Subject:
Signal-Averaged Electrocardiography (SAECG)
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Signal-averaged electrocardiography (SAECG) is a technique involving computerized analysis of small segments of a standard EKG to detect abnormalities, termed ventricular late potentials (VLP), that would be otherwise obscured by “background” skeletal muscle activity. VLPs reflect aberrant, asynchronous electrical impulses arising from viable isolated cardiac muscle bordering an infarcted area and are thought to be responsible for ventricular tachyarrhythmias. Therefore, VLPs, as measured by SAECG, have been investigated as a risk factor for arrhythmic events in patients with a variety of cardiac conditions, including cardiomyopathy and prior history of myocardial infarction (MI). Patients considered at high risk of ventricular arrhythmias and thus sudden death may be treated with drugs to suppress the emergence of arrhythmias or implantable cardiac defibrillators (ICD) to promptly detect and terminate tachyarrhythmias when they occur. Because sudden cardiac death, whether from arrhythmias or pump failure, is one of the most common causes of death after a previous myocardial infarction, there is intense interest in risk stratification to target therapy. Patient groups are divided into those who have not experienced a life-threatening arrhythmia (i.e., primary prevention) and those who have (i.e., secondary prevention). SAECG is just one of many risk factors that have been investigated. Others include left ventricular ejection fraction, arrhythmias detected on Holter monitor or electrophysiologic studies, heart rate variability, and baroreceptor sensitivity. T-wave alternans is another technique for risk stratification. T-wave alternans, addressed in a separate policy (Policy # 010), measures beat-to-beat variability, while SAECG measures beat-averaged conduction.
Policy:
(NOTE: For Medicare Advantage, Medicaid and FIDE-SNP, please refer to the Coverage Sections below for coverage guidance.)
Signal-averaged electrocardiography is considered investigational, including, but not limited to, its use:
- as a technique of risk stratification for arrhythmias after prior myocardial infarction;
- in patients with cardiomyopathy;
- in patients with syncope;
- as an assessment of success after surgery for arrhythmia;
- in the detection of acute rejection of heart transplants;
- as an assessment of efficacy of antiarrhythmic drug therapy; or
- in the assessment of success of pharmacological, mechanical, or surgical interventions to restore coronary artery blood flow.
Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage will follow the Horizon BCBSNJ Medical Policy.
Medicaid Coverage:
For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.
FIDE SNP:
For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.
[RATIONALE: Use of signal-averaged ECG in risk stratification for ventricular arrhythmias
Signal-averaged electrocardiography (SAECG) has been thoroughly studied as a risk stratification tool for potentially fatal arrhythmias in patients with a previous myocardial infarction (MI). As reviewed by the Agency for Health Care Policy and Research (AHCPR) in 1998, SAECG is associated with a low positive predictive value, ranging from 8–44%, depending on the population studied. (1) In contrast, the negative predictive value (i.e., the ability to identify those patients who will not experience ventricular arrhythmias) ranges from 88–97%, suggesting that the negative predictive value may be used to identify patients who would not benefit from antiarrhythmic therapy. However, a key statistic underlying the negative predictive value is the underlying incidence rate of the outcome. Although sudden cardiac death is the most common cause of death in the 1-year period after infarction, it is relatively uncommon (2.5–11.3%) and declining, as a result of increasing use of thrombolytic therapy, aspirin, and beta-blockers. (2) Thus, given the relative low incidence rate of ventricular arrhythmias, the high negative predictive value is not surprising.
Bailey and colleagues performed a systematic review and meta-analysis on the utility of various tests for risk stratification of ventricular arrhythmias. (3) This study reviewed 44 reports for which values of major arrhythmic events (MAE) and predictive accuracy of several tests (SAECG, heart rate variability, severe ventricular arrhythmia on ambulatory electrocardiography, left ventricular ejection fraction [LVEF], and electrophysiological studies [EPSs]) could be inferred. A meta-analysis of reports used receiver-operating characteristic (ROC) curves to estimate mean values for sensitivity and specificity for each test, and 95% confidence limits. Test sensitivities (all tests) ranged from 42.8% to 62.4%; specificities ranged from 77.4% to 85.8%. For SAECG, sensitivity was 62% and specificity was 77%. A 3-stage stratification yielded a low-risk group (80.0% with a 2-year MAE risk of 2.9%), a high-risk group (11.8% with a 41.4% risk), and an unstratified group (8.2% with an 8.9% risk equivalent to a 2-year incidence of 7.9%). The authors concluded that sensitivities and specificities for the 5 tests were relatively similar, and no test alone was satisfactory for predicting risk. Combinations of tests in stages allowed the authors to stratify 92% of patients as either high risk or low risk. The authors noted that these data suggest that a large prospective study to develop a robust prediction model is feasible and desirable.
