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Circulating Serum Markers and QRS Scar Score in Chagas Cardiomyopathy
Eva H. Clark
Eva H. Clark
University 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. Marks
Morgan A. Marks
University 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. Gilman
Robert H. Gilman
University 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. Fernandez
Antonio B. Fernandez
University 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. Crawford
Thomas C. Crawford
University 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. Samuels
Aaron M. Samuels
University 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. Hidron
Alicia I. Hidron
University 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-Cardenas
Gerson Galdos-Cardenas
University 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-Mendez
Gilberto Silvio Menacho-Mendez
University 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-Gutierrez
Ricardo W. Bozo-Gutierrez
University 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. Martin
Diana L. Martin
University 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 Bern
Caryn Bern
University 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
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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RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Rassi A Jr, Rassi A, Marin-Neto JA, 2010. Chagas disease. Lancet 375: 1388–1402.
-
2.
Dias JC, 1995. Natural history of Chagas' disease. Arq Bras Cardiol 65: 359–366.
-
3.
Maguire JH, Mott KE, Hoff R, Guimaraes A, Franca JT, Almeida de Souza JA, Ramos NB, Sherlock IA, 1982. A 3-year follow-up study of Trypanosoma cruzi infection and electrocardiographic abnormalities in a rural community in northeastern Brazil. Am J Trop Med Hyg 31: 42–47.
-
4.
Puigbo JJ, Nava Rhode JR, Carcia Barrios H, Gil Yepez C, 1968. A 4-year follow-up study of a rural community with endemic Chagas' disease. Bull World Health Organ 39: 341–348.
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5.
Sabino EC, Ribeiro AL, Salemi VM, Di Lorenzo Oliveira C, Antunes AP, Menezes MM, Ianni BM, Nastari L, Fernandes F, Patavino GM, Sachdev V, Capuani L, de Almeida-Neto C, Carrick DM, Wright D, Kavounis K, Goncalez TT, Carneiro-Proietti AB, Custer B, Busch MP, Murphy EL, 2013. Ten-year incidence of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi-seropositive former blood donors. Circulation 127: 1105–1115.
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6.
Rassi A Jr, Rassi A, Little WC, 2000. Chagas' heart disease. Clin Cardiol 23: 883–889.
-
7.
Ribeiro AL, Sabino EC, Marcolino MS, Salemi VM, Ianni BM, Fernandes F, Nastari L, Antunes A, Menezes M, Oliveira CD, Sachdev V, Carrick DM, Busch MP, Murphy EL, 2013. Electrocardiographic abnormalities in Trypanosoma cruzi seropositive and seronegative former blood donors. PLoS Negl Trop Dis 7: e2078.
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Dutra WO, Gollob KJ, 2008. Current concepts in immunoregulation and pathology of human Chagas disease. Curr Opin Infect Dis 21: 287–292.
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11.
Garcia-Alvarez A, Sitges M, Pinazo MJ, Regueiro-Cueva A, Posada E, Poyatos S, Ortiz-Perez JT, Heras M, Azqueta M, Gascon J, Sanz G, 2010. Chagas cardiomyopathy: the potential of diastolic dysfunction and brain natriuretic peptide in the early identification of cardiac damage. PLoS Negl Trop Dis 4: e826.
-
12.
Altieri P, Brunelli C, Garibaldi S, Nicolino A, Ubaldi S, Spallarossa P, Olivotti L, Rossettin P, Barsotti A, Ghigliotti G, 2003. Metalloproteinases 2 and 9 are increased in plasma of patients with heart failure. Eur J Clin Invest 33: 648–656.
-
13.
Li YY, Feng Y, McTiernan CF, Pei W, Moravec CS, Wang P, Rosenblum W, Kormos RL, Feldman AM, 2001. Downregulation of matrix metalloproteinases and reduction in collagen damage in the failing human heart after support with left ventricular assist devices. Circulation 104: 1147–1152.
-
14.
Spinale FG, 2007. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 87: 1285–1342.
-
15.
Araujo-Jorge TC, Waghabi MC, Soeiro M de N, Keramidas M, Bailly S, Feige JJ, 2008. Pivotal role for TGF-beta in infectious heart disease: the case of Trypanosoma cruzi infection and consequent Chagasic myocardiopathy. Cytokine Growth Factor Rev 19: 405–413.
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