Heart failure with mid-range or mildly reduced ejection fraction.
Nature reviews. Cardiology
Left ventricular ejection fraction (EF) remains the major parameter for diagnosis, phenotyping, prognosis and treatment decisions in heart failure. The 2016 ESC heart failure guidelines introduced a third EF category for an EF of 40-49%, defined as heart failure with mid-range EF (HFmrEF). This category has been largely unexplored compared with heart failure with reduced EF (HFrEF; defined as EF <40% in this Review) and heart failure with preserved EF (HFpEF; defined as EF ≥50%). The prevalence of HFmrEF within the overall population of patients with HF is 10-25%. HFmrEF seems to be an intermediate clinical entity between HFrEF and HFpEF in some respects, but more similar to HFrEF in others, in particular with regard to the high prevalence of ischaemic heart disease in these patients. HFmrEF is milder than HFrEF, and the risk of cardiovascular events is lower in patients with HFmrEF or HFpEF than in those with HFrEF. By contrast, the risk of non-cardiovascular adverse events is similar or greater in patients with HFmrEF or HFpEF than in those with HFrEF. Evidence from post hoc and subgroup analyses of randomized clinical trials and a trial of an SGLT1-SGLT2 inhibitor suggests that drugs that are effective in patients with HFrEF might also be effective in patients with HFmrEF. Although the EF is a continuous measure with considerable variability, in this comprehensive Review we suggest that HFmrEF is a useful categorization of patients with HF and shares the most important clinical features with HFrEF, which supports the renaming of HFmrEF to HF with mildly reduced EF.
10.1038/s41569-021-00605-5
Effect of Sex on Reverse Remodeling in Chronic Systolic Heart Failure.
Aimo Alberto,Vergaro Giuseppe,Castiglione Vincenzo,Barison Andrea,Pasanisi Emilio,Petersen Christina,Chubuchny Vladyslav,Giannoni Alberto,Poletti Roberta,Maffei Silvia,Januzzi James L,Passino Claudio,Emdin Michele
JACC. Heart failure
OBJECTIVES:This study sought to investigate sex-related differences in reverse remodeling (RR). BACKGROUND:RR, that is, the recovery from left ventricular (LV) dilation and dysfunction in response to treatment for heart failure (HF), is associated with improved prognosis. METHODS:Data from patients with stable systolic HF (LV ejection fraction [LVEF] of <50%) undergoing 2 transthoracic echocardiograms within 12 ± 2 months were analyzed. Reverse remodeling was defined as a ≥15% reduction in LV end-systolic volume index. RESULTS:A total of 927 patients were evaluated (68 ± 12 years; median LVEF = 35% [interquartile range: 30% to 43%]; 27% women). Ischemic HF was less often encountered in women (33% vs. 60%, respectively; p < 0.001), whereas most characteristics did not differ with regard to sex. Women showed a higher incidence of RR (41% vs. 27%, respectively; p < 0.001), despite similar baseline LV volume and function. RR was more frequent among women in the subgroups with either ischemic or nonischemic HF, as well as in all categories of systolic dysfunction (LVEF ≤35% or >35%, according to current indication for device implantation, and LVEF <40% or 40% to 50% according to the definition of HF with reduced or mid-range EF). In the whole population, female sex was an independent predictor of RR (hazard ratio: 1.54; 95% confidence interval: 1.11 to 2.14; p = 0.011), together with cause of HF, disease duration, and left bundle branch block. Female sex was again an independent predictor of RR in all LVEF categories. CONCLUSIONS:Reverse remodeling is more frequent among women, regardless of cause and severity of LV dysfunction. Female sex is an independent predictor of RR in all categories of LV systolic dysfunction.
10.1016/j.jchf.2017.07.011
Normalization of cardiac substrate utilization and left ventricular hypertrophy precede functional recovery in heart failure regression.
Byrne Nikole J,Levasseur Jody,Sung Miranda M,Masson Grant,Boisvenue Jamie,Young Martin E,Dyck Jason R B
Cardiovascular research
AIMS:Impaired cardiac substrate metabolism plays an important role in heart failure (HF) pathogenesis. Since many of these metabolic changes occur at the transcriptional level of metabolic enzymes, it is possible that this loss of metabolic flexibility is permanent and thus contributes to worsening cardiac function and/or prevents the full regression of HF upon treatment. However, despite the importance of cardiac energetics in HF, it remains unclear whether these metabolic changes can be normalized. In the current study, we investigated whether a reversal of an elevated aortic afterload in mice with severe HF would result in the recovery of cardiac function, substrate metabolism, and transcriptional reprogramming as well as determined the temporal relationship of these changes. METHODS AND RESULTS:Male C57Bl/6 mice were subjected to either Sham or transverse aortic constriction (TAC) surgery to induce HF. After HF development, mice with severe HF (% ejection fraction < 30) underwent a second surgery to remove the aortic constriction (debanding, DB). Three weeks following DB, there was a near complete recovery of systolic and diastolic function, and gene expression of several markers for hypertrophy/HF were returned to values observed in healthy controls. Interestingly, pressure-overload-induced left ventricular hypertrophy (LVH) and cardiac substrate metabolism were restored at 1-week post-DB, which preceded functional recovery. CONCLUSIONS:The regression of severe HF is associated with early and dramatic improvements in cardiac energy metabolism and LVH normalization that precede restored cardiac function, suggesting that metabolic and structural improvements may be critical determinants for functional recovery.
10.1093/cvr/cvw051
Hydrochlorothiazide modulates ischemic heart failure-induced cardiac remodeling via inhibiting angiotensin II type 1 receptor pathway in rats.
Luo Jinghong,Chen Xuanlan,Luo Chufan,Lu Guihua,Peng Longyun,Gao Xiuren,Zuo Zhiyi
Cardiovascular therapeutics
AIMS:Our previous study indicates that hydrochlorothiazide inhibits transforming growth factor (TGF)-β/Smad signaling pathway, improves cardiac function and reduces fibrosis. We determined whether these effects were common among the diuretics and whether angiotensin II receptor type 1 (AT1) signaling pathway played a role in these effects. METHODS:Heart failure was produced by ligating the left anterior descending coronary artery in adult male Sprague Dawley rats. Two weeks after the ligation, 70 rats were randomly divided into five groups: sham-operated group, control group, valsartan group (80 mg/kg/d), hydrochlorothiazide group (12.5 mg/kg/d) and furosemide group (20 mg/kg/d). In addition, neonatal rat ventricular fibroblasts were treated with angiotensin II. RESULTS:After eight-week drug treatment, hydrochlorothiazide group and valsartan group but not furosemide group had improved cardiac function (ejection fraction was 49.4±2.1%, 49.5±1.8% and 39.9±1.9%, respectively, compared with 40.1±2.2% in control group), reduced cardiac interstitial fibrosis and collagen volume fraction (9.7±1.2%, 10.0±1.3% and 14.1±0.8%, respectively, compared with 15.9±1.1% in control group), and decreased expression of AT1, TGF-β and Smad2 in the cardiac tissues. In addition, hydrochlorothiazide reduced plasma angiotensin II and aldosterone levels. Furthermore, hydrochlorothiazide inhibited angiotensin II-induced TGF-β1 and Smad2 protein expression in the neonatal rat ventricular fibroblasts. CONCLUSIONS:Our study indicates that the cardiac function and remodeling improvement after ischemic heart failure may not be common among the diuretics. Hydrochlorothiazide may reduce the left ventricular wall stress and angiotensin II signaling pathway to provide these beneficial effects.
10.1111/1755-5922.12246
Progression of matrixin and cardiokine expression patterns in an ovine model of heart failure and recovery.
