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(Circulation. 2005;112:2411-2416.)
© 2005 American Heart Association, Inc.

Exercise Physiology

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

A Multicenter, Randomized, Placebo-Controlled Clinical Trial

Annie Dore, MD; Christine Houde, MD; Kwan-Leung Chan, MD; Anique Ducharme, MD, MSc; Paul Khairy, MD, PhD; Martin Juneau, MD; François Marcotte, MD; Lise-Andrée Mercier, MD

From the Department of Medicine, Montreal Heart Institute, Montreal (A.D., A.D., P.K., M.J., F.M., L.A.M.); Department of Pediatric Cardiology, Quebec Heart Institute, Quebec (C.H.); and Department of Cardiology, Ottawa Heart Institute, Ottawa (K.L.C.), Canada.

Correspondence to Annie Dore, MD, Adult Congenital Heart Center, Montreal Heart Institute, 5000 Belanger St E, Montreal, Quebec, Canada H1T 1C8. E-mail annie.dore{at}icm-mhi.org

Received February 16, 2005; revision received June 22, 2005; accepted July 29, 2005.

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: O₂max, 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 O₂max (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.

Key Words: angiotensin • exercise • transposition of great vessels

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