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Purpose: Drug-induced type I Brugada syndrome (BrS) is associated with a ventricular arrhythmia (VA) rate of 1 case per 100 person-years. This study aims to evaluate changes in electrocardiographic (ECG) parameters such as microvolt T wave alternans (mTWA) and heart rate variability (HRV) at baseline and during ajmaline testing for BrS diagnosis. Methods: Consecutive patients diagnosed with BrS during ajmaline testing with 5-year follow-up were included in this study. For comparison, a negative ajmaline control group and an isoproterenol control group were also included. ECG recordings during ajmaline or isoproterenol test were divided in two timeframes from which ECG parameters were calculated: a 5-min baseline timeframe and a 5-min drug timeframe. Results: A total of 308 patients with BrS were included, 22 (0.7%) of which suffered VAs during follow-up. One hundred patients were included in both isoproterenol and negative ajmaline control groups. At baseline, there was no difference in ECG parameters betweencontrol groups and patients with BrS, nor between BrS with and without VAs. During ajmaline testing, BrS with VAs presented longer QRS duration [159 ± 34 ms versus 138 (122–155) ms, p = 0.006], higher maximum mTWA [33.8 (14.0–114) µV versus 8.00 (3.67–28.2) µV, p = 0.001], and lower power in low frequency band [25.6 (5.8–53.8) ms 2 versus 129.5 (52.7–286) ms 2, p < 0.0001] when compared to BrS without VAs. Conclusions: Ajmaline induced important HRV changes similar to those observed during isoproterenol. Increased mTWA was observed only in patients with BrS. BrS with VAs during follow-up presented worse changes during ajmaline test, including lower LF power and higher maximum mTWA which were independent predictors of events.

Prevention of premature death in patients with chronic epilepsy remains a major challenge. Multiple pathophysiologic factors have been implicated, with intense investigation of cardiorespiratory mechanisms. Up to four in five patients with chronic epilepsy exhibit cardiovascular comorbidities. These findings led us to propose the concept of an "epileptic heart," defined as "a heart and coronary vasculature damaged by chronic epilepsy as a result of repeated surges in catecholamines and hypoxemia leading to electrical and mechanical dysfunction." Among the most prominent changes documented in the literature are high incidence of myocardial infarction and arrhythmia, altered autonomic tone, diastolic dysfunction, hyperlipidemia, and accelerated atherosclerosis. This suite of pathologic changes prompted us to propose for the first time in this review a syndromic approach for improved clinical detection of the epileptic heart condition. In this review, we discuss the key pathophysiologic mechanisms underlying the candidate criteria along with standard and novel techniques that permit evaluation of each of these factors. Specifically, we present evidence of the utility of standard 12-lead, ambulatory, and multiday patch-based electrocardiograms, along with measures of cardiac electrical instability, including T-wave alternans, heart rate variability to detect altered autonomic tone, echocardiography to detect diastolic dysfunction, and plasma biomarkers for assessing hyperlipidemia and accelerated atherosclerosis. Ultimately, the proposed clinical syndromic approach is intended to improve monitoring and evaluation of cardiac risk in patients with chronic epilepsy to foster improved therapeutic strategies to reduce premature cardiac death.

Patients with heart failure with reduced left ventricular ejection fraction (LVEF) (HFrEF) experience long-term deterioration of autonomic function and cardiac electrical stability linked to increased mortality risk. The Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Heart Failure (ANTHEM-HF) trial reported improved heart rate variability (HRV) and heart rate turbulence (HRT) and reduced T-wave alternans (TWA) after 12 months of vagus nerve stimulation (VNS). We investigated whether the benefits of chronic VNS persist in the long term.Effects of chronic VNS on heart rate, HRV, HRT, TWA, R-wave and T-wave heterogeneity (RWH, TWH), and nonsustained ventricular tachycardia (NSVT) incidence were evaluated in all ANTHEM-HF patients with ambulatory ECG data at 24 and 36 months (n = 25). Autonomic markers improved significantly at 24 and 36 months compared to baseline [heart rate, square root of the mean squared differences of successive normal-to-normal intervals (rMSSD), standard deviation of the normal-to-normal intervals (SDNN), HF-HRV, HRT slope, P0.05]. Peak TWA levels remained reduced at 24 and 36 months (P0.0001). Reductions in RWH and TWH at 6 and 12 months persisted at 24 and 36 months (P0.01). NSVT decreased at 12, 24, and 36 months (P0.025). No sudden cardiac deaths, ventricular fibrillation, or sustained ventricular tachycardia occurred.In symptomatic patients with HFrEF, chronic VNS appears to confer wide-ranging, persistent improvements in autonomic tone (HRV), baroreceptor sensitivity (HRT), and cardiac electrical stability (TWA, RWH, TWH).

