Usefulness of Immunostaining for Plakoglobin as a Diagnostic Marker of Arrhythmogenic Right Ventricular Cardiomyopathy

Munkholm, Julie; Christensen, Alex Hørby; Svendsen, Jesper Hastrup; Andersen, Claus B.

doi:10.1016/j.amjcard.2011.08.044

Cited by 34 publications

(27 citation statements)

References 14 publications

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“…In the present study, 90% sensitivity and 54% specificity were achieved by immunostaining myocardial biopsies for plakoglobin with comparison between ARVC and non-ARVC, ie, HCM and DCM. Munkholm, et al 8) also studied biopsied specimens of patients with and without ARVC but with other diseases (ventricular arrhythmia, DCM, Takotsubo cardiomyopathy, and polymyositis), and their study achieved 85% sensitivity and 75% specificity, similar to the present results. Moreover, plakoglobin expression is decreased in some patients with DCM 6) and granulomatous myocarditis, but in very few of those with lymphocytic myocarditis.…”

Section: Discussionsupporting

confidence: 73%

“…It has been reported that plakoglobin redistribution is one of the candidates that play a crucial role in the final common pathway of ARVC pathogenesis, [9][10][11] and previous studies have reported the usefulness of immunostaining for plakoglobin in the diagnosis of ARVC by endomyocardial biopsy. 6,8,12) However, the diagnostic values for ARVC differ among these studies (sensitivity, 76-91%; specificity, 57-84%), as myocardial specimens obtained by biopsy were compared with various controls, including those from hearts with ventricular arrhythmia, dilated cardiomyopathy (DCM), other cardiac diseases, and even hearts without heart disease. Asimaki, et al 6) achieved the highest sensitivity (91%) and specificity (82%) in a biopsy study compared with controls including many normal subjects and patients with idiopathic ventricular tachycardia.…”

Section: Discussionmentioning

confidence: 99%

“…8) All findings were compared between these two groups of patients. Statistical analysis: All values are expressed as the mean ± standard deviation (SD).…”

Section: Patients and Clinical Analysismentioning

confidence: 99%

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Relationships Between Clinical Characteristics and Decreased Plakoglobin and Connexin 43 Expressions in Myocardial Biopsies From Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

et al. 2015

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SummaryReduced expressions of plakoglobin and connexin 43 have been reported in the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). However, the relationships between these expression abnormalities and the clinical features of ARVC remain unknown.The expressions of plakoglobin and connexin 43 in myocardial biopsy specimens from 10 patients with confirmed ARVC, and 13 control patients without ARVC (non-ARVC; hypertrophic cardiomyopathy, n = 7; dilated cardiomyopathy, n = 6), were examined by immunostaining to evaluate the relationships between these expressions and the clinical characteristics of ARVC. The ratios of plakoglobin/N-cadherin and of plakoglobin/connexin 43 expressions were significantly lower in the ARVC group than in the control group. Significantly more patients had decreased plakoglobin expression in the ARVC group than in the control group (9/10 versus 7/13; P = 0.0376). Sustained ventricular tachycardia occurred more frequently in patients with ARVC and with decreased expressions of both plakoglobin and connexin 43 than in those with decreased expression of plakoglobin alone (5/5 versus 1/4, P = 0.048).Decreased expressions of both connexin 43 and plakoglobin in the myocardium might be associated with the development of arrhythmia in ARVC. (Int Heart J 2015; 56: 626-631) Key words: Arrhythmia, Intercalated disc, Pathology A rrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder of the heart muscle that predominantly affects the right ventricle and is associated with ventricular tachycardia, syncope, sudden death, and the characteristic pathological feature of cardiac myocytes being replaced with adipocytes and fibrosis. 1) Implantation of an implantable cardioverter-defibrillator is one of the treatments of sustained ventricular arrhythmia for prevention of sudden cardiac death in ARVC patients.2) However, there is no specific biomarker or predictor of arrhythmic events in ARVC, while a number of biomarkers reflective of myocardial stress and damage have been developed, 3) and P wave analysis has been reported to be useful for predicting new onset of atrial fibrillation. 4) One of the reasons for a lack of specific biomarkers was because the precise mechanisms of ARVC had not been determined.Cardiac myocytes have three different types of intercellular junctions at the cardiac intercalated disc (adherens junctions, desmosomes, and gap junctions), and the identified gene mutations of ARVC include the intracellular junction proteins, plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2. 5)It has recently been demonstrated that the expression of plakoglobin, a component of both the adherens junctions and desmosomes, was decreased in uninvolved myocardium of ARVC with normal expression of N-cadherin by immunostaining.6) Moreover, the previous study showed that immunoreactive signals for connexin 43, a gap junction component, as well as plakoglobin, were also disturbed in around 70% of patients with ARVC. 7)However, no report has ...

