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[Figure: see text].

Background Anti-Sjögren's syndrome-related antigen A-antibodies (anti-Ro/SSA-antibodies) are responsible for a novel form of acquired long-QT syndrome, owing to autoimmune-mediated inhibition of cardiac human ether-a-go-go-related gene-potassium channels. However, current evidence derives only from basic mechanistic studies and relatively small sample-size clinical investigations. Hence, the aim of our study is to estimate the risk of QTc prolongation associated with the presence of anti-Ro/SSA-antibodies in a large population of unselected subjects. Methods and Results This is a retrospective observational cohort study using the Veterans Affairs Informatics and Computing Infrastructure. Participants were veterans who were tested for anti-Ro/SSA status and had an ECG. Descriptive statistics and univariate and multivariate logistic regression analyses were performed to identify risk factors for heart rate-corrected QT interval (QTc) prolongation. The study population consisted of 7339 subjects (61.4±12.2 years), 612 of whom were anti-Ro/SSA-positive (8.3%). Subjects who were anti-Ro/SSA-positive showed an increased prevalence of QTc prolongation, in the presence of other concomitant risk factors (crude odds ratios [OR], 1.67 [1.26-2.21] for QTc >470/480 ms; 2.32 [1.54-3.49] for QTc >490 ms; 2.77 [1.66-4.60] for QTc >500 ms), independent of a connective tissue disease history. Adjustments for age, sex, electrolytes, cardiovascular risk factors/diseases, and medications gradually attenuated QTc prolongation estimates, particularly when QT-prolonging drugs were added to the model. Nevertheless, stepwise-fully adjusted OR for the higher cutoffs remained significantly increased in anti-Ro/SSA-positive subjects, particularly for QTc >500 ms (2.27 [1.34-3.87]). Conclusions Anti-Ro/SSA-antibody positivity was independently associated with an increased risk of marked QTc prolongation in a large cohort of US veterans. Our data suggest that within the general population individuals who are anti-Ro/SSA-positive may represent a subgroup of patients particularly predisposed to ventricular arrhythmias/sudden cardiac death.

Since its initial description by Jervell and Lange-Nielsen in 1957, the congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. A prolonged QT interval in the surface electrocardiogram is the sine qua non of the LQTS and is a surrogate measure of the ventricular action potential duration (APD). Congenital as well as acquired alterations in certain cardiac ion channels can affect their currents in such a way as to increase the APD and hence the QT interval. The inhomogeneous lengthening of the APD across the ventricular wall results in dispersion of APD. This together with the tendency of prolonged APD to be associated with oscillations at the plateau level, termed early afterdepolarizations (EADs), provides the substrate of ventricular tachyarrhythmia associated with LQTS, usually referred to as torsade de pointes (TdP) VT. This review will discuss the genetic, molecular, and phenotype characteristics of congenital LQTS as well as current management strategies and future directions in the field., (© 2017 Wiley Periodicals, Inc.)

Background: In patients with autoimmune disease, anti-Ro/SSA antibodies (anti-Ro/SSA) are responsible for a novel autoimmune-associated long-QT syndrome by targeting the hERG potassium channel and inhibiting the related current (IKr). Because anti-Ro/SSA are also present in a significant proportion of healthy subjects and may be associated with torsades de pointes (TdP) arrhythmia, we tested the hypothesis that anti-Ro/SSA may represent a silent risk factor in patients developing TdP., Methods and Results: Twenty-five consecutive patients who experienced TdP were prospectively collected independent of ongoing therapies and concomitant diseases. Anti-Ro/SSA were detected by fluoroenzyme immunoassay, immuno-Western blotting, and line-blot immunoassay. Purified IgGs from anti-Ro/SSA-positive and anti-Ro/SSA-negative patients were tested on IKr using HEK293 cells stably expressing the hERG channel. As expected, in TdP patients, many known corrected QT interval-prolonging risk factors were simultaneously present, including hypokalemia that was the most common (52%). Anti-Ro/SSA were present in 60% of the subjects, mostly the anti-Ro/SSA-52-kD subtype detected by immuno-Western blotting only. A history of autoimmune disease was found in only 2 of anti-Ro/SSA-positive patients. Experimental data demonstrated that purified anti-Ro/SSA-positive IgGs significantly inhibited IKr and cross reacted with hERG-channel proteins. Moreover, anti-Ro/SSA-positive sera exhibited high reactivity with a peptide corresponding to the hERG-channel pore-forming region., Conclusions: Anti-Ro/SSA may represent a clinically silent novel risk factor for TdP development via an autoimmune-mediated electrophysiological interference with the hERG channel. We propose that TdP patients may benefit from specific anti-Ro/SSA testing even in the absence of autoimmune diseases as immunomodulating therapies may be effective in shortening corrected QT interval and reducing TdP recurrence risk., (© 2016 American Heart Association, Inc.)

