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

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract; all primary CIs exclude the null (OR 1.0), implying statistical significance

• Effect Size: OR 1.43 for all-cause mortality; OR 1.34 for heart failure; OR 1.41 for atrial fibrillation; SMD 0.58 for impaired global longitudinal strain; SMD -0.26 for reduced LV end-diastolic volume

• Primary Outcome: All-cause mortality in HCM patients with versus without comorbid diabetes mellitus

• Nnt Or Sensitivity: Hazard/odds ratios for prognostic outcomes: AF risk most pronounced in patients aged <50 years (OR 2.55) and attenuated in BMI ≥30 kg/m² subgroup; GLS SMD 0.58 indicates moderate-to-large subclinical systolic dysfunction signal

• Confidence Interval: Mortality: 95% CI 1.29–1.58; Heart failure: 95% CI 1.25–1.43; Atrial fibrillation: 95% CI 1.18–1.68

Clinical Application

The monitoring recommendations implied by these findings (enhanced rhythm surveillance, echocardiographic GLS assessment, closer heart failure monitoring) are feasible within existing cardiology infrastructure. GLS measurement requires appropriate echocardiographic software but is increasingly standard in tertiary and many secondary centres. No new pharmacological intervention is mandated by this evidence. HCM affects approximately 1 in 500 Australians and is managed under RACGP and CSANZ guidelines. Type 2 diabetes prevalence in Australia exceeds 5% of the adult population, making HCM-DM co-occurrence clinically common. One co-author (Asghari Jafarabadi) is affiliated with Cabrini Health, Malvern, Victoria, indicating Australian institutional involvement. SGLT2 inhibitors (empagliflozin, dapagliflozin) and GLP-1 receptor agonists are PBS-listed for Type 2 diabetes with cardiovascular risk; their potential role in HCM-DM warrants prospective evaluation given their established cardioprotective effects, though no direct evidence exists from this meta-analysis. TGA-approved antidiabetic agents with heart failure benefits may be preferentially considered in this population pending further evidence. RACGP guidelines support integrated cardiometabolic risk management, consistent with the authors' conclusions. Adults with established HCM diagnosis who have comorbid diabetes mellitus, across the full spectrum of HCM phenotypes (obstructive and non-obstructive). Subgroup findings are particularly relevant for younger HCM-DM patients (under 50 years) who carry disproportionately elevated AF risk.

Abstract

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.

References

1. 1.Mirzohreh, S.-T., Deravi, N., Javanshir, E., Asghari Jafarabadi, M., & Roshanravan, N. (2026). Impact of diabetes on outcomes in hypertrophic cardiomyopathy: a GRADE meta-analysis. Heart (British Cardiac Society). https://doi.org/10.1136/heartjnl-2025-326085