The signal averaged surface electrocardiogram and the identification of late potentials

The Signal Averaged Surface Electrocardiogram Identification of Late Potentials Patrick

A.X.

Hall,

J. Edwin

Atwood,

ENTRICULAR TACHYARRHYTHMIAS are a major cause of sudden cardiac death, especially in patients after myocardial infarction.‘** Accurate detection of those prone to malignant ventricular arrhythmias is essential to the prevention of sudden death. Many parameters, including clinical findings, and results from exercise testing, holter monitoring, and cardiac catheterization have been used to identify patients at high risk of sudden death.3-8 More recently, electrophysiologic stimulation testing in the cardiac catheterization laboratory has been used as a method of evaluating these patients.g*‘O The cost and invasive nature of this procedure, however, makes it impractical for use as a screening test for large numbers of patients. Tests designed to evaluate large populations at risk should be noninvasive, relatively inexpensive, and easily performed. The signal averaged electrocardiogram (ECG) may be such a screening test. This noninvasive, inexpensive procedure incorporates high gain amplification and signal averaging techniques to detect from ECG recordings on the body surface low amplitude, high frequency signals in or near the terminal portion of the QRS complex (Fig 1). There are many synonyms for these signals including delayed depolarization, arrhythmogenic ventricular activity (AVA), delayed wave-form activity (D wave), and ventricular late potentials (VLPs). These signals, called late potentials or LPs in this review (Fig 2) are rarely identified on routine ECG. Late potentials are thought to represent slow or delayed conduction through the myocardium. Within the last 10 years, numerous studies have provided convincing evidence that delayed conduction plays an important role in the genesis of ventricular arrhythmias.“-” Additional studies have corroborated the capacity of the highly amplified signal averaged ECG to detect such delayed activity.“-*’ Many investigators have used direct epicardial and endocardial mapping techniques to record delayed, fragmented electrical activity in patients and animals with ventricular arrhythmias.‘1-20,26-30Several investigators have used both the body surface signal averaged ECG and

V

Progress

in Cardiovascular

Diseases,

Vol XXXI,

No 4 (January/February),

Jonathan

Myers,

and Victor

and the

F. Froelicher

endocardial catheter techniques to record delayed potentials in man and animals with ventricular tachyarrhythmias. They have found a close temporal correlation between the delayed potentials recorded by the two methods.‘g*20~30 While many studies lend theoretical support to the use of signal averaging techniques in identifying patients at risk of developing dangerous ventricular arrhythmias, the clinical role of this technique has not been defined. The intention of this review is to summarize the methodology and principles of signal averaged electrocardiography and to analyze critically many of the published reports to better define its current status. METHODOLOGY

AND AVERAGING

PRINCIPLES OF

THE

OF SIGNAL ECG

Lead Systems

For recording late potentials from the surface of the body, most investigators use an XYZ lead system formed by three orthogonal bipolar electrode combinations. Some have combined the signals from the three bipolar electrode combinations into a spatial vector magnitude (SVM) where SVM equals the square root of X2 + Y* + Z* (Fig 3).2*,23This yields a composite waveform which includes the information from all three bipolar electrode combinations. Breithardt et al** and Rozansky et a13’ use a precordial lead system designed to minimize potential artifact derived from having leads placed over cardiac movements. Breithardt et al uses four precordial electrodes to obtain four bipolar tracings which are individually analyzed for LPs.~~ Rozansky et al uses four precordial leads from which three bipolar and three augmented (unipolar) tracings are obtained and individually analyzed for LPs.~’ Hombach et al uses precordial leads and analyzes three separate bipolar and three augmented From Cardiology Section, Long Beach VA Medical Center, Long Beach, CA. Address reprint requests to Patrick A.X. Hall, Cardiology Section, Long Beach VA Medical Center, 5901 E Seventh St, Long Beach, CA 90822. 0 1988 by Grune & Stratton, Inc. 0033-0620/89/3104-0003$5.00/O

1989:

pp 295-317

295

296

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ET AL

I

STORAGE

SURFACE ELECTRODES f

1

(unipolar) recordings.32 The Rozanski and Hombath lead placement systems are illustrated in Fig 4. Few studies have compared the various types of lead systems. The question remains as to whether LPs are actually localized phenomena, and if so, whether electrodes placed in proximity to the left ventricle would have an advantage over the commonly used orthogonal lead systems. Oeff et al compared three different lead systems for detecting LPs and found considerable inconsistencies.” In a separate study, Oeff noted that when unipolar leads are used, LPs often can be recorded only from well circumscribed areas.34 A similar phenomenon however, has also been seen

,

--

Schematic late potential

generaelec-

with the bipolar lead system. Berbari et al compared signal averaged recordings from a bipolar XYZ lead system with recordings from a set of 24 electrodes positioned across the left precordium and referenced to the back.35 All eight patients tested had old inferior wall myocardial infarctions with a history of ventricular tachycardia and were being treated with amiodarone. In three patients, precordial leads located between the third and fifth intercostal spaces in the region of V4 to V6 had significantly longer QRS duration (based on LP activity) than in the XYZ lead system. They felt a precordial lead system might better identify localized LPs. Conversely, Goldberger used fourier transform anal-

ORSD 97me HFTO lOOma HFO40 19ma HFl?NSA 63. BUV HFNO IS 0. SuV CYCLES 251

Fig 2. Example of normal and abnormal signal averaged ECG, using Arrhythmia Research. Technology system. Note the normal HFTD (100 milliseconds). HFD40 (18 millisecondsl. and HFRMS (63.6 aV) on the left, and the abnormal HFTD (122 milliseconds), HFD40 (41 millisecondsk and HFRMS (10.5 pV) on the right. The arrow denotes LP activity.

Fig 1. tion of the trocardiogram.

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Fig 4. The lead placement mirrored on the Fig 3. Positive and negative electrode placements for the XYZ lead system. The negative 2 placement is on the back.

ysis of the ECG and concluded that inferior leads offered no advantages over a conventional lead system.36 Faugere et al characterized the spatial distribution of late ventricular potentials by body surface mapping in patients with ventricular tachycardia (VT).3’ They concluded that LPs can be detected best with only three orthogonal leads because their distributions are bipolar. They felt that maps provide additional information about location and that electrodes near the torso produce stronger signals than electrodes further away. Ampli$cation

Electrocardiogram electrode signals are initially amplified between lo3 to IO8 times with a wide frequency band pass. Usually this is done prior to analog-to-digital conversion. Some investigators further amplify the signals following analog to digital conversion. Analog-Digital

Conversion

A computer is used to convert the original continuous analog electrocardiographic signal into a digital signal of voltages sampled at frequent, fixed time intervals. As with all digitized signals, resolution is governed by three factors: computer storage capacity, sampling interval,

Rozanski systems. back.

(xl and Hombach (0) precordial The Hombach V4 placement

is

and the analog sampling window. For visualizing LPs, analog signals are usually digitized with 12 Bit word or byte accuracy. The larger the word or byte size a computer can process, the greater the resolution. Thus, a computer capable of processing 12 Bit words will give greater signal resolution than one able to process only eight Bit words. Micro processors are now capable of 32 bit accuracy. Resolution is also dependent on the sampling interval. The greater the sampling interval the more detail is retained from the original analog signal. Sampling rates for LP evaluations vary from 1,000 samples to 10,000 samples per second. Sampling rates in standard computerized exercise ECG equipment are usually 250/set or 5OO/sec. The analog input voltage windows in modern A to D converters ensures maximal resolution. Noise

The noise encountered in the highly amplified recordings of electrical signals from the heart has numerous origins including: 1. Artifact arising from skeletal muscle noise, principally respiratory muscles. While not random, this type of high frequency (HF) noise is independent of electrical activity arising from the heart and will theoretically cancel out with signal averaging. 2. Artifact due to electrode placement over the cardiac impulses; while neither random or

298

independent it is minimized by not locating electrodes over such impulses. 3. Respiration causing baseline wander; this artifact is minimized by recording with patients relaxed and breathing comfortably in a supine position and by signal averaging. 4. Electronic noise arising from recording equipment (eg, amplifiers, electrodes). Poor skin preparation or bubble entrapment in electrode gel can cause a low frequency contact noise. This can be reduced by meticulous skin preparation (ie, shaving, cleaning with alcohol, and buffing skin lightly with an abrasive surface). Another type of electrode artifact is motion noise. This type of HF noise, caused by movement of skin against electrodes, is usually not a problem since subjects are resting comfortably in the supine position. 5. Line-frequency noise generated by the 60 Hz electrical power lines. This noise can be reduced by using shielded electrode cables or filters applied in series with the ECG amplifier. A 60 Hz notched filter should remove only a narrow band of frequencies around 60 Hz without attenuating any other frequencies. 6. High frequency stray electrical signals, devices such as radiologic machines, radio or radar transmitters, televisions and computers generate HF radio range signals. This noise can be avoided by either turning these devices off or

HALL

ET AL

by making recordings in an electrically shielded room. Through use of properly isolated amplifiers, appropriately placed and shielded lead systems, filters, and by averaging enough cycles, total noise can be reduced to less than 1 PV (or one hundredth of a millimeter on the standard ECG recordings). An example of how noise can affect the late potential recording is illustrated in Fig 5. The greatest reduction of noise is achieved by increasing the number of cycles averaged. The signal to noise ratio is proportional to the square root of the number of cycles averaged (eg, noise is reduced by a factor of 10 when 100 cycles are averaged). Filtering Filters have a great effect on the recognition and measurement of LPs. Most studies use high band pass filters with cutoffs ranging from 25 to 100 Hz. The high pass filter is used to allow the higher frequency signal derived from the depolarization phase of the action potential to pass without attenuation while reducing the low frequency, large amplitude signals originating from the plateau, or repolarization phase of the action potential. The high pass filter also lessens low frequency artifact. While filters have the capacity to isolate frequencies of interest, they can introduce artifact.

Fig 5. An illustration of the effect of noise on the LP recording. Note the difference between an acceptable amount of noise on the left (0.6 BV) and sn unacceptable amount (2.2 PV) on the right.

