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

• Published in: Frontiers in cardiovascular medicine 2023-06, Vol.10, p.1093201-1093201
• Main Authors: Neijenhuis, Ralph M L, Nederend, Marieke, Jongbloed, Monique R M, Kiès, Philippine, Rotmans, Joris I, Vliegen, Hubert W, Jukema, J Wouter, Egorova, Anastasia D
• Format: Article
• Language: English
• Subjects: adult congenital heart disease (ACHD); Cardiovascular Medicine; congenital heart disease; heart failure; sodium glucose co-transport-2 (SGLT2) inhibitors; systemic right ventricle; transposition of the great arteries (TGA)
• ISSN: 2297-055X; 2297-055X
• DOI: 10.3389/fcvm.2023.1093201

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. 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,  = 0.036, and 72 ± 14 vs. 66 ± 16 ml/min/1.73m ,  = 0.020, respectively). At 6 months follow-up (  = 8), median NT-proBNP decreased significantly from 736.6 [589.3-1193.3] to 531.6 [400.8-1018] ng/L (  = 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 (  = 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. 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.