Predictive value of microvolt T-wave alternans for sudden cardiac death in patients with preserved cardiac function after acute myocardial infarction: results of a collaborative cohort study.

OBJECTIVES: We conducted a collaborative cohort study to evaluate the predictive power of microvolt T-wave alternans (TWA) in patients with preserved left ventricular ejection fraction (LVEF) after myocardial infarction (MI). BACKGROUND: There is little information available about the prognostic value of risk stratification markers in this population. Although these patients have a relatively good prognosis, identifying high-risk patients is important in clinical practice. METHODS: This study enrolled 1,041 post-MI patients with an LVEF > or =40% (average 55 +/- 10%). Microvolt TWA testing was performed 48 +/- 66 days after acute MI, and 10 other risk variables were also evaluated. The end points were prospectively defined as sudden cardiac death or life-threatening arrhythmic events. RESULTS: During a follow-up of 32 +/- 14 months, 38 patients (3.7%) died of nonarrhythmic causes and were not considered for analysis. Of the 1,003 evaluable patients, 18 (1.8%) reached an end point. Microvolt TWA was positive in 169 patients (17%), negative in 747 (74%), and indeterminate in 87 (9%). A positive microvolt TWA test, nonsustained ventricular tachycardia, and ventricular late potentials were predictors of events, and percutaneous coronary intervention decreased the risk rate. On multivariate analysis, a positive microvolt TWA test was the most significant predictor, with a hazard ratio of 19.7 (p < 0.0001). This marker had the highest sensitivity and negative predictive value for events. CONCLUSIONS: In patients with preserved cardiac function, the incidence of indeterminate results of microvolt TWA is low, and a positive test result is associated with arrhythmic events. Microvolt TWA could be used for risk stratification in this low-risk population.     

微伏级T波电交替及窦性心律震荡对心肌梗死后患者猝死的预测价值

目的评价窦性心律震荡(HRT)和微伏级T波电交替(mTWA)对心肌梗死(简称心梗)后患者猝死的预测价值。方法入选心梗后患者212例,根据24h动态心电图记录,计算HRT的两个参数震荡初始(TO)和震荡斜率(TS),同时检测mTWA;随访2年,主要终点为心源性猝死(SCD),次要终点为全因死亡率,心血管疾病相关死亡,比较死亡组与存活组,死亡各亚组(SCD组及非SCD组)之间HRT及mTWA。结果 1死亡组中慢性肾病、心功能IV及胺碘酮使用率增多;SCD亚组左室射血分数(LVEF)下降更明显。2死亡组mTWA及HRT2明显升高。其中SCD亚组mTWAmax和HRT2异常较非SCD组明显升高。3LVEF、HRT、mTWA(06∶00AM)为最有意义的独立致死因子;LVEF、HRT、mTWA(100次/分)和室性早搏数量为SCD的危险因素。4异常TO/TS联合mTWA(100次/分)大于58.5mcV则显著增加全因死亡率[RR,32.5(95%CI 4.2~188.5),P0.001]及SCD风险[RR,60.5(95%CI 6.2~508.5),P0.001]。结论当患者HRT和mTWA异常时总死亡率及SCD风险明显增加。     

Prediction of sudden death in patients discharged after acute myocardial infarction.

A follow-up was made of 475 patients discharged after an acute myocardial infarction. Sudden death, i.e. death within 2 hours after the onset of the final attack, was more common in patients below 60 years on admission than in the older age groups. Patients succumbing suddenly often had a history of an earlier myocardial infarction. They also had a higher incidence of inferior infarcts and more frequently showed ventricular tachycardia during the early hospital period than those dying more than 24 hours after the onset of the final episode. When comparisons were made with all patients dying after more than 2 hours' duration of the terminal attack no significant differences were noted for these or other parameters. Prediction of sudden death in immediate survivors of acute myocardial infarction thus seems elusive. Further studies of the relations between the incidence of ventricular ectopic activity during the early and late hospital phase of acute myocardial infarction and sudden death after discharge from hospital are implicated.     

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.     

