T-wave Alternans In Patients Research Articles

COMPARISON OF T WAVE ALTERNANS IN PATIENTS WITH ISCHEMIC AND NON-ISCHEMIC CARDIOMYOPATHY

Background: Early detection of T-wave alternans in patients with cardiomyopathy can help in risk stratification of ventricular arrhythmias leading to sudden cardiac death. The present study was designed to compare T-wave alternans in patients with ischemic and non-ischemic cardiomyopathy. Methods: This cross-sectional comparative study was carried out at Department of Cardiac Electrophysiology, Armed Forces Institute of Cardiology, Rawalpindi during 2019. Thirty patients with ischemic cardiomyopathy along with equal number of non-ischemic cardiomyopathy of matched age and gender were recruited through non-probability purposive sampling. Patients with diabetes mellitus, cerebrovascular accident, heart failure, bundle branch block, systemic arterial hypertension and ongoing anti-arrhythmic therapy were excluded from the study. DMS 300-4L Holters were used to obtain ambulatory ECG recordings. Cardio Scan Premier 12 Lux software was used for analysis of T-wave alternans. Results: A total of 60 subjects were studied. The mean value of T-wave alternans was 52.73±30.76 µV and 57.47±36.54 µV for patients with ischemic and non-ischemic cardiomyopathy respectively. The difference between mean values was statistically insignificant (p=0.59). T-wave alternans was present in 8 (26.7%) patients with ischemic cardiomyopathy, while 5 (16.7%) patients with non-ischemic cardiomyopathy showed positive T-wave alternans and the difference was statistically insignificant (p=0.35). Conclusion: The mean value of T-wave alternans and frequency of patients with positive T-wave alternans is not significantly different in ischemic and non-ischemic cardiomyopathy. Pak J Physiol 2022;18(1):9?12

Microvolt T-Wave Alternans Is Modulated by Acute Low-Level Tragus Stimulation in Patients With Ischemic Cardiomyopathy and Heart Failure.

Aims: Microvolt T-wave alternans (TWA), an oscillation in T-wave morphology of the electrocardiogram (ECG), has been associated with increased susceptibility to ventricular tachy-arrhythmias, while vagus nerve stimulation has shown promising anti-arrhythmic effects in in vivo and ex vivo animal studies. We aimed to examine the effect of non-invasive, acute low-level tragus stimulation (LLTS) on TWA in patients with ischemic cardiomyopathy and heart failure.Methods: 26 patients with ischemic cardiomyopathy (left ventricular ejection fraction <35%) and chronic stable heart failure, previously implanted with an automatic implantable cardioverter defibrillator (ICD) device with an atrial lead (dual chamber ICD or cardiac resynchronization therapy defibrillator), were enrolled in the study. Each patient sequentially received, (1) Sham LLTS (electrode on tragus, but no stimulation delivered) for 5 min; (2) Active LLTS at two different frequencies (5 and 20 Hz, 15 min each); and (3) Active LLTS, during concomitant atrial pacing at 100 bpm at two different frequencies (5 and 20 Hz, 15 min each). LLTS was delivered through a transcutaneous electrical nerve stimulation device (pulse width 200 μs, frequency 5/20 Hz, amplitude 1 mA lower than the discomfort threshold). TWA burden was assessed using continuous ECG monitoring during sham and active LLTS in sinus rhythm, as well as during atrial pacing.Results: Right atrial pacing at 100 bpm led to significantly heightened TWA burden compared to sinus rhythm, with or without LLTS. Acute LLTS at both 5 and 20 Hz, during sinus rhythm led to a significant rise in TWA burden in the precordial leads (p < 0.05).Conclusion: Acute LLTS results in a heart-rate dependent increase in TWA burden.

