Predictive value of microvolt T-wave alternans for cardiac death or ventricular tachyarrhythmic events in ischemic and nonischemic cardiomyopathy patients: a meta-analysis

Background: Microvolt T‐wave alternans (MTWA) has been proposed as a predictor of the risk of ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Aim of this study was to perform a systematic review of the literature and a meta‐analysis of MTWA in primary prevention patients with ischemic and nonischemic cardiomyopathy. Methods: The positive predictive value (PPV), negative predictive value (NPV), and relative risk (RR) of MTWA in predicting death, cardiac death, and SCD during follow‐up were reported. Results: Fifteen studies involving 5681 patients (mean age 62 years, mean ejection fraction 32%) were included. The summary PPV during the average 26‐month follow‐up was 14% (95% CI: 13–15); NPV was 95% (95% CI: 94–96), and the univariate RR was 2.35 (95% CI: 1.68–3.28). The predictive value of MTWA was similar in patients with ischemic and nonischemic cardiomyopathy. The average RR for SCD or VT events of an abnormal MTWA was 2.40, similar to that for cardiac death. When we grouped the studies together depending upon whether beta‐blockers were withheld prior to MTWA screening, the beta‐blockers group showed an RR of 5.88. By contrast, the group in which beta‐blocker therapy was withheld had an RR of 1.63. Conclusion: A positive MTWA determined an approximately 2.5‐fold higher risk of cardiac death and life‐threatening arrhythmia and showed a very high NPV both in ischemic and nonischemic patients. An abnormal MTWA test was associated with a 5‐fold increased risk for cardiac mortality in the low‐indeterminate group and about a 6‐fold increased risk in beta‐blockers group. Ann Noninvasive Electrocardiol 2011;16(4):388–402     

Association of heart rate variability with arrhythmic events in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is associated with an increased risk of sudden cardiac death (SCD). Risk stratification of ARVC/D patients, however, remains an unresolved issue. In this study we investigated whether heart rate variability (HRV) can be helpful in identifying ARVC/D patients with increased risk of arrhythmic events. METHODS AND RESULts: We studied 30 consecutive patients (17 males; 45.4 ± 18 years) with ARVC/D, diagnosed according to guideline criteria; 15 patients (50%) had received an implantable cardioverter defibrillator (ICD) for primary SCD prevention. HRV was assessed on 24-h ECG Holter monitoring. The primary endpoint was the occurrence of major arrhythmic events (SCD, sustained ventricular tachycardia (VT), ICD therapy for sustained VT or ventricular fibrillation (VF)). During the follow-up period (19 ± 7 months), no deaths occurred, but 5 patients (17%) experienced arrhythmic events (4 VTs and 1 VF, all in the ICD group). All HRV parameters were significantly lower in patients with, compared with those without, arrhythmic events. Low-frequency amplitude was the most significant HRV variable associated with arrhythmic events in univariate Cox regression analysis (P=0.017), and was the only significant predictor of arrhythmic events in multivariable regression analysis (hazard ratio 0.88, P=0.047), together with unexplained syncope (hazard ratio 16.1, P=0.039). CONCLUSIONS: Our data show that among ARVC/D patients HRV analysis might be helpful in identifying those with increased risk of major arrhythmic events.     

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.     

Different predictive values of electrophysiological testing and autonomic assessment in patients surviving a sustained arrhythmic episode.

BACKGROUND: Recent data suggest that the electrophysiological study (EPS) has limited value in the identification of high risk patients, so the aim of the present study was to evaluate if non-invasive measurement of baroreflex sensitivity (BRS), a marker of autonomic balance, provides additional prognostic information in patients surviving a sustained arrhythmic episode. METHODS AND RESULTS: The study group comprised 112 post myocardial infarction patients consecutively referred for EPS following documented ventricular fibrillation (VF) (20), sustained ventricular tachycardia (VT) (74) or a syncopal episode with subsequently documented non-sustained VT at Holter monitoring (18). BRS was assessed according to the transfer function method. A cardioverter - defibrillator (ICD) was implanted in 97 patients. During follow-up (median 315 days), appropriate ICD discharge occurred in 53 patients, and 3 more patients died suddenly. Sustained VT was induced in 84% and 77% of patients who did or did not develop arrhythmia at follow-up (p=0.34). No differences were found in age, sex, infarct site, drug therapy, resting RR interval or cycle of induced VT. Left ventricular ejection fraction (LVEF) < or =35%, New York Heart Association (NYHA) class >2 and BRS < or =3.3 ms/mmHg were found to be univariate predictors of arrhythmia recurrence. Multivariate models were obtained after grouping patients according to a moderately or severely depressed LVEF. Among the patients with LVEF < or =35%, BRS < or =3.3 ms/mmHg emerged as the only significant risk predictor of arrhythmia occurrence (sensitivity, specificity, positive and negative predictive value = 79%, 74%, 83% and 68%, respectively), whereas NYHA class >2 was a significant predictor among patients with LVEF >35%. CONCLUSIONS: Noninvasive BRS, but not EPS, is of value in predicting VT/VF episode recurrence in patients surviving a major arrhythmic event.     

