Non-linear trend estimation of cardiac repolarization using wavelet thresholding for improved T-wave alternans analysis

Detection and estimation of t-wave alternans (TWA) in presence of indispensable physiological artifacts is still a challenging task, as in most of the cases, the signal of interest resides well below the noise levels. In this paper, a generalized detection theoretic framework (GDFT) is proposed for the detection and estimation of TWA from the stress test ECG signal. The analytical foundations, TWA signal modeling, and finally simulations of nine TWA detectors and estimators belonging to median match filtering, empirical mode decomposition (EMD) based match filtering, and generalized likelihood ratio test (GLRT) for GDTF are presented. GLRT schemes require noise statistics for parameter estimation and are computationally efficient. GLRT detectors outperform all the detectors including the benchmark spectral method by ≥ 2 dB for a broad spectrum of SNR ranging from -15 dB to 30 dB under Gaussian noise. EMD based strategies also outperform spectral method under Gaussian and Laplacian noise by ≥ 1 dB.

<p><strong>Background</strong></p> <p>T wave alternans (TWA) is an electrocardiographic marker of heightened sudden death risk from ventricular tachyarrhythmias in patients with cardiomyopathy. TWA is evaluated from the 12-lead electrocardiogram, Frank lead, or Holter lead recordings, however these clinical lead configurations will not record TWA from adjacent regions of the body torso.</p> <p><strong>Objective</strong></p> <p>We tested the hypothesis that changing heart rate or ventricular activation may alter the body surface distribution of TWA such that the clinical ECG leads fail to detect TWA in some patients; thereby producing a false-negative test.</p> <p><strong>Methods </strong></p> <p>In 28 cardiomyopathy patients (left ventricular ejection fraction 28±6%), 114 unipolar electrograms were recorded across the body torso during incremental atrial pacing, followed by atrioventricular pacing at 100, 110 and 120bpm. TWA was measured from each unipolar electrogram using the spectral method. A clinically positive TWA test was defined as TWA magnitude (Valt) ≥1.9 uV with k ≥3 at ≤ 110bpm.</p> <p><strong>Results </strong></p> <p>Maximum V<sub>alt</sub> (TWA<sub>max</sub>) was greater from the body torso than clinical leads during atrial (p<0.005) and atrioventricular pacing (p<0.005). TWA<sub>max</sub> was most prevalent in the right lower chest with atrial pacing 100 bpm and shifted to the left lower chest at 120 bpm. TWA<sub>max</sub> was most prevalent in left lower chest with atrioventricular pacing at 100 bpm and shifted to the left upper chest at 120 bpm. Using the body torso as a gold standard, the false-negative rate for clinically positive TWA with clinical leads was 21% during atrial and 11% duringatrioventricular pacing. Due to TWA signal migration outside the clinical leads, clinically positive TWA became false-negative when pacing mode was switched (atrial->atrioventricular pacing) in 21% of patients.</p> <p><strong>Conclusions</strong></p> <p>The body surface distribution of TWA is modulated by heart rate and the sequence of ventricular activation in patients with cardiomyopathy, which can give rise to modest false-negative TWA signal detection using standard clinical leads</p> <p><br></p>

