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J Am Coll Cardiol, 1999; 34:912-948 © 1999 by the American College of Cardiology Foundation |
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| Preamble |
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The American College of Cardiology (ACC) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. This effort is directed by the ACC/AHA Task Force on Practice Guidelines. Its charge is to develop and revise practice guidelines for important cardiovascular diseases and procedures. Experts in the subject under consideration are selected from both organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups where appropriate. Writing groups are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered as well as frequency of follow-up and cost-effectiveness.
These practice guidelines are intended to assist physicians in clinical decision making by describing a range of generally acceptable approaches for the diagnosis, management, or prevention of specific diseases or conditions. These guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment regarding care of a particular patient must be made by the physician and patient in light of all of the circumstances presented by that patient.
The executive summary and recommendations are published in the August 24, 1999, issue of Circulation. The full text is published in the Journal of the American College of Cardiology. Reprints of both the full text and the executive summary and recommendations are available from both organizations.
These guidelines have been officially endorsed by the North American Society for Pacing and Electrophysiology.
Raymond J. Gibbons, MD, FACC
Chair, ACC/AHA Task Force on Practice Guidelines
| I. Introduction |
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Traditional uses of AECG for arrhythmia detection have expanded as the result of increased use of multichannel and telemetered signals. The clinical application of arrhythmia monitoring to assess drug and device efficacy has been further defined by new studies. The analysis of transient ST-segment deviation remains controversial, but considerably more data are now available, especially about the prognostic value of detecting asymptomatic ischemia. Heart rate variability (HRV) analysis has shown promise for predicting mortality rates in high-risk cardiac patients. Technological advances with long-term event recorders have permitted the self-activation of AECG monitors, but the reliability of fully automatic recording systems has not been established for routine clinical use. Rapid technological advances portend further improvements in equipment in the near future.
These guidelines focus on the use of AECG to aid clinical decision making. Thus, emphasis will be placed on the most common clinical uses of the technique. Evaluation of the clinical utility of a diagnostic test is more difficult than assessing the efficacy of a therapeutic intervention because diagnostic tests do not usually have the same direct impact on patient outcomes (2). In considering the use of AECG in individual patients, the following factors were important:
The usefulness of AECG techniques in specific clinical situations is indicated by means of the following classification:
Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective
Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment
Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy
Class IIb: Usefulness/efficacy is less well established by evidence/opinion
Class III: Conditions for which there is evidence and/or general agreement that the procedure/treatment is not useful/effective, and in some cases may be harmful
This report includes brief descriptions of instrumentation and systems and reviews the use of AECG for 1) arrhythmia detection; 2) prognosis; 3) efficacy of antiarrhythmic therapy; 4) assessing pacemaker function and implantable cardioverter-defibrillator (ICD) function; 5) detecting myocardial ischemia; and 6) use in children. Tables appear in each section that summarize the recommendations for that particular application.
The Committee reviewed and compiled pertinent published reports by computerized and hand searches, excluding abstracts, and the recommendations made are based on these reports. Data tables are presented where multiple reports are available, but formal meta-analyses were not performed because of the nature of the available data and cost constraints. When few or no data existed, this is identified in the text, and recommendations are based on committee consensus. A complete list of the multiple publications on AECG is beyond the scope of this communication, and only selected references are included, emphasizing new data since 1989. Finally, although cost considerations are important, there were insufficient data to present formal cost-effectiveness analyses. However, cost was considered in general terms for the recommendations.
The Committee membership consisted of acknowledged experts in AECG, general cardiologists, cardiologists with expertise in arrhythmias and pacing, 1 family practitioner, and 1 general internist. Both the academic and private practice sectors are represented. No member reported a conflict of interest bearing on committee participation. The guidelines will be considered current unless the Task Force publishes revisions or a withdrawal.
| II. AECG equipment |
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There are 2 categories of AECG recorders. Continuous recorders, typically used for 24 to 48 hours, investigate symptoms or ECG events that are likely to occur within that time frame. Intermittent recorders may be used for long periods of time (weeks to months) to provide briefer, intermittent recordings to investigate events that occur infrequently. Two basic types of intermittent recorders have slightly different utility. A loop recorder, which is worn continuously, may be particularly useful if symptoms are quite brief or if symptoms include only very brief incapacitation such that the patient can still activate the recorder immediately afterward and record the stored ECG. It is sometimes possible for a family member to activate the recorder if the patient actually loses consciousness. However, even a loop recorder with a long memory may not be useful if loss of consciousness includes prolonged disorientation on awakening that would prohibit the patient from activating the device. Newer loop recorders can be implanted under the skin for long-term recordings, which may be particularly useful for patients with infrequent symptoms. Another type of intermittent recorder is the event recorder, which is attached by the patient and activated after the onset of symptoms. It is not useful for arrhythmias that cause serious symptoms such as loss of consciousness or near loss of consciousness because these devices take time to find, apply, and activate. They are more useful for infrequent, less serious but sustained symptoms that are not incapacitating. For this review, equipment will be described for the recorders first and then for the playback systems. Only selected technical details are presented in this review. A more complete description of the technical requirements for AECG equipment can be found in the 1994 American National Standard developed by the Association for the Advancement of Medical Instrumentation (3).
