Background Although electrical alternans (alternating amplitudefrom beat to beat on the electrocardiogram) has been associatedwith ventricular arrhythmias in many clinical settings, itsphysiologic importance and prognostic implications remain unknown.
Methods To test the hypothesis that electrical alternans isa marker of vulnerability to ventricular arrhythmias, we developeda technique to detect subtle alternation in the morphologicfeatures of the electrocardiogram (which would not be detectableby visual inspection of the electrocardiogram). In a group of83 patients referred for diagnostic electrophysiologic testing,we prospectively examined whether levels of alternans predictedvulnerability to arrhythmias as defined by the outcome of electrophysiologictesting and arrhythmia-free survival.
Results Sustained ventricular arrhythmias were induced duringelectrophysiologic testing in 32 of the patients (39 percent).In this group, low-level electrical alternans (a beat-to-beatchange in amplitude of <15 microV) was detected over a broadrange of physiologic heart rates (from 95 to 150 beats per minute)and primarily involved the ST segment and the T wave (i.e.,the phase of repolarization). Alternans during repolarizationwas a significant and independent predictor of inducible arrhythmiason electrophysiologic testing (sensitivity, 81 percent; specificity,84 percent; relative risk, 5.2). Of 66 patients followed forup to 20 months, 13 had arrhythmic events. Alternans affectingthe T wave and inducibility of ventricular arrhythmias weresignificant and essentially equivalent predictors of survivalwithout arrhythmia (P<0.001). Actuarial survival withoutarrhythmia at 20 months was significantly lower among the patientswith T-wave alternans (19 percent) than among the patients withoutT-wave alternans (94 percent).
Conclusions Electrical alternans affecting the ST segment andT wave is common among patients at increased risk for ventriculararrhythmias. Subtle electrical alternans on the electrocardiogrammay serve as a noninvasive marker of vulnerability to ventriculararrhythmias.
Although electrical alternans (alternating amplitude from beatto beat on the electrocardiogram) has remained an electrocardiographiccuriosity for more than three quarters of a century,1,2,3,4we have only recently recognized that it can be a harbingerof sudden cardiac death5,6,7. Electrical alternans can precedeventricular fibrillation in patients undergoing coronary angioplasty8or those with Prinzmetal's angina,9,10 the congenital prolongedQT syndrome,5,11 acute myocardial infarction,12,13 catecholamineexcess,14,15 and electrolyte derangements16,17. These reports,though numerous, are largely anecdotal, and the prevalence andprognostic importance of alternans among the patients with theseconditions or in the much larger group of patients with ventriculartachyarrhythmias due to chronic ischemic heart disease havenot been systematically evaluated.
Using methods for analyzing the statistical properties of beat-to-beatfluctuations in the morphologic features of the electrocardiogram,we7,18 and others19,20 have confirmed that alternans affectingthe T wave (i.e., T-wave or repolarization alternans) may beclosely associated with the genesis of ventricular arrhythmiasin dogs. Moreover, repolarization alternans in vivo that maybe physiologically important can be subtle enough to precludevisual detection on the electrocardiogram yet readily measurablewith appropriate techniques7. In the present study, we useda technique with the capacity to detect visually inapparentbeat-to-beat oscillations of the surface electrocardiogram totest the hypothesis that repolarization alternans is a markerof vulnerability to arrhythmias in humans. If this hypothesisproves correct, electrical alternans measured from the surfaceelectrocardiogram may ultimately serve as a noninvasive markerof susceptibility to life-threatening ventricular arrhythmias.
Methods
Study Design
All patients referred for diagnostic electrophysiologic testingwere eligible for this study. Patients were excluded if atrialpacing was not possible (for example, because of atrial arrhythmias),if a permanent pacemaker had previously been implanted (to excludesecondary T-wave changes), or if excessive ventricular ectopicbeats (>9 percent) were present. Electrical alternans wasmeasured in 83 consecutive patients who met these entry criteria.Informed written consent was obtained from all patients.
