Biomarkers and Mortality in Severe Chagas Cardiomyopathy

Abstract

Background Chagas cardiomyopathy is a chronic sequela of infection by the parasite, Trypanosoma cruzi. Advanced cardiomyopathy is associated with a high mortality rate, and clinical characteristics have been used to predict mortality risk. Though multiple biomarkers have been associated with Chagas cardiomyopathy, it is unknown how these are related to survival. Objectives Our study aimed to identify biomarkers associated with mortality in individuals with severe Chagas cardiomyopathy in an urban Bolivian hospital. Methods The population included individuals with and without T. cruzi infection recruited in an urban hospital in Santa Cruz, Bolivia. Baseline characteristics, ECG findings, medications, and serum cardiac biomarker levels (BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2) were ascertained. Echocardiograms were preferentially performed on those with cardiac symptoms or electrocardiogram abnormalities. Participants were contacted by phone approximately 1 year after initial evaluation; deaths were reported by family members. Receiver operating characteristic curves were used to optimize cut-off values for each marker. For markers with area under curve > 0.55, Cox proportional hazards models were performed to determine the hazards ratio (HR) and 95% confidence interval (CI) for the association of each marker with mortality. Results The median follow-up time was 14.1 months (interquartile range 12.5- 16.7 months). Of 254 individuals with complete cardiac data, 220 (87%) had follow-up data. Of 50 patients with severe Chagas cardiomyopathy, 20 (40%) had died. Higher baseline levels of BNP (HR[95% CI]:3.1 [1.2, 8.4]), NTproBNP (4.4[1.8,11.0]), CKMB (3.3[1.3, 8.0]), and MMP-2 (4.2[1.5, 11.8]) were significantly associated with subsequent mortality. Conclusions Severe Chagas cardiomyopathy is associated with high short-term mortality. BNP, NTproBNP, CKMB and MMP2 have added predictive value for mortality, even in the presence of decreased ejection fraction and other clinical signs of congestive heart failure.

An ImmunoSignature test distinguishes Trypanosoma cruzi, hepatitis B, hepatitis C and West Nile virus seropositivity among asymptomatic blood donors

“…It would also be desirable to predict which indeterminate-stage individuals will remain asymptomatic from those that will progress to suffering life-threatening complications. A recent study identified four biomarkers that added predictive value of short-term mortality in patients suffering severe cardiomyopathy [ 26 ]. Another study identified a set of inflammatory cytokines and cardiac biomarkers that were elevated in patients with severe disease [ 25 ].…”

Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable!

“…According to the data from these studies, BNP is comparable to echocardiogram in terms of the assessment of cardiological patients. To reinforce those prior findings, another study performed in an independent setting found that BNP, pro-BNP, creatine kinase (CK)-MB, and MMP-2 have high predictive values for short-term mortality even in the presence of a decreased ejection fraction and other clinical signs of congestive heart failure, which were all found to be associated with severe chagasic cardiomyopathy in a Bolivian cohort ( 9 ). Because the BNP procedure is simple and quick, this biomarker can be used in endemic zones of Chagas disease with limited access to echocardiographic housing facilities.…”

Genetic association study of NLRP1, CARD, and CASP1 inflammasome genes with chronic Chagas cardiomyopathy among Trypanosoma cruzi seropositive patients in Bolivia

“…cruzi transmission is unlikely to occur in the city, the population includes many migrants from rural areas who acquired Chagas disease earlier in life. Specific methodology, screening, and follow-up as it relates to the overarching study design is detailed in our previous publications from the study [ 22 – 26 ].…”