‘Hot phase’ clinical presentation in arrhythmogenic cardiomyopathy

Abstract

Aims The aim of this study is to evaluate the clinical features of patients affected by arrhythmogenic cardiomyopathy (AC), presenting with chest pain and myocardial enzyme release in the setting of normal coronary arteries (‘hot phase’). Methods and results We collected detailed anamnestic, clinical, instrumental, genetic, and histopathological findings as well as follow-up data in a series of AC patients who experienced a hot phase. A total of 23 subjects (12 males, mean age at the first episode 27 ± 16 years) were identified among 560 AC probands and family members (5%). At first episode, 10 patients (43%) already fulfilled AC diagnostic criteria. Twelve-lead electrocardiogram recorded during symptoms showed ST-segment elevation in 11 patients (48%). Endomyocardial biopsy was performed in 11 patients, 8 of them during the acute phase showing histologic evidence of virus-negative myocarditis in 88%. Cardiac magnetic resonance was performed in 21 patients, 12 of them during the acute phase; oedema and/or hyperaemia were detected in 7 (58%) and late gadolinium enhancement in 11 (92%). At the end of follow-up (mean 17 years, range 1–32), 12 additional patients achieved an AC diagnosis. Genetic testing was positive in 77% of cases and pathogenic mutations in desmoplakin gene were the most frequent. No patient complained of sustained ventricular arrhythmias or died suddenly during the ‘hot phase’. Conclusion ‘Hot phase’ represents an uncommon clinical presentation of AC, which often occurs in paediatric patients and carriers of desmoplakin gene mutations. Tissue characterization, family history, and genetic test represent fundamental diagnostic tools for differential diagnosis.

Sudden Death without a Clear Cause after Comprehensive Investigation: An Example of Forensic Approach to Atypical/Uncertain Findings

“…However, this feature was only found in the antero-lateral region of the right ventricle, a localization that is typical of physiological conditions [ 38 ]. Moreover, the fatty infiltration was clearly separated by the myocardium, and there were no signs of necrosis/atrophy of the myocytes (that are typical of ACM), no fibrous or fibro-fatty infiltration of the myocardium (common among young cases of ACM) and no inflammatory infiltrates (that can be present, for example, in ACM hot phases, i.e., the phases of acute myocarditis that can suddenly complicate the disease) [ 37 , 39 ]. Finally, NGS found no variant pathogenic for ACM.…”

Acute Myocardial Infarction-Like Events in Related Patients With a Desmoplakin-Associated Arrhythmogenic Cardiomyopathy

“…The pathophysiology of myocyte death and fibrofatty infiltration in ACM is incompletely understood. It has been proposed that the disease progresses in “hot phases” representative of acute necrosis rather than gradual apoptosis ( 1 , 4 , 6 , 7 , 8 ). This is consistent with the injury sequence observed in these 2 patients.…”

Arrhythmogenic Cardiomyopathy—Current Treatment and Future Options

“…The presence of inflammatory infiltrates (mainly T-cells) among dying myocytes has been demonstrated in histopathologic analysis of ventricular myocardium at postmortem or in experimental studies on transgenic animals, raising questions about the role of the immune system in the pathogenesis of the disease [2,3]. Arrhythmogenic cardiomyopathy in its early stages may present with acute chest pain and troponins release ("hot phase"), which resembles the infarct-like manifestation of some clinically suspected myocarditis [2,[32][33][34]. The presence of autoantibodies has been reported in ACM patients and in their relatives, with a positive status being more frequent in a familial than in a sporadic pattern [35,36].…”