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[[File: Minkkinen fig.jpeg]]
 
File: Minkkinen fig.jpeg]]


(Reprinted with permission from John Wiley & Sons, Inc., from <ref>Minkkinen et al, “Enhanced predictive power of quantitative TWA during routine exercise testing in the Finnish Cardiovascular Study,” published in J Cardiovasc Electrophysiol 2009; 20: 408-415.</ref>) This patient's peak TWA level was 124 microvolts, indicating severely abnormal risk.  He died 12 months later of cardiovascular causes.  
(Reprinted with permission from John Wiley & Sons, Inc., from <ref>Minkkinen et al, “Enhanced predictive power of quantitative TWA during routine exercise testing in the Finnish Cardiovascular Study,” published in J Cardiovasc Electrophysiol 2009; 20: 408-415.</ref>) This patient's peak TWA level was 124 microvolts, indicating severely abnormal risk.  He died 12 months later of cardiovascular causes.  
Line 115: Line 113:
Both methods use CPT code 93025.   
Both methods use CPT code 93025.   


==References==
{{Reflist|2}}


==External Links==
==External Links==

Revision as of 17:21, 15 March 2015

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Editors-In-Chief: Richard L. Verrier, PhD, FACC, and Tuomo Nieminen, MD, PhD; Assistant Editors-in-Chief: Jose Roberto Pegler, MD, and Caio Tavares, MD.

Overview

T-wave alternans is a beat-to-beat alternation in the repolarization cycle of the heartbeat. It can be observed in the electrocardiogram (ECG) as a difference in the amplitude and morphology of the ST-segment and/or the T wave among successive odd and even beats in an ABAB pattern (Figure).


File:Minkkinen fig.jpeg

(Reprinted with permission from John Wiley & Sons, Inc., from [1]) This patient's peak TWA level was 124 microvolts, indicating severely abnormal risk. He died 12 months later of cardiovascular causes.

Interest is focused on this phenomenon because of its promise in identifying individuals with elevated risk for lethal heart rhythm disturbances and sudden cardiac death, the leading cause of death in the industrially developed world. The video of the ABAB pattern of TWA heralds the onset of ventricular fibrillation during myocardial ischemia. The arrhythmia was successfully terminated by defibrillation countershock.

{{#ev:youtube|ZSJB3sB5Oi0}}

History of T Wave Alternans

Hering, in 1908, was the first to observe and describe visible macroscopic TWA and its association with increased susceptibility to ventricular tachyarrhythmias.[2] The advent of digital signal processing techniques allowed identification and measurement of nonvisible levels of TWA.

Causes


Antiarrhythmic Interventions Reduce TWA Level Allowing TWA to Serve as a Therapeutic Target

Differentiating Electrical Alternans from other Disorders

The electrical form of alternans should be differentiated from the mechanical form alternans in which case there is alternation of the strength of the pulse as is observed in pulsus alternans. Electrical and mechanical alternans may coexist.

Microvolt TWA and Test Methods

In the 1980’s, Drs. Richard J. Cohen, Joseph M. Smith, David S. Rosenbaum, and colleagues at Massachusetts Institute of Technology and Massachusetts General Hospital [31] [32] and Drs. Richard L. Verrier and Bruce D. Nearing at Georgetown University School of Medicine and later at Beth Israel Deaconess Medical Center, Harvard Medical School, [33] [34] applied signal processing techniques to detect visually indiscernible levels of TWA and established that at a microvolt level, TWA discloses risk for lethal cardiac arrhythmias and sudden cardiac death.

Two techniques for TWA analysis currently cleared by the United States Food and Drug Administration for risk stratification for arrhythmic death are the Spectral Method, which emanated from Dr. Cohen’s laboratory and is commercialized by Cambridge Heart, Inc. and Cardiac Sciences, Inc. and the Modified Moving Average method, which resulted from Drs. Verrier and Nearing’s collaboration and is commercialized by GE Healthcare, Inc. and in Europe by Getemed AG.

