Incidence of Chagas Cardiomyopathy and Relative Diagnostic Value of Electrocardiogram (ECG) Versus Echocardiogram (ECHO) Among T. cruzi Seropositive Donors

Abstract

Background/Case Studies: Few studies have prospectively evaluated the natural history of Chagas cardiomyopathy, including disease penetrance, prognostic factors and indications for treatment. Nor has the diagnostic utility of ECHO been compared to the simpler and less costly ECG screening. Study Design/Methods: In a retrospective cohort study, T. cruzi seropositive blood donors with an index blood donation in 1996-2002 in Sao Paulo and Montes Claros, Brazil were matched to seronegative donors on index donation date, age, gender and city. 101 Chagas cardiomyopathy patients served as positive controls. In 2009-2010, all subjects underwent a health history questionnaire, medical examination, standardized ECG and ECHO. Subjects with abnormal screening EKG or ECHO were referred to a blinded panel of 3 cardiologists who adjudicated the outcome of Chagas cardiomyopathy. Diagnostic sensitivity, specifi city, positive predictive value (PPV) and negative predictive value (NPV) were calculated separately for ECHO and ECG. Results/Findings: Mean follow-up time was 10.5 years for the sero-positives and 11.1 years for the seronegatives. The sensitivity of the combined ECHO/ECG and expert panel algorithm was 98%, based on diagnoses of cardiomyopathy in 99 of 101 previously diagnosed Chagas cardiomyopathy patients, of whom 1 (1%) expert referral was triggered by ECHO alone, none by ECG alone and 98 (99%) by both ECHO and ECG. In contrast, 24 (5%) of 488 T. cruzi-seronegative control donors were falsely classifi ed as having Chagas cardiomyopathy (specifi city = 95%). Among the 499 T. cruzi seropositives, 315 (63%) were referred to the expert panel and 120 (24%) had defi nite Chagas-like cardiomyopathy, leading to an incidence difference of 1.85 per 100 person-years attributable to T. cruzi infection. The Table summarizes the sensitivity, specifi city and predictive values of ECHO and ECG screening for cardiomyopathy diagnosis among the T. cruzi seropositive individuals. Conclusion: There is a substantial (~2%) annual incidence of Chagas cardiomyopathy among initially asymptomatic T. cruzi seropositive blood donors. Among seropositives, ECG had better sensitivity and ECHO had better specifi city. Both tests had poor positive predictive value, but ECG had better negative predictive value. Future studies could use a two-step algorithm in which ECG is used to exclude those with a negative test and low likelihood of disease. ECHO would be done to refine the diagnosis only in patients with abnormal ECG fi ndings. Disclosure of Commercial Conflict of Interest M. P. Busch: NIH, Grants or Research Support; Novartis/Gen-Probe, Grants or Research Support; Terumo/Caridian, Grants or Research Support; Gen-Probe, Consulting or Board of Director Fees; Johnson & Johnson/Merck, Ortho, Consulting or Board of Director Fees; Abbott, Travel Support or Honorarium; Novartis, Travel Support or Honorarium; L. D. Capuani: Nothing to disclose; D. M. Carrick: Nothing to disclose; B. Custer: Nothing to disclose; C. de Almeida-Neto: Nothing to disclose; C. Di Lorenzo Oliveira: No Answer; E. L. Murphy: Nothing to disclose; G. M. Patavino: Nothing to disclose; A. Ribeiro: Nothing to disclose; E. C. Sabino: Nothing to disclose Disclosure of Grants Conflict of Interest M. P. Busch: Novartis, Grants or Research Support; Ortho, Grants or Research Support; Terumo/Caridian, Grants or Research Support; L. D. Capuani: Nothing to disclose; D. M. Carrick: Nothing to disclose; B. Custer: Nothing to disclose; C. de Almeida-Neto: Nothing to disclose; C. Di Lorenzo Oliveira: No Answer; E. L. Murphy: Nothing to disclose; G. M. Patavino: Nothing to disclose; A. Ribeiro: Nothing to disclose; E. C. Sabino: Nothing to disclose Expert Panel Diagnosis of Cardiomyopathy in T. cruzi seropositives ECHO YES (N = 120) NO (N = 379) Triggered by ECHO 75 77 PPV = 49% Not Triggered by ECHO 45 302 NPV = 87% Sens = 63% Spec = 80% ECG Triggered by ECG 114 151 PPV = 43% Not Triggered by ECG 6 228 NPV = 97% Sens = 95% Spec = 60%