International Journal of Cardiology 187 (2015) 7–8
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Microvolt T-wave alternans in Chagas disease Lotte Raadschilders a,b, Marco Paulo T. Barbosa a, Andre Assis Carmo a, Jan L. Nouwen b, Manoel Otávio Costa Rocha a, Antonio Luiz P. Ribeiro a,⁎ a b
Hospital das Clínicas and School of Medicine, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190, Campus Saúde, 30130-100 Belo Horizonte, Brazil Department of Medical Microbiology and Infectious Disease, Erasmus MC, Erasmus University, Rotterdam, ′s-Gravendijkwal 230, Room L-327, 3015 CE Rotterdam, The Netherlands
a r t i c l e
i n f o
Article history: Received 23 February 2015 Accepted 17 March 2015 Available online 18 March 2015 Keywords: Chagas disease T-wave alternans Sudden death Electrocardiography
Chagas disease (ChD), caused by the protozoa Trypanosoma cruzi, is a leading cause of cardiopathy and death in Latin America. Due to migratory movements, it is also epidemiologically relevant in the United States and Europe. [1] Sudden cardiac death (SCD) is a major complication of ChD and is generally related to the occurrence of malignant ventricular arrhythmias. [1] Prediction of which patients are at risk of SCD is a challenge: depressed left ventricular (LV) ejection fraction, generally used to select patients for primary prevention of SCD with implantable cardiac defibrillators (ICD) in heart failure, is a poor predictor of the risk of malignant ventricular arrhythmias in ChD. [2] Microvolt T-wave alternans (MTWA) is a noninvasive test of arrhythmic vulnerability [3] which can effectively risk-stratify patients at risk of arrhythmias in LV systolic dysfunction [4]. There is no systematic study on the prevalence and prognostic significance of MTWA in ChD; a case report describes a ChD patient with non-sustained ventricular tachycardia and positive MTWA test [5]. In this study, we evaluated if ChD patients without heart failure have higher frequency of abnormal MTWA test than control subjects. This cross-sectional observational study was performed at Hospital das Clínicas of the Universidade Federal de Minas Gerais (UFMG), from September 2011 to July 2012. The study was approved by the Institutional Review Board of the UFMG and all subjects gave written informed consent. We selected patients between 20 and 60 years old with a definite serological status for ChD with LV ejection fraction ≥ 45%. Healthy individuals in the same age range, including family of ⁎ Corresponding author at: Rua Campanha, 98/101, 30310-770 Belo Horizonte, MG, Brazil. E-mail address: [email protected] (A.L.P. Ribeiro).
http://dx.doi.org/10.1016/j.ijcard.2015.03.253 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
patients and voluntary hospital employees, were concomitantly recruited as controls. Exclusion criteria were: (1) atrial fibrillation or flutter, artificial pacemaker rhythm or any other non-sinus cardiac rhythms; and (2) any evidence of other cardiovascular or systemic disease, including diabetes, hypertension (BP N 150/95 mm Hg), thyroid dysfunction, chronic obstructive pulmonary disease, and renal and hepatic failure All subjects were submitted to a standardized assessment that included clinical evaluation, ECG, echocardiogram (ECHO) and treadmill stress to evaluate MTWA. All tests were performed within 4 weeks, preferably in sequence in the same day. Drugs in usage, including amiodarone and beta-blockers, were not suspended. ECG was analyzed using standard criteria; special attention was given in finding typical for ChD, as right bundle branch block, left anterior fascicular block and ventricular ectopic beats. ECHO was