Mixed Cardiogenic Shock: A Proposal for Standardized Classification, a Hemodynamic Definition, and Framework for Management.
Circulation
The classification of cardiogenic shock (CS) has evolved from a singular cold-and wet-hemodynamic profile. Data from registries and clinical trials have contributed to a broader recognition that although all patients with CS have insufficient cardiac output leading to end organ hypoperfusion, there is considerable variability in CS acuity, underlying etiologies, volume status, and systemic vascular resistance. Mixed CS can be broadly categorized as . Mixed CS states are now the second leading cause of shock in contemporary coronary intensive care units, but there is little high-quality evidence to guide routine care, and there are no standardized classification frameworks or well-established hemodynamic definitions. This primer summarizes the current epidemiology and proposes a classification framework and invasive hemodynamic parameters to guide categorization that could be applied to help better phenotype patients captured in registries and trials, as well as guide management of mixed CS states.
10.1161/CIRCULATIONAHA.124.069508
Large-bore Mechanical Thrombectomy Versus Catheter-directed Thrombolysis in the Management of Intermediate-risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial.
Circulation
BACKGROUND:There is a lack of randomized controlled trial (RCT) data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism (PE). METHODS:PEERLESS is a prospective, multicenter, RCT that enrolled 550 intermediate-risk PE patients with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary endpoint was a hierarchal win ratio (WR) composite of the following: 1) all-cause mortality, 2) intracranial hemorrhage, 3) major bleeding, 4) clinical deterioration and/or escalation to bailout, and 5) postprocedural intensive care unit (ICU) admission and length of stay, assessed at the sooner of hospital discharge or 7 days post-procedure. Assessments at the 24-hour visit included respiratory rate, mMRC dyspnea score, NYHA classification, right ventricle (RV)/left ventricle (LV) ratio reduction, and RV function. Endpoints through 30 days included total hospital stay, all-cause readmission, and all-cause mortality. RESULTS:The primary endpoint occurred significantly less frequently with LBMT vs CDT (WR 5.01 [95% CI: 3.68-6.97]; <0.001). There were significantly fewer episodes of clinical deterioration and/or bailout (1.8% vs 5.4%; =0.04) with LBMT vs CDT and less postprocedural ICU utilization (<0.001), including admissions (41.6% vs 98.6%) and stays >24 hours (19.3% vs 64.5%). There was no significant difference in mortality, intracranial hemorrhage, or major bleeding between strategies, nor in a secondary WR endpoint including the first 4 components (WR 1.34 [95% CI: 0.78-2.35]; =0.30). At the 24-hour visit, respiratory rate was lower for LBMT patients (18.3±3.3 vs 20.1±5.1; <0.001) and fewer had moderate to severe mMRC dyspnea scores (13.5% vs 26.4%; <0.001), NYHA classifications (16.3% vs 27.4%; =0.002), and RV dysfunction (42.1% vs 57.9%; =0.004). RV/LV ratio reduction was similar (0.32±0.24 vs 0.30±0.26; =0.55). LBMT patients had shorter total hospital stays (4.5±2.8 vs 5.3±3.9 overnights; =0.002) and fewer all-cause readmissions (3.2% vs 7.9%; =0.03), while 30-day mortality was similar (0.4% vs 0.8%; =0.62). CONCLUSIONS:PEERLESS met its primary endpoint in favor of LBMT vs CDT in treatment of intermediate-risk PE. LBMT had lower rates of clinical deterioration and/or bailout and postprocedural ICU utilization compared with CDT, with no difference in mortality or bleeding.
10.1161/CIRCULATIONAHA.124.072364
Microvascular obstruction in cardiac amyloidosis.