Baseline elevation and reduction in cardiac electrical instability assessed by quantitative T-wave alternans in patients with drug-resistant epilepsy treated with vagus nerve stimulation in the AspireSR E-36 trial

Reports of cardiac arrhythmias and cardiac pathology at postmortem examination of patients with epilepsy suggest a possible cardiac component of risk for sudden unexpected death in epilepsy (SUDEP). T-wave alternans (TWA) is an established marker of cardiac electrical instability and risk for sudden death in patients with cardiovascular disease. We determined the TWA level before vagus nerve stimulation (VNS) system implantation and subsequently the effect of VNS on TWA in patients with drug-resistant epilepsy. Patients (n=28) from the Seizure Detection and Automatic Magnet Mode Performance Study (E-36), a clinical trial of the AspireSR® VNS Therapy System® (NCT01325623), were monitored with ambulatory electrocardiograms (ECGs) ~2weeks before de novo VNS system implantation and following 2- to 4-week VNS titration during a protocol-specified 3- to 5-day epilepsy monitoring unit stay with concurrent EEG/ECG recordings. The TWA level was assessed interictally by the Modified Moving Average (MMA) method. At preimplantation baseline, TWA was elevated above the 47-μV abnormality cutpoint in 23 (82%) patients with drug-resistant epilepsy. In 16 (70%) patients, TWA level was reduced during VNS treatment to <47μV, thereby converting positive TWA test results to negative. Peak TWA level in all 28 patients improved (group mean, 43%, from 72±4.3 to 41±2.3μV; p<0.0001). Vagus nerve stimulation was not associated with reduced heart rate (77±1.4 to 75±1.4beats/min; p=0.18). Heart rate variability was unchanged. These findings suggest significant interictal cardiac electrical instability in this population of patients with drug-resistant epilepsy and suggest that VNS may be a novel approach to reducing risk.

The Application of Ambulatory Electrocardiographically-Based T-Wave Alternans in Patients with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

BackgroundPatients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carry the risk of ventricular arrhythmias and sudden cardiac death (SCD). This study investigated the prognostic information of modified moving average T-wave alternans (MMA TWA) in patients with ARVD/C. MethodsA total of 63 consecutive patients (mean age, 44.7 ± 14.8 years; 38 men) with ARVD/C were enrolled. Baseline characteristics and structural and electrocardiographic parameters were obtained. All patients underwent ambulatory electrocardiographic examination at the time of diagnosis, and MMA TWA data were exported for further analysis. Events were defined as documented SCD or ventricular tachyarrhythmias during clinical follow-up. ResultsDuring a mean follow-up of 28.1 ± 15.4 months, 19 of 63 (30.2%) patients experienced events, including SCD in 2 patients (10.5%) and ventricular tachyarrhythmias in 17 patients (89.5%). Patients with events had higher TWA within modified V5 and V1 channels than did those without events (54.7 ± 24.9 μV vs 35.0 ± 18.3 μV; P = 0.004; 58.8 ± 27.6 μV vs 38.4 ± 18.6 μV; P = 0.007, respectively). After multivariate Cox regression analysis, maximal TWA derived from either the modified CM5 or NASA channel predicted the occurrence of events (P < 0.001; hazard ratio, 1.06; 95% confidence interval, 1.03-1.10). At the cutoff value of > 66 μV, maximal TWA yielded a sensitivity and a specificity of 89.5% and 90.5%, respectively, in predicting SCD or ventricular tachyarrhythmias. ConclusionsThe initial analysis of MMA TWA could provide prognostic implications in the prediction of SCD or ventricular tachyarrhythmias in patients with ARVD/C.

Distinguishing Right Ventricular Cardiomyopathy From Idiopathic Right Ventricular Outflow Tract Tachycardia with T-wave Alternans

BackgroundThe 2 predominant etiologies of right ventricular tachycardia (VT) are arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic VT arising from the right ventricular outflow tract. Discrimination between these 2 entities is critical, as their prognoses and therapeutic options differ. The microvolt T-wave alternans (TWA) is widely used to predict lethal ventricular arrhythmias in various diseases. However, the clinical significance of TWA in patients with VT originating from the right ventricle has been unknown. This study aims to investigate the possible role of TWA to discriminate ARVC from idiopathic right ventricular outflow tract tachycardia (RVOT-VT). MethodsThis study enrolled 38 patients (23 male, 43 ± 16 years) with VT originating from the right ventricle. TWA was measured during exercise testing using the modified moving average method. TWA results were compared among patients with ARVC and RVOT-VT. ResultsTwenty-five patients (16 male, 42 ± 16 years) met the Task Force criteria for the diagnosis of ARVC, and 13 patients (7 male, 45 ± 14 years) had idiopathic RVOT-VT. Twenty patients with ARVC had positive TWA test, whereas only 1 patient with RVOT-VT had (80% versus 8%,P <0.001). Conclusions:In patients with VT of right ventricle origin, positive TWA test supports the diagnosis of ARVC.