A. continuous recorders. Conventional AECG recorders typically are small, lightweight devices (8 to 16 oz) that record 2 or 3 bipolar leads. They contain a quartz digital clock and a separate recording track to keep time. They are generally powered by a 9-V disposable alkaline battery and a calibration signal automatically inserted when the device is energized. A patient-activated event marker is conveniently placed on the device for the patient to indicate the presence of symptoms or to note an event. The frequency response of the recording and playback system should be reasonably flat, from 0.67 to 40 Hz.
The conventional format for recording has been magnetic cassette-type tape. Tape speed typically is 1 mm/s, and speed is kept constant by an optical speed sensor on the flywheel and a crystal controlled phase locked loop. This technology has been the standard for many years and has the advantage of being inexpensive and providing a permanent record of all electrical activity throughout the recording period. This format allows for playback and interrogation of the entire recording period (so-called "full disclosure"). It is adequate to detect abnormalities of rhythm or conduction, but it may be limited for recording low-frequency signals such as the ST segment. An inadequate low-frequency response or marked phase shift from the higher-frequency QRS signal can lead to artifactual distortion of the ST segment that may be incorrectly interpreted as ischemic, particularly using some amplitude-modulated (AM) systems (4). More recent AM systems have been designed with improved low-frequency recording and playback characteristics and have been documented to record accurately ST-segment deviation (5) and even T-wave alternans (6). The frequency-modulated (FM) systems avoid this bias because they can be designed with an ideal low-frequency response without a low-frequency "boost" and are less prone to phase shift (4). However, FM systems are not as widely available, are more costly, and are subject to more baseline "noise" than AM systems (4). Regardless of whether AM or FM recording techniques are used, the tape itself may stretch and consequently distort the electrical signal.
Rapidly evolving technologies now allow for direct recording of the ECG signal in a digital format by use of solid-state recording devices. The direct digital recording avoids all of the biases introduced by the mechanical features of tape recording devices and the problems associated with recording data in an analog format, which requires analog-to-digital conversion before analysis. ECG signals can be recorded at up to 1000 samples per second, which allows for the extremely accurate reproduction of the ECG signal necessary to perform signal averaging and other sophisticated ECG analyses. These solid-state recordings can be analyzed immediately and rapidly, and some recorders are now equipped with microprocessors that can provide "on-line analysis" of the QRS-T complex as it is acquired. If specific abnormalities are detected, such as ST-segment deviation, immediate feedback can be provided to the patient. The solid-state format also provides for ready electronic data transfer to a central analysis facility. Limitations of this technology include its expense, the limited storage capacity of digital data, and, in the case of on-line analysis, reliance on a computer algorithm to identify abnormalities accurately. A 24-hour recording includes approximately 100,000 QRS-T complexes and requires almost 20 megabytes of storage per channel. Problems of storage capacity have been approached with 2 techniques of "compressing" the recorded data: 1) "lossy" compression of QRS-T complexes with very high compression ratios and 2) "loss-less" compression combined with enhanced storage capacity. Much of the reluctance of physicians to use solid-state methodologies in the past has been due to lack of faith in the "lossy" compression methods because their accuracy is dependent on the ability of the microprocessor to distinguish important physiological abnormalities from artifact or a wandering baseline. Confirmation of the "decisions" by the microprocessor cannot be made because the primary data are not recorded in their entirety and cannot be retrieved nor reproduced without error (ie, non-full disclosure). Because it is essential that representative ECG complexes from all ischemic episodes or arrhythmias be confirmed by an experienced technician or physician, the lack of full disclosure may limit the reliability of the compressed storage method (7,8). Accuracy of the on-line interpretations also may be different for ischemia versus arrhythmia analyses (9). The clinical usage of "lossy" compressed recordings and on-line interpretations is limited. There are insufficient data comparing analyses based on full-disclosure recordings versus "lossy" compressed recordings that are interpreted on-line to determine the suitability of the high-ratio compression methodologies for widespread use.
