Detection of T-wave alternans using an implantable cardioverter-defibrillator

BACKGROUND: Microvolt T-wave alternans (TWA) increases acutely prior to ventricular tachycardia (VT) or ventricular fibrillation (VF) in computer simulations and animal models, suggesting that TWA may provide a warning for VT/VF in patients with an implantable cardioverter-defibrillator (ICD). OBJECTIVES: The purposes of this study were to develop a method for analyzing TWA recorded from ICD electrograms (EGMs) and to evaluate the degree of concordance between EGM TWA and TWA recorded from the surface ECG. METHODS: We developed a software program to measure EGM TWA in the frequency domain and then used simulated EGMs to determine the effects of ICD signal processing, electrical noise, and variation in the EGM fiducial point on the recorded amplitude and K score (signal-to-noise ratio) of TWA. We then applied this method to analyze TWA simultaneously using both surface ECGs and ICD EGMs during incremental pacing in 25 ICD patients. Pacing modes and EGM sources were varied in repeated trials. EGMs with dynamic range adjusted to achieve a large T wave were telemetered to a digital Holter recorder and measured offline. ECG TWA was analyzed using a commercial system. A positive (+) ECG test had sustained alternans >or=1.9 microV with K score >or=3. Stored EGMs were reviewed for VT/VF during a 6-month follow-up period. RESULTS: Simulations demonstrated that the EGM method accurately identified TWA >or=10 microV. Overall, 10 (40%) patients had at least one ECG TWA+ test and 15 patients (60%) had no ECG TWA+ tests. The maximum value of TWA was greater in EGMs than in ECGs (median 64 microV vs 2.2 microV, P <.0001). EGM TWA was greater in ECG TWA+ tests than in ECG TWA- tests (169 +/- 175 microV vs 71 +/- 61 microV, P <.001). Using a sustained EGM TWA threshold of 30 microV, EGM TWA was concordant with ECG TWA in 63 (84%) of 75 analyzed tests (P <.0001) and predicted ECG TWA results with 85% sensitivity and 84% specificity. Both ECG and EGM TWA predicted VT/VF during follow-up (ECG: P = .006; EGM: P = .035). CONCLUSION: The amplitude of TWA is at least 10 times greater on ICD EGMs than on surface ECGs. EGM and ECG TWA have substantial concordance and comparable predictive value for spontaneous VT/VF. These observations support the hypothesis that ECG and EGM TWA detect the same electrical alternans phenomenon.     

Electrophysiology of T-wave alternans: Mechanisms and pharmacologic influences

Extensive experimental evidence indicates a fundamental link between T-wave alternans (TWA) and arrhythmogenesis. Diverse physiologic and pathophysiologic influences alter TWA magnitude in parallel with their effects on vulnerability to ventricular tachyarrhythmias. Specifically, interventions that impede intracellular calcium handling, such as elevated heart rate, heightened adrenergic activity, myocardial ischemia, and heart failure, predispose to greater levels of TWA, reflecting heightened risk for arrhythmias. Conversely, vagus nerve stimulation, blockade of beta-adrenergic receptors and late sodium and L-type calcium channels, and sympathetic denervation decrease TWA magnitude, reflecting the potential of these interventions to reduce risk for ventricular tachycardia and fibrillation. TWA thus appears able to detect the influence of pathophysiologically relevant triggers as well as the efficacy of antiarrhythmic drugs without reducing the predictive capacity of the phenomenon.     

