Abstract 12639: Ventricular Energetics in Fontan Circulation: A Potential Therapeutic Target for Preserving Myocardial Function
Background: Cardiac dysfunction is one of the vital determinants of long-term outcome in patients with Fontan circulation. However, underlying mechanisms for the development of ventricular dysfunction remain unclear. Energy depletion is a key feature of failing ventricles, and heart failure alters ventricular energy consumption for intracellular Ca2+ handling during excitation-contraction (E-C) coupling. We hypothesized that ventricular energetic efficiency for Ca2+ handling as well as for external work production is reduced in Fontan circulation compared with biventricular circulation.
Method: A pressure-volume (PV) relationship was constructed during cardiac catheterization in 14 Fontan patients and 29 controls with biventricular heart. Myocardial oxygen consumption (MVO2) was estimated by PV area (PVA), and ventricular mechanical efficiency (Ve) was calculated as the ratio of stroke work (SW) and PVA. The fraction of the total amount of Ca2+ recycled by the sarcoplasmic reticulum during E-C coupling, termed recirculation fraction (RF), was computed by fitting the decay of contractile index after rapid atrial pacing to a combined sinusoid and logistic function.
Result: MVO2 was significantly higher (3.2 ± 1.0 vs. 2.6 ± 0.5 mLO2/beat/100g, p < .05), whereas SW was significantly lower in Fontan patients than in controls, indicating higher oxygen cost for ventricular work in Fontan patients. This was consistent with a significantly lower Ve in Fontan patients than in controls (p < .01). Furthermore, oxygen cost for Ca2+ handling was significantly higher in Fontan patients than in controls, as indicated by a lower RF in Fontan patients than in controls (0.66 ± 0.04 vs. 0.77 ± 0.02, p < .05). Importantly, RF was significantly correlated with Ve independent of ventricular contractility and afterload (p < .05).
Conclusion: Higher oxygen cost for E-C coupling in the Fontan ventricle appears to affect the mechanical efficiency. Since RF is known to be independent of catecholamine status, these features of Fontan ventricular energetics can lead to myocardial energy depletion throughout a patient’s life. Strategies involving Ca2+ handling may effectively terminate the vicious cycle of developing ventricular dysfunction in Fontan circulation.
Author Disclosures: H. Saiki: None. S. Kuwata: None. C. Kurishima: None. Y. Iwamoto: None. H. Ishido: None. S. Masutani: None. H. Senzaki: None.
- © 2014 by American Heart Association, Inc.