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Conventionally designed digital filters can “impulse ring,” resulting in low amplitude artifact resembling LPs.*’ Impulse ringing can be reduced by using digital filters with flat characteristics or eliminated by using bidirectional digital filters. Simson developed a bidirectional filter that completely eliminates impulse ringing.‘l This filter operates by processing the ECG forward in time until the middle of the QRS (40 milliseconds from onset). Then the ECG is processed retrograde starting late in the ST segment until the middle of the QRS complex is reached again. Breithardt et al avoids the potential problems with digital filters by using an analog high pass filter to process the ECG signal prior to digitizing.” He has found, however, that ringing persisting for less than 10 milliseconds can still occur. Inappropriate filters can also exclude signals of interest. Limited studies have been performed evaluating the effect of filters on LPs. Rozansky used high pass filters of 0, 20, 40 and 80 Hz and found the presence of LPs to be independent of frequency filtration. 31 Because LPs were identified by visual analysis and no specific criteria were given, it is difficult to determine whether filtration altered the LP duration or amplitude. Both Denes et alz3 and Simson et a138used the same recording system to evaluate 25 Hz and 40 Hz bidirectional digital high pass filters, but had conflicting results.23=38Denes found that the 40 Hz filter markedly improved the separation between normal subjects and a group of patients with a history of symptomatic sustained VT.23 Reproducibility was improved and variability between different LP measurements was reduced with the 40 Hz filter. Conversely, Simson showed that both 25 Hz and 40 Hz filters correctly classified patients with a 1% accuracy.38 Two recent studies using the same Arrhythmia Research Technology (ART) system also evaluated the effect filters have on LP measurements.39*40 Gomes et al prospectively evaluated the optimal bandpass in 86 patients: 24 normal subjects, 29 patients with heart disease without a history of ventricular arrhythmias, and 33 patients that had a history of sustained VT.39 Bidirectional high pass filter settings of 10, 15, 20, 25,40, 80 and 100 Hz were used with spatial vector magnitude of the terminal 40 milliseconds

299

of the QRS determined for each filter setting. Normal values for each filter setting were determined from the group of normal subjects. The 80 Hz filter setting provided the best sensitivity (88%) and specificity (72%). The highest specificity (90%) was achieved with the 25 Hz high pass filter setting. Sensitivity at the 25 Hz filter setting, however, was significantly diminished to 42%. Whether the other parameters, HFQRSD (the total duration of HF signals in the QRS complex) and HFD40 (the duration of HF signals measured from the end of the QRS backwards until the amplitude of the signals exceeds 40 pV), show as much variability over the spectrum of filter settings cannot be determined from the study. Berbari et al also noted that the spatial vector magnitude parameters derived from the terminal 40 milliseconds of the QRS were dependent on filtering processing schemes.40 Bidirectional digital filtering settings of 20, 30, 40, 50, and 60 Hz were used to evaluate 15 normal subjects and 11 patients with documented VT. Spatial vector magnitude was calculated for the terminal 40 milliseconds of the QRS high frequency root mean square (HFRMS) complex as well as for total QRS duration. The SVM of the terminal 40 milliseconds of the QRS complex differentiated normal subjects from VT patients only at the 40 Hz filter setting. The SVM of the total QRS complex distinguished the two groups at all high pass filter settings. Studies using the ART signal averaging system yield conflicting results, and have not identified the optimal filtering frequency for LP evaluation. Some of the late potential parameters change significantly with adjustments in the high pass filter setting, thereby affecting overall test sensitivity and specificity in identifying those at risk of developing sustained ventricular arrhythmias. In contrast, Denniss et al have developed and used a DEC 1 l/34 based signal averaging system which processes ECG signals at wide band pass (.05 Hz to 50 Hz), and report good test sensitivity and specificity in populations with and without sustained ventricular arrhythmias.4’ Analysis of the energy spectra of the ECG has yielded information that may be of help when selecting high pass filters. In 1960, Scher and Young found that the contribution of frequencies greater than 80 Hz was less than 3% of the total

300

HALL

normal ECG voltage. 42 In 1973, Golden et al used fast fourier transform analysis to evaluate the effect that various low pass filters (60, 80, 100,200, and 500 Hz) had on the energy spectra of the EGG in 10 normal adults.43 With 500 Hz and 200 Hz low pass filters there was no measurable amplitude decrease while with 100 Hz filters there was only a 0.5% decrease. When 60 Hz and 80 Hz filters were used the voltage was more significantly diminished. Golden et al and subsequently Riggs et al have shown that most of the energy in the normal QRS is less than 35 Hz.43944 The analysis of the energy spectra of the ECG in patients with ischemic heart disease or ventricular arrhythmias is less well studied. Craelius et al used direct endocardial mapping techniques in patients with VT to show that fragmented, delayed depolarizations have a peak frequency in the range of 25 to 50 Hz.~’ These fragmented potentials obtained from direct electrograms have been shown to correlate with the LPs recorded on the body surface by signal averaging techniques. 19*20*30 More recently, Cain et al used fast fourier transform analysis (FFTA) to quantitate differences in the frequency content of the signal averaged ECG in patients with and without sustained VT (Fig 6).46 The study included two groups of patients with documented remote myocardial infarction; one with subsequent epi-

TERMINAL QRS and ST SEGMENT

FREQUENCY

(Hz)

ET AL

sodes of sustained VT and a second group without a history of sustained VT. A group of normal subjects was also included in the study. In the patients with VT, the last 40 milliseconds of the QRS and the ST segment contained a lo-fold to loo-fold greater proportion of components in the 20 to 50 Hz range compared to normals or the post MI patients without a history of VT. The two peak frequencies were comparable between groups: 28 to 30 Hz and 41 to 43 Hz. In all groups, most of the energy comprising the terminal QRS and ST segments was less than 20 Hz. Frequencies greater than 50 Hz did not contribute significantly to the energy spectra of the terminal QRS and ST segments in any of the three groups. The distinguishing feature was not attributable to differences in frequency content, but rather to differences in amplitudes within a relatively narrow range of frequencies (20 to 50 Hz). These studies suggest that high pass filters set above 50 Hz could exclude or attenuate LPs. Averaging

After A to D conversion, signals are averaged. The purpose of signal averaging is to reduce the noise encountered when recording a highly amplified waveform such as the ECG. Regular samples of a periodic waveform along with noise are averaged together using an alignment marker that has a consistent temporal alignment

Fig 6. Fast Fourier Transform Analysis of the signal averaged ECG. Late potential recording of lead 2 with demarcation of the terminal 46 milliseconds of the QRS complex and ST segment. The initial (solid curve) and magnified (broken curve) energy spectra of the complex are illustrated below with their respective scales, the computer defined area ratio, frequency peaks (arrows), and magnitude ratios (MAG). Values for the erea and magnitude ratios have been multiplied by 10’ to facilitate graphic display. (Reprinted with permission.?

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within the wave form of interest. The net effect after averaging is an increase in the signal to noise amplitude ratio. The ensemble waveform produced by this signal averaged process is relatively smooth and continuous because the sampling interval is so frequent. There are several assumptions made and prerequisites that must be met when using signal averaging techniques for noise reduction.47 First, the signal of interest (in this case, the ECG) must be periodic so that serial samples can be obtained then subsequently summed and averaged to produce a composite waveform. As a corollary to this requirement, each periodic waveform must have a specific feature that can be used as a fiducial or reference point so that each waveform can be appropriately aligned. The reference point is usually some marker within the QRS complex. Second, the signal of interest and the noise must be independent. Third, the noise must be random and have a gaussian distribution. Most investigators include between 100 to 400 beats in an average though some average up to 1,000 beats. Early signal averaging studies used visual analysis to reject ectopic or grossly noisy beats prior to averaging.4s However, computer template recognition is currently used to properly align QRS complexes and to reject ectopic and noisy beats.21*23.25 The first step in the signal averaging process is to find a fiducial or reference point. This is essential because misalignment of beats during averaging or introduction of beats that are morphologically different will introduce artifact into the signal averaging process. Many investigators use the time interval of maximum slope change in the R wave as the fiducial point.2’-23*34 This usually occurs in the downslope of the R wave or in the upslope of the QS. A single lead is used as a reference lead and generally is the lead with the tallest R wave. Other investigators use less reliable reference points. The MAC 1 system uses the QRS onset to align the beats.3’“2 Cain and Zimmerman use the R wave peak, which is an unreliable fiducial point.25v49Since the peak is a difficult point to sample consistently for digitization, using it as the fiducial point results in a misalignment of complexes.” Other investigators have used frequency components of the QRS complex or auto correlation techniques to align complexes.

After a fiducial point is set, beats can be aligned and averaged. Most investigators use a template recognition system to properly align beats and to exclude premature ventricular contractions (PVCs), aberrant beats, or grossly noisy complexes. Simson uses an eight-point template starting from the reference time (maximum slope of R wave) and extending into the early ST segment.*l An initial eight-beat template is accepted if mean standard deviation is less than 20 pV. The template is updated every four beats with all beats accepted if they conform to within twice the standard deviation of the template. Cain uses a template recognition program and incorporates cross correlation techniques. *’ The lead with the largest R wave amplitude (ie, peak) is used to determine the R wave interval. QRS amplitude is quantitated in all three leads of a Frank X, Y, and Z lead system. Beats are accepted for averaging only if the R wave to R wave (R-R) interval is within *20% of the previously set R-R interval, the QRS amplitude remains unchanged in two of three leads, and if the fiducial point *20 sample values on either side of the fiducial point had a correlation coefficient of 98% in comparison with the template beat. The method of Breithardt et al for signal averaging differs somewhat from other investigators.** Four bipolar tracings are amplified, and the signal connected to a dual channel signal averager. The averager is externally triggered from two additional bipolar leads chosen for yield of high amplitude R waves. Maximum slope change is the fiducial point. A circuit is included that automatically measures RR intervals on a beat by beat basis thereby eliminating the possibility of triggering by premature complexes. Other methods that could be used to align appropriately and average the ECG such as classification by multivariate cluster analysis and calculation of area differences, or use of spatial constructs from more than one lead, have not been clinically applied for late potential measurements. QUANTITATIVE OF LATE

ANALYSIS POTENTIALS

Initially investigators visually identified ventricular LPs, but more recently computer algo-

