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 during fascicular ventricular tachycardia due to digitalis toxicity

This report describes a digitalis-induced regular fascicular ventricular tachycardia characterized by marked QRS alternans a manifestation not usually associated with this arrhythmia. The striking alternation of QRS configuration suggested alternating ventricular activation from either a single focus with two exits in distal branches of the left anterior fascicle or 2 different foci localized in the Purkinje-myocardial network of the left anterior fascicle.     

Implantable cardioverter defibrillator sensing failure due to endocardial R wave electrical alternans

A 71-year-old patient underwent routine single-chamber implantable cardioverter defibrillator (ICD) generator replacement. During defibrillation threshold testing, ventricular tachycardia was induced but the ICD failed twice to properly detect the tachycardia due to endocardial R wave alternans and sensing of every other beat. The problem was resolved by inserting a separate sensing/pacing lead positioned further away from the existing ICD lead.     

Undersensing by an ICD Due to Alternans of the Ventricular Electrogram

Alternans of the ventricular electrogram (VEGM) during ventricular tachycardia (VT) is a rare cause of ventricular undersensing by an implantable cardioverter‐defibrillator (ICD). This report describes a patient with a St. Jude ICD who exhibited sustained monomorphic VT associated with surface QRS alternans, alternating cycle lengths, alternans of the VEGM causing intermittent undersensing of the smaller component, and intermittent 2:1 counting of ventricular intervals during 1:1 sensing in response to the ICD detection algorithm. VEGM undersensing was corrected noninvasively simply by programming the threshold start from 62.5% to 50% which increased the sensitivity based on the amplitude of the VEGM. This maneuver did not affect the satisfactory and stable defibrillation threshold.     

Utility of implantable cardioverter defibrillator electrograms to estimate repolarization alternans preceding a tachyarrhythmic event

Electrical alternans is a pattern of variation in the shape of the ECG waveform that appears on an every-other-beat basis. In humans, alternation in ventricular repolarization, namely, repolarization alternans, has been associated with increased vulnerability to ventricular tachycardia/ventricular fibrillation and sudden cardiac death. This study investigates the utility of implantable cardioverter defibrillator electrograms to estimate repolarization alternans preceding a tachyarrhythmic event. It is demonstrated that microvolt-level repolarization alternans is present prior to an arrhythmic event, and one can record low-amplitude-noise signals that can be used to obtain reliable estimates of repolarization alternans. This study eventually may lead to new methods that would prevent the onset of malignant tachyarrhythmias.     

A Comparison of T-Wave Alternans and QT Dispersion as Noninvasive Predictors of Ventricular Arrhythmias

Background: The purpose of this study was to compare the utility of T-wave alternans and dispersion markers for predicting vulnerability to ventricular arrhythmias. Microvolt level T-wave alternans, QT dispersion (QT_d), JT dispersion, and other dispersion indices have been postulated as noninvasive markers of vulnerability to ventricular arrhythmias. However, T-wave alternans has not been directly compared to dispersion markers in the same patient population. Methods: Twenty-four patients underwent electrophysiological study to investigate recent syncope, ventricular tachycardia, or ventricular fibrillation. Digitized orthogonal ECGs were obtained to investigate the presence of T-wave alternans using spectral analysis, and standard 12-lead ECGs were obtained for QT and JT dispersion analysis. Results: T-wave alternans measurements showed greater sensitivity than QT or JT dispersion, but similar results as the variation coefficient of the JT interval. There was no statistically significant difference in specificity, predictive values, or clinical accuracy between T-wave alternans and any of the dispersion markers (P = N.S.). The combination of increased QT or JT dispersion and T-wave alternans was the most specific predictor. Conclusions: Heterogeneity of repolarization amplitude and duration may both be important noninvasive ECG markers of ventricular vulnerability. In this small group of high-risk patients, T-wave alternans has similar clinical accuracy as the ECG interlead repolarization dispersion markers. The predictive ability of these markers may improve with standardization of methodology or a combination of these approaches. A.N.E. 1999;4(3):274–280     

Wide complex irregularly regular tachycardia with QRS alternation

A 44-year-old white man was referred to our service because of a history of symptomatic rapid palpitations that had begun on January 2007. He had no previous history of syncope or family history of sudden cardiac death. The patient was otherwise well and had not been taking any medications. The electrocardiogram (ECG) recorded during sinus rhythm was within normal limits. A 12-lead ECG was performed during the last episode on July 2007 while he was working at his office. An irregular wide complex tachycardia with varying QRS morphology (left bundle-branch block with an alternating pattern) was documented.The differential diagnoses based on the 12-lead electrocardiogram (ECG) were supraventricular tachycardia with aberrant conduction and QRS alternans, atrial tachycardia with anterograde conduction over an accessory pathway, or ventricular tachycardia. An electrophysiology study was performed and the results are discussed.     