T-wave alternans: lessons learned from a biophysical ECG model

T-wave alternans (TWA) is an alteration of the ECG T-wave which repeats every other beat. An alternating pattern has been also observed at myocytes level, involving both action potential duration and morphology (mainly in phases 2 and 3). While this might happen in a specific region (i.e., myocardial ischemia), it can also involve the entire myocardium. It is still unclear how alternations at the myocytes level are reflected on surface ECG modification of T-waves, especially when in vivo human hearts are considered. We have recently proposed a simple stochastic model of ventricular repolarization (IEEE Trans. Biomed. Eng., 2011), which takes into account both repolarization heterogeneity across the myocardium as well as random beat-to-beat variations in cells' activity. In this work, we generalized that model incorporating a term which describes myocytes alternans related to T-wave variability. Starting from the model and using the electrophysiological formulation developed by van Oosterom, we derived an analytical formula relating surface ECG to variations at the myocytes' level. Several theoretical results were then obtained. First, temporal small random variations in repolarization heterogeneity affect the precision of TWA estimates in a significant way. Second, TWA theoretically differs across leads, but multilead configuration can be used to reduce the effect of noise. Finally, the dependency between TWA and T-wave amplitude was analyzed.     

Microvolt T-wave alternans in early repolarization syndrome associated with ventricular arrhythmias: A case report

Despite early repolarization (ER) syndrome being usually considered benign, its association with severe/malignant ventricular arrhythmias (VA) was also reported. Microvolt T-wave alternans (MTWA) is an electrocardiographic marker for the development of VA, but its role in ER syndrome remains unknown. A 90-second 6-lead electrocardiogram from an ER syndrome patient, acquired with the Kardia recorder, was analyzed by the enhanced adaptive matched filter for MTWA quantification. On average, MTWA was 50 μV, higher than what was previously observed on healthy subjects using the same method. In our ER syndrome patient, MTWA plays a potential role in VA development in ER syndrome.     

Analysis of T-wave alternans using the dominant T-wave paradigm

The dominant T wave (DTW) reflects the derivative of the repolarization phase of the transmembrane potential of myocytes. T-wave alternans (TWA) is defined as an alteration of this repolarization that repeats every other beat. We investigate if the DTW can offer new insight on TWA.We first proved that the DTW estimate obtained through singular value decomposition is optimal, because it minimizes the norm of the residuals. Then we suggested an optimal estimate of the vector of lead factors, in the case in which the DTW is given. Finally, we derived a mathematical relationship between observable TWA on electrocardiogram and DTW morphology. The relationship depends on the slope of the repolarization phase of the myocytes' transmembrane potentials and on the dispersion of the repolarization times. Based on this finding, a new index meant to quantify TWA was defined and termed amplitude of dominant T-wave alternans (ADTWA).A preliminary validation of the index was performed using the synthetic records contained in the Computers in Cardiology 2008 data set. They were obtained from 5 electrocardiogram models to which TWA was added at different extents. We found a linear relationship between the TWA amplitude and the ADTWA metric (R² = 0.9898 ± 0.100 across all models). Moreover, the root mean square error between actual and estimated TWA amplitudes was 10.9 μV (ADTWA) vs 12.9 μV obtained with the classical spectral method.     

Optimizing ambulatory ECG monitoring of T-wave alternans for arrhythmia risk assessment

Considerable scientific data support the potential value of T-wave alternans (TWA) as anindex of vulnerability to ventricular fibrillation. This chapter summarizes our state of knowledge regardingthe use of routine ambulatory ECGs to evaluate TWA and discusses recent methodologic approaches designed tooptimize AECG-based TWA analysis for arrhythmia risk stratification. Newer methods, including the nonspectraltechnique of Modified Moving Average analysis, appear promising in detecting TWA during the changingconditions associated with daily activities. The Modified Moving Average approach does not requirespecialized electrodes and is not encumbered by the need to achieve target heart rates, as is the case forconventional spectral-based methods. Guidelines are provided for evaluating latent cardiac electricalinstability using AECG-based TWA testing. These recent developments make possible the TWA analysis ofambulatory ECGs not only in prospective trials but also in vast stores of archival data.     