302

rithms have been used for quantitative identificaA ventricular LP is seen as tion. 21,22.24,25,31.32,41,48 low amplitude electrical activity in the terminal portion of the QRS complex, which may extend into the ST segment. At the present time, there are no absolute criteria to define LPs. The visual analysis of these potentials is made difficult because often there is no clear distinction between the end of the QRS and the beginning of the LP. Most often LPs constitute the terminal portion of the QRS complex from which they continuously emerge.22 Recognition of QRS end depends upon the leads used, the algorithm applied, and the filtering performed on the ECG signal. Since LPs are depolarization phenomena, it becomes a matter of semantics as to whether they are considered as part of the QRS complex or as occurring in the ST segment (ie, during repolarization). It makes sense to use standard visual or computer criteria that depend upon normally amplified unfiltered ECG signals to access QRS end. Therefore, LPs can be considered late depolarizations that may occur during repolarization. Endocardial catheter mapping studies delineate fractionated delayed low amplitude potentials starting within the QRS complex, which sometimes extend into the early ST segment.30 Breithardt et al takes this into consideration when they attempt to quantitate LP activity. He detects onset visually in one of two ways.22First, occasionally an isoelectric point is present that clearly separates the QRS complex from the LP. Most often, however, the QRS complex and LP are continuously merged, in which case the onset is defined as the point at which the QRS amplitude markedly exceeds the amplitude of the mid and terminal portions of the LP. Breithardt et al define the late potential offset as that point where the low amplitude signal exceeds by two to three times the baseline noise contained late in the ST segment. To be called a LP, the signal must be greater than 10 milliseconds in duration. Oeff et al used the same recorder as Breithardt et al, but visually quantitates the LP in a slightly different manner. 33 He uses six separate low resolution reference leads to determine the maximum QRS width. Delayed low amplitude electrical activity that exceeds the maximum QRS duration by at least 10 milliseconds is defined as

HALL

ET AL

a LP. Homback et al uses a six lead system (three bipolar, three augmented).32 A LP of 10 milliseconds duration must be present within at least three of six averaged leads and have an amplitude at least twice the baseline noise amplitude. Unlike with Breithardt et al, a clear distinction or isoelectric point must be present that separates the QRS complex from the LP. Thus, Homback et al does not consider LPs that emerge from the QRS complex. Denniss et al from Australia use high gain amplification signal averaging at wide bandpass (ie, no high pass filtration) to record ventricular activation times (VAT).41 These VATS are measured as the time from the earliest QRS onset in any lead to the latest offset in any lead with abnormal being greater than 140 milliseconds. By this method, prolonged QRS duration inclusive of LPs is the marker for abnormal. Zimmerman uses yet another method to visually quantitate ventricular LP activity!9 The peak of the R wave is both the fiducial point and the onset marker of the LP. The offset is the transition period between baseline noise and ventricular electrical activity. This period is termed the R wave to end ventricular activity (R-EVEA) interval. He does not clearly specify what constitutes an abnormal R-EVEA. Neither has Rozansky et al clearly defined LP activity.3’ This summary clearly points out that many different methods for measuring LPs have been used. Some of the methods are based on sound pathophysiologic principles and attempt to objectively quantitate LP activity. Naturally, all visual analysis methods have potential for observer bias. A more objective approach to quantify LP activity was developed by Simson using comTable

1.

Summary

of ART

Potential Term Voltage of terminal QRS high frequency (HF) signal Duration of termi-

Averaged

ECG Late

Abreviation

Definition

HFRMS

Root mean square (RMS) voltage summation of HF signals in terminal 40 milliseconds of

HFD40

nal QRS high frequency signal

High Frequency QRS Duration

Signal

(LPI Measurements

filtered QRS complex Measurement of duration of HF signal in terminal QRS. Duration is measured from end of filtered QRS complex to point

HFQRSD

amplitude Total duration

exceeds 40 PV of the filtered

QRS complex

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303

puter algorithms.*’ A Frank XYZ lead system is used with the signals being combined into vector magnitude to yield a total energy measurement for LP activity. A LP is considered present when the vector magnitude of the terminal 40 milliseconds of the filtered and averaged QRS complex is less than 25 PV (HFRMS). Using the same computerized system, Denes developed other indices that quantitate LP activity (see Table 1).23 The low amplitude signal duration is one such measurement (HFD40). This is measurement in milliseconds of the HF signal contained in the terminal portion of the filtered QRS complex. It is determined from the point where the QRS amplitude falls below 40 PV to the end of the filtered QRS complex. The endpoint is determined by computer algorithm as the point at which 2.5 times the standard deviation of baseline noise is exceeded. The longer the duration the more abnormal, with most studies

reporting abnormal as 40 to 42 milliseconds depending on the filter used. Examples of the HFRMS and HFD40 measurements are illustrated in Fig 7. Normal, abnormal HFRMS, and abnormal HFD40 are presented in Figs 8, 9, and 10, respectively. The duration of the filtered QRS complex or HF QRS duration (HFQRSD) is another computer algorithmic measurement endpoint that is set in the same manner as previously described. Onset I

125-25& 2oolnm/s 1.00ntduv Vautor

QRSD SOae HFTD a7mlB ltFD40 7ne mm 92. ~UV ltfwlrs 0.3uv

,

HFRMS

msec HFD40 41 msec

1 4olJv

2ouv

3@

4’1

1’5

msec

Fig 7. Illustration and amplification of an abnormal high frequency root mean square measurement fHFRMS, top insert) and low amplitude signal duration below 40 pV (HFD4D. bottom insert). HFRMS is an amplitude measurement of the HF signals occurring in the terminal 40 milliseconds of the filtered QRS. HFD4D is the duration of HF signals measured from the end of the filtered QRS backward until the amplitude signals exceed 40 gV.

Fig 8. Normal HF ECG onds, HFRMS > 25 pV.

recording

(HFD~CI

< 40 millisec-

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ET AL

I QRSD 93me HFTD 106me HfD40 23me HFRMSA 23.luV HFNOIS 0.3uV CYCLES 254

P Fig 9. aV) signals complex.

Abnormal in the

HFRMS. terminal

Note the low 40 milliseconds

amplitude of the

(~25 QRS

is calculated in a similar fashion. Prolonged HFQRSD is abnormal with most studies reporting abnormal as greater than 120 milliseconds. The differences between HFQRSD and QRSD determined by normal means may also be an indicator of LP activity. Recently, Berbari et al found that the root mean square voltage of the total QRS complex also distinguished normal subjects from patients with sustained VT.40

Fig 10. Abnormal amplitude (c4DfiV) QRS complex.

HFD4D. Note the signals in the terminal

duration portion

of low of the

Table 1 presents a summary of the ART late potential measurements and a brief definition of each measurement. Figure 2 presents both a normal and an abnormal ART signal averaged ECG tracing. Fast fourier transform analysis (FFTA) of the signal averaged ECG is a final method used to noninvasively quantitate late potential activity (Fig 6).25 It is a powerful computer-based mathe-

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matical algorithm that can determine the amplitudes and frequencies of the various harmonic components that comprise a complex periodic signal such as the ECG. This analytic method of signal processing in the frequency domain allows some of the inherent limitations of high-gain amplification and signal filtering by traditional methods to be avoided.” FFTA has been used extensively for energy spectra analysis of the ECG. Cain et a146and Lindsay et als2 used FFTA of the ECG to identify patients prone to sustained ventricular arrhythmias. A XYZ lead system is used, signals are amplified, digitized, and averaged prior to performing a 512 point FFTA. FFTA has been done on the entire QRS complex, the terminal 40 milliseconds of the QRS, the ST segment, and the T wave of each of the bipolar leads. FFTA of the terminal QRS and ST segments as a single unit yields information that best distinguishes patients with a history of sustained ventricular arrhythmias. This region is identified visually and marked with a computer graphics cursor. The FFTA generates a spectral plot which can be analyzed for the relative presence of HF signals. Cain et a146and Lindsay et als2 use the area ratio of the terminal QRS and Table

2.

Filters

Author

Gomes7’

and

Cutpoints

Used

by Other

Filter (Hz)

Criteria

85

80

HFQRSD

< 20 $I z 120 msec < 40 pV < 40 $J

Simson”

81

25

HFRMS HFQRSD

Den&

83

25

HFRMS HFRMS

Breithard?

82

Rozansk?’ Josephson29

81 82 85

Zimmerman49 Dene.?

investigators

YeEN

100 0, 20, 40, 40 50

84

Late 80

40

for Abnormal

z 120

potential

Undefined HFRMS Undefined

msec

> 10 msec

< 25 $I

1; HFRMS 2; HFQRSD

< 20 FV > 120 msec

3: HFD40 > 39 msec 4: HFRMSSO* < 30 pV CaiP

84

Fast-fourier analysis terminal

Goldberge? Marc@

81 84

Lower RMS voltage Greater HFQRSD Lower HFRMS voltage

segments

Abbreviations: *Root mean square onds of QRS.

