What Limits Cardiac Performance during Exercise in Normal Subjects and in Healthy Fontan Patients?

Abstract

Exercise is an important determinant of health but is significantly reduced in the patient with a univentricular circulation. Normal exercise physiology mandates an increase in pulmonary artery pressures which places an increased work demand on the right ventricle (RV). In a biventricular circulation with pathological increases in pulmonary vascular resistance and/or reductions in RV function, exercise-induced augmentation of cardiac output is limited. Left ventricular preload reserve is dependent upon flow through the pulmonary circulation and this requires adequate RV performance. In the Fontan patient, the reasons for exercise intolerance are complex. In those patients with myocardial dysfunction or other pathologies of the circulatory components, it is likely that these abnormalities serve as a limitation to cardiac performance during exercise. However, in the healthy Fontan patient, it may be the absence of a sub-pulmonary pump which limits normal increases in pulmonary pressures, trans-pulmonary flow requirements and cardiac output. If so, performance will be exquisitely dependent on pulmonary vascular resistance. This provides a potential explanation as to why pulmonary vasodilators may improve exercise tolerance. As has recently been demonstrated, these agents may offer an important new treatment strategy which directly addresses the physiological limitations in the Fontan patient.

Figure 1

Theoretical schema to illustrate circulatory pressure changes in normal and Fontan patients at rest and during exercise. In the normal circulation, pressure is generated in the systemic ventricle (LV) to produce flow in the aorta (Ao) and systemic circulation (S). Pressure dissipates across the systemic microcirculation such that right atrial (RA) pressures are low. The pre-pulmonary pump (RV) provides the pressure to generate the flow in the pulmonary artery (PA) which then dissipates in the pulmonary circulation (P) but is sufficient to maintain preload in the left atrium (LA). During exercise, systemic vascular resistance falls such that there is little increase in mean LV pressure requirements. However, more substantial pressure increases are required in the RV (purple arrow), and these pressure requirements increase with exercise intensity. In the Fontan patient (below), the cavopulmonary bypass (CPB) does not provide any contractile force and, therefore, flow through the pulmonary circulation is dependent on the pressure difference between the RA and LA. During exercise, trans-pulmonary flow can only be augmented by reductions in pulmonary vascular resistance. Beyond mild to moderate exercise, pulmonary vasodilation is maximal and flow increases require a pre-pulmonary pump. Without this, pulmonary pressure does not rise, trans-pulmonary flow does not increase, LA pressure (preload) does not increase, and cardiac output cannot supply the metabolic demands of exercise.

Figure 2

Relationship of output during exercise, pulmonary vascular resistance (PVR), and ventricular function. Cardiac output can increase 5-fold in a normal (N) subject with a biventricular circuit. If ventricular function is impaired, this will first result in decreased maximal output and subsequently in reduced output at low level of exercise. In Fontan patients (F) output is more influenced by PVR than by ventricular function but all have significantly impaired exercise capacity. EF: ejection fraction.