Bosentan Improves Exercise Capacity in Adolescents and Adults After Fontan Operation: The TEMPO Study

Study Questions:

Given that the Fontan circulation is dependent on passive pulmonary blood flow, what is the utility of bosentan to improve clinical outcomes in Fontan patients?

Methods:

TEMPO (Treatment with Endothelin receptor antagonist in Fontan patients, a randoMized, Placebo-controlled, double-blind study measuring peak Oxygen consumption) is a study of Fontan patients >12 years old recruited from a population database. Exclusions included New York Heart Association (NYHA) class IV and treatment with other pulmonary vasodilators. Subjects on bosentan received 62.5 mg bid for 2 weeks, followed by 125 mg bid for 12 weeks. The primary outcome was change in exercise capacity. Secondary outcomes included changes in additional exercise parameters and health state.

Results:

Of 107 eligible subjects, 75 were enrolled and 69 (92%) completed the study. Mean age was 20 ± 7.4 years. Separate analyses were performed for observed cases (n = 69) and randomized cases (n = 75) with imputed missing data. For observed cases, peak VO2 increased by 2 ml/kg/min in the bosentan group and by 0.7 ml/kg/min in the placebo group (p = 0.02); exercise time also increased by 28 vs. 5 seconds, respectively (p = 0.04). However, a significant treatment effect was not shown in all permutations of the imputed data. Nine of 32 patients on bosentan improved from NYHA class II to class I; there were no NYHA improvements in the placebo group. There were no serious adverse effects.

Conclusions:

The authors concluded that bosentan improves exercise capacity, exercise time, and functional class in Fontan patients without serious adverse events.

Perspective:

This well-designed trial shows statistically significant improvements in exercise capacity in Fontan patients treated with bosentan; however, the clinical significance is minimal, especially considering the cost of the medication. Noted by the authors was a skewed baseline distribution of NYHA class between treatment and placebo groups, which may have affected these results. The study does provide a foundation for additional investigation.

Clinical Topics: Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Diabetes and Cardiometabolic Disease, Invasive Cardiovascular Angiography and Intervention, Prevention, Cardiac Surgery and CHD and Pediatrics, Congenital Heart Disease, CHD and Pediatrics and Interventions, CHD and Pediatrics and Prevention, Statins, Exercise

Keywords: Adolescent, Receptors, Endothelin, Adult, Oxygen Consumption, Fontan Procedure, Exercise, Hemodynamics, Sulfonamides


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