T-wave Alternans Research Articles

Microvolt T-wave alternans complemented with electrophysiologic study for prediction of ventricular tachyarrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy: a long-term follow-up study.

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 anti-tachycardia 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.

An Efficient and Robust Digital Fractional Order Differentiator Based ECG Pre-Processor Design for QRS Detection.

This paper presents an efficient infinite impulse response type digital fractional order differentiator (DFOD) based electrocardiogram (ECG) pre-processor to detect QRS complexes. First, an efficient optimizer namely, Antlion optimization algorithm is employed to solve the proposed DFOD design problem. Then, the designed DFOD is deployed in the pre-processing stage of a threshold independent R-peak detection technique. Finally, the proposed QRS complex detector is thoroughly assessed on the standard ECG datasets of MIT/BIH Arrhythmia, MIT/BIH ST Change, MIT/BIH Supraventricular Arrhythmia, European ST-T, QT, and T-Wave Alternans Challenge databases to show the wide sense practicability of the proposed DFOD-based QRS detector. The root-means-square magnitude error (RMSME) and the average group delay (τDD) metrics of the proposed DFOD are as low as -38.17 dB and 0.04 samples, respectively. The percentage of improvement in terms of RMSME metric compared to the best-reported approach is 15%. The overall sensitivity of 99.89% and positive predictivity of 99.88% are incurred by considering all the six databases. To the best of the authors' knowledge, it is the first time when the evolutionary algorithm based IIR-type DFOD is employed for the QRS complex detection and establishing its performance superiority. The results so obtained are compared with the results of all the recently reported QRS detectors. The proposed DFOD based ECG pre-processor has a great potential to robustly generate the feature signal related to the ECG QRS complex irrespective of the ECG morphology. Thus, the proposed DFOD based QRS detector can be employed in clinical ECG monitoring devices to augment the QRS detection performance.

Is the spiked helmet sign the manifestation of long QT syndrome?

We present the case of a patient with Takotsubo syndrome developing simultaneous inferior, anterior spiked helmet sign (SHS) and macroscopic T-wave alternans (TWA) leading to torsade de pointes ventricular tachycardia (TdP VT). Based on our observations we propose that the SHS is a type of manifestation of critically prolonged QT(U).

Body surface distribution of T wave alternans is modulated by heart rate and ventricular activation sequence in patients with cardiomyopathy.

BackgroundT 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.ObjectiveWe 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.MethodsIn 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.ResultsMaximum Valt (TWAmax) was greater from the body torso than clinical leads during atrial (p<0.005) and atrioventricular pacing (p<0.005). TWAmax was most prevalent in the right lower chest with atrial pacing 100 bpm and shifted to the left lower chest at 120 bpm. TWAmax 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% during atrioventricular 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.ConclusionsThe 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.

Effect of beta-blockade on quantitative microvolt T-wave alternans in 24-hour continuous 12-lead ECG recordings in patients with long QT syndrome.

The aim of study was to investigate effects of beta-blockade on microvolt T-wave alternans (TWA), a precursor of lethal arrhythmia, in patients with long QT syndrome (LQTS). Eleven consecutive LQTS patients, types 1 (n=6), 3 (n=2), and "non-1, non-2, non-3" (n=3) were enrolled. All patients underwent 24-hr continuous 12-lead ECG monitoring before and after initiation of beta-blockade therapy. TWA was measured using the modified moving average method. Seven (63.6%) of the 11 patients studied were symptomatic, with history of cardiac arrest or documented Torsade de Pointes (TdP) in 4 and syncope in three patients. After a median follow-up of 34months, beta-blockade reduced the number of symptomatic patients to 1 with TdP (p<0.02), in whom TdP frequency decreased from 25 events/60months (0.42 event/month) to seven events/69months (0.1 event/month). In association with this reduction in symptoms, peak TWA decreased by 47% in the cohort after a median of eight months of beta-blockade therapy [from 95 (74-130) to 50 (39.5-64.5) µV, p=0.01]. All patients exhibited TWA ≥42µV before beta-blockade therapy, which eliminated these episodes in four patients. Daily frequency of TWA ≥42µV episodes decreased by 87% [from 15 (6-26) to 2 (0-5) episodes/day, p=0.009]. This study is limited by the small sample size and is mainly hypothesis generating. TWA monitoring deserves further evaluation as a risk marker and a guide to therapy in LQTS patients in future large-scale studies.