Heart Rate Turbulence and T-Wave Alternans in Patients with Coronary Artery Disease: The Influence of Diabetes.

Patients with diabetes mellitus (DM) have a higher risk of sudden cardiac death. Factors associated with the risk profiles of coronary artery disease (CAD) patients with DM are not well established. Heart rate turbulence (HRT) and T-wave alternans (TWA) are often used to predict arrhythmia events. HRT and TWA were measured in two independent groups: the ARTEMIS cohort study and the REFINE-ICD randomized trial. ARTEMIS assesses risk 3-12 months after coronary angiography in patients with CAD. The initial 1001 patients in ARTEMIS, 526 with and 475 without DM, are included in this analysis. REFINE-ICD compares usual care versus usual care plus ICD therapy in patients with left ventricular (LV) ejection fraction (EF) values of 36-50% assessed 2-15 months after myocardial infarction. The initial 275 patients screened in REFINE ICD are included in this analysis. Abnormal HRT plus TWA was more common in patients with versus without DM in ARTEMIS (125/526, 24% vs 63/475, 13%; P < 0.001) and REFINE-ICD (43/55, 78% vs 55/220, 25%; P < 0.001), respectively. Abnormal HRT plus TWA was also more common in patients with LVEF values < 50% (28%) vs ≥ 50% (18%; P < 0.001) in ARTEMIS and LVEF values below the population median of 42% (60/138, 43%) versus above the median (38/137, 28%; P < 0.01) in REFINE-ICD. Abnormal HRT plus TWA is more common in CAD patients with DM compared with the patients without DM and is related to the severity of LV dysfunction. http://www.clinicaltrials.gov, NCT01426685; http://www.clinicaltrials.gov, NCT00673842.

Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy.

The cardiac component of risk for sudden unexpected death in epilepsy (SUDEP) and alterations in cardiac risk by vagus nerve stimulation (VNS) are not well understood. We determined changes in T-wave alternans (TWA), a proven noninvasive marker of risk for sudden cardiac death in patients with cardiovascular disease, and heart rate variability (HRV), an indicator of autonomic function, in association with VNS in patients with drug-resistant focal epilepsy. Ambulatory 24-h electrocardiograms (N = 9: ages 29-63, six males) were analyzed. Mean TWA during the interictal period was 37 ± 3.1 μV (mean ± SEM) in lead V1 for nine patients monitored following implantation of the VNS system (n = 7) or battery change (n = 2). Of these, six patients also monitored prior to implantation (n = 5) or battery change (n = 1) showed abnormally high TWA levels pre-VNS (60.0 ± 4.3 μV), which were significantly reduced by 24.3 μV (to 35.7 ± 4.8 μV, p = 0.02) after VNS settings were adjusted for desired clinical response. TWA in four (67%) of the six patients was reduced in association with VNS to levels below the 47-μV cut point of abnormality. The decrease in TWA was correlated with VNS intensity (r = 0.88, p < 0.02). In addition, low-frequency HRV was reduced by 60% (805.61 ± 253.96 to 323.49 ± 102.74 msec(2) , p = 0.05) and low-to high-frequency HRV ratio by 32% (3.34 ± 0.57 to 2.26 ± 0.31, p = 0.025), indicating a change in autonomic balance in favor of parasympathetic dominance. This is the first report that elevated levels of TWA in patients with drug-refractory partial-onset seizures were reduced in association with VNS, potentially by improving sympathetic/parasympathetic balance. VNS may have a cardioprotective role at stimulation settings typically used for seizure control. These findings indicate the utility of TWA for tracking improvement in cardiac status in this population.

Cardiac resynchronization therapy reduces T-wave alternans in patients with heart failure.

T-wave alternans (TWA) represents myocardial instability. The present study was to determine the impact of cardiac resynchronization therapy (CRT) on TWA and left ventricular ejection fraction (LVEF) in heart failure patients. T-wave alternans was analysed using a spectral method in 27 CRT-ICD patients. Ambulatory device electrograms were collected and LVEF and New York Heart Association (NYHA) classification were assessed at baseline prior to CRT and 3 months following CRT. Patients were followed for 6 months to monitor cardiac events. Spectral TWA of device electrograms was measured during AAI and CRT pacing tests. Each pacing mode had the up-titration pacing rate from 90 to 105 b.p.m. with 90 s for each pacing rate. At baseline, 20 (76.9%) patients had TWA during AAI pacing tests and 13 (50%) during CRT pacing tests (P = 0.044 between two pacing modes). Following 3-month CRT, TWA was identified in 11 patients (45.8%) during AAI pacing tests (a 31.1% reduction from the baseline value, P = 0.023) and 7 patients (28%) during CRT pacing tests (a 22% reduction, P = 0.108). Six of seven patients who had cardiac events had TWA (three patients had arrhythmic events, two died of heart failure, one received heart transplant). Overall, LVEF improved from 27.3 ± 5.8 to 35.9 ± 10.5% (P < 0.001) and NYHA classification improved from 2.8 ± 0.6 to 1.6 ± 0.6 after 3-month CRT (P < 0.001). In heart failure patients who receive a CRT-ICD, CRT reduces TWA that is associated to cardiac events, suggesting that CRT promotes clinically significant reverse electrical and mechanical remodelling.

Relationship between cardiac mechanics evaluated by two-dimensional strain imaging and T-wave alternans in patients with hypertrophic cardiomyopathy

Objective The aim of this study was to assess the relationship between left ventricular (LV) deformational abnormalities, measured by two-dimensional strain imaging, and T-wave alternans (TWA) in hypertrophic cardiomyopathy (HCM). Background HCM is a prevalent hereditary cardiac disorder linked to arrhythmia and sudden cardiac death. Microvolt TWA involves periodic beat-to-beat variation in the amplitude or the shape of the T wave in an ECG. In HCM, TWA has been linked to increased LV mass and used previously as noninvasive prognostic tools in the evaluation and patient risk stratification. Patients and methods The study group consisted of 40 consecutive HCM patients. The HCM group was compared with 33 age-matched and sex-matched healthy participants. All patients and control participants underwent 12-lead ECG, conventional echocardiographic examination, two-dimensional strain imaging, treadmill exercise test, and measurement of TWA, 24-h Holter monitoring. Results Depending on TWA results, the patients were divided into two groups: TWA+ patients, and TWA- patients. There were no significant differences among the most conventional echocardiographic measures between TWA groups. Absolute values of esys, SRsys, SRe, and SRa were significantly smaller in HCM patients than the controls at rest and peak exercise (P Conclusion The considerable association of myocardial dysfunction with TWA+ outcome provides important new evidence on arrhythmia vulnerability in HCM.

Clinical use of microvolt T-wave alternans in patients with depressed left ventricular function eligible for ICD implantation: mortality outcomes after long term follow-up

Implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with left ventricular dysfunction. However, left ventricular dysfunction alone has significant limitations as a risk stratifier for guiding ICD therapy [1,2]. In the SCD-HeFT trial [3], the ICDmediated reduction in absolute mortality was 1.4% per year (7.2% over 5 years) indicating that only a very small fraction of patients with ICDs actually receive life saving therapy from the devices. Moreover, ICD implantation [4] is associated with a high rate of subsequent complications suchas infections, inappropriate shocks, leadand generator failures and recalls. Consequently there is a need to more accurately identify those individuals who will benefit from ICD implantation. Microvolt T-wave alternans (MTWA) has been linked mechanistically to the development of ventricular tachyarrhythmias [5] and is a clinical marker of increased risk of sudden cardiac death (SCD) [6–8]. Conversely, patients with a negative MTWA test have a very low risk of SCD [8]. In our departmentwe routinely measureMTWA in patients without a history of cardiac arrest being considered for prophylactic ICD implantation [9] and the result is a major determinant of the decision of whether or not to implant an ICD. From 2001 to March 2011 MTWA tests were performed on 178 consecutive patients with ischemic and non-ischemic cardiomyopathy who were eligible for ICD implantation according to clinical guidelines in place at the time of evaluation. Patientswith a normal testwere offered the option to not receive an ICD. We conducted long-term follow-up of these patients. The primary endpointwas defined as all-causemortality and the secondary endpoint was defined as cardiac mortality. Patients underwent an MTWA exercise bicycle testing that was interpreted both automatically within the HearTwave system and by two expert readers. Because patients with positive and indeterminate MTWA tests results display elevated event rates [8], all comparisons in this analysis were made between patients with normal (negative) and abnormal (positive or indeterminate) MTWA tests. The baseline characteristics of the 178 patients are listed in Table 1. All participantswere in NewYorkHeart Association functional class II or III and had left ventricular ejection fraction ≤ 40% (mean 30 ± 6). The MTWAabnormal patients compared to theMTWAnormal patients, on a statistically univariate basis, had higher NYHA class, wider QRS, and lower LVEF.MTWAwasabnormal in129 (72%)andnormal in49patients (28%). Substantially fewer patients (15/49, 31%) in the MTWA normal group received an ICD than did patients in the MTWA abnormal group (103/129, 80%), p = 0.0001. During the follow-up (median 64 months) a total of 35 deaths occurred. In the MTWA normal group 4 patients died – all of noncardiac cause; in the MTWA abnormal group 31 deaths occurred and were classified as follows: 20 cardiac deaths, 7 non-cardiac and 4 unknown.

