Usefulness of microvolt T-wave alternans on predicting outcome in patients with ischemic cardiomyopathy with and without defibrillators.

Microvolt T-wave alternans (MTWA) was proposed as an effective tool to identify high-risk patients with ischemic cardiomyopathy. However, previous studies suggested that the prognostic utility of MTWA may be limited to only patients with normal QRS duration. It therefore was assessed whether MTWA and QRS duration >120 ms independently predict mortality in patients with ischemic cardiomyopathy and whether the prognostic utility of MTWA differs by QRS duration. A total of 768 consecutive patients with ischemic cardiomyopathy (left ventricular ejection fraction < or =35%) and no history of ventricular arrhythmia were enrolled, of whom 514 (67%) screened MTWA non-negative (positive or indeterminate) and 223 (29%) had a QRS >120 ms on resting electrocardiogram. After multivariable adjustment, a non-negative MTWA test result was associated with a significantly higher risk for all-cause mortality in patients without an implantable cardioverter-defibrillator (ICD) (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.22 to 4.24, p = 0.01) and for all-cause mortality and appropriate ICD shocks in patients with an ICD (HR 2.42, 95% CI 1.07 to 5.41, p = 0.04). In contrast, a QRS >120 ms was not associated with all-cause mortality and ICD shocks in patients without (HR 0.96, 95% CI 0.52 to 1.75, p = 0.88) or with an ICD (HR 1.25, 95% CI 0.76 to 2.08, p = 0.40). No significant interaction was found between MTWA and QRS >120 ms (non-ICD p = 0.19, ICD p = 0.73). In conclusion, MTWA, but not QRS duration, predicted mortality outcomes in patients with ischemic cardiomyopathy. Moreover, the prognostic utility of MTWA did not appear to differ by QRS duration.

Prognostic implication of redefining indeterminate microvolt T-wave alternans studies as abnormal or normal.

BACKGROUND: Prior studies involving microvolt T-wave alternans (MTWA) have combined positive and indeterminate studies into a high-risk "nonnegative" category. However, studies examining the prognostic utility of specific reasons for an indeterminate study are limited. The objective of this study was to assess if patients have differences in survival prognosis based on the reasons for an indeterminate MTWA result. METHODS: We enrolled 768 consecutive patients with ischemic cardiomyopathy (left ventricular ejection fraction < or = 35%) and no prior history of sustained ventricular arrhythmia. Microvolt T-wave alternans studies were classified as positive, negative, or indeterminate. Prespecified multivariable Cox regression analyses, stratified by implantable cardioverter/defibrillator status, were used to determine whether there was heterogeneity in survival prognosis among the individual reasons for an indeterminate study. RESULTS: We identified 159 (21%) patients with an indeterminate MTWA test. Reasons for indeterminate studies included frequent ectopy (46%), inability to reach adequate heart rate (IHR) (32%), unsustained alternans (9%), and excessive noise (13%). After multivariable adjustment, indeterminate studies due to ectopy/IHR were associated with a significantly higher risk for all-cause (stratified hazard ratio [HR] 4.63, 95% CI 1.32-16.18, P = .02) and arrhythmic mortality (stratified HR 17.57, 95% CI 1.62-190.50, P = .02) but not for nonarrhythmic mortality (stratified HR 1.30, 95% CI 0.27-6.29, P = .75). The prognostic utility of MTWA testing was improved when indeterminate studies were reclassified as abnormal (positive + ectopy/IHR) or normal (negative + unsustained alternans), with only 3% of all studies thereafter remaining inconclusive (noise). CONCLUSION: Patients with indeterminate MTWA studies exhibit heterogeneity in survival prognosis. Reclassifying indeterminate studies as abnormal or normal improves the predictive power of MTWA.

Microvolt T-wave alternans identifies patients with ischemic cardiomyopathy who benefit from implantable cardioverter-defibrillator therapy.

