Response To Letters Regarding Article, "Ten-Year Incidence Of Chagas Cardiomyopathy Among Asymptomatic, Trypanosoma Cruzi-Seropositive Former Blood Donors"

HomeCirculationVol. 128, No. 9Response to Letters Regarding Article, “Ten-Year Incidence of Chagas Cardiomyopathy Among Asymptomatic, Trypanosoma cruzi–Seropositive Former Blood Donors” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse to Letters Regarding Article, “Ten-Year Incidence of Chagas Cardiomyopathy Among Asymptomatic, Trypanosoma cruzi–Seropositive Former Blood Donors” Ester C. Sabino, MD, PhD Antonio L. Ribeiro, MD, ScD Vera M.C. Salemi, MD, PhD, Barbara M. Ianni, MD, PhD, Luciano Nastari, MD, PhD and Fabio Fernandes, MD, PhD Claudia Di Lorenzo Oliveira, MD, PhD Andre P. Antunes, MD and Marcia M. Menezes, MD Giuseppina M. Patavino, MD, Ligia Capuani, BSc and Cesar de Almeida-Neto, MD, MSc Vandana Sachdev, MD Danielle M. Carrick, PhD, MHS, David Wright, PhD and Katherine Kavounis, MPH Thelma T. Gonzalez, MD, PhD, Brian Custer, PhD, MPH and Michael P. Busch, MD, PhD Edward L. Murphy, MD, MPH Anna-Barbara Carneiro-Proietti, MD, PhD Ester C. SabinoEster C. Sabino Department of Infectious Disease and Institute of Tropical Medicine, University of Sao Paulo, Sao Paulo, Brazil Search for more papers by this author Antonio L. RibeiroAntonio L. Ribeiro Hospital das Clínicas and the Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Search for more papers by this author Vera M.C. SalemiVera M.C. Salemi Cardiomyopathy Unit of the Heart Institute (InCor) da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil Search for more papers by this author , Barbara M. IanniBarbara M. Ianni Cardiomyopathy Unit of the Heart Institute (InCor) da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil Search for more papers by this author , Luciano NastariLuciano Nastari Cardiomyopathy Unit of the Heart Institute (InCor) da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil Search for more papers by this author and Fabio FernandesFabio Fernandes Cardiomyopathy Unit of the Heart Institute (InCor) da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil Search for more papers by this author Claudia Di Lorenzo OliveiraClaudia Di Lorenzo Oliveira Campus Dona Lindu da Universidade Federal de São João del-Rei, Divinópolis, Brazil Search for more papers by this author Andre P. AntunesAndre P. Antunes Centro de CiênciasBiológicas e da Saúde, Prontosocor de Montes Claros, Minas Gerais, Brazil Search for more papers by this author and Marcia M. MenezesMarcia M. Menezes Centro de CiênciasBiológicas e da Saúde, Prontosocor de Montes Claros, Minas Gerais, Brazil Search for more papers by this author Giuseppina M. PatavinoGiuseppina M. Patavino Fundação Pró-Sangue Hemocentro de Sao Paulo, Sao Paulo, Brazil Search for more papers by this author , Ligia CapuaniLigia Capuani Fundação Pró-Sangue Hemocentro de Sao Paulo, Sao Paulo, Brazil Search for more papers by this author and Cesar de Almeida-NetoCesar de Almeida-Neto Fundação Pró-Sangue Hemocentro de Sao Paulo, Sao Paulo, Brazil Search for more papers by this author Vandana SachdevVandana Sachdev National Heart, Lung, and Blood Institute, Bethesda, MD Search for more papers by this author Danielle M. CarrickDanielle M. Carrick Westat, Inc, Rockville, MD Search for more papers by this author , David WrightDavid Wright Westat, Inc, Rockville, MD Search for more papers by this author and Katherine KavounisKatherine Kavounis Westat, Inc, Rockville, MD Search for more papers by this author Thelma T. GonzalezThelma T. Gonzalez Blood Systems Research Institute, San Francisco, CA Search for more papers by this author , Brian CusterBrian Custer Blood Systems Research Institute, San Francisco, CA Search for more papers by this author and Michael P. BuschMichael P. Busch Blood Systems Research Institute, San Francisco, CA Search for more papers by this author Edward L. MurphyEdward L. Murphy University of California San Francisco, San Francisco, CA Search for more papers by this author Anna-Barbara Carneiro-ProiettiAnna-Barbara Carneiro-Proietti Hemominas, Belo Horizonte, Brazil Search for more papers by this author Originally published27 Aug 2013https://doi.org/10.1161/CIRCULATIONAHA.113.004018Circulation. 2013;128:e137–e138We are grateful that our article has stimulated interest in and discussion of the incidence of clinical cardiomyopathy among asymptomatic persons infected with Trypanosoma cruzi.1 Rassi and Rassi comment that without more frequent interval examinations, we are unable to determine whether the incidence density of cardiomyopathy was constant over the 10 years of follow-up. This is true. However, their comment that “T cruzi–infected individuals who develop cardiomyopathy usually do so within 20 years after being infected” is not referenced in their letter; in a recent review article, the same authors postulated a 10- to 30-year incubation period.2 We are therefore unsure that the question of a constant versus declining incidence density has been settled. We also caution that the 18-year estimate for duration of exposure to T cruzi in our article was derived from an analysis of subject-reported risk factors and residence in endemic areas and should not be overinterpreted. However, we agree that the question of whether incidence density is constant or declines with time is important, and funding permitting, we plan to perform additional outcomes assessment in the cohort to gather data on the incidence of new cases of cardiomyopathy after longer follow-up.Rassi and Rassi also comment on our diagnostic criteria for cardiomyopathy. Regarding the inclusion of diastolic dysfunction on echocardiogram associated with signs or symptoms