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Background: Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI)., Objectives: This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI., Methods: In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months., Results: Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status., Conclusions: In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674)., Competing Interests: Funding Support and Author Disclosures Funding support was provided by Boehringer Ingelheim and Eli Lilly and Company. Dr Udell has served on the advisory boards of Boehringer Ingelheim, Novavax, Novo Nordisk, and Sanofi; has received speaker honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly; and has received research funding to his institution from Amgen, Bayer, Boehringer Ingelheim, and Novartis. Dr Petrie has received research funding from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos; and has served as a consultant and on trial committees for Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Horizon Therapeutics, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, and 3R Lifesciences. Dr Jones has received research grants from Bayer, Boehringer Ingelheim, Merck, Novartis, PCORI, and the National Institutes of Health (NIH). Dr Mattheus is an employee of Boehringer Ingelheim. Dr Seide is an employee of Boehringer Ingelheim. Dr Amir has served as a national principal investigator and as a steering committee member for the study; has participated in paid lectures and advisory board meetings and has clinical trials with Boehringer Ingelheim. Dr Bahit has received modest honoraria from MSD, Pfizer, Bristol Myers Squibb, CSL Behring, Janssen, Boehringer Ingelheim, and Anthos Therapeutics. Dr Bauersachs has received honoraria for lectures or consulting from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, CVRx, BMS, Amgen, Corvia, Norgine, Edwards Lifesciences, and Roche, unrelated to this work; and has received research support for the department from Zoll, CVRx, Abiomed, Norgine, and Roche, unrelated to this work. Dr Bayes-Genis has lectured and/or participated in advisory boards for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Novo Nordisk, Roche, and Vifor. Dr Goodman has received research grant support (steering committee or data and safety monitoring committee) and/or speaker or consulting honoraria (advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CYTE Ltd, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, Idorsia, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, and Valeo Pharma; and has received salary support or honoraria from the Canadian Heart Failure Society, Canadian Heart Research Centre, and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Center for Clinical Research, Duke Clinical Research Institute, Jewish General Hospital, New York University Clinical Coordinating Centre, PERFUSE Research Institute, Peter Munk Cardiac Centre Clinical Trials and Translation Unit, and the TIMI Study Group (Brigham Health). Dr Goto has served on the advisory boards of Antos Therapeutic and Janssen; and has received honoraria from the American Heart Association (Associate Editor); and has served on the grant evaluation committee for the Nakatani Foundation and the Kaketsuken Foundation. Dr Gasior is an employee of Boehringer Ingelheim. Dr Jamal is an employee of Boehringer Ingelheim. Dr Januzzi has served as a trustee of the American College of Cardiology; has served as a board member of Imbria Pharmaceuticals; has served as director at Jana Care; has received research support from Abbott, Applied Therapeutics, Bayer, Bristol Myers Squibb, HeartFlow, Innolife, Medtronic, and Roche; has received consulting income from Abbott, AstraZeneca, Bayer, Beckman, Boehringer Ingelheim, Cytokinetics, Janssen, Merck, Novartis, Prevencio, Quidel/Ortho, and Roche; and has participated in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Axon, Bayer, CVRx, Medtronic, Pfizer, Roche, and Takeda. Dr Lopes has received research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; has received funding for educational activities or lectures from Pfizer, Daiichi-Sankyo, and Novo Nordisk; and has received funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk. Dr Martinez-Traba is an employee of Boehringer Ingelheim. Dr Parikh has served as a consultant for Medtronic; and has received institutional research grants from Abbott and Edwards Lifesciences. Dr Parkhomenko has received research grants and personal fees from Bayer, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squib/Pfizer, and Daiichi-Sankyo. Dr Schou has received lecture fees from Novartis, AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr van der Meer has received grant support from the European Research Council (ERC CoG 101045236, DISSECT-HF) and the University Medical Centre Groningen; and Dr van der Meer’s employer, has received consultancy fees and/or grants from Novartis, Pharmacosmos, Vifor Pharma, AstraZeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Daiichi-Sankyo, Boehringer Ingelheim, and Ionis. Dr Vinereanu has received research grants and consultancy fees from Boehringer Ingelheim; and has received research grants from Bayer Healthcare, Novartis, and Servier. Dr Zieroth has received research grant support, served on advisory boards for, or participated in speaker engagements with AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Janssen, Medtronic, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Salubrisbio, Servier, and Vifor Pharma; has served on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, and Pfizer; and has nonindustry relationships with the Canadian Medical and Surgical KT Group, CCS, CHFS, Charite, EOCI, Liv, Medscape, Ology, PACE-CME, Radcliffe, Reach MD, and the Translational Medicine Academy. Dr Brueckmann is an employee of Boehringer Ingelheim. Dr Sumin is an employee of Boehringer Ingelheim. Dr Bhatt has served on the advisory boards of Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; has served on the Board of Directors of the American Heart Association New York City, Angiowave (with stock options), Bristol Myers Squibb (with stock), DRS.LINQ (with stock options), and High Enroll (with stock); has served as a consultant for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, and Youngene; has served on 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, 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; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; and Rutgers University (for the NIH-funded MINT Trial); has received honoraria from the 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; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; 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), CSL Behring (American Heart Association lecture), 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), WebMD (CME steering committees), Wiley (steering committee); has served as Deputy Editor for Clinical Cardiology; has been named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital, which assigned it to Lexicon; neither Dr Bhatt nor Brigham and Women’s Hospital receives any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Eli Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); has served as site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; has served as a trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo. Dr Hernandez has served as a consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cytokinetics, Eidos, GlaxoSmithKline, Intellia, Intercept, Myokardia, Novartis, Novo Nordisk, Prolaio, and TikkunLev; and has received research funding from American Regent, Amgen, Bayer, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Novo Nordisk, and Verily. Dr Butler has served as a consultant for Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Eli Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown., Methods: EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of <45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes., Results: Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; P =0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; P =0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all P <0.05)., Conclusions: Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04509674., Competing Interests: Disclosures Dr Hernandez has served as a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cytokinetics, Eidos, GlaxoSmithKline, Intellia, Intercept, MyoKardia, Novartis, Novo Nordisk, Prolaio, and TikkunLev; and has received research funding from American Regent, Amgen, Bayer, Boehringer Ingelheim, Lilly, Merck, Novartis, Novo Nordisk, and Verily. Dr Bhatt has served on advisory boards for ANGIOWave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; on the board of directors for American Heart Association New York City, ANGIOWave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); has served as a consultant for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, and Youngene; has served on 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, 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; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute, and 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; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; 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), CSL Behring (AHA lecture), 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), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor); is named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital, which was assigned to Lexicon (neither Dr Bhatt nor Brigham and Women’s Hospital receives any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, 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, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (editor, Braunwald’s Heart Disease); has served as site coinvestigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; has served as trustee for American College of Cardiology; and performed unfunded research for FlowCo. Dr Butler has served as a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Lilly, LivaNova, Janssen, Medtronic, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. Dr Goto reports serving as Associate Editor for Circulation and receipt of a steering committee fee from the Duke Clinical Research Institute for EMPACT-MI. Dr Lopes reports research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and 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, and Novo Nordisk. Dr Amir reports serving as National PI-Steering committee member for the study and participated in paid lectures and advisory board meetings and clinical trials in Dr Amir’s department at Boehringer Ingelheim. Dr Beyes-Genis has lectured or participated in advisory boards for Abbott, AstraZeneca, Bayer, Boehringer-Ingelheim, Medtronic, Novartis, Novo Nordisk, Roche Diagnostics, and Vifor. Dr Bahit reports modest honorarium from MSD, Pfizer, Bristol Myers Squibb, CSL Behring, Janssen, Boehringer Ingelheim, and Anthos Therapeutics. Dr Bauersachs received honoraria for lectures/consulting from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, CVRx, BMS, Amgen, Corvia, Norgine, Edwards, and Roche not related to this article; and research support for Dr Bauersachs’ department from Zoll, CVRx, Abiomed, Norgine, and Roche, not related to this article. Dr Schou reports lecture fees from Novartis, Astra Zeneca, Bohringer, and Novo Nordisk. Dr Steg reports research grants from Amarin and Sanofi; clinical trial participation for Amarin, Amgen, AstraZeneca, Idorsia, Janssen, Novartis, Novo-Nordisk, and Sanofi; consulting or speaking for Amarin, Amgen, and Novo-Nordisk; and serving as senior associate editor at Circulation. Dr Parikh reports serving as a consultant for Medtronic, Inc and receipt of an institutional research grant from Abbott and Edwards Lifesciences. Dr Januzzi reports participation as a trustee of the American College of Cardiology, board member of Imbria Pharmaceuticals, and director at Jana Care; has received research support from Abbott, Applied Therapeutics, Bayer, BBMS, HeartFlow Inc, Innolife, and Roche Diagnostics, and consulting income from Abbott, AstraZeneca, Bayer, Beckman, Boehringer-Ingelheim, Janssen, Medtronic, Novartis, Prevencio, Quidel/Ortho, Roche Diagnostics, and Vascular Dynamics; and participates in clinical end point committees or data safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Medtronic, Pfizer, Roche Diagnostics, and Takeda. Dr Goodman reports research grant support (eg, steering committee or data and safety monitoring committee) or speaker or consulting honoraria (eg, advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CYTE Ltd, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, Idorsia, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, and Valeo Pharma; and salary support or honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Failure Society, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, and TIMI Study Group (Brigham Health). Dr van der Meer reports support from the European Research Council (ERC CoG 101045236, DISSECT-HF); the UMCG, which employs Dr van der Meer, received consultancy fees or grants from Novartis, Pharmacosmos, Vifor Pharma, Astra Zeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Daiichi Sankyo, Boehringer Ingelheim, and Ionis. Dr Petrie reports research funding from Boehringer Ingelheim, Roche, SQ Innovations, Astra Zeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos; and consultancy or trial committee participation from Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Novartis, Astra Zeneca, Novo Nordisk, AbbVie, Bayer, Horizon Therapeutics, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, and 3R Lifesciences. Dr Parkhomenko reports research grants and personal fees from Bayer, Amgen, Astra Zeneca, Boehringer Ingelheim, BMS/Pfizer, and Daiichi-Sankyo. Dr Vinereanu reports research grants and consultancy fees from Boehringer Ingelheim and research grants from Bayer Healthcare, Novartis, and Servier Pharmaceuticals LLC. Dr Zieroth reports research grant support, served on advisory boards for, or had speaker engagements with AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Janssen, Medtronic, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Salubrisbio, Servier, and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis and Pfizer; nonindustry participation includes Canadian Medical and Surgical KT Group, CCS, CHFS, Charite, EOCI, Liv, Medscape, Ology, PACE-CME, Radcliffe, Reach MD, and Translational Medicine Academy. Dr Jones reports research grants from Bayer, Boehringer Ingelheim, Merck, Novartis, PCORI, and the National Institutes of Health. Drs Seide, Mattheus, Zwiener, Sumin, Gasior, Jamal, and Brueckmann are employees of Boehringer Ingelheim.

