Abstract:ObjectivesTo describe a cohort of patients with arrhythmogenic left ventricular cardiomyopathy (ALVC), focusing on the spectrum of the clinical presentations.MethodsPatients were retrospectively evaluated between January 2012 and June 2020. Diagnosis was based on (1) ≥3 contiguous segments with subepicardial/midwall late gadolinium enhancement in the left ventricle (LV) at cardiac magnetic resonance plus a likely pathogenic/pathogenic arrhythmogenic cardiomyopathy (AC) associated genetic mutation and/or famili… Show more
“…Of the remaining 35 articles, 23 were excluded as consisting of case reports, and 3 due to the presence of duplicate data in other selected papers of the same research group [ 6 , 7 , 17 ]. Overall, 9 papers were finally considered for this review ( Table 1 ) [ 5 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. A PRISMA flow diagram depicts the flow of information through the different literature review phases ( Figure 1 ).…”
Section: Resultsmentioning
confidence: 99%
“…While in the last few years the possible role of inflammation in ACM onset and progression led to a significant number of publications, few detailed clinical studies on a large cohort of patients with “hot-phases” can be found [ 23 , 24 , 25 , 26 ]. We were able to select only 9 studies describing cohorts of patients affected with ACM who showed myocarditis-like episodes [ 5 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. This is probably due to the low prevalence of these episodes in the overall ACM population, and on the other hand, to the problem of differential diagnosis with acute myocarditis.…”
Section: Discussionmentioning
confidence: 99%
“…It should be emphasized that in two of our selected studies, one of the inclusion criteria was the presence of pathogenic variant of the DSP gene, and this may have resulted in an overestimation of the incidence of hot-phase episodes in this genotype [ 14 , 15 ]. Despite this, even excluding these two studies, DSP remains the gene most frequently found associated with hot-phase [ 8 , 10 , 11 , 12 , 13 , 14 , 16 ]. On the other hand, genetic variants of PKP2 and DSG2 were detected in 17% of cases.…”
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.
“…Of the remaining 35 articles, 23 were excluded as consisting of case reports, and 3 due to the presence of duplicate data in other selected papers of the same research group [ 6 , 7 , 17 ]. Overall, 9 papers were finally considered for this review ( Table 1 ) [ 5 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. A PRISMA flow diagram depicts the flow of information through the different literature review phases ( Figure 1 ).…”
Section: Resultsmentioning
confidence: 99%
“…While in the last few years the possible role of inflammation in ACM onset and progression led to a significant number of publications, few detailed clinical studies on a large cohort of patients with “hot-phases” can be found [ 23 , 24 , 25 , 26 ]. We were able to select only 9 studies describing cohorts of patients affected with ACM who showed myocarditis-like episodes [ 5 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. This is probably due to the low prevalence of these episodes in the overall ACM population, and on the other hand, to the problem of differential diagnosis with acute myocarditis.…”
Section: Discussionmentioning
confidence: 99%
“…It should be emphasized that in two of our selected studies, one of the inclusion criteria was the presence of pathogenic variant of the DSP gene, and this may have resulted in an overestimation of the incidence of hot-phase episodes in this genotype [ 14 , 15 ]. Despite this, even excluding these two studies, DSP remains the gene most frequently found associated with hot-phase [ 8 , 10 , 11 , 12 , 13 , 14 , 16 ]. On the other hand, genetic variants of PKP2 and DSG2 were detected in 17% of cases.…”
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.
“…In addition, Casella et al (2020) evaluated a series of ALVC patients and among 12 with a positive genetic result found three DSG2 and 9 DSP genetic variant carriers [ 75 ]. Recently, Graziosi et al (2022) described a large series of ALVC patients and reported the presence of genetic variants of SCN5A and TMEM43 genes [ 76 ].…”
In recent years a phenotypic variant of Arrhythmogenic cardiomyopathy has been described, characterized by predominant left ventricular (LV) involvement with no or minor right ventricular abnormalities, referred to as Arrhythmogenic left ventricular cardiomyopathy (ALVC). Different disease-genes have been identified in this form, such as Desmoplakin (DSP), Filamin C (FLNC), Phospholamban (PLN) and Desmin (DES). The main purpose of this critical systematic review was to assess the level of knowledge on genetic background and clinical features of ALVC. A search (updated to April 2022) was run in the PubMed, Scopus, and Web of Science electronic databases. The search terms used were “arrhythmogenic left ventricular cardiomyopathy” OR “arrhythmogenic cardiomyopathy” and “gene” OR “arrhythmogenic dysplasia” and “gene”. The most represented disease-gene turned out to be DSP, accounting for half of published cases, followed by FLNC. Overall, ECG abnormalities were reported in 58% of patients. Major ventricular arrhythmias were recorded in 26% of cases; an ICD was implanted in 29% of patients. A total of 6% of patients showed heart failure symptoms, and 15% had myocarditis-like episodes. DSP is confirmed to be the most represented disease-gene in ALVC patients. An analysis of reported clinical features of ALVC patients show an important degree of electrical instability, which frequently required an ICD implant. Moreover, myocarditis-like episodes are common.
“…The phenotypic spectrum of DSP cardiomyopathy is wide ( Table 1 ) [ 20 ]. 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 ].…”
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.
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