Abstract 5934: Arrhythmogenic Right Ventricular Cardiomyopathy Due to Desmosomal Gene Mutations Is a Progressive Biventricular Disease

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Cristina Basso ◽  
Elisa Carturan ◽  
Nikos Protonotarios ◽  
Barbara Bauce ◽  
Alessandra Rampazzo ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Fatty Infiltration ◽  
Gene Mutations ◽  
Ventricular Myocardium ◽  
Relative Role ◽  
Inherited Disease ◽  
Ventricular Cardiomyopathy ◽  
Pathologic Features ◽  
Fatty Replacement

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by a gradual loss of myocytes with fibro-fatty replacement. Mutations of gene encoding desmosomal proteins have been demonstrated in up to 50% of probands. The aim of this study was to assess the morphologic spectrum and the relative role of viruses on genotyped ARVC hearts. Design: Fourteen ARVC hearts (10 M/4 F, age range 7–64, mean 30 yrs), coming from sudden death (8), cardiac transplantation (4), heart failure (1) and extracardiac death (1) were investigated. Familial recurrence of ARVC was ascertained in 12 (86%). Genetic screening identified pathogenetic mutations in plakophilin-2 (5), desmoplakin (4), desmoglein-2 (2) and plakoglobin (3). Five hearts from patients with in ryanodine receptor 2 (Ryr2) gene mutations were also investigated. Morphopathologic investigation consisted of gross examination, histology, immunohistochemistry and molecular pathology (PCR) for cardiotropic viruses. Result: Cardiac involvement was biventricular in all but 1 case, a 7 year old girl who died of extracardiac causes and presented a structurally normal heart. Ventricular myocardium abnormalities consisted of fibro-fatty replacement in 12 cases and of subepicardial myocyte necrosis with acute inflammation and granulation tissue in a 15 year old boy who died suddenly. Inflammatory infiltrates were evident in 93% of cases, either diffuse (23%) or focal (77%), and mostly consisted of T-lymphocytes and macrophages. Molecular investigation was negative in all but one with Hepatitis C virus (7%). Ryr2 gene hearts showed only mild fatty infiltration confined to the antero-apical wall of the right ventricle. Conclusion: ARVC hearts from patients with desmosomal gene mutations are characterized by biventricular myocardial atrophy and fibro-fatty replacement. In early adolescence, the phenotype can be either absent or consistent with acute myocyte damage without fibro-fatty replacement, thus confirming the progressive nature of the disease. While myocarditis is a usual feature, viral genome is exceptionally detected in the myocardium as to support the reactive nature of inflammation. The pathologic features of Ryr2 hearts are not in keeping with ARVC.

Evidence-based management of arrhythmogenic right ventricular cardiomyopathy in pregnancy

2020 ◽  
Author(s):  
Jagjit Khosla ◽  
Reshma Golamari ◽  
Alice Cai ◽  
Jamal Benson ◽  
Wilbert S Aronow ◽  
...  
Keyword(s):  
Heart Failure ◽  
Right Ventricular ◽  
Retrospective Studies ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Genetic Disorder ◽  
Ventricular Myocardium ◽  
Evidence Based ◽  
Ventricular Cardiomyopathy ◽  
Genes Encoding ◽  
In Pregnancy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder resulting in fibrofatty replacement of the myocardium. Genetic mutations in genes encoding for desmosome proteins result in a ventricular myocardium prone to arrhythmias and heart failure. Although ARVC is known for a few decades, most of the outcomes in pregnancy are reported recently. Pregnancy leads to significant physiological changes with excess mechanical stress on the myocardium. All the retrospective studies suggest that pregnancy is well tolerated in these patients despite the high risk of arrhythmias and heart failure. Our review focuses on the most up-to-date evidence on the management of ARVC patients during the antepartum and postpartum period.