Prediction of sudden cardiac death after myocardial infarction in the beta-blocking era

OBJECTIVES: This study assessed the predictive power of arrhythmia risk markers after an acute myocardial infarction (AMI). BACKGROUND: Several risk variables have been suggested to predict the occurrence of sudden cardiac death (SCD), but the utility of these variables has not been well established among patients using medical therapy according to contemporary guidelines. METHODS: A consecutive series of 700 patients with AMI was studied. The end points were total mortality, SCD, and nonsudden cardiac death (non-SCD). Nonsustained ventricular tachycardia (nsVT), ejection fraction (EF), heart rate variability, baroreflex sensitivity, signal-averaged electrocardiogram (SAECG), QT dispersion, and QRS duration were analyzed (n = 675). Beta-blocking therapy was used by 97% of the patients at discharge and by 95% at one and two years after AMI. RESULTS: During a mean (+/-SD) follow-up of 43 +/- 15 months, 37 non-SCDs (5.5%) and 22 SCDs (3.2%) occurred. All arrhythmia risk variables differed between the survivors and those with non-SCD (e.g., the standard deviation of N-N intervals was 98 +/- 32 vs. 74 +/- 21 ms [p < 0.001] and the QRS duration was 103 +/- 22 vs.89 +/- 16 ms [p < 0.001]). Sudden cardiac death was weakly predicted only by reduced EF (<0.40; p < 0.05), nsVT (p < 0.05), and abnormal SAECG (p < 0.05), but not by autonomic markers or standard ECG variables. The positive predictive accuracy of EF, nsVT, and abnormal SAECG as predictors of SCD was relatively low (8%, 12%, and 13%, respectively). CONCLUSIONS: The common arrhythmia risk variables, particularly the autonomic and standard ECG markers, have limited predictive power in identifying patients at risk of SCD after AMI in the beta-blocking era.     

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.     

T-wave alternans for risk stratification and prevention of sudden cardiac death

Despite considerable progress in the management of ischemic heart disease, a substantial proportion of patients continue to experience life-threatening arrhythmic events. The Multicenter Automatic Defibrillator Implantation Trial 2 has recently shown the superiority of implantable cardioverter defibrillators (ICDs) over conventional strategies to prevent sudden death in patients with reduced ejection fraction, but at the expense of potentially unnecessary ICD implantation in a large percentage of patients. T-wave alternans (TWA), which reflects alternation of cellular repolarization, results in a substantial increase in dispersion of repolarization, a prerequisite for reentrant arrhythmias. Recent trials, cumulating close to 3000 patients, have established TWA analysis as a powerful tool for arrhythmia prevention. Based on the most recent estimates, at least one third of post-myocardial infarction patients are expected to be tested negative. With a negative predictive value greater than 90%, TWA might allow for targeting of patients most likely to benefit from ICD therapy. Accurate identification of high-risk patients by noninvasive TWA may allow for improved widespread screening for sudden death prevention in the general population.     

微伏级T波电交替对心性猝死高危人群的预测价值

目的 探讨微伏级T波电交替(MTWA)对恶性室性心律失常(MVA)及心性猝死(SCD)的预测价值,探索时域法MTWA检测的正、异常值范围.方法 连续选取2002年1月至2007年10月到昆明医学院第一附属医院就诊或健康体检者545例(男285例,女260例,平均年龄52岁),其中105例健康受检者设为对照组,既往有室性心动过速、心室颤动发作史或确诊为器质性心脏病且左室射血分数(LVEF)≤45%的138例设为SCD高危组.两组均成功检测MTWA、LVEF、心率变异性、非持续性室速、QRS、QTc等指标并完成随访,动态随访比较组间死亡及死因、MVA、再次住院、晕厥等事件的发生情况及其与MTWA等观测指标的相关性.结果 时域法MTWA检测95%的正常参考值范围为MTWA<37μV.平均(12.0±1.3)个月的随访期内,对照组无心血管事件发生;高危组死亡11例中SCD 7例(MTWA阳性率分别为81.8%、85.7%),发生MVA的17例中MTWA阳性率88.2%,发生晕厥的9例中MTWA阳性率77.8%,随访期住院的21例中MTWA阳性率85.7%.多因素回归分析预测MVA的危险因素依次为MTWA阳性、LVEF≤35%、有心肺复苏史、有晕厥史.仅MTWA阳性与SCD显著相关.MTWA阳性、LVEF≤35%分别是预测MVA的独立指标(P<0.01).MTWA与LVEF≤35%联合预测MVA的敏感性91%、特异性66%、阳性预测价值27%、阴性预测价值98%,优于二者单独使用.41例埋藏式自动复律除颤器(ICD)患者,MTWA阳性率68.3%.随访中发生MVA并被ICD自动电除颤者的MTWA阳性率87.5%.结论 (1)国人时域法MTWA正常参考值为<37μV.(2)MTWA与LVEF一样对MVA有独立预测价值且其预测SCD的价值优于LVEF,二者联合可进一步提高预测价值.(3)MTWA阳性似可成为ICD置入的初筛指标之一.(4)时域法检测MTWA具有无创、简便、高效、易重复、经济等优点,有良好的推广应用前景.     

