Empagliflozin's role in reducing ventricular repolarization heterogeneity: insights into cardiovascular mortality decline from the EMPATHY-HEART trial

• Published in: Cardiovascular diabetology 2024-06, Vol.23 (1), p.221-10, Article 221
• Main Authors: Lauretti, Cristiane, Antonio, Graziella L, Fernandes, Ariana E, Stocco, Fernando G, Girardi, Adriana C C, Verrier, Richard L, Caramelli, Bruno
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Aged; Arrhythmias, Cardiac - diagnosis; Arrhythmias, Cardiac - mortality; Arrhythmias, Cardiac - physiopathology; Benzhydryl Compounds - adverse effects; Benzhydryl Compounds - therapeutic use; Blood pressure; Cardiac arrhythmia; Cardiovascular disease; Cardiovascular diseases; Cardiovascular mortality; Clinical outcomes; Clinical trials; Coronary artery disease; Coronary Disease - diagnosis; Coronary Disease - drug therapy; Coronary Disease - mortality; Coronary Disease - physiopathology; Coronary heart disease; Coronary vessels; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - mortality; Diabetes Mellitus, Type 2 - physiopathology; EKG; Electrocardiography; Emotions; Empagliflozin; Female; Glucosides - adverse effects; Glucosides - therapeutic use; Heart attacks; Heart rate; Heart Rate - drug effects; Humans; Hypoglycemia; Hypotheses; Ischemia; Male; Medical diagnosis; Medical records; Middle Aged; Mortality; Myocardial infarction; Patients; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors - adverse effects; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; Software; Statistical analysis; T-wave heterogeneity; Time Factors; Treatment Outcome; Type 2 diabetes Mellitus; Ventricle; Ventricular Arrhythmias
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-024-02311-1

The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH. Participants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p