To assess the relation between electrical alternans and susceptibilityto inducible ventricular arrhythmias, base-line measurementsof electrical alternans were compared with the results of base-lineelectrophysiologic testing in each patient. We also assessedthe relation of electrical alternans to arrhythmia-free survival,which was assessed prospectively and was defined as the lengthof time from electrophysiologic testing until electrocardiographicallydocumented sustained ventricular tachycardia, ventricular fibrillation,or sudden cardiac death (as defined elsewhere21). To ensurethat alternans and survival were assessed under comparable treatmentconditions, the measurement of alternans used to predict survivalin patients undergoing serial drug testing was the one obtainedwhile the patients were receiving their long-term drug regimen.Of the 83 patients who entered this study, 17 were excludedfrom the survival analysis because antiarrhythmic-drug therapywas initiated or changed during the follow-up period.
Characteristics of the Patients
Sixty-nine of 83 patients underwent the base-line study whilereceiving no antiarrhythmic drugs. Most patients (76 percent)had organic heart disease, of which the majority of cases weredue to coronary artery disease (Table 1). Forty of the 53 patientswith documented coronary disease (75 percent) also had a historyof myocardial infarction. Bundle-branch block was present in23 patients.
Patients were studied while fasting and lightly sedated. Sevensilver-silver chloride electrocardiographic electrodes werepositioned in a Frank orthogonal (XYZ) configuration22. Eachlead was secured with a skin drill to ensure uniform impedanceat all sites. Electrocardiographic signals were amplified (1cm per millivolt) and filtered (band width, 0.01 Hz to 100 Hz)with a standard electrocardiographic recorder (Hewlett-Packard7400A, Rockville, Md.) and were digitized (500 Hz with 12-bitresolution) in real time with customized data-acquisition software23.
Endocardial recording-stimulating catheters were inserted transvenouslyby standard techniques. To control for patient-to-patient variationsin heart rate, electrical alternans was measured while the rightatrium was paced at a rate as close to 100 beats per minuteas possible (mean [±SD], 103 ±13). After fiveminutes of steady-state atrial pacing, 300 consecutive electrocardiographiccomplexes were recorded and analyzed for electrical alternans.Previously, we had found that five minutes is sufficient toensure that alternans is not affected by the change in rateassociated with the initiation of pacing24.
A technique for detecting alternans of electrocardiographicamplitude at the microvolt level7 was modified for clinicaluse in this study. The investigators performing the alternansanalysis were blinded to the outcome of electrophysiologic testing.The analysis was performed with a Unix workstation (SUN Sparcstation,Mountain View, Calif.) on the magnitude of the electrocardiographicvector derived from the three orthogonal leads. The magnitudeof the vector was used to reduce the effect of mechanical rotationof the heart22. Because of the sensitivity of this techniqueto subtle fluctuations in the morphologic features of the electrocardiogram,the computer algorithm selected 128 consecutive complexes soas to minimize the number of ectopic wave forms (such as prematureventricular contractions). Ectopic complexes that were includedamong the 128 beats analyzed were replaced by the averaged complexto maintain a consistent phase relation between consecutivebeats.
Beat-to-beat fluctuations in electrocardiographic amplitudewere represented as power spectra7 by calculating the squaredmagnitude of the fast Fourier transformation of beat-to-beatfluctuations in the amplitude of each sample point of the 128time-aligned electrocardiographic complexes7. Power spectracalculated for each point within the QRS complex, ST segment,and T wave were then summed, and the final results were representedby three aggregate spectra corresponding to the sums over eachof these intervals. A representative example of an aggregateT-wave power spectrum is shown in Figure 1 (3 of the 128 electrocardiographiccomplexes used to calculate the spectrum are shown in the inset).The spectrum depicts the frequencies at which beat-to-beat fluctuationsin the amplitude of the T wave occur. For example, the spectralpeak at the frequency of 0.1 cycle per beat corresponds to periodicfluctuations in T-wave amplitude that repeat every 10th beat.Similarly, the peak at 0.5 cycle per beat is due to fluctuationsin T-wave amplitude on every other beat; hence, the magnitudeof this peak is a direct measure of electrical alternans.