Predictors of VT/VF-occurrence in ICD patients: results from the PROFIT-Study.

AIMS: Identification of risk factors for ventricular tachycardia/ventricular fibrillation (VT/VF) occurrence in patients with implantable cardioverter-defibrillators (ICD) is reasonable, because ICD patients with multiple risk factors might benefit from more aggressive anti-arrhythmic therapy for the prevention of arrhythmic events. Furthermore, in the era of prophylactic ICD therapy and limited healthcare resources, additional markers are needed for improved patient selection. METHODS AND RESULTS: Thus, in Prospective Analysis of Risk Factor for Appropriate ICD Therapy (PROFIT), we prospectively analyzed the role of ejection fraction (EF), N-terminal probrain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) class, atrial fibrillation, and QRS-duration as independent predictors for VT/VF occurrence in 250 ICD patients. Kaplan-Meier analysis showed that EF<40% (log-rank P=0.001), NT-proBNP levels higher than median (>or=405 ng/L; log-rank P=0.04), QRS-duration >or=150 ms (log-rank P=0.016), permanent atrial fibrillation (log-rank P=0.008), and higher NYHA class (log-rank P=0.029) were associated with VT/VF occurrence. By multivariate Cox regression analysis EF, QRS-duration and atrial fibrillation remained significantly associated with appropriate VT/VF therapy, whereas there was no relationship among NT-proBNP, NYHA class, and VT/VF occurrence. Stratifying patients according to the number of their independent risk factors (EF<40%, AF, QRS-width>or=150 ms) showed that patients with greater than or equal to two risk factors had a 100% 2-year risk of VT/VF occurrence, whereas patients with no or one risk factor had a 19.3 and 25% 2-year risk, respectively. CONCLUSIONS: EF<40%, permanent atrial fibrillation, and QRS>or=150 ms are independent predictors for VT/VF occurrence in predominantly secondary prophylactic ICD patients. Combining all independent predictors, we developed a risk score for VT/VF occurrence identifying a subgroup of patients with two or more risk factors who had a 100% 2-year risk. Future studies will reveal if this risk score helps to identify ICD patients suitable for empirical anti-arrhythmic therapy and to improve patient selection for prophylactic ICD therapy.     

Do Beta‐Blockers Impact Microvolt T‐Wave Alternans Testing in Patients at Risk for Ventricular Arrhythmias? A Meta‐Analysis

Beta‐Blockers and Microvolt T‐Wave Alternans. Introduction: Results of microvolt T‐wave alternans (MTWA) studies vary and may be influenced by whether beta‐blocker therapy was withheld prior to MTWA assessment. We conducted a meta‐analysis of the predictive value of MTWA screening for ventricular arrhythmic events in primary prevention patients with left ventricular dysfunction and examined whether results differed depending upon whether beta‐blocker use was withheld prior to MTWA testing. Methods and Results: Prospective studies that evaluated whether MTWA predicted ventricular arrhythmic events published between January 1980 and September 2008 were identified. Summary estimates for the predictive value of MTWA were derived with random‐effects models. Nine studies involving 3,939 patients were identified. Overall, an abnormal MTWA (positive and indeterminate) test was associated with an almost 2‐fold increased risk for arrhythmic events (pooled RR = 1.95, 95% CI: 1.29–2.96; P = 0.002). However, significant heterogeneity across studies was observed (P = 0.024). In the 4 studies in which beta‐blocker therapy was not withheld prior to MTWA assessment, an abnormal MTWA test was associated with a 5‐fold increased risk for arrhythmic events (pooled RR = 5.39, 95% CI: 2.68–10.84; P < 0.001) and was robust to sensitivity analyses. In contrast, the association was much weaker in those studies where the use of beta‐blocker therapy was withheld prior to MTWA testing (pooled RR = 1.40, 95% CI: 1.06–1.84; P = 0.02). Conclusions: In primary prevention patients with left ventricular dysfunction, the predictive power of MTWA varied widely, based on whether beta‐blocker therapy was withheld prior to its assessment. This observation may explain the inconsistent results of MTWA studies in this population. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1009‐1014, September 2010)     

