Signal-Averaged Electrocardiography (SAECG)

Number: 0664

Policy

Aetna considers signal-averaged electrocardiography experimental and investigational because no prospective clinical studies have demonstrated the utility of this testing in improving clinical outcomes.

Aetna considers remote algorithmic analysis of electrocardiographic-derived data (Premier Heart's Multifunction Cardiogram (MCG); also known as 3DMP Computerized EKG System) experimental and investigational because the clinical value of the system in managing persons suspected of having significant coronary artery disease has not been established.

See also CPB 0579 - T-Wave Alternans.

Background

Signal-Averaged Electrocardiography (SAECG)

Signal-averaged electrocardiography (SAECG) is a technique involving computerized analysis of segments of a standard electrocardiogram that allows the detection of ventricular late potentials.  Ventricular late potentials in patients with cardiac abnormalities, especially coronary artery disease or following an acute myocardial infarction (MI), have been associated with an increased risk of ventricular tachyarrhythmias and sudden cardiac death.  Proponents of SAECG claim that it can obviate the need for invasive techniques commonly used to identify high-risk patients for interventions that treat or prevent ventricular tachyarrhythmia and sudden death.

An Agency for Healthcare Policy and Research's assessment (AHCPR, 1998) found that the current data on SAECG show relatively consistent high negative-predictive values, poor positive-predictive values, and variable sensitivity and specificity when the technique is used on patients with cardiomyopathy or following a MI.   However, the high negative- predictive value of SAECG is largely due to the fact that the incidence of fatal arrhythmic events among post-MI patients is now below 10 %.  The incidence of fatal arrhythmias has declined among post-MI patients, a large percentage of whom are on anti-thrombotic therapy, most likely following the trend of decreased mortality rate following MI.

In 1996, an American College of Cardiology (ACC) consensus statement on SAECG concluded that SAECG has “established value” in assessing the risk of development of sustained ventricular arrhythmias in patients recovering from MI.  However, subsequently published guidelines from the ACC on management of acute MI (1999) stated that the usefulness of SAECG for risk assessment after MI is less well-established by evidence/opinion.  In addition, subsequently published ACC guidelines on implantable anti-arrhythmia devices (1998) do not recommend SAECG for selecting patients for automated implantable cardioverter defibrillators (AICDs).

Although it has been proposed that SAECG may be used to select post-MI patients for anti-arrhythmic drugs or AICD implantation, there are no prospective clinical studies demonstrating the clinical utility of SAECG in selecting patients for these therapies.  In addition, there are no prospective clinical studies proving that SAECG can be used successfully to select patients for electrophysiologic studies or Holter monitoring, or to use SAECG for risk stratification in lieu of these other tests.

Grimm et al (2003) studied arrhythmia risk stratification with regard to prophylactic implantable cardioverter-defibrillator patients with in idiopathic dilated cardiomyopathy (IDC).  These researchers concluded that reduced left ventricular ejection fraction (LVEF) and lack of beta-blocker use are important arrhythmia risk predictors in IDC, whereas SAECG, baroreflex sensitivity, heart rate variability, and T-wave alternans do not seem to be helpful for arrhythmia risk stratification.  Furthermore, in a review on electrocardiographic arrhythmia risk testing, Engel et al (2004) evaluated the various electrocardiographic (ECG) techniques that appear to have potential in assessment of risk for arrhythmia.  The resting ECG (premature ventricular contractions, QRS duration, damage scores, QT dispersion, and ST segment and T wave abnormalities), T-wave alternans, late potentials identified on SAECG, and heart rate variability were explored.  The authors stated that unequivocal evidence to support the widespread use of any single non-invasive technique is lacking; further research in this area is needed.

Guidelines from the European Society for Cardiology (Brignole, et al., 2004) concluded that the systematic use of SAECG in syncope is “not recommended.”