Myocyte Transdifferentiation

2000 ◽  
Vol 124 (2) ◽  
pp. 287-290 ◽  
Author(s):  
Giulia d'Amati ◽  
Cira R. T. di Gioia ◽  
Carla Giordano ◽  
Pietro Gallo
Keyword(s):  
Right Ventricular ◽  
Transplant Patient ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Ventricular Myocardium ◽  
Ventricular Cardiomyopathy ◽  
Familial Dilated Cardiomyopathy ◽  
Familial Cardiomyopathy ◽  
New Type ◽  
The Right ◽  
Gross Examination

Abstract Adipose substitution of ventricular myocardium is characteristic of arrhythmogenic right ventricular cardiomyopathy, but is also found in other heart conditions. It is thought to be a consequence of myocyte loss due to myocarditis or other noxious stimuli. We describe a unique case of cardiomyopathy with a morphologic pattern suggestive of transdifferentiation from myocytes to mature adipocytes. Gross, histologic, and ultrastructural examination were performed on the heart of a female transplant patient with a clinical diagnosis of familial dilated cardiomyopathy. Gross examination showed fibroadipose substitution of the left ventricle and adipose replacement of the right. Histology, immunohistochemistry, and ultrastructure were highly suggestive of transdifferentiation from cardiac muscle to adipose tissue. Myocyte transdifferentiation could represent an alternative pathogenetic pathway to the myocyte-loss and adipose-replacement mechanism in arrhythmogenic right ventricular cardiomyopathy, or it could be the basis of a new type of familial cardiomyopathy.

scholarly journals Characteristics of Patients With Arrhythmogenic Left Ventricular Cardiomyopathy

2020 ◽  
Vol 13 (12) ◽  
Author(s):  
Michela Casella ◽  
Alessio Gasperetti ◽  
Rita Sicuso ◽  
Edoardo Conte ◽  
Valentina Catto ◽  
...  
Keyword(s):  
Late Gadolinium Enhancement ◽  
Right Ventricular ◽  
Genetic Variants ◽  
Task Force ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Left Ventricular ◽  
Ventricular Cardiomyopathy ◽  
Gadolinium Enhancement ◽  
Voltage Mapping ◽  
Fatty Replacement

Background: Arrhythmogenic left ventricular cardiomyopathy (ALVC) is an under-characterized phenotype of arrhythmogenic cardiomyopathy involving the LV ab initio. ALVC was not included in the 2010 International Task Force Criteria for arrhythmogenic right ventricular cardiomyopathy diagnosis and data regarding this phenotype are scarce. Methods: Clinical characteristics were reported from all consecutive patients diagnosed with ALVC, defined as a LV isolated late gadolinium enhancement and fibro-fatty replacement at cardiac magnetic resonance plus genetic variants associated with arrhythmogenic right ventricular cardiomyopathy and of an endomyocardial biopsy showing fibro-fatty replacement complying with the 2010 International Task Force Criteria in the LV. Results: Twenty-five patients ALVC (53 [48–59] years, 60% male) were enrolled. T wave inversion in infero-lateral and left precordial leads were the most common ECG abnormalities. Overall arrhythmic burden at study inclusion was 56%. Cardiac magnetic resonance showed LV late gadolinium enhancement in the LV lateral and posterior basal segments in all patients. In 72% of the patients an invasive evaluation was performed, in which electroanatomical voltage mapping and electroanatomical voltage mapping-guided endomyocardial biopsy showed low endocardial voltages and fibro-fatty replacement in areas of late gadolinium enhancement presence. Genetic variants in desmosomal genes (desmoplakin and desmoglein-2) were identified in 12/25 of the cohort presenting pathogenic/likely pathogenic variants. A definite/borderline 2010 International Task Force Criteria arrhythmogenic right ventricular cardiomyopathy diagnosis was reached only in 11/25 patients. Conclusions: ALVC presents with a preferential involvement of the lateral and postero-lateral basal LV and is associated mostly with variants in desmoplakin and desmoglein-2 genes. An amendment to the current International Task Force Criteria is reasonable to better diagnose patients with ALVC.