Cardiac mortality predictability of T-wave alternans in young ST-elevated myocardial infarction patients with preserved cardiac function.

Primary prevention of sudden cardiac death in ST-elevation myocardial infarction (STEMI) is a complicated issue due to the highly heterogeneous population. The effect of T-wave alternans (TWA) on cardiac mortality has been examined in various populations, most often in patients with a high risk of fatal arrhythmia, such as patients with a low left ventricular ejection fraction (LVEF). The aim of the present study was to investigate the prevalence of TWA and its relationship to cardiac mortality in young STEMI patients with preserved LVEF. A total of 108 STEMI patients with preserved cardiac function who were under the age of 45 and underwent single-vessel primary percutaneous coronary intervention were enrolled in this prospective study. Preserved cardiac function was defined as an LVEF of ≥50% as detected with echocardiography 24 to 72 hours after the procedure. The TWA test was performed approximately 1 year after the STEMI occurrence. TWA positivity was defined with a maximal voltage of >64 μV and a heart rate of 125 beats per minute, as in previous studies. The patients were followed up for 5 years and overall cardiac mortality was measured. There was a positive TWA finding in 24 patients (22.2%). There was no significant difference in the use of medications, traditional risk factors, or LVEF in those with TWA positivity. During a follow-up period of 5 years, 7 patients (6.5%) reached the endpoint. Patients with TWA positivity had 10.7 times greater odds for 5-year cardiac mortality, independent of other risk factors. Clinicians should consider using the TWA test in young STEMI patients, as TWA positivity may be associated with increased cardiac mortality in this population.

Взаимосвязь альтернации зубца Т с особенностями кардиальной патологии у пациентов с ревматоидным артритом

Взаимосвязь альтернации зубца Т с особенностями кардиальной патологии у пациентов с ревматоидным артритом

Action potential shortening rescues atrial calcium alternans.

Cardiac alternans refers to a beat-to-beat alternation in contraction, action potential (AP) morphology and Ca2+ transient (CaT) amplitude, and represents a risk factor for cardiac arrhythmia, including atrial fibrillation. We developed strategies to pharmacologically manipulate the AP waveform with the goal to reduce or eliminate the occurrence of CaT and contraction alternans in atrial tissue. With combined patch-clamp and intracellular Ca2+ measurements we investigated the effect of specific ion channel inhibitors and activators on alternans. In single rabbit atrial myocytes, suppression of Ca2+ -activated Cl- channels eliminated AP duration alternans, but prolonged the AP and failed to eliminate CaT alternans. In contrast, activation of K+ currents (IKs and IKr ) shortened the AP and eliminated both AP duration and CaT alternans. As demonstrated also at the whole heart level, activation of K+ conductances represents a promising strategy to suppress alternans, and thus reducing a risk factor for atrial fibrillation. At the cellular level alternans is observed as beat-to-beat alternations in contraction, action potential (AP) morphology and magnitude of the Ca2+ transient (CaT). Alternans is a well-established risk factor for cardiac arrhythmia, including atrial fibrillation. This study investigates whether pharmacological manipulation of AP morphology is a viable strategy to reduce the risk of arrhythmogenic CaT alternans. Pacing-induced AP and CaT alternans were studied in rabbit atrial myocytes using combined Ca2+ imaging and electrophysiological measurements. Increased AP duration (APD) and beat-to-beat alternations in AP morphology lowered the pacing frequency threshold and increased the degree of CaT alternans. Inhibition of Ca2+ -activated Cl- channels reduced beat-to-beat AP alternations, but prolonged APD and failed to suppress CaT alternans. In contrast, AP shortening induced by activators of two K+ channels (ML277 for Kv7.1 and NS1643 for Kv11.1) abolished both APD and CaT alternans in field-stimulated and current-clamped myocytes. K+ channel activators had no effect on the degree of Ca2+ alternans in AP voltage-clamped cells, confirming that suppression of Ca2+ alternans was caused by the changes in AP morphology. Finally, activation of Kv11.1 channel significantly attenuated or even abolished atrial T-wave alternans in isolated Langendorff perfused hearts. In summary, AP shortening suppressed or completely eliminated both CaT and APD alternans in single atrial myocytes and atrial T-wave alternans at the whole heart level. Therefore, we suggest that AP shortening is a potential intervention to avert development of alternans with important ramifications for arrhythmia prevention and therapy.

