Abstract Introduction Melatonin is widely used as a sleep aid and is available over the counter in many countries. Although generally perceived as safe, recent studies have raised concerns about its cardiovascular effects, particularly in relation to heart failure (HF). A large multinational study presented at the American Heart Association (AHA) 2025 Scientific Sessions reported increased risk of HF and mortality with long term melatonin use, while other investigations suggested potential protective benefits. We conducted a retrospective cross sectional analysis as a preliminary evaluation of these associations in our patient population. Methods We defined three patient groups from October 2024 to October 2025: (1) all patients prescribed melatonin (n=4,697; demographic baseline), (2) patients with HF and melatonin use (n=1,054), and (3) patients who developed HF after melatonin use (n=109). Eligibility required age ≥10 years, documented melatonin prescription, or HF diagnosis using ICD 10 I50.x codes. Patients using melatonin combined with other herbal preparations or with incomplete demographic data were excluded. Age, race, and gender distributions were compared between Groups 2 and 3 using chi square tests. Results HF prevalence increased sharply with age, rising from 3% in patients 35 years to 35% in those ≥75 years. Male patients had slightly higher HF prevalence than females (23% vs. 21%). Racial differences were observed: White and Black patients showed similar absolute HF prevalence (~22–23%), but Black patients carried proportionally higher burden relative to their smaller population size. Among melatonin users who developed HF (Group 3), older adults (≥55 years) accounted for the majority of cases. Chi-square analysis revealed no statistically significant differences in age (χ²=8.2, p=0.315), sex (χ²=0.00, p=1.000), or race (χ²=1.3, p=0.730) distributions between Groups 2 and 3. Conclusion Although HF prevalence among melatonin users was substantial, particularly in older adults, statistical comparisons did not demonstrate significant demographic differences between patients with HF and those who developed HF after melatonin use. These findings suggest melatonin may not independently drive HF risk, but the clustering of new HF diagnoses among melatonin users raises concern for potential harm in susceptible populations. Prospective studies are needed to clarify causality and guide safe prescribing practices. Support (if any)
Gangar et al. (Fri,) studied this question.