other HF predictors. METHODS:Included in the study were 7,539 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with baseline urinary albumin-to-creatinine ratio (UACR) data, who had completed 4 years of follow-up and had ≥ 3 eGFR measurements during that period (median eGFR/year = 1.9, IQR 1.7-3.2). The association between rapid kidney function decline (eGFR loss ≥ 5 ml/min/1.73 m/year) and odds of HF hospitalization or HF death during the first 4 years of follow-up was estimated by logistic regression. The improvement in risk discrimination provided by adding rapid kidney function decline to other HF risk factors was evaluated as the increment in the area under the Receiving Operating Characteristics curve (ROC AUC) and integrated discrimination improvement (IDI). RESULTS:Over 4 years of follow-up, 1,573 participants (20.9%) experienced rapid kidney function decline and 255 (3.4%) experienced a HF event. Rapid kidney function decline was associated with a ~ 3.2-fold increase in HF odds (3.23, 95% CI, 2.51-4.16, p < 0.0001), independent of baseline CVD history. This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline as well as at censoring (3.74; 95% CI 2.63-5.31). Adding rapid kidney function decline during follow-up to other clinical predictors (WATCH-DM score, eGFR, and UACR at study entry and end of follow-up) improved HF risk classification (ROC AUC = + 0.02, p = 0.027; relative IDI = + 38%, p < 0.0001). CONCLUSIONS:In patients with T2D, rapid kidney function decline is associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF risk estimation in T2D.
10.1186/s12933-023-01869-6
Prevalence, clinical characteristics and outcomes of heart failure patients with or without isolated or combined mitral and tricuspid regurgitation: An analysis from the ESC-HFA Heart Failure Long-Term Registry.
European journal of heart failure
AIM:Mitral regurgitation (MR) and tricuspid regurgitation (TR) are common in patients with heart failure (HF). The aim of this study was to investigate prevalence, clinical characteristics and outcomes of patients with or without isolated or combined MR and TR across the entire HF spectrum. METHODS AND RESULTS:The ESC-HFA EORP HF Long-Term Registry is a prospective, multicentre, observational study including patients with HF and 1-year follow-up data. Outpatients without aortic valve disease were included and stratified according to isolated or combined moderate/severe MR and TR. Among 11 298 patients, 7541 (67%) had no MR/TR, 1931 (17%) isolated MR, 616 (5.5%) isolated TR and 1210 (11%) combined MR/TR. Baseline characteristics were differently distributed across MR/TR categories. Compared to HF with reduced ejection fraction, HF with mildly reduced ejection fraction was associated with a lower risk of isolated MR (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.60-0.80), and distinctly lower risk of combined MR/TR (OR 0.51; 95% CI 0.41-0.62). HF with preserved ejection fraction (HFpEF) was associated with a distinctly lower risk of isolated MR (OR 0.42; 95% CI 0.36-0.49), and combined MR/TR (OR 0.59; 95% 0.50-0.70), but a distinctly increased risk of isolated TR (OR 1.94; 95% CI 1.61-2.33). All-cause death, cardiovascular death, HF hospitalization and combined outcomes occurred more frequently in combined MR/TR, isolated TR and isolated MR versus no MR/TR. The highest incident rates were observed in isolated TR and combined MR/TR. CONCLUSION:In a large cohort of outpatients with HF, prevalence of isolated and combined MR and TR was relatively high. Isolated TR was driven by HFpEF and was burdened by an unexpectedly poor outcome.
10.1002/ejhf.2929
Differential effects of overweight/obesity depending on the severity of heart failure complicating acute myocardial infarction in Japan.
Progress in cardiovascular diseases
BACKGROUND:The existence of a paradoxical association between overweight/obesity and survival benefits, the so-called obesity paradox, in heart failure (HF) as well as coronary artery disease (CAD) remains contentious. Previously, we reported that a past history of CAD negated the obesity paradox in the general population with acute HF. Herein, we further focused on HF complicating acute myocardial infarction (AMI) and compared the prognostic effects of overweight/obesity with respect to the severity of HF. METHODS:We conducted a multicenter retrospective study of 7265 consecutive patients with AMI. The severity of HF was categorized according to the Killip classification. Overweight/obesity was defined as a body mass index (BMI) of ≥25 kg/m. The interaction between overweight/obesity and the Killip classification for in-hospital mortality was tested in the entire cohort. Multivariable logistic regression analyses were performed to examine the effects of overweight/obesity on in-hospital mortality. RESULTS:Across the entire study cohort, 1931 patients had HF. Overweight/obesity had a significant association with reductions in in-hospital mortality in patients with mild HF (Killip class II; odds ratio [OR], 0.284; P = 0.019). Conversely, overweight/obesity was a significant risk factor for in-hospital mortality in patients with severe HF (Killip class IV; OR, 2.152; P = 0.001). The effects of overweight/obesity on in-hospital mortality in patients with moderate HF (Killip class III) were intermediate between those with mild HF and severe HF. CONCLUSION:Opposing effects of overweight/obesity on in-hospital mortality in patients with mild HF versus severe HF were demonstrated, suggesting a balance between beneficial and deleterious effects of overweight/obesity may be inclined toward the latter with the severity of HF complicating AMI.
10.1016/j.pcad.2022.11.020
Diabetes and Progression of Heart Failure: The Atherosclerosis Risk In Communities (ARIC) Study.
Journal of the American College of Cardiology
BACKGROUND:The influence of diabetes on progression from preclinical heart failure (HF) stages to overt HF is poorly understood. OBJECTIVES:The purpose of this study was to characterize the influence of diabetes on the progression from preclinical HF stages (A or B based on the 2021 Universal Definition) to overt HF. METHODS:We included 4,774 adults with preclinical HF (stage A [n = 1,551] or B [n = 3,223]) who attended the ARIC (Atherosclerosis Risk In Communities) study Visit 5 (2011-2013). Within each stage (A or B), we assessed the associations of diabetes and glycemic control (hemoglobin A [HbA] <7% vs ≥7%) with progression to HF, and of cross-categories of HF stages (A vs B), diabetes, and glycemic control with incident HF. RESULTS:Among the participants (mean age 75.4 years, 58% women, 20% Black), there were 470 HF events during 8.6 years of follow-up. Stage B participants with HbA ≥7% experienced clinical HF at a younger age than those with controlled diabetes or without diabetes (mean age 80 years vs 83 years vs 82 years; P < 0.001). HbA ≥7% was more strongly associated with HF in stage B (HR: 1.83; 95% CI: 1.33-2.51) compared with stage A (HR: 1.52; 95% CI: 0.53-4.38). In cross-categories of preclinical HF stage and HbA, participants with stage B and HbA ≥7% had increased risk of HF progression compared with stage A without diabetes (HR: 7.56; 95% CI: 4.68-12.20). CONCLUSIONS:Among older adults with preclinical HF stages, uncontrolled diabetes was associated with substantial risk of HF progression. Our results suggest that targeting diabetes early in the HF process is critical.
10.1016/j.jacc.2022.03.378
Disparities in Postdischarge Ambulatory Care Follow-Up Among Medicaid Beneficiaries With Diabetes, Hospitalized for Heart Failure.
Journal of the American Heart Association
Background Ambulatory follow-up for all patients with heart failure (HF) is recommended within 7 to 14 days after hospital discharge to improve HF outcomes. We examined postdischarge ambulatory follow-up of patients with comorbid diabetes and HF from a low-income population in primary and specialty care. Methods and Results Adults with diabetes and first hospitalizations for HF, covered by Alabama Medicaid in 2010 to 2019, were included and the claims analyzed for ambulatory care use (any, primary care, cardiology, or endocrinology) within 60 days after discharge using restricted mean survival time regression and negative binomial regression. Among 9859 Medicaid-covered adults with diabetes and first hospitalization for HF (mean age, 53.7 years; SD, 9.2 years; 47.3% Black; 41.8% non-Hispanic White; 10.9% Hispanic/Other [Other included non-White Hispanic, American Indian, Pacific Islander and Asian adults]; 65.4% women, 34.6% men), 26.7% had an ambulatory visit within 0 to 7 days, 15.2% within 8 to 14 days, 31.3% within 15 to 60 days, and 26.8% had no visit; 71% saw a primary care physician and 12% a cardiology physician. Black and Hispanic/Other adults were less likely to have any postdischarge ambulatory visit (<0.0001) or the visit was delayed (by 1.8 days, =0.0006 and by 2.8 days, =0.0016, respectively) and were less likely to see a primary care physician than non-Hispanic White adults (adjusted incidence rate ratio, 0.96 [95% CI, 0.91-1.00] and 0.91 [95% CI, 0.89-0.98]; respectively). Conclusions More than half of Medicaid-covered adults with diabetes and HF in Alabama did not receive guideline-concordant postdischarge care. Black and Hispanic/Other adults were less likely to receive recommended postdischarge care for comorbid diabetes and HF.
10.1161/JAHA.122.029094
Association Between Change in Ambulatory Pulmonary Artery Pressures and Natriuretic Peptides in Patients with Heart Failure: Results From the EMBRACE-HF Trial.
Journal of cardiac failure
BACKGROUND:Remote monitoring of pulmonary artery (PA) pressures and serial N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements guide heart failure (HF) treatment, but their association has yet to be described. METHODS AND RESULTS:In the Empagliflozin Evaluation by Measuring the Impact on Hemodynamics in Patients with Heart Failure (EMBRACE-HF) trial, patients with HF and a remote PA pressure monitoring device were randomized to empagliflozin vs placebo. PA diastolic pressures (PADP) and NT-proBNP levels were obtained at baseline and 6 and 12 weeks. We used linear mixed models to examine the association between change in PADP and change in NT-proBNP, adjusting for baseline covariates. Of 62 patients, the mean patient age was 66.2 years, and 63% were male. The mean baseline PADP was 21.8 ± 6.4 mm Hg, and the mean NT-proBNP was 1844.6 ± 2767.7 pg/mL. The mean change between baseline and averaged 6- and 12-week PADP was -0.4 ± 3.1 mm Hg, and the mean change between baseline and averaged 6- and 12-week NT-proBNP was -81.5 ± 878.6 pg/mL. In adjusted analyses, every 2-mm Hg decrease in PADP was associated with an NT-proBNP reduction of 108.9 pg/mL (95% confidence interval -4.3 to 222.0, P = .06). CONCLUSIONS:We observed that short-term decreases in ambulatory PADP seem to be associated with decreases in NT-proBNP. This finding may provide additional clinical context when tailoring treatment for patients with HF.
10.1016/j.cardfail.2023.05.009
Rate-Adaptive Atrial Pacing for Heart Failure With Preserved Ejection Fraction: The RAPID-HF Randomized Clinical Trial.
JAMA
Importance:Reduced heart rate during exercise is common and associated with impaired aerobic capacity in heart failure with preserved ejection fraction (HFpEF), but it remains unknown if restoring exertional heart rate through atrial pacing would be beneficial. Objective:To determine if implanting and programming a pacemaker for rate-adaptive atrial pacing would improve exercise performance in patients with HFpEF and chronotropic incompetence. Design, Setting, and Participants:Single-center, double-blind, randomized, crossover trial testing the effects of rate-adaptive atrial pacing in patients with symptomatic HFpEF and chronotropic incompetence at a tertiary referral center (Mayo Clinic) in Rochester, Minnesota. Patients were recruited between 2014 and 2022 with 16-week follow-up (last date of follow-up, May 9, 2022). Cardiac output during exercise was measured by the acetylene rebreathe technique. Interventions:A total of 32 patients were recruited; of these, 29 underwent pacemaker implantation and were randomized to atrial rate responsive pacing or no pacing first for 4 weeks, followed by a 4-week washout period and then crossover for an additional 4 weeks. Main Outcomes and Measures:The primary end point was oxygen consumption (V̇o2) at anaerobic threshold (V̇o2,AT); secondary end points were peak V̇o2, ventilatory efficiency (V̇e/V̇co2 slope), patient-reported health status by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Results:Of the 29 patients randomized, the mean age was 66 years (SD, 9.7) and 13 (45%) were women. In the absence of pacing, peak V̇o2 and V̇o2 at anaerobic threshold (V̇o2,AT) were both correlated with peak exercise heart rate (r = 0.46-0.51, P < .02 for both). Pacing increased heart rate during low-level and peak exercise (16/min [95% CI, 10 to 23], P < .001; 14/min [95% CI, 7 to 21], P < .001), but there was no significant change in V̇o2,AT (pacing off, 10.4 [SD, 2.9] mL/kg/min; pacing on, 10.7 [SD, 2.6] mL/kg/min; absolute difference, 0.3 [95% CI, -0.5 to 1.0] mL/kg/min; P = .46), peak V̇o2, minute ventilation (V̇e)/carbon dioxide production (V̇co2) slope, KCCQ-OSS, or NT-proBNP level. Despite the increase in heart rate, atrial pacing had no significant effect on cardiac output with exercise, owing to a decrease in stroke volume (-24 mL [95% CI, -43 to -5 mL]; P = .02). Adverse events judged to be related to the pacemaker device were observed in 6 of 29 participants (21%). Conclusions and Relevance:In patients with HFpEF and chronotropic incompetence, implantation of a pacemaker to enhance exercise heart rate did not result in an improvement in exercise capacity and was associated with increased adverse events. Trial Registration:ClinicalTrials.gov Identifier: NCT02145351.
10.1001/jama.2023.0675
The incremental value of multi-organ assessment of congestion using ultrasound in outpatients with heart failure.
European heart journal. Cardiovascular Imaging
AIMS:We investigated the prevalence and clinical value of assessing multi-organ congestion by ultrasound in heart failure (HF) outpatients. METHODS AND RESULTS:Ultrasound congestion was defined as inferior vena cava of ≥21 mm, highest tertile of lung B-lines, or discontinuous renal venous flow. Associations with clinical characteristics and prognosis were explored. We enrolled 310 HF patients [median age: 77 years, median NT-proBNP: 1037 ng/L, 51% with a left ventricular ejection fraction (LVEF) <50%], and 101 patients without HF. There were no clinical signs of congestion in 224 (72%) patients with HF, of whom 95 (42%) had at least one sign of congestion by ultrasound (P < 0.0001). HF patients with ≥2 ultrasound signs were older, and had greater neurohormonal activation, lower urinary sodium concentration, and larger left atria despite similar LVEF. During a median follow-up of 13 (interquartile range: 6-15) months, 77 patients (19%) died or were hospitalized for HF. HF patients without ultrasound evidence of congestion had a similar outcome to patients without HF [reference; hazard ratio (HR) 1.02, 95% confidence interval (CI) 0.86-1.35], while those with ≥2 ultrasound signs had the worst outcome (HR 26.7, 95% CI 12.4-63.6), even after adjusting for multiple clinical variables and NT-proBNP. Adding multi-organ assessment of congestion by ultrasound to a clinical model, including NT-proBNP, provided a net reclassification improvement of 28% (P = 0.03). CONCLUSION:Simultaneous assessment of pulmonary, venous, and kidney congestion by ultrasound is feasible, fast, and identifies a high prevalence of sub-clinical congestion associated with poor outcomes.
10.1093/ehjci/jeac254
Hepatic Venous Stasis Index Reflects Hepatic Congestion and Predicts Adverse Outcomes in Patients With Heart Failure.
Journal of the American Heart Association
Background It has been reported that the hepatic vein waveforms determined by abdominal ultrasonography can assess hepatic congestion in patients with heart failure (HF). However, the parameter that quantifies hepatic vein waveforms has not been established. We suggest the hepatic venous stasis index (HVSI) as the novel indicator to evaluate hepatic congestion quantitatively. To examine the clinical significance of HVSI in patients with HF, we aimed to clarify the associations of HVSI with the parameters of cardiac function and right heart catheterization, as well as that with prognosis, in patients with HF. Methods and Results We performed abdominal ultrasonography, echocardiography, and right heart catheterization in patients with HF (n=513). The patients were divided into 3 groups based on HVSI as follows: HVSI 0 (HVSI=0, n=253), low HVSI (HVSI 0.01-0.20, n=132), and high HVSI (HVSI>0.20, n=128). We examined the associations of HVSI with parameters of cardiac function and right heart catheterization and followed up for cardiac events defined as cardiac death or worsening HF. There was a significant increase in level of B-type natriuretic peptide, inferior vena cava diameter, and mean right atrial pressure with increasing HVSI. During the follow-up period, cardiac events occurred in 87 patients. In the Kaplan-Meier analysis, cardiac event rate increased across increasing HVSI (log-rank, =0.002). Conclusions HVSI assessed by abdominal ultrasonography reflects hepatic congestion and right-sided HF and is associated with adverse prognosis in patients with HF.
10.1161/JAHA.122.029857
Skeletal Muscle Mitochondrial Respiration and Exercise Intolerance in Patients With Heart Failure With Preserved Ejection Fraction.
JAMA cardiology
Importance:The pathophysiology of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) remains incompletely understood. Multiple lines of evidence suggest that abnormal skeletal muscle metabolism is a key contributor, but the mechanisms underlying metabolic dysfunction remain unresolved. Objective:To evaluate the associations of skeletal muscle mitochondrial function using respirometric analysis of biopsied muscle fiber bundles from patients with HFpEF with exercise performance. Design, Setting, and Participants:In this cross-sectional study, muscle fiber bundles prepared from fresh vastus lateralis biopsies were analyzed by high-resolution respirometry to provide detailed analyses of mitochondrial oxidative phosphorylation, including maximal capacity and the individual contributions of complex I-linked and complex II-linked respiration. These bioenergetic data were compared between patients with stable chronic HFpEF older than 60 years and age-matched healthy control (HC) participants and analyzed for intergroup differences and associations with exercise performance. All participants were treated at a university referral center, were clinically stable, and were not undergoing regular exercise or diet programs. Data were collected from March 2016 to December 2017, and data were analyzed from November 2020 to May 2021. Main Outcomes and Measures:Skeletal muscle mitochondrial function, including maximal capacity and respiration linked to complex I and complex II. Exercise performance was assessed by peak exercise oxygen consumption, 6-minute walk distance, and the Short Physical Performance Battery. Results:Of 72 included patients, 50 (69%) were women, and the mean (SD) age was 69.6 (6.1) years. Skeletal muscle mitochondrial function measures were all markedly lower in skeletal muscle fibers obtained from patients with HFpEF compared with HCs, even when adjusting for age, sex, and body mass index. Maximal capacity was strongly and significantly correlated with peak exercise oxygen consumption (R = 0.69; P < .001), 6-minute walk distance (R = 0.70; P < .001), and Short Physical Performance Battery score (R = 0.46; P < .001). Conclusions and Relevance:In this study, patients with HFpEF had marked abnormalities in skeletal muscle mitochondrial function. Severely reduced maximal capacity and complex I-linked and complex II-linked respiration were associated with exercise intolerance and represent promising therapeutic targets.