BackgroundThe utility of T wave alternans (TWA) in identifying arrhythmia risk has been demonstrated. During myocardial ischemia (MI), TWA could be induced by cellular alternans. However, the relationship between cellular alternans patterns and TWA patterns in MI has not been investigated thoroughly. MethodsWe set MI conditions to simulate alternans. Either prolonging Ca2+ release or increasing spark-induced sparks (secondary sparks) can give rise to different patterns of APD alternans and TWA. In addition, different ischemic zones and reduced conduction velocity are also considered in one dimensional simulation. ResultsDelay of Ca2+ release can produce discordant Ca2+-driven alternans in single cell simulation. Increasing secondary sparks leads to concordant alternans. Correspondingly, morphology and magnitude of TWA vary in two different cellular alternans. Epi ischemia results in alternans concentrating in the first half of T wave. Endo and transmural ischemia lead to fluctuations in the second half of T wave. In addition, slowing conduction velocity has no effect on TWA magnitude. ConclusionSpecific ionic channel dysfunction and ischemic zones affect TWA patterns.

Background Early during the current coronavirus disease 19 (COVID-19) pandemic, hydroxychloroquine (HCQ) received a significant amount of attention as a potential antiviral treatment, such that it became one of the most commonly prescribed medications for COVID-19 patients. However, not only has the effectiveness of HCQ remained questionable, but mainly based on preclinical and a few small clinical studies, HCQ is known to be potentially arrhythmogenic, especially as a result of QT prolongation. Objective The purpose of this study was to investigate the arrhythmic effects of HCQ, as the heightened risk is especially relevant to COVID-19 patients, who are at higher risk for cardiac complications and arrhythmias at baseline. Methods An optical mapping technique utilizing voltage-sensitive fluorescent dyes was used to determine the arrhythmic effects of HCQ in ex vivo guinea pig and rabbit hearts perfused with the upper therapeutic serum dose of HCQ (1000 ng/mL). Results HCQ markedly increased action potential dispersion, resulted in development of repolarization alternans, and initiated polymorphic ventricular tachycardia. Conclusion The study results further highlight the proarrhythmic effects of HCQ.

Macroscopic T-wave alternans (TWA) is the beat-to-beat variation in the amplitude or shape of the T wave on a surface electrocardiogram (ECG) and known to be a harbinger of impending malignant ventricular arrhythmias such as polymorphic ventricular tachycardia. We herein report a case with hepatic encephalopathy, who developed TWA, followed by polymorphic ventricular tachycardia.

Heterogeneity in depolarization and repolarization among regions of cardiac cells has long been recognized as a major factor in cardiac arrhythmogenesis. This fundamental principle has motivated development of noninvasive techniques for quantification of heterogeneity using the surface electrocardiogram (ECG). The initial approaches focused on interval analysis such as interlead QT dispersion and Tpeak–Tend difference. However, because of inherent difficulties in measuring the termination point of the T wave and commonly encountered irregularities in the apex of the T wave, additional techniques have been pursued. The newer methods incorporate assessment of the entire morphology of the T wave and in some cases of the R wave as well. This goal has been accomplished using a number of promising vectorial approaches with the resting 12‐lead ECG. An important limitation of vectorcardiographic analyses is that they require exquisite stability of the recordings and are not inherently suitable for use in exercise tolerance testing (ETT) and/or ambulatory ECG monitoring for provocative stress testing or evaluation of the influence of daily activities on cardiac electrical instability. The objectives of the present review are to describe a technique that has been under clinical evaluation for nearly a decade, termed “interlead ECG heterogeneity.” Preclinical testing data will be briefly reviewed. We will discuss the main clinical findings with regard to sudden cardiac death risk stratification, heart failure evaluation, and myocardial ischemia detection using standard recording platforms including resting 12‐lead ECG, ambulatory ECG monitoring, ETT, and pharmacologic stress testing in conjunction with single‐photon emission computed tomography myocardial perfusion imaging.

