Utility of immunofluorescence and electron microscopy in endomyocardial biopsies from patients with unexplained heart failure

Abstract 

Background

With our increasing understanding of inflammatory heart disease, the relevance of Dallas criteria has come into question. Immunofluorescence (IF) and electron microscopy (EM) can potentially identify immune reactants and ultrastructural changes not visible by light microscopy (LM), particularly in cases not meeting Dallas criteria.

Methods

This was a retrospective, descriptive study of native endomyocardial biopsies (MBx) performed 1981 to 2006, undertaken to assess the utility of these methods. All patients had decreased cardiac function but normal coronary angiographic studies. LM identified cases as myocarditis (Dallas+), borderline myocarditis (Dallas+/−), or cardiomyopathy (Dallas−). IF studies (human leukocyte antigen (HLA)-DR, IgG, IgM, IgA, C3d, C1q, and fibrinogen) reported interstitial, capillary, or heart-reactive, antibody-like staining patterns. EM findings were also reviewed.

Results

Of 472 records from 429 patients (6 months–78 years old), 44 were Dallas+, 47 Dallas+/−, and 381 Dallas−. Significant IF and/or EM findings were identified in 421 cases (89%). By IF, 142 (37%) Dallas− cases had significant capillary HLA-DR expression. Thirty-four of 37 cases with vascular immune complex deposition were Dallas−. LM commonly failed to detect myofilament loss (138 cases) and endothelial cell changes (126 cases) that were observed by EM.

Conclusions

IF is a useful strategy for defining inflammatory phenomenon as it revealed significant immune-related heart disease not demonstrable by LM. EM better defined myofilament loss, a finding previously found to be associated with adverse clinical outcome. We strongly recommend that a portion of tissue obtained from all MBx be routinely frozen for IF and fixed appropriately for EM studies. Future studies characterizing the inflammatory molecular profile of myocardial tissues may better define myocarditis.

Keywords: Myocarditis, Electron microscopy, Immunoglobulin, Complement