T wave alternans in idiopathic long QT syndrome

Objectives. The study evaluates the association between T wave alternans and the risk of cardiac events (syncope, aborted cardiac arrest or cardiac death) in a large population of patients with idiopathic long QT syndrome.Background. T wave alternans is an infrequently recorded electrocardiographic (ECG) finding in patients with delayed repolarization, and its clinical significance is not clear.Methods. A total of 4,656 ECG recordings in 2,442 patients enrolled in the International Long QT Syndrome Registry were reviewed for episodes of T wave alternans. To determine the risk associated with T wave alternans, independent of corrected QT interval (QTc) duration, patients with T wave alternans were matched for QTc value (every 0.025 s^1/2) to patients with long QT syndrome without T wave alternans.Results. T wave alternans was identified in 39 patients (25 of whom had a QTc interval >0.50 s^1/2). A strong association between QTc prolongation and T wave alternans was observed (odds ratio 1.23 per 0.01-s^1/2unit increase in QTc, p < 0.0001). Conditional logistic regression analyses with adjustment for age, gender, status and QTc value revealed that T wave alternans did not make a significant independent contribution to the risk of cardiac events. The risk of experiencing a major cardiac event was primarily related to length of QTc.Conclusions. T wave alternans, a marker of electrical instability and regional heterogeneity of repolarization, identifies a high risk subset of patients with prolonged repolarization. Patients with T wave alternans have an increased risk of cardiac events, but this risk is primarily related to the magnitude of repolarization delay (QTc prolongation). T wave alternans does not make an independent contribution to the risk of cardiac events after adjustment for QTc length.     

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。     

T-U wave alternans. A case report and review of the literature.

A patient with severe hypertension, hypokalemia and marked T-U wave alternans on electrocardiogram is reported for its rarity. Relevant literature is reviewed. Recent data indicate that electric alternans is related to changes in action potential configuration, and that it may be a marker of cardiac electrical instability.     

Pneumomediastinum mimicking acute ST-segment elevation myocardial infarction

Pneumomediastinum is characterized by dissecting air within the connective tissues supporting the mediastinum. This condition has been associated with multiple electrocardiographic abnormalities including T-wave inversion, electrical alternans, loss of R wave progression, and low voltage QRS. We describe a case of pneumomediastinum with electrocardiographic changes mimicking acute ST-segment elevation myocardial infarction. Laboratory studies and echocardiography demonstrated no evidence of myocardial injury, and the electrocardiographic abnormality promptly resolved with resolution of the pneumomediastinum. The apparent ST-segment elevation appeared to be the result of electrocardiographic artifact, possibly related to epidermal stretch synchronous with the cardiac cycles.     

Repolarization alternans: implications for the mechanism and prevention of sudden cardiac death

For nearly 100 years, beat to beat alternation of T wave amplitude, termed T wave alternans (TWA), has been closely linked to electrical instability in the heart. TWA is now established among the strongest markers of susceptibility to sudden cardiac death. Since computer technology allows for detection of very subtle yet clinically significant TWA during standard exercise testing, TWA has been used increasingly as a noninvasive clinical tool for identifying and treating patients at risk for sudden cardiac death. The observation of TWA hastening ventricular tachyarrhythmias in an extraordinary variety of clinical and experimental conditions suggest potential universality of TWA in the pathophysiological mechanism of sudden death. High resolution optical mapping studies have shown that TWA arises from alternans of repolarization at the level of the ventricular myocyte. Cellular alternans is likely due to the actions of one or more ionic currents and is closely related to, if not directly dependent on, the kinetics of intracellular calcium cycling. Impairment in calcium cycling at the cellular and sub-cellular levels has been implicated in the mechanism of cellulcar alternans. Importantly, spatially discordant alternans between cells is most likely a consequence of heterogeneities of electrophysiological properties between cells which span the ventricular wall, serving to amplify spatial heterogeneities of repolarization, and forming a substrate for reentrant excitation. Through this mechanism, TWA is linked directly and mechanistically to the pathogenesis of arrhythmias. Although available data would suggest that TWA is certainly closely related to a mechanism of arrhythmogenesis, and is a strong marker of clinical risk, the precise sequence of events which triggers sudden cardiac death, and the potential role of TWA in this process remains elusive.     