Some more recent reports on the use of signal-averaged for risk stratification have been published since the prior analyses. Grimm and colleagues reported on the results of the Marburg Cardiomyopathy study, a prospective observational study designed to determine the clinical value of potential noninvasive arrhythmia risk predictors among 343 patients with idiopathic dilated cardiomyopathy and followed up for 52 +/- 21 months for major arrhythmic events. (4) Reduced LVEF and lack of beta blocker use were important risk factors, but results of SAECG and T-wave alternans were not. Results of SAECG were found to only be a weak predictor of sudden cardiac death in a consecutive series of 700 patients with a history of acute myocardial infarction (AMI). (5) In another study of 1,800 consecutive survivors of AMI who underwent reperfusion therapy, late potentials identified by SAECG were not significantly associated with the endpoints of cardiac death or serious arrhythmias. (6)
Conclusions. Signal-averaged ECG has moderate predictive ability in risk-stratification of ventricular arrhythmias. Systematic reviews and meta-analyses have concluded that the positive predictive value of an abnormal signal-averaged ECG is in the low to moderate range. The negative predictive value is high, but this may reflect more the low overall incidence of ventricular arrhythmias than the predictive ability of signal-averaged ECG. Some more recent studies have found a weak association, or no association, between signal-averaged ECG results and ventricular arrhythmias. Other methods of risk stratification are available, but there is not one method that is clearly better than the others.
Use of signal-averaged ECG to select patients for anti-arrhythmic treatment
The ultimate validation of any diagnostic test is to determine how it is used in the management of patients and whether the management decisions result in improved health outcomes. The following discussion focuses on the clinical use of SAECG as a selection criterion for antiarrhythmic therapies in clinical trials.
Over the past two decades, a large number of randomized clinical trials (RCTs) have evaluated the effectiveness of either antiarrhythmic drugs or implantable cardiac defibrillator (ICD) implantation in post-MI patients. These trials have generally used a variety of risk stratification criteria to positively select patients for intervention. By selecting patients with a sufficiently high risk of arrhythmia, the benefits of treating arrhythmia will hopefully outweigh any adverse effects of the treatment. For the purposes of this discussion, the most relevant studies are those that look at patients who have not experienced a prior episode of near fatal ventricular arrhythmia or aborted sudden death. Patients with a prior history of a potentially fatal arrhythmia are already at sufficiently high risk and are considered candidates for either antiarrhythmic therapy or ICD.
Initially it was thought that pharmacologic suppression of premature ventricular contractions (PVCs), identified on post-MI monitoring, would reduce the incidence of subsequent sustained, symptomatic arrhythmias. The Cardiac Arrhythmia Suppression Trial (CAST) was a placebo-controlled, randomized trial that tested the efficacy of encainide, flecainide, or moricizine in reducing arrhythmic death in patients with a lowered ejection fraction (EF) and 6 or more PVCs per hour. (7) CAST was terminated prematurely when an interim analysis suggested that the drug therapy was associated with an increase in the incidence of arrhythmic death. This trial raised concerns about proarrhythmic effects of antiarrhythmic drugs and has led to caution in the use of any antiarrhythmic drug therapy.
The drugs in the CAST trial are known as class I antiarrhythmics, defined as agents that slow conduction. After the failure of the CAST trial, research was focused on class III agents, which prolong repolarization. The most commonly researched member of this class of drugs is amiodarone. There have been a number of small randomized studies of amiodarone, but the largest are the European Myocardial Infarct Amiodarone Trial (EMIAT) and the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT), both of which assessed the effect of amiodarone on mortality in patients with high-risk markers after myocardial infarction (MI). (8, 9) In EMIAT, patients with a history of MI were stratified according to their EF. In CAMIAT, patients were recruited based on results of Holter monitoring. Therefore, neither of these key trials used SAECG as a patient selection criterion.