Quttainah Mohammed,Al-Hejailan Reem,Saleh Soad,Parhar Ranjit,Conca Walter,Bulwer Bernard,Moorjani Narain,Catarino Pedro,Elsayed Raafat,Shoukri Mohammed,AlJufan Mansour,AlShahid Maie,Ouban Abderrahman,Al-Halees Zohair,Westaby Stephen,Collison Kate,Al-Mohanna Futwan
International journal of cardiology
BACKGROUND:The molecular mechanisms underlying the geometrical changes of the left ventricle during the progression to heart failure and recovery are not well defined. OBJECTIVE:Here we investigate the involvement of matrixins and cardiokines in an ovine model of pressure-induced left ventricular failure (LVF). METHODS:Fifteen sheep underwent supracoronary aortic banding with an inflatable cuff. A controlled and progressive increase of LV pressure was monitored echocardiographically. Endomyocardial biopsies were collected throughout the development of LVF and subsequent recovery after pressure unloading. RESULTS:Thirteen sheep developed LVF with a subsequent recovery. Peak left ventricular hypertrophy (LVH) and dilatation (LVD) occurred at 31.5 ± 1.6 weeks and 102.7 ± 2.2 weeks post-banding respectively, with an increase in LV internal diameter in diastole (LVIDd 5.11 ± 0.12 compared to the control 3.37 ± 0.07 cm, p<0.001), with preserved LV ejection fraction (LVEF). Reduced LVEF became evident 116.5 ± 2.7 weeks post-banding. Clinical and echocardiographic improvements were observed following deflation of the aortic banding cuff. By 138.1 ± 3.1 weeks cardiac performance recovered with restoration of LVEF. Significant changes in the expression of matrix metalloproteinases (MMP)-1, -2, -3, vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF)-2, interferon (INF)-α-2 and soluble CD40 ligand (sCD40L) were observed throughout the progression to failure and recovery. CONCLUSIONS:We used an ovine model to study reversible LV remodelling without interruption and found significant changes in matrixin and cardiokine expression during LV progression to failure and recovery.
10.1016/j.ijcard.2015.03.156
Left ventricular ejection fraction as therapeutic target: is it the ideal marker?
Katsi V,Georgiopoulos G,Laina A,Koutli E,Parissis J,Tsioufis C,Nihoyannopoulos P,Tousoulis D
Heart failure reviews
Heart failure (HF) consists the fastest growing clinical cardiac disease. HF patients are categorized on the basis of underlying left ventricular ejection fraction (LVEF) into HF with preserved EF (HFpEF), reduced LVEF (HFrEF), and mid-range LVEF (HFmrEF). While LVEF is the most commonly used surrogate marker of left ventricular (LV) systolic function, the implementation of two-dimensional echocardiography in estimating this parameter imposes certain caveats on current HF classification. Most importantly, LVEF could fluctuate in repeated measurements or even recover after treatment, thus blunting the borders between proposed categories of HF and enabling upward classification of patients. Under this prism, we sought to summarize possible procedures to improve systolic function in patients with HFrEF either naturally or by the means of pharmacologic and non-pharmacologic treatment and devices. Therefore, we reviewed established pharmacotherapy, including beta-blockers, inhibitors of renin-angiotensin-aldosterone axis, statins, and digoxin as well as novel treatments like sacubitril-valsartan, ranolazine, and ivabradine. In addition, we assessed evidence in favor of cardiac resynchronization therapy and exercise training programs. Finally, innovative therapeutic strategies, including stem cells, xanthine oxidase inhibitors, antibiotic regimens, and omega-3 polyunsaturated fatty acids, were also taken into consideration. We concluded that LVEF is subject to changes in HF after intervention and besides the aforementioned HFrEF, HFpEF, and HFmrEF categories, a new entity of HF patients with recovered LVEF should be acknowledged. An improved global and refined LV function assessment by sophisticated imaging modalities and circulating biomarkers is expected to render HF classification more accurate and indicate patients with viable-yet dysfunctional-myocardium and favorable characteristics as the ideal candidates for LVEF recovery by individualized HF therapy.
10.1007/s10741-017-9624-5
Outcomes and predictors of recovery in acute-onset cardiomyopathy: A single-center experience of patients undergoing endomyocardial biopsy for new heart failure.
Gilotra Nisha A,Bennett Mosi K,Shpigel Adam,Ahmed Haitham M,Rao Shaline,Dunn Justin M,Harrington Colleen,Freitag Tasha B,Halushka Marc K,Russell Stuart D
American heart journal
BACKGROUND:About one-third of patients with unexplained acute-onset heart failure (HF) recover left ventricular (LV) function; however, characterization of these patients in the setting of contemporary HF therapies is limited. We aim to describe baseline characteristics and predictors of recovery in patients with acute-onset cardiomyopathy. METHODS:We previously described 851 patients with unexplained HF undergoing endomyocardial biopsy. In this study, 235 patients with acute-onset HF were further retrospectively examined. RESULTS:Follow-up LV ejection fraction (LVEF) was available for 138 patients. At 1 year, 48 of 138 (33%) had LVEF recovery (follow-up LVEF ≥50%), and 90 of 138 (65%) had incomplete or lack of recovery. Higher cardiac index (P=.019), smaller LV diastolic diameter (P=.002), and lack of an intraventricular conduction delay (IVCD) (P=.002) were associated with LVEF recovery. IVCD (P=.001) and myocarditis (P=.016) were independent predictors of the composite end point of death, LV assist device placement, and/or transplant at 1 year. Those with an IVCD had a significantly lower 1-year survival than those without (P=.007). CONCLUSIONS:Patients with a smaller LV end-diastolic diameter, higher cardiac index, and lack of IVCD at presentation for acute-onset HF were more likely to have LVEF recovery. IVCD was a poor prognostic marker in all patients presenting with acute cardiomyopathy.
10.1016/j.ahj.2016.06.019
Characteristics and outcomes of HFpEF with declining ejection fraction.
Park Jin Joo,Park Chan Soon,Mebazaa Alexandre,Oh Il-Young,Park Hyun-Ah,Cho Hyun-Jai,Lee Hae-Young,Kim Kye Hun,Yoo Byung-Su,Kang Seok-Min,Baek Sang Hong,Jeon Eun-Seok,Kim Jae-Joong,Cho Myeong-Chan,Chae Shung Chull,Oh Byung-Hee,Choi Dong-Ju
Clinical research in cardiology : official journal of the German Cardiac Society
OBJECTIVE:Some patients with heart failure with preserved ejection fraction (HFpEF) experience declining of left-ventricular ejection fraction (LVEF) during follow-up. We aim to investigate the characteristics and outcomes of patients with HF with declining ejection fraction (HFdEF). METHODS:We analyzed a prospective, nationwide multicenter cohort with consecutive patients with acute HF enrolled from March 2011 to December 2014. HFpEF was defined as LVEF ≥ 50% at index admission. After 1 year, HFpEF patients were further classified as HFdEF (LVEF ≥ 50% at admission and < 50% at 1 year), and persistent HFpEF (LVEF ≥ 50% both at admission and 1 year). Primary outcome was 4-year all-cause mortality according to HF type from HFdEF diagnosis. RESULTS:Of patients with HFpEF, 426 (90.4%) were diagnosed as having persistent HFpEF and 45 (9.6%) as having HFdEF. Natriuretic peptide level was an independent predictor of HFdEF (natriuretic peptide level > median: odds ratio: 3.20, 95% confidence interval [CI]: 1.42-7.25, P = 0.005). During 4-year follow-up, patients with HFdEF had higher mortality than those with persistent HFpEF (Log-rank P < 0.001). After adjustment, HFdEF was associated with an almost twofold increased risk for mortality (hazard ratio 1.82, 95% CI 1.13-2.96, P = 0.015). The use of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists was not associated with improved prognosis of patients with HFdEF. CONCLUSIONS:HFdEF is a distinct HF type with grave outcomes. Further investigations that focus on HFdEF are warranted to better understand and develop treatment strategies for these high-risk patients. CLINICAL TRIAL REGISTRATION:ClinicalTrial.gov identifier: NCT01389843. URL: https://clinicaltrials.gov/ct2/show/NCT01389843.
10.1007/s00392-019-01505-y
Biomarkers to Predict Reverse Remodeling and Myocardial Recovery in Heart Failure.
