Right from the heart: when should myocardial biopsy be performed for suspected arrhythmogenic right ventricular cardiomyopathy/dysplasia?

A host of uncommon but clinically important myocardial diseases including arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) have unique prognoses and treatments and should be strongly suspected in their characteristic clinical scenarios. ARVC/D is an inherited or sporatic form of predominantly right ventricular cardiomyopathy characterized by a progressive loss of myocytes that are replaced by fibrofatty tissue. The typical patient is in their third to fifth decade, and presents with ventricular arrhythmias, palpitations, syncope, or sudden death. The ECG may reveal epsilon waves, T-wave inversions, and/or localized QRS complex duration .110 ms in V1–V3. Imaging of the right ventricle by echocardiography, computed tomography (CT), or magnetic resonance imaging (MRI) may reveal focal or global dilatation or aneurysm formation. Because cardiac sarcoidosis or focal noncompaction syndrome, which have distinct aetiologies and treatments, can share AVRC/D’s clinical features, and non-invasive testing can be inconclusive, histological confirmation of ARVC/D is sometimes necessary. Basso et al. have presented a case series of 300 simulated biopsies, one each from five sites in 60 hearts obtained at transplantation or autopsy. They performed endomyocardial biopsy (EMB) on hearts with diffuse or segmental ARVC/D and compared the histological features of hearts from aged, obese, and normal people, and hearts with idiopathic dilated cardiomyopathy. The author’s primary finding is that the degree of residual myocardium from the right ventricular outflow tract, free wall, and apex can reliably distinguish focal and diffuse ARVC/D from these other conditions. In contrast, histology from the right ventricular septum, where myocardial tissue is typically sampled, and the left ventricle cannot distinguish ARVC/D from the comparator conditions. This study adds substantially to the knowledge of ARVC/ D by informing us where to biopsy for suspected ARVC/D and what the precise histological criteria should be for diagnosis. The Basso study used hearts obtained at autopsy or transplantation, presumably from patients with advanced histological disease. Patients in a typical clinical population may present earlier with palpitations or mild heart failure, and have less severe histological disease, which could result in a lower sensitivity of EMB. Because the authors did not include a control group with cardiac sarcoidosis, a typically focal disorder for which EMB has only a 20–30% sensitivity, the ability of EMB to distinguish ARVC/D from cardiac sarcoidosis remains unknown. Although the investigators used a single piece of myocardium from each site to derive their diagnostic criteria, we do not know the amount of myocardium needed to establish the diagnosis of ARVC/D in the clinical setting where several regional inflammatory and non-inflammatory disorders are possible. Despite its limitations, the Basso study has clearly established that there is no role for right ventricular septal biopsy to establish a diagnosis solely for suspected AVRC/D. The clinician’s choice is either to rely on non-invasive tests to infer the diagnosis or to recommend EMB in the ‘triangle of dysplasia’, that includes the free wall, apex and right ventricular outflow tract. Unfortunately, we do not yet know whether cardiac MRI can ‘guide’ EMB to regions with characteristic histological findings, as has been demonstrated with lymphocytic myocarditis. When should EMB be performed in the clinical scenario of suspected ARVC/D? The consensus recommendation in the 2007 AHA/ACCF/ESC scientific statement on the role of EMB in