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Circulating Serum Markers and QRS Scar Score in Chagas Cardiomyopathy

Eva H. ClarkUniversity of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, Connecticut; Department of Cardiology, University of Michigan Health System, Ann Arbor, Michigan; Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Hospital Universitario Japones, Santa Cruz, Bolivia; Centro de Salud Eiti, Gutierrez, Bolivia; Hospital Municipal Camiri, Camiri, Bolivia; University of California San Francisco, San Francisco, California

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Morgan A. MarksUniversity of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, Connecticut; Department of Cardiology, University of Michigan Health System, Ann Arbor, Michigan; Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Hospital Universitario Japones, Santa Cruz, Bolivia; Centro de Salud Eiti, Gutierrez, Bolivia; Hospital Municipal Camiri, Camiri, Bolivia; University of California San Francisco, San Francisco, California

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Robert H. GilmanUniversity of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, Connecticut; Department of Cardiology, University of Michigan Health System, Ann Arbor, Michigan; Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Hospital Universitario Japones, Santa Cruz, Bolivia; Centro de Salud Eiti, Gutierrez, Bolivia; Hospital Municipal Camiri, Camiri, Bolivia; University of California San Francisco, San Francisco, California

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Antonio B. FernandezUniversity of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, Connecticut; Department of Cardiology, University of Michigan Health System, Ann Arbor, Michigan; Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Hospital Universitario Japones, Santa Cruz, Bolivia; Centro de Salud Eiti, Gutierrez, Bolivia; Hospital Municipal Camiri, Camiri, Bolivia; University of California San Francisco, San Francisco, California

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Thomas C. CrawfordUniversity of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, Connecticut; Department of Cardiology, University of Michigan Health System, Ann Arbor, Michigan; Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Hospital Universitario Japones, Santa Cruz, Bolivia; Centro de Salud Eiti, Gutierrez, Bolivia; Hospital Municipal Camiri, Camiri, Bolivia; University of California San Francisco, San Francisco, California

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Aaron M. SamuelsUniversity of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, Connecticut; Department of Cardiology, University of Michigan Health System, Ann Arbor, Michigan; Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Hospital Universitario Japones, Santa Cruz, Bolivia; Centro de Salud Eiti, Gutierrez, Bolivia; Hospital Municipal Camiri, Camiri, Bolivia; University of California San Francisco, San Francisco, California

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Alicia I. HidronUniversity of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, Connecticut; Department of Cardiology, University of Michigan Health System, Ann Arbor, Michigan; Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Hospital Universitario Japones, Santa Cruz, Bolivia; Centro de Salud Eiti, Gutierrez, Bolivia; Hospital Municipal Camiri, Camiri, Bolivia; University of California San Francisco, San Francisco, California

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Gerson Galdos-CardenasUniversity of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, Connecticut; Department of Cardiology, University of Michigan Health System, Ann Arbor, Michigan; Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Hospital Universitario Japones, Santa Cruz, Bolivia; Centro de Salud Eiti, Gutierrez, Bolivia; Hospital Municipal Camiri, Camiri, Bolivia; University of California San Francisco, San Francisco, California

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Gilberto Silvio Menacho-MendezUniversity of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, Connecticut; Department of Cardiology, University of Michigan Health System, Ann Arbor, Michigan; Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Hospital Universitario Japones, Santa Cruz, Bolivia; Centro de Salud Eiti, Gutierrez, Bolivia; Hospital Municipal Camiri, Camiri, Bolivia; University of California San Francisco, San Francisco, California

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Ricardo W. Bozo-GutierrezUniversity of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, Connecticut; Department of Cardiology, University of Michigan Health System, Ann Arbor, Michigan; Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Hospital Universitario Japones, Santa Cruz, Bolivia; Centro de Salud Eiti, Gutierrez, Bolivia; Hospital Municipal Camiri, Camiri, Bolivia; University of California San Francisco, San Francisco, California

