Effect of Heart Rate on T Wave Alternans

Heart Rate and T Wave Alternans. Introduction : T wave alternans (TWA) is a promising technique for detecting arrhythmia vulnerability. Previous studies in animals demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of heart rate on TWA in humans and the clinical relevance of this effect remain controversial.
Methods and Results : This was a prospective evaluation of pacing rate and monitoring lead configuration on TWA in subjects undergoing electrophysiologic study. Measurements of TWA were performed on 45 patients in the absence of antiarrhythmic drugs. Recordings were made in normal sinus rhythm and during atrial pacing at 100 and 120 beats/min. Sustained monomorphic ventricular tachycardia (VT) was induced in 29 patients with programmed stimulation. TWA in the vector magnitude lead increased with heart rate, independent of VT inducibility (0.4 ± 0.7 μ V, 1.6 ± 1.9 μ V, and 2.4 ± 2.1 μ V in sinus rhythm and at 100 and at 120 beats/min, respectively; P < 0.001). In addition, the diagnostic performance of TWA for inducible VT was dependent on heart rate (sensitivity 4%, 42%, and 65%, and specificity 100%, 93%, and 63% at 77, 100, and 120 beats/min, respectively). By analyzing orthogonal leads rather than the vector magnitude lead, the sensitivity is increased from 42% to 59% at 100 beats/min, but the specificity is reduced from 93% to 72%.
Conclusion : These results indicate that TWA in humans is strongly dependent on heart rate with regard to both magnitude and diagnostic performance. The optimal heart rate for the measurement of TWA is between 100 and 120 beats/min and multiple leads should be monitored.     

Comparison of Quantitative T‐Wave Alternans Profiles of Healthy Subjects and ICD Patients

Background: Current relevance of T‐wave alternans is based on its association with electrical disorder and elevated cardiac risk. Quantitative reports would improve understanding on TWA augmentation mechanisms during mental stress or prior to tachyarrhythmias. However, little information is available about quantitative TWA values in clinical populations. This study aims to create and compare TWA profiles of healthy subjects and ICD patients, evaluated on treadmill stress protocols. Methods: Apparently healthy subjects, not in use of any medication were recruited. All eligible ICD patients were capable of performing an attenuated stress test. TWA analysis was performed during a 15‐lead treadmill test. The derived comparative profile consisted of TWA amplitude and its associated heart rate, at rest (baseline) and at peak TWA value. Chi‐square or Mann‐Whitney tests were used with p values ≤ 0.05. Discriminatory performance was evaluated by a binary logistic regression model. Results: 31 healthy subjects (8F, 23M) and 32 ICD patients (10F, 22M) were different on baseline TWA (1 ± 2 μV; 8 ± 9 μV; p < 0.001) and peak TWA values (26 ± 13 μV; 37 ± 20 μV; p = 0,009) as well as on baseline TWA heart rate (79 ± 10 bpm; 67 ± 15 bpm; p < 0.001) and peak TWA heart rate (118 ± 8 bpm; 90 ± 17 bpm; p < 0.001). The logistic model yielded sensitivity and specificity values of 88.9% and 92.9%, respectively. Conclusions: Healthy subjects and ICD patients have distinct TWA profiles. The new TWA profile representation (in amplitude‐heart rate pairs) may help comparison among different research protocols.     

微伏级T波电交替的研究进展

T波电交替是心肌电活动不稳定的标志,可作为室性心律失常高危患者的危险分层,是人类及动物缺血心肌发生室性心动过速、心室颤动的标志,是发生恶性室性心律失常及心性猝死的无创预测指标。现结合文献对T波电交替的机制、检测方法、研究现状、适应证、临床意义及优缺点作一综述。     

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

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

Microvolt T‐Wave Alternans during Holter Monitoring in Children and Adolescents

Background: Time‐domain microvolt T‐wave alternans (TWA) has been described as a noninvasive marker of sudden cardiac death in adults. The incidence of TWA in pediatric populations has not been defined well. The aim of the study was to determine peculiarities of TWA in children. Methods: We examined 68 healthy patients—newborns (20) and children in age group of 7–17 years (48)—and 85 pediatric patients: ventricular premature beats—65; dilated cardiomyopathy (DCMP)—2; long QT syndrome (LQTS)—10; Brugada syndrome (BrS)—5, catecholaminergic ventricular tachycardia (CVT)—3. All underwent Holter monitoring (HM) with definition of the peak value of TWA by modified moving average method. Results: In healthy newborns, TWA was 32 ± 8 (12–55) μV (HR 123–156 bmp). In healthy children (7–17 years) it was 30 ± 11 (10–l 55) μV, (HR 64–132 bmp) without any differences between boys and girls. In all group of patients, TWA were significantly higher (P < 0.05) than in healthy. Circadian peak of TWA was found (90%) in a second part of day and at sleep (8%). Among them 60% (LQTS, BrS, and DCPM) had TWA > 55 μV. Conclusion: Time‐domain TWA during HM in children was independent of age, gender, and heart rate. In 94% healthy children, values of TWA do not exceed 55 μV but 20–50% children with cardiac pathology had TWA more than 55 μV. Night circadian type of TWA in diseases with risk of life‐threatening arrhythmias associated with TWA was more than 55 μV. Ann Noninvasive Electrocardiol 2010;15(2):138–144     

