Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes

Abstract

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.

Right ventricular scar‐related ventricular tachycardia in nonischemic cardiomyopathy: Electrophysiological characteristics, mapping, and ablation of underlying heart disease

“…Prior studies have shown RV disease progression (RV dilatation, reduction in RVEF, but not necessarily scar progression) in the majority of patients with ARVC/D with mean follow‐up ranging from 28 to 57 months . As is well known, ARVC/D patients may demonstrate phenotypic heterogeneity from mild to severe disease, and many patients can manifest electrical abnormalities prior to development of structural abnormalities' “concealed phase.” Longer duration of follow‐up is necessary with regular monitoring of RV electrical and mechanical function, and ECG, imaging, and arrhythmic assessment (e.g., with Holter monitoring) may allow further differentiation of the R‐CUS patients into the ARVC/D or CS phenotype and to more definitively characterize disease progression in these patients. It is plausible that frequent reassessment over longer follow‐up may identify electrical and/or structural progression in R‐CUS patients, akin to that seen with at‐risk ARVC/D relatives .…”

“…Some patients with myocarditis may exhibit RV‐scar related VT. Adaptation of the RV to increased workload in endurance athletes and genetic mutations in nondesmosomal proteins such as titin, phospholamban, and lamin can also demonstrate phenotypic manifestation akin to ARVC/D . In the R‐CUS cohort of patients, no typical type I Brugada ECG features were noted, but systematic provocation testing with flecainide or ajmaline was not performed.…”

“…Adaptation of the RV to increased workload in endurance athletes 25 and genetic mutations in nondesmosomal proteins such as titin, phospholamban, and lamin can also demonstrate phenotypic manifestation akin to ARVC/D. 1,[26][27][28] In the R-CUS cohort of patients, no typical type I Brugada ECG features were noted, but systematic provocation testing with flecainide or ajmaline was not performed. The R-CUS group may well represent a heterogeneous group of disorders manifesting as RVscar related VT.…”

“…Patients with nonischemic cardiomyopathy with right ventricular (RV) scar‐related ventricular tachycardia (VT) constitute a diagnostic challenge, as the underlying cause may be unclear. RV scar‐related VT may be a common to phenotypic expression for many conditions such as arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), cardiac sarcoidosis (CS), myocarditis, Brugada syndrome, or other inherited dilated cardiomyopathies . Task force criteria for ARVC/D and an expert consensus statement for CS provide a standardized method for diagnosis.…”

“…RV scar-related VT may be a common to phenotypic expression for many conditions such as arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), cardiac sarcoidosis (CS), myocarditis, Brugada syndrome, or other inherited dilated cardiomyopathies. [1][2][3][4][5][6] Task force criteria for ARVC/D 7 and an expert consensus statement for CS 8 provide a standardized method for diagnosis. There are, however, some patients with non-ischemic cardiomyopathy and predominant RV scar, and RVrelated VT who do not fulfill diagnostic criteria for either ARVC/D or CS.…”