Endothelin receptor antagonists improve exercise tolerance and oxygen saturations in patients with Eisenmenger syndrome and congenital heart defects

Tex Heart Inst J. 2008;35(3):256-61.

Abstract

Patients with Eisenmenger syndrome experience substantial morbidity and decreased survival rates. In advanced cases, lung transplantation with cardiac repair or heart-lung transplantation is often the only option. The efficacy of endothelin receptor antagonists in Eisenmenger syndrome, which has similar pathophysiology to idiopathic pulmonary hypertension, remains unknown.We retrospectively studied adults with congenital heart disease and Eisenmenger syndrome who were treated with endothelin receptor antagonists. Analysis included chart reviews of clinical evaluations, oxygen saturation levels, functional class, 6-minute walk distances, and pulmonary artery pressures. In the 24 patients studied, Eisenmenger syndrome was caused by ventricular septal defect (6 patients), atrial septal defect (5), atrioventricular canal defect (3), complex congenital heart disease (9), and patent ductus arteriosus (1).Eisenmenger syndrome was treated with bosentan (21 patients) and sitaxsentan (3 patients). On average, therapy lasted 19 +/- 12 months. Subsequently, mean 6-minute walk distances improved from 226 +/- 159 m to 351 +/- 113 m (P = 0.004), and World Health Organization functional class improved > or =1 grade (P < 0.0001). Oxygen saturations increased on therapy from 80.5% to 87% (P < 0.0001). Pulmonary arterial systolic pressures decreased from 97 +/- 21 mmHg to 78 +/- 27 mmHg, and mean pressures from 59 +/- 16 mmHg to 47 +/- 17 mmHg (both P < 0.0001). Neither major complications from therapy nor changes in pulmonary capillary wedge pressure occurred.Endothelin receptor antagonists may play an important role in improving 6-minute walk distance, oxygen saturation, pulmonary artery pressures, and symptoms in adults who have congenital heart defects and Eisenmenger syndrome.

Keywords: Antihypertensive agents/administration & dosage/therapeutic use; Eisenmenger complex/complications/drug therapy/mortality/physiopathology; bosentan; endothelin-1/antagonists & inhibitors; exercise tolerance/drug effects; heart defects/congenital; hypertension, pulmonary/classification/complications/drug therapy/physiopathology; oximetry; patient selection; receptors, endothelin/antagonists & inhibitors/physiology; treatment outcome.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Adult
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Bosentan
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Eisenmenger Complex / drug therapy*
  • Endothelin A Receptor Antagonists*
  • Endothelin B Receptor Antagonists*
  • Exercise Test / drug effects*
  • Female
  • Heart Defects, Congenital / drug therapy*
  • Humans
  • Isoxazoles / adverse effects
  • Isoxazoles / therapeutic use*
  • Male
  • Middle Aged
  • Oxygen / blood*
  • Retrospective Studies
  • Sulfonamides / therapeutic use*
  • Thiophenes / adverse effects
  • Thiophenes / therapeutic use*

Substances

  • Antihypertensive Agents
  • Endothelin A Receptor Antagonists
  • Endothelin B Receptor Antagonists
  • Isoxazoles
  • Sulfonamides
  • Thiophenes
  • sitaxsentan
  • Bosentan
  • Oxygen