Motiwala Shweta R,Gaggin Hanna K
Current heart failure reports
Left ventricular remodeling appears to be a critical link between cardiac injury and the development and progression of heart failure with reduced ejection fraction (HFrEF). Several drug and device therapies that modify and reverse the remodeling process in patients with HFrEF are closely associated with improvement in clinical outcomes. Reverse remodeling, including partial or complete recovery of systolic function and structure, is possible but its determinants are incompletely understood. Methods to predict reverse remodeling in response to therapy are not well defined. Though non-invasive imaging techniques remain the most widely used methods of assessing reverse remodeling, serum biomarkers are now being investigated as more specific, mechanistically driven, and clinically useful predictors of reverse remodeling. Biomarkers that reflect myocyte stretch and stress, myocyte injury and necrosis, inflammation and fibrosis, and extracellular matrix turnover may be particularly valuable for predicting pathophysiologic changes and prognosis in individual patients. Their use may ultimately allow improved application of precision medicine in chronic HF.
10.1007/s11897-016-0303-y
Is heart failure with midrange ejection fraction similar to preserved ejection fraction? Against.
Formiga F
Revista clinica espanola
The new European guidelines (2016) for heart failure (HF) include the concept of HF with intermediate left ventricular ejection fraction (LVEF), i.e. an LVEF between 40 and 49%. Although few studies have been carried out, there are claims that HF with intermediate LVEF is not the same as HF with preserved LVEF. Perhaps the most consistent claim is the high percentage of associated ischemic heart disease, which could reflect LVEF recovery after adequate anti-ischemic treatment of HF with depressed LVEF, or even the progressive deterioration of LVEF following an ischemic event.
10.1016/j.rce.2017.01.012
Parameters of repolarization heterogeneity are associated with myocardial recovery in acute heart failure.
Prenner Stuart B,Swat Stanley A,Ng Jason,Baldridge Abigail,Wilcox Jane E
International journal of cardiology
BACKGROUND:Heart failure (HF) with recovered ejection fraction (HFrecEF) is an increasingly recognized yet not well understood phenotype. Little is known about electrical parameters associated with myocardial recovery in acute systolic HF. METHODS:We identified a subset of 87 patients from a non-ischemic cardiomyopathy cohort with left ventricular ejection fraction (LVEF) < 40% during index HF hospitalization. HFrecEF was defined as follow-up LVEF ≥40% and ≥ 10% improvement from baseline. We analyzed baseline and follow up electrocardiograms (ECG) in this group for several electrical parameters known to reflect repolarization heterogeneity. RESULTS:Among 87 patients, 30 (34%) patients recovered in a median of 122 (IQR: 58-275) days after index hospitalization. Baseline demographics were similar among HFrecEF versus persistent HFrEF except for increased diabetes in the persistent HFrEF cohort. Patients with HFrecEF had baseline decreased QRST angle, decreased QT dispersion, and less negative signed JT area compared to persistent HFrEF. Patients with HFrecEF had greater decrease in QT dispersion and QTc duration, and greater increase in the signed JT and TpTe areas over time. Baseline QRST angle correlated with longitudinal and circumferential strain and myocardial systolic performance (MSP). Signed JT area correlated with increased baseline LVEF, smaller baseline LV dimensions, increased longitudinal and circumferential strain, and MSP. Signed TpTe correlated with increased longitudinal and circumferential strain, and MSP. CONCLUSIONS:Several conventional and novel ECG parameters that reflect repolarization heterogeneity may differentiate patients with acute HF who ultimately recover LVEF. These parameters are associated with baseline structural parameters and are dynamic during recovery.
10.1016/j.ijcard.2019.08.048
Baseline Longitudinal Strain Predicts Recovery of Left Ventricular Ejection Fraction in Hospitalized Patients With Nonischemic Cardiomyopathy.
Swat Stanley A,Cohen David,Shah Sanjiv J,Lloyd-Jones Donald M,Baldridge Abigail S,Freed Benjamin H,Vorovich Esther E,Yancy Clyde W,Jonnalagadda Siddhartha R,Prenner Stuart,Kim Daniel,Wilcox Jane E
Journal of the American Heart Association
Background Heart failure ( HF ) with "recovered" ejection fraction ( HF rec EF ) is an emerging phenotype, but no tools exist to predict ejection fraction ( EF ) recovery in acute HF . We hypothesized that indices of baseline cardiac structure and function predict HF rec EF in nonischemic cardiomyopathy and reduced EF . Methods and Results We identified a nonischemic cardiomyopathy cohort with EF <40% during the first HF hospitalization (n=166). We performed speckle-tracking echocardiography to measure longitudinal, circumferential, and radial strain, and the average of these measures (myocardial systolic performance). HF rec EF was defined as follow-up EF ≥40% and ≥10% improvement from baseline EF . Fifty-nine patients (36%) achieved HF rec EF (baseline EF 26±7%; follow-up EF 51±7%) within a median of 135 (interquartile range 58-239) days after the first HF hospitalization. Baseline demographics, biomarker profiles, and comorbid conditions (except lower chronic kidney disease in HF rec EF ) were similar between HF rec EF and persistent reduced- EF groups. HF rec EF patients had smaller baseline left ventricular end-systolic dimension (3.6 versus 4.8 cm; P<0.01), higher baseline myocardial systolic performance (9.2% versus 8.1%; P=0.02), and improved survival (adjusted hazard ratio 0.27, 95% confidence interval 0.11, 0.62). We found a significant interaction between baseline left ventricular end-systolic dimension and absolute longitudinal strain. Among patients with left ventricular end-systolic dimension >4.35 cm, higher absolute longitudinal strain (≥8%) was associated with HF rec EF (unadjusted odds ratio=3.9, 95% CI )confidence interval 1.2, 12.8). Incorporation of baseline indices of cardiac mechanics with clinical variables resulted in a predictive model for HF rec EF with c-statistic=0.85. Conclusions Factors associated with achieving HF rec EF were specific to cardiac structure and indices of cardiac mechanics. Higher baseline absolute longitudinal strain is associated with HF rec EF among nonischemic cardiomyopathy patients with reduced EF and larger left ventricular dimensions.
10.1161/JAHA.118.009841
Left ventricular ejection fraction recovery in patients with heart failure treated with intravenous iron: a pilot study.
Núñez Julio,Monmeneu José Vicente,Mollar Anna,Núñez Eduardo,Bodí Vicent,Miñana Gema,García-Blas Sergio,Santas Enrique,Agüero Jaume,Chorro Francisco J,Sanchis Juan,López-Lereu Maria Pilar
ESC heart failure
AIMS:In patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency, treatment with intravenous iron has shown a clinical improvement regardless of anaemic status. Cardiac magnetic resonance (CMR) T2* sequence has shown a potential utility for evaluating myocardial iron deficiency. We aimed to evaluate whether T2* sequence significantly changes after ferric carboximaltose (FCM) administration, and if such changes correlate with changes in left ventricle ejection fraction (LVEF). METHODS AND RESULTS:In this pilot study, we included eight patients with chronic symptomatic (New York Heart Association II-III) HFrEF and iron deficiency. A CMR, including T2* analysis, was performed before and at a median of 43 days (interquartile range = 35-48) after intravenous FCM administration. Pearson or Spearman correlation coefficient (r) was used for bivariate contrast as appropriate. A partial correlation analysis was performed between ΔLVEF and ΔT2* while controlling for anaemia status at baseline. Anaemia was present in half of patients. After FCM administration, T2* decreased from a median of 39.5 (35.9-48) to 32 ms (32-34.5), = 0.012. Simultaneously, a borderline increase in median of LVEF [40% (36-44.5) to 48.5% (38.5-53), = 0.091] was registered. In a bivariate correlational analysis, ΔT2* was highly correlated with ΔLVEF ( = -0.747, = 0.033). After controlling for anaemia at baseline, the association between ΔT2* and ΔLVEF persisted [(partial): -0.865, (partial): 0.748, = 0.012]. A median regression analysis backed-up these findings. CONCLUSIONS:In a small sample of patients with HFrEF and iron deficiency, myocardial iron repletion assessed by CMR was associated to left ventricular remodelling. Further studies are warranted.
