Search

Severe left ventricular dysfunction and ventricular wall motion abnormalities predispose individuals to thrombosis and thromboembolism. Thromboembolism is one of the main causes of increased mortality in patients with heart failure and reduced ejection fraction (HFrEF). However, regarding thromboembolism due to HFrEF in sinus rhythm, most cases to date have reported ischemic strokes, and repeated embolization of peripheral arteries has been reported not uncommon. Herein, we report the case of a 48-year-old man with a definite diagnosis of sinus rhythm HFrEF and recurrent peripheral arterial embolization within a short period. The condition is caused by severe left ventricular systolic dysfunction and abnormal left ventricular wall motion, resulting in blood stasis and abnormal blood composition, with or without left ventricular thrombosis, and can lead to thromboembolism. Current guidelines state that patients with heart failure and clear indication(s) for anticoagulation (e.g., atrial fibrillation, heart valve replacement) should be administered appropriate anticoagulation therapy. However, controversy persists regarding whether patients with HFrEF in sinus rhythm can benefit from anticoagulation therapy. This case highlights the utility and necessity of anticoagulation for the prevention of intracardiac thrombosis and the treatment of peripheral arterial embolism in patients with HFrEF in sinus rhythm.

IntroductionAlthough angiotensin receptor-neprilysin inhibitor (ARNI) has shown promise in patients with heart failure and reduced ejection fraction (HFrEF), the treatment effect in HFrEF patients with end-stage renal disease (ESRD) undergoing dialysis is uncertain. This study aimed to examine the real-world effects of ARNI vs. angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in this subpopulation.MethodsThis multi-institutional, retrospective study identified 349 HFrEF patients with ESRD on dialysis, who initiated either ARNI or ACEI/ARB therapy. Efficacy outcomes included rates of hospitalization for heart failure (HHF) and mortality, as well as changes in echocardiographic parameters. Safety outcomes encompassed hypotension and hyperkalemia. Treatment effects were assessed using Cox proportional hazards models, with additional sensitivity analyses for robustness.ResultsOut of 349 patients screened, 89 were included in the final analysis (42 in the ARNI group and 47 in the ACEI/ARB group). After 1 year of treatment, echocardiographic measures between the two groups were comparable. The primary composite rate of HHF or mortality was 20.6 events per 100 patient-years in the ARNI group and 26.1 in the ACEI/ARB group; the adjusted hazard ratio was 0.98 (95% CI: 0.28–3.43, P = 0.97). Their safety outcomes did not differ significantly. Sensitivity analyses, including repetitive sampling, propensity score matching, and extended follow-up, corroborated these findings.ConclusionARNI has proven effective in treating HFrEF patients; however, significant benefits were not observed in these patients with ESRD undergoing dialysis compared with ACEI/ARB in this real-world cohort. Future research employing a more extended follow-up period, larger sample size, or randomized design is warranted to investigate the treatment effects in this subpopulation.

BackgroundIschaemic heart failure with reduced ejection fraction (HFrEF) caused by coronary artery disease accounts for the largest proportion of heart failure cases with the worst prognosis. Coronary artery bypass grafting (CABG) is the most effective treatment for ischaemic HFrEF. On-pump and off-pump are the two surgical methods used for CABG. Whether patients with HFrEF should undergo on- or off-pump CABG is controversial in coronary heart disease surgery. The left ventricular end-systolic volume index (LVSEVI) is the gold standard for evaluating the severity of left ventricular remodelling; however, its effect on the perioperative risk and long-term survival rate of patients with HFrEF undergoing CABG remains unclear.MethodsThis single centre prospective cohort analysis included 118 coronary heart disease patients with symptoms and signs of heart failure and a left ventricular ejection fraction (LVEF) of