Spectral Method (SM)

The Fast Fourier Transform is employed to analyze 128 consecutive beats from the J-point to the end of the T wave and produces a power spectrum at 0.5 cycle/beat (on every other beat), which is defined as the alternans power. Since the Spectral Method requires a graded heart-rate increase to a target heart rate, it is usually performed during bicycle ergometry or treadmill exercise. Specialized electrodes are required for noise reduction.

Interpreting Results of Spectral Method

If the TWA level calculated by the Spectral Method exceeds 1.9µV, then the test is considered positive.[35] These patients should be referred to a cardiac electrophysiologist for further evaluation. Results below 1.9µV are interpreted as negative. Several prospective studies have demonstrated that a negative TWA test result with the Spectral Method confirms a low level of risk for an arrhythmic episode, since the test displays a negative predictive value ≥97% [36] [37] indicating that a negative test correctly identifies ≥97% of patients with diminished risk of developing a lethal cardiac arrhythmia or sudden cardiac death during the next year to two years. Test results may be indeterminate for technical reasons (noise from muscle, respiration, or movement artifact) or because of patient factors (inability to reach a target heart rate of 105-110 beats/min, excessive ectopy, or nonsustained TWA). Indeterminate test results due to patient factors indicate a level of the risk that is equivalent to or greater than a positive test result.[38] and these patients should be immediately retested.

Prognostic Value of the Spectral Method

Over 8000 subjects have been enrolled in Spectral Method studies that predicted outcomes, including the ALPHA study [39] and the ABCD study [40]. An additional 3145 (28% of total) subjects were enrolled in Spectral Method studies that did not predict outcomes, including the SCD-HeFT TWA substudy [41], the MASTER study [42], and the CARISMA study [43].

Modified Moving Average (MMA) Method

This approach employs the noise-rejection principle of recursive averaging.[44] It was designed to allow TWA measurement during routine exercise stress testing and ambulatory ECG monitoring, as it circumvents the requirement of heart-rate stabilization and uses standard precordial leads. The algorithm continuously streams odd and even beats into separate bins and creates median complexes for each bin. The complexes are then superimposed and the peak difference between the odd and even median complexes at any point from the J point to the end of the T wave is defined as the TWA value and is updated every 10 to 15 seconds. The influence of new incoming beats is controlled through use of an adjustable update factor; the sensitive 1/8 update factor is recommended. Artifacts due to respiration and motion are reduced by software.

The MMA method reports TWA values in microvolts and presents high-resolution templates of superimposed beats to display the alternation pattern and permit visual overreading to verify the automated TWA measurement. Watch the video "TWA Analysis in Ambulatory ECG recording - Tutorial" to learn how to analyze TWA using the Modified Moving Average (MMA) Method. Click [[

Media:Excel_Model_for_TWA_analysis.xls|here‎]]

to obtain the excel file with the formulas mentioned in the video. For more details, see the following from GE Healthcare, Inc.

{{#ev:youtube|-oC3GLoFXFo}}


The MMA method uses routine, symptom-limited exercise stress testing or ambulatory ECG monitoring and standard electrodes and requires that chronic medications be retained. Both methods achieve 1-microvolt resolution.

Interpreting Results of Modified Moving Average Method

Higher TWA values indicate greater risk for sudden cardiac death and cardiovascular and total mortality along a continuum. TWA <20µV indicates no increased risk, while TWA ≥47µV and ≥60µV are associated with abnormal and severely abnormal risk, respectively.

Prognostic Value of Modified Moving Average Method

Over 5000 patients have been enrolled in MMA studies. The largest investigation of TWA by any method is the Finnish Cardiovascular Study (FINCAVAS), which enrolled >3500 generally low-risk patients who were referred for routine, symptom-limited exercise testing.[45] Approximately 1500 patients were studied during ambulatory ECG monitoring.[46] All MMA-based TWA studies have predicted outcomes. A trial of MTWA-guided ICD implantation by the MMA method, REFINE-ICD (NCT00673842), is underway [47].

