Effect of carvedilol on exercise performance in Fontan patients
Study ID: STU 062016-101
The strategy for managing single ventricle physiology over the past 25 years has been a three- stage surgical palliation scheme leading to an eventual Fontan procedure. However, Fontan patients still suffer from significant morbidities. This patient population has increased need for heart transplantation, suffer from chronic arrhythmias, congestive heart failure and poor exercise capacity. Poor exercise capacity leads to a decreased quality of life, therefore, not only does it have significant cardiovascular effects but also significant psychosocial consequences. Fontan patients are rarely able to participate in sports or join with peers in sustained physical activity. Carvedilol and beta blockers are frequently used in adult heart failure, however, the beneficial cardiovascular effects of carvedilol in this single ventricle population are not known. in this proposal, 30 patients who have met all inclusion criteria and met no exclusion criteria will be randomized to take 12 weeks of either carvedilol or placebo. a 6 week washout will take place weeks 13-18 followed by a second 12 week treatment arm where each subject will receive the opposite treatment from what they took in the first 12 week treatment phase. The dose of study medication will be decreased to zero over the first week of the washout period and at the end of the second treatment period. The primary outcome will be exercise performance as measured by cycle ergometry with a metabolic cart to measure maximal oxygen consumption and will be assessed in each subject at baseline and end of treatment. The intent of this work is to provide preliminary efficacy data for carvedilol in Fontan patients and ultimately inform the design and sample size necessary for a large multicenter trial. improved exercise capacity and cardiac function in subjects with a Fontan circulation has been positively associated with improved health related quality of life. This in turn could result in reduced morbidity and resource utilization. improved understanding of the mechanisms that lead to heart failure will improve medical management of this population. The goal of this and future proposals is to provide a better understanding of the utility of traditional heart medications in this population and therefore direct future research in management strategies.
Screening Phase 1) Informed consent of parent(s) or legal guardian; informed consent or assent of subject as applicable. 2) Male or female children between the ages of 10 and 35 years with congenital heart disease that has been palliated with a Fontan circulation. Treatment Phase 1) Ability of perform a maximal exercise test as defined by a respiratory exchange ratio (RER) greater than 1.0 at the time of maximal exercise