The results of both trials suggested that, while amiodarone was associated with a decreased risk of arrhythmias, no overall reduction was noted in all-cause mortality. Therefore, the major finding of these trials focused on the safety of amiodarone, in contrast to the class I agents studied in the CAST trial. The clinical effectiveness of amiodarone is less certain and may be associated with a reduction of morbidity and quality of life associated with symptomatic arrhythmias, although this outcome has not been specifically studied. It is possible that a normal SAECG could be considered to deselect patients who would be unlikely to benefit from amiodarone therapy. However, this outcome has not been specifically studied, particularly since the overall benefit of amiodarone therapy is still controversial.
With the somewhat disappointing results of these drug trials, attention has turned toward the use of ICDs, particularly as these devices have become more sophisticated. Early generations of ICDs required thoracotomy for insertion, but miniaturization has permitted outpatient insertion with the use of local anesthesia. With this reduction in the risk associated with ICDs, there was an interest in exploring their use in patients without a prior history of sustained, symptomatic ventricular arrhythmias. Several randomized studies have now been completed. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) recruited post-MI patients with left ventricular ejection fraction (LVEF) of less than 35%, non-sustained ventricular tachycardia identified on Holter monitoring or stress test, and inducible, procainamide-resistant, sustained ventricular arrhythmia on electrophysiologic study. (10) These characteristics were thought to identify a very-high-risk group for ventricular arrhythmias, in part due to the desire to have very high event rates to increase the power of the trial. The MADIT trial reported a marked reduction in mortality in those receiving a defibrillator compared to patients treated conventionally, mostly with amiodarone. Following publication of the results, the U.S. Food and Drug Administration (FDA) approved expanded labeling for defibrillators in patients who met the MADIT criteria; Medicare announced coverage for ICD in this patient population; and the American College of Cardiology (ACC) has published guidelines endorsing the study results. (11) As noted here, SAECG was not used as a patient selection criterion and thus is not included as a recommended test as part of the ACC guidelines.
In contrast to the other trials reviewed here, the Coronary Artery Bypass Graft (CABG) Patch trial used SAECG as a positive patient selection criterion. (12) The CABG-Patch trial recruited patients scheduled for CABG who had an EF of less than 36% and abnormalities on SAECG. The use of SAECG was based on a pilot study that showed that an abnormal finding on SAECG was associated with a mortality rate that was double that seen in those with a normal SAECG in the 2 years after CABG. (11) Patients were randomly assigned to a defibrillator group or a control group, and all received CABG. After an average follow-up of 32 months, there was no evidence of improved survival among those in the defibrillator group. However, it cannot be determined whether the failure of this trial was due to the selection criteria or the treatments being compared.
One study from Japan evaluated the use of SAECG in a study of 222 hospitalized patients found to have non-sustained ventricular tachycardia. Forty-three patients with ischemic heart disease and 50 with non-ischemic cardiomyopathy were evaluated using an algorithm for risk-stratification. (13) The algorithm included LVEF, SAECG (in 69 patients), programmed ventricular stimulation, and family history of sudden cardiac death; in follow-up, programmed stimulation was done for all positive SAECG studies. Of the 222 patients, 151 (68.0%) were successfully risk-stratified, and 32 patients consequently received an ICD (21.2% of the algorithm). The remaining 119 patients without an ICD (algorithm-observation group) were observed. During an average of 28 months of follow-up, the patients in the algorithm-ICD group had a significantly higher prevalence of tachyarrhythmic events than those in the algorithm-observation group (9/32 vs. 1/119, respectively; p<0.05). In the algorithm-ICD group, 2, 1, and 6 patients experienced sudden cardiac death, aborted sudden cardiac death, and appropriate ICD intervention, respectively. The authors concluded that this proposed algorithm for risk-stratification of patients with non-sustained ventricular tachycardia may be feasible for appropriate selection of candidates for prophylactic ICD implantation.
More recent trials investigating the use of ICD in post-MI patients have not provided clarity regarding the issue of risk stratification. The MADIT-II trial selected patients solely on the basis of LVEF and showed a survival benefit among those randomly assigned to ICD. (14) No additional data have directly linked risk stratification information provided by SAECG to improved patient outcomes, improved efficiency, or reduced costs.