Summary Some patients with hypertrophic cardiomyopathy (HCM) are at significant risk of premature sudden death. Identification of the risk factors may enable effective prevention of adverse cardiac events in these patients. Assessment of the microvolt T-wave alternans (MTWA) is a recognized non-invasive diagnostic test used in risk stratification of sudden cardiac death (SCD). However, the number of reports on the frequency of occurrence of MTWA in HCM is small. Aim: Evaluation of the prognostic value of MTWA in predicting the risk of arrhythmic events (sudden cardiac death, documented VT/VF, appropriate ICD discharge) in patients with HCM. Material and methods 122 patients with HCM underwent detailed clinical assessment and ECG- and echocardiographic examination. They underwent 24-hour ambulatory ECG monitoring, and the following elements were analysed: 1) arrhythmias, 2) heart rate variability (HRV) and the QT segment, 3) the presence of ventricular late potentials (LP), 4) heart rate turbulence (HRT). MTWA assessment was made during a test on a treadmill (Cambridge Heart). In accordance with the adopted criteria, the test was interpreted as negative, positive or indeterminate. Subsequently, positive and indeterminate results were described collectively as MTWA(+) and negative results as MTWA(−). Then the patients were divided into two groups: Group 1 – 57 patients (46,7%) with MTWA(−), and Group 2 – 65 patients (53,2%) with MTWA(+). In order to stratify the risk, the following were adopted as composite primary endpoints: sudden cardiac death or hospitalization for life-threatening arrhythmias (VT/VF), and appropriate ICD discharge. Results The mean follow-up period of the patients was 57±8 months; during that time, events that met the criteria for the endpoint occurred in 16 patients. On the basis of univariate analysis, 10 variables with a significant influence on the occurrence of an event were selected (unexplained syncope, NT-proBNP values elevated above 411 pg/ml, size of the left atrium over 44mm, diastolic thickness of the interventricular septum over 25 mm, the presence of MTWA(+), the QRS width >90 msec, QTc >467 msec, QTd >70 msec, SDNN Conclusions 1) Patients with hypertrophic cardiomyopathy had a significant percentage of positive results of the microvolt T-wave alternans test (MTWA+), 2) Positive MTWA test result in patients with hypertrophic cardiomyopathy can help to identify patients at risk of sudden cardiac death. Funding Acknowledgement Type of funding sources: None.

Absztrakt: Akut légzési elégtelenség miatt felvett 70 éves férfi betegnél a felvételi EKG pitvari tachycardiát és makro-T-hullám-alternánst mutatott, amely a sinusrhythmus helyreállása után megszűnt. Az EKG-jelenséget sem QT-megnyúlás, sem heveny ischaemia nem kísérte. Az eset arra hívja fel a figyelmet, hogy makro-T-hullám-alternáns jelentkezhet pitvari tachycardia következtében is, amely esetünkben akut respiratoricus insufficientia miatt lépett fel. Orv Hetil. 2020; 161(7): 275–277.

Microvolt T-wave alternans (MTWA), which reflects electrical dispersion of repolarization, is known to be associated with arrhythmia or sudden cardiac death in high risk patients. In this study we investigated the relationship between MTWA and postoperative mortality in 330 cardiac surgery patients. Electrocardiogram, official national data and electric chart were analysed to provide in-hospital and mid-term outcome. MTWA at the end of surgery was significantly associated with in-hospital mortality in both univariate analysis (OR = 27.378, 95% CI 5.616–133.466, p