Mechanistic insight into spontaneous transition from cellular alternans to arrhythmia-A simulation study.

Cardiac electrical alternans (CEA), manifested as T-wave alternans in ECG, is a clinical biomarker for predicting cardiac arrhythmias and sudden death. However, the mechanism underlying the spontaneous transition from CEA to arrhythmias remains incompletely elucidated. In this study, multiscale rabbit ventricular models were used to study the transition and a potential role of INa in perpetuating such a transition. It was shown CEA evolved into either concordant or discordant action potential (AP) conduction alternans in a homogeneous one-dimensional tissue model, depending on tissue AP duration and conduction velocity (CV) restitution properties. Discordant alternans was able to cause conduction failure in the model, which was promoted by impaired sodium channel with either a reduced or increased channel current. In a two-dimensional homogeneous tissue model, a combined effect of rate- and curvature-dependent CV broke-up alternating wavefronts at localised points, facilitating a spontaneous transition from CEA to re-entry. Tissue inhomogeneity or anisotropy further promoted break-up of re-entry, leading to multiple wavelets. Similar observations have also been seen in human atrial cellular and tissue models. In conclusion, our results identify a mechanism by which CEA spontaneously evolves into re-entry without a requirement for premature ventricular complexes or pre-existing tissue heterogeneities, and demonstrated the important pro-arrhythmic role of impaired sodium channel activity. These findings are model-independent and have potential human relevance.

Diurnal variation of frequency domain T-wave alternans on 24-hour ambulatory electrocardiogram in subjects without heart disease: Significant effect of autonomic nervous activity of the heart.

T-wave alternans (TWA) is a risk stratification predictor for sudden cardiac death. However, little is known about the diurnal variation of TWA. Whether TWA are affected by heart rate (HR) or cardiac autonomic nervous activity in the subjects without significant structural heart disease in daily life is not fully understood. Thus, this study was aimed to clarify these issues. Frequency domain (FD)-TWA analysis was conducted in 47 subjects without significant structural heart disease using 24-hr ambulatory electrocardiogram (AECG). Measurement of heart rate variability (HRV) was performed in order to evaluate the autonomic activity of the heart. The maximum FD-TWA value in each period was measured four times per day (A, 00:00-6:00hr; B, 06:00-12:00hr; C, 12:00-18:00hr; D, 18:00-24:00hr). Correlations between FD-TWA and either HR or HRV parameters (LF/HF, LFnu, HFnu, SDNN, CVNN, pNN50) were analyzed in each period (A-D). There was diurnal variation of FD-TWA (median, inter-quartile range [IQR]: A, 8.2 [6.5, 10.6] μV; B, 10.1 [8.4, 15.0] μV; C, 17.6 [12.3, 25.0] μV: D, 11.9 [9.1, 19.9] μV; p<0.0001). Maximum FD-TWA had positive correlations with HR and LF/HF (HR, r=0.496, p<0.0001; LF/HF, r=0.414, p=0.004), while FD-TWA had a negative correlation with HFnu (r=-0.291, p=0.048). On multiple linear regression analysis, HR had an independent effect on log FD-TWA amplitude (β=0.461, p=0.001). FD-TWA has marked diurnal variation in the daily life of the subjects without significant structural heart disease. This variation could be more strongly affected by HR than the HRV indices.