Modulation of Electrical Microvolt Level T‐Wave Alternans and Left Ventricular Late Potentials Evaluated by Heart Rate Variability Indices,QT Dispersion,and Plasma Catecholamine Levels

Objective: The purpose of this study was to investigate how the modulation of electrical microvolt level T‐wave alternans (Twa) relates to left ventricular late potentials as evaluated by heart rate variability (HRV), QT dispersion, and plasma catecholamine levels. Background: The Twa and left ventricular late potentials are promising noninvasive powerful markers for risk prediction in patients with ischemic heart disease (IHD) and/or cardiomyopathy. However, their relation to autonomic activity is unclear. Methods: In 56 patients with stable IHD‐measured Twa at rest and during controlled bicycle ergometer testing, we simultaneously recorded recent noninvasive electrocardiographic approaches, such as HRV, QT dispersion, and left ventricular late potentials. Plasma norepinephrine (NE) and epinephrine (E) were also measured. Results: (1) There were no significant differences in clinical findings, NE, and E levels between positive (group A) and negative (group B) Twa. Left ventricular late potentials, LF (low frequency spectra), as well as HF (high frequency spectra) in group A were significantly lower than in group B, but LF/HF did not differ significantly between the two groups. There was a significant inverse correlation between Twa microvoltage and LF/HF that was higher during exercise (r = ‐0.51, P = 0.006) than at rest (r = ‐0.34, P < 0.01). (2) There were no significant differences in clinical findings between positive (group C) and negative (group D) left ventricular late potentials. Plasma NE in group C was significantly higher than in group D (1060 ± 429 pg/mL vs 395 ± 219, P < 0.05). Furthermore, LF/HF in group C was significantly lower than in group D (0.96 ± 0.27 vs 1.1 ± 0.11, P < 0.05). There were no significant correlations between left ventricular late potential parameters and QT or QT_c dispersion. Conclusions: The Twa microvoltage in patients with stable IHD exhibits similar physiologic conditions as in patients with lower HRV indices. The presence of left ventricular late potentials might be affected by sympathetic nerve modulation.     

Microvolt T‐Wave Alternans for Risk Stratification in Athletes with Ventricular Arrhythmias: Correlation with Programmed Ventricular Stimulation

Background: Aim of our study is to evaluate the role of T‐wave alternans (TWA) to stratify the risk of sudden cardiac death in athletes (Ath) with complex ventricular arrhythmias (VA), and to document a possible correlation between TWA and electrophysiological testing (EPS) results. Methods : We studied 85 Ath with VA (61 M, mean age 32 ± 11 years). In all cases a cardiological evaluation was performed, including TWA and EPS. The patients were evaluated during a follow‐up of 30 ± 21 months. The end point was the occurrence of sudden death (SD) or malignant ventricular tachyarrhythmias (VT). Results: TWA was negative in 57 Ath (68%), positive in 15 (18%) and indeterminate in 13 (14%). All subjects with negative TWA did not show induction of VT at EPS, with significant correlation between negative TWA and negative EPS (P < 0.001). All Ath with positive TWA also had VT induced by a EPS, with significant correlation (P < 0.001). By contrast, our data did not show significant correlation between indeterminate TWA and positive or negative EPS. However, there was significant correlation between abnormal TWA test (positive + indeterminate) and inducibility of VT at EPS (P < 0.001). During follow‐up we observed a significant difference in end point occurrence (VT or SD) between Ath with negative or abnormal TWA and between Ath with negative or positive EPS. Conclusion: TWA confirm its role as a simple and noninvasive test, and it seems useful for prognostic stratification of Ath with VA.     

Comparison of Standard versus Orthogonal ECG Leads for T‐Wave Alternans Identification

T‐wave alternans (TWA), an electrophysiologic phenomenon associated with ventricular arrhythmias, is usually detected from selected ECG leads. TWA amplitude measured in the 12‐standard and the 3‐orthogonal (vectorcardiographic) leads were compared here to identify which lead system yields a more adequate detection of TWA as a noninvasive marker for cardiac vulnerability to ventricular arrhythmias. Our adaptive match filter (AMF) was applied to exercise ECG tracings from 58 patients with an implanted cardiac defibrillator, 29 of which had ventricular tachycardia or fibrillation during follow‐up (cases), while the remaining 29 were used as controls. Two kinds of TWA indexes were considered, the single‐lead indexes, defined as the mean TWA amplitude over each lead (MTWAA), and lead‐system indexes, defined as the mean and the maximum MTWAA values over the standard leads and over the orthogonal leads. Significantly (P < 0.05) higher TWA in the cases versus controls was identified only occasionally by the single‐lead indexes (odds ratio: 1.0–9.9, sensitivity: 24–76%, specificity: 76–86%), and consistently by the lead‐system indexes (odds ratio: 4.5–8.3, sensitivity: 57–72%, specificity: 76%). The latter indexes also showed a significant correlation (0.65–0.83) between standard and orthogonal leads. Hence, when using the AMF, TWA should be detected in all leads of a system to compute the lead‐system indexes, which provide a more reliable TWA identification than single‐lead indexes, and a better discrimination of patients at increased risk of cardiac instability. The standard and the orthogonal leads can be considered equivalent for TWA identification, so that TWA analysis can be limited to one‐lead system.     

