TEC Assessment Index
Microvolt T-Wave Alternans Testing to Risk-Stratify Patients Being Considered for ICD Therapy for Primary Prevention of Sudden Death
Assessment Program
Volume 21, No. 14
June 2007
Executive Summary
Background
This Assessment evaluates the evidence on the use of microvolt T-wave alternans (MTWA) testing to risk-stratify patients who are candidates for an implantable cardioverter-defibrillator (ICD). MTWA is proposed as a noninvasive means to predict the likelihood of subsequent ventricular tachyarrhythmic events (VTE, e.g., sudden cardiac death, sustained ventricular tachycardia, ventricular fibrillation). For example, in the study population in the "Multicenter Automatic Defibrillator Implantation Trial II" (MADIT II), the number-needed-to-treat (NNT) to avoid one death over a 20-month period was 17.9. Thus, negative MTWA results might identify a subgroup of patients who could safely forego or defer ICD implantation because they are at low risk of fatal VTE.
It is also possible that if used in patients not currently eligible for an ICD, abnormal MTWA results might identify a subgroup of patients at high risk who could potentially benefit from an ICD. However, the clinical evidence for this indication is too sparse to merit review in this Assessment.
Objective
This Assessment examines evidence to compare outcomes of selecting patients for ICD placement for primary prevention of sudden death with and without MTWA. There are no noninvasive alternative tests, other than left-ventricular ejection fraction (LVEF), considered conventional alternatives.
Search Strategy
MEDLINE® search (via PubMed) through March 2007; also, pertinent abstracts presented at the 2006 American Heart Association Scientific Sessions were included.
Selection Criteria
Because of lack of direct clinical trial evidence supporting MTWA, observational studies that provided indirect evidence were selected. Studies that reported death and arrhythmic events in patients who were otherwise eligible for ICD therapy but tested MTWA negative were selected. Studies that might inform the question of what level of risk of death or arrhythmic event precludes benefit from ICD therapy were also selected.
Main Results
Three studies were identified that evaluated MTWA in patients eligible for ICD therapy. The first study followed 177 patients (57 MTWA negative) over an average of 20 months for all-cause mortality. The second selected ICD-eligible patients from 2 previously published studies (35 total MTWA-negative subjects) and followed them over 2 years for sudden cardiac death or cardiac arrest. The third studied 768 patients who would be eligible for ICD therapy and followed them over a mean of 18 months for all-cause mortality and cause-specific mortality. Of these 768 patients, however, over half had ICD therapy, and thus only 376 patients (124 MTWA negative) could be assessed for natural history.
Although MTWA testing did risk-stratify patients in these studies, those with negative tests still had arrhythmic events and deaths. All-cause mortality for patients testing MTWA negative varied from 3.8% to 12.5% over 2 years, which was lower than for patients testing MTWA non-negative. Various arrhythmic event outcomes also varied between studies. Arrhythmic events varied from 0% to 5.7% over 2 years in MTWA-negative patients, depending on the specific outcome studied.
In trying to address at what level of risk ICD therapy for primary prevention would cause more harm than benefit, one study was found that explicitly modeled this question. Using death and event rates derived from the previously described 3 studies, the study showed greater benefit of ICD therapy in MTWA non-negative patients (i.e., those with positive or uninterpretable test results), but also found benefit in MTWA-negative patients. Although such a modeling study is not definitive evidence supportive or against efficacy, it suggests that under reasonable assumptions of the predictive capability of MTWA tests, clinical use of the test to determine ICD placement may not improve health outcomes.
Of further concern, analysis of SCD-HeFT data presented in abstract form at the 2006 American Heart Association Scientific Sessions found that MTWA results were not predictive of the primary endpoint of sudden cardiac death, sustained ventricular arrhythmia, or appropriate ICD discharge.
