Medical Policies - Medicine


Computerized 2-lead Resting Electrocardiogram Analysis for the Diagnosis of Coronary Artery Disease

Number:MED202.063

Effective Date:10-15-2017

Coverage:

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Computerized 2-lead resting electrocardiogram analysis (e.g., multifunction cardiogram) is considered experimental, investigational and/or unproven for diagnosing coronary artery disease.

Description:

Computerized 2-lead resting electrocardiogram (ECG) analysis (e.g., multifunction cardiogram) is a computerized analysis of a 2-lead resting electrocardiogram that has been proposed for use as a diagnostic test for coronary artery disease (CAD). This review assesses the evidence on accuracy and clinical utility of the multifunction cardiogram.

The standard 12-lead resting ECG has limited diagnostic accuracy in the detection of CAD. For this reason, the resting ECG has only a limited role in the diagnosis of chronic CAD. Stress testing, either at rest or with exercise, combined with single-photon emission computed tomography or echocardiographic imaging, is the most common initial test in the diagnostic work-up of chronic CAD. Sensitivities and specificities for stress testing vary but generally fall in the 75% to 90% range. Cardiac angiography is the criterion standard for diagnosing CAD and is used in situations in which CAD needs to be confirmed following stress testing.

The multifunction cardiogram is intended to improve on the performance of the standard ECG for diagnosing CAD. The study device records a 2-lead ECG tracing for 82 seconds, using leads II and V5 together with proprietary hardware and software. The analog ECG tracing is then amplified, digitized, down-sampled to a rate of 100 Hz, and encrypted for digital transmission. The digitized information is transmitted to a central server for further analysis. At the central server, the tracings undergo a series of mathematical transformations and signal averaging. There are 6 mathematical transformations included: power spectrum, coherence, phase angle shift, impulse response, cross-correlation, and transfer function. Following these transformations, the patterns found in the tracing are compared with a large reference database collected by the manufacturer. A severity score is generated, indicating the likelihood that CAD is present. The severity score ranges from 0 to 20, with a score of 4.0 suggested as the threshold for the presence of clinically significant CAD.

Regulatory Status

There is at least 1 commercially available multifunction cardiogram. In April 2003, the Premier Heart MCG™ system (Premier Heart, Port Washington, NY) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process. The FDA determined that this device was substantially equivalent to existing devices for use in ECG analysis.

Rationale:

This policy evidence review was created with a literature review in September 2011. It has been updated with literature searches of the MEDLINE database, with the last update covering the period through March 15, 2016.

Articles were retrieved that included primary data on the diagnostic accuracy, or clinical utility, of multifunction cardiogram for the diagnosis of coronary artery disease (CAD). The available evidence on the accuracy of multifunction cardiogram includes several cross-sectional studies that evaluate the performance characteristics of the test in patients with suspected CAD, using coronary angiography as the criterion standard.

Diagnostic Accuracy

Systematic Reviews

A systematic review and meta-analysis was published by Strobeck et al. (1) This combined analysis included 1076 patients from 44 diagnostic accuracy studies. Hemodynamically significant CAD was diagnosed in 43.4% (467/1076) of patients. The calculated sensitivity and specificity of the multifunction cardiograms were 91.2% and 84.6%, respectively. The positive predictive value (PPV) was 78% and the negative predictive value (NPV) was 94%. The area under the curve (AUC) by receiver operating characteristic (ROC) analysis was 88.1% (95% confidence interval [CI], 86% to 90.3%). Using a severity score of 4.0 as the cutoff for a positive test, the likelihood ratio positive was 5.9, and the likelihood ratio negative was 0.10. There were only minor differences between centers in the sensitivity and specificity; the statistical significance of these differences was not tested.

Diagnostic Accuracy Studies

Grube et al. published the largest study on the accuracy of the multifunction cardiogram for diagnosing CAD. (2) The study population consisted of 562 patients with no prior history of coronary revascularization who were scheduled to receive coronary angiography over a 1-year period at 1 institution in Germany. All patients underwent multifunction cardiogram and coronary angiography, with results of each modality interpreted independently and blinding of the results of the other test(s). A total of 139 (24.7% of total) patients were excluded from analysis; 17 because of poor-quality electrocardiogram (ECG) tracing and 122 because full risk-factor data were not available, leaving 423 patients in the final analysis. Obstructive coronary disease, defined as at least 1 stenosis greater than 70%, was diagnosed in 47.5% of patients (201/423). Multifunction cardiograms in this group had a reported sensitivity of 89.1% and a specificity of 81.1%; the PPV was 79% and the NPV was 90%. The calculated AUC by ROC analysis was 84.3% (95% CI, 80.2% to 88.4%).

