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

Background: 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.

Exercise and pharmacologic stress-induced interlead T-wave heterogeneity analysis to detect clinically significant coronary artery stenosis.

Background: Despite widespread use of ETT and vasodilator-stress with myocardial perfusion imaging (MPI) for noninvasive detection of flow-limiting coronary artery disease, there is continued need to improve diagnostic accuracy. We examined whether measurement of interlead T-wave heterogeneity (TWH) during exercise tolerance testing (ETT) or pharmacologic stress testing improves detection of stenoses in large epicardial coronary arteries.

Methods: All 137 patients at our institution who underwent diagnostic coronary angiography within 0 to 5 days after ETT (N = 81) or dipyridamole IV infusion (N = 58) in 2016 were studied, including 2 patients with both tests.

Pulmonary delivery of flecainide causes a rate-dependent predominant effect on atrial compared with ventricular depolarization duration revealed by intracardiac recordings in an intact porcine model.

Background: Pulmonary delivery of flecainide results in the rapid conversion of atrial fibrillation (AF) to normal sinus rhythm in large-animal models and is safe and well-tolerated by normal human volunteers.

Objective: We investigated the effects of pulmonary delivery of flecainide on atrial and ventricular depolarization and repolarization duration.

Methods: Intratracheal instillation (1.

Accelerated conversion of atrial fibrillation to normal sinus rhythm by pulmonary delivery of flecainide acetate in a porcine model.

Background: Pulmonary delivery of antiarrhythmic agents has the potential to increase rapidly targeted drug concentrations in pulmonary veins and left atrium to terminate atrial fibrillation (AF).

Objective: We evaluated the efficacy of flecainide administered via intratracheal instillation in terminating AF in a reliable preclinical model.

Methods: In 11 closed-chest anesthetized Yorkshire pigs, AF was induced by intrapericardial administration of acetylcholine (1 mL of 102.

Comparative Pharmacokinetic and Electrocardiographic Effects of Intratracheal and Intravenous Administration of Flecainide in Anesthetized Pigs.

We compared the pharmacokinetic (PK) profile and electrocardiographic (ECG) changes in response to intratracheal instillation of flecainide acetate into the left atrium and ventricle with intravenous (IV) flecainide acetate administration. In 12 closed-chest anesthetized Yorkshire pigs, we monitored the QRS complex and PR, JTc, and QTc intervals during sinus rhythm and correlated changes with venous plasma drug concentrations before and at 2, 5, 10, 15, and 30 minutes after drug administration. Intratracheal instillation of flecainide (0.

Marked exercise-induced T-wave heterogeneity in symptomatic diabetic patients with nonflow-limiting coronary artery stenosis.

Background: T-wave heterogeneity (TWH) independently predicted cardiovascular mortality in Health Survey 2000 based on 12-lead ECGs recorded at rest. We investigated whether TWH is elevated during exercise tolerance testing (ETT) in symptomatic diabetic patients with nonflow-limiting coronary artery stenosis compared to control subjects without diabetes.

Methods: Cases were all patients (n = 20) with analyzable ECG recordings during both rest and ETT who were enrolled in the Effects of Ranolazine on Coronary Flow Reserve (CFR) in Symptomatic Patients with Diabetes and Suspected or Known Coronary Artery Disease (RAND-CFR) study (NCT01754259); median CFR was 1.

Ranolazine reduces repolarization heterogeneity in symptomatic patients with diabetes and non-flow-limiting coronary artery stenosis.

Background: Experimental evidence suggests that ranolazine decreases susceptibility to ischemia-induced arrhythmias independent of effects on coronary artery blood flow.

Objective: In symptomatic diabetic patients with non-flow-limiting coronary artery stenosis with diffuse atherosclerosis and/or microvascular dysfunction, we explored whether ranolazine reduces T-wave heterogeneity (TWH), an electrocardiographic (ECG) marker of arrhythmogenic repolarization abnormalities shown to predict sudden cardiac death.

Methods: We studied all 16 patients with analyzable ECG recordings during rest and exercise tolerance testing before and after 4 weeks of ranolazine in the double-blind, crossover, placebo-controlled RAND-CFR trial (NCT01754259).