interpreted using standard technique and LV ejection fraction was obtained through Simpson's method. MTWA was measured during treadmill exercise, using the HearTwave II system (Cambridge Heart, Bedford, MA). High-resolution electrodes were placed in the standard 12-lead and Frank orthogonal position. Patients were requested to walk until they reach a heart rate (HR) of 110– 120 bpm, for 90 s, followed by a period of 150 s with a target rate of 100–110 bpm. ECG data were collected digitally, analyzed using spectral analysis and reported using standard automated classification. A positive MTWA result was defined as the presence of sustained alternans for at least 1 min at HR b110 bpm on exercise or at rest even if N110 bpm. A negative MTWA test result was defined as the absence of positive test criteria with a maximum HR ≥105 bpm. A test that did not satisfy positive or negative criteria was classified as indeterminate and classified, by the software, as indeterminate due to inconsistent T-wave alternans or defective recording. If the test was indeterminate due to defective recording it was repeated. Tests that remain indeterminate after repetition of the test were considered abnormal and named as non-negative. [6] Standard statistical tests were used for comparison of proportions (Fisher's exact test or chi-square test), means (ANOVA) or medians (Kruskal–Wallis); Bonferroni correction was used for group comparisons. The study population consisted of 117 subjects, 39 controls and 78 ChD patients, categorized in ChD group 1, without ECG changes (n = 33), and ChD group 2, with typical ECG changes (n = 45). Results are presented in Table 1. Controls are significantly younger than ChD groups, with a higher proportion of males, higher HR and LV ejection fraction and slightly lower LV and left atrial diameters. ChD groups differed only regarding the presence of ECG abnormalities and the use of amiodarone. Fifteen subjects presented non-negative MTWA tests, 14 ChD patients and one control (18.0 vs 2.6%, p = 0.007); the
8
L. Raadschilders et al. / International Journal of Cardiology 187 (2015) 7–8
Table 1 Clinical, eletrocardiographic and echocardiographic characteristics and micro T-wave alternans test results in controls and Chagas disease patients. Variable Clinical features Age Male n (%) Systolic BP (mm Hg) Diastolic BP (mm Hg) Medication Betablocker Diuretics Amiodarone Aspirine Digoxin ECG Heart rate (bpm) PR interval (ms) QRS duration (ms) * QTc interval (ms) Ventricular extrassystoles Right bundle branch block Left anterior hemiblock ECHO LV ejection fraction (%) LV diastolic diameter (mm) Left atrial diameter (mm) MTWA Non-negative Positive
Control (N = 39)
Chagas disease group 1 (N = 33)
Chagas disease group 2 (N = 45)
p-Value
41 (10) 24 (61.5) 123 (14) 77 (10)
47 (9) 10 (30.3) 126 (12) 80 (8)
47 (8) 21 (38.2) 123 (11) 77 (7)
1 (2.6) 1 (2.6) 0 0 0
2 (6.1) 1 (3.0) 0 0 0
2 (4.4) 2 (4.4) 7 (15.6) 1 (2.2) 1 (2.2)
0.707 0.758 0.008 0.516 0.516
73 (13) 155 (23) 84 (78-93) 412 (38) 0 0 0
67 (9) 167 (40) 80 (78-89) 411 (33) 0 0 0
67 (12) 171 (36) 134 (120-146) 425 (58) 5 (11) 34 (76) 24 (54)
0.048 0.128 b0.001 0.308 0.012 b0.001 b0.001
67 (5) 48 (4) 33 (4)
63 (5) 51 (4) 35 (4)
60 (7) 53 (5) 35 (4)
b0.001 b0.001 0.003
0 N (1 = 2) 0 b (1 = 2) 0 b (1 = 2)
1 (2.6) 0 (0)
4 (12.1) 1 (3.0)
10 (22.2) 2 (4.4)
0.027 0.429
(0 = 1) b 2
0.011 0.030 0.380 0.396
0 b (1 = 2) 0 N (1 = 2)
(0 = 1) b 2
0 N (1 = 2) (0 = 1) b 2 (0 = 1) b 2 (0 = 1) b 2 (0 = 1) b 2
Values were expressed by absolute number (percentage) or mean (SD) when appropriate, except *, expressed by medians (interquartile range). BP: blood pressure systolic, LV: left ventricular.
