The Fontan circulation When first described in the
The Fontan circulation
When first described in 1971, the Fontan operation ushered in a new paradigm in the care of children born with the varied forms of complex congenital cholinesterase inhibitor disease (CHD) characterized by a single effective pumping chamber.1., 2. This procedure, which creates a total cavopulmonary connection, separates the systemic and pulmonary circuits and reduces both hypoxemia and ventricular volume overload. However, although life-saving or life-prolonging for many, the circulation created by the Fontan operation is not normal. After the Fontan, there is no ventricular pump to propel blood through the pulmonary arteries. Instead, blood returns to the lungs via passive flow from the systemic veins and is dependent on low pulmonary vascular resistance and optimal diastolic ventricular function. This creates a circulation characterized by elevated central venous pressure and chronically low cardiac output. Over time, these inherent characteristics of Fontan physiology result in a predictable, persistent deterioration of cardiovascular efficiency marked by a progressive decline in exercise performance as well as impaired ventricular and vascular function.3., 4., 5., 6., 7., 8. Medical therapies that can favorably alter the deficiencies of the Fontan circulation might help to slow the decline associated with Fontan physiology and lead to improved outcomes over a lifetime.
Exercise performance in the Fontan circulation The Fontan circulation significantly limits the ability to increase cardiac output in the setting of increased metabolic demand. In a 2-ventricle circulation, the subpulmonary ventricle facilitates the increased blood flow and augmented preload required to increase cardiac output during exercise.11., 12. In the single-ventricle circulation, the central venous pressure provides the driving force that propels blood through the pulmonary vasculature. Central venous pressure can rise during periods of increased demand, but the increase in pressure is substantially less than that which can be generated by a subpulmonary ventricle. As a result of limited transpulmonary blood flow, ventricular preload and cardiac output are likewise limited. These limitations of the Fontan physiology are demonstrated in evaluations of exercise performance. Although many patients with CHD have lower maximal exercise capacity (maximal oxygen consumption; VO2 max) than age- and gender-matched peers, those with the Fontan physiology have among the lowest.15., 16. In the Pediatric Heart Network’s (PHN’s) cross-sectional study of exercise performance in 411 children following Fontan, VO2 max was 65% of predicted for age and gender at 12 years of age and decreased progressively in the older cohorts.3., 4. In multiple subsequent longitudinal studies, the progressive decline in exercise capacity has been confirmed, although the slope of the decline has varied by study, ranging from 0.8% to 2.6% of the predicted VO2 max per year.3., 5., 6., 7. The quantification of exercise capacity is not only a useful descriptor of functional capacity; it is also a reliable predictor of morbidity and mortality in those with congenital or acquired heart disease. In studies of young adults with CHD, a VO2 max of approximately 45%-50% of predicted for age and gender (an absolute VO2 max of 18 to 20 mL/kg/min in young adults) appears to be the threshold value for an increased risk of symptomatic heart failure and death. This finding is consistent across many diagnostic categories of CHD.17., 18., 19., 20. In one study of 321 subjects with Fontan physiology, the maximal VO2 was 52% of predicted at a mean age of 21 years. During a median follow-up time of 21 months, 41% of patients required hospitalization for heart failure, and 9% either died or underwent heart transplantation.
Pulmonary vasodilation and the Fontan circulation In the absence of a subpulmonary ventricle, the importance of pulmonary vascular resistance (PVR) as a determinant of cardiac preload and output is magnified. Any small elevation in PVR necessitates an increase in central venous pressure to maintain cardiac output and/or results in a decrease in cardiac output for any given central venous pressure. Likewise, any small decrease in PVR allows for a decrease in central venous pressure for any given cardiac output and/or an increase in cardiac output for any given central venous pressure. Additional evidence suggests that even in the setting of a normal resting PVR, the typical decrease in PVR that occurs with exercise in 2-ventricle circulations—facilitating substantial augmentation in cardiac output—does not occur during exercise in those with the Fontan circulation.21., 22. Given the importance of PVR in the Fontan circulation, pulmonary vasodilators make intuitive sense as a class of drug that might be successful at improving the Fontan physiology.