Angiotensin Receptor Blockade and Exercise Capacity in Adults With Systemic Right Ventricles: A Multicenter, Randomized, Placebo-Controlled Clinical Trial

Abstract

Background— Pharmacological blockade of the renin-angiotensin system improves exercise tolerance in patients with left ventricular dysfunction, yet its impact on patients with systemic right ventricles (RVs) remains unknown. Methods and Results— A multicenter, randomized, double-blind, placebo-controlled, crossover clinical trial was performed to assess the effects of losartan on exercise capacity and neurohormonal levels in patients with systemic RVs. Of 29 patients studied (age, 30.3±10.9 years), 21 had transposition of the great arteries with a Mustard baffle, and 8 had congenitally corrected transposition of the great arteries. Baseline values were as follows: V̇ o 2 max, 29.8±5.6 mL · kg −1 · min −1 (73.5±12.9% predicted value); RV ejection fraction, 41.6±9.3%; N-terminal pro brain natriuretic peptide (NT-proBNP), 257.7±243.4 pg/mL (normal <125 pg/mL); and angiotensin II, 5.7±4.9 pg/mL (normal <5.0 pg/mL). Comparing losartan to placebo showed no differences in V̇ o 2 max (29.9±5.4 versus 29.4±6.2 mL · kg −1 · min −1 ; P =0.43), exercise duration (632.3±123.0 versus 629.9±140.7 seconds; P =0.76), and NT-proBNP levels (201.2±267.8 versus 229.7±291.5 pg/mL; P =0.10), despite a trend toward increased angiotensin II levels (15.2±13.8 versus 8.8±12.5 pg/mL; P =0.08). Conclusions— In adults with systemic RVs, losartan did not improve exercise capacity or reduce NT-proBNP levels. Minimal baseline activation of the renin-angiotensin system may explain this lack of benefit and imply an alternative pathophysiological mechanism for the progressive ventricular dysfunction and impaired exercise capacity observed in such patients.