Comparison of Spectral and Modified Moving Average Methods

The MTWA consensus guideline, authored by 11 international experts in both methods, compared the methods and their utility in risk assessment [48]. Briefly, they reported that the Spectral and MMA methods were found in prospective investigations to exhibit similar hazard ratios for predicting sudden cardiac death and cardiovascular mortality when tested in the same population of post-MI patients with better-preserved left ventricular ejection fraction [49] or in overall hazard ratios. A high negative predictive accuracy of ≥97% is found with both methods. A head-to-head comparison of the Spectral and MMA methods revealed similar hazard ratios, kappa statistics, and areas under the receiver-operator characteristic curve [50].

TWA values reported by MMA are typically 4- to 10-fold higher than Spectral Method test results. This difference is mainly attributable to the fact that the Spectral Method reports the average TWA level across the entire JT segment for 128 beats, whereas the MMA method reports the peak TWA value for each 15 seconds at any point within the JT interval.

Clinical Significance

MTWA testing has been recommended for arrhythmia risk assessment by the American College of Cardiology, American Heart Association and European Society of Cardiology [51] and by CMS in National Coverage Analysis for Implantable Cardioverter Defibrillators (CAG-00157N).

One proposed application of TWA testing has been to identify patients who would not benefit from implantation of an ICD,which rescues patients from a lethal arrhythmia. The current guidelines for ICD implantation state that the main parameter to be analyzed is left ventricular ejection fraction, a measure that does not reveal direct information about the electrical substrate of the heart.

A second proposed application of TWA testing is in guiding medical therapy, since many agents that have been shown to reduce incidence of arrhythmias, sudden cardiac death, or cardiovascular mortality also diminish TWA magnitude clinically. Thus, drug-induced changes in TWA magnitude may provide an indication of therapeutic efficacy on an individual patient basis.

Frontiers of TWA testing include improvement in prediction based on quantification of TWA magnitude, risk stratification among patients with preserved ejection fraction, the patient group with the highest number of sudden cardiac deaths, and combined use with other noninvasive risk markers to optimize identification of patients whose risk for lethal arrhythmias and sudden cardiac death is elevated.

Reimbursement for T-Wave Alternans Testing

The 2006 decision summary from the U.S. Center for Medicare and Medicaid Services regarding reimbursement for T-wave alternans testing (CAG-00293N) states: “CMS has determined that there is sufficient evidence to conclude that Microvolt T-wave Alternans (MTWA) diagnostic testing is reasonable and necessary for the evaluation of patients at risk of sudden cardiac death, only when the spectral analytic method is used, and CMS is issuing the following national coverage determination (NCD) for this indication. Microvolt T-wave Alternans (MTWA) diagnostic testing is covered for the evaluation of patients at risk of sudden cardiac death, only when the spectral analytic method is used.”

A 2015 CMS decision memo regarding the MMA method for MTWA analysis (CAG-00293R2) states: “The Centers for Medicare & Medicaid Services has decided that no National Coverage Determination (NCD) is appropriate at this time for microvolt T-wave alternans (MTWA) testing using the modified moving average (MMA) method for the evaluation of patients at risk for sudden cardiac death (SCD). National non-coverage will be removed. Medicare coverage of MTWA using the MMA method will be determined by the local contractors.”

Both methods use CPT code 93025.

