Arrhythmogenic right ventricular cardiomyopathy (ARVC): case report and review of literature.
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ABSTRACT:
SUBMITTER: Rao U
PROVIDER: S-EPMC4832774 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
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Arrhythmogenic right ventricular cardiomyopathy (ARVC): case report and review of literature.
Rao Usha U Agarwal S S Gilbert T J TJ
Heart Asia 20141001 1
Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited condition characterised by fibrofatty replacement of the right ventricle. It causes sudden death in 30% of young adults and in 5% of those less than 65 years of age. As the presentation is non-specific, ARVD can be a diagnostic challenge leading to delayed treatment. We report a case along with the review of literature, of a 63-year-old man who presented (atypical) with a history of palpitations, dizziness and raised cardiac enzym ...[more]
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Project description:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown. We therefore analyzed the transcriptomes of 6 ARVC specimen derived from heart transplantation candidates and compared our findings to 6 non-failing donor hearts (NF) which could not be transplanted for technical reasons. In addition, we compared our findings to 7 hearts from patients with idiopathic dilated cardiomyopathy. From each heart left (LV) and right ventricular (RV) myocardial samples were analyzed by Affymetrix HG-U133 Plus 2.0 arrays, adding up to six sample groups. Unsupervised cluster analyses of the six sample groups revealed a clear separation of NF and cardiomyopathy samples. However, in contrast to the other samples, unsupervised cluster analyses revealed no distinct expression pattern in LV and RV samples from ARVC-hearts. We further identified differentially expressed transcripts using t-tests and found transcripts separating diseased and NF ventricular myocardium. Of note, in failing myocardium only about 15-16% of the genes are commonly regulated compared to NF samples. In addition both cardiomyopathies are clearly distinct on the transcriptome level. Comparison of the expression patterns between the failing RV and LV using a paired t-test revealed a lack of major differences between LV and RV gene expression in ARVC hearts. Microarrays were used to elucidate the differences between non-failing control hearts and those, suffering from arrhythmogenic right ventricular cardiomyopathy (ARVC).
2011-11-30 | E-GEOD-29819 | biostudies-arrayexpress
Project description:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown. We therefore analyzed the transcriptomes of 6 ARVC specimen derived from heart transplantation candidates and compared our findings to 6 non-failing donor hearts (NF) which could not be transplanted for technical reasons. In addition, we compared our findings to 7 hearts from patients with idiopathic dilated cardiomyopathy. From each heart left (LV) and right ventricular (RV) myocardial samples were analyzed by Affymetrix HG-U133 Plus 2.0 arrays, adding up to six sample groups. Unsupervised cluster analyses of the six sample groups revealed a clear separation of NF and cardiomyopathy samples. However, in contrast to the other samples, unsupervised cluster analyses revealed no distinct expression pattern in LV and RV samples from ARVC-hearts. We further identified differentially expressed transcripts using t-tests and found transcripts separating diseased and NF ventricular myocardium. Of note, in failing myocardium only about 15-16% of the genes are commonly regulated compared to NF samples. In addition both cardiomyopathies are clearly distinct on the transcriptome level. Comparison of the expression patterns between the failing RV and LV using a paired t-test revealed a lack of major differences between LV and RV gene expression in ARVC hearts.
2011-11-30 | GSE29819 | GEO
Project description:BackgroundArrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable heart muscle disorder that predominantly affects the right ventricle. Mutations in genes that encode components of desmosomes, the adhesive junctions that connect cardiomyocytes, are the predominant cause of ARVC. A case with novel heterozygous mutation in the LAMA2 gene is reported here. The protein encoded by LAMA2 gene is the α2 chain of laminin-211 protein, which establishes a stable relationship between the muscle fiber membrane and the extracellular matrix. We explored the potential mechanism and the relationship between the mutation and ARVC.Case presentationAt the age of 8, the patient developed syncope and palpitation after exercise. Dynamic electrocardiogram recorded continuous premature ventricular beats, and MRI showed the right ventricle was significantly enlarged and there were many localized distensions at the edge of the right ventricular wall. The patient was diagnosed with ARVC and received heart transplantation at the age of 14 due to severe heart dysfunction. The myocardial histological pathological staining revealed a large amount of fibrosis and adipose migration. Whole exome sequencing (WES) identified the heterozygous mutation in the LAMA2 gene [NM_000426.3: c.8842G > A (p.G2948S)]. This is the first report of these variants. Analysis was performed on genetic disorders to reveal splice site changes and damage to protein structure. LAMA2 p.G2948S predicted unstable protein structure and impaired function. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were established. RNA-seq and the western blot were performed on IPSC-CMs to explore the ARVC-related signaling pathway.ConclusionThis is the first case report to describe an ARVC phenotype in patients possessing a novel LAMA2 c.8842G > A (p.G2948S) mutation. Our results aid in understanding of the pathogenesis of ARVC. The molecular mechanism of LAMA2 leading to ARVC disease still needs further study.
