Journal Article

Arrhythmogenic left ventricular cardiomyopathy

Basso, Cristina, Corrado, Domenico

2022

Overview

Introduction Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease characterised by substitution of the ventricular myocardium by fibrofatty tissue.1 The disease was originally termed ‘arrhythmogenic right ventricular (dysplasia/) cardiomyopathy’ (ARVC) to define a condition which distinctively affected the right ventricle (RV) and predisposed to potentially fatal ventricular arrhythmias, particularly in young individuals and athletes.2–4 New insights arising from postmortem investigations, genotype–phenotype correlation studies and myocardial tissue characterisation by contrast-enhanced cardiac magnetic resonance (CMR) led to increased awareness that the disease often also involves the left ventricle (LV).5–11 The current designation of ‘arrhythmogenic cardiomyopathy’ better reflects the evolving concept of a heart muscle disease affecting both ventricles, with some phenotypic variants characterised by a parallel or predominant involvement of the LV. According to the HRS document, the vague common denominator of this miscellaneous group of ‘arrhythmogenic cardiomyopathies’ was the ‘clinical presentation with symptoms or documentation of atrial fibrillation, conduction disease, and/or RV and/or LV arrhythmia’. CMR studies in living patients fulfilling the 2010 International Task Force (ITF) criteria have consistently shown that LV involvement in terms of morphofunctional (LV global or regional systolic dysfunction) and/or structural (LV late gadolinium enhancement (LGE)) abnormalities is identified in more than half of patients.9 22 24 According to the available findings of clinical studies, phenotypic features of left-sided ACM include the following (figure 1): (1) ECG abnormalities such as low-amplitude QRS complexes (peak to peak <0.5 mV) in limb leads and T-wave inversion or flattening in the lateral (or inferolateral) leads, although the ECG is often normal; (2) ventricular arrhythmias with a right bundle branch block (RBBB) morphology of the ectopic QRS (denoting the origin from the LV); (3) normal or slightly depressed LV systolic function with no (or mild) dilatation; (4) large amount of myocardial fibrosis evidenced by contrast-enhanced CMR as LGE; and (5) ‘non-ischemic’ pattern of LGE, predominantly involving the subepicardial layers of the inferior and the inferolateral regions. A number of human DSP gene mutations have been linked with ACM, which manifest characteristically with early LV involvement occurring in isolation or preceding RV disease.28 Of note, in the initial report of the DSP gene mutation responsible for ‘Carvajal syndrome’, the cardiac phenotype resembled that of DCM as opposed to the classic ARVC phenotype.29 Phospholamban normally inhibits the sarcoendoplasmic reticulum calcium transport ATPase, and PLN gene mutations cause dysregulated calcium flux, predisposing to prominent arrhythmia and ventricular dysfunction.

• Publisher: BMJ Publishing Group Ltd and British Cardiovascular Society,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: arrhythmogenic right ventricular dysplasia / Arrhythmogenic Right Ventricular Dysplasia - diagnosis / Arrhythmogenic Right Ventricular Dysplasia - therapy / Cardiac arrhythmia / cardiac magnetic resonance (CMR) imaging / Cardiomyopathies - diagnosis / Cardiomyopathy / Disease / Education in Heart / educational goals and objectives / Genes / Genotype & phenotype / Humans / Magnetic Resonance Imaging / Morphology / Mutation / Proteins / ventricular fibrillation