Clinical Utility of T-Wave Alternans

Electrical alternans represents a variation in the morphology of electrocardiographic complexes on an every-other-beat basis in an ABABAB... pattern. Apparent electrical alternans associated with pericardial effusion results from rotation of the heart in the pericardial sac, and not true alternation in electrical conduction patterns. In contrast, true electrical alternans results from an alternation in electrical conduction patterns in the heart itself. Repolarization alternans is true electrical alternans associated with the ST segment and T wave of the electrocardiogram (ECG). Here we will focus on T-wave alternans (TWA) and its association with susceptibility to ventricular tachyarrhythmias. Electrical alternans was reported in the literature as early as 1909. Historically, electrical alternans has been regarded as a fairly rare electrocardiographic abnormality. Case reports of electrical alternans have been associated with a variety of disease states, including acute ischemia, Prinzmetal's angina, a variety of electrolyte abnormalities, and the long QT syndrome. Interestingly, patients born with the prolonged QT syndrome have a very high incidence of sudden cardiac death at an early age. Schwartz and Malliani showed that patients with the prolonged QT syndrome who do not demonstrate alternans at rest, may evidence alternans during stress such as emotional excitement. Thus, over the years electrical alternans has been associated anecdotally with conditions associated with an increased risk of ventricular arrhythmias. In 1948, Kalter reviewed the world literature on electrical alternans and found a total of 41 reported cases. In addition, he reviewed clinical ectrocardiograms from 6059 patients and found five new cases (incidence of less than 1 in 1000 patients). Interestingly, he found a very high mortality, 62%, associated with this condition. Despite the clinical associations reported in the literature, the consensus view of electrical alternans until recent years has been that alternans is an electrocardiographic curiosity rarely encountered in clinical practice which, when identified, does not have specific clinical significance.     

Cardiac alternans: diverse mechanisms and clinical manifestations.

OBJECTIVES. The purpose of this review is to assemble the widely dispersed information about cardiac alternans and to categorize the types and mechanisms of alternans, their clinical manifestations and possible therapeutic implications. BACKGROUND. The phenomena of mechanical and electrical alternans have been of continuing interest to both physiologists and clinicians. Recent studies have enhanced this interest because of the reported association of alternans with experimental myocardial ischemia and cardiac arrhythmias. METHODS. The review formulates concepts based on extensive review of published studies and personal observations. RESULTS. Cardiac alternans has been subdivided into the following four categories: 1) mechanical, 2) electrical, 3) in association with myocardial ischemia, and 4) in association with cardiac motion. Mechanical alternans can be explained by hemodynamic or inotropic alterations, or both. Mechanical alternans in the ventricular muscle is accompanied by alternans of action potential shape. In the Purkinje fibers, action potential duration alternates without change in shape and is determined by the duration of the preceding diastolic interval. However, in ventricular muscle fiber, alternans can occur in the presence of constant diastolic intervals. T wave alternans reflects changes in action potential duration and is frequently associated with a long QT interval. Electrocardiographic manifestations of conduction alternans occur at many different sites within the conducting system and myocardium. During myocardial ischemia, additional mechanisms of repolarization alternans have been proposed. Alternans occurring in the presence of a large pericardial effusion is attributed to swinging motion of the heart maintaining two-beat periodicity. CONCLUSIONS. Since its origin as "pulsus alternans" described by Traube in 1872, the definition of alternans has evolved into a term encompassing multiple physiologic and pathologic phenomena that, although united by the term cardiac alternans, diverge widely with respect to etiology, mechanism and clinical significance.     

Microvolt T wave alternans in human cardiac hypertrophy: electrical instability and abnormal myocardial arrangement

INTRODUCTION: Although T wave alternans (TWA) is a promising risk marker for myocardial electrical instability, it remains unclear how the presence of TWA is related to myocardial damage. METHODS AND RESULTS: TWA was measured in 28 patients with hypertrophic cardiomyopathy (HCM), 29 patients with hypertensive left ventricular hypertrophy (HLVH), and 15 normal volunteers using a CH2000 system. The amplitude of TWA (Valt) was measured at the lead with the maximum amplitude. Cardiac biopsy was performed in 12 HCM patients, who were divided into two groups (severe and mild) based on histologic findings of myocardial disarray and fibrosis. TWA was positive (Valt > 1.9 microV) in 61% of HCM and 31% of HLVH, despite a nearly identical left ventricular mass index (176 +/- 65 g/m2 vs 175 +/- 39 g/m2). Valt at heart rate = 110 beats/min was significantly greater in HCM with severe disarray and fibrosis than in HCM with mild disarray and in HLVH. CONCLUSION: In HCM patients, a positive TWA test probably is related to abnormal myocardial arrangement (disarray) and/or fibrosis, and it may reflect electrical instability of the myocardium.     