Heart rate turbulence and microvolt T-wave alternans in patients after myocardial infarction

Sulimov et al .,1 in a study published online in the Journal on 31 July 2012, report on the predictive value of heart rate turbulence (HRT) and microvolt T-wave alternans (mTWA) measured in 24 h ambulatory electrocardiogram monitoring, for sudden cardiac death (SCD) in patients after myocardial infarction (MI). The work is important because it focuses on patients with preserved or moderately impaired left ventricular function (who are the ones dying from SCD at higher absolute numbers than the patients with a left ventricular ejection fraction [LVEF] ≤35%), and considers HRT, mTWA, and a host of …

Risk stratification after myocardial infarction: it is time for intervention

This editorial refers to ‘Non-invasive risk stratification for sudden cardiac death by heart rate turbulence and microvolt T-wave alternans in patients after myocardial infarction’ by V. Sulimov et al ., on page 1786 Despite significant advances in interventional and pharmacological therapies, late mortality after acute myocardial infarction (MI) is still high. Approximately 50% of cardiovascular deaths after MI occur suddenly and are potentially preventable by prophylactic implantation of a cardioverter-defibrillator (ICD). In recent decades, substantial efforts have been made to identify high-risk patients who may benefit from prophylactic therapy. While initial risk stratification strategies guiding ICD therapy were based on the comprehensive electrophysiological testing in highly selected subgroups of patients, a revolutionary concept was proposed in 2002, when Moss et al. 1 presented the results of MADIT-2 (Multicentre Automatic Defibrillator Implantation Trial). In contrast with all previous attempts, MADIT-2 used the finding of a reduced left ventricular ejection fraction (LVEF) as the single selection criterion for prophylactic ICD-implantation. In terms of efficacy and effectiveness, the MADIT-2 criterion was a great success. Subsequent trials confirmed the concept of prophylactic ICD-implantation in patients with impaired LVEF, and later economic analyses verified the cost-effectiveness of this approach. However, when looking from an epidemiological point of view at the global impact of ICD …

Ambulatory Electrocardiogram-Based T-Wave Alternans in Patients With Vasospastic Angina During Asymptomatic Periods

T-wave alternans (TWA) is a useful method for evaluating repolarization abnormalities and as a predictor of life-threatening ventricular arrhythmias. Although life-threatening ventricular arrhythmias are occasionally observed during ischemic attacks in patients with vasospastic angina (VSA), there have been no studies to detect repolarization abnormalities using TWA analysis in these patients during the asymptomatic phase. The aim of this study was to analyze modified moving average (MMA) TWA using Holter recordings in 40 patients with VSA and in 40 control subjects. The incidence of positive TWA was higher in the VSA group than in the control group (24 of 40 [60%] vs 0 of 40 [0%], p <0.01). The value of the maximum MMA TWA was also greater in the VSA group than in the control group (68.6 ± 21 vs 34.0 ± 11 μV, p <0.01). In the VSA group, although there was no significant difference in maximum MMA TWA values between patients with multiple- and single-vessel spasm, patients with ventricular tachycardias had higher values than those without (83.0 ± 15 vs 65.9 ± 20 μV, p <0.05). Patients taking calcium channel blockers exhibited decreased values of maximum MMA TWA compared with subjects not taking these drugs (73.8 ± 18 vs 59.5 ± 21 μV, p <0.05). In conclusion, high values and incidences of TWA events were observed in patients with VSA. In the VSA group, maximum values of MMA TWA were high in patients with ventricular tachycardias but decreased in those taking calcium channel blockers. The results suggest that the patients with VSA during asymptomatic phases exhibit repolarization abnormalities leading to a potential risk for life-threatening arrhythmias.

