Angiotensin receptor blockade and exercise capacity in adults with systemic right ventricles: a multicenter, randomized, placebo-controlled clinical trial.
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.


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.
Dore
Annie
A
Department of Medicine, Montreal Heart Institute, Montreal, Canada. annie.dore@icm-mhi.org
Houde
Christine
C
Chan
Kwan-Leung
KL
Ducharme
Anique
A
Khairy
Paul
P
Juneau
Martin
M
Marcotte
François
F
Mercier
Lise-Andrée
LA
D000328:Adult; D000804:Angiotensin II / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017548:Echocardiography, Transesophageal; D004837:Epinephrine / Q000097:blood; D015444:Exercise; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption / Q000502:physiology*; D010446:Peptide Fragments / Q000097:blood; D014188:Transposition of Great Vessels / Q000188:drug therapy / Q000534:rehabilitation* / Q000601:surgery; D016896:Treatment Outcome; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy / Q000534:rehabilitation*
D047228:Angiotensin II Type 1 Receptor Blockers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D019808:Losartan; D009638:Norepinephrine; D004837:Epinephrine