title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Yale-New Haven Hospital, New Haven, CT, USA.
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Sherbuk
authors.affiliation: Hospital of University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Emi E
authors.initials: EE
authors.lastname: Okamoto
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA; Merck and Co. Inc., West Point, PA, USA.
authors.forename: Morgan A
authors.initials: MA
authors.lastname: Marks
authors.affiliation: Universidad Catolica Boliviana, Santa Cruz, Plurinational State of Bolivia.
authors.forename: Enzo
authors.initials: E
authors.lastname: Fortuny
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Eva H
authors.initials: EH
authors.lastname: Clark
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA; Universidad Catolica Boliviana, Santa Cruz, Plurinational State of Bolivia.
authors.forename: Gerson
authors.initials: G
authors.lastname: Galdos-Cardenas
authors.affiliation: Hospital Nacional Guillermo Almenara Ingoyen, Lima, Peru.
authors.forename: Angel
authors.initials: A
authors.lastname: Vasquez-Villar
authors.affiliation: Hartford Hospital, Hartford, CT, USA.
authors.forename: Antonio B
authors.initials: AB
authors.lastname: Fernandez
authors.affiliation: University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Crawford
authors.affiliation: Veterans Affairs Medical Center and University of Colorado School of Medicine, Denver, CO, USA.
authors.forename: Rose Q
authors.initials: RQ
authors.lastname: Do
authors.affiliation: Universidad Catolica Boliviana, Santa Cruz, Plurinational State of Bolivia.
authors.forename: Jorge Luis
authors.initials: JL
authors.lastname: Flores-Franco
authors.affiliation: Universidad Catolica Boliviana, Santa Cruz, Plurinational State of Bolivia.
authors.forename: Rony
authors.initials: R
authors.lastname: Colanzi
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.affiliation: University of California San Francisco, San Francisco, CA, USA. Electronic address: Caryn.Bern2@UCSF.EDU.
authors.forename: Caryn
authors.initials: C
authors.lastname: Bern
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D001838:Bolivia / Q000453:epidemiology; D002598:Chagas Cardiomyopathy / Q000378:metabolism* / Q000401:mortality; D015331:Cohort Studies; D052279:Creatine Kinase, MB Form / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D009765:Obesity / Q000453:epidemiology*; D050177:Overweight / Q000453:epidemiology; D010446:Peptide Fragments / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D065840:Protective Factors; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D019210:Troponin I
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D019210:Troponin I; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D019716:Tissue Inhibitor of Metalloproteinase-2; D052279:Creatine Kinase, MB Form; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9