doi: 10.1161/01.CIR.0000165124.18526.25
(Circulation. 2005;111:e299-e300.)
© 2005 American Heart Association, Inc.
Correspondence |
Letters Regarding Article by Bloomfield et al, "Microvolt T-Wave Alternans Distinguishes Between Patients Likely and Patients Not Likely to Benefit From Implanted Cardiac Defibrillator Therapy"
Department of Cardiology, Wansbeck General Hospital, Ashington, UK
The recent article by Bloomfield and colleagues described the use of microvolt T-wave alternans (MTWA) testing for identifying groups at high and low risk of dying among heart failure patients who met Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II) criteria for implantable cardioverter-defibrillator (ICD) prophylaxis.1 Their study adds to the current literature and suggests that MTWA testing may be a useful guide to mortality prediction. The authors emphasize the potential impact on resources that the MADIT-II findings could have if applied to current clinical practice and the need for additional, noninvasive risk-stratification tools. Their results complement a recent meta-analysis in The Lancet, which proposed that a normal MTWA result identified a low-risk group among MADIT-II patients who may benefit less from defibrillator therapy.2
MTWA testing may be helpful in delivering ICD implantation to those with the greatest need; however, uncertainties remain regarding the timing of testing after myocardial infarction (MI) and the effects of medical treatment on the result. The authors’ report 74% of patients in their study were taking ß-blockers; additional data on drug doses, resting heart rate, and blood pressure may have indicated whether there was scope to further increase medical treatment before testing and how this influenced the result. Activation of the sympathetic nervous system augments MTWA, with Klingenheben and colleagues having previously shown that selective ß-adrenergic blockade with metoprolol or sotalol significantly reduced MTWA magnitude in patients susceptible to ventricular arrhythmias (P
0.001).3 Bloomfield and coworkers reported a mean time of 
5 years after MI before testing, although temporal variations in MTWA levels post-MI have been demonstrated previously, and the optimal time for testing to maximize its predictive accuracy has not yet been identified.4 The primary end point in both the Bloomfield et al study and MADIT-II was all-cause mortality. In terms of ICD screening, however, the proportion of arrhythmic deaths relative to heart failure and ischemic deaths would be of greater relevance in determining the usefulness of MTWA.
It has been suggested that an alternative interpretation of a positive MTWA test could be that it identifies a high-risk group of patients who are not yet optimally medically treated5 and that MTWA testing should be performed only after optimization of pharmacological therapy. Further studies are therefore needed before establishing the precise role of MTWA testing in screening for ICD prophylaxis.
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1. Bloomfield DM, Steinman RC, Namerow PB, Parides M, Davidenko J, Kaufman ES, Shinn T, Curtis A. Fontaine J, Holmes D, Russo A, Tang C, Bigger JT Jr. 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: 1885–1889.
2. Hohnloser SH, Ikeda T, Bloomfield DM, Dabbous OH, Cohen RJ. T-wave alternans negative coronary patients with low ejection fraction and benefit from defibrillator implantation. Lancet. 2003; 362: 125–126.[CrossRef][Medline] [Order article via Infotrieve]
3. Klingenheben T, Gronefeld G, Li Y, Hohnloser SH. Effect of metoprolol and d,l-sotalol on microvolt T-wave alternans. J Am Coll Cardiol. 2001; 38: 2013–2019.
4. Klingenheben T, Hohnloser SH. Clinical value of T-wave alternans assessment. Cardiac Electrophysiol Rev. 2002; 6: 323–328.[CrossRef][Medline] [Order article via Infotrieve]
5. Jauhaur S, Chinitz L, Jorde U. Drug therapy and microvolt T-wave alternans testing. Lancet. 2003; 362: 1417–1418.[Medline] [Order article via Infotrieve]
Mount Sinai School of Medicine, Cardiology Division, Elmhurst Hospital Center, Elmhurst, NY, madiasj{at}nychhc.org
To the Editor:
I read with great interest the article by Bloomfield et al,1 which reported on the differential in the performance of the QRS duration, as recommended by the Centers for Medicare and Medicaid Services for suitability for implanted cardiac defibrillator (ICD) therapy, and the microvolt T-wave alternans as predictors of mortality in patients with heart failure. It is important that the authors’ cohort is representative of the Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II) criteria for ICD implantation,2 and thus their findings become relevant to the quest of identifying the essentials for a practical and accurate "profiling" of the patients who will benefit from device therapy. The study group of 177 patients is small, the mean follow-up of 20 months is short, and some methodological issues are reasons for tempering one’s enthusiasm about the recommendations of the authors and for scrutiny of what is currently in circulation and what is coming.
In reference to 2 of these 3 issues, there is no other way but to start with small cohorts and report on data from limited follow-up studies; larger studies and lengthier follow-up periods are sure to come. The methodology aspect needs to be carefully defined early on, however, so that all of us receive the benefit of the comparability of the already published work and future studies. In this vein, it is of concern that the authors did not provide information as to how many patients had their QRS duration determined by automation or manual measurement, which ECG record was employed for patients who had a number of tracings in their files, and why they feel that indeterminate microvolt T-wave alternans can appropriately be included as a positive response by this modality. Is it possible that had the authors used only the patients with positive microvolt T-wave alternans and the longest QRS duration measured by automation from all of the ECG tracings available per patient, the conclusions would be different?