An 84 year-old man with history of recurrent dizziness presented with first degree atrio-ventricular block (1° AVB) and periods of 2:1 AVB. An electrophysiological study revealed a predominant 1:1 AV conduction with markedly prolonged AH interval and frequent His bundle extrasystoles (H). A properly timed H could induce periods of 2:1 AV nodal block and 1:1 AV conduction could only resume following another properly timed H. Procainamide suppressed H. However, because of persistence of the patient symptoms, a permanent pacemaker was eventually inserted. The case illustrates a hitherto not described manifestation of H.

A 74-year-old man with past history of near syncope presented with frequent periods of second-degree atrioventricular block (2° AVB). An electrophysiological study revealed prolonged atrial-His and His-ventricular (HV) intervals and frequent His bundle (H) extrasystoles. The latter manifested in the surface electrocardiogram as premature atrial, junctional, or ventricular beats, as well as 2° AVB that mimicked Wenckebach or Mobitz II block. Procainamide markedly suppressed H extrasystole. However, because of the presence of prolonged HV interval and history of presyncope, a permanent pacemaker was inserted. The case illustrates the varied manifestation of H extrasystole and presents guidelines for management., (©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc.)

Aims: To compare patients with atrial flutter (AFl) and 1:1 atrioventricular conduction (AVC) with patients with AFl and higher AVC., Methods: The characteristics of 19 patients with AFl and 1:1 AVC (group A) were compared with those of 116 consecutive patients with AFl and 2:1 AVC or higher degree AV block (group B)., Results: Age, gender, and left ventricular function were similar in the two groups. In group A versus group B, more patients had no structural heart disease (42% vs 17%, P < 0.05) and syncope/presyncope (90% vs 12%, P < 0.05). The AFl cycle length (CL) in group A was longer than in group B (265 +/- 24 ms vs 241 +/- 26 ms, P < 0.01). The transition from AFl with 1:1 to 2:1 AVC or vice versa was associated with small but definite changes in AFl CL, which showed larger variations in response to sympathetic stimulation. In group A patients who were studied off drugs, the atrial-His interval was not different from group B, but maximal atrial pacing rate with 1:1 AVC was faster. In group A, five patients were misdiagnosed as ventricular tachyarrhythmias, and three with a defibrillator received inappropriate shocks. Four patients had ablation of AVC and six had ablation of AFl circuit., Conclusions: The main difference between groups A and B may be an inherent capacity of the AV node for faster conduction, especially in response to increased sympathetic tone. The latter affects not only AVC but also the AFl CL. One should be aware of the different presentations of AFl with 1:1 AVC to avoid misdiagnosis/mismanagement and to consider the diagnosis in patients with narrow or wide QRS tachycardia and rates above 220/min.

Introduction: Compared to concordant T wave alternans (CA), discordant T wave alternans (DA) may be associated with an increased dispersion of repolarization (DR) and a greater propensity to develop reentrant ventricular tachyarrhythmias. The electrophysiologic mechanisms of DA in the in vivo heart are not well understood., Methods and Results: The mechanisms of DA were investigated in the canine anthopleurin-A surrogate model of long QT3 syndrome using tridimensional analysis of activation and repolarization patterns from 256 to 384 unipolar electrograms. Cardiac repolarization was evaluated as the activation-recovery interval (ARI) of local electrograms. Two mechanisms for the development of DA were observed. (1) Stepwise shortening of cycle length (CL) superimposed on preexisting DR resulted in different diastolic intervals (DI) at midmyocardial sites compared to epicardial and endocardial sites. The dispersion of DI coupled with different restitution kinetics at those sites induced DA. (2) The dependence of conduction velocity on DI as the CL is abruptly shortened could result in differential conduction delays at mid sites. This enhanced the dispersion of DI between sites and, coupled with the different restitution kinetics, induced DA. The critical step for the development of DA in both mechanisms was the occurrence of short ARI in two consecutive beats either at epicardial sites in the first mechanism or at mid sites in the second mechanism. Sites with DA had significantly more DR compared to sites with concordant T wave alternans, and ventricular tachyarrhythmias developed mainly in the presence of DA., Conclusion: In the in vivo heart, DA developed due to critical interaction between dispersion of DI and differences in restitution kinetics at different myocardial sites. The dispersion of DI could result from preexisting DR or differential conduction delay at a critical short CL. DA is critically linked to the development of malignant tachyarrhythmias.

