Losartan in Tetralogy of Fallot and RV Dysfunction
What is the effect of losartan on right ventricular (RV) dysfunction in adults after repair of tetralogy of Fallot (rTOF)?
A multicenter, prospective, randomized, double-blind, placebo-controlled study was performed. Patients were identified using the Dutch national registry of adult congenital heart disease patients (CONCOR database). Patients with rTOF and RV ejection fraction (EF) <50% without significant valvular dysfunction were eligible for participation. Patients were randomized to losartan (target dose 150 mg daily) or placebo with duration of treatment from 18-24 months. The primary outcome was change in RVEF, as determined by cardiovascular magnetic resonance imaging (MRI).
Ninety-five patients were enrolled, of which 47 patients received 150 mg losartan daily and 48 received placebo. There was no change in RVEF in either patients receiving losartan (44.4 ± 5.1% to 45.2 ± 5%) or placebo (43.2 ± 6.3% to 43.6% to 43.6 ± 6.9%). Losartan did not improve RVEF as compared with placebo (+0.51%; 95% confidence interval [CI], -1.0, +2.0; p = 0.5). There was no effect of losartan on secondary outcomes including left ventricular EF, peak aerobic capacity, or N-terminal brain natriuretic peptide. Predefined subgroup analyses included symptomatic patients, restrictive RV physiology, RVEF <40% pulmonary valve replacement, or QRS fragmentation. No benefit was seen with losartan for any of these subgroups. In a post hoc analysis, losartan was associated with improved RVEF in a subset of patients (n = 30) with nonrestrictive RV and incomplete remodeling (QRS fragmentation and previous pulmonary valve replacement) (+2.7%; 95% CI, +0.1, +5.4).
The authors concluded that losartan had no significant effect on RV dysfunction or secondary outcome measures in adults with rTOF. Further study may determine whether there is a role for losartan in specific subgroups of patients.
This well-designed study showed no significant benefit with an angiotensin II receptor blocker on RV function and other clinical parameters in adults with rTOF. The study demonstrates the importance of not extrapolating data from other patient populations (i.e., the role of renin-angiotensin-aldosterone system inhibitors in patients with systemic left ventricular dysfunction) to patients with various types of congenital heart disease. The study did leave the door open for a role for such agents in subgroups of patients, with a post hoc analysis suggesting improvement in RVEF in patients with nonrestrictive right ventricles and incomplete remodeling after pulmonary valve replacement. Further study will be required, but will be a challenge because of small patient numbers.
Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Congenital Heart Disease, CHD and Pediatrics and Imaging, CHD and Pediatrics and Quality Improvement, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Magnetic Resonance Imaging
Keywords: Angiotensin Receptor Antagonists, Heart Defects, Congenital, Heart Failure, Losartan, Magnetic Resonance Imaging, Natriuretic Peptide, Brain, Outcome Assessment (Health Care), Pulmonary Valve, Registries, Renin-Angiotensin System, Stroke Volume, Tetralogy of Fallot, Ventricular Dysfunction, Ventricular Dysfunction, Right, Ventricular Dysfunction, Left
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