scholarly journals Possibility of the Subcutaneous Implantable Cardioverter-Defibrillator for Prevention of Sudden Cardiac Death in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy

2021 ◽  
Author(s):  
Shingo Sasaki
Keyword(s):  
Sudden Cardiac Death ◽  
Right Ventricular ◽  
Implantable Cardioverter Defibrillator ◽  
Cardiac Death ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Young Patients ◽  
Ventricular Myocardium ◽  
Hereditary Disease ◽  
Ventricular Cardiomyopathy ◽  
Cardioverter Defibrillator

The EMBLEM™ entirely subcutaneous implantable cardioverter-defibrillator (S-ICD) system (Boston Scientific, Marlborough, Massachusetts, USA) was introduced as a new alternative to the conventional transvenous implantable cardioverter-defibrillator and has been expected to reduce device-related complications, especially in young patients who require long-term lead placement. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a well-known hereditary disease recognized as a cause of sudden cardiac death (SCD) in young adults. However, the precise clinical role of S-ICD in patients with ARVC remains to be defined because of the low QRS amplitude of subcutaneous electrocardiogram (S-ECG) followed by the high incidence of inappropriate shock (IAS) delivery due to oversensing. It is well known that the sensing of S-ICD is largely dependent on the QRS/T ratio of S-ECG. The decrease in the QRS amplitude is more likely to lead to oversensing such as T wave or myopotential oversensing. In patients with ARVC, the decrease in the QRS amplitude due to degeneration of the right ventricular myocardium progresses overtime. In this chapter, we would like to discuss the usefulness of S-ICD lead repositioning for young adult patients with ARVC based on our experience of patients with IAS.

scholarly journals Spectrum of desmosomal gene variations in patients with arrhythmogenic right ventricular cardiomyopathy

2021 ◽  
Vol 26 (10) ◽  
pp. 4692
Author(s):  
A. G. Shestak ◽  
O. V. Blagova ◽  
Yu. A. Lutokhina ◽  
S. L. Dzemeshkevich ◽  
E. V. Zaklyazminskaya
Keyword(s):  
Right Ventricular ◽  
Genetic Variants ◽  
Diagnostic Yield ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Severe Disease ◽  
Positive Family History ◽  
Gene Mutations ◽  
Ventricular Cardiomyopathy ◽  
Detection Of Mutations ◽  
Class Iv

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary myocardial disease with a high risk of sudden cardiac death. The most common genetic forms of the disease are associated with desmosomal gene mutations.Aim. To study the prevalence of desmosomal forms of ARVC and to analyze variations in the PKP2, DSG2, DSP, DSC2 and JUP genes in a sample of Russian patients with ARVC.Material and methods. Included patients with ARVC underwent resting electrocardiography (ECG), 24-hour Holter ECG monitoring, echocardiography, chest x-ray, myocardial biopsy (if indicated), contrast-enhanced cardiac magnetic resonance imaging. All patients underwent medical genetic counseling. Mutations in the PKP2, DSG2, DSP, DSC2, and JUP genes was detected using highthroughput sequencing on the IonTorrent platform, followed by Sanger sequencing of uncovered gene regions. The pathogenicity of identified genetic variations was assessed according to modern guidelines.Results. ARVC was established in 80 Russian unrelated patients. More than half of the probands (57%) in the study sample had definite diagnosis of ARVC, while 30% and 13% — borderline and possible ARVC, respectively. A positive family history of heart disease and/or SCD was noted in 30%. Genetic variants of pathogenicity class IV-V were detected in 15 (18,75%) probands in the PKP2, DSG2, DSP genes. The detection of genetic variants of pathogenicity class IV-V was different in the subgroups of patients with varying degrees of diagnosis reliability: 13 probands (28,3%) in the subgroup with definite ARVC and 2 probands (8,3%) in the subgroup with borderline ARVC. No genotype-positive probands were found in the subgroup with possible ARVC. Variations of unknown clinical significance were found in 13 (16,25%) probands.Conclusion. The diagnostic yield of the desmosomal genes PKP2, DSG2, DSP, DSC2, and JUP was 19% with initial diagnosis of ARVC. The detection of mutations was significantly higher in patients with definite ARVC and severe disease manifestations.

