The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.
(459)| Volume 41, ISSUE 4, SUPPLEMENT , S200, April 2022

Management of Pulmonary Hypertension Secondary to Valvular Heart Disease with Angiotensin-Receptor Neprilysin Inhibitor


      Pulmonary hypertension secondary to left-sided valvular disease (VHD-PH) is associated with high morbidity and mortality. Angiotensin-receptor neprilysin inhibitor (ARNI) is a novel pharmacotherapy, which reduces afterload with natriuresis and peripheral vasodilation. Whether ARNI can also reduce pulmonary vasculature resistance is unknown. We present two cases of VHD-PH that improved after treatment with ARNI.

      Case Report

      Case 1: Ms. M is a 63-year-old woman with past medical history of rheumatic mitral valve (MV) stenosis (mean gradient = 12 mm Hg at a heart rate = 69 beats/minute) who presented with New York Heart Association (NYHA) Class IIIB symptoms. The initial workup showed normal left ventricular function (LV) but severe combined pre- and post-capillary PH (Cpc-PH). She was deemed to be a high-risk surgical candidate given the severity of PH. Subsequently, she was treated with ARNI for three months, and repeat right heart catheterization showed significant improvement in Cpc-PH (see Table). Case 2: Mr. S is a 59-year-old man with past medical history of MV endocarditis s/p remote bovine MV replacement in 1984 complicated by paravalvular leak and redo replacements who presented with worsening shortness of breath. The workup demonstrated a well-functioning MV prosthesis and normal LV function, but elevated filling pressures. After two months of diuresis, Mr. S continued to have NYHA Class IIIB symptoms with persistent Cpc-PH. He was subsequently started on ARNI, and two months later had complete resolution of his symptoms. Repeat evaluation showed normalization of pulmonary vascular resistance (PVR, see Table).


      This report is the first to describe treatment of VHD-PH with ARNI along with invasive hemodynamic data showing successful reduction in PVR. In these two cases, treatment with ARNI led to reduction in not only mean pulmonary arterial pressures but also PVR. Future prospective trials are needed to evaluate role of ARNIs in treatment of VHD-PH.
      Tabled 1
      Right heart catheterization (RHC) results before and after ARNI initiation and up-titration
      Case 1RHC initial conditionsRHC after ARNI
      Mean mitral valve gradient12 mm Hg4 mm Hg
      Right atrial pressure7 mm Hg5 mm Hg
      Pulmonary arterial pressure117/33 (66) mm Hg65/32 (46) mm Hg
      Pulmonary capillary wedge pressure25 mm Hgg21 mm Hg
      Transpulmonary gradient41 mm Hg25 mm Hg
      Diastolic pulmonary gradient8 mm Hg11 mm Hg
      Pulmonary vascular resistance11.4 woods units6.1 woods units
      Cardiac output, cardiac index3.6 L/min, 1.8 L/min/m24.1 L/min, 2.0 L/min/m2
      Case 2RHC initial conditionsRHC after diuresisRHC after ARNI
      Right atrial pressure19 mm Hg9 mm Hg10 mm Hg
      Pulmonary arterial pressure112/44 (67) mm Hg77/31 (46) mm Hg49/21 (24) mm Hg
      Pulmonary capillary wedge pressure30 mm Hg20 mm Hg17 mm Hg
      Transpulmonary gradient37 mm Hg26 mm Hg7 mm Hg
      Diastolic pulmonary gradient14 mm Hg11 mm Hg4 mm Hg
      Pulmonary vascular resistance6.7 woods units4.3 woods units1.1 woods units
      Cardiac output, cardiac index6.2 L/min, 2.8 L/min/m26.1 L/min, 2.8 L/min/m26.5 L/min, 3.0 L/min/m2