Introduction Several noninvasive risk factors for ventricular arrhythmias have been described in postmyocardial infarction (MI) patients, whose relationships with scar characteristics and modifications by ablation are unknown. Methods Twenty-two patients with previous MI referred for ventricular tachycardia ablation were prospectively included. ECG, heart rate variability (HRV), signal-averaged ECG (SA-ECG), and T wave alternans (TWA) were performed before and after radiofrequency ablation. Scar areas were correlated to preablation parameters. Pre and postablation parameters were furthermore compared. Results Left ventricular ejection fraction and some spectral and time-domain HRV parameters were significantly correlated to the scar areas. QRS duration was larger after vs before ablation (120 ± 29 vs 105 ± 22 msec, P = .01). No significant modification in time or spectral domain of HRV was observed. There was no significant change in TWA and SA-ECG before and after ablation. Borderline decreases in quantitative TWA parameters were noted in patients with positive TWA and successful ablation procedure. Conclusion Some noninvasive risk factors were linked to the scar areas, but few were significantly modified after ablation. Larger populations are needed to demonstrate significant differences or correlations.

Background: The long-term predicted value of microvolt T-wave alternans (MTWA) for ventricular tachyarrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains unclear. Our study explored the characteristics of MTWA and its prognostic value when combined with an electrophysiologic study (EPS) in patients with ARVC. Methods: All patients underwent non-invasive MTWA examination with modified moving average (MMA) analysis and an EPS. A positive event was defined as the first occurrence of sudden cardiac death, documented sustained ventricular tachycardia (VT), ventricular fibrillation, or the administration of appropriate implantable cardioverter defibrillator therapy including shock or antitachycardia pacing. Results: Thirty-five patients with ARVC (age 38.6 ± 11.0 years; 28 males) with preserved left ventricular (LV) function were recruited. The maximal TWA value (MaxValt) was 17.0 (11.0–27.0) μV. Sustained VT was induced in 22 patients by the EPS. During a median follow-up of 99.9 ± 7.7 months, 15 patients had positive clinical events. When inducible VT was combined with the MaxValt, the area under the curve improved from 0.739 to 0.797. The receiver operating characteristic curve showed that a MaxValt of 23.5 μV was the optimal cutoff value to identify positive events. The multivariate Cox regression model for survival showed that MTWA (MaxValt, hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01–1.11; P = 0.01) and inducible VT (HR, 5.98; 95% CI, 1.33–26.8; P = 0.01) independently predicted positive events in patients with ARVC. Conclusions: MTWA assessment with MMA analysis complemented by an EPS might provide improved prognostic ability in patients with ARVC with preserved LV function during long-term follow-up. Key words: Modified moving average analysis; Microvolt T-wave alternans; Electrophysiologic study; Ventricular tachyarrhythmia; Arrhythmogenic right ventricular cardiomyopathy

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 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.

T-wave alternans (TWA) reflects every-other-beat alterations in the morphology of the electrocardiogram ST segment or T wave in the setting of a constant heart rate, hence, in the absence of heart rate variability. It is believed to be associated with the dispersion of repolarization and has been used as a non-invasive marker for predicting the risk of malignant cardiac arrhythmias and sudden cardiac death as numerous studies have shown. This review aims to provide up-to-date review on both experimental and simulation studies in elucidating possible mechanisms underlying the genesis of TWA at the cellular level, as well as the genesis of spatially concordant/discordant alternans at the tissue level, and their transition to cardiac arrhythmia. Recent progress and future perspectives in antiarrhythmic therapies associated with TWA are also discussed.