References

  1. ↑ Minkkinen et al, “Enhanced predictive power of quantitative TWA during routine exercise testing in the Finnish Cardiovascular Study,” published in J Cardiovasc Electrophysiol 2009; 20: 408-415.
  2. ↑ Hering HE. Das Wesen des Herzalternans. Muenchener Med Wochenschr 1908; 4:1417-1421.
  3. ↑ Bardaji A, Vidal F, Richart C. T wave alternans associated with amiodarone. J Electrocardiol. Apr 1993;26(2):155-7.
  4. ↑ Kop WJ, Krantz DS, Nearing BD, et al: Effects of acute mental and exercise stress on T-wave alternans in patients with implantable cardioverter defibrillators and controls. Circulation 2004 109:1864-1869.
  5. ↑ Lampert R, Shusterman V, Burg M, et al: Anger-induced T-wave alternans predicts future ventricular arrhythmias in patients with implantable cardioverter-defibrillators. J Am Coll Cardiol 2009 53:774–778.
  6. ↑ Stein PK, Sanghavi D, Domitrovich PP, et al. Ambulatory ECG-based T-wave alternans predicts sudden cardiac death in high-risk post-MI patients with left ventricular dysfunction in the EPHESUS study. J Cardiovasc Electrophysiol 2008 19:1037–1042.
  7. ↑ Exner DV, Kavanagh KM, Slawnych MP, et al. Noninvasive risk assessment early after a myocardial infarction the REFINE study. J Am Coll Cardiol 2007 Dec 11; 50:2275-84.
  8. ↑ Slawnych MP, Nieminen T, Kahonen M, et al. Post-exercise assessment of cardiac repolarization alternans in patients with coronary artery disease using the modified moving average method. J Am Coll Cardiol 2009 Mar 31; 53:1130-7.
  9. ↑ Ren L-N, Fang XH, Ren LD, Gong J, Wang Yq, Qi G-x,et al. Ambulatory ECG-based T-wave alternans and heart rate turbulence can predict cardiac mortality in patients with myocardial infarction with or without diabetes mellitus. Cardiovasc Diabetol2012;11:104–11.
  10. ↑ Strzelczyk A, Adjei P, Scott CA, et al. Postictal increase in T-wave alternans after generalized tonic–clonic seizures. Epilepsia 2011 52:2112-2117.
  11. ↑ Schomer AC, Nearing BD, Schachter SC, Verrier RL. Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy. Epilepsia 2014; 55:1996–2002.
  12. ↑ Lampert R, Soufer R, McPherson CA, et al. Implantable cardioverter-defibrillator shocks increase T-wave alternans. J Cardiovasc Electrophysiol 2007 18:512-517.
  13. ↑ Sakaki K, Ikeda T, Miwa Y, et al. Time-domain T-wave alternans measured from Holter electrocardiograms predicts cardiac mortality in patients with left ventricular dysfunction: a prospective study. Heart Rhythm 2009 6:332–337.
  14. ↑ Cruz Filho FE, Maia IG, Fagundes ML, et al. Electrical behavior of T-wave polarity alternans in patients with congenital long QT syndrome. J Am Coll Cardiol. Jul 2000;36(1):167-73.
  15. ↑ Verrier RL, Nearing BD, LaRovere MT, Pinna GD, Mittleman MA, Bigger JT, Schwartz PJ for the ATRAMI Investigators. Ambulatory ECG-based tracking of T-wave alternans in post-myocardial infarction patients to assess risk of cardiac arrest or arrhythmic death. J Cardiovasc Electrophysiol 2003; 14:705-711.
  16. ↑ Hoshida K, Miwa Y, Miyakoshi M, et al. Simultaneous assessment of T-wave alternans and heart rate turbulence on Holter electrocardiograms as predictors for serious cardiac events in patients after myocardial infarction. Circ J 2013 77:432-438.
  17. ↑ Hou Y, Fang PH, Wu Y, et al. Prediction of sudden cardiac death in patients after acute myocardial infarction using T-wave alternans: a prospective study. J Electrocardiol 2012 45:60–65
  18. ↑ Sulimov V, Okisheva E, Tsaregorodtsev D. Non-invasive risk stratification for sudden cardiac death by heart rate turbulence and microvolt T wave alternans in patients after myocardial infarction. Europace 2012 14:1786-1792.
