Risk stratification for sudden cardiac death in dilated cardiomyopathy using microvolt-level T-wave alternans

Predicting sudden cardiac death (SCD) in patients with dilated cardiomyopathy (DCM) is difficult, so the present study evaluated the efficacy of microvolt-level T-wave alternans (TWA) and compared it with conventional parameters for prospective risk stratification of SCD in patients with DCM. Eighty-two patients with DCM (53+/-15 years old, 67M/15F) underwent assessment of TWA, left ventricular end-diastolic diameter (LVDd), left ventricular ejection fraction (LVEF), signal-averaged ECG, and analysis of 24-h Holter monitoring and QT dispersion (QTd). The endpoint of the study was defined as either SCD or documented sustained ventricular tachycardia/ventricular fibrillation (SVT/VF) during the follow-up period. During an average follow-up period of 24 months, 1 patient died suddenly and 9 patients had SVT/VF. Kaplan-Meier survival analysis showed that TWA, LVEF (< or =35%), nonsustained ventricular tachycardia, and QTd (>90ms) were significant univariate risk stratifiers (p<0.005, p<0.005, p<0.005, and p<0.05, respectively). Multivariate Cox regression analysis showed that TWA and the LVEF were statistically significant independent risk stratifiers (p<0.05 and p<0.01, respectively). A combination of TWA and LVEF identified high risk DCM patients (p<0.01); TWA for the electrical substrate and the LVEF for the hemodynamic function.     

Onset heart rate of microvolt-level T-wave alternans provides clinical and prognostic value in nonischemic dilated cardiomyopathy.

OBJECTIVES: This study was designed to determine the prognostic value of onset heart rate (OHR) in T-wave alternans (TWA) in patients with nonischemic dilated cardiomyopathy (DCM). BACKGROUND: One of the current major issues in DCM is to prevent sudden cardiac death (SCD). However, the value of the OHR of TWA as a prognostic indicator in DCM remains to be elucidated. METHODS: We prospectively investigated 104 patients with DCM undergoing TWA testing. The end point of this study was defined as SCD, documented sustained ventricular tachycardia/ventricular fibrillation. Relations between clinical parameters and subsequent outcome were evaluated. RESULTS: Forty-six patients presenting with TWA were assigned to one of the following two subgroups according to OHR for TWA of < or = 100 beats/min: group A (n = 24) with OHR < or = 100 beats/min and group B (n = 22) with 100 < OHR < or = 110 beats/min. T-wave alternans was negative in 37 patients (group C) and indeterminate in 21 patients. The follow-up result comprised 83 patients with determined TWA. During a follow-up duration of 21 +/- 14 months, there was a total of 12 arrhythmic events, nine of which included three SCDs in group A, two in group B and one in group C. The forward stepwise multivariate Cox hazard analysis revealed that TWA with an OHR < or = 100 beats/min and left ventricular ejection fraction were independent predictors of these arrhythmic events (p = 0.0001 and p = 0.0152, respectively). CONCLUSIONS: The OHR of TWA is of additional prognostic value in DCM.     

扩张型心肌病患者微伏级T波电交替检测分析

目的研究扩张型心肌病患者微伏级T波电交替(MTWA)的发生情况及与心率的关系。方法对31例扩张型心肌病患者用频谱法检测MTWA,分析扩张型心肌病MTWA的阳性率及不确定结果的原因,静息和运动时MTWA的发生情况,心率与交替压(Valt)的关系。结果①扩张型心肌病患者MTWA的阳性率为35.48%;②扩张型心肌病者,运动时的心率大于静息时,运动时各导联的Valt值大于静息时(P均<0.01)。静息时MTWA阳性2例,运动时MTWA阳性11例,运动时MTWA的阳性率高于静息时(35.48%vs 6.45%,P<0.01);③心率与综合导联Valt呈正相关,随心率的增加,Valt增大(r=0.984,P<0.01)。结论①扩张型心肌病患者MTWA阳性率高于正常人;②MTWA的发生与心率相关,随心率增快,Valt增大,MTWA阳性检出率增加。     

Relation between microvolt-level T-wave alternans and cardiac sympathetic nervous system abnormality using iodine-123 metaiodobenzylguanidine imaging in patients with idiopathic dilated cardiomyopathy

We examined the relation between microvolt-level T-wave alternans and cardiac sympathetic nervous system abnormality using iodine-123 metaiodobenzylguanidine imaging in patients with idiopathic dilated cardiomyopathy. Our results strongly indicate that cardiac sympathetic denervation and accelerated sympathetic nervous activity play important roles in the presence of microvolt-level T-wave alternans in patients with idiopathic-dilated cardiomyopathy.     

Clinical significance of T-wave alternans in hypertrophic cardiomyopathy.