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

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Relationships Between Clinical Characteristics and Decreased Plakoglobin and Connexin 43 Expressions in Myocardial Biopsies From Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

et al. 2015

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“…2 However, there has been some debate regarding the reliability of the test, with the largest study showing a sensitivity of 85% and a specificity of 57%. 25 In addition, interpreting the results of anti-plakoglobin and anti-desmoglein immunoanalysis of chimpanzees has further challenges. These antibodies are not validated for use in this species, and we cannot assume good cross-reactivity or that equivalent optimal methods, such as antibody dilution values, will apply to chimpanzees.…”

Section: Diagnostic Immunoanalysis Of Arvc In Chimpanzeesmentioning

confidence: 99%

Fatal Arrhythmogenic Right Ventricular Cardiomyopathy in 2 Related Subadult Chimpanzees (Pan troglodytes)

et al. 2013

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Cardiovascular disease is increasingly recognized as an important cause of morbidity and mortality in captive chimpanzees (Pan troglodytes). This report records 2 cases of sudden cardiac death in closely related subadult captive chimpanzees with marked replacement fibrosis and adipocyte infiltration of the myocardium, which resemble specific atypical forms of the familial human disease arrhythmogenic right ventricular cardiomyopathy. Changes were consistent with left-dominant and biventricular subtypes, which are both phenotypic variants found within human families with familial arrhythmogenic right ventricular cardiomyopathy. Previously reported fibrosing cardiomyopathies in chimpanzees were characterized by nonspecific interstitial fibrosis, in contrast to the replacement fibrofatty infiltration with predilection for the outer myocardium seen in these 2 cases. To the authors' knowledge, this case report is the first to describe cardiomyopathy resembling arrhythmogenic right ventricular cardiomyopathy in nonhuman primates and the first to describe left-dominant arrhythmogenic cardiomyopathy-type lesions in an animal.

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“…A report suggested that immunohistochemical demonstration of reduced plakoglobin signal in myocardial biopsies has a sensitivity of 85% and specificity of 57% for ARVC. The authors suggested the test could be used in diagnosis, 50 but the performance of the assay in prephenotypic cases-where it is most valuable -has not been assessed. Another group of investigators observed a marked reduction in immunoreactive signal for plakoglobin at cardiac myocyte junctions in patients with sarcoidosis and giant cell myocarditis.…”

Section: 49mentioning

confidence: 99%

Almanac 2014: Cardiomyopathies.

Guttmann¹,

Mohiddin²,

Elliott³

2015

Cardiol Croat.

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SAŽETAK: Kardiomiopatije su bolesti miokarda koje se ne mogu objasniti abnormalnim uvjetima punjenja niti promjenama koronarnih arterija. One se klasifi ciraju u više morfoloških i funkcionalnih fenotipova čiji uzrok mogu biti genetički i negenetički mehanizmi. Dominantne teme u radovima objavljenima u razdoblju 2012.-2013. slične su onima navedenima u Almanahu 2011.: uporaba (i interpretacija) genetskog testiranja, razvoj i primjena novih neinvazivnih tehnika slikovne dijagnostike te uporaba serumskih biomarkera u procesu dijagnoze i za prognozu. Važna inovacija od posljednjeg Almanaha jest razvoj sofi sticiranijih modela za predviđanje neželjenih kliničkih događaja. SUMMARY:Cardiomyopathies are myocardial disorders that are not explained by abnormal loading conditions and coronary artery disease. They are classifi ed into a number of morphological and functional phenotypes that can be caused by genetic and non-genetic mechanisms. The dominant themes in papers published in 2012-2013 are similar to those reported in Almanac 2011, namely, the use (and interpretation) of genetic testing, development and application of novel non-invasive imaging techniques and use of serum biomarkers for diagnosis and prognosis. An important innovation since the last Almanac is the development of more sophisticated models for predicting adverse clinical events.CITATION: Cardiol Croat. 2014;9(11-12):543-557. | DOI: http://dx

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Usefulness of Immunostaining for Plakoglobin as a Diagnostic Marker of Arrhythmogenic Right Ventricular Cardiomyopathy

Cited by 34 publications

References 14 publications

Relationships Between Clinical Characteristics and Decreased Plakoglobin and Connexin 43 Expressions in Myocardial Biopsies From Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

Relationships Between Clinical Characteristics and Decreased Plakoglobin and Connexin 43 Expressions in Myocardial Biopsies From Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

Fatal Arrhythmogenic Right Ventricular Cardiomyopathy in 2 Related Subadult Chimpanzees (Pan troglodytes)

Almanac 2014: Cardiomyopathies.

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