T wave alternans as a predictor of spontaneous ventricular tachycardia in a canine model of sudden cardiac death

INTRODUCTION: We recently developed an ambulatory canine model of spontaneous ventricular tachycardia (VT) and sudden cardiac death by creating myocardial infarction, complete AV block, and infusion of nerve growth factor to the left stellate ganglion. Whether or not T wave alternans is associated with the spontaneously occurring episodes of VT in our model was unclear. METHODS AND RESULTS: Through intracardiac electrograms obtained from an implantable cardioverter defibrillator, we manually measured T wave amplitudes prior to VT and while the dogs were at rest (baseline, no VT). Of the 79 VT episodes analyzed, 28 (35.4%) exhibited repolarization alternans. In contrast, only 3 (4.7%) of 64 baseline data cases displayed alternans (P < 0.0001). The magnitude of T wave alternans for dogs that died of sudden cardiac death, dogs that did not die suddenly, and for the total 28 episodes that exhibited repolarization alternans were 4.8 +/- 2.8 mm, 4.9 +/- 3.5 mm, and 4.9 +/- 3.3 mm, respectively (P = NS). We also found the sensitivity, specificity, positive predictive value, negative predictive value, and relative risk of repolarization alternans in predicting VT to be 35.4%, 95.3%, 90.3%, 54.5%, and 1.98, respectively. The ventricular rate prior to VT (65 +/- 11 beats/min) was significantly higher than that at rest (49 +/- 12 beats/min; P < 0.0001). CONCLUSION: T wave alternans often occurred immediately before the onset of VT in dogs with myocardial infarction, complete AV block, and nerve growth factor infusion to the left stellate ganglion. Increased sympathetic activity might be responsible for the occurrence of the T wave alternans.     

Linkage between mechanical and electrical alternans in patients with chronic heart failure

INTRODUCTION: Progressive heart failure and ventricular fibrillation are major causes of death in patients with chronic heart failure. Mechanical alternans (pulsus alternans) has been observed in patients with severe congestive heart failure. Visible T wave alternans occasionally is a precursor of ventricular fibrillation. We investigated the occurrence of both cardiac alternans in 94 patients with chronic heart failure. Methods AND RESULTS: Mean left ventricular ejection fraction (LVEF) of the study population was 35 +/- 10%. Mechanical alternans was detected in left ventricular pressure during diagnostic cardiac catheterization. Only sustained mechanical alternans was included in the study. Visible T wave alternans, not microvolt alternans, was noted on standard surface ECG. Cardiac alternans was examined at rest, during physiologic tachycardia, and during stepwise dobutamine loading (2-4-8 microg/kg/min). Prevalences of mechanical and electrical alternans were 19.1% and 4.4% at rest, 45.5% and 8.0% during physiologic tachycardia, and 62.1% and 9.5% under dobutamine loading. Overall, 70 patients (74.5%) showed mechanical alternans and 10 patients (10.6%) showed T wave alternans. T wave alternans always appeared with large mechanical alternans. Among patients with mechanical alternans, cases with T wave alternans showed lower LVEF than those without (27.5 +/- 4.4 and 35.1 +/- 10.2, P < 0.002). CONCLUSION: Visible T wave alternans was detectable in patients with chronic heart failure, especially under tachycardia or catecholamine exposure. Investigating mechanical and mechanoelectrical alternans may bring new insights into the management of patients with chronic heart failure.     

Alternans of the repolarization wave in a case of hypochloremic alkalosis with hypopotassemia.

A case of profound hypochloremic alkalosis with hypopotassemia is reported, showing electrocardiographic changes of electrical alternans of the repolarization wave (probably the U wave) without any change in the QRS complex. Transient concomitant P-pulmonale was noted. Hypopotassemia is discussed as a possible mechanism for the development of the electrical alternans.     

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.     

