Investigation of the Presence and Mechanisms of Action Potential Alternans in Hypertrophic Cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder. It is a leading cause of sudden cardiac death in young adults, yet most patients remain asymptomatic. T wave alternans (TWA) have been proposed as a potential tool for HCM risk stratification [1] [2] [3] but the mechanisms at stake remain unclear [4] [5]. HCM has been associated with a dysregulation of Ca 2+ cycling and an elevation in intracellular calcium concentration [6] that may affect the cardiac action potential (AP). Our goal is to investigate whether these electrophysiological abnormalities may be a mechanism responsible for the presence of TWA in HCM. We use a population of 9,118 control and HCM models defined in [7] and measure alternans in AP and Ca 2+ transient biomarkers for pacing cycle lengths from 250ms to 700ms. HCM cardiomyocytes show a distinct AP phenotype with longer AP and Ca 2+ duration (486±84ms vs 286±52ms, 691±82ms vs 522±65ms p<0.001). However, there is no significant difference in alternans propensity in HCM compared to controls, except for AP amplitude at low pacing lengths (300ms: 13.4% HCM models, 2.6% control models, p<0.001). HCM amplitude and duration alternans also presented larger magnitude than Controls. These findings suggest that TWA in HCM may be related to whole-organ tissue heterogeneities rather than an alteration of the cellular substrate.

Tracking the Position of the Heart From Body Surface Potential Maps and Electrograms

“…More systematic experiments on animal models and synthetic data provided methods to estimate the average BSPM and the variance that can occur due to movement of the heart in a subject (MacLeod et al, 2000; Swenson et al, 2011). More recently, cardiac magnetic resonance imaging allowed characterization of the relationship between standard clinical metrics of the ECG and changes in the heart geometry (Lyon et al, 2017) and, specific to ECGI, Cluitmans et al explored the effects of these geometry errors on inverse solutions (Cluitmans and Volders, 2017).…”