Conclusions. Based on this review, SAECG has not been successfully used as a patient selection criterion in the critical randomized trials investigating both drug and device antiarrhythmic therapy in the post-MI patient, or other patient populations at high risk for ventricular arrhythmias. In the majority of trials, it has not been included as a patient selection criterion, and the one trial in which it was used reported negative results.
Use of signal-averaged ECG for other indications
Data are inadequate to evaluate the impact on patient management of other applications of SAECG including, but not limited to, its use in patients with cardiomyopathy; assessment of success after surgery for arrhythmia; detection of acute rejection of heart transplants; assessment of efficacy of antiarrhythmic drug therapy; assessment of success of pharmacological, mechanical, or surgical interventions to restore coronary artery blood flow; or risk stratification of patients with Brugada syndrome. Regarding the use of SAECG to identify patients with syncope who may have inducible ventricular tachycardia, even though an ACC consensus document from 1996 concluded that SAECG had an established role, data from the report reported only modest sensitivity (73%) and poor positive predictive values. (15) Thus, if used to determine who should have electrophysiologic studies, the test will fail to detect many patients who have positive electrophysiologic studies.
In 2011, studies were also published on the utility of signal-averaged ECG for arrhythmogenic right ventricular cardiomyopathy, cardiac sarcoidosis, and epilepsy. (16-18) Kamath et al. (16) tested the utility of signal-averaged ECG in diagnosing arrhythmogenic right ventricular cardiomyopathy. These authors reported a sensitivity ranging from 47-69%, using different criteria for a positive test, and a specificity of 95%. Schuller et al. (18) reported a sensitivity of 52% and specificity of 82% for detecting cardiac involvement in patients with sarcoidosis. Rejdak et al. (17) studied 45 consecutive patients with epilepsy and compared results of signal-averaged ECG with 19 healthy controls. An abnormal signal-averaged ECG was found in 48% (22/45) of patients with epilepsy compared with 5% (1/19) of control patients.
A number of studies have evaluated the use of p-wave signal averaged ECG to predict atrial arrhythmias. Militaru et al. (19) performed p-wave signal-averaged ECG in 88 patients with paroxysmal atrial fibrillation, and compared the results to 330 normal subjects. The patients with atrial fibrillation had a significantly longer p-wave duration and a higher p-wave integral compared to normal subjects. Furukawa et al. (20) evaluated p-wave signal averaged ECG in 20 patients with Brugada syndrome and 20 age- and gender-matched controls. These authors reported that patients with Brugada syndrome had a longer p-wave duration and a higher p-wave voltage compared to controls. The authors also noted substantial heterogeneity of these measures among the patients with Brugada syndrome. A study published in 2012 assessed the association of abnormal p-wave duration and complications during the acute course of myocardial infarction in 89 patients. (21) Abnormal p-wave duration correlated with complications such as ventricular arrhythmias, heart failure, atrial fibrillation, and recurrent angina. However, it is uncertain whether knowledge of p-wave duration would meaningfully affect management of the patient and improve outcomes.
Conclusions. The association of abnormalities in signal-averaged ECG with a variety of cardiac and non-cardiac etiologies has been tested. These studies demonstrate that abnormalities in signal-averaged ECG are found more commonly in conditions such as arrhythmogenic right ventricular cardiomyopathy, Brugada syndrome, atrial fibrillation, and epilepsy. However, it is not certain how this information would be used in clinical care; therefore clinical utility has not been demonstrated for any of these conditions.
Clinical Input Received from Specialty Societies and Academic Medical Centers
In response to requests, input was received from no physician specialty society and 4 academic medical centers (5 reviews) while this policy was under review in 2009. While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. All but 1 of the reviewers providing input while this policy was under review for April 2009 supported the conclusions of this policy.
Summary
Signal-averaged ECG (SAECG) has some ability to risk-stratify patients at risk for ventricular arrhythmias. However, this predictive ability is modest, and this technique has not been used to stratify patients into clinically relevant categories of risk. Some RCTs have used signal-averaged ECG for selection of patients at high risk of ventricular arrhythmias, but these studies have not demonstrated outcome benefits for the treatments under study. SAECG has also been tested as a diagnostic test for a variety of cardiac-related disorders, but the evidence is insufficient to demonstrate clinical utility for any of the conditions tested. Therefore, signal-averaged ECG has not demonstrated improvements in health outcomes and remains investigational for all indications.
