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.