ABC | Volume 110, Nº5, May 2018

Original Article Almeida et al MTWA and malignant arrhythmias in Chagas disease Arq Bras Cardiol. 2018; 110(5):412-417 The MTWA test has been widely studied in heart diseases of several etiologies, and countless studies have evidenced the association between the non-negative result of the test and the occurrence of malignant ventricular arrhythmias. 13-17 The present study corroborates previous studies from our search group that have suggested a role for MTWA in the stratification of risk for sudden death in CCC. Initially, Ribeiro et al. have observed that the T-wave amplitude variability measured in 11-minute high-resolution ECG tracings – a phenomenon analogous to MTWA – related to higher risk of death in patients with CCC after following 113 patients up at an outpatient clinic for 106 months [HR = 5.76 (95%CI: 1.31–25.23)]. 28 In a subsequent study, Raadschilders et al. have demonstrated a higher occurrence of non-negative MTWA test among patients with CCC as compared to individuals with Chagas disease but no heart impairment and patients with negative serology for Chagas disease. 29 Barbosa et al., performing the test in patients with indication for ICD implantation and diagnosed with Chagas heart disease and heart diseases of other etiologies, have assessed the association betweenMTWA and the occurrence of the outcomes ‘proper therapy’ and ‘death’. Those authors have concluded that there is a relationship between a non‑negative (positive and indeterminate) MTWA test and higher occurrence of proper therapy during the follow up of patients with Chagas disease, which was not observed among patients with heart disease of other etiologies. For patients with CCC, the test had sensitivity and negative predictive value of 100%. 26 The higher occurrence of an altered MTWA test in CCC can be explained by the inflammatory and fibrosing nature of the disease. Chagas heart disease is a chronic myocarditis, with damage to the tissue of the cardiac chambers and conduction system. 30 The destruction of cardiomyocytes and the resulting fibrosis cause architectural myocardial disarray, which can result in intercellular decoupling. This decoupling could cause a variability in cardiomyocyte membrane repolarization due to the difference in duration of their action potentials. Therefore, myocardial zones refractory to depolarization appear, tending to divide the depolarization current, the mechanism by which the variability would be linked to arrhythmogenesis, favoring conduction blocks and reentry induction. 31 The spatial heterogeneity of ventricular repolarization is considered a predisposing condition to initiate and perpetuate ventricular arrhythmias. That heterogeneity can be measured by use of the MTWA test, which would justify finding more changes in the MTWA test of patients with CCC and previous history of malignant arrhythmias. The MTWA test has difficulties related to the high cost of high-resolution electrodes and its own performance. Many individuals submitted to the test cannot reach and sustain the heart rate required or cannot undergo the exertion phase on the treadmill. The amount of indeterminate results due to noise or early interruption because of the patient’s conditions are also a limiting factor. In addition, the result is classified qualitatively, which can be considered another limitation. This study has limitations related partially to its observational, case-control design. The number of patients found for the case group was 45, not the 50 predicted in the sample calculation. The case group, defined by a previous history of malignant arrhythmias and indication for ICD, had a greater number of patients with reduced LVEF, of beta-blocker users and of patients with more advanced age. This is justified by the inclusion criterion in the group, because the patients with reduced LVEF would be more predisposed to develop ventricular arrhythmias. In addition, according to the 2007 ordinance, 19 patients with LVEF < 35% have an indication for priority to undergo ICD implantation. A logistic regression model was created to correct the disparity between the groups, maintaining the association between non-negative test and the occurrence of arrhythmias. The model may, however, not have corrected all differences between patients. Nevertheless, the large proportional difference of non-negativity between the case and control groups, corroborated by the magnitude of the association obtained on logistic regression, suggest that the phenomenon observed is real and significant. Conclusion This study assessed the presence of MTWA in patients with CCC and previous history of malignant ventricular arrhythmias and in patients with no previous history of those arrhythmias. The association between non-negativity of the MTWA test and the occurrence of malignant ventricular arrhythmias in CCC was evidenced. Further assessment in a prospective study is required to establish the causality and clinical application of the test in those patients. Author contributions Conception and design of the research: Almeida BCS, Carmo AAL, Ribeiro ALP; Acquisition of data: Almeida BCS, CarmoAAL, BarbosaMPT; Analysis and interpretation of the data: Almeida BCS, Carmo AAL, Barbosa MPT, Silva JLP, Ribeiro ALP; Statistical analysis: Almeida BCS, Silva JLP, Ribeiro ALP; Obtaining financing: Ribeiro ALP; Writing of themanuscript: Almeida BCS, Ribeiro ALP; Critical revision of the manuscript for intellectual content: Carmo AAL, Barbosa MPT, Silva JLP, Ribeiro ALP. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding This study was funded by CNPq and FAPEMIG. Study Association This article is part of the thesis of master submitted by Bárbara Carolina Silva Almeida, from Universidade Federal de Minas Gerais. Ethics approval and consent to participate This study was approved by the Ethics Committee of the Universidade Federal de Minas Gerais under the protocol number COEP 7918/12. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study. 415