Differentiation of Narrow QRS Complex Tachycardia Types Using the 12‐Lead Electrocardiogram

Background: Previous studies have shown that only 80% of narrow QRS supraventricular tachycardia (SVT) types can be differentiated by standard 12‐lead electrocardiographic (ECG) criteria. This study was designed to determine the value of some new ECG criteria in differentiating narrow QRS SVT. Methods and Results : 120 ECGs demonstrating paroxysmal narrow QRS complex tachycardia (QRS s 0.11 ms and rate > 120 beats/min) were analyzed. Forty atrioventricular reciprocating tachycardia (AVRT), 70 atrioventricular nodal reentrant tachycardia (AVNRT), and 10 atrial tachycardia defined with electrophysiologic study (EPS) consisted the study group. Eight surface ECG criteria were found to be significantly different between tachycardia types by univariate analysis. P waves separate from the QRS complex were observed more frequently in AVRT (70%) and atrial tachycardia (80%). Pseudo r’deflection in lead V¹, pseudo S wave in inferior leads, and cycle length alternans were more common in AVNRT (55, 20, and 6%, respectively). QRS alternans was also present during AVRT (28%). ST‐segment depression (≧ 2 mm) or T‐wave inversion, or both, were present more often in AVRT (60%) than in AVNRT (27%). During sinus rhythm, manifest preexcitation was observed more often in patients with AVRT (42%). When a P wave was present, RP/PR interval ratio > 1 was more common in atrial tachycardia (90%). By multivariate analysis, presence of a P wave separate from the QRS complex, pseudo r’deflection in lead V¹, QRS alternans, preexcitation during sinus rhythm, ST‐segment depression > 2 mm or T‐wave inversion, or both, were independent predictors of tachycardia type. Conclusions: Several new ECG criteria may be useful in differentiation of SVT types. Prediction of mechanism prior to EPS may provide additional benefits concerning the fluoroscopic exposure time and cardiac catheterization procedure. A.N.E. 2002;7(2):120–126     

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.     

Determinants of QRS alternans during narrow QRS tachycardia

This study was designed to prospectively determine the incidence of QRS alternans during various types of narrow QRS tachycardia and to clarify the determinants of QRS alternans. An electrophysiologic study was performed in 28 consecutive patients with a narrow QRS tachycardia. Persistent QRS alternans was observed in 6 (43%) of 14 patients during orthodromic reciprocating tachycardia, 5 (71%) of 7 patients during atrial tachycardia and 3 (43%) of 7 patients during atrioventricular (AV) node reentrant tachycardia. Incremental atrial pacing during sinus rhythm resulted in QRS alternans in patients who had QRS alternans during tachycardia, unless the shortest pacing cycle length associated with 1:1 AV conduction exceeded the tachycardia cycle length. In patients without QRS alternans during narrow QRS tachycardia, incremental atrial pacing during sinus rhythm resulted in persistent QRS alternans in five patients in whom the shortest pacing cycle length associated with 1:1 AV conduction was 60 to 180 ms less than the tachycardia cycle length. In an additional 20 patients without a narrow QRS tachycardia, persistent QRS alternans was observed during incremental atrial pacing in 11 (55%) of the patients. In six of six patients who had QRS alternans during abrupt rapid atrial pacing, QRS alternans was not observed when the same pacing rates were achieved gradually. Among the patients with narrow QRS tachycardia, the mean tachycardia cycle length in those who had QRS alternans (mean +/- SD 288 +/- 44 ms) was significantly shorter than in those who did not (369 +/- 52 ms, p less than 0.001). The presence of QRS alternans was not related to the tachycardia mechanism, relative or functional refractory period of the His-Purkinje system (at a drive cycle length of 500 ms), age, presence of structural heart disease, direction of input into the AV node or concealed retrograde conduction in the His-Purkinje system. In conclusion, QRS alternans during narrow QRS tachycardias is a rate-related phenomenon that depends on an abrupt increase to a critical rate and is independent of the tachycardia mechanism.     

