Effects of ranolazine on right ventricular function, fluid dynamics, and metabolism in patients with precapillary pulmonary hypertension: insights from a longitudinal, randomized, double-blinded, placebo controlled, multicenter study

Q Joyce Han; Paul Forfia; Anjali Vaidya; Gautam Ramani; Robert A deKemp; Robert H Mach; David A Mankoff; Paco E Bravo; Marcelo DiCarli; Stephen Y Chan; Aaron B Waxman; Yuchi Han

doi:10.3389/fcvm.2023.1118796

Effects of ranolazine on right ventricular function, fluid dynamics, and metabolism in patients with precapillary pulmonary hypertension: insights from a longitudinal, randomized, double-blinded, placebo controlled, multicenter study

Front Cardiovasc Med. 2023 Jun 13:10:1118796. doi: 10.3389/fcvm.2023.1118796. eCollection 2023.

Authors

Q Joyce Han¹, Paul Forfia², Anjali Vaidya², Gautam Ramani³, Robert A deKemp⁴, Robert H Mach⁵, David A Mankoff⁵, Paco E Bravo^{5

6}, Marcelo DiCarli⁷, Stephen Y Chan⁸, Aaron B Waxman⁹, Yuchi Han^{6

10}

Affiliations

¹ Cardiovascular Division, Massachusetts General Hospital, Boston, MA, United States.
² Pulmonary Hypertension, Right Heart Failure, and CTEPH Program, Department of Cardiology, Temple University Hospital, Philadelphia, PA, United States.
³ Cardiovascular Division, University of Maryland, Baltimore, MD, United States.
⁴ Cardiac PET Center, University of Ottawa Heart Institute, Ottawa, ON, Canada.
⁵ Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States.
⁶ Cardiovascular Division, University of Pennsylvania, Philadelphia, PA, United States.
⁷ Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, United States.
⁸ Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
⁹ Center for Pulmonary Heart Disease, Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, United States.
¹⁰ Cardiovascular Division, Wexner Medical Center, The Ohio State University, Columbus, OH, United States.

Abstract

Introduction: Right ventricular (RV) function is a major determinant of outcome in patients with precapillary pulmonary hypertension (PH). We studied the effect of ranolazine on RV function over 6 months using multi-modality imaging and biochemical markers in patients with precapillary PH (groups I, III, and IV) and RV dysfunction [CMR imaging ejection fraction (EF) < 45%] in a longitudinal, randomized, double-blinded, placebo-controlled, multicenter study of ranolazine treatment.

Methods: Enrolled patients were assessed using cardiac magnetic resonance (CMR) imaging, ¹¹C-acetate and ¹⁸-F-FDG positron emission tomography (PET), and plasma metabolomic profiling, at baseline and at the end of treatment.

Results: Twenty-two patients were enrolled, and 15 patients completed all follow-up studies with 9 in the ranolazine arm and 6 in the placebo arm. RVEF and RV/Left ventricle (LV) mean glucose uptake were significantly improved after 6 months of treatment in the ranolazine arm. Metabolomic changes in aromatic amino acid metabolism, redox homeostasis, and bile acid metabolism were observed after ranolazine treatment, and several changes significantly correlated with changes in PET and CMR-derived fluid dynamic measurements.

Discussion: Ranolazine may improve RV function by altering RV metabolism in patients with precapillary PH. Larger studies are needed to confirm the beneficial effects of ranolazine.

Keywords: 4D flow MRI; cardiac magnetic resonance imaging; metabolism; positron emission tomography; pulmonary hypertension.

Abstract

Grants and funding