Background: Empagliflozin improves cardiovascular outcomes in patients with heart failure, patients with type 2 diabetes who are at high cardiovascular risk, and patients with chronic kidney disease. The safety and efficacy of empagliflozin in patients who have had acute myocardial infarction are unknown., Methods: In this event-driven, double-blind, randomized, placebo-controlled trial, we assigned, in a 1:1 ratio, patients who had been hospitalized for acute myocardial infarction and were at risk for heart failure to receive empagliflozin at a dose of 10 mg daily or placebo in addition to standard care within 14 days after admission. The primary end point was a composite of hospitalization for heart failure or death from any cause as assessed in a time-to-first-event analysis., Results: A total of 3260 patients were assigned to receive empagliflozin and 3262 to receive placebo. During a median follow-up of 17.9 months, a first hospitalization for heart failure or death from any cause occurred in 267 patients (8.2%) in the empagliflozin group and in 298 patients (9.1%) in the placebo group, with incidence rates of 5.9 and 6.6 events, respectively, per 100 patient-years (hazard ratio, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P = 0.21). With respect to the individual components of the primary end point, a first hospitalization for heart failure occurred in 118 patients (3.6%) in the empagliflozin group and in 153 patients (4.7%) in the placebo group (hazard ratio, 0.77; 95% CI, 0.60 to 0.98), and death from any cause occurred in 169 (5.2%) and 178 (5.5%), respectively (hazard ratio, 0.96; 95% CI, 0.78 to 1.19). Adverse events were consistent with the known safety profile of empagliflozin and were similar in the two trial groups., Conclusions: Among patients at increased risk for heart failure after acute myocardial infarction, treatment with empagliflozin did not lead to a significantly lower risk of a first hospitalization for heart failure or death from any cause than placebo. (Funded by Boehringer Ingelheim and Eli Lilly; EMPACT-MI ClinicalTrials.gov number, NCT04509674.)., (Copyright © 2024 Massachusetts Medical Society.)

Aim: It is unknown whether safety and clinical endpoints by use of sacubitril/valsartan (an angiotensin receptor-neprilysin inhibitor [ARNI]) are affected by mineralocorticoid receptor antagonists (MRA) in high-risk myocardial infarction (MI) patients. The aim of this study was to examine whether MRA modifies safety and clinical endpoints by use of sacubitril/valsartan in patients with a MI and left ventricular systolic dysfunction (LVSD) and/or pulmonary congestion., Methods and Results: Patients (n = 5661) included in the PARADISE MI trial (Prospective ARNI vs. ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI) were stratified according to MRA. Primary outcomes in this substudy were worsening heart failure or cardiovascular death. Safety was defined as symptomatic hypotension, hyperkalaemia >5.5 mmol/L, or permanent drug discontinuation. A total of 2338 patients (41%) were treated with MRA. Safety of ARNI compared to ramipril was not altered significantly by ± MRA, and both groups had similar increase in symptomatic hypotension with ARNI. In patients taking MRA, the risk of hyperkalaemia or permanent drug discontinuation was not significantly altered by ARNI (p > 0.05 for all comparisons). The effect of ARNI compared with ramipril was similar in those who were and were not taking MRA (hazard ratio [HR] MRA 0.96, 95% confidence interval [CI] 0.77-1.19 and HR MRA- 0.87, 95% CI 0.71-1.05, for the primary endpoint; p = 0.51 for interaction [Clinical Endpoint Committee adjudicated]); similar findings were observed if investigator-reported endpoints were evaluated (p = 0.61 for interaction)., Conclusions: Use of a MRA did not modify safety or clinical endpoints related to initiation of ARNI compared to ramipril in the post-MI setting in patients with LVSD and/or congestion., (© 2023 European Society of Cardiology.)

Background and Aims: Guidelines recommend revascularization of intermediate epicardial artery stenosis to be guided by evidence of ischaemia. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are equally recommended. Individual 5-year results of two major randomized trials comparing FFR with iFR-guided revascularization suggested increased all-cause mortality following iFR-guided revascularization. The aim of this study was a study-level meta-analysis of the 5-year outcome data in iFR-SWEDEHEART (NCT02166736) and DEFINE-FLAIR (NCT02053038)., Methods: Composite of major adverse cardiovascular events (MACE) and its individual components [all-cause death, myocardial infarction (MI), and unplanned revascularisation] were analysed. Raw Kaplan-Meier estimates, numbers at risk, and number of events were extracted at 5-year follow-up and analysed using the ipdfc package (Stata version 18, StataCorp, College Station, TX, USA)., Results: In total, iFR and FFR-guided revascularization was performed in 2254 and 2257 patients, respectively. Revascularization was more often deferred in the iFR group [n = 1128 (50.0%)] vs. the FFR group [n = 1021 (45.2%); P = .001]. In the iFR-guided group, the number of deaths, MACE, unplanned revascularization, and MI was 188 (8.3%), 484 (21.5%), 235 (10.4%), and 123 (5.5%) vs. 143 (6.3%), 420 (18.6%), 241 (10.7%), and 123 (5.4%) in the FFR group. Hazard ratio [95% confidence interval (CI)] estimates for MACE were 1.18 [1.04; 1.34], all-cause mortality 1.34 [1.08; 1.67], unplanned revascularization 0.99 [0.83; 1.19], and MI 1.02 [0.80; 1.32]., Conclusions: Five-year all-cause mortality and MACE rates were increased with revascularization guided by iFR compared to FFR. Rates of unplanned revascularization and MI were equal in the two groups., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Due to improved management, diagnosis, and care of myocardial infarction (MI), patients may now survive long enough to increasingly develop serious noncardiovascular conditions., Objectives: This study aimed to test this hypothesis by investigating the temporal trends in noncardiovascular morbidity and mortality following MI., Methods: We conducted a registry-based nationwide cohort study of all Danish patients with MI during 2000 to 2017. Outcomes were cardiovascular and noncardiovascular mortality, incident cancer, incident renal disease, and severe infectious disease., Results: From 2000 to 2017, 136,293 consecutive patients were identified (63.2% men, median age 69 years). The 1-year risk of cardiovascular mortality between 2000 to 2002 and 2015 to 2017 decreased from 18.4% to 7.6%, whereas noncardiovascular mortality decreased from 5.8% to 5.0%. This corresponded to an increase in the proportion of total 1-year mortality attributed to noncardiovascular causes from 24.1% to 39.5%. Furthermore, increases in 1-year risk of incident cancer (1.9%-2.4%), incident renal disease (1.0%-1.6%), and infectious disease (5.5%-9.1%) were observed (all P trend <0.01). In analyses standardized for changes in patient characteristics, the increased risk of cancer in 2015 to 2017 compared with 2000 to 2002 was no longer significant (standardized risk ratios for cancer: 0.99 [95% CI: 0.91-1.07]; renal disease: 1.28 [95% CI: 1.15-1.41]; infectious disease: 1.28 [95% CI: 1.23-1.34])., Conclusions: Although cardiovascular mortality following MI improved substantially during 2000 to 2017, the risk of noncardiovascular morbidity increased. Moreover, noncardiovascular causes constitute an increasing proportion of post-MI mortality. These findings suggest that further attention on noncardiovascular outcomes is warranted in guidelines and clinical practice and should be considered in the design of future clinical trials., Competing Interests: Funding Support and Author Disclosures This study was fully supported by a research grant from the Danish Heart Foundation (grant identification number 20-R146-A9798). Dr Nouhravesh has received honoraria from Bayer A/S and AstraZeneca not related to the current study. Prof Torp-Pedersen has received grants for studies from Bayer and Novo Nordisk not related to current study. Prof Schou has received lecture fees from Novo Nordisk, AstraZeneca, Novartis, and Boehringer Ingelheim outside of the current study. Dr Sehested has received a speaker fee from AstraZeneca. All other 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.)

Background Guidelines recommend that patients with myocardial infarction (MI) receive equal care regardless of age. However, withholding treatment may be justified in elderly and frail patients. This study aimed to investigate trends in treatments and outcomes of older patients with MI according to frailty. Methods and Results All patients aged ≥75 years with first-time MI during 2002 to 2021 were identified through Danish nationwide registries. Frailty was categorized using the Hospital Frailty Risk Score. One-year risk and hazard ratios (HRs) for days 0 to 28 and 29 to 365 were calculated for all-cause death. A total of 51 022 patients with MI were included (median, 82 years; 50.2% women). Intermediate/high frailty increased from 26.7% in 2002 to 2006 to 37.1% in 2017 to 2021. Use of treatment increased substantially regardless of frailty: for example, 28.1% to 48.0% (statins), 21.8% to 33.7% (dual antiplatelet therapy), and 7.6% to 28.0% (percutaneous coronary intervention) for high frailty (all P -trend <0.001). One-year death decreased for low frailty (35.1%-17.9%), intermediate frailty (49.8%-31.0%), and high frailty (62.8%-45.6%), all P -trend <0.001. Age- and sex-adjusted 29- to 365-day HRs (2017-2021 versus 2002-2006) were 0.53 (0.48-0.59), 0.62 (0.55-0.70), and 0.62 (0.46-0.83) for low, intermediate, and high frailty, respectively ( P -interaction=0.23). When additionally adjusted for treatment, HRs attenuated to 0.74 (0.67-0.83), 0.83 (0.74-0.94), and 0.78 (0.58-1.05), respectively, indicating that increased use of treatment may account partially for the observed improvements. Conclusions Use of guideline-based treatments and outcomes improved concomitantly in older patients with MI, irrespective of frailty. These results indicate that guideline-based management of MI may be reasonable in the elderly and frail.

