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Biomarkers and mortality in severe Chagas cardiomyopathy
Jacqueline E Sherbuk1, Emi E Okamoto2, Morgan A Marks3
1Yale-New Haven Hospital, New Haven, CT, USA.
Insights
Biomarkers such as B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase-myocardial band (CK-MB), and matrix metalloproteinase-2 (MMP-2) can predict mortality in severe Chagas cardiomyopathy. These markers offer valuable prognostic information for patients with this serious condition.
Area of Science:
- Cardiology
- Infectious Diseases
- Biomarker Research
Background:
- Chagas cardiomyopathy, a chronic consequence of Trypanosoma cruzi infection, presents a significant mortality risk in advanced stages.
- While clinical factors aid in risk stratification, the relationship between specific biomarkers and survival in Chagas cardiomyopathy remains underexplored.
Purpose of the Study:
- To identify biomarkers associated with mortality in patients diagnosed with severe Chagas cardiomyopathy.
- To investigate the predictive value of cardiac biomarkers in an urban Bolivian hospital setting.
Main Methods:
- Serum levels of various cardiac biomarkers including BNP, NT-proBNP, CK-MB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGF-beta 1, and TGF-beta 2 were measured.
- Echocardiograms were performed for individuals with cardiac symptoms or ECG abnormalities.
- Cox proportional hazards models were used to assess the association between biomarker levels and mortality over a 1-year follow-up period.
Main Results:
- Higher baseline levels of BNP, NT-proBNP, CK-MB, and MMP-2 were significantly associated with increased mortality.
- These associations remained significant even after accounting for factors like reduced ejection fraction and clinical signs of heart failure.
Conclusions:
- Severe Chagas cardiomyopathy is linked to high short-term mortality.
- BNP, NT-proBNP, CK-MB, and MMP-2 serve as valuable predictive biomarkers for mortality in this patient population.
- These biomarkers enhance risk prediction beyond traditional clinical assessments.
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:
This 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, electrocardiogram findings, medications, and serum cardiac biomarker levels (B-type natriuretic peptide [BNP], N-terminal pro-B-type natriuretic peptide [NT-proBNP], creatine kinase-myocardial band [CK-MB], troponin I, matrix metalloproteinase [MMP]-2, MMP-9, tissue inhibitor of metalloproteinases [TIMP] 1 and 2, transforming growth factor [TGF] beta 1 and 2) were ascertained. Echocardiograms were performed on those with cardiac symptoms or electrocardiogram abnormalities at baseline. Participants were contacted approximately 1 year after initial evaluation; deaths were reported by family members. Receiver-operating characteristic curves (ROC) were used to optimize cutoff values for each marker. For markers with area under the curve (AUC) >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). Of 254 individuals with complete cardiac data, 220 (87%) had follow-up data. Of 50 patients with severe Chagas cardiomyopathy at baseline, 20 (40%) had died. Higher baseline levels of BNP (HR: 3.1, 95% CI: 1.2 to 8.4), NT-proBNP (HR: 4.4, 95% CI: 1.8 to 11.0), CK-MB (HR: 3.3, 95% CI: 1.3 to 8.0), and MMP-2 (HR: 4.2, 95% CI: 1.5 to 11.8) were significantly associated with subsequent mortality.
Conclusions:
Severe Chagas cardiomyopathy is associated with high short-term mortality. BNP, NT-proBNP, CK-MB, and MMP-2 have added predictive value for mortality, even in the presence of decreased ejection fraction and other clinical signs of congestive heart failure.
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