10.1002/ehf2.12101
Heart Failure with Myocardial Recovery - The Patient Whose Heart Failure Has Improved: What Next?
Nijst Petra,Martens Pieter,Mullens Wilfried
Progress in cardiovascular diseases
In an important number of heart failure (HF) patients substantial or complete myocardial recovery occurs. In the strictest sense, myocardial recovery is a return to both normal structure and function of the heart. HF patients with myocardial recovery or recovered ejection fraction (EF; HFrecEF) are a distinct population of HF patients with different underlying etiologies, demographics, comorbidities, response to therapies and outcomes compared to HF patients with persistent reduced (HFrEF) or preserved ejection fraction (HFpEF). Improvement of left ventricular EF has been systematically linked to improved quality of life, lower rehospitalization rates and mortality. However, mortality and morbidity in HFrecEF patients remain higher than in the normal population. Also, persistent abnormalities in biomarker and gene expression profiles in these patients lends weight to the hypothesis that pathological processes are ongoing. Currently, there remains a lack of data to guide the management of HFrecEF patients. This review will discuss specific characteristics, pathophysiology, clinical implications and future needs for HFrecEF.
10.1016/j.pcad.2017.05.009
Abnormal Global Longitudinal Strain Predicts Future Deterioration of Left Ventricular Function in Heart Failure Patients With a Recovered Left Ventricular Ejection Fraction.
Adamo Luigi,Perry Andrew,Novak Eric,Makan Majesh,Lindman Brian R,Mann Douglas L
Circulation. Heart failure
BACKGROUND:Patients with recovery of left ventricular ejection fraction (LVEF) remain at risk for future deterioration of LVEF. However, there are no tools to risk stratify these patients. We hypothesized that global longitudinal strain (GLS) could predict sustained recovery within this population. METHODS AND RESULTS:We retrospectively identified 96 patients with a reduced LVEF <50% (screening echocardiogram), whose LVEF had increased by at least 10% and normalized (>50%) on evidence-based medical therapies (baseline echocardiogram). We examined absolute GLS on the baseline echocardiogram in relation to changes in LVEF on a follow-up echocardiogram. Patients with recovered LVEF had a wide range of GLS. The GLS on the baseline study correlated with the LVEF at the time of follow-up (=0.33; <0.001). The likelihood of having an LVEF >50% on follow-up increased by 24% for each point increase in absolute GLS on the baseline study (odds ratio, 1.24; =0.001). An abnormal GLS (≤16%) at baseline had a sensitivity of 88%, a specificity of 46%, and an accuracy of 0.67 (<0.001) as a predictor of a decrease in LVEF >5% during follow-up. A normal GLS (>16%) on the baseline study had a sensitivity of 47%, a specificity of 83%, and an accuracy of 0.65 (=0.002) for predicting a stable LVEF (-5% to 5%) on follow-up. CONCLUSIONS:In patients with a recovered LVEF, an abnormal GLS predicts the likelihood of having a decreased LVEF during follow-up, whereas a normal GLS predicts the likelihood of stable LVEF during recovery.
10.1161/CIRCHEARTFAILURE.116.003788
Characteristics and Outcomes of Adult Outpatients With Heart Failure and Improved or Recovered Ejection Fraction.
Kalogeropoulos Andreas P,Fonarow Gregg C,Georgiopoulou Vasiliki,Burkman Gregory,Siwamogsatham Sarawut,Patel Akash,Li Song,Papadimitriou Lampros,Butler Javed
JAMA cardiology
IMPORTANCE:Heart failure (HF) guidelines recognize that a subset of patients with HF and preserved left ventricular ejection fraction (LVEF) previously had reduced LVEF but experienced improvement or recovery in LVEF. However, data on these patients are limited. OBJECTIVE:To investigate the characteristics and outcomes of adult outpatients with HF and improved or recovered ejection fraction (HFrecEF). DESIGN, SETTING, AND PARTICIPANTS:Retrospective cohort study (inception period, January 1, 2012, to April 30, 2012) with 3-year follow-up at cardiology clinics (including HF subspecialty) in an academic institution. The dates of the analysis were May 21, 2015, to August 10, 2015. Participants were all outpatients 18 years or older who received care for a verified diagnosis of HF not attributed to specific cardiomyopathies or other special causes during the inception period. EXPOSURES:Type of HF at baseline, classified as HF with reduced ejection fraction (HFrEF) (defined as current LVEF ≤40%), HF with preserved ejection fraction (HFpEF) (defined as current and all previous LVEF reports >40%), and HF with recovered ejection fraction (HFrecEF) (defined as current LVEF >40% but any previously documented LVEF ≤40%). MAIN OUTCOMES AND MEASURES:Mortality, hospitalization rates, and composite end points. RESULTS:The study cohort comprised 2166 participants. Their median age was 65 years, 41.4% (896 of 2166) were female, 48.7% (1055 of 2166) were white and 45.2% (1368 of 2166) black, and 63.2% (1368 of 2166) had coronary artery disease. Preserved (>40%) LVEF at inception was present in 816 of 2166 (37.7%) patients. Of these patients, 350 of 2166 (16.2%) had previously reduced (≤40%) LVEF and were classified as having HFrecEF, whereas 466 of 2166 (21.5%) had no previous reduced LVEF and were classified as having HFpEF. The remaining 1350 (62.3%) patients were classified as having HFrEF. After 3 years, age and sex-adjusted mortality was 16.3% in patients with HFrEF, 13.2% in patients with HFpEF, and 4.8% in patients with HFrecEF (P < .001 vs HFrEF or HFpEF). Compared with patients with HFpEF and patients with HFrEF, patients with HFrecEF had fewer all-cause (adjusted rate ratio [RR] vs HFpEF, 0.71; 95% CI, 0.55-0.91; P = .007), cardiovascular (RR, 0.50; 95% CI, 0.35-0.71; P < .001), and HF-related (RR, 0.48; 95% CI, 0.30-0.76; P = .002) hospitalizations and were less likely to experience composite end points commonly used in clinical trials (death or cardiovascular hospitalization and death or HF hospitalization). CONCLUSIONS AND RELEVANCE:Outpatients with HFrecEF have a different clinical course than patients with HFpEF and HFrEF, with lower mortality, less frequent hospitalizations, and fewer composite end points. These patients may need to be investigated separately in outcomes studies and clinical trials.
10.1001/jamacardio.2016.1325
Systolic function recovery in Heart Failure: Frequency, prognostic impact and predictors.
Pereira Joana,Chaves Vanessa,Tavares Sofia,Albuquerque Inês,Gomes Clara,Guiomar Verónica,Monteiro Ana,Ferreira Inês,Lourenço Patrícia,Bettencourt Paulo
International journal of cardiology
BACKGROUND:Systolic function recovery in patients with Heart failure (HF) with reduced ejection fraction (EF) is well recognized but not completely understood. We aimed to characterize HF patients with systolic function recovery, its prognostic impact and predictors. METHODS:We analysed patients followed in a HF clinic (2006-2015) with 2 echocardiograms performed. Partial recovery: EF recovery without attaining EF ≥ 50%; total recovery: patients reached EF ≥ 50%. Median follow-up from first echocardiogram: 69 months. Multivariate logistic regression models to determine recovery predictors. RESULTS:We analysed 304 patients with at least mild left ventricular dysfunction. During a median 34 months between echocardiogram re-evaluation 150 (49.3%) patients showed no EF recovery; 55 (18.1%) had partial recovery and 99 (32.6%) totally recovered. Mean patients age: 66; 71.1% men, high comorbidity burden; ischemic HF: 35.5%. Non-recovered patients were mostly men (80.7% vs 61.8% in partially; 61.6% in fully-recovered) with ischemic HF (46.0% vs 32.5% in partially; 21.2% in fully-recovered). Comorbidity burden, NYHA class and therapy were similar. During follow-up, 156 patients (46.7%) died. Patients with total recovery had a multivariate-adjusted 54% lower risk of dying when compared to non-recovered. Partially-recovered patients showed a non-significant adjusted 8% mortality reduction. Independent predictors of systolic function recovery were female gender(OR: 2.17, 95% CI 1.11-4.35), non-ischemic aetiology (OR: 2.78, 95% CI 1.35-5.56), and end diastolic left ventricular diameter < 60 mm (OR: 3.12, 95% CI 1.56-6.25). CONCLUSIONS:HF-recovered patients were mainly women with non-ischemic HF and smaller left ventricles. These patients had significantly better prognosis than those with persistently reduced EF.
