Microvolt T-Wave Alternans and Risk of VT Events
Microvolt T-Wave Alternans and Risk of VT Events
Background: Prior studies have indicated that the magnitude of risk association of microvolt T-wave alternans (MTWA) testing appears to vary with the population studied. We performed a meta-analysis to determine the ability of MTWA to modify risk assessment of ventricular tachyarrhythmic events (VTEs) and sudden cardiac death (SCD) across a series of patient risk profiles using likelihood ratio (LR) testing, a measure of test performance independent of disease prevalence.
Methods: We identified original research articles published from January 1990 to January 2011 that investigate spectrally derived MTWA. Ventricular tachyarrhythmic event was defined as the total and arrhythmic mortality and nonfatal sustained or implantable cardioverter-defibrillator–treated ventricular tachyarrhythmias. Summary estimates were created for positive and nonnegative MTWA results using a random-effects model and were expressed as positive (LR+) and negative (LR−) LRs.
Results: Of 1,534 articles, 20 prospective cohort studies met our inclusion criteria, consisting of 5,945 subjects predominantly with prior myocardial infarction or left ventricular dysfunction. Although there was a modest association between positive MTWA and VTE (relative risk 2.45, 1.58–3.79) and nonnegative MTWA and VTE (3.68, 2.23–6.07), test performance was poor (positive MTWA: LR+ 1.78, LR− 0.43; nonnegative MTWA: LR+ 1.38, LR− 0.56). Subgroup analyses of subjects classified as prior VTE, post–myocardial infarction, SCD-HeFT type, and MADIT-II type had a similar poor test performance. A negative MTWA result would decrease the annualized risk of VTE from 8.85% to 6.37% in MADIT-II–type patients and from 5.91% to 2.60% in SCD-HeFT–type patients.
Conclusions: Despite a modest association, results of spectrally derived MTWA testing do not sufficiently modify the risk of VTE to change clinical decisions.
Depressed left ventricular ejection fraction (LVEF) remains the most widely used criterion for identifying patients at high risk for sudden cardiac death (SCD) and for selecting candidates for prophylactic implantable cardioverter-defibrillators (ICDs). However, EF has a poor negative and positive predictive value for SCD, with only 21% to 24% of patients with reduced EF receiving appropriate ICD therapies in randomized trials.
Microvolt T-wave alternans (MTWA) testing is a noninvasive test that characterizes small beat-to-beat fluctuations in T-wave morphology, amplitude, or timing. These changes may reflect temporal and spatial dispersions of ventricular repolarization, which are hypothesized mechanisms that precede ventricular tachyarrhythmias. Prior studies have shown that an abnormal spectrally derived MTWA result is modestly associated with ventricular tachyarrhythmic events (VTEs) and that a normal result has a high negative predictive value. Although risk ratios and predictive values are useful in characterizing the magnitude of association, they are highly dependent on disease prevalence. Therefore, they do not appropriately describe a test's ability to modify the risk of disease when the pretest or baseline risk is more clearly defined, such as in patients who meet the criteria for prophylactic defibrillator implantation based on the MADIT-II or SCD-HeFT trials. We therefore performed a meta-analysis to evaluate the likelihood ratio (LR)–based test performance of MTWA based on its ability to modify risk assessment of VTE across a range of patient risk profiles.
Abstract and Introduction
Abstract
Background: Prior studies have indicated that the magnitude of risk association of microvolt T-wave alternans (MTWA) testing appears to vary with the population studied. We performed a meta-analysis to determine the ability of MTWA to modify risk assessment of ventricular tachyarrhythmic events (VTEs) and sudden cardiac death (SCD) across a series of patient risk profiles using likelihood ratio (LR) testing, a measure of test performance independent of disease prevalence.
Methods: We identified original research articles published from January 1990 to January 2011 that investigate spectrally derived MTWA. Ventricular tachyarrhythmic event was defined as the total and arrhythmic mortality and nonfatal sustained or implantable cardioverter-defibrillator–treated ventricular tachyarrhythmias. Summary estimates were created for positive and nonnegative MTWA results using a random-effects model and were expressed as positive (LR+) and negative (LR−) LRs.
Results: Of 1,534 articles, 20 prospective cohort studies met our inclusion criteria, consisting of 5,945 subjects predominantly with prior myocardial infarction or left ventricular dysfunction. Although there was a modest association between positive MTWA and VTE (relative risk 2.45, 1.58–3.79) and nonnegative MTWA and VTE (3.68, 2.23–6.07), test performance was poor (positive MTWA: LR+ 1.78, LR− 0.43; nonnegative MTWA: LR+ 1.38, LR− 0.56). Subgroup analyses of subjects classified as prior VTE, post–myocardial infarction, SCD-HeFT type, and MADIT-II type had a similar poor test performance. A negative MTWA result would decrease the annualized risk of VTE from 8.85% to 6.37% in MADIT-II–type patients and from 5.91% to 2.60% in SCD-HeFT–type patients.
Conclusions: Despite a modest association, results of spectrally derived MTWA testing do not sufficiently modify the risk of VTE to change clinical decisions.
Introduction
Depressed left ventricular ejection fraction (LVEF) remains the most widely used criterion for identifying patients at high risk for sudden cardiac death (SCD) and for selecting candidates for prophylactic implantable cardioverter-defibrillators (ICDs). However, EF has a poor negative and positive predictive value for SCD, with only 21% to 24% of patients with reduced EF receiving appropriate ICD therapies in randomized trials.
Microvolt T-wave alternans (MTWA) testing is a noninvasive test that characterizes small beat-to-beat fluctuations in T-wave morphology, amplitude, or timing. These changes may reflect temporal and spatial dispersions of ventricular repolarization, which are hypothesized mechanisms that precede ventricular tachyarrhythmias. Prior studies have shown that an abnormal spectrally derived MTWA result is modestly associated with ventricular tachyarrhythmic events (VTEs) and that a normal result has a high negative predictive value. Although risk ratios and predictive values are useful in characterizing the magnitude of association, they are highly dependent on disease prevalence. Therefore, they do not appropriately describe a test's ability to modify the risk of disease when the pretest or baseline risk is more clearly defined, such as in patients who meet the criteria for prophylactic defibrillator implantation based on the MADIT-II or SCD-HeFT trials. We therefore performed a meta-analysis to evaluate the likelihood ratio (LR)–based test performance of MTWA based on its ability to modify risk assessment of VTE across a range of patient risk profiles.
