A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients.

The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331).

Cardiomyopathies in children: An overview.

Paediatric cardiomyopathies form a heterogeneous group of disorders characterized by structural and electrical abnormalities of the heart muscle, commonly due to a gene variant of the myocardial cell structure. Mostly inherited as a dominant or occasionally recessive trait, they might be part of a syndromic disorder of underlying metabolic or neuromuscular defects or combine early developing extracardiac abnormalities (i.e.

Importance of genotype for risk stratification in arrhythmogenic right ventricular cardiomyopathy using the 2019 ARVC risk calculator.

Aims: To study the impact of genotype on the performance of the 2019 risk model for arrhythmogenic right ventricular cardiomyopathy (ARVC).

Methods And Results: 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.

Analysis of buccal mucosa as a prognostic tool in children with arrhythmogenic cardiomyopathy.

Background: The diagnosis of arrhythmogenic cardiomyopathy (ACM) is challenging especially in children at risk of adverse events. Analysis of cardiac myocyte junctional protein distribution may have diagnostic and prognostic implications, but its utility is limited by the need for a myocardial sample. We previously reported that buccal mucosa cells show junctional protein redistribution similar to that seen in cardiac myocytes of adult patients with ACM.

Arrhythmogenic Right Ventricular Cardiomyopathy in Pediatric Patients: An Important but Underrecognized Clinical Entity.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by fibrofatty infiltration of predominantly the right ventricular (RV) myocardium. Affected patients typically present as young adults with hemodynamically stable ventricular tachycardia, although pediatric cases are increasingly recognized. These young subjects often have a more severe phenotype with a high risk of sudden cardiac death (SCD) and progression toward heart failure.

Clinical and Molecular Aspects of Naxos Disease.

Naxos disease is a recessively inherited pattern of arrhythmogenic cardiomyopathy with palmoplantar keratoderma and woolly hair. The causative mutation identified in plakoglobin protein gene indicated a potential role of the desmosomal protein complex as culprit for cardiomyopathy. In the context of a family, the early evident cutaneous features may serve as a clinical screening tool to spot arrhythmogenic cardiomyopathy in subclinical stage.

Definition and treatment of arrhythmogenic cardiomyopathy: an updated expert panel report.

It is 35 years since the first description of arrhythmogenic right ventricular cardiomyopathy (ARVC) and more than 20 years since the first reports establishing desmosomal gene mutations as a major cause of the disease. Early advances in the understanding of the clinical, pathological and genetic architecture of ARVC resulted in consensus diagnostic criteria, which proved to be sensitive but not entirely specific for the disease. In more recent years, clinical and genetic data from families and the recognition of a much broader spectrum of structural disorders affecting both ventricles and associated with a propensity to ventricular arrhythmia have raised many questions about pathogenesis, disease terminology and clinical management.

Common presentation of rare diseases: Arrhythmogenic right ventricular cardiomyopathy and its mimics.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is the most common phenotype described within the spectrum of arrhythmogenic cardiomyopathies. It usually presents in early adolescence with severe ventricular arrhythmias along with cardiac structural and functional alterations mainly of the right ventricular myocardium. Though the estimated prevalence of ARVC in the general population is only 1:5000, it represents one of the most common causes of juvenile sudden death.

Characterizing the Molecular Pathology of Arrhythmogenic Cardiomyopathy in Patient Buccal Mucosa Cells.

Background: Analysis of myocardium has revealed mechanistic insights into arrhythmogenic cardiomyopathy but cardiac samples are difficult to obtain from probands and especially from family members. To identify a potential surrogate tissue, we characterized buccal mucosa cells.

Methods And Results: Buccal cells from patients, mutation carriers, and controls were immunostained and analyzed in a blinded fashion.

Treatment of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia: An International Task Force Consensus Statement.

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Clinical Significance of Epsilon Waves in Arrhythmogenic Cardiomyopathy.

Introduction: Epsilon waves are hallmark features of arrhythmogenic cardiomyopathy (ACM) but information about their clinical significance is variable. We evaluated epsilon wave prevalence, characteristics, and their clinical significance in an ACM population.

Methods And Results: Eighty-six unselected patients fulfilling the 2010 Task Force criteria were enrolled.

Arrhythmic risk assessment in genotyped families with arrhythmogenic right ventricular cardiomyopathy.

Aims: Arrhythmogenic right-ventricular cardiomyopathy (ARVC) is a genetically determined disorder, mostly caused by mutations in genes encoding desmosomal proteins. We evaluated phenotype/genotype characteristics to predict the risk for the first major arrhythmic event in desmosomal-mutation-associated ARVC families.

Methods And Results: A cohort of 105 desmosomal-mutation carriers belonging to 39 consecutive ARVC families was evaluated.

Altered desmosomal proteins in granulomatous myocarditis and potential pathogenic links to arrhythmogenic right ventricular cardiomyopathy.

Background: Immunoreactive signal for the desmosomal protein plakoglobin (γ-catenin) is reduced at cardiac intercalated disks in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a highly arrhythmogenic condition caused by mutations in genes encoding desmosomal proteins. Previously, we observed a false-positive case in which plakoglobin signal was reduced in a patient initially believed to have ARVC but who actually had cardiac sarcoidosis. Sarcoidosis can masquerade clinically as ARVC but has not been previously associated with altered desmosomal proteins.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia on the basis of the revised diagnostic criteria in affected families with desmosomal mutations.

Aims: To evaluate arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) in affected families with desmosome mutations on the basis of the recently revised Task Force Criteria (TFC).

Methods And Results: One hundred and three consecutive carriers of pathogenic desmosome mutations and 102 mutation-negative relatives belonging to 22 families with dominant and 14 families with recessive ARVC/D were evaluated according to the original and revised TFC. Serial cardiac assessment with 12-lead, signal-averaged, and 24 h ambulatory ECG and two-dimensional echocardiography was performed.

Mechanistic insights into arrhythmogenic right ventricular cardiomyopathy caused by desmocollin-2 mutations.

Aims: Recent immunohistochemical studies observed the loss of plakoglobin (PG) from the intercalated disc (ID) as a hallmark of arrhythmogenic right ventricular cardiomyopathy (ARVC), suggesting a final common pathway for this disease. However, the underlying molecular processes are poorly understood.

Methods And Results: We have identified novel mutations in the desmosomal cadherin desmocollin 2 (DSC2 R203C, L229X, T275M, and G371fsX378).

Isolated left ventricular apical hypoplasia: a newly recognized unclassified cardiomyopathy.

We describe two relatively asymptomatic cases diagnosed with the newly recognized unclassified cardiomyopathy, isolated left ventricular apical hypoplasia. The disease has been described mainly in cardiac magnetic resonance, whereas this study presents the echocardiographic characteristics of this new cardiomyopathy.