10.1016/j.ijcard.2019.11.126
Heart failure with recovered ejection fraction.
Tanabe Kazuaki,Sakamoto Takahiro
Journal of echocardiography
Substantial or complete myocardial recovery occurs in many patients with heart failure (HF). HF patients with myocardial recovery or recovered left ventricular (LV) ejection fraction (EF; HFrecEF) are a distinct population of HF patients with different underlying etiologies, comorbidities, response to therapies, and outcomes compared with HF patients with persistent reduced or preserved EF. Improvement in LVEF has been systematically linked to improved quality of life, and lower rehospitalization rates and mortality. However, the mortality and morbidity in HFrecEF patients remain higher than those in the normal population. Currently, data to guide the management of HFrecEF patients are lacking. This review discusses specific characteristics, pathophysiology, and clinical implications for HFrecEF.
10.1007/s12574-018-0396-2
Benefits of chronic total coronary occlusion percutaneous intervention in patients with heart failure and reduced ejection fraction: insights from a cardiovascular magnetic resonance study.
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
BACKGROUND:Chronic total occlusion percutaneous coronary intervention (CTO-PCI) can improve angina and left ventricular ejection fraction (LVEF). These benefits were not assessed in populations with heart failure with reduced ejection fraction (HFrEF). We studied the effect of CTO-PCI on left ventricular function and clinical parameters in patients with HFrEF. METHODS:Using cardiovascular magnetic resonance (CMR), we studied 29 patients with HFrEF and evidence of viability and/or ischemia in the territory supplied by a CTO who were successfully treated with CTO-PCI. In patients with multi-vessel disease, non-CTO PCI was also performed. Imaging parameters, clinical status, and brain natriuretic peptide (BNP) levels were evaluated before and 6 months after CTO-PCI. RESULTS:A decrease in left ventricular end-systolic volume (160 ± 54 ml vs. 143 ± 58 ml; p = 0.029) and an increase in LVEF (31.3 ± 7.4 % vs. 37.7 ± 8 %; p < 0.001) were observed. There were no differences in LVEF improvement between patients who underwent non-CTO PCI (n = 11) and those without this intervention (n = 18); (p = 0.73). The number of segments showing perfusion defects was significantly reduced (0.5 ± 1 vs. 0.2 ± 0.5; p = 0.043). Angina (p = 0.002) and NYHA functional class (p = 0.004) improved, and BNP levels decreased (p = 0.004) after CTO-PCI. CONCLUSIONS:In this group of patients with HFrEF showing CMR evidence of viability and/or ischemia within the territory supplied by the CTO, an improvement in ejection fraction, left ventricular end-systolic volume and ischemia burden was observed after CTO-PCI. Clinical and laboratory parameters also improved. TRIAL REGISTRATION:ClinicalTrials.gov NCT02570087 . Registered 6 October 2015.
10.1186/s12968-016-0287-5
"Targeting the Heart" in Heart Failure: Myocardial Recovery in Heart Failure With Reduced Ejection Fraction.
Wilcox Jane E,Fonarow Gregg C,Ardehali Hossein,Bonow Robert O,Butler Javed,Sauer Andrew J,Epstein Stephen E,Khan Sadiya S,Kim Raymond J,Sabbah Hani N,Díez Javier,Gheorghiade Mihai
JACC. Heart failure
Myocardial recovery in heart failure (HF) is possible, but its determinants are not fully defined. At least partial functional improvement is possible with current evidence-based therapies. However, once significant HF symptoms develop, patients have varied trajectories, including: 1) structural and functional recovery; 2) stabilization (remission); and 3) acceleration to end-stage HF/death. All 3 trajectories may be interrupted by sudden death. These trajectories may represent the interplay of heterogeneous causality, genetic predeterminants, and disease phenotypes. Enhanced phenotypic description with cardiac magnetic resonance imaging, molecular imaging, or circulating biomarkers of the heterogeneous HF population may provide insights regarding specific biological targets amenable to existing and novel therapeutic strategies. The identification of patients in "remission," before progression to the end stage of predominantly nonviable tissue (e.g., fibrosis), has implications for clinical practice and future trials because such patients may be more likely to experience myocardial recovery (cardiac reserve). The identification of dysfunctional but viable myocardium and its diverse pathophysiological causes may provide opportunities to investigate existing and novel therapeutics aimed at enhancing myocardial recovery.
10.1016/j.jchf.2015.04.011
Heart failure with preserved ejection fraction: current management and future strategies : Expert opinion on the behalf of the Nucleus of the "Heart Failure Working Group" of the German Society of Cardiology (DKG).
Tschöpe Carsten,Birner Christoph,Böhm Michael,Bruder Oliver,Frantz Stefan,Luchner Andreas,Maier Lars,Störk Stefan,Kherad Behrouz,Laufs Ulrich
Clinical research in cardiology : official journal of the German Cardiac Society
About 50% of all patients suffering from heart failure (HF) exhibit a reduced ejection fraction (EF ≤ 40%), termed HFrEF. The others may be classified into HF with midrange EF (HFmrEF 40-50%) or preserved ejection fraction (HFpEF, EF ≥ 50%). Presentation and pathophysiology of HFpEF is heterogeneous and its management remains a challenge since evidence of therapeutic benefits on outcome is scarce. Up to now, there are no therapies improving survival in patients with HFpEF. Thus, the treatment targets symptom relief, quality of life and reduction of cardiac decompensations by controlling fluid retention and managing risk factors and comorbidities. As such, renin-angiotensin-aldosterone inhibitors, diuretics, calcium channel blockers (CBB) and beta-blockers, diet and exercise recommendations are still important in HFpEF, although these interventions are not proven to reduce mortality in large randomized controlled trials. Recently, numerous new treatment targets have been identified, which are further investigated in studies using, e.g. soluble guanylate cyclase stimulators, inorganic nitrates, the angiotensin receptor neprilysin inhibitor LCZ 696, and SGLT2 inhibitors. In addition, several devices such as the CardioMEMS, interatrial septal devices (IASD), cardiac contractility modulation (CCM), renal denervation, and baroreflex activation therapy (BAT) were investigated in different forms of HFpEF populations and some of them have the potency to offer new hopes for patients suffering from HFpEF. On the basic research field side, lot of new disease-modifying strategies are under development including anti-inflammatory drugs, mitochondrial-targeted antioxidants, new anti-fibrotic and microRNA-guided interventions are under investigation and showed already promising results. This review addresses available data of current best clinical practice and management approaches based on expert experiences and summarizes novel approaches towards HFpEF.
10.1007/s00392-017-1170-6
Revisiting the physiological effects of exercise training on autonomic regulation and chemoreflex control in heart failure: does ejection fraction matter?
