Impact of bosentan on exercise capacity in adults after the Fontan procedure: a randomized controlled trial.
OBJECTIVE
An endothelin-1 receptor blocker, shown to be effective in patients with pulmonary arterial hypertension, might decrease pulmonary vascular resistance to increase cardiac filling and consequently improve exercise capacity in Fontan patients.


RESULTS
This was a prospective, multicentre randomized open label trial in Fontan patients. One group received bosentan for 6 months. The other group did not receive study medication for the first 3 months, followed by bosentan for 6 months. The primary endpoint was exercise capacity, and secondary endpoints were NT-proBNP level, cardiac output, SF-36 (Short Form-36) quality of life (QoL), and NYHA class. Forty-two adults (median age 29 (range 18-56) years, 52% male, 88% NYHA class I-II) from five tertiary referral centres participated in the study. Ten patients were on diuretics. Ten patients were not motivated to finish the study. Analysis of all 32 patients who finished the study at 6 months of treatment showed that mean peak V'O2 (24 vs. 25 mL/kg/min), median SQUASH score (6614 vs. 6390), median NT-proBNP (314 vs. 274 ng/L), and mental QoL (50 vs. 51) remained unchanged as compared with baseline (P = NS, for all). After treatment, NYHA class had improved in 6 (19%), was unchanged in 24 (75%), and declined in 2 (6%) patients. Subgroup analysis on age, ventricular morphology, type of Fontan circulation, or baseline NT-proBNP level did not reveal efficacy of bosentan. Six transient adverse effects were reported.


CONCLUSIONS
An increased NT-proBNP level was present in the majority of Fontan patients. Six months of bosentan treatment was not beneficial. Trial registration NTR1557.
Department of Cardiology, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Mark J
MJ
Schuuring
Jeroen C
JC
Vis
Arie P J
AP
van Dijk
Joost P
JP
van Melle
Hubert W
HW
Vliegen
Petronella G
PG
Pieper
Gertjan T
GT
Sieswerda
Rianne H A C M
RH
de Bruin-Bon
Barbara J M
BJ
Mulder
Berto J
BJ
Bouma
D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077300:Bosentan; D002302:Cardiac Output / Q000502:physiology; D004452:Echocardiography; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D018729:Fontan Procedure; D006330:Heart Defects, Congenital / Q000188:drug therapy* / Q000503:physiopathology* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011184:Postoperative Period; D011446:Prospective Studies; D011788:Quality of Life; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D013449:Sulfonamides; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000077300:Bosentan
Bosentan; Exercise capacity; Fontan