scholarly journals An International Evidence Based Reappraisal of Genes Associated with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) using the ClinGen Framework

2021 ◽  
Author(s):  
Cynthia A. James ◽  
Jan D.H. Jongbloed ◽  
Ray E. Hershberger ◽  
Ana Morales ◽  
Daniel P. Judge ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Ventricular Arrhythmias ◽  
Task Force ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Model Systems ◽  
Polymorphic Ventricular Tachycardia ◽  
Inherited Disease ◽  
Ventricular Cardiomyopathy ◽  
Moderate Evidence ◽  
Major Criterion

Background - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by ventricular arrhythmias and progressive ventricular dysfunction. Genetic testing is recommended and a pathogenic variant in an ARVC-associated gene is a major criterion for diagnosis according to the 2010 Task Force Criteria (TFC). As incorrect attribution of a gene to ARVC can contribute to misdiagnosis, we assembled an international multidisciplinary ARVC ClinGen Gene Curation Expert Panel to reappraise all reported ARVC genes. Methods - Following a comprehensive literature search, six two-member teams conducted blinded independent curation of reported ARVC genes using the semi-quantitative ClinGen framework. Results - Of 26 reported ARVC genes, only six ( PKP2 , DSP , DSG2 , DSC2 , JUP , TMEM43 ) had strong evidence and were classified as definitive for ARVC causation. There was moderate evidence for two genes, DES and PLN . The remaining 18 genes had limited or no evidence. RYR2 was refuted as an ARVC gene since clinical data and model systems exhibited a catecholaminergic polymorphic ventricular tachycardia (CPVT) phenotype. In ClinVar, only 5 pathogenic / likely pathogenic (P/LP) variants (1.1%) in limited evidence genes had been reported in ARVC cases in contrast to 450 desmosome gene variants (97.4%). Conclusions - Using the ClinGen approach to gene-disease curation, only eight genes, ( PKP2 , DSP , DSG2 , DSC2 , JUP , TMEM43 , PLN , DES ) had definitive or moderate evidence for ARVC and these genes accounted for nearly all P/LP ARVC variants in ClinVar. Therefore, only P/LP variants in these eight genes should yield a major criterion for ARVC diagnosis. P/LP variants identified in other genes in a patient should prompt further phenotyping as variants in many of these genes are associated with other cardiovascular conditions.

scholarly journals Role of ventricular tachycardia ablation in arrhythmogenic right ventricular cardiomyopathy

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Alberto Cipriani ◽  
Riccardo Bariani ◽  
Manuel De Lazzari ◽  
Federico Migliore ◽  
Carlo Angheben ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Catheter Ablation ◽  
Right Ventricular ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Ventricular Cardiomyopathy ◽  
Ventricular Tachycardia Ablation ◽  
Fatty Replacement ◽  
Technical Issues ◽  
Long Term Prognosis

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive fibro-fatty replacement of the myocardium that represents the substrate for recurrent sustained ventricular tachycardia (VT). These arrhythmias characterize the clinical course of a sizeable proportion of patients and have significant implications for their quality of life and long-term prognosis. Antiarrhythmic drugs are often poorly tolerated and usually provide incomplete control of arrhythmia relapses. Catheter ablation is a potentially effective strategy to treat frequent VT episodes and ICD shocks in ARVC patients. The aims of this review are to discuss the electrophysiological and electroanatomic substrates of ventricular tachycardia in patients with ARVC and to analyze the role of catheter ablation in their management with particular reference to selection of patients, technical issues, potential complications and outcomes.

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