Computational Modeling of Pathophysiologic Responses to Exercise in Fontan Patients
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Reduced exercise capacity is nearly universal among Fontan patients. Although many factors have emerged as possible contributors, the degree to which each impacts the overall hemodynamics is largely unknown. Computational modeling provides a means to test hypotheses of causes of exercise intolerance via precisely controlled virtual experiments and measurements. We quantified the physiological impacts of commonly encountered, clinically relevant dysfunctions introduced to the exercising Fontan system via a previously developed lumped-parameter model of Fontan exercise. Elevated pulmonary arterial pressure was observed in all cases of dysfunction, correlated with lowered cardiac output (CO), and often mediated by elevated atrial pressure. Pulmonary vascular resistance was not the most significant factor affecting exercise performance as measured by CO. In the absence of other dysfunctions, atrioventricular valve insufficiency alone had significant physiological impact, especially under exercise demands. The impact of isolated dysfunctions can be linearly summed to approximate the combined impact of several dysfunctions occurring in the same system. A single dominant cause of exercise intolerance was not identified, though several hypothesized dysfunctions each led to variable decreases in performance. Computational predictions of performance improvement associated with various interventions should be weighed against procedural risks and potential complications, contributing to improvements in routine patient management protocol.
KeywordsLumped-parameter model Dysfunction Single-ventricle Closed-loop Simulation Pulmonary pressure Regurgitation
Abnormal pulmonary vascular response
1st degree AV block
AV valve insufficiency
Cardiac output in L/min
Metabolic equivalent in units of 3.5 mL O2 kg−1 min−1
Pulmonary vascular resistance
This work was supported by the Leducq Foundation as part of the Transatlantic Network of Excellence for Cardiovascular Research, a Burroughs Wellcome Fund Career award at the Scientific Interface, and an American Heart Association Postdoctoral Fellowship.
Conflict of Interest
No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.
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