The newer technologies of enhanced storage capacity allow for all of the technical advantages of solid-state recording and now allow "full disclosure" by using loss-less compression methods, which reduce the amount of storage required by a factor of 3 to 5 but still permit reconstruction of the waveform with no loss of information. The storage methodologies available include a flash memory card or a portable hard drive. Flash cards are very small, compact storage devices, which are about the size of a credit card and have the capacity to store 20 to 40 megabytes of data. The flash cards are removed from the recording device once the recording is completed and are inserted into a separate device where the data can be played back and analyzed or the data can be transmitted electronically to another location for analysis. Miniature hard drives utilize the same technology used in laptop computers and can store more than 100 megabytes of data. Unlike flash cards, the hard drives are not removed from the recorder but the data are downloaded to another storage device or electronically transferred.
B. methods of electrode preparation and lead systems used.
The skin over the electrode area should be shaved, if necessary, gently abraded with emery tape, and thoroughly cleansed with an alcohol swab. To optimize recordings of the low-frequency ST segment, skin resistance may be measured with an impedance meter once the electrodes are applied. The measured resistance between electrodes should be
5 k
and preferably
2 k
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Most recorders utilize 5 or 7 electrodes attached to the chest, which record the signal from 2 or 3 bipolar leads onto 2 or 3 channels. The third channel may be dedicated to recording pacemaker activity. A variety of bipolar lead configurations are used, the most common being a chest modified V5 (CM5), a chest modified V3 (CM3), and a modified inferior lead. If a patient undergoing AECG monitoring for ischemia has had an exercise test with ischemic changes, the AECG lead configuration should mimic those leads with the greatest ST-segment change during exercise. A test cable can be connected from the recorder to a standard ECG machine when the device is attached to the patient to verify amplitude, rate, and morphology of waveforms that will be recorded. Once the leads have been applied, before the patient leaves the laboratory, supervised recordings should be made with the patient in the standing, sitting, right and left lateral decubitus, and supine positions to ensure that artifactual ST-segment deviation does not occur.
In a recent study of simultaneous recordings of a 3-lead AECG and a conventional 12-lead ECG recording during an exercise treadmill test (10), CM5 was the single lead with the highest sensitivity (89%) in detecting myocardial ischemia. The addition of CM3 to CM5 increased sensitivity to 91%, and the addition of an inferior lead to CM5 increased the sensitivity to 94%, particularly improving detection of isolated inferior ischemia. The combination of all 3 AECG leads had a sensitivity of 96%, only 2% more than the best combination of 2 leads (CM5 plus an inferior lead). Thus, routine identification of ischemic ST-segment deviation may only require 2 leads. Use of an inverse Nehb J lead, in which the positive electrode is placed on the left posterior axillary line, may enhance sensitivity to detect ischemia (11). Some new AECG monitor systems can record a true 12-lead ECG, whereas others derive a 12-lead ECG from 3-lead data through the use of a mathematical transform.
C. variability of arrhythmias and ischemia and optimal duration of recording. The day-to-day variability of the frequency of arrhythmias or ST-segment deviation is substantial (1222). Most arrhythmia studies use a 24-hour recording period, although yield may be increased slightly with longer recordings or repeated recordings (23). Major reductions in arrhythmia frequency are necessary to prove a treatment effect. To ensure that a change is due to the treatment effect and not to spontaneous variability, a 65% to 95% reduction in arrhythmia frequency after an intervention is necessary (12).
The variability of the frequency, duration, and depth of ischemic ST-segment depression is also marked (2428). Because most ischemic episodes during routine daily activities are related to increases in heart rate (29), the variability of ischemia between recording sessions may be due to day-to-day variability of physical or emotional activities (30). It is therefore essential to encourage similar daily activities at the time of AECG recording. The optimal and most feasible duration of recording to detect and quantify ischemia episodes is probably 48 hours (25). Most patients are quite comfortable wearing the recorder for 48 hours.
The variability of AECG ischemia strongly influences clinical trial design to identify the efficacy of a therapeutic intervention (26,28). For example, a 75% reduction in the number of ischemic episodes would be necessary to achieve statistical significance within an individual patient monitored for 48 hours before and after an intervention (28). Families of relations have been calculated for sample size estimates and statistical power for intervention trials (26,28).