25

HFQRSD, amplitude

HFD40,

and

of signals

HFRMS

transform wave forms in QRS and ST (area

defined

in the last 50

ratio)

in text. millisec-

ST segments to differentiate normal subjects or patients without a history of VT from those with a history of sustained VT. The area ratio is expressed as the area under the curve for frequencies between 20 Hz and 50 Hz divided by the area under the curve for frequencies between 0 and 20 Hz. An area ratio of less than 20 Hz is considered normal. This has the advantage over time domain systems of being less filter dependent while yielding more quantitative information. One disadvantage, however, is that the onset (terminal 40 milliseconds of the QRS) and the offset (start of T wave) are visually identified. The potential for error was noted by Henkin et al who found area ratios to be greatly effected by small changes in the analyzed segment.53 He reported that a 10 millisecond change in estimate of T wave onset could move the area ratio for normals well across the proposed normal boundary of 20. Table 2 summarizes some of the LP measurements used by different investigators. REPRODUCIBILITY

A limited number of studies have evaluated the reproducibility of methods for demonstrating LPS. 22.23,41s4 However, reproducibility is dependent on several factors including electrode position, noise and reference jitter, and the stability of medical conditions. Observer reproducibility is dependent on the criteria for onset and offset of QRS and of the LPs. Visual analysis is also dependent on the experience of the readers. Day to day and interobserver reproducibility has been good. Interobserver reproducibility is primarily of importance when using visual methods. Using visual analysis, Rozansky et al evaluated patients with ventricular aneurysms.31 They found that the precise amplitude and morphology of LPs varied from day to day, but that they were reproducible in all leads and at all filter settings. Breithardt et al evaluated reproducibility in normal subjects and patients with coronary artery disease.22 He showed that there were only slight day to day differences in amplitude and greater than 90% agreement. In one patient, a LP was absent on initial evaluation but present on a day in which he developed unstable angina. After the patient’s angina was stabilized, the LPs were not seen. Denniss et al investigated both day to day and

306

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interobserver variability in 12 patients with a history of VT and eight patients without a history of VT.4’ Two observers were correctly able to identify LPs in all cases. Eleven of the 12 patients with VT had reproducible LPs, although there was significant day to day variability in three patients. These three patients had positive tests on both testing days but had more than 20 millisecond differences in ventricular activation times. Reproducibility of the ART device using the Simpson algorithm was tested in 15 normal subjects who had two recordings done within one month of each other.23 Denes24 used both 25 Hz and 40 Hz high pass filters to evaluate four indices for quantitating late potential activity: HFRMS of the terminal 40 and 50 milliseconds of the QRS, HFQRSD, and HFD40. Using the 40 Hz filter significantly improved the correlation coefficients for each of the measurements. Reproducibility was also better with the 40 Hz filter. Pollak et al also tested the day to day reproducibility of the ART device.54 Fifteen stable cardiac patients with mixed diagnoses were studied. Thirteen of the 15 patients had ventricular tachyarrhythmias and six of these had LPs by HFRMS criteria. On repeat testing within 24 Table

3.

Sensitivity,

Author

et al*’

Value

of Signal

Sust Vl/VF

NSVT M NOVT

HFRMS

36139

2127

ULP

45163 27130

441146

Josephson et al*’ Simson et al”

HFRMS HFRMS

Rozanski

ULP

et als’

Predictive

Criteria For +

year

Simson” Breithardt

Specificity,

618

l/12

20130 14116

341136 5135

HFRMS 2 of 4 60dB. 40 Hz

Kanovaky

HFRMS or HFQRSD

88198

23176

ULP HFRMS

14117

18125 614 1

Zimmerman

et al”

Pollak et alM Gomes et al” Poll et al’3 Marcus

et al”

Total

or average

Abbreviations: Sust, fibrillation, VT, ventricular

HFD40 HFRMS

10116

515

A number of investigations have been published that compared recording systems. A European multicenter study assessed three separate systems and compared four methods of quantitating LP.33 The system used by both Breithardt et al and Oeff et a1,34s35 based on a Princeton 4202 signal averager (New Jersey), was compared to other commercially available systems by Marquette (the MAC-l, Milwaukee) and by Arrhythmia Research Technology. The ART device uses computer algorithms developed by Simson to quantitatively analyze LPs while the other three rely on visual analysis. Each of the four systems were used to evaluate 109 patients with either angiographically proven coronary artery disease or dilated cardiomyopathy. All recordings were done within two hours. Significant differences were found between the systems in analyzing LP activity. Both Oeff et a134*35and Hombach et a13* (using the Mac-l) take into account the maximum HFQRS duration and visually determine a LP to be present if the Averaged

ECG in Identifying

Sust VT/VF

Sustained

Ventricular

Sensitivity

4129

ValUe

48%

75% 50%

100%

75%

92%

4142

83% 66%

90% 75%

89% 71%

O/IO

88% 90%

85% 70%

o/25

51%

82% 85%

l/55

63% 100% 83%

71% 90%

95%

37% 74% 79% 44%

62% 94%

63% 28% 66%

78%

64%

76%

28137

NSVT, nonsustained Criteria for abnormal:

Specificity 93% 72%

O/27

0110

Arrhythmia Predict

NSVT or NOVT

92%

IO/12

31 l/387 sustained; tachycardia.

COMPARISONS BETWEEN RECORDING SYSTEMS

17145

end

HFQRSD HFRMS

was high for both QRS

o/11

8116 10112

Denes et alz3 Denes et al*’ Cain et aI” et al’*

hours, reproducibility duration and LPs.

ET AL

155/604 ventricular HFRMS

10122 tachycardia; (as described

4129

5/159

NOVA, no ventricular in Table 1 and text, 20-25

78%

tachycardia; VF, ventricular pV is abnormal); HFQRSD (as

described in Table 1 and text, > 1 10 ms cr 120 ms is abnormal); HFD40 (as described in Table 1 and text); two of four indices two of the following four indices: HFQRSD; HFRMS: HFD40; HFRMS50 (root mean square amplitude in last 50 ms); 60dB40H area and 40Hz intercept that are fast fourier transform analysis measurements in the terminal 40 ms of the QRS complexes.

represents is 60db

HIGH

FREWENCY

307

ECG

HFQRSD, HFRMS, and HFD40 as measurement indices correctly identified 93%, 86%, and 86% of the normal subjects but only 50%, 25%, and 8% of the VT patients. Both systems identified all of the patients with sustained VT who had prior inferior wall myocardial infarction. Cain’s system more effectively identified those patients with sustained VT and prior anterior myocardial infarction (95% v 58%). In contrast, when the same two systems were compared by Worley et al only HFQRSD provided independent information for separating VT patients from normal subjects.56 The conflicting results of these three studies point out the lack of a true gold standard for identifying LPs.

terminal low amplitude signal is greater then 10 milliseconds after the end of the QRS complex. Breithardt et al, however, visually quantitates terminal low amplitude signals irrespective of QRS duration or endpoint with a positive result being a low amplitude signal in the terminal QRS or early ST segment that is greater than 10 milliseconds. Similarly, Simson’s system uses computer algorithms to assess terminal low amplitude signals without regard for QRS endpoint. Agreement was best between the three methods of visual analysis. Not surprisingly, the methods of Oeff and Hombach, taking QRS duration and endpoint into account, correlate best with each other. The two methods that include both LPs that are incorporated into the terminal QRS and those occurring after the end of the QRS (Breithardt et alz2 and Simson24) had results that best correlated with each other. It was not possible to determine which system best identified patients with malignant arrhythmias. Two recently published studies compared frequency and time domain recording devices.55*56In each of these studies, the time domain system analyzed was the ART device and the frequency domain system was Cain’s. This latter system uses FFTA to quantitate LPs. Cain et al prospectively compared the two systems in 12 patients with sustained VT and 15 normal subjects.5’ Cain’s frequency domain system using calculated area ratios of the terminal QRS and ST segments as measurement indices correctly identified 100% of the normal subjects and 92% of the VT patients. Simson’s system using Table

4.

Prevalence

Author

Sust vT/VF

36134

Simson”

Breithardt

Denes

NSVT or NOVT

45163

2127 491146

et al”

27130

27130

et alJo

Rozansky

Signal

et aI”

Josephson Simson

of Abnormal

et al” et al’*

Total

in Patients

With

P~WslZi~lX in Sust W/VF

38166 941204

92% 71% 90% 75%

8116

l/l2

9128

50%

IO/l2 341136 5135

Zimmerman et al” Pollack et alM Gomes et al79

14/17 10116 515 28137

3 for abbreviations.

ECG

6/19

IO/l2

See Table

Averaged

O/11

20130 14116 %8/98

et a?’

Table 3 presents a summary of many published signal averaging studies. A problem with demonstrating an overall sensitivity, specificity, and predictive value is the variety of criteria and cutpoints used to define an abnormal signal averaged ECG. These different criteria are listed in the left hand margin of Table 2. Overall, 1,201 patients had a signal averaged ECG performed. Forty seven percent had an abnormal test. Of the 991 patients with coronary artery disease, 48% had an abnormal test. Only 9% of the 210 patients without coronary artery disease had an abnormal test. Separate analysis of the data from patients with coronary artery disease revealed that 25% of 604 patients without a history of sustained ven-

6/8

Denes et a? Cain et alz5 Kanovsky et al”

Marcus

SUMMARY OF THE MAJOR PREDICTIVE STUDIES

23176 1a/75 6141 17145 28137

541166 19/51 Ill/174 32192 16157 22150

03% 66% 88% 90% 51% 63% 100% 76%

Coronary

Artery

Disease

PWJ~l~lXX? in NSVT or NOVT

PWJalenCe Total

58%

7% 33.6%

45%

0% 8%

31.6% 32%

25% 14%

33% 37%

30%

64% 35% 28%

24% 15% 38%

44%

Type

pass

filter

Tvpe

by investigator.

settings

filter

l DevaWd

+Variws

abnamal

25-100

algorithm

Hz BTB also

used

this

system.

>lOIllS

endpoint

of QRS

HFD40

~tontials OT ST segment

Late

Vimal

HFRMS

HFORSD

by computer

for

time

Criteria

Sampling

Antmatic

4202

Signal

of beat

lasting

regardless

at end

of (1RS

Research Model

RR intervals Applied Average

Princeton

to bat

Automatic

Late

three

QRS leads

present

of 10 occuring

of six

( 1st

char=-

20

three

after in

ms and

techniqu,

flat

10’

of (1RS

with

Y

1

precadial MAC

endpoint

potentials duation

Visual

12 bit aczur~cy

1 Rozanskv

precadial.

MAC

Breakdown

matching

onset

2,DOO/sec

Pwtern

md

Time

l8dB/atave

Hz

60HrtolC0Hz

filtm

look300

106-2.5

tffistica

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(a

6dBloctava

comparison

, x 50

bipolar

domain

Hombach.

augmented

Three

Time

Component

300

intewstation

with

sys-

leads

Reseach

bipolrr

Research

5.

