scholarly journals Histopathological Features and Protein Markers of Arrhythmogenic Cardiomyopathy

2021 ◽  
Vol 8 ◽  
Author(s):  
Carlos Bueno-Beti ◽  
Angeliki Asimaki
Keyword(s):  
Cardiac Myocytes ◽  
Left Ventricular ◽  
Muscle Disease ◽  
Incomplete Penetrance ◽  
Protein Markers ◽  
Cell Coupling ◽  
Arrhythmogenic Cardiomyopathy ◽  
Right Ventricular Free Wall ◽  
Cascade Screening ◽  
Age Related

Arrhythmogenic cardiomyopathy (ACM) is a heritable heart muscle disease characterized by syncope, palpitations, ventricular arrhythmias and sudden cardiac death (SCD) especially in young individuals. It is estimated to affect 1:5,000 individuals in the general population, with >60% of patients bearing one or more mutations in genes coding for desmosomal proteins. Desmosomes are intercellular adhesion junctions, which in cardiac myocytes reside within the intercalated disks (IDs), the areas of mechanical and electrical cell-cell coupling. Histologically, ACM is characterized by fibrofatty replacement of cardiac myocytes predominantly in the right ventricular free wall though left ventricular and biventricular forms have also been described. The disease is characterized by age-related progression, vast phenotypic manifestation and incomplete penetrance, making proband diagnosis and risk stratification of family members particularly challenging. Key protein redistribution at the IDs may represent a specific diagnostic marker but its applicability is still limited by the need for a myocardial sample. Specific markers of ACM in surrogate tissues, such as the blood and the buccal epithelium, may represent a non-invasive, safe and inexpensive alternative for diagnosis and cascade screening. In this review, we shall cover the most relevant biomarkers so far reported and discuss their potential impact on the diagnosis, prognosis and management of ACM.

Left Side Right Ventricular Cardiomyopathy

2002 ◽  
Vol 42 (4) ◽  
pp. 313-317 ◽  
Author(s):  
M Michalodimitrakis ◽  
A Papadomanolakis ◽  
J Stiakakis ◽  
K Kanaki
Keyword(s):  
Right Ventricular ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Left Ventricular ◽  
Muscle Disease ◽  
Pathologic Examination ◽  
Arrhythmogenic Cardiomyopathy ◽  
Ventricular Cardiomyopathy ◽  
First Case ◽  
Fibrofatty Tissue ◽  
Myocardial Muscle

Arrhythmogenic right ventricular cardiomyopathy or dysplasia, a heart muscle disease of unknown cause, is anatomically characterized by variable replacement of myocardial muscle with adipose or fibroadipose tissue. It is usually considered a selective disorder whereas concomitant left ventricular involvement has been noted in a few cases. Two cases of the disease with evidence of extensive left ventricular involvement at pathologic examination are described. Hearts from two patients who died suddenly showed extensive biventricular infiltration by fibrofatty tissue in the first case and exclusively in the wall of the left ventricle the localization of the fatty and fibrotic lesions. These findings might suggest that the various localizations of the fibroadipose tissue are rather different expressions of the same disease and it is preferable to be termed ‘arrhythmogenic cardiomyopathy’ as other studies also indicate.

scholarly journals Arrhythmogenic Cardiomyopathy—Further Insight into the Clinical Spectrum of Desmoplakin Disease

2021 ◽  
Vol 11 (4) ◽  
pp. 219-229
Author(s):  
Joanne Simpson ◽  
Joan Anusas ◽  
Denise Oxnard ◽  
Sylvia Wright ◽  
Ruth McGowan ◽  
...  
Keyword(s):  
Ethical Issues ◽  
Task Force ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Left Ventricular ◽  
Muscle Disease ◽  
Clinical Spectrum ◽  
Dna Testing ◽  
Arrhythmogenic Cardiomyopathy ◽  
Ventricular Cardiomyopathy ◽  
Insight Into

Arrhythmogenic cardiomyopathy is a familial heart muscle disease characterized by structural, electrical, and pathological abnormalities. Recognition of left ventricular (LV) involvement in arrhythmogenic right ventricular cardiomyopathy (ARVC) has led to the newer term of arrhythmogenic cardiomyopathy (ACM). We report on a family with autosomal dominant desmoplakin (DSP) related ACM to illustrate the broad clinical spectrum of disease. The importance of evaluation of relatives with cardiac magnetic resonance imaging and consideration of genetic testing in the absence of Task Force diagnostic criteria is discussed. The practical and ethical issues of access to the Guthrie collection for deoxyribonucleic acid (DNA) testing are considered.

