Biomarkers in Trypanosoma cruzi-Infected and Uninfected Individuals with Varying Severity of Cardiomyopathy in Santa Cruz, Bolivia

Abstract

BackgroundTwenty to thirty percent of persons with Trypanosoma cruzi infection eventually develop cardiomyopathy. If an early indicator were to be identified and validated in longitudinal studies, this could enable treatment to be prioritized for those at highest risk. We evaluated cardiac and extracellular matrix remodeling markers across cardiac stages in T. cruzi infected (Tc+) and uninfected (Tc−) individuals.MethodsParticipants were recruited in a public hospital in Santa Cruz, Bolivia and assigned cardiac severity stages by electrocardiogram and echocardiogram. BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2 were measured in specimens from 265 individuals using multiplex bead systems. Biomarker levels were compared between Tc+ and Tc− groups, and across cardiac stages. Receivers operating characteristic (ROC) curves were created; for markers with area under curve>0.60, logistic regression was performed.ResultsAnalyses stratified by cardiac stage showed no significant differences in biomarker levels by Tc infection status. Among Tc+ individuals, those with cardiac insufficiency had higher levels of BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 than those with normal ejection fraction and left ventricular diameter. No individual marker distinguished between the two earliest Tc+ stages, but in ROC-based analyses, MMP-2/MMP-9 ratio was significantly higher in those with than those without ECG abnormalities.ConclusionsBNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 levels rose with increasing severity stage but did not distinguish between Chagas cardiomyopathy and other cardiomyopathies. Among Tc+ individuals without cardiac insufficiency, only the MMP-2/MMP-9 ratio differed between those with and without ECG changes.

Metalloproteinases 2 and 9 in different stages of chronic Chagas disease

“…MMP-2 and MMP-9 were also determined in serum samples from Bolivian patients who were in different stages of chronic Chagas disease and compared to non-chagasic cardiac patients, by means of Milliplex MAP Human MMP Magnetic Bead Panel 2. MMP-2 and MMP-9 were increased only in the advanced stages of chronic Chagas and non-chagas cardiac diseases [5,6].MMP-9 was not augmented in our chagasic and non-chagasic patients with compensated heart failure [4]. Possible explanations, for these apparently contradictory results, could be the clinical status and the degree of cardiac remodeling of the patients.…”

“…Thus, the compensated status of our chagasic and non-chagasic patients with eccentric ventricular hypertrophy could explain the lower levels of MMP-9 and still increased values of MMP-2. It should be emphasized that, the MMP-2-MMP-9 ratio did differ between Bolivian chagasic patients with and without abnormal electrocardiograms [6]. Finally, although follow up clinical investigations indicate that, most chagasic patients in the indeterminate…”

“…MMP-2 and MMP-9 were also determined in serum samples from Bolivian patients who were in different stages of chronic Chagas disease and compared to non-chagasic cardiac patients, by means of Milliplex MAP Human MMP Magnetic Bead Panel 2. MMP-2 and MMP-9 were increased only in the advanced stages of chronic Chagas and non-chagas cardiac diseases [5,6].…”

“…Therefore, several investigations have been conducted to identify predictive biomarkers of progression of this disease. To this purpose, matrix metaloproteinases 2 (MMP-2) and 9 (MMP-9) were studied in patients with positive serology for Chagas' disease from different endemic areas of South America [3][4][5][6].…”

Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia

“…Class I was defined based on normal results on electrocardiogram and a normal ejection fraction [(EF); >50%] on echocardiogram 26 . Class II was defined if any of the following were present on echocardiography: intraventricular conduction delay, right bundle branch block, left bundle branch block, left anterior hemiblock, left posterior hemiblock, 1 st , 2 nd or 3 rd degree atrioventricular block, multifocal or paired ventricular premature beats, atrial fibrillation or flutter, pacemaker, atrioventricular dissociation or severe bradycardia (<50bpm) 2,27 . Participants were assigned to class III (EF 40-50%) or to class IV (EF < 40%) based on echocardiogram findings 26 .…”