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The Use of Microvolt T-Wave Alternans in Chagas Disease

Keywords
Chagas Disease; Electrocardiography; Cardiac Death, Sudden; Cardiac Risk Stratification; Cardiac Complexes, Premature

Visible T-wave alternans (TWA) has been reported since 1909, being, thus, not a recent finding.11 Rubart D, Zipes P. Mechanisms of sudden cardiac death. J Clin Invest. 2005;115(9):2305-15. However, non-visible and far less rare microvolt TWA has gained importance because of its association with electrical disorders and the high risk for sudden cardiac death (SCD) or arrhythmic events,22 Fabre A, Sheppard MN. Sudden adult death syndrome and other nonischaemic causes of sudden cardiac death. Heart. 2006;92(3):316-20.

3 Thompson PD, Franklin BA, Balady GJ, Blair SN, Corrado N, Estes NA rd, et al. Exercise and acute cardiovascular events: Placing the risks into perspective: A scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism and the Council on Clinical Cardiology - In collaboration with the American College of Sports Medicine. Circulation. 2007;115(17):2358-68.

4 Weiss JN, Karma A, Shiferaw Y, Chen PS, Garfinkel A, Chu Z. From pulsus to pulseless: The saga of cardiac alternans. Circ Res. 2006;98(10):1244-53.

5 Hering HE. Experimentelle studien an s¨augetieren ¨uber das elektrocardiogram. Zeitschrift f ¨ur experimentelle Pathologie und Therapie. 1909;7:363-78.
-66 Adam DR, Akselrod S, Cohen RJ. Estimation of ventricular vulnerability to fibrillation through T-wave time series analysis. Comput Cardiol. 1981;8:307-10. being assessed in several clinical trials and population studies, such as TWA in HF,77 Zareba W, Piotrowicz K, McNitt S, Moss AJ, MADIT II Investigators. Implantable cardioverter-defibrillator efficacy in patients with heart failure and left ventricular dysfunction (from the MADIT II Population). Am J Cardiol. 2005;95(12):1487-91. ALPHA Study,88 Salerno-Uriarte JA, De Ferrari GM, Klersy C, Pedretti RF, Tritto M, Sallusti L, et al.Prognostic value of T-wave alternans in patients with heart failure due to nonischemic cardiomyopathy-results of the ALPHA study. J Am Coll Cardiol. 2007;50(19):1896-904. REFINE Study,99 Exner DV, Kavanagh KM, Slawnych MP, Mitchell LB, Ramadan D, Aggarwal SG, et al. Noninvasive risk assessment early after a myocardial infarction- the REFINE study. J Am Coll Cardiol. 2007;50(24):2275-84. FINCAVAS,1010 Nieminen T, Lehtimaki T, Viik J, Lehtinen R, Nikus K, Koobi T, et al. T-wave alternans predicts mortality in a population undergoing a clinically indicated exercise test. Eur Heart J. 2007;28(19):2332-7. the collaborative study by Ikeda et al.1111 Ikeda T, Yoshino H, Sugi K, Tanno K, Shimizu H, Watanabe J, et al. Predictive value of microvolt T-wave alternans for sudden cardiac death in patients with preserved cardiac function after acute myocardial infarction results of a collaborative cohort study. J Am Coll Cardiol. 2006;48(11):2268-74. and the MADIT-II-type research by Bloomfield et al.1212 Bloomfield DM, Steinman RC, Namerow PB, Paredes M, Davidenko J, Kaufman ES, et al. Microvolt T-wave alternans distinguishes between patients likely and patients not likely to benefit from implanted cardiac defibrillator therapy: A solution to the multicenter automatic defibrillator implantation trial (MADIT) II conundrum. Circulation. .2004;110(14):1885-9. All those studies have in common the fact that they evidence the high negative predictive value of TWA regarding SCD or arrhythmic events, with low to intermediate positive predictive value.

A specialized software is used to analyze the microvolt TWA, the beat-to-beat variability that occurs in ventricular repolarization (ST segment and T wave) and that cannot be seen by the naked eye.1313 Bloomfield D, Hohnloser SH, Cohen RJ. Interpretation and classification of microvolt T wave alternans tests. J Cardiovasc Electrophysiol. 2002;13(5):502-12.

14 Hohnloser SH. T wave alternans. In: Zipes D, Jalife J, eds. Cardiac electrophysiology, 6th ed. Philadelfia, PA: Elsevier Inc.; 2013. p.665-76.

