Anti-arrhythmic or proarrhythmic?
As with any treatment (eg, ablation or drugs) targeting regions of heterogeneous conduction, therapies meant to alter local conduction should be considered in light of their potential for proarrhythmia. We propose injecting conductive materials into regions of damaged myocardium as a means of “normalizing” conduction. However, it should be noted that we did not account in our study for conduction endocardially or mid-myocardially. Furthermore, while conduction post-nanotube injection seemed similar to baseline, it cannot be assumed to be precisely the same. Use of omnipolar smaller electrodes or optical mapping may allow for enhanced understanding of local conduction direction. While globally it appears that conduction follows the same path as baseline, heterogeneity due to disarray of conduction or conduction abnormalities only revealed with a different wavefront of activation may result in continued arrhythmic potential, as seen in studies of ventricular mapping for substrate characterization.
It is also possible that with chronic retention in tissue, myocardial fibrosis or immune reaction may occur that may alter the tissue-material interface. Furthermore, conductivity may change over time that may result in proarrhythmia in the long-term even if activation appeared to be normalized acutely. Many of these concerns may be clarified in chronic in vivo studies. However, animal-based studies may never fully recapitulate human tissue reactions. Furthermore, how integration varies in different types of substrate, whether related to myocardial ischemia and infarction, inflammation-mediated injury, genetic abnormalities, or other causes, needs to be considered.