Microvolt T-wave alternans for the risk stratification of ventricular tachyarrhythmic events: a meta-analysis

OBJECTIVES: The objective of this study was to perform a meta-analysis of the predictive value of microvolt T-wave alternans (MTWA) testing for arrhythmic events in a wide variety of populations. BACKGROUND: Previous studies describing the use of MTWA as a predictor of ventricular tachyarrhythmic events have been limited by small sample sizes and disparate populations. METHODS: Prospective studies of the predictive value of exercise-induced MTWA published between January 1990 and December 2004 were retrieved. Data from each article were abstracted independently by two authors using a standardized protocol. Summary estimates of the predictive value of MTWA were made using a random-effects model. RESULTS: Data were accumulated from 19 studies (2,608 subjects) across a wide range of populations. Overall, the positive predictive value of MTWA for arrhythmic events was 19.3% at an average of 21 months' follow-up (95% confidence interval [CI] 17.7% to 21.0%), the negative predictive value was 97.2% (95% CI 96.5% to 97.9%), and the univariate relative risk of an arrhythmic event was 3.77 (95% CI 2.39 to 5.95). There was no difference in predictive value between ischemic and nonischemic heart failure subgroups. The positive predictive value varied depending on the population of patients studied (p < 0.0001). CONCLUSIONS: Microvolt T-wave alternans testing has significant value for the prediction of ventricular tachyarrhythmic events; however, there are significant limitations to its use. The predictive value of MTWA varies significantly depending on the population studied. Careful standardization is needed for what constitutes abnormal MTWA. The incremental prognostic value of MTWA when used with other methods of risk stratification is unclear.     

Predictive value of programmed ventricular stimulation in patients with ischaemic cardiomyopathy: implications for the selection of candidates for an implantable defibrillator.

AIMS: The present study assessed the role of programmed ventricular stimulation (PVS) in risk stratification of patients with ischaemic cardiomyopathy (ICM), candidates for implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: Consecutive patients with ICM and LVEF < or = 40% (n = 106, age 61 +/- 7 years, LVEF 27 +/- 7%) underwent PVS. This was considered positive in case of inducibility of monomorphic ventricular tachycardia (VT) with < or =3 extrastimuli; polymorphic VT, ventricular fibrillation (VF), and fast monomorphic VT (CL < or = 230 ms) with < or =2 extrastimuli. Primary end-point was the combination of arrhythmic death and VF requiring ICD shock. Forty-nine patients (46%) were inducible at PVS; 74 (70%) were implanted with ICD. During a 24-month follow-up, the primary end-point occurred more frequently in positive PVS patients among the overall population, among patients with LVEF < or = 30% (n = 80) and among patients with an ICD. The negative predictive value of PVS was 96% in each group. In the overall population, both PVS (HR 7.32, 95% CI 1.6-32) and LVEF (HR 4.59, 95% CI 1.6-13) predicted the primary end-point. CONCLUSION: PVS may still have a role in predicting the arrhythmic risk in patients with ICM. A negative PVS identifies a subgroup with a very low risk of arrhythmic events even in patients with LVEF < or = 30%.     