frequency is significantly higher in ChD group 2 in relation to group 1 and control (22.2 vs 12.1 and 2.6%, p = 0.027). Only three tests showed positive, all in ChD patients: two in group 2, one in group 1. Chagas cardiomyopathy is characterized by muscle cell destruction and interstitial fibrosis, which leads to intraventricular blocks, [7] prolonged depolarization duration [8] and abnormalities in ventricular repolarization. [9,10], all of them with prognostic significance. These features create a favorable milieu to the emergence of malignant ventricular arrhythmias that can lead to SCD, a potentially preventable occurrence in the course of ChD natural history. Our findings showed that ChD is associated with higher frequency of abnormal MTWA test, an established marker of the risk of SCD, especially in those abnormal ECG and Chagas cardiomyopathy. Since we recruited only patients without heart failure with preserved LV ejection, we infer that the presence of this abnormality does not depend on the existence of LV dysfunction. Moreover, both ChD groups have similar LV function indexes. However, the design of the study does not allow the evaluation of the effect of LV function on the prevalence of abnormal MTWA. The present study has limitations related to its cross-sectional design and limited sample size, which do not interfere with our main findings: repolarization electrical alternans occurs in Chagas cardiomyopathy and may play a role in the development of malignant ventricular arrhythmias. MTWA test is potentially useful in risk stratification in Chagas cardiomyopathy, specially in those with abnormal ECG without heart failure. Since ChD is prevalent mostly in Latin American countries, generally with limited resources for health care, the MTWA test may prove to be a tool, in addition to ECG, ECHO and Holter studies, in the selection of patients for ICD implantation for prevention of SCD in Chagas cardiomyopathy. Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
Acknowledgments This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG, grant PPM-00161-13) and Conselho Nacional do Desenvolvimento Científico e Tecnológico (CNPq - grants 309073/2011-1 and 476668/2012-3), Brazil, and from Dutch Heart Foundation (Student Grant of LR), The Netherlands. References [1] M.C. Nunes, W. Dones, C.A. Morillo, J.J. Encina, A.L. Ribeiro, Chagas disease: an overview of clinical and epidemiological aspects, J. Am. Coll. Cardiol. 62 (9) (2013) 767–776. [2] M.P. Barbosa, M.O. da Costa Rocha, A.B. de Oliveira, F. Lombardi, A.L. Ribeiro, Efficacy and safety of implantable cardioverter-defibrillators in patients with Chagas disease, Europace 15 (7) (2013) 957–962. [3] D.S. Rosenbaum, L.E. Jackson, J.M. Smith, H. Garan, J.N. Ruskin, R.J. Cohen, Electrical alternans and vulnerability to ventricular arrhythmias, N. Engl. J. Med. 330 (4) (1994) 235–241. [4] C.J. van der Avoort, K.B. Filion, N. Dendukuri, J.M. Brophy, Microvolt T-wave alternans as a predictor of mortality and severe arrhythmias in patients with leftventricular dysfunction: a systematic review and meta-analysis, BMC Cardiovasc. Disord. 9 (2009) 5. [5] O. Nasario Jr., P.R. Benchimol-Barbosa, J. Nadal, Time-frequency analysis of microvolt T-wave alternans in chronic Chagas heart disease, Int. J. Cardiol. 148 (2) (2011) 251–253. [6] E.S. Kaufman, D.M. Bloomfield, R.C. Steinman, P.B. Namerow, O. Costantini, R.J. Cohen, et al., “Indeterminate” microvolt T-wave alternans tests predict high risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction, J. Am. Coll. Cardiol. 48 (7) (2006) 1399–1404. [7] A.L. Ribeiro, M.S. Marcolino, R.J. Prineas, M.F. Lima-Costa, Electrocardiographic abnormalities in elderly Chagas disease patients: 10-year follow-up of the Bambui Cohort Study of Aging, J. Am. Heart Assoc. 