Effect of respiration on cardiac filling at rest and during exercise in Fontan patients: A clinical and computational modeling study

Due to the absence of a sub-pulmonary ventricle, the Fontan circulation is sensitive to respiration-induced changes in intrathoracic pressure. However, the importance of a ‘respiratory pump’ in creating forward flow remains controversial. We aimed at evaluating the effect of respiration on ventricular filling during exercise using clinical data and computational modeling predictions. Ten Fontan patients (6 male, 20 ± 4 years) underwent ungated cardiac magnetic resonance (CMR) imaging at rest and during supine bicycle exercise to evaluate systemic ventricular volumes (end-diastolic volume index (EDVi), end-systolic volume index (ESVi) and stroke volume index (SVi)) during normal respiration and a Valsalva maneuver. Respiratory-dependent SV was calculated. Clinical results were compared to predictions made by a closed-loop lumped-parameter (LPN) computational model of Fontan circulation. Inspiration resulted in increased EDVi (98 ± 16 to 103 ± 15 mL; P = 0.001), SVi (55 ± 9 to 59 ± 9 mL; P = 0.001) and cardiac index (3.9 ± 0.7 to 4.2 ± 0.8 L/min; P = 0.002), whereas ESVi (P = 0.096) remained unchanged. The effect of inspiration on EDVi (mean effect + 6 ± 1 mL; P < 0.0001) and SVi (+ 4 ± 1 mL; P < 0.0001) was maintained during exercise. Respiratory-dependent SVi tended to increase during exercise (3 ± 2% to 5 ± 3%; P = 0.084). Valsalva resulted in decreased EDVi (P = 0.001), ESVi (P = 0.003) and SVi (P = 0.005). Computational modeling indicated higher EDV and SV at end-inspiration and expiration, showing a phased time delay between peak caval vein flow and peak SV. In Fontan patients, inspiration resulted in increased ventricular filling at rest and during exercise. Results were confirmed using a computational model indicating a phased time delay between peak SV and peak caval vein flow.