Abstract 13710: Acute Beneficial Effects of a Rho-Kinase Inhibitor, Fasudil in Patients With Pulmonary Hypertension Due to Left Heart Disease

Abstract

Introduction: The prognosis of reactive pulmonary hypertension (PH) due to left heart disease is poor, and the pathogenesis of the disease is not well understood. Rho-Kinase inhibitor, fasudil dilates vascular smooth muscle and may improve pulmonary hypertension. We evaluated the acute effects of fasudil on hemodynamic parameters in patients with pulmonary hypertension due to left heart disease prospectively. Methods: From 2016 June to 2022 May, 100 consecutive patients requiring hospitalization for worsening chronic heart failure were enrolled. All patients underwent invasive hemodynamic measurement though right heart catheterization.In patients with mean pulmonary arterial pressure greater than 25 mmHg at baseline, 30 mg of fasudil was administered intravenously for 30 minutes. The hemodynamic measurements were performed at baseline and after 30 minutes of fasudil. PH due to left heart disease is defined as mean pulmonary arterial pressure (mPAP) ≥25mmHg and mean pulmonary capillary wedge pressure (mPCWP) >15mmHg. Patients with PH were classified into 2 types, depending on the elevation of pulmonary vascular resistance (PVR) or the diastolic pressure gradient (DPG): Reactive-PH with elevated PVR (>3.0 Wood units: WU) and/or DPG (>7mmHg), and Passive-PH with normal PVR (≤3.0 WU) and DPG (≤7mmHg). Results: Fifty patients (mean age 70 years; 14 women and 36 men) received administration of fasudil. 30 patients had Passive-PH, and 20 patients had Reactive-PH. PVR significantly decreased after administration of fasudil in both Passive-PH and Reactive-PH group (1.7 to 1.4 WU, 3.5 to 2.7 WU, P<0.001). The rate of change in PVR after administration of fasudil was significantly higher in the Reactive-PH group compared to the Passive-PH group (33% vs 21 %, P<0.05). mPAP and cardiac index significantly improved in both Passive-PH (34±8.5 vs. 28±8.2 mmHg, 2.7±0.7 vs. 2.9±0.8 l/min/m 2 , p<0.05) and Reactive-PH group (41±7.9 vs. 33±9.0 mmHg, 2.2±0.6 vs. 2.4±0.6 l/min/m 2 , p<0.05). Mean blood pressure and arterial oxygen saturation were unaffected by fasudil (87 to 84 mmHg, 99 to 90 mmHg, 98 to 97%, 97 to 97%, not significant). Conclusions: Fasudil improves pulmonary hypertension due to left heart disease without any detrimental effects on hemodynamics.