15 Merchant FM, Armoundas AA. Role of substrate and triggers in the genesis of cardiac alternans, from myocyte to the whole heart: implications for therapy. Circulation. 2012;125(3):539-49.
-1616 Hagjoo M, Arya A, Sadr-Ameli MA. Microvolt T-wave alternans: a review of techniques, interpretation, utility, clinical studies and future perspectives. Int J Cardiol. 2006;109(3):293-306. The TWA allows indirect access to the increase in the dispersion to the action potentials of cardiac cells, a primordial factor in a sequence of events that will lead to reentry mechanisms and ventricular fibrillation, which will culminate with SCD. A fundamental property of its analysis is the high negative predictive power for the SCD risk that a normal TWA test has.1212 Bloomfield DM, Steinman RC, Namerow PB, Paredes M, Davidenko J, Kaufman ES, et al. Microvolt T-wave alternans distinguishes between patients likely and patients not likely to benefit from implanted cardiac defibrillator therapy: A solution to the multicenter automatic defibrillator implantation trial (MADIT) II conundrum. Circulation. .2004;110(14):1885-9.

Of the different methodologies to assess TWA, the two most used and relevant techniques in medical literature are: the spectral method (SM) and the modified moving average (MMA) method.1717 Garcia EV, Pastore CA, Samesima N, Pereira Filho HG. T-wave alternans: desempenho clínico, limitações, metodologias de análise. Arq Bras Cardiol. 2011;96(3):e53-e61.

The SM measures T-wave fluctuations by computing the point to point differences between 128 equally spaced sites in the ST-T complex, in a series of 128 consecutive aligned beats (having already ruled out ectopic beats and ECG noise).1818 Smith JM, Clancy EA, Valeri CR,Ruskin JN, Cohen RJ. Electrical alternans and cardiac electrical instability. Circulation. 1988;77(1):110-21. There are 128 tachograms similar to those used in the analysis of heart rate variability. Then, 128 heart rate variability spectra, hence the name of the methodology, SM, are computed, and their mean is calculated. The value of TWA is then assessed at the frequency of 0.5 cycle per beat. In 1994, the adaptation of that technique to human patients was published for the first time.1919 Rosenbaum DS, Jackson LE, Smith JM, Garan H, Ruskin JN, Cohen RJ. Electrical alternans and vulnerability to ventricular arrhythmias. N Engl J Med. 1994;330(4):235-41. Since then, SM is the most used method to analyze TWA, with the widest range of applications.

The MMA method repeatedly creates two patterns (models) of beats from any sequence of valid beats, one pattern associated only with the even beats, and the other associated with the odd beats. To clarify each pattern of the beats, the algorithm is as follows: the differences of amplitude between the current pattern (even or odd beats) and the next valid beat (even or odd) are measured along several equally spaced sites in the ST-T complex. Each of those differences is divided into X equal parts (where X can be 8, 16, 32 or 64), and the contribution of the current valid beat in the update of the standard beat is then limited to 1/X (named ‘the update factor’ or ‘limiting fraction’) of the differences between the model and the beat. Finally, the TWA values are made available every 15 seconds, as the difference between two representative patterns (and continuously updated) of the even beats and the odd beats.2020 Nearing BD, Verrier RL. Modified moving average analysis of T-wave alternans to predict ventricular fibrillation with high accuracy. J Appl Physiol. 2002;92(2):541-9. That technique has been assessed in academic studies with good reproducibility.2121 de Oliveira Antunes M, Samesima N, Pereira Filho HG, Matsumoto AY, Pastore CA, Arteaga-Fernandez E, et al. Exercise-induced quantitative microvolt T-wave alternans in hypertrophic cardiomyopathy. J Electrocardiol. 2017;50(2):184-90.

In a study of Chagas disease, published in this issue of the Arquivos Brasileiros de Cardiologia,2222 Odozynski G, Dal Forno AR, Lewandowski A, Nascimento HG, d’Avila A. Ablação de fibrilação atrial paroxística em mulheres:compreendendo a diferença entre gêneros. Arq Bras Cardiol. 2018; 110(5):412-417 patients with chronic Chagasic cardiomyopathy and history of malignant ventricular arrhythmia most often had a non-negative result of microvolt TWA as compared to those with no previous arrhythmia, suggesting that TWA can play a role in the SCD risk stratification in Chagas disease. That study used the Cambridge Heart software with special electrodes (high resolution) and the SM. Its results are shown in terms of negative and non-negative (positive + indeterminate) TWA, the latter being compared to the former. That study emphasizes that Chagas cardiomyopathy has a true arrhythmogenic substrate confirmed by TWA.

  • Short Editorial regarding the article Association between Microvolt T-Wave Alternans and Malignant Ventricular Arrhythmias in Chagas Disease

