Funding Support and Author Disclosures This study was supported by Sanofi and Lexicon Pharmaceuticals. Dr Pitt has received consulting fees from Lexicon, Bayer, AstraZeneca, Boehringer Ingelheim, Merck, and Phasebio; has received consulting fees and/or stock options from Viror, KBP Biosciences, Cereno Scientific, Tricida, SCPharmaceuticals, SQinnovatiions, G-3 Pharmaceuticals, Protonintel, and Brainstorm medical; holds U.S. Patent 9931412 on site specific delivery of eplerenone to the myocardium; and U.S. Patent pending 63/045,783 on histone-modulating agents for the protection and treatment of organ damage. Dr Bhatt is the Chair of SOLOIST with research funding paid by Lexicon to Brigham and Women’s Hospital; he is on the Advisory Board for AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; is on the Board of Directors for AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; is Inaugural Chair for the American Heart Association Quality Oversight Committee; is a consultant for Broadview Ventures; is on the Data Monitoring Committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; is on the RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; is on the AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned it to Lexicon; neither he nor Brigham and Women’s Hospital receive any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, and 89Bio; has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); is site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; is a trustee for the American College of Cardiology; and has done unfunded research for FlowCo and Takeda. Dr Szarek has received salary support from CPC, a nonprofit academic research organization affiliated with the University of Colorado, that receives research grant/consulting funding from Abbott, Agios, Alexion Pharma, Alnylam, Amgen, Angionetics, ARCA Biopharma, Array, AstraZeneca, Atentiv, Audentes, Bayer, Better Therapeutics, Brigham and Women’s Hospital, Bristol-Myers Squibb, Cardiol Therapeutics, CellResearch, Cook Medical, Cook, CSL Behring, Eidos Therapeutics, EP Trading Co, Esperion Therapeutics, Everly Health, Faraday, Fortress Biotech, HDL Therapeutics, Heartflow, Hummingbird Bioscience, Insmed, Janssen, Kowa Research, Lexicon, Merck, MedPace, Medtronic, Moderna, Novate Medical, NovoNordisk, Pfizer, PhaseBio, PPD Development, Prairie Education and Research, Prothena Biosciences, Regeneron, Regio Biosciences, Sanifit Therapeutics, Sanofi, Smith and Nephew, Stealth BioTherapeutics, University of Colorado, University of Pittsburgh, Worldwide Clinical Trials, Wraser, and the Yale Cardiovascular Research Group; has received fees for performing analyses, steering committee fees, and travel support from Sanofi and Regeneron; has received consulting fees from CiVi, Esperion, and Amarin; has received Data Safety and Monitoring Board membership fees from Resverlogix and Janssen; and is a member of the JACC editorial board. Dr Cannon has received research grants from Amgen, Better Therapeutics, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Merck, Novo Nordisk, Pfizer; consulting fees from Aegerion/Amryt, Alnylam, Amarin, Amgen, Applied Therapeutics, Ascendia, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen, Lexicon, Merck, Pfizer, Rhoshan, and Sanofi; and service on the Data and Safety Monitoring Boards for the Veteran’s Administration, Applied Therapeutics, and NovoNordisk. Dr Leiter has received research funding from, has provided CME on behalf of, and/or has acted an adviser to AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Lexicon, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Servier. Dr McGuire has received honoraria for trial leadership from Lexicon, Sanofi, Boehringer Ingelheim, Merck & Co, Pfizer, AstraZeneca, Novo Nordisk, Esperion, Lilly USA, CSL Behring; and has received honoraria for consultancy from Lilly USA, Boehringer Ingelheim, Novo Nordisk, CSL Behring, Bayer, GlaxoSmithKline, and Lexicon. Dr Lewis has received consultant fees from Sanofi. Dr Riddle has received honoraria for consulting from Adocia, Anji, Xeris, DalCor, and Theracos. Dr Voors has received consultancy and speaker fees and research support from AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, BMS, Cyrokinetics, Merck, Myokardia, Novartis, NooNordisk, and Roche diagnostics. Dr Metra has received personal fees from Actelion, Amgen, Livanova, and Vifor pharma as a member of Executive or Data Monitoring Committees of sponsored clinical trials; from AstraZeneca, Bayer, Boheringer Ingelhelm, Edwards Lifesciences, Novartis for participation in advisory boards and/or speeches at sponsored meetings. Dr Lund has received support from the Karolinska Institutet, the Swedish Research Council [grant 523-2014-2336], and the Swedish Heart Lung Foundation [grants 20150557, 20190310] and grants from AstraZeneca, Vifor, Boston Scientific, Boehringer Ingelheim, Novartis, and MSD; consulting honoraria from Vifor, AstraZeneca, Bayer, Pharmacosmos, MSD, MedScape, Sanofi, Lexicon, Myokardia, Boehringer Ingelheim, Servier, Edwards Lifesciences, and Alleviant; and speaker honoraria from Abbott, OrionPharma, MedScape, Radcliffe, AstraZeneca, Novartis, Boehringer Ingelheim, and Bayer; and has patents with AnaCardio and stock ownership in AnaCardio. Dr Komajda has received honoraria from Servier, Novartis, Boehringer Ingelheim, AstraZeneca, Bayer, and Sanofi as adviser/member of clinical trials committees. Dr Testani has received grants and/or personal fees from 3ive labs, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, AstraZeneca, Novartis, Cardionomic, MagentaMed, Reprieve Inc, FIRE1, W. L. Gore & Associates, Sanofi, Sequana Medical, Otsuka, Abbott, Merck, Windtree Therapeutics, Lexicon pharmaceuticals, Precardia, Relypsa, Regeneron, BD, Edwards Lifesciences, and Lilly; and has a patent treatment of diuretic resistance issued to Yale and Corvidia Therapeutics Inc, a patent methods for measuring Renalase issued to Yale, and a patent treatment of diuretic resistance pending with Reprieve Inc. Dr Ponikowski has received consultancy fees and speaker honoraria from Boehringer Ingelheim, AstraZeneca, Vifor Pharma, Amgen, Servier, Novartis, Bayer, MSD, Pfizer, Impulse Dynamics, Renal Guard Solutions, BMS, AbbottVascular, and the Radcliffe Group. Dr Lopes has received research grants or contracts from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, Sanofi-Aventis; funding for educational activities or lectures from Pfizer, Daiichi Sankyo, and Novo Nordisk; and funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Novo Nordisk. Dr Ezekowitz has received research support for trial leadership from Bayer, Merck & Co, Novo Nordisk, Cytokinetics, Applied Therapeutics, American Regent; and honoraria for consultancy from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Otsuka, Bayer, and Novartis. Dr Davies and Mr Sun are employed by and may have stock or stock options in Lexicon Pharmaceuticals, Inc. Dr Verma has received research and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, CMS, HLS, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio, and Sanofi; and is the President of the Canadian Medical and Surgical Knowledge Translation Research Group and holds the Tier 1 Canada Research Chair in Cardiovascular Surgery. Dr Kosiborod has received research grants from AstraZeneca and Boehringer Ingelheim; served as a consultant or advisory board member for Alnylam, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Sanofi, Vifor Pharma; has received other research support from AstraZeneca; and honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr Steg has received research grants from Amarin, Bayer, Sanofi, and Servier; speaker or consultant fees from Amarin, Amgen, AstraZeneca, Bayer, Bristol-Myers-Squibb, Janssen, Kowa, Idorsia, Lexicon, Merck, Novartis, Novo-Nordisk, PhaseBio, Pfizer, Regeneron, Sanofi, Servier; and is a Senior Associate Editor of Circulation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.