Figure 1. Representative Example of the Use of a Computer Algorithm to Detect Low-Level Beat-to-Beat Oscillations of the Surface Morphology of the Electrocardiogram.
We used 128 consecutive electrocardiographic complexes recorded from three orthogonal leads to generate the representation of beat-to-beat oscillations in the amplitude of the electrocardiogram. The inset shows a segment of one electrocardiographic lead (X) from which the T-wave power spectrum was derived. T-wave alternans is measured from the amplitude of the peak of the power spectrum at the alternans frequency (0.5 cycle per beat) and is compared with the amplitude of the power spectrum measured in a predetermined noise window (see the Methods section). Despite the absence of any visible beat-to-beat alternation of T-wave amplitude (inset), a clear peak is evident at the alternans frequency that cannot be attributed to noise.
Electrical alternans was expressed as follows:
cumulative alternans voltage (in microvolts) = square root of(alternans peak - mean(noise)),
and alternans ratio = (alternans peak - mean(noise))/noise)
with the mean (noise), standard deviation (noise) of spectralnoise estimated from a predefined noise window (Figure 1). Sincethe cumulative alternans voltage is derived from the aggregatespectra, it represents the square root of the spectral alternansvoltages summed over all sample points in the defined electrocardiographicsegment (QRS complex, ST segment, or T wave). The average alternansvoltage may be obtained by dividing the cumulative alternansvoltage by the square root of the number of sample points inthe segment. For example, a 10-microV cumulative alternans voltagein a 150-msec T-wave segment sampled at intervals of 2 msecyields an average alternans voltage of (10 µV) / (150msec x 0.5 sample points/msec) = 1.2 µV.
The alternans ratio reflects the extent to which the measuredalternans exceeds the uncertainty (noise) of the measurementand conveys the statistical degree of confidence in the alternansmeasurement. Because the alternans ratio is influenced by ambientnoise, our recording equipment and computer-analysis systemwere designed to produce consistently low noise levels, thusminimizing the likelihood that substantial alternans would beconcealed by noise. Spectral noise levels were low and did notdiffer between patients with positive (noise level, 6.0 microV2)and negative (noise level, 5.7 microV2) electrophysiologic studies.
Electrophysiologic Studies
Recordings of electrical alternans were followed immediatelyby electrophysiologic testing. Up to three extrastimuli weredelivered from up to two right ventricular sites. The numberof extrastimuli and stimulation sites used were determined beforeeach study without any knowledge of the patient's alternanslevels; the decision was guided solely by the clinical indicationsfor the study. A minimum of two extrastimuli were deliveredfrom at least one ventricular site in all patients. Electrophysiologictests were considered positive if sustained ventricular tachycardia(lasting more than 30 seconds or requiring termination becauseof hemodynamic collapse) or ventricular fibrillation was induced.
Statistical Analysis
In addition to electrical alternans, relevant clinical variablessuch as the patient's age, sex, left ventricular ejection fraction,findings on Holter recordings, cause of heart disease, indicationsfor electrophysiologic study, and use of beta-blocking and antiarrhythmicdrugs were analyzed with a multivariate stepwise logistic-regressionmodel to identify independent predictors of inducible ventriculararrhythmias. The role of electrophysiologic testing and electricalalternans in predicting arrhythmia-free survival was evaluatedwith a Cox proportional-hazards technique (Research and StatisticsManagement, Bolt, Beranek and Newman Research Systems, Cambridge,Mass.). Data are expressed as means ±SD.
Results
Characteristics of Electrical Alternans
The algorithm used in this study was highly sensitive to subtlealternation in the amplitude of the electrocardiogram. As shownin Figure 1, despite the absence of any visible T-wave fluctuationson the surface electrocardiogram, the spectrum reveals a clearpeak at the alternans frequency. Alternans was visually apparentin only 2 of 36 base-line electrophysiologic studies in whicha statistically significant alternans peak was evident in thefrequency spectrum. Electrical alternans was not uniformly distributedthroughout all phases of the cardiac cycle. Typically, alternansinvolved the ST segment and, to a greater extent, the T wave,with relative sparing of the QRS complex (Figure 2).