HomeCirculationVol. 115, No. 1Letter by Selvaraj and Chauhan Regarding Article, “Upsurge in T-Wave Alternans and Nonalternating Repolarization Instability Precedes Spontaneous Initiation of Ventricular Tachyarrhythmias in Humans” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Selvaraj and Chauhan Regarding Article, “Upsurge in T-Wave Alternans and Nonalternating Repolarization Instability Precedes Spontaneous Initiation of Ventricular Tachyarrhythmias in Humans” Raja J. Selvaraj and Vijay S. Chauhan Raja J. SelvarajRaja J. Selvaraj Division of Cardiology, University Health Network, Toronto, Canada Search for more papers by this author and Vijay S. ChauhanVijay S. Chauhan Division of Cardiology, University Health Network, Toronto, Canada Search for more papers by this author Originally published2 Jan 2007https://doi.org/10.1161/CIRCULATIONAHA.106.650952Circulation. 2007;115:e9To the Editor:We read with interest the article by Shusterman et al1 concerning repolarization dynamics preceding spontaneous initiation of ventricular tachyarrhythmias in humans. Two related time-domain methods measured a larger magnitude of “alternans” at 30 minutes compared with 60 to 120 minutes preceding arrhythmia onset. Spectral analysis of T-wave amplitude showed a nonuniform increase in power in all frequency ranges. The authors interpret these findings as a surge in alternans and nonalternating repolarization complexity preceding the arrhythmia.An increase in sympathetic activity preceding the onset of ventricular arrhythmia was reported by the authors in the same population.2 This can lead to increased noise in the ECG recordings from perspiration and an increase in motion and respiratory artifact.3The modified moving average and, to a larger extent, the intrabeat average measurements are affected by noise that cannot be completely removed by preprocessing.3 Using these time-domain methods, the authors have previously emphasized the need to measure surrogate alternans in the isoelectric T end to P onset segment to show that an increase in T-wave alternans magnitude is not artifactually attributable to noise.3 It is unclear why the authors did not use a similar analysis of surrogate alternans in the present study1 to ensure that noise was not a confounder.Using the spectral method, white noise can spuriously increase the spectral power in the alternans frequency, and subtraction of the spectral power in a “noise band” is required to measure true alternans.4 Therefore, the increase in spectral power seen in all frequency ranges could be explained by an increase in noise rather than an increase in “nonalternating repolarization complexity.” The possibility of subharmonics influencing the measured power in the alternans range is another important confounder, particularly respiratory subharmonics (0.15 to 0.25 cpb), which increase in spectral power before the tachyarrhythmia. The authors feel the contribution of respiratory subharmonics is improbable because the increase in T-wave alternans magnitude has been confirmed by 3 independent methods. However, the concordant findings do not exclude the confounding effects of subharmonics, because these methods are all inherently influenced by subharmonics.3 Although the increase in alternans may not be accounted for entirely by respiratory subharmonics, this is likely an important contribution and is not unexpected, because respiratory excursions that influence T-wave amplitude can increase during sympathetic surges preceding tachyarrhythmia. Thus, we feel that white noise and respiratory oscillations may significantly contribute to the apparent increase in alternating and nonalternating repolarization instability.DisclosuresNone.1 Shusterman V, Goldberg A, London B. Upsurge in T-wave alternans and nonalternating repolarization instability precedes spontaneous initiation of ventricular tachyarrhythmias in humans. Circulation. 2006; 113: 2880–2887.LinkGoogle Scholar2 Shusterman V, Aysin B, Gottipaty V, Weiss R, Brode S, Schwartzman D, Anderson KP. Autonomic nervous system activity and the spontaneous initiation of ventricular tachycardia. ESVEM Investigators. Electrophysiologic Study Versus Electrocardiographic Monitoring Trial. J Am Coll Cardiol. 1998; 32: 1891–1899.CrossrefMedlineGoogle Scholar3 Shusterman V, Goldberg A. Tracking repolarization dynamics in real-life data. J Electrocardiol. 2004; 37 (suppl): 180–186.CrossrefMedlineGoogle Scholar4 Bloomfield DM, Hohnloser SH, Cohen RJ. Interpretation and classification of microvolt T wave alternans tests. J Cardiovasc Electrophysiol. 2002; 13: 502–512.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails January 2, 2007Vol 115, Issue 1 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.106.650952PMID: 17200449 Originally publishedJanuary 2, 2007 PDF download Advertisement SubjectsArrhythmias

B-PO03-162 MICROVOLT QRS ALTERNANS WITHOUT MICROVOLT T WAVE ALTERNANS IN HYPERTROPHIC CARDIOMYOPATHY: A NOVEL RISK MARKER OF LATE VENTRICULAR ARRHYTHMIAS

The analysis of t wave alternans (TWA) was introduced to identify patients with an increased risk of ventricular tachyarrhythmias. The inducibility of ventricular tachyarrhythmias and the spontaneous arrhythmic events are correlated with a positive TWA in patients with a reduced left ventricular ejection fraction and survived myocardial infarction. In contrast, this study is the first to investigate the correlation of a survived sudden cardiac death and TWA in patients without coronary heart disease and only slightly decreased left ventricular function. Sixty patients were included in the study. The TWA analysis was performed using the Cambridge Heart system (CH2000). Patients were sitting on a bicycle ergometer and exercised with a gradual increase of workload to maintain a heart rate of at least 105 beats/min. The exercise test was stopped after recording 254 consecutive low noise level heart beats. The electrocardiographic signals were digitally processed using a spectral analysis method. The magnitude of TWA was measured at a frequency of 0.5 cycles/beat. A TWA was defined as positive if the ratio between TWA and noise level was > 3.0 and the amplitude of the TWA was > 1.8 microV. Twelve (20%) of the included 60 patients showed a positive TWA. The sensitivity concerning a previous arrhythmic event amounted to 65%, the specificity up to 98%, respectively. The alternans ratio was significantly higher in patients with a previous event (30.3 +/- 53.2 vs 2.9 +/- 5.9, P < 0.001) and cumulative alternans voltage (4.67 +/- 3.55 vs 1.75 +/- 1.88 microV, P < 0.001). In 19 patients, invasively investigated by an electrophysiological study, a significant correlation between inducibility of tachyarrhythmias and a positive TWA result was found (Spearman R = 0.51, P = 0.01). In conclusion, the TWA analysis seems to identify patients with nonischemic cardiomyopathy who are at an increased risk of ventricular tachyarrhythmias.