Non-invasive risk stratification for sudden cardiac death by heart rate turbulence and microvolt T-wave alternans in patients after myocardial infarction

To evaluate the predictive value of heart rate turbulence (HRT) and microvolt T-wave alternans (mTWA) for sudden cardiac death (SCD) in patients after myocardial infarction (MI). We studied 111 patients with MI in the previous 60 days (median, 27 [9;84] months) before inclusion (84 men, mean age 64.1 ± 10.5 years, mean left ventricular ejection fraction 46.6 ± 12.2%). Heart rate turbulence and mTWA were evaluated using 24 h ambulatory electrocardiogram monitoring. The primary endpoint was SCD, and the secondary endpoint was all-cause mortality and non-sudden death from cardiovascular causes. During follow-up of 12 months, 15 SCD and 8 non-sudden cardiovascular deaths (including five fatal MI and three fatal strokes) occurred. Non-survivors had significantly higher mTWA values (83 [74;165] vs. 79 [78;94] mcV, P= 0.002), absolute turbulence onset (TO) values (0 [-0.005;0.01] vs. -0.01 [-0.013;-0.004], P= 0.004), and significantly lower absolute turbulence slope (TS) values (3.34 [2.10;4.83], vs. 3.82 [4.48;7.27], P< 0.001) compared with survivors. In patients with SCD, mTWA, and TO were significantly higher (92 [72;213] vs. 74 [65;86] mcV, P= 0.004 and 0 [-0.001;0.01] vs. -0.01 [-0.03;0.01], P= 0.007, respectively) and TS values were significantly lower (2.14 [1.10;4.56] vs. 4.41 [2.1;7.18], P= 0.005) than in patients with non-sudden death. All parameters were significantly worse in non-survivors than in survivors. We defined cut-off values for increased risk of SCD: for TO = -0.005, relative risk (RR) was 12.4 [95% confidence interval (CI) 2.6-38.2, P< 0.001; positive predictive value (PPV) 28.3%, negative predictive value (NPV) 96.9%], and for mTWA > 53.5 mcV at 100 b.p.m., RR was 5.01 (95% CI 1.5-17.0, P= 0.005; PPV 24.4%, NPV 93.9%). Notably, mTWA > 18.5 mcV at 05.00 AM significantly increased all-cause mortality [RR 7.5 (95% CI 1.4-38.7), P= 0.01; PPV 19.6%, NPV 90.8%]. In patients who died from cardiovascular causes, mTWA, and TO values were significantly higher and TS values were significantly lower than in survivors, and the subgroup with SCD was characterized by significantly increased mTWA and TO values and decreased TS values. mTWA > 53.5 mcV at 100 b.p.m. was an independent significant predictor of SCD and increased risk of SCD by five-fold.

Postictal increase in T-wave alternans after generalized tonic-clonic seizures

Sudden unexpected death in epilepsy (SUDEP) occurs most frequently in people with chronic uncontrolled epilepsy. Tonic-clonic seizures are a well-recognized risk factor for SUDEP. T-wave alternans (TWA) is a novel independent marker of risk of sudden cardiac death and cardiovascular mortality. The aim of this study was to determine if the level of TWA in patients with epilepsy differed after complex-partial and secondary generalized tonic-clonic seizures (sGTCS). Electrocardiography (ECG) and electroencephalography (EEG) data from patients with drug-resistant focal epilepsy who had both complex partial and sGTCS during video-EEG telemetry were retrospectively reviewed. Periictal TWA, heart rate (HR), and heart rate variability (HRV) were analyzed. ECG and EEG data of 16 patients (31.6 ± 8.7 years, nine male) with focal epilepsies were analyzed. sGTCS led to a postictal increase in TWA for 15 min as well as a higher postictal HR and decreased postictal HRV for the whole observation time of 30 min. There was no significant association between postictal TWA or HR and seizure duration or duration of the tonic-clonic phase. Our study demonstrates that derangements in autonomic function and TWA are highly prevalent after sGTCS in patients with chronic uncontrolled epilepsy. Further studies are warranted to investigate the value of TWA for risk stratification in epilepsy patients for sudden cardiac death and SUDEP.