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Diana L. MartinUniversity of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, Connecticut; Department of Cardiology, University of Michigan Health System, Ann Arbor, Michigan; Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Hospital Universitario Japones, Santa Cruz, Bolivia; Centro de Salud Eiti, Gutierrez, Bolivia; Hospital Municipal Camiri, Camiri, Bolivia; University of California San Francisco, San Francisco, California

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Caryn BernUniversity of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, Connecticut; Department of Cardiology, University of Michigan Health System, Ann Arbor, Michigan; Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Hospital Universitario Japones, Santa Cruz, Bolivia; Centro de Salud Eiti, Gutierrez, Bolivia; Hospital Municipal Camiri, Camiri, Bolivia; University of California San Francisco, San Francisco, California

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Approximately 8 million people have Trypanosoma cruzi infection, and nearly 30% will manifest Chagas cardiomyopathy (CC). Identification of reliable early indicators of CC risk would enable prioritization of treatment to those with the highest probability of future disease. Serum markers and electrocardiogram (EKG) changes were measured in 68 T. cruzi-infected individuals in various stages of cardiac disease and 17 individuals without T. cruzi infection or cardiac disease. T. cruzi-infected individuals were assigned to stage A (normal EKG/chest x-ray [CXR]), B (abnormal EKG/normal CXR), or C (abnormal EKG/cardiac structural changes). Ten serum markers were measured using enzyme-linked immunosorbent assay (ELISA)/Luminex, and QRS scores were calculated. Higher concentrations of transforming growth factor-β1 (TGFβ1), and TGFβ2 were associated with stage B compared with stage A. Matrix Metalloproteinase 2 (MMP2), Tissue Inhibitors of MMP 1, QRS score, and Brain Natriuretic Protein rose progressively with increasing CC severity. Elevated levels of several markers of cardiac damage and inflammation are seen in early CC and warrant additional evaluation in longitudinal studies.

Author Notes

* Address correspondence to Eva H. Clark, University of Alabama at Birmingham, Room SHEL 121, 1825 University Boulevard, Birmingham, AL 35209. E-mail: eva.clark@bcm.edu

Financial support: This work was supported by National Institute of Health (NIH) Grant 5 P50 AI074285, NIH Fogarty Scholars Program Grant R24TW007988, NIH Training Grant in Infectious and Tropical Diseases 5 T35 AI065385, and NIH Global Research Training Grant D43 TW006581. The participation of A.B.F. was supported by NIH-funded “Interdisciplinary Framework in Global Health at Brown University” Grant 5R25TW008102. Support was also provided by the Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention for the participation of A.M.S. and D.L.M. and specimen processing.

Authors' addresses: Eva H. Clark, University of Alabama at Birmingham, Birmingham, AL, E-mail: eva.clark@bcm.edu. Morgan A. Marks, Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, E-mail: mmarksster@gmail.com. Robert H. Gilman, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mail: gilmanbob@gmail.com. Antonio B. Fernandez, Department of Medicine, Division of Cardiology, Hartford Hospital, Hartford, CT, E-mail: antoinefernandezt@hotmail.com. Thomas C. Crawford, Department of Cardiology, University of Michigan Health System, Ann Arbor, MI, E-mail: thomcraw@med.umich.edu. Aaron M. Samuels and Diana L. Martin, Centers for Disease Control and Prevention, Atlanta, GA, E-mails: iyp2@cdc.gov and hzx3@cdc.gov. Alicia I. Hidron, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, E-mail: aliciahidron@gmail.com. Gerson Galdos-Cardenas, Hospital Universitario Japones, Santa Cruz, Bolivia, E-mail: gersongaldos@gmail.com. Gilberto Silvio Menacho-Mendez, Centro de Salud Eiti, Gutierrez, Bolivia, E-mail: gsmmjovero@gmail.com. Ricardo W. Bozo-Gutierrez, Hospital Municipal Camiri, Camiri, Bolivia, E-mail: ricardobozo_1966@hotmail.com. Caryn Bern, University of California San Francisco, San Francisco, CA, E-mail: Caryn.Bern2@ucsf.edu.

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