Cardiac arrest recorded on ambulatory electrocardiograms

To characterize the events that precede and precipitate sudden cardiac death (SCD), the long-term electrocardiograms of 27 patients who had SCD while being monitored were analyzed. In 20 patients, SCD was associated with ventricular tachyarrhythmias (ventricular tachyardia [VT]/ventricular fibrillation [VF]) and in 7 it was associated with bradyarrhythmias. Seventeen of the patients were men and 10 were women. Twenty-one patients had coronary artery disease, 2 had idiopathic dilated cardiomyopathy, 2 had mitral stenosis and 1 patient had mitral valve prolapse. Four patients with VT/VF had a previous nonfatal cardiac arrest. In the 20 patients with tachyarrhythmia-related SCD, 3 or more VT beats always preceded degeneration to VF. In 5 patients, the frequency or complexity of ventricular arrhythmias increased in the hour before SCD. In 11 of 20, there was a 20% or greater increase in underlying heart rate in the hour before SCD. The R-on-T phenomenon was observed in 4 patients. The long-short phenomenon initiated VT/VF in 2 patients. Only 2 patients with VT/VF were resuscitated. No patient with bradyarrhythmia-related SCD had manifest atrioventricular block or bundle branch block. Two of 7 patients had an episode of nonsustained bradycardia in the hour before arrest. No patient was resuscitated. In conclusion, VT that degenerates into VF is the most common arrhythmia associated with SCD. VT/VF is frequently preceded by an increase in heart rate and complex ectopy. VT is most often initiated by late ventricular premature complexes. Twenty-five percent of patients who have SCD have associated bradyarrhythmias that may occur without premonitory events.     

Microvolt T-wave alternans for risk stratification of cardiac events in ischemic cardiomyopathy: A meta-analysis

Background

The ability of microvolt T-wave alternans (MTWA) for risk stratification of cardiac events in patients with ischemic cardiomyopathy (ICM) has not been well established.

Methods

The authors systematically reviewed current literature and carried out a meta-analysis to determine the ability of MTWA to predict the outcome severity after ICM. Major endpoints include composite endpoint of cardiac mortality and severe arrhythmic events in primary prevention of patients with ICM, as well as all-cause mortality (cardiac death, and/or non-cardiac death).

Results

Seven trials were included by using MTWA for risk stratification of cardiac events in 3385 patients with ICM. All patients were distributed into two groups according to the results of MTWA tests: non-negative group included positive and indeterminate, and negative group. Compared with the negative group, non-negative group showed increased rates of cardiac mortality or severe arrhythmic events (RR = 1.65, 95%CrI = 1.32, 2.071), sudden cardiac death (SCD) (RR = 2.04 95%CrI = 1.11, 3.75), and all-cause mortality (RR = 2.11, 95%CrI = 1.60, 2.79). The funnel plot revealed that there might be bias within current publications. The fail-safe number of composite endpoint and all-cause mortality was 14.42 and 18.93, respectively (when P = 0.01). The fail-safe number of SCD was 1.07 (when P = 0.05), which may be caused by the small case number of included studies and some patients with ICD included.

Conclusions

The non-negative group of MTWA had a nearly double risk of severe outcomes compared with the negative group. Therefore, MTWA represents a potential useful tool for judging the severity of ICM.     

微伏极T波电交替对心肌梗死急性期患者发生恶性心律失常的预测价值

目的评估微伏极T波电交替（MTWA）能否预测急性心肌梗死早期患者恶性心律失常的发生。方法起病7d内的急性ST段抬高型心肌梗死患者175例入选,根据起病12h内有无行直接经皮冠脉介入治疗（PCI）分为两亚组：Ia组（n=68行直接PCI）,Ib组（n=107未行直接PCI）。另选无心肌梗死来我院健康体检者82例作为对照组。所有入选者均做动态心电图用时域分析法检测MTWA最大值,用超声心动图检测左心室射血分数（LVEF）,用心室晚电位分析仪检测心室晚电位,观察住院期间有无恶性心律失常发生,并比较上述这些指标组间有无差异,用Logistic回归分析筛选恶性心律失常的预测因子。结果心肌梗死组合并糖尿病者高于对照组,Ib组合并糖尿病者高于Ia组。急性心肌梗死组恶性心律失常发生率、心室晚电位阳性率和MTWA最高值均高于对照组,而LVEF值低于对照组。急性心肌梗死两亚组间比较,Ib组恶性心律失常发生率、心室晚电位阳性率和MTWA最大值均高于Ia组,而LVEF值低于Ia组。Logistic回归分析结果显示MTWA最大值、LVEF、心室晚电位阳性率和有无糖尿病是患者是否发生恶性心律失常的独立预测因子,相关系数R分别为0．34、0．29、0．21、0．13,相对危险度（OR）分别为2．82、1．55、1．36、0．87,MTWA的相关性最强（R=0．34）,相对危险度最高（OR=2．82）。当LVEF和心室晚电位进入回归方程时,决定系数R^20．448,增加MTWA最大值进入回归方程后,决定系数R^2显著增加至0．628。结论MTWA最大值、LVEF和心室晚电位是早期急性心肌梗死患者恶性心律失常发生的预测因子,MTWA的预测价值优于LVEF和心室晚电位。如果三者联合运用能更好地预测早期急性心肌梗死患者恶性心律失常发生。     

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.     

