Angiotensin Receptor Blockade and Exercise Capacity in Adults With Systemic Right Ventricles

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: VO2max, 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 VO2max (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.