Practice Guidelines and Position Statements
The 2006 ACC, American Heart Association (AHA), and European Society of Cardiology (ESC) guidelines for management of patients with ventricular arrhythmias and prevention of sudden death list SAECG with a Class IIb recommendation (Class IIb noted as usefulness/efficacy is less well-established by evidence/opinion). (22) The report notes that SAECG may be useful to improve the diagnosis and risk stratification of patients with ventricular arrhythmias or of those at risk for life-threatening ventricular arrhythmias.
A 2008 consensus document from the AHA, ACC Foundation, and Heart Rhythm Society indicates the SAECG may identify patients with prior MI at risk for sudden cardiac death and that further studies are required to assess the utility of this test. (23)
In 1996, the American College of Cardiology (ACC) published an expert consensus document that concluded that SAECG had an established or valuable role in clinical care in the following situations (15):
- Stratification of risk of developing sustained ventricular arrhythmias in patients recovering from MI who are in sinus rhythm without electrocardiographic evidence of bundle branch block or intraventricular conduction delay
- Identification of patients with ischemic heart disease and unexplained syncope who are likely to have inducible sustained ventricular tachycardia
- Stratification of risk of developing sustained ventricular arrhythmia in patients with nonischemic cardiomyopathy
- Assessment of success of operation for sustained ventricular tachycardia]
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Signal-Averaged Electrocardiography
Signal Averaged Electrocardiography
Electrocardiography, Signal-Averaged
SAECG
References:
1. Signal-averaged electrocardiography. US Department of Health and Human Services, Health Technology Assessment. 1998; Number 11 (Publication No. PB98-137227).
2. Hohnloser SK, Zabel M. Identification of patients after myocardial infarction at risk of life-threatening arrhythmias. Eur Heart J 1999; 1(suppl C):C11-20.
3. Bailey JJ, Berson AS, Handelsman H et al. Utility of current risk stratification tests for predicting major arrhythmic events after myocardial infarction. J Am Coll Cardiol 2001; 38(7):1902-11.
4. Grimm W, Christ M, Bach J et al. Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study. Circulation 2003; 108(23):2883-91.
5. Huikuri HV, Tapanainen JM, Lindgren K et al. Prediction of sudden cardiac death after myocardial infarction in the beta-blocking era. J Am Coll Cardiol 2003; 42(4):652-8.
6. Bauer A, Guzik P, Barthel P et al. Reduced prognostic power of ventricular late potentials in post-infarction patients of the reperfusion era. Eur Heart J 2005; 26(8):755-61.
7. Touboul P. A decade of clinical trials; CAST to AVID. Eur Heart J 1999; 1(suppl C):C2-10.
8. Cairns JA, Connolly SJ, Roberts RRtooamiipwforvpdC et al. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Lancet 1997; 349(9053):675-82.
9. Julian DG, Camm AJ, Frangin GRtoeoaomipwl-vdarmiE et al. European Myocardial Infarct Amiodarone Trial Investigators. Lancet 1997; 349(9053):667-74.
10. Moss AJ, Hall WJ, Cannom DSIswaidipwcdahrfva et al. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996; 335(26):1933-40.
11. Gregoratos G, Abrams J, Epstein AE et al. ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). J Am Coll Cardiol 2002; 40(9):1703-19.
12. Bigger JT, Jr Puoicdipahrfvaac-abgs. Coronary Artery Bypass Graft (CABG) Patch Trial Investigators. N Engl J Med 1997; 337(22):1569-75.
13. Ueno A, Kobayashi Y, Yodogawa K et al. A prospective study on the risk-stratification for patients with non-sustained ventricular tachycardia using a novel algorithm. Circ J 2007; 71(7):1107-14.
14. Moss AJ, Zareba W, Hall WJ et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002; 346(12):877-83.
15. Cain MA, Arnsdorf MFACCecd, et al. Signal-averaged electrocardiography. J Am Coll Cardiol 1996; 27(1):238-49.
16. Kamath GS, Zareba W, Delaney J et al. Value of the signal-averaged electrocardiogram in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Heart Rhythm 2011; 8(2):256-62.