European journal of heart failure
AIMS:Cardiac amyloidosis (CA) is characterized by deposition of amyloid fibrils within the extracellular space, causing disarray of the myocardial structure and capillary architecture. This study aims to characterize the prevalence of microvascular obstruction (MVO) in patients with CA and to assess the association between MVO and prognosis. METHODS AND RESULTS:The study population comprised 800 patients, of which 400 had light-chain CA (AL-CA) and 400 had transthyretin CA (ATTR-CA). MVO was present in 221 (27.6%) patients, and more common in ATTR-CA than AL-CA (124 [56.1%] vs. 97 [43.9%], p = 0.033). Patients with MVO had a more severe cardiac phenotype evidenced by higher N-terminal pro-brain natriuretic peptide (3516 ng/L [1944-6247] vs. 2508 ng/L [1203-5752], p < 0.001), worse global longitudinal strain (-10.5% [-12.6; -7.9] vs. -12.0% [-16.0; -8.9], p < 0.001), and higher extracellular volume (56% [51-61] vs. 50% [45-57], p < 0.001). Patients with AL-CA and MVO had a higher serum troponin (86 ng/L [47-148] vs. 59 ng/L [44-78], p < 0.001), and higher T2 (53 ms [50-56] vs. 50 ms [48-52], p < 0.001), but lower extracellular volume (55% [50-60] vs. 58% [53-61], p = 0.008) and lower indexed myocyte cell volume (48.6 g/m [41.1-59.8] vs. 55.7 g/m [47.5-68.4], p < 0.001) than patients with ATTR-CA and MVO. MVO was associated with an increased risk of mortality in the overall population (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.03-1.59, p = 0.025), and the subgroup with AL-CA (HR 1.59, 95% CI 1.17-2.17, p = 0.003) but not ATTR-CA (HR 1.04, 95% CI 0.77-1.40, p = 0.814). CONCLUSIONS:Microvascular obstruction is common in CA and is related to markers of amyloid infiltration. MVO is associated with an increased risk of mortality in AL-CA, but not in ATTR-CA. This reflects the intrinsic differences in disease biology between these two forms of CA, with MVO likely related to multiple myocardial processes, amyloid infiltration, oedema and myocyte death.
10.1002/ejhf.3481
The global, regional, and national burden of myocarditis in 204 countries and territories, 1990-2021: Results from the Global Burden of Disease Study 2021.
European journal of heart failure
AIMS:To estimate the global burden of myocarditis in the general population from 1990 to 2021. METHODS AND RESULTS:Data on myocarditis were retrieved from the Global Burden of Disease Study 2021. Incidence, deaths, and disability-adjusted life years (DALYs), along with their age-standardized rates (ASRs) per 100 000 population, were used to measure the burden of myocarditis. Global, regional, and national analyses were performed for the period between 1990 and 2021. Further sub-analyses were conducted based on age group, sex, and sociodemographic index (SDI). In 2021, there were 1.3 million (95% uncertainty interval [UI]: 1.1 to 1.6) incident cases, 31.7 thousand (95% UI: 25.5 to 37.1) deaths, and 96.3 thousand (95% UI: 79.6 to 114.8) DALY cases globally. The ASRs of incidence, death, and DALYs significantly decreased from 1990 to 2021, with percentage changes of -3.9% (95% UI: -4.7% to -2.9%), -28.2% (95% UI: -42.2% to -12.5%), and -37.8% (95% UI: -50.5% to -24.3%), respectively. The global burden of myocarditis was higher in males, children, and the elderly. Additionally, the burden of myocarditis varied widely across different SDI regions, with high SDI regions having the highest ASR of incidence, and high-middle SDI regions having the highest ASRs of deaths and DALYs. CONCLUSION:Although the ASRs of incidence, deaths, and DALYs significantly decreased from 1990 to 2021, the global number of incidences, deaths, and DALYs increased substantially. Certain populations, including males, children, the elderly, and regions with advanced sociodemographic levels, experienced a heavier burden of myocarditis.
10.1002/ejhf.3483
Effects of atrial fibrillation ablation on arrhythmia burden and ventricular function in end-stage heart failure: Lessons from CASTLE-HTx.
European journal of heart failure
AIMS:The CASTLE-HTx trial showed the benefit of atrial fibrillation (AF) ablation compared to medical therapy in decreasing mortality, need for left ventricular assist device implantation or heart transplantation (HTx) in patients with end-stage heart failure (HF). Herein we describe the effects of catheter ablation on AF burden, arrhythmia recurrences, and ventricular function in end-stage HF. METHODS AND RESULTS:The CASTLE-HTx protocol randomized 194 patients in end-stage HF with AF to catheter ablation and medical therapy or medical therapy alone. AF burden, left ventricular ejection fraction (LVEF), and type of AF were assessed at baseline and at each follow-up visit. Overall, 97 patients received ablation; 66 patients (68%) underwent pulmonary vein isolation (PVI) and 31 patients (32%) were treated with PVI and additional ablation. Electroanatomic mapping showed the extent of left atrial low voltage (cardiomyopathy) >10% in 31 (31.9%) patients. At 12 months post-ablation, persistent AF was present in 31/89 patients (34.8%), which was significantly less frequent compared to baseline (p = 0.0001). Median AF burden reduction was 36.3 (interquartile range 13.6-63.3) percentage points at 12 months and LVEF improved from 29.2 ± 6.2% to 39.1 ± 8.3% (p < 0.001) following ablation. AF burden reduction <50% was significantly associated with LVEF improvement ≥5% at 12 months after ablation (p = 0.017). CONCLUSION:Atrial fibrillation ablation in end-stage HF leads to a substantial decrease in AF burden, a regression from persistent to paroxysmal AF and notably improved LVEF. Favourable ablation outcomes were observed in patients regardless of the presence or absence of signs indicating left atrial cardiomyopathy.