  19. ↑ Exner DV, Kavanagh KM, Slawnych MP, et al. Noninvasive risk assessment early after a myocardial infarction the REFINE study. J Am Coll Cardiol 2007 Dec 11; 50:2275-84.
  20. ↑ Slawnych MP, Nieminen T, Kahonen M, et al. Post-exercise assessment of cardiac repolarization alternans in patients with coronary artery disease using the modified moving average method. J Am Coll Cardiol 2009 Mar 31; 53:1130-7.
  21. ↑ Arisha MM, Girerd N, Chauveau S, Bresson D, Scridon A, Bonnefoy E, et al. In-hospital heart rate turbulence and microvolt T-wave alternans abnormalities for prediction of early life-threatening ventricular arrhythmia after acute myocardial infarction. Ann Noninvasive Electrocardiol 2013;18:530–7.
  22. ↑ Takasugi N, Kubota T, Nishigaki K, et al. Continuous T-wave alternans monitoring to predict impending life-threatening cardiac arrhythmias during emergent coronary reperfusion therapy in patients with acute coronary syndrome. Europace 2011 13:708-715.
  23. ↑ Verrier RL, Nieminen T. T-wave alternans as a therapeutic marker for antiarrhythmic agents. J Cardiovasc Pharmacol 2010; 55(6):544-554.
  24. ↑ Secemsky EA, Verrier RL, Cooke G, et al: High prevalence of cardiac autonomic dysfunction and T-wave alternans in dialysis patients. Heart Rhythm 2011 8:592-598.
  25. ↑ Shimada H, Nishizaki M, Fujii H, et al. Ambulatory electrocardiogram-based T-wave alternans in patients with vasospastic angina during asymptomatic periods. Am J Cardiol 2012 110:1446-1451.
  26. ↑ Schomer AC, Nearing BD, Schachter SC, Verrier RL. Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy. Epilepsia 2014; 55:1996–2002.
  27. ↑ Klingenheben T, Gronefeld G, Li YG, Hohnloser SH. Effect of metoprolol and d,l-sotalol on microvolt-level T-wave alternans. Results of a prospective, double-blind, randomized study. J Am Coll Cardiol 2001; 38:2013-9.
  28. ↑ Kavesh NG, Shorofsky SR, Sarang SE, Gold MR. The effect of procainamide on T wave alternans. J Cardiovasc Electrophysiol 1999 May; 10:649-54.
  29. ↑ Kubo S, Yoshida A, Kitamura H, Yokoyama M. Acute effects of angiotensin II receptor blocker on ventricular repolarization alternans in chronic heart failure. Kobe J Med Sci 2008 Feb 8; 53:365-74.
  30. ↑ Kentta T, Tulppo MP, Nearing BD, Karjalainen JJ, Hautala AJ, Kiviniemi AM, Huikuri HV, Verrier RL. Effects of exercise rehabilitation on cardiac electrical instability assessed by T-wave alternans during ambulatory electrocardiogram monitoring in coronary artery disease patients without and with diabetes mellitus. Am J Cardiol 2014; 114:832-837.
  31. ↑ Smith JM, Clancy EA, Valeri CR, Ruskin JM, Cohen RJ. Electrical alternans and cardiac electrical instability. Circulation 1988; 77:110-121.
  32. ↑ Rosenbaum DS, Jackson LE, Smith JM, Garan H, Ruskin JN, Cohen RJ. Electrical alternans and vulnerability to ventricular arrhythmias. N Engl J Med 1994 Jan 27; 330:235-41.
  33. ↑ Nearing BD, Verrier RL. Modified moving average method for T-wave alternans analysis with high accuracy to predict ventricular fibrillation. J Appl Physiol 2002; 92:541-49.
  34. ↑ Verrier RL, Nearing BD, LaRovere MT, Pinna GD, Mittleman MA, Bigger JT, Schwartz PJ for the ATRAMI Investigators. Ambulatory ECG-based tracking of T-wave alternans in post-myocardial infarction patients to assess risk of cardiac arrest or arrhythmic death. J Cardiovasc Electrophysiol 2003; 14:705-711.
  35. ↑ Bloomfield DM, Hohnloser SH, Cohen RJ. Interpretation and classification of microvolt T wave alternans tests. J Cardiovasc Electrophysiol 2002 May; 13:502-12.