Figure 2. Representative Electrocardiogram (Top), with the Magnitude of Electrical Alternans (Bottom) Measured at Each Point of the QRS Complex (QRS), ST Segment (ST), and T Wave (T).
Electrical alternans is much more prominent during repolarization (T) than during depolarization (QRS). The alternans ratio reflects the extent to which measured alternans exceeds the uncertainty of the measurement (see the Methods section).
To determine whether electrical alternans is a rate-dependentphenomenon, we measured alternans at multiple stimulation ratesin 10 patients. The magnitudes of ST-segment and T-wave alternanswere constant over a broad range of rates (from 95 through 150beats per minute). In contrast, QRS alternans increased at fasterrates. Finally, bundle-branch block did not prevent the detectionof alternans.
Characteristics of Inducible Arrhythmias
Thirty-nine percent of the patients had positive electrophysiologicstudies (21 had sustained ventricular tachycardia and 11 hadventricular fibrillation). The mean length of the ventricular-tachycardiacycle was 297 ±65 msec. Sustained ventricular tachycardiawas induced with single (10 percent), double (67 percent), andtriple (23 percent) extrastimuli, whereas ventricular fibrillationwas induced with double extrastimuli (45 percent) and tripleextrastimuli (55 percent).
Predictors of Inducible Arrhythmias
Two independent and statistically significant groups of predictorsof inducible ventricular arrhythmia were identified: repolarizationalternans (i.e., ST-segment or T-wave alternans), and impairedleft ventricular function (i.e., reduced left ventricular ejectionfraction or a history of myocardial infarction). Predictorswithin each group were statistically interdependent. A quantitativerelation was found between repolarization alternans and theresults of electrophysiologic testing; that is, the magnitudeof ST-segment and T-wave alternans directly correlated withthe probability that ventricular tachycardia or ventricularfibrillation would be induced. QRS alternans was not a significantpredictor of inducibility, nor were the cause of the heart disease,the patient's sex, the number of premature ventricular complexeson Holter recordings, or the use of beta-blocking agents.
Levels of T-wave alternans measured in patients with positiveand negative electrophysiologic tests are compared in Figure 3.Median T-wave alternans ratios were significantly greaterin patients in whom ventricular arrhythmias were induced thanin patients without inducible arrhythmias (4.9 vs. 0.0, P =0.001). The sensitivity and specificity of alternans in predictingresponses to programmed ventricular stimulation (Figure 3 andTable 2) were maximized by a T-wave alternans ratio of 2.5 (relativerisk, 5.2; 95 percent confidence interval, 3.2 to 11.1) anda cumulative alternans voltage of 10 microV (relative risk,5.1; 95 percent confidence interval, 2.4 to 10.9). Subgroupanalysis of the 69 patients who underwent base-line electrophysiologictesting while receiving no antiarrhythmic drugs revealed a similarrelation between the T-wave alternans ratio and susceptibilityto inducible arrhythmias (P = 0.001).
Figure 3. T-Wave Alternans Ratios Measured during the Base-Line Electrophysiologic Study in Patients with and without Inducible Ventricular Arrhythmias.
The horizontal line (alternans ratio, 2.5) shows the level of alternans that maximally discriminates between the two patient groups. The data points shown at an alternans ratio of 1.0 signify values of 1.0 or less.
Table 2. T-Wave Alternans as a Predictor of Susceptibility to Inducible Ventricular Arrhythmia.
Multivariate analysis showed that repolarization alternans identifiedunderlying electrical instability, independent of structuralheart disease. In Figure 4, alternans is compared in three subgroupsof patients: those with structurally normal hearts (none ofwhom had positive electrophysiologic studies) and those withstructural heart disease who had either positive or negativeelectrophysiologic tests. Both groups of patients with structuralheart disease had reduced left ventricular ejection fractionsand a high prevalence of myocardial infarction; however, onlythose in whom arrhythmias could be induced had elevated alternanslevels.
