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

Can Respir J. 2018 Mar 26:2018:3148259. doi: 10.1155/2018/3148259. eCollection 2018.

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.

Publication types

  • Clinical Study

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / therapeutic use
  • Aged
  • Aged, 80 and over
  • Echocardiography
  • Female
  • Heart / diagnostic imaging
  • Heart / drug effects
  • Heart Failure / complications*
  • Heart Function Tests
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / etiology
  • Male
  • Middle Aged
  • Prospective Studies
  • Protein Kinase Inhibitors / therapeutic use*

Substances

  • Protein Kinase Inhibitors
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • fasudil