Objective. High morphological variability magnitude (MVM) and microvolt T wave alternans (TWA) within an electrocardiogram (ECG) signifies increased electrical instability and risk of sudden cardiac death. However, the influence of breathing rate (BR), heart rate (HR), and signal-to-noise ratio (SNR) is unknown and may inflate measured values. Approach. We synthesize ECGs with morphologies derived from the Physikalisch-Technische Bundesanstalt Database. We calculate MVM and TWA at varying BRs, HRs and SNRs. We compare the MVM and TWA of signal with versus without breathing at varying HRs and SNRs. We then quantify the percentage of MVM and TWA estimates affected by BR and HR in a healthy population and assess the effect of removing these affected estimates on a method for classifying individuals with and without post-traumatic stress disorder (PTSD). Main results. For signals with high SNR (>15 dB), MVM is significantly increased when BRs are > 9 respirations/minute (rpm) and HRs are < 100 beats/minute (bpm). Increased TWAs are detected for HR/BR pairs of 60/15, 60/30 and 120/30 bpm/rpm. For 18 healthy participants, 8.33% of TWA windows and 66.76% of MVM windows are affected by BR and HR. On average, the number of windows with TWA elevations > 47 μV decreases by 23% after excluding regions with significant BR and HR effect. Adding HR and BR to a morphological variability feature increases the classification performance by 6% for individuals with and without PTSD. Significance. Physiological BR and HR significantly increase MVM and TWA , indicating that BR and HR should be considered separately as confounders. The code for this work has been released as part of an open-source toolbox.

Prolonged heart rate-corrected QT (QTc) interval is an independent risk factor for sudden cardiac death, which is the hallmark of Timothy syndrome (TS). There are little data on children with syndactyly and QTc prolongation. To evaluate the characteristics and long-term outcomes in children with syndactyly, and to attempt to identify TS in patients with syndactyly and QTc prolongation. This is a retrospective case-control study of children with syndactyly who visited Beijing Jishuitan Hospital between July 2003 and February 2013. The patients with prolonged QTc intervals are matched 1:4 with patients without prolongation. Genetic testing of the CACNA1C gene is routinely performed in patients with QTc prolongation. The mean age at admission is 3.4 ± 2.3 years. Compared with the normal QTc group, those with QTc prolongation showed higher frequencies of congenital heart disease (11.8% vs 1.5%, P = .042), mental retardation and facial dysmorphia (11.8% vs 0, P = .004), and T wave alternans (23.5% vs 4.4%, P = .01). In the multivariable analysis, only T wave alternans (OR = 10.61, 95%CI: 1.39–81.16, P = .023) is independently associated with QTc prolongation in patients with syndactyly. One child with QTc prolongation had a mutation in the CACNA1C gene. No patients with prolonged QTs interval met the threshold for TS. Children with syndactyly and prolonged QTc interval had more multisystem diseases and electrocardiography abnormalities. T wave alternans is independently associated with QTc prolongation in patients with syndactyly.

The fetal electrocardiogram (FECG) is the recording of the electrical activity of the fetal heart. Morphologically, FECG shows the standard P-QRS-TU electrocardiographic pattern and a heart rate (HR) of 120–160 bpm. There are two techniques to acquire FECG: the direct one (DI-FECG), with a spiral wire electrode located on the fetal scalp; and the indirect one (IN-FECG), with electrodes located on the mother’s abdomen. Fetal T-wave alternans (TWA) represents a possible cause of unexplained fetal deaths; its investigation, however, is challenging. This chapter discusses about this scientific and clinical problem, and proposes a procedure to identify TWA from both DI-FECG and IN-FECG. The procedure includes the following 3 steps: (1) automatic identification of fetal R peaks, performed through the improved fetal Pan-Tompkins Algorithm; (2) FECG filtering, performed through linear filtering and the segmented-beat modulation method; and (3) automatic TWA identification, performed through the heart-rate adaptive match filter. Application of this procedure to 5 DI-FECG and 20 IN-FECG from 5 fetuses confirmed its goodness for fetal applications and suggested that fetuses show TWA even when healthy. Moreover, TWA detected in DI-FECG was comparable to that in IN-FECG, suggesting that TWA identification was reliable also in IN-FECG, which is much more affected by artifacts and interferences than DI-FECG.

