Pacing in proximity to scar during cardiac resynchronization therapy increases local dispersion of repolarization and susceptibility to ventricular arrhythmogenesis

Abstract

BackgroundCardiac resynchronization therapy (CRT) increases the risk of ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) when the left ventricular (LV) epicardial lead is implanted in proximity to scar.ObjectiveThe purpose of this study was to determine the mechanisms underpinning this risk by investigating the effects of pacing on local electrophysiology (EP) in relation to scar that provides a substrate for VT in ICM patients undergoing CRT.MethodsImaging data from ICM patients (n = 24) undergoing CRT were used to create patient-specific LV anatomic computational models including scar morphology. Simulations of LV epicardial pacing at 0.2–4.5 cm from the scar were performed using EP models of chronic infarct and heart failure (HF). Dispersion of repolarization and the vulnerable window were computed as surrogates for VT risk.ResultsSimulations predict that pacing in proximity to scar (0.2 cm) compared to more distant pacing to a scar (4.5 cm) significantly (P <.01) increased dispersion of repolarization in the vicinity of the scar and widened (P <.01) the vulnerable window, increasing the likelihood of unidirectional block. Moreover, slow conduction during HF further increased dispersion (∼194%). Analysis of variance and post hoc tests show significantly (P <.01) reduced repolarization dispersion when pacing ≥3.5 cm from the scar compared to pacing at 0.2 cm.ConclusionIncreased dispersion of repolarization in the vicinity of the scar and widening of the vulnerable window when pacing in proximity to scar provides a mechanistic explanation for VT induction in ICM-CRT with lead placement proximal to scar. Pacing 3.5 cm or more from scar may avoid increasing VT risk in ICM-CRT patients.

Left ventricular endocardial pacing is less arrhythmogenic than conventional epicardial pacing when pacing in proximity to scar

“…We used 24 image-based patient-specific models of LV anatomy and scar morphology, as described previously. 5 In brief, LV endocardium and epicardium contours were manually drawn in each short-axis slice of late gadolinium enhanced magnetic resonance imaging. Scar and BZ were segmented and reconstructed in 3 dimensions (3D).…”

“…Activation and repolarization sequences were simulated, as in our previous study. 5 In brief, the reaction-eikonal model 11 coupled to the ten Tusscher model 12 of human ventricular action potential were used, and activation was initiated at each pacing location. Transversely isotropic conduction velocities (CVs) of 0.67 and 0.3 m/s 13 were prescribed to healthy tissue in the longitudinal and transverse directions, respectively.…”

“…Our previous study predicted that conventional epicardial LV pacing in proximity to scar increases repolarization gradients, which in turn increases ventricular tachycardia (VT) risk by increasing the vulnerable window for unidirectional block. 5 Endocardial pacing increases the area accessible for lead implantation because it is not constrained by coronary sinus anatomy, allowing operators to target lead position based on the individual’s anatomy and scar. 6 , 7 This enables pacing at an optimal location to maximize response while avoiding increasing VT risk.…”

“…The primary aim of this study was to investigate the relative arrhythmogenic risk of endocardial pacing compared with epicardial pacing. We also investigated the role of pacing location relative to scar during endocardial pacing, as done previously for epicardial pacing, 5 and the role of the direction of transmural propagation during endocardial and epicardial pacing on VT risk. We used a virtual cohort of patient-specific computational models of LV anatomy, scar, and border zone (BZ) to run electrophysiological (EP) simulations and compute dispersion of repolarization as a surrogate for VT risk.…”

“…We used a virtual cohort of patient-specific computational models of LV anatomy, scar, and border zone (BZ) to run electrophysiological (EP) simulations and compute dispersion of repolarization as a surrogate for VT risk. 5 …”