Figure 4. Left Ventricular Ejection Fraction (LVEF), Percentage of Patients with a History of Myocardial Infarction (MI), and Alternans Ratios in the ST Segment and T Wave in Subgroups of Patients.
Included in this analysis were 20 patients without organic heart disease (OHD), all of whom had negative electrophysiologic (EP) tests; 31 patients with OHD in whom ventricular arrhythmias could not be elicited by programmed stimulation during EP testing; and 32 patients with OHD who had positive EP tests. As expected, patients with organic heart disease had a lower LVEF and a higher prevalence of MI. The presence of OHD, by itself, was not associated with increased T-wave or ST-segment alternans ratios (i.e., alternans ratios >2.5). Alternans ratios were significantly elevated only in patients who were susceptible to inducible ventricular arrhythmias. Therefore, repolarization alternans was a marker of electrical and not mechanical cardiac dysfunction. The values shown are means +SE.
Repolarization Alternans and Arrhythmia-free Survival
Of 66 patients followed for up to 20 months, 13 had arrhythmicevents (median time to event, 4.2 months; range, 1.0 to 19.4).Five of these events were sudden cardiac deaths; the remainderwere documented ventricular arrhythmias. The anatomical andelectrophysiologic substrate for arrhythmias may have been modifiedin some patients by coronary artery bypass grafting (n = 3),catheter ablation (n = 2), or map-guided aneurysmectomy (n =1).
Levels of T-wave alternans were significantly greater (P = 0.01)in patients who had arrhythmic events (median alternans ratio,5.2) than in patients without events (median alternans ratio,0.7). On the basis of the results of an earlier pilot studyof an independent patient population,7 patients were classifiedas "alternans-positive" if their T-wave alternans ratio exceeded3.0. Alternans-positivity was associated with a markedly reducedrate of arrhythmia-free survival (relative risk, 9.0), sincearrhythmia-free survival according to Kaplan-Meier life-tableanalysis decreased early in the follow-up period (Figure 5).By 20 months, arrhythmia-free survival was 19 percent amongpatients with T-wave alternans, as compared with 94 percentamong patients without alternans (P<0.001). The use of awider range of T-wave alternans ratios (from 1.5 to 4.6) todefine alternans-positivity yielded similar results. Twenty-montharrhythmia-free survival in a subgroup of 45 patients who werenot treated with antiarrhythmic drugs was similarly reducedamong patients with T-wave alternans (44 percent, vs. 94 percentamong patients without alternans; P = 0.005). Two patients fulfilledthe criteria for sudden cardiac death,21 because they receivedshocks from internal defibrillators that were preceded by syncope.When determining survival rates after reclassifying these patientsas "survivors" (so that the survival criteria were identicalfor patients with and without internal defibrillators), 20-montharrhythmia-free survival for alternans-positive patients was32 percent and that for alternans-negative patients was 94 percent(P<0.001). Arrhythmia-free survival as predicted by electrophysiologictesting (Figure 5) was nearly identical to that predicted bythe presence of T-wave alternans.
Figure 5. T-Wave Alternans and Results of Electrophysiologic (EP) Testing in Relation to Arrhythmia-free Survival among 66 Patients.
In the left-hand panel, arrhythmia-free survival according to Kaplan-Meier life-table analysis is compared in patients with T-wave alternans (alternans ratio, >3.0) and without it (ratio, 3.0). Note that the presence of T-wave alternans is a strong predictor of reduced arrhythmia-free survival. In the right-hand panel, arrhythmia-free survival among patients with positive EP tests is compared with that among patients in whom ventricular arrhythmias were not induced on EP testing (negative EP test). The predictive value of EP testing and T-wave alternans is essentially the same in these plots.
