Abstract 18974: A Pilot Study of the Effects of Ranolazine on Right Ventricular Structure and Function, Exercise Capacity, and Symptoms in Pulmonary Arterial Hypertension

Abstract

Introduction: Right ventricular (RV) failure is a major cause of death in pulmonary arterial hypertension (PAH). RV ischemia, which is common in PAH, plays a major role in the development of RV failure. We hypothesized that ranolazine, a late Na+ current inhibitor, would be beneficial in patients with PAH by increasing RV perfusion. Methods: We prospectively enrolled 10 patients with World Health Organization (WHO) Group I PAH and symptoms of angina (or anginal equivalent) in an observational, 3-month study of the effects of ranolazine (1000 mg PO BID) in PAH. All patients were on chronic pulmonary vasodilator therapy. At baseline and 3 months, patients underwent functional class assessment, 6-minute walk test, bicycle echocardiography with speckle-tracking for assessment of RV mechanics, right heart catheterization, and adenosine perfusion cardiac MRI. Data was compared at baseline vs. 3-months using paired t-tests. Results: The mean age was 47±13 y, and 80% were female. At baseline, patients had moderate or greater PAH (Table 1) with evidence of RV dysfunction (7/10 patients had reduced RV fractional area change [<0.35], and all patients had septal flattening indicative of RV overload). Ranolazine was well tolerated in 90% of patients (7 patients tolerated the full dose and 2 patients required a dose reduction due to side effects, after which the drug was well tolerated). Ranolazine was discontinued in 1 patient due to a medication interaction. After 3 mo. of ranolazine therapy, symptoms improved, exercise capacity increased, RV size decreased, and tricuspid annular plane systolic excursion (TAPSE) increased (Table 1). There were no changes in invasive hemodynamics, and no major adverse events. Conclusions: Ranolazine is well tolerated and safe in patients with WHO Group I PAH. After 3 mo. of therapy, ranolazine improved RV size and function and resulted in symptomatic improvement. These findings support the development of clinical trials for ranolazine in PAH.