Histopathological Correlates of Global and Segmental Left Ventricular Systolic Dysfunction in Experimental Chronic Chagas Cardiomyopathy Luciano Fonseca Lemos de Oliveira, PT, Ms; Minna Moreira Dias Romano, MD, PhD; Eduardo Elias Vieira de Carvalho, PT, Ms; Jorge Mejia Cabeza, PhD; H elio Cesar Salgado, MD, PhD; Rubens Fazan J unior, MD, PhD; Renata Sesti Costa, PhD; Jo~ ao Santana da Silva, PhD; Maria de Lourdes Higuchi, MD, PhD; Benedito Carlos Maciel, MD, PhD; Ed ecio Cunha-Neto, MD, PhD; Jos e Ant^ onio Marin-Neto, MD, PhD; Marcus Vin  ıcius Sim~ oes, MD, PhD Background-—Chronic Chagas cardiomyopathy in humans is characterized by segmental left ventricular wall motion abnormalities (WMA), mainly in the early stages of disease. This study aimed at investigating the detection of WMA and its correlation with the underlying histopathological changes in a chronic Chagas cardiomyopathy model in hamsters. Methods and Results- —Female Syrian hamsters (n=34) infected with 3.5910 4 or 10 5 blood trypomastigote Trypanosoma cruzi (Y strain) forms and an uninfected control group (n=7) were investigated. After 6 or 10 months after the infection, the animals were submitted to in vivo evaluation of global and segmental left ventricular systolic function by echocardiography, followed by euthanasia and histological analysis for quantitative assessment of fibrosis and inflammation with tissue sampling in locations coinciding with the left ventricular wall segmentation employed at the in vivo echocardiographic evaluation. Ten of the 34 infected animals (29%) showed reduced left ventricular ejection fraction (<73%). Left ventricular ejection fraction was more negatively correlated with the intensity of inflammation (r=À0.63; P<0.0001) than with the extent of fibrosis (r=À0.36; P=0.036). Among the 24 animals with preserved left ventricular ejection fraction (82.9Æ5.5%), 8 (33%) showed segmental WMA predominating in the apical, inferior, and posterolateral segments. The segments exhibiting WMA, in comparison to those with normal wall motion, showed a greater extent of fibrosis (9.3Æ5.7% and 7Æ6.3%, P<0.0001) and an even greater intensity of inflammation (218.0Æ111.6 and 124.5Æ84.8 nuclei/mm², P<0.0001). Conclusions-—Isolated WMA with preserved global systolic left ventricular function is frequently found in Syrian hamsters with experimental chronic Chagas cardiomyopathy whose underlying histopathological features are mainly inflammatory. ( J Am Heart Assoc. 2016;5:e002786 doi: 10.1161/JAHA.115.002786) Key Words: Chagas heart failure • echocardiography • pathology C hronic Chagas cardiomyopathy (CCC) is a significant cause of morbidity and mortality in Central and South America, with estimates of about 8 to 10 million infected people and 25 million people at risk. 1 Moreover, migratory currents have caused the spread of the disease, with thousands of infected people identified in the United States 2 and Europe. 3–5 Despite its relevance, several clinical and pathophysio- logical aspects of CCC progression remain unknown, mainly due to the lack of long-term clinical cohort studies. The main aspect preventing the execution of these studies is the very long time period, about 3 decades, usually elapsing between the initial asymptomatic acute phase and the late chronic phase in which myocardial dysfunction and a dilated cardiomyopathy pattern become manifest. 6 Considering this scenario, appropriate animal models of CCC may constitute a relevant tool to investigate the mechanisms leading to chronic myocardial damage in this disease. 7–9 An experimental model of chronic Trypanosoma cruzi infection in Syrian hamsters has been described, which mimics human CCC in many aspects, 10,11 including progres- sive left ventricular (LV) systolic dysfunction and dilation starting about 4 months after T. cruzi inoculation. 12,13 From the Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil (L.F.L.O., M.M.D.R., E.E.V.C., H.C.S., R.F.J., R.S.C., J.S.S., B.C.M., J.A.M.-N., M.V.S.); Heart Institute (InCor), Faculty of Medicine, University of Sao Paulo, Brazil (M.L.H., E.C.-N.); Hospital Israelita Albert Einstein, Sao Paulo, Brazil (J.M.C.). Correspondence to: Marcus Vinicius Sim~ oes, MD, PhD, Cardiology Division, Internal Medicine Department, Hospital das Cl  ınicas, Faculdade de Medicina de Ribeir~ ao Preto, 3900 Bandeirantes Ave, Ribeir~ ao Preto, S~ ao Paulo 14048900, Brazil. E-mail: msimoes@fmrp.usp.br Received October 22, 2015; accepted December 8, 2015. ª 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. DOI: 10.1161/JAHA.115.002786 Journal of the American Heart Association 1 ORIGINAL RESEARCH