D. intermittent recorders. These devices, which are also termed "event recorders," include those that record and store only a brief period of ECG activity when activated by the patient in response to symptoms and those that record the ECG in a continuous manner but store only a brief period of ECG recording (eg, 5 to 300 seconds) in memory when the event marker is activated by the patient at the time of a symptom (loop recorder). These devices often use solid-state memory and can transfer data readily over conventional telephone lines. These recorders can be used for prolonged periods of time (many weeks) to identify infrequently occurring arrhythmias or symptoms that would not be detected with a conventional 24-hour AECG recording. Newer loop recorders can be implanted for longer-term monitoring. An event recorder relies on rapid placement of electrodes, such as paddles connected to the recorder or a wrist bracelet, to record the ECG at the time of the symptom. Loop recorders use continuously worn electrodes. The recorded signal can be transmitted to a receiving station or may be saved in memory and transferred at a later time to a central analysis facility.
Intermittent recorders have the advantage of being small and light, easy to use, and can be programmed to record many short episodes during an extended period of time (in most cases up to 30 days). Single-, 2-, 3-, and reconstructed 12-lead formats are available.
E. AECGzcasex> Recording Capabilities Associated With Pacemakers and ICDs. Most current ICDs continually monitor the intracardiac electrogram and store in memory a summary of tachycardia and bradycardia episodes as well as a brief electrogram meeting prespecified criteria preceding and following each therapeutic discharge.
Intracardiac electrograms may be recorded from a variety of leads and electrode pairs, depending on the equipment used (31). These devices can store only a limited number or duration of recordings (32). Many pacemakers have the capability to calculate heart rate for a selected period of time. See Section VII for further description of recording capabilities of current pacemakers and ICD devices.
F. playback systems and methods of analysis. Most current playback systems use generic computer hardware platforms running proprietary software protocols for data analysis and report generation. Facsimile, modem, network, and Internet integration allow for rapid distribution of AECG data and analyses throughout a healthcare system. Signals recorded in analog format (ie, magnetic tape) are digitized at either a rate of 128 or 256 samples per second for subsequent analysis. The clock track on the tape can compensate for variations in tape speed by a phase lock loop circuit. The resolution is usually at least 8 bits and the sampling rate is nominally 128 samples per second. The signal amplitude can be adjusted by the technician on the basis of the calibration signal recorded automatically at the initiation of each recording. Tape playback and scanning options include rapid playback with either superimposition (up to 1000 times real time) or page-type displays.
It is critical that each classification of arrhythmia morphology and each ischemic episode be reviewed by an experienced technician or physician to ensure accurate diagnosis because AECG recordings during routine daily activities frequently have periods of motion artifact or baseline wander that may distort the ST-segment or QRS morphology. The presence of artifacts can be minimized by good skin preparation, use of high-quality ECG electrodes and monitoring leads, lead placement secured by loops of the electrode cable, and awareness of ST-segment deviation caused by changes in body position. Although the identification of ischemia made by the computer algorithm alone may be helpful, the interpretations are frequently found to be incorrect when assessed by an experienced observer. Overreading is essential. In an experienced laboratory, the interobserver and intraobserver agreement for the presence and characterizations of ischemic episodes should be high. Preliminary studies suggest that there may be differences in interpretation of ST-segment activity among different laboratories. Much more investigation concerning the uniformity of interpretations of ischemic ST-segment deviation is necessary before widespread application of ischemia monitoring is feasible and reliable. Interobserver and intraobserver agreement is excellent for categorization of arrhythmias, but discrepancies of 10% to 25% in total ventricular arrhythmia counts for the same recording may occur if frequent or complex arrhythmias are present (33).
1. Arrhythmia analysis
Each beat is classified as normal, ventricular ectopic, supraventricular ectopic, paced, other, or unknown, and a template for each type of abnormality is created. The computer tabulates the number of ectopic beats in each template. Summary data describing the frequency of atrial and ventricular arrhythmias are displayed typically in both tabular and graphical formats. The system automatically stores strips of significant arrhythmia events detected as well as patient events and entered diary notation times.
2. Ischemia analysis
The QRS-T morphology must be carefully scrutinized to ensure that it is suitable for interpretation to identify ischemic changes (34). The rhythm should be normal sinus rhythm. The baseline ST segment should have
0.1 mV deviation, and the morphology ideally should be gently upsloping with an upright T wave. Although an ST segment that is flat or associated with an inverted T wave may still be interpretable, downsloping or scooped ST-segment morphology should be avoided. The R-wave height of the monitored lead should be
10 mm. Patients whose 12-lead ECG demonstrates left ventricular (LV) hypertrophy, preexcitation, left bundle-branch block, or nonspecific intraventricular conduction delay
0.10 second are not suitable for detecting ischemia by AECG. The lead selected for AECG ischemia monitoring should not have a Q wave
0.04 second or marked baseline ST-segment distortion. ST-segment deviation in the presence of right bundle-branch block may be interpretable, especially in the left precordial leads. Medications such as digoxin and some antidepressants distort the ST segment and preclude accurate interpretation of ST-segment deviation. ST-segment deviation is usually tracked by the use of cursors at the P-R segment to define the isoelectric reference point and at the J-point and/or 60 to 80 ms beyond the J-point to identify the presence of ST-segment deviation. Ischemia is diagnosed by a sequence of ECG changes that include flat or downsloping ST-segment depression
0.1 mV, with a gradual onset and offset that lasts for a minimum period of 1 minute. Each episode of transient ischemia must be separated by a minimum duration of at least 1 minute, during which the ST segment returns back to baseline (1 x 1 x 1 rule) (35), although many investigators prefer a duration of at least 5 minutes between episodes. We recommend a 5-minute interval between episodes because the end of one episode and the onset of another episode will take longer than 1 minute to be physiologically distinct.