3 (1) (2014) e000632. [8] A.L. Ribeiro, P.S. Cavalvanti, F. Lombardi, M.D. Nunes, M.V. Barros, M.O. Rocha, Prognostic value of signal-averaged electrocardiogram in Chagas disease, J. Cardiovasc. Electrophysiol. 19 (5) (2008) 502–509. [9] R. Sassi, M.W. Rivolta, L.T. Mainardi, R.C. Reis, M.O. Rocha, A.L. Ribeiro, et al., Spatial repolarization heterogeneity and survival in Chagas disease, Methods Inf. Med. 53 (4) (2014). [10] A.L. Ribeiro, M.O. Rocha, P. Terranova, M. Cesarano, M.D. Nunes, F. Lombardi, T-wave amplitude variability and the risk of death in Chagas disease, J. Cardiovasc. Electrophysiol. 22 (7) (2011) 799–805.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Microvolt T-wave alternans in Chagas disease Lotte Raadschilders a,b, Marco Paulo T. Barbosa a, Andre Assis Carmo a, Jan L. Nouwen b, Manoel Otávio Costa Rocha a, Antonio Luiz P. Ribeiro a,⁎ a b
Hospital das Clínicas and School of Medicine, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190, Campus Saúde, 30130-100 Belo Horizonte, Brazil Department of Medical Microbiology and Infectious Disease, Erasmus MC, Erasmus University, Rotterdam, ′s-Gravendijkwal 230, Room L-327, 3015 CE Rotterdam, The Netherlands
a r t i c l e
i n f o
Article history: Received 23 February 2015 Accepted 17 March 2015 Available online 18 March 2015 Keywords: Chagas disease T-wave alternans Sudden death Electrocardiography
Chagas disease (ChD), caused by the protozoa Trypanosoma cruzi, is a leading cause of cardiopathy and death in Latin America. Due to migratory movements, it is also epidemiologically relevant in the United States and Europe. [1] Sudden cardiac death (SCD) is a major complication of ChD and is generally related to the occurrence of malignant ventricular arrhythmias. [1] Prediction of which patients are at risk of SCD is a challenge: depressed left ventricular (LV) ejection fraction, generally used to select patients for primary prevention of SCD with implantable cardiac defibrillators (ICD) in heart failure, is a poor predictor of the risk of malignant ventricular arrhythmias in ChD. [2] Microvolt T-wave alternans (MTWA) is a noninvasive test of arrhythmic vulnerability [3] which can effectively risk-stratify patients at risk of arrhythmias in LV systolic dysfunction [4]. There is no systematic study on the prevalence and prognostic significance of MTWA in ChD; a case report describes a ChD patient with non-sustained ventricular tachycardia and positive MTWA test [5]. In this study, we evaluated if ChD patients without heart failure have higher frequency of abnormal MTWA test than control subjects. This cross-sectional observational study was performed at Hospital das Clínicas of the Universidade Federal de Minas Gerais (UFMG), from September 2011 to July 2012. The study was approved by the Institutional Review Board of the UFMG and all subjects gave written informed consent. We selected patients between 20 and 60 years old with a definite serological status for ChD with LV ejection fraction ≥ 45%. Healthy individuals in the same age range, including family of ⁎ Corresponding author at: Rua Campanha, 98/101, 30310-770 Belo Horizonte, MG, Brazil. E-mail address: [email protected] (A.L.P. Ribeiro).
http://dx.doi.org/10.1016/j.ijcard.2015.03.253 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
patients and voluntary hospital employees, were concomitantly recruited as controls. Exclusion criteria were: (1) atrial fibrillation or flutter, artificial pacemaker rhythm or any other non-sinus cardiac rhythms; and (2) any evidence of other cardiovascular or systemic disease, including diabetes, hypertension (BP N 150/95 mm Hg), thyroid dysfunction, chronic obstructive pulmonary disease, and renal and hepatic failure All subjects were submitted to a standardized assessment that included clinical evaluation, ECG, echocardiogram (ECHO) and treadmill stress to evaluate MTWA. All tests were performed within 4 weeks, preferably in sequence in the same day. Drugs in usage, including amiodarone and