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 & Pediatrics, Congenital Heart Disease, CHD & Pediatrics and Interventions, CHD & Pediatrics and Prevention, Statins, Exercise

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


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