During superimposition scanning, the system displays the normal complexes used for ST-segment measurement. The magnitude of ST-segment deviation and the slope of the ST segment typically is identified and presented as part of a 24-hour trend. Episodes of ST-segment deviation are characterized by identification of an onset and offset time, magnitude of deviation, and heart rate before and during the episode. Representative ECG strips at the time of ST-segment deviation in real time may be provided in the report format. Ischemic episodes are displayed in a summary table. Miniaturized full-disclosure display can be printed for all or part of the 24-hour recording.
G. emerging technologies. There are a number of important new technologies that hold promise for the future. During the playback of the recorded ECG signal and the analysis process, there are electrophysiological variables that can be measured other than arrhythmias and ST-segment deviation. These include T-wave alternans (6), Q-T interval dispersion (36), and signal-averaged analysis (37). For these analyses, high-resolution data are necessary, which may require data acquisition at rates up to 1000 samples per second (38).
| III. Heart rate variability |
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Analysis of the beat-to-beat oscillation in the R-R interval is generally performed by 2 methods. Spectral analysis provides an assessment of the vagal modulation of the R-R interval. Spectral analysis is most commonly accomplished by fast Fourier transformation to separate R-R intervals into characteristic high (0.15 to 0.40 Hz), low (0.04 to 0.15 Hz), very low (0.0033 to 0.04 Hz), and ultra low (up to 0.0033 Hz) frequency bands. Spectral measures are collected over different time intervals (approximately 2.5 to 15 minutes), depending on the frequency being analyzed (39). Parasympathetic tone is primarily reflected in the high-frequency (HF) component of spectral analysis (4042). The low-frequency (LF) component is influenced by both the sympathetic and parasympathetic nervous systems (43,44). The LF/HF ratio is considered a measure of sympathovagal balance and reflects sympathetic modulations (45).
Nonspectral or time domain parameters involve computing indexes that are not directly related to specific cycle lengths. This method offers a simple means of defining patients with decreased variability in the mean and standard deviations of R-R intervals. Time domain parameters analyzed include mean R-R, the mean coupling interval between all normal beats; SDANN, standard deviation of the averaged normal sinus R-R intervals for all 5-minute segments of the entire recording; SDNN, standard deviation of all normal sinus R-R intervals; SDNN index, mean of the standard deviations of all normal R-R intervals for all 5-minute segments of the entire recording; pNN50, the percentage of adjacent R-R intervals that varied by more than 50 ms; and rMSSD, the root mean square of the difference between the coupling intervals of adjacent R-R intervals. Another time domain measure of HRV is the triangular index, a geometric measure obtained by dividing the total number of all R-R intervals by the height of the histogram of all R-R intervals measured on a discrete scale with bins of 7.8 ms. The height of the histogram equals the total number of intervals found in the modal bin. These 2 analytical techniques are complementary in that they are different mathematical analyses of the same phenomenon. Therefore certain time and frequency domain variables correlate strongly with each other (Table 1).
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2. Artifact and arrhythmias
No matter whether short- or long-term data are analyzed, the analysis of HRV depends on the integrity of the input data. Most systems obtain computer-digitized ECG signals. The R-R intervals are derived either on-line or off-line. The rate of digitization varies from system to system. Many commercial AECG systems have a digitization rate of 128 Hz, which is not optimal for some experimental short-term recordings but is useful for long-term recordings in adults (46).
To optimize the temporal accuracy of R-wave peak identification, especially when the digitization rate is below 250 Hz, a template matching or interpolation algorithm should be used (45,47,48). Similarly, artifact or noise in the ECG signal can create errors in R-wave timing. Several approaches to this problem have been taken and include smoothing or filtering the digitized data (4749). Although these methods help to reduce inaccuracies created by recorded noise, careful patient preparation and maintenance of recording equipment is very important to eliminate noise before it occurs.