Tamaki and colleagues (2009) prospectively compared the predictive value of cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging for sudden cardiac death (SCD) with that of the SAECG, heart rate variability (HRV), and QT dispersion in patients with chronic heart failure (CHF).  At entry, cardiac MIBG imaging, SAECG, 24-hr Holter monitoring, and standard 12-lead ECG were performed in 106 consecutive stable CHF outpatients with a radionuclide LVEF less than 40 %.  The cardiac MIBG washout rate (WR) was obtained from MIBG imaging.  Furthermore, the time and frequency domain HRV parameters were calculated from 24-hr Holter recordings, and QT dispersion was measured from the 12-lead ECG.  During a follow-up period of 65 +/- 31 months, 18 of 106 patients died suddenly.  A multi-variate Cox analysis revealed that WR and LVEF were significantly and independently associated with SCD, whereas the SAECG, HRV parameters, or QT dispersion were not.  Patients with an abnormal WR (greater than 27 %) had a significantly higher risk of SCD (adjusted hazard ratio: 4.79, 95 % confidence interval: 1.55 to 14.76).  Even when confined to the patients with LVEF greater than 35 %, SCD was significantly more frequently observed in the patients with than without an abnormal WR (p = 0.02).  The authors concluded that cardiac MIBG WR, but not SAECG, HRV, or QT dispersion, is a powerful predictor of SCD in patients with mild-to-moderate CHF, independently of LVEF.

Park and colleagues (2009) examined the correlation between parameters of 2-dimensional ECG and SAECG in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC).  A total of 33 patients (13 females, 40.3 +/- 14.4 years old) were included in this study.  Both the right and left ventricular dimensions and systolic function were assessed with 2-dimensional ECG.  The SAECG was performed with high-gain amplification and filtered using bi-directional Butterworth filters between 40 and 250 Hz.  The right ventricular (RV) outflow tract was the most frequently (n = 18, 54 %) involved segment.  Six (18 %) patients had only mildly decreased RV systolic function.  All the other patients had normal RV systolic function.  Although localized left ventricular wall motion abnormalities were observed in 14 (42 %) patients, the LVEF was normal in most (n = 32, 97 %).  Late potentials were positive in 22 (63 %) patients.  There was no significant correlation between parameters of the SAECG and 2-dimensional ECG for the entire patient population.  The authors concluded that the SAECG parameters exhibited no correlation to any of 2-dimensional ECG parameters in the patients with ARVC.  Fragmented electrical activity may develop with no significant relation to the anatomical changes in the patients with ARVC.

The Agency for Healthcare Research and Quality's systematic review of ECG-based signal analysis technologies for evaluating patients with acute coronary syndrome (Coeytaux et al, 2012) concluded that “Existing research is largely insufficient to confidently inform the appropriate use of ECG-based signal analysis technologies in diagnosing coronary artery disease (CAD) and/or ACS.  Further research is needed to better describe the performance characteristics of these devices to determine in what circumstances, if any, these devices might precede, replace, or add to the standard ECG in test strategies to identify clinically significant CAD in the patient population of interest.  To fully assess the impact of these devices on diagnostic strategies for patients with chest pain, test performance needs to be linked to clinically important outcomes through modeling or longitudinal studies”.

Proclemer et al (2013) examined the current clinical practice of screening and risk evaluation for SCD in ischemic and non-ischemic cardiomyopathy with a focus on selection of candidates for ICD therapy, timing of ICD implantation, and use of non-invasive and invasive diagnostic tests across Europe.  A systematic screening program for SCD existed in 19 out of 31 centers (61.3 %).  Implantation of ICDs according to the inclusion criteria of MADIT-II and SCD-HeFT trials was reported in 30 and 29 % of centers, respectively, followed by MADIT-CRT (18 %), COMPANION (16 %), and combined MADIT and MUSTT (7 %) indications.  In patients with severe renal impairment, ICD implantation for primary prevention of SCD was always avoided in 8 centers (33.3%), was not used only if creatinine level was greater than 2.5 mg/dL in 10 centers (32.2 %), and in patients with permanent dialysis in 8 centers (33.3 %).  Signal-averaged electrocardiography and heart rate variability were never considered as risk stratification tools in 23 centers (74.2 %).  Implantation of a loop recorder was performed in patients with borderline indications for ICD therapy in 6 centers (19.4 %), for research purposes in 5 (16.1 %), and was never performed in 20 (64.5 %) centers.  The authors concluded that the majority of participating European centers have a screening program for SCD and the selection of candidates for ICD therapy was mainly based on the clinical risk stratification and not on non-invasive and invasive diagnostic tests or implantable loop recorder use.

Furthermore, an UpToDate review on “Clinical applications of the signal-averaged electrocardiogram: Overview” (Narayan and Cain, 2014) states that “Guideline Recommendations -- We agree with the 2008 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Rhythm Society (HRS) scientific statement on noninvasive risk stratification and the 2006 ACC/AHA/European Society of Cardiology (ESC) guidelines for management of patients with ventricular arrhythmias, which concluded that the SAECG may be useful to identify patients at low risk for SCD, but its routine use to identify patients at high risk for SCD is not yet adequately supported.  Similarly, the 2006 AHA/ACC scientific statement on syncope concluded that routine use of T-wave alternans combined with signal-averaged ECG and assessment of heart rate variability in patients with syncope and a negative initial evaluation is not yet established and currently is not indicated”.

