Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

Carmine Dario Vizza, Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, Università di Roma La Sapienza, Rome, Italy.
Irene M. Lang, Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Roberto Badagliacca, Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, Università di Roma La Sapienza, Rome, Italy.
Raymond L. Benza, Division of Cardiovascular Diseases, The Ohio State University, Columbus, Ohio.
Stephan Rosenkranz, Department of Cardiology, Clinic III for Internal Medicine, Cologne, Germany.
R James White, Department of Pulmonary and Critical Care Medicine, University of Rochester, Rochester, New York.
Yochai Adir, Pulmonary Division, Carmel Medical Center, Haifa, Israel.
Arne K. Andreassen, Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Vijay Balasubramanian, Division of Pulmonary and Critical Care, Department of Medicine, University of California San Francisco Fresno, Fresno, California.
Sonja Bartolome, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Isabel Blanco, Department of Pulmonary Medicine, The August Pi i Sunyer Biomedical Research Institute, University of Barcelona, Barcelona, Spain.
Robert C. Bourge, Department of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama.
Jørn Carlsen, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Rafael Enrique Camacho, Critical Medicine and Intensive Care, Pulmonology, Vascular Pulmonary Center, Pulmonology Foundation of Colombia, University Clinic Colombia, Bogota, Colombia.
Michele D'Alto, Department of Cardiology, University "L. Vanvitelli," Monaldi Hospital, Naples, Italy.
Harrison W. Farber, Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts.
Robert P. Frantz, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.
H James Ford, Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Stefano Ghio, Division of Cardiology, San Matteo Hospital, Scientific Institute for Research, Hospitalization, and Healthcare, Pavia, Italy.
Mardi Gomberg-Maitland, Department of Cardiology, School of Medicine & Health Sciences, George Washington University, Washington, D.C.
Marc Humbert, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtr, France.
Robert Naeije, Department of Cardiology, Erasme University Hospital, Brussels, Belgium.
Stylianos E. Orfanos, 1st Department of Critical Care, National and Kapodistrian University of Athens Medical School, Athens, Greece.
Ronald J. Oudiz, Division of Cardiology, Lundquist Institute for Biomedical Research at Harbor-University of California Los Angeles Medical Center, Torrance, California.
Sergio V. Perrone, Departamento Cardiologia, Instituto Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Buenos Aires, Argentina.
Oksana A. Shlobin, Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia.
Marc A. Simon, Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California.
Olivier Sitbon, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtr, France.
Fernando Torres, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Jean Luc Vachiery, Pulmonary Vascular Diseases and Heart Failure Clinic, Department of Cardiology, Cliniques Universitaires de Bruxelles-Hôpital Erasme, Brussels, Belgium.
Kuo-Yang Wang, Center for Pulmonary Hypertension and Pulmonary Vascular Disease, China University Hospital, Taichung, Taiwan.
Magdi H. Yacoub, National Heart and Lung Institute, Heart Science Centre, Harefield Hospital, London, United Kingdom.

Document Type

Journal Article

Publication Date

4-1-2022

Journal

American journal of respiratory and critical care medicine

Volume

205

Issue

7

DOI

10.1164/rccm.202109-2079PP

Keywords

combination therapy; prostacyclin; pulmonary arterial hypertension; pulmonary arterial pressure; right ventricular afterload

Abstract

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

Department

Medicine

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