Aim: We investigated temporal trends in major cardiovascular events following first-time myocardial infarction (MI) and trends in revascularization and pharmacotherapy from 2000 to 2017., Methods and Results: Using nationwide registries, we identified 120 833 Danish patients with a first-time MI between 2000 and 2017. We investigated 30-day and 1-year mortality and the 1-year risk of first-time admission for heart failure (HF) and recurrent MI. Patients were younger with a higher prevalence of hypertension and diabetes in 2015-2017 compared with 2000-2002. The patients were predominantly male (65.6%), and the median age declined by 3 years through the periods. Percutaneous coronary interventions within 7 days after first-time MI increased significantly (2000: 11.4% vs. 2017: 68.6%; Ptrend < 0.001). Cardiovascular medication after first-time MI changed significantly in the same period. Absolute risks and adjusted rates of outcomes were significantly lower in 2015-2017 compared with 2000-2002: 30-day mortality: 6.5% vs. 14.1% [hazard ratio (HR) 0.52, 95% confidence interval (CI): 0.48-0.55); 1-year mortality 10.7% vs. 21.8% (HR 0.52, 95% CI: 0.50-0.55); recurrent MI: 4.0% vs. 7.8% (HR 0.56, 95% CI: 0.51-0.62); and first-time admission for HF: 2.9% vs. 3.7% (HR 0.82, 95% CI: 0.73-0.92). The rates of 30-day/1-year mortality and recurrent MI showed significantly decreasing trends (Ptrend < 0.001). The rates of first-time admission for HF were borderline significant (Ptrend = 0.045)., Conclusion: From 2000 to 2017, we observed a decreasing risk of recurrent MI, first-time admission for HF, and all-cause mortality in patients with a first-time MI. In the same period, we observed a high rate of guideline-recommended pharmacological treatment after first-time MI as well as increasing rate of early revascularization in Denmark., Translational Perspectives: The results from the current study portrait the risk of all-cause mortality, recurrent MI, and first-time admission for HF in a real-life setting with a very high utilization of early revascularization and guideline-recommended pharmacological therapy. We observed a temporal trend of improved survival, reduced risk of recurrent MI, as well as reduced risk of first-time admission for HF after first-time MI from 2000 through 2017. We observed an increase in the overall use of revascularization, as well as early revascularization and use of guideline-recommended pharmacotherapy. Our study reveals important results from real-life, nationwide data, showing a reduced risk of cardiovascular outcomes after first-time MI during the past 20 years. Current guidelines are based on results from clinical trials. Our real-life results add additionally important knowledge on patients' prognosis after first-time MI and underline the importance of treating MI according to guideline recommendations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The present study aimed to determine the association between Type 2 diabetes mellitus (T2DM) and third-degree (complete) atrioventricular block., Methods and Results: This nationwide nested case-control study included patients older than 18 years, diagnosed with third-degree atrioventricular block between 1 July 1995 and 31 December 2018. Data on medication, comorbidity, and outcomes were collected from Danish registries. Five controls, from the risk set of each case of third-degree atrioventricular block, were matched on age and sex to fit a Cox regression model with time-dependent exposure and time-dependent covariates. Subgroup analysis was conducted with Cox regression models for each subgroup. We located 25 995 cases with third-degree atrioventricular block that were matched with 130 004 controls. The mean age was 76 years and 62% were male. Cases had more T2DM (21% vs. 11%), hypertension (69% vs. 50%), atrial fibrillation (25% vs. 10%), heart failure (20% vs. 6.3%), and myocardial infarction (19% vs. 9.2%), compared with the control group. In Cox regression analysis, adjusting for comorbidities and atrioventricular nodal blocking agents, T2DM was significantly associated with third-degree atrioventricular block (hazard ratio: 1.63, 95% confidence interval: 1.57-1.69). The association remained in several subgroup analyses of diseases also suspected to be associated with third-degree atrioventricular block. There was a significant interaction with comorbidities of interest including hypertension, atrial fibrillation, heart failure, and myocardial infarction., Conclusion: In this nationwide study, T2DM was associated with a higher rate of third-degree atrioventricular block compared with matched controls. The association remained independent of atrioventricular nodal blocking agents and other comorbidities known to be associated with third-degree atrioventricular block., Competing Interests: Conflict of interest: S.H. reports educational grant from Medtronic covering conference fee to attend European Heart Rhythm association Congress 2022 in Copenhagen. C.T.P. reports grants from Bayer and Novo Nordisk unrelated to the current study. U.P.B. reports personal fee from Novo Nordisk and Sanofi for advisory work unrelated to current study. All other authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Outcomes after myocardial infarction (MI) improved during recent decades alongside better risk factor management and implementation of guideline-recommended treatments. However, it is unknown whether this applies to stable patients who are event-free 1 year after MI., Methods and Results: Using nationwide Danish registries, we included all patients with first-time MI during 2000-17 who survived 1 year free from bleeding and cardiovascular events (n = 82 108, median age 64 years, 68.2% male). Follow-up started 1 year after MI and continued through January 2022. Crude risks of mortality, cardiovascular events, and bleeding were estimated in consecutive 3-year periods. Standardized risks were calculated with respect to the distribution of age, sex, comorbidities, and treatments in the latter period. Guideline-recommended treatment use increased during the study period: e.g. statins (68.6-92.5%) and percutaneous coronary intervention (23.9-68.2%). The crude 5-year risks of outcomes decreased (all P-trend <0.001): Mortality, 18.6% (95% confidence interval [CI]: 17.9-19.2) to 12.5% (CI: 11.9-13.1); Recurrent MI, 7.5% (CI: 7.1-8.0) to 5.5% (CI: 5.1-6.0); Bleeding, 3.9% (CI: 3.6-4.3) to 2.7% (CI: 2.4-3.0). Crude 5-year risk of mortality in 2015-17 was as low as 2.6% for patients aged <60 years. Use of guideline-recommended treatments was associated with improved outcomes: After standardization for changes in treatments, 5-year risk of mortality in 2000-02 was 15.5% (CI: 14.9-16.2)., Conclusions: For patients who were event-free 1 year after MI, the long-term risks of mortality, cardiovascular events, and bleeding decreased significantly, along with an improved use of guideline-recommended treatments between 2000 and 2017. In the most recent period, 1 year after MI, the risk of additional events was lower than previously reported., Competing Interests: Conflict of interest: LS is employed by Novo Nordisk without relation to the current study. ACR reports aspeaker’s fee from Novartis. EF reports independent research grants from the Novo Nordisk Foundation and the Danish Heart Foundation without relation to the current study. LK reports speaker’s fees from Novo Nordisk, Novartis, Boehringer Ingelheim,AstraZeneca, and Bayer. CTP reports study grants from Bayer and Novo Nordisk without relation to the current study. MS reports lecture fees from Novo Nordisk, Astra Zeneca, Novartis, and Boehringer Ingelheim outside the current study. All author authors had no conflicts of interest to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Women report worse health-related patient-reported outcomes (PROs) compared with men following acute myocardial infarction (AMI). However, this association is not well established when accounting for demographic and clinical patient characteristics at discharge. This knowledge is essential for clinicians when planning individualised care for patients following AMI. The aim of this study is to examine whether gender is associated with health-related PROs at discharge from a Danish heart centre, combining PROs with data from the national health and administrative registries., Methods and Results: A cross-sectional study of 2131 patients with AMI discharged from a Danish heart centre responding to the following health-related PRO questionnaires: the Health-survey Short-Form-12 (SF-12), generating a physical component summary (PCS) and a mental component summary (MCS) score; the HeartQoL, providing a global, emotional, and physical score; the EuroQol five-dimensional questionnaire (EQ-5D-5L) and the EQ visual analogue scale (EQ VAS); the Hospital Anxiety and Depression Scale (HADS), generating an anxiety and depression score (HADS-A and HADS-D); the Edmonton Symptom Assessment Scale (ESAS); the Brief Illness Perception Questionnaire (B-IPQ). Patient-reported outcomes were linked to registry-based information adjusting for potential demographic and clinical confounding factors. In adjusted regression models, women reported worse health-related PROs compared with men in SF-12 PCS and SF-12 MCS, HeartQoL global, the HeartQoL emotional and HeartQoL physical score, EQ-5D-5L and EQ VAS, the HADS-A, ESAS, and in six out of eight B-IPQ items., Conclusions: Women reported worse health-related PROs compared with men. Health-related PROs have the potential to be further investigated to facilitate a more individualised healthcare follow-up after AMI., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Atrial fibrillation (AF) is the most common arrythmia following ST-segment elevation myocardial infarction (STEMI) and can lead to stroke and other heart-related diseases. This study aimed to determine the prognostic value of left atrial (LA) strain, obtained by speckle tracking echocardiography (STE), in predicting incident AF outcomes following STEMI treated with primary percutaneous coronary intervention (pPCI)., Methods and Results: This prospective study comprised of 392 STEMI patients treated with pPCI. The patients had an echocardiography performed at a median of two days after their STEMI. Along with conventional measures, LA strain was obtained by speckle tracking from two apical projections. The outcome was new-onset atrial fibrillation. LA reservoir, contractile and conduit strain were measurable from echocardiograms of 303 included patients. At a median follow-up time of 5.6 years (IQR: 5.0-6.1 years), 18 patients (6,3%) developed incident AF. Mean age was 62.0 years ±11.5 and follow-up was 100%. Significantly lower LA strain values were observed in patients who experienced AF during follow-up as compared to patients who didn't. Both reservoir, contractile and conduit strain were significant univariable predictors. In the multivariable model, only LA reservoir strain remained a significant independent predictor of AF., Conclusion: Left atrial reservoir strain obtained by two-dimensional speckle tracking echocardiography is an independent predictor of incident AF following STEMI., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Study Objective: The aim of this study was to investigate whether myocardial infarction can be safely ruled in or out after 30 minutes as an alternative to 1 hour., Methods: This was a prospective, single-center clinical study enrolling patients admitted to the emergency department. Patients with chest pain suggestive of myocardial infarction were eligible for inclusion. There was no walk-in to the emergency department, and patients with highly elevated out-of-hospital troponin were transferred directly to an invasive heart center. High-sensitivity troponin I was measured at admission (0 hour), 30 minutes, 1 hour, and 3 hours. Diagnostic performance was assessed using the sensitivity and negative predictive value (primary endpoints) as measures of ability to rule out myocardial infarction. Specificity and positive predictive value of myocardial infarction were used as measures for the ability to rule in myocardial infarction (secondary endpoints)., Results: In total, 1,003 patients qualified for analysis. Median age was 64 (interquartile range 52 to 74) years, and 42% were women. Myocardial infarction was confirmed in 9% of patients. In the validation cohort (n=503), the 0-h/30-min algorithm assigned 242 (48%) patients to rule out, 54 (11%) to rule in, and 207 (41%) to the observational zone. This resulted in a sensitivity of 100% (92.0% to 100%), negative predictive value of 100% (95% confidence interval 98.5% to 100%), specificity of 96.7% (94.7% to 98.2%), and positive predictive value of 72.2% (58.4% to 83.5%). In comparison, the 0-h/1-h algorithm performed with a sensitivity of 100% (92.0% to 100%), negative predictive value of 100% (98.5% to 100%), specificity of 97.2% (95.2% to 98.5%), and positive predictive value of 75.5% (61.7% to 86.2%)., Conclusion: The accelerated 0-h/30-min algorithm allowed for safe rule-out of myocardial infarction 30 minutes after admission. The rule-in ability of the 0-h/30-min algorithm was comparable to that of the 0-h/1h algorithm., (Copyright © 2021 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Aims: To assess the association between past level of physical activity (PA) and risk for death during the acute phase of myocardial infarction (MI) in a pooled analysis of cohort studies., Methods and Results: European cohorts including participants with a baseline assessment of PA, conventional cardiovascular (CV) risk factors, and available follow-up on MI and death were eligible. Patients with an incident MI were included. Leisure-time PA was grouped as sedentary (<7 MET-hours), low (7-16 MET-hours), moderate (16.1-32 MET-hours), or high (>32 MET-hours) based on calculated net weekly energy expenditure. The main outcome measures were instant and 28-day case fatality of MI. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multivariate random-effects models. Adjustments for age, sex, CV risk factors, alcohol consumption, and socioeconomic status were made. From 10 cohorts including a total of 1 495 254 participants, 28 140 patients with an incident MI comprised the study population. A total of 4976 (17.7%) died within 28 days-of these 3101 (62.3%) were classified as instant fatal MI. Compared with sedentary individuals, those with a higher level of PA had lower adjusted odds of instant fatal MI: low PA [OR, 0.79 (95% CI, 0.60-1.04)], moderate PA [0.67 (0.51-0.89)], and high PA [0.55 (0.40-0.76)]. Similar results were found for 28-day fatal MI: low PA [0.85 (0.71-1.03)], moderate PA [0.64 (0.51-0.80)], and high PA [0.72 (0.51-1.00)]. A low-to-moderate degree of heterogeneity was detected in the analysis of instant fatal MI (I2 = 47.3%), but not in that of 28-day fatal MI (I2 = 0.0%)., Conclusion: A moderate-to-high level of PA was associated with a lower risk of instant and 28-day death in relation to a MI., (© The Author(s) 2021. Published on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: An accelerated diagnostic algorithm for ruling-in or ruling-out myocardial infarction (MI) after 1 hour (1 h) has recently been derived and internally validated for the Siemens ADVIA Centaur TNIH assay. We aimed to validate the diagnostic performance of the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in a Danish cohort., Methods and Results: Patients with chest pain suggestive of MI were prospectively enrolled. High-sensitive troponin I (TNIH) was measured at admission (0 h) and after 30 minutes (30 m), 1 h, and 3 hours (3 h). We externally validated the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in Danish patients. Moreover, we applied the algorithm using the second TNIH measurement at 30 m instead of 1 h. We enrolled 1003 patients: median (Q1-Q3) age 64 (52-74) years, 42% female, and 23% with previous MI. Myocardial infarction was the final diagnosis in 9% of patients. Median (Q1-Q3) times from admission to 30 m and 1 h blood draw were 35 min (30-37 min) and 67 min (62-75 min), respectively. Using the 0 h and 1 h results, 468 (47%) patients were assigned to rule-out, 104 (10%) to rule-in, and 431 (43%) to the observational zone. This resulted in a negative predictive value of 100% (95% confidence interval: 99.2-100%), sensitivity of 100% (95.9-100%), positive predictive value of 79.8 (70.8-87.0%), and specificity of 97.7% (96.5-98.6%). The diagnostic performance after 30 m was similar., Conclusions: The TNIH 0 h/1 h algorithm ad modum Boeddinghaus performed excellently for rule-out of MI in a Danish cohort. The Boeddinghaus algorithm also performed excellently after only 30 m., Trial Registration Number: NCT03634384., Trial Registry Name and Url: Rapid Use of High-Sensitive Cardiac Troponin I for Ruling-in and Ruling-out Acute Myocardial Infarction (RACING-MI), https://clinicaltrials.gov/ct2/show/NCT03634384., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking., Methods: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first., Results: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group., Conclusions: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: During the COVID-19 pandemic, decreasing rates of hospitalisations for cardiovascular disease raised concerns for undertreatment, particularly for vulnerable groups. We investigated how the initial COVID-19 public lockdown, impacted the risk of being hospitalised with a major cardiovascular event (MCE: myocardial infarction/stroke/heart failure) according to educational level., Methods: We grouped all Danish residents according to educational attainment level (low, medium, high) and age (40-59, 60-69, ≥70 years). In each group, we calculated the age-standardised and sex standardised risk of MCE hospitalisation in the initial COVID-19 lockdown-period (13 March 2020-3 May 2020) and in the corresponding calendar period in 2019. We calculated age-standardised and sex-standardised risks to investigate whether the COVID-19 lockdown had a differential effect on MCE incidence according to educational level., Results: In the period in 2019, 2700 Danish residents were hospitalised with MCE, compared with only 2290 during the lockdown. During lockdown, the risk of hospitalisation for MCE decreased among residents aged ≥70 with low education (risk difference (RD) -46.2 (-73.2; -19.2) per 100,000) or medium education (RD -23.2 (-50.8; 4.3) per 100 000), but not among residents with high education (RD 5.1 (-32.3; 42.5), per 100 000). The risk of hospitalisation for MCE did not decrease significantly for the younger age groups., Conclusions: The COVID-19 lockdown is associated with a reduced incidence for MCE, especially among low educated, elderly residents. This raises concern for undertreatment that without clinical awareness and action may widen the educational gap in cardiovascular morbidity and mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) may be a more accurate measure of LV filling pressure then ratio of early filling pressure to early tissue velocity. The aim of the study was to investigate the impact of age, sex, obesity, smoking, hypertension, hypercholesterolemia, diabetes, physical activity level, socioeconomic, and psychosocial status on E/e'sr over a decade. Additionally, the predictive value of ΔE/e'sr on future major adverse cardiovascular events (MACE) has never been explored., Method: The study included 623 participants from the general population, who participated in the 4th and 5th Copenhagen City Heart Study (CCHS4 and CCHS5). Examinations were median 10 years apart. MACE was the composite endpoint of heart failure, myocardial infarction, and all-cause death., Results: Follow-up time was median 5.7 years, and 43 (7%) experienced MACE. Mean age was 51 ± 14 years, and 43% were male. Mean ΔE/e'sr was 2.1 ± 23.0 cm. After multivariable adjustment for demographic, clinical, and biochemistry variables, high age (stand. β-coef. = .24, P < .001) and mean arterial blood pressure (MAP) (stand. β-coef. = .17, P < .001) were significantly associated with an accelerated increase in E/e'sr In multivariable Cox regression, E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of MACE (HR = 1.20, 95% CI [1.01; 1.42] per 10 cm increase for both). ΔE/e'sr did only provide incremental prognostic value to change in left atrial volume index of the conventional diastolic measurements., Conclusion: In the general population, age and MAP were predictors of an accelerated increase in E/e'sr over a decade. E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of future MACE., (© 2021 Wiley Periodicals LLC.)