300

100

AIMlog

Tvpe

filter

10’

ACCW3CV

recognition

digital

loo-30D

5 x

Model

Applmd 1113

Far

Princetcm

domain pacordial

Time

12 bit accuracy

HP 9626

tern

Template

2w 250

Mr

Modal

sy%tml

Applied

Table

Breithardt

1o,ooo/wc

from

10’

Directional

.OS-300

I x

2635

Analog

XYS

devices

domsin

Princeton

12 bit accuracy

point

Fiducial

Time

GTthogonsl

(ARTI

Ressarch

1 .m/oec

lreqwncv

IHZ)

LowPass

canu

(Hz)

HighPass

IHzl

ampliicatian

Band

analysis

Total

Lead

Technologiis Simson

Arrhythmia

used

used

214Omsl

(HFQRSD

Ventricul=

-

-

ORS

from

lead

ECG

time

technique

equivs!at

activation

-

template

miue

11 I34

carelation

PDP

1 .ooo/sec

DEC

Cross

magdtudn

dmii

Optimized

Not

Not

Filters

Hz

multibus COlllPUtW

.05-6M)

lntsl

XKZ

Dennis8

.

Averaged

domain

Orthogonal

lime

of Signal

>ma

Hz

intercap,

11/23

lead

values

lwge

in temtinal

-

XYZ

OT ST swment

FFTA

. Cain domain

103

ratio

1 .ooO/seC 12&t

Hz

R wave

uPed

used

103

105TA

DECVT

Peak

Not

Not

Fihws

.05470

1 x

NP

Orthogonal

Frequency

Systems

40

ORS

bipalir

domain

>R

precordiil

pea

not

absolute

specSed

for

(R-

ywltric

valy~s

activitv

to end

recognition

ebctdwl

Hz

abrwrmaf

EMA)

ulm

wave

Template

PeakRwaw

12dEloctaw

1,ooO

1COHz

A=+3

lOO-l.OOOM

104100

Three

Tin-m

. Zimmerman

Hz

Hz

FFTA

lOBit

1,26O/sx

CDC

6600

c$ossmmJaiont0dmii

tshniw

Optimizedbycorrelstm

260

3oHz

Digital

.3-500

Threampdarpmcdial

Freqwncydomain

. Abbwd

HIGH

FREQUENCY

309

ECG

tricular arrhythmias had LPs. Of 387 patients with a history of sustained ventricular tachyarrhythmias, 80% had LPs. Only 3% of normal subjects (5 of 159) had an abnormal test. Of 29 patients with a cardiomyopathy and no history of sustained ventricular arrhythmias, only 14% had LPs. Among those with a history of sustained ventricular tachyarrhythmias 45% had LPs. Sensitivity, specificity, and predictive value of the signal averaged ECG for sustained ventricular arrhythmias was 78%, 78%, and 64%, respectively. There is a large interstudy variability in predictive value for sustained ventricular arrhythmias. The range of test sensitivity is 50% to 100%. The range of test specificity is 62% to 100%. The range of test predictive values is 28% to 95%. The prevalence of LPs in patients with coronary artery disease was also examined (Table 4). Overall prevalence of LPs in patients with coronary artery disease was 47%. In those with no history of sustained ventricular arrhythmias, the prevalence of LPs was 26%. There was considerable interstudy variability in the prevalence of LPs in this subgroup with prevalences ranging from 0% to 38%. Finally, in coronary artery disease patients with a history of sustained ventricular arrhythmias, 80% had LPs. Many investigators have used signal averaging techniques to detect HF low amplitude LP activity. 24-37 As pointed out previously, there are numerous different systems, each with different methodologic approaches to obtain and average signals as well as different methods to quantitate LP activity. This is summarized in Table 5. The prevalence of a LP has ranged from 92% to 100% in patients with a history of sustained ventricular tachycardia.21*24,37 Simson studied 66 patients postmyocardial infarction.2’ Of 39 with a history of sustained ventricular tachycardia that could be induced with ventricular stimulation, 36 (92%) had LPs while only two (7%) of 27 patients with no history of significant ventricular arrhythmia had LPs. Denes et al also found LPs in patients with sustained ventricular tachyarrhythmias.23 Four criteria were considered: amplitude of the signals in the last 40 to 50 milliseconds of filtered QRS complex (HFRMS), total low amplitude signal duration less than 40 PV (HFHD40), and total filtered QRS duration (HFQRSD). These four

criteria correctly identified 1OO%, 90%, 98% and 90% of the normal patients, respectively. In the VT group, 58%, 83%, 83%, and 83% were correctly identified. Other investigators have reported similar results in retrospective analysis of post myocardial infarction patients.22~25J2 In the 14 signal averaging studies summarized, the overall sensitivity, specificity, and predictive value of the test in distinguishing patients with ventricular arrhythmias was only fair (sensitivity 78% and specificity 78%). It is difficult to make comparisons between studies because of different methodologies and analytical techniques. However, it appears that appropriate quantitative analysis of the signal averaged ECG high frequency signals is better than qualitative analysis. Two investigators (Rozanski et a13i and Zimmerman et a149)used undefined visual criteria for LPs and obtained relatively low sensitivities of 50% and 71% respectively. Respective specificities were 92% and 82%. EFFECT OF ACUTE

ISCHEMIA

Several investigators have evaluated the effect of acute ischemia or myocardial infarction on LPs. Kertes found LPs to be infrequent in the first 24 hours postmyocardial infarction with prevalence decreasing even further over the following 24 hours. Denniss et al found the prevalence of LPs to diminish over a 2 to 12 month period following myocardial infarction.58 In the absence of recurrent ischemic events or infarctions, patients without documented LPs initially did not develop them during the follow-up period. More recently, Potratz et al confirmed the findings of Kertes et al and Denniss et al that LPs diminish with time after acute myocardial infarction.59 In this study, 138 patients with acute myocardial infarction were studied on days 1, 3, and 21 and 6 months after their myocardial infarction. Late potential activity consistently diminished on each successive testing day. The higher prevalence of LP activity in the early postmyocardial infarction period is possibly related to the effect acute ischemia has on conduction through the ventricle. In the initial phase, conduction is slowed through the ischemic areas of myocardium. When myocardium has infarcted, there remain areas of focal scar and inflammation which may impair conduction through the ventricle. As the myocardial infarc-

310

HALL

tion evolves, inflammation resolves and scarring is reduced. With the diminution of local anatomic barriers that impede conduction, the incidence of LPs also declines. The point at which LPs do become significant predictors of risk of future arrhythmic events is unclear. It seems certain, however, that LPs in the periinfarction period or in the setting of continued ischemia do not signify an increase in the risk of arrhythmic events, but rather reflect the effect of ischemia on slowing ventricular conduction. EFFECT OF TYPE OF MYOCARDIAL

INFARCTION

Numerous studies have shown the prevalence of LPs to be higher in patients with inferior wall infarctions than anterior wall infarctions. Using the Princeton applied research signal averager, Breithardt et al noted a prevalence of LPs in inferior wall of 63% compared with 34% in anterior wall myocardial infarction.60 Simson evaluated a group of 176 patients including both inferior and anterior wall myocardial infarction patients both with and without a history of VT and anterior wall myocardial infarction patients with and without VT.6’ In patients with or without a history of VT, the terminal 40 milliseconds of the QRS (HFRMS) was lower in patients with inferior wall myocardial infarction compared to anterior wall myocardial infarction. The mean HF QRS duration (HFQRSD) was significantly longer in those patients with VT. Interestingly, the HFQRSD does not differ between infarct locations. Buxton et al compared electrophysiologic study (EPS) and signal averaged ECG findings in 36 consecutive postmyocardial infarction patients with a history of nonsustained VT.62 Twenty-seven patients had prior inferior and nine had prior anterior wall myocardial infarctions. An abnormal signal averaged ECG (HFRMS t25 PV and/or HFQRSD < 110 milliseconds) was more helpful in providing a prediction of inducible VT in those patients with prior inferior wall infarction. One plausible reason for the disparity in prevalence of LPs between location of myocardial infarction may be related to local differences in ventricular conduction. Since the inferior and basal portions of the heart are activated last, LPs would be expected to occur later in the QRS complex and, thus, be recorded more easily. Since the anterior wall is activated earlier, LPs would likely occur earlier in the QRS and thus may be obscured or hidden within

ET AL

QRS complex. For this reason, quantitative measurements that take into account total HFQRS duration or those that measure the root mean square voltage of the total QRS complex may better distinguish patients vulnerable to ventricular arrhythmias. RELATIONSHIP VENTRICULAR

TO TYPE OF ARRHYTHMIA

The prevalence of LPs varies depending on the type of documented ventricular tachyarrhythmia, with the prevalence being higher in those patients with VT. In the setting of an acute myocardial infarction, Kertes recorded LPs in only 15% of patients with documented (prior or subsequent) ventricular fibrillation.” Simson compared the results of EPS and signal averaged ECG in 102 patients with prior transmural infarct and a history of sustained ventricular tachyarrhythmia (>30 milliseconds) and found the incidence of an abnormal signal averaged ECG (HFQRSD > 120 milliseconds, HFRMS 425 pV) was highest in the group with a history of sustained VT (9 1%) and lowest in the ventricular fibrillation group (57%).63 The group with a history of VT and ventricular fibrillation fit into an intermediate category with the incidence of a positive signal averaged ECG being 75%. In each group, the incidence of inducible VT at EPS roughly paralleled the prevalence of an abnormal signal averaged ECG. Denniss et al reported similar results in a population of patients late after myocardial infarction.64 Late potentials were detected in 32% of those with VF, 58% of those with sustained VT at rates >270 beats/ min, and 95% in those patients with VT documented at rates greater than 270 beats/min. Freedman et al noted the prevalence of (HFRMS t25 pV) to be almost three times higher in patients with a history of sustained VT than in those patients with prior documented VF.6s EFFECT OF ANTIARRHYTHMIC

DRUGS

Most investigations have shown that antiarrhythmic drugs do not change the prevalence or duration of LPs. Simson et al noted that quinidine, procainamide, and amiodarone increased HFQRSD by 8%, 12%, and 18%, respectively.” HFRMS was not changed by therapy with the same three drugs. Norpace and mexilitine therapy did not alter HFQRSD or HFRMS. Denniss

HIGH

FREQUENCY

311

ECG

et al found that Class I or Class II antiarrhythmic agents, had no consistent effects on LPs.~’ Jauernig et a168 and Rozansky et a13’ also reported that antiarrhythmic therapy had little or no affect on LPs. In contrast, frequency domain analysis may be of value in assessing the efficacy of antiarrhythmic drug therapy. Using FFTA, Cain found that in 8 of 10 successful antiarrhythmic trials, the area ratio of the terminal QRS and ST segment was reduced.69 Conversely, a reduced terminal QRS area ratio was found in only 1 of 10 unsuccessful trials. EFFECT OF BUNDLE

