Myocardial T-Lymphocytes as a Prognostic Risk-Stratifying Marker of Dilated Cardiomyopathy - Results of the Multicenter Registry to Investigate Inflammatory Cell Infiltration in Dilated Cardiomyopathy in Tissues of Endomyocardial Biopsy (INDICATE Study)

Abstract

Background: Dilated cardiomyopathy (DCM) associated with inflammation is diagnosed by endomyocardial biopsy; patients with this have a poorer prognosis than patients without inflammation. To date, standard diagnostic criteria have not been established.

Methods and results: This study analyzed clinical records and endomyocardial biopsy samples of 261 patients with DCM (201 males, median left ventricular ejection fraction; 28%) from 8 institutions in a multicenter retrospective study. Based on the European Society of Cardiology criteria and CD3 (T-lymphocytes) and CD68 (macrophages) immunohistochemistry, 48% of patients were categorized as having inflammatory DCM. For risk-stratification, we divided patients into 3 groups using Akaike Information Criterion/log-rank tests, which can determine multiple cut-off points: CD3⁺-Low, <13/mm²(n=178, 68%); CD3⁺-Moderate, 13-24/mm²(n=58, 22%); and CD3⁺-High, ≥24/mm²(n=25, 10%). The survival curves for cardiac death or left ventricular assist device implantation differed significantly among the 3 groups (10-year survival rates: CD3⁺-Low: 83.4%; CD3⁺-Moderate: 68.4%; CD3⁺-High: 21.1%; Log-rank P<0.001). Multivariate Cox analysis revealed CD3⁺count as a potent independent predictive factor for survival (fully adjusted hazard ratio: CD3⁺-High: 5.70, P<0.001; CD3⁺-Moderate: 2.64, P<0.01). CD3⁺-High was also associated with poor left ventricular functional and morphological recovery at short-term follow up.

Conclusions: Myocardial CD3⁺T-lymphocyte infiltration has a significant prognostic impact in DCM and a 3-tiered risk-stratification model could be helpful to refine patient categorization.

Keywords: CD3; Chronic myocarditis; Dilated cardiomyopathy; Endomyocardial biopsy; Multiple cut-off points.