References

  • 1
    Rubart D, Zipes P. Mechanisms of sudden cardiac death. J Clin Invest. 2005;115(9):2305-15.
  • 2
    Fabre A, Sheppard MN. Sudden adult death syndrome and other nonischaemic causes of sudden cardiac death. Heart. 2006;92(3):316-20.
  • 3
    Thompson PD, Franklin BA, Balady GJ, Blair SN, Corrado N, Estes NA rd, et al. Exercise and acute cardiovascular events: Placing the risks into perspective: A scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism and the Council on Clinical Cardiology - In collaboration with the American College of Sports Medicine. Circulation. 2007;115(17):2358-68.
  • 4
    Weiss JN, Karma A, Shiferaw Y, Chen PS, Garfinkel A, Chu Z. From pulsus to pulseless: The saga of cardiac alternans. Circ Res. 2006;98(10):1244-53.
  • 5
    Hering HE. Experimentelle studien an s¨augetieren ¨uber das elektrocardiogram. Zeitschrift f ¨ur experimentelle Pathologie und Therapie. 1909;7:363-78.
  • 6
    Adam DR, Akselrod S, Cohen RJ. Estimation of ventricular vulnerability to fibrillation through T-wave time series analysis. Comput Cardiol. 1981;8:307-10.
  • 7
    Zareba W, Piotrowicz K, McNitt S, Moss AJ, MADIT II Investigators. Implantable cardioverter-defibrillator efficacy in patients with heart failure and left ventricular dysfunction (from the MADIT II Population). Am J Cardiol. 2005;95(12):1487-91.
  • 8
    Salerno-Uriarte JA, De Ferrari GM, Klersy C, Pedretti RF, Tritto M, Sallusti L, et al.Prognostic value of T-wave alternans in patients with heart failure due to nonischemic cardiomyopathy-results of the ALPHA study. J Am Coll Cardiol. 2007;50(19):1896-904.
  • 9
    Exner DV, Kavanagh KM, Slawnych MP, Mitchell LB, Ramadan D, Aggarwal SG, et al. Noninvasive risk assessment early after a myocardial infarction- the REFINE study. J Am Coll Cardiol. 2007;50(24):2275-84.
  • 10
    Nieminen T, Lehtimaki T, Viik J, Lehtinen R, Nikus K, Koobi T, et al. T-wave alternans predicts mortality in a population undergoing a clinically indicated exercise test. Eur Heart J. 2007;28(19):2332-7.
  • 11
    Ikeda T, Yoshino H, Sugi K, Tanno K, Shimizu H, Watanabe J, et al. Predictive value of microvolt T-wave alternans for sudden cardiac death in patients with preserved cardiac function after acute myocardial infarction results of a collaborative cohort study. J Am Coll Cardiol. 2006;48(11):2268-74.
  • 12
    Bloomfield DM, Steinman RC, Namerow PB, Paredes M, Davidenko J, Kaufman ES, et al. Microvolt T-wave alternans distinguishes between patients likely and patients not likely to benefit from implanted cardiac defibrillator therapy: A solution to the multicenter automatic defibrillator implantation trial (MADIT) II conundrum. Circulation. .2004;110(14):1885-9.
  • 13
    Bloomfield D, Hohnloser SH, Cohen RJ. Interpretation and classification of microvolt T wave alternans tests. J Cardiovasc Electrophysiol 2002;13(5):502-12.
  • 14
    Hohnloser SH. T wave alternans. In: Zipes D, Jalife J, eds. Cardiac electrophysiology, 6th ed. Philadelfia, PA: Elsevier Inc.; 2013. p.665-76.
  • 15
    Merchant FM, Armoundas AA. Role of substrate and triggers in the genesis of cardiac alternans, from myocyte to the whole heart: implications for therapy. Circulation 2012;125(3):539-49.
  • 16
    Hagjoo M, Arya A, Sadr-Ameli MA. Microvolt T-wave alternans: a review of techniques, interpretation, utility, clinical studies and future perspectives. Int J Cardiol 2006;109(3):293-306.
  • 17
    Garcia EV, Pastore CA, Samesima N, Pereira Filho HG. T-wave alternans: desempenho clínico, limitações, metodologias de análise. Arq Bras Cardiol 2011;96(3):e53-e61.
  • 18
    Smith JM, Clancy EA, Valeri CR,Ruskin JN, Cohen RJ. Electrical alternans and cardiac electrical instability. Circulation. 1988;77(1):110-21.
  • 19
    Rosenbaum DS, Jackson LE, Smith JM, Garan H, Ruskin JN, Cohen RJ. Electrical alternans and vulnerability to ventricular arrhythmias. N Engl J Med. 1994;330(4):235-41.
  • 20
    Nearing BD, Verrier RL. Modified moving average analysis of T-wave alternans to predict ventricular fibrillation with high accuracy. J Appl Physiol. 2002;92(2):541-9.
  • 21
    de Oliveira Antunes M, Samesima N, Pereira Filho HG, Matsumoto AY, Pastore CA, Arteaga-Fernandez E, et al. Exercise-induced quantitative microvolt T-wave alternans in hypertrophic cardiomyopathy. J Electrocardiol. 2017;50(2):184-90.
  • 22
    Odozynski G, Dal Forno AR, Lewandowski A, Nascimento HG, d’Avila A. Ablação de fibrilação atrial paroxística em mulheres:compreendendo a diferença entre gêneros. Arq Bras Cardiol. 2018; 110(5):412-417

Publication Dates

  • Publication in this collection
    May 2018
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