Non-arrhythmic therapy of ventricular tachyarrhythmias and sudden cardiac death after acute myocardial infarction

The management of ventricular tachyarrhythmias and prevention of sudden cardiac death after acute myocardial infarction (AMI) underwent important evolution. In the CAST study, encanaide and other antiarrhythmic drugs were not only ineffective but also increased mortality after myocardial infarction. Amiodarone had some beneficial effect on arrhythmic events without improving survival, and ICDs failed to improve outcome early after AMI. In comparison, short and long term survival benefits of beta blockers, angiotensine converting enzyme inhibitors and aldosterone antagonists after AMI is well established. This review discusses the role of non-arrhythmic therapy in the prevention of ventricular tachyarrhythmia's and sudden cardiac death after AMI.     

KCNJ11 polymorphisms and sudden cardiac death in patients with acute myocardial infarction

PURPOSE: Patients with an acute myocardial infarction (AMI) are of high risk to develop ischemia-induced ventricular arrhythmias, leading to sudden cardiac death (SCD) in about one third of all AMI patients. The individual susceptibility to ischemia-induced arrhythmias may be modified by polymorphisms in genes encoding ion channels. The cardiac ATP-dependent potassium channel (K(ATP)) current is generated by ion channels encoded by the KCNJ11 gene and the SUR2a gene. Opening of the K(ATP) channel during ischemia results in action potential shortening in various studies and may therefore influence the outcome of AMI patients. METHODS: Using a three-primer strategy, we sequenced the complete coding and adjacent 5' and 3' sequences of the intronless KCNJ11 gene (1.3 kb) prospectively in two groups. Patients of group 1 (n = 84) survived three or more transmyocardial infarctions without developing any ventricular arrhythmias. Patients of group 2 died suddenly from their first myocardial infarction (n = 86), most of them witnessed SCDs. RESULTS: We identified a total of six known polymorphisms (K23E, A190A, L267V, L270V, I337V, and K281K) and two new polymorphisms (L267L, 3'UTR +62 G/A). The allele, genotype, and haplotype frequencies did not differ between the two groups. All polymorphisms were found to be in Hardy-Weinberg equilibrium. In addition, we identified two novel missense mutations in a highly conserved region of the gene in two patients of group 2 (P266T and R371H) with yet unknown functional consequences. CONCLUSION: In this study of AMI patients, SCD was not related to polymorphisms in the KCNJ11 gene.     

T-wave alternans: marker,mechanism, and methodology for predicting sudden cardiac death

Sudden cardiac death (SCD) is a leading cause of cardiovascular mortality. Therefore, identifying patients at highest risk for SCD is crucial. Conventional noninvasive markers of SCD are inadequate because of low positive predictive value. The presence of visible T-wave alternans (TWA) on electrocardiogram often predicts the occurrence of lethal ventricular arrhythmias. Signal processing methods have made it possible to detect microvolt-level and visually inapparent TWA on electrocardiogram. TWA is caused by underlying regional inhomogeneities of ventricular repolarization, which predispose patients to have ventricular arrhythmias. Microvolt TWA provoked either by atrial pacing, pharmacological stress, or exercise is a promising marker of arrhythmia vulnerability. Several large trials have shown TWA to be comparable or superior to other noninvasive markers and electrophysiologic study in the prediction of SCD. The patient populations in these trials include post myocardial infarction, both ischemic and nonischemic heart failure, and suspected arrhythmias. Prospective trials regarding benefits of implantation of cardioverter-defibrillator therapy based on TWA results are ongoing.     

Prediction of sudden cardiac death after acute myocardial infarction: role of Holter monitoring in the modern treatment era.

AIMS: Current treatment may have changed the risk profiles of survivors of acute myocardial infarction (AMI). We evaluated the utility of Holter-based risk variables in the prediction of sudden cardiac death (SCD) among survivors of AMI treated with modern therapy. METHODS AND RESULTS: A total of 2130 AMI patients (mean age 59 +/- 10 years) were included. The patients were treated with modern therapeutic strategies, for example, 94% were on beta-blocking therapy and 70% underwent coronary revascularization. Various risk parameters from Holter monitoring were analysed. During a median follow-up of 1012 days (interquartile range: 750-1416 days), cardiac mortality was 113/2130, including 52 SCDs. All Holter variables predicted the occurrence of SCD (P<0.01), but only reduced post-ectopic turbulence slope (TS) (P<0.001) and non-sustained ventricular tachycardia (P<0.01) remained as marked SCD predictors after adjustment for age, diabetes, and ejection fraction (EF). In a subgroup analysis, none of the Holter variables predicted SCD among those with an EF < or = 0.35, but many variables predicted SCD among those with an EF >0.35, particularly TS (hazard ratio 5.9; 95% CI 2.9-11.7, P<0.001). CONCLUSION: Among the post-AMI patients treated according to the current guidelines, the incidence of SCD is low. Various Holter variables still predict the occurrence of SCD, particularly among the patients with preserved left ventricular function.     