of heart failure or arrhythmias as a criterion for definite Chagas cardiomyopathy, we stress that, as stated in the article, the recognition of definite cases of Chagas cardiomyopathy was obtained, by consensus, by physicians with experience and clinical expertise in this field.1 The classification rules were used as general guidelines to this classification, but the whole clinical, ECG, and echocardiogram evaluation, including comorbidities, was considered. None of the T cruzi–seropositive subjects who were classified as having Chagas cardiomyopathy with normal ECG had this combination of diastolic dysfunction on echocardiogram associated with signs or symptoms of heart failure or arrhythmias. Regarding the presence of frequent supraventricular premature beats, we recognize that the referenced article discussed low QRS voltage and ventricular premature beats but not supraventricular premature beats. However, we included supraventricular premature beats because we have found that this abnormality is significantly related to left ventricular systolic dysfunction in T cruzi–seropositive donors3 and had prognostic significance in a large cohort study.4In their comment on possible selection bias, Bestetti and Cardinalli-Neto appear to have misinterpreted our Figure 2 showing enrollment in the cohort.1 In fact, 499 T cruzi seropositives (not 315) had complete cardiac outcome assessment, including physical examination, ECG, and echocardiogram. We also tried to account for selection bias by performing Brazilian death index searches and found a higher rate of mortality in nonenrolled seropositives compared with nonenrolled seronegatives. Therefore, if selection bias did occur, we suspect we may have underestimated rather than overestimated disease incidence in the cohort.Regarding the diagnostic value of an ECG versus an echocardiogram, the study cited regarding left ventricular dilation and systolic dysfunction in those with normal ECGs concerned prognosis in patients already diagnosed with Chagas cardiomyopathy.5 Instead, our study reported the sensitivity and specificity of the ECG for diagnosing cardiomyopathy among T cruzi seropositives, a different research question. In this different population, our data did not support the occurrence of significant pathology in those with normal ECGs.In conclusion, we welcome this collegial discussion and hope that our study has contributed to the knowledge of the natural history of T cruzi infection and Chagas cardiomyopathy. Further study of our cohort will help to determine whether the incidence of cardiomyopathy continues with longer follow-up and whether disease severity worsens among patients already diagnosed with cardiomyopathy. We reiterate that our data support the absence of left ventricular abnormalities in those with a normal ECG (high negative predictive value) and therefore do not support the routine use of echocardiography for primary screening of asymptomatic, T cruzi–seropositive individuals.Ester C. Sabino, MD, PhDDepartment of Infectious Disease and Institute of Tropical MedicineUniversity of Sao PauloSao Paulo, BrazilAntonio L. Ribeiro, MD, ScDHospital das Clínicas and the Faculdade de MedicinaUniversidade Federal de Minas GeraisBelo Horizonte, BrazilVera M.C. Salemi, MD, PhDBarbara M. Ianni, MD, PhDLuciano Nastari, MD, PhDFabio Fernandes, MD, PhDCardiomyopathy Unit of the Heart Institute (InCor) da Faculdade de Medicina da Universidade de São PauloSao Paulo, BrazilClaudia Di Lorenzo Oliveira, MD, PhDCampus Dona Lindu da Universidade Federal de São João del-ReiDivinópolis, BrazilAndre P. Antunes, MDMarcia M. Menezes, MDCentro de CiênciasBiológicas e da SaúdeProntosocor de Montes ClarosMinas Gerais, BrazilGiuseppina M. Patavino, MDLigia Capuani, BScCesar de Almeida-Neto, MD, MScFundação Pró-Sangue Hemocentro de Sao PauloSao Paulo, BrazilVandana Sachdev, MDNational Heart, Lung, and Blood InstituteBethesda, MDDanielle M. Carrick, PhD, MHSDavid Wright, PhDKatherine Kavounis, MPHWestat, IncRockville, MDThelma T. Gonzalez, MD, PhDBrian Custer, PhD, MPHMichael P. Busch, MD, PhDBlood Systems Research InstituteSan Francisco, CAEdward L. Murphy, MD, MPHUniversity of California San FranciscoSan Francisco, CAAnna-Barbara Carneiro-Proietti, MD, PhDHemominasBelo Horizonte, BrazilDisclosuresNone.References1. 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; National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study-II (REDS-II), International Component. Ten-year incidence of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi–seropositive former blood donors.Circulation. 2013; 127:1105–1115.LinkGoogle Scholar2. Rassi A, Rassi A, Marin-Neto JA. Chagas disease.Lancet. 2010; 375:1388–1402.CrossrefMedlineGoogle Scholar3. 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; NHLBI Retrovirus Epidemiology Donor Study-II (REDS-II), International Component. Electrocardiographic abnormalities in Trypanosoma cruzi seropositive and seronegative former blood donors.PLoS Negl Trop Dis. 2013; 7:e2078.CrossrefMedlineGoogle Scholar4. Marcolino MS, Lima-Costa MF, Ribeiro AL. Electrocardiographic abnormalities as predictors of mortality in community-dwelling elderly Chagas disease patients: 10-year follow-up of the Bambui Health and Aging Study.Circulation.2012; 125:E854.Google Scholar5. Bestetti RB. Predictors of unfavourable prognosis in chronic Chagas’ disease.Trop Med Int Health. 2001; 6:476–483.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails August 27, 2013Vol 128, Issue 9 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.113.004018PMID: 23979636 Originally publishedAugust 27, 2013 PDF download Advertisement SubjectsEchocardiographyElectrocardiology (ECG)Heart Failure