Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models

Abstract

Sudden cardiac death (SCD) from arrhythmias is a leading cause of mortality. For patients at high SCD risk, prophylactic insertion of implantable cardioverter defibrillators (ICDs) reduces mortality. Current approaches to identify patients at risk for arrhythmia are, however, of low sensitivity and specificity, which results in a low rate of appropriate ICD therapy. Here, we develop a personalized approach to assess SCD risk in post-infarction patients based on cardiac imaging and computational modelling. We construct personalized three-dimensional computer models of post-infarction hearts from patients' clinical magnetic resonance imaging data and assess the propensity of each model to develop arrhythmia. In a proof-of-concept retrospective study, the virtual heart test significantly outperformed several existing clinical metrics in predicting future arrhythmic events. The robust and non-invasive personalized virtual heart risk assessment may have the potential to prevent SCD and avoid unnecessary ICD implantations.

Figure 1. VARP methodology.

(a) Flow chart summarizing the VARP protocol. (b) Contrast-enhanced cardiac MRI stack (left), with landmark points and splines delineating the endocardial and epicardial surfaces (middle), respectively, and the resulting ventricular segmentation (right) into non-infarcted myocardium, grey zone and scar. (c) High-resolution ventricular structure model (left) with estimated fibre orientations (middle). Although fibre orientation is assigned to each finite element in the computational mesh, a tractography approach is used here to visualize the general fibre orientation. Action potential traces from the non-infarcted myocardium (red) and grey zone (green) are in right panel. (d) VARP pacing sites on the endocardial surface of the ventricles (left panels) and a corresponding colour schematic (right) of the myocardial wall segments (numbered), as per the American Heart Association nomenclature, in which these sites are located. The train of pacing pulses is shown on the bottom right. Additional detail is provided in Methods.

Figure 2. Illustrative examples of VARP results for 9 of the 41 personalized heart models.

Shown is the induced arrhythmia in four hearts (top), for which geometrical models are presented together with electrical activation isochronal maps, obtained following pacing from the site indicated by the star. White arrows represent the direction of propagation of the re-entrant arrhythmias. All induced arrhythmias were monomorphic ventricular tachycardias. The geometrical models of the five hearts, in which no arrhythmia was induced from any pacing site, are shown at the bottom.

Figure 3. Initiation of ventricular tachycardia in patients 1 and 2.

Shown are patient heart geometries and transmembrane potential maps at three time points. White arrows show direction of propagation. The time instant below each map is counted from the delivery of the last pacing stimulus. In patient 1, conduction block occurs in a GZ region located in the anterior portion of the ventricles. The wavefront propagates around that GZ region and forms a figure-of-8 re-entrant circuit. In patient 2, unidirectional block occurs in GZ region located in the septum. The wavefront re-enters via an isthmus of excitable myocardium and forms a re-entrant circuit that eventually anchors to intramural scar. See Supplementary Movies 1 and 2 for corresponding movies of the VT initiation and resulting VTs.