BACKGROUND AND AIMS: Risk stratification of sudden cardiac death after myocardial infarction and prevention by defibrillator rely on left ventricular ejection fraction (LVEF). Improved risk stratification across the whole LVEF range is required for decision-making on defibrillator implantation. METHODS: The analysis pooled 20 data sets with 140 204 post-myocardial infarction patients containing information on demographics, medical history, clinical characteristics, biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance imaging. Separate analyses were performed in patients (i) carrying a primary prevention cardioverter-defibrillator with LVEF ≤ 35% [implantable cardioverter-defibrillator (ICD) patients], (ii) without cardioverter-defibrillator with LVEF ≤ 35% (non-ICD patients ≤ 35%), and (iii) without cardioverter-defibrillator with LVEF > 35% (non-ICD patients >35%). Primary outcome was sudden cardiac death or, in defibrillator carriers, appropriate defibrillator therapy. Using a competing risk framework and systematic internal-external cross-validation, a model using LVEF only, a multivariable flexible parametric survival model, and a multivariable random forest survival model were developed and externally validated. Predictive performance was assessed by random effect meta-analysis. RESULTS: There were 1326 primary outcomes in 7543 ICD patients, 1193 in 25 058 non-ICD patients ≤35%, and 1567 in 107 603 non-ICD patients >35% during mean follow-up of 30.0, 46.5, and 57.6 months, respectively. In these three subgroups, LVEF poorly predicted sudden cardiac death (c-statistics between 0.50 and 0.56). Considering additional parameters did not improve calibration and discrimination, and model generalizability was poor. CONCLUSIONS: More accurate risk stratification for sudden cardiac death and identification of low-risk individuals with severely reduced LVEF or of high-risk individuals with preserved LVEF was not feasible, neither using LVEF nor using other predictors.

Albert Einstein College of Medicine Bronx NY

Arrhythmia and Robotic Electrophysiology Unit La Paz University Hospital Madrid Spain

Aston Medical School Aston University Aston Triangle Birmingham UK

Barmer Germany

Boston Scientific Corporation St Paul MN USA

Brigham and Women's Hospital Harvard Medical School Boston MA USA

Cardiology Heart Rhythm Management Department Clinique Pasteur Toulouse France

Cardiology University Hospitals Leuven Leuven Belgium

Center for Cardiac Arrhythmias of Genetic Origin IRCCS Istituto Auxologico Italiano Milan Italy

Centre for Health Economics University of York York UK

Clinical Epidemiology and Biostatistics The AMC Amsterdam The Netherlands

Département de Cardiologie CHRU de Nancy Nancy France

Department of Cardiology Aarhus University Hospital Aarhus Denmark

Department of Cardiology Amsterdam UMC location University of Amsterdam Amsterdam The Netherlands

Department of Cardiology and Pneumology Heart Center University Medical Center Goettingen Göttingen Germany

Department of Cardiology Angiology and Intensive Care Medicine Deutsches Herzzentrum der Charité Campus Charité Mitte Charitéplatz 1 10117 Berlin Germany

Department of Cardiology Department of Cardiology Odense Odense University Hospital Syddanmark Denmark

Department of Cardiology Karolinska University Hospital Stockholm Sweden

Department of Cardiology Rambam Health Care Campus Haifa Israel

Department of Cardiology Smidt Heart Institute Cedars Sinai Medical Center Los Angeles CA USA

Department of Cardiology The Heart Centre Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Cardiology University Hospital Basel University Basel Basel Switzerland

Department of Cardiovascular Imaging Centro Cardiologico Monzino IRCCS Milan Italy

Department of Cardiovascular Sciences University of Leuven Leuven Belgium

Department of Clinical and Experimental Cardiology Amsterdam University Medical Center AMC University of Amsterdam Amsterdam Netherlands

Department of Clinical Medicine Aarhus University Aarhus Denmark

Department of Electrophysiology Heart Center Leipzig Strumpellstr 39 04289 Leipzig Germany

Department of General Practice and Elderly Care Medicine Vrije Universiteit Amsterdam Amsterdam The Netherlands

Department of Information Engineering University of Padova Padova Italy

Department of Internal Medicine 1 Cardiology Olomouc University Hospital Moravia Czech Republic

Department of Medical Statistics University Medical Center Göttingen Göttingen Germany

Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden

Department of Radiology Leiden University Medical Center Leiden The Netherlands

Division of Cardiology European Georges Pompidou Hospital Paris France

Division of Cardiology Johns Hopkins University School of Medicine Baltimore MD USA

Division of Cardiovascular Sciences School of Medical Sciences Faculty of Biology Medicine and Health University of Manchester Manchester Academic Health Science Centre Manchester UK

Division of Informatics Imaging and Data Science Faculty of Biology Medicine and Health University of Manchester Manchester UK

Division of Medical Sciences in Zabrze Department of Cardiology Congenital Heart Diseases and Electrotherapy Silesian Center of Heart Diseases The Medical University of Silesia Katowice Poland

Heart Center Leipzig at the University of Leipzig Leipzig Germany

Hospital Clinic University of Barcelona Catalonia Spain

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Brno Czech Republic

Institute of Clinical and Experimental Medicine University Hospital Olomouc Moravia Czech Republic

Klinikum rechts der Isar Technische Universität München Munich Germany

Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds Leeds UK

Medical and Surgical Department of Cardiology Georges Pompidou European Hospital Paris France

Research Unit of Internal Medicine Medical Research Center Oulu University of Oulu and Oulu University Hospital Oulu Finland

School of Medicine Northwestern University Feinberg Chicago USA

Service de Cardiologie et Maladies Vasculaires CHU Pontchaillou Rennes France

Spectra Analytics London UK

The Healthcare Improvement Studies Institute Department of Public Health and Primary Care University of Cambridge Cambridge UK

University of Rochester Medical Center Clinical Cardiovascular Research Center Rochester NY USA

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