Abstract 16953: Prospective Negative Microvolt T-Wave Alternans Testing is a Marker for Lower Risk of Cardiovascular Death and Appropriate Shock Therapy

Introduction: Microvolt T-wave alternans (MTWA) refers to a pattern of beat-to-beat oscillations in T-wave morphology. Hypothesis: We hypothesized that patients with negative MTWA testing were at decreased risk for cardiovascular death and appropriate shock therapy. Methods: We studied 913 patients from a prospective international registry from Europe, Asia and USA (9 centers total). All recruited patients qualified for primary prevention of sudden cardiac death with ICD or CRT-D. Beta-blockers were discontinued prior to MTWA testing. We used best-subsets analysis of our study population to identify predictors of all-cause mortality. Ten clinical and demographic variables were included in the analysis. We then used these predictors to evaluate the predictive capacity of MTWA in a multivariate model. Results: The mean follow-up was 4.0 ± 3.0 years, mean age was 69.5 ± 12.5 years, 84% were male, and 63% had ischemic cardiomyopathy. 52% and 11% of patients received ICD and CRT-D, respectively. LVEF &lt;25% (HR 2.17, p&lt;0.001), NYHA class&gt;II (HR 1.75, p=0.01) and use of diuretics (HR 2.64, p&lt;0.001) were significantly associated with all-cause mortality in a multivariate model. Using this multivariate model, a negative MTWA outcome was not associated with all-cause mortality (HR 0.95, p=0.80), however a negative MTWA outcome was associated with the risk of cardiovascular death (HR 0.40, p=0.01) and the combined endpoint of cardiovascular death and ICD-rendered shock therapy (HR 0.28, p&lt;0.001). This was consistent in both ischemic and nonischemic cardiomyopathy (p value for interaction=0.999). Conclusions: These findings suggest that non-negative MTWA testing is indicative of an underlying arrhythmogenic substrate, manifested as cardiovascular death and appropriate shock therapy. MTWA testing can provide further information for patient selection for ICD placement. Figure 1 . Kaplan-Meier Curve demonstrating the time-dependent endpoint of cardiovascular death. The follow-up time displayed on this graph is measured in days.

TWARMI pilot trial: The value and optimal criteria of microvolt T-wave alternans in the diagnosis of reversible myocardial ischemia in patients without structural cardiac disease.

Microvolt T-wave alternans (MTWA) testing is a beat-to-beat fluctuation in the amplitude of T wave. We investigated whether: (a) MTWA can be new non-invasive tool for detection of reversible ischemia in patients with suspected CAD without structural heart disease, (b) MTWA can detect ischemia earlier and with greater test accuracy compared with exercise ECG ST-segment testing, and (c) threshold value of MTWA and heart rate at which the alternans is estimated can be different compared to standard values. A total of 101 patients with suspected stable coronary disease, but without structural heart disease, were included. Echocardiography, exercise ECG test, MTWA with classical and modified threshold alternans values, and coronary angiography were performed. About 33.3% patients had a false-positive result on exercise ECG test. The sensitivity of exercise ECG ST-segment test in the detection of coronary artery disease was 97.8%, and the specificity was 42.5% (DOR 33.89). In a group of angiographically positive patients, standard MTWA accurately identified 60% of patients, while 40% had a false-negative result. About 91.8% patients with negative angiography result were accurately identified with 8.2% false positives. The sensitivity of MTWA was 59.61% and specificity 91.83%. Best ratio of sensitivity and specificity (86.53% and 95.91%, DOR 151.06) had modified criteria for positive MTWA (MTWA >1.5µV at heart rate 115-125/min). This study showed that MTWA can be the new non-invasive tool for the detection of reversible ischemia in patients with suspected CAD without structural heart disease. Also, MTWA can detect ischemia earlier and with greater accuracy compared with exercise ECG testing.