An UpToDate review on “Use of the signal-averaged electrocardiogram in nonischemic heart disease and cardiac transplantation” (Narayan and Cain, 2015) concludes that:

  • Data are conflicting on the efficacy of SAECG in predicting clinical outcome or ventricular arrhythmias in patients with non-ischemic dilated cardiomyopathy.
  • There are insufficient data to recommend the use of the SAECG for risk stratification of patients with non-ischemic cardiomyopathy.
  • Although small studies have identified SAECG alterations in patients with cardiac transplant rejection, the utility of SAECG for detection of rejection has not been established.

Dinov and colleagues (2016) correlated SAECG with the endocardial scar characteristics in patients with ischemic ventricular tachycardia (VT).  These researchers suggested that successful catheter ablation (CA) can result in normalization of the SAECG.  A total of 50 patients (42 men; aged 67 ± 10 years, EF 34 ± 12 %) with ischemic VTs were prospectively enrolled; SAECG was performed before and after CA.  Patients with at least 2 abnormal criteria (filtered QRS greater than or equal to 114 ms; root mean square 40 less than 20 μV, and low-amplitude potentials 40 greater than 38 ms) were defined as having positive SAECG.  There was a linear correlation between endocardial scar area (less than 1.5 mV) and filtered QRS (r = 0.414; p = 0.003); CA resulted in normalization of the SAECG in 6 patients.  In patients with filtered QRS less than or equal to 120 ms, 13 (40.6 %) patients had normal SAECG after CA compared with 7 (21.9 %) before ablation (p = 0.034).  Patients with normal or normalized SAECG after CA had better VT-free survival compared with those whose SAECG remained abnormal.  Abnormal SAECG after CA was a predictor for VT recurrence: hazard ratio (HR) = 3.64; p = 0.039 for the overall population, and HR = 5.80; p = 0.022 for patients having QRS less than or equal to 120 ms.  The authors concluded that there was a significant correlation between the surface SAECG and endocardial scar size in patients with ischemic VTs.  A successful CA could result in normalization of SAECG that was associated with more favorable long-term outcomes.

The main drawbacks of this study were its small sample size (n = 50) and the relatively short follow-up (median of 12 months).  The authors stated that this study should be considered as a hypothesis-generating one. The presented results are valid for patients with ischemic heart disease and must be confirmed in other clinical conditions (e.g., dilated cardiomyopathy, and arrhythmogenic right ventricular dysplasia).  They noted that as long as the post-ablation SAECGs were recorded before the hospital discharge, it remained unclear if the VT recurrences during the follow-up were accompanied by perturbations in the SAECG.  The localization of the scar may influence the sensitivity of the method because the abnormal low-amplitude potentials less than 40 μV and root mean square voltage in the last 40 ms of the filtered QRS were less pronounced in patients with anterior or septal MIs.

Gatzoulis and colleagues (2018) noted that SAECG records delayed depolarization of myocardial areas with slow conduction that can form the substrate for monomorphic VT.  This technique has been examined mostly in patients with CAD, but its use has been declined over the years.  However, several lines of evidence, derived from clinical data in patients with healed MI, indicated that SAECG remains a valuable tool in risk stratification, especially when incorporated into algorithms encompassing invasive and non-invasive indices.  Such an approach can aid the more precise identification of candidates for device therapy, in the context of primary prevention of SCD.  These investigators examined the value of SAECG as a predictor of arrhythmic outcome in patients with ischemic heart disease and discussed potential future indications.  These researchers stated that given the relative paucity of data, clinical studies are needed, examining the prognostic value of SAECG in post‐MI patients treated with primary percutaneous coronary interventions (PCIs), even in the absence of significant LV dysfunction.  The authors stated that late potentials (LPs) in primary electrical disorders, such as Brugada syndrome, are intriguing, however, the underlying pathophysiology and clinical significance are still under investigation.

