T wave alternans: a marker of myocardial instability

T wave alternans is an electrocardiographic marker of myocardial electrical instability considered predictive for the development of lethal ventricular rhythms. Direct observation of this phenomenon on the electrocardiogram is rare. Subtle, nonvisible alternation of the T wave may be detected at the microvolt level using advanced signal processing techniques. This technology has enabled investigators and clinicians to identify and risk-stratify certain groups at high risk for sudden cardiac death. The purpose of this review is to discuss the concept of T wave alternans in relation to all cardiac alternans, provide an overview of its proposed mechanisms, and address the clinical utility of this electrocardiographic marker of myocardial electrical instability.     

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。     

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.     

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.     

Mechanism of electrical alternans in patients with pericardial effusion

Electrical alternans concomitant with pericardial effusion has been considered a pathognomonic sign suggestive of a large effusion with cardiac tamponade, particularly if there is P wave alternans as well as QRS alternans. However, the mechanism of this phenomonon remains controversial. A patient with pericardial effusion secondary to adenocarcinoma of the lung with metastases, pericardial effusion, electrical alternans, and cardiac tamponade was studied by echocardiography, right and left heart catheterization, and pericardiocentesis. Hemodynamic data were consistent with cadiac tamponade. The echocardiogram demonstrated a large anterior and posterior pericardial effusion. Noncongruous motion of the septum and posterior wall was pericardial effusion. Noncongruous motion of the septum and posterior wall was recorded at a rate equal to the heart rate. In addition, congruous motion of the septum and posterior wall was recorded at a rate that was half the heart rate and corresponded to the electrical alternans. The congruous movement disappeared after pericardiocentesis, as did the electrical alternans. The electrical alternans is synchronous with and due to the pendulous movement of the heart within the pericardial sac, as demonstrated by echocardiogram and cineangiograms.     

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.     

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.     

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.     

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.     

Isolated T wave electrical alternans in man (author's transl)]

A case of electrical T wave alternans without change of P wave and QRS complex is reported here. Literature on this subject is reviewed. It is emphasized that the alternation of T wave always exists when important morphological anomalies of QT tract and prolongation of QT are present.     

Electrical alternans of the T-U wave without change in the QRS complex.

A patient with myelocytic leukemia who showed electrical alternans of the T-U wave with no change in the QRS complex following chemotherapy is described. Electrocardiogram taken 4 days later showed ventricular quadrigeminy in which the T-U wave of the first sinus beat after the ventricular premature contraction was markedly less prominent compared to the successive two sinus beats which showed marked prolongation and inverted T-U waves. The causative factors for alternans of T-U waves may include hypochloremic alkalosis with hypopotassemia and myocardial damage by anticancer drugs such as daunomycin and aclarubicin chloride used for the underlying disease.     

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.     

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.     

Cellular and ionic basis for T-wave alternans under long-QT conditions

BACKGROUND: T-wave alternans (TWA), an ECG phenomenon characterized by beat-to-beat alternation of the morphology, amplitude, and/or polarity of the T wave, is commonly observed in the acquired and congenital long-QT syndromes (LQTS). This study examines the cellular and ionic basis for TWA induced by rapid pacing under conditions mimicking the LQT3 form of the congenital LQTS in an arterially perfused canine left ventricular wedge preparation. METHODS AND RESULTS: Transmembrane action potentials from epicardial, M, and endocardial cells and 6 to 8 intramural unipolar electrograms were simultaneously recorded together with a transmural ECG and isometric tension development. In the presence of sea anemone toxin (ATX-II; 20 nmol/L), an increase in pacing rate (from a cycle length [CL] of 500 to 400 to 250 ms) produced a wide spectrum of T-wave and mechanical alternans. Acceleration to CLs of 400 to 300 ms produced mild to moderate TWA principally due to beat-to-beat alternation of repolarization of cells in the M region. Transmural dispersion of repolarization during alternans was exaggerated during alternate beats. Acceleration to CLs of 300 to 250 ms caused more pronounced beat-to-beat alternation of action potential duration (APD) of the M cell, resulting in a reversal of repolarization sequence across the ventricular wall, leading to alternation in the polarity of the T wave. The peak of the negative T waves coincided with repolarization of the M region, whereas the end of the negative T wave coincided with the repolarization of epicardium. In almost all cases, electrical alternans was concordant with mechanical alternans. Torsade de pointes occurred after an abrupt acceleration of CL, which was associated with marked TWA. Both ryanodine and low [Ca2+]o completely suppressed alternans of the T wave, APD, and contraction, suggesting a critical role for intracellular Ca2+ cycling in the maintenance of TWA. CONCLUSIONS: Our results suggest that TWA observed at rapid rates under long-QT conditions is largely the result of alternation of the M-cell APD, leading to exaggeration of transmural dispersion of repolarization during alternate beats, and thus the potential for development of torsade de pointes. Our data also suggest that unlike transient forms of TWA that damp out quickly and depend on electrical restitution factors, the steady-state electrical and mechanical alternans demonstrated in this study appears to be largely the result of beat-to-beat alternans of [Ca2+]i.     