10.1001/jamacardio.2023.0957
Hand Grip Strength Predicts Mortality and Quality of Life in Heart Failure: Insights From the Singapore Cohort of Patients With Advanced Heart Failure.
Journal of cardiac failure
BACKGROUND:Frailty is prevalent among patients with heart failure (HF) and is associated with increased mortality rates and worse patient-centered outcomes. Hand grip strength (GS) has been proposed as a single-item marker of frailty and a potential screening tool to identify patients most likely to benefit from therapies that target frailty so as to improve quality of life (QoL) and clinical outcomes. We assessed the association of longitudinal decline in GS with all-cause mortality and QoL. Decline in GS is associated with increased risk of all-cause mortality and worse overall and domain-specific (physical, functional, emotional, social) QoL among patients with advanced HF. METHODS:We used data from a prospective, observational cohort of patients with New York Heart Association class III or IV HF in Singapore. Patients' overall and domain-specific QoL were assessed, and GS was measured every 4 months. We constructed a Kaplan-Meier plot with GS at baseline dichotomized into categories of weak (≤ 5th percentile) and normal (> 5th percentile) based on the GS in a healthy Singapore population of the same sex and age. Missing GS measurements were imputed using chained equations. We jointly modeled longitudinal GS measurements and survival time, adjusting for comorbidities. We used mixed effects models to evaluate the associations between GS and QoL. RESULTS:Among 251 patients (mean age 66.5 ± 12.0 years; 28.3% female), all-cause mortality occurred in 58 (23.1%) patients over a mean follow-up duration of 3.0 ± 1.3 years. Patients with weak GS had decreased survival rates compared to those with normal GS (log-rank P = 0.033). In the joint model of longitudinal GS and survival time, a decrease of 1 unit in GS was associated with a 12% increase in rate of mortality (hazard ratio: 1.12; 95% confidence interval: 1.05-1.20; P = < 0.001). Higher GS was associated with higher overall QoL (β (SE) = 0.36 (0.07); P = < 0.001) and higher domain-specific QoL, including physical (β [SE] = 0.13 [0.03]; P = < 0.001), functional (β [SE] = 0.12 [0.03]; P = < 0.001), and emotional QoL (β [SE] = 0.08 [0.02]; P = < 0.001). Higher GS was associated with higher social QoL, but this was not statistically significant (β [SE] = 0.04 [0.03]; P = 0.122). CONCLUSIONS:Among patients with advanced HF, longitudinal decline in GS was associated with worse survival rates and QoL. Further studies are needed to evaluate whether incorporating GS into patient selection for HF therapies leads to improved survival rates and patient-centered outcomes.
10.1016/j.cardfail.2022.11.009
Right Ventricular Free Wall Strain and Effect of Defibrillator Implantation in Patients With Nonischemic Systolic Heart Failure.
Journal of cardiac failure
BACKGROUND:Patients with nonischemic systolic heart failure have an increased risk of malignant ventricular arrhythmias and sudden cardiovascular death. Because the risk is less pronounced than for patients with ischemic cause of heart failure more discriminating tools are needed to identify patients most likely to benefit from implantable cardioverter-defibrillator (ICD) implantation. Right ventricular (RV) dysfunction is associated with a worse prognosis, but whether RV free wall strain (RV-FWS) measured with echocardiography can identify the patients most likely to benefit from ICD implantation is not known. METHODS AND RESULTS:In this extended follow-up analysis of the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial, RV-FWS was measured with echocardiography in 445 patients before randomization. RV dysfunction was defined as an RV-FWS of greater than -20%. The primary end point was all-cause mortality. The median RV-FWS was -18% (quartiles -23% to -14%), and RV dysfunction was measured in 255 patients (57%). During a median follow-up of 5.7 years, 170 patients (38%) died. There was a statistically significant interaction between RV dysfunction and the effect of ICD implantation (P = .003), also after adjusting for known cardiovascular risk factors (P = .01). ICD implantation significantly decreased all-cause mortality in patients with RV dysfunction (hazard ratio 0.54, 95% confidence interval 0.36-0.80, P = .002), but not in patients with normal RV function (hazard ratio 1.34, 95% confidence interval 0.84-2.12, P = .22). CONCLUSIONS:In patients with nonischemic systolic heart failure, RV dysfunction on echocardiography was associated with a greater effect of ICD implantation and could be used to select patients with benefit from ICD treatment.
10.1016/j.cardfail.2022.12.018
Impact of multimorbidity on mortality in heart failure with reduced ejection fraction: which comorbidities matter most? An analysis of PARADIGM-HF and ATMOSPHERE.
European journal of heart failure
AIMS:Multimorbidity, the coexistence of two or more chronic conditions, is synonymous with heart failure (HF). How risk related to comorbidities compares at individual and population levels is unknown. The aim of this study is to examine the risk related to comorbidities, alone and in combination, both at individual and population levels. METHODS AND RESULTS:Using two clinical trials in HF - the Prospective comparison of ARNI (Angiotensin Receptor-Neprilysin Inhibitor) with ACEI (Angiotensin-Converting Enzyme Inhibitor) to Determine Impact on Global Mortality and morbidity in HF trial (PARADIGM-HF) and the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure trials (ATMOSPHERE) - we identified the 10 most common comorbidities and examined 45 possible pairs. We calculated population attributable fractions (PAF) for all-cause death and relative excess risk due to interaction with Cox proportional hazard models. Of 15 066 patients in the study, 14 133 (93.7%) had at least one and 11 867 (78.8%) had at least two of the 10 most prevalent comorbidities. The greatest individual risk among pairs was associated with peripheral artery disease (PAD) in combination with stroke (hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.28-2.33) and anaemia (HR 1.71; 95% CI 1.39-2.11). The combination of chronic kidney disease (CKD) and hypertension had the highest PAF (5.65%; 95% CI 3.66-7.61). Two pairs demonstrated significant synergistic interaction (atrial fibrillation with CKD and coronary artery disease, respectively) and one an antagonistic interaction (anaemia and obesity). CONCLUSIONS:In HF, the impact of multimorbidity differed at the individual patient and population level, depending on the prevalence of and the risk related to each comorbidity, and the interaction between individual comorbidities. Patients with coexistent PAD and stroke were at greatest individual risk whereas, from a population perspective, coexistent CKD and hypertension mattered most.
10.1002/ejhf.2856
Distinct Associations Between Postdischarge Cognitive Change Patterns and 1-year Outcomes in Patients Hospitalized for Heart Failure.
Journal of cardiac failure
BACKGROUND:The patterns of patients' cognitive function after hospital discharge for heart failure (HF), their prognostic implication and the predictors for new-onset cognitive impairment remain unknown. METHODS AND RESULTS:We included 2307 patients (64 ± 14 years, 36.4% female sex) hospitalized for HF from a cohort who completed cognitive testing before discharge and after 1 month. Among 1658 patients with normal cognition before discharge, 229 (13.8%) and 1429 (86.2%) had new-onset cognitive impairment and normal cognition at 1 month, respectively. Of the 649 with cognitive impairment, 315 (48.5%) and 334 (51.5%) had transient and persistent cognitive impairment, respectively. Multivariable analyses showed that, compared with normal cognition, patients with new-onset cognitive impairment had an increased risk of cardiovascular death or HF rehospitalization (hazard ratio 1.35, 95% confidence interval 1.07-1.70); patients with persistent cognitive impairment showed an increased risk, but it was not statistically significant (hazard ratio 1.17, 95% confidence interval 0.95-1.44); patients with transient cognitive impairment had a similar risk (hazard ratio 0.91, 95% confidence interval 0.73-1.13). Older age, females, lower education level, prior atherosclerotic cardiovascular diseases, lower health status, and lower Mini-Cog score before discharge predicted new-onset cognitive impairment. CONCLUSIONS:Acute HF substantially affects short-term cognition. Patients who have developed new-onset cognitive impairment have an increased risk of adverse outcomes. Monitoring cognition is necessary, particularly in high-risk patients.
10.1016/j.cardfail.2023.01.006
The Difference Between Cystatin C- and Creatinine-Based Estimated GFR in Heart Failure With Reduced Ejection Fraction: Insights From PARADIGM-HF.
American journal of kidney diseases : the official journal of the National Kidney Foundation
RATIONALE & OBJECTIVE:The clinical implications of the discrepancy between cystatin C (cysC)- and serum creatinine (Scr)-estimated glomerular filtration rate (eGFR) in patients with heart failure (HF) and reduced ejection fraction (HFrEF) are unknown. STUDY DESIGN:Post-hoc analysis of randomized trial data. SETTING & PARTICIPANTS:1,970 patients with HFrEF enrolled in PARADIGM-HF with available baseline cysC and Scr measurements. EXPOSURE:Intraindividual differences between eGFR based on cysC (eGFR) and Scr (eGFR; eGFRdiff). OUTCOMES:Clinical outcomes included the PARADIGM-HF primary end point (composite of cardiovascular [CV] mortality or HF hospitalization), CV mortality, all-cause mortality, and worsening kidney function. We also examined poor health-related quality of life (HRQoL), frailty, and worsening HF (WHF), defined as HF hospitalization, emergency department visit, or outpatient intensification of therapy between baseline and 8-month follow-up. ANALYTICAL APPROACH:Fine-Gray subdistribution hazard models and Cox proportional hazards models were used to regress clinical outcomes on baseline eGFRdiff. Logistic regression was used to investigate the association of baseline eGFRdiff with poor HRQoL and frailty. Linear regression models were used to assess the association of WHF with eGFR, eGFR, and eGFRdiff at 8-month follow-up. RESULTS:Baseline eGFRdiff was higher than +10 and lower than-10mL/min/1.73m in 13.0% and 35.7% of patients, respectively. More negative values of eGFRdiff were associated with worse outcomes ([sub]hazard ratio per standard deviation: PARADIGM-HF primary end point, 1.18; P=0.008; CV mortality, 1.34; P=0.001; all-cause mortality, 1.39; P<0.001; worsening kidney function, 1.31; P=0.05). For a 1-standard-deviation decrease in eGFRdiff, the prevalences of poor HRQoL and frailty increased by 29% and 17%, respectively (P≤0.008). WHF was associated with a more pronounced decrease in eGFR than in eGFR, resulting in a change in 8-month eGFRdiff of-4.67mL/min/1.73m (P<0.001). LIMITATIONS:Lack of gold-standard assessment of kidney function. CONCLUSIONS:In patients with HFrEF, discrepancies between eGFR and eGFR are common and are associated with clinical outcomes, HRQoL, and frailty. The decline in kidney function associated with WHF is more marked when assessed with eGFR than with eGFR. PLAIN-LANGUAGE SUMMARY:Kidney function assessment traditionally relies on serum creatinine (Scr) to establish an estimated glomerular filtration rate (eGFR). However, this has been challenged with the introduction of an alternative marker, cystatin C (cysC). Muscle mass and nutritional status have differential effects on eGFR based on cysC (eGFR) and Scr (eGFR). Among ambulatory patients with heart failure enrolled in PARADIGM-HF, we investigated the clinical significance of the difference between eGFR and eGFR. More negative values (ie, eGFR>eGFR) were associated with worse clinical outcomes (including mortality), poor quality of life, and frailty. In patients with progressive heart failure, which is characterized by muscle loss and poor nutritional status, the decline in kidney function was more pronounced when eGFR was estimated using cysC rather than Scr.
10.1053/j.ajkd.2023.03.005
The Effect of Sacubitril/Valsartan on Left Ventricular Myocardial Deformation in Heart Failure with Preserved Ejection Fraction (PARAMOUNT trial).
Journal of cardiac failure
BACKGROUND:Global longitudinal strain (GLS) and global circumferential strain (GCS) have been shown to be impaired in heart failure with preserved ejection fraction. We sought to assess whether treating patients with heart failure with preserved ejection fraction with sacubitril/valsartan would significantly improve GLS and GCS compared with valsartan alone. METHODS AND RESULTS:PARAMOUNT (Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction Trial) was a phase II, randomized, parallel-group, double-blind multicenter trial in 301 patients with New York Heart Association functional class II-III heart failure, a left ventricular ejection fraction of 45%, and an N-terminal pro-B-type natriuretic peptide of ≥400 pg/mL. Participants were randomly assigned (1:1) to sacubitril/valsartan titrated to 200 mg twice daily or valsartan titrated to 160 mg twice daily for 36 weeks. We assessed changes in the GLS and the GCS from baseline to 36 weeks, adjusting for baseline value, in patients with sufficient imaging quality for 2-dimensitonal speckle tracking analysis at both timepoints (n = 60 sacubitril/valsartan, n = 75 valsartan only). GCS was significantly improved at 36 weeks in the sacubitril/valsartan group when compared with the valsartan group (Δ4.42%, 95% confidence interval [CI] 0.67-8.17, P = .021), with no significant difference observed in GLS (Δ0.25%, 95% CI, -1.19 to 1.70, P = .73). Patients with a history of hospitalization for heart failure had a differentially greater improvement in GCS when treated with sacubitril/valsartan. CONCLUSIONS:In patients with heart failure with preserved ejection fraction, sacubitril/valsartan improved GCS but not GLS when compared with valsartan during a 36-week period. This trial is registered at ClinicalTrials.gov, NCT00887588.
10.1016/j.cardfail.2023.03.019
Circulating Angiokines Are Associated With Reverse Remodeling and Outcomes in Chronic Heart Failure.
Journal of cardiac failure
BACKGROUND:We sought to determine whether circulating modifiers of endothelial function are associated with cardiac structure and clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). METHODS:We measured 25 proteins related to endothelial function in 99 patients from the GUIDE-IT study. Protein levels were evaluated for association with echocardiographic parameters and the incidence of all-cause death and hospitalization for heart failure (HHF). RESULTS:Higher concentrations of angiopoietin 2 (ANGPT2), vascular endothelial growth factor receptor 1 (VEGFR1) and hepatocyte growth factor (HGF) were significantly associated with worse function and larger ventricular volumes. Over time, decreases in ANGPT2 and, to a lesser extent, VEGFR1 and HGF, were associated with improvements in cardiac size and function. Individuals with higher concentrations of ANGPT2, VEGFR1 or HGF had increased risks for a composite of death and HHF in the following year (HR 2.76 (95% CI 1.73-4.40) per 2-fold change in ANGPT2; HR 1.76 (95% CI 1.11-2.79) for VEGFR1; and HR 4.04 (95% CI 2.19-7.44) for HGF). CONCLUSIONS:Proteins related to endothelial function associate with cardiac size, cardiac function and clinical outcomes in patients with HFrEF. These results support the concept that endothelial function may be an important contributor to the progression to and the recovery from HFrEF.
10.1016/j.cardfail.2022.12.011
Use of and association between heart failure pharmacological treatments and outcomes in obese versus non-obese patients with heart failure with reduced ejection fraction: data from the Swedish Heart Failure Registry.
European journal of heart failure
AIMS:To investigate the use of guideline-directed medical therapies (GDMT) and associated outcomes in obese (body mass index ≥30 kg/m ) versus non-obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). METHODS AND RESULTS:Patients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non-obese patients, use of treatments was 91% versus 86% for renin-angiotensin system inhibitors (RASi)/angiotensin receptor-neprilysin inhibitors (ARNi), 94% versus 91% for beta-blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta-blockers being independently associated with lower risk of all-cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non-obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non-obese patients, whereas beta-blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity. CONCLUSION:Obese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta-blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non-obese patients when considering competing risk.
10.1002/ejhf.2795
Association of Beta-Blocker Therapy With Cardiovascular Outcomes in Patients With Stable Ischemic Heart Disease.
Journal of the American College of Cardiology
BACKGROUND:Previous studies have failed to show a cardioprotective benefit of beta-blockers in patients with stable coronary artery disease (CAD). OBJECTIVES:This study sought to determine the association between beta-blockers and cardiovascular events in patients with stable CAD using a new user design. METHODS:All patients aged >66 years undergoing elective coronary angiography in Ontario, Canada, from 2009 to 2019 with diagnosed obstructive CAD were included. Exclusion criteria included heart failure or a recent myocardial infarction, as well as having a beta-blocker prescription claim in the previous year. Beta-blocker use was defined as having at least 1 beta-blocker prescription claim in the 90 days preceding or after the index coronary angiography. The main outcome was a composite of all-cause mortality and hospitalization for heart failure or myocardial infarction. Inverse probability of treatment weighting using the propensity score was used to account for confounding. RESULTS:This study included 28,039 patients (mean age: 73.0 ± 5.6 years; 66.2% male), and 12,695 of those (45.3%) were newly prescribed beta-blockers. The 5-year risks of the primary outcome were 14.3% in the beta-blocker group and 16.1% in the no beta-blocker group (absolute risk reduction: -1.8%; 95% CI: -2.8 to -0.8; HR: 0.92; 95% CI: 0.86-0.98; P = 0.006). This result was driven by reductions in myocardial infarction hospitalization (cause-specific HR: 0.87; 95% CI: 0.77-0.99; P = 0.031), whereas no differences were observed in all-cause death or heart failure hospitalization. CONCLUSIONS:In patients with angiographically documented stable CAD without heart failure or a recent myocardial infarction, beta-blockers were associated with a small but significant reduction in cardiovascular events at 5 years.
10.1016/j.jacc.2023.04.021
Early glomerular filtration rates changes and risk of mortality in acute heart failure. The modifying role of admission renal function and decongestion.