If analog recording devices are used, rates of digitization are not a factor, but noise and other errors in R-wave timing remain important. AECG systems that record on magnetic tape for off-line processing can introduce errors related to tape stretch. The ESC/NASPE Task Force (45) provided guidelines for the routine evaluation of recording systems through simulated calibration signals with known characteristics.
A problem with ambulatory recordings for the determination of HRV is motion-related artifact. Missing R waves or spuriously detected beats can lead to large deviations in the R-R interval. Manual overview can usually detect these errors but can be tedious. Distribution-based artifact detection algorithms are best used to assist the visual approach (5052).
An additional factor that introduces difficulties in the analysis of HRV is the presence of cardiac arrhythmias. HRV analysis is not possible with persistent atrial fibrillation. Intermittent abnormal heartbeats can distort the normal R-R intervals. Although HRV may be useful in predicting or characterizing abnormal rhythms, the presence of abnormal heartbeats must be processed in some way to avoid errors in the assessment of HRV. Two methods for handling abnormal heartbeats include interpolation of occasional abnormal beats (53) and limiting analysis to segments that are free of abnormal beats. Both methods have limitations, and application of both may be appropriate. However, in publications in which assumptions have been made, they must be stated clearly.
C. day-to-day variability. In normal subjects, Kleiger et al (54) found 24-hour ambulatory recordings to reveal large circadian differences in the R-R interval, LF power, HF power, and LF/HF ratio. Kleiger et al also described 3- to 4-fold changes in R-R variability between 5-minute segments of the same hour. However, the mean values for the LF and HF power were almost identical from day to day. Power spectral measures of R-R variability averaged across a 24-hour period were also essentially constant. Large differences were seen among the 5-minute intervals during the day (55). HRV in the normal population is affected by age and sex. Recent data have shown that SDNN index, rMSSD, and pNN50 in healthy people over the age of 60 years may actually fall below levels that have been associated with increased mortality rates. Younger women have less HRV than their age-matched counterparts, but these differences disappear by age 50 years. In subjects with coronary artery disease (CAD), Bigger et al (56) found no significant differences between 2 consecutive 24-hour recordings. Recommendations for the use of HRV analysis follow in Section V. K.
| IV. Assessment of symptoms that may be related to disturbances of heart rhythm |
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If arrhythmias are thought to be causative in patients with transient symptoms, the crucial information needed is the recording of an ECG during the precise time that the symptom is occurring. With such a recording, one can determine if the symptom is related to an arrhythmia. Four outcomes are possible with AECG recordings. First, typical symptoms may occur with the simultaneous documentation of a cardiac arrhythmia capable of producing such symptoms. Such a finding is most useful and may help to direct therapy. Second, symptoms may occur while an AECG recording shows no arrhythmias. This finding is also useful because it demonstrates that the symptoms are not related to rhythm disturbances. Third, a patient may remain asymptomatic during cardiac arrhythmias documented on the recording. This finding has equivocal value. The arrhythmia may be useful as a clue to a more severe arrhythmia that actually causes symptoms. For example, nonsustained ventricular tachycardia recorded while the patient is asymptomatic may be a clue that the patient has a more serious ventricular tachycardia at other times, causing near syncope or syncope. Likewise, asymptomatic bradycardia may be a clue that symptoms may occur when the heart rate is even slower. However, asymptomatic arrhythmias are common, even in the general population without heart disease (6063). Therefore the recorded arrhythmia may or may not be relevant to the symptoms. Fourth, the patient may remain asymptomatic during the AECG recording, and no arrhythmias are documented. This finding is not useful.
It is imperative that the physician and patient be persistent in attempting to record the cardiac rhythm simultaneous with transient symptoms. This may require multiple 24- or 48-hour AECG recordings or event recorders (23,6469), especially for infrequent symptoms. The rhythm must be recorded during and not after the symptoms have occurred. The utility of AECG will be determined by the frequency, severity, duration, and conditions under which the symptoms occur. Less frequent arrhythmias will require more attempts to record. Significant cardiac arrhythmias are more likely to occur in patients with serious heart disease, so it is more likely that transient symptoms can be correlated to arrhythmias in the severely ill cardiac patient. It is essential that a complete and detailed history and physical examination be taken, and it is often necessary to perform blood work, a chest radiograph, a 12-lead ECG, and/or an echocardiogram as a part of the initial evaluation. Careful clinical judgment must be exercised. Causes of symptoms other than arrhythmias must be considered and appropriate additional studies obtained. Under some circumstances, particularly in patients with exertional symptoms, an exercise test might give a higher yield for correlation between symptoms and cardiac rhythm. Electrophysiological studies and tilt-table testing also may be considered in certain circumstances. If symptoms are severe, monitoring may need to be performed in-hospital continuously on telemetry. However, the sensitivity and specificity of automatic rhythm monitoring alarms may be inferior to analysis of AECGs.