Introduction: Although angiotensin receptor-neprilysin inhibitor (ARNI) has shown promise in patients with heart failure and reduced ejection fraction (HFrEF), the treatment effect in HFrEF patients with end-stage renal disease (ESRD) undergoing dialysis is uncertain. This study aimed to examine the real-world effects of ARNI vs. angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in this subpopulation., Methods: This multi-institutional, retrospective study identified 349 HFrEF patients with ESRD on dialysis, who initiated either ARNI or ACEI/ARB therapy. Efficacy outcomes included rates of hospitalization for heart failure (HHF) and mortality, as well as changes in echocardiographic parameters. Safety outcomes encompassed hypotension and hyperkalemia. Treatment effects were assessed using Cox proportional hazards models, with additional sensitivity analyses for robustness., Results: Out of 349 patients screened, 89 were included in the final analysis (42 in the ARNI group and 47 in the ACEI/ARB group). After 1 year of treatment, echocardiographic measures between the two groups were comparable. The primary composite rate of HHF or mortality was 20.6 events per 100 patient-years in the ARNI group and 26.1 in the ACEI/ARB group; the adjusted hazard ratio was 0.98 (95% CI: 0.28-3.43, P  = 0.97). Their safety outcomes did not differ significantly. Sensitivity analyses, including repetitive sampling, propensity score matching, and extended follow-up, corroborated these findings., Conclusion: ARNI has proven effective in treating HFrEF patients; however, significant benefits were not observed in these patients with ESRD undergoing dialysis compared with ACEI/ARB in this real-world cohort. Future research employing a more extended follow-up period, larger sample size, or randomized design is warranted to investigate the treatment effects in this subpopulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yang, Huang, Yang, Toh, Chang, Su, Lin, Wang, Wang and Liao.)

Background: Ischaemic heart failure with reduced ejection fraction (HFrEF) caused by coronary artery disease accounts for the largest proportion of heart failure cases with the worst prognosis. Coronary artery bypass grafting (CABG) is the most effective treatment for ischaemic HFrEF. On-pump and off-pump are the two surgical methods used for CABG. Whether patients with HFrEF should undergo on- or off-pump CABG is controversial in coronary heart disease surgery. The left ventricular end-systolic volume index (LVSEVI) is the gold standard for evaluating the severity of left ventricular remodelling; however, its effect on the perioperative risk and long-term survival rate of patients with HFrEF undergoing CABG remains unclear., Methods: This single centre prospective cohort analysis included 118 coronary heart disease patients with symptoms and signs of heart failure and a left ventricular ejection fraction (LVEF) of <40% who were enrolled consecutively from January 2019 to December 2023. Operative mortality, perioperative complications, and long-term survival were compared among patients treated with various LVESVIs and surgical methods. The primary outcomes were cardiac death, myocardial infarction, heart failure, stroke, and revascularization, (percutaneous coronary intervention or redo CABG) with a median follow-up of 38 ± 10 months., Results: The 30-day postoperative mortality of 118 patients was 6.8%. Patients in the off-pump group had significantly higher perioperative mortality than those in the on-pump group (12.5% vs. 3.8%, p  = 0.03). In the off-pump group, a higher proportion of patients required perioperative mechanical assistance, such as intra-aortic artery balloon pump (IABP) or extracorporeal membrane oxygenation (ECMO), compared to those in the on-pump group (IABP: 75% vs. 47.4%, p  = 0.004; ECMO: 22.5% vs. 1.3%, p  = 0.000). Patients in the off-pump group were more likely to have postoperative atrial fibrillation (AF) (35% vs. 14.1%, p  = 0.01). In the on-pump group, the incidence of postoperative AF (25% vs. 6.5%, p  = 0.02) and IABP use (62.5% vs. 36.9%, p  = 0.03) were significantly higher in patients with more severe left ventricular remodelling than in those with less severe left ventricular remodelling. In the off-pump group, patients with more severe left ventricular remodelling had higher ECMO usage (38.9% vs. 9.1%, p  = 0.04), incidence of postoperative AF (61.1% vs. 13.6%, p  = 0.02), and perioperative mortality (22.2%). Major adverse cardiac event (MACE)-free survival rate was significantly higher in the on-pump group than in the off-pump group, and there was no significant difference in MACE free survival rates between the two groups of patients with different degrees of left ventricular remodelling., Conclusion: On-pump bypass is a better surgical procedure for patients with ischaemic HFrEF, especially those with severe left ventricular remodelling. Left ventricular remodelling increases perioperative mortality but has no effect on long-term survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Cao, Yu, Xiao, Dong and Wang.)

