Myocarditis-like Episodes in Patients with Arrhythmogenic Cardiomyopathy: A Systematic Review on the So-Called Hot-Phase of the Disease

Abstract

Arrhythmogenic cardiomyopathy (ACM) is a genetically determined myocardial disease, characterized by myocytes necrosis with fibrofatty substitution and ventricular arrhythmias that can even lead to sudden cardiac death. The presence of inflammatory cell infiltrates in endomyocardial biopsies or in autoptic specimens of ACM patients has been reported, suggesting a possible role of inflammation in the pathophysiology of the disease. Furthermore, chest pain episodes accompanied by electrocardiographic changes and troponin release have been observed and defined as the “hot-phase” phenomenon. The aim of this critical systematic review was to assess the clinical features of ACM patients presenting with “hot-phase” episodes. According to PRISMA guidelines, a search was run in the PubMed, Scopus and Web of Science electronic databases using the following keywords: “arrhythmogenic cardiomyopathy”; “myocarditis” or “arrhythmogenic cardiomyopathy”; “troponin” or “arrhythmogenic cardiomyopathy”; and “hot-phase”. A total of 1433 titles were retrieved, of which 65 studies were potentially relevant to the topic. Through the application of inclusion and exclusion criteria, 9 papers reporting 103 ACM patients who had experienced hot-phase episodes were selected for this review. Age at time of episodes was available in 76% of cases, with the mean age reported being 26 years ± 14 years (min 2–max 71 years). Overall, 86% of patients showed left ventricular epicardial LGE. At the time of hot-phase episodes, 49% received a diagnosis of ACM (Arrhythmogenic left ventricular cardiomyopathy in the majority of cases), 19% of dilated cardiomyopathy and 26% of acute myocarditis. At the genetic study, Desmoplakin (DSP) was the more represented disease-gene (69%), followed by Plakophillin-2 (9%) and Desmoglein-2 (6%). In conclusion, ACM patients showing hot-phase episodes are usually young, and DSP is the most common disease gene, accounting for 69% of cases. Currently, the role of “hot-phase” episodes in disease progression and arrhythmic risk stratification remains to be clarified.

Evaluation of autoantibodies to desmoglein-2 in dogs with and without cardiac disease

“…Myocardial lymphocytic infiltration has also been shown in Boxers with ARVC and such inflammation was significantly associated with dogs that experienced sudden cardiac death. 4 In humans, such myocardial inflammation is thought to be associated with the so called “hot phase” of disease in which patients are often initially misdiagnosed with myocarditis and may be associated with more severe arrhythmias and a greater risk of sudden cardiac death 6 , 30 . Again, it remains unclear whether this inflammation results in cardiomyocyte death and progression of disease or is the immune system’s reaction to cardiomyocyte destruction.…”

Myocarditis as a trigger for the expression of biventricular arrhythmogenic cardiomyopathy in desmosomal gene mutation

“…We propose that in this case the earlier myocarditis could have been the trigger to the gene expression of BVACM on a background of desmosomal gene mutation. Animal studies suggest that inflammation has a role in the pathogenesis of ACM in desmosomal form of disease, 13,14 however, this has not been translated to human disease 15 …”

Desmoplakin Cardiomyopathy: Comprehensive Review of an Increasingly Recognized Entity

“…The main clinical presentations include extensive subepicardial late gadolinium enhancement (LGE) on CMR, which is often disproportionate to the degree of LV dysfunction, in association with frequent premature ventricular contractions (PVC) and a propensity to life-threatening ventricular arrhythmias [ 9 , 17 , 18 , 19 ]. Another cardinal clinical feature of DSP cardiomyopathy is the occurrence of recurrent “myocarditis-like” episodes of chest pain with documented myocardial injury [ 19 , 21 ].…”

“…The presence of inflammatory cell infiltrates in endomyocardial biopsies or autopsy samples has been reported in ACM patients since the first description of the disease in the early 1980s, thus suggesting a possible role of inflammation in its pathophysiology [ 5 , 21 ].…”

“…The majority of papers reporting the occurrence of “hot phases” consists of case reports. In a recent systematic review including 103 ACM patients with these myocarditis-like episodes, DSP was also the most frequently implicated gene (69%) [ 21 ]. Furthermore, patients were mostly young (mean age 26 ± 14 years) and affected by ALVC forms (68%).…”