Assessment of Microvolt T‐Wave Alternans in High‐Risk Patients with the Congenital Long‐QT Syndrome

Background: Microvolt T‐wave alternans (MTWA) has been used for arrhythmogenic risk stratification in cardiac disease conditions associated with increased risk of sudden cardiac death. Macroscopic T‐wave alternans has been observed in patients with congenital long‐QT syndrome (LQTS). The role of MTWA testing in patients with LQTS has not been established. Objective: To determine the diagnostic value of MTWA testing in high‐risk patients with LQTS. Methods and results: We assessed MTWA in 10 consecutive LQTS index patients who survived cardiac arrest or had documented torsade de pointes tachycardia and 6 first‐degree family members with congenital LQTS which had been genotyped in 13 of 16 subjects (7 index patients, 6 family members). No LQTS‐causing mutation was identified in 3 index patients with overt QT prolongation. MTWA was assessed during standardized bicycle exercise testing using the spectral method and yielded negative (n = 8) or indeterminate (n = 2) results in index patients, respectively. Similarly, all first‐degree family members tested MTWA negative except for one indeterminate result. Two genotype positive family members could not be tested (two children—4 and 9 years of age). Conclusion: In patients with congenital LQTS, free from structural heart disease and with a history of life‐threatening cardiac arrhythmias, assessment of MTWA does not yield diagnostic value. Hence, determination of MTWA in lower risk LQTS patients without spontaneous arrhythmic events is likely not to be useful for arrhythmia risk stratification.     

"Indeterminate" microvolt T-wave alternans tests predict high risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction.

OBJECTIVES: This study tested the hypothesis that an "indeterminate" microvolt T-wave alternans (MTWA) test, when due to ectopy, unsustained MTWA, or low exercise heart rate (HR), has prognostic significance similar to a positive MTWA test. BACKGROUND: MTWA testing, used to stratify risk of sudden or total mortality in patients with structural heart disease, has been limited by a substantial number of "indeterminate" tests. Indeterminate tests are due to patient factors--excessive ventricular ectopy during exercise, unsustained MTWA, or failure to achieve a HR of 105 beats/min for 1 min--or technical factors such as a noisy recording or an exercise protocol that causes an excessively rapid rise in HR. METHODS: Patients in sinus rhythm with left ventricular ejection fraction < or =0.40 underwent MTWA exercise tests, analyzed with the spectral method and classified by a computerized interpretation algorithm. The primary end point was all-cause mortality or documented non-fatal sustained ventricular arrhythmia (SVA). "Indeterminate" tests were reviewed jointly by 2 readers blinded to subsequent events to determine the primary reason for indeterminacy. RESULTS: Participants (N = 549) were 56 +/- 13 years and 71% male; 49% had ischemic cardiomyopathy. There were 40 deaths and 11 non-fatal SVA. Most (94%) indeterminate results were due to patient factors. The 2-year rate for death or SVA was 17.8% in patients with an "indeterminate" MTWA test compared with 12.3% in those with a positive test. CONCLUSIONS: In patients with left ventricular dysfunction, an "indeterminate" MTWA test due to patient factors predicted death or SVA at least as well as a positive test.     

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.     