Background: Although clinical studies have demonstrated the association between a single N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement and clinical outcomes in chronic heart failure, the biomarker is frequently measured serially in clinical practice., Objectives: The aim of this study was to determine the added prognostic value of repeated NT-proBNP measurements compared with single measurements alone for chronic heart failure patients., Methods: In the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study, 894 study participants with chronic heart failure with reduced ejection fraction were enrolled at 45 outpatient sites in the United States and Canada. Repeated NT-proBNP levels were measured over a 2-year study period. Associations between repeated NT-proBNP measurements and trial endpoints were assessed using a joint longitudinal and survival model., Results: After adjustment for baseline covariates, each doubling of the baseline NT-proBNP level was associated with a HR of 1.17 (95% CI: 1.08-1.28; P = 0.0003) for the primary trial endpoint of cardiovascular death or heart failure hospitalization. Serial measurements increased the adjusted HR for the primary trial endpoint to 1.66 (95% CI: 1.50-1.84; P < 0.0001), and a similar increased risk was observed across secondary trial endpoints. In joint modeling, an increase in NT-proBNP occurred weeks before the onset of adjudicated events., Conclusions: Repeated NT-proBNP measurements are a strong predictor of outcomes in heart failure with reduced ejection fraction with an increase in concentration occurring well before event onset. These results may support routine NT-proBNP monitoring to assist in clinical decision making. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840)., Competing Interests: Funding Support and Author Disclosures The GUIDE-IT trial was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Additional substudies were supported by Roche Diagnostics. The sponsors had no role in the design and conduct of the present study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Dr O’Connor has received grant or research support from Merck; and has received consulting fees from Merck, Bayer, and Abiomed. Dr Fiuzat has received grant support from the National Institutes of Health and Roche Diagnostics. Dr Ezekowitz has received research grant support and consulting fees from Bayer, Merck, Servier, Amgen, Sanofi, Novartis, Cytokinetics, American Regent, Otsuka, and Applied Therapeutics. Dr Piña has participated on Advisory Boards for Vifor and AstraZeneca; and is a Steering Committee member for Novartis. Dr Whellan has received grants from National Heart, Lung, and Blood Institute, Merck, Amgen, Cytokinetcis, and Norvo Nordisk; has acted as a consultant to Cytokinetics and Novo Nordisk; and has served on Clinical Endpoint Committees/Data and Safety Monitoring Boards for CVRx and National Institutes of Health. Dr Mark reports grant support to institution from HeartFlow and Merck. Dr Felker has received research grants from National Heart, Lung, and Blood Institute, American Heart Association, Amgen, Bayer, BMS, Merck, Cytokinetics, and CSL-Behring; has acted as a consultant to Novartis, Amgen, BMS, Cytokinetics, Innolife, Medtronic, Cardionomic, Boehringer-Ingelheim, American Regent, Abbott, AstraZeneca, Regeneron, Reprieve, Myovant, Sequana, Windtree Therapuetics, Rocket Pharma, and Whiteswell; and has served on Clinical Endpoint Committees/Data and Safety Monitoring Boards for Amgen, Merck, Medtronic, EBR Systems, V-Wave, and LivaNova. Dr Desai works under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures used for public reporting and pay for performance programs; and reports research grants and consulting for Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Novartis, SCPharmaceuticals, and Vifor. Dr Januzzi is a Trustee of the American College of Cardiology and a Director at Jana Care and Imbria; has received grant support from Abbott, Applied Therapeutics, HeartFlow Inc, Innolife, and Roche Diagnostics, has received consulting income from Abbott, AstraZeneca, Beckman-Coulter, Boehringer-Ingelheim, Janssen, Novartis, Merck, Quidel, Roche Diagnostics, and Siemens; and participates in Clinical Endpoint Committees/Data and Safety Monitoring boards for Abbott, AbbVie, Bayer, CVRx, Pfizer, and Takeda. Dr Ahmad has received consulting fees from Sanofi, Amgen, and Cytokinetics; and has received research funding from Boehringer Ingelheim, AstraZeneca, Cytokinetics, and Relypsa. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims In the DAPA-HF trial, the SGLT2 inhibitor dapagliflozin reduced the risk of worsening heart failure (HF) and death in patients with HF and reduced ejection fraction. We examined whether this benefit was consistent in relation to background HF therapy. Methods and results In this post hoc analysis, we examined the effect of study treatment in the following yes/no subgroups: diuretic, digoxin, mineralocorticoid receptor antagonist (MRA), sacubitril/valsartan, ivabradine, implanted cardioverter-defibrillating (ICD) device, and cardiac resynchronization therapy. We also examined the effect of study drug according to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose, beta-blocker (BB) dose, and MRA (≥50% and <50% of target dose). We analysed the primary composite endpoint of cardiovascular death or a worsening HF event. Most randomized patients (n  = 4744) were treated with a diuretic (84%), renin–angiotensin system (RAS) blocker (94%), and BB (96%); 52% of those taking a BB and 38% taking a RAS blocker were treated with ≥50% of the recommended dose. Overall, the dapagliflozin vs. placebo hazard ratio (HR) was 0.74 [95% confidence interval (CI) 0.65–0.85] for the primary composite endpoint (P  < 0.0001). The effect of dapagliflozin was consistent across all subgroups examined: the HR ranged from 0.57 to 0.86 for primary endpoint, with no significant randomized treatment-by-subgroup interaction. For example, the HR in patients taking a RAS blocker, BB, and MRA at baseline was 0.72 (95% CI 0.61–0.86) compared with 0.77 (95% CI 0.63–0.94) in those not on all three of these treatments (P -interaction 0.64). Conclusion The benefit of dapagliflozin was consistent regardless of background therapy for HF. [ABSTRACT FROM AUTHOR]