OBJECTIVES: This study sought to assess whether implantable cardioverter-defibrillators (ICDs) have different mortality benefits among patients with ischemic cardiomyopathy who screen negative and non-negative (positive and indeterminate) for microvolt T-wave alternans (MTWA). BACKGROUND: Microvolt T-wave alternans has been proposed as an effective tool for risk stratification. However, no studies have examined whether ICD benefits differ by MTWA group. METHODS: We developed a prospective cohort of 768 patients with ischemic cardiomyopathy (left ventricular ejection fraction < or =35%) and no prior sustained ventricular arrhythmia, of which 392 (51%) received ICDs. The mean follow-up time was 27 +/- 12 months. Propensity scores for ICD implantation based on the variables most likely to influence defibrillator implantation were developed for each MTWA cohort. Multivariable Cox analyses that controlled for propensity score, demographics, and clinical variables evaluated the degree to which ICDs decreased mortality risk for each MTWA group. RESULTS: We identified 514 (67%) patients with a non-negative MTWA test result. After multivariable adjustment, ICDs were associated with lower all-cause mortality in MTWA-non-negative patients (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.27 to 0.76, p = 0.003) but not in MTWA-negative patients (HR 0.85, 95% CI 0.33 to 2.20, p = 0.73) (for interaction, p = 0.04), with the mortality benefit in MTWA-non-negative patients largely mediated through arrhythmic mortality reduction (HR 0.30, 95% CI 0.13 to 0.68, p = 0.004). The number needed to treat with an ICD for 2 years to save 1 life was 9 among MTWA-non-negative patients and 76 among MTWA-negative patients. CONCLUSIONS: In patients with ischemic cardiomyopathy and no prior history of ventricular arrhythmia, mortality reduction with ICD implantation differs by MTWA status, with implications for risk stratification and health policy.

Prognostic utility of microvolt T-wave alternans in risk stratification of patients with ischemic cardiomyopathy.

OBJECTIVES: The purpose of this study was to assess if microvolt T-wave alternans (MTWA) is an independent predictor of mortality in patients with ischemic cardiomyopathy. BACKGROUND: Microvolt T-wave alternans has been proposed as an effective tool for identifying high-risk patients with ischemic cardiomyopathy who are likely to benefit from implantable cardioverter-defibrillator (ICD) therapy. However, earlier studies have been limited in their ability to control for baseline differences between MTWA-negative and -non-negative (positive and indeterminate) patients. METHODS: We enrolled 768 consecutive patients with ischemic cardiomyopathy (left ventricular ejection fraction < or =35%) and no prior history of ventricular arrhythmia. All patients underwent baseline MTWA testing and were classified as MTWA negative or non-negative. Multivariable Cox regression analyses, stratified by ICD status, were used to determine the association between MTWA testing and mortality after adjusting for demographic, clinical, and treatment differences between MTWA-negative and -non-negative patients. RESULTS: We identified 514 (67%) patients with a non-negative MTWA test. After multivariable adjustment, a non-negative MTWA test was associated with a significantly higher risk for all-cause (stratified hazard ratio [HR] = 2.24 [95% confidence interval 1.34 to 3.75]; p = 0.002) and arrhythmic mortality (stratified HR = 2.29 [1.00 to 5.24]; p = 0.049) but not for nonarrhythmic mortality (stratified HR = 1.77 [0.84 to 3.74]; p = 0.13). In subgroup analyses, a non-negative MTWA test was also associated with a higher risk for all-cause mortality in patients with ejection fractions < or =30% (stratified HR = 2.10 [1.18 to 3.73]; p = 0.01) and after excluding those with indeterminate MTWA tests (stratified HR = 2.08 [1.18 to 3.66]; p = 0.01). CONCLUSIONS: Microvolt T-wave alternans is a strong and independent predictor of all-cause and arrhythmic mortality in patients with ischemic cardiomyopathy.