Sacubitril/valsartan may be safe, effective to treat failing systemic right ventricle
Sacubitril/valsartan was safe and effective for reverse remodeling and improving systolic function and functional status in patients with a failing systemic right ventricle, researchers reported.
The results of a single-arm, single-center prospective study evaluating the efficacy and safety of sacubitril/valsartan (Entresto, Novartis) for patients with failing systemic right ventricle were published in Circulation: Heart Failure.
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“Patients with a systemic right ventricle tend to present progressive decline of the systemic right ventricle function during follow-up, eventually culminating in the development of HF symptoms,” Flavia Fusco, MD, of the adult congenital heart disease unit at Monaldi Hospital in Naples, Italy, and colleagues wrote. “Treatment of the failing systemic right ventricle is still mainly guided by clinicians’ personal experience and based on data derived from patients with acquired heart disease.
“In our population comprising 50 patients with a systemic right ventricle, treatment with sacubitril/valsartan was found to be safe, resulting in a steady clinical and echocardiographic improvement, consistent with previous results in patients with acquired heart disease and heart failure with reduced ejection fraction,” the researchers wrote. “No major adverse event occurred.”
Patient population and trail design
Fusco and colleagues prospectively enrolled 50 patients with congenitally corrected transposition of the great arteries or transposition of the great arteries after Senning/Mustard repair from September 2020 to April 2021 at Monaldi Hospital’s tertiary adult congenital heart disease center (mean age, 38 years; 60% men). Enrolled patients were already on optimal medical therapy and for at least 3 months with systemic right ventricle ejection fraction of 40% or less or fractional area change of 35% or less and assessed by echocardiography.
The primary efficacy endpoints included change in N-terminal pro-B-type natriuretic peptide and systolic function improvement at 1 year. The primary safety endpoint was absence of adverse events or drug discontinuation. Secondary endpoints included change in NYHA class, 6-minute walking distance and patient-reported quality of life.
Efficacy and safety of sacubitril/valsartan
Researchers observed no major adverse events. Four percent of patients discontinued sacubitril/valsartan due to hypotension and 2% developed a nephrotic syndrome.
The target dose of 97/103 mg twice daily was achieved in 46% of the total cohort.
From baseline to 1 year, patients assigned to sacubitril/valsartan had a progressive increase in fractional area change (29.2% vs. 34.9%; P < .001), right ventricle global longitudinal strain (13.9% vs. 15.3%; P < .001) and free-wall global longitudinal strain (14.3% vs. 17.2%; P < .001). Tricuspid regurgitation severity only improved in transposition of the great arteries patients (P = .006), according to the study.
On 3D echocardiography at 1 year, researchers observed right ventricle volume reduction (end-diastolic volume, 181 vs. 156 mL; P = .002; end-systolic volume, 117 vs. 89 mL; P < .001) and increased systemic right ventricle EF (35.6% vs. 41.5%; P < .001).
NYHA class improved by at least one in nearly half of the overall cohort. Improvement was also observed in 6-minute walking distance (425 vs. 500 m; P < .001) and patient-reported quality of life factors, including physical functioning (P < .001) and pain (P = .01) at 1 year.
“Our results appear promising, providing the basis for a wider-scale evaluation of the effects of sacubitril/valsartan in the management of HF in this complex population,” the researchers wrote.
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