Clinical value of T-wave alternans assessment

Microvolt-level T-wave alternans (TWA) is a new arrhythmia risk marker to assess subtle changesin repolarization that has been introduced for arrhythmia risk stratification. Recent experimental studies havedemonstrated that it reflects a heartrate dependent increased spatial dispersion of repolarization associated withunidirectional conduction block, and reentry that may result in the occurrence of ventricular fibrillation.Clinical studies have convincingly demonstrated that TWA is closely related to arrhythmia induction in theelectrophysiology (EP) laboratory as well as to the occurrence of spontaneous ventriculartachyarrhythmias in patients undergoing EP study. Subsequent studies showed that TWA—assessednoninvasively—is predictive of future arrhythmic events in patients with implanted ICDs as well as forventricular tachyarrhythmias in patients with congestive heart failure without a prior history of arrhythmias.There is still controversy, however, about the predictive value of TWA in patients following acute myocardialinfarction (MI). Several studies which differ in patient selection, pharmacologic treatment of thepatients, and endpoint definitions, have reported conflicting results. Therefore, studies with a large number ofunselected patients after acute MI on optimal treatment according to contemporary therapeutic guidelines as wellas of patients with reduced left ventricular ejection fraction following MI are needed to define its role withregard to identifying patients who may benefit from primary preventive ICD therapy. Future research should alsofocus on evaluation of alternative methods to increase heart rate (i.e., pharmacological stimulation) inan attempt to reduce the proportion of incomplete tests in patients with insufficient increase in heart rateduring exercise testing.     

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

Background/Purpose

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

国人微伏级T波电交替试验正常参考值探讨

目的　探讨国人微伏级T波电交替 (microvoltTwavealternanstest,MTWA)试验的正常参考值。方法　频谱法检测 4 4例健康志愿者微伏级T波电交替 ,分析交替压 (alternansvoltage ,Valt)的大小及其与性别、心率 (HR)的关系。结果　 (1)正常中青年国人T波电交替压大小与性别无关 (P >0 0 5 )。 (2 )HR <90 /min时 ,Valt均值 <1 0 μV ,95 %可信区间 0 4 5～ 1 0 2 μV ;90 /min≤HR≤ 110 /min时 ,Valt均值 <1 9μV ,95 %可信区间 1 4 7～ 2 0 8μV ;HR>110 /min时 ,Valt可 >1 9μV ,95 %可信区间 1 5 2～ 2 4 1μV。各组间比较 ,Valt差异有非常显著性意义 (P均 <0 0 1)。尤以综合导联及胸前导联差异有显著性 (P均 <0 0 1)。 (3)随心率增加 ,交替压增大 ,心率与综合导联Valt有相关性 (r=0 4 94 ,P <0 0 1)。结论　微伏级T波电交替具有频率依赖性。运动试验方案测定T波电交替 ,正常中青年国人 90 /min≤HR≤ 110 /min时 ,正交导联及综合导联Valt<1 9μV ,胸前导联Valt<2 0 μV。     

Predictive power of T-wave alternans and of ventricular gradient hysteresis for the occurrence of ventricular arrhythmias in primary prevention cardioverter-defibrillator patients

Background and purpose

Left ventricular ejection fraction lacks specificity to predict sudden cardiac death in heart failure. T-wave alternans (TWA; beat-to-beat T-wave instability, often measured during exercise) is deemed a promising noninvasive predictor of major cardiac arrhythmic event. Recently, it was demonstrated that TWA during recovery from exercise has additional predictive value. Another mechanism that potentially contributes to arrhythmogeneity is exercise-recovery hysteresis in action potential morphology distribution, which becomes apparent in the spatial ventricular gradient (SVG). In the current study, we investigated the performance of TWA amplitude (TWAA) during a complete exercise test and of exercise-recovery SVG hysteresis (SVGH) as predictors for lethal arrhythmias in a population of heart failure patients with cardioverter-defibrillators (ICDs) implanted for primary prevention.

Methods

We performed a case-control study with 34 primary prevention ICD patients, wherein 17 patients (cases) and 17 patients (controls) had no ventricular arrhythmia during follow-up. We computed, in electrocardiograms recorded during exercise tests, TWAA (maximum over the complete test) and the exercise-recovery hysteresis in the SVG. Statistical analyses were done by using the Student t test, Spearman rank correlation analysis, receiver operating characteristics analysis, and Kaplan-Meier analysis. Significant level was set at 5%.

