Andersons pediatric cardiology 1908

patients, suggesting that remodeling is inadequate.34,36,48–51 Diastolic dysfunction transmits increased filling pressures to the pulmonary veins This has a progressive negative impact on the pulmonary vascular bed and systemic venous return, leading to further restriction of exercise performance.52 Increased systemic venous stiffness and reduced capacitance augment systemic return in the Fontan circulation at rest, but these adaptive mechanisms are less effective with exercise.52,53 Pulmonary vascular resistance limits systemic ventricle preload and cardiac output in the Fontan circulation because it sets the level of energy required to deliver blood from the systemic veins to the systemic ventricle.37,39,54,55 A number of factors have the potential to adversely impact on pulmonary vascular resistance For example, vascular compliance may be compromised by the lack of pulsatile flow, whereas reduced wall shear stress may lead to maladaptive changes in lung vasculature and increased pulmonary vascular resistance.56 Abnormal microscopic pulmonary vascular changes have been described in the Fontan circulation, as has impaired pulmonary artery growth.57–60 Others have described abnormal pulmonary vascular reactivity with exercise.52 Although the mechanism of abnormal pulmonary vascular behavior is unclear, even a small increment of pulmonary vascular resistance has the capacity to reduce the ability to augment cardiac output with exercise This has generated interest in the use of pulmonary vasodilator therapy in the Fontan population However, the mixed results of these medications on Fontan exercise performance suggest that the factors responsible for exercise restriction are complex.61–65 Chronotropic Incompetence (See also Chapter 22) The inability of the heart to increase rate commensurate with demand is a recognized predictor of future cardiovascular events and overall mortality in other settings of cardiovascular disease, including heart failure.66 Chronotropic incompetence is a marker of dysautonomic function and reduced sinus node reserve.66,67 In the Fontan population an impaired heart rate response to exercise is a common finding.37–40,45,46 There is some debate as to its relative contribution to impaired exercise capacity,39,68 with some even suggesting that it may form a useful adaptive response when there is diastolic dysfunction.69 Sinus node dysfunction may be related to damage to the sinus node and its arterial supply during cardiac surgery More modern cavopulmonary connections have resulted in better preserved chronotropy,39,44 but sinus node dysfunction is not eliminated completely because contributors may include prior bidirectional Glenn or hemi-Fontan surgeries.70 The prognostic implication of chronotropic incompetence within the Fontan population is unclear.31,71 Restrictive Lung Disease In the absence of a subpulmonary ventricle, the Fontan circulation relies on efficient lung mechanics, with changes in intrathoracic pressure during respiration acting as a suction pump to draw blood through the lungs It is increasingly recognized that optimized lung parenchyma is an important positive contributor to the Fontan circulation both at rest and under exercise conditions Restrictive pulmonary function, as demonstrated by reduced forced vital capacity and forced expiratory volume in 1 second is well described in patients with congenital heart disease and is particularly apparent in those with a Fontan circulation.58,72–75 This pattern of abnormal respiratory function is multifactorial with contributions from thoracic surgeries, pleural stiffness, intrinsic lung development abnormalities, and Fontan pulmonary vascular flow dynamics Side effects from the use of medications, especially amiodarone, may also play a role.72,74–76 Under exercise conditions, restrictive lung function can manifest with reduced O2 pulse, higher peak minute ventilation (VE), and reduced ventilation efficiency with higher VE/VCO2 slope.31,45,77 In addition, several studies have found a significant correlation between impaired resting pulmonary function and reduced peak VO2 max on exercise in the Fontan population.31,58,73 A small interventional study focused on reduced inspiratory muscle strength in Fontan patients by instituting inspiratory respiratory muscle training Following training, resting inspiratory muscle strength, cardiac output, and ejection fraction increased, whereas during exercise there was an improvement in ventilatory efficiency.78 The relative contribution of the pulmonary circulation and cardiovascular mechanics to exercise restriction in Fontan patients is yet to be fully understood.79 Further research will improve the understanding of these limitations and lead to new ways of “empowering” the Fontan circulation under exercise conditions Impaired Somatic Growth Somatic growth is impaired during and following staged reconstruction for children with a functionally univentricular heart.80–85 Weight and height parameters are most often within the normal range at birth in the absence of prematurity or genetic abnormalities.80,82,85,86 Following the initial surgical procedure, there is a significant decrease in both height and weight z score.80–85 Weight follows a trajectory of relative recovery after the bidirectional Glenn or hemi-Fontan operation, and following Fontan completion in most children.80–86 However, height does not demonstrate the same trend.80–83,85–87 Heart failure, PLE, the presence of venovenous collaterals, and significant atrioventricular valve regurgitation may have a negative impact on weight and height trajectory, although these associations have not been demonstrated in a consistent way.80–83,85 By adulthood, males with a Fontan are shorter than normal population.87 This relationship is less striking in females.87 Mechanisms for the reduction in height potential may include lower bone density and reduced muscle mass.85,88 Of interest, but as yet unconfirmed, lower exercise participation in Fontan patients may impact on bone growth and subsequent bone/muscle development.81,82,88,89 Another potential contributor to reduced bone growth is prolonged hypoxemia prior to Fontan completion,85,88 although a fenestration after the Fontan operation (a marker for hypoxemia) does not appear to influence height recovery.83,86 The impact of the Fontan circulation on insulin-like growth factors (IGFs) and growth hormone and their interaction with somatic growth is yet to be established.90,91 In a cross-sectional study, lower IGF was found in Fontan patients with a higher brain natriuretic peptide (a marker for heart failure) and lower cardiac output However, there was no relationship between IGF and somatic growth The authors concluded that longitudinal studies were required to determine if these relationships contributed to impaired somatic growth in this population.92 There is concern that obesity trends seen in the general population93,94 will be similarly seen in the Fontan population Although obesity is less prevalent in Fontan cohorts compared with the general population, as well as other forms of congenital heart disease, the rate is not insignificant and ranges from 8% to 30%.85,88,95 Moreover, there is a tendency toward increasing weight and body mass index further out from Fontan surgery.95,96 Given the reliance of the Fontan circulation on optimal ventricular and vascular function, additional acquired