European journal of internal medicine
BACKGROUND:The pathophysiology of changes in estimated glomerular filtration rate (eGFR) in acute heart failure (AHF) is complex and multifactorial. We evaluated the associated mortality risk of early changes in eGFR across baseline renal function on admission and early changes in natriuretic peptides in patients admitted with AHF. METHODS:We retrospectively evaluated 2,070 patients admitted with AHF. Renal dysfunction on admission was defined as eGFR<60 ml/min/1.73m and successful decongestion as NT-proBNP decreased >30% from baseline. We assessed the mortality risk associated with eGFR changes from baseline at 48-72 h after admission (ΔeGFR%) according to baseline renal function, and NT-proBNP changes at 48-72 h through Cox regression analyses. RESULTS:The mean age was 74.4 ± 11.2 years, and 930 (44.9%) were women. The proportion of admission eGFR<60 ml/min/1.73m and 48-72 h changes in NT-proBNP>30% were 50.5% and 32.8%, respectively. At a median follow-up of 1.75 years, 928 deaths were registered. In the whole sample, changes in renal function were not associated with mortality (p = 0.208). The adjusted analysis revealed that the risk of mortality related to ΔeGFR% was heterogeneous across baseline renal function and changes in NT-proBNP (p-value for interaction=0.003). ΔeGFR% was not associated with mortality in patients with baseline eGFR≥60 ml/min/1.73m. In those with eGFR<60 ml/min/1.73m, a decrease in eGFR was associated with higher mortality, particularly in those with a reduction in NT-proBNP<30%. CONCLUSION:In patients with AHF, early ΔeGFR% was associated with the risk of long-term mortality only in patients with renal dysfunction on admission and no early decline in NT-proBNP.
10.1016/j.ejim.2023.05.037
Prognostic Value of Hemodynamic Gain Index in Patients With Heart Failure With Reduced Ejection Fraction.
JACC. Heart failure
BACKGROUND:Assessment of functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) is essential for risk stratification, and it traditionally relied on cardiopulmonary exercise testing (CPET)-derived peak oxygen consumption (peak Vo). OBJECTIVES:This study sought to investigate the prognostic value of alternative nonmetabolic exercise testing parameters in a contemporary cohort with HFrEF. METHODS:Medical records of 1,067 consecutive patients with chronic HFrEF who underwent CPET from December 2012 to September 2020 were reviewed for a primary outcome that was a composite of all-cause mortality, left ventricular assist device implantation, and/or heart transplantation. Multivariable Cox regression and log-rank testing were used to determine prognostic values of various exercise testing variables. RESULTS:The primary outcome was identified in 331 of 954 patients (34.7%) of the HFrEF cohort (median follow-up time, 946 days). After adjustment for demographics, cardiac parameters, and comorbidities, higher hemodynamic gain index (HGI) and peak rate-pressure product (RPP) were associated with greater event-free survival (adjusted HR per doubling: 0.76 and 0.36; 95% CI: 0.67-0.87 and 0.28-0.47; all P < 0.001, respectively). Moreover, HGI (area under the curve [AUC]: 0.69; 95% CI: 0.65-0.72) and peak RPP (AUC: 0.71; 95% CI: 0.68-0.74) were comparable to the standard peak Vo (AUC: 0.70; 95% CI: 0.66-0.73; P for comparison = 0.607 and 0.393, respectively) for primary outcome discrimination. CONCLUSIONS:HGI and peak RPP show good correlation with peak Vo in terms of prognostication and outcome discrimination in patients with HFrEF and may serve as suitable alternatives to CPET-derived prognostic variables.
10.1016/j.jchf.2023.05.005
Cardio-Renal-Metabolic Overlap, Outcomes, and Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction.
JACC. Heart failure
BACKGROUND:Cardio-renal-metabolic (CRM) conditions are individually common among patients with heart failure (HF), but the prevalence and influence of overlapping CRM conditions in this population have not been well-studied. OBJECTIVES:This study aims to evaluate the impact of overlapping CRM conditions on clinical outcomes and treatment effects of dapagliflozin in HF. METHODS:In this post hoc analysis of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure), we evaluated the prevalence of comorbid CRM conditions (atherosclerotic cardiovascular disease, chronic kidney disease, and type 2 diabetes), their impact on the primary outcome (cardiovascular death or worsening HF), and treatment effects of dapagliflozin by CRM status. RESULTS:Among 6,263 participants, 1,952 (31%), 2,245 (36%), and 1,236 (20%) had 1, 2, and 3 additional CRM conditions, respectively. HF alone was uncommon (13%). Greater CRM multimorbidity was associated with older age, higher body mass index, longer-duration HF, worse health status, and lower left ventricular ejection fraction. Risk of the primary outcome increased with higher CRM overlap, with 3 CRM conditions independently associated with highest risk of primary events (adjusted HR: 2.16 [95% CI: 1.72-2.72]; P < 0.001) compared with HF alone. Relative benefits of dapagliflozin on the primary outcome were consistent irrespective of the type of CRM overlap (P = 0.773) and by the number of CRM conditions (P = 0.734), with greatest absolute benefits among those with highest CRM multimorbidity. Estimated 2-year numbers needed to treat with dapagliflozin to prevent 1 primary event were approximately 52, 39, 33, and 24 for participants with 0, 1, 2, and 3 additional CRM conditions at baseline, respectively. Adverse events between treatment arms were similar across the CRM spectrum. CONCLUSIONS:CRM multimorbidity was common and associated with adverse outcomes among patients with HF and left ventricular ejection fraction >40% in DELIVER. Dapagliflozin was safe and effective across the CRM spectrum, with greater absolute benefits among those with highest CRM overlap (Dapagliflozin Evaluation to Improve the LIVEs of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).
10.1016/j.jchf.2023.05.015
Hypoxaemia in patients with heart failure and preserved ejection fraction.
European journal of heart failure
AIMS:It is widely held that heart failure (HF) does not cause exertional hypoxaemia, based upon studies in HF with reduced ejection fraction, but this may not apply to patients with HF and preserved ejection fraction (HFpEF). Here, we characterize the prevalence, pathophysiology, and clinical implications of exertional arterial hypoxaemia in HFpEF. METHODS AND RESULTS:Patients with HFpEF (n = 539) and no coexisting lung disease underwent invasive cardiopulmonary exercise testing with simultaneous blood and expired gas analysis. Exertional hypoxaemia (oxyhaemoglobin saturation <94%) was observed in 136 patients (25%). As compared to those without hypoxaemia (n = 403), patients with hypoxaemia were older and more obese. Patients with HFpEF and hypoxaemia had higher cardiac filling pressures, higher pulmonary vascular pressures, greater alveolar-arterial oxygen difference, increased dead space fraction, and greater physiologic shunt compared to those without hypoxaemia. These differences were replicated in a sensitivity analysis where patients with spirometric abnormalities were excluded. Regression analyses revealed that increases in pulmonary arterial and pulmonary capillary pressures were related to lower arterial oxygen tension (PaO ), especially during exercise. Body mass index (BMI) was not correlated with the arterial PaO , and hypoxaemia was associated with increased risk for death over 2.8 (interquartile range 0.7-5.5) years of follow-up, even after adjusting for age, sex, and BMI (hazard ratio 2.00, 95% confidence interval 1.01-3.96; p = 0.046). CONCLUSION:Between 10% and 25% of patients with HFpEF display arterial desaturation during exercise that is not ascribable to lung disease. Exertional hypoxaemia is associated with more severe haemodynamic abnormalities and increased mortality. Further study is required to better understand the mechanisms and treatment of gas exchange abnormalities in HFpEF.
10.1002/ejhf.2930
Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction According to Polypharmacy Status.
JACC. Heart failure
BACKGROUND:Patients with heart failure (HF) have a high burden of multimorbidity, often necessitating numerous medications. There may be clinical concern about introducing another medication, especially among individuals with polypharmacy. OBJECTIVES:This study examined the efficacy and safety of addition of dapagliflozin according to the number of concomitant medications in HF with mildly reduced or preserved ejection fraction. METHODS:In this post hoc analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, 6,263 participants with symptomatic HF with left ventricular ejection fraction >40% were randomized to dapagliflozin or placebo. Baseline medication use (including vitamins and supplements) was collected. Efficacy and safety outcomes were assessed by medication use categories ("nonpolypharmacy": <5 medications; "polypharmacy": 5 to 9 medications; and "hyperpolypharmacy": ≥10 medications) and continuously. The primary outcome was worsening HF or cardiovascular death. RESULTS:Overall, 3,795 (60.6%) patients met polypharmacy and 1,886 (30.1%) met hyperpolypharmacy criteria. Higher numbers of medications were strongly associated with higher comorbidity burden and increased rates of the primary outcome. Compared with placebo, dapagliflozin similarly reduced the risk of the primary outcome irrespective of polypharmacy status (nonpolypharmacy HR: 0.88 [95% CI: 0.58-1.34]; polypharmacy HR: 0.88 [95% CI: 0.75-1.03]; hyperpolypharmacy HR: 0.73 [95% CI: 0.60-0.88]; P = 0.30). Similarly, benefits with dapagliflozin were consistent across the spectrum of total medication use (P = 0.06). Although adverse events increased with higher number of medications, they were not more frequent with dapagliflozin, regardless of polypharmacy status. CONCLUSIONS:In the DELIVER trial, dapagliflozin safely reduced worsening HF or cardiovascular death across a broad range of baseline medication use, including among individuals with polypharmacy (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).
10.1016/j.jchf.2023.05.014
Association between a hospitalization for heart failure and the initiation/discontinuation of guideline-recommended treatments: An analysis from the Swedish Heart Failure Registry.
European journal of heart failure
AIMS:To investigate whether a heart failure (HF) hospitalization is associated with initiation/discontinuation of guideline-directed medical HF therapy (GDMT) and consequent outcomes. METHODS AND RESULTS:Among patients in the Swedish HF registry with an ejection fraction <50% enrolled in 2009-2018, initiation/discontinuation of GDMT was investigated by assessing dispensations of GDMT in those with versus without a HF hospitalization. Of 14 737 patients, 6893 (47%) were enrolled when hospitalized for HF. Initiation of GDMT was more likely than discontinuation following a HF hospitalization compared to a control group of patients without a HF hospitalization (odds ratio range 2.1-4.0 vs. 1.4-1.6 for the individual medications), although the proportion of patients not on GDMT was still high (8.1-44.0%). Key patient characteristics triggering less use of GDMT (i.e. less initiation or more discontinuation) were older age and worse renal function. Following a HF hospitalization, initiation of renin-angiotensin system inhibitors/angiotensin receptor-neprilysin inhibitors or beta-blockers was associated with lower and their discontinuation with higher mortality risk, but no association with mortality was observed for initiation/discontinuation of mineralocorticoid receptor antagonists. CONCLUSIONS:Following a HF hospitalization, initiation of GDMT was more likely than discontinuation, although still limited. Perceived or actual low tolerance were barriers to GDMT implementation. Early re-/initiation of GDMT was associated with better survival. Our findings represent a call for further implementing the current guideline recommendation for an early re-/initiation of GDMT following a HF hospitalization.
10.1002/ejhf.2928
Prognostic value of temporal patterns of left atrial reservoir strain in patients with heart failure with reduced ejection fraction.
Clinical research in cardiology : official journal of the German Cardiac Society
BACKGROUND:We investigated whether repeatedly measured left atrial reservoir strain (LASr) in heart failure with reduced ejection fraction (HFrEF) patients provides incremental prognostic value over a single baseline LASr value, and whether temporal patterns of LASr provide incremental prognostic value over temporal patterns of other echocardiographic markers and NT-proBNP. METHODS:In this prospective observational study, 153 patients underwent 6-monthly echocardiography, during a median follow-up of 2.5 years. Speckle tracking echocardiography was used to measure LASr. Hazard ratios (HRs) were calculated for LASr from Cox models (baseline) and joint models (repeated measurements). The primary endpoint (PEP) comprised HF hospitalization, left ventricular assist device, heart transplantation, and cardiovascular death. RESULTS:Mean age was 58 ± 11 years, 76% were men, 82% were in NYHA class I/II, mean LASr was 20.9% ± 11.3%, and mean LVEF was 29% ± 10%. PEP was reached by 50 patients. Baseline and repeated measurements of LASr (HR per SD change (95% CI) 0.20 (0.10-0.41) and (0.13 (0.10-0.29), respectively) were both significantly associated with the PEP, independent of both baseline and repeated measurements of other echo-parameters and NT-proBNP. Although LASr was persistently lower over time in patients with PEP, temporal trajectories did not diverge in patients with versus without the PEP as the PEP approached. CONCLUSION:LASr was associated with adverse events in HFrEF patients, independent of baseline and repeated other echo-parameters and NT-proBNP. Temporal trajectories of LASr showed decreased but stable values in patients with the PEP, and do not provide incremental prognostic value for clinical practice compared to single measurements of LASr.
10.1007/s00392-023-02244-x
Quality of Care and Clinical Outcomes for Patients With Heart Failure at Hospitals Caring for a High Proportion of Black Adults: Get With The Guidelines-Heart Failure Registry.
JAMA cardiology
Importance:Black adults with heart failure (HF) disproportionately experience higher population-level mortality than White adults with HF. Whether quality of care for HF differs at hospitals with high proportions of Black patients compared with other hospitals is unknown. Objective:To compare quality and outcomes for patients with HF at hospitals with high proportions of Black patients vs other hospitals. Design, Setting, and Participants:Patients hospitalized for HF at Get With The Guidelines (GWTG) HF sites from January 1, 2016, through December 1, 2019. These data were analyzed from May 2022 through November 2022. Exposures:Hospitals caring for high proportions of Black patients. Main Outcomes and Measures:Quality of HF care based on 14 evidence-based measures, overall defect-free HF care, and 30-day readmissions and mortality in Medicare patients. Results:This study included 422 483 patients (224 270 male [53.1%] and 284 618 White [67.4%]) with a mean age of 73.0 years. Among 480 hospitals participating in GWTG-HF, 96 were classified as hospitals with high proportions of Black patients. Quality of care was similar between hospitals with high proportions of Black patients compared with other hospitals for 11 of 14 GWTG-HF measures, including use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitors for left ventricle systolic dysfunction (high-proportion Black hospitals: 92.7% vs other hospitals: 92.4%; adjusted odds ratio [OR], 0.91; 95% CI, 0.65-1.27), evidence-based β-blockers (94.7% vs 93.7%; OR, 1.02; 95% CI, 0.82-1.28), angiotensin receptor neprilysin inhibitors at discharge (14.3% vs 16.8%; OR, 0.74; 95% CI, 0.54-1.02), anticoagulation for atrial fibrillation/flutter (88.8% vs 87.5%; OR, 1.05; 95% CI, 0.76-1.45), and implantable cardioverter-defibrillator counseling/placement/prescription at discharge (70.9% vs 71.0%; OR, 0.75; 95% CI, 0.50-1.13). Patients at high-proportion Black hospitals were less likely to be discharged with a follow-up visit made within 7 days or less (70.4% vs 80.1%; OR, 0.68; 95% CI, 0.53-0.86), receive cardiac resynchronization device placement/prescription (50.6% vs 53.8%; OR, 0.63; 95% CI, 0.42-0.95), or an aldosterone antagonist (50.4% vs 53.5%; OR, 0.69; 95% CI, 0.50-0.97). Overall defect-free HF care was similar between both groups of hospitals (82.6% vs 83.4%; OR, 0.89; 95% CI, 0.67-1.19) and there were no significant within-hospital differences in quality for Black patients vs White patients. Among Medicare beneficiaries, the risk-adjusted hazard ratio (HR) for 30-day readmissions was higher at high-proportion Black vs other hospitals (HR, 1.14; 95% CI, 1.02-1.26), but similar for 30-day mortality (HR 0.92; 95% CI,0.84-1.02). Conclusions and Relevance:Quality of care for HF was similar across 11 of 14 measures at hospitals caring for high proportions of Black patients compared with other hospitals, as was overall defect-free HF care. There were no significant within-hospital differences in quality for Black patients vs White patients.
10.1001/jamacardio.2023.0695
Effect of Dapagliflozin on Total Heart Failure Events in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Analysis of the DELIVER Trial.
JAMA cardiology
Importance:In the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial, dapagliflozin reduced the risk of time to first worsening heart failure (HF) event or cardiovascular death in patients with HF with mildly reduced or preserved ejection fraction (EF). Objective:To evaluate the effect of dapagliflozin on total (ie, first and recurrent) HF events and cardiovascular death in this population. Design, Setting, and Participants:In this prespecified analysis of the DELIVER trial, the proportional rates approach of Lin, Wei, Yang, and Ying (LWYY) and a joint frailty model were used to examine the effect of dapagliflozin on total HF events and cardiovascular death. Several subgroups were examined to test for heterogeneity in the effect of dapagliflozin, including left ventricular EF. Participants were enrolled from August 2018 to December 2020, and data were analyzed from August to October 2022. Interventions:Dapagliflozin, 10 mg, once daily or matching placebo. Main Outcomes and Measures:The outcome was total episodes of worsening HF (hospitalization for HF or urgent HF visit requiring intravenous HF therapies) and cardiovascular death. Results:Of 6263 included patients, 2747 (43.9%) were women, and the mean (SD) age was 71.7 (9.6) years. There were 1057 HF events and cardiovascular deaths in the placebo group compared with 815 in the dapagliflozin group. Patients with more HF events had features of more severe HF, such as higher N-terminal pro-B-type natriuretic peptide level, worse kidney function, more prior HF hospitalizations, and longer duration of HF, although EF was similar to those with no HF events. In the LWYY model, the rate ratio for total HF events and cardiovascular death for dapagliflozin compared with placebo was 0.77 (95% CI, 0.67-0.89; P < .001) compared with a hazard ratio of 0.82 (95% CI, 0.73-0.92; P < .001) in a traditional time to first event analysis. In the joint frailty model, the rate ratio was 0.72 (95% CI, 0.65-0.81; P < .001) for total HF events and 0.87 (95% CI, 0.72-1.05; P = .14) for cardiovascular death. The results were similar for total HF hospitalizations (without urgent HF visits) and cardiovascular death and in all subgroups, including those defined by EF. Conclusions and Relevance:In the DELIVER trial, dapagliflozin reduced the rate of total HF events (first and subsequent HF hospitalizations and urgent HF visits) and cardiovascular death regardless of patient characteristics, including EF. Trial Registration:ClinicalTrials.gov Identifier: NCT03619213.
10.1001/jamacardio.2023.0711
Three-dimensional echocardiographic left ventricular strain analysis in Fabry disease: correlation with heart failure severity, myocardial scar, and impact on long-term prognosis.