Andrade David C,Arce-Alvarez Alexis,Toledo Camilo,Díaz Hugo S,Lucero Claudia,Quintanilla Rodrigo A,Schultz Harold D,Marcus Noah J,Amann Markus,Del Rio Rodrigo
American journal of physiology. Heart and circulatory physiology
Heart failure (HF) is a global public health problem that, independent of its etiology [reduced (HFrEF) or preserved ejection fraction (HFpEF)], is characterized by functional impairments of cardiac function, chemoreflex hypersensitivity, baroreflex sensitivity (BRS) impairment, and abnormal autonomic regulation, all of which contribute to increased morbidity and mortality. Exercise training (ExT) has been identified as a nonpharmacological therapy capable of restoring normal autonomic function and improving survival in patients with HFrEF. Improvements in autonomic function after ExT are correlated with restoration of normal peripheral chemoreflex sensitivity and BRS in HFrEF. To date, few studies have addressed the effects of ExT on chemoreflex control, BRS, and cardiac autonomic control in HFpEF; however, there are some studies that have suggested that ExT has a beneficial effect on cardiac autonomic control. The beneficial effects of ExT on cardiac function and autonomic control in HF may have important implications for functional capacity in addition to their obvious importance to survival. Recent studies have suggested that the peripheral chemoreflex may also play an important role in attenuating exercise intolerance in HFrEF patients. The role of the central/peripheral chemoreflex, if any, in mediating exercise intolerance in HFpEF has not been investigated. The present review focuses on recent studies that address primary pathophysiological mechanisms of HF (HFrEF and HFpEF) and the potential avenues by which ExT exerts its beneficial effects.
10.1152/ajpheart.00407.2017
Frequency, predictors, and prognosis of ejection fraction improvement in heart failure: an echocardiogram-based registry study.
Ghimire Anukul,Fine Nowell,Ezekowitz Justin A,Howlett Jonathan,Youngson Erik,McAlister Finlay A
European heart journal
AIMS:To identify variables predicting ejection fraction (EF) recovery and characterize prognosis of heart failure (HF) patients with EF recovery (HFrecEF). METHODS AND RESULTS:Retrospective study of adults referred for ≥2 echocardiograms separated by ≥6 months between 2008 and 2016 at the two largest echocardiography centres in Alberta who also had physician-assigned diagnosis of HF. Of 10 641 patients, 3124 had heart failure reduced ejection fraction (HFrEF) (EF ≤ 40%) at baseline: while mean EF declined from 30.2% on initial echocardiogram to 28.6% on the second echocardiogram in those patients with persistent HFrEF (defined by <10% improvement in EF), it improved from 26.1% to 46.4% in the 1174 patients (37.6%) with HFrecEF (defined by EF absolute improvement ≥10%). On multivariate analysis, female sex [adjusted odds ratio (aOR) 1.66, 95% confidence interval (CI) 1.40-1.96], younger age (aOR per decade 1.16, 95% CI 1.09-1.23), atrial fibrillation (aOR 2.00, 95% CI 1.68-2.38), cancer (aOR 1.52, 95% CI 1.03-2.26), hypertension (aOR 1.38, 95% CI 1.18-1.62), lower baseline ejection fraction (aOR per 1% decrease 1.07 (1.06-1.08), and using hydralazine (aOR 1.69, 95% CI 1.19-2.40) were associated with EF improvements ≥10%. HFrecEF patients demonstrated lower rates per 1000 patient years of mortality (106 vs. 164, adjusted hazard ratio, aHR 0.70 [0.62-0.79]), all-cause hospitalizations (300 vs. 428, aHR 0.87 [0.79-0.95]), all-cause emergency room (ER) visits (569 vs. 799, aHR 0.88 [0.81-0.95]), and cardiac transplantation or left ventricular assist device implantation (2 vs. 10, aHR 0.21 [0.10-0.45]) compared to patients with persistent HFrEF. Females with HFrEF exhibited lower mortality risk (aHR 0.94 [0.88-0.99]) than males after adjusting for age, time between echocardiograms, clinical comorbidities, medications, and whether their EF improved or not during follow-up. CONCLUSION:HFrecEF patients tended to be younger, female, and were more likely to have hypertension, atrial fibrillation, or cancer. HFrecEF patients have a substantially better prognosis compared to those with persistent HFrEF, even after multivariable adjustment, and female patients exhibit lower mortality risk than men within each subgroup (HFrecEF and persistent HFrEF) even after multivariable adjustment.
10.1093/eurheartj/ehz233
Characteristics and prognosis of heart failure with improved compared with persistently reduced ejection fraction: A systematic review and meta-analyses.
Jørgensen Mads E,Andersson Charlotte,Vasan Ramachandran S,Køber Lars,Abdulla Jawdat
European journal of preventive cardiology
Aims We assessed the clinical characteristics and prognosis of chronic heart failure patients with improved ejection fraction (HFIEF) compared with persistently reduced ejection fraction (HFpREF) after evidence-based therapy. Methods and results We performed a meta-analysis including 24 eligible observational studies comparing 2663 HFIEF (≥5% left ventricular ejection fraction (LVEF) improvement) versus 8355 HFpREF patients who received recommended drug therapy, cardiac resynchronization therapy and/or intracardiac defibrillator. LVEF was assessed at baseline and reassessed after 19 ± 19 months. The primary endpoints were all-cause mortality and appropriate shocks. The mean duration of follow-up was 39 ± 12 months. Among HFIEF patients, LVEF improved 16.3 percentage points (95% confidence interval 15.9-16.6, p < 0.0001). Compared with HFpREF patients, HFIEF patients had a comparable mean age (60.9 years vs. 62.4 years, p = 0.11), were more often women (33% vs. 25%), had a higher prevalence of non-ischaemic heart failure (58% vs. 53%), less diabetes (27% vs. 28%), higher systolic blood pressure (127.5 ± 9 vs. 122 ± 12 mmHg) and lower left ventricle end-diastolic diameter (64.1 ± 3.7 vs. 67.4 ± 4.9 mmHg), all p-values < 0.05. Absolute risk of all-cause mortality was lower in HFIEF (5.8%) compared with HFpREF (17.5%) with a risk ratio of 0.34 (95% confidence interval 0.28-0.41), p < 0.001. Risk of appropriate shocks was significantly lower in HFIEF versus HFpREF (risk ratio 0.58 (95% confidence interval 0.46-0.74), p < 0.001). Conclusion In heart failure patients, we identified several baseline characteristics in favour of an improved LVEF, in response to evidence based therapy. Patients with improved LVEF had significantly lower risks of mortality and appropriate shocks compared with patients with persistently reduced LVEF.
10.1177/2047487317750437
Heart failure with preserved ejection fraction: controversies, challenges and future directions.
Zakeri Rosita,Cowie Martin R
Heart (British Cardiac Society)
Heart failure with preserved ejection fraction (HFpEF) comprises almost half of the population burden of HF. Because HFpEF likely includes a range of cardiac and non-cardiac abnormalities, typically in elderly patients, obtaining an accurate diagnosis may be challenging, not least due to the existence of multiple HFpEF mimics and a newly identified subset of patients with HFpEF and normal plasma natriuretic peptide concentrations. The lack of effective treatment for these patients represents a major unmet clinical need. Heterogeneity within the patient population has triggered debate over the aetiology and pathophysiology of HFpEF, and the neutrality of randomised clinical trials suggests that we do not fully understand the syndrome(s). Dysregulated nitric oxide-cyclic guanosine monophosphate-protein kinase G signalling, driven by comorbidities and ageing, may be the fundamental abnormality in HFpEF, resulting in a systemic inflammatory state and microvascular endothelial dysfunction. Novel informatics platforms are also being used to classify HFpEF into subphenotypes, based on statistically clustered clinical and biological characteristics: whether such subclassification will lead to more targeted therapies remains to be seen. In this review, we summarise current concepts and controversies, and highlight the diagnostic and therapeutic challenges in clinical practice. Novel treatments and disease management strategies are discussed, and the large gaps in our knowledge identified.
10.1136/heartjnl-2016-310790
Heart Failure and Midrange Ejection Fraction: Implications of Recovered Ejection Fraction for Exercise Tolerance and Outcomes.