BRANCH

BLOCK

Most studies on LPs have excluded patients with bundle branch block from investigation. Bundle branch blocks are thought to mask LPs. In two separate investigations, Kindwall, et al” used the ART system to evaluate LPs in patients with bundle branch block.70.71 In one study, 20 patients with right bundle branch block (15 with and five without VT and 59 patients with QRS duration less than 110 milliseconds (16 with VT, 43 without VT) were evaluated with a signal averaged ECG.” The patients with right bundle branch pattern had lower total QRS amplitude and lower voltage in the terminal 40 milliseconds of the QRS than the patients without a bundle branch pattern. The lower total QRS amplitude in right bundle branch block patients was present when a 25 Hz high pass filter was used as well as when the high pass filter was not used, indicating a relative loss of both low and high frequency signals throughout the QRS. When the groups with right bundle branch block were compared, no parameter including the terminal 40 milliseconds of the QRS, could distinguish those with VT. In contrast, patients with left bundle branch block were found to have characteristic abnormalities in HF content late in the QRS which distinguished them from left bundle branch block patients without VT.” The study included 37 patients with left bundle branch patterns; 24 with inducible sustained VT and 13 with no ventricular arrhythmias. Using a 25 Hz high pass bidirectional filter and a value of less than 30 /IV for the terminal 40 milliseconds of the QRS as abnormal (voltage less than 25 PV is usually the cutpoint for abnormal) VT was predicted with a sensitivity of 79%, a specificity of 61%, and a predictive value of 79%. Mean QRS duration was longer in the VT group.

EFFECT OF VENTRICULAR ANEURYSMS LEFT VENTRICULAR DYSFUNCTION

AND

Many studies have evaluated patients with left ventricular dysfunction or aneurysms to determine whether these patients have a higher prevalence of LPs.22~24~25~‘4~72~73 The essential question is whether LPs are independent predictors of arrhythmic events or just a reflection of ventricular wall motion abnormalities. Early studies reported an association between LPs and the presence of impaired left ventricular function, wall motion abnormalities, or left ventricular aneurysms. **s*~ Breithardt et al found LPs to be related to ventricular dysfunction.** They reported an association between LPs and contraction abnormalities, regardless of prior clinical occurance of ventricular tachyarrhythmias. In this study, however, LPs were identified by visual analysis. Denes et al used quantitative techniques and reported similar findings.24 By applying multivariate analysis to variables they showed that LPs, wall motion abnormalities, and depressed ejection fraction were not’ independently related. Wall motion abnormalities included ventricular aneurysms, left ventricular wall akinesis, or hypokinesis. Thus, from this study it is not possible to assessthe association of LPs with the individual types of wall motion abnormalities. Conversely, a study by Pollak et al analyzed the influence of various types of left ventricular wall motion abnormalities on LPs.~~ They concluded that LPs are independent of global or regional left ventricular function. Similarly, Poll et al found no relationship between the presence of an abnormal signal averaged ECG and impaired ventricular function in a study involving 41 patients with nonischemic congestive cardiomyopathy. 73 Although the investigations by Pollak et al and Poll et al were retrospective and involved small numbers of patients, they do support the concept that LPs independently identify those prone to sustained ventricular arrhythmias. EFFECTS OF SURGERY

Map-guided antitachycardia surgery has assumed an important role in the treatment of patients with sustained ventricular arrhythmias refractory to antiarrhythmia medications.74-76 Recent investigations on patients who have

312

HALL

undergone successful map guided antitachycardia surgery show a high correlation between loss or significant dimunition of LP activity and absence of inducible VT.“,” In contrast, if LPs persisted following surgery, VT could often times be induced. Using the ART system, Marcus et al showed that the incidence of LPs diminished from 71% to 33% in 24 of 37 patients who could no longer be induced following endocardial resection. HFQRS duration decreased from 137 to 121 milliseconds and mean voltage in the terminal 40 milliseconds and mean voltage in the terminal 40 milliseconds of the QRS increased from 16.5 to 39 PV.” In 13 patients with inducible VT following surgery HFQRS duration was unchanged. Loss of a LP after surgery in nine of ten patients was associated with absence of inducible VT on electrophysiologic study. Eight of 18 patients with a persistant LP did not have inducible VT indicating that loss of a LP was not necessary for surgical success. Breithardt et al used the Princeton Applied Research Signal Averaging System and visual analysis of LPs and reported abolition of LPs and inducible ventricular arrhythmias in 11 of 12 patients following map guided partial or complete encircling endocardial ventriculotomy.78 Of six patients with persistant LPs following surgery, three had inducible sustained or nonsustained VT. There are several proposed mechanisms as to how VT is controlled following antitachycardia surgery. Endocardial resection probably removes part or all of the slowly conducting tissue involved in reentry. Disappearance of LPs correlates with the absence of inducible VT. In those patients with persistant LPs following surgery, sufficient anatomical substrate may have been excised to damage or interrupt the reentrant circuit and thus, prevent VT. There may remain, however, areas of focal delayed conduction that are substantial enough to be recorded on the body surface. PROGNOSTIC

SIGNIFICANCE

OF LPs

Several recent studies have evaluated the prognostic significance of LPs. A retrospective study by Kanovsky et al found that the signal averaged ECG provided independent information in identifying patients with VT after myocardial infarction.” In this study, holter monitoring, cardiac catheterization, and signal averaged

ET AL

ECG data were analyzed. The ART signal averaged ECG system was used. One hundred seventy four postmyocardial infarction patients were studied, 98 of whom had recurrent sustained VT. There were no significant differences in mean patient age, sex, or myocardial infarction location between the two groups. Median age of infarction was lower in the control group (8 weeks) than in the group with a history of sustained VT (46 weeks). By multivariate logistic regression only three parameters were found independently to be significant predictors of VT. Listed in order of power, these were LPs (B = 2.8, p < .OOl), peak premature ventricular contraction rate greater than lOO/hr (B = 2.5, p < .OOl) and presence of a left ventricular aneurysm (B = 2.2, p < .OOl). Patients with all three parameters had a 99% probability of developing VT, while those with none of the parameters had a 4% probability of developing VT. Those with any two of the parameters had 82% to 88% probability of developing VT and those with one parameter, a 30% probability. Thus, multivariate analysis demonstrated that LPs were an independent predictor of VT, and more predictive for VT than data obtained from holter monitoring or cardiac catheterization. While such findings are promising, there is a bias inherent in this study because only postmyocardial infarction patients who required either cardiac catheterization or electrophysiologic study or both were selected. Gomes et al evaluated 50 acute myocardial infarction patients and correlated prolonged low amplitude signal duration, presence of a LP and prolonged filter QRS duration with subsequent development of sustained ventricular arrhythmia or sudden death.79 The best predictive index was LP duration. This criteria identified five of five patients with sustained ventricular arrhythmia and/or sudden death. Seven of 14 patients (50%) with nonsustained VT and 20 of 31 patients (32%) with no VT had prolonged LPs duration?’ While sensitivity for sudden death was lOO%, specificity was only 62%, and predictive value was 28%. Limitations in this study were the small number, short follow-up (30 days), and inclusion of patients with bundle branch blocks. Another concern is that recordings were made early (3 to 3.5 days) post-acute event. A prospective study by Kuchar also used a combination of findings on noninvasive testing to

HIGH

FREQUENCY

313

ECG

stratify postmyocardial infarction patients according to their risk of serious arrhythmic events.** Two hundred ten consecutive postmyocardial infarction patients were evaluated with radionuclide left ventriculography, holter monitoring, and with signal averaged ECG using the ART system. An abnormal signal averaged ECG was defined by the presence of a LP potential (low voltage signal less the 20 PV in the terminal 40 milliseconds of the QRS) or a HF QRS duration greater than 120 milliseconds. Patient follow-up period was 6 months to 2 years with medium follow-up of 14 months. There were 15 patients with presumed or documented arrhythmia events: eight died suddenly and seven had episodes of witnessed sustained, symptomatic VT. Stepwise logistic regression showed that abnormalities on each of the noninvasive tests were independently significant in predicting outcome. In contrast to the study by Kanovsky et al,‘* left ventricular ejection fraction less than 40% was the most powerful variable (B = 2.8, p < .005). An abnormal signal averaged ECG was the next most powerful variable (B = 2.0, p < .Ol). Complex ventricular ectopy (Lown’s grade III-V) was the least powerful variable (B = 1.5, p < .04). Combinations of these independent variables, increased sensitivity and specificity, and appropriate identification of risk to arrhythmogenic event. The combination of left ventricular dysfunction and a normal signal averaged ECG was associated with a 4% risk for arrhythmic events. In contrast, a combination of an abnormal signal averaged ECG and left ventricular function less than 40% was associated with a 34% incidence of arrhythmic event. The sensitivity of this combination of variables was 80% and the specificity was 89%. Denniss and coworkers prospectively evaluated 403 clinically well survivors of documented transmural infarction, aged 65 years or younger.8’ The relative long-term prognostic significance of VT and ventricular fibrillation inducible by programmed stimulation within 1 month of acute myocardial infarction was compared with the signal averaged ECG in a subset of 306 patients without bundle branch block. Programmed stimulation was performed 7 to 28 days after infarction. Signal averaged ECG was performed on the same day as electrophysiologic study using a system developed by the investiga-

tors. Ventricular activation times were measured in milliseconds from earliest QRS onset in any lead to latest QRS offset in any lead. Delayed potentials were considered present if they extended more than 140 milliseconds after the QRS onset. Patients were followed for up to 2 years with median follow up of 1 year. Study endpoints were death or documented spontaneous ventricular arrhythmia. Twenty percent of patients had inducible VT, 14% had inducible ventricular fibrillation (included patients with inducible polymorphic VT), and 66% had no inducible ventricular arrhythmia. Twenty-six percent had delayed potentials. The 2-year probability of remaining free from sudden cardiac death or nonfatal ventricular arrhythmia was 95% for patients without inducible arrhythmia, 95% for patients with inducible ventricular fibrillation, and 84% for patients with inducible VT. The 2-year probability of remaining free from sudden death or nonfatal ventricular arrhythmia was only 79% in patients with delayed potentials and 96% in patients without delayed potentials. There was a significant correlation between presence of delayed potentials and the inducibility of ventricular tachycardia. Although each test had similar sensitivity, specificity, predictive accuracy, and odds radio in identifying those patients who suffered cardiac events during follow-up, the correlation was incomplete. Specificity was higher and sensitivity lower if both delayed potentials and inducible VT were present. Presence of either delayed potentials or inducible VT predicted events with high sensitivity but low specificity. In contrast to other prognostic studies, multiple logistic regression analysis showed that inducible VT and delayed potentials were not independent predictors of either mortality or primary ventricular tachyarrhythmic events. CONCLUSION