European heart journal. Cardiovascular Imaging
AIMS:Fabry disease (FD) is a multisystemic lysosomal storage disorder caused by a defect in the alpha-galactosidase A gene that manifests as a phenocopy of hypertrophic cardiomyopathy. We assessed the echocardiographic 3D left ventricular (LV) strain of patients with FD in relation to heart failure severity using natriuretic peptides, the presence of a cardiovascular magnetic resonance (CMR) late gadolinium enhancement scar, and long-term prognosis. METHODS AND RESULTS:3D echocardiography was feasible in 75/99 patients with FD [aged 47 ± 14 years, 44% males, LV ejection fraction (EF) 65 ± 6% and 51% with hypertrophy or concentric remodelling of the LV]. Long-term prognosis (death, heart failure decompensation, or cardiovascular hospitalization) was assessed over a median follow-up of 3.1 years. A stronger correlation was observed for N-terminal pro-brain natriuretic peptide levels with 3D LV global longitudinal strain (GLS, r = -0.49, P < 0.0001) than with 3D LV global circumferential strain (GCS, r = -0.38, P < 0.001) or 3D LVEF (r = -0.25, P = 0.036). Individuals with posterolateral scar on CMR had lower posterolateral 3D circumferential strain (CS; P = 0.009). 3D LV-GLS was associated with long-term prognosis [adjusted hazard ratio 0.85 (confidence interval 0.75-0.95), P = 0.004], while 3D LV-GCS and 3D LVEF were not (P = 0.284 and P = 0.324). CONCLUSION:3D LV-GLS is associated with both heart failure severity measured by natriuretic peptide levels and long-term prognosis. Decreased posterolateral 3D CS reflects typical posterolateral scarring in FD. Where feasible, 3D-strain echocardiography can be used for a comprehensive mechanical assessment of the LV in patients with FD.
10.1093/ehjci/jead121
Recency of Heart Failure Hospitalization, Outcomes, and the Effect of Empagliflozin: An EMPEROR-Pooled Analysis.
JACC. Heart failure
BACKGROUND:Patients with a recent heart failure (HF) hospitalization have a high risk of rehospitalization and mortality. Early treatment may have a substantial impact on patient outcomes. OBJECTIVES:This study sought to study the outcomes and effect of empagliflozin according to timing of prior HF hospitalization. METHODS:EMPEROR-Pooled (EMPEROR-Reduced [EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction] and EMPEROR-Preserved [EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction] combined) included 9,718 HF patients who were grouped according to the recency of HF hospitalization (none, <3 months, 3-6 months, 6-12 months, >12 months). The primary outcome was a composite of time to first of HF hospitalization or cardiovascular death, over a median follow-up of 21 months. RESULTS:The primary outcome event rates (per 100 person-years) in the placebo group were 26.7, 18.1, 13.7, and 2.8 for patients hospitalized within 3 months, 3-6 months, 6-12 months, and >12 months, respectively. The relative risk reduction of primary outcome events with empagliflozin was similar across HF hospitalization categories (P interaction = 0.67). The primary outcome absolute risk reduction was more pronounced among patients with a recent HF hospitalization but without statistical heterogeneity of treatment effect: -6.9, -5.5, -0.8, and -0.6 events prevented per 100 person-years for patients hospitalized within <3 months, 3-6 months, 6-12 months, and >12 months, respectively, and -2.4 events prevented per 100 person-years of follow-up in those without a prior HF hospitalization (P interaction = 0.64). Empagliflozin was safe irrespective of HF hospitalization recency. CONCLUSIONS:Patients with a recent HF hospitalization have a high risk of events. Empagliflozin reduced HF events regardless of HF hospitalization recency.
10.1016/j.jchf.2023.01.018
Impact of Malnutrition in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.
Journal of the American College of Cardiology
BACKGROUND:Although malnutrition is associated with poor prognosis in several diseases, its prognostic impact in patients with heart failure (HF) and secondary mitral regurgitation (SMR) is not understood. OBJECTIVES:The purpose of this study was to assess the prevalence and impact of malnutrition in HF patients with severe SMR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip plus guideline-directed medical therapy (GDMT) vs GDMT alone in the COAPT trial. METHODS:Baseline malnutrition risk was calculated using the validated geriatric nutritional risk index (GNRI) score. Patients were categorized as having "malnutrition" (GNRI ≤98) vs "no malnutrition" (GNRI >98). Outcomes were assessed through 4 years. The primary endpoint of interest was all-cause mortality. RESULTS:Among 552 patients, median baseline GNRI was 109 (IQR: 101-116); 94 (17.0%) had malnutrition. All-cause mortality at 4 years was greater in patients with vs those without malnutrition (68.3% vs 52.8%; P = 0.001). Using multivariable analysis, both baseline malnutrition (adjusted-HR [adj-HR]: 1.37; 95% CI: 1.03-1.82; P = 0.03) and randomization to TEER plus GDMT compared with GDMT alone (adj-HR: 0.65; 95% CI: 0.51-0.82; P = 0.0003) were independent predictors of 4-year mortality. In contrast, GNRI was unrelated to the 4-year rate of heart failure hospitalization (HFH), although TEER treatment reduced HFH (adj-HR: 0.46; 95% CI: 0.36-0.56). The reductions in death (adj-P = 0.46) and HFH (adj-P = 0.67) with TEER were consistent in patients with and without malnutrition. CONCLUSIONS:Malnutrition was present in 1 of 6 patients with HF and severe SMR enrolled in COAPT and was independently associated with increased 4-year mortality (but not HFH). TEER reduced mortality and HFH in patients with and without malnutrition. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079).
10.1016/j.jacc.2023.04.047
Degree of Joint Risk Factor Control and Incident Heart Failure in Hypertensive Patients.
JACC. Heart failure
BACKGROUND:Heart failure (HF) is a major complication in patients with hypertension. OBJECTIVES:This study aimed to investigate the extent to which joint risk factor control could attenuate hypertension-related excess risk of HF. METHODS:The study included a total of 75,293 participants with diagnosed hypertension from the UK Biobank and matched with 256,619 nonhypertensive control subjects, followed up until May 31, 2021. The degree of joint risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, body mass index, low-density lipoprotein cholesterol, hemoglobin A1c, albuminuria, smoking, and physical activity. The Cox proportional hazards models were used to estimate associations between the degree of risk factor control and risk of HF. RESULTS:Among hypertensive patients, joint risk factor control showed an association with a stepwise reduction of incident HF risk. Each additional risk factor control was related to a 20% lower risk, and the optimal risk factor control (controlling ≥6 risk factors) was associated with a 62% lower risk (HR: 0.38; 95% CI: 0.31-0.45). In addition, the study found that the hypertension-related excess risk of HF among participants jointly controlling ≥6 risk factors were even lower than in nonhypertensive control subjects (HR: 0.79; 95% CI: 0.67-0.94). The protective associations of joint risk factor control and risk of incident HF were broadly stronger among men than women and among medication users than nonusers (P for interaction < 0.05). CONCLUSIONS:The joint risk factor control is associated with a lower risk of incident HF in an accumulative and sex-specific manner. Optimal risk factor control may eliminate hypertension-related excess risk of HF.
10.1016/j.jchf.2023.01.006
International validation of the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score in heart failure.
European journal of preventive cardiology
AIMS:Current European heart failure (HF) guidelines suggest the use of risk score: among them, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score has demonstrated to be one of the most accurate. However, the risk scores are still poorly implemented in clinical practice, also due to the lack of strong evidence regarding their external validation in different populations. Thus, the current study was designed as an external validation test of the MECKI score in an international multicentre setting. METHODS AND RESULTS:The study cohort consisted of patients diagnosed with HF with reduced ejection fraction (HFrEF) across international centres (not Italian), retrospectively recruited. Collected data included demographics, HF aetiology, laboratory testing, electrocardiogram (ECG), echocardiographic findings, and cardiopulmonary exercise testing (CPET) results as described in the original MECKI score publication. A total of 1042 patients across 8 international centres (7 European and 1 Asian) were included and followed up from 1998 till 2019. Patients were divided according to the calculated MECKI scores into three subgroups: (i) MECKI score <10%, (ii) 10-20%, and (iii) ≥ 20%. Survival analysis comparison among the three MECKI score subgroups showed a worse prognosis in patients with higher MECKI score value: median event-free survival times were 4396 days for MECKI score <10%, 3457 days for 10-20%, and 1022 days for ≥20% (P < 0.0001). Receiver operating characteristic (ROC) curves and area under the ROC curves (AUC) were like those reported in the original internal validation studies. CONCLUSION:In patients diagnosed with HFrEF, the power of the MECKI score was confirmed in terms of prognosis and risk stratification, supporting its implementation as advised by the HF guidelines.
10.1093/eurjpc/zwad191
Pulmonary Artery Catheter Use and Risk of In-hospital Death in Heart Failure Cardiogenic Shock.
Journal of cardiac failure
BACKGROUND:Pulmonary artery catheters (PACs) are increasingly used to guide management decisions in cardiogenic shock (CS). The goal of this study was to determine if PAC use was associated with a lower risk of in-hospital mortality in CS owing to acute heart failure (HF-CS). METHODS AND RESULTS:This multicenter, retrospective, observational study included patients with CS hospitalized between 2019 and 2021 at 15 US hospitals participating in the Cardiogenic Shock Working Group registry. The primary end point was in-hospital mortality. Inverse probability of treatment-weighted logistic regression models were used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CI), accounting for multiple variables at admission. The association between the timing of PAC placement and in-hospital death was also analyzed. A total of 1055 patients with HF-CS were included, of whom 834 (79%) received a PAC during their hospitalization. In-hospital mortality risk for the cohort was 24.7% (n = 261). PAC use was associated with lower adjusted in-hospital mortality risk (22.2% vs 29.8%, OR 0.68, 95% CI 0.50-0.94). Similar associations were found across SCAI stages of shock, both at admission and at maximum SCAI stage during hospitalization. Early PAC use (≤6 hours of admission) was observed in 220 PAC recipients (26%) and associated with a lower adjusted risk of in-hospital mortality compared with delayed (≥48 hours) or no PAC use (17.3% vs 27.7%, OR 0.54, 95% CI 0.37-0.81). CONCLUSIONS:This observational study supports PAC use, because it was associated with decreased in-hospital mortality in HF-CS, especially if performed within 6 hours of hospital admission. CONDENSED ABSTRACT:An observational study from the Cardiogenic Shock Working Group registry of 1055 patients with HF-CS showed that pulmonary artery catheter (PAC) use was associated with a lower adjusted in-hospital mortality risk (22.2% vs 29.8%, odds ratio 0.68, 95% confidence interval 0.50-0.94) compared with outcomes in patients managed without PAC. Early PAC use (≤6 hours of admission) was associated with a lower adjusted risk of in-hospital mortality compared with delayed (≥48 hours) or no PAC use (17.3% vs 27.7%, odds ratio 0.54, 95% confidence interval 0.37-0.81).
10.1016/j.cardfail.2023.05.001
Lung ultrasound and diuretic therapy in chronic heart failure: a randomised trial.
Clinical research in cardiology : official journal of the German Cardiac Society
BACKGROUND:Lung congestion is frequent in heart failure (HF) and is associated with symptoms and poor prognosis. Lung ultrasound (LUS) identification of B-lines may help refining congestion assessment on top of usual care. Three small trials comparing LUS-guided therapy to usual care in HF suggested that LUS-guided therapy could reduce urgent HF visits. However, to our knowledge, the usefulness of LUS in influencing loop diuretic dose adjustment in ambulatory chronic HF has not been studied. AIMS:To study whether to show or not LUS results to the HF assistant physician would change loop diuretic adjustments in "stable" chronic ambulatory HF patients. METHODS:Prospective randomised single-blinded trial comparing two strategies: (1) open 8-zone LUS with B-line results available to clinicians, or (2) blind LUS. The primary outcome was change in loop diuretic dose (up- or down-titration). RESULTS:A total of 139 patients entered the trial, 70 were randomised to blind LUS and 69 to open LUS. The median (percentile) age was 72 (63-82) years, 82 (62%) were men, and the median LVEF was 39 (31-51) %. Randomisation groups were well balanced. Furosemide dose changes (up- and down-titration) were more frequent among patients in whom LUS results were open to the assistant physician: 13 (18.6%) in blind LUS vs. 22 (31.9%) in open LUS, OR 2.55, 95%CI 1.07-6.06. Furosemide dose changes (up- and down-titration) were more frequent and correlated significantly with the number of B-lines when LUS results were open (Rho = 0.30, P = 0.014), but not when LUS results were blinded (Rho = 0.19, P = 0.13). Compared to blind LUS, when LUS results were open, clinicians were more likely to up-titrate furosemide dose if the result "presence of pulmonary congestion" was identified and more likely to decrease furosemide dose in the case of an "absence of pulmonary congestion" result. The risk of HF events or cardiovascular death did not differ by randomisation group: 8 (11.4%) in blind LUS vs. 8 (11.6%) in open LUS. CONCLUSIONS:Showing the results of LUS B-lines to assistant physicians allowed more frequent loop diuretic changes (both up- and down-titration), which suggests that LUS may be used to tailor diuretic therapy to each patient congestion status.
10.1007/s00392-023-02238-9
Relation of Left Ventricular Diastolic Function to Global Fibrosis Burden: Implications for Heart Failure Risk Stratification.
JACC. Cardiovascular imaging
BACKGROUND:Left ventricular (LV) diastolic function is primarily assessed by means of echocardiography, which has limited utility in detecting fibrosis. Cardiac magnetic resonance (CMR) readily detects and quantifies fibrosis. OBJECTIVES:In this study, the authors sought to determine the association of LV diastolic function by echocardiography with CMR-determined global fibrosis burden and the incremental value of fibrosis with diastolic function grade in prediction of total mortality and heart failure hospitalizations. METHODS:A total of 549 patients underwent comprehensive echocardiography and CMR within 30 days. Echocardiography was used to assess LV diastolic function, and CMR was used to determine LV volumes, mass, ejection fraction, replacement fibrosis, and percentage extracellular volume fraction (ECV). RESULTS:Normal diastolic function was present in 142 patients; the rest had diastolic dysfunction grades I to III, except for 18 (3.3%) with indeterminate results. The event rate was higher in patients with diastolic dysfunction compared with patients with normal diastolic function (33.4% vs 15.5; P < 0.001). The model including LV diastolic function grades II and III predicted composite outcome (C-statistic: 0.71; 95% CI: 0.67-0.76), which increased by adding global fibrosis burden (C-statistic: 0.74, 95% CI: 0.70-0.78; P = 0.02). For heart failure hospitalizations, the competing risk model with LV diastolic function grades II and III was good (C-statistic: 0.78; 95% CI: 0.74-0.83) and increased significantly with the addition of global fibrosis burden (C-statistic: 0.80; 95% CI: 0.76-0.85; P = 0.03). CONCLUSIONS:Higher grades of diastolic dysfunction are seen in patients with replacement fibrosis and increased ECV. Fibrosis burden as determined with the use of CMR provides incremental prognostic information to echocardiographic evaluation of LV diastolic function.
10.1016/j.jcmg.2022.12.027
Atrial Fibrillation Ablation for Heart Failure With Preserved Ejection Fraction: A Randomized Controlled Trial.
JACC. Heart failure
BACKGROUND:Patients with heart failure with preserved ejection fraction (HFpEF) frequently develop atrial fibrillation (AF). There are no randomized trials examining the effects of AF ablation on HFpEF outcomes. OBJECTIVES:The aim of this study is to compare the effects of AF ablation vs usual medical therapy on markers of HFpEF severity, including exercise hemodynamics, natriuretic peptide levels, and patient symptoms. METHODS:Patients with concomitant AF and HFpEF underwent exercise right heart catheterization and cardiopulmonary exercise testing. HFpEF was confirmed with pulmonary capillary wedge pressure (PCWP) of 15 mm Hg at rest or ≥25 mm Hg on exercise. Patients were randomized to AF ablation vs medical therapy, with investigations repeated at 6 months. The primary outcome was change in peak exercise PCWP on follow-up. RESULTS:A total of 31 patients (mean age: 66.1 years; 51.6% females, 80.6% persistent AF) were randomized to AF ablation (n = 16) vs medical therapy (n = 15). Baseline characteristics were comparable across both groups. At 6 months, ablation reduced the primary outcome of peak PCWP from baseline (30.4 ± 4.2 to 25.4 ± 4.5 mm Hg; P < 0.01). Improvements were also seen in peak relative VO (20.2 ± 5.9 to 23.1 ± 7.2 mL/kg/min; P < 0.01), N-terminal pro-B-type natriuretic peptide levels (794 ± 698 to 141 ± 60 ng/L; P = 0.04), and MLHF (Minnesota Living with Heart Failure) score (51 ± -21.9 to 16.6 ± 17.5; P < 0.01). No differences were detected in the medical arm. Following ablation, 50% no longer met exercise right heart catheterization-based criteria for HFpEF vs 7% in the medical arm (P = 0.02). CONCLUSIONS:AF ablation improves invasive exercise hemodynamic parameters, exercise capacity, and quality of life in patients with concomitant AF and HFpEF.
10.1016/j.jchf.2023.01.008
Hemodynamic-Guided Heart Failure Management in Patients With Either Prior HF Hospitalization or Elevated Natriuretic Peptides.
JACC. Heart failure
BACKGROUND:In patients with symptomatic heart failure (HF) and previous heart failure hospitalization (HFH), hemodynamic-guided HF management using a wireless pulmonary artery pressure (PAP) sensor reduces HFH, but it is unclear whether these benefits extend to patients who have not been recently hospitalized but remain at risk because of elevated natriuretic peptides (NPs). OBJECTIVES:This study assessed the efficacy and safety of hemodynamic-guided HF management in patients with elevated NPs but no recent HFH. METHODS:In the GUIDE-HF (Hemodynamic-Guided Management of Heart Failure) trial, 1,000 patients with New York Heart Association (NYHA) functional class II to IV HF and either previous HFH or elevated NP levels were randomly assigned to hemodynamic-guided HF management or usual care. The authors evaluated the primary study composite of all-cause mortality and total HF events at 12 months according to treatment assignment and enrollment stratum (HFH vs elevated NPs) by using Cox proportional hazards models. RESULTS:Of 999 evaluable patients, 557 were enrolled on the basis of a previous HFH and 442 on the basis of elevated NPs alone. Those patients enrolled by NP criteria were older and more commonly White persons with lower body mass index, lower NYHA class, less diabetes, more atrial fibrillation, and lower baseline PAP. Event rates were lower among those patients in the NP group for both the full follow-up (40.9 per 100 patient-years vs 82.0 per 100 patient-years) and the pre-COVID-19 analysis (43.6 per 100 patient-years vs 88.0 per 100 patient-years). The effects of hemodynamic monitoring were consistent across enrollment strata for the primary endpoint over the full study duration (interaction P = 0.71) and the pre-COVID-19 analysis (interaction P = 0.58). CONCLUSIONS:Consistent effects of hemodynamic-guided HF management across enrollment strata in GUIDE-HF support consideration of hemodynamic monitoring in the expanded group of patients with chronic HF and elevated NPs without recent HFH. (Hemodynamic-Guided Management of Heart Failure [GUIDE-HF]; NCT03387813).
