Impact of diabetes on outcomes in hypertrophic cardiomyopathy: a GRADE meta-analysis.

Background: Diabetes mellitus (DM) is a common comorbidity in hypertrophic cardiomyopathy (HCM) and may exacerbate arrhythmic risk, promote structural remodelling and worsen heart failure outcomes. Its overall prognostic impact and effect on cardiac structure and function in adults with HCM remain uncertain.

Method: We systematically searched PubMed, Scopus, Web of Science and Cochrane to January 2025 for observational studies comparing adults with HCM-DM versus HCM without DM. Random-effects meta-analyses were performed to pool ORs for clinical outcomes and standardised mean differences (SMDs) for echocardiographic parameters. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework after Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) evaluation. Subgroup, sensitivity and heterogeneity analyses were undertaken.

Result: Eight studies encompassing approximately 47 592 patients met inclusion criteria. DM was associated with higher odds of all-cause mortality (OR 1.43, 95% CI 1.29 to 1.58; high certainty), heart failure (OR 1.34, 95% CI 1.25 to 1.43; moderate certainty) and atrial fibrillation (OR 1.41, 95% CI 1.18 to 1.68; high certainty). The association with atrial fibrillation was most pronounced in patients younger than 50 years (OR 2.55) and attenuated in those with body mass index ≥30 kg/m². HCM-DM was also linked to smaller left ventricular end-diastolic volumes (SMD -0.26) and impaired global longitudinal strain (SMD 0.58), consistent with subclinical systolic dysfunction, although heterogeneity was high and certainty low to moderate. Evidence for left ventricular ejection fraction, mass and septal thickness was inconclusive. Results were robust across sensitivity analyses.

Conclusions: DM is a clinically important risk marker in HCM, associated with excess mortality, heart failure and atrial fibrillation, as well as adverse structural-functional changes. These findings support closer rhythm and function monitoring in HCM-DM and highlight the need for prospective studies to determine whether targeted metabolic interventions can improve outcomes.

Prospero registration number: CRD420250650799.