JACC Heart Fail. 2026 Jun 29:103185. doi: 10.1016/j.jchf.2026.103185. Online ahead of print.
ABSTRACT
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.
PMID:42376715 | DOI:10.1016/j.jchf.2026.103185