Pilot Study of Endothelin Receptor Blockade in Heart Failure with Diastolic Dysfunction and Pulmonary Hypertension (BADDHY-Trial).
BACKGROUND
In this multi-centre, randomised, placebo-controlled pilot trial, we investigated the clinical and haemodynamic effects of the endothelin-receptor blocker Bosentan in patients with heart failure, preserved ejection fraction and pulmonary hypertension (PH-HFpEF).


METHODS
Eligible patients received either 12 weeks of Bosentan therapy, or a placebo drug. Patients were thereafter followed for a further period of 12 weeks without the study medication. At three points during the study (study Commencement, Week 12 and Week 24), a six-minute walk test (6MWT), echocardiographic and laboratory assessments were performed, as well as a quality of life survey. Right heart catheterisation (RHC) was undertaken at commencement only. The study was aborted early, after an interim analysis favoured the placebo.


RESULTS
Six-minute walk distance (6MWD) did not change in the Bosentan group (309.7±96.3m (Commencement), 317.0±126.1m (Week 12), 307.0±84.4m (Week 24); p=0.86), but almost reached statistical significance in the placebo group from 328.8±79.6m, to 361.6±98.2m and 384.0±74.9m (Week 24); p=0.075. In the placebo group, estimated systolic pulmonary artery pressure (measured via echocardiography) significantly decreased (from 62.3±16.7mmHg [Commencement], 45.3±13.9mmHg [Week 12], to 44.6±14.5mmHg [Week 24]; p=0.014) as did right atrial pressure (13.1±5.3 [Commencement], 10.0±3.8 [Week 12], to 9.4±3.2 [Week 24]; p=0.046).


CONCLUSIONS
Despite this study's limited sample size and premature cessation, it nevertheless suggests that endothelin receptor blockade in patients with PH-HFpEF may have no beneficial effects and could even be detrimental in comparison to a placebo.
University Teaching Hospital Hall in Tyrol, Department for Internal Medicine, Hall in Tyrol, Austria.
B
B
Koller
Convent Hospital Elisabethinen, Linz, Internal Department II- Cardiology, Angiology, Internal Intensive Medicine, Linz, Austria.
R
R
Steringer-Mascherbauer
Convent Hospital Elisabethinen, Linz, Internal Department II- Cardiology, Angiology, Internal Intensive Medicine, Linz, Austria.
C H
CH
Ebner
Community Hospital Wels-Grieskirchen, Internal Department II - Cardiology and Intensive Care Medicine, Wels, Austria.
Th
T
Weber
Community Hospital Wels-Grieskirchen, Internal Department II - Cardiology and Intensive Care Medicine, Wels, Austria.
M
M
Ammer
University Hospital Salzburg, Internal Department II - Cardiology and Intensive Care Medicine, Salzburg, Austria.
J
J
Eichinger
University Hospital Salzburg, Internal Department II - Cardiology and Intensive Care Medicine, Salzburg, Austria.
I
I
Pretsch
Medical University Innsbruck, Department for Internal Medicine VI, Innsbruck, Austria.
M
M
Herold
University Teaching Hospital Hall in Tyrol, Department for Internal Medicine, Hall in Tyrol, Austria.
J
J
Schwaiger
Medical University Innsbruck, Department for Medical Statistics, Informatics and Health Economics, Innsbruck, Austria.
H
H
Ulmer
University Teaching Hospital Hall in Tyrol, Department for Internal Medicine, Hall in Tyrol, Austria. Electronic address: wilhelm.grander@tirol-kliniken.at.
W
W
Grander
D000368:Aged; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D054144:Heart Failure, Diastolic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects
D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan
6minute walk test; Endothelin receptor blockade; Heart failure preserved ejection fraction; Pulmonary hypertension