Background: The representation of women in heart failure studies has been inadequate, resulting in a knowledge gap regarding the prognostic impact of coronary artery disease (CAD) on all-cause mortality in women with newly diagnosed heart failure and reduced ejection fraction (HFrEF)., Objectives: This study aims to assess the prognostic impact of CAD in women with HFrEF., Methods: Using the Western Denmark Heart Registry, the authors identified 891 women and 2,403 men referred for first-time coronary angiography because of HFrEF. The authors stratified for presence of CAD, estimated 10-year all-cause mortality, and calculated crude and adjusted HRs (aHRs) with 95% CIs., Results: The 10-year mortality was 60% in women with CAD and 27% in women without CAD; for men, the corresponding numbers were 54% and 36%. When adjusted for comorbidities, women without CAD had a lower relative 10-year mortality than men without CAD (aHR: 0.73; 95% CI: 0.58-0.91), whereas women with CAD had similar relative mortality as men with CAD (aHR: 1.00; 95% CI: 0.81-1.24) (P interaction  = 0.037). Assessed by the number of coronary vessels with significant stenosis, CAD extent was associated with mortality for both women (P < 0.01) and men (P < 0.01). However, compared to those without CAD, the aHR was higher for women with any degree of CAD (aHR ranging from 1.61 [95% CI: 1.09-2.38] for diffuse CAD to 2.01 [95% CI: 1.19-3.40] for 3-vessel disease) than for men with 3-vessel disease (aHR: 1.51; 95% CI: 1.19-1.91)., Conclusions: In patients with newly diagnosed HFrEF, the presence and extent of CAD has significantly greater prognostic impact among women than among men., Competing Interests: Funding Support and Author Disclosures This study was funded by the Research Unit, Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Factors associated with mortality for patients with heart failure and reduced ejection fraction (HFrEF) are known; however, the association between initial pharmacotherapy (IPT) and mortality is unclear in real-world settings.Methods: Using a retrospective design and claims database, 14,359 Medicare patients with HFrEF from August 2010 to July 2015 were identified. Index date was first HF claim. IPT was mono- or combo-angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), beta-blocker (BB), hydralazine-nitrate (HN), and aldosterone antagonist (AA) within 1 year post-index. A multivariable time-dependent Cox model estimated associations between IPT and 2-year all-cause mortality.Results: Patients' median age was 76 (70-82) years; 45.1% were female. Within 1 month post-index, 61.4% had IPT, 6.1% started after the first month, and 32.4% had no IPT in the first year. Of IPTs, 47.5% were mono-vasodilators (ACEI, ARB or HN), 23.3% mono-vasodilator + BB, 16.9% mono-BB, and 3.5% triple therapy [(ACEI or ARB) + BB + (HN or AA)]. Two-year mortality rate was 27.9%. Compared to mono-vasodilator therapy, patients initiating triple therapy had 29.3% lower risk of 2-year mortality; those on mono-BB or no IPT had higher mortality risk.Conclusion: IPT was associated with decreased 2-year mortality risk. Timely consideration of triple IPT therapies may be warranted once HFrEF diagnosis is confirmed.Funding: Novartis Pharmaceuticals Corp. located in East Hanover, NJ, USA. [ABSTRACT FROM AUTHOR]