10.1002/ejhf.3505
Heart Failure and Obesity: Unraveling Molecular Mechanisms of Excess Adipose Tissue.
Journal of the American College of Cardiology
Obesity is an ongoing pandemic and is associated with the development of heart failure (HF), and especially HF with preserved ejection fraction. The definition of obesity is currently based on anthropometric measurements but neglects the location and molecular properties of excess fat. Important depots associated with HF development are subcutaneous adipose tissue and visceral adipose tissue, both located in the abdominal region, and epicardial adipose tissue (EAT) surrounding the myocardium. However, mechanisms linking these different adipose tissue depots to HF development are incompletely understood. EAT in particular is of great interest because of its close proximity to the heart. In this review, we therefore focus on the characteristics of different adipose tissue depots and their response to obesity. In addition, we evaluate how different mechanisms associated with EAT expansion potentially contribute to HF and in particular HF with preserved ejection fraction development.
10.1016/j.jacc.2024.07.016
Prognostic Impact of Admission Time in Infarct-Related Cardiogenic Shock: An ECLS-SHOCK Substudy.
JACC. Cardiovascular interventions
BACKGROUND:The outcomes of patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) and the efficacy and safety of extracorporeal life support (ECLS) may be affected by the timing of hospital admission. OBJECTIVES:The present ECLS-SHOCK substudy sought to investigate the prognostic impact of on-hours vs off-hours admission and the efficacy of ELCS according to the timing of hospital admission time in AMI-CS. METHODS:Patients with AMI-CS enrolled in the multicenter, randomized ECLS-SHOCK trial from 2019 to 2022 were included. The prognosis of patients admitted during regular hours (ie, on-hours) was compared to patients admitted during off-hours. Thereafter, the prognostic impact of ECLS was investigated stratified by the timing of hospital admission. The primary endpoint was 30-day all-cause mortality. Statistical analyses included Kaplan-Meier, univariable, and multivariable logistic regression analyses. RESULTS:Of 417 patients enrolled in the ECLS-SHOCK trial, 48.4% (n = 202) were admitted during off-hours. Patients admitted during off-hours were younger (median age = 62 years [Q1-Q3: 55-69 years] vs 63 years [Q1-Q3: 58-71 years]; P = 0.036) and more commonly treated using initial femoral access for coronary angiography (79.0% [n = 158/200] vs 67.9% [n = 146/215]; P = 0.011). However, off-hours admission was not associated with an increased risk of 30-day all-cause mortality (off-hours vs on-hours: 46.0% [n = 93/202] vs 50.7% [n = 109/215]; OR: 0.83; 95% CI: 0.56-1.22). Furthermore, ECLS had no prognostic impact on 30-day all-cause mortality in patients with AMI-CS admitted during on-hours (50.5% [n = 52/103] vs 50.9% [n = 57/112]; P = 0.95; OR: 0.98; 95% CI: 0.58-1.68) or in patients admitted during off-hours (45.3% [n = 48/106] vs 46.9% [n = 45/96]; P = 0.82; OR: 0.94; 95% CI: 0.54-1.63). Finally, ECLS was associated with an increased risk of bleeding events, especially in patients admitted during on-hours. CONCLUSIONS:The prognosis in AMI-CS was not affected by admission time with a similar effect of ECLS during on- and off-hours.
10.1016/j.jcin.2024.08.013
Antithrombotic Therapy in High Bleeding Risk, Part I: Percutaneous Cardiac Interventions.
JACC. Cardiovascular interventions
Antithrombotic therapy after cardiac percutaneous interventions is key for the prevention of thrombotic events but is inevitably associated with increased bleeding, proportional to the number, duration, and potency of the antithrombotic agents used. Bleeding complications have important clinical implications, which in some cases may outweigh the expected benefit of reducing thrombotic events. Because the response to antithrombotic agents varies widely among patients, there has been a relentless effort toward the identification of patients at high bleeding risk (HBR), in whom modulation of antithrombotic therapy may be needed to optimize the balance between safety and efficacy. Among patients undergoing cardiac percutaneous interventions, recent advances in technology have allowed for strategies of de-escalation to reduce bleeding without compromising efficacy, and HBR patients are expected to benefit the most from such approaches. Guidelines do not extensively expand upon the topic of de-escalation strategies of antithrombotic therapy in HBR patients. In this review, we discuss the evidence and provide practical recommendations on optimal antithrombotic therapy in HBR patients undergoing various cardiac percutaneous interventions.
10.1016/j.jcin.2024.08.022
Targeting immune-fibroblast cell communication in heart failure.
