Repolarization Heterogeneity in Human Post-Infarct Ventricular Tachycardia

Abstract

Background: Slow conduction, caused by fibrosis between surviving myocytes and connexin remodeling, is an important prerequisite for post-infarction ventricular tachycardia (VT); however, slow conduction is present throughout the infarct whereas VT circuits are finite in number and discrete. In a porcine model of VT, re-entrant circuits occur at region of significant repolarization heterogeneity caused by up-regulation of potassium channel β-subunits KCNE3 (increasing repolarization current) and KCNE4 (decreasing repolarization current), causing heterogeneous action potential durations.

Objectives: This study was designed to determine whether re-entrant circuits in human post-infarction VT are associated with repolarization heterogeneity.

Methods: In 6 patients, left ventricular mapping was performed during induced VT to identify sites within the VT circuit. Subsequently, unipolar mapping (3.5-mm tip ablation catheter) was performed to characterize activation-recovery intervals (ARIs), which are surrogates for local action potential durations, at sites documented within the VT circuit isthmus (IN) compared to sites within the infarct scar but outside of the VT circuit (OUT).

Results: ARIs were significantly shorter in the IN compared with the OUT sites (420.2 ± 79.3 ms vs 462 ± 52.8 ms; P = 0.01). In all patients. sites that were associated with the circuit always had shorter ARI values than did those sampled from OUT regions.

Conclusions: VT circuit sites in human post-infarct VT are associated with repolarization heterogeneity, similar to what was previously reported in a porcine model. This suggests the possibility of a common mechanism between humans and the porcine model of post-infarct VT, and that development of ablation strategies or small molecule or genetic therapies to restore normal repolarization kinetics may be antiarrhythmic.

Keywords: cellular electrophysiology; molecular therapy; myocardial infarction; ventricular tachycardia.

FIGURE 1. ARI at IN Compared With OUT Sites

Relationship of activation-recovery intervals (ARIs) recorded from sites within the scar but outside of the circuit (OUT), within the ventricular tachycardia circuit isthmus (IN), and remote from the infarct (REMOTE). Data are presented at a patient-specific level with each patient represented by a different color-coded symbol. In general, ARIs are longest in OUT regions, shorter in IN regions (456.2 ± 64.3 ms OUT vs 421 ± 76.7 ms IN; P < 0.002), and shortest (normal) in REMOTE regions.

FIGURE 2. Comparison of Voltage and ARI Maps

Left ventricular voltage map (left) and ARI map (right) in a patient with ventricular tachycardia (VT) following anterior infarction. The voltage map is constructed with color ranges of 0.5 and 1.5 mV; the ARI maps are displayed as in the Central Illustration. In this example, a large portion of the VT circuit was characterized with entrainment, from entrance (light green icons, near apical region of scar), isthmus (light blue icons), and exit (dark green icons) sites. The pink icon was the site of VT termination with the first ablation. Note that IN sites have shorter ARI values than OUT sites do. Abbreviations as in Figure 1.

CENTRAL ILLUSTRATION. Activation-Recovery Interval Defines the Ventricular Tachycardia Circuit Isthmus

An activation-recovery interval (ARI) map (center) in a patient with ventricular tachycardia (VT) following anterior infarction with representative bipolar and unipolar electrograms from sites within the VT circuit isthmus (IN) (left) and sites within the infarct but outside of the circuit (OUT) (right). Color-coded ARI maps were constructed by manually entering the site’s ARI value on the electroanatomic map. In a similar manner to voltage or activation mapping, the shortest ARI sites are portrayed in red and the longest in purple. Purple icons represent sites that were demonstrated by entrainment mapping to be within the VT circuit; periwinkle icons denote sites out of the circuit. Black icons represent fractionated electrograms. The blue icon represents the site of VT termination with the initial radiofrequency delivery. Bipolar electrograms from OUT sites have abnormalities with fractionated and late components; bipolar electrograms from IN sites (site numbers 2 and 5) also have abnormalities, but to no greater extent than OUT sites do. A color-coded ARI map (center) is superimposed on the anatomy of the voltage map in the same projection. Sites within the VT circuit isthmus are associated with shorter ARI values than are sites outside of the circuit; the shortest ARI values were often very close to sites where single ablation lesions terminated VT, as in this example.