Surge of T-Wave Alternans in the Absence of Heart-Rate Acceleration: A New Predictor of Sustained Ventricular Tachyarrhythmias in Patients with Low Ejection Fraction?

T-wave alternans (TWA) manifests as beat-to-beat fluctuations of T-wave morphology on the electrocardiogram (ECG), with physiological bases not fully understood. Using a biophysical model of the ECG, we demonstrate and give explicit relations that TWA depends on the i) spatial covariance between myocytes' repolarization time and alternans; and ii) global alternans (common to every myocyte). We quantified the spatial covariance and global alternans by means of two new metrics, R index and δ, respectively. They were validated on both synthetic and real signals. Computerized simulations were generated using a biophysical model linking the action potentials with the surface ECG. Then, the metrics were computed in STAFF-III dataset, containing ECGs from patients who underwent coronary angioplasty with prolonged balloon inflations, and the time courses of the metrics were analyzed together with TWA measured on the surface ECG. The metrics properly estimated the spatial covariance and global alternans in the synthetic data. In the STAFF-III dataset, the R index progressively increased from baseline to the fourth minute of inflation (median ∆R=0.81 ms; p 0.05), whereas δ was mostly unaltered during the intervention ( δ=0 ms). We reported, for the first time, that TWA is significantly driven by the myocyte's spatial covariance between their repolarization times and alternans, and not by global alternans, when TWA is generated by regional ischemia. The metrics may reveal new complementary insights into the mechanisms underlying TWA.

We present a nonparametric adaptive surrogate test that allows for the differentiation of statistically significant T-wave alternans (TWA) from alternating patterns that can be solely explained by the statistics of noise. The proposed test is based on estimating the distribution of noise-induced alternating patterns in a beat sequence from a set of surrogate data derived from repeated reshuffling of the original beat sequence. Thus, in assessing the significance of the observed alternating patterns in the data, no assumptions are made about the underlying noise distribution. In addition, since the distribution of noise-induced alternans magnitudes is calculated separately for each sequence of beats within the analysis window, the method is robust to data nonstationarities in both noise and TWA. The proposed surrogate method for rejecting noise was compared to the standard noise-rejection methods used with the spectral method (SM) and the modified moving average (MMA) techniques. Using a previously described realistic multilead model of TWA and real physiological noise, we demonstrate the proposed approach that reduces false TWA detections while maintaining a lower missed TWA detection, compared with all the other methods tested. A simple averaging-based TWA estimation algorithm was coupled with the surrogate significance testing and was evaluated on three public databases: the Normal Sinus Rhythm Database, the Chronic Heart Failure Database, and the Sudden Cardiac Death Database. Differences in TWA amplitudes between each database were evaluated at matched heart rate (HR) intervals from 40 to 120 beats per minute (BPM). Using the two-sample Kolmogorov-Smirnov test, we found that significant differences in TWA levels exist between each patient group at all decades of HRs. The most-marked difference was generally found at higher HRs, and the new technique resulted in a larger margin of separability between patient populations than when the SM or MMA were applied to the same data.