scholarly journals Natural History of Arrhythmogenic Cardiomyopathy

2020 ◽  
Vol 9 (3) ◽  
pp. 878 ◽  
Author(s):  
Giulia Mattesi ◽  
Alessandro Zorzi ◽  
Domenico Corrado ◽  
Alberto Cipriani
Keyword(s):  
Natural History ◽  
Genetic Basis ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
The Elderly ◽  
Ventricular Myocardium ◽  
Muscle Disease ◽  
Arrhythmogenic Cardiomyopathy ◽  
Age Related ◽  
Genes Encoding ◽  
History Of

Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease characterized by a scarred ventricular myocardium with a distinctive propensity to ventricular arrhythmias (VAs) and sudden cardiac death, especially in young athletes. Arrhythmogenic right ventricular cardiomyopathy (ARVC) represents the best characterized variant of AC, with a peculiar genetic background, established diagnostic criteria and management guidelines; however, the identification of nongenetic causes of the disease, combined with the common demonstration of biventricular and left-dominant forms, has led to coin the term of “arrhythmogenic cardiomyopathy”, to better define the broad spectrum of the disease phenotypic expressions. The genetic basis of AC are pathogenic mutations in genes encoding the cardiac desmosomes, but also non-desmosomal and nongenetic variants were reported in patients with AC, some of which showing overlapping phenotypes with other non-ischemic diseases. The natural history of AC is characterized by VAs and progressive deterioration of cardiac performance. Different phases of the disease are recognized, each characterized by pathological and clinical features. Arrhythmic manifestations are age-related: Ventricular fibrillation and SCD are more frequent in young people, while sustained ventricular tachycardia is more common in the elderly, depending on the different nature of the myocardial lesions. This review aims to address the genetic basis, the clinical course and the phenotypic variants of AC.

Arrhythmogenic right ventricular cardiomyopathy: diagnosis

2018 ◽  
Author(s):  
Cristina Bass ◽  
Barbara Bauce ◽  
Gaetano Thiene
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Right Ventricular ◽  
Diagnostic Criteria ◽  
Left Ventricular ◽  
Muscle Disease ◽  
Ventricular Free Wall ◽  
Diagnostic Tools ◽  
Free Wall ◽  
Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias and pathologically by an acquired and progressive dystrophy of the ventricular myocardium with fibrofatty replacement. The clinical manifestations of arrhythmogenic cardiomyopathy vary according to the ‘phenotypic’ stage of the underlying disease process. Since there is no ‘gold standard’ to reach the diagnosis of arrhythmogenic cardiomyopathy, multiple categories of diagnostic information have been combined. Different diagnostic categories include right ventricular morphofunctional abnormalities (by echocardiography and/or angiography and/or cardiovascular magnetic resonance imaging), histopathological features on endomyocardial biopsy, electrocardiogram, arrhythmias, and family history, including genetics. The diagnostic criteria were revised in 2010 to improve diagnostic sensitivity, but with the important prerequisite of maintaining diagnostic specificity. Quantitative parameters have been put forward and abnormalities are defined based on the comparison with normal subject data. A definite diagnosis of arrhythmogenic cardiomyopathy is achieved when two major, or one major and two minor, or four minor criteria from different categories are met. The main differential diagnoses are idiopathic right ventricular outflow tract tachycardia, myocarditis, sarcoidosis, dilated cardiomyopathy, right ventricular infarction, congenital heart diseases with right ventricular overload, and athlete’s heart. Among diagnostic tools, contrast-enhanced cardiovascular magnetic resonance is playing a major role in detecting subepicardial-midmural left ventricular free wall involvement, even preceding morphofunctional abnormalities. Moreover, electroanatomical mapping is an invasive tool able to detect early right ventricular free wall involvement in terms of low-voltage areas. Both techniques are increasingly used in the diagnostic work-up although are not yet part of diagnostic criteria.

