The potential of sodium-glucose cotransporter 2 inhibitors for the treatment of systemic right ventricular failure in adults with congenital heart disease.

Aims: Given the compelling evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the conventional heart failure population, SGLT2i deserve exploration in systemic right ventricular (sRV) failure. The initial experience with dapagliflozin in sRV failure patients is described, with a focus on tolerability and short-term effects on clinical outcomes.
Methods and Results: Ten patients (70% female, median age 50 years [46.5-52]) with symptomatic sRV failure who received dapagliflozin 10 mg per day on top of optimal medical therapy between 04-2021 and 01-2023 were included. Within 4 weeks, no significant changes in blood pressure, electrolytes, or serum glucose occurred. Creatinine and estimated glomerular filtration rate (eGFR) showed a slight decline (88 ± 17 to 97 ± 23 µmol/L, p  = 0.036, and 72 ± 14 vs. 66 ± 16 ml/min/1.73m ² , p  = 0.020, respectively). At 6 months follow-up ( n  = 8), median NT-proBNP decreased significantly from 736.6 [589.3-1193.3] to 531.6 [400.8-1018] ng/L ( p  = 0.012). Creatinine and eGFR recovered to baseline levels. There were no significant changes in echocardiographic systolic sRV or left ventricular function. New York Heart Association class improved significantly in 4 out of 8 patients ( p  = 0.046), who also showed an improvement in the 6-minute walk test or bicycle exercise test performance. One female patient developed an uncomplicated urinary tract infection. No patients discontinued treatment.
Conclusion: Dapagliflozin was well-tolerated in this small cohort of sRV failure patients. While the early results on the reduction of NT-proBNP and clinical outcome parameters are encouraging, large-scale prospective studies are warranted to thoroughly evaluate the effects of SGLT2i in the growing sRV failure population.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(© 2023 Neijenhuis, Nederend, Jongbloed, Kiès, Rotmans, Vliegen, Jukema and Egorova.)