The methodology proposed by the authors needs to be better standardized before it can be recommended as the preferred method to select patients for ICD placement.
Relevant issues requiring clarification are the reproducibility of the microvolt T-wave alternans (and, of course, of the QRS duration) and the preferred method of measurement of QRS duration (manual versus automation). In comparative studies of microvolt T-wave alternans and QRS duration, one also should grapple with what values of QRS duration should be adopted as "threshold" when selecting patients for ICD implantation, and the effect of peripheral edema in patients with heart failure, which has been shown to produce an apparent shortening of the QRS duration.3
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TopReferencesReferences References |
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1. Bloomfield DM, Steinman RC, Namerow PB, Parides M, Davidenko J, Kaufman ES, Shinn T, Curtis A. Fontaine J, Holmes D, Russo A, Tang C, Bigger JT Jr. 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: 1885–1889.
2. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML; Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002; 346: 877–883.
3. Madias JE. Significance of shortening of the mean QRS duration of the standard electrocardiogram in patients developing peripheral edema. Am J Cardiol. 2002; 89: 1444–1446.[CrossRef][Medline] [Order article via Infotrieve]
Response
Department of Medicine, Columbia University, New York, NY
New York Heart Center, Syracuse, NY
MetroHealth, Case Western Reserve University, Cleveland, Ohio
Michigan Heart PC, Ypsilanti, Mich
University of Florida, Gainesville, Fla
Drexel University College of Medicine, Philadelphia, Pa
New York University, New York, NY
University of Pennsylvania, Philadelphia, Pa
Minneapolis Heart Institute Foundation, Minneapolis, Minn
Before our study and subsequent article,1 the literature suggested that microvolt T-wave alternans (TWA) has an extremely high negative predictive accuracy; high-risk patients with a normal TWA test have an excellent prognosis. We prospectively tested this hypothesis in a group of patients considered to be at high-enough risk to warrant implanted cardiac defibrillator (ICD) prophylaxis without further risk stratification (the Multicenter Automatic Defibrillator Implantation Trial-II [MADIT-II]2 indication). Our data demonstrate that even in this high-risk group of patients, a normal TWA test successfully identifies a low-risk group of patients unlikely to benefit from ICD therapy.
Jachuck and Satchithananda argue that intensifying medical therapy for heart failure may change the results of TWA testing. We agree that ß-blocker treatment of patients with left ventricular dysfunction may convert some TWA tests from positive to negative. Their fear that false-negative TWA tests would deny some patients an ICD is not warranted; we found a low (<2%) false-negative rate in our study, even though 74% were taking ß-blockers at the time of the TWA test. Among MADIT-II–like patients, this low false-negative rate of TWA in the presence of ß-blockers obviates the need to adjust medical therapy in connection with testing, thereby substantially simplifying the logistics of TWA testing.
Dr Madias raised a question about our decision to combine patients with indeterminate and positive TWA tests into a single abnormal group. Several previous studies showed that patients with positive TWA tests and those with indeterminate tests have similarly poor outcomes, and thus proposed combining these 2 TWA high-risk groups.3,4 Our current study tested this hypothesis prospectively and accepted it as correct. Excluding patients with indeterminate test results and limiting our comparison to patients with positive and negative TWA tests has no effect on our results: MADIT-II–like patients with a normal (negative) TWA test have an excellent prognosis.
Madias also raised concerns about the measurement of QRS duration. The methods used to measure QRS duration in our study are similar to those used clinically. Since the initial Centers for Medicare and Medicaid Services MADIT–II coverage decision, several reports demonstrated that QRS duration does not effectively risk stratify MADIT-II–like patients, findings that are consistent with our results. Accordingly, the Centers for Medicare and Medicaid Services has decided to remove the QRS requirement, making the method of QRS measurement a moot point. TWA tests have substantially better positive and negative predictive accuracies than does QRS duration. MADIT-II patients with a normal TWA test are unlikely to benefit from ICD prophylaxis.
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References |
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TopReferencesReferences References |
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1. Bloomfield DM, Steinman RC, Namerow PB, Parides M, Davidenko J, Kaufman ES, Shinn T, Curtis A. Fontaine J, Holmes D, Russo A, Tang C, Bigger JT Jr. 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: 1885–1889.
2. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML; Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002; 346: 877–883.
3. Hohnloser SH, Ikeda T, Bloomfield DM, Dabbous OH, Cohen RJ. T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation. Lancet. 2003; 362: 125–126.[CrossRef][Medline] [Order article via Infotrieve]
4. Bloomfield DM, Hohnloser SH, Cohen RJ. Interpretation and classification of microvolt T wave alternans tests. J Cardiovasc Electrophysiol. 2002; 13: 502–512.[CrossRef][Medline] [Order article via Infotrieve]
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