The Effect of Procainamide on T Wave Alternans

INTRODUCTION: The measurement of microvolt level T wave alternans (TWA) is a technique for detecting arrhythmia vulnerability. Previous studies demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of antiarrhythmic drugs on TWA are unknown. METHODS AND RESULTS: This was a prospective evaluation of intravenous procainamide on TWA in 24 subjects with inducible sustained ventricular tachycardia (VT). Measurements of TWA were performed at baseline in the drug-free state and after procainamide loading (1,204+/-278 mg). Recordings were made in normal sinus rhythm, and during atrial pacing at 100 beats/min and 120 beats/min. The magnitude of TWA in the vector magnitude lead was decreased by procainamide at all heart rates: 0.6+/-0.8 to 0.3+/-0.4 microV in sinus rhythm, 2.0+/-1.6 to 0.7+/-0.7 microV at 100 beats/min, and 3.0+/-2.0 to 1.7+/-1.8 microV at 120 beats/min (P<0.001 by analysis of variance). The sensitivity of TWA for the induction of VT at baseline was 5% in sinus, 60% at 100 beats/min, and 87% at 120 beats/min, while it decreased with procainamide to 5%, 19%, and 60%, respectively. Decreases in TWA in response to procainamide were independent of the antiarrhythmic effects on VT inducibility. CONCLUSIONS: These results indicate that the magnitude of TWA decreases with acute procainamide loading and this effect decreases the sensitivity of TWA for the induction of sustained VT.     

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.     

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。     

右心室室性心动过速患者时域法微伏级T波电交替特征及其临床意义

目的探讨右心室室性心动过速患者时域法微伏级T波电交替（MTWA）特征及其临床意义。方法采用活动平板时域法分别对35例致心律失常性右心室心肌病（ARVC）患者[其中男性28例,平均年龄（38．6±11,0）岁]、10例特发性右心室室性心动过速（IRVT）患者[其中男性7例,平均年龄（41．9±15．4）岁]和60例健康对照者[男性42例,平均年龄（41．0±14．9）岁]进行MTWA检测,记录胸前V1～V6导联的MTWA值,确定胸前各导联的最大值,以Max Valt表示。分析比较不同组别各导联MTWA值及Max Valt值的差异。结果ARVC组各导联MTWA值和Max Valt值均明显高于对照组（P〈0．01）;IRVT组各导联的MTWA值和Max Valt值比对照组升高,但差异无统计学意义（P〉0．05）;ARVC组和IRVT组比较,V4导联MTWA值及MaxVah值明显较高（P〈0．05）;接受者操作特性（receiver operating characteristic,ROC）曲线分析表明,以Max Valt〉11．5μV鉴别诊断ARVC的敏感性为74．3％,特异性为80．0％;ARVC组中,近一年内有持续性室速发生的患者较无室速发作患者V2～V6导联的MTWA值以及Max Valt值的差异有统计学意义。结论渐量修正平均时域法检测显示,ARVC患者MTWA值和Max Valt值均明显升高．MTWA佰可以反映ARVC患者近期室性心动过速的发作。     

Electrical and mechanical alternans during ventricular tachycardia with moderate chronic heart failure

A chronic heart failure (CHF) rat underwent epicardial programmed electrical stimulation (PES). Ventricular tachycardia (VT) developed during PES. Mechanical alternans was noted despite fixed tachycardia cycle length. Anti-tachycardia pacing attempts initiated a second VT that generated pulse intermittently and then degenerated into pulseless VT with electrical alternans.To our knowledge electrical and mechanical alternans have not been recorded in animal models of CHF during VT. The distinct events of mechanical alternans and electrical alternans may be indicative of progressively worsened calcium handling in the compromised cardiomyocytes.Although ion channel differences between rodents and humans exist, this work attempts to demonstrate this rat model's usefulness in understanding cardiac electrophysiology in CHF.     

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.     

