Safety and Efficacy of Dapagliflozin in Patients With Systemic Right Ventricular Dysfunction: DAPA-SRV Trial

Abstract

Background: Heart failure is the leading cause of death in adults with a systemic right ventricle (sRV). While dapagliflozin has proven benefits in patients with acquired heart diseases and heart failure with reduced ejection fraction, its impact remains unknown in patients with an sRV. We aimed to evaluate the safety and efficacy of dapagliflozin in this population.

Methods: We conducted a prospective, observational, single-center study including symptomatic patients (New York Health Association [NYHA] functional class ≥2) with sRV dysfunction despite medical treatment, enrolled from February 2023 to February 2024. Patients were assessed at baseline and 3 and 6 months after dapagliflozin introduction. The primary end point was 6-Minute Walk Distance (6MWD). Secondary end points included N-terminal pro-B-type natriuretic peptide, quality of life (according to the Kansas City Cardiomyopathy Questionnaire-12-item version [KCCQ-12]), NYHA class, systemic and subpulmonary ventricular systolic function, and treatment-related side effects.

Results: A total of 32 patients were included. The mean age of the participants was 48 years (range, 19-79 years), 20 (62%) patients were men, 12 (38%) had congenitally corrected transposition of the great arteries, and 20 (62%) had transposition of the great arteries with atrial switch. At 6 months, 6MWD significantly improved (585 m versus 558 m, P=0.04). Quality of life (91.5 versus 80.5, P<0.001), sRV function (fractional area change: 33% versus 28% [P=0.02]; global longitudinal strain: -13.1% versus -11.2% [P=0.04]) also improved. No significant side effects were observed.

Conclusions: This is the first study, to our knowledge, demonstrating the functional benefits and safety of dapagliflozin in symptomatic patients with sRV dysfunction under medical treatment with sacubitril/valsartan. These results support the need for larger randomized trials to further evaluate this therapeutic option in this population.

Keywords: SGLT2 inhibitor; atrial switch; dapagliflozin; systemic right ventricle; transposition of great arteries.

Figure 1. Evolution of baseline functional and biological characteristics at 3 and 6 months.

A, Box plot of baseline 6‐Minute Walk Test evolution at 3 and 6 months. The medians of the 6MWD were as follows: at baseline, 558 m (IQR, 459–614.2 m); at 3 months, 575.5 m (IQR, 479.2–627.8 m); and at 6 months, 585 m (IQR, 495–641.5 m). B, Box plot of baseline NT‐proBNP evolution at 3 and 6 months. The medians of the NT‐proBNP were as follows: at baseline, 355.5 pg/mL (IQR, 195.8–669 pg/mL); at 3 months, 300 pg/mL (IQR, 173.5–540.5 pg/mL); and at 6 months, 283 pg/mL (IQR, 191.5–498 pg/mL). C, Box plot of KCCQ‐12 overall summary scale evolution at 3 and 6 months. The medians of the KCCQ‐12 overall summary scale were as follows: at baseline, 80.5 (IQR, 68.9–90.3); at 3 months, 89.4 (IQR, 76.4–94.4); and at 6 months, 91.5 (IQR, 79.9–97.3). 6MWD indicates 6‐Minute Walk Distance; IQR, interquartile range; KCCQ‐12‚ Kansas City Cardiomyopathy Questionnaire—12‐item version; and NT‐proBNP‚ N‐terminal pro‐B‐type natriuretic peptide.

Figure 2. Summary of the DAPA‐SRV study.

ccTGA indicates congenitally corrected transposition of the great arteries; DAPA‐SRV, Safety and Efficacy of Dapagliflozin in Adult Patients With a Systemic Right Ventricle; and D‐TGA, D‐transposition of the great arteries.