beta-blockers, were not suspended. ECG was analyzed using standard criteria; special attention was given in finding typical for ChD, as right bundle branch block, left anterior fascicular block and ventricular ectopic beats. ECHO was interpreted using standard technique and LV ejection fraction was obtained through Simpson's method. MTWA was measured during treadmill exercise, using the HearTwave II system (Cambridge Heart, Bedford, MA). High-resolution electrodes were placed in the standard 12-lead and Frank orthogonal position. Patients were requested to walk until they reach a heart rate (HR) of 110– 120 bpm, for 90 s, followed by a period of 150 s with a target rate of 100–110 bpm. ECG data were collected digitally, analyzed using spectral analysis and reported using standard automated classification. A positive MTWA result was defined as the presence of sustained alternans for at least 1 min at HR b110 bpm on exercise or at rest even if N110 bpm. A negative MTWA test result was defined as the absence of positive test criteria with a maximum HR ≥105 bpm. A test that did not satisfy positive or negative criteria was classified as indeterminate and classified, by the software, as indeterminate due to inconsistent T-wave alternans or defective recording. If the test was indeterminate due to defective recording it was repeated. Tests that remain indeterminate after repetition of the test were considered abnormal and named as non-negative. [6] Standard statistical tests were used for comparison of proportions (Fisher's exact test or chi-square test), means (ANOVA) or medians (Kruskal–Wallis); Bonferroni correction was used for group comparisons. The study population consisted of 117 subjects, 39 controls and 78 ChD patients, categorized in ChD group 1, without ECG changes (n = 33), and ChD group 2, with typical ECG changes (n = 45). Results are presented in Table 1. Controls are significantly younger than ChD groups, with a higher proportion of males, higher HR and LV ejection fraction and slightly lower LV and left atrial diameters. ChD groups differed only regarding the presence of ECG abnormalities and the use of amiodarone. Fifteen subjects presented non-negative MTWA tests, 14 ChD patients and one control (18.0 vs 2.6%, p = 0.007); the
8
L. Raadschilders et al. / International Journal of Cardiology 187 (2015) 7–8
Table 1 Clinical, eletrocardiographic and echocardiographic characteristics and micro T-wave alternans test results in controls and Chagas disease patients. Variable Clinical features Age Male n (%) Systolic BP (mm Hg) Diastolic BP (mm Hg) Medication Betablocker Diuretics Amiodarone Aspirine Digoxin ECG Heart rate (bpm) PR interval (ms) QRS duration (ms) * QTc interval (ms) Ventricular extrassystoles Right bundle branch block Left anterior hemiblock ECHO LV ejection fraction (%) LV diastolic diameter (mm) Left atrial diameter (mm) MTWA Non-negative Positive
Control (N = 39)
Chagas disease group 1 (N = 33)
Chagas disease group 2 (N = 45)
p-Value
41 (10) 24 (61.5) 123 (14) 77 (10)
47 (9) 10 (30.3) 126 (12) 80 (8)
47 (8) 21 (38.2) 123 (11) 77 (7)
1 (2.6) 1 (2.6) 0 0 0
2 (6.1) 1 (3.0) 0 0 0
2 (4.4) 2 (4.4) 7 (15.6) 1 (2.2) 1 (2.2)
0.707 0.758 0.008 0.516 0.516
73 (13) 155 (23) 84 (78-93) 412 (38) 0 0 0
67 (9) 167 (40) 80 (78-89) 411 (33) 0 0 0
67 (12) 171 (36) 134 (120-146) 425 (58) 5 (11) 34 (76) 24 (54)
0.048 0.128 b0.001 0.308 0.012 b0.001 b0.001
67 (5) 48 (4) 33 (4)
63 (5) 51 (4) 35 (4)
60 (7) 53 (5) 35 (4)
b0.001 b0.001 0.003
0 N (1 = 2) 0 b (1 = 2) 0 b (1 = 2)
1 (2.6) 0 (0)
4 (12.1) 1 (3.0)
10 (22.2) 2 (4.4)
0.027 0.429
(0 = 1) b 2
0.011 0.030 0.380 0.396
0 b (1 = 2) 0 N (1 = 2)
(0 = 1) b 2
0 N (1 = 2) (0 = 1) b 2 (0 = 1) b 2 (0 = 1) b 2 (0 = 1) b 2
Values were expressed by absolute number (percentage) or mean (SD) when appropriate, except *, expressed by medians (interquartile range). BP: blood pressure systolic, LV: left ventricular.