Ventricular tachycardia during follow-up in patients resuscitated from ventricular fibrillation: experience from stored electrograms of implantable cardioverter-defibrillators

Objective. The purpose of this study was to use the electrogram storage capabilities of the implantable cardioverter-defibrillator (ICD) to categorize any arrhythmic event during follow-up in a group of patients who had survived an episode of ventricular fibrillation (VF) and to possibly identify clinical predictors of future arrhythmic events.Background. Little is known about the electrophysiologic characteristics of ventricular arrhythmias recurring during follow-up in survivors of VF as the sole documented arrhythmia at the time of resuscitation.Methods. Forty patients (58 ± 10 years; 73% men; left ventricular ejection fraction 42 ± 18%; 70% with coronary artery disease) who had survived an episode of VF and subsequently received an ICD capable of intracardiac electrogram recording and storage were followed for 23 ± 11 months. In all patients, the arrhythmogenic substrate was investigated by means of programmed electrical stimulation (PES).Results. Among the 40 patients, 41 episodes of ventricular arrhythmias were documented in 13 patients (33%): 36 episodes of ventricular tachycardias (VT) were recorded in 11 patients (28%) and 5 episodes of VF were recorded in the remaining 2 patients (5%). Age, gender, cardiac disease and left ventricular ejection fraction failed to distinguish between patients with clinical recurrences and patients without. The sensitivity, specificity and positive accuracy of PES were 29%, 63% and 46%, respectively, for prediction of ventricular arrhythmia recurrence; 45%, 70% and 36%, respectively, for prediction of VT; and 50%, 98% and 50%, respectively, for prediction of VF during follow-up.Conclusions. In survivors of VF receiving ICD therapy, VT is the most common ventricular arrhythmia recorded on device-incorporated electrograms during follow-up. This finding, associated with the relatively well-preserved ventricular function, may account for the ability of these patients to survive at time of the index arrhythmia; the use of antitachycardia pacing as a modality to treat arrhythmia recurrences may contribute to reduce the incidence of shock during follow-up in these patients.     

Programmed ventricular stimulation after myocardial infarction does not help reduce the risk of ventricular events

Summary Programmed ventricular stimulation could be a useful technique to detect patients at high risk for ventricular arrhythmias and sudden death after acute myocardial infarction. However, prevention of arrhythmic events using this technique has never been demonstrated. To determine whether prophylactic antiarrhythmic therapy influences prognosis after acute myocardial infarction, 196 patients without spontaneous ventricular tachycardia (VT) but with inducible sustained monomorphic VT were followed for 3±1 years. Ninety-seven patients were not treated (control group). In 99 patients (study group), the antiarrhythmic therapy was guided by electrophysiologic study: One to four trials using class I, II, and III antiarrhythmic drugs were performed until the VT was not inducible or the induced VT was slower and was associated with hemodynamic stability. An effective antiarrhythmic drug prevented VT induction in 34 patients (34%; group I). Sixty-five patients (group II) still had inducible VT with the antiarrhythmic drug. Group II differed from group I in having a higher incidence of an inferior myocardial infarction location (57% vs. 47%; NS), a lower left ventricular ejection fraction (36.5% vs. 41%; NS), a slower rate of induced VT in the control state (227 vs. 255 beats/min; p<0.05), and a higher number of drug trials (1.9 vs. 1.3; p<0.001). During the follow-up in the control group and in groups I and II, the incidence of total cardiac events was 25%, 15%, and 16% (NS), respectively, and the incidence of total arrhythmic events (VT, sudden death) was 18.5%, 9%, and 12% (NS). Only the risk of VT was reduced (14%, 0%, and 4%; p<0.05). In conclusion, guided-antiarrhythmic therapy, including class III agents after acute myocardial infarction, was successful in only 34% of patients, and the incidence of arrhythmic events was not significantly decreased. Therefore, programmed ventricular stimulation does not help in managing patients at risk of ventricular arrhythmia after myocardial infarction but could help to indicate the need for nonmedical treatment, such as device therapy.     

Ventricular arrhythmias and sudden cardiac death

The evaluation of a patient at risk for ventricular arrhythmias and CAD begins with a thorough medical history and the standard ECG, followed by an assessment of LVEF and the presence of ischemia. The SAECG, HRV, microvolt TWA, and invasive EPS should be used in particular subgroups of patients to assist the clinician in risk stratification for VT, VF, and SCD. Amiodarone is the superior antiarrhythmic agent in reducing the recurrence of VT/VF and subsequent ICD shocks. In addition, amiodarone has been shown to reduce arrhythmic death, but has fallen short in reducing total mortality. At present, patients who have a severely reduced LVEF (≤30%) and a history of MI are at extremely high risk for SCD and require an ICD. Aggressive risk stratification of patients is crucial in reducing the incidence of SCD. Understanding the role of pharmacotherapy and device therapy alike in the treatment of these patients will decrease future arrhythmic events and death.

