Exercise Testing in Asymptomatic Gene Carriers Exposes a Latent Electrical Substrate of Arrhythmogenic Right Ventricular Cardiomyopathy

Perrin, Mark; Angaran, Paul; Laksman, Zachary; Zhang, Hanfei; Porepa, Liane; Rutberg, Julie; James, Cynthia A.; Krahn, Andrew D.; Judge, Daniel P.; Calkins, Hugh; Gollob, Michael H.

doi:10.1016/j.jacc.2013.04.084

Cited by 65 publications

(41 citation statements)

References 14 publications

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“…The by guest on May 11, 2018 http://circep.ahajournals.org/ Downloaded from distribution of continuous variables was examined for normality using the Kolmogorov-Smirnov test and histogram plots. Continuous variables were compared using the Student t test.…”

Section: Discussionmentioning

confidence: 99%

“…Cardiac MRI was considered normal or borderline in 14% and 26%, respectively, of patients newly identified with ARVC 13 and 36% of patients with ARVC with a history of sustained ventricular arrhythmias, and cardiac arrest did not have major or minor criteria on cardiac imaging (MRI or echocardiogram). 14 The diagnosis of ARVC is based on the1994 Task Force Criteria (TFC), 15 which were updated in 2010. 16 Although correct identification may be straightforward in severe and diffuse ARVC cases, it remains challenging in patients presenting in the early stages.…”

Section: Editorial See P 565 Clinical Perspective On P 597mentioning

confidence: 99%

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Diagnostic Value of Isoproterenol Testing in Arrhythmogenic Right Ventricular Cardiomyopathy

Denis

Sacher

Derval

et al. 2014

Circ: Arrhythmia and Electrophysiology

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Background-Although the Task Force Criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) have recently been updated, the diagnosis remains challenging in the early stages. .4 years, 6 additional patients met diagnostic criteria for ARVC. Importantly, initial isoproterenol testing was positive in 6 of 6 (100%) of these patients. Survival free from ARVC diagnosis was significantly lower in the positive isoproterenol group than in the negative isoproterenol group (P<0.0001, exact log-rank test). Conclusions-Ventricular arrhythmogenicity during isoproterenol testing is highly sensitive (sensitivity, 91.4%) for the diagnosis of ARVC, particularly in its early stages. (Circ Arrhythm Electrophysiol. 2014;7:590-597.)

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Section: Discussionmentioning

confidence: 99%

Section: Editorial See P 565 Clinical Perspective On P 597mentioning

confidence: 99%

Diagnostic Value of Isoproterenol Testing in Arrhythmogenic Right Ventricular Cardiomyopathy

Denis

Sacher

Derval

et al. 2014

Circ: Arrhythmia and Electrophysiology

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“…PKP2 is the most common causal gene for ARVC [11]. The variant is predicted to disrupt the canonical splice acceptor site in exon 10 of the PKP2 gene and has been reported in multiple independent probands/families to cause ARVC [11–14]. The variant was read 183 times in the WES data and was confirmed by Sanger sequencing (Fig.…”

Section: Case Presentationmentioning

confidence: 96%

Identification of established arrhythmogenic right ventricular cardiomyopathy mutation in a patient with the contrasting phenotype of hypertrophic cardiomyopathy