frequency is significantly higher in ChD group 2 in relation to group 1 and control (22.2 vs 12.1 and 2.6%, p = 0.027). Only three tests showed positive, all in ChD patients: two in group 2, one in group 1. Chagas cardiomyopathy is characterized by muscle cell destruction and interstitial fibrosis, which leads to intraventricular blocks, [7] prolonged depolarization duration [8] and abnormalities in ventricular repolarization. [9,10], all of them with prognostic significance. These features create a favorable milieu to the emergence of malignant ventricular arrhythmias that can lead to SCD, a potentially preventable occurrence in the course of ChD natural history. Our findings showed that ChD is associated with higher frequency of abnormal MTWA test, an established marker of the risk of SCD, especially in those abnormal ECG and Chagas cardiomyopathy. Since we recruited only patients without heart failure with preserved LV ejection, we infer that the presence of this abnormality does not depend on the existence of LV dysfunction. Moreover, both ChD groups have similar LV function indexes. However, the design of the study does not allow the evaluation of the effect of LV function on the prevalence of abnormal MTWA. The present study has limitations related to its cross-sectional design and limited sample size, which do not interfere with our main findings: repolarization electrical alternans occurs in Chagas cardiomyopathy and may play a role in the development of malignant ventricular arrhythmias. MTWA test is potentially useful in risk stratification in Chagas cardiomyopathy, specially in those with abnormal ECG without heart failure. Since ChD is prevalent mostly in Latin American countries, generally with limited resources for health care, the MTWA test may prove to be a tool, in addition to ECG, ECHO and Holter studies, in the selection of patients for ICD implantation for prevention of SCD in Chagas cardiomyopathy. Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
Acknowledgments This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG, grant PPM-00161-13) and Conselho Nacional do Desenvolvimento Científico e Tecnológico (CNPq - grants 309073/2011-1 and 476668/2012-3), Brazil, and from Dutch Heart Foundation (Student Grant of LR), The Netherlands. References [1] M.C. Nunes, W. Dones, C.A. Morillo, J.J. Encina, A.L. Ribeiro, Chagas disease: an overview of clinical and epidemiological aspects, J. Am. Coll. Cardiol. 62 (9) (2013) 767–776. [2] M.P. Barbosa, M.O. da Costa Rocha, A.B. de Oliveira, F. Lombardi, A.L. Ribeiro, Efficacy and safety of implantable cardioverter-defibrillators in patients with Chagas disease, Europace 15 (7) (2013) 957–962. [3] D.S. Rosenbaum, L.E. Jackson, J.M. Smith, H. Garan, J.N. Ruskin, R.J. Cohen, Electrical alternans and vulnerability to ventricular arrhythmias, N. Engl. J. Med. 330 (4) (1994) 235–241. [4] C.J. van der Avoort, K.B. Filion, N. Dendukuri, J.M. Brophy, Microvolt T-wave alternans as a predictor of mortality and severe arrhythmias in patients with leftventricular dysfunction: a systematic review and meta-analysis, BMC Cardiovasc. Disord. 9 (2009) 5. [5] O. Nasario Jr., P.R. Benchimol-Barbosa, J. Nadal, Time-frequency analysis of microvolt T-wave alternans in chronic Chagas heart disease, Int. J. Cardiol. 148 (2) (2011) 251–253. [6] E.S. Kaufman, D.M. Bloomfield, R.C. Steinman, P.B. Namerow, O. Costantini, R.J. Cohen, et al., “Indeterminate” microvolt T-wave alternans tests predict high risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction, J. Am. Coll. Cardiol. 48 (7) (2006) 1399–1404. [7] A.L. Ribeiro, M.S. Marcolino, R.J. Prineas, M.F. Lima-Costa, Electrocardiographic abnormalities in elderly Chagas disease patients: 10-year follow-up of the Bambui Cohort Study of Aging, J. Am. Heart Assoc. 3 (1) (2014) e000632. [8] A.L. Ribeiro, P.S. Cavalvanti, F. Lombardi, M.D. Nunes, M.V. Barros, M.O. Rocha, Prognostic value of signal-averaged electrocardiogram in Chagas disease, J. Cardiovasc. Electrophysiol. 19 (5) (2008) 502–509. [9] R. Sassi, M.W. Rivolta, L.T. Mainardi, R.C. Reis, M.O. Rocha, A.L. Ribeiro, et al., Spatial repolarization heterogeneity and survival in Chagas disease, Methods Inf. Med. 53 (4) (2014). [10] A.L. Ribeiro, M.O. Rocha, P. Terranova, M. Cesarano, M.D. Nunes, F. Lombardi, T-wave amplitude variability and the risk of death in Chagas disease, J. Cardiovasc. Electrophysiol. 22 (7) (2011) 799–805.