SAECG for Brugada Syndrome

Nagamoto and colleagues (2017) stated that ventricular fibrillation (VF) and atrial fibrillation (AF) are well-known arrhythmias in patients with Brugada syndrome.  These researchers  evaluated the characteristics of the atrial arrhythmogenic substrate using (SAECG in patients with Brugada syndrome.  SAECGs were performed during normal sinus rhythm in 23 normal volunteers (control group), 21 patients with paroxysmal AF (PAF group), and 21 with Brugada syndrome (Brugada group).  The filtered P wave duration (fPd) in the control, Brugada, and PAF groups was 113.9 ± 12.9 ms, 125.3 ± 15.0 ms, and 137.1 ± 16.3 ms, respectively.  The fPd in the PAF group was significantly longer compared to that in the control and Brugada groups (p < 0.05).  The fPd in the Brugada group was significantly longer than that in the control group (p < 0.05) and significantly shorter than that in the PAF group (p < 0.05).  The authors concluded that patients with Brugada syndrome had abnormal P waves on the SAECG.  The abnormal P waves on the SAECG in Brugada syndrome patients may have intermediate characteristics between control and PAF patients.

The authors stated that this study had 2 drawbacks.  First, although there is a well-known potential correlation with a susceptibility to AF in Brugada patients, the abnormal fPD on the SAECG was not correlated with the development of AF in this study as only 2 patients had a history of AF.  The patient number in the Brugada group was rather small with 21 patients, which might have affected these findings.  Moreover, this study was a retrospective analysis, thus, a prospective analysis is needed to evaluate the development of AF in Brugada patients with an abnormal fPD.  Second, a coved- or saddle back-type ST segment elevation was determined by the electrogram (ECG) at the time of the SAECG.  There was some temporal variability in the ECGs in Brugada syndrome patients.  Thus, this timing issue could explain the lack of a difference in the fPd between the patients in the Brugada group with the 2 types of ST segment elevation.

SAECG for Prediction of Recurrences after Catheter Ablation of Ventricular Arrhythmias in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Liao and colleagues (2017) noted that the changes of SAECG in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) undergoing radiofrequency catheter ablation (RFCA) of ventricular arrhythmias (VAs) remains unknown.  Between 2010 and 2014, a total of 81 ARVD/C patients underwent endocardial and/or epicardial RFCA for drug-refractory VAs; 70 patients (mean age of 46.2 ± 14.1 years, 37 men) achieving acute procedure success (negative inducibility) were enrolled.  Baseline characteristics, non-invasive examinations and SAECG (before and 3 months after RFCA) were collected retrospectively.  After successful RFCA, the electrical parameters of SAECG changed in 39 patients (55.7 %), including 28 patients (40 %) with electrical regression (group 1), and 11 patients (15.7 %) with electrical progression (group 3); 31 patients (44.3 %) showed no significant SAECG change (group 2).  During a mean follow-up of 17.8 ± 10.7months, 23 patients (32.9 %) had VA recurrences, including 4 in group 1, 12 in group 2, and 7 in group 3.  In comparisons with groups 2 and 3, group 1 patients had a significantly better VA recurrence-free survival (p = 0.02).  In multi-variable Cox regression analysis, electrical regression was found to be associated with fewer VA recurrences (p = 0.02, odds ratio [OR]: 0.28, 95 % CI: 0.10 to 0.83).  The authors concluded that electrical regression of SAECG after RFCA in ARVD/C was found to be associated with fewer VA recurrences.  This was a retrospective study with a relatively small sample size (n = 70).  Well-designed studies with larger sample size are needed to validate these findings.

Multifunction Cardiogram

The Premier Heart digital database-driven multi-phase (3DMP) electrocardiograph (EKG) System provides a computer analysis of digitalized 12-lead EKG waveforms in the frequency domain (power spectral estimate) to aid in the detection of significant coronary artery disease.  The 3DMP system was cleared by the Food and Drugs Administration (FDA) based on a 510(k) application.  Weiss et al (2002) reported on a cross-sectional analysis of the use of the 3DMP system in 136 patients with symptoms of potential coronary artery disease who were scheduled for angiography.  Originally, 200 patients were selected for the study, but 64 of the patients were not included in the study because of various technical problems in their 3DMP readings.

Although the 3DMP system was positive for CAD in 76 of 78 patients with greater than 60 % narrowing by angiography, the 3DMP system also read positive in 8 of 12 patients with 40 to 60 % narrowing.  None of the 10 patients with greater than 0 to 40 % narrowing read as positive by the 3DMP system, but 8 of 36 patients with 0 % narrowing read as positive for CAD.

