The outcome of Chagas disease is ultimately, defined in the patients’ hearts, as a consequence of inflammation and myocardial tissue response. We thus hypothesize that expression of many pathogenetically relevant genes and proteins in the myocardial tissue of CCC patients is controlled by genetic polymorphisms. The corollary is that it may be possible to establish a host genetic signature with prognostic value based on such polymorphic genes. We develop a multi OMIC approach to decipher the pathogenic process associated to clinical severe forms.