Criteria for diagnosis of arrhythmogenic cardiomyopathy (ACM) were first proposed in 1994 and revised in 2010 by a Task Force. Although the Task Force criteria demonstrated a good accuracy for diagnosis of the original right ventricular phenotype (arrhythmogenic right ventricular cardiomyopathy), they lacked sensitivity for identification of the expanding phenotypic spectrum of ACM, which includes left‐sided variants and did not incorporate late‐gadolinium enhancement findings by cardiac magnetic resonance. The 2020 International criteria (“Padua criteria”) have been developed by International experts with the aim to improve the diagnosis of ACM by providing new criteria for the diagnosis of left ventricular phenotypic features. The key upgrade was the incorporation of tissue characterization findings by cardiac magnetic resonance for noninvasive detection of late‐gadolinium enhancement/myocardial fibrosis that are determinants for characterization of arrhythmogenic biventricular and left ventricular cardiomyopathy. The 2020 International criteria are heavily dependent on cardiac magnetic resonance, which has become mandatory to characterize the ACM phenotype and to exclude other diagnoses. New criteria regarding left ventricular depolarization and repolarization ECG abnormalities and ventricular arrhythmias of left ventricular origin were also provided. This article reviews the evolving approach to diagnosis of ACM, going back to the 1994 and 2010 International Task Force criteria and then grapple with the modern 2020 International criteria.

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’). 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’. ‘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.

To study the impact of genotype on the performance of the 2019 risk model for arrhythmogenic right ventricular cardiomyopathy (ARVC). The study cohort comprised 554 patients with a definite diagnosis of ARVC and no history of sustained ventricular arrhythmia (VA). During a median follow-up of 6.0 (3.1,12.5) years, 100 patients (18%) experienced the primary VA outcome (sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator intervention, aborted sudden cardiac arrest, or sudden cardiac death) corresponding to an annual event rate of 2.6% [95% confidence interval (CI) 1.9–3.3]. Risk estimates for VA using the 2019 ARVC risk model showed reasonable discriminative ability but with overestimation of risk. The ARVC risk model was compared in four gene groups: PKP2 (n = 118, 21%); desmoplakin (DSP) (n = 79, 14%); other desmosomal (n = 59, 11%); and gene elusive (n = 160, 29%). Discrimination and calibration were highest for PKP2 and lowest for the gene-elusive group. Univariable analyses revealed the variable performance of individual clinical risk markers in the different gene groups, e.g. right ventricular dimensions and systolic function are significant risk markers in PKP2 but not in DSP patients and the opposite is true for left ventricular systolic function. The 2019 ARVC risk model performs reasonably well in gene-positive ARVC (particularly for PKP2) but is more limited in gene-elusive patients. Genotype should be included in future risk models for ARVC. ARVC, arrhythmogenic right ventricular cardiomyopathy; AUC, area under the curve; ECHO, echocardiography; CMR, cardiac magnetic resonance; HR, hazard ratio; LGE, late gadolinium enhancement; LV, left ventricular; LVEDD, left ventricular enddiastolic diameter; LVEF, left ventricular ejection fraction; PLAX, parasternal long-axis; PVC, premature ventricular complex; RV, right ventricular; RVEDV, right ventricular end-diastolic volume; RVEF, right ventricular ejection fraction; RVOT, right ventricular outflow tract; TWI, T-wave inversion; VT, ventricular tachycardia.

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.

Desmoplakin (DSP) is a desmosomal protein that plays an essential role for cell-to-cell adhesion within the cardiomyocytes. The first association between DSP genetic variants and the presence of a myocardial disease referred to patients with Carvajal syndrome. Since then, several reports have linked the DSP gene to familial forms of arrhythmogenic (ACM) and dilated cardiomyopathies. Left-dominant ACM is the most common phenotype in individuals carrying DSP variants. More recently, a new entity—“Desmoplakin cardiomyopathy”—was described as a distinct form of cardiomyopathy characterized by frequent left ventricular involvement with extensive fibrosis, high arrhythmic risk, and episodes of acute myocardial injury. The purpose of this review was to summarize the available evidence on DSP cardiomyopathy and to identify existing gaps in knowledge that need clarification from upcoming research.

Desmoplakin (DSP) genetic variants have been reported in arrhythmogenic cardiomyopathy with particular regard to predominant left ventricular (LV) involvement. The purpose of this study was to improve our understanding of clinical phenotype and outcome of DSP variant carriers. The clinical picture and outcome of 73 patients (36% probands) harboring a pathogenic/likely pathogenic DSP variant were evaluated. The phenotype during follow-up (mean 11 years; range 1-39 years) changed in 25 patients (35%), arrhythmogenic LV cardiomyopathy (ALVC) forms being the most frequent (n = 26 [36%]), followed by biventricular (BIV; n = 20 [27%]) and arrhythmogenic right ventricular cardiomyopathy (ARVC; n = 16 [22%]) forms. Major ventricular arrhythmias were detected in 21 patients (29%), and they were more common in ARVC (n = 6, 56%) and BIV forms (n = 8, 40%) than in ALVC forms (n = 4, 15%). In patients with ALVC, major ventricular arrhythmias occurred in the setting of a normal/mildly reduced systolic function. Heart failure (HF) occurred in 6 patients (8%); none affected with ALVC. Females showed more commonly LV involvement, while ARVC forms were more frequently detected in males (21 [61%] vs 15 [38%]; P = .147). Males showed a higher incidence of major ventricular arrhythmias (18 [52%] vs 9 [24%]; P = .036), HF (11 [31%] vs 1 [3%]; P = .004), and cardiac death (11 [31%] vs 0 [0%]; P < .001). The clinical phenotype in pathogenic/likely pathogenic DSP variant carriers is wide. Although most patients show LV involvement, 16 (22%) has right ventricular abnormalities in keeping with a "classical" arrhythmogenic cardiomyopathy form. In ALVC, HF and major ventricular arrhythmias seem less common than in right ventricular and BIV variants. Females show more frequently LV involvement and a better outcome.