Introduction: Microvolt T wave alternans (TWA) has been proposed as a strong independent predictor of malignant ventricular tachyarrhythmias and sudden cardiac death. TWA reproducibility during bicycle stress test has not been previously investigated. We sought to assess the short-term reproducibility of TWA, as well as heart rate (HR) threshold for TWA, and its spatial distribution and magnitude., Methods and Results: The study enrolled 42 patients who were able to complete two bicycle stress tests with HR at peak exercise >110 beats/min within 4 hours of each other and who had technically adequate recordings for TWA analysis during both tests. Concordant results for TWA determination were obtained in 39 (93%) of 42 cases. TWA was present during both tests in 23 patients and was absent during both tests in 16 patients. In the 23 patients with two positive tests, HR at the onset of TWA was not significantly different during the two tests. Further, the number of leads showing TWA and the magnitude of TWA were not significantly different between the two tests., Conclusion: TWA is characterized by satisfactory short-term reproducibility and, when present, by high temporal and spatial stability.

We describe a patient with bifascicular block, who developed transient high-degree atrioventricular block during dipyridamole infusion. This patient was subsequently found to have significant His-Purkinje disease at electrophysiology study, and underwent permanent pacemaker implantation. Spontaneous atrioventricular block was documented during follow-up. This case report raises the issue of dipyridamole safety in patients with intraventricular conduction defects, and contributes an additional mechanism to the possible explanation of dipyridamole-induced atrioventricular block.

Abstract: Since its initial description by Jervell and Lange‐Nielsen in 1957, the congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. Although congenital LQTS continues to remain the domain of cardiologists, cardiac electrophysiologists, and specialized centers, the by far more frequent acquired drug‐induced LQTS is the domain of all physicians and other members of the health care team who are required to make therapeutic decisions. This report will review the electrophysiological mechanisms of LQTS and torsade de pointes, electrocardiographic characteristics of acquired LQTS, its clinical presentation, management, and future directions in the field. [ABSTRACT FROM AUTHOR]

Objective: Increasing evidence indicates systemic inflammation as a new potential cause of acquired long QT syndrome (LQTS), via cytokine-mediated changes in cardiomyocyte ion channels. Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia occurring in patients with LQTS, usually when multiple QT-prolonging factors are simultaneously present. Since classical risk factors cannot fully explain TdP events in a number of patients, we hypothesised that systemic inflammation may represent a currently overlooked risk factor contributing to TdP development in the general population.Methods: Forty consecutive patients who experienced TdP (TdP cohort) were consecutively enrolled and circulating levels of C-reactive protein (CRP) and proinflammatory cytokines (interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα), interleukin-1 (IL-1)) were compared with patients with active rheumatoid arthritis (RA), comorbidity or healthy controls. An additional 46 patients with different inflammatory conditions (acute infections, n=31; immune-mediated diseases, n=12; others, n=3) and elevated CRP (inflammatory cohort) were prospectively enrolled, and corrected QT (QTc) and cytokine levels were measured during active disease and after a CRP decrease of >75% subsequent to therapy.Results: In the TdP cohort, 80% of patients showed elevated CRP levels (median: ~3 mg/dL), with a definite inflammatory disease identifiable in 18/40 cases (acute infections, n=12; immune-mediated diseases, n=5; others, n=1). In these subjects, IL-6, but not TNFα and IL-1, was ~15-20 times higher than in controls, and comparable to RA patients. In the inflammatory cohort, where QTc prolongation was common (mean values: 456.6±30.9 ms), CRP reduction was associated with IL-6 level decrease and significant QTc shortening (-22.3 ms).Conclusion: The data are first to show that systemic inflammation via elevated IL-6 levels may represent a novel QT-prolonging risk factor contributing to TdP occurrence in the presence of other classical risk factors. If confirmed, this could open new avenues in antiarrhythmic therapy. [ABSTRACT FROM AUTHOR]