Grube et al. published a companion article on 213 patients scheduled for angiography who had previously undergone revascularization. (3) The protocol and analysis for this study was identical to the earlier article, except for the presence or absence of prior revascularization. A total of 41 patients were excluded from analysis, leaving a final sample of 172 patients. In this sample, obstructive coronary disease, defined as at least 1 stenosis greater than 70%, was diagnosed in 32% (55/172) of patients. The estimated sensitivity and specificity were 90.9% and 88.0%, respectively. The PPV was 62.7% and the NPV was 97.8%.

Weiss et al. included 200 ambulatory patients who were scheduled to undergo coronary angiography at 1 institution in New York. (4) All patients underwent multifunction cardiogram; however, 64 (32% of total) patients had ECG tracings of insufficient quality and were excluded from analysis, leaving 136 patients in the final sample. The authors did not state whether the test results were interpreted in an independent and blinded manner. Obstructive coronary disease, defined as at least 1 stenosis greater than 70%, was diagnosed in 57.4% (78/136) of patients. The reported sensitivity and specificity of multifunction cardiogram were 93.3% and 83%, respectively. The PPV was 91.2%, and the NPV was 86.7%. The calculated AUC by ROC analysis was not reported.

Hosokawa et al. enrolled 222 patients who were scheduled to receive coronary angiography over an approximately 6-month period from 5 medical centers in Asia. (5) All patients underwent multifunction cardiogram and coronary angiography, with results of each modality interpreted independently and blinded to the results of the other test(s). A total of 33 (14.9% of total) patients were excluded from analysis, 3 because of poor-quality ECG tracing and 30 because coronary angiograms were not available for interpretation, leaving 189 patients in the final analysis. Obstructive coronary disease, defined as at least 1 stenosis greater than 60%, was diagnosed in 40.7% (77/189) of patients. The reported sensitivity and specificity of multifunction cardiogram were 94.8% and 86.6%, respectively. The PPV was 78.4% and the NPV was 97.1%. The calculated AUC by ROC analysis was 91.4% (95% CI, 86.8% to 96.1%).

The 4 studies described above were included in the systematic review by Strobeck et al. Three additional studies of the diagnostic accuracy of the multifunction cardiogram have been published since that time. In 2011, Strobeck et al. (6) compared its accuracy to single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using angiography as the criterion standard. This study enrolled 165 consecutive patients with known or suspected coronary disease and/or valvular heart disease who agreed to participate. Of the 165 patients, 49 did not undergo angiography due to a normal SPECT exam and no other indications for angiography; of these, 8% (4/49 patients) had an abnormal computerized 2-lead electrocardiogram. These patients were excluded from further analysis, leaving 116 patients in the study who received all 3 tests (computerized 2-lead resting ECG, SPECT MPI, angiography). The sensitivity and specificity of the computerized 2-lead resting ECG were 91% (95% CI, 0.79 to 0.97) and 87% (95% CI, 0.76 to 0.94), respectively, compared with a sensitivity of 85% (95% CI, 0.72 to 0.93) and a specificity of 14% (95% CI, 0.07 to 0.25) for SPECT MPI. Subgroup analyses revealed similar accuracy by gender, severity of coronary obstruction, and age. The specificity for SPECT MPI in this study was markedly lower than that reported previously. In a recent meta-analysis of 13 studies (total N=1323 subjects), the pooled estimate for specificity of SPECT was 0.77 (95% CI, 0.64 to 0.86), and the pooled sensitivity was 0.83 (95% CI, 0.81 to 0.91). (7) The reduced specificity reported in the Strobeck study may have been related to the performance of angiography in patients with valvular disease, because these patients may have had higher rates of false-positive SPECT exams than patients with suspected ischemia.

Two smaller studies of diagnostic accuracy were published in 2014 and 2015. (8, 9) They enrolled 100 and 112 patients, respectively, who were scheduled to undergo coronary angiography. In both, individuals interpreting the computerized 2-lead resting ECG were independent and blinded to the results of angiography. In 1 study, the reported specificity of computerized 2-lead resting ECG was high (90.4%; 95% CI, 87.0% to 93.9%), and the sensitivity was lower (48.1%; 95% CI, 38.5% to 57.8%), with an NPV of 82.5% (95% CI, 78.3% to 86.7%). In the other study, the reported specificity (67%) and sensitivity (32%) for functional ischemia were lower, with an NPV of 57%.

Clinical Utility

There were no published articles that directly addressed the clinical utility of a computerized 2-lead resting electrocardiogram. The impact of this technology on patient management decisions is uncertain. While it is possible that the results of this test may influence patient management (e.g., decisions to perform angiography), the evidence on this question is incomplete. As a result, clinical utility has not been demonstrated and the impact on health outcomes is unknown.

Ongoing and Unpublished Clinical Trials

A search of ClinicalTrials.gov did not identify any ongoing or unpublished trials that would likely influence this review.

Practice Guidelines and Position Statements

No guidelines or statements were identified.