Isolated T wave alternans

Two patients with isolated T wave alternans are reported, with their vectocardiograms, their response to carotid sinus stimulation, and the response to calcium infusion in one of them with documented severe hypocalcemia. Eleven cases of the literature are briefly reviewed. The alternans of the T wave appears with severe QT prolongation, QT alternans, and an increased tendency to ventricular fibrillation. The findings are consistent with the hypothesis that T wave alternans may be the electrocardiographic manifestation of the transmembrane action potential alternans and could be related in some cases to hypocalcemia.     

Electrophysiologic Basis for T Wave Alternans as an Index of Vulnerability to Ventricular Fibrillation

Electrophysiologic Basis for T Wave Alternans. Substantial evidence indicates that T wave alternans is an intrinsic property of ischemic myocardium. The electrophysiologic basis appears to be spatial and temporal heterogeneity of repolarization resulting from changes in action potential morphology rather than in activation sequence. Ischemia-induced changes in postrepolarization refractoriness and depressed electrical restitution of action potential duration have also been implicated. The main underlying ionic basis for T-wave alternans during coronary occlusion appears to be derangements in intracellular cycling of calcium. Accumulation of potassium in the extracellular space adjoining ischemic cells and disruption in electro-genie sodium-calcium exchange may also be involved. In humans, T wave alternans has been observed in Prinzmetal's and classical angina, angioplasty, and bypass graft occlusion. Under these conditions associated with acute myocardial ischemia, alternans is restricted to the ischemic zone, and alternation in action potential morphology is an underlying factor. Recently, repolarization alternans has been shown to be a statistically significant predictor of the results of electro physiologic testing and arrhythmia-free survival in individuals with and without organic heart disease. Collectively, these observations provide a rationale for quantitation of T-wave alternans magnitude for assessment of vulnerability to life-threatening ventricular arrhythmias both in response to and independent of the effects of myocardial ischemia.     

U wave alternans: an electrocardiographic sign of left ventricular failure

All postextrasystolic complexes seen over a twelve year period were carefully analyzed. Normally only the first complex is different, showing a slightly altered T and a larger U wave. Ten patients with left ventricular failure and postextrasystolic pulsus alternans consistently showed postextrasystolic U wave alternans. Besides introducing an electrocardiographic sign of heart failure, this provides some insight into the underlying etiology of the U wave.     

Angerlike behavioral state potentiates myocardial ischemia-induced T-wave alternans in canines

OBJECTIVES: The main goal of this study was to determine whether induction of an angerlike state can result in significant levels of T-wave alternans, a marker of electrical instability, in the normal and ischemic heart. BACKGROUND: Outbursts of anger have been implicated in the occurrence of myocardial infarction and sudden cardiac death, but the pathophysiologic mechanisms remain unknown. METHODS: A standardized behavioral challenge of eliciting an angerlike state was conducted before and during a 3-min period of coronary artery occlusion in six canines. RESULTS: Precordial T-wave alternans increased from 0.04 +/- 0.02 at baseline to 1.40 +/- 0.32 mV X ms (p < 0.05) during the angerlike response. When the angerlike state and myocardial ischemia were superimposed, the augmentation in T-wave alternans magnitude (to 3.27 +/- 0.61 mV X ms, p < 0.05) exceeded their additive effects, increasing by 130% over the angerlike state alone (p < 0.05) and by 390% over occlusion alone (p < 0.05). Adrenergic influences were reduced by the beta1-adrenergic receptor blocking agent metoprolol (1.5 mg/kg, intravenous), which diminished T-wave alternans magnitude (p < 0.0004 for all) during the angerlike response (from 1.40 +/- 0.32 to 0.80 +/- 0.17 mV x ms) and during the combined intervention (from 3.27 +/- 0.61 to 1.23 +/- 0.13 mV X ms). In five additional normal anesthetized canines, atrial pacing at 180 beats/min did not increase T-wave alternans magnitude monitored from lead II electrocardiogram. CONCLUSIONS: Provocation of an angerlike state results in T-wave alternans in the normal heart and potentiates the magnitude of ischemia-induced T-wave alternans. Elevation in heart rate during arousal does not appear to be the main factor in the development of alternans in the normal heart but may be an important component during myocardial ischemia. Enhanced adrenergic activity appears to mediate the effects in both the normal and ischemic hearts. T-wave alternans may constitute a useful electrophysiologic measure for clinical use in conjunction with behavioral stress testing or ambulatory monitoring.     