  36. ↑ Bloomfield DM, Steinman RC, Namerow PB, 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 Oct 5; 110:1885-9.
  37. ↑ Gehi AK, Stein RH, Metz LD, Gomes JA. Microvolt T-wave alternans for the risk stratification of ventricular tachyarrhythmic events: A meta-analysis. J Am Coll Cardiol 2005 Jul 5; 46:75-82.
  38. ↑ Kaufman ES, Bloomfield DM, Steinman RC, 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 2006 Oct 3; 48:1399-404.
  39. ↑ Salerno-Uriarte JA, De Ferrari GM, Klersy C, Pedretti RF, Tritto M, Sallusti L, Libero L, Pettinati G, Molon G, Curnis A, Occhetta E, Morandi F, Ferrero P, Accardi F; ALPHA Study Group Investigators. 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 Nov 6;50(19):1896-904. Epub 2007 Oct 22.
  40. ↑ Costantini O, Hohnloser SH, Kirk MM, et al. The ABCD (Alternans Before Cardioverter Defibrillator) trial: strategies using T-wave alternans to improve efficiency of sudden cardiac death prevention. J Am Coll Cardiol 2009;53:471–9
  41. ↑ Gold MR, Ip JH, Costantini O, et al. Role of microvolt T-wave alternans in assessment of arrhythmia vulnerability among patients with heart failure and systolic dysfunction: Primary results from the T-wave Alternans Sudden Cardiac Death in Heart Failure Trial substudy. Circulation 2008;118:2022–8.
  42. ↑ Chow T, Kereiakes DJ, Onufer J, et al. Does microvolt T-wave alternans testing predict ventricular tachyarrhythmias in patients with ischemic cardiomyopathy and prophylactic defibrillators? The MASTER (Microvolt T-wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients) trial. J Am Coll Cardiol 2008; 52:1607–15.
  43. ↑ Huikuri HV, Raatikainen MJ, Moerch-Joergensen R, et al. Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction. Eur Heart J 2009;30:689–98.
  44. ↑ Nearing BD, Verrier RL. Modified moving average method for T-wave alternans analysis with high accuracy to predict ventricular fibrillation. J Appl Physiol 2002; 92:541-49.
  45. ↑ Nieminen T, Lehtimäki T, Viik J, Lehtinen R, Nikus K, Kööbi T, Niemelä K, Turjanmaa V, Kaiser W, Huhtala H, Verrier RL, Huikuri H, Kähönen M. T-wave alternans predicts mortality in a population undergoing a clinically indicated exercise test. Eur Heart J 2007; 28:2332-37.
  46. ↑ Verrier RL, Malik M. Quantitative T-wave alternans analysis for guiding medical therapy: An underexploited opportunity. Trends in Cardiovascular Medicine 2015. http://dx.doi.org/10.1016/j.tcm.2014.10.006
  47. ↑ Exner D. Noninvasive risk stratification after myocardial infarction:rationale, current evidence and the need for definitive trials. Can J Cardiol 2009;25 Suppl A:21A–7A.
  48. ↑ Verrier R. Klingenheben T, Malik M, et al. Microvolt T-wave alternans: physiological basis, methods of measurement, and clinical utility: consensus guideline by International Society for Holter and Noninvasive Electrocardiology. J Am Coll Cardiol. 2011;58:1309-1324
  49. ↑ Exner DV, Kavanagh KM, Slawnych MP, et al. Noninvasive risk assessment early after a myocardial infarction the REFINE study. J Am Coll Cardiol 2007 Dec 11; 50:2275-84
  50. ↑ Exner DV, Kavanagh KM, Slawnych MP, et al. Noninvasive risk assessment early after a myocardial infarction the REFINE study. J Am Coll Cardiol 2007 Dec 11; 50:2275-84
  51. ↑ Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol 2006;48:e247–346 (see e401, e402).

External Links

  • GE Healthcare Manufacturer of Marquette MMA T-wave Alternans Stress Test and Holter Systems

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