10.1016/j.jchf.2023.01.007
Trajectories of renal biomarkers and new-onset heart failure in the general population: Findings from the PREVEND study.
European journal of heart failure
AIMS:Renal dysfunction is one of the most critical risk factors for developing heart failure (HF). However, the association between repeated measures of renal function and incident HF remains unclear. Therefore, this study investigated the longitudinal trajectories of urinary albumin excretion (UAE) and serum creatinine and their association with new-onset HF and all-cause mortality. METHODS AND RESULTS:Using group-based trajectory analysis, we estimated trajectories of UAE and serum creatinine in 6881 participants from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study and their association with new-onset HF and all-cause death during the 11-years of follow-up. Most participants had stable low UAE or serum creatinine. Participants with persistently higher UAE or serum creatinine were older, more often men, and more often had comorbidities, such as diabetes, a previous myocardial infarction or dyslipidaemia. Participants with persistently high UAE had a higher risk of new-onset HF or all-cause mortality, whereas stable serum creatinine trajectories showed a linear association for new-onset HF and no association with all-cause mortality. CONCLUSION:Our population-based study identified different but often stable longitudinal patterns of UAE and serum creatinine. Patients with persistently worse renal function, such as higher UAE or serum creatinine, were at a higher risk of HF or mortality.
10.1002/ejhf.2925
Weight change and clinical outcomes in heart failure with reduced ejection fraction: insights from EMPEROR-Reduced.
European journal of heart failure
AIMS:Baseline body mass index (BMI) and weight loss promoted by sodium-glucose cotransporter 2 inhibitors may impact outcomes in patients with heart failure with reduced ejection fraction (HFrEF). We assessed in the EMPEROR-Reduced population treated with empagliflozin versus placebo the relationship between baseline BMI, weight loss and effects on the primary (time to first hospitalization for heart failure [HHF] or cardiovascular death) and key secondary outcomes. METHODS AND RESULTS:We categorized patients according to their baseline BMI: <20 kg/m (n = 180); 20 to <25 kg/m (n = 1038); 25 to <30 kg/m (n = 1345); 30 to <35 kg/m (n = 774) and ≥35 kg/m (n = 393). The treatment effect of empagliflozin on the primary outcome was consistent across all BMI categories (hazard ratios in subgroups 0.66-0.88, interaction trend p = 0.32), as was the effect on total (first plus recurrent) HHF (interaction trend p = 0.31). Empagliflozin reduced the rate of estimated glomerular filtration rate decline consistently across the BMI categories (interaction trend p = 0.67). Overall, incidence rates of any or serious adverse events were comparable between the treatment groups across all BMI categories. A total of 313 (17.4%) patients treated with empagliflozin experienced a weight loss of more than 5% at week 52 versus 230 (12.8%) in placebo. When analysed separately within each treatment group, presence of weight loss was similarly associated with an increased risk of all-cause mortality. CONCLUSION:The benefits of empagliflozin versus placebo were consistently present across all BMI categories in HFrEF patients. Weight loss was associated with higher risk of all-cause mortality, regardless of treatment group.
10.1002/ejhf.2728
Prognostic Significance of Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction.
The Canadian journal of cardiology
BACKGROUND:The prognostic impact of coronary microvascular dysfunction (CMD) has been scarcely addressed in heart failure with preserved ejection fraction (HFpEF). This study investigated the prevalence and prognostic significance of CMD as measured by a novel pressure wire-free coronary angiography-derived index of microcirculatory resistance (caIMR) on clinical outcomes. METHODS:Patients diagnosed with HFpEF from 2019 to 2021 were enrolled retrospectively. caIMR was used to quantify microvascular function, and patients were categorised into 2 groups based on their caIMR. The primary end points were composite of all-cause death and heart failure rehospitalisation. RESULTS:Of 137 HFpEF patients, CMD (defined as caIMR ≥ 25) was present in 88 patients (64.2%). Forty-five patients (32.8%) experienced composite events during a mean follow-up of 15 months. Compared with patients with caIMR < 25, those with caIMR ≥ 25 had a notably higher incidence of composite events (16.3% vs 42.0%; P = 0.002). On survival analysis, patients with caIMR ≥ 25 demonstrated a worse prognosis than those with caIMR < 25 for composite events (P = 0.006). Patients with caIMR ≥ 25 in multiple coronary arteries showed a trend to worse outcome than those with caIMR ≥ 25 in a single coronary artery (log-rank P = 0.056). In adjusted analysis, caIMR ≥ 25 was independently predictive of adverse outcomes (adjusted hazard ratio 2.93, 95% confidence interval [CI] 1.28-6.70; P = 0.010). caIMR displayed a significant predictive power for adverse event prediction (area under the receiver operating characteristic curve 0.767, 95% CI 0.677-0.858; P < 0.001). CONCLUSIONS:CMD is highly prevalent and is an independent predictor of adverse outcomes in HFpEF patients. Assessment of CMD may identify high-risk patients early for intensified treatment and risk-factor management.
10.1016/j.cjca.2023.04.011
Liver tests, cardiovascular outcomes and effects of empagliflozin in patients with heart failure and preserved ejection fraction: The EMPEROR-Preserved trial.
European journal of heart failure
AIM:The prognostic implication of elevated liver tests in heart failure with preserved ejection fraction (HFpEF) is uncertain. This analysis investigates the association of liver markers with hospitalization for heart failure (HHF) and cardiovascular death (CVD), and the treatment effect of empagliflozin across the range of liver marker levels. METHODS AND RESULTS:The double-blind, placebo-controlled EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure with Preserved Ejection Fraction) enrolled 5988 patients with HFpEF (ejection fraction >40%). Patients in New York Heart Association class II-IV and elevated N-terminal pro-B-type natriuretic peptide were randomized to receive empagliflozin 10 mg daily or placebo in addition to usual therapy. Patients with significant liver disease were excluded. The primary endpoint was time to first adjudicated HHF or CVD. We explored the association of liver function abnormalities with heart failure outcomes in patients on placebo, the effects of empagliflozin on liver tests and the treatment effects of empagliflozin on heart failure outcomes across categories of liver laboratory values. High alkaline phosphatase (p trend < 0.0001), low albumin (p trend < 0.0001) and high bilirubin (p = 0.02) were associated with poorer outcomes for HHF or CVD, while high aspartate aminotransferase was not, and high alanine aminotransferase was associated with better outcomes. Empagliflozin had no significant effects on liver tests compared to placebo except for albumin which was significantly increased. The treatment effect of empagliflozin on outcomes was not modified by liver tests. CONCLUSION:Abnormalities of liver function tests are associated differently with heart failure outcomes. Salutary effects of empagliflozin on liver tests were not observed although albumin increased. The treatment benefits of empagliflozin were not affected by baseline values of liver parameters.
10.1002/ejhf.2922
Prevalence, characteristics and cardiovascular and non-cardiovascular outcomes in patients with heart failure with supra-normal ejection fraction: Insight from the JROADHF study.
European journal of heart failure
AIMS:We aimed to investigate the characteristics and prognosis of patients with heart failure (HF) with supra-normal ejection fraction (HFsnEF) compared to HF with normal ejection fraction (HFnEF). METHODS AND RESULTS:Among 11 573 patients enrolled in the nationwide registry of hospitalized patients with HF in Japan, 1943 patients (16.8%) were classified as HFsnEF (left ventricular ejection fraction [LVEF] >65%), 3277 (28.3%) as HFnEF (50% ≤ LVEF ≤65%), 2024 (17.5%) as HF with mildly reduced ejection fraction (40% ≤ LVEF <50%) and 4329 (37.4%) as HF with reduced ejection fraction (LVEF <40%). Patients with HFsnEF were older, more likely to be women, had lower natriuretic peptide values, and had smaller left ventricles than those with HFnEF. The primary endpoint, the composite of cardiovascular death or HF readmission, did not differ between HFsnEF (802/1943, 41.3%) and HFnEF (1413/3277, 43.1%) during a median follow-up period of 870 days (hazard ratio [HR] 0.96, 95% confidence interval 0.88-1.05, p = 0.346). The incidence of secondary outcomes, including all-cause, cardiovascular, and non-cardiovascular deaths and HF readmission, did not differ between HFsnEF and HFnEF. In the multivariable Cox regression analysis, HFsnEF compared to HFnEF was associated with a lower adjusted HR for HF readmission but not with the primary and other secondary endpoints. HFsnEF was associated with a higher HR for the composite endpoint and all-cause death in women, and a higher HR for all-cause death in patients with renal dysfunction. CONCLUSIONS:Heart failure with supra-normal ejection fraction is a common and distinctive phenotype, and has different characteristics and prognoses from HFnEF.
10.1002/ejhf.2895
Prognostic Impact of Right Ventricular Strain in Isolated Severe Tricuspid Regurgitation.
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
BACKGROUND:Right ventricular (RV) systolic function is an established marker of outcomes in patients with severe tricuspid regurgitation (TR). Timely detection of RV dysfunction using conventional two-dimensional echocardiography is challenging. RV strain has emerged as an accurate and sensitive tool for the evaluation of RV function, with the capability to detect subclinical RV dysfunction. The aim of this study was to evaluate the prognostic value of RV strain parameters in early stages of severe TR. METHODS:Consecutive patients with at least severe TR (severe, massive, or torrential) and the absence of a formal indication for tricuspid valve intervention in secondary TR evaluated in the Heart Valve Clinic were prospectively included. RV systolic function was measured using conventional echocardiographic indices (RV fractional area change, tricuspid annular plane systolic excursion, and Doppler tissue imaging S wave [S']) and speckle-tracking echocardiography-derived automatic peak global longitudinal strain and free wall longitudinal strain (FWLS) using an automated two-dimensional strain analytic software. A combined end point of hospital admission due to heart failure or all-cause mortality was defined. RESULTS:A total of 266 patients were enrolled in the study, and 151 were ultimately included. Strain parameters detected a higher percentage of abnormal RV values compared with conventional indices. During a median follow-up period of 26 months (interquartile range, 13-42 months), 35% of the patients reached the combined end point. Cumulative event-free survival was significantly worse in patients with impaired RV global longitudinal strain and RV FWLS. Conventional indices of RV systolic function were not associated with outcomes (P > .05 for all). On multivariate analysis, RV FWLS was independently associated with mortality and heart failure (adjusted hazard ratio for abnormal RV FWLS, 5.90; 95% CI, 3.17-10.99; P < .001). CONCLUSION:In early stages of severe TR, RV FWLS is more frequently impaired compared with conventional indices of RV function. Among all parameters, RV FWLS is the strongest predictor of mortality and heart failure, independent of additional prognostic markers.
10.1016/j.echo.2023.02.009
Pulmonary Hypertension Phenotype Can Be Identified in Heart Failure With Reduced Ejection Fraction Using Echocardiographic Assessment of Pulmonary Artery Pressure With Supportive Use of Pressure Reflection Variables.
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
BACKGROUND:Pulmonary hypertension (PH) is frequent in patients with heart failure and reduced ejection fraction (HFrEF) with 2 different phenotypes: isolated postcapillary PH (IpcPH) and, with the worst prognosis, combined pre- and postcapillary PH (CpcPH). The aims of the present echocardiography study were to investigate (1) the ability to identify PH phenotype in patients with HFrEF using the newly adopted definition of PH (mean pulmonary artery pressure >20 mm Hg) and (2) the relationship between PH phenotype and right ventricular (RV) function. METHODS:One hundred twenty-four patients with HFrEF consecutively referred for heart transplant or heart failure workup were included with echocardiography and right heart catheterization within 48 hours. We estimated systolic pulmonary artery pressure (sPAP) and used a method to detect increased pulmonary vascular resistance (>3 Wood units) based on predefined thresholds of 3 pressure reflection (PRefl) variables (the acceleration time in the RV outflow tract [RVOT], the interval between peak RVOT and peak tricuspid regurgitant velocity, and the RV pressure augmentation following peak RVOT velocity). RESULTS:Using receiver operator characteristic analysis in a derivation group (n = 62), we identified sPAP ≥35 mm Hg as a cutoff that in a test group (n = 62) increased the likelihood of PH 6.6-fold. The presence of sPAP >40 mm Hg and 2 or 3 positive PRefl variables increased the probability of CpcPH 6- to 8-fold. A 2-step approach with primarily assessment of sPAP and the supportive use of PRefl variables in patients with mild/moderate PH (sPAP 41-59 mm Hg) showed 76% observer agreement and a weighted kappa of 0.63. The steady-state (pulmonary vascular resistance) and pulsatile (compliance, elastance) vascular loading are increased in both IpcPH and CpcPH with a comparable degree of RV dysfunction. CONCLUSIONS:The PH phenotype can be identified in HFrEF using standard echocardiographic assessment of pulmonary artery pressure with supportive use of PRefl variables in patients with mild to moderate PH.
10.1016/j.echo.2023.01.011
Association of left ventricular strain-volume loop characteristics with adverse events in patients with heart failure with preserved ejection fraction.
European heart journal. Cardiovascular Imaging
AIMS:Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by impaired diastolic function. Left ventricular (LV) strain-volume loops (SVL) represent the relation between strain and volume during the cardiac cycle and provide insight into systolic and diastolic function characteristics. In this study, we examined the association of SVL parameters and adverse events in HFpEF. METHODS AND RESULTS:In 235 patients diagnosed with HFpEF, LV-SVL were constructed based on echocardiography images. The endpoint was a composite of all-cause mortality and Heart Failure (HF)-related hospitalization, which was extracted from electronic medical records. Cox-regression analysis was used to assess the association of SVL parameters and the composite endpoint, while adjusting for age, sex, and NYHA class. HFpEF patients (72.3% female) were 75.8 ± 6.9 years old, had a BMI of 29.9 ± 5.4 kg/m2, and a left ventricular ejection fraction of 60.3 ± 7.0%. Across 2.9 years (1.8-4.1) of follow-up, 73 Patients (31%) experienced an event. Early diastolic slope was significantly associated with adverse events [second quartile vs. first quartile: adjusted hazards ratio (HR) 0.42 (95%CI 0.20-0.88)] after adjusting for age, sex, and NYHA class. The association between LV peak strain and adverse events disappeared upon correction for potential confounders [adjusted HR 1.02 (95% CI 0.96-1.08)]. CONCLUSION:Early diastolic slope, representing the relationship between changes in LV volume and strain during early diastole, but not other SVL-parameters, was associated with adverse events in patients with HFpEF during 2.9 years of follow-up.
10.1093/ehjci/jead117
Association Between Hemoglobin Levels and Efficacy of Intravenous Ferric Carboxymaltose in Patients With Acute Heart Failure and Iron Deficiency: An AFFIRM-AHF Subgroup Analysis.
Circulation
BACKGROUND:Iron deficiency, with or without anemia, is an adverse prognostic factor in heart failure (HF). In AFFIRM-AHF (a randomized, double-blind placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalizations and mortality in iron-deficient subjects admitted for acute heart failure), intravenous ferric carboxymaltose (FCM), although having no significant effect on the primary end point, reduced the risk of HF hospitalization (hHF) and improved quality of life versus placebo in iron-deficient patients stabilized after an acute HF (AHF) episode. These prespecified AFFIRM-AHF subanalyses explored the association between hemoglobin levels and FCM treatment effects. METHODS:AFFIRM-AHF was a multicenter, double-blind, randomized, placebo-controlled trial of FCM in hospitalized AHF patients with iron deficiency. Patients were stratified by baseline hemoglobin level (<12 versus ≥12 g/dL). In each subgroup, the primary composite (total hHF and cardiovascular death) and secondary (total hHF; total cardiovascular hospitalizations and cardiovascular death; time to cardiovascular death, and time to first/days lost due to hHF or cardiovascular death) outcomes were assessed with FCM versus placebo at week 52. Sensitivity analyses using the World Health Organization anemia definition (hemoglobin level <12 g/dL [women] or <13 g/dL [men]) were performed, among others. RESULTS:Of 1108 AFFIRM-AHF patients, 1107 were included in these subanalyses: 464 (FCM group, 228; placebo group, 236) had a hemoglobin level <12 g/dL, and 643 (FCM, 329; placebo, 314) had a hemoglobin level ≥12 g/dL. Patients with a hemoglobin level <12 g/dL were older (mean, 73.7 versus 69.1 years), with more frequent previous HF (75.0% versus 68.7%), serum ferritin <100 μg/L (75.4% versus 68.1%), and transferrin saturation <20% (87.9% versus 81.4%). For the primary outcome, annualized event rates per 100 patient-years with FCM versus placebo were 71.1 and 73.6 (rate ratio, 0.97 [95% CI, 0.66-1.41]), respectively, and 48.5 versus 72.9 (RR, 0.67 [95% CI, 0.48-0.93]) in the hemoglobin levels <12 and ≥12 g/dL subgroups, respectively. No significant interactions between hemoglobin subgroup and treatment effect were observed for primary (=0.15) or secondary outcomes. Changes from baseline in hemoglobin, serum ferritin and transferrin saturation were significantly greater with FCM versus placebo in both subgroups between weeks 6 and 52. Findings were similar using the World Health Organization definition for anemia. CONCLUSIONS:The effects of intravenous FCM on outcomes in iron-deficient patients stabilized after an AHF episode, including improvements in iron parameters over time, did not differ between patients with hemoglobin levels <12 and ≥12 g/dL. REGISTRATION:URL: https://www. CLINICALTRIALS:gov; Unique identifier: NCT02937454.
10.1161/CIRCULATIONAHA.122.060757
Prognostic value of functional tricuspid regurgitation quantified by cardiac magnetic resonance in heart failure.
European heart journal. Cardiovascular Imaging
AIMS:Quantitative assessment of tricuspid regurgitation (TR) is challenging, and the prognostic implications of cardiac magnetic resonance (CMR)-quantified measures of TR remain unclear in patients with heart failure with reduced ejection fraction (HFrEF). This study investigated the prognostic value of functional TR quantified by CMR in patients with HFrEF. METHODS AND RESULTS:A total of 262 patients with HFrEF who underwent CMR were analysed. Patients who had primary TR, who had acute HF, or for whom cardiac surgery was planned were excluded. TR volume and fraction were indirectly calculated via subtracting methods. The primary outcome was defined as a composite of all-cause death and hospitalization for HF. Renal outcome was defined as a composite of a decrease in estimated glomerular filtration rate ≥50% or progression to end-stage renal disease. During the follow-up period (median 921 days), 62 primary outcomes and 48 renal outcomes occurred. When divided into two or three groups based on TR fraction in Kaplan-Meier analysis, patients with higher TR fractions showed worse primary outcomes and renal outcomes than those with lower TR fractions. In Cox regression analysis, a 10% increase in TR fraction was significantly associated with primary outcome [hazard ratio (HR) 1.49, 95% confidence interval (CI) 1.29-1.73, P < 0.001] and renal outcome (HR 1.31, 95% CI 1.12-1.55, P = 0.001). TR fraction exhibited a strong positive linear relationship with primary outcomes and renal outcomes in restricted cubic spline curves. CONCLUSION:CMR-quantified measures of TR were independently associated with adverse clinical outcomes in patients with HFrEF.
