Use of high-resolution imaging methods for in vivo study of perfusion and myocardial inflammatory changes in an experimental model of chronic Chagas cardiomyopathy in hamster

Author(s)

Luciano Fonseca Lemos de Oliveira

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2018-10-10

Examining board members

Marcus Vinícius Simões; Jose Antonio Marin Neto; Celso Dario Ramos

• Advisor: Marcus Vinícius Simões

Abstract

Background: Myocardial perfusion defects (MPD) is a common finding in Chronic Chagas cardiomyopathy (CCC), but it is unclear if the perfusion late derangement can precede the left ventricular (LV) systolic dysfunction and fibrosis. We investigated the time-course of myocardial perfusion changes and the correlation with the histology and the progression of LV systolic dysfunction in an experimental model of CCC. Methods: The study included 40 female Syrian hamsters infected with 3.5x104 trypomastigotes forms of T. cruzi Y-strain and their respective controls (n=10). Surviving animals (22 infected and 10 controls) were submitted to in vivo imaging 2, 4, 6, 8 and 10- months afterwards. Rest high-resolution SPECT imaging using 99mTc-sestamibi was used to assess MPD extension that was analyzed by using polar maps considering the threshold <50% uptake compared to the maximum. The left ventricular ejection fraction (LVEF) and the systolic and diastolic diameter (LVSD and LVDD) were assessed by using 2Dechocardiogram. The animals underwent PET imaging using 18F-FDG for assessment of myocardial viability and inflammation. Histological analysis included quantification of myocardial inflammation intensity and fibrosis extension. Two way ANOVA was used for mixed models of repeated measured between two groups over the time. Additionally, one way ANOVA was used for three groups regarding the myocardial involvement within infected animals. Results: The two way ANOVA did not reveal difference in the LVEF between the groups over the time (p-value of interaction groups#time= 0.06). LVSD, LVDD and MPD presented progressive increase in infected animals (p-value of interaction groups#time< 0.05) and the differences were observed from 8 months after infection. Eight out of 22 (36%) surviving infected animals showed significant LV ejection fraction (LVEF) deterioration after 8-months (%; 60±11 vs 70±3 vs 70±5, p=0.007) and 10-months (%; 54±9 vs 70±3 vs 70±3, p<0.0001) compared to control and infected animals without systolic disfunction, respectively. However, MPD in infected animals showing LV systolic disfunction displayed significant progressive deterioration 6 monts after infection. Early stages of MPD correlated with the late values of LVEF, LVSD, LVDD and myocardial fibrosis. Moreover, MPD at 6-months correlated with the LVEF decrease from 6 to 10 months after infection (r= 0,56, p=0,0008). MPD exhibited frequency and topographic similarities with human CCC. Also, MPD correspond to metabolically viable myocardium and correlates topographically with higher 18F-FDG uptake suggesting MPD due to myocardial inflammation which was confirmed by histologic analysis. Conclusions: Rest MPD precedes the development and correlates with the ulterior fibrosis and deterioration of LV systolic dysfunction in experimental CCC. The MPD was topographically associated with elevated 18F-FDG uptake, suggesting a correlation between inflammation and the myocardial perfusion derangement. Our findings suggest that MPD maybe a surrogated marker of myocardial inflammation in CCC and raise the possibility of using perfusion imaging for risk stratification and monitoring the course of this myocardial disease. (AU)

• FAPESP's process: 15/25209-5 - Use of high-resolution imaging methods for in vivo study of perfusion and myocardial inflammatory changes in an experimental model of chronic Chagas cardiomyopathy in hamster
• Grantee: Luciano Fonseca Lemos de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate