Elsevier

Cardiovascular Pathology

Volume 34, May–June 2018, Pages 15-21
Cardiovascular Pathology

Original Article
Endomyocardial biopsy in differential diagnosis between arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy: an in vitro simulated study

https://doi.org/10.1016/j.carpath.2018.02.003Get rights and content

Highlights

  • Proportion of tissue components differs in transmural sections between ARVC and DCM.

  • Diagnostic efficacy of EMB between ARVC and DCM is a positive fact and meaningful.

  • Perforation risk in EMB at RV wall in some advanced ARVC stages is not negligible.

  • Perforation risk can be avoided by CT to select patients with ample RV wall thickness.

  • The best EMB sampling site between ARVC with low perforation risk and DCM is ARV.

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) and dilated cardiomyopathy (DCM), despite being two dramatically different entities, have overlapping phenotypes. As it is easy to misdiagnose between ARVC and DCM, there is a need to establish a new differential diagnostic parameter to differentiate the two. We investigated the utility of endomyocardial biopsy (EMB) for the differential diagnosis, and our study had three aims. The first was to verify the EMB high diagnostic efficacy. The second was to investigate the EMB perforation risk at the right ventricle (RV) free wall of end-stage ARVC. The third was to determine the best EMB sampling site in differential diagnosis between ARVC and DCM. Transmural tissues were sampled at six sites on the ventricular free walls and interventricular septum of recipient hearts (35 ARVCs and 35 DCMs). Participants with wall thickness <1.7 mm were included in the subgroup with high perforation risk, and the rest were included in a subgroup with low perforation risk. The best EMB sampling site was determined by the largest area under curve (AUC) among receiver operating characteristic curves. We found significant differences (P<.01) in percentages of tissue components in transmural sections between ARVC and DCM. In the subgroup with high perforation risk, there were 12 ARVCs and no DCMs, and paper-like RV walls and transmural fat replacement were their features in the cardiac enhancement computed tomography images. In the subgroup with low perforation risk, the largest AUC was on the myocardium at the ARV: AUC=0.839, cutoff=74.76%, sensitivity=73.68%, specificity=97.14%. We conclude that EMB high differential diagnostic efficacy is a meaningful fact regardless of limited sampling range, that EMB perforation risk at the RV free wall of end-stage ARVC cannot be neglected, and that the best EMB sampling site is the ARV. Among participants with low perforation risk, ARV is still recommended as an EMB sampling site with good differential diagnostic efficacy.

Introduction

The clinical characterizations of arrhythmogenic right ventricular cardiomyopathy (ARVC) are frequent ventricular tachycardia, heart failure, and high risk of sudden cardiac death (SCD) [1], [2]. Although the morbidity incidence of ARVC is estimated at 1:1000 to 5000 [2], more than 20% of SCDs are considered to be caused by ARVC [3], [4]. The pathological characterization of ARVC is progressive fibrofatty replacement of ventricular myocardium [1], [2], [5], [6], [7], and the fibrofatty replacement occurs primarily in the right ventricular (RV) anteroapical region and at the RV midoutflow tract (RVOT) and inferior subtricuspid. These three regions are called the “triangle of dysplasia” [7], [8]. Other regions, including the left ventricle (LV), can also be involved [2], [9].

The clinical characterizations of dilated cardiomyopathy (DCM) are contractile progressive dysfunction of the LV often with arrhythmias but less prominent [10].

The Taskforce Criteria 2010 (TFC-2010) are the latest criteria proposed to diagnose ARVC, composed of six categories. In each category, it has major and minor criteria. Tissue characterization of endomyocardial biopsy (EMB) sections is one of the six categories in TFC-2010, and the major criterion of this category is residual myocytes less than 60% by morphometric analysis (or <50% if estimated), with fibrous replacement of the RV free wall in one or more samples in EMB sections [11]. This major criterion in TFC-2010 comes from an article in the European Heart Journal by Basso et al. [12]. As mentioned by Basso et al., EMB has the highest specificity among testing for ARVC, so EMB is the most important test for diagnosing ARVC, but there is no comparison of tissue components in transmural sections between ARVC and DCM to demonstrate that the diagnostic efficacy of EMB is not a false-positive finding caused by a limited sampling range.

Although some authors reported that EMB sampling at the RV free wall has low perforation risk in patients at an early stage whose pathological change is not advanced and not severe [13], data about EMB perforation risk are still lacking on end-stage ARVC hearts.

Although ARVC and DCM are seemingly two dramatically different entities, they have overlapping phenotypes. As is shown in some articles [2], [9], involvement of the LV was discovered in 76% of the ARVC hearts studied postmortem. On the other hand, RV could also be involved in end-stage DCM. Therefore, it is easy to misdiagnose between ARVC and DCM, and there is a need to establish a new differential diagnostic parameter for ARVC and DCM. As was mentioned above, EMB is the most important test for ARVC diagnosis. Therefore, we investigated the utility of EMB in differential diagnosis between ARVC and DCM and sought to determine the best EMB sampling site for the differential diagnosis.

Section snippets

Patients

All 35 ARVC patients who had a heart transplantation (HTx) fulfilled the ARVC TFC-2010 (without a tissue characterization of the wall category) and the current pathological criteria in ARVC transmural sections [8]. All 35 DCM HTx patients fulfilled the DCM inclusion and exclusion criteria [14]: left ventricular end-diastolic diameter (LVEDD) greater than 27 mm/m2 and left ventricular ejection fraction (LVEF) less than 45%, and no significant coronary heart disease or congenital heart disease.

Diagnostic details of ARVC participants

All 35 ARVCs were diagnosed by TFC-2010 (without tissue characterization of wall category) (Table S1). Thirty-two of the 35 ARVC participants were definitely diagnosed; 1 of the 35 fulfilled the borderline criteria, and 2 of the 35 met criteria for possible diagnosis.

Baseline and clinical data

The 35 matched DCMs were from 186 DCM HTx patients (Fig. S3). Baseline data were not significantly different between groups (Table S2). Comparison of clinical data between ARVC and DCM showed that RV diameter and LVEF in the ARVC

Discussion

The baseline parameters were balanced between the ARVC and DCM, and comparison of clinical and gross pathological data between ARVC and DCM demonstrated that these data are consistent with the theoretical phenotype of ARVC and DCM.

Conclusion

ARVC and DCM can be differentiated in transmural sections, so the good EMB differential diagnostic efficacy between ARVC and DCM is a meaningful fact regardless of the limited sampling range. EMB perforation risk at the RV free wall with end-stage ARVC cannot be neglected. The best EMB sampling site is ARV. Among participants with low perforation risk, ARV is still recommended as an EMB sampling site with good differential diagnostic efficacy between ARVC and DCM.

Clinical significance

We propose a path of differential diagnosis between ARVC and DCM using EMB among patients with low perforation risk. First, select patients whose RV wall thickness is sufficient for EMB beforehand by cardiac enhancement CT, and RV wall thickness more than 1.7 mm is considered thick enough for EMB. Then EMB is performed in these patients, and the remainder can be diagnosed as ARVC by paper-like RV wall and transmural fat replacement in the CT image.

The following are the supplementary data

Funding statements

The current study was sponsored by the CAMS Innovation Fund for Medical Sciences (2016-I2M-1-015) and the National Natural Science Foundation of China (grant no. 81670376) and was also supported by the PUMC Youth Fund and the Fundamental Research Funds for the Central Universities.

Conflict of interest

None.

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