17. Rejdak K, Rubaj A, Glowniak A et al. Analysis of ventricular late potentials in signal-averaged ECG of people with epilepsy. Epilepsia 2011; 52(11):2118-24.
18. Schuller JL, Lowery CM, Zipse M et al. Diagnostic utility of signal-averaged electrocardiography for detection of cardiac sarcoidosis. Ann Noninvasive Electrocardiol 2011; 16(1):70-6.
19. Militaru C, Donoiu I, Ionescu DD. P Wave Signal-Averaged ECG in Normal Population and in Patients with Converted Atrial Fibrillation. Ann Noninvasive Electrocardiol 2011; 16(4):351-6.
20. Furukawa Y, Yamada T, Okuyama Y et al. Increased intraatrial conduction abnormality assessed by P-wave signal-averaged electrocardiogram in patients with Brugada syndrome. Pacing Clin Electrophysiol 2011; 34(9):1138-46.
21. Shturman A, Bickel A, Atar S. The predictive value of P-wave duration by signal-averaged electrocardiogram in acute ST elevation myocardial infarction. The Israel Medical Association journal : IMAJ 2012; 14(8):493-7.
22. Zipes DP, Camm AJ, Borggrefe M et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114(10):e385-484.
23. Goldberger JJ, Cain ME, Hohnloser SHAHAACoCFHRSSSoNRSTfIPaRfSCD et al. A scientific statement from the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention. J Am Coll Cardiol 2008; 52(14):1179-99.
24. Proclemer A, Lewalter T, Bongiorni MG, et al; conducted by the Scientific Initiative Committee, European Heart Rhythm Association. Screening and risk evaluation for sudden cardiac death in ischaemic and non-ischaemic cardiomyopathy: Results of the European Heart Rhythm Association survey. Europace. 2013;15(7):1059-1062.
25. UpToDate. Clinical applications of the signal-averaged electrocardiogram: Overview. Literature current through August 2016. Topic last updated September 7, 2016.
26. Bae MH, Kim JH, Jang SY, Park SH et al. Changes in follow-up ECG and signal-averaged ECG in patients with arrhythmogenic right ventricular cardiomyopathy. Pacing Clin Electrophysiol. 2014 Apr;37(4):430-8. Epub 2013 Oct 25.
27. Buzea CA, Dan GA, Dan AR, et al. Role of signal-averaged electrocardiography and ventricular late potentials in aptients with chronic obstructive pulmonary disease. Rom J Intern Med. 2015 Apr-Jun;53(2):133-9.
28. UpToDate. Use of the signal-averaged electrocardiogram in nonischemic heart disease and cardiac transplantation. Literature review current through July 2016. Topic last updated March 1, 2016.
29. UpToDate. Use of the signal-averaged electrocardiogram in ischemic heart disease. Literature review current through July 2016. Topic last updated January 12, 2016.
30. UpToDate. Use of the signal-averaged electrocardiogram in arrhythmia evaluation and management. Literature review current through July 2016. Topic last updated January 7, 2016.
31. Narayan MS, Cain ME. Clinical applications of the signal-averaged electrocardiogram: Overview. In: UpToDate, Goldberger AL, Downey BC (Eds), UpToDate, Waltham, MA. (Accessed on August 7, 2017.)
32. McKenna WJ. Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis. In: UpToDate, Calkins H, Downey BC (Eds), UpToDate, Waltham, MA. (Accessed on August 7, 2017.)
33. Narayan MS, Cain ME. Signal-averaged electrocardiogram: Overview of technical aspects and clinical applications. In: UpToDate, Goldberger AL, Downey BC (Eds), UpToDate, Waltham, MA. (Accessed on June 29, 2018.)
34. Narayan MS, Cain ME. Signal-averaged electrocardiogram: Overview of technical aspects and clinical applications. In: UpToDate, Goldberger AL, Downey BC (Eds), UpToDate, Waltham, MA. (Accessed on July 1, 2019.)
35. Narayan MS, Cain ME. Signal-averaged electrocardiogram: Overview of technical aspects and clinical applications. In: UpToDate, Goldberger AL, Downey BC (Eds), UpToDate, Waltham, MA. (Accessed on July 23, 2020.)
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