Discussion
Since the early description of electrical alternans by Lewis,1several hundred cases have been reported in association withan apparently disparate set of clinical and experimental conditions.With the exception of rare circumstances in which alternansis caused by mechanical motion of the heart within the thorax,25,26,27conditions that provoke repolarization (i.e., ST-T wave) alternanshave one common feature: they are arrhythmogenic. Hellersteinand Liebow3 were the first to suggest, on the basis of theirstudies in animals in 1950, that repolarization alternans ismechanistically linked to arrhythmogenesis. A pilot study bySmith et al.7 raised the possibility that alternans may alsobe a marker of vulnerability to clinical arrhythmias. In thepresent study, we systematically tested the hypothesis thatelectrical alternans is linked to the genesis of ventriculararrhythmias in humans.
In this study, we used a signal-processing technique to measureelectrical alternans at a microvolt level. The sensitivity andreliability of this technique derive from its capacity to distinguishalternans-type fluctuations in the electrocardiogram from muchlarger fluctuations due to noise or to other physiologic fluctuations,such as respiration. The maximal level of T-wave alternans recordedin this study was only 116 microV, reaffirming the need forsensitive signal-processing techniques and explaining why alternansis not commonly recognized on standard electrocardiographictracings4. Furthermore, our measurement technique does not simplyindicate the presence or absence of alternans but determinesthe magnitude of alternans present in any electrocardiographicsegment. This method was critical to our results, because alternansis not an all-or-nothing phenomenon. Instead, there is a continuumof proarrhythmic influence of electrical alternans.
Properties of Electrical Alternans
Although our patient population was diverse, several commonproperties of electrical alternans were evident. First, electricalalternans was present in a large majority of patients who hadincreased vulnerability to arrhythmias. Alternans of the STsegment or T wave (alternans ratio, >2.5) was present in85 percent of patients with positive electrophysiologic tests.Second, alternans involved primarily the repolarization phasesof the cardiac cycle (i.e., ST-T wave), and the magnitude ofrepolarization alternans was relatively insensitive to the heartrate. In contrast, alternans of the QRS complex was smallerin magnitude, did not correlate with vulnerability to arrhythmias,and was rate-dependent (QRS alternans was typically evidentonly at relatively rapid heart rates).
Repolarization Alternans and Vulnerability to Arrhythmia
A principal aim of this study was to establish the prognosticimportance of electrical alternans in humans. As demonstratedpreviously, a depressed left ventricular ejection fraction28and a history of myocardial infarction29 contributed in importantways to the inducibility of ventricular arrhythmia in our patients.Irrespective of left ventricular mechanical function, however,subtle alternation of the ST segment or T wave (i.e., repolarizationalternans) was an independent marker of vulnerability to inducibleventricular arrhythmias and clinical arrhythmic events. Ourfindings are consistent with those of earlier experimental studiesin which alternans of the electrocardiogram in dogs was foundprimarily to affect the T wave, was often in the microvolt range,and was closely related to ventricular electrical instability7,20.
In the current study, repolarization alternans was as effectiveas invasive electrophysiologic testing in predicting arrhythmicevents. Although it would be premature to suggest that repolarizationalternans be used as an alternative to electrophysiologic testing,our results suggest that repolarization alternans may be usefulfor evaluating several groups of patients. For example, screeningpatients with syncope might provide a means of identifying patientsat high risk for arrhythmias who are suitable candidates forelectrophysiologic testing. Indeed, among the 18 patients whopresented with syncope in this study, 3 of the 5 who were positivefor T-wave alternans also had positive electrophysiologic studies.In the absence of T-wave alternans, ventricular arrhythmiaswere induced in only 1 of 13 patients with syncope (P = 0.02).
Limitations of the Study
In this study, vulnerability to arrhythmia was defined in partby the outcome of electrophysiologic testing. Although highlypredictive of arrhythmic events,30 electrophysiologic testingmay not be an ideal gold standard, especially for patients withnonischemic cardiomyopathy and those in whom ventricular fibrillationcan be induced. The inclusion of such patients was expected,since consecutive patients were tested in order to eliminateselection bias. These considerations obviously did not affectour data on arrhythmia-free survival, which was used as an independentand probably more relevant clinical end point for the assessmentof vulnerability to arrhythmias. Since our experimental designrequired that we test patients undergoing electrophysiologicstudies, the risk of arrhythmias in the study population wasundoubtedly greater than that in the general population. Thisfactor should be considered when our results are extrapolatedto broader patient groups.
