Potential clinical value and influence of conductivity in conductive cardiac patches for reducing post-MI arrythmia risks

Abstract

Conductive cardiac patches can help to restore electric signal conduction of the diseased myocardium after myocardial infarction (MI). However, none of the conductive cardiac patches reported in literature has entered clinical trials. Bench-to-bedside translation of conductive patches has long been hindered by the lack of knowledge of the optimal patch conductivity and deep understanding of the potential clinical benefits and risks in patients. Here, we first prepared conductive cardiac patches with conductivities covering 5 orders of magnitude (10-3-101 S/cm). Disagreeing with the mainstream opinion that patch conductivity close to native myocardium (10-3-10-2 S/cm) is most favorable, our results showed that patches with conductivity two orders of magnitudes higher than native myocardium (10-1-100 S/cm) are most effective in restoring cardiac conduction and lowering inducibility quotient. Conduction velocity (CV) is the essence of the observed results. Rat experiments showed that the low-conductivity patch could increase the CV of infarcted myocardium, but did not fully compensate the mismatch in the CVs of infarct and healthy myocardium. Moderate-conductivity patches could increase myocardial CV to the same level of healthy myocardium, while high-conductivity patches further increased myocardial CV, causing a reversed mismatch. The relationship between patch conductivity and improved CVs in myocardium can be explained by monodomain model theory. Based on the theory, 3D finite element simulation of a MI patient heart predicted that a suitable, patch-improved myocardial CV could reduce the number of reentrants, and stabilize the remaining reentry circuits in the myocardium of the MI patient, which indicated its clinical value.