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Available data suggest that improvement in left ventricular ejection fraction (LVEF) is a major predictor of improved survival in heart failure (HF). Although certain factors are associated with improvements in LVEF in select patients with HF enrolled in clinical trials, relatively little is known about such factors among patients in clinical practice. This study evaluated changes in LVEF and associated factors in outpatients with systolic HF or post-myocardial infarction with reduced LVEF during 24 months of follow-up.IMPROVE HF is a prospective evaluation of a practice-based performance improvement intervention implemented at outpatient cardiology/multispecialty practices to increase use of guideline-recommended care for eligible patients. Data were analyzed by patient groups based on absolute improvement in LVEF (<0%, 0-≤10%, and >10%) from baseline to 24 months and by change in LVEF as a continuous variable.A total of 3,994 patients from 155 of 167 practices were eligible for analysis. The overall mean LVEF increased from 25.8% at baseline to 32.3% (+6.4%) at 24 months (P < .001), and 28.6% of patients had a >10% improvement in ejection fraction (from 24.5% to 46.2%, 92% relative improvement). Age, race, and practice setting were similar between the 3 LVEF improvement groups. Multivariate analysis revealed female sex, no prior myocardial infarction, nonischemic HF etiology, and no digoxin use were associated with >10% improvement in LVEF.Among patients with HF receiving care in cardiology/multispecialty practices participating in a performance measure intervention, surviving, and having repeat LVEF assessment, close to one third of patients had a >10% improvement in LVEF at 24 months. These findings indicate that HF is not always a progressive disease and that differentiation of the heterogeneous HF phenotypes may set the stage for future research and therapeutic targets.