Background: Limited data suggest that hydroxychloroquine may affect risk of cardiovascular disease in patients with lupus erythematosus (LE)., Objective: To investigate whether hydroxychloroquine treatment is associated with major adverse cardiovascular events (MACE) (myocardial infarction, ischemic stroke, or cardiovascular-associated death) in patients with cutaneous LE (CLE) or systemic LE (SLE)., Methods: Based on the Danish nationwide registers, an observational cohort study was conducted including patients with first-time diagnosis of CLE or SLE (between 1997 and 2017). Cox regression models calculating the hazard ratio (HR) analyzing the risk of MACE were performed comparing time on and off hydroxychloroquine (including never users). The models were adjusted for age, sex, socioeconomic status, concomitant treatment, and cardiovascular risk factors., Results: Among 4587 patients with LE, 51% (n = 2343) were treated with hydroxychloroquine during the study period. An inverse association between use of hydroxychloroquine and MACE risk was observed among patients with SLE (adjusted HR, 0.65; 95% confidence interval, 0.46-0.90) and patients with CLE (adjusted HR, 0.71; 95% confidence interval, 0.42-1.19). Consistent results were found in sensitivity analyses including a case-time control design., Limitations: No information on disease activity/severity was available., Conclusion: Our findings indicate an opportunity to reduce the risk of cardiovascular events in patients with LE through use of hydroxychloroquine., Competing Interests: Conflicts of interest Dr Kofoed reports personal fees from Eli Lilly, AbbVie, Leo Pharma, Bristol Meyers Squibb, Galderma, and Takeda Pharma during the conduct of the study. Dr Egeberg reports grants and personal fees from Pfizer, grants and personal fees from Eli Lilly, grants from Danish National Psoriasis Foundation, grants from Kgl Hofbundtmager Aage Bang Foundation, grants and personal fees from AbbVie, personal fees from Bristol Meyers Squibb, personal fees from Leo Pharma, personal fees from Samsung Bioepis Co Ltd, grants and personal fees from Novartis, personal fees from Galderma, and personal fees from Janssen Pharmaceuticals during the conduct of the study. Drs Haugaard and Dreyer, Author Ottosen, and Dr Gislason have no conflicts of interest to declare., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Aims: We aimed to investigate the long-term cardio-protective effect associated with beta-blocker (BB) treatment in stable, optimally treated myocardial infarction (MI) patients without heart failure (HF)., Methods and Results: Using nationwide registries, we included patients with first-time MI undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) during admission and treated with both acetyl-salicylic acid and statins post-discharge between 2003 and 2018. Patients with prior history of MI, prior BB use, or any alternative indication or contraindication for BB treatment were excluded. Follow-up began 3 months following discharge in patients alive, free of cardiovascular (CV) events or procedures. Primary outcomes were CV death, recurrent MI, and a composite outcome of CV events. We used adjusted logistic regression and reported standardized absolute risks and differences (ARD) 3 years after MI. Overall, 30 177 stable, optimally treated MI patients were included (58% acute PCI, 26% sub-acute PCI, 16% CAG without intervention). At baseline, 82% of patients were on BB treatment (median age 61 years, 75% male) and 18% were not (median age 62 years, 68% male). BB treatment was associated with a similar risk of CV death, recurrent MI, and the composite outcome of CV events compared with no BB treatment [ARD (95% confidence intervals)] correspondingly; 0.1% (-0.3% to 0.5%), 0.2% (-0.7% to 1.2%), and 1.2% (-0.2% to 2.7%)., Conclusions: In this nationwide cohort study of stable, optimally treated MI patients without HF, we found no long-term effect of BB treatment on CV prognosis following the patients from 3 months to 3 years after MI admission., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Introduction: Patients with chronic obstructive pulmonary disease (COPD) are undertreated with beta-blockers following myocardial infarction (MI), possibly due to fear for acute exacerbations of COPD (AECOPD). Is beta-blocker use associated with increased risk of AECOPD in patients following first-time MI?, Methods: Danish nationwide study of patients with COPD following hospitalisation for MI from 2003 to 2015. Multivariable, time-dependent Cox regression accounting for varying beta-blocker use based on claimed prescriptions during up to 13 years of follow-up., Results: A total of 10 884 patients with COPD were discharged after first-time MI. The 1-year rate of AECOPD was 35%, and 65% used beta-blockers at 1 year. Beta-blocker use was associated with a lower risk of AECOPD (multivariable-adjusted HR 0.78, 95% CI 0.74-0.83). This association was independent of the type of MI (HR 0.70, 95% CI 0.59-0.83 in ST-elevation MI (STEMI) and HR 0.80, 95% CI 0.75-0.84 in non-STEMI), presence or absence of heart failure (HR 0.82, 95% CI 0.74-0.90 and HR 0.77, 95% CI 0.72-0.82, respectively), beta-blocker dosage and type, as well as exacerbation severity. Results were similar in 1118 patients with full data on COPD severity and symptom burden (median forced expiratory volume in 1 s as percentage of predicted was 46 and majority had moderate dyspnoea), and in 1358 patients with severe COPD and frequent AECOPD with a high 1-year rate of AECOPD of 70%., Discussion: Beta-blocker use was not associated with increased risk of AECOPD following MI. This finding was independent of COPD severity, symptom burden and exacerbation history, and supports the safety of beta-blockers in patients with COPD, including high-risk patients with severe disease., Competing Interests: Competing interests: CT-P reports grants from Bayer, grants from Novo Nordisk, outside the submitted work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To determine whether beta-blockers, aspirin, and statins are underutilized after first-time myocardial infarction (MI) in patients with chronic obstructive pulmonary disease (COPD) compared with patients without COPD. Further, to determine temporal trends and risk factors for non-use., Methods and Results: Using Danish nationwide registers, we performed a cross-sectional study investigating the utilization of beta-blockers, aspirin, and statins after hospitalization for first-time MI among patients with and without COPD from 1995 to 2015. Risk factors for non-use were examined in multivariable logistic regression models. During 21 years of study, 140 278 patients were included, hereof 13 496 (9.6%) with COPD. Patients with COPD were less likely to use beta-blockers (53.2% vs. 76.2%, P < 0.001), aspirin (73.9% vs. 78.8%, P < 0.001), and statins (53.5% vs. 61.9%, P < 0.001). Medication usage increased during the study period but in multivariable analyses, COPD remained a significant predictor for non-use: odds ratio (95% confidence interval) for non-use of beta-blockers 1.86 (1.76-1.97); aspirin 1.24 (1.16-1.32); statins 1.50 (1.41-1.59). Analyses stratified by ST-segment elevation myocardial infarction (STEMI) and non-STEMI showed similar undertreatment of COPD patients. Risk factors for non-use of beta-blockers in COPD included increasing age, female sex, and increasing severity of COPD (frequent exacerbations, use of multiple inhaled medications, and low lung function). Similar findings were demonstrated for aspirin and statins., Conclusion: Beta-blockers, and to a lesser extent aspirin and statins, were systematically underutilized by patients with COPD following hospitalization for MI despite an overall increase in the utilization over time. Increasing severity of COPD was a risk factor for non-use of the medications., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: A growing population is living with ischemic heart disease (IHD). Patient-reported outcomes (PROs) are reliable prognostic tools. Studies exploring PROs are needed to identify vulnerable patients and guide targeted healthcare strategies., Objectives: The aims of this study were to (i) describe PROs at hospital discharge across 3 diagnostic subgroups: (1) chronic IHD/stable angina, (2) non-ST-elevation myocardial infarction (non-STEMI)/unstable angina, and (3) ST-elevation myocardial infarction (STEMI), and (ii) examine determinants for PROs at hospital discharge in patients with IHD., Methods: This study included a national cohort with register-data linkage including 14 115 adults with IHD discharged from Danish heart centers. Eligible patients (n = 13 476) were invited to complete a questionnaire, and 7 167 (53%) responded. Questionnaires included the Medical Outcome Study Short-Form 12, the Hospital Anxiety and Depression Scale, EuroQoL, HeartQoL, the Edmonton Symptom Assessment Scale, and ancillary questions. Sociodemographic and clinical characteristics were obtained from national registers. Student t test, χ test, and adjusted linear and logistic regression analyses were conducted to investigate subgroup differences, and adjusted linear and logistic regression analyses were conducted to explore determinants for PROs., Results: Statistically significant subgroup differences were found, with groups reporting worst to best scores for most of PROs being as follows: chronic IHD/stable angina, non-STEMI/unstable angina, and STEMI. Symptoms of anxiety were highly prevalent in the non-STEMI/unstable angina group, with 33.8% exceeding a Hospital Anxiety and Depression Scale-Anxiety cutoff score indicating a possible anxiety disorder. Determinants for worse PROs included female sex, lower educational level, obesity, and poor physical fitness., Conclusions: Significant differences in PROs across IHD subgroups were observed and determinants for poor outcomes suggested. Results may guide differentiated care initiatives and resource allocation for preventative strategies.