Possible Favorable Marker of Positive Head-up Tilt and Negative T-wave Alternans during Test in Suspected High Risk Reflex Syncope Patients

Possible Favorable Marker of Positive Head-up Tilt and Negative T-wave Alternans during Test in Suspected High Risk Reflex Syncope Patients

PO335 Is Microvolt T-Wave Alternans Testing Could be Helpful in Decision Making About Implantation of ICD in Primary Prevention of Sudden Cardiac Death in Patients With Non-Ischemic Cardiomyopathy – New Results After Danish Study

In the present review, we summarize current approaches to the prevention of sudden cardiac death (SCD) in children and young adults, focusing on age < 35 years. SCD in the young is rare, but devastating from the societal perspective. While coronary artery disease is the main etiology of SCD in the older age groups, conditions such as cardiomyopathies and electrical channelopathies are more likely to be found in the young. In the majority of younger cases, cardiac arrest can be the first recognized manifestation of the underlying cardiac pathology, although some have experienced cardiovascular symptoms prior to the SCD. Since identification of a cardiac disease is pivotal for implementation of appropriate prevention, measures such as electrocardiographic screening in subpopulations such as athletes have been proposed. However, these efforts are impeded by the large number of individuals needed to test in order to find one with cardiac disease, leading to significant rates of false positive findings and high costs. When a high-risk cardiac condition is identified in a young person, measures of lifestyle modification, appropriate medical treatment and ICD implantation in selected individuals based on risk stratification are warranted. Nevertheless, the benefits of lifelong ICD therapy need to be balanced with long-term complications and quality of life.

Electrocardiographic conduction and repolarization markers associated with sudden cardiac death: moving along the electrocardiography waveform.

The QT interval along with its heart rate corrected form (QTc) are well-established ECG markers that have been found to be associated with malignant ventricular arrhythmogenesis. However, extensive preclinical and clinical investigations over the years have allowed for novel clinical ECG markers to be generated as predictors of arrhythmogenesis and sudden cardiac death. Repolarization markers include the older QTc, QT dispersion and newer Tpeak - Tend intervals, (Tpeak - Tend) / QT ratios, T-wave alternans (TWA), microvolt TWA and T-wave area dispersion. Meanwhile, conduction markers dissecting the QRS complex, such as QRS dispersion (QRSD) and fragmented QRS, were also found to correlate conduction velocity and unidirectional block with re-entrant substrates in various cardiac conditions. Both repolarization and conduction parameters can be combined into the excitation wavelength (λ). A surrogate marker for λ is the index of Cardiac Electrophysiological Balance (iCEB: QT / QRSd). Other markers based on conduction-repolarization are [QRSD x (Tpeak-Tend) / QRSd] and [QRSD x (Tpeak-Tend) / (QRSd x QT)]. Advancement in technology permitted sophisticated electrophysiological analyses such as principal component analysis and periodic repolarization dynamics to further improve risk stratification. This was closely followed by other novel indices including ventricular ectopic QRS interval, the f99 index and EntropyXQT, which integrates mathematical and physical calculations for determining the risk markers. Though proven to be effective in limited patient cohorts, more clinical studies across different cardiac pathologies are required to confirm their validity. As such, this review seeks to encapsulate the development of old and new ECG markers along with their associated utility and shortcomings in clinical practice.

Effect of Empagliflozin Versus Placebo on Cardiac Sympathetic Activity in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Rationale.