Objective This study was conducted to assess the incidence of sudden cardiac death (SCD) in post myocardial infarction patients and to determine the predictive value of various risk markers in identifying cardiac mortality and SCD. Methods Left ventricular function, arrhythmias on Holter and microvolt T wave alternans (MTWA) were assessed in patients with prior myocardial infarction and ejection fraction ≤ 40%. The primary outcome was a composite of cardiac death and resuscitated cardiac arrest during follow up. Secondary outcomes included total mortality and SCD. Results Fifty-eight patients were included in the study. Eight patients (15.5%) died during a mean follow-up of 22.3 ± 6.6 months. Seven of them (12.1%) had SCD. Among the various risk markers studied, left ventricular ejection fraction (LVEF) ≤ 30% (Hazard ratio 5.6, 95% CI 1.39 to 23) and non-sustained ventricular tachycardia (NSVT) in holter (5.7, 95% CI 1.14 to 29) were significantly associated with the primary outcome in multivariate analysis. Other measures, including QRS width, heart rate variability, heart rate turbulence and MTWA showed no association. Conclusions Among patients with prior myocardial infarction and reduced left ventricular function, the rate of cardiac death was substantial, with most of these being sudden cardiac death. Both LVEF ≤30% and NSVT were associated with cardiac death whereas only LVEF predicted SCD. Other parameters did not appear useful for prediction of events in these patients. These findings have implications for decision making for the use of implantable cardioverter defibrillators for primary prevention in these patients.

Background Action potential alternans can induce ventricular tachyarrhythmias and manifest on the surface ECG as T‐wave alternans (TWA) and QRS alternans (QRSA). We sought to evaluate microvolt QRSA in cardiomyopathy patients in relation to TWA and ventricular tachyarrhythmia outcomes. Methods and Results Prospectively enrolled cardiomyopathy patients (n=100) with prophylactic defibrillators had 12‐lead ECGs recorded during ventricular pacing from 100 to 120 beats/min. QRSA and TWA were quantified in moving 128‐beat segments using the spectral method. Segments were categorized as QRSA positive (QRSA+) and/or TWA positive (TWA+) based on ≥2 precordial leads having alternans magnitude >0 and signal:noise >3. Patients were similarly categorized based on having ≥3 consecutive segments with alternans. TWA+ and QRSA+ occurred together in 31% of patients and alone in 18% and 14% of patients, respectively. Although TWA magnitude (1.4±0.4 versus 4.7±1.0 µV, P P P P =0.02) but similar in TWA+ and TWA‐negative patients. Among QRSA+ patients, the event rate was greater in those without TWA (62% versus 21%, P =0.02). Multivariable Cox analysis revealed QRSA+ (hazard ratio [HR], 4.6; 95% CI, 1.5–14; P =0.009) and QRS duration >120 ms (HR, 4.1; 95% CI, 1.3–12; P =0.014) to predict events. Conclusions Microvolt QRSA is novel phenomenon in cardiomyopathy patients that can exist without TWA and is associated with QRS prolongation. QRSA increases the risk of ventricular tachyarrhythmia 4‐fold, which merits further study as a risk stratifier.

During the last years, attention and controversy have been present for the first commercially available equipment being used in Electrocardiographic Imaging (ECGI), a new cardiac diagnostic tool which opens up a new field of diagnostic possibilities. Previous knowledge and criteria of cardiologists using intracardiac Electrograms (EGM) should be revisited from the newly available spatial&ndash, temporal potentials, and digital signal processing should be readapted to this new data structure. Aiming to contribute to the usefulness of ECGI recordings in the current knowledge and methods of cardiac electrophysiology, we previously presented two results: First, spatial consistency can be observed even for very basic cardiac signal processing stages (such as baseline wander and low-pass filtering), second, useful bipolar EGMs can be obtained by a digital processing operator searching for the maximum amplitude and including a time delay. In addition, this work aims to demonstrate the functionality of ECGI for cardiac electrophysiology from a twofold view, namely, through the analysis of the EGM waveforms, and by studying the ventricular repolarization properties. The former is scrutinized in terms of the clustering properties of the unipolar an bipolar EGM waveforms, in control and myocardial infarction subjects, and the latter is analyzed using the properties of T-wave alternans (TWA) in control and in Long-QT syndrome (LQTS) example subjects. Clustered regions of the EGMs were spatially consistent and congruent with the presence of infarcted tissue in unipolar EGMs, and bipolar EGMs with adequate signal processing operators hold this consistency and yielded a larger, yet moderate, number of spatial&ndash, temporal regions. TWA was not present in control compared with an LQTS subject in terms of the estimated alternans amplitude from the unipolar EGMs, however, higher spatial&ndash, temporal variation was present in LQTS torso and epicardium measurements, which was consistent through three different methods of alternans estimation. We conclude that spatial&ndash, temporal analysis of EGMs in ECGI will pave the way towards enhanced usefulness in the clinical practice, so that atomic signal processing approach should be conveniently revisited to be able to deal with the great amount of information that ECGI conveys for the clinician.