The Prevalence and the Prognostic Value of Microvolt T-Wave Alternans in Patients with Hypertrophic Cardiomyopathy

Nonsustained ventricular tachycardia (nVT) may have ominous implications for patients with hypertrophic cardiomyopathy (HCM). The microvolt T-wave alternans (TWA) has been proposed as a noninvasive tool-identifying patients at risk of sudden cardiac death and ventricular tachycardia/fibrillation (VT/VF). The aim of the study was to determine the significance of TWA in predicting nVT episodes and compare how other electrocardiographic parameters can predict the occurrence of nVT. The study group consisted of 88 patients with HCM. TWA was assessed during exercise test using the CH2000 system. All patients underwent Holter monitoring (HM) within 2-4 weeks before TWA test (preexercise HM1) and immediately after (postexercise HM2). During HM, we analyzed: arrhythmias, QT intervals, the presence of late ventricular potentials (LP), heart rate variability, heart rate turbulence. Depending on TWA results, the patients were divided into two groups: TWA+; 46 patients (52.3%) with positive/indeterminate results, and TWA-; 42 patients (47.7%) with negative results. The nVT episodes were more frequent among TWA(+) both in HM1 and HM2. The presence of TWA increases the risk of postexercise nVT over twenty times (OR = 21.03). Moreover, in HM1, QTc and LP, and in HM2, again QTc and N-terminal precursor of brain natriuretic peptide proved to be significant predictors of nVT. The addition of TWA to the models did not improve the arrhythmia risk assessment. Repolarization abnormality plays an important role in generating nVT in patients with HCM, but TWA does not specifically predict the risk of arrhythmic end point.

T-Wave Alternans Testing in Pacemaker Patients: Comparison of Pacing Modes and Long-Term Prognostic Relevance

T-wave alternans (TWA) is a useful method for identifying patients who are at risk for sudden cardiac death. We aimed to determine the effects of different pacing modes on test results and long-term prognostic relevance of TWA in patients following a dual-chamber (DDD) pacemaker implantation. Sixty-three patients (mean age 68 ± 13 years) with structural heart disease and recently implanted DDD pacemakers were enrolled. Left ventricular (LV) function was normal or moderately impaired (mean LV ejection fraction 61 ± 13%). All patients underwent sequential TWA testing using atrial and ventricular pacing. During atrial pacing requiring physiologic conduction to the ventricles, 21% of TWA tests were positive, 43% negative, and 36% indeterminate. When using right ventricular (RV) pacing in the same patients, 19% of tests were positive, 40% negative, and 41% indeterminate. When positive and indeterminate tests were grouped as nonnegative, the concordance between atrial and ventricular pacing was 62% (κ= 0.22). After a mean follow-up of 5.9 ± 1.9 years, 18 (29%) patients had died. Improved survival was predicted by a negative TWA test using atrial pacing (P = 0.028), but not with ventricular pacing (P = 0.722). In patients with dual-chamber pacemakers, there is a low concordance of TWA test results between atrial pacing with intrinsic conduction to the ventricles and apical RV pacing via pacemaker electrode. However, TWA during atrial pacing clearly exerts long-term prognostic relevance in a patient group with preserved LV function and structural heart disease.

Increased microvolt T-wave alternans in patients with repaired tetralogy of Fallot

