Effect of sodium-glucose cotransporter 2 inhibitors on ventricular function in systemic right ventricular failure

Systemic right ventricle (sRV) patients are at an increased risk of developing heart failure. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) could be a valuable treatment option. This study investigated the changes in ventricular function in sRV failure patients in the first year after starting SGLT2i.

Adult sRV patients from the international, real-world ACHIEVE-SGLT2i registry were included if they had a clinical diagnosis of sRV failure, a transthoracic echocardiogram before starting SGLT2i, and at least one in the first year after starting available for analysis. The primary outcomes were changes in sRV global longitudinal strain (GLS) and fractional area change (FAC). Longitudinal changes were evaluated using linear mixed models.

Thirty-nine sRV failure patients (46±9.3 years old, 41% female) were included. Twenty-five (64%) had transposition of the great arteries after an atrial switch procedure and 14 (36%) had congenitally corrected transposition. sRV GLS improved significantly in the first 50 days (-1.4%-point per month, p<0.001) and stabilised afterwards (<0.1%-point per month, p=0.520). Though age had a significant overall negative effect on sRV GLS (0.1%-point per year of age, p=0.049), it did not influence the longitudinal changes after starting SGLT2i. sRV FAC also improved in the first 50 days (3.2%-point per month, p=0.002), after which sRV FAC deteriorated in patients with subpulmonary left ventricular pacing (-0.9%-point per month, p=0.012) while it stabilised in patients without pacing (0.1%-point per month, p=0.573). In the first 50 days, tricuspid annular plane systolic excursion also improved significantly in all patients (1.2 mm per month, p=0.006), and stabilised afterwards (p=0.721).

SGLT2i therapy is associated with improvements in systolic ventricular function in sRV failure patients. Despite early improvement in sRV FAC, there was a negative longer term correlation with subpulmonary left ventricular pacing, potentially reflecting adverse effects of subpulmonary ventricular pacing on sRV function.