10.1093/ehjci/jeac224
Ventricular rate in atrial fibrillation and the risk of heart failure and death.
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
AIMS:While clinical trials have suggested that a high ventricular rate is associated with increased risk of heart failure (HF) and mortality, all-comers studies are warranted. OBJECTIVE:To assess 1-year risk of new-onset diagnosed HF and all-cause mortality among rate-control treated patients presenting with atrial fibrillation (AF) on an electrocardiogram (ECG) according to ventricular rate. METHODS AND RESULTS:ECGs recorded at the Copenhagen General Practitioners Laboratory (2001-15) were used to identify patients with AF. Multivariate Cox proportional hazard regression models were used to compare risk of new-onset HF and all-cause mortality after first ECG presenting with AF according to ventricular rate on ECG [<60, 60-79, 80-99, and 100-110, > 110 beats per minute (bpm)]. We identified 7408 patients in treatment with rate control drugs at time of first ECG presenting with AF [median age 78 years (Q1,Q3 = 70-85 years)], 45.8% male, median ventricular rate 83 bpm, (Q1,Q3 = 71-101 bpm)]. During 1-year follow-up, 666 (9.0%) of all patients with AF developed HF and 858 (11.6%) died. Patients with AF ventricular rates 100-110 bpm and >110 bpm had a hazard ratio (HR) of 1.46 (CI: 1.10-1.95) and 2.41 (CI: 1.94-3.00) respectively for new-onset HF, compared with 60-79 bpm. Similarly, patients with AF ventricular rates 100-110 bpm and >110 bpm had a HR of 1.44 (CI: 1.13-1.82) and 1.34 (CI: 1.08-1.65) respectively for all-cause mortality, compared with 60-79 bpm. CONCLUSIONS:Ventricular rates ≥100 bpm among patients presenting with AF on ECG in treatment with rate control drugs were associated with greater risk of both new-onset HF and all-cause mortality.
10.1093/europace/euad088
Increased circulating phenylacetylglutamine concentration elevates the predictive value of cardiovascular event risk in heart failure patients.
Journal of internal medicine
BACKGROUND:Phenylacetylglutamine (PAGln)-a newly discovered microbial metabolite produced by phenylalanine metabolism-is reportedly associated with cardiovascular events via adrenergic receptors. Nonetheless, its association with cardiovascular outcomes in heart failure (HF) patients remains unknown. OBJECTIVES:This study aimed to prospectively investigate the prognostic value of PAGln for HF. METHODS:Plasma PAGln levels were quantified by liquid chromatography-tandem mass spectrometry. We first assessed the association between plasma PAGln levels and the incidence of adverse cardiovascular events in 3152 HF patients (including HF with preserved and reduced ejection fraction) over a median follow-up period of 2 years. The primary endpoint was the composite of cardiovascular death or heart transplantation. We then assessed the prognostic role of PAGln in addition to the classic biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP). The correlation between PAGln levels and β-blocker use was also investigated. RESULTS:In total, 520 cardiovascular deaths or heart transplantations occurred in the HF cohort. Elevated PAGln levels were independently associated with a higher risk of the primary endpoint in a dose-response manner, regardless of HF subtype. Concurrent assessment of PAGln and NT-proBNP levels enhanced risk stratification among HF patients. PAGln further showed prognostic value at low NT-proBNP levels. Additionally, the interaction effects between PAGln and β-blocker use were not significant. CONCLUSIONS:Plasma PAGln levels are an independent predictor of an increased risk of adverse cardiovascular events in HF. Our work could provide joint and complementary prognostic value to NT-proBNP levels in HF patients.
10.1111/joim.13653
Indexing cardiac volumes for peak oxygen uptake to improve differentiation of physiological and pathological remodeling: from elite athletes to heart failure patients.
European heart journal. Cardiovascular Imaging
AIMS:Cardiovascular structures adapt to meet metabolic demands, but current methodology for indexing by body size does not accurately reflect such variations. Therefore, we aimed to investigate how left ventricular end-diastolic volume (LVEDV) and left atrial maximal volume (LAVmax) are associated with absolute (L/min) peak oxygen uptake (VO2peak) and fat-free mass (FFM) compared to body surface area (BSA). We subsequently assessed the impact of indexing by absolute VO2peak, FFM, and BSA to discriminate pathological from physiological remodeling. METHODS AND RESULTS:We used data from 1190 healthy adults to explore relationships for BSA, FFM, and absolute VO2peak with LVEDV and LAVmax by regression and correlation analyses. We then compared these indexing methods for classification to normalcy/pathology in 61 heart failure patients and 71 endurance athletes using the chi-squared and Fisher exact tests and the net reclassification and integrated discrimination indices. Absolute VO2peak correlated strongly with LVEDV, explaining 52% of variance vs. 32% for BSA and 44% for FFM. Indexing LVEDV for VO2peak improved discrimination between heart failure patients and athletes on top of indexing to BSA. Seventeen out of 18 athletes classified to pathology by BSA were reclassified to normalcy by VO2peak indexing (P < 0.001), while heart failure patients were reclassified to pathology (39-95%, P < 0.001). All indexing methods explained below 20% of the variance in LAVmax in univariate models. CONCLUSIONS:Indexing LVEDV to VO2peak improves the ability to differentiate physiological and pathological enlargement. The LVEDV to absolute VO2peak ratio may be a key index in diagnosing heart failure and evaluating the athlete's heart.
10.1093/ehjci/jead034
Endothelin-1, Outcomes in Patients With Heart Failure and Reduced Ejection Fraction, and Effects of Dapagliflozin: Findings From DAPA-HF.
Circulation
BACKGROUND:ET-1 (endothelin-1) is implicated in the pathophysiology of heart failure and renal disease. Its prognostic importance and relationship with kidney function in patients with heart failure with reduced ejection fraction receiving contemporary treatment are uncertain. We investigated these and the efficacy of dapagliflozin according to ET-1 level in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure). METHODS:We investigated the incidence of the primary outcome (cardiovascular death or worsening heart failure), change in kidney function, and the effect of dapagliflozin according to baseline ET-1 concentration, adjusting in Cox models for other recognized prognostic variables in heart failure including NT-proBNP (N-terminal pro-B-type natriuretic peptide). We also examined the effect of dapagliflozin on ET-1 level. RESULTS:Overall, 3048 participants had baseline ET-1 measurements: tertile 1 (T1; ≤3.28 pg/mL; n=1016); T2 (>3.28-4.41 pg/mL; n=1022); and T3 (>4.41 pg/mL; n=1010). Patients with higher ET-1 were more likely male, more likely obese, and had lower left ventricular ejection fraction, lower estimated glomerular filtration rate, worse functional status, and higher NT-proBNP and hs-TnT (high-sensitivity troponin-T). In the adjusted Cox models, higher baseline ET-1 was independently associated with worse outcomes and steeper decline in kidney function (adjusted hazard ratio for primary outcome of 1.95 [95% CI, 1.53-2.50] for T3 and 1.36 [95% CI, 1.06-1.75] for T2; both versus T1; estimated glomerular filtration rate slope: T3, -3.19 [95% CI, -3.66 to -2.72] mL/min per 1.73 m per y, T2, -2.08 [95% CI, -2.52 to -1.63] and T1 -2.35 [95% CI, -2.79 to -1.91]; =0.002). The benefit of dapagliflozin was consistent regardless of baseline ET-1, and the placebo-corrected decrease in ET-1 with dapagliflozin was 0.13 pg/mL (95% CI, 0.25-0.01; =0.029). CONCLUSIONS:Higher baseline ET-1 concentration was independently associated with worse clinical outcomes and more rapid decline in kidney function. The benefit of dapagliflozin was consistent across the range of ET-1 concentrations measured, and treatment with dapagliflozin led to a small decrease in serum ET-1 concentration. REGISTRATION:URL: https://www. CLINICALTRIALS:gov; Unique identifier: NCT03036124.
10.1161/CIRCULATIONAHA.122.063327
Association of ischemic heart disease with long-term risk of cognitive decline and dementia: A cohort study.
Alzheimer's & dementia : the journal of the Alzheimer's Association
INTRODUCTION:The independent and joint effect of ischemic heart disease (IHD) and coexisting atrial fibrillation (AF) and heart failure (HF) on dementia risk is largely unknown. METHODS:This population-based cohort study included 2568 dementia-free participants (age ≥60 years) in SNAC-K, who were regularly examined from 2001-2004 through 2013-2016. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. Global cognitive function was assessed using a global cognitive composite z-score derived from five cognitive domains. Data were analyzed using Cox, Fine-Gray, and linear mixed-effects models. RESULTS:Overall, IHD at baseline was associated with multivariable-adjusted hazard ratio (HR) of 1.39 (95% confidence interval = 1.06-1.82) for dementia and multivariable-adjusted β-coefficient of -0.02 (-0.03 to -0.01) for annual changes in global cognitive z-score, independent of AF, HF, and cerebrovascular disease. Coexisting AF or HF did not add further risk to dementia and cognitive decline. DISCUSSION:IHD is independently associated with dementia and cognitive decline in older adults, whereas coexisting AF/HF is not associated with an increased risk. HIGHLIGHTS:Is a history of ischemic heart disease (IHD) associated with a risk for dementia? How do coexisting heart diseases affect this association? IHD was an independent risk factor for dementia in older adults. This association was independent of coexisting heart and cerebrovascular diseases. The coexistence of heart diseases did not confer additional risk for dementia.
10.1002/alz.13114
Atrial Fibrillation can adversely impact Heart Failure with Preserved Ejection Fraction by its association with Heart Failure Progression and Mortality: A Post-Hoc Propensity Score-Matched Analysis of the TOPCAT Americas Trial.
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
AIMS:Prevalent atrial fibrillation (AF) is associated with excess cardiovascular (CV) death (D) and hospitalizations (H) in heart failure (HF) with preserved ejection fraction (pEF). We evaluated if it had an independent role in excess CVD in HFpEF and studied its impact on cause-specific mortality and HF morbidity. METHODS AND RESULTS:We used propensity score-matched (PSM) cohorts from the TOPCAT Americas trial to account for confounding by other co-morbidities. Two prevalent AF presentations at study entry were compared: (i) subjects with Any AF event by history or on electrocardiogram (ECG) with PSM subjects without an AF event and (ii) subjects in AF on ECG with PSM subjects in sinus rhythm. We analyzed cause-specific modes of death and HF morbidity during a mean follow-up period of 2.9 years. A total of 584 subjects with Any AF event and 418 subjects in AF on ECG were matched. Any AF was associated with increased CVH [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11-1.61, P = 0.003], HFH (HR 1.44, 95% CI 1.12-1.86, P = 0.004), pump failure death (PFD) (HR 1.95, 95% CI 1.05-3.62, P = 0.035), and HF progression from New York Heart Association (NYHA) classes I/II to III/IV (HR 1.30, 95% CI 1.04-1.62, P = 0.02). Atrial fibrillation on ECG was associated with increased risk of CVD (HR 1.46, 95% CI 1.02-2.09, P = 0.039), PFD (HR 2.21, 95% CI 1.11-4.40, P = 0.024), and CVH and HFH (HR 1.37, 95% CI 1.09-1.72, P = 0.006 and HR 1.65, 95% CI 1.22-2.23, P = 0.001, respectively). Atrial fibrillation was not associated with risk of sudden death. Both Any AF and AF on ECG cohorts were associated with PFD in NYHA class III/IV HF. CONCLUSION:Prevalent AF can be an independent risk factor for adverse CV outcomes by its selective association with worsening HF, HFH, and PFD in HFpEF. Prevalent AF was not associated with excess sudden death risk in HFpEF. Atrial fibrillation was also associated with HF progression in early symptomatic HFpEF and PFD in advanced HFpEF. TRIAL REGISTRATION:TOPCAT trial is registered at www.clinicaltrials.gov:identifier NCT00094302.
10.1093/europace/euad095
Phenotyping of Elderly Patients With Heart Failure Focused on Noncardiac Conditions: A Latent Class Analysis From a Multicenter Registry of Patients Hospitalized With Heart Failure.
Journal of the American Heart Association
Background The burden of noncardiovascular conditions is becoming increasingly prevalent in patients with heart failure (HF). We aimed to identify novel phenogroups incorporating noncardiovascular conditions to facilitate understanding and risk stratification in elderly patients with HF. Methods and Results Data from a total of 1881 (61.2%) patients aged ≥65 years were extracted from a prospective multicenter registry of patients hospitalized for acute HF (N=3072). We constructed subgroups of patients with HF with preserved ejection fraction (HFpEF; N=826, 43.9%) and those with non-HFpEF (N=1055, 56.1%). Latent class analysis was performed in each subgroup using 17 variables focused on noncardiovascular conditions (including comorbidities, Clinical Frailty Scale, and Geriatric Nutritional Risk Index). The latent class analysis revealed 3 distinct clinical phenogroups in both HFpEF and non-HFpEF subgroups: (1) robust physical and nutritional status (Group 1: HFpEF, 41.2%; non-HFpEF, 46.0%); (2) multimorbid patients with renal impairment (Group 2: HFpEF, 40.8%; non-HFpEF, 41.9%); and (3) malnourished patients (Group 3: HFpEF, 18.0%; non-HFpEF, 12.1%). After multivariable adjustment, compared with Group 1, patients in Groups 2 and 3 had a higher risk for all-cause death over the 1-year postdischarge period (hazard ratio [HR], 2.79 [95% CI, 1.64-4.81] and HR, 2.73 [95% CI, 1.39-5.35] in HFpEF; HR, 1.96 [95% CI, 1.22-3.14] and HR, 2.97 [95% CI, 1.64-5.38] in non-HFpEF; respectively). Conclusions In elderly patients with HF, the phenomapping focused on incorporating noncardiovascular conditions identified 3 phenogroups, each representing distinct clinical outcomes, and the discrimination pattern was similar for both patients with HFpEF and non-HFpEF. This classification provides novel risk stratification and may aid in clinical decision making.
10.1161/JAHA.122.027689
Vitamin D Levels in Black Americans and the Association With Left Ventricular Remodeling and Incident Heart Failure With Preserved Ejectin Fraction: The Jackson Heart Study.
Journal of cardiac failure
BACKGROUND:In observational studies, a lower serum vitamin D concentration has been associated with an increased risk of cardiovascular disease. However, the associations between serum vitamin D levels and left ventricular (LV) structure and heart failure with preserved ejection fraction (HFpEF) have not been well-characterized among Black Americans. The prevalence of vitamin D deficiency is higher among Black Americans than in other race/ethnicity groups. We hypothesized that serum vitamin D levels are associated with LV concentric remodeling and incident HFpEF in Black Americans. METHODS AND RESULTS:Among 5306 Black Americans in the Jackson Heart Study cohort, we investigated the relationships between serum vitamin D levels and LV structure and function, evaluated with echocardiography, and incident HF hospitalization, categorized as either HF with reduced EF (HFrEF; an EF of <50%) or HFpEF (an EF of ≥50%). After adjustment for possible confounding factors, lower vitamin D levels were associated with greater relative wall thickness (β for 1 standard deviation [SD] increase -0.003, 95% confidence interval -0.005 to -0.000). Over a median follow-up period of 11 years (range 10.2-11.0 years), 340 participants developed incident HF (7.88 cases per 1000 person-years), including 146 (43%) HFrEF and 194 (57%) HFpEF cases. After adjustment, higher serum vitamin D levels were associated with decreased hazard for HF overall (hazard ratio for 1 SD increase 0.88, 95% confidence interval 0.78-0.99) driven by a significant association with HFpEF (hazard ratio for 1 SD increase 0.84, 95% confidence interval 0.71-0.99). CONCLUSIONS:In this community-based Black American cohort, lower serum vitamin D levels were associated with LV concentric remodeling and an increased hazard for HF, mainly HFpEF. Further investigation is required to examine whether supplementation with vitamin D can prevent LV concentric remodeling and incident HFpEF in Black Americans.
10.1016/j.cardfail.2022.07.049
Longitudinal Changes in Cardiac Troponin and Risk of Heart Failure Among Black Adults.
Journal of cardiac failure
BACKGROUND:Among Black adults, high-sensitivity cardiac troponin I (hs-cTnI) is associated with heart failure (HF) risk. The association of longitudinal changes in hs-cTnI with risk of incident HF, HF with reduced and preserved ejection fraction (HFrEF and HFpEF, respectively), among Black adults is not well-established. METHODS AND RESULTS:This study included Black participants from the Jackson Heart Study with available hs-cTnI data at visits 1 (2000-2004) and 2 (2005-2008) and no history of cardiovascular disease. Cox models were used to evaluate associations of categories of longitudinal change in hs-cTnI with incident HF risk. Among 2423 participants, 11.6% had incident elevation in hs-cTnI at visit 2, and 16.9% had stable or improved elevation (≤50% increase in hs-cTnI), and 4.0% had worsened hs-cTnI elevation (>50% increase). Over a median follow-up of 12.0 years, there were 139 incident HF hospitalizations (64 HFrEF, 58 HFpEF). Compared with participants without an elevated hs-cTnI, those with incident, stable or improved, or worsened hs-cTnI elevation had higher HF risk (adjusted hazard ratio 3.20 [95% confidence interval, 1.92-5.33]; adjusted hazard ratio 2.40, [95% confidence interval, 1.47-3.92]; and adjusted hazard ratio 8.10, [95% confidence interval, 4.74-13.83], respectively). Similar patterns of association were observed for risk of HFrEF and HFpEF. CONCLUSIONS:Among Black adults, an increase in hs-cTnI levels on follow-up was associated with a higher HF risk. LAY SUMMARY:The present study included 2423 Black adults from the Jackson Heart Study with available biomarkers of cardiac injury and no history of cardiovascular disease at visits 1 and 2. The majority of participants did not have evidence of cardiac injury at both visits (67.5%), 11.6% had evidence of cardiac injury only on follow-up, 14.5% had stable elevations, 4.0% had worsened elevations, and 2.4% had improved elevations of cardiac injury biomarkers during follow-up. Compared with participants without evidence of cardiac injury, those with new, stable, and worsened levels of cardiac injury had a higher risk of developing heart failure. TWEET:Among Black adults, persistent or worsening subclinical myocardial injury is associated with an elevated risk of HF.