Author's Conclusions and Comments
Given the lack of randomized clinical trials, the argument for use of MTWA testing to select patients who might not benefit from ICD therapy rests on two types of information—knowledge of the natural history of persons with MTWA-negative tests, and knowledge of the degree of risk that would confer no benefit from ICD therapy. The knowledge base for both issues is insufficient. Only 3 studies of modest size evaluated outcomes of MTWA-negative subjects who were eligible for ICD placement for primary prevention. Due to the modest number of studies, there is still some uncertainty regarding the outcomes of such patients. Whether these 3 studies actually represent the same population eligible for ICD placement is uncertain. The high negative predictive value for MTWA-negative tests derived from other populations may not generalize to the population eligible for ICD placement. Furthermore, even though MTWA testing is predictive of outcome, it is uncertain if the level of risk is low enough such that ICD therapy is of no benefit. One published decision analysis suggests that ICD therapy is still of net benefit to MTWA-negative patients. Finally, lack of randomized clinical trial evidence precludes any expansion of ICD therapy to a group of newly identified patients who have positive or indeterminate MTWA tests.
Based on the available evidence, the Blue Cross and Blue Shield Association Medical Advisory Panel made the following judgments about whether microvolt T-wave alternans testing for risk-stratifying patients being considered for ICD therapy for primary prevention of sudden death meets the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria.
1. The technology must have final approval from the appropriate governmental bodies.
Microvolt T-wave alternans (MTWA) testing may be performed using a commercially available system called the Heartwave™ Alternans Processing System marketed by Cambridge Heart, Inc. This system received 510(k) clearances on November 17, 2002 (K03564) and July 16, 2002 (K022152).
2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes.
The evidence is insufficient. Three observational studies of ICD-eligible patients with negative MTWA tests are relatively small. Although the test does stratify risk in these studies, the absolute risk of events remains uncertain. Furthermore, it is uncertain how low a level of risk precludes benefit from ICD therapy.
There are no clinical trials of ICD therapy in patients not currently eligible for ICD therapy who have been selected using MTWA testing. Thus, there is no evidence for using MTWA to expand the pool of patients eligible for ICD placement.
3. The technology must improve the net health outcome, and
4. The technology must be as beneficial as any established alternatives.
The evidence is insufficient to determine whether the use of MTWA improves net health outcome or whether it is as beneficial as any established alternatives.
5. The improvement must be attainable outside the investigational settings.
Whether the use of MTWA improves health outcomes is not established in the investigational settings.
Therefore, the use of microvolt T-wave alternans testing for risk-stratifying patients being considered for implantable cardioverter-defibrillator therapy for primary prevention of sudden death does not meet the TEC criteria.
TEC Assessment Index
NOTICE OF PURPOSE:TEC Assessments are scientific opinions, provided solely for informational purposes. TEC Assessments should not be construed to suggest that the Blue Cross Blue Shield Association, Kaiser Permanente Medical Care Program or the TEC Program recommends, advocates, requires, encourages, or discourages any particular treatment, procedure, or service; any particular course of treatment, procedure, or service; or the payment or non-payment of the technology or technologies evaluated.
KEYWORDS: DiagnosticandMonitoringTests (category); CardiovascularMedicine (category); ACC; AHA; alternans; American College of Cardiology; American Heart Association; antiarrhythmic; arrhythmia; arrhythmic; averaged; beat; brugada; cardiology; cardiomyopathy; cardioverter; CHF; congestive; defibrillator; dilated; ECG; ejection fraction; electrocardiography; elevation; heart attack; heart failure; Heartwave; ICD; IDC; idiopathic; implantable; implantation; ischemia; ischemic; late; left ventricular; likelihood; LVEF; Multicenter Automatic Defibrillator Implantation Trial; MADIT; MADIT II; microvolt; MTWA; myocardial infarction; noninvasive; nonischemic; potentials; prophylactic; ratio; reproducibility; risk; SAECG; SCD; SCD HeFT; sensitivity; signal; specificity; ST; risk-stratify; stratification; stratify; stress test; sudden cardiac death; syncope; t wave; tachyarrhythmia; tachycardia; t-wave; ventricle; ventricular;