IntroductionProtection from lethal ventricular arrhythmias leading to sudden cardiac death is one of the most important problems after myocardial infarction. Cardiac sympathetic hyperactivity is related to poor prognosis and fatal arrhythmias and can be non-invasively assessed with heart rate variability, heart rate turbulence, T-wave alternans, late potentials, and 123I-meta-iodobenzylguanide (123I-MIBG) scintigraphy. Sodium glucose cotransporter 2 (SGLT2) inhibitors potentially reduce sympathetic nervous system activity that is augmented in part due to the stimulatory effect of hyperglycemia. The EMBODY trial is designed to determine whether the suppression of cardiac sympathetic activity induced by the SGLT2 inhibitor is accompanied by protection against adverse cardiovascular outcomes.MethodsThe EMBODY trial is a prospective, multicenter, randomized, double-blind, placebo-controlled trial in patients with acute MI and type 2 diabetes in Japan. A total of 98 patients will be randomized (1:1) to receive once-daily placebo or empagliflozin, an SGLT2 inhibitor, 10 mg. The primary end point is the change from baseline to 24 weeks in heart rate variability. Secondary end points include the change from baseline for other sudden cardiac death surrogate-markers such as heart rate turbulence, T-wave alternans, late potentials, and 123I-MIBG scintigraphy imaging. Adverse effects will be evaluated throughout the trial period.Planned OutcomesThe EMBODY trial will evaluate the potential cardioprotective effect of empagliflozin and will provide additional important new data regarding its preventative effects on sudden cardiac death.Trial RegistrationUnique Trial Number, UMIN000030158 (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000034442).FundingNippon Boehringer Ingelheim and Eli Lilly and Company.

Automatic T-Wave Alternans Identification in Indirect and Direct Fetal Electrocardiography.

Fetal T-wave alternans (TWA) is a still littleknown marker for severe fetus-heart instabilities and may be related to some currently unjustified fetal deaths. Automatically detecting TWA on direct fetal electrocardiograms (DFECG) means possibility of providing fetuses the right treatment during delivery. Instead, automatically identifying TWA on indirect fetal electrocardiograms (IFECG) means possibility of providing fetuses the right treatment even during pregnancy, when taking actions for outcome improvement is still possible. Moreover, TWA identification from IFECG is noninvasive, and thus safe for both fetuses and mothers. The aim of this work was testing the heart-rate adaptive match filter (HRAMF) for automatic TWA identification in IFECG and comparing HRAMF performance in IFECG against DFECG. To this aim, simultaneously recorded DFECG and IFECG tracings from 5 healthy fetuses were used ("Abdominal and Direct Fetal Electrocardiogram Database" from Physionet). TWA measurements (frequency, mean amplitude, maximum amplitude, and amplitude standard deviation) in IFECG (1.09±0.04 Hz, 11±5 μV, 21±12 μV and 7±3 μV) were of the same order of magnitude of those in DFECG (1.07±0.02 Hz, 9±2 μV, 30±11 μV and 6±2 μV). Moreover, a direct correlation (ñ) was found between maximum TWA and fetal heart rate (IFECG: ρ=0.999; P=0.022; DEFEG: ρ=0.642; P=0.243). Thus, HRAMF was able to detect TWA from IFECG as well as from DFECG.

Phase Relation between Depolarization and Repolarization Alternans in ECG.

T-Wave Alternans (TWA) in the electro cardiogram (ECG) has been widely investigated as a potential predictor of ventricular arrhythmia. However, large clinical trials show that TWA has a high negative predictive value (NPV) but poor positive predictive value (PPV). Therefore, there is need for exploration of approaches to improve PPV of TWA. More recent studies suggest that whether alternans is spatially concordant or discordant affects arrhythmic potential. Results of our previous animal and simulation studies show that the phase relation between depolarization and repolarization alternans has an effect on the transition of concordant to discordant alternans. Towards the eventual goal of developing indexes that complement TWA and improve prediction of arrhythmia, the objectives in this study were to verify the existence of R wave amplitude alternans (RWAA, a surrogate of depolarization alternans) and investigate the phase relationship between RWAA and TWA in clinical grade ECGs. Results show that RWAA does occur in ECGs and that the phase relationship between RWAA and TWA can be labile. These results support further investigation of the co-occurrence of these alternans for prediction of arrhythmic events.

