Endomyocardial Biopsy-Based Inflammatory Phenotypes Predict Outcomes in Virus-Negative Dilated and Inflammatory Cardiomyopathy

BACKGROUND: Inflammatory cardiomyopathy (CMi) is a major cause of heart failure, but the prognostic significance of different inflammatory phenotypes remains uncertain. Advanced immunohistochemical analyses of endomyocardial biopsies (EMBs) may improve risk stratification. OBJECTIVES: This study aims to evaluate the prognostic value of quantitative inflammatory phenotypes in virus-negative CMi. METHODS: Among 1,467 patients with unexplained heart failure undergoing EMB, 478 virus-negative patients were included and followed for a median of 26 months (Q1-Q3: 10-49 months). None received immunosuppressive therapy. Myocardial inflammation was characterized by histology and immunohistochemistry (CD3-positive, macrophage-1 antigen positive, CD45R0-positive, leukocyte function antigen-1 positive), with prognostic thresholds defined for each marker. Associations with mortality, deterioration in left ventricular ejection fraction, and persistent systolic dysfunction were evaluated using multivariable Cox regression and Kaplan-Meier analyses. RESULTS: ) cell counts were also associated with poorer survival and ventricular function (P < 0.01), even without elevated CD3 cells. These additional markers identified intramyocardial inflammation in 26% of patients who would otherwise not have been diagnosed. CD3-positive inflammation was associated with a higher hazard of the outcome (HR: 5.15 [95% CI: 3.4-7.67]; P < 0.001), while CD3-negative inflammation was also associated with an increased risk compared with patients without inflammation (HR: 2.44 [95% CI: 1.31-4.55]; P > 0.01). Higher quantitative immune cell counts were associated with progressively worse clinical outcomes, indicating a dose-response relationship between inflammatory burden and prognosis. CONCLUSIONS: Quantitative inflammatory phenotyping of EMB provides independent prognostic information in virus-negative CMi. These findings reflect the natural course of the disease without treatment and support refined biopsy-based diagnostics for improved risk stratification and personalized treatment strategies.