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).

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/mm(n=178, 68%); CD3-Moderate, 13-24/mm(n=58, 22%); and CD3-High, ≥24/mm(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 CD3count 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 CD3T-lymphocyte infiltration has a significant prognostic impact in DCM and a 3-tiered risk-stratification model could be helpful to refine patient categorization.