Biomarkers and Mortality in Severe Chagas Cardiomyopathy

Jacqueline E. Sherbuk, Emi E. Okamoto, Morgan A. Marks, Enzo Fortuny, Eva H. Clark, Gerson Galdos-Cardenas, Angel Vasquez-Villar, Antonio B. Fernandez, Thomas C. Crawford, Rose Q. Do, Jorge Luis Flores-Franco, Rony Colanzi, Robert H Gilman, Caryn Bern

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)173-180
Number of pages8
JournalGlobal Heart
Volume10
Issue number3
DOIs
StatePublished - Sep 1 2015

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Chagas Cardiomyopathy
Brain Natriuretic Peptide
Biomarkers
Mortality
MB Form Creatine Kinase
Confidence Intervals
Matrix Metalloproteinase 2
Trypanosoma cruzi
Urban Hospitals
Electrocardiography
Bolivia
Tissue Inhibitor of Metalloproteinase-2
Parasitic Diseases
Tissue Inhibitor of Metalloproteinase-1
Troponin I
Matrix Metalloproteinase 9
Cardiomyopathies
Proportional Hazards Models
ROC Curve
Transforming Growth Factor beta

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Epidemiology
  • Community and Home Care

Cite this

Sherbuk, J. E., Okamoto, E. E., Marks, M. A., Fortuny, E., Clark, E. H., Galdos-Cardenas, G., ... Bern, C. (2015). Biomarkers and Mortality in Severe Chagas Cardiomyopathy. Global Heart, 10(3), 173-180. https://doi.org/10.1016/j.gheart.2015.07.003

Biomarkers and Mortality in Severe Chagas Cardiomyopathy. / Sherbuk, Jacqueline E.; Okamoto, Emi E.; Marks, Morgan A.; Fortuny, Enzo; Clark, Eva H.; Galdos-Cardenas, Gerson; Vasquez-Villar, Angel; Fernandez, Antonio B.; Crawford, Thomas C.; Do, Rose Q.; Flores-Franco, Jorge Luis; Colanzi, Rony; Gilman, Robert H; Bern, Caryn.

In: Global Heart, Vol. 10, No. 3, 01.09.2015, p. 173-180.

Research output: Contribution to journalArticle

Sherbuk, JE, Okamoto, EE, Marks, MA, Fortuny, E, Clark, EH, Galdos-Cardenas, G, Vasquez-Villar, A, Fernandez, AB, Crawford, TC, Do, RQ, Flores-Franco, JL, Colanzi, R, Gilman, RH & Bern, C 2015, 'Biomarkers and Mortality in Severe Chagas Cardiomyopathy', Global Heart, vol. 10, no. 3, pp. 173-180. https://doi.org/10.1016/j.gheart.2015.07.003
Sherbuk JE, Okamoto EE, Marks MA, Fortuny E, Clark EH, Galdos-Cardenas G et al. Biomarkers and Mortality in Severe Chagas Cardiomyopathy. Global Heart. 2015 Sep 1;10(3):173-180. https://doi.org/10.1016/j.gheart.2015.07.003
Sherbuk, Jacqueline E. ; Okamoto, Emi E. ; Marks, Morgan A. ; Fortuny, Enzo ; Clark, Eva H. ; Galdos-Cardenas, Gerson ; Vasquez-Villar, Angel ; Fernandez, Antonio B. ; Crawford, Thomas C. ; Do, Rose Q. ; Flores-Franco, Jorge Luis ; Colanzi, Rony ; Gilman, Robert H ; Bern, Caryn. / Biomarkers and Mortality in Severe Chagas Cardiomyopathy. In: Global Heart. 2015 ; Vol. 10, No. 3. pp. 173-180.
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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 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.",
author = "Sherbuk, {Jacqueline E.} and Okamoto, {Emi E.} and Marks, {Morgan A.} and Enzo Fortuny and Clark, {Eva H.} and Gerson Galdos-Cardenas and Angel Vasquez-Villar and Fernandez, {Antonio B.} and Crawford, {Thomas C.} and Do, {Rose Q.} and Flores-Franco, {Jorge Luis} and Rony Colanzi and Gilman, {Robert H} and Caryn Bern",
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T1 - Biomarkers and Mortality in Severe Chagas Cardiomyopathy

AU - Sherbuk, Jacqueline E.

AU - Okamoto, Emi E.

AU - Marks, Morgan A.

AU - Fortuny, Enzo

AU - Clark, Eva H.

AU - Galdos-Cardenas, Gerson

AU - Vasquez-Villar, Angel

AU - Fernandez, Antonio B.

AU - Crawford, Thomas C.

AU - Do, Rose Q.

AU - Flores-Franco, Jorge Luis

AU - Colanzi, Rony

AU - Gilman, Robert H

AU - Bern, Caryn

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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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