title: Effect of Ambrisentan on Exercise Capacity in Adult Patients After the Fontan Procedure.
abstract: The Fontan operation is a common end point for children born with a single functional ventricle. Fontan patients typically experience physiological deterioration leading to transplant or death in their third or fourth decades of life. This deterioration is partially attributable to progressive increases in pulmonary vascular resistance (PVR) and as such endothelin receptor antagonists, which are known to decrease pulmonary vascular resistance, have been proposed as potentially beneficial in this population. We conducted a single-center, randomized, double-blind, placebo-controlled, crossover study of 12 weeks of ambrisentan therapy (10 mg per day) versus placebo to test the hypothesis that endothelin receptor antagonism will improve cardiopulmonary exercise test parameters and 36-item short form (SF-36) assessed quality of life in adult Fontan patients. Twenty-eight patients entered the trial, 19 patients completed the protocol. Ambrisentan therapy improved peak oxygen consumption by 1.7 ml/kg/min in patients who achieved a respiratory exchange ratio of >0.95 (p = 0.05) and decreased the slope of the ventilatory equivalent ratio for oxygen (-2.8, p = 0.019) in all completers. It did not change SF-36 physical function score compared with placebo (p = 0.28). Ambrisentan therapy resulted in a decrease in (-1.4 g/dl, p <0.001) with no change in liver or renal function. Therapy was generally well tolerated, with no greater rate of side effects than placebo. In conclusion, ambrisentan is well tolerated and improves exercise capacity in adult Fontan patients.
authors.affiliation: Department of Cardiology, Baylor University Hospital, Dallas, Texas. Electronic address: acedars97@gmail.com.
authors.forename: Ari M
authors.initials: AM
authors.lastname: Cedars
authors.affiliation: Department of Cardiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Joshua
authors.initials: J
authors.lastname: Saef
authors.affiliation: Department of Cardiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Linda R
authors.initials: LR
authors.lastname: Peterson
authors.affiliation: Department of Cardiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Coggan
authors.affiliation: Department of Cardiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Novak
authors.affiliation: Department of Cardiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Debra
authors.initials: D
authors.lastname: Kemp
authors.affiliation: Department of Cardiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Ludbrook
mesh_terms: D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D018729:Fontan Procedure; D006330:Heart Defects, Congenital / Q000188:drug therapy / Q000503:physiopathology* / Q000601:surgery*; D006801:Humans; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D010666:Phenylpropionates / Q000627:therapeutic use*; D011724:Pyridazines / Q000627:therapeutic use*; D011788:Quality of Life; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010666:Phenylpropionates; D011724:Pyridazines; C467894:ambrisentan