Available online 29 October 2022, 107494

Author links open overlay panelAbstractBackground

Dallas criteria (DC) and European Society of Cardiology criteria (ESCC) have provided valuable frameworks for the histologic diagnosis and classification of myocarditis in endomyocardial biopsy (EMB) specimens. However, the adaptation and the usage of these criteria are variable and depend on local practice settings and regions/countries. Moreover, several ancillary tests that are not included in the current criteria, such as immunohistochemistry (IHC) or viral polymerase chain reaction (PCR), have proven useful for the diagnosis of myocarditis.

Method

As a joint effort from the Association for European Cardiovascular Pathology (AECVP) and the Society for Cardiovascular Pathology (SCVP), we conducted an online survey to understand the current practice of diagnosing myocarditis.

Result

A total of 100 pathologists from 23 countries responded to the survey with the majority practicing in North America (45%) and Europe (45%). Most of the pathologists reported to examine less than 200 native heart biopsies per year (85%), and to routinely receive 3-5 fragments of tissue per case (90%). The number of hematoxylin-eosin-stained levels for each case varies from 1 to more than 9 levels, with 20% of pathologists routinely asking for more than 9 levels per case. Among the 100 pathologists, 52 reported to use the DC alone, 12 the ESCC alone, 28 both DC and ESCC and 8 reported to use neither the DC nor the ESCC. Overall, 80 pathologists reported to use the DC and 40 the ESCC. Use of DC alone is more common among North American pathologists compared to European ones (80% vs 32.6%) while use of ESCC alone is more common in Europe (20.9% vs 2.5%). IHC is utilized in either every case or selected cases by 79% of participants, and viral PCR is performed by 35% of participants. Variable terminologies are used in reporting, including both histological and clinical terms. The diagnosis of myocarditis is rendered even in the absence of myocyte injury (e.g., in cases of borderline or inactive/chronic myocarditis) by 46% respondents. The majority of the participants think it is time to update the current criteria (83%).

Conclusions

The survey data demonstrated that pathologists who render a myocarditis diagnosis practice with variable tissue preparation methods, use of ancillary studies, guideline usage, and reporting. This result highlights the clinically unmet need to update and standardize the current diagnostic criteria for myocarditis on EMB. Additional studies are warranted to establish standard of practice.

Introduction

Endomyocardial biopsy (EMB) is still considered the gold standard for the diagnosis of myocarditis, providing also important information on the inflammatory pattern. Although used infrequently, EMB could identify the etiology of the inflammatory process which is strictly linked to prognosis and to treatment [1]. EMB is clinically recommended in life-threatening clinical presentations and the reported complication rates related to the procedure are low (about 1%) [2], [3], [4]. In order to achieve optimal diagnostic accuracy and reduce sampling error, there are minimum requirements for EMBs: at least three fragments of endomyocardium need to be sampled and processed for histology; extra fragments can be used for molecular tests or ultrastructural studies, if indicated [5]. Biopsy sampling can be guided by imaging techniques in some circumstances [6,7]. Two sets of diagnostic criteria are commonly used by pathologists performing the diagnosis of myocarditis on EMB: the Dallas criteria (DC) and the European Society of Cardiology criteria (ESCC) [1,8]. The DC were introduced in 1987 with the qualitative assessment of three parameters (edema, inflammation, and necrosis) and the recognition of borderline and ongoing myocarditis. Based on the Marburg consensus [9], quantitative criteria for inflammatory infiltrates coupled with immunohistochemical analysis have been adopted as standard practice in many but not all institutions since the introduction of the ESCC in 2013 [1]. In addition to histological diagnosis, ancillary testing for viral genomes in myocardial tissue through polymerase chain reaction (PCR) has been used in certain scenarios and can provide useful information for the etiological diagnosis of myocarditis. Despite these advances, anecdotal reports suggest that considerable variability may persist among pathologists in the application of the diagnostic criteria, leading to differences in the rates of myocarditis diagnosed across institutions. In recent years, reports of myocarditis occurring as a presumed consequence of immune checkpoint inhibitor therapy or coronavirus (SARS-CoV-2) infection in patients with COVID-19 illustrate the potential problems associated with poorly reproducible or inconsistently applied diagnostic criteria and further highlight the need for improvements in the histopathologic diagnosis of myocarditis. An evaluation of the current application of the DC or ESCC for myocarditis diagnosis on EMBs by cardiovascular pathologists has never been performed. This investigation was performed to assess current usage of diagnostic criteria and variations in practice among cardiovascular pathologists who routinely evaluate EMBs obtained from patients with clinical suspicion for myocarditis.

Section snippetsScope of the survey

Between September 1 and September 16, 2021, we performed a survey of practicing cardiovascular pathologists worldwide who routinely evaluate EMBs from patients with clinically suspected myocarditis. The survey was undertaken to assess the variability in diagnosing myocarditis.

Survey creation and administration

Initial survey questions were generated by four experienced cardiovascular pathologists at academic institutions (two from European institutions and two working in the United States). The 39-question survey was sent to six

Characteristics of survey respondents

In total, survey results were received from 104 pathologists. Four entries were excluded because the respondents indicated they do not sign out EMBs. The 100 responses included in this study came from 79 centers (1-5 responses from each center) from 23 countries. Most of the pathologists practiced in North America (45%) and Europe (45%) (Fig. 1). Among these 79 centers, the majority represent academic hospitals (69, 87.3%), and the remainder represent non-academic hospital/private practice

Discussion

In this study, we surveyed 100 cardiovascular pathologists from around the world about their practice of diagnosing myocarditis. We demonstrated that there is a wide range of practice, from specimen preparation, ancillary studies performed, guidelines used, and terminology/nomenclature. The results of the survey highlight the need to update the current guidelines and to unify the practice of diagnosing myocarditis on EMB specimens.

Some of the differences in practice are regional. For instance,

Limitations

This survey-based analysis has all of the intrinsic limitations of the survey method including possible incomplete access to the population of concern, participant selection bias due to our modes of reaching out to the community, recall bias or participants, missing information, and collection of data at a single point in time without any possibility to measure changes in the population. The 15-day open period of the survey administration could implicate a limited sampling, but the total number

Conclusion

In conclusion, in a survey of 100 pathologists, a diverse number of practices regarding the diagnosis of myocarditis were given. These inconsistencies suggest the DC and ESCC are not sufficient for practicing pathologists and that it is time to update guidelines that will be reproducible and used more consistently to render the diagnosis of myocarditis. Our survey is a preliminary action of the main societies of cardiovascular pathology, that is, AECVP and SCVP, to start from the routine work

Declaration of Competing Interest

None.

Acknowledgments

The authors thank Drs. Ulrik Baandrup, Gregory Fishbein, Karin Klingel, Ornella Leone, Joseph Maleszewski, and Carmela Tan for their critical assessment of our survey questions and all respondents who participated in our survey. There were no sources of support for this research.

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