B. selection of recording technique. The characteristics of the patients symptoms will often determine the choice of recording techniques. Selection of technique must be individualized. Specific indications for the different types of recorders should not be defined here because such detail would place undue limits on clinical judgment. Continuous AECG recording may be particularly useful in patients who have complete loss of consciousness and would not be able to attach or activate an event recorder. Continuous AECG recording is particularly useful if symptoms occur daily or almost daily, although most patients do not have episodic symptoms this frequently. Such a recording should include a patient diary of symptoms and activities and the use of an event marker. The event marker is activated whenever the patient has typical symptoms, simplifying the identification of the point in time during the recording when symptoms occurred. Usually 24-hour recordings are performed, although yield may be increased slightly with longer recordings or repeated recordings (23).
Many patients have symptoms occurring weekly or monthly, in which case a single continuous AECG recording probably will not be useful. An intermittent or event recorder (which is often capable of transtelephonic downloading) is more useful for infrequent symptoms (7075).
Some rhythm recording devices are implanted surgically and include pacemakers, cardioverter-defibrillators, and newly developed ECG recorders (76,77). Their utility is limited by the need for an invasive procedure.
C. specific symptoms. Few studies have evaluated the sensitivity, specificity, positive and negative predictive values, and cost-effectiveness of the various recording techniques in patients with symptoms potentially related to cardiac arrhythmias. Only in the subset of patients with syncope are detailed data available.
1. Syncope
The diagnostic evaluation of syncope is determined by many clinical factors (59,6467,69,76,78,79). Many studies combine evaluation of syncope with near syncope and/or dizziness (Table 3) and use different arrhythmia end points to define a "positive" study (6669,78,79). Unfortunately, the yield of AECG monitoring is relatively low. The majority of such patients have no symptoms during ambulatory recording, and further evaluation is necessary. However, because of the severity of the symptoms, such testing is usually warranted. Nevertheless, the rhythm during asymptomatic periods may be useful. For example, a patient may have syncope only during severe bradycardia. An ambulatory ECG that shows intermittent episodes of asymptomatic bradycardia may suggest the diagnosis and prompt further evaluation. One study (23) evaluated the utility of repeated 24-hour ambulatory recording on 3 separate occasions. The first 24-hour recording exhibited a major abnormality in 15% of the patients. The additive yield was 11% on the second and 4.2% on the third sequential recordings. Factors that identified a useful recording were advanced age, male sex, history of heart disease, and initial rhythm other than normal sinus. When continuous AECG monitoring is not useful, intermittent recorders (both patient-applied and loop) add incremental value to continuous recording. Furthermore, the memory capability of previously implanted pacemakers and ICDs can add diagnostic value.
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2. Palpitation
The yield of ambulatory monitoring that captures an episode of palpitation (Table 4) is higher than the yield for patients with syncope, probably because the frequency of occurrence of palpitation is higher than the occurrence of syncopal episodes, though findings are likely to be more variable in patients with palpitation (58,71). Palpitation accounts for 31% to 43% of indications for outpatient AECG monitoring (68,69). Furthermore, in patients with preexisting palpitation, asymptomatic episodes of supraventricular arrhythmias are more common than symptomatic episodes (80,81).
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| Indications for AECG to assess symptoms possibly related to rhythm disturbances |
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Class IIb.
Class III.
| V. Assessment of risk in patients without symptoms of arrhythmias |
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A. after myocardial infarction. Myocardial infarction (MI) survivors are at an increased risk of sudden death, with the incidence highest in the first year after infarction (84,85). The major causes of sudden death are ventricular tachycardia and ventricular fibrillation. The risk of developing an arrhythmic event has declined with the increasing use of thrombolytic agents and coronary revascularization (8688). Currently, the 1-year risk of developing a malignant arrhythmia in an MI survivor after hospital discharge is 5% or less (86,87,8991). The goal in risk-stratifying patients is to identify a population of patients at high risk of developing an arrhythmic event and reduce such events with an intervention. Ideally, these patients would be identified by a test or combination of tests with a high sensitivity and a very high positive predictive accuracy, so that as few patients as possible are unnecessarily exposed to treatment.
