Key result
Chronic Trypanosoma cruzi infection in dogs significantly reduced left ventricular ejection fraction compared to controls, with 28% of infected dogs developing severe systolic dysfunction (EF ≤ 40%), closely mimicking human disease.
Why the study?
Preclinical translation often fails because animal models may not reproduce distinctive human disease features, and methods to measure treatment effects lack established reproducibility.
Does the canine model of chronic Trypanosoma cruzi infection reproduce the left ventricular dysfunction seen in human chronic chagasic cardiomyopathy?
Does the canine model of chronic Trypanosoma cruzi infection reproduce the left ventricular dysfunction seen in human chronic chagasic cardiomyopathy?
Absolute Event Rate: 45.11% vs 55.3%
p-value: p=<0.05
The canine model of chronic Chagasic cardiomyopathy mimics human disease by reproducing the ~30% incidence of systolic dysfunction, highlighting the need for strict inclusion criteria (EF ≤ 40%) in preclinical trials.
Animal model and echo reproducibility issues warrant caution in preclinical LV endpoints; leaves open reliable clinical translation.
Background: The failure to translate preclinical results to the clinical setting is the rule, not the exception. One reason that is frequently overlooked is whether the animal model reproduces distinctive features of human disease. Another is the reproducibility of the method used to measure treatment effects in preclinical studies. Left ventricular (LV) function improvement is the most common endpoint in preclinical cardiovascular disease studies, while echocardiography is the most frequently used method to evaluate LV function. In this work, we conducted a robust echocardiographic evaluation of LV size and function in dogs chronically infected by Trypanosoma cruzi. Methods and Results: Echocardiography was performed blindly by two distinct observers in mongrel dogs before and between 6 and 9 months post infection. Parameters analyzed included end-systolic volume, end-diastolic volume, ejection fraction (EF) and fractional shortening (FS). We observed a significant LVEF and FS reduction in infected animals compared to controls, with no significant variation in volumes. However, the effect of chronic infection in systolic function was quite variable, with EF ranging from 17 to 66%. Using the cut-off value of EF ≤ 40%, established for dilated cardiomyopathy in dogs, only 28% of the infected dogs were affected by the chronic infection. Conclusions: The canine model of CCC mimics human disease, reproducing the percentage of individuals that develop heart failure during the chronic infection. It is thus mandatory to establish inclusion criteria in the experimental design of canine preclinical studies to account for the variable effect that chronic infection has on systolic function.
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Carvalho et al. (2019) studied Chronic Chagasic Cardiomyopathy (n=88). Trypanosoma cruzi infection vs. Non-infected controls was evaluated on Left ventricular ejection fraction (EF) (p=<0.05). Chronic Trypanosoma cruzi infection in dogs significantly reduced left ventricular ejection fraction compared to controls, with 28% of infected dogs developing severe systolic dysfunction (EF ≤ 40%), closely mimicking human disease.
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