Late potentials appear to be signals derived from slowly conducting myocardium. There is strong correlation between signals recorded from the body surface and delayed potentials recorded from catheter or intraoperative mapping studies. Investigators have pointed out some methodologic problems with signal averaged evaluation of LPs. The optimal lead system for LP evaluation has not been identified, although standard orthogonal lead system may be adequate. When

314

recording of signals so minute it is essential to accurately align beats as misalignment of beats in the process of recording microvolt potentials may serve to obscure or even create low amplitude LPs. Use of reliable fiducial points is vital to the signal averaged process. Ternplating or cross correlation techniques aid in appropriate alignment of ECG complexes. Other methods such as classification by multivariate cluster analysis calculation of area differences or use of spatial constructs from more than one lead could be used to ensure optimal ECG alignment prior to signal averaging. Clinical signal averaged ECG studies and spectral analysis of the ECG studies yield conflicting results on optimal high pass filtering frequency. In systems dependent on amplication and filtering, use of high pass filter frequencies greater than 50 Hz may exclude signals of interest. Quantitative analysis of LP varies considerably between signal averaged ECG systems. Correlations of measurements made by individual signal averaged ECG systems is poor with none of the systems being shown superior. At times the disparity between each systems LP measurements are significant, raising questions as to whether they are a measure of the same phenomenon. There should be continued efforts to identify the optimal measurements of LP activity with these efforts including catheter endocardial or intraoperative mapping correlation whenever possible. While reproducibility has been shown to be good in normal populations, no study has methodically addressed the issue of reproducibility in diseased populations. Clinical studies to date have both identified some of the limitations as well as clinical applications of this noninvasive technology. As is the case with many screening tests sensitivity, specificity, and predictive value is only fair. Use of continuous quantitative analysis clearly improves the appropriate identification of those susceptible to arrhythmic events. One of the limitations of this technology is the differing prevalence of LPs in subsets of patients. Patients with prior inferior wall infarctions have

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a higher prevalence of LPs than those with prior anterior wall infarctions possibly owing to regional differences in conduction times. Similarly, the presence of LPs better identifies those with sustained VT than ventricular fibrillation. Investigations have shown the prevalence of LPs to be highest in the peri-infarct period with slow diminuation in prevalence over a 6-month period. The optimal time to record the signal averaged ECG has not been determined. Antiarrhythmic drugs have now been shown to alter consistently the prevalence or duration of LPs. A recent study has shown that it is feasible to record LPs in patients with left bundle branch block. Slight adjustments in LP indices must be made to distinguish those with, from those without, VT. This is not the case with right bundle branch block. There are no LP parameters that distinguish those with, from those without, VT. In patients who have undergone successful mapguided antitachycardia surgery, there is a strong correlation between loss of LP activity and absence of inducible VT. Persistence of LPs following antitachycardia surgery, however, does not portend surgical failure. Several small studies have established the capacity of the signal averaged ECG to yield information that is independent of left ventricular wall motion abnormalities. Nonetheless, there is a higher prevalence of LPs in patients with cardiomyopathy even in the absence of clinically significant ventricular arrhythmia. Late potentials appear to offer prognostic information that is independent of other variables. The combination of LPs, high density or complex ventricular arrhythmia and low ejection fraction correlates with a higher incidence of sustained ventricular arrhythmia. As with most screening procedures, one drawback to the noninvasive recording of LPs is the high rate of false positives. However, the use of the signal averaged ECG in combination with other noninvasively obtained information may have a role in the appropriate stratification and identification of those at risk to sustained ventricular arrhythmia or sudden death.

REFERENCES 1. Josephson ME, Horowitz LN, Spielman SR, et al: 2. Ruskin JN, DiMarco JP, Garan H: Out of hospital cardiac arrest. electrophysiologic observations and selection Electrophysiologic and hemodynamic studies in patients of long-term antiarrhythmic therapy. N Engl J Med 303:607, resuscitated from cardiac arrest. Am J Cardiol 46:948-955, 1980 1980

HIGH

FREQUENCY

ECG

3. Hammermeister KI, DeRouen TA, Dodge HT: Variables predictive of survival in patients with coronary artery disease. Circulation 59:421-430, 1979 4. Davis HT, Decamilla J, Bayer LW, et al: Survivorship patterns in the post hospital phase of myocardial infarction. Circulation 60:1252-1258, 1979 5. Schulze RA, Humphries JO, Griffith LS, et al: Left ventricular and coronary angiographic anatomy: Relationship to ventricular irritability in the late hospital phase of acute myocardial infarction. Circulation 55: 839-843, 1977 6. Weaver WD, Lorsch GS, Alvarez HA, et al: Angiographic findings and prognostic indicators in patients resuscitated from sudden cardiac death. Circulation 54:895-900, 1976 7. Cohen M, Weinar I, Pichard A, et al: Determinants of ventricular tachycardia in patients with coronary artery disease and ventricular aneurysm. Am J Cardiol 51:61-64, 1983 8. Greene HL, Reid PR, Schaeffer AH: The repetitive ventricular response in man: A predictor of sudden death. N Engl J Med 299:729-734, 1978 9. Ruskin JN, DiMarco JP, Garan H: Repetitive responses to single ventricular extra stimuli in patients with serious arrhythmias: Incidence and clinical significance. Circulation 63:767-772, 1981 10. Richards DA, Cody DV, Denniss AR, et al: Ventricular electrical instability: A predictor of death after myocardial infarction. Am J Cardiol 51:75-80, 1983 11. Boineau JP, Cox JC: Slow ventricular activation in acute myocardial infarction. A source of reentrant premature ventricular contraction. Circulation 48:702-713, 1973 12. Zipes DP: Electrophysiological mechanisms involved in ventricular fibrillation. Circulation 52:120-130, 1975 (suppl III) 13. Waldo AL, Kaiser GA: A study of ventricular arrhythmias associated with acute myocardial infarction in the canine heart. Circulation 47:1222-1228, 1973 14. Scherlag BJ, El-Sherif N, Hope RR, et al: Characterization and localization of ventricular arrhythmias due to myocardial ischemia and infarction. Circ Res 35:372-383, 1974 15. El-Sherif N, Scherlag BJ, Lazzara R, et al: Reentrant ventricular arrhythmias in the late myocardial infarction period: 1. Conduction characteristics in the infarction zone. Circulation 55:686-702, 1977 16. El-Sherif N, Hope RR, Scherlag BJ, et al: Reentrant ventricular arrhythmias in the late myocardial infarction period: 2. Patterns of initiation and termination of re-entry. Circulation 55:702-719, 1977 17. El-Sherif N, Lazzara R, Hope RR, et al: Reentrant arrhythmias in the late myocardial infarction period: 3. Manifest and concealed extrasystolic grouping. Circulation 561225-234, 1977 18. Josephson ME, Horowitz LN, Farshidi A: Continuous electrical activity: A mechanism of recurrent ventricular tachycardia. Circulation 57:659-665, 1978 19. Berbari EJ, Scherlag BJ, et al: Recording from the body surface of arrhythmogenic ventricular activity during the ST segment. Am J Cardiol41:697-702, 1978 20. Simson MB, Euler D, Michelson EL, et al: Detection of delayed ventricular activation on the body surface in dogs. Am J Physiol241 (Heart Circ Physiol lO):H363-369, 1981

315

21. Simson MB: Use of signals in the terminal QRS complex to identify patients with ventricular tachycardia after myocardial infarction. Circulation 64:235-242, 1981 22. Breithardt G, Borggrefe M, Karbenn A, et al: Prevalence of late potentials in patients with and without ventricular tachycardia: Correlation with angiographic findings. Am J Cardiol49:1932-1937, 1982 23. Denes P, Uretz E, Santarelli P, et al: Determinants of arrhythmogenic ventricular activity detected on the body surface QRS in patients with coronary artery disease. Am J Cardiol53:1519-1523, 1984 24. Denes P, Santarelli P, Hauser RG, et al: Quantitative analysis of the high-frequency components of the terminal portion of the body surface QRS in normal subjects and in patients with ventricular tachycardia. Circulation 67:11291138,1983 25. Cain ME, Ambos HD, Witkowski FX, et al: Fast fourier transform analysis of signal averaged electrocardiograms for identification of patients prone to sustained ventricular tachycardia. Circulation 69:7 1 l-720, 1984 26. Josephson ME, Horowitz LN, Farshidi A, et al: Sustained ventricular tachycardia: Evidence for protected localized re-entry. Am J Cardiol42:416-424, 1978 27. Josephson ME, Horowitz LN, Spielman SR, et al: Comparison of endocardial catheter mapping with intraoperative mapping of ventricular tachycardia. Circulation 61:395-404, 1980 28. Horowitz LN, Josephson ME, Harken AH, et al: Epicardial and endocardial activation during sustained ventricular tachycardia in man. Circulation 61:1227-1238, 1980 29. Josephson ME, Simson MB, Harken AH, et al: The incidence and clinical significance of epicardial late potentials in patients with recurrent sustained ventricular tachycardia and coronary artery disease. Circulation 66: 11991204,1982 30. Simson MB, Untereker WJ, Spielman R, et al: Relation between late potentials on the body surface and directly recorded fragmented electrograms in patients with ventricular tachycardia. Am J Cardiol 51:105-112, 1983 31. Rozanski JJ, Mortara D, Myerburg RJ, et al: Body surface detection of delayed depolarizations in patients with recurrent ventricular tachycardia and left ventricular aneurysm. Circulation 63:1172-l 178, 1981 32. Hombach V, Braun V, Hopp HW, et al: The applicability of the signal averaging technique in clinical cardiology. Clin Cardiol 5:107-124, 1982 33. Oeff M, Leitner E-RV, Sthapit R, et al: Methods for non-invasive detection of ventricular late potentials-A comparative multicenter study. Eur Heart J 7:25-33, 1986 34. Oeff M, Leitner E-RV, Bruggermann T, et al: Bedentung der electrodenposition fur die erfassung ventrikularer spatpotentiale von der korperobeflache. Z Kardiol 71:637642, 1982 (abstr) 35. Berbari EJ, Friday KJ, Jackman WM. et al: Precordial mapping of signal averaged late potentials compared to XYZ leads. J Am Co11Cardiol7:127, 1986 (abstr) 36. Goldberger AL, Bhargava V, Froelicher VF, et al: Effect of myocardial infarction on high-frequency QRS potentials. Circulation 64:34-42, 1981 37. Faugere G, Savard P, Nadeau RA, et al: Characterization of the spatial distribution of late ventricular potentials