As a significant number (2 of 78) of patients with significant angiographic lesions were missed by the 3DMP system, it is not clear that the device is sufficiently accurate to either be used in lieu of angiography or to select patients for angiography.

There are no evidence-based guidelines from national professional organizations that address the clinical utility of 3DMP in evaluating patients suspected of having coronary artery disease.  Prospective clinical studies are necessary to demonstrate the clinical utility of the 3DMP system in managing patients suspected of having significant coronary artery disease.

A technology assessment prepared for the AHCPR on ECG-based signal analysis technologies (Coeytaux et al, 2010) stated that the reliability and test performance of 3DMP in subjects at high-risk or with known CAD is promising.  The horizon scan identified 7 potentially relevant devices, including 3 that use body surface mapping and 1 that uses mathematical signal analysis.  Of the 7 devices, only the PRIME ECG by Heartscape Technologies (body surface mapping) and the 3DMP/MCG/ mfEMT by Premier Heart (mathematical signal analysis; referred to as the 3DMP) are cleared for marketing by the FDA and commercially available.  One body surface mapping device (Visual ECG/Cardio3KG by NewCardio) is commercially available but not cleared; the other devices are not commercially available.  The assessment concluded: "There is currently little available evidence that pertains to the utility of ECG-based signal analysis technologies as a diagnostic test among patients at low to intermediate risk of CAD who present in the outpatient setting with the chief complaint of chest pain.  The limited evidence that is available demonstrates proof of concept, particularly for the PRIME ECG and 3DMP devices.  Further research is needed to better characterize the performance characteristics of these devices to determine in what circumstances, if any, these devices might precede, replace, or add to the standard ECG for the diagnosis of CAD among patients who present with chest pain in the outpatient setting.  The randomized controlled trial (RCT) study design is best suited for evaluating the impact that ECG-based signal analysis technologies may have on clinical decision-making and patient outcomes, but there are indirect approaches that might be applied to answer these questions".

Kawaji and colleagues (2015) stated that multifunction cardiogram (MCG) is a computer-enhanced, resting electrocardiogram analysis developed to detect hemodynamically relevant CAD.  Based on data from previous studies suggesting excellent diagnostic accuracy in detecting CAD, MCG (approved by the FDA) received a Current Procedure Terminology (CPT) code in 2010 in United States.  However, there is no previous study validating MCG by using fractional flow reserve (FFR) as the reference standard.  Multifunction cardiogram Evaluation in Diagnosis of Functional coronary Ischemia sTudy (MED-FIT) was designed as a single-center, prospective study enrolling 100 stable patients with suspected CAD scheduled for coronary angiography.  The primary and secondary analyses evaluated the diagnostic performance of the MCG severity score to detect functional myocardial ischemia by FFR less than or equal to 0.80, and angiographically significant coronary stenosis (percent diameter stenosis greater than or equal to 50 %) by quantitative coronary angiography.  The current analysis set consisted of 91 patients in whom MCG data with adequate quality was obtained.  The prevalence of positive functional myocardial ischemia and angiographically significant stenosis in the current study was 42.7 % and 41.8 %, respectively.  Area under the receiver operating characteristics curve (AUC) of the MCG severity score for functional myocardial ischemia and angiographically significant stenosis was low (AUC 0.51, 95 % confidence interval [CI]: 0.38 to 0.63, and AUC 0.58, 95 % CI: 0.46 to 0.70, respectively).  Sensitivity, and specificity of the MCG severity score for functional myocardial ischemia and angiographically significant stenosis was also low (32 %/67 %, and 37 %/72 %) using a cut-off value of 4.0.  The authors concluded that diagnostic performance of the MCG severity score was poor for both functional myocardial ischemia, and angiographically significant stenosis.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":

CPT codes not covered for indications listed in the CPB:

0206T Computerized database analysis of multiple cycles of digitized cardiac electrical data from two or more ECG leads, including transmission to a remote center, application of multiple nonlinear mathematical transformations, with coronary artery obstruction severity assessment
93278 Signal-averaged electrocardiography (SAECG) with or without ECG

Other CPT codes related to the CPB:

93000 - 93010 Electrocardiogram, routine ECG with at least 12 leads; with interpretation and report, tracing only, without interpretation and report, or interpretation and report only

ICD-10 codes not covered for indications listed in the CPB :

I05.0 - I52 Chronic rheumatic heart disease, hypertensive disease, ischemic heart disease, diseases of pulmonary circulation, and other forms of heart disease

The above policy is based on the following references:

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