Nature
Inflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction. However, the molecular mechanisms driving immune-fibroblast cell communication in human cardiac disease remain unexplored and there are at present no approved treatments that directly target cardiac fibrosis. Here we performed multiomic single-cell gene expression, epitope mapping and chromatin accessibility profiling in 45 healthy donor, acutely infarcted and chronically failing human hearts. We identified a disease-associated fibroblast trajectory that diverged into distinct populations reminiscent of myofibroblasts and matrifibrocytes, the latter expressing fibroblast activator protein (FAP) and periostin (POSTN). Genetic lineage tracing of FAP fibroblasts in vivo showed that they contribute to the POSTN lineage but not the myofibroblast lineage. We assessed the applicability of experimental systems to model cardiac fibroblasts and demonstrated that three different in vivo mouse models of cardiac injury were superior compared with cultured human heart and dermal fibroblasts in recapitulating the human disease phenotype. Ligand-receptor analysis and spatial transcriptomics predicted that interactions between C-C chemokine receptor type 2 (CCR2) macrophages and fibroblasts mediated by interleukin-1β (IL-1β) signalling drove the emergence of FAP/POSTN fibroblasts within spatially defined niches. In vivo, we deleted the IL-1 receptor on fibroblasts and the IL-1β ligand in CCR2 monocytes and macrophages, and inhibited IL-1β signalling using a monoclonal antibody, and showed reduced FAP/POSTN fibroblasts, diminished myocardial fibrosis and improved cardiac function. These findings highlight the broader therapeutic potential of targeting inflammation to treat tissue fibrosis and preserve organ function.
10.1038/s41586-024-08008-5
Malnutrition in older adults.
Lancet (London, England)
Malnutrition is a highly prevalent condition in older adults, and poses a substantial burden on health, social, and aged-care systems. Older adults are vulnerable to malnutrition due to age-related physiological decline, reduced access to nutritious food, and comorbidity. Clinical guidelines recommend routine screening for malnutrition in all older adults, together with nutritional assessment and individually tailored nutritional support for older adults with a positive screening test. Nutritional support includes offering individualised nutritional advice and counselling; oral nutritional supplements; fortified foods; and enteral or parenteral nutrition as required. However, in clinical practice, the incorporation of nutritional guidelines is inadequate and low-value care is commonplace. This Review discusses the current evidence on identification and treatment of malnutrition in older adults, identifies gaps between evidence and practice in clinical care, and offers practical strategies to translate evidence-based knowledge into improved nutritional care. We also provide an overview of the prevalence, causes, and risk factors of malnutrition in older adults across health-care settings.
10.1016/S0140-6736(22)02612-5
Clinical Correlates and Prognostic Impact of Cognitive Dysfunction in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF.
Circulation
BACKGROUND:Cognitive impairment is common in patients with heart failure and preserved ejection fraction but its clinical correlates and prognostic associations are poorly understood. METHODS:We analyzed cognitive function, using the Mini-Mental State Examination (MMSE), in patients with heart failure and preserved ejection fraction enrolled in a prespecified substudy of the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). Logistic regression analyses were performed to determine the variables associated with lower MMSE scores at baseline and postbaseline decline in MMSE scores at 48 weeks. Cox proportional hazards regression and semiparametric proportional rates models were used to examine the risk of clinical outcomes related to baseline MMSE scores, and decline in MMSE scores during follow-up, adjusted for prognostic variables including NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS:At baseline, cognitive function was normal (MMSE score 28-30) in 1809 of 2895 patients (62.5%), borderline (score 24-27) in 794 (27.4%), and impaired (score <24) in 292 (10.1%). Variables associated with both a lower MMSE score at baseline and a decline in score from baseline included older age, a history of stroke or transient ischemia attack, and lower serum albumin. Compared with those with baseline MMSE scores of 28 to 30, patients in the lower MMSE score categories had a stepwise increase in the risk of the composite of time to first HF hospitalization or cardiovascular death, with an adjusted hazard ratio of 1.27 (95% CI, 1.06-1.53) for those with scores of 24 to 27 and 1.58 (95% CI, 1.21-2.06) for those with scores <24, respectively. These associations were also found for the individual components of the composite and all-cause death. Likewise, cognitive impairment was associated with a 50% higher risk of total (first and repeat) heart failure hospitalizations and cardiovascular deaths. Examining the change in MMSE score from baseline, a decrease in MMSE score during follow-up was associated with a higher risk of death. CONCLUSIONS:In patients with heart failure and preserved ejection fraction, even modest baseline impairment of cognitive function was associated with worse outcomes, including death. A decline in MMSE score during follow-up was a strong predictor of mortality, independent of other prognostic variables.
10.1161/CIRCULATIONAHA.124.070553