Background Renin–angiotensin–aldosterone system (RAAS) blockers are effective therapies for heart failure and reduced ejection fraction (HFrEF) or left ventricular dysfunction (LVD). We aimed to assess the efficacy and safety of RAAS blockers in these patients. Methods We searched MEDLINE, EMBASE, and Cochrane Library in May 2015. Twenty-one double-blind randomized controlled trials (RCTs) with 69,229 patients were included this network meta-analysis. Results Compared with placebo, an angiotensin receptor–neprilysin inhibitor (ARNI) had the highest probability of reducing all-cause mortality (odds ratio [OR] = 0.67, 95% credible interval [CrI]: 0.48–0.86), followed by an aldosterone receptor antagonist (ARA, OR = 0.74, 95% CrI: 0.62–0.88) and an angiotensin-converting enzyme inhibitor (ACEI, OR = 0.80, 95% CrI: 0.71–0.89). The most efficacious therapy for preventing heart failure hospitalization was ARNI (OR = 0.55, 95% CrI: 0.40–0.71), followed by combination therapy with an angiotensin II receptor blocker (ARB) plus an ACEI (OR = 0.61, 95% CrI: 0.49–0.75), then an ACEI alone (OR = 0.69, 95% CrI: 0.61–0.77). Sensitivity analysis restricted to nine RCTs with a high background use of ACEI and/or ARB (> 80%) indicated that adding an ARA to current standard therapy significantly reduced mortality (OR = 0.73, 95% CrI: 0.51–0.95) and hospitalization risk (OR = 0.67, 95% CrI: 0.47–0.87), but did not significantly increase the discontinuation risk (OR = 1.29, 95% CrI: 0.83–2.31). Conclusions ARNI has the highest probability of being the most efficacious therapy for HFrEF in reducing death and hospitalization for heart failure. ARA has the most favorable benefit–risk profile as an adjunct to background ACEI and/or ARB therapy. [ABSTRACT FROM AUTHOR]

This mini-review summarizes the literature regarding the mechanisms of exercise intolerance in patients with heart failure and reduced or preserved ejection fraction (HFREF and HFPEF, respectively). Evidence to date suggests that the reduced peak pulmonary oxygen uptake (pulm ...O2) in patients with HFREF compared with healthy controls is due to both central (reduced convective O2 transport) and peripheral factors (impaired skeletal muscle blood flow, decreased diffusive O2 transport coupled with abnormal skeletal morphology, and metabolism). Although central and peripheral impairments also limit peak pulm ...O2 in HFPEF patients compared with healthy controls, emerging data suggest that the latter may play a relatively greater role in limiting exercise performance in these patients. Unlike HFREF, currently there is limited evidence-based therapies that improve exercise capacity in HFPEF patients, therefore future studies are required to determine whether interventions targeted to improve peripheral vascular and skeletal muscle function result in favorable improvements in peak pulm and leg ...O2 and their determinants in HFPEF patients. [ABSTRACT FROM AUTHOR]