Nadruz Wilson,West Erin,Santos Mário,Skali Hicham,Groarke John D,Forman Daniel E,Shah Amil M
Circulation. Heart failure
BACKGROUND:Evidence-based therapies for heart failure (HF) differ significantly according to left ventricular ejection fraction (LVEF). However, few data are available on the phenotype and prognosis of patients with HF with midrange LVEF of 40% to 55%, and the impact of recovered systolic function on the clinical features, functional capacity, and outcomes of this population is not known. METHODS AND RESULTS:We studied 944 patients with HF who underwent clinically indicated cardiopulmonary exercise testing. The study population was categorized according to LVEF as follows: HF with reduced LVEF (HFrEF; LVEF<40%; n=620); HF with midrange ejection fraction and no recovered ejection fraction (LVEF was consistent between 40% and 55%; n=107); HF with recovered midrange ejection fraction (LVEF, 40%-55% but previous LVEF<40%; n=170); and HF with preserved LVEF (HFpEF; LVEF>55%; n=47). HF with midrange ejection fraction and no recovered ejection fraction and HF with recovered midrange ejection fraction had similar clinical characteristics, which were intermediate between those of HFrEF and HFpEF, and comparable values of predicted peak oxygen consumption and minute-ventilation/carbon dioxide production slope, which were better than HFrEF and similar to HFpEF. After a median of 4.4 (2.9-5.7) years, there were 253 composite events (death, left ventricular assistant device implantation, or transplantation). In multivariable Cox-regression analysis, HF with recovered midrange ejection fraction had lower risk of composite events than HFrEF (hazard ratio, 0.25; 95% confidence interval, 0.13-0.47) and HF with midrange ejection fraction and no recovered ejection fraction (hazard ratio, 0.31; 95% confidence interval, 0.15-0.67), and similar prognosis when compared with HFpEF. In contrast, HF with midrange ejection fraction and no recovered ejection fraction tended to show intermediate risk of outcomes in comparison with HFpEF and HFrEF, albeit not reaching statistical significance in fully adjusted analyses. CONCLUSIONS:Patients with HF with midrange LVEF demonstrate a distinct clinical profile from HFpEF and HFrEF patients, with objective measures of functional capacity similar to HFpEF. Within the midrange LVEF HF population, recovered systolic function is a marker of more favorable prognosis.
10.1161/CIRCHEARTFAILURE.115.002826
IL-1 Blockade in Patients With Heart Failure With Preserved Ejection Fraction.
Van Tassell Benjamin W,Trankle Cory R,Canada Justin M,Carbone Salvatore,Buckley Leo,Kadariya Dinesh,Del Buono Marco G,Billingsley Hayley,Wohlford George,Viscusi Michele,Oddi-Erdle Claudia,Abouzaki Nayef A,Dixon Dave,Biondi-Zoccai Giuseppe,Arena Ross,Abbate Antonio
Circulation. Heart failure
Background Enhanced inflammation may lead to exercise intolerance in heart failure with preserved ejection fraction. The aim of the current study was to determine whether IL (interleukin)-1 blockade with anakinra improved cardiorespiratory fitness in heart failure with preserved ejection fraction. Methods and Results Thirty-one patients with heart failure with preserved ejection fraction and CRP (C-reactive protein) >2 mg/L were randomized to anakinra (100 mg subcutaneously daily, N=21) or placebo (N=10) for 12 weeks. We measured peak oxygen consumption (Vo), ventilatory efficiency (V/Vco slope), and high-sensitivity CRP and NT-proBNP (N-terminal pro-B-type natriuretic peptide) at 4, 12, and 24 weeks. Twenty-eight patients completed ≥2 visits, 18 women (64%), 27 (96%) obese. There were no differences in peak Vo or V/Vco slope between groups at baseline. Peak Vo was not changed after 12 weeks of anakinra (from 13.6 [11.8-18.0] to 14.2 [11.2-18.5] mL·kg·min, P=0.89), or placebo (14.9 [11.7-17.2] to 15.0 [13.8-16.9] mL·kg·min, P=0.40), without significant between-group differences in changes at 12 weeks (-0.4 [95% CI, -2.2 to +1.4], P=0.64). V/Vco slope was also unchanged with anakinra (from 28.3 [27.2-33.0] to 30.5 [26.3-32.8], P=0.97) or placebo (from 31.6 [27.3-36.9] to 31.2 [27.8-33.4], P=0.78), without significant between-group differences in changes at 12 weeks (+1.2 [95% CI, -1.8 to +4.3], P=0.97). Within the anakinra-treated patients, high-sensitivity CRP and NT-proBNP levels were lower at 4 weeks compared with baseline ( P=0.026 and P=0.022 versus placebo [between-group analysis], respectively). Conclusions Treatment with anakinra for 12 weeks failed to improve peak Vo and V/Vco slope in a group of obese heart failure with preserved ejection fraction patients. The favorable trends in high-sensitivity CRP and NT-proBNP with anakinra deserve exploration in future studies. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02173548.
10.1161/CIRCHEARTFAILURE.118.005036
Epidemiology of "Heart Failure with Recovered Ejection Fraction": What do we do After Recovery?
Kuttab Johny S,Kiernan Michael S,Vest Amanda R
Current heart failure reports
Improvement in functional status, long-term survival, and quality of life has always been the goal of therapy in patients with heart failure with reduced ejection fraction. Neurohormonal modulating medications help patients achieve these goals and, in a subgroup of patients, can promote "reverse remodeling" resulting in the recovery of left ventricular systolic function. In the era of durable mechanical support, myocardial recovery that leads to explantation of the ventricular assist device occurs in a minority of cases. Optimal medical therapy appears to be a key component of achieving myocardial recovery, with recovery more likely in patients with a shorter duration of heart failure and a non-ischemic etiology. However, little is known about future management of patients who attain myocardial recovery, either with or without mechanical support. This review explores the epidemiology, physiology, cellular biology, and long-term outcomes for this subgroup of heart failure patients and outlines areas for future study.
10.1007/s11897-015-0274-4
Characteristics, Outcomes, and Treatment of Heart Failure With Improved Ejection Fraction.
Park Chan Soon,Park Jin Joo,Mebazaa Alexandre,Oh Il-Young,Park Hyun-Ah,Cho Hyun-Jai,Lee Hae-Young,Kim Kye Hun,Yoo Byung-Su,Kang Seok-Min,Baek Sang Hong,Jeon Eun-Seok,Kim Jae-Joong,Cho Myeong-Chan,Chae Shung Chull,Oh Byung-Hee,Choi Dong-Ju
Journal of the American Heart Association
Background Many patients with heart failure ( HF ) with reduced ejection fraction ( HF r EF ) experience improvement or recovery of left ventricular ejection fraction ( LVEF ). Data on clinical characteristics, outcomes, and medical therapy in patients with HF with improved ejection fraction (HFiEF) are scarce. Methods and Results Of 5625 consecutive patients hospitalized for acute HF in the KorAHF (Registry [Prospective Cohort] for Heart Failure in Korea) study, 5103 patients had baseline echocardiography and 2302 patients had follow-up echocardiography at 12 months. HF phenotypes were defined as persistent HF r EF ( LVEF ≤40% at baseline and at 1-year follow-up), HF i EF ( LVEF ≤40% at baseline and improved up to 40% at 1-year follow-up), HF with midrange ejection fraction (LVEF between 40% and <50%), and HF with preserved ejection fraction ( LVEF ≥50%). The primary outcome was 4-year all-cause mortality from the time of HF i EF diagnosis. Among 1509 HF r EF patients who had echocardiography 1 year after index hospitalization, 720 (31.3%) were diagnosed as having HF i EF . Younger age, female sex, de novo HF , hypertension, atrial fibrillation, and β-blocker use were positive predictors and diabetes mellitus and ischemic heart disease were negative predictors of HF i EF . During 4-year follow-up, patients with HF i EF showed lower mortality than those with persistent HF r EF in univariate, multivariate, and propensity-score-matched analyses. β-Blockers, but not renin-angiotensin system inhibitors or mineralocorticoid receptor antagonists, were associated with a reduced all-cause mortality risk (hazard ratio: 0.59; 95% CI , 0.40-0.87; P=0.007). Benefits for outcome seemed similar among patients receiving low- or high-dose β-blockers (log-rank, P=0.304). Conclusions HF i EF is a distinct HF phenotype with better clinical outcomes than other phenotypes. The use of β-blockers may be beneficial for these patients. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT01389843.
