Impact of SGLT2 Inhibitors on Heart Failure in Genetic Cardiomyopathy Variants

Overview

This study evaluates the effect of dapagliflozin on heart failure outcomes in individuals with genetic variants linked to cardiomyopathy. The findings indicate that carriers of these variants have a significantly higher risk of hospitalization for heart failure compared to noncarriers.

Background

Heart failure (HF) poses a major health challenge, contributing to high morbidity and mortality rates. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin, have demonstrated efficacy in reducing HF hospitalization across various patient populations. Understanding the impact of SGLT2 inhibitors in patients with genetic predispositions to cardiomyopathy is crucial for optimizing treatment strategies.

Data Highlights

Key Findings

• 1% of patients in the study carried CMP-associated genetic variants.
• Carriers of CMP variants had an 8-fold increased risk of hospitalization for heart failure compared to noncarriers.
• Prior history of heart failure was more prevalent in carriers (18.2%) than noncarriers (9.8%).
• NT-proBNP levels were significantly higher in carriers than in noncarriers.
• Carriers had a lower left ventricular ejection fraction (LVEF) compared to noncarriers.

Clinical Implications

The identification of CMP variants in patients may necessitate closer monitoring and consideration of SGLT2 inhibitor therapy, even in asymptomatic individuals. Clinicians should be aware of the heightened risk of heart failure hospitalization in carriers of these genetic variants.

Conclusion

The study highlights the significant risk of heart failure hospitalization in carriers of CMP-associated genetic variants and suggests a potential role for SGLT2 inhibitors in this population.

Related Resources & Content

1. Frontiers in Cardiovascular Medicine, 2026 -- Expanding the scope of SGLT inhibitors in underrepresented cardiac populations: from pathophysiology to clinical evidence
2. Frontiers in Endocrinology, 2026 -- Glucose cotransporter-2 inhibitors on mortality and hospitalization in heart failure patients: a comprehensive meta-analysis
3. Frontiers in Cardiovascular Medicine, 2026 -- Efficacy of SGLT2 inhibitors in Patients Recently Hospitalized for Heart Failure: An Exploratory Prespecified Pooled Analysis of the DELIVER and EMPEROR-Preserved Trials
4. Clinical Research in Cardiology, 2026 -- Characteristics and outcomes of patients with heart failure and reduced left ventricular ejection fraction in relation to sodium-glucose cotransporter-2 inhibitor treatment: real-world data from the multicentre H2-registry
5. Diabetes Care, 2025 -- 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes
6. Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction - American College of Cardiology
7. Predicted Deleterious Variants in Cardiomyopathy Genes Prognosticate Mortality and Composite Outcomes in the UK Biobank | JACC: Heart Failure
8. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 | Diabetes Care | American Diabetes Association