Precision sampling of discrete sites identified during in-vivo functional testing in the mammalian heart.

Ventricular arrhythmias after myocardial infarction (MI) originate from discrete areas within the MI border zone (BZ), identified during functional electrophysiology tests. Accurate sampling of arrhythmogenic sites for ex-vivo study remains challenging, yet is critical to identify their tissue, cellular and molecular signature. In this study, we developed, validated, and applied a targeted sampling methodology based on individualized 3D prints of the human-sized pig heart.

Electric Field-Based Spatial Analysis of Noncontact Unipolar Electrograms to Map Regional Activation-Repolarization Intervals.

Background: Spatial heterogeneity in repolarization plays an important role in generating and sustaining cardiac arrhythmias. Reliable determination of repolarization times remains challenging.

Objectives: The goal of this study was to improve processing of densely sampled noncontact unipolar electrograms to yield reliable high-resolution activation and repolarization maps.

Heterogeneity of Repolarization and Cell-Cell Variability of Cardiomyocyte Remodeling Within the Myocardial Infarction Border Zone Contribute to Arrhythmia Susceptibility.

Background: After myocardial infarction, the infarct border zone (BZ) is the dominant source of life-threatening arrhythmias, where fibrosis and abnormal repolarization create a substrate for reentry. We examined whether repolarization abnormalities are heterogeneous within the BZ in vivo and could be related to heterogeneous cardiomyocyte remodeling.

Methods: Myocardial infarction was induced in domestic pigs by 120-minute ischemia followed by reperfusion.

Ventricular Arrhythmias in Ischemic Cardiomyopathy-New Avenues for Mechanism-Guided Treatment.

Ischemic heart disease is the most common cause of lethal ventricular arrhythmias and sudden cardiac death (SCD). In patients who are at high risk after myocardial infarction, implantable cardioverter defibrillators are the most effective treatment to reduce incidence of SCD and ablation therapy can be effective for ventricular arrhythmias with identifiable culprit lesions. Yet, these approaches are not always successful and come with a considerable cost, while pharmacological management is often poor and ineffective, and occasionally proarrhythmic.

Discrete sites of frequent premature ventricular complexes cluster within the infarct border zone and coincide with high frequency of delayed afterdepolarizations under adrenergic stimulation.

Background: Sympathetic activation in ischemic heart disease can cause lethal arrhythmias. These often are preceded by premature ventricular complexes (PVCs), which at the cellular level could result from delayed afterdepolarizations.

Objective: The purpose of this study was to identify and map vulnerable areas for arrhythmia initiation after myocardial infarction (MI) and to explore the link between PVCs and cellular events.