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

Circulation. 2005 Oct 18;112(16):2411-6. doi: 10.1161/CIRCULATIONAHA.105.543470. Epub 2005 Oct 10.

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: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiotensin II / blood
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Echocardiography, Transesophageal
  • Epinephrine / blood
  • Exercise*
  • Humans
  • Losartan / therapeutic use*
  • Natriuretic Peptide, Brain / blood
  • Norepinephrine / blood
  • Oxygen Consumption / physiology*
  • Peptide Fragments / blood
  • Transposition of Great Vessels / drug therapy
  • Transposition of Great Vessels / rehabilitation*
  • Transposition of Great Vessels / surgery
  • Treatment Outcome
  • Ventricular Dysfunction, Right / drug therapy
  • Ventricular Dysfunction, Right / rehabilitation*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Angiotensin II
  • Natriuretic Peptide, Brain
  • Losartan
  • Norepinephrine
  • Epinephrine