AECG monitoring usually is performed over a 24-hour period before hospital discharge. Some studies suggest that 4 hours of AECG monitoring provides as much information as 24 hours (92,93). In many studies, AECG monitoring was performed at least 6 and often approximately 10 days after the acute MI (Table 5). Frequent premature ventricular contractions (PVCs) (eg, 10 per hour) and high-grade ventricular ectopy (eg, repetitive PVCs, multiform PVCs, ventricular tachycardia) after MI have been associated with a higher mortality rate among MI survivors (86,8991,94100). However, once patients have at least 6 PVCs per hour, the risk of an arrhythmic event does not increase with more frequent PVCs (101). The association between ventricular arrhythmias and adverse cardiac events has been demonstrated primarily in men (102,103).
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Low values for high frequency measures of HRV (eg, rMSSD or pNN50) and baroreflex sensitivity (BRS) indicate decreased vagal modulation of R-R intervals (45,106). The specific mechanism by which HRV and BRS are reduced after MI remains unknown, but they decrease in patients early after MI (reaching a nadir after 2 to 3 weeks) and then increase back to normal levels by 6 to 12 months. Decreased HRV and BRS are independent predictors of increased mortality rates, including sudden death, in patients after MI (89,95,100,104,106108) (Table 6). However, the predictive value of both HRV and BRS after MI, although statistically significant, is poor when used alone.
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Although each of these tests has a predictive value independent of other well-established risk factors after MI, such as depressed LV function, their overall value is low. Combining these tests with each other and other clinical factors markedly improves their PPVs. As seen in Table 7, a variety of combinations has been used; however, it is not clear which is the best combination to use at the present time. The prognostic capability of these tests is reviewed in Table 8.
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40% (100) because malignant arrhythmias occur infrequently in such patients.
Long-term survivors of MI with reduced LV function remain at increased risk of dying from a cardiovascular event. However, the primary reason for patients to undergo AECG monitoring is to identify those with a poorer prognosis and ultimately to improve outcomes through active treatment. Recently, the Multicenter Automatic Defibrillator Implantation Trial (MADIT) showed that ICD therapy reduces mortality rates by approximately 50% in MI survivors who had a reduced LV ejection fraction (
35%), who had at least 1 asymptomatic nonsustained ventricular arrhythmia, and in whom ventricular fibrillation or sustained ventricular tachycardia was reproducibly induced during electrophysiological testing and not suppressed by use of intravenous procainamide (113). Unfortunately, the study does not provide data on how many patients after MI had this combination of findings nor how many were identified as having asymptomatic ventricular arrhythmias detected only by AECG.
Similarly, a recent meta-analysis examined whether amiodarone prevented sudden death in a series of randomized controlled trials (114). Amiodarone reduced the incidence of sudden death, cardiac death, and total mortality rates in these trials. However, the patient populations were heterogeneous, and only two thirds of the trials required ventricular ectopy for study entry. In addition, survival for patients who received amiodarone was only different from the usual and active care groups; there was no significant difference when compared with placebo (ie, the alternative treatment may have been harmful, and this could have artificially increased the effect of amiodarone). Thus the role of AECG in identifying this population remains unanswered.
B. congestive heart failure. Patients with congestive heart failure (CHF), whether caused by an ischemic cardiomyopathy or an idiopathic dilated cardiomyopathy, often have complex ventricular ectopy and a high mortality rate (115,116). There were conflicting findings in a series of small studies, with some suggesting a relation between ventricular arrhythmias and death (117119) and others finding no such relation (115,116,120). Several more recent studies with larger populations have found that ventricular arrhythmias (eg, ventricular tachycardia, nonsustained ventricular tachycardia) are sensitive but not specific markers of death (121,122) and sudden death (122) (Table 9). Despite identifying a population with an increased relative risk of an adverse event, these tests are either not sensitive or have low PPVs.
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C. hypertrophic cardiomyopathy. Sudden death and syncope are common among patients with hypertrophic cardiomyopathy. The exact relation between ventricular arrhythmias or HRV and outcomes for patients with hypertrophic cardiomyopathy remains open to question. Three studies show that there is some association between ventricular arrhythmias and adverse events, but they differ on the nature of the association (133135). Another study found no association between HRV indexes and adverse events (136). Although AECG monitoring may add to the prognostic information provided by known risk factors for patients with hypertrophic cardiomyopathy, treatment of these ventricular arrhythmias has not consistently been shown to increase life expectancy. Hence the specific role of AECG in the day-to-day treatment of these patients remains unclear.
D. valvular heart disease. A few studies have examined the relation between valvular heart disease and HRV or ventricular ectopy. At the present time, the presence of mitral valve prolapse (137), chronic mitral