Initial experience with bosentan therapy in patients considered ineligible for heart transplantation because of severe pulmonary hypertension.
BACKGROUND
Pre-operative elevated pulmonary vascular resistance (PVR) has been associated with increased right ventricular failure and mortality after heart transplantation. The aim of this study was to assess the efficacy of bosentan, an oral endothelin-receptor antagonist, to reduce PVR in patients considered ineligible for heart transplantation because of severe pulmonary hypertension.


METHODS
Seven patients with end-stage congestive heart failure and considered ineligible for heart transplantation because of severe pulmonary hypertension (PVR>2.5 Wood units after nitroprusside infusion) were included in the study. They received bosentan 62.5 mg b.i.d. for four wk and 125 mg b.i.d. thereafter. Right heart catheterization was repeated after six wk of therapy.


RESULTS
After six wk of bosentan therapy, there was a significant decrease in PVR (6.0 +/- 2 vs. 3.8 +/- 2 Wood units, before vs. after bosentan; p = 0.02), in PVR during nitroprusside infusion (3.3 +/- 1 vs. 2.1 +/- 1 Wood units, before vs. after bosentan; p = 0.02) and in diastolic pulmonary artery pressure (33 +/- 7 vs. 23 +/- 7 mmHg, before vs. after bosentan; p = 0.04). No significant adverse events were observed. After bosentan therapy, five patients had PVR<or=2.5 Wood units. They were included in the waiting list and all five had a successful heart transplantation, although two of them required bosentan after surgery.


CONCLUSIONS
In patients considered ineligible for heart transplantation because of high PVR, bosentan therapy significantly reduced PVR. These data suggest that therapy with endothelin-receptor blockers might be useful to identify a subgroup of patients with high PVR who can benefit from heart transplantation.
Perez-Villa
Felix
F
Heart Failure and Heart Transplantation Program, Hospital Clinic, IDIBAPS, Barcelona, Spain. fperez@clinic.ub.es
Cuppoletti
Alfredo
A
Rossel
Victor
V
Vallejos
Isabel
I
Roig
Eulalia
E
D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000077300:Bosentan; D006333:Heart Failure / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D006334:Heart Function Tests; D016027:Heart Transplantation / Q000706:statistics & numerical data; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000209:etiology*; D019808:Losartan / Q000627:therapeutic use*; D018579:Patient Selection; D012449:Safety; D013449:Sulfonamides / Q000627:therapeutic use; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D013449:Sulfonamides; D019808:Losartan; D000077300:Bosentan