Results

Both SVGH and TWAA differed significantly (P < .05) between cases (mean ± SD, SVGH: −18% ± 26%, TWAA: 80 ± 46 μV) and controls (SVGH: 5% ± 26%, TWAA: 49 ± 20 μV). Values of TWAA and SVGH showed no significant correlation in cases (r = −0.16, P = .56) and in controls (r = −0.28, P = .27). Receiver operating characteristics of SVGH (area under the curve = 0.734, P = .020) revealed that SVGH less than 14.8% discriminated cases and controls with 94.1% sensitivity and 41.2% specificity; hazard ratio was 3.34 (1.17-9.55). Receiver operating characteristics of TWA (area under the curve = 0.699, P = .048) revealed that TWAA greater than 32.5 μV discriminated cases and controls with 93.8% sensitivity and 23.5% specificity; hazard ratio was 2.07 (0.54-7.91).

Discussion and conclusion

Spatial ventricular gradient hysteresis bears predictive potential for arrhythmias in heart failure patients with an ICD for primary prevention, whereas TWA analysis seems to have lesser predictive value in our pilot group. Spatial ventricular gradient hysteresis is relatively robust for noise, and, as it rests on different electrophysiologic properties than TWA, it may convey additional information. Hence, joint analysis of TWA and SVGH may, possibly, improve the noninvasive identification of high-risk patients. Further research, in a large group of patients, is required and currently carried out by our group.     

Relationship between extracellular T-wave height, T-wave alternans amplitude, and tissue action potential alternans: a 1-dimensional computer modeling study

T-wave alternans (TWA) is a useful marker of cardiac instability, but not much is known about the factors that affect its measurement, such as electrode placement. We used a 1-dimensional myocardial fiber computer model of alternans to investigate the effect of electrode position on TWA measurement. Results demonstrated that TWA amplitude and T-wave amplitude change proportionally if both recording electrodes are symmetrically moved toward or away from the tissue. However, TWA amplitude and T-wave amplitude change out of proportion to one another when one electrode is moved while the other electrode remains stationary. These disproportionate changes result from beatwise alternation in the asymmetric potential field around the tissue. In summary, nonlinear changes in tissue repolarization during alternans result in nonlinear changes in T-wave amplitude and TWA amplitude.     

Evaluation of T-wave alternans in pediatric patients with chronic renal failure

Introduction

Microvolt T-wave alternans (TWA) is known to be useful in prediction of ischemia and sudden death in high-risk populations and there are no studies in children with chronic renal failure (CRF). Cardiac problems seem to be responsible for an important part of death in children and young adults with CRF. The aim of this study is to evaluate Holter microvolts TWA measurements in children with CRF comparing to the control group.

Quantitative assessment of microvolt T-wave alternans in patients with congestive heart failure

INTRODUCTION: T-wave alternans has been shown to be linked to the genesis of ventricular tachyarrhythmias. Currently, only qualitative assessment of microvolt T-wave alternans (MTWA) is recommended in clinical practise. Whether quantitative assessment of MTWA yields complementary information is unknown. METHODS AND RESULTS: Noninvasive MTWA determination was performed in 204 consecutive patients with ischemic or nonischemic cardiomyopathy. Of those, 100 tested MTWA positive. In these recordings, MTWA magnitude was quantitatively assessed (alternans voltage, V(alt)). Patients were followed for a mean of 17 months. Ventricular tachyarrhythmic events constituted the study endpoint. Patients with nonischemic cardiomyopathy had a higher V(alt) than patients with ischemic cardiomyopathy (10.3 +/- 9.2 [median 7.2] vs 6.2 +/- 3.2 [median 4.6] microV; P = 0.007). The number of MTWA-positive ECG leads was also higher in patients nonischemic cardiomyopathy (7.3 +/- 2.4 [median 8] vs 6.0 +/- 2.5 [median 6]; P = 0.016). Patients who suffered an arrhythmic event during follow-up had higher MTWA voltages (10.8 +/- 10.0 [median 8.8] vs 7.4 +/- 5.7 [median 6.4] microV; P = 0.05) a higher number of MTWA-positive ECG leads (7.6 +/- 2.4 [median 8] vs 6.4 +/- 2.5 [median 6]; P = 0.05) compared to patients with an uncomplicated course. CONCLUSION: Patients with nonischemic cardiomyopathy and patients with tachyarrhythmic complications have more extensive MTWA possibly reflecting more extensive myocardial damage and a higher arrhythmia propensity.     