T‐Wave Alternans and Heart Rate Variability: A Comparison in Patients with Myocardial Infarction with or without Diabetes Mellitus

Background : The aim of this study was to investigate the differences in T‐wave alternans (TWA) and heart rate variability (HRV) among patients with myocardial infarction with or without diabetes mellitus and the relationship between TWA and HRV. Methods: The study population included 133 patients: 59 patients with myocardial infarction (MI) (group post‐MI without diabetes); 40 myocardial infarction with diabetes (group post‐MI with diabetes); and 34 controls (group control). Cardiac autonomic neuropathy assessment was made using frequency domain (low‐frequency [LF] power, high‐frequency [HF] power, LF/HF) and time domain (SDNN, standard deviation of the averaged normal sinus RR intervals for all 5‐minute segments [SDANN]) of HRV indexes. Both TWA and HRV were measured on the Holter monitor, and TWA was calculated automatically using the time‐domain modified moving average method. Results: TWA values differed significantly between controls (40 ± 16 μV) and group post‐MI with (62 ± 17 μV, P < 0.05) or without (60 ± 15 μV, P < 0.05) diabetes. In addition, group post‐MI with diabetes had lower standard deviation of all normal sinus RR intervals (SDNN), standard deviation of the averaged normal sinus RR intervals for all 5‐minute segments (SDANN), and HF, indicating depressed vagus nerve activity, and higher LF/HF ratio, indicating elevated sympathetic nerve activity, than controls and group post‐MI without diabetes (P < 0.05). TWA correlated with SDNN and SDANN (r = 0.29, 0.31; P < 0.001). Conclusions: TWA was elevated in patients following myocardial infarction, both in those with or without diabetes. Myocardial infarction patients had a lower time domain, HF, and a higher LF/HF ratio HRV, especially in those with diabetes. The analysis of modified moving agerage (MMA)‐based TWA and HRV can be a useful tool for identifying post–myocardial infarction patients at high risk of arrhythmic events. Ann Noninvasive Electrocardiol 2011;16(3):232–238     

Noninvasive Sudden Death Risk Stratification by Ambulatory ECG‐Based T‐Wave Alternans Analysis: Evidence and Methodological Guidelines

Extensive experimental and clinical evidence supports the utility of T‐wave alternans (TWA) as a marker of risk for ventricular fibrillation. This entity appears to reflect the fundamental arrhythmogenic property of enhanced dispersion of repolarization. This relationship probably accounts for its relative ubiquity in patients with diverse types of cardiac disease, as has been recognized with the development of analytical tools. A basic premise of this review is that ambulatory ECG monitoring of TWA as patients experience the provocative stimuli of daily activities can expose latent electrical instability in individuals at heightened risk for arrhythmias. We will discuss the literature that supports this concept and summarize the current state of knowledge regarding the use of routine ambulatory ECGs to evaluate TWA for arrhythmia risk stratification. The dynamic, nonspectral modified moving average analysis method for assessing TWA, which is compatible with ambulatory ECG monitoring, is described along with methodological guidelines for its implementation. Finally, the rationale for combined monitoring of autonomic markers along with TWA will be presented.     

T‐Wave Alternans: Reviewing the Clinical Performance,Understanding Limitations,Characterizing Methodologies

Accurate recognition of individuals at higher immediate risk of sudden cardiac death (SCD) is still an open question. The fortuitous nature of acute cardiovascular events just does not seem to fit the well‐known model of ventricular tachycardia/fibrillation induction in a static arrhythmogenic substrate by a synchronous trigger. On the mechanism of SCD, a dynamical electrical instability would better explain the rarity of the simultaneous association of a correct trigger and an appropriate cardiac substrate. Several studies have been conducted trying to measure this cardiac electrical instability (or any valid surrogate) in an ECG beat stream. Among the current possible candidates we can number QT prolongation, QT dispersion, late potentials, T‐wave alternans (TWA), and heart rate turbulence. This article reviews the particular role of TWA in the current cardiac risk stratification scenario. TWA findings are still heterogeneous, ranging from very good to nearly null prognostic performance depending on the clinical population observed and clinical protocol in use. To fill the current gaps in the TWA base of knowledge, practitioners, and researchers should better explore the technical features of the several technologies available for TWA evaluation and pay greater attention to the fact that TWA values are responsive to several factors other than medications. Information about the cellular and subcellular mechanisms of TWA is outside the scope of this article, but the reader is referred to some of the good papers available on this topic whenever this extra information could help the understanding of the concepts and facts covered herein.