Objective: The effect of renin-angiotensin system inhibitors (RASIs) in patients with heart failure (HF) and atrial fibrillation (AF) remains unclear. This study aimed to investigate associations between RASI use and all-cause mortality and cardiovascular outcomes in patients with AF and HF., Methods: Using data from the China Atrial Fibrillation Registry study, we included 938 patients with AF and HF with a left ventricular ejection fraction <50%. Cox regression models for RASIs vs. non-RASIs with all-cause mortality as the primary outcome were fitted in a 1:1 propensity score-matched cohort. A sensitivity analysis was performed by using a multivariable time-dependent Cox regression model. As an internal control, we assessed the relation between β-blocker use and all-cause mortality., Results: During a mean follow-up of 35 months, the risk of all-cause mortality was similar in RASI users compared with non-users (hazard ratio: 0.92; 95% confidence interval: 0.67-1.26). Similar results were obtained in the sensitivity analysis. In contrast, β-blocker use was associated with significantly lower all-cause mortality in the same population., Conclusions: RASI use was not associated with better outcomes in patients with AF and HF in this prospective cohort, which raises questions about their value in this specific subset.Trail Registration: ChiCTR-OCH-13003729.

Objectives: The aim of this study was to examine patterns of care and clinical outcomes among patients with heart failure with reduced ejection fraction (HFrEF) in the United States and Canada., Background: In the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment) trial, the use of N-terminal pro-B-type natriuretic peptide-guided titration of guideline-directed medical therapy (GDMT) was compared with usual care alone for patients with HFrEF in the United States and Canada. It remains unknown whether the country of enrollment had an impact on outcomes or GDMT use., Methods: A total of 894 patients at 45 sites across the United States and Canada with HFrEF (ejection fraction ≤40%) were enrolled in the trial. Kaplan-Meier survival estimates stratified by country of enrollment were developed for the trial outcomes, and log-rank testing was compared between the groups. GDMT use and titration were also compared., Results: U.S. patients were more likely to be younger, to be Black, to have higher body mass index, and to have histories of defibrillator placement or sleep apnea. Use of β-blockers was significantly higher in Canada at baseline (99.3% vs. 94.0%; p = 0.01) and 6 months (99.0% vs. 94.1%; p = 0.04), and use of mineralocorticoid receptor antagonists was higher in Canada at 6 months (68.3% vs. 55.1%; p = 0.01). Canadian patients were less likely to experience the primary study endpoint (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.45 to 0.93; p = 0.01) due to decreased rates of HF hospitalization (HR: 0.57; 95% CI: 0.38 to 0.86; p = 0.003). The differences in outcomes were driven by increased heart failure hospitalization among U.S. Black patients., Conclusions: In GUIDE-IT, patients with HFrEF in Canada were significantly less likely to be hospitalized for heart failure. Differences in GDMT use, along with differences in sociodemographics and care delivery structures, may contribute to these differences, highlighting the importance of increasing diversity in clinical trials. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840)., Competing Interests: Funding Support and Author Disclosures The GUIDE-IT trial was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Additional substudies were supported by Roche Diagnostics. The sponsors had no role in the design and conduct of the present study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Dr. Januzzi is a trustee of the American College of Cardiology; has received grant support from Roche Diagnostics, Novartis Pharmaceuticals, and Applied Therapeutics; has received consulting income from Abbott, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees and data and safety monitoring boards for Abbott, AbbVie, Amgen, CVRx, Janssen, MyoKardia, and Takeda. Dr. Desai works under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures used for public reporting and pay-for-performance programs; and has received research grants and consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim, Cytokinetics, The Medicines Company, Relypsa, Novartis, and SCPharmaceuticals. Dr. Felker has received research grants from the National Heart, Lung, and Blood Institute, the American Heart Association, Amgen, Bayer Merck, Cytokinetics, and Myokardia; has acted as a consultant to Novartis, Amgen, Bristol Myers Squibb, Cytokinetics, Medtronic, Cardionomic, Innolife, Boehringer Ingelheim, Abbott, Eidos Therapeutics, Reprieve, and Sequana; and has served on clinical endpoint committees and data and safety monitoring boards for Amgen, Merck, Medtronic, EBR Systems, V-Wave, LivaNova, and Rocket Pharma. Dr. Fiuzat has received grant support from the National Institutes of Health and Roche Diagnostics. Dr. O’Connor has received grant support from Roche Diagnostics and the National Institutes of Health. Dr. Ahmad is a consultant for Amgen, Cytokinetics, Relypsa, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)