The clinical significance of T-wave alternans (TWA) in hypertrophic cardiomyopathy (HCM) is unclear, so SV1+RV5 and QT dispersion on 12-lead electrocardiograms (ECG), the parameters of the left ventricle on echocardiography and the family history of HCM and sudden death were investigated in 53 patients with HCM who experienced TWA. The maximal numbers of successive ventricular ectopic beats (max VE) and nonsustained ventricular tachycardia (NSVT) were measured by Holter monitoring. In 13 patients, genetic abnormalities were examined. In 22 patients, the hypertrophy of myocytes, disarray and fibrosis were histopathologically examined using a scoring method. TWA was positive in 27 patients (TWA+ group), negative in 14 (TWA- group) and indeterminate in 12. The ECG and echocardiographic parameters, family history and genetic abnormalities did not significantly differ between the TWA+ and TWA- groups. Max VE, the percentage of patients with NSVT and disarray score in the TWA+ group were significantly higher than those in the TWA- group (3.6+/-3.6 vs 1.3+/-0.7, 37% vs 0%, 1.9+/-1.1 vs 0.7+/-0.5; p<0.05). TWA in HCM correlates with histopathological changes, especially disarray and ventricular tachyarrhythmia, and measuring it may be a noninvasive means of detecting high-risk patients with HCM.     

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.     

Exercise-induced quantitative microvolt T-wave alternans in hypertrophic cardiomyopathy

Background/Purpose

Patients with hypertrophic cardiomyopathy (HCM) have elevated risk for sudden cardiac death (SCD). Our study aimed to quantitatively characterize microvolt T-wave alternans (TWA), a potential arrhythmia risk stratification tool, in this HCM patient population.

T-wave alternans associated with heart failure and hypomagnesemia in alcoholic cardiomyopathy.

Marked T wave abnormality developed in a patient with alcoholic cardiomyopathy. The T negativity was of giant size and occurred in an alternating sequence in the presence of sinus rhythm. This change was rapidly transient, disappearing in 3 days. The complete electrocardiographic recovery was temporally related to successful treatment of severe heart failure, normalization of initially low serum magnesium level, and abolition of recurrent ventricular fibrillation.     

Utility of microvolt T-wave alternans to predict sudden cardiac death in patients with cardiomyopathy

PURPOSE OF REVIEW: Sudden cardiac death remains a major cause of mortality among patients with cardiomyopathy and implantable cardioverter-defibrillator therapy has been shown to improve survival in these patients. Effective use of prophylactic implantable cardioverter-defibrillator therapy requires accurate risk stratification beyond assessment of ejection fraction, however. Repolarization alternans is a harbinger of ventricular arrhythmias and its measurement from body-surface recordings, also known as microvolt T-wave alternans, is emerging as an effective prognostic tool in these patients based on recent clinical trials. RECENT FINDINGS: We review the pathogenesis and determinants of repolarization alternans. The current techniques for measuring T-wave alternans from the body surface are compared, including the spectral and modified moving average methods. Recent clinical trials evaluating the prognostic utility of T-wave alternans in patients with ischemic and nonischemic cardiomyopathy and no prior arrhythmic events are summarized. The findings of these studies are discussed in the context of implantable cardioverter-defibrillator prophylaxis. Body-surface T-wave alternans is an evolving technique and its limitations are presented along with approaches to improve its predictive accuracy. SUMMARY: Risk stratification with T-wave alternans has the potential to guide prophylactic implantable cardioverter-defibrillator therapy in a growing population of patients with cardiomyopathy.     

Relationship between the QT indices and the microvolt-level T wave alternans in cardiomyopathy.

The relationship between the QT indices and microvolt-level T wave alternans (TWA) is unknown in cardiomyopathy, so the present study examined 86 patients with cardiomyopathy who experienced TWA during exercise testing (EXT). The QT interval (QT), duration from the Q wave to the peak of the T wave (QTp), duration from the peak to the end of the T wave and the dispersion of these parameters were measured by 12-lead electrocardiogram at rest and during EXT. In dilated cardiomyopathy (DCM), TWA was positive (TWA+) in 19 patients and negative (TWA-) in 17. No significant difference was observed between the TWA+ and TWA- groups in any parameter. In hypertrophic cardiomyopathy (HCM), TWA was positive in 24 patients and negative in 12. Max QTc, max QTpc and mean QTpc during EXT in the TWA+ group were significantly longer than those in the TWA- group. The sensitivity of TWA for ventricular tachycardia (VT) was high in DCM and HCM, and that of max QTc >500 ms during EXT for VT was high in HCM (93%). TWA is a useful predictor for VT in DCM and HCM, and prolonged max QTc during exercise has a prognostic value in HCM. Repolarization abnormality during exercise plays an important role in the genesis of VT in cardiomyopathy.     

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.     

Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study

OBJECTIVES: This study was designed to evaluate the ability of microvolt-level T-wave alternans (MTWA) to identify prospectively patients with idiopathic dilated cardiomyopathy (DCM) at risk of ventricular tachyarrhythmic events and to compare its predictive accuracy with that of conventional risk stratifiers. BACKGROUND: Patients with DCM are at increased risk of sudden death from ventricular tachyarrhythmias. At present, there are no established methods of assessing this risk. METHODS: A total of 137 patients with DCM underwent risk stratification through assessment of MTWA, left ventricular ejection fraction, baroreflex sensitivity (BRS), heart rate variability, presence of nonsustained ventricular tachycardia (VT), signal-averaged electrocardiogram, and presence of intraventricular conduction defect. The study end point was either sudden death, resuscitated ventricular fibrillation, or documented hemodynamically unstable VT. RESULTS: During an average follow-up of 14 +/- 6 months, MTWA and BRS were significant univariate predictors of ventricular tachyarrhythmic events (p < 0.035 and p < 0.015, respectively). Multivariate Cox regression analysis revealed that only MTWA was a significant predictor. CONCLUSIONS: Microvolt-level T-wave alternans is a powerful independent predictor of ventricular tachyarrhythmic events in patients with DCM.     

T-wave alternans in patients with right ventricular tachycardia

Microvolt T-wave alternans has been proposed as a new risk marker for ventricular arrhythmias. However, the clinical significance of T-wave alternans in patients with ventricular tachycardia (VT) originating from the right ventricle has been unknown. The study population consisted of 20 patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) or idiopathic VT. T-wave alternans was measured during bicycle exercise testing using the CH 2000 system. Of the 7 patients with ARVC, 6 (86%) were positive for T-wave alternans. On the other hand, only 1 (8%) of 13 patients with idiopathic VT originating from the right-ventricular outflow tract was positive for T-wave alternans.     

Comparison of T-wave alternans and QT interval dispersion to predict ventricular tachyarrhythmia in patients with dilated cardiomyopathy and without antiarrhythmic drugs: a prospective study.

Microvolt T-wave alternans (TWA) and QT interval dispersion (QTD), which reflect temporal and spatial repolarization abnormalities, respectively, have been proposed as useful indices to identify patients at risk for ventricular tachyarrhythmias (VTs). The purpose of this study was to clarify which repolarization abnormality marker is more useful in predicting arrhythmic events in patients with dilated cardiomyopathy (DCM). Forty-two consecutive nonischemic DCM patients underwent the assessment of TWA and QTD. Patients undergoing antiarrhythmic pharmacotherapy, except beta-blockers and those with irregular basic rhythms, were excluded from entry. Eight patients were also excluded because of indeterminate test results. Therefore, 34 DCM patients were prospectively assessed. The end point of the study was the documentation of VT defined as > or = 5 consecutive ectopic beats during the follow-up period. TWA and QTD (> or = 65 msec) were positive in 24 (80%) and 11 (37%) of 30 patients with available follow-up data, respectively. There was no relationship between TWA and QTD. During a follow-up of 13+/-11 months, VTs occurred in 13 patients (43%). In Cox regression analysis, TWA was a significant risk stratifier (p=0.02), whereas QTD was not. The sensitivity, specificity, and positive and negative predictive values of TWA in predicting VTs were 100%, 35%, 54%, and 100%, respectively. TWA could be a useful noninvasive index to identify patients at risk for VTs in the setting of DCM. This study may suggest that temporal repolarization abnormality is associated more with arrhythmogenesis than with spatial repolarization abnormality in DCM patients.     

Usefulness of microvolt T-wave alternans to predict outcomes in patients with ischemic cardiomyopathy beyond one year

Previous studies have demonstrated that microvolt T-wave alternans (MTWA) screening effectively risk-stratifies patients with ischemic cardiomyopathy. Whether the prognostic utility of MTWA diminishes over 3 years of follow-up remains unknown. In this study, a prospective cohort of 768 patients with ischemic cardiomyopathy (left ventricular ejection fraction <35%) and no previous sustained ventricular arrhythmia was developed, of whom 514 (67%) screened MTWA nonnegative (positive and indeterminate). The mean follow-up period was 18 +/- 11 months. The primary end point was all-cause mortality and appropriate implantable cardioverter-defibrillator shocks. Stratified Cox regression analyses (by implantable cardioverter-defibrillator status) estimated the predictive power of MTWA within each year of follow-up and determined whether this diminished over time. There were 99 deaths (MTWA negative: 21 [8.3%]; MTWA nonnegative: 78 [15.2%]) and 33 appropriate implantable cardioverter-defibrillator shocks (MTWA negative: 3 [4.0%]; MTWA nonnegative: 30 [9.5%]). After multivariate adjustment, a nonnegative MTWA test result was associated with a greater than twofold increased risk for events in each of the 3 years of follow-up (year 1: stratified hazard ratio 2.19, 95% confidence interval 1.10 to 4.34, p = 0.03; year 2: stratified hazard ratio 3.36, 95% confidence interval 1.28 to 8.83, p = 0.01; year 3: stratified hazard ratio 2.06, 95% confidence interval 0.81 to 5.22, p = 0.13). There were no significant interactions between the time periods (year 1 vs year 2: p = 0.47; year 1 vs year 3: p = 0.92). In conclusion, MTWA reliably and consistently predicts mortality and arrhythmic risk throughout the first 2 to 3 years of follow-up. Although these findings need further validation, they suggest that rescreening with MTWA may not need to be performed more frequently than once every 2 years.     

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.