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

Elevated CD3-positive T cells (≥7.8 cells/mm2) were the strongest independent predictor of mortality and deterioration of left ventricular ejection fraction (HR: 1.037 [95% CI: 1.027-1.047]; P < 0.001). Increased macrophage-1 antigen positive (≥40 cells/mm2), CD45R0-positive (≥21 cells/mm2), or leukocyte function antigen-1-positive (≥12.5 cells/mm2) 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.