Differential multivariable risk prediction of appropriate shock versus competing mortality - A prospective cohort study to estimate benefits from ICD therapy

Background and objectiveWe prospectively investigated combinations of risk stratifiers including multiple EP diagnostics in a cohort study of ICD patients. MethodsFor 672 enrolled patients, we collected history, LVEF, EP study and T-wave alternans testing, 24-h Holter, NT-proBNP, and the eGFR. All-cause mortality and first appropriate ICD shock were predefined endpoints. ResultsThe 635 patients included in the final analyses were 63 ± 13 years old, 81% were male, LVEF averaged 40 ± 14%, 20% were inducible at EP study, 63% had a primary prophylactic ICD. During follow-up over 4.3 ± 1.5 years, 108 patients died (4.0% per year), and appropriate shock therapy occurred in n = 96 (3.9% per year). In multivariate regression, age (p < 0.001), LVEF (p < 0.001), NYHA functional class (p = 0.007), eGFR (p = 0.024), a history of atrial fibrillation (p = 0.011), and NT-pro-BNP (p = 0.002) were predictors of mortality. LVEF (p = 0.002), inducibility at EP study (p = 0.007), and secondary prophylaxis (p = 0.002) were identified as independent predictors of appropriate shocks. A high annualized risk of shocks of about 10% per year was prevalent in the upper quintile of the shock score. In contrast, a low annual risk of shocks (1.8% per year) was found in the lower two quintiles of the shock score. The lower two quintiles of the mortality score featured an annual mortality <0.6%. ConclusionsIn a prospective ICD patient cohort, a very good approximation of mortality versus arrhythmic risk was possible using a multivariable diagnostic strategy. EP stimulation is the best test to assess risk of arrhythmias resulting in ICD shocks.

Utility of heart rate turbulence and T-wave alternans to assess risk for readmission and cardiac death in hospitalized heart failure patients.

Heart failure (HF) patients have a higher risk of recurrent HF and cardiac death, and electrical remodeling is considered to be an important factor for HF progression. The present study aimed to validate the utility of electrocardiogram and Holter monitoring for the risk stratification of HF patients. Our study comprised 215 patients (144 males, mean age 62 years) who had been hospitalized due to acute decompensated HF. Electrocardiogram (QRS duration and QTc interval) and 24-hour Holter monitoring (heart rate variability, heart rate turbulence, and T-wave alternans [TWA]) were performed in stable condition before discharge. The clinical characteristics and outcomes were then investigated. During a median follow-up period of 2.7 years, there were 83 (38.6%) cardiac events (rehospitalization due to worsening HF [n=51] or cardiac death [n=32]). The patients with cardiac events had a lower turbulence slope (TS) and higher TWA compared to those without cardiac events (TS, 3.0 ± 5.5ms/RR vs. 5.3 ± 5.6ms/RR, P=0.001; TWA, 66.1 ± 19.6 μV vs. 54.7 ± 15.1 μV, P<0.001). Univariable analysis showed that TS, TWA, QRS duration, and QTc interval were associated with cardiac events (P=0.004, P<0.001, P=0.037, and P=0.024, respectively), while the multivariable analysis after the adjustment of multiple confounders showed that TS and TWA were independent predictive factors of cardiac events with a hazard ratio of 0.936 and 1.015 (95% confidence interval [CI]: 0.860-0.974, P=0.006; and 95% CI: 1.003-1.027, P=0.016), respectively. The measurement of TS and TWA is useful for assessing risk for rehospitalization and cardiac death in HF patients.