Context: Hypothyroidism has detrimental effects on the cardiovascular system, but controversy remains concerning the benefits of levothyroxine (L-T4) substitution in patients with heart failure (HF)., Objective: Examining the effects of L-T4 in patients with HF., Design: Retrospective cohort study., Setting and Participants: All Danish citizens aged ≥18 years diagnosed with HF between 1997 and 2012. L-T4 treatment was identified from nationwide registers. Incidence rate ratios (IRRs) were calculated with Poisson regression models., Main Outcome Measures: All-cause mortality, myocardial infarction (MI), cardiovascular death, and major adverse cardiovascular events (MACEs)., Results: A total of 224,670 patients were diagnosed with HF [mean age 70.7 (SD ± 14.7) years, 53% male]. Of these, 6560 patients were treated with L-T4 at baseline, and 9007 patients initiated L-T4 during follow-up. A total of 209,103 patients did not receive L-T4. During a median follow-up of 4.8 years [interquartile range (IQR) 9.2] 147,253 patients died. Increased risk of all-cause mortality (IRR 1.25; 95% CI, 1.21 to 1.29; IRR 1.13; 95% CI, 1.10 to 1.16), cardiovascular death (IRR 1.23; 95% CI, 1.18 to 1.27; IRR 1.11; 95% CI, 1.08 to 1.15), and MACE (IRR 1.26; 95% CI, 1.22 to 1.31; IRR 1.05; 95% CI, 1.02 to 1.09) was observed for treatment ongoing at baseline and initiated during follow-up, respectively. Increased risk of MI (IRR 1.32; 95% CI, 1.23 to 1.41) was observed for ongoing treatment, and reduced risk (IRR 0.87; 95% CI, 0.81 to 0.93) was observed for incident treatment., Conclusion: Ongoing and incident L-T4 treatment in patients with HF was associated with an increased risk of all-cause mortality, cardiovascular death, and MACE. Increased risk of MI was observed for ongoing treatment, and reduced risk was observed for incident treatment., (Copyright © 2019 Endocrine Society.)

Background: Data on nursing home admission after myocardial infarction (MI) in the elderly are scarce. We investigated nursing home admission within 6 months and 2 years after MI including predictors for nursing home admission in a nationwide cohort of elderly patients., Methods: Using Danish nationwide registries, we identified all subjects 65 years or older residing at home who were discharged following first-time MI in the period 2008-2015. We determined sex- and age-stratified incidence rates per 1000 person years (IRs) and incidence rate ratios (IRRs) of nursing home admissions using Poisson regression models compared to the Danish population 65 years or older with no prior MI. Poisson regression models were also applied to identify predictors of nursing home admission., Results: The 26,539 patients who were discharged after MI had a median age of 76 (quartile 1-quartile 3: 70-83) years. The IRs of nursing home admission after MI increased with increasing age and for 80-84-year-old women IRs after 6 months and 2 years were 113.9 and 62.9, respectively, compared to 29.4 for women of the same age with no prior MI. The IRs for 80-84-year-old men after MI were 56.0 and 36.2, respectively, compared to 24.3 for men of the same age with no prior MI. In adjusted analyses the 6 months and 2 years IRRs for 80-84-year-old subjects were 2.56 (95% CI 2.11-3.10) and 1.41 (95% CI 1.22-1.65) for women and 1.74 (95% CI 1.34-2.25) and 1.05 (95% CI 0.88-1.26) for men, respectively. Predictors were advanced age, dementia, home care, Parkinson's disease, cerebrovascular disease, living alone, depression, and arrhythmia., Conclusion: In elderly patients discharged following first-time MI, the risk of subsequent nursing home admission within 6 months was 2-fold higher compared to an age-stratified population with no prior MI. After 2 years this risk remained higher in women., Competing Interests: LS is supported by Helsefonden and the Danish Heart Foundation, outside the submitted work. AN is supported by P. Carl Petersen Foundation and Helsefonden, outside the submitted work. KK has received grants from The Laerdal Foundation and The Danish Heart Foundation, as well as speaker’s honorarium from Novartis, outside the submitted work. GHG is supported by an unrestricted clinical research scholarship from the Novo Nordisk Foundation and has received research grants from Bayer, Pfizer, AstraZeneca, Boehringer-Ingelheim and Bristol Meyer Squibb (BMS) and speaker honoraria from Pfizer, AstraZeneca and BMS, outside the submitted work. PRH has received travelling honoraria from Abbott, and is recipient of a Borregaard Clinical Scientist Fellowship from the Novo Nordisk Foundation and an unrestricted research grant from the LEO Cover Letter Foundation, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The long-term probability of developing atrial fibrillation (AF) considering genetic predisposition and clinical risk factor burden is unknown., Methods: We estimated the lifetime risk of AF in individuals from the community-based Framingham Heart Study. Polygenic risk for AF was derived using a score of ≈1000 AF-associated single-nucleotide polymorphisms. Clinical risk factor burden was calculated for each individual using a validated risk score for incident AF comprised of height, weight, systolic and diastolic blood pressure, current smoking status, antihypertensive medication use, diabetes mellitus, history of myocardial infarction, and history of heart failure. We estimated the lifetime risk of AF within tertiles of polygenic and clinical risk., Results: Among 4606 participants without AF at 55 years of age, 580 developed incident AF (median follow-up, 9.4 years; 25th-75th percentile, 4.4-14.3 years). The lifetime risk of AF >55 years of age was 37.1% and was substantially influenced by both polygenic and clinical risk factor burden. Among individuals free of AF at 55 years of age, those in low-polygenic and clinical risk tertiles had a lifetime risk of AF of 22.3% (95% confidence interval, 15.4-9.1), whereas those in high-risk tertiles had a risk of 48.2% (95% confidence interval, 41.3-55.1). A lower clinical risk factor burden was associated with later AF onset after adjusting for genetic predisposition ( P <0.001)., Conclusions: In our community-based cohort, the lifetime risk of AF was 37%. Estimation of polygenic AF risk is feasible and together with clinical risk factor burden explains a substantial gradient in long-term AF risk., (© 2018 American Heart Association, Inc.)

Importance: Women with acute myocardial infarction (MI) undergoing mechanical reperfusion remain at increased risk of adverse cardiac events and mortality compared with their male counterparts. Whether the benefits of new-generation drug-eluting stents (DES) are preserved in women with acute MI remains unclear., Objective: To investigate the long-term safety and efficacy of new-generation DES vs early-generation DES in women with acute MI., Design, Setting, and Participants: Collaborative, international, individual patient-level data of women enrolled in 26 randomized clinical trials of DES were analyzed between July and December 2016. Only women presenting with an acute coronary syndrome were included. Study population was categorized according to presentation with unstable angina (UA) vs acute MI. Acute MI included non-ST-segment elevation MI (NSTEMI) or ST-segment elevation MI (STEMI)., Interventions: Randomization to early- (sirolimus- or paclitaxel-eluting stents) vs new-generation (everolimus-, zotarolimus-, or biolimus-eluting stents) DES., Main Outcomes and Measures: Composite of death, MI or target lesion revascularization, and definite or probable stent thrombosis at 3-year follow-up., Results: Overall, the mean age of participants was 66.8 years. Of 11 577 women included in the pooled data set, 4373 (37.8%) had an acute coronary syndrome as clinical presentation. Of these 4373 women, 2176 (49.8%) presented with an acute MI. In women with acute MI, new-generation DES were associated with lower risk of death, MI or target lesion revascularization (14.9% vs 18.4%; absolute risk difference, -3.5%; number needed to treat [NNT], 29; adjusted hazard ratio, 0.78; 95% CI, 0.61-0.99), and definite or probable stent thrombosis (1.4% vs 4.0%; absolute risk difference, -2.6%; NNT, 46; adjusted hazard ratio, 0.36; 95% CI, 0.19-0.69) without evidence of interaction for both end points compared with women without acute MI (P for interaction = .59 and P for interaction = .31, respectively). A graded absolute benefit with use of new-generation DES was observed in the transition from UA, to NSTEMI, and to STEMI (for death, MI, or target lesion revascularization: UA, -0.5% [NNT, 222]; NSTEMI, -3.1% [NNT, 33]; STEMI, -4.0% [NNT, 25] and for definite or probable ST: UA, -0.4% [NNT, 278]; NSTEMI, -2.2% [NNT, 46]; STEMI, -4.0% [NNT, 25])., Conclusions and Relevance: New-generation DES are associated with consistent and durable benefits over 3 years in women presenting with acute MI. The magnitude of these benefits appeared to be greater per increase in severity of acute coronary syndrome.

