Abnormal potential signals distribution
The main findings of this study are that: (1) abnormal potentials are more prevalent in the MR-defined gray zone and (2) this relationship is more evident during RVA pacing. CMR determined gray zone has been shown to correlate with all-cause post-MI mortality and with inducibility for VT for patients with myocardial infarct scars; therefore it would be important to characterize the prevalence of abnormal potentials in areas labeled as gray zone as quantified by LGE–CMR. Our data suggest that abnormal potentials are more prevalent in the MR-defined gray zone, particularly during pacing. This is a novel finding, and provides additional insights into the analysis of RVA stimulation; It is believed that overlapping activation fronts may limit the identification of multiple components during sinus rhythm, where overlapping refers to the activation of various parts of the myocardium due to non-uniform activation of the endocardium generated by the Purkinje fibers as well as to beat-to-beat heart rhythm variability in sinus rhythm. This limitation can be mitigated by simplifying the evaluation to one propagation front; specifically, RVA pacing from a known location creates a dominant action potential wavefront that can identify abnormal potentials otherwise not detected [
6]. Our results are consistent with this notion as RVA pacing suppresses overlapping signals and reduces the influence of adrenergic and cholinergic nerve fibers present on the swine endocardium. The heterogeneous nature of gray zone with bundles of surviving myocytes responsible for the irregular propagation of the action potential may well explain our observation. Also, our results are in line with previous studies that hypothesized that overlapping of EGMs or a particular orientation of a line of block with respect to the activation front may preclude the identification of multiple components during SR [
6]. This limitation can be overcome by changing the activation front, such as during RVA pacing, to identify otherwise undetected abnormal EGMs. This is important because the authors of the previous study also claim that these EGMs could better identify VT-related slow conduction areas relative to low-amplitude electrograms [
6]. Further, we noticed that in both sinus and paced rhythm there was a percentage of low volume abnormal potentials in healthy tissue. Based on visual inspection we noticed that such points were recorded recorded in healthy myocardium, which was located adjacent to the infarct region. In addition, a few points of low voltage in healthy myocardium were also acquired very close or touching the valve, while others probably did not have a very good contact with the ventricular.
Our results showes a lower prevalence of low voltage points in gray zone than health myocardium in the paced rhythm case; Although gray zone in that case showed a lower prevalence of low voltage points, the average signal amplitude was lower than in the healthy myocardium. So while the average signal in the healthy myocardium was above 1.5 mV, there were several low voltage points. We also found that, in the paced case, a higher relative percentage of abnormal signal potentials was associated with sites in the presumed slow central pathway compared to entry or exit, based on activation activation times. These findings are in line with findings of Nakahara
et al. [
13], where a higher concentration of abnormal EGMs (late potentials) was found in the putative isthmus and also with Hsia et al. [
7], where the majority of these delayed and fractionated endocardial electrogram recordings were found in critical central pathway sites. In this study we did not report nor conduct a rigorous correlation study between low-voltage and MR-defined dense scar, since it was the focus of our previous publication [
15].
Abnormal potentials are more associated with the location of the VT isthmus than low amplitude potentials [
6,
7,
11,
16]. Locations of VT-related conducting channels have been shown to be only grossly estimated by low peak bipolar voltages (<1.5 mV) measured during SR without tachycardia induction. Also, recently it has been shown that the presence of isolated potentials inside the voltage channel significantly increases the specificity for identifying the clinical VT isthmus [
17]. Furthermore, linear radiofrequency ablation lesions designed to transect these channels of slow conduction have been shown to be on average longer in length by several centimeters when the isthmus has not been effectively identified and only voltage maps are known (e.g. in hemodynamically unstable patients) [
18]. In contrast, abnormal EGMs reflecting anisotropic late activation times can identify VT-related slow conduction regions. Specifically, sites with isolated/late potentials and fractionated potentials during sinus/paced rhythm reflect late local activation of bundles of healthy myocytes that enable conduction and become critical components of a reentry circuit. Abnormal potentials acquired during endocardial mapping have been shown to correspond to appropriate ablation targets with greater specificity than simple peak voltage mapping [
10,
19].
Identifying abnormal potentials becomes especially important in cases where the patient has hemodynamically unstable VT, or non-inducible VT; otherwise, in these patients, electrophysiologists only have the information from the voltage maps, which as noted above, have low specificity for VT substrate identification [
2,
6]. Point-by-point mapping of the LV is time consuming and leads to prolonged procedure/anesthesia time, and the low specificity of this technique requires additional diagnostic procedures [
6]. The point-by-point mapping also has limitations related to catheter-tissue contact and largely unspecified spatial resolution. In our previous study [
15] we showed that CMR information used in electrophysiology studies can accurately predict areas of myocardial fibrosis identified with bipolar voltage mapping. We believe that a strategy for identification of sites for mapping and ablation is achievable when using CMR combined with abnormal electrical signal information; this added information is desirable to due to its greater specificity compared to peak voltage mapping alone. More specifically, gray zone volume with LGE-CMR has been shown to correlate with all-cause post-MI mortality and with inducibility for ventricular tachycardia (VT) [
20,
21].