Neuroautonomic stress in familial arrhythmic syndromes

Familial arrhythmic syndromes relate to the inherited cardiac disorders characterized by electrical instability of the myocardium and a high risk of sudden cardiac death (SCD) in young individuals. Among them, catecholaminergic polymorphic ventricular tachycardia (CPVT) is a prototypical non-structural syndrome caused mainly by mutations in the ryanodine receptor 2 (RyR2). Unlike arrhythmogenic cardiomyopathy (ACM), where fibrofatty replacement underlies arrhythmogenesis, CPVT occurs in structurally normal hearts and is triggered primarily by sympathetic activation during physical or emotional stress. The central mechanism involves abnormal intracellular calcium handling, resulting in spontaneous Ca²⁺ release from the sarcoplasmic reticulum, delayed afterdepolarizations (DADs), and ventricular tachycardia. The present work is designed to involve automated methods of analysis and compare it with manual one methods that analyses calcium dynamics in cardiomyocytes from a murine model of CPVT compared with wild-type controls. The focus will be placed on two aspects of calcium handling: paced Ca²⁺ transients, and spontaneous Ca²⁺ release events during β-adrenergic stimulation. These parameters are critical to understanding how RYR2 mutations destabilize excitation–contraction coupling (ECC) under stress conditions. An additional aim of the work is to explore the use of artificial intelligence as a complementary tool for calcium imaging analysis. By applying prompt-based AI workflows, the project seeks to evaluate whether automated methods can reproduce conventional results, reduce analysis time, and improve reproducibility in the study of familial arrhythmic syndromes.