Efficacy and safety of SGLT2 inhibitors in patients with adult congenital heart disease and a systemic right ventricle: a retrospective, observational study

BACKGROUND: Among the adults with congenital heart disease (ACHD) population, patients with a systemic right ventricle (sRV), are at an increased risk of heart failure (HF). Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have demonstrated a significant reduction in the risk of worsening heart failure and death from cardiovascular causes in patients with chronic heart failure with reduced left ventricular ejection fraction. However, data on their efficacy and safety in patients with sRV are scarce. 

METHODS: In a retrospective observational study, we aimed to assess the efficacy and safety of SGLT2 inhibitors in ACHD patients with an sRV. Right heart dimensions and function were analysed using transthoracic echocardiography [TTE] (tricuspid annular plane systolic excursion [TAPSE], fractional area change [FAC], right ventricular end diastolic diameter [RVEDD]) and magnetic resonance imaging [MRI] (right ventricular ejection fraction [RVEF], right ventricular end-diastolic volume index [RVEDVi] and right ventricular end-systolic volume index [RVESVi]). Clinical parameters such as NTproBNP levels, the New York Heart Association functional class [NYHA-FC], 6-minute walking distance [6-MWD] and the exercise capacity as measured by the peak oxygen consumption (peak VO2) value were assessed at baseline and after follow-up period of six months. 

RESULTS: A total of 11 patients with sRV (10 with dTGA after atrial switch operation [Senning or Mustard procedure] and 1 with ccTGA) were included in the study. The mean age was 46.0 ± 7.6 years (64 % female). The majority of patients were already receiving stable background therapy for heart failure. Baseline evaluation revealed a dilated sRV (RVEDD 57.3 ± 6.4 mm, RVEDVi 118.8 ± 22.7 ml/m², RVESVi 67.8 ± 5.1ml/m²) with a reduced systolic function (FAC 25.1 ± 4.3%, TAPSE 13.0 ± 4.2 mm, RVEF 41.5 ± 9.2%). NTproBNP levels were increased (380.8 ± 277.9 ng/L) and 6-MWD (515.6 ± 68.1 m), NYHA-FC (1.3 ± 0.5) and peak VO2 (26.4 ± 12.0 ml/min/kg) were reduced. After a follow-up of six months, we observed significant improvements in right heart dimensions measured by MRI (RVESVi 65.4 ± 5.5 ml/m²; p=0.042) and NTproBNP levels (277.4 ± 146.5 ng/l; p=0.025). There was a tendency towards improvement in RVEF measured by MRI (44.0 ± 6.3 %, p = 0.066), whereas all other clinical and morphological parameters showed no significant difference. There were no side effects associated with SGLT2 inhibitor intake during the observation period. 

CONCLUSIONS: In this retrospective observational study, SGLT2 inhibitors demonstrated beneficial effects and a good safety profile in ACHD patients with sRV and heart failure. 

Table 1 - Baseline characteristics. Abbreviations: dTGA, dextro-transposition of the great arteries; ccTGA, congenital corrected transposition of the great arteries; ARNI, angiotensin receptor/neprilysin inhibitor; ACE, Angiotensin-converting enzyme; ARB, angiotensin receptor blocker; SGLT2-Inhibitor, Sodium-glucose cotransporter 2 inhibitors