Deriving a parsimonious cardiac endpoint for use in epidemiological studies of Chagas disease: results from the Retrovirus Epidemiology Donor Study-II (REDS-II) cohort

Chagas cardiomyopathy (ChCM) is a severe consequence of Trypanosoma cruzi infection and has a range of electrocardiographic (ECG) and echocardiographic (ECHO) manifestations. There is a need for a standard and parsimonious research cardiac end point that does not rely on expert panel adjudication, and it is not intended to change the ChCM definition. We use data from the REDS-II cohort to propose a simplified cardiac endpoint. A total of 499 T. cruzi-seropositive blood donors were included. All participants underwent a 12-lead ECG, echocardiogram and clinical examination, and those with abnormal findings were reviewed by a panel of cardiologists who classified cases as having Chagas cardiomyopathy or not. We created an exhaustive set of ECG and ECHO finding combinations and compared these with the panel’s classification. We selected the simplest combination that most accurately reproduced the panel’s results. Individual ECG and ECHO variables had low sensitivity for panel-defined cardiomyopathy. The best performing combination was right bundle branch block and/or ECHO evidence of left ventricular hypocontractility. This combination had 98% specificity and 85% sensitivity for panel-defined ChCM. It was not possible to improve the overall accuracy by addition of any other ECG or ECHO variable. Substituting right bundle branch block for the more inclusive finding of QRS interval > 120 ms produced similar results. The combination of prolonged QRS interval and/or left ventricular hypocontractility closely reproduced the REDS-II expert panel classification of Chagas ChCM. In conclusion, the simple and reproducible research endpoint proposed here captures most of the spectrum of cardiac abnormalities in Chagas disease.