Biventricular arrhythmogenic cardiomyopathy – current diagnostic approach, pitfalls and risk stratification

A 27 year old man was referred by his cardiologist for a stress cardiac magnetic resonance imaging (CMR) in order to clarify a right bundle branch block in the electrocardiogram (ECG) with increased premature ventricle contractions during exercise ECG. The patient reported one episode of syncope, some months previously, but was otherwise asymptomatic, taking part in sports several times a week. Clinical examination was unremarkable, apart from plantar keratoderma with acanthosis and hypergranulosis (Figure 1). CMR demonstrated biventricular dilatation with preserved left ventricular ejection fraction, despite lateral hypokinesia with basal inferolateral myocardial thinning (Figure 2a). Late gadolinium enhancement demonstrated extensive subepicardial scar of the left ventricular ventricular (LV) free wall with transmural involvement of the right ventricle (Figure 2b). T2 mapping was normal but T1 mapping revealed significantly elevated values in the septum (LGE) (Figure 2c). On closer examination, the ECG (figure 3) demonstrated an unspecific bundle branch block with prominent inverted T-waves in the precordial leads (V1-V6). There was an epsilon wave present in V1 and V2. The patient’s father had died at the age of 50 of unknown cause. Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease characterized by replacement of the ventricular myocardium by fibrofatty tissue which can lead to potentially fatal ventricular arrhythmias, especially in young patients.  ACM has been characterized by wide spectrum of RV and LV abnormalities. Pathogenic mutations of ACM affect genes encoding structural proteins responsible for intercellular junctions, such as cardiac desmosomal proteins (i.e. Desmoplakin, DSP). The 2020 published “Padua criteria” represent a modern approach to diagnosis of ACM with integration of clinical and image findings without necessarily needing myocardial biopsy. The main differential diagnoses of dominant left ACV (ALVC) include dilated cardiomyopathy (DCM), myocarditis and sarcoidosis. In our case, fulfilling four major criteria (global RV and LV dilatation, regional LV hypokinesia, LGE in LV and RV, T-wave inversions) the diagnosis of ACM seems to be definite.
Surprisingly, the first pathological report shows a chronic myocardial injury, consistent with restrictive cardiomyopathy.
However, our patient also showed palmoplantar keratoderma which speaks for the entity of Desmoplakin Cardiomyopathy with the phenotype of ALVC since DSP is expressed in both the skin and myocardium. The final diagnosis can only be confirmed by the outstanding results of the second pathology report and genetic testing. This case demonstrates the oftentimes difficult differentiation between ACM and other genetic cardiomyopathies or non-genetic disorders as well as the challenging risk-stratification with the question of implanting a cardioverted defibrillator as primary prevention in young patients. We look forward to discuss the current diagnostic approach of ACM with emphasis on the uprising role of cardiovascular genetic testing.

Figure 1: