The Frequency of CD3+ Lymphocytes in Non-myocarditis Endomyocardial Biopsies

Lymphocytic myocarditis is a serious disease with significant morbidity and mortality. Cardiovascular pathology has an important role in its diagnosis, a diagnosis historically made using the presence of a lymphocytic infiltrate and myocyte injury (Dallas Criteria). The European Society of Cardiology (ESC) criteria, additionally, use a threshold of immune cells, determined by CD3 immunohistochemical stains to render the diagnosis of myocarditis on endomyocardial biopsy. However, the frequency of immune cells in non-myocarditis endomyocardial biopsy cases is unclear and dependent on different evaluation methods. Therefore, an international consortium of 6 centers assessed endomyocardial biopsies on patient populations for the count of CD3+ lymphocytes in the one busiest high-powered field (hpf) per case. In total, 359 biopsies, performed for reasons other than a clinical suspicion of myocarditis, were evaluated. The clinical decision to biopsy was mainly for the differential diagnosis of hypertrophic cardiomyopathy (n=133, 37%); amyloidosis (n=103, 29%); hypertensive heart disease (n=96, 27%) or other non-inflammatory diseases. The average number of CD3+ lymphocytes in the busiest hpf was 3.1 (median 2). Over 96% of cases had fewer than 10 lymphocytes in the busiest hpf. There were no significant differences by sex or age, but institutional differences in the count of CD3+ lymphocytes were significant. These findings will help classify the abundance of lymphocytes on non-myocarditis endomyocardial biopsies for use in myocarditis criteria classifications.