Sodium-glucose cotransporter-2 inhibitors in patients with pulmonary arterial hypertension and heart failure with preserved ejection fraction as cardiovascular comorbidity.

INTRODUCTION: The clinical phenotype of pulmonary arterial hypertension (PAH) has shifted increasingly towards older patients with more cardiovascular comorbidities. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are used to treat symptomatic chronic heart failure. This study aimed to evaluate the impact of add-on SGLT2i in PAH patients with heart failure with preserved ejection fraction (HFpEF) as comorbidity. METHODS: PAH patients on stable therapy receiving SGLT2i as add-on were included in this single-center, retrospective cohort study. The primary endpoint comprised the change in echocardiographic right atrial (RA) area and right ventricular (RV) function after treatment with SGLT2i. Further clinical and echocardiographic parameters were analyzed. RESULTS: In total 198 patients on stable PAH therapy for at least three months receiving SGLT2i treatment and available follow-up assessments were analyzed (74±28 years, 61% female; 83.9% WHO functional class III-IV). During SGLT2i treatment, a significant reduction in RA area -1.93 ± 4.45 cm² (p<0.001) and improvement in RV function (p<0.001) during the mean follow-up of 6.7±3.3 months could be detected. RV area (-1.69±4.83 cm²), left atrial diameter (-2.17±4.43 mm) and systolic pulmonary arterial pressure (-9.26±16.10 mmHg) decreased significantly (all p<0.001). The mean 6-minute walking distance increased by 51.68±58.5 meters (p<0.001) and risk stratification significantly improved. Five patients discontinued the medication due to side effects. CONCLUSION: In patients with PAH and HFpEF as comorbidity SGLT2i as add-on to targeted therapy significantly improved right heart size and function, as well as further clinical parameters and was well tolerated. Further prospective studies are necessary to confirm these results.