BackgroundMicrovolt T wave alternans (MTWA) is an indicator of repolarization heterogeneity and a predictor of ventricular arrhythmia in adults with ischemic or dilated cardiomyopathy. Its implication in patients with repaired tetralogy of Fallot (TOF) is still unclear. This study sought to define the changes and the clinical implication of MTWA in these patients. MethodsTreadmill examination with modified moving average beat analysis (MMA) for MTWA was performed in 101 repaired TOF patients (60.4% male). Data from 103 age- and sex-matched subjects with normal hearts served as controls. ResultsThe age at latest follow-up was 20.0±10.6years. Total repair (60.4% received a transannular right ventricular outflow patch) was performed at a mean age of 4.8(±5.8) years. After excluding 11 patients with indeterminate data, the MTWA data in 90 TOF patients revealed higher values than those in the control (25.1±14.0 vs. 17.6±9.2μV, p<0.001). The values were best correlated to the presence of severe pulmonary regurgitation (p=0.006). Ten (9.9%) patients experienced late ventricular arrhythmic events. They tended to have higher MTWA values than those without (34.0±16.5 vs. 24.2±13.5 and p=0.053). Although the MTWA per se would not predict the late arrhythmia events better than QRS duration alone, the positive and negative predictive values increased slightly after adding the MTWA to QRS duration. ConclusionsMTWA, as measured by MMA, increased in repaired TOF patients particularly in those with severe pulmonary regurgitation and late arrhythmia events. To predict late ventricular arrhythmia, MTWA however was not superior to QRS duration alone.

Influence of Diabetes and/or Myocardial Infarction on Prevalence of Abnormal T‐Wave Alternans

Subjects with microvolt-level T-wave alternans (TWA) in association with structural heart disease have an increased risk for sudden cardiac death. The presence of diabetes (DM) is associated with an increased risk of sudden death but there is limited data on the impact of DM and previous myocardial infarction (MI) on TWA prevalence. We performed a case-control cross-sectional study in 140 patients referred for routine exercise testing within a large multispecialty clinic. All patients with a history of DM and MI status within the past year were eligible: group 1 (no DM or MI), group 2 (DM only), group 3 (MI only), group 4 (DM and MI). Patients performed a symptom-limited Bruce protocol exercise test with assessment of TWA by the spectral method using commercially available equipment. We used published criteria for the blinded interpretation of TWA; all tests not unequivocally negative were considered abnormal. Age and gender were similar in all groups. The prevalence of abnormal TWA in groups 1-4 was 24%, 20%, 48%, and 62%, respectively (between group P = 0.002). Logistic regression analysis in all patients showed that abnormal TWA was related to prior MI [OR (95% CI): 4.0 (1.8-8.9), P < 0.001] but not to prevalent DM [0.9 (0.4-1.8), P = 0.72]. In patients with DM, the prevalence of abnormal TWA was related to reduced ejection fraction (P = 0.034) but not to BMI, DM duration, glycemic control, insulin use, or the presence of microvascular complications. The presence of DM alone does not increase risk of abnormal TWA. Prospective studies are required to establish the prognostic value of TWA in patients with DM.

QT Variability during Rest and Exercise in Patients with Implantable Cardioverter Defibrillators and Healthy Controls

Increased QT Variability (QTVI) is predictive of life threatening arrhythmias in vulnerable patients. The predictive value of QTVI is based on resting ECGs, and little is known about the effect of acute exercise on QTVI. The relation between QTVI and arrhythmic vulnerability markers such as T-wave alternans (TWA) has also not been studied. This study examined the effects of exercise on QTVI and TWA in patients with arrhythmic vulnerability. Digitized ECGs were obtained from 47 ICD patients (43 males; age 60.9 +/- 10.1) and 23 healthy controls (18 males; age 59.7 +/- 9.5) during rest and bicycle exercise. QTVI was assessed using a previously validated algorithm and TWA was measured as both a continuous and a categorical variable based on a priori diagnostic criteria. QTVI increased with exercise in ICD patients (-0.79 +/- 0.11 to 0.36 +/- 0.08, P < 0.001) and controls (-1.50 +/- 0.07 to -0.19 +/- 0.12, P < 0.001), and QTVI levels were consistently higher in ICD patients than controls during rest and exercise (P < 0.001). The magnitude of QTVI increase from baseline levels was not larger among ICD patients versus controls (P > 0.20). Among ICD patients, elevated exercise QTVI was related to lower LV ejection fraction and inducibility of ischemia (P < 0.05). QTVI at rest correlated with exercise TWA (r = 0.54, P = 0.0004). QT variability increases significantly with exercise, and exercise QTVI is related to other well-documented markers of arrhythmic vulnerability, including low ejection fraction, inducible ischemia, and TWA. Resting QTVI may be useful in the risk stratification of individuals incapable of performing standard exercise protocols.