Key result
Intrapericardial cardiosphere-derived cells cut dense scar expansion ~88% vs control in a porcine post-infarction model.
Why the study?
The arrhythmic substrate of ventricular tachycardias is often epicardial and yields poor outcomes with current therapies, while cardiosphere-derived cells have been shown to modify myocardial scarring.
Does intrapericardial administration of cardiosphere-derived cells reduce epicardial scar expansion and electrical heterogeneity in a porcine post-infarction model?
Does intrapericardial administration of cardiosphere-derived cells reduce epicardial scar expansion and electrical heterogeneity in a porcine post-infarction model?
Absolute Event Rate: 10.5% vs 84.8%
p-value: p=<0.01
Intrapericardial administration of cardiosphere-derived cells reduces epicardial scar expansion and improves electrical homogeneity in a porcine model of myocardial infarction, suggesting a potential anti-arrhythmic effect.
Intrapericardial cardiosphere-derived cells attenuated scar in pigs; hypothesis-generating for human anti-arrhythmic translation.
The arrhythmic substrate of ventricular tachycardias in many structural heart diseases is located in the epicardium, often resulting in poor outcomes with currently available therapies. Cardiosphere-derived cells (CDCs) have been shown to modify myocardial scarring. A total of 19 Large White pigs were infarcted by occlusion of the mid-left anterior descending coronary artery for 150 min. Baseline cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement sequences was obtained 4 weeks post-infarction and pigs were randomized to a treatment group (intrapericardial administration of 300,000 allogeneic CDCs/kg), ( n = 10) and to a control group ( n = 9). A second CMR and high-density endocardial electroanatomical mapping were performed at 16 weeks post-infarction. After the electrophysiological study, pigs were sacrificed and epicardial optical mapping and histological studies of the heterogeneous tissue of the endocardial and epicardial scars were performed. In comparison with control conditions, intrapericardial CDCs reduced the growth of epicardial dense scar and epicardial electrical heterogeneity. The relative differences in conduction velocity and action potential duration between healthy myocardium and heterogeneous tissue were significantly smaller in the CDC-treated group than in the control group. The lower electrical heterogeneity coincides with heterogeneous tissue with less fibrosis, better cardiomyocyte viability, and a greater quantity and better polarity of connexin 43. At the endocardial level, no differences were detected between groups. Intrapericardial CDCs produce anatomical and functional changes in the epicardial arrhythmic substrate, which could have an anti-arrhythmic effect.
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Carta‐Bergaz et al. (2022) studied Myocardial infarction (n=19). Intrapericardial allogeneic cardiosphere-derived cells (CDCs) vs. Placebo (CDCs diluting solution) was evaluated on Epicardial relative percentage change in dense scar (p=<0.01). Intrapericardial administration of cardiosphere-derived cells significantly reduced the relative percentage change in epicardial dense scar compared to control (10.5% vs 84.8%, p<0.01) in a porcine post-infarction model.
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