The amount of MF, either by histopathology or by ce-MRI, is associated with the degree of left ventricular functional improvement and all-cause mortality late after aortic valve replacement in patients with severe aortic valve disease.

In the present review we have summarized remarkable historical data on Chagas' disease studies putting special emphasis on histopathological findings and pathogenetic theories as well as recent discoveries based on the use of advanced modern technologies in pathology and immunology. A unified theory that links almost all of these findings is proposed. Chronic cardiac Chagas' disease represents the result of a close interaction between the host and the parasite, causing different clinical pictures: patients with an efficient immune response may adequately circumvent the parasitic infection and the individual will develop the indeterminate form. Deficient immune response of the host and/or a high initial parasitemia favor an immune imbalance that might lead to development of a permanent inadequate immunological response against the parasite. The inflammatory response, which is probably recurrent, undergoing periods of more accentuated exacerbation, is most likely responsible for progressive neuronal damage, microcirculatory alterations, heart matrix deformations and consequent organ failure.

Chronic Chagas' disease cardiomyopathy is a leading cause of congestive heart failure in Latin America, affecting more than 3 million people. Chagas' cardiomyopathy is more aggressive than other cardiomyopathies, but little is known of the molecular mechanisms responsible for its severity. We characterized gene expression profiles of human Chagas' cardiomyopathy and dilated cardiomyopathy to identify selective disease pathways and potential therapeutic targets. Both our customized cDNA microarray (Cardiochip) and real-time reverse transcriptase-polymerase chain reaction analysis showed that immune response, lipid metabolism, and mitochondrial oxidative phosphorylation genes were selectively up-regulated in myocardial tissue of the tested Chagas' cardiomyopathy patients. Interferon (IFN)-gamma-inducible genes represented 15% of genes specifically up-regulated in Chagas' cardiomyopathy myocardial tissue, indicating the importance of IFN-gamma signaling. To assess whether IFN-gamma can directly modulate cardio-myocyte gene expression, we exposed fetal murine cardiomyocytes to IFN-gamma and the IFN-gamma-inducible chemokine monocyte chemoattractant protein-1. Atrial natriuretic factor expression increased 15-fold in response to IFN-gamma whereas combined IFN-gamma and monocyte chemoattractant protein-1 increased atrial natriuretic factor expression 400-fold. Our results suggest IFN-gamma and chemokine signaling may directly up-regulate cardiomyocyte expression of genes involved in pathological hypertrophy, which may lead to heart failure. IFN-gamma and other cytokine pathways may thus be novel therapeutic targets in Chagas' cardiomyopathy.

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Cellular subpopulations that infiltrate the heart in human chronic chagasic myocarditis were defined immunohistochemically in endomyocardial biopsy (EMB) specimens. T cells formed 96.3% of the inflammatory infiltrate, predominantly CD8+ (cytotoxic/suppressor) T cells. The mean numbers of CD8+ and CD4+ (helper) T cells in the myocarditis were compared to those present in the myocardial rejection process. Mean numbers of CD8+ T cells were similar in both groups of EMB specimens while CD4+ T cell counts, CD4+/CD8+ ratios and CD4+ antigen expression were significantly lower in the chagasic group compared to the myocardial rejection group (P < 0.002). The persistent lower number and diminished expression of CD4+ T cells suggest an immunological imbalance in patients with chronic chagasic myocarditis. A possible participation of Trypanosoma cruzi parasites in the development of such immunological abnormalities is also discussed.