| S-EPMC9339636 | biostudies-literature
Project description:ObjectivesThis study sought to examine the efficacy of empiric antiarrhythmic drugs in a rigorously characterized cohort of arrhythmogenic right ventricular cardiomyopathy (ARVC) patients.BackgroundAntiarrhythmic drugs are important in protecting against ventricular arrhythmias in ARVC, but no studies have provided data in a group rigorously screened for the disease.MethodsAntiarrhythmic medicines were examined in all subjects with implantable cardioverter-defibrillators (ICDs) enrolled in the North American ARVC Registry. A Cox proportional hazards model was used to account for time on each drug, and a hierarchical analysis was performed for repeated measures within individuals.ResultsNinety-five patients were studied, with a mean follow-up of 480 +/- 389 days. Fifty-eight (61%) received beta-blockers, and these medicines were not associated with an increased or decreased risk of ventricular arrhythmias. Sotalol was associated with a greater risk of any clinically relevant ventricular arrhythmia as defined by sustained ventricular tachycardia or ICD therapy (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.02 to 6.39, p = 0.045), but this was not statistically significant after adjusting for potential confounders. An increased risk of any ICD shock and first clinically relevant ventricular arrhythmia while on sotalol remained significant after multivariable adjustment. Those on amiodarone (n = 10) had a significantly lower risk of any clinically relevant ventricular arrhythmia (HR: 0.25, 95% CI: 0.07 to 0.95, p = 0.041), a finding that remained significant after multivariable adjustment.ConclusionsIn a cohort of well-characterized ARVC subjects, neither beta-blockers nor sotalol seemed to be protective. Evidence from a small number of patients suggests that amiodarone has superior efficacy in preventing ventricular arrhythmias.
| S-EPMC2748738 | biostudies-literature
Project description:AimsEnd-stage heart failure necessitating evaluation for heart transplantation is increasingly recognized in arrhythmogenic right ventricular cardiomyopathy (ARVC). These patients present unique challenges in pre-transplant and peri-transplant management given their predominantly right ventricular (RV) failure and propensity for ventricular arrhythmias. We sought to utilize a tertiary ARVC referral and heart transplant centre experience to describe management of a series of patients with ARVC undergoing heart transplantation at our centre.Methods and resultsWe queried the Johns Hopkins ARVC Registry for all patients who underwent heart transplantation and further studied the subset undergoing transplantation at the Johns Hopkins Hospital. Patient demographics, clinical characteristics, and pre-transplant clinical course were obtained from the registry and electronic medical records. Of the 532 patients in the ARVC Registry, 63 (12%) underwent heart transplantation. Nine (six male) of these patients both had known ARVC prior to transplant and were transplanted at Johns Hopkins Hospital between 2006 and 2020 at a mean age of 42 ± 14 years old. Pathogenic ARVC genetic variants were identified in six (67%) patients, all of whom had variants in the plakophilin-2 (PKP2) gene. RV failure was universal with median right atrial to pulmonary capillary wedge pressure (RA/PCWP) ratio of 1.4 [interquartile range (IQR) 1.2-1.5] and median right ventricular stroke work index (RVSWI) of 0 g·m/m2 /beat (IQR 0-0.3). Six had a history of catheter ablation for ventricular arrhythmia with five of the six having at least three ablations. Transplant evaluation was initiated an average of 344 ± 407 days after first developing heart failure symptoms. The most common bridge to transplant support included inotropes (n = 3) and extracorporeal membrane oxygenation (ECMO) (n = 2). Contraindication to inotropes or mechanical support was common due to ventricular arrhythmia and RV predominant cardiomyopathy.ConclusionsHeart transplantation is a curative treatment for ARVC, but due to frequent ventricular arrhythmias and RV predominant pathology, patients require unique considerations in regard to timing of evaluation, haemodynamic support options, and wait listing qualification.
| S-EPMC8934913 | biostudies-literature
Project description:BackgroundCardiac sarcoidosis (CS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) are rare causes of ventricular arrhythmias and are associated with sudden cardiac death. Differentiation between both is important for proper management.Case summaryWe present a 56-year-old man with sudden cardiac arrest and was diagnosed to have ARVC based on cardiac magnetic resonance imaging (MRI). He developed gradually worsening shortness of breath over the next 1 year. CS was unmasked after a cardiac positron emission tomography (PET). Patient was treated with methotrexate. A repeat cardiac PET scan showed improvement.DiscussionThe distinction between ARVC and CS is challenging. Both these entities have a patchy involvement and can have similar presentations. ARVC has a predominant right heart involvement. It is diagnosed with the help of an MRI, which shows regional right ventricular wall motion abnormality. These findings can have an overlap with CS. It is important to note that, even though sarcoidosis is a pathologic diagnosis, cardiac biopsy is rarely done owing to its patchy involvement. Cardiac PET scan has a high sensitivity and specificity to diagnose this entity. Once diagnosis is made, patients should be treated with immunosuppressants and should be closely followed. Repeat imaging should be considered at intervals to monitor disease progression. This case highlights the importance of multimodality imaging and tissue diagnosis to unmask the diagnosis of CS, a treatable infiltrative disorder which shares features with a potentially untreatable ARVC.
