Inflammatory Hot Phases in Arrhythmogenic Cardiomyopathy

Abstract

Arrhythmogenic cardiomyopathy (ACM) has traditionally been conceptualized as a progressive inherited cardiomyopathy characterized by fibrofatty replacement and ventricular arrhythmias. Emerging clinical and translational evidence suggests that selected patients experience episodic inflammatory exacerbations, or "hot phases," that mimic acute myocarditis and may accelerate myocardial injury, scar formation, and arrhythmic vulnerability. Proposed mechanisms include desmosomal instability, maladaptive mechanotransduction, inflammasome activation, cytokine signaling, and humoral immune reactivity, including anti-desmoglein-2 responses. Cardiac magnetic resonance tissue characterization, particularly T2 mapping combined with late gadolinium enhancement, may help distinguish active edema from chronic scar and support genotype-informed phenotyping. This review synthesizes mechanistic, imaging, genetic, and electrophysiologic evidence for the ACM hot-phase paradigm and proposes a structured approach to evaluation. At present, suspected hot phase should prompt exclusion of mimics, rhythm surveillance, genotype assessment, family screening, and standard ACM risk-based care, whereas immunomodulatory therapy remains investigational or context-dependent.