Background The aim of the study is to contrast the role of conventional ambulatory electrocardiographic monitoring (AEM) artifacts with a less emphasized problem with potentially more serious implications, that is, the failure to recognize, and therefore misinterpret, a genuine arrhythmia episode in the AEM recording. Methods The study material included 500 Holter recordings and 500 recordings from the cardiac telemetry unit. Results Electrocardiographic (ECG) artifacts were more common in telemetry recordings (5.6%) compared to Holter recordings (4%) for a total of 4.8%. There were 35 examples of misinterpretation of AEM recordings (3.5%). These were significantly more common in telemetry recordings (2.6%) compared to Holter recordings (0.9%). The most common ECG artifacts were examples of pseudo ventricular tachyarrhythmia (VT). The majority of misinterpretation (26 of 35 examples) were fast supraventricular tachyarrhythmias with aberrant QRS (including six examples of atrial flutter with periods of 1:1 atrioventricular conduction) that were misdiagnosed as ventricular VT. Other examples were misinterpretation of arrhythmic episodes consistent with sick sinus syndrome, pacemaker malfunction, and long QT syndrome. Only 5 of 48 examples of AEM artifacts resulted in management errors of commission or errors of omission compared to all 35 examples of misinterpretation. Conclusions Compared to conventional artifacts in AEM, misinterpretation of nonartifactual arrhythmic episodes consistently resulted in management errors. Misinterpretation was significantly more common with telemetry recordings compared to Holter ECG. This highlights the need for more appropriate training of the entire clinical team in charge of the management of the cardiac telemetry unit. [ABSTRACT FROM AUTHOR]

Repolarization Distribution in LQT3. Introduction: The occurrence of significant spatial dispersion of repolarization in vivo as it relates to the mechanism of arrhythmia formation in the long QT syndrome (LQTS) continues to be questioned. Methods and Results: We investigated a guinea pig model of LQT3 using anthopleurin-A (AP-A) to study the contribution of rate-dependent spatial dispersion of repolarization in the intact heart to the arrhythmogenicity of LQTS. Optical action potentials were measured using potentiometric fluorescent dye di-4ANEPPS in Langendorff-perfused hearts with induced AV block. AP-A exacerbated the normal uniform epicardial apex-base action potential duration (APD) gradient, resulting in rate-dependent increased APD dispersion and nonuniform APD gradient. Spontaneous focal premature beats induced functional conduction block along boundaries where large nonuniform APD gradient occurred setting the stage for circulating wavefronts and ventricular tachyarrhythmia (VT). Endocardial ablation abolished spontaneous VT, but nonuniform epicardial APD gradient persisted and could be challenged by a stimulated premature stimulus to induce VT. Conclusion: The study shows that in LQT3, spatial variations in steady-state properties result in zones of nonuniform APD gradients. These provide a substrate for functional conduction block and reentrant excitation when challenged by subendocardial “early afterdepolarization-triggered” premature beats. The study emphasizes the key importance of spatial dispersion of repolarization, whether located in epicardial or intramyocardial layers, in arrhythmia formation in LQTS. (J Cardiovasc Electrophysiol, Vol. 15, pp. 323-331, March 2004) [ABSTRACT FROM AUTHOR]

A case is described in which ventricular pacing from the middle cardiac vein produced an electrocardiographic pattern which mimicked the morphology of the normally conducted beats. The possible etiologies of this unusual phenomenon and its implications concerning the functional anatomy of the normal conduction system in the human heart are discussed. [ABSTRACT FROM AUTHOR]

The signal averaged electrocardiogram (SA-ECG), programmed electrical stimulation (PES), and left ventricular ejection fraction (EF) studies were utilized for risk stratification and management of patients with complex ventricular arrhythmias and nonsustained ventricular tachycardia (VT). The study population included 90 patients (63 with coronary artery disease and 27 with dilated cardiomyopathy). Sustained monomorphic VT was induced in 22 cases (24%), ventricular fibrillation (VF) in 10 (11%), and no sustained VT/VF in 58 (64%). An abnormal SA-ECG was recorded in 23 patients (26%) and was more common in patients with than in those without induced sustained VT (68% vs 12%, P < 0.0001). None of 33 patients with normal SA-ECG and EF ≥ 40% had induced VT. Patients were followed-up for 2.5 ± 0.8 years off antiarrhythmic therapy, unless they had induced sustained VT. The 3-year sudden death rate was 19% in the group with induced sustained VT, 0 in that with induced VF, and 9% in that without induced VT/VF (P = NS). The 3-year total cardiac mortality was higher in patients with than in those without EF < 40% (27% vs 7%, P < 0.05). It is concluded that patients with organic heart disease and spontaneous nonsustained VT may not need PES or antiarrhythmic therapy if SA-ECG is normal and EF is ≥ 40%, since their risk of induced VT and sudden death is low. On the other hand, patients with abnormal SA-ECG and/or EF < 40% may require PES, since their risk for induced VT is high. Antiarrhythmic therapy may also be considered in these patients. [ABSTRACT FROM AUTHOR]