In our study alternans was measured during atrial pacing inorder to eliminate any possible influence of heart rate or beat-to-beatvariability in heart rate on measured T-wave alternans. To makethe measurement of repolarization alternans a suitable testfor ambulatory patients, improvements in the algorithm may beneeded to compensate for fluctuations in heart rate associatedwith sinus rhythm.
Implications of the Study
Sudden cardiac death is the most devastating manifestation ofcardiac disease, and accurate identification of the patientsat greatest risk for sudden death remains the preeminent challengeto physicians who care for arrhythmia-prone patients. Assessmentof left ventricular ejection fraction,28 Holter monitoring,31and signal-averaged late potentials32 have become the principalnoninvasive means of determining the risk of ventricular arrhythmiasafter myocardial infarction. Unlike repolarization alternans,these measures of vulnerability to arrhythmias have previouslybeen found to be less predictive of arrhythmic events than electrophysiologictesting30. Furthermore, the clinical value of any of these techniquesis often limited in individual patients. For example, sustainedventricular arrhythmias are rarely observed during ambulatorymonitoring, and ventricular ectopic activity is highly variableand unpredictable from day to day.
Signal averaging is applicable only to a limited patient population,since late potentials are not easily identified in the presenceof conduction abnormalities such as bundle-branch block. Unlikesignal averaging, electrical alternans is a measure of beat-to-beatchanges in amplitude and not absolute amplitude. Hence, onewould predict that bundle-branch block should not preclude itsdetection. In this study, electrical alternans was indeed detectedin patients with bundle-branch block and bore the same relationto the results of electrophysiologic study and arrhythmia-freesurvival in those patients as in patients without bundle-branchblock.
Our data indicate that repolarization alternans at the microvoltlevel can be successfully detected with existing technologyand a commercially available electrocardiographic recorder.We have described a quantitative relation between repolarizationalternans and vulnerability to arrhythmias, which could be exploitedto define the risk of ventricular arrhythmias and determinewhich patients are most likely to benefit from invasive electrophysiologictesting. Further studies are required to clarify the pathophysiologicbasis of electrical alternans and to determine whether its presencereflects an underlying disturbance of cardiac repolarizationin patients at risk for sudden cardiac death.
Supported by a grant (R01-HL39291) from the National Institutesof Health and a fellowship from the North American Society ofPacing and Electrophysiology (to Dr. Rosenbaum).
Dr. Cohen is a consultant to, a director of, and an equity holderin Cambridge Heart, Inc., a company that has licensed technologyfor the measurement of electrical alternans. Dr. Ruskin is aconsultant to Cambridge Heart, Inc., and has been granted theoption to purchase equity in the company.
We are indebted to John B. Newell, Ph.D., for his expert assistancein the statistical analysis.
Source Information
From the Cardiac Unit, Massachusetts General Hospital, Boston (D.S.R., H.G., J.N.R.); the Harvard University-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Mass. (D.S.R., L.E.J., J.M.S., R.J.C.); and the Departments of Medicine and Biomedical Engineering, Case Western Reserve University, Cleveland (D.S.R.). Presented in part as the Samuel A. Levine Young Investigator Award presentation to the American Heart Association, Anaheim, Calif., Nov. 12, 1991.
Address reprint requests to Dr. Rosenbaum at the Department of Biomedical Engineering, Case Western Reserve University, Wickenden Bldg., Rm. 504, Cleveland, OH 44106.
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noise)
Previous
3.0). Note that the presence of T-wave alternans is a strong predictor of reduced arrhythmia-free survival. In the right-hand panel, arrhythmia-free survival among patients with positive EP tests is compared with that among patients in whom ventricular arrhythmias were not induced on EP testing (negative EP test). The predictive value of EP testing and T-wave alternans is essentially the same in these plots.