316

by body surface mapping in patients with ventricular tachycardia. Circulation 74:1323-1333, 1986 38. Simson MB, Falcone RA, Dresden CA, et al: Identification of patients with ventricular tachycardia after myocardial infarction from the signal averaged electrocardiogram. J Am Co11Cardiol3:622, 1984 39. Gomes JA, Winters S, Weiss A, et al: The optimal band pass filter for signal averaging of the surface QRS complex to detect late potentials: A prospective study. Circulation 74:II-181, 1984 (abstr) 40. Berbari EJ, Ozinga L, Friday KJ, et al: New methods for analyzing cardiac late potentials. Circulation 74:II-180, 1986

41. Denniss AR, Ross DL, Uther JB: Reproducibility of measurements of ventricular activation time using the signalaveraged frank vectorcardiogram. Am J Cardio157: 156- 160, 1986 42. Scher AM, Young AC: Frequency analysis of the electrocardiogram. Circ Res 8:344-346,196O 43. Golden DP, Wolthius RA, Hoffler GW: A spectral analysis of the normal resting electrocardiogram. IEEE Trans Biomed Eng 20:366-372, 1973 44. Riggs T, Isenstein B, Thomas C: Spectral analysis of the normal elecyrocardiogram in children and adults. J Electrocardiol 12:377-379, 1979 45. Craelius W, Hussain SM, Pantapoulos D, et al: Intraoperative spectral analysis of ventricular potentials during sinus rhythm and ventricular tachycardia. Pace 6:321, 1983 (abstr) 46. Cain ME, Ambas HD, Markham J, et al: Quantification of differences in frequency content of signal averaged electrocardiograms in patients with compared to those without sustained ventricular tachycardia. Am J Cardiol 55:1500-1505,1985 47. Evanich MJH, Newberry 0, Partidge LD: Some limitations of the removal of periodic noise by averaging. J Appl Physiol33:536, 1972 48. Breithardt G, Becker R, Seipel L, et al: Non-invasive detection of late potentials in man-A new marker for ventricular tachycardia. Eur Heart J 2:1-l 1, 1981 49. Zimmerman M, Adamec R, Simonin P, et al: Prognostic sigiticance of ventricular late potentials in coronary artery disease. Am Heart J 109:725-732, 1985 50. Froelicher VF: Exercise and the Heart, Clinical Applications. Chicago, Year Book Medical Publishers, 1987, p 44 5 1. Oppenhaim A, Schafer R: Digital Signal Processing. Englewood Cliffs, NJ, Prentice Hall, 1975, p 87 52. Lindsay BD, Ambos HD, Schechtman KB, et al: Improved selection of patients for programmed ventricular stimulation by frequency analysis of signal-averaged electrocardiograms. Circulation 73:675-683, 1986 53. Henkin R, Kelen G, El-Sherif N: Correlation between late potentials and frequency (FFT) analysis of signal averaged ECG’s-Importance of analyzed segment duration. Circulation 74:11-181, 1986 (abstr) 54. Pollak SJ, Kertes PJ, Bredlau CE, et al: Influence of left ventricular function on signal averaged late potentials in patients with coronary artery disease with and without ventricular tachycardia. Am Heart J 1 l&747-752,1985 55. Cain ME, Lindsay BD, Fischer AE, et al: Prospective comparison of frequency-and time-domain analysis of signal-

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averaged ECGs from patients with ventricular tachycardia. Circulation 7411-471, 1986 (abstr) 56. Worley SJ, Mark DB, Manwaring MG, et al: Fast fourier transformation v filtration and amplification of the signal averaged ECG: A multivariable analysis. Circulation 74:11-471, 1986 (abstr) 57. Kertes P, Glabus M, Murray A, et al: Signal averaged late potentials in the acute phase of myocardial infarctionRelevance to ventricular fibrillation. Circulation 7O:II-373, 1984 (abstr) 58. Denniss AR, Cody DV, Fenton SM, et al: Significance of delayed activation potentials in survivors of myocardial infarction. J Am Co11Cardiol 1:582, 1983 (abstr) 59. Potratz J, Mentzel H, Djonla-gic H, et al: The significance of late potentials in the acute and chronic infarction period. Circulation 7411-470, 1986 (abstr) 60. Breithardt G, Schwarzmaier J, Borggrefe M, et al: Prognostic significance of late ventricular potentials after acute myocardial infarction. Eur Heart J 4:487-495, 1983 61. Simson MB, Falcone RA, Dresden CA, Josephson ME: Late potentials in anterior versus inferior myocardial infarction. J Am Co11Cardiol3:624, 1984 (abstr) 62. Buxton AE, Simson MB, Falcone R, et al: The signalaveraged ECG predicts results of programmed stimulation in patients with nonsustained ventricular tachycardia after inferior infarction. J Am Co11Cardiol7:103, 1986 (abstr) 63. Simson MB, Falcone R, Dresden C, et al: The signal averaged ECG and electrophysiologic studies in patients with ventricular tachycardia and fibrillation. Circulation 68:111173, 1983 (abstr) 64. Denniss AR, Holley LK, Cody DV, et al: Ventricular tachycardia and fibrillation: Differences in ventricular activation times and ventricular function. J Am Co11 Cardiol 1:606, 1983 (abstr) 65. Freedman RA, Gillis AM, Keren A, et al: Signalaveraged ECG late potentials correlate with clinical arrhythmia and electrohysiology study in patients with ventricular tachycardia or fibrillation. Circulation 70:11-252, 1984 (abstr) 66. Simson MB, Spielman SR, Horowitz LN, et al: Effects of antiarrhythmic drugs on body surface late potentials in patients with ventricular tachycardia. Am J Cardiol 49:1030, 1982 (abstr) 67. Denniss AR, Ross DL, Richards DA, et al: Effect of antiarrhythmic therapy on delayed potentials detected by the signal-averaged electrocardiogram in patients with ventricular tachycardia after acute myocardial infarction. Am J Cardiol58:261-265, 1986 68. Jauernig RA, Senges J, Longfeller W, et al: Effect of antiarrhythmic drugs on ventricular late potentials at sinus rhythm and at constant heart rate, in Steinbach K, Glogar D, Laszkovics A, et al (eds): Cardiac Pacing, Steinkopff Verlag, 1983,767-772 69. Cain ME, Ambos HD, Fischer AE, et al: Non-invasive prediction of antiarrhythmic drug efficacy in patients with sustained ventricular tachycardia from frequency analysis of signal averaged ECGs. Circulation 70:11-252, 1984 (abstr) 70. Kindwall KE, Simson MB, Auletto R, et al: The signal averaged QRS in patients with right bundle branch block. Circulation 74:11-402, 1986 (abstr) 71. Kindwall KE, Auletto R, Falcone R, et al: Abnormali-

HIGH

FREQUENCY

317

ECG

ties in the signal averaged electrocardiogram in patients with ventricular tachycardia and left bundle branch block. J Am Co11 Cardiol 7:103, 1986 (abstr) 72. Kanovsky MS, Falcone RA, Dresden CA, et al: Identification of patients with ventricular tachycardia after myocardial infarction: Signal-averaged electrocardiogram, holter monitoring, and cardiac catheterization. Circulation 70:264270,1984 73. Poll DS, Marchlinski FE, Falcone RA, et al: Abnormal signal-averaged electrograms in patients with nonischemic congestive cardiomyopathy: Relationship to sustained ventricular tachyarrhythmias. Circulation 72,6:1308, 1985 74. Josephson ME, Harken AH, Horowitz LN: Endocardial excision: A new surgical technique for the treatment of recurrent ventricular tachycardia. Circulation 60:1430-1439, 1979 75. Josephson ME, Horowitz LN, Farshidi A, et al: Recurrent sustained ventricular tachycardia. 2. Endocardial mapping. Circulation 57:440-447, 1978 76. Horowitz LN, Josephson ME, Kastor JA: Ventricular resection guided by epicardial and endocardial mapping for treatment of recurrent ventricular tachycardia. N Engl J Med 302:589-593, 1980

77. Marcus NH, Falcone RA, Harken AH, et al: Body surface late potentials: Effects of endocardial resection in patients with ventricular tachycardia. Circulation 70,4:632637,1984 78. Breithardt G, Seipel J, Ostermeyer U, et al: Effects of antiarrhythmic surgery on late ventricular potentials recorded by precordial signal averaging in patients with ventricular tachycardia. Am Heart J 104:996-1003, 1982 79. Gomes JA, Mehra R, Barreca P, et al: Quantitative analysis of the high-frequency components of the signalaveraged QRS complex in patients with acute myocardial infarction: A prospective study. Circulation 72, 1:105-l 11, 1985 80. Kuchar tials detected and prognostic

DL, Thorburn MB, Sammel NL. Late potenafter myocardial infarction: Natural history significance. Circulation 74: 1280- 1289, 1986

8 1. Denniss AR, Richards DA, Cody DV, et al: Prognostic significance of ventricular tachycardia and fibrillation induced at programmed stimulation and delayed potentials detected on the signal-averaged electrocardiograms of survivors of acute myocardial infarction. Circulation 74:731-745, 1986