The presence of late potentials on the body surface recording was correlated with ventricular activation maps of reentrant circuits in the postinfarction canine model of reentrant excitation. Late potentials were found to correlate with delayed myocardial activation. However, during a reentrant rhythm complete diastolic activity on the body surface could not be detected if the mass of electrically active cells was too small and/or if very slow conduction in part of the reentrant circuit generated low amplitude extracellular potentials. Myocardial zones responsible for late potentials during a basic rhythm (e.g., sinus rhythm) may not necessarily be part of the critical zone of slow conduction during reentrant activation. Dynamic changes in late potentials are not amenable to temporal signal averaging techniques but could be detected by a high resolution beat-to-beat recording. A thorough understanding of the electrophysiological limitations of late potentials in the signal-averaged ECG could result in better utilization of the technique in clinical practice as well as in the development of new approaches for the detection of the arrhythmogenic substrate. [ABSTRACT FROM AUTHOR]

There are three current prognostic indicators of ventricular electrical instability: (1) categorization and stratification of spontaneous ventricular arrhythmias from standard EGG recordings; (2) programmed electrical stimulation; (3) direct recording of delayed depolarization potentials, usually referred to as late potentials. Of the three, the latter offers a new and promising approach. Late potentials represent delayed activation potentials of diseased myocardial zones and may prove to be a strong independent marker of the propensity to develop reentrant ventricular arrhythmias and sudden cardiac electrical death. The problem in identifying late potentials on the body surface is that the signal is smaller than the electrical noise produced by various sources. Two different techniques have been utilized to improve the signal-to-noise ratio: first, signal averaging, which is applicable to regular repetitive electrocardiographic signals but cannot detect moment-to-moment dynamic changes in the signal; second, low-noise or high-resolution electrocardiography that utilizes spatial averaging techniques as well as other noise-reducing measures to record the late potentials on a heat-to-beat basis. This technique has the potential of directly identifying malignant "reentrant" versus benign "focal" ventricular rhythms. The present report discusses the electrophysiologic basis of late potentials and the clinical results of both signal-averaged and low-noise recordings for evaluation of ventricular electrical instability, particularly in patients with ischemic heart disease. [ABSTRACT FROM AUTHOR]

Introduction: To identify the optimal criteria for activation time (AT) determination of bipolar electrograms from normal hearts, a high-resolution cross electrode array comprising 128 unipolar electrodes of 500-µm spacing was used to record extracellular potentials from the left ventricular epicardium of 12 dog hearts. Methods and Results: Recordings were made during broad wavefront propagation (B wave) and local elliptical wavefront propagation (E wave). Characteristics of 863 bipolar electrograms (1-mm spacing) were constructed from unipolar data standardized for differences in polarity, then clarified morphologically. Features for bipolar AT determination were compared to the time of the negative peak of the first temporal derivative of a unipolar electrogram situated mid-way between the bipoles. During B wave, three distinct morphologies were observed: uniphasic (61%), biphasic (23%), and triphasic (16%). Peak voltage of uniphasic and triphasic signals was the best predictor of AT (error: 0.6 ± 0.6 msec and 0.6 ± 0.8 msec, respectively). During E wave, parallel orientation of the bipoles with respect to the direction of impulse propagation wavefront resulted in uniphasic signals (> 99%), while for perpendicular orientation of the bipoles, electrogram morphology was variable. For parallel orientation of the bipoles, peak negative voltage was the best predictor of AT for both longitudinal and transverse propagation, while for perpendicular bipole orientation, peak negative voltage was a less reliable predictor for propagation along both fiber axes. Increasing interpolar distance resulted in a degradation in AT accuracy for B wave (from 0.6 ± 0.6 msec at 1 mm to 1.1 ± 1.2 msec at 7 mm) and for E wave (from 0.4 ± 0.3 msec at 1 mm to 3.1 ± 2.9 msec at 7 mm). Conclusions: (1) The accuracy of bipolar electrograms is sensitive to wavefront direction, bipole orientation, and interpolar distance; (2) peak negative voltage of uniphasic and triphasic signals is a reliable predictor of AT, but only for B wave; (3) a maximum interpolar distance of 2 mm and bipole orientation parallel to the direction of the impulse wavefront are minimally required for accurate determination of AT during impulse propagation initiated near the recording electrodes; and (4) for impulses initiated near the recording site in normal tissue, a biphasic or triphasic morphology almost certainly indicates that the bipolar electrode is oriented perpendicular to the wavefront direction, irrespective of fiber orientation. [ABSTRACT FROM AUTHOR]