The lay of the land

To evaluate the presence and clinical significance of electrical alternans during PTCA, intracoronary electrocardiography (ic-ECG) was performed in 65 consecutive lesions. ST-T alternans, defined as a beat-to-beat difference in the ST elevation ?1 mm, was present in five lesions (7.7%), all in the proximal left anterior descending (LAD) coronary artery. The phenomenon was seen only after 130 sec (mean 174 ± 57) of balloon inflation. Only two of the five showed ST-T alternans simultaneously on both surface and ic-ECG. One of five patients had premature ventricular contractions following ST-T alternans. Three of these five lesions required a second balloon inflation with duration of ? 300 sec; there was no ST-T alternans on the second inflation in any of these lesions. We conclude: (1) the detection of ST-T alternans during PTCA is enhanced by use of ic-ECG, (2) electrical alternans during PTCA was seen only in proximal LAD lesions, implicating a large amount of ischemic myocardium as a requisite for the phenomenon, (3) electrical alternans is not immediate, requiring a certain duration of balloon occlusion and hence ischemia to occur, and (4) the absence of ST-T alternans during second balloon inflations suggests ischemic preconditioning may abolish this phenomenon.     

Mechanism of repolarization alternans has restitution of action potential duration dependent and independent components

INTRODUCTION: Investigation of relationship between diastolic-interval (DI)-dependent restitution of action potential duration (APD) and alternans of APD has produced conflicting results. We used a novel pacing protocol to determine the role of restitution in alternans by minimizing changes in DI preceding each activation. METHODS: Transmembrane potentials were recorded from right ventricular endocardial tissue isolated from five dogs. We used three pacing sequences: (i) The tissue was paced at a constant DI for 100 beats. (ii) The DIs were changed randomly between two sequences of constant DI. (iii) Each constant DI trial was followed by constant cycle length trial where pacing cycle length was equal to average cycle length during previous constant DI trial. RESULTS: Alternans of APD occurred even when DIs preceding each activation were invariant. Slopes of restitution during constant DI pacing were both negative and positive and were much larger than unity. Alternans amplitude during constant cycle length pacing was larger than during constant DI, 32.2 +/- 12.3 versus 7.5 +/- 2.8 msec, P < 0.01. Random perturbation of DI decreased alternans amplitude during constant DI pacing from 14.7 +/- 4.8 to 10.5 +/- 3.4 msec, P < 0.01. CONCLUSION: Our results indicate that mechanism of repolarization alternans has restitution-dependent and restitution-independent components. However, our results also provide direct evidence that shows that DI-dependent restitution of APD is not a necessary mechanism for the alternans to exist. Ability to pace with explicit control of DI provides a novel approach to dissect mechanisms of alternans into restitution-dependent and restitution-independent effects.     

Relationship between extracellular T-wave height, T-wave alternans amplitude, and tissue action potential alternans: a 1-dimensional computer modeling study

T-wave alternans (TWA) is a useful marker of cardiac instability, but not much is known about the factors that affect its measurement, such as electrode placement. We used a 1-dimensional myocardial fiber computer model of alternans to investigate the effect of electrode position on TWA measurement. Results demonstrated that TWA amplitude and T-wave amplitude change proportionally if both recording electrodes are symmetrically moved toward or away from the tissue. However, TWA amplitude and T-wave amplitude change out of proportion to one another when one electrode is moved while the other electrode remains stationary. These disproportionate changes result from beatwise alternation in the asymmetric potential field around the tissue. In summary, nonlinear changes in tissue repolarization during alternans result in nonlinear changes in T-wave amplitude and TWA amplitude.     

Intravenous administration of class I antiarrhythmic drugs induced T wave alternans in a patient with Brugada syndrome

A 71-year-old man who experienced aborted sudden death was referred to our hospital. Coronary artery disease and cerebral accident were ruled out by conventional tests. The 12-lead ECG obtained at rest showed a right bundle branch block pattern and ST segment elevation in leads V1 to V3. Double ventricular extrastimuli at coupling intervals >180 msec induced ventricular fibrillation (VF) twice during electrophysiologic study. Intravenous administration of procainamide accentuated ST segment elevation in leads V1 to V3, and visible T wave alternans was induced in leads V2 and V3 at a dose of 450 mg. Initiation of T wave alternans was not associated with changes of the cardiac cycle or development of premature beats. When procainamide infusion was discontinued, T wave alternans disappeared before the elevated ST segment returned to the control level. Pilsicainide also accentuated ST segment elevation and induced similar T wave alternans in leads V2 and V3. Class I antiarrhythmic drug-related T wave alternans has been reported rarely in Brugada syndrome, but it may represent enhanced arrhythmogenicity of VF. We need to monitor closely and study the clinical implications of T wave alternans in Brugada syndrome.