10.1016/j.cardfail.2022.05.013
Right Ventricular Function and Pulmonary Coupling in Patients With Heart Failure and Preserved Ejection Fraction.
Journal of the American College of Cardiology
BACKGROUND:Limited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction (HFpEF). OBJECTIVES:This study sought to assess the clinical implications of RV function, the association with N-terminal pro-B-type natriuretic peptide, and the risk for adverse events among patients with HFpEF. METHODS:This study analyzed measures of RV function by assessing absolute RV free wall longitudinal strain (RVFWLS) and its ratio to estimated pulmonary artery systolic pressure (PASP) (RVFWLS/PASP ratio) in 528 patients (mean age 74 ± 8 years, 56% female) with adequate echocardiographic images quality enrolled in the PARAGON-HF trial. Associations with baseline N-terminal pro-B-type natriuretic peptide and with total HF hospitalizations and cardiovascular death were assessed, after accounting for confounders. RESULTS:Overall, 311 patients (58%) had evidence of RV dysfunction, defined as absolute RVFWLS <20%, and among the 388 patients (73%) with normal tricuspid annular planar systolic excursion and RV fractional area change, more than one-half showed impaired RV function. Lower values of RVFWLS and RVFWLS/PASP ratios were significantly associated with higher circulating N-terminal pro-B-type natriuretic peptide. With a median follow-up of 2.8 years, there were 277 total HF hospitalizations and cardiovascular deaths. Both absolute RVFWLS (HR: 1.39; 95% CI: 1.05-1.83; P = 0.018) and RVFWLS/PASP ratio (HR: 1.43; 95% CI: 1.13-1.80; P = 0.002) were significantly associated with the composite outcome. Treatment effect of sacubitril/valsartan was not modified by measures of RV function. CONCLUSIONS:Worsening RV function and its ratio to pulmonary pressure is common and significantly associated with an increased risk of HF hospitalizations and cardiovascular death in patients with HFpEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
10.1016/j.jacc.2023.05.010
Clinical and Echocardiographic Diversity Associated With Physical Fitness in the Project Baseline Health Study: Implications for Heart Failure Staging.
Journal of cardiac failure
BACKGROUND:Clinical and echocardiographic features may carry diverse information about the development of heart failure (HF). Therefore, we determined heterogeneity in clinical and echocardiographic phenotypes and its association with exercise capacity. METHODS:In 2036 community-dwelling individuals, we defined echocardiographic profiles of left and right heart remodeling and dysfunction. We subdivided the cohort based on presence (+) or absence (-) of HF risk factors (RFs) and echocardiographic abnormalities (RF-/Echo-, RF-/Echo+, RF+/Echo-, RF+/Echo+). Multivariable-adjusted associations between subgroups and physical performance metrics from 6-minute walk and treadmill exercise testing were assessed. RESULTS:The prevalence was 35.3% for RF-/Echo-, 4.7% for RF-/Echo+, 39.3% for RF+/Echo-, and 20.6% for RF+/Echo+. We observed large diversity in echocardiographic profiles in the Echo+ group. Participants with RF-/Echo+ (18.6% of Echo+) had predominantly echocardiographic abnormalities other than left ventricular (LV) diastolic dysfunction, hypertrophy and reduced ejection fraction, whereas their physical performance was similar to RF-/Echo-. In contrast, participants with RF+/Echo+ presented primarily with LV hypertrophy or dysfunction, features that related to lower 6-minute walking distance and lower exercise capacity. CONCLUSIONS:Subclinical echocardiographic abnormalities suggest HF pathogenesis, but the presence of HF risk factors and type of echo abnormality should be considered so as to distinguish adverse from benign adaptation and to stratify HF risk.
10.1016/j.cardfail.2023.04.008
The Risk of Heart Failure Progression in Patients With Patent Foramen Ovale: Differential Risk Associated With Device Closure.
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
BACKGROUND:A patent foramen ovale (PFO) can unload left atrial pressure via an interatrial shunt. We investigated whether device closure of PFO is associated with a subsequent risk of heart failure (HF), particularly in patients with structural heart disease or atrial fibrillation (AF). METHODS:We enrolled 4,804 consecutive patients who underwent transesophageal echocardiography at tertiary medical centers in Korea between 2007 and 2019. The primary outcome was the 4-year risk of HF hospitalization. Underlying structural heart disease was determined by echocardiography. RESULTS:A PFO was observed in 981 (20.4%) patients, where 161 underwent device closure. During follow-up (median, 3.5 [1.4-6.4] years), the primary outcome was lower in patients with PFO than in those without (2.6% vs 4.0%; adjusted hazard ratio [aHR], 0.65; 95% CI, 0.45-0.94; P = .021). Among the patients with PFO, the primary outcome was higher in the device closure group than in the no-closure group (5.5% vs 1.2%; aHR, 5.59; 95% CI, 4.26-7.34; P < .001). A consistent result was found in patients with structural heart disease or AF (9.6% vs 3.9%; aHR, 2.55; 95% CI, 1.95-3.33; P < .001), demonstrating an increased risk of the primary outcome proportionate to the number of combined structural abnormalities. However, no significant association was observed between the primary outcome and PFO closure in those without structural heart disease or AF (1.7% vs 1.5%; aHR, 1.22; 95% CI, 0.99-1.50; P = .054). CONCLUSION:Patients with underlying structural heart disease or AF may be predisposed to symptomatic HF progression after PFO closure. Therefore, careful medical surveillance with optimal risk management is needed in these patients.
10.1016/j.echo.2023.04.010
Ventricular Remodeling and Outcomes After Mitral Transcatheter Edge-to-Edge Repair in Heart Failure: The COAPT Trial.
JACC. Cardiovascular interventions
BACKGROUND:The relationship between left ventricular (LV) remodeling and clinical outcomes after treatment of severe mitral regurgitation (MR) in heart failure (HF) has not been examined. OBJECTIVES:The aim of this study was to evaluate the association between LV reverse remodeling and subsequent outcomes and assess whether transcatheter edge-to-edge repair (TEER) and residual MR are associated with LV remodeling in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. METHODS:Patients with HF and severe MR who remained symptomatic on guideline-directed medical therapy (GDMT) were randomized to TEER plus GDMT or GDMT alone. Baseline and 6-month core laboratory measurements of LV end-diastolic volume index and LV end-systolic volume index were examined. Change in LV volumes from baseline to 6 months and clinical outcomes from 6 months to 2 years were evaluated using multivariable regression. RESULTS:The analytical cohort comprised 348 patients (190 treated with TEER, 158 treated with GDMT alone). A decrease in LV end-diastolic volume index at 6 months was associated with reduced cardiovascular death between 6 months and 2 years (adjusted HR: 0.90 per 10 mL/m decrease; 95% CI: 0.81-1.00; P = 0.04), with consistent results in both treatment groups (P = 0.26). Directionally similar but nonsignificant relationships were present for all-cause death and HF hospitalization and between reduced LV end-systolic volume index and all outcomes. Neither treatment group nor MR severity at 30 days was associated with LV remodeling at 6 or 12 months. The treatment benefits of TEER were not significant regardless of the degree of LV remodeling at 6 months. CONCLUSIONS:In patients with HF and severe MR, LV reverse remodeling at 6 months was associated with subsequently improved 2-year outcomes but was not affected by TEER or the extent of residual MR. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079).
10.1016/j.jcin.2023.02.031
Effect of Canagliflozin on Heart Failure Hospitalization in Diabetes According to Baseline Heart Failure Risk.
JACC. Heart failure
BACKGROUND:In the CANVAS (Canagliflozin Cardiovascular Assessment Study) program, canagliflozin reduced the risk of heart failure (HF) hospitalization among individuals with type 2 diabetes mellitus (T2DM). OBJECTIVES:The purpose of this study was to evaluate heterogeneity in absolute and relative treatment effects of canagliflozin on HF hospitalization according to baseline HF risk as assessed by diabetes-specific HF risk scores (WATCH-DM [Weight (body mass index), Age, hyperTension, Creatinine, HDL-C, Diabetes control (fasting plasma glucose) and QRS Duration, MI and CABG] and TRS-HF [TIMI Risk Score for HF in Diabetes]). METHODS:Participants in the CANVAS trial were categorized into low, medium, and high risk for HF using the WATCH-DM score (for participants without prevalent HF) and the TRS-HF score (for all participants). The outcome of interest was time to first HF hospitalization. The treatment effect of canagliflozin vs placebo for HF hospitalization was compared across risk strata. RESULTS:Among 10,137 participants with available HF data, 1,446 (14.3%) had HF at baseline. Among participants without baseline HF, WATCH-DM risk category did not modify the treatment effect of canagliflozin (vs placebo) on HF hospitalization (P interaction = 0.56). However, the absolute and relative risk reduction with canagliflozin was numerically greater in the high-risk group (cumulative incidence, canagliflozin vs placebo: 8.1% vs 12.7%; HR: 0.62 [95% CI: 0.37-0.93]; P = 0.03; number needed to treat: 22) than in the low- and intermediate-risk groups. When overall study participants were categorized according to the TRS-HF score, a statistically significant difference in the treatment effect of canagliflozin across risk strata was observed (P interaction = 0.04). Canagliflozin significantly reduced the risk of HF hospitalization by 39% in the high-risk group (HR: 0.61 [95% CI: 0.48-0.78]; P < 0.001; number needed to treat: 20) but not in the intermediate- or low-risk groups. CONCLUSIONS:Among participants with T2DM, the WATCH-DM and TRS-HF can reliably identify those at high risk for HF hospitalization and most likely to benefit from canagliflozin.
10.1016/j.jchf.2023.03.025
Duration of Heart Failure With Preserved Ejection Fraction and Outcomes With Sacubitril/Valsartan: Insights From the PARAGON-HF Trial.
Journal of cardiac failure
OBJECTIVE:In this post hoc analysis of the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) trial, we evaluated clinical outcomes and responses to sacubitril/valsartan by duration of heart failure (HF) with left ventricular ejection fraction ≥ 45% at initial diagnosis. METHODS AND RESULTS:The primary outcome was a composite of total hospitalizations due to HF and cardiovascular deaths, analyzed by using a semiparametric proportional rates method, stratified by geographic region. Among 4784 (99.7%) randomized participants in the PARAGON-HF trial for whom baseline HF duration was captured, 1359 (28%) had durations of HF of < 6 months, 1295 (27%) of 6 months-2 years, and 2130 (45%) of > 2 years. Longer HF duration was associated with higher comorbidity burdens, worse health status and lower rates of prior hospitalization due to HF. Over a median follow-up of 35 months, longer HF duration was associated with a higher risk of first and recurrent primary events (per 100 patient-years): < 6 months, 12.0 (95% CI, 10.4-14.0); 6 months-2 years, 12.2 (10.6-14.2); > 2 years, 15.8 (14.2-17.5). Relative treatment effects of sacubitril/valsartan vs valsartan were consistent, irrespective of baseline HF duration on the primary endpoint (P = 0.112). Clinically meaningful (≥ 5 point) improvements in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Scores were also similarly observed, irrespective of HF duration; (P = 0.112). Adverse events were similar between treatment arms across HF duration categories. CONCLUSIONS:In PARAGON-HF, longer HF duration was independently predictive of adverse HF outcomes. Treatment effects of sacubitril/valsartan were consistent, irrespective of baseline HF duration, suggesting that even ambulatory patients with longstanding HFpEF and predominantly mild symptoms stand to benefit from treatment optimization.
10.1016/j.cardfail.2023.05.003
Dapagliflozin and diuretic utilization in heart failure with mildly reduced or preserved ejection fraction: the DELIVER trial.
European heart journal
AIMS:Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure with mildly reduced or preserved ejection fraction. In this study, the safety and efficacy of dapagliflozin according to background diuretic therapy and the influence of dapagliflozin on longitudinal diuretic use were evaluated. METHODS AND RESULTS:In this pre-specified analysis of the Dapagliflozin Evaluation to Improve the LIVEs of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial, the effects of dapagliflozin vs. placebo were assessed in the following subgroups: no diuretic, non-loop diuretic, and loop diuretic furosemide equivalent doses of <40, 40, and >40 mg, respectively. Of the 6263 randomized patients, 683 (10.9%) were on no diuretic, 769 (12.3%) were on a non-loop diuretic, and 4811 (76.8%) were on a loop diuretic at baseline. Treatment benefits of dapagliflozin on the primary composite outcome were consistent by diuretic use categories (Pinteraction = 0.64) or loop diuretic dose (Pinteraction = 0.57). Serious adverse events were similar between dapagliflozin and placebo arms, irrespective of diuretic use or dosing. Dapagliflozin reduced new initiation of loop diuretics by 32% [hazard ratio (HR) 0.68; 95% confidence interval (CI): 0.55-0.84, P < 0.001] but did not influence discontinuations/disruptions (HR 0.98; 95% CI: 0.86-1.13, P = 0.83) in follow-up. First sustained loop diuretic dose increases were less frequent, and sustained dose decreases were more frequent in patients treated with dapagliflozin: net difference of -6.5% (95% CI: -9.4 to -3.6; P < 0.001). The mean dose of loop diuretic increased over time in the placebo arm, a longitudinal increase that was significantly attenuated with treatment with dapagliflozin (placebo-corrected treatment effect of -2.5 mg/year; 95% CI: -1.5, -3.7, P < 0.001). CONCLUSION:In patients with heart failure with mildly reduced or preserved ejection fraction, the clinical benefits of dapagliflozin relative to placebo were consistent across a wide range of diuretic categories and doses with a similar safety profile. Treatment with dapagliflozin significantly reduced new loop diuretic requirement over time.
10.1093/eurheartj/ehad283
Association of Dapagliflozin vs Placebo With Individual Kansas City Cardiomyopathy Questionnaire Components in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Secondary Analysis of the DELIVER Trial.
JAMA cardiology
Importance:Dapagliflozin has been shown to improve overall health status based on aggregate summary scores of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction enrolled in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial. A comprehensive understanding of the responsiveness of individual KCCQ items would allow clinicians to better inform patients on expected changes in daily living with treatment. Objective:To examine the association of dapagliflozin treatment with changes in individual components of the KCCQ. Design, Setting, and Participants:This is a post hoc exploratory analysis of DELIVER, a randomized double-blind placebo-controlled trial conducted at 353 centers in 20 countries from August 2018 to March 2022. KCCQ was administered at randomization and 1, 4, and 8 months. Scores of individual KCCQ components were scaled from 0 to 100. Eligibility criteria included symptomatic HF with left ventricular ejection fraction greater than 40%, elevated natriuretic peptide levels, and evidence of structural heart disease. Data were analyzed from November 2022 to February 2023. Main Outcomes and Measures:Changes in the 23 individual KCCQ components at 8 months. Interventions:Dapagliflozin, 10 mg, once daily or placebo. Results:Baseline KCCQ data were available for 5795 of 6263 randomized patients (92.5%) (mean [SD] age, 71.5 [9.5] years; 3344 male [57.7%] and 2451 female [42.3%]). Dapagliflozin was associated with larger improvements in almost all KCCQ components at 8 months compared with placebo. The most significant improvements with dapagliflozin were observed in frequency of lower limb edema (difference, 3.2; 95% CI, 1.6-4.8; P < .001), sleep limitation by shortness of breath (difference, 3.0; 95% CI, 1.6-4.4; P < .001), and limitation in desired activities by shortness of breath (difference, 2.8; 95% CI, 1.3-4.3; P < .001). Similar treatment patterns were observed in longitudinal analyses integrating data from months 1, 4, and 8. Higher proportions of patients treated with dapagliflozin experienced improvements, and fewer had deteriorations across most individual components. Conclusions and Relevance:In this study of patients with HF with mildly reduced or preserved ejection fraction, dapagliflozin was associated with improvement in a broad range of individual KCCQ components, with the greatest benefits in domains related to symptom frequency and physical limitations. Potential improvements in specific symptoms and activities of daily living might be more readily recognizable and easily communicated to patients. Trial Registration:ClinicalTrials.gov Identifier: NCT03619213.
10.1001/jamacardio.2023.1342
Prognostic value of ventricle epicardial fat volume by cardiovascular magnetic resonance in chronic heart failure.
iScience
The purpose of this study is to explore the prognostic values of ventricle epicardial fat volume (EFV) calculated by cardiac magnetic resonance in patients with chronic heart failure (CHF). A total of 516 patients with CHF (left ventricular ejection fraction ≤ 50%) were recruited, and 136 (26.4%) of whom experienced major adverse cardiovascular events (MACE) within median follow-up of 24 months. The target marker-EFV was found to be associated with MACE in both univariate and multivariable analysis adjusted for various clinical variables (p < 0.01), regardless as a continuous variable and categorized by X-tile program. EFV also showed promising predictive ability, with an area under the curve of 0.612, 0.618, and 0.687 for the prediction of 1-year, 2-year, and 3-year MACE, respectively. In conclusion, EFV could be a useful prognostic marker for CHF patients, helping to identify individuals at greater risk of MACE.
10.1016/j.isci.2023.106755
Conventional heart failure therapy in cardiac ATTR amyloidosis.
European heart journal
AIMS:The aims of this study were to assess prescription patterns, dosages, discontinuation rates, and association with prognosis of conventional heart failure medications in patients with transthyretin cardiac amyloidosis (ATTR-CA). METHODS AND RESULTS:A retrospective analysis of all consecutive patients diagnosed with ATTR-CA at the National Amyloidosis Centre between 2000 and 2022 identified 2371 patients with ATTR-CA. Prescription of heart failure medications was greater among patients with a more severe cardiac phenotype, comprising beta-blockers in 55.4%, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin II receptor blockers (ARBs) in 57.4%, and mineralocorticoid receptor antagonists (MRAs) in 39.0% of cases. During a median follow-up of 27.8 months (interquartile range 10.6-51.3), 21.7% had beta-blockers discontinued, and 32.9% had ACEi/ARBs discontinued. In contrast, only 7.5% had MRAs discontinued. A propensity score-matched analysis demonstrated that treatment with MRAs was independently associated with a reduced risk of mortality in the overall population [hazard ratio (HR) 0.77 (95% confidence interval (CI) 0.66-0.89), P < .001] and in a pre-specified subgroup of patients with a left ventricular ejection fraction (LVEF) >40% [HR 0.75 (95% CI 0.63-0.90), P = .002]; and treatment with low-dose beta-blockers was independently associated with a reduced risk of mortality in a pre-specified subgroup of patients with a LVEF ≤40% [HR 0.61 (95% CI 0.45-0.83), P = .002]. No convincing differences were found for treatment with ACEi/ARBs. CONCLUSION:Conventional heart failure medications are currently not widely prescribed in ATTR-CA, and those that received medication had more severe cardiac disease. Beta-blockers and ACEi/ARBs were often discontinued, but low-dose beta-blockers were associated with reduced risk of mortality in patients with a LVEF ≤40%. In contrast, MRAs were rarely discontinued and were associated with reduced risk of mortality in the overall population; but these findings require confirmation in prospective randomized controlled trials.
