Sildenafil and Diastolic Dysfunction After Acute Myocardial Infarction Trial: Rationale and Design

Abstract

Diastolic dysfunction following myocardial infarction is an important predictor of outcome, irrespective of left ventricular systolic function. Previous studies suggest that phosphordiesterase-5 inhibition has a favorable effect on the myocardium as well as on the pulmonary and systemic vasculature. Patients≥50 years old with recent myocardial infarction, preserved left ventricular ejection fraction (≥45%), and echocardiographic evidence of diastolic dysfunction (ratio between early [E] transmitral filling velocity and early diastolic tissue Doppler velocity [e']≥8 and left atrial volume≥34 mL/m2) will be double-blindly randomized 1:1 to receive 9 weeks of treatment with 40 mg sildenafil, 3 times per day, or comparable placebo. Before randomization and after 9 weeks of treatment, resting Doppler echocardiography, resting right heart catheterization, and symptom-limited supine cycle exercise testing with simultaneous echocardiography and right heart catheterization will be performed. The primary end point is filling pressure at rest and at peak exercise. With a power of 80% and a significance level of .05, a study group of 60 patients is needed to detect a 15% reduction at peak exercise, which is considered clinically relevant. To account for dropouts and noncompliance, 70 patients will be enrolled in the study. In addition to determining if sildenafil can reduce filling pressure at rest and at peak exercise, the Sildenafil and Diastolic Dysfunction After Acute Myocardial Infarction trial will provide additional hemodynamic information to help phenotypically classify this growing population of patients with diastolic dysfunction and preserved ejection fraction following myocardial infarction.