Impact of Sodium‐Glucose Co‐Transporter‐2 Inhibitors on Exercise‐Induced Pulmonary Hypertension

ABSTRACT Patients with borderline pulmonary hypertension (PH) often experience shortness of breath or exacerbation of PH during exercise, known as exercise‐induced PH. However, the pathogenesis of exercise‐induced post‐capillary PH (post‐EIPH) and its treatment strategies remain unclear. Recent guidelines and consensus documents have highlighted the benefits of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors in heart failure and chronic kidney disease (CKD). This study aimed to investigate the effects of SGLT2 inhibitors in patients with post‐EIPH and CKD. This single‐center prospective cohort study enroled 10 patients with CKD (age, 68 years; female, 60%) who exhibited post‐EIPH between 1 July 2022 and 31 December 2023. Post‐EIPH was defined as a pulmonary capillary wedge pressure (PCWP)/cardiac output (CO) slope > 2 and peak PCWP during exercise ≥ 25 mmHg measured by catheterization. The patients received SGLT2 inhibitor treatment for 6 months. At rest, patients with post‐EIPH had borderline‐PH (21.5 ± 1.8 mmHg), with preserved left and right ventricular function. SGLT2 inhibitors treatment significantly reduced the PCWP/CO slope during exercise (3.9 ± 1.2 vs. 2.4 ± 1.2 mmHg/L/min, p = 0.013) and improved the 6‐min walking distance (489.9 ± 80.2 vs. 568.3 ± 91.9 m, p = 0.014). Magnetic resonance imaging revealed a lower left ventricular global longitudinal strain in patients with post‐EIPH, which was increased by SGLT2 inhibitor treatment (−13.8 ± 2.0 vs. −17.3 ± 2.0%, p = 0.003). SGLT2 treatment inhibitors mitigated post‐EIPH hemodynamic abnormalities and exercise intolerance, suggesting their potential as its therapeutic option.