Abstract
Backgrounds: Patients with single ventricular physiology undergoing staged palliations may present myocardial fibrosis detected by late gadolinium enhancement (LGE) of cardiac MRI. Recent studies suggest that cardiosphere-derived cell (CDC) therapy may reduce substantial fibrosis to improve cardiac function. Purpose: The aim of this study is to investigate whether intracoronary CDC infusion may reverse the focal fibrotic area to functional myocardium. Methods: Thirty-three patients (age: 3.1±1.0 years) were evaluated by cMRI during enrollment and randomized to treat by Fontan palliation with or without intracoronary injection of CDCs 1 month after surgery. Eight out of 33 patients had LGE initial screening by cMRI (LGE+) and 25 patients were classified as LGE (-) group. Area of focal fibrosis was quantitated by standard deviation method. Echocardiography and cMRI were performed to evaluate ventricular strain before enrollment and during the 3 months of follow-up. Results- Baseline examination revealed that LGE (+) group showed reduced ejection fraction (P=0.01), increased cardiac volume (P=0.03), and reduced circumferential strain (base: P=0.02, mid: P=0.02, apex: P=0.0005) compared with LGE (-) group. These changes were associated with decreased ventricular elastance (P=0.02) and increased myocardial stiffness (P=0.03) approximated by catheter examination. When patients with LGE received CDC infusion, a significant reduction of scar mass (P=0.01), scar size (P=0.01), and scar volume (P=0.02) could be detected, while these parameters remained unchanged in patients received Fontan without CDC injection. In addition, CDC infusion significantly improved regional circumferential strain (P=0.0001) within the target segments with LGE. Conclusions: In patients with single ventricular physiology, LGE identified by cMRI before Fontan procedure may be associated with the pathogenesis of decreased cardiac elastance and increased myocardial stiffness, leading to the development of right ventricular dysfunction. Although latent heart failure could be predicted in these patients after palliations, CDC therapy may have a potential to reverse cardiac dysfunction by direct conversion of the extent and severity of myocardial fibrosis.
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