Conclusions

Sudden cardiac death is the major cause of death in this country. Great strides have been made in recognizing which patients are candidates for ICD insertion. What remains is a greater public awareness, increased access to external defibrillators in the community, and a better understanding both among medical practitioners and patients alike as to who would benefit from aggressive SCD risk stratification.     

Heart rate variability in heart failure

BACKGROUND: Heart rate variability (HRV) depicts the functional status of the autonomic nervous system and its effects on sinus node. Recently, HRV analysis has been introduced in patients with heart failure (CHF) to identify those who are at risk of cardiac death. AIM: To analyse HRV in patients with CHF with depressed left ventricular ejection fraction (EF) and to relate HRV parameters to EF, NYHA functional class and other clinical parameters. METHODS: The study group consisted of 105 patients with CHF (88 males, 17 females, mean age 54+/-12 years); 77 patients had ischaemic cardiomyopathy, and 28 - dilated cardiomyopathy. All patients were in NYHA class II-IV and had EF <40%. The mean value of echocardiographically assessed EF was 26.9+/-8.3%. The control group consisted of 30 gender- and age-matched healthy subjects. HRV analysis was performed in the time-domain from 24-hour Holter ECG. RESULTS: All HRV variables were significantly lower in patients with CHF than in controls. Patients with NYHA class II had higher values of SDNN and SDANN than those in class III or IV. Patients with sustained or non-sustained ventricular tachycardia (VT) detected during Holter monitoring had lower SDNN and SDANN values than those without VT. Patients with diabetes had significantly lower SDNN and rMSSD values than the patients without diabetes. Similar results were found when patients with or without hypertension were compared. HRV parameters were similar in patients either with ischaemic or dilated cardiomyopathy. Also the values of EF were similar (27.4+/-8.4 vs 25.0+/-8.3%, respectively, NS). In the whole group of patients with CHF the values of SDNN and SDANN significantly correlated with EF (SDNN p<0.001, r=0.42; SDANN p<0.001, r=0.51). This correlation was stronger in the subset of patients with ischaemic cardiomyopathy (SDNN p=0.002. r=0.54; SDANN p=0.002; r=0.53) than in those with dilated cardiomyopathy (SDNN p=0.012, r=0.23; SDANN p=0.008, r=0.42). A significant negative correlation was found between all HRV parameters and NYHA class (SDNN p<0.001, r = -0.33; SDANN p<0.001, r = -0.38; rMSSD p<0.001, r = -0.13). CONCLUSIONS: HRV is depressed in patients with CHF compared with healthy subjects. Among patients with CHF, HRV is further decreased in patients with more advanced NYHA class, lower EF and in those with diabetes, hypertension or VT on Holter monitoring.     

The clinical implications of cumulative right ventricular pacing in the multicenter automatic defibrillator trial II

INTRODUCTION: This study was designed to assess whether right ventricular pacing in the implantable cardioverter defibrillator (ICD) arm of the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II was associated with an unfavorable outcome. METHODS AND RESULTS: Data on the number of ventricular paced beats were available in 567 (76%) of 742 MADIT II patients with ICDs. The number of ventricular paced beats over the total number of beats showed a bimodal distribution with patients being predominantly paced or nonpaced. Therefore, patients were dichotomized at 0-50% and 51-100% of cumulative pacing with median pacing rate 0.2% and 95.6%, respectively. Endpoints included new or worsening heart failure, appropriate ICD therapy for VT/VF, and the combined endpoint of heart failure or death. Clinical features associated with frequent ventricular pacing included age >or=65 years, advanced NYHA heart failure class, LVEF < 0.25, first degree AV and bundle branch block, and amiodarone use. During follow-up, 119 patients (21%) had new or worsened heart failure, 130 (23%) had new or worsened heart failure or death, and 142 (25%) had appropriate therapy for VT/VF. In comparison to patients with infrequent pacing, those with frequent pacing had significantly higher risk of new or worsened heart failure (hazard ratio = 1.93; P = 0.002) and VT/VF requiring ICD therapy (HR = 1.50; P = 0.02). CONCLUSIONS: Patients in MADIT II who were predominantly paced had a higher rate of new or worsened heart failure and were more likely to receive therapy for VT/VF. These results suggest the deleterious consequences of RV pacing, particularly in the setting of severe LV dysfunction.