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Arrhythmogenic right ventricular cardiomyopathy

Evolving from unique clinical features to a complex pathophysiological concept

Arrhythmogene rechtsventrikuläre Kardiomyopathie

Entwicklung von der Beschreibung pathognomonischer klinischer Charakteristika zu einem komplexen pathophysiologischen Konzept

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Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited heart muscle disease, is characterized by a progressive replacement of viable, in its classic form predominantly right ventricular myocardium by fibro-fatty tissue. These pathological alterations may provide the substrate for the occurrence of life-threatening ventricular tachyarrhythmias, heart failure, and sudden cardiac death. The clinical course in this young patient population is highly variable, diagnostic algorithms complex, and individualized treatment strategies yet to be refined. Molecular genetic analyses have revealed both heterozygous and compound mutations in genes encoding for desmosomal proteins that are an integral part of the intercellular architecture. However, its diagnostic and prognostic impact remains to be elucidated. Over time, other genetic (i.e., non-desmosomal) and non-genetic causes (phenocopies) have been identified, and biventricular and left dominant manifestations (ALVC) are known. Based on a qualitative scoring system, initially published in 1994, diagnostic criteria were revised and substantiated by quantitative criteria in 2010 followed by a critical appraisal 9 years later. In 1995, ARVC was included in the classification of cardiomyopathies of the World Health Organization but was recently proposed to be subsumed in a broader concept termed “arrhythmogenic cardiomyopathy” (AC). This review provides an update on the clinical diagnosis and differential diagnoses of ARVC as well as our current understanding of the underlying pathogenesis, and it sheds light on new efforts in risk stratification.

Zusammenfassung

Die arrhythmogene rechtsventrikuläre Kardiomyopathie (ARVC) ist als hereditäre Herzmuskelerkrankung charakterisiert durch einen progressiven Ersatz v. a. rechtsventrikulären Myokards durch Binde‑/Fettgewebe. Diese pathomorphologischen Alterationen können das Substrat für das Auftreten lebensbedrohlicher ventrikulärer Tachyarrhythmien, die Entwicklung einer klinischen Herzinsuffizienzsymptomatik und den plötzlichen Herztod bilden. Der klinische Verlauf in dieser überwiegend jungen Patientenpopulation ist sehr variabel, diagnostische Algorithmen sind komplex und individualisierte Therapiestrategien derzeit noch im Entwicklungszustand. In molekulargenetischen Analysen wurden sowohl heterozygote als auch Mehrfachmutationen in Genen detektiert, die für desmosomale Proteine, den integralen Bestandteil der interzellulären Architektur, kodieren. Allerdings ist sowohl ihre diagnostische als auch prognostische Bedeutung noch unklar. Im Verlauf konnten andere genetische, nichtdesmosomale und auch nichtgenetische Phänotypen identifiziert werden; biventrikuläre oder linksdominante Erkrankungsformen sind zudem bekannt. Ausgehend von einem 1994 publizierten, klinisch-qualitativen diagnostischen Algorithmus wurden die diagnostischen Kriterien in einer Revision 2010 quantitativ substanziiert und weitere 9 Jahre später auf der Grundlage neuerer wissenschaftlichen Daten in einzelnen Punkten modifiziert. Die ARVC wurde 1995 in die Klassifikation der Kardiomyopathien der Weltgesundheitsorganisation als eigenständige Erkrankungsentität integriert, wobei erst kürzlich ein mehrere Erkrankungen (inklusiv der ARVC) umfassendes neues Konzept einer „arrhythmogenen Kardiomyopathie“ (AC) vorgestellt wurde. Dieser Artikel beschreibt die aktuelle klinische Diagnostik, Differenzialdiagnostik und Therapieoptionen der ARVC vor dem Hintergrund der zugrunde liegenden Pathogenetik und bietet einen Ausblick auf laufende Anstrengungen zu einer individualisierten Risikostratifikation betroffener Patienten.

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Authors and Affiliations

  1. Department of Cardiology I – Coronary and peripheral vascular disease, heart failure – Division of Cardiovascular Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany

    Matthias Paul

  2. Institute for Genetics of Heart Diseases (IfGH), Division of Cardiovascular Medicine, University Hospital Münster, Münster, Germany

    Eric Schulze-Bahr

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  1. Matthias Paul
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Correspondence to Matthias Paul.

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M. Paul and E. Schulze-Bahr declare that they have no competing interests.

For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case.

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Paul, M., Schulze-Bahr, E. Arrhythmogenic right ventricular cardiomyopathy. Herz 45, 243–251 (2020). https://doi.org/10.1007/s00059-020-04907-1

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