10.1093/eurheartj/ehad347
Hyponatraemia and changes in natraemia during hospitalization for acute heart failure and associations with in-hospital and long-term outcomes - from the ESC-HFA EORP Heart Failure Long-Term Registry.
European journal of heart failure
AIMS:To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes. METHODS AND RESULTS:Of 8298 patients in the European Society of Cardiology Heart Failure Long-Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers. In-hospital death occurred in 3.3%. The prevalence of hyponatraemia and in-hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in-hospital mortality 6.9%), 11% Yes/No (in-hospital mortality 4.9%), 8% No/Yes (in-hospital mortality 4.7%), and 72% No/No (in-hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In-hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12-month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35-1.89), Yes/No 1.35 (1.14-1.59), and No/Yes 1.18 (0.96-1.45). For death or heart failure hospitalization they were 1.38 (1.21-1.58), 1.17 (1.02-1.33), and 1.09 (0.93-1.27), respectively. CONCLUSION:Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in-hospital and post-discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk.
10.1002/ejhf.2873
Impact of dapagliflozin on cardiac remodelling in patients with chronic heart failure: The DAPA-MODA study.
European journal of heart failure
AIMS:Dapagliflozin improves the prognosis of patients with heart failure (HF), regardless of left ventricular ejection fraction (LVEF). However, its effect on cardiac remodelling parameters, specifically left atrial (LA) remodelling, is not well established. METHODS AND RESULTS:The DAPA-MODA trial (NCT04707352) is a multicentre, single-arm, open-label, prospective and interventional study that aimed to evaluate the effect of dapagliflozin on cardiac remodelling parameters over 6 months. Patients with stable chronic HF receiving optimized guideline-directed therapy, except for any sodium-glucose cotransporter 2 inhibitor, were included. Echocardiography was performed at baseline, 30 and 180 days, and analysed by a central core-lab in a blinded manner to both patient and time. The primary endpoint was the change in maximal LA volume index (LAVI). A total of 162 patients (64.2% men, 70.5 ± 10.6 years, 52% LVEF >40%) were included in the study. At baseline, LA dilatation was observed (LAVI 48.1 ± 22.6 ml/m ) and LA parameters were similar between LVEF-based phenotypes (≤40% vs. >40%). LAVI showed a significant reduction at 180 days (-6.6% [95% confidence interval -11.1, -1.8], p = 0.008), primarily due to a decrease in reservoir volume (-13.8% [95% confidence interval -22.5, -4], p = 0.007). Left ventricular geometry improved with significant reductions in left ventricular mass index (-13.9% [95% confidence interval -18.7, -8.7], p < 0.001), end-diastolic volume (-8.0% [95% confidence interval -11.6, -4.2], p < 0.001) and end-systolic volume (-11.9% [95% confidence interval -16.7, -6.8], p < 0.001) at 180 days. N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed a significant reduction at 180 days (-18.2% [95% confidence interval -27.1, -8.2], p < 0.001), without changes in filling Doppler measures. CONCLUSION:Dapagliflozin administration in stable out-setting patients with chronic HF and optimized therapy results in global reverse remodelling of cardiac structure, including reductions in LA volumes and improvement in left ventricular geometry and NT-proBNP concentrations.
10.1002/ejhf.2884
Effect of Torsemide Versus Furosemide on Symptoms and Quality of Life Among Patients Hospitalized for Heart Failure: The TRANSFORM-HF Randomized Clinical Trial.
Circulation
BACKGROUND:Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As prespecified secondary end points, the TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) compared the effect of torsemide versus furosemide on patient-reported outcomes among patients with HF. METHODS:TRANSFORM-HF was an open-label, pragmatic, randomized trial of 2859 patients hospitalized for HF (regardless of ejection fraction) across 60 hospitals in the United States. Patients were randomly assigned in a 1:1 ratio to a loop diuretic strategy of torsemide or furosemide with investigator-selected dosage. This report examined effects on prespecified secondary end points, which included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; assessed as adjusted mean difference in change from baseline; range, 0-100 with 100 indicating best health status; clinically important difference, ≥5 points) and Patient Health Questionnaire-2 (range, 0-6; score ≥3 supporting evaluation for depression) over 12 months. RESULTS:Baseline data were available for 2787 (97.5%) patients for KCCQ-CSS and 2624 (91.8%) patients for Patient Health Questionnaire-2. Median (interquartile range) baseline KCCQ-CSS was 42 (27-60) in the torsemide group and 40 (24-59) in the furosemide group. At 12 months, there was no significant difference between torsemide and furosemide in change from baseline in KCCQ-CSS (adjusted mean difference, 0.06 [95% CI, -2.26 to 2.37]; =0.96) or the proportion of patients with Patient Health Questionnaire-2 score ≥3 (15.1% versus 13.2%: =0.34). Results for KCCQ-CSS were similar at 1 month (adjusted mean difference, 1.36 [95% CI, -0.64 to 3.36]; =0.18) and 6-month follow-up (adjusted mean difference, -0.37 [95% CI, -2.52 to 1.78]; =0.73), and across subgroups by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent before hospitalization. Irrespective of baseline KCCQ-CSS tertile, there was no significant difference between torsemide and furosemide on change in KCCQ-CSS, all-cause mortality, or all-cause hospitalization. CONCLUSIONS:Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 months. The effects of torsemide and furosemide on patient-reported outcomes were similar regardless of ejection fraction, previous loop diuretic use, and baseline health status. REGISTRATION:URL: https://www. CLINICALTRIALS:gov; Unique identifier: NCT03296813.
10.1161/CIRCULATIONAHA.123.064842
Impact of mental disorders on the risk of heart failure among Korean patients with diabetes: a cohort study.
Cardiovascular diabetology
BACKGROUND:Few studies have assessed the correlation between coexisting mental disorders in participants with diabetes mellitus (DM) and the risk of heart failure (HF). Herein, we conducted a cohort study to determine the association between the accumulation of mental disorders in participants with DM and the risk of HF. METHODS:The Korean National Health Insurance Service records were assessed. 2,447,386 adults with DM who underwent health screening between 2009 and 2012 were analyzed. Participants with major depressive disorder, bipolar disorder, schizophrenia, insomnia, or anxiety disorders were included. In addition, participants were categorized based on the number of coexisting mental disorders. Each participant was followed until December 2018 or until the onset of HF. Cox proportional hazard modelling with confounding factors adjustment was conducted. In addition, a competing risk analysis was conducted. Subgroup analysis assessed the impact of clinical variables on the association between the accumulation of mental disorders and the risk of HF. RESULTS:The median follow-up duration was 7.09 years. The accumulation of mental disorders was associated with a risk of HF (zero mental disorder (0), reference; 1 mental disorder, adjusted hazard ratio (aHR): 1.222, 95% confidence intervals (CI): 1.207-1.237; 2 mental disorders, aHR: 1.426, CI: 1.403-1.448; ≥3 mental disorders, aHR: 1.667, CI: 1.632-1.70. In the subgroup analysis, the strength of association was the strongest in the younger age group (< 40 years, 1 mental disorder, aHR 1.301, CI 1.143-1.481; ≥2 mental disorders, aHR 2.683, CI 2.257-3.190; 40-64 years, 1 mental disorder, aHR 1.289, CI 1.265-1.314; ≥2 mental disorders, aHR 1.762, CI 1.724-1.801; ≥65 years, 1 mental disorder, aHR 1.164, CI 1.145-1.183; ≥2 mental disorders, aHR 1.353, CI 1.330-1.377; P<0.001). In addition, income, BMI, hypertension, chronic kidney disease, history of cardiovascular disease, insulin use, and duration of DM showed significant interactions. CONCLUSIONS:Comorbid mental disorders in participants with DM are associated with an increased risk of HF. In addition, the association was stronger in a younger age group. Participants with DM and mental disorders should be monitored with increased frequency for signs of HF; for which they have a higher risk than the general population.
10.1186/s12933-023-01809-4
Exercise-induced B-lines for the diagnosis of heart failure with preserved ejection fraction: a two-centre study.
Clinical research in cardiology : official journal of the German Cardiac Society
BACKGROUND:Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging despite the use of scores/algorithms. This study intended to assess the diagnostic value of exercise lung ultrasound (LUS) for HFpEF diagnosis. METHODS:We studied two independent case-control studies of HFpEF patients and control subjects undergoing different exercise protocols: (i) submaximal exercise stress echocardiography (ESE) with LUS performed by expert cardiologists (N = 116, HFpEF = 65.5%), and (ii) maximal cycle ergometer test (CET) (N = 54, HFpEF = 50%) with LUS performed by unexperienced physicians shortly trained for the study. B-line kinetics (i.e. peak values and their changes from rest) were assessed. RESULTS:In the ESE cohort, the C-index (95% CI) of peak B-lines for HFpEF diagnosis was 0.985 (0.968-1.000), whereas the C-index of rest and exercise HFA-PEFF scores (i.e. including stress echo findings) were < 0.90 (CI 0.823-0.949), and that of H2FPEF score was < 0.70 (CI 0.558-0.764). The C-index increase of peak B-lines on top of the above-mentioned scores was significant (C-index increase > 0.090 and P-value < 0.001 for all). Similar results were observed for change B-lines. Peak B-lines > 5 (sensitivity = 93.4%, specificity = 97.5%) and change B-lines > 3 (sensitivity = 94.7%, specificity = 87.5%) were the best cutoffs for HFpEF diagnosis. Adding peak or change B-lines on top of HFpEF scores and BNP significantly improved diagnostic accuracy. Peak B-lines showed a good diagnostic accuracy in the LUS beginner-led CET cohort (C-index = 0.713, 0.588-0.838). CONCLUSIONS:Exercise LUS showed excellent diagnostic value for HFpEF diagnosis regardless of different exercise protocols/level of expertise, with additive diagnostic accuracy on top of available scores and natriuretic peptides.
10.1007/s00392-023-02219-y
Survival prediction of heart failure patients using motion-based analysis method.
Computer methods and programs in biomedicine
BACKGROUND AND OBJECTIVE:Survival prediction of heart failure patients is critical to improve the prognostic management of the cardiovascular disease. The existing survival prediction methods focus on the clinical information while lacking the cardiac motion information. we propose a motion-based analysis method to predict the survival risk of heart failure patients for aiding clinical diagnosis and treatment. METHODS:We propose a motion-based analysis method for survival prediction of heart failure patients. First, our method proposes the hierarchical spatial-temporal structure to capture the myocardial border. It promotes the model discrimination on border features. Second, our method explores the dense optical flow structure to capture motion fields. It improves the tracking capability on cardiac images. The cardiac motion information is obtained by fusing boundary information and motion fields of cardiac images. Finally, our method proposes the multi-modality deep-cox structure to predict the survival risk of heart failure patients. It improves the survival probability of heart failure patients. RESULTS:The motion-based analysis method is confirmed to be able to improve the survival prediction of heart failure patients. The precision, recall, F1-score, and C-index are 0.8519, 0.8333, 0.8425, and 0.8478, respectively, which is superior to other state-of-the-art methods. CONCLUSIONS:The experimental results show that the proposed model can effectively predict survival risk of heart failure patients. It facilitates the application of robust clinical treatment strategies.
10.1016/j.cmpb.2023.107547
Patient profiles in heart failure with reduced ejection fraction: Prevalence, characteristics, treatments and outcomes in a real-world heart failure population.
European journal of heart failure
AIMS:The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guideline-directed medical treatments according to patient's profiles. The aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles. METHODS AND RESULTS:Patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013 and 2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate [eGFR]), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The nine most frequent profiles accounting for 70.5% of the population had eGFR 30-60 or ≥60 ml/min/1.73 m , sBP 90-140 mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30-60 ml/min/1.73 m and AF. We also identified nine profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR <30 ml/min/1.73 m and AF. The three profiles with eGFR 30-60 ml/min/1.73 m also showed sBP <90 mmHg. CONCLUSIONS:In a real-world cohort, most patients fit in a few easily identifiable profiles; the nine profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drug implementation and follow-up.
10.1002/ejhf.2892
Echocardiographic Features Beyond Ejection Fraction and Associated Outcomes in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction.
Circulation. Heart failure
BACKGROUND:Heart failure (HF) guidelines recommend assessment of left ventricular ejection fraction (LVEF) to classify patients and guide therapy implementation. However, LVEF alone may be insufficient to adequately characterize patients with HF, especially those with mildly reduced or preserved LVEF. Recommendations on additional testing are lacking, and there are limited data on use of echocardiographic features beyond LVEF in patients with heart failure with mildly reduced or preserved LVEF. METHODS:In patients with HF with mildly reduced or preserved LVEF identified in a large US health care system, the association of the following metrics with mortality was evaluated: LV global longitudinal strain (LV GLS>-16), left atrial volume index (>28 mL/m), left ventricular hypertrophy (LVH), and E/e´>13 and e´<9. A multivariable model for mortality was constructed including age, sex, and key comorbidities followed by stepwise selection of echocardiographic features. Characteristics and outcomes of subgroups with normal versus abnormal LV GLS and LVEF were evaluated. RESULTS:Among 2337 patients with complete echocardiographic data assessed between 2017 and 2020, the following features were associated with all-cause mortality on univariate analysis over 3 years of follow-up: E/e´+e´, LV GLS, left atrial volume index (all <0.01). In the multivariable model (-index=0.65), only abnormal LV GLS was independently associated with all-cause mortality (HR, 1.35 [95% CI, 1.11-1.63]; =0.002). Among patients with LVEF>55%, 498/1255 (40%) demonstrated abnormal LV GLS. Regardless of specific LVEF, patients with abnormal LV GLS demonstrated a higher burden of multiple comorbidities and higher event rates compared with patients with normal LV GLS. CONCLUSIONS:In a large, real-world HF with mildly reduced or preserved LVEF population, echocardiographic features, led by LV GLS, were associated with adverse outcomes irrespective of LVEF. A large proportion of patients demonstrate adverse myocardial function by LV GLS despite preserved LVEF and may represent a key cohort of interest for HF medical therapies and future clinical studies.
10.1161/CIRCHEARTFAILURE.122.010252
Heart Failure-Type Symptom Score Trajectories in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.
American journal of kidney diseases : the official journal of the National Kidney Foundation
RATIONALE & OBJECTIVE:Quality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individuals with CKD to understand the patterns and trajectories of HF-type symptoms in this setting. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF. PREDICTORS:Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and electrocardiographic parameters. OUTCOME:Trajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire [KCCQ] Overall Summary Score with a range of 0-100 where<75 reflects clinically significant symptoms). ANALYTICAL APPROACH:Latent class mixed models were used to model trajectories. Multinomial logistic regression was used to model relationships of predictors with trajectory group membership. RESULTS:Five trajectories of KCCQ score were identified in the cohort of 3,044 adults, 45% of whom were female, and whose median age was 61 years. Group 1 (41.7%) had a stable high score (minimal symptoms, average score of 96); groups 2 (35.6%) and 3 (15.6%) had stable but lower scores (mild symptoms [average of 81] and clinically significant symptoms [average of 52], respectively). Group 4 (4.9%) had a substantial worsening in symptoms over time (mean 31-point decline), and group 5 (2.2%) had a substantial improvement (mean 33-point increase) in KCCQ score. A majority of group 1 was male, without diabetes or obesity, and this group had higher baseline kidney function. A majority of groups 2 and 3 had diabetes and obesity. A majority of group 4 was male and had substantial proteinuria. Group 5 had the highest proportion of baseline cardiovascular disease (CVD). LIMITATIONS:No validation cohort available, CKD management changes in recent years may alter trajectories, and latent class models depend on the missing at random assumption. CONCLUSIONS:Distinct HF-type symptom burden trajectories were identified in the setting of CKD, corresponding to different baseline characteristics. These results highlight the diversity of HF-type symptom experiences in individuals with CKD.
10.1053/j.ajkd.2022.09.016
Identifying distinct clinical clusters in heart failure with mildly reduced ejection fraction.
International journal of cardiology
INTRODUCTION:Heart failure (HF) is a heterogeneous syndrome, and the specific sub-category HF with mildly reduced ejection fraction (EF) range (HFmrEF; 41-49% EF) is only recently recognised as a distinct entity. Cluster analysis can characterise heterogeneous patient populations and could serve as a stratification tool in clinical trials and for prognostication. The aim of this study was to identify clusters in HFmrEF and compare cluster prognosis. METHODS AND RESULTS:Latent class analysis to cluster HFmrEF patients based on their characteristics was performed in the Swedish HF registry (n = 7316). Identified clusters were validated in a Dutch cross-sectional HF registry-based dataset CHECK-HF (n = 1536). In Sweden, mortality and hospitalisation across the clusters were compared using a Cox proportional hazard model, with a Fine-Gray sub-distribution for competing risks and adjustment for age and sex. Six clusters were discovered with the following prevalence and hazard ratio with 95% confidence intervals (HR [95%CI]) vs. cluster 1: 1) low-comorbidity (17%, reference), 2) ischaemic-male (13%, HR 0.9 [95% CI 0.7-1.1]), 3) atrial fibrillation (20%, HR 1.5 [95% CI 1.2-1.9]), 4) device/wide QRS (9%, HR 2.7 [95% CI 2.2-3.4]), 5) metabolic (19%, HR 3.1 [95% CI 2.5-3.7]) and 6) cardio-renal phenotype (22%, HR 2.8 [95% CI 2.2-3.6]). The cluster model was robust between both datasets. CONCLUSION:We found robust clusters with potential clinical meaning and differences in mortality and hospitalisation. Our clustering model could be valuable as a clinical differentiation support and prognostic tool in clinical trial design.
10.1016/j.ijcard.2023.05.024