Safety and Efficacy of Sacubitril/Valsartan in Patients With a Failing Systemic Right Ventricle: A Prospective Single-Center Study

• Published in: Circulation. Heart failure Vol. 16; no. 2; p. e009848
• Main Authors: Fusco, Flavia, Scognamiglio, Giancarlo, Merola, Assunta, Iannuzzi, Angela, Palma, Michela, Grimaldi, Nicola, Sarubbi, Berardo
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 01-02-2023
• Subjects: Aminobutyrates - therapeutic use; Angiotensin Receptor Antagonists - therapeutic use; Biphenyl Compounds - therapeutic use; Congenitally Corrected Transposition of the Great Arteries - complications; Drug Combinations; Female; Heart Failure; Heart Ventricles; Humans; Male; Prospective Studies; Quality of Life; Stroke Volume; Tetrazoles - therapeutic use; Transposition of Great Vessels - complications; Valsartan - therapeutic use; congenital heart disease; heart failure; transposition of the great arteries; valsartan; sacubitril
• ISSN: 1941-3297; 1941-3289; 1941-3297
• DOI: 10.1161/CIRCHEARTFAILURE.122.009848

Sacubitril/valsartan was demonstrated to reduce hospitalization rate and mortality in patients with heart failure with reduced ejection fraction. Data on the effects of sacubitril/valsartan in patients with a systemic right ventricle are still lacking.
Patients with transposition of the great arteries following Senning/Mustard procedure or congenitally corrected transposition of the great arteries with impaired systemic right ventricle systolic function were prospectively included. Primary end points included sacubitril/valsartan safety and efficacy. Primary efficacy end points were NT-proBNP (N-terminal pro-B-type natriuretic peptide) and systolic function improvement. Secondary end points included New York Heart Association class, 6-minute walking distance, and quality of life change.
Fifty patients (38±12 years, 60% male, 35% congenitally corrected transposition of the great arteries) were included and followed for 1 year. No major adverse events occurred. Two (4%) patients ceased treatment due to hypotension and 1 (2%) developed a nephrotic syndrome. The target dose was reached in 20 (42%) patients. NT-proBNP values decreased significantly immediately after treatment initiation, while returned to baseline at 1 year. Echocardiography showed progressive fractional area change increase (29.2±5.8 versus 34.9±5.1%;
<0.001), and right ventricle global longitudinal strain (-13.9 [-15.1, -11.8] versus -15.3 [-17.2, -13.4]%;
<0.001) and free-wall global longitudinal strain (-14.3 [-17.3, -12.3] versus -17.2 [-19.3, -15.8]%;
<0.001) raise, whereas tricuspid regurgitation severity improved only in transposition of the great arteries patients (
=0.006). Moreover, 3-dimensional echocardiography demonstrated right ventricle volumes reduction (end-diastolic volume: 181±63 versus 156±50 mL;
=0.002; end-systolic volume: 117±48 versus 89±33 mL;
<0.001), and significantly increased systemic right ventricle ejection fraction (35.6±8.1 versus 41.5±7.5%;
<0.001). Clinical improvement was suggested by New York Heart Association class change (
<0.001), increased 6-minute walking distance (425 [333, 480] versus 500 [443, 560] m;
<0.001) as well as improved quality of life at 1-year follow-up. Beneficial effects were observed irrespective of the underlying anatomy and were more pronounced in those on target dose.
Our data showed that sacubitril/valsartan is well tolerated and is associated with systemic right ventricle remodeling and improved systolic function as well as improved clinical status, supporting its use in this complex population.