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Background Isolated non-specific ST-T abnormalities (NSSTTAs), a common finding on ECGs, were associated with an increased risk of coronary heart disease (CHD) and stroke. However, their association with heart failure (HF) is not well documented.Methods This analysis included REasons for Geographic and Racial Differences in Stroke participants who were free of HF, CHD or major ECG abnormalities at baseline (2003–2007). NSSTTAs were defined from baseline ECG using the standards of Minnesota ECG classification. Incident HF events through 2020 were determined from a physician-adjudicated review of hospitalisation medical records and cause of death. Participants with ejection fraction (EF) ≥50% were considered to have HF with preserved EF (HFpEF), and the rest with EF <50% represented HF with either reduced or mildly reduced EF (HFrEF/HFmrEF). Multivariable Cox proportional hazards models examined the association between isolated NSSTTAs and HF. Separate, cause-specific Cox models were used to examine the association with HF subtypes, treating them as competing risks.Results Among 13 914 participants (mean age: 63.1±9.0 years; 60.1% women; 40.0% black), 3859 (28%) had isolated NSSTTAs. Over a median follow-up of 13.5 years (IQR: 7.9–15.6), isolated NSSTTAs were associated with an increased risk of incident HF (HR: 1.83, 95% CI 1.53 to 2.19). Isolated NSSTTAs were associated with an increased risk of both HFrEF/HFmrEF (HR: 2.19; 95% CI 1.64 to 2.93) and HFpEF (HR: 1.66; 95% CI 1.23 to 2.24).Conclusions Isolated NSSTTAs were associated with an increased risk of developing both HFrEF/HFmrEF and HFpEF. These findings challenge the assumption that NSSTTAs are benign and suggest their potential role in HF risk stratification.