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................... on CMR, younger age, or with a specific familial/genetic phenotype (Tables 2729). Risk models for the prediction of ICD benefits were applied to the patients enrolled in DANISH and may help for the indication to ICD implantation in DCM.166,913 Treatment of HCM and AC, including indications for ICD, are detailed in previous documents.895,896,899,912,914,915 14.3 Left ventricular non-compaction

LVNC is a very rare congenital CMP characterized by endomyocardial trabeculations that increase in number and prominence. In most cases, including when the condition is caused by mutations in the MYH7 or MYBPC3 gene, LVNC is inherited in an autosomal dominant pattern.644,937,938 A clear overlap exists in families with

Table 29 Arrhythmogenic cardiomyopathy: specific aspects of diagnosis and treatment912,915,932

Definition Inherited heart muscle disease characterized by progressive fibrofatty replacement of the RV myocardium which may act as a substrate for ventricular arrhythmias, unexplained syncope and/or sudden cardiac death. LV involvement and systolic dysfunction occurs in >30% of AC patients, therefore its phenotype may overlap with DCM. Diagnosis933 Based upon the evaluation of a combination of the genetic factors (most cases autosomal dominant desmosomal mutations), documentation of ventricular arrhythmias and imaging criteria (echocardiography and MRI) of RV dysplasia with the fibrofatty replacement either or not confirmed by EMB. Specific ECG abnormalities can be present or absent. Genetic counselling/testing898,912 Indication. Must be offered to all patients with a suspected AC and has to be offered to all first-degree adult relatives of patients with AC and a definite disease-causing mutation, regardless of their phenotype in order to identify genetically affected individuals at a preclinical phase. Genetic family screening can be also indicated for arrhythmic risk stratification purposes. Clinical evaluation, ECG, echocardiography and possibly CMR have to be performed in first-degree relatives who have the same definite disease-causing mutation as the index patient. When no definite genetic mutation is identified in the index patient or genetic testing is not performed, clinical evaluation with ECG and echocardiography should be considered in first-degree adult relatives and repeated every 25 years or less if non-diagnostic abnormalities are present. Minimal set of genes: Desmosomal, mostly with isolated RV involvement: plakoglobin, DSP, PKP2, DSG2 and DSC2a With frequent LV involvement/DCM: DSP, FLNC, SCN5A, TMEM43, FLN, LDB3, desmin, a-actinin, BAG3, NKX2-5, RBM20, SCN5A, KCNQ1, KCNH2, TRPM4 or PLN variants in particular. If mild LV hypertrophy: consider TNNT variants. Cutaneous abnormalities, palmar and plantar hyperkeratosis: consider rare recessive mutations leading to Carvajal syndrome and Naxos disease. Plakoglobin (JUP). With CMR presentation of myocarditis along AC: consider DSP gene variants.934,935 Endomyocardial biopsy It should be reserved to highly selected cases after all non-invasive studies have been assessed. Fibrofatty replacement with or without replacement type fibrosis at RV septal biopsies are the characteristic findings. EMB has low sensitivity for the diagnosis of AC in cases of focal distribution. Therapeutic options HF treatment for HFrEF (see sections 5 and 6). Competitive sports should be avoided, limit activities to leisure-time activities.936 In patients with ventricular arrhythmias: beta-blockers must be titrated to the maximally tolerated dose as first-line therapy. Amiodarone can be considered in addition to beta-blockers or if beta-blockers contraindicated or not tolerated; ICD implantation is indicated if history of aborted sudden cardiac death or sustained and/or haemodynamically poorly tolerated ventricular tachycardia.910912 In patients with no ventricular arrhythmias: ICD can be considered (see section 6.1) even in patients with LMNA or FLNC gene mutations and LVEF <45%.912

AC = arrhythmogenic cardiomyopathy; BAG3 = Bcl2-associated athanogene 3; CMR = cardiac magnetic resonance; DCM = dilated cardiomyopathy; DSC2 = desmocollin 2; DSG2 = desmoglein 2; DSP = desmoplakin; ECG = electrocardiogram; EMB = endomyocardial biopsy; FLN = filamin; FLNC = filamin C; HF = heart failure; HFrEF = heart failure with reduced ejection fraction; ICD = implantable cardioverter-defibrillator; JUP = junction plakoglobin; KCNH2 = potassium voltage-gated channel subfamily H member 2; KCNQ1 = potassium voltage-gated channel subfamily Q member 1; LDB3 = LIM domain binding 3; LMNA = lamin A/C; LV = left ventricular; LVEF = left ventricular ejection fraction; MRI = magnetic resonance imaging; NKX2-5 = NK2 transcription factor related, locus 5; PLN = phospholamban; PKP2 = plakophilin 2; RMB20 = ribonucleic acid binding motif 20; RV = right ventricular; SCN5A = sodium channel alpha subunit 5; TMEM43 = transmembrane protein 43; TNNT = troponin-T; TRPM4 = transient receptor potential cation channel subfamily M member 4. ESC 2021 Downloaded from academic.oup.com/eurheartj/article/42/36/3599/6358045 by guest on 07 October 2026