Clinical applications of T-wave alternans assessed during exercise stress testing and ambulatory ECG monitoring

Analytical methods to measure T-wave alternans (TWA), a beat-to-beat fluctuation in the morphology of the ST-segment and T wave in the electrocardiogram (ECG), have been developed to address the unmet challenge of identifying individuals at increased risk for sudden cardiac death. Conventional noninvasive markers including left ventricular ejection fraction have significant limitations as many individuals who die suddenly have relatively preserved ventricular mechanical function. TWA is an attractive marker as it is closely linked to ECG heterogeneity and abnormalities in calcium handling, key factors in arrhythmogenesis. The objectives of this review are to summarize the clinical evidence supporting use of TWA in risk stratification and to discuss its current and potential applications in guiding device and medical therapy.     

T-wave alternans phase following ventricular extrasystoles predicts arrhythmia-free survival

OBJECTIVE: The purpose of this study was to assess the value of T-wave alternans (TWA) following ventricular extrasystoles in predicting arrhythmia-free survival. BACKGROUND: Stratifying risk for sudden death in patients with coronary disease and moderate left ventricular (LV) dysfunction remains a challenge. We hypothesized that, in such patients, a discontinuity in beat-to-beat T-wave alternation (TWA phase reversal) following single ventricular extrasystoles reflects transiently exaggerated repolarization dispersion, and predicts spontaneous ventricular arrhythmias. METHODS: We studied 59 patients with ischemic LV dysfunction (mean LV ejection fraction 38.7 +/- 5.3%) and nonsustained ventricular tachycardia undergoing programmed stimulation. TWA was computed spectrally from the ECG during ventricular pacing, and TWA phase reversal was reflected by a discontinuity in T-wave oscillation after single ventricular extrasystoles. RESULTS: Patients induced into ventricular arrhythmias (n = 36) had greater TWA magnitude (V(alt): 6.60 +/- 6.46 microV vs 2.61 +/- 1.97 microV; P = .001) and more frequent TWA phase reversal (62.1% vs 44.4%; P = .02) than those who were not (n = 23). During a mean follow-up of 36 +/- 12 months, positive TWA (V(alt) > or =1.9 microV) and TWA phase reversal both (P < .05) predicted events (all-cause mortality, ventricular tachycardia, ventricular fibrillation). Univariate predictors of arrhythmia-free survival were TWA phase reversal (P < .005), positive TWA (P < .05), age (P = .008), and LV mass index (P = .043). On multivariate analysis, only TWA phase reversal and age predicted events; if TWA phase was excluded, only positive TWA and age predicted events. CONCLUSION: Phase reversal in TWA following ventricular extrasystoles predicts spontaneous ventricular arrhythmias and all-cause mortality in patients with moderate ischemic LV dysfunction and was a better predictor than positive TWA or programmed ventricular stimulation.     

Implantable cardioverter-defibrillator malfunction due to mechanical failure of the header connection

Four cases of ICD system malfunction occurring within the Medtronic Marquis family over a limited time frame are reported. These cases shared a common element of defective connections between the header post and the right ventricular pace/sense terminal pin that required intervention and reconnection. Inappropriate shocks occurred in two cases. The circumstances of these cases provide important information about the potential difficulties with these devices and highlight the deficiencies of the current system in tracking and analyzing device-related problems.