Background: The safety and efficacy of new-generation drug-eluting stents (DES) in women with multiple atherothrombotic risk (ATR) factors is unclear., Methods and Results: We pooled patient-level data for women enrolled in 26 randomized trials. Study population was categorized based on the presence or absence of high ATR, which was defined as having history of diabetes mellitus, prior percutaneous or surgical coronary revascularization, or prior myocardial infarction. The primary end point was major adverse cardiovascular events defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up. Out of 10,449 women included in the pooled database, 5333 (51%) were at high ATR. Compared with women not at high ATR, those at high ATR had significantly higher risk of major adverse cardiovascular events (15.8% versus 10.6%; adjusted hazard ratio: 1.53; 95% confidence interval: 1.34-1.75; P=0.006) and all-cause mortality. In high-ATR risk women, the use of new-generation DES was associated with significantly lower risk of 3-year major adverse cardiovascular events (adjusted hazard ratio: 0.69; 95% confidence interval: 0.52-0.92) compared with early-generation DES. The benefit of new-generation DES on major adverse cardiovascular events was uniform between high-ATR and non-high-ATR women, without evidence of interaction (Pinteraction=0.14). At landmark analysis, in high-ATR women, stent thrombosis rates were comparable between DES generations in the first year, whereas between 1 and 3 years, stent thrombosis risk was lower with new-generation devices., Conclusions: Use of new-generation DES even in women at high ATR is associated with a benefit consistent over 3 years of follow-up and a substantial improvement in very-late thrombotic safety., (© 2016 American Heart Association, Inc.)

Natriuretic peptides (NPs) may regulate adipocyte metabolism including adiponectin. Infusion of atrial natriuretic peptide (ANP) increases plasma adiponectin in patients with heart failure. However, this relation has not been examined in a clinical setting or in myocardial infarction (MI). Accordingly, we investigated the interplay between proANP and adiponectin and the prognostic implications in patients with MI. We prospectively included 680 patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention from September 2006 to December 2008. Blood samples were drawn immediately before percutaneous coronary intervention. Additionally, we included 40 patients with 4 obtained blood samples during STEMI. Adiponectin and proANP were measured in all plasma samples. All patients were followed for 5 years. End points were all-cause mortality (n = 137) and the combined end point (n = 170) of major adverse cardiovascular events (MACEs). Plasma adiponectin and proANP were strongly associated at admission (r = 0.34, p <0.001). In patients with increasing proANP during STEMI, adiponectin also increased (0.5 ± 0.3 vs -0.1 ± 0.1 mg/L, p = 0.026). During follow-up, patients with higher adiponectin at admission had increased risk of all-cause mortality and MACE (both, p <0.001). After adjustment for confounding risk factors by Cox regression analysis, adiponectin remained an independent predictor of all-cause mortality and MACE: hazard ratio 1.31 (95% confidence interval 1.07 to 1.60; p = 0.009) and 1.31 (95% confidence interval 1.09 to 1.57; p = 0.004), respectively, for each SD increase. However, the association vanished when proANP was included in the analysis. In conclusion, adiponectin is associated with an increased risk of all-cause mortality and MACE. However, concomitantly elevated proANP levels appear to confound the association between adiponectin and worsened outcome., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Although intracoronary abciximab failed to improve prognosis compared with intravenous route in unselected ST-segment elevation myocardial infarction (STEMI) patients, little is known about the role of intracoronary abciximab in diabetic patients., Objectives: To evaluate the efficacy of intracoronary abciximab administration in diabetic patients with STEMI undergoing primary percutaneous coronary intervention (PCI)., Methods: Reperfusional and clinical outcomes of intracoronary abciximab compared with intravenous bolus abciximab according to diabetic status were evaluated in a pooled analysis of five randomized trials including 3158 STEMI patients. The primary clinical endpoint of the study was the composite of death or reinfarction at 30-day follow-up., Results: Among 584 diabetic patients (18.5%), the composite of death or reinfarction was significantly reduced with intracoronary abciximab compared to intravenous abciximab (4.7% vs. 8.8%; rate ratio [RR], 0.50; 95% confidence intervals [CI], 0.26-0.99; p=0.04), driven by numerically lower deaths (3.7% vs. 6.4%; RR, 0.56; 95% CI, 0.26-1.20; p=0.13). Moreover, a significant reduction in definite or probable stent thrombosis was observed in patients receiving intracoronary abciximab (1% vs. 3.5%; RR, 0.27; 95% CI, 0.07-0.99; p=0.04). Although formal tests for interaction were not significant, no clinical benefit was apparent in the cohort of STEMI patients without diabetes (n=2574)., Conclusions: In diabetic patients with STEMI undergoing primary PCI, intracoronary abciximab may improve clinical outcomes as compared with standard intravenous use. These findings require confirmation in a dedicated randomized trial., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p <0.01). Conversely, no differences in crude mortality rates were observed between 1 and 3 years across clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio [HR] 3.45; 95% confidence interval [CI] 1.99 to 5.98; p <0.01), whereas no differences were observed between UAP or NSTEMI and SAP (HR 0.99; 95% CI 0.73 to 1.34; p = 0.94). In women with ACS, use of new-generation DES was associated with reduced risk of major adverse cardiac events (HR 0.58; 95% CI 0.34 to 0.98). The magnitude and direction of the effect with new-generation DES was uniform between women with or without ACS (pinteraction = 0.66). In conclusion, in women across the clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women., (Published by Elsevier Inc.)

Background: Subclinical hypothyroidism is associated with a number of cardiovascular risk factors, yet only limited data exist on long-term outcome of levothyroxine treatment of this condition with respect to hard end-points. The aim of this retrospective cohort study was to determine effects of levothyroxine treatment on myocardial infarction (MI), cardiovascular death and all-cause mortality, in patients with subclinical hypothyroidism., Methods and Results: Primary care patients aged 18 years and older that underwent thyroid function tests between 2000 and 2009 were enrolled. Participants were identified by individual-level linkage of nationwide registers. Patients with subclinical hypothyroidism at baseline were included in the study. Exclusion criteria included a history of thyroid disease, related medication or medication affecting thyroid function. The total cohort comprised 628,953 patients of which 12,212 (1.9%) had subclinical hypothyroidism (mean age 55.2 [SD ± 18.8] years; 79.8% female). Within the first six months 2,483 (20.3%) patients claimed a prescription for levothyroxine. During a median follow-up of 5.0 (IQR: 5.2) years, 358 MI's and 1,566 (12.8%) deaths were observed. Out of these, 766 of the deaths were cardiovascular related. No beneficial effects were found in levothyroxine treated patients on MI (IRR 1.08 [95% CI: 0.81 to 1.44]), cardiovascular death (IRR 1.02 [95% CI: 0.83 to 1.25]) or all-cause mortality (IRR 1.03 [95% CI: 0.90 to 1.19]), except in patients under the age of 65 years (IRR 0.63 [95% CI: 0.40 to 0.99])., Conclusion: Levothyroxine substitution in subclinical hypothyroid patients does not indicate an association with lower mortality or decreased risk of MI.

Background: Atrial natriuretic peptide (ANP) is released from the atria (on cleavage of proANP) in response to elevated intra-atrial pressure and wall stretch. Clinical data on proANP are still limited, mainly due to limitations in assaying the protein, which recently have been solved. ProANP is elevated in cardiovascular disease and predicts outcome in heart failure. However, knowledge of the prognostic value in acute myocardial infarction remains limited., Methods: We prospectively included 680 patients with STEMI treated with primary-PCI, from September 2006 to December 2008. Blood samples were drawn immediately before PCI. Plasma MR-proANP was measured using an automated processing assay. Endpoints were all-cause mortality (n = 137) and the combined endpoint (n = 170) of major adverse cardiovascular events (MACE) defined as cardiovascular mortality and admission due to recurrent MI, ischaemic stroke or heart failure., Results: During 5-year follow-up, MR-proANP was associated with increased risk of all-cause mortality and MACE (both p < 0.001). After adjustment for confounding risk factors (age, gender, hypertension, diabetes, hypercholesterolaemia, smoking, previous MI, BMI, eGFR, CRP, peak-TnI, symptom-to-balloon time, multivessel disease, complex lesion, LAD-lesion and use of glycoprotein inhibitor), MR-proANP remained an independent predictor of all-cause mortality and MACE - hazard ratio: 1.68 (95% CI 1.35-2.10; p < 0.001) and 1.68 (95% CI 1.39-2.03; p < 0.001) per standard deviation increase in MR-proANP. MR-proANP significantly increased C-statistics and reclassified 26% of the patients for all-cause mortality and 34% for MACE into higher or lower risk categories, matching actual event rates more accurately., Conclusions: Plasma MR-proANP independently predicts all-cause mortality and MACE in patients with STEMI., (© The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Objectives: Soluble receptor of advanced glycation end-products (sRAGE) may be a predictive biomarker in coronary artery disease (CAD). Patients with acute myocardial infarction (AMI) have higher sRAGE levels compared to healthy subjects. Accordingly, the aim of this study was to investigate the dynamic changes in sRAGE levels during AMI and relationship with cardiac dysfunction., Design and Methods: We prospectively included 80 patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). sRAGE concentrations were measured before pPCI, immediately after pPCI and again on the first and second following days. Left ventricular ejection fraction (LVEF) was evaluated 1-3 days after the pPCI and again at a median of 7months by echocardiography, and infarct size was measured by cardiac magnetic resonance., Results: sRAGE levels were high in the early phase of AMI; sRAGE levels significantly increased after pPCI compared with sRAGE before pPCI (median ratio: 1.25, 95% CI: 1.15-1.35, P<0.001), and the increase was observed prior to Troponin I (TnI). sRAGE levels decreased notably the first day after pPCI (median ratio: 0.34, 95% CI: 0.30-0.39, P<0.001). Peak sRAGE independently associated with long-term cardiac dysfunction estimated by LVEF (P=0.008). Furthermore, sRAGE measured after pPCI associated with infarct size (P=0.038)., Conclusions: sRAGE levels were high in the early phase rather than in the days after AMI and pPCI. The increase in sRAGE was seen before detectable changes in TnI. In addition, sRAGE was independently associated with long-term cardiac dysfunction., (Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: Circulating levels of pregnancy-associated plasma protein-A (PAPP-A) predict outcome in patients with acute coronary syndrome (ACS). Unfortunately, administration of heparin to patients with ACS increases circulating PAPP-A, probably by a detachment of PAPP-A from cell surfaces, inducing a considerable bias when using PAPP-A as a biomarker. It remains unknown whether PAPP-A-derived N- and C-terminal fragments of insulin-like growth factor binding protein-4 (NT-IGFBP-4/CT-IGFBP-4) are acutely affected by the increase in PAPP-A., Methods: We prospectively included 78 patients with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). Prior to PCI, patients were injected with 10,000IU of unfractionated heparin (UFH). Blood samples were collected immediately before PCI, but after UFH-injection, immediately after PCI and on day 1 and day 2. Plasma IGFBP-4, CT-IGFBP-4 and NT-IGFBP-4 levels were determined by specific, novel immunoassays, and PAPP-A and IGF-I by commercial immunoassays., Results: Plasma PAPP-A was strongly elevated upon STEMI, UFH-administration and PCI with mean concentrations (95%-confidence interval) pre-PCI, post-PCI, day 1, and day 2 of 13.0 (11.2;15.2), 14.8 (13.1;16.8), 1.03 (0.90;1.18), and 1.08 (0.92;1.28) μg/L, respectively (p<0.0001). Pre-PCI concentrations of IGFBP-4, CT-IGFBP-4 and NT-IGFBP-4 were 154 (142;166), 53 (47;60) and 136 (122;150) μg/L, and levels were unaltered post-PCI. Concentrations increased on day 1 by 63 (43;87)%, 69 (36;110)%, and 47 (21;79)%, respectively (p<0.0001), i.e. at a time point when PAPP-A levels had normalized., Conclusion: Plasma IGFBP-4-fragment levels are not acutely altered in patients with STEMI treated with UFH and PCI. Thus, they possess potentials as prognostic markers in ACS patients., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate the prognostic significance of hospitalization for worsening heart failure (WHF), myocardial infarction (MI), and stroke in patients with chronic heart failure (HF)., Methods and Results: We studied 5011 patients with HF and reduced EF (HF-REF) in the CORONA trial and 4128 patients with HF and preserved EF (HF-PEF) in the I-Preserve trial. Adjusted hazard ratios (HRs) for death were estimated for 0-30 days and ≥31 days after first post-randomization WHF, MI, or stroke used as a time-dependent variable, compared with patients with none of these events. In CORONA, 1616 patients (32%) had post-randomization first events (1223 WHF, 216 MI, 177 stroke), and the adjusted HR for mortality ≤30 days after an event was: WHF 7.21 [95% confidence interval (CI) 2.05-25.40], MI 23.08 (95% CI 6.44-82.71), and stroke 32.15 (95% CI 8.93-115.83). The HR for mortality at >30 days was: WHF 3.62 (95% CI 3.11-4.21), MI 4.41 (95% CI 3.23-6.02), and stroke 3.19 (95% CI 2.21-4.61). In I-Preserve, 896 patients (22%) experienced a post-randomization event (638 WHF, 111 MI, 147 stroke). The HR for mortality ≤30 days was WHF 31.77 (95% CI 7.60-132.81), MI 154.77 (95% CI 34.21-700.17), and stroke 223.30 (95% CI 51.42-969.78); for >30 days it was WHF 3.36 (95% CI 2.79-4.05), MI 3.29 (95% CI 2.14-5.06), and stroke 5.13 (95% CI 3.61-7.29)., Conclusions: In patients with both HF-REF and HF-PEF, hospitalization for WHF was associated with high early and late mortality. The early relative risk of death was not as great as following MI or stroke, but the longer term relative risk of death was similar following all three types of event. Numerically, more deaths occurred following WHF because it was a much more common event., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