Seasonal variation in sudden cardiac death after experimental myocardial infarction

The authors studied the incidence of sudden death by monitoring the ECG after ligation of the left anterior descending coronary artery in 184 dogs. A significant number of sudden deaths (46 dogs) occurred in the cold weather months, November-February (42%), compared to the summer months, July and August (6%). All deaths resulted from ventricular tachyarrhythmias (greater than or equal to 300/min) and occurred between 13 and 22 hours after coronary artery ligation. The survivors (138 dogs) were subjected to electrophysiological study, during which a significantly higher number showed induced sustained monomorphic ventricular tachycardia (VT) (heart rate greater than or equal to 300/min) during the winter months than during the summer months. Heart weight and infarct mass were not significantly different throughout the year. Higher sympathetic tone or catecholamine levels may account for the seasonal variation in sudden death during evolving myocardial infarction.     

Ambulatory ECG-based T-wave alternans predicts sudden cardiac death in high-risk post-MI patients with left ventricular dysfunction in the EPHESUS study

Background: Exercise microvolt T‐wave alternans (TWA) identifies sudden cardiac death (SCD) risk. TWA can be measured from ambulatory ECGs (AECGs) using modified moving average (MMA) method. Whether MMA TWA from AECGs predicts SCD in post‐MI patients with left ventricular dysfunction (LVD) is unknown. Methods: EPHESUS enrolled hospitalized post‐MI patients with heart failure and/or diabetes with LVD. Before randomization to drug treatment, AECGs were obtained in 493 patients. Of them, 46 died of cardiovascular causes, including 18 of SCD. Patients alive at end of follow‐up (N = 92) were matched with 46 nonsurvivors based on age, gender, and diabetes. MMA TWA was analyzed using MARSPC system (GE Healthcare, Milwaukee, WI, USA). The three highest TWA values from artifact‐free periods were averaged for AECG channels corresponding to leads V₁ and V₃. SCD prediction was tested with a prespecified 47 μV cutpoint and at a cutpoint maximizing the separation between SCD patients versus survivors or non‐SCD. Results: TWA in either lead was higher for patients with SCD (P ≤ 0.05) versus survivors or non‐SCD. TWA ≥ 47 μV was associated with RR = 5.2 (95%CI = 1.8–13.6, P = 0.002) in V₁ and RR = 5.5 (95% CI = 2.2–13.8, P < 0.001) in V₃ for SCD. The optimal cutpoint for TWA in V₁ was ≥43 μV (RR = 5.9 [95%CI = 2.2–15.8, P < 0.001]). The optimal cutpoint in V₃ was ≥47 μV. TWA greater than the optimal cutpoint in either lead was associated with RR = 7.1 (95%CI = 2.7–18.3, P < 0.001) for SCD, with 11 out of 18 patients dying of SCD. Conclusions: AECG‐based TWA measured with MMA is a powerful predictor of SCD in high‐risk post‐MI patients with LV dysfunction.     

Psychosocial and physiological predictors of sudden cardiac death after healing of acute myocardial infarction

Several major prospective studies that have examined the relation between type A behavior and cardiac mortality have failed to find an association. Since psychosocial factors have been implicated in the etiology of sudden cardiac death, it is possible that this association may emerge if sudden cardiac death is distinguished as an outcome distinct from other cardiac mortality. Predictors of sudden death and other cardiac outcomes were examined using data from the Recurrent Coronary Prevention Project, a 4.5-year prospective clinical trial of 1,012 postinfarction patients begun in San Francisco in 1978. A unique set of risk factors was found for the differing outcomes: sudden cardiac death had predominantly psychosocial predictors while nonsudden cardiac death and nonfatal recurrences were predominantly predicted by biologic factors. Type A behavior was an independent predictor of sudden, but not nonsudden, cardiac death in this population (p = 0.04). These results are the first demonstration of a direct relation between stress and sudden cardiac death in a large prospective clinical study, and provide insight into the failure of past prospective studies to find an association between type A behavior and cardiac mortality.