Looking into a whale’s heart: investigating a genetic basis for cardiomyopathy in a non-model species

Genome ◽  
2017 ◽  
Vol 60 (8) ◽  
pp. 695-705
Author(s):  
Amélia Viricel ◽  
Patricia E. Rosel
Keyword(s):  
Mammalian Species ◽  
Mutation Screening ◽  
Sperm Whale ◽  
Muscle Disease ◽  
Control Group ◽  
Incomplete Penetrance ◽  
Model Species ◽  
Cetacean Species ◽  
Deep Diving ◽  
Age Related

Understanding the pathogenesis of complex diseases can benefit from multi-species comparative studies. Yet these studies rarely include natural populations of non-model species. Here, we focused on the cause of a heart muscle disease, cardiomyopathy (CM), affecting multiple mammalian species including humans, cats, dogs, and certain species of whales. Mutations in genes coding for sarcomeric proteins have been identified as a leading cause for CM in humans, and some were also revealed to be responsible for CM in cats. We investigated whether similar mutations could be detected in the deep-diving pygmy sperm whale (Kogia breviceps), which is one of two cetacean species known to display CM. We sequenced portions of two candidate genes (MYH7: 3153 bp and MYBPC3: 3019 bp) in 55 whales including affected and unaffected individuals. Mutation screening revealed six nonsynonymous substitutions that were predicted to have an effect on protein function. However, the etiology of CM is likely complex and probably multi-factorial as three of these mutations were observed in unaffected individuals from our control group. This incomplete penetrance could be partly age-related and could also be due to the influence of environmental factors on the development of CM, as seen in humans.

scholarly journals Update on Genes Associated with Arrhythmogenic Cardiomyopathy

2020 ◽  
Author(s):  
Marta Vallverdú-Prats ◽  
Mireia Alcalde ◽  
Georgia Sarquella-Brugada ◽  
Sergi Cesar ◽  
Elena Arbelo ◽  
...  
Keyword(s):  
Rare Variants ◽  
Correct Diagnosis ◽  
Phenotypic Expression ◽  
Genetic Alterations ◽  
Left Ventricular ◽  
Incomplete Penetrance ◽  
Arrhythmogenic Cardiomyopathy ◽  
Young Males ◽  
Genes Encoding ◽  
The Right

Arrhythmogenic cardiomyopathy is a rare genetic entity characterized by progressive fibro-fatty replacement of myocardium leading to malignant arrhythmias, syncope, and sudden cardiac death. Mostly it affects the right ventricle, but cases have also been described with biventricular and even isolated left ventricular involvement. The disease affects mainly young males and arrhythmias are usually induced by exercise. Arrhythmogenic cardiomyopathy has a genetic origin and is basically caused by deleterious alterations in genes encoding desmosomal proteins, especially plakophilin-2. To date, more than 400 rare genetic alterations have been identified in 18 genes, mainly with autosomal dominant inheritance, but some recessive forms have also been reported (Naxos disease and Carvajal syndrome). A comprehensive genetic analysis identifies a rare variant as potential cause of the disease in around 60% of patients, suggesting the existence of unknown genes as well as other genome alterations not yet discovered. Genetic interpretation classifies some of these rare variants as ambiguous, playing an uncertain role in arrhythmogenic cardiomyopathy. This makes a proper translation of genetic data into clinical practice difficult. Moreover, incomplete penetrance and variable phenotypic expression makes it difficult to arrive at the correct diagnosis. In the present chapter, we focus on recent advances in the knowledge regarding the genetic basis of arrhythmogenic cardiomyopathy.

scholarly journals Phenotypic Variability of a Pathogenic PKP2 Mutation in an Italian Family Affected by Arrhythmogenic Cardiomyopathy and Juvenile Sudden Death: Considerations From Molecular Autopsy to Sport Restriction

2021 ◽  
Vol 8 ◽  
Author(s):  
Maria Pia Leone ◽  
Pietro Palumbo ◽  
Johan Saenen ◽  
Sandra Mastroianno ◽  
Stefano Castellana ◽  
...  
Keyword(s):  
Task Force ◽  
Phenotypic Variability ◽  
Genetic Disorder ◽  
Physical Exertion ◽  
Dominant Mode ◽  
Specific Gene ◽  
Incomplete Penetrance ◽  
Arrhythmogenic Cardiomyopathy ◽  
Cascade Screening ◽  
Molecular Autopsy

Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder with an estimated prevalence between 1:2,000 and 1:5,000 and is characterized by the fibrofatty replacement of cardiomyocytes that predisposes to malignant arrhythmias, heart failure, and sudden cardiac death. The diagnosis is based on the 2010 Task Force Criteria including family history, electrocardiographic traits and arrhythmogenic pattern, specific gene mutations, and structural and/or histological abnormalities. Most ACMs display an autosomal dominant mode of inheritance often with incomplete penetrance and variable expressivity. Genetic screening of patients with ACM identifies pathogenic or likely pathogenic variants, prevalently in genes encoding the cardiac desmosome (PKP2, DSP, DSC2, DSG2, and JUP) or less frequently in non-desmosomal genes (CTNNA3, PLN, TMEM43, RYR2, SCN5A, CDH2, and DES).Methods: In the present study, we performed molecular autopsy in a boy who died suddenly during physical exertion. In addition to post-mortem examination, a DNA sample was analyzed with next-generation sequencing (NGS).Results: The genetic analysis revealed the presence of pathogenic heterozygous c.314del (p.Pro105Leufs*7) frameshift variant in the PKP2 gene. Cascade screening of family members allowed us to identify 12 mutation carriers and to intervene on subjects at risk, many of whom were athletes.Conclusions: Molecular autopsy can establish cardiogenetic diagnosis and allow appropriate preventative measures in high-risk relatives.

scholarly journals B-PO02-124 NONISCHEMIC LEFT VENTRICULAR CARDIOMYOPATHY WITH PRESERVED LEFT VENTRICULAR FUNCTION: A TYPE OF ARRHYTHMOGENIC CARDIOMYOPATHY

Heart Rhythm ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. S148
Author(s):  
Ikutaro Nakajima ◽  
Kenichi Tokutake ◽  
Asad A. Aboud ◽  
Oluwaseun Adeola ◽  
Travis D. Richardson ◽  
...  
Keyword(s):  
Left Ventricular Function ◽  
Ventricular Function ◽  
Left Ventricular ◽  
Arrhythmogenic Cardiomyopathy ◽  
Ventricular Cardiomyopathy

The utility of strain imaging in the cardiac surveillance of bone marrow transplant patients

Heart ◽  
2021 ◽  
pp. heartjnl-2021-319359
Author(s):  
Tejas Deshmukh ◽  
Peter Emerson ◽  
Paul Geenty ◽  
Shehane Mahendran ◽  
Luke Stefani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Global Longitudinal Strain ◽  
Group Versus ◽  
Marrow Transplant ◽  
Cross Sectional Study ◽  
Left Ventricular ◽  
Right Ventricular Free Wall ◽  
Cross Sectional ◽  
Allogenic Bone ◽  
Transplant Patients

ObjectiveTo evaluate the utility of two-dimensional multiplanar speckle tracking strain to assess for cardiotoxicity post allogenic bone marrow transplantation (BMT) for haematological conditions.MethodsCross-sectional study of 120 consecutive patients post-BMT (80 pretreated with anthracyclines (BMT+AC), 40 BMT alone) recruited from a late effects haematology clinic, compared with 80 healthy controls, as part of a long-term cardiotoxicity surveillance study (mean duration from BMT to transthoracic echocardiogram 6±6 years). Left ventricular global longitudinal strain (LV GLS), global circumferential strain (LV GCS) and right ventricular free wall strain (RV FWS) were compared with traditionl parameters of function including LV ejection fraction (LVEF) and RV fractional area change.ResultsLV GLS (−17.7±3.0% vs −20.2±1.9%), LV GCS (−14.7±3.5% vs −20.4±2.1%) and RV FWS (−22.6±4.7% vs −28.0±3.8%) were all significantly (p=0.001) reduced in BMT+AC versus controls, while only LV GCS (−15.9±3.5% vs −20.4±2.1%) and RV FWS (−23.9±3.5% vs −28.0±3.8%) were significantly (p=0.001) reduced in BMT group versus controls. Even in patients with LVEF >53%, ~75% of patients in both BMT groups demonstrated a reduction in GCS.ConclusionMultiplanar strain identifies a greater number of BMT patients with subclinical LV dysfunction rather than by GLS alone, and should be evaluated as part of post-BMT patient surveillence. Reduction in GCS is possibly due to effects of preconditioning, and is not fully explained by AC exposure.

Sign in / Sign up

Export Citation Format

Share Document