实验性家兔急性心肌梗死的心脏电交替现象

目的 :探讨实验性家兔急性心肌梗死 （ AMI）模型的心脏电交替现象的发生率及其原因。方法 :开胸结扎冠状动脉的不同分支 ,制造 AMI模型 ,连续观察 12导联心电图。结果 :结扎冠脉后 ,QRS波群、ST段及 T波电交替的发生率分别为 92 % ,81%及 62 %。结论 :实验性家兔 AMI模型的心脏电交替发生率高。     

Brugada波电交替及临床意义探讨

目的分析Brugada波的电交替现象。方法回顾性分析存在1型Brugada波且伴ST段和/或T波电交替现象的5例患者的心电图及临床特点。结果 5例患者均为男性,年龄18~50岁,入院时均存在1型Brugada波,并且分别在病因诊断确立或病情得到纠正过程中见到ST段和/或T波的电交替现象。ST段电交替可表现为抬高程度(高和低)的交替和抬高类型的(穹隆型和马鞍型)的交替,T波电交替表现为振幅(高和低)的交替和方向(双向和倒置)的交替。结论 Brugada波电交替现象可以发生于多种情况,同样具有多变性的特点。     

T wave alternans can decrease after coronary revascularization

Clinical observations and animal experiments indicate that T wave alternans (TWA) is associated with an increased propensity for ventricular fibrillation, and thus it may be considered as a noninvasive marker of life-threatening ventricular arrhythmias. There is substantial evidence indicating that TWA is an intrinsic property of ischemic myocardium. This study was performed to determine the role of percutaneous transluminal coronary angioplasty (PTCA)-induced myocardial ischemia in the development of TWA and the effects of revascularization. The authors recorded bipolar X, Y, and Z leads of 111 consecutive patients (mean age: 56 years) undergoing PTCA before, during, and 24 hours after the procedure. T wave alternans signal was calculated in 97 patients (43 left anterior descending, 26 right coronary artery, and 28 circumflex or major obtuse margin branch) by fast Fourier transformation technique after signal processing. Twenty-four hours after the procedure, the mean and peak X, Y, and Z values for TWA had all been significantly reduced from baseline and during balloon inflation (p<0.01). The findings point out that induced ischemia could be a trigger for T wave alternans, and successful revascularization can reduce alternans.     

Arrhythmogenesis of T wave alternans associated with surface QRS complex alternans and the role of ventricular prematurity: observations from a canine model of LQT3 syndrome

INTRODUCTION: T wave alternans (TWA) is characterized by cycle-to-cycle changes in the QT interval and/or T wave morphology. It is believed to amplify the underlying dispersion of ventricular repolarization. The aim of this study was to examine the mechanisms and arrhythmogenesis of TWA accompanied by QRS complex and/or blood pressure (BP) waveform alternans, using transmural ventricular electrogram recordings in an anthopleurin-A model of long QT syndrome. METHODS AND RESULTS: The cardiac cycle length was gradually shortened by interruption of vagal stimulation, and TWA was induced in six canine hearts. Transmural unipolar electrograms were recorded with plunge needle electrodes from endocardial (Endo), mid-myocardial (Mid), and epicardial (Epi) sites, along with the surface ECG and BP. The activation-recovery interval (ARI) was measured to estimate local refractoriness. During TWA, ARI alternans was greater at the Mid than the Epi/Endo sites, and it was associated with the development of marked spatial dispersion of ventricular repolarization. As TWA increased, ventricular activation of the cycles associated with shorter QT intervals displayed delayed conduction at the Mid sites as a result of a critically longer ARI of the preceding cycle and longer QT interval, while normal conduction was preserved at the Epi site. Delayed conduction at the Mid sites manifested as surface ECG QRS and BP waveform alternans, and spontaneous ventricular tachyarrhythmias developed in absence of ventricular prematurity. In other instances, in absence of delayed conduction during TWA, ventricular premature complexes infringed on a prominent spatial dispersion of ventricular repolarization of cycles with long QT intervals and initiated ventricular tachyarrhythmia. CONCLUSION: TWA accompanied by QRS alternans may signal a greater ventricular electrical instability, since it is associated with intramural delayed conduction, which can initiate ventricular tachyarrhythmia without ventricular premature complexes.