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

Carmine Dario Vizza, Irene M. Lang, Roberto Badagliacca, Raymond L. Benza, Stephan Rosenkranz, R. James White, Yochai Adir, Arne K. Andreassen, Vijay Balasubramanian, Sonja Bartolome, Isabel Blanco, Robert C. Bourge, Jørn Carlsen, Rafael Enrique Conde Camacho, Michele D'Alto, Harrison W. Farber, Robert P. Frantz, H. James Ford, Stefano Ghio, Mardi Gomberg-MaitlanMarc Humbert, Robert Naeije, Stylianos E. Orfanos, Ronald J. Oudiz, Sergio V. Perrone, Oksana A. Shlobin, Marc A. Simon, Olivier Sitbon, Fernando Torres, Jean Luc Vachiery, Kuo Yang Wang, Magdi H. Yacoub, Yan Liu, Gil Golden, Hiromi Matsubara

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 selfperpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved longterm 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.

Original languageEnglish (US)
Pages (from-to)751-760
Number of pages10
JournalAmerican journal of respiratory and critical care medicine
Volume205
Issue number7
DOIs
StatePublished - Apr 1 2022

Keywords

  • Combination therapy
  • prostacyclin
  • pulmonary arterial hypertension
  • pulmonary arterial pressure
  • right ventricular afterload

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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