Threshold testing of cardiac rhythm devices is essential to monitoring the proper functioning of such devices (1). However, the currently method of applying multiple ECG leads to the patient is burdensome and time consuming (2). We are presenting a completely new way to perform cardiac rhythm device threshold testing using pulse oximetry. Twenty patients, with varying cardiac rhythm devices and pacing modes, were enrolled and had their atrial and ventricular thresholds tested. A comparison was made between simultaneous threshold determinations via the standard EGM based method and the new pulse oximetry based method. 75% of the ventricular threshold tested and 58% of the atrial thresholds tested were the same with the two testing methods. The remainder of the tests (25% of ventricular threshold and 42% of the atrial threshold tests) varied by +0.25 V. This study shows that pulse oximetry based testing is an accurate, reliable, and easy way to perform cardiac rhythm device threshold testing and may complement traditional methods to perform such tests in the future. [ABSTRACT FROM AUTHOR]

This consensus guideline was prepared on behalf of the International Society for Holter and Noninvasive Electrocardiology and is cosponsored by the Japanese Circulation Society, the Computers in Cardiology Working Group on e-Cardiology of the European Society of Cardiology, and the European Cardiac Arrhythmia Society. It discusses the electrocardiographic phenomenon of T-wave alternans (TWA) (i.e., a beat-to-beat alternation in the morphology and amplitude of the ST- segment or T-wave). This statement focuses on its physiological basis and measurement technologies and its clinical utility in stratifying risk for life-threatening ventricular arrhythmias. Signal processing techniques including the frequency-domain Spectral Method and the time-domain Modified Moving Average method have demonstrated the utility of TWA in arrhythmia risk stratification in prospective studies in >12,000 patients. The majority of exercise-based studies using both methods have reported high relative risks for cardiovascular mortality and for sudden cardiac death in patients with preserved as well as depressed left ventricular ejection fraction. Studies with ambulatory electrocardiogram-based TWA analysis with Modified Moving Average method have yielded significant predictive capacity. However, negative studies with the Spectral Method have also appeared, including 2 interventional studies in patients with implantable defibrillators. Meta-analyses have been performed to gain insights into this issue. Frontiers of TWA research include use in arrhythmia risk stratification of individuals with preserved ejection fraction, improvements in predictivity with quantitative analysis, and utility in guiding medical as well as device-based therapy. Overall, although TWA appears to be a useful marker of risk for arrhythmic and cardiovascular death, there is as yet no definitive evidence that it can guide therapy. [Copyright &y& Elsevier]

This investigation was performed to evaluate the feasibility of detecting repolarization alternans with the heart rate elevated with a bicycle exercise protocol. Sensitive spectral signal-processing techniques are able to detect beat-to-beat alternation of the amplitude of the T wave, which is not visible on standard electrocardiogram. Previous animal and human investigations using atrial or ventricular pacing have demonstrated that T-wave alternans is a marker of vulnerability to ventricular arrhythmias. Using a spectral analysis technique incorporating noise reduction signal-processing software, we evaluated electrical alternans at rest and with the heart rate elevated during a bicycle exercise protocol. In this study we defined optimal criteria for electrical alternans to separate patients from those without inducible arrhythmias. Alternans and signal-averaged electrocardiographic results were compared with the results of vulnerability to ventricular arrhythmias as defined by induction of sustained ventricular tachycardia or fibrillation at electrophysiologic evaluation. In 27 patients alternans recorded at rest and with exercise had a sensitivity of 89%, specificity of 75%, and overall clinical accuracy of 80% (p <0.003). In this patient population the signal-averaged electrocardiogram was not a significant predictor of arrhythmia vulnerability. This is the first study to report that repolarization alternans can be detected with heart rate elevated with a bicycle exercise protocol. Alternans measured using this technique is an accurate predictor of arrhythmia inducibility. [ABSTRACT FROM AUTHOR]