WASHINGTON, June 26, 2025 (APMnews) – In patients with heart failure and a systemic right ventricle, the SGLT2 inhibitor dapagliflozin (Forxiga*, AstraZeneca) improved functional capacity, quality of life, and right ventricular function at six months, according to the observational DAPA-SRV trial published in the Journal of the American Heart Association (JAHA).
“In patients with transposition of the great vessels after atrial switch surgery (Mustard or Senning procedure) or with congenitally corrected transposition of the great vessels, the morphologic right ventricle supports systemic circulation, while the left ventricle supports pulmonary circulation,” explained Mathieu Albertini from the M3C Reference Center for Complex Congenital Heart Defects in Paris and colleagues.
“This unique physiological condition has been clearly associated with a significantly increased risk of heart failure.”
While the management of heart failure in patients with acquired cardiopathy has benefitted from new drug classes such as SGLT2 inhibitors, clinical trials have not included patients with a systemic right ventricle, leaving the benefits in this population uncertain.
In this prospective, observational, single-center study, 32 patients with systemic right ventricular heart failure and altered ejection fraction were enrolled between February 2023 and February 2024 at the Georges-Pompidou European Hospital in Paris. All had NYHA functional class ≥ 2.
Among them, 62.5% had undergone atrial switch surgery for transposition of the great vessels, and 37.5% had congenitally corrected transposition.
All patients were receiving sacubitril-valsartan (Entresto*, Novartis) and were started on dapagliflozin.
The six-minute walk test distance (primary endpoint) significantly increased after six months, from 558 m at baseline to 585 m.
No significant difference was observed between the subgroup with atrial switch and the subgroup with congenitally corrected transposition.
The reduction in NT-proBNP levels between baseline and six months was not statistically significant.
However, NYHA class, overall quality of life measured by the KCCQ-12 global score, and all individual components of the score (physical limitations, symptom frequency, quality of life, social limitations) showed improvements at six months.
Echocardiographic data also demonstrated improved systemic right ventricular function at six months.
No specific adverse events related to dapagliflozin were reported during follow-up.
“To our knowledge, this is the largest evaluation of dapagliflozin in patients with systemic right ventricular dysfunction and heart failure to date,” the authors noted.
In an accompanying editorial, William Marshall and Curt Daniels from the Nationwide Children’s Hospital Heart Center in Columbus, U.S., wrote that the study “represents a step in the right direction toward building evidence for the use of SGLT2 inhibitors in systemic right ventricular systolic dysfunction.”
“While ambitious, the ideal way to rigorously assess the impact of SGLT2 inhibitors in this population would be to conduct multicenter, placebo-controlled prospective trials focusing on mortality and heart failure hospitalisations,” they added.
According to Marshall and Daniels, “the congenital heart disease community appears to have embraced the use of SGLT2 inhibitors in patients with systemic right ventricular systolic dysfunction and should continue doing so while steadily expanding the evidence base.”
(JAHA)
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