10.1161/JAHA.118.011077
Heart Failure With Improved Ejection Fraction: Is it Possible to Escape One's Past?
Gulati Gaurav,Udelson James E
JACC. Heart failure
Among patients with heart failure with reduced ejection fraction, investigators have repeatedly identified a subgroup whose left ventricular ejection fraction and structural remodeling can improve to normal or nearly normal levels with or without medical therapy. This subgroup of patients with "heart failure with improved ejection fraction" has distinct clinical characteristics and a more favorable prognosis compared with patients who continue to have reduced ejection fraction. However, many of these patients also manifest clinical and biochemical signs of incomplete resolution of heart failure pathophysiology and remain at some risk of adverse outcomes, thus indicating that they may not have completely recovered. Although rigorous evidence on managing these patients is sparse, there are several reasons to recommend continuation of heart failure therapies, including device therapies, to prevent clinical deterioration. Notable exceptions to this recommendation may include patients who recover from peripartum cardiomyopathy, fulminant myocarditis, or stress cardiomyopathy, whose excellent long-term prognoses may imply true myocardial recovery. More research on these patients is needed to better understand the mechanisms that lead to improvement in ejection fraction and to guide their clinical management.
10.1016/j.jchf.2018.05.004
Heart Failure With Recovered Ejection Fraction in African Americans: Results From the African-American Heart Failure Trial.
Chang Kay-Won,Beri Neil,Nguyen Nghia H,Arbit Boris,Fox Sutton,Mojaver Sean,Clopton Paul,Tam S William,Taylor Anne L,Cohn Jay N,Maisel Alan S,Anand Inder S
Journal of cardiac failure
BACKGROUND:Recent studies have described the entity of heart failure with recovered ejection fraction (HFrecEF), but population-specific studies remain lacking. The aim of this study was to characterize patients enrolled in the African-American Heart Failure Trial (A-HeFT) who had significant improvement in their ejection fraction (EF) during the 1st 6 months of follow-up. METHODS AND RESULTS:Subjects with HFrecEF (improvement in EF from <35% to >40% in 6 months; n = 59) were compared with 259 subjects with heart failure and persistently reduced EF (HFrEF), defined as EF ≤40% at 6-month follow-up. The effects of improvement in EF on all-cause mortality and 1st and all hospitalizations were analyzed. Compared with HFrEF, subjects with HFrecEF had a nonsignificant trend toward lower mortality (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.02-1.15; P = .068), fewer 1st HF hospitalizations (HR 0.22, 95% CI 0.07-0.71; P = .011), fewer recurrent HF hospitalizations (HR 0.13, 95% CI 0.05-0.37; P <.001), similar 1st all-cause hospitalizations (HR 0.67, 95% CI 0.39-1.15; P = .150), and fewer recurrent all-cause hospitalizations (HR 0.41, 95% CI 0.24-0.68; P <.001). CONCLUSIONS:These data confirm that, as in other populations, a small subgroup of black patients receiving standard care improve their EF with favorable outcomes. Further studies are required to determine whether myocardial recovery is permanent and the best management strategies in such patients.
10.1016/j.cardfail.2017.09.005
Heart Failure With Improved Ejection Fraction: Clinical Characteristics, Correlates of Recovery, and Survival: Results From the Valsartan Heart Failure Trial.
Florea Viorel G,Rector Thomas S,Anand Inder S,Cohn Jay N
Circulation. Heart failure
BACKGROUND:Heart failure with recovered or improved ejection fraction (HFiEF) has been proposed as a new category of HF. Whether HFiEF is clinically distinct from HF with persistently reduced ejection fraction remains to be validated. METHODS AND RESULTS:Of the 5010 subjects enrolled in the Valsartan Heart Failure Trial (Val-HeFT), 3519 had a baseline left ventricular EF of <35% and a follow-up echocardiographic assessment of EF at 12 months. Of these, 321 (9.1%) patients who had a 12-month EF of >40% constituted the subgroup with HFiEF. EF improved from 28.7±5.6% to 46.5±5.6% in the subgroup with HFiEF and remained reduced (25.2±6.2% and 27.5±7.1%) in the subgroup with HF with reduced ejection fraction. The group with HFiEF had a less severe hemodynamic, biomarker, and neurohormonal profile, and it was treated with a more intense HF medication regimen. Subjects who had higher blood pressure and those treated with a β-blocker or randomized to valsartan had greater odds of being in the HFiEF group, whereas those with an ischemic pathogenesis, a more dilated left ventricle, and a detectable hs-troponin had lower odds of an improvement in EF. Recovery of the EF to >40% was associated with a better survival compared with persistently reduced EF. CONCLUSIONS:Our data support HFiEF as a stratum of HF with reduced ejection fraction with a more favorable outcome, which occurs in a minority of patients with HF with reduced ejection fraction who have a lower prevalence of ischemic heart disease, a less severe hemodynamic, biomarker, and neurohormonal profile, and who are treated with a more intense HF medication regimen. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336.
10.1161/CIRCHEARTFAILURE.116.003123
Heterogeneous Outcomes of Heart Failure with Better Ejection Fraction.
Van Kirk Jenny,Fudim Marat,Green Cynthia L,Karra Ravi
Journal of cardiovascular translational research
We evaluated the heterogeneity of outcomes among heart failure patients with ventricular recovery. The BEST trial studied patients with left ventricular ejection fraction (LVEF) ≤ 35%. Serial LVEF assessment was performed at baseline, 3 months, and 12 months. Heart failure with better ejection fraction (HFbEF) was defined as an LVEF > 40% at any point. Of the patients who survived to 1 year, 399 (21.3%) had HFbEF. Among subjects with HFbEF, 173 (43.4%) had "extended" recovery, 161 (40.4%) had "late" recovery, and 65 (16.3%) patients had "transient" recovery. Subjects with HFbEF had an improved event-free survival from death or first HF hospitalization compared to subjects without recovery (HR 0.50, 95% CI, 0.39-0.64, p < 0.001). Compared to "transient" recovery, "late" and "extended" recovery were associated with an improved event-free survival from all-cause death and HF hospitalization (HR 0.55, 95% CI, 0.34-0.90, p = 0.016). Our study shows patients with HFbEF to be a heterogeneous population with differing prognoses.
10.1007/s12265-019-09919-9
Association of Genetic Polymorphisms in the Beta-1 Adrenergic Receptor with Recovery of Left Ventricular Ejection Fraction in Patients with Heart Failure.
Luzum Jasmine A,English Joseph D,Ahmad Umair S,Sun Jessie W,Canan Benjamin D,Sadee Wolfgang,Kitzmiller Joseph P,Binkley Philip F
Journal of cardiovascular translational research
Two common genetic polymorphisms in the beta-1 adrenergic receptor (ADRB1 Ser49Gly [rs1801252] and Arg389Gly [rs1801253]) significantly affect receptor function in vitro. The objective of this study was to determine whether ADRB1 Ser49Gly and Arg389Gly are associated with recovery of left ventricular ejection fraction (LVEF) in patients with heart failure. Patients with heart failure and baseline LVEF ≤ 40% were genotyped (n = 98), and retrospective chart review assessed the primary outcome of LVEF recovery to ≥ 40%. Un/adjusted logistic regression models revealed that Ser49Gly, but not Arg389Gly, was significantly associated with LVEF recovery in a dominant genetic model. The adjusted odds ratio for Ser49 was 8.2 (95% CI = 2.1-32.9; p = 0.003), and it was the strongest predictor of LVEF recovery among multiple clinical variables. In conclusion, patients with heart failure and reduced ejection fraction that are homozygous for ADRB1 Ser49 were significantly more likely to experience LVEF recovery than Gly49 carriers.
10.1007/s12265-019-09866-5