This paper presents the modeling approach artificial electrocardiograms (ECG) with T -wave alternans based on extracted parameters from the T -wave alternas (TWA) database. The developed optimal TWA classification system was evaluated by signals from a mixed database, which consisted of the TWA database and artificial ECG modeled records. F1-score about 95,9 % was received for the Random Forest Classifier (RFC) and Sequential Forward Floating Feature Selection method. Using a wrapper method for feature selection, 14 significant features were selected that associate with TWA.

Background: Major adverse cardiovascular events (MACE) constitutes the main cause of morbidity and mortality in ischemic heart failure (HF) patients. The prognostic value of the autonomic nervous system (ANS) parameters and microvolt T-wave alternans (MTWA) in this issue has not been identified to date. The aim herein, was to assess the usefulness of the abovementioned parameters in the prediction of MACE in HF patients with left ventricular systolic dysfunction of ischemic origin. Methods: Baroreflex sensitivity (BRS), heart rate variability (HRV), MTWA and other well-known clinical parameters were analyzed in 188 ischemic HF outpatients with left ventricular ejection fraction (LVEF) ≤ 50%. During 34 (14–71) months of follow-up, 56 (30%) endpoints were noted. Results: Univariate Cox analyses revealed BRS (but not HRV), MTWA, age, New York Heart Association III, LVEF, implantable cardioverter-defibrillator presence, use of diuretics and antiarrhythmic drugs, diabetes, and kidney insufficiency were defined as significant predictors of MACE. Pre-specified cut-off values for MACE occurrence for the aforementioned continuous parameters (age, LVEF, and BRS) were: ≥ 72 years, ≤ 33%, and ≤ 3 ms/mmHg, respectively. In a multivariate Cox analysis only BRS (HR 2.97, 95% CI 1.35–6.36, p < 0.006), and LVEF (HR 1.98, 95% CI 0.61–4.52, p < 0.038) maintained statistical significance in the prediction of MACE. Conclusions: BRS and LVEF are independent of other well-known clinical parameters in the prediction of MACE in patients with HF of ischemic origin and LVEF up to 50%. BRS ≤ 3 ms/mmHg and LVEF ≤ 33% identified individuals with the highest probability of MACE during the follow-up period.

Background Sudden infant death syndrome is more frequent in preterm infants (PTI) than term infants and may be due to cardiac repolarization instability, which may manifest as T-wave alternans (TWA) on the electrocardiogram (ECG). Therefore, the aim of the present work was to analyze TWA in nonpathological PTI and to open an issue on its physiological interpretation. Methods Clinical population consisted of ten nonpathological PTI (gestational age ranging from 29 3 7 to 34 2 7 weeks; birth weight ranging from 0.84 to 2.10 kg) from whom ECG recordings were obtained ("Preterm infant cardio-respiratory signals database" by Physionet). TWA was identified through the heart-rate adapting match filter method and characterized in terms of mean amplitude values (TWAA). TWA correlation with several other clinical and ECG features, among which gestational age-birth weight ratio, RR interval, heart-rate variability, and QT interval, was also performed. Results TWA was variable among infants (TWAA = 26 ± 11 µV). Significant correlations were found between TWAA versus birth weight (ρ = -0.72, p = .02), TWAA versus gestational age-birth weight ratio (ρ = 0.76, p = .02) and TWAA versus heart-rate variability (ρ = -0.71, p = .02). Conclusions Our preliminary retrospective study suggests that nonpathological PTI show TWA of few tens of µV, the interpretation of which is still an open issue but could indicate a condition of cardiac risk possibly related to the low development status of the infant. Further investigations are needed to solve this issue.

