Sacubitril/valsartan in the treatment of systemic right ventricular failure

Abstract

ObjectivePharmacological options for patients with a failing systemic right ventricle (RV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are not well defined. This study aims to investigate the feasibility and effects of sacubitril/valsartan treatment in a single-centre cohort of patients.MethodsData on all consecutive adult patients (n=20, mean age 46 years, 50% women) with a failing systemic RV in a biventricular circulation treated with sacubitril/valsartan in our centre are reported. Patients with a systemic RV ejection fraction of ≤35% who were symptomatic despite treatment with β-blocker and ACE-inhibitor/angiotensin II receptor-blockers were started on sacubitril/valsartan. This cohort underwent structural follow-up including echocardiography, exercise testing, laboratory investigations and quality of life (QOL) assessment.ResultsSix-month follow-up data were available in 18 out of 20 patients, including 12 (67%) patients with TGA after atrial switch and 6 (33%) patients with ccTGA. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) decreased significantly (950–358 ng/L, p<0.001). Echocardiographic systemic RV fractional area change and global longitudinal strain showed small improvements (19%–22%, p<0.001 and −11% to −13%, p=0.014, respectively). The 6 min walking distance improved significantly from an average of 564 to 600 m (p=0.011). The QOL domains of cognitive function, sleep and vitality improved (p=0.015, p=0.007 and p=0.037, respectively).ConclusionsWe describe the first patient cohort with systemic RV failure treated with sacubitril/valsartan. Treatment appears feasible with improvements in NT-pro-BNP and echocardiographic function. Our positive results show the potential of sacubitril/valsartan for this patient population.

The first experience with sodium‐glucose cotransporter 2 inhibitor for the treatment of systemic right ventricular failure

“…3 In 2021, the first sRV patient cohort treated with sacubitril/valsartan was described. 10 In this cohort, sacubitril/valsartan resulted in significant improvements in NT-proBNP and echocardiographic sRV function, as well as functional improvements at 6 months of follow-up. However, large trials are often hampered by the small cohort size and heterogeneity of this population and data on the impact of sacubitril/valsartan treatment on mortality and heart-failure-related hospitalizations in the group of sRV failure are still lacking.…”

“…Although small, the effect size of dapagliflozin treatment on GLS is comparable with the previously reported range for effect of 6 months of treatment with sacubitril/valsartan on sRV GLS (increase from À11% to À13%). 10 Despite the fact that the exact mechanisms underlying the protective cardiovascular and renal effects of SGLT-2 inhibitors are not fully elucidated, several studies show that this class of drugs decreases the renin-angiotensin and sympathetic nervous system activation, halts the pressure overload-induced myocardial fibrosis, and reverses the cardiac remodelling as well as improves myocardial energetics. 5,11 These mechanisms have previously been described to play an important role in sRV failure and data obtained on subpulmonary RV failure pressure overload from animal models suggest that sRV patients might also benefit from SGLT-2 inhibition in the clinical setting.…”

“…Pharmacological treatment of sRV dysfunction remains a challenge and data to support the hypothesis that ‘traditional’ left ventricular heart failure medication for patients with reduced left ventricular ejection fraction also improves clinical outcomes in sRV patients remain scarce 3 . In 2021, the first sRV patient cohort treated with sacubitril/valsartan was described 10 . In this cohort, sacubitril/valsartan resulted in significant improvements in NT‐proBNP and echocardiographic sRV function, as well as functional improvements at 6 months of follow‐up.…”

Selección de lo mejor del año 2021 en cardiopatías congénitas

“…Las opciones farmacológicas para los pacientes con ventrículo derecho sistémico disfuncionante son limitadas, en contraposición al arsenal farmacológico de la disfunción del ventrículo izquierdo. Se han descrito por primera vez los resultados del uso de sacubitrilo-valsartán en una pequeña cohorte de pacientes con ventrículo derecho sistémico 11 , mostrando resultados prometedores en cuando a mejoría de los valores del péptido natriurético NT-proBNP y de la función ventricular medida por ecocardiografía (cálculo del área fraccional y strain global longitudinal), así como mejoría en la clase funcional.…”

Right Heart Failure Management: The Achilles Heel

“…This study highlighted statistically significant improvement in N-terminal pro-B-type natriuretic peptide, echocardiographic systemic RV fractional area change, global longitudinal strain, 6-minute walking distance, and the QOL domains of cognitive function, sleep, and vitality. 3 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 right ventricles, but it failed to improve exercise capacity or reduce NT-proBNP levels, and lack of success was attributed to minimal baseline activation of the renin–angiotensin system. 4…”