BackgroundUnlike T‐wave alternans (TWA), the relation between QRS alternans (QRSA) and ventricular arrhythmia (VA) risk has not been evaluated in hypertrophic cardiomyopathy (HCM). We assessed microvolt QRSA/TWA in relation to HCM risk factors and late VA outcomes in HCM.Methods and ResultsProspectively enrolled patients with HCM (n=130) with prophylactic implantable cardioverter‐defibrillators underwent digital 12‐lead ECG recordings during ventricular pacing (100–120 beats/min). QRSA/TWA was quantified using the spectral method. Patients were categorized as QRSA+ and/or TWA+ if sustained alternans was present in ≥2 precordial leads. The VA end point was appropriate implantable cardioverter‐defibrillator therapy over 5 years of follow‐up. QRSA+ and TWA+ occurred together in 28% of patients and alone in 7% and 7% of patients, respectively. QRSA magnitude increased with pacing rate (1.9±0.6 versus 6.2±2.0 µV; P=0.006). Left ventricular thickness was greater in QRSA+ than in QRSA− patients (22±7 versus 20±6 mm; P=0.035). Over 5 years follow‐up, 17% of patients had VA. The annual VA rate was greater in QRSA+ versus QRSA− patients (5.8% versus 2.0%; P=0.006), with the QRSA+/TWA− subgroup having the greatest rate (13.3% versus 2.6%; P<0.001). In those with <2 risk factors, QRSA− patients had a low annual VA rate compared QRSA+ patients (0.58% versus 7.1%; P=0.001). Separate Cox models revealed QRSA+ (hazard ratio [HR], 2.9 [95% CI, 1.2–7.0]; P=0.019) and QRSA+/TWA− (HR, 7.9 [95% CI, 2.9–21.7]; P<0.001) as the most significant VA predictors. TWA and HCM risk factors did not predict VA.ConclusionsIn HCM, microvolt QRSA is a novel, rate‐dependent phenomenon that can exist without TWA and is associated with greater left ventricular thickness. QRSA increases VA risk 3‐fold in all patients, whereas the absence of QRSA confers low VA risk in patients with <2 risk factors.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02560844.

Latent microvolt T-wave alternans in survivors of unexplained cardiac arrest unmasked by epinephrine challenge

Exercise recordings for the detection of T wave alternans: Promises and pitfalls

T-wave alternans (TWA) in electrocardiogram (ECG) is associated with an increasing propensity to ventricular arrhythmic and is regarded as an independent indicator of sudden cardiac death (SCD). Various methods have been proposed to detect and quantify TWA in recent years, however, less attention was paid on the pretreatment stage before the final decision step. A detector with spectral method (SM) using multi-pretreatment was designed to detect TWA in this paper. It was tested with ECGs in the PhysioNet database, and the testing results showed that this improved system was effective to obtain enhanced detection results in comparison of ordinary methods in three aspects.

Microvolt-level T-wave alternans (TWA) assessed by spectral method during an exercise stress test has been widely studied for risk stratification. Several studies have documented the association of a positive TWA with total mortality and arrhythmic events. Nevertheless, the need to achieve an elevated and stabilized heart rate resulting in a considerable proportion of indeterminate test results constitutes one of the main limitations of this method. It is well recognized that arrhythmic events may be triggered not only by physical but also by mental stress and are not necessarily associated with exercise. Detection of TWA in ambulatory electrocardiogram recordings during daily activities might be a valuable option in risk stratification. This review describes the modified moving average (MMA) technique for detection of TWA and summarizes the results of clinical studies on the prognostic value of MMA-TWA. So far, MMA-TWA has been studied in over 5000 patients including those evaluated during exercise as well as during daily activities with ambulatory ECG recordings. The results of these studies indicate that increased MMA-TWA is associated with higher risk of cardiac mortality and arrhythmic events.

T-wave alternans (TWA) allows for identification of patients at an increased risk of ventricular arrhythmia. Stress test, which increases heart rate in controlled manner, is used for TWA measurement. However, the TWA detection and analysis are often disturbed by muscular interference. The evaluation of wavelet based denoising methods was performed to find optimal algorithm for TWA analysis. ECG signals recorded in twelve patients with cardiac disease were analyzed. In seven of them significant T-wave alternans magnitude was detected. The application of wavelet based denoising method in the pre-processing stage increases the T-wave alternans magnitude as well as the number of BSPM signals where TWA was detected. Keywords: T-wave alternans, wavelet denoising, stress test, arrhythmia, sudden cardiac death

Repolarization alternans is related to the initiation of life threatening cardiac arrhythmias. Experimental and computational studies suggest that the abolishment of alternans using dynamic pacing protocols may prevent abnormal heart rhythms. In a recent animal study, refractory period pacing (RPP) on every other beat has shown promising results in alternans reduction. However, the cellular mechanisms underlying this therapy and its efficiency in human patients remain unclear. In this study, in vivo unipolar electrograms acquired during RPP from 240 epicardial sites from one patient were analysed. Current clamp of 18 channels was performed in silico to elucidate the ionic mechanisms underlying action potential modulation by RPP. Its efficacy with positive and negative polarities was tested on a population of 87 calibrated human ventricular models exhibiting alternans. In vivo electrograms showed significant changes in T-wave alternans when applying RPP. In silico, results showed APD shortening for RPP with positive polarity and APD prolongation with RPP negative. Under current clamp protocols, voltage rectification of L-type Ca2+ (ICaL) and inward rectifier K+ (IK1) currents were identified as the key determinants for the observed changes. RPP pacing successfully reduced alternans on the in silico models using a negative polarity stimulus in the short beat.