Dofetilide is an antiarrhythmic drug that selectively inhibits the rapid component of the delayed rectifier potassium current. The administration of dofetilide may cause ventricular arrhythmias and torsade de pointes. Electrocardiographic (ECG) microvolt T-wave alternans (TWA), an electrophysiologic phenomenon consisting in the beat-to-beat alternation of the T-wave amplitude requiring computerized algorithms to be detected, has also been associated to malignant ventricular arrhythmias. Aim of the present study was to evaluate if dofetilide induces TWA during the 24 hours following administration. The study population consisted of 22 healthy subjects ("ECG Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects" database by Physionet) to whom a 500 μg-dose of dofetilide was administered. For each subject, 10 s ECG were acquired at baseline (0.5 hour before dofetilide administration) and at 15 time points during the 24 hours following the drug administration. ECG were then processed for automatic TWA detection by correlation method. In 21 subjects out of 22, after dofetilide administration, TWA significantly increased to a peak value (median TWA values went from 6 μV at baseline to a max 32 μV; p; 0.05), on average after 5 hours, to then come back to values closer to baseline. Thus, in healthy subjects, dofetilide increases occurrence and levels (6 times baseline value on average) of TWA in the hours following its administration.

Although the standard ECG provides substantial information on cardiac electrical activity, it fails to record signals in the microvolt range. Signal averaging technique enables recording and identification of low amplitude signals by improving the signal-to-noise ratio. Thus, the signal-averaged ECG (SAECG) was initially used for noninvasive recording of His bundle potential and subsequently to detect “late potentials” (LPs) for risk assessment for sudden cardiac death (SCD) and/or VT in various clinical settings. However, the initial enthusiasm for the SAECG waned following the results of the MADIT-II Trial that opted the use of ejection fraction (EF) as the main risk stratifying modality. In this chapter, the role of the SAECG in other conditions such as infiltrative heart disease, right ventricular dysplasia, evaluation of syncope, tetralogy of Fallot-associated VT, the Brugada syndrome, post-ablation of VT, and atrial fibrillation is discussed.

Identification of individuals at risk for sudden cardiac death (SCD), the primary cause of adult mortality in industrially developed countries, persists as a major challenge. The main contemporary noninvasive marker, left ventricular ejection fraction (LVEF), has not proved adequately reliable, as the majority of individuals who succumb to SCD have relatively preserved LVEF. Monitoring of T-wave alternans (TWA), a beat-to-beat fluctuation in ST-segment or T-wave morphology, on ambulatory electrocardiogram is an attractive approach on both scientific and clinical grounds. Specifically, TWA's capacity to assess risk for life-threatening ventricular arrhythmias has been shown to rest on sound electrophysiologic principles, and TWA monitoring can be carried out during the conduct of routine clinical evaluation. This review (1) summarizes briefly the electrophysiology basis for TWA's predictive capacity and the underlying physiologic factors that influence its level; (2) discusses the contemporary methodologies and clinical evidence supporting TWA's predictive value; and (3) reviews available evidence indicating potential sex-related differences in this phenomenon.

A 42-year-old woman presented with fever, dyspnea, lower-leg edema, significant pulmonary congestion, pleural effusion, and severely reduced left ventricular contractions. She was resistant to treatment for heart failure, including catecholamines, furosemide, phosphodiesterase III inhibitors, and human atrial natriuretic peptide, and antibiotics failed to reduce her inflammation. She had renal dysfunction and hypocomplementemia and was positive for anti-nuclear and anti-ds-DNA antibodies. The patient was diagnosed with myocarditis and pleurisy associated with systemic lupus erythematosus (SLE). Prednisolone administration improved her general condition, reducing inflammation and improving left ventricular function. On day 1, an electrocardiography (ECG) revealed a T-wave inversion similar to a T-U complex configuration in leads II, aVF, and V3-6. By day 8, however, ECG showed prolonged corrected QT (QTc) and T-wave alternans (alternating beat-to-beat T-wave patterns) in lead V3-6. Careful ECG monitoring should be used to identify potentially fatal ventricular arrhythmias during the recovery phase of SLE-related myocarditis. .