Bainbridge

Tan

et al. 2017

BMC Med Genet

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BackgroundAdvances in the nucleic acid sequencing technologies have ushered in the era of genetic-based “precision medicine”. Applications of the genetic discoveries to practice of medicine, however, are hindered by phenotypic variability of the genetic variants. The report illustrates extreme pleiotropic phenotypes associated with an established causal mutation for hereditary cardiomyopathy.Case presentationWe report a 61-year old white female who presented with syncope and echocardiographic and cardiac magnetic resonance (CMR) imaging findings consistent with the diagnosis of hypertrophic cardiomyopathy (HCM). The electrocardiogram, however, showed a QRS pattern resembling an Epsilon wave, a feature of arrhythmogenic right ventricular cardiomyopathy (ARVC). Whole exome sequencing (mean depth of coverage of exons 178X) analysis did not identify a pathogenic variant in the known HCM genes but identified an established causal mutation for ARVC. The mutation involves a canonical splice accepter site (c.2146-1G > C) in the PKP2 gene, which encodes plakophillin 2. Sanger sequencing confirmed the mutation. PKP2 is the most common causal gene for ARVC but has not been implicated in HCM. Findings on echocardiography and CMR during the course of 4-year follow up showed septal hypertrophy and a hyperdynamic left ventricle, consistent with the diagnosis of HCM. However, neither baseline nor follow up echocardiography and CMR studies showed evidence of ARVC. The right ventricle was normal in size, thickness, and function and there was no evidence of fibro-fatty infiltration in the myocardium.ConclusionsThe patient carries an established pathogenic mutation for ARVC and a subtle finding of ARVC but exhibits the classic phenotype of HCM, a contrasting phenotype to ARVC. The case illustrates the need for detailed phenotypic characterization for patients with hereditary cardiomyopathies as well as the challenges physicians face in applying the genetic discoveries in practicing genetic-based “precision medicine”.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-017-0385-8) contains supplementary material, which is available to authorized users.

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“…Thus, treadmill testing can reveal VT/ 113 In another study, the evaluation of the arrhythmic potential during very high dose isoproterenol infusion was sensitive for diagnosis of early forms of ARVC/D. 114 …”

Section: Stress Testingmentioning

confidence: 99%

Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes

Akdiş

Brunckhorst

Duru

et al. 2016

Arrhythmia &Amp; Electrophysiology Review

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This overview gives an update on the molecular mechanisms, clinical manifestations, diagnosis and therapy of arrhythmogenic cardiomyopathy (ACM). ACM is mostly hereditary and associated with mutations in genes encoding proteins of the intercalated disc. Three subtypes have been proposed: the classical right-dominant subtype generally referred to as ARVC/D, biventricular forms with early biventricular involvement and left-dominant subtypes with predominant LV involvement. Typical symptoms include palpitations, arrhythmic (pre)syncope and sudden cardiac arrest due to ventricular arrhythmias, which typically occur in athletes. At later stages, heart failure may occur. Diagnosis is established with the 2010 Task Force Criteria (TFC). Modern imaging tools are crucial for ACM diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting functional and structural alternations. Of note, structural findings often become visible after electrical alterations, such as premature ventricular beats, ventricular fibrillation (VF) and ventricular tachycardia (VT). 12-lead ECG is important to assess for depolarisation and repolarisation abnormalities, including T-wave inversions as the most common ECG abnormality. Family history and the detection of causative mutations, mostly affecting the desmosome, have been incorporated in the TFC, and stress the importance of cascade family screening. Differential diagnoses include idiopathic right ventricular outflow tract (RVOT) VT, sarcoidosis, congenital heart disease, myocarditis, dilated cardiomyopathy, athlete’s heart, Brugada syndrome and RV infarction. Therapeutic strategies include restriction from endurance and competitive sports, β-blockers, antiarrhythmic drugs, heart failure medication, implantable cardioverter-defibrillators and endocardial/epicardial catheter ablation.

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Exercise Testing in Asymptomatic Gene Carriers Exposes a Latent Electrical Substrate of Arrhythmogenic Right Ventricular Cardiomyopathy

Cited by 65 publications

References 14 publications

Diagnostic Value of Isoproterenol Testing in Arrhythmogenic Right Ventricular Cardiomyopathy

Diagnostic Value of Isoproterenol Testing in Arrhythmogenic Right Ventricular Cardiomyopathy

Identification of established arrhythmogenic right ventricular cardiomyopathy mutation in a patient with the contrasting phenotype of hypertrophic cardiomyopathy

Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes

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