Effects of Fasudil on Patients with Pulmonary Hypertension Associated with Left Ventricular Heart Failure with Preserved Ejection Fraction: A Prospective Intervention Study

Abstract

Background Pulmonary hypertension due to left ventricular heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly medical problem. The aim of the study was to evaluate the clinical efficacy of fasudil on PH-HFpEF elderly patients and to figure out the subtype of PH-HFpEF which may be the therapeutic object of fasudil. Method 58 PH-HFpEF elderly patients were enrolled. Patients were diagnosed with passive pulmonary hypertension (PPH) or reactive pulmonary hypertension (RPH) by right heart catheterization and all receiving Rho kinase inhibitor fasudil for 2 weeks. The endpoint includes changes in SpO2, NT-pro BNP, cardiac functional classification, and echocardiography measurements after 2 weeks treatment. Results The course of disease in the RPH group was longer than the PPH group (p < 0.05). Cardiac output was found to be worse in the RPH group than the PPH group (p < 0.01). Besides, the RPH group demonstrated a greater transpulmonary pressure gradient (TPG) and pulmonary vascular resistance (PVR) than the PPH group (p < 0.01 for both) as well as pulmonary arterial systolic pressure (PASP) and mean pulmonary arterial pressure (mPAP) (p < 0.01 for both), which fits the feature of RPH. After treatment of fasudil, in RPH group, PASP significantly decreased (p < 0.01) with decreased E/E′ and increased E/A (p < 0.05 for both), indicating that pulmonary haemodynamics and cardiac diastolic function were ameliorated, but the measurements in the PPH group had no significant changes. NT-pro BNP and 6 MWD of both groups were improved (p < 0.05). The total effective rate of the RPH group was 74.29%, which was higher than 47.83% of the PPH group (p < 0.05). Conclusion The Rho kinase inhibitor fasudil can improve pulmonary and left ventricular haemodynamics in patients with PH-HFpEF. The total effective rate was higher in the RPH group. Fasudil may be a promising targeted drug for the RPH in PH-HFpEF patients. This trial is registered with ChiCTR-INR-16009511.

Histologic and Proteomic Remodeling of the Pulmonary Veins and Arteries in a Porcine Model of Chronic Pulmonary Venous Hypertension

“…30 Opportunities and barriers to development of other methods to oppose EndoMT in cardiovascular disease have been well described. 19 Rho-kinase inhibitors have already been tested and showed benefits in human and experimental Group 2 PH 33, 58 and the current data provide further support for this strategy. Novel strategies to enhance caveolin in animal models of PH had dramatic beneficial effects and caveolin deficiency was clear in PV here.…”

Inhibition of Rho-associated kinases suppresses cardiac myofibroblast function in engineered connective and heart muscle tissues

“…Moreover, deletion of ROCK2 from cardiac myofibroblasts in mice reduced the diastolic dysfunction after chronic Ang II treatment [10]. Finally, in two clinical studies Fasudil was shown to improve diastolic dysfunction in patients with Diabetes type 2 and in patients with reactive pulmonary hypertension both associated with left ventricular impairment, but with preserved ejection fraction [59,60]. Fig.…”

Reverse Remodeling in Human Heart Failure after Cardiac Resynchronization Therapy Is Associated With Reduced RHO-Kinase Activation

“…In a previous study, the ROCK inhibitor fasudil was administered for two weeks to patients with HF with preserved ejection fraction (HFpEF) and passive pulmonary hypertension. That study showed that fasudil improved pulmonary and left ventricular hemodynamics, suggesting that ROCK inhibition may be a promising target for HFpEF patients with a pulmonary hypertension phenotype (Zhang et al, 2018).…”