| S-EPMC8186921 | biostudies-literature
Project description:Cardiovascular disease is an important contributor to maternal mortality in both developing and developed countries. Systematic search for cardiac disease is usually not performed during pregnancy despite hypertensive disease, undiagnosed pulmonary hypertension and cardiomyopathies being recognized as major health problems in these settings. This article reported a 27-year-old female who was normal on clinical examination and basic investigations, and on an antenatal visit was found collapsed in the toilet of her house and was pronounced dead on admission to hospital. She was found to be in the 11th week of pregnancy and had no history of significant illness in the past. Autopsy did not reveal any obvious macroscopic pathology except for a significant amount of epicardial fat infiltrating into myocardium of right ventricle. Detailed histopathological examination of the heart demonstrated fibro-fatty replacement of the heart muscle. The cause of death was arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). ARVC/D can cause unexpected sudden death during pregnancy. Therefore, it is recommended that an ECG and echocardiogram be included as screening tests during antenatal follow-up to minimize preventable cardiac deaths like ARVC/D.
| S-EPMC6197088 | biostudies-other
Project description:Background:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease with an estimated prevalence of up to 1:5000 in the general population. Few cases of ARVC during pregnancy are described in literature. Case summary:A 32-year-old primigravida was referred to our clinic during the 32nd gestational week. Arrhythmogenic right ventricular cardiomyopathy diagnosis with biventricular involvement was made according to Task Force criteria. Beta-blocker therapy was started and an elective caesarean section was planned, during the 37th gestational week; no complications occurred. Thirteen months after delivery, the patient was readmitted in our hospital due to an episode of pre-syncope and after team discussion, an implantable cardioverter-defibrillator (ICD) was implanted. Discussion:This case suggests that the absence of signs and symptoms of heart failure (HF) at a first evaluation plays a major role to predict maternal and foetal outcome in ARVC. Our experience is consistent with the evidence that indicates a favourable outcome in asymptomatic patients treated with optimal medical therapy during pregnancy. In our case, despite no major HF or arrhythmic complications during pregnancy, delivery, and puerperium, we observed an arrhythmic disease progression more likely independent from pregnancy, leading to ICD implantation.
| S-EPMC6939797 | biostudies-literature
Project description:Summary backgroundArrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiomyopathy, characterized by fibrofatty replacement of myocytes in the right ventricular, left ventricular or both ventricles. It is caused by pathogenic variants of genes encoding desmosomal (JUP, DSP, PKP2, DSG2, DSC2) and non-desmosomal proteins, and is one of the most common causes of sudden cardiac death in young athletes. Therefore, early identification, correct prevention and treatment can prevent adverse outcomes.Case reportOur case presents a 65-years-old man with recurrent ventricular tachycardia. The ischemic cause was the first to rule out. Echocardiography revealed right ventricular structural and functional abnormalities. After suspicion of ARVC, magnetic resonance imaging was performed showing reduced right ventricular ejection fraction with local aneurysms, structural changes ir the right and left myocardium. Subsequently performed genetic testing identified a novel ARVC likely pathogenic variant in DSC2 gene and variant of uncertain significance in RYR2 gene.ConclusionsDiagnostic evaluation of ARVC is challenging and requires multidisciplinary team collaboration. Further functional tests for elucidation of the clinical significance of the two novel variants of ARVC-associated genes could be suggested.
| S-EPMC8311837 | biostudies-literature
Project description:Desmosomes are anchoring junctions that exist in cells that endure physical stress such as cardiac myocytes. The importance of desmosomes in maintaining the homeostasis of the myocardium is underscored by frequent mutations of desmosome components found in human patients and animal models. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a phenotype caused by mutations in desmosomal components in ? 50% of patients, however, the causes in the remaining 50% of patients still remain unknown. A deficiency of inhibitor of apoptosis-stimulating protein of p53 (iASPP), an evolutionarily conserved inhibitor of p53, caused by spontaneous mutation recently has been associated with a lethal autosomal recessive cardiomyopathy in Poll Hereford calves and Wa3 mice. However, the molecular mechanisms that mediate this putative function of iASPP are completely unknown. Here, we show that iASPP is expressed at intercalated discs in human and mouse postmitotic cardiomyocytes. iASPP interacts with desmoplakin and desmin in cardiomyocytes to maintain the integrity of desmosomes and intermediate filament networks in vitro and in vivo. iASPP deficiency specifically induces right ventricular dilatation in mouse embryos at embryonic day 16.5. iASPP-deficient mice with exon 8 deletion (Ppp1r13l(?8/?8)) die of sudden cardiac death, displaying features of ARVC. Intercalated discs in cardiomyocytes from four of six human ARVC cases show reduced or loss of iASPP. ARVC-derived desmoplakin mutants DSP-1-V30M and DSP-1-S299R exhibit weaker binding to iASPP. These data demonstrate that by interacting with desmoplakin and desmin, iASPP is an important regulator of desmosomal function both in vitro and in vivo. This newly identified property of iASPP may provide new molecular insight into the pathogenesis of ARVC.
| S-EPMC4352828 | biostudies-other