Summary of Evidence

For individuals who are being screened for coronary artery disease (CAD) with computerized 2-lead electrocardiography, the evidence includes several diagnostic accuracy studies. Relevant outcomes include test accuracy, test validity, and morbid events. Most published studies have reported high specificities in the range of 90% or greater, although 1 study reported a lower specificity (67%). Reported sensitivities are somewhat lower, ranging from 48% to 88.9%. However, these studies have several methodologic limitations that reduce their internal validity. In all but one, the population is a convenience sample of patients who underwent angiography. These patient populations are thus subject to a referral or “work-up” bias in that the population of patients that might be considered for the multifunction cardiogram in clinical practice are not the same population being referred for angiography. Also, the number of patients enrolled but not included in the analysis was relatively high, ranging from 14.9% to 32% of the total number of enrollees. These high rates of exclusion raise the potential for biased estimates of test sensitivity and specificity. Finally, in one of the cohorts, angiogram and multifunction cardiogram results were not interpreted in an independent and blinded manner. These methodologic limitations create a substantial degree of uncertainty regarding the reported results for diagnostic accuracy. The clinical utility of the multifunction cardiogram is uncertain. Even if this test has good accuracy for diagnosing CAD, its application in clinical practice would still need to be determined. Use of the multifunction cardiogram to screen for CAD would depart from usual practice, because screening for CAD has not been shown to improve outcomes. In the nonacute setting, the most common method for diagnosing CAD is stress testing. There is no evidence comparing the accuracy of multifunction cardiogram with stress testing. The evidence is insufficient to determine the effects of the technology on health outcomes.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

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CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

0206T

HCPCS Codes

None

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. Strobeck JE, Shen JT, Singh B, et al. Comparison of a two-lead, computerized, resting ECG signal analysis device, the MultiFunction-CardioGram or MCG (a.k.a. 3DMP), to quantitative coronary angiography for the detection of relevant coronary artery stenosis (>70%) - a meta-analysis of all published trials performed and analyzed in the US. Int J Med Sci. 2009; 6(4):143-155. PMID 19381351

2. Grube E, Bootsveld A, Yuecel S, et al. Computerized two-lead resting ECG analysis for the detection of coronary artery stenosis. Int J Med Sci. 2007; 4(5):249-263. PMID 18026565

3. Grube E, Bootsveld A, Buellesfeld L, et al. Computerized two-lead resting ECG analysis for the detection of coronary artery stenosis after coronary revascularization. Int J Med Sci. 2008; 5(2):50-61. PMID 18345283

4. Weiss MB, Narasimhadevara SM, Feng GQ, et al. Computer-enhanced frequency-domain and 12-lead electrocardiography accurately detect abnormalities consistent with obstructive and nonobstructive coronary artery disease. Heart Dis. Jan-Feb 2002; 4(1):2-12. PMID 11975826

5. Hosokawa J, Shen JT, Imhoff M. Computerized 2-lead resting ECG analysis for the detection of relevant coronary artery stenosis in comparison with angiographic findings. Congest Heart Fail. Sep-Oct 2008; 14(5):251-260. PMID 18983288

6. Strobeck JE, Mangieri A, Rainford N. A paired-comparision of the Multifunction Cardiogram (MCG) and sestamibi SPECT myocardial perfusion imaging (MPI) to quantitative coronary angiography for the detection of relevant coronary artery obstruction (>/=70%) - a single-center study of 116 consecutive patients referred for coronary angiography. Int J Med Sci. 2011; 8(8):717-724. PMID 22135619

7. de Jong MC, Genders TS, van Geuns RJ, et al. Diagnostic performance of stress myocardial perfusion imaging for coronary artery disease: a systematic review and meta-analysis. Eur Radiol. Sep 2012; 22(9):1881-1895. PMID 22527375

8. Amano T, Shinoda N, Kunimura A, et al. Non-invasive assessment of functionally significant coronary stenoses through mathematical analysis of spectral ECG components. Open Heart. 2014; 1(1):e000144. PMID 25469309

9. Kawaji T, Shiomi H, Morimoto T, et al. Noninvasive detection of functional myocardial ischemia: Multifunction Cardiogram Evaluation in Diagnosis of Functional Coronary Ischemia Study (MED-FIT). Ann Noninvasive Electrocardiol. Sep 2015; 20(5):446-453. PMID 25594689

10. Computerized 2-lead Resting Electrocardiogram Analysisfor the Diagnosis of Coronary Artery Disease. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2016 May) Medicine 2.02.25.

Policy History:

Date Reason
10/15/2017 Reviewed. No changes.
11/1/2016 Document updated with literature review. Coverage unchanged.
3/15/2015 Reviewed. No changes.
4/15/2014 Document updated with literature review. Coverage unchanged.
8/1/2013 Document updated with literature review. Coverage unchanged.
9/1/2011 New medical document. Computerized 2-lead resting electrocardiogram analysis (e.g., multifunction cardiogram) is considered experimental, investigational and unproven for diagnosing coronary artery disease.

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