European Heart Journal Advance Access originally published online on September 26, 2008
European Heart Journal 2008 29(22):2760-2771; doi:10.1093/eurheartj/ehn415
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Quantitative assessment of endomyocardial biopsy in arrhythmogenic right ventricular cardiomyopathy/dysplasia: an in vitro validation of diagnostic criteria
1 Pathological Anatomy, Department of Medico-Diagnostic Sciences and Special Therapies, University of Padua Medical School, Via A. Gabelli, 61, 35121 Padua, Italy
2 Department of Medicine, Section of Cardiology, University of Arizona, Tucson, AZ, USA
3 Department of Environmental Medicine and Public Health, University of Padua Medical School, Padua, Italy
4 Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua Medical School, Padua, Italy
Received 23 January 2008; revised 21 August 2008; accepted 22 August 2008; online publish-ahead-of-print 26 September 2008.
* Corresponding author. Tel: +39 0498272283, Fax: +39 0498272284, Email: gaetano.thiene{at}unipd.it or cardpath{at}unipd.it
See page 2705 for the editorial comment on this article (doi:10.1093/eurheartj/ehn471)
Aims: To provide a standardized endomyocardial biopsy (EMB) protocol and diagnostic quantitative parameters for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). The Task Force criteria for the in vivo diagnosis of ARVC/D include tissue characterization by EMB as a major criterion.
Methods and results: EMBs were simulated in vitro with a Cordis bioptome in explanted hearts from six groups: diffuse (n = 10) and segmental (n = 10) ARVC/D, dilated cardiomyopathy (DC) (n = 10), controls (n = 10), adipositas cordis (n = 10), elderly >80 years (n = 10). Sampling sites were the RV inferior-subtricuspid, antero-apical, and mid-outflow tract (RVOT), the septum, and the left ventricle (LV). Histomorphometry was performed to evaluate the amount of myocardium and fibrous and fatty tissues. Myocyte diameters and abnormalities were also assessed. By selecting a 95% specificity, the ARVC/D diagnostic cut-offs on cumulative RV EMB samples are myocardium <59%, fibrosis >31% and fat >22% (80, 50, and 50% sensitivity, respectively). By excluding elderly and obese people groups a lower cut-off for fat was found (>9%). A high variability between different RV sampling sites was observed; the antero-apical was the most informative region although fat at this level is non-specific. No useful diagnostic cut-off for fatty tissue was identified at the antero-apical and RVOT area. No significant difference was found for any tissue parameter either in septal or in LV EMB. Increased RV myocyte diameters and cytological changes were detected in ARVC/D and DC.
Conclusion: The residual myocardium is the main diagnostic morphometric parameter in ARVC/D, whereas fat at the apex is non-specific. Sensitivity and specificity vary according to the RV region. Target sampling of the triangle of dysplasia is required, although only a single region is often informative, emphasizing the usefulness of imaging-guided EMB. There is no diagnostic value of either septal or LV EMB. Cardiomyopathic changes of the myocytes also appear important for establishing a pathological diagnosis.
Key Words: Arrhythmogenic right ventricular cardiomyopathy • Diagnostic criteria • Endomyocardial biopsy • Pathology
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