Clopidogrel is an oral antiplatelet prodrug, the majority of which is hydrolyzed to an inactive metabolite by hepatic carboxylesterase 1 (CES1). Most angiotensin-converting enzyme inhibitors (ACEIs) are also metabolized by this enzyme. We examined the effects of ACEIs on clopidogrel bioactivation in vitro and linked the results with a pharmacoepidemiological study. In vitro, ACEIs inhibited CES1-mediated hydrolysis of a model substrate, and trandolapril and enalapril increased formation of clopidogrel active metabolite. In 70,934 patients with myocardial infarction, hazard ratios for clinically significant bleeding in ACEI-treated patients cotreated with or without clopidogrel were 1.10 (95% confidence interval (CI): 0.97-1.25, P = 0.124) and 0.90 (95% CI: 0.81-0.99, P = 0.025), respectively, as compared with patients who did not receive ACEIs. This difference was statistically significant (P = 0.002). We conclude that cotreatment with selected ACEIs and clopidogrel may increase the risk of bleeding. Combination of in vitro and pharmacoepidemiological studies may be a useful paradigm for assessment of drug-drug interactions.

Background: The prognostic significance of age and continuous positive airway pressure (CPAP) therapy on cardiovascular disease in patients with sleep apnoea has not been assessed previously., Methods: Using nationwide databases, the entire Danish population was followed from 2000 until 2011. First-time sleep apnoea diagnoses and use of CPAP therapy were determined. Incidence rate ratios (IRRs) of ischaemic stroke and myocardial infarction (MI) were analysed using Poisson regression models., Results: Amongst 4.5 million individuals included in the study, 33 274 developed sleep apnoea (mean age 53, 79% men) of whom 44% received persistent CPAP therapy. Median time to initiation of CPAP therapy was 88 days (interquartile range 34-346). Patients with sleep apnoea had more comorbidities compared to the general population. Crude rates of MI and ischaemic stroke were increased for sleep apnoea patients (5.4 and 3.6 events per 1000 person-years compared to 4.0 and 3.0 in the general population, respectively). Relative to the general population, risk of MI [IRR 1.71, 95% confidence interval (CI) 1.57-1.86] and ischaemic stroke (IRR 1.50, 95% CI 1.35-1.66) was significantly increased in patients with sleep apnoea, in particular in patients younger than 50 years (IRR 2.12, 95% CI 1.64-2.74 and IRR 2.34, 95% CI 1.77-3.10, respectively). Subsequent CPAP therapy was not associated with altered prognosis., Conclusions: Sleep apnoea is associated with increased risk of ischaemic stroke and MI, particularly in patients younger than 50 years of age. CPAP therapy was not associated with a reduced rate of stroke or MI., (© 2014 The Association for the Publication of the Journal of Internal Medicine.)

Background: High levels of circulating osteoprotegerin (OPG) predicts long-term outcome in patients with ST-elevation myocardial infarction (STEMI), possibly because of increased vascular inflammation resulting in myocardial damage. In the present study we aimed at elucidating the dynamic progress of OPG levels during STEMI treated with percutaneous coronary intervention (PCI) and additionally, the effect of OPG levels on cardiac function., Methods: We prospectively included 42 patients with STEMI treated with primary PCI. Four consecutive blood samples were obtained before and after PCI treatment. Plasma OPG levels were determined using an in-house immunoassay. Cardiac function was increased according to echocardiography, estimating left ventricular ejection fraction (LVEF) 1-3 days after STEMI., Results: During STEMI, OPG levels peaked after PCI and then decreased; mean concentrations (95% confidence interval) before PCI, after PCI, and on day 1 and day 2 of 2650 ng/L (2315-3036 ng/L), 2778 ng/L (2442-3363 ng/L), 2024 ng/L (1775-230 6 ng/L), and 1808 ng/L (1551-2106 ng/L), respectively (P < 0.001). Interestingly, the OPG response was observed before the response in troponin I and C-reactive protein. Patients with reduced LVEF (< 40%) exhibited an increased OPG response before, during, and after PCI (mean increase, 38%; 9%-75%; repeated measures analysis of variance, P = 0.009). Adjustment for age, sex, body mass index, and cardiovascular risk factors did not significantly affect the association between reduced LVEF and increased OPG response (mean increase 33% (4%-70%; F = 5.784; P = 0.023)., Conclusions: Circulating OPG levels are altered during STEMI treated with primary PCI. A high OPG level is independently associated with impaired LVEF., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objective: Patients with acute myocardial infarction (MI) have increased risk of developing type 2 diabetes mellitus (T2DM). Adiponectin is an insulin-sensitizing hormone produced in adipose tissue, directly suppressing hepatic gluconeogenesis, stimulating fatty acid oxidation and glucose uptake in skeletal muscle and insulin secretion. In healthy humans, low plasma adiponectin levels associate with increased risk of T2DM; however, the relationship between adiponectin and T2DM in patients with MI has never been investigated., Research Design and Methods: We prospectively included 666 patients with ST-segment elevation MI, without diabetes, treated with percutaneous coronary intervention, from September 2006 to December 2008 at a tertiary cardiac center. Blood samples were drawn before intervention, and total plasma adiponectin was measured in all samples. During follow-up (median 5.7 years [interquartile range 5.3-6.1]) 6% (n = 38) developed T2DM. Risk of T2DM was analyzed using a competing risk analysis., Results: Low adiponectin levels were associated with increased risk of T2DM (P < 0.001). Even after adjustment for confounding risk factors (age, sex, hypertension, hypercholesterolemia, current smoking, previous MI, BMI, blood glucose, total cholesterol, HDL, LDL, triglyceride, estimated glomerular filtration rate, C-reactive protein, peak troponin I, and proatrial natriuretic peptide), low adiponectin levels remained an independent predictor of T2DM (hazard ratio [HR] 5.8 [2.3-15.0]; P < 0.001). Importantly, plasma adiponectin added to the predictive value of blood glucose, with the combination of high blood glucose and low plasma adiponectin, vastly increasing the risk of developing T2DM (HR 9.6 [3.7-25.3]; P < 0.001)., Conclusions: Low plasma adiponectin levels are independently associated with increased risk of T2DM in patients with MI and added significantly to the predictive value of blood glucose., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Several studies have highlighted the prognostic role of preprocedural Thrombolysis In Myocardial Infarction (TIMI) flow in the infarct-related artery (IRA) in patients with ST-segment elevation myocardial infarction (STEMI). However, the impact of preprocedural IRA occlusion in patients with diabetes with STEMI has been insufficiently studied. The aim of this study was to evaluate the effects of baseline IRA occlusion and diabetic status in patients with STEMI who underwent primary percutaneous coronary intervention by using data from a pooled analysis of randomized trials comparing intracoronary with intravenous abciximab bolus administration. A total of 3,046 patients with STEMI who underwent primary percutaneous coronary intervention were included. Diabetes was present in 578 patients (19%). The primary outcome was mortality after a median follow-up period of 375 days. Secondary end points were reinfarction and stent thrombosis. In patients without diabetes, IRA occlusion versus no occlusion was not associated with increased rates of mortality (4.3% vs 2.7%, p = 0.051) and reinfarction (3.3% vs 2.5%, p = 0.33). Patients with diabetes with IRA occlusion compared with those without occlusion showed higher rates of mortality (10.6% vs 4.6%, p = 0.01) and reinfarction (5.6% vs 2.1%, p = 0.03). Baseline IRA occlusion increased the rate of stent thrombosis in the nondiabetic (2.1% vs 1.0%, p = 0.04) and diabetic (3.2% vs 0.8%, p = 0.05) cohorts. Interaction analysis demonstrated that the risk for death and reinfarction was significantly increased when diabetes and IRA occlusion occurred concomitantly. In conclusion, patients with STEMI with diabetes and baseline IRA occlusion had disproportionately higher rates of death and reinfarction. Preprocedural IRA occlusion increased the risk for stent thrombosis, irrespective of diabetic status., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: Pharmacological and revascularization strategies following myocardial infarction (MI) have changed substantially during the last two decades. We investigated the temporal trends in heart failure (HF) incidence and mortality during the first 90 days following first-time MI between 1997 and 2010 in Denmark., Methods and Results: Through administrative nationwide registers we identified 89,389 patients without prior HF hospitalized with first MI. The number of patients treated with percutaneous coronary intervention (PCI) days 0-1 after index MI increased from 2.5% in 1997-98 to 38.2% in 2009-10. Treatment with clopidogrel increased from 0.02% in 1997-98 to 68.1% in 2009-10 and statins from 8.1% in 1997-98 to 78.3% in 2009-10. The incidence of HF (defined as HF diagnosis or incident use of loop diuretics) decreased from 23.6% in 1997-98 to 19.6% in 2009-10 (p<0.001). Adjusted for age, sex, and comorbidity, hazard ratio was 0.77 (95% confidence interval [CI] 0.74-0.79) for developing HF in 2009-10, compared with 1997-98. Adjusted for coronary interventions, and pharmacotherapy HR increased to 0.82 (95% confidence interval (CI) 0.79-0.85) compared with 1997-98. The 90-day mortality decreased from 19.6% in 1997-98 to 11.7% in 2009-10 (p<0.001). Adjusted for age, sex, and comorbidity HR was 0.59 (CI 0.55-0.64) in 2009-10 compared with 1997-98; upon additional adjustment for coronary interventions and pharmacotherapy the estimate was 0.75 (95% CI 0.69-0.81)., Conclusion: We found a temporal decrease in HF incidence and mortality during the first 90 days after MI in 1997-2010. This could partly be explained by changes in interventional and pharmacological treatment strategies., (Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: Millions of patients were treated with the sirolimus-eluting Cypher™ and the paclitaxel-eluting Taxus™ coronary stents with potential late-occurring increase in event rates. Therefore, the long-term outcome follow-up is of major clinical interest., Design: In total, 2.098 unselected patients with ST-segment elevation myocardial infarction (STEMI), non-STEMI, stable or unstable angina pectoris were randomized to receive Cypher™ (n = 1.065) or Taxus™ (n = 1.033) stents and were followed for 5 years., Results: The primary end-point; the composite of cardiac death, myocardial infarction and target vessel revascularization (major adverse cardiac event, MACE), occurred in 467 patients (22.3%); Cypher™ n = 222 (20.8%), Taxus™ n = 245 (23.7%), ns. Definite and probable stent thrombosis occurred in 107 patients (5.1%); Cypher™ n = 51 (4.8%), Taxus™ n = 56 (5.4%), ns. No statistically significant differences were found in the elements of the primary end-point or in other secondary end-points between the two stent groups. After one year, the annual rates of stent thrombosis and MACE remained constant., Conclusions: During 5-year follow-up, the Cypher™ and the Taxus™ coronary stents had similar clinical outcome with no signs of increasing rates of adverse events over time.

Background: Previous studies have shown substantially increased risk of cardiac arrhythmias and sudden cardiac death in post-myocardial infarction (MI) patients. However it remains difficult to identify the patients who are at highest risk of arrhythmias in the post-MI setting. The purpose of this study was to investigate if CHADS₂ score (congestive heart failure, hypertension, age ≥75 years, diabetes and previous stroke/TCI [doubled]) can be used as a risk tool for predicting cardiac arrhythmias after MI., Methods: The study included 297 post-MI patients from the CARISMA study with left ventricular ejection fraction (LVEF) ≤40%. All patients were implanted with an implantable cardiac monitor (ICM) within 5 to 21 days post-MI and followed every three months for two years. Atrial fibrillation, bradyarrhythmias and ventricular tachycardias were diagnosed using the ICM, pacemaker or ICD. Patients were stratified according to CHADS₂ score at enrollment. Congestive heart failure was defined as LVEF ≤40% and NYHA class II, III or IV., Results: We found significantly increased risk of an arrhythmic event with increasing CHADS₂ score (CHADS₂ score=1-2: HR=2.1 [1.1-3.9], p=0.021, CHADS₂ score ≥ 3: HR=3.7 [1.9-7.1], p<0.001). This pattern was identical when dividing the arrhythmias into subgroups of atrial fibrillation, ventricular tachycardias and bradyarrhythmias. CHADS₂ score was similarly associated with the development of major cardiovascular events defined as reinfarction, stroke, and hospitalization for heart failure or cardiovascular death., Conclusion: In the post-MI setting, CHADS₂ score efficiently identifies populations at high risk for cardiac arrhythmias., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Importance: Clinical guidelines have been criticized for encouraging the use of β-blockers in noncardiac surgery despite weak evidence. Relevant clinical trials have been small and have not convincingly demonstrated an effect of β-blockers on hard end points (ie, perioperative myocardial infarction, ischemic stroke, cardiovascular death, and all-cause death)., Objective: To assess the association of β-blocker treatment with major cardiovascular adverse events (MACE) and all-cause mortality in patients with ischemic heart disease undergoing noncardiac surgery. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: Individuals with ischemic heart disease with or without heart failure (HF) and with and without a history of myocardial infarction undergoing noncardiac surgery between October 24, 2004, and December 31, 2009, were identified from nationwide Danish registries. Adjusted Cox regression models were used to calculate the 30-day risks of MACE (ischemic stroke, myocardial infarction, or cardiovascular death) and all-cause mortality associated with β-blocker therapy., Main Outcomes and Measures: Thirty-day risk of MACE and all-cause mortality., Results: Of 28,263 patients with ischemic heart disease undergoing surgery, 7990 (28.3%) had HF and 20,273 (71.7%) did not. β-Blockers were used in 4262 (53.3%) with and 7419 (36.6%) without HF. Overall, use of β-blockers was associated with a hazard ratio (HR) of 0.90 (95% CI, 0.79-1.02) for MACE and 0.95 (0.85-1.06) for all-cause mortality. Among patients with HF, use of β-blockers was associated with a significantly lower risk of MACE (HR, 0.75; 95% CI, 0.70-0.87) and all-cause mortality (0.80; 0.70-0.92), whereas among patients without HF, there was no significant association of β-blocker use with MACE (1.11; 0.92-1.33) or mortality (1.15; 0.98-1.35) (P < .001 for interactions). Among patients without HF, β-blockers were also associated with a lowered risk among those with a recent myocardial infarction (<2 years), with HRs of 0.54 (95% CI, 0.37-0.78) for MACE and 0.80 (0.53-1.21) for all-cause mortality (P < .02 for interactions between β-blockers and time period after myocardial infarction), but with no significant association in the remaining patients. Results were similar in propensity score-matched analyses., Conclusions and Relevance: Among patients with ischemic heart disease undergoing noncardiac surgery, use of β-blockers was associated with lower risk of 30-day MACE and mortality only among those with HF or recent myocardial infarction.

Background: Doppler tissue imaging (DTI) detects early signs of left ventricular (LV) dysfunction; however, the prognostic significance of DTI after ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this study was to evaluate the prognostic value of DTI after STEMI in patients treated with primary percutaneous coronary intervention., Method: In total, 391 patients who were admitted with STEMIs and treated with primary percutaneous coronary intervention were prospectively included. All participants were examined by echocardiography 2 days (interquartile range, 1-3 days) after STEMI. Longitudinal systolic (s'), early diastolic (e'), and late diastolic (a') myocardial velocities were measured using color DTI at six mitral annular sites and averaged to provide global estimates., Results: The median follow-up period was 25 months (interquartile range, 19-32 months). The primary end point was a composite of death, heart failure, or a new myocardial infarction. Patients with low global systolic function (s') or low global diastolic function (e') had >2 times greater risk for the combined end point compared with patients with high global s' (hazard ratio, 2.60; 95% confidence interval, 1.64-4.13; P < .001) or e' (hazard ratio, 2.26; 95% confidence interval, 1.44-3.55; P < .001), respectively. After adjustment for age, gender, peak troponin I, previous myocardial infarction, LV ejection fraction, LV mass index, and LV dimension in a multivariate Cox model, patients with low values of both global s' and e' remained at significantly higher risk than patients with high s' and/or e' (hazard ratio, 1.69; 95% confidence interval, 1.02-2.81; P = .043)., Conclusions: A pattern of low systolic and diastolic performance as assessed by DTI is a paramount marker of adverse prognosis for patients with STEMIs independent of conventional echocardiographic parameters. DTI velocities should be evaluated together as they interact with the prognosis., (Copyright © 2014 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Cardiovascular events (stroke or myocardial infarction) are often associated with poorer prognosis in younger, compared with older individuals. We examined the associations between prepregnancy obesity and the risks of myocardial infarction and stroke in young, healthy women., Methods and Results: All Danish women giving birth during 2004-2009 without a history of renal disease or cardiovascular disease were identified from national registers and followed for a median time of 4.5 years (interquartile range, 2.8-5.8). They were grouped according to prepregnancy body mass index (BMI) in underweight (BMI<18.5 kg/m(2)), normal weight (BMI=18.5-<25 kg/m(2)), overweight (BMI=25-<30 kg/m(2)), and obese (BMI≥30 kg/m(2)). The hazard ratios of myocardial infarction, ischemic stroke, and a composite outcome (myocardial infarction, stroke, cardiovascular death) were assessed using multivariable Cox regression models. We included 273 101 women with a median age of 30.4 years (interquartile range, 27.2-33.8). A total of 68 women experienced a myocardial infarction, and 175 women experienced an ischemic stroke. The adjusted hazard ratios of myocardial infarction compared with normal weight were 2.50 (95% confidence interval [95% CI], 0.97-6.50) in underweight, 1.68 (95% CI, 0.92-3.06) in overweight, and 2.63 (95% CI, 1.41-4.91) in obese women. For ischemic stroke the adjusted hazard ratios were 1.06 (95% CI, 0.44-2.28) in underweight, 1.27 (95% CI, 0.87-1.85) in overweight, and 1.89 (95% CI, 1.25-2.84) in obese women, respectively. For the composite outcome, hazard ratios were 1.34 (95% CI, 0.81-2.20), 1.43 (95% CI, 1.11-1.84), and 1.76 (95% CI, 1.31-2.34) for underweight, overweight, and obese women., Conclusions: In apparently healthy women of fertile age, prepregnancy obesity was associated with increased risks of ischemic stroke and myocardial infarction in the years after childbirth.

Background: Prior studies have found that obese patients have paradoxically lower in-hospital mortality after non-ST-segment-elevation myocardial infarction than their normal-weight counterparts, yet whether these associations persist long term is unknown., Methods and Results: We linked detailed clinical data for patients with non-ST-segment-elevation myocardial infarction aged ≥65 years in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) Registry to Medicare claims data to obtain longitudinal outcomes. Using height and weight measured on admission, patients were categorized into 6 body mass index (BMI [kilograms per meter squared]) groups. Multivariable Cox proportional hazards models were used to estimate the association between BMI and (1) all-cause mortality, (2) all-cause readmission, (3) cardiovascular readmission, and (4) noncardiovascular readmission for 3 years after hospital discharge. Among older patients with non-ST-segment-elevation myocardial infarction (n=34,465), 36.3% were overweight and 27.7% were obese. Obese patients were younger and more likely to have hypertension, diabetes mellitus, and dyslipidemia than normal or underweight patients. Relative to normal-weight patients, long-term mortality was lower for patients classified as overweight (BMI, 25.0-29.9), obese class I (BMI, 30.0-34.9), and obese class II (BMI, 35.0-39.9), but not obese class III (BMI ≥40.0). In contrast, 3-year all-cause and cardiovascular readmission were similar across BMI categories. Relative to normal-weight patients, noncardiovascular readmissions were similar for obese class I but higher for obese class II and obese class III., Conclusions: All-cause long-term mortality was generally lower for overweight and obese older patients after non-ST-segment-elevation myocardial infarction relative to those with normal weight. Longitudinal readmissions were similar or higher with increasing BMI.