Mechanisms for discordant alternans

INTRODUCTION: Discordant alternans has the potential to produce larger alternans of the ECG T wave than concordant alternans, but its mechanism is unknown. METHODS AND RESULTS: We demonstrate by one- and two-dimensional simulation of action potential propagation models that discordant alternans can form spontaneously in spatially homogeneous tissue through one of two mechanisms, due to the interaction of conduction velocity and action potential duration restitution at high pacing frequencies or through the dispersion of diastolic interval produced by ectopic foci. In discordant alternans due to the first mechanism, the boundaries marking regions of alternans with opposite phase arise far from the stimulus site, move toward the stimulus site, and stabilize. Dynamic splitting of action potential duration restitution curves due to electrotonic coupling plays a crucial role in this stability. Larger tissues and faster pacing rates are conducive to multiple boundaries, and inhomogeneities of tissue properties facilitate or inhibit formation of boundaries. CONCLUSION: Spatial inhomogeneities of electrical restitution properties are not required to produce discordant alternans.     

Effects of the ventricular premature beat on the alternation of the repolarization phase in ischemic myocardium during acute coronary occlusion in dogs

Effects of ventricular premature beats (VPB) on the alternans of the ST segment (ST alternans, STA) in the epicardial ECG and of the monophasic action potential (MAP) were examined during acute coronary occlusion in dogs. When STA was recorded simultaneously from four different points it was discordant in most cases. The discordant STA was accompanied by discordant alternation of the repolarization phase of MAP. A VPB transformed the discordant alternans into a concordant one and potentiated the degree of alternans. Transient prolongation or shortening of the cycle length showed effects similar to those of the VPB. The concordant alternans which was transformed from a discordant one by a VPB was not remarkably potentiated by a VPB, or by prolongation or shortening of the cycle length. It is possible that the transformation of the discordant alternans into a concordant one may contribute to the potentiation of STA by a VPB, and that the effects of VPB are due to the effects of the compensatory pause as well as the short cycle length associated with the VPB.     

Spatiotemporal transition to conduction block in canine ventricle

Interruption of periodic wave propagation by the nucleation and subsequent disintegration of spiral waves is thought to mediate the transition from normal sinus rhythm to ventricular fibrillation. This sequence of events may be precipitated by a period doubling bifurcation, manifest as a beat-to-beat alternation, or alternans, of cardiac action potential duration and conduction velocity. How alternans causes the local conduction block required for initiation of spiral wave reentry remains unclear, however. In the present study, a mechanism for conduction block was derived from experimental studies in linear strands of cardiac tissue and from computer simulations in ionic and coupled maps models of homogeneous one-dimensional fibers. In both the experiments and the computer models, rapid periodic pacing induced marked spatiotemporal heterogeneity of cellular electrical properties, culminating in paroxysmal conduction block. These behaviors resulted from a nonuniform distribution of action potential duration alternans, secondary to alternans of conduction velocity. This link between period doubling bifurcations of cellular electrical properties and conduction block may provide a generic mechanism for the onset of tachycardia and fibrillation.     

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。     

Electrical alternans of TU wave in Romano-Ward syndrome.

A case is presented in which an exceptional electrical alternans of the TU wave occurred in association with the Romano-Ward syndrome. This appears to be the first reported example of this association. Ventricular fibrillation was documented during the syncopal attacks. There was no evidence of abnormality of the serum electrolytes.     

Occult T Wave Alternans in Long QT Syndrome

T Wave Alternans in LQTS. T wave alternans that is visually apparent on the ECG is a known risk factor for sudden death in idiopathic long QT syndrome (LQTS). To determine if occult and visually undetectable forms of T wave alternans are also present in LQTS, we measured T wave alternans from a 16-year-old girl with LQTS during exercise using spectral analysis methods and a recording system designed to minimize exercise-related noise. While there was no alternans at rest, statistically significant, yet visually inapparent T wave alternans were measured both during exercise and recovery. Using identical recording techniques, no significant T wave alternans was detected from the subject's mother, who had a prolonged QT interval but was not experiencing arrhythmias, nor from five healthy volunteers with normal QT intervals. This report suggests that electrocardiographically occult, yet prognostically important forms of T wave alternans may be present in patients with LQTS.