Pending Policies - Medicine


Endothelial Function (EF) Assessment

Number:MED202.067

Effective Date:08-15-2017

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

Endothelial function (EF) assessment is considered experimental, investigational and/or unproven as a method to evaluate coronary artery disease (CAD).

Description:

Coronary artery disease (CAD) is a form of atherosclerosis in which fatty plaque accumulates inside the coronary arteries and obstructs the supply of oxygenated blood to the heart. CAD typically develops slowly and asymptomatically over many years. (1) It is believed the damage or injury is to the coronary artery’s inner layer, endothelial cell layer. Once the artery has been injured, the accumulation of fatty deposits may increase the risk of CAD, along with the individual’s family history of heart disease. Some patients experience or develop symptoms, such as angina (chest pressure or tightness), shortness of breath, heart attack or myocardial infarction (MI), while others do not, known as asymptomatic. Some patients never experience overt CAD symptoms until they suffer a major cardiovascular event (MACE), such as a MI.

An ECRI 2012 review of CAD stated, “About 16.3 million U.S. adults (i.e., 20 years of age and older) are living with CAD and about 1.26 million cases of new (785,000) or recurrent (470,000) CAD are diagnosed annually. About 450,000 Americans die of CAD each year, of whom more than 80% are 65 years of age or older. The lifetime risk of developing CAD after 40 years of age is about 49% for men and 32% for women.” (1)

Background

Endothelial function (EF) assessment or testing (also known as peripheral arterial tonometry [PAT]) has been explored as a diagnostic aid to identify endothelial dysfunction and potential risk of CAD. Endothelial dysfunction has been measured by the percentage of flow-mediated dilation (FMD %) index with a proposed correlation to atherosclerotic outcomes. The FMD is obtained by using a device to slow the blood flow of a feeding artery in the finger (similar to a blood pressure cuff on the upper arm). When the pressure is released, the blood surge causes an endothelial-dependent FMD response. The results are given in percentages, showing the post-occlusion to pre-occlusion ratio that is calculated by the device’s computer software. EF testing is not designed as a screening method in the general population, but a supplement to the physician’s decision-making process, along with the patient’s history and other clinical findings. (2)

The Endo PAT 2000™ (representing endothelial-peripheral arterial tonometry) testing device, consists of a main control unit, finger probes and tubing and a software package. The Endo PAT 2000™ main control unit is connected to two independent, thimble-shaped, finger mountable probes via two air-conducting tubes. A standard computer is connected to the Endo PAT 2000™ main control unit for online display and archiving of device recordings and off-line analysis. The output of the Endo PAT 2000™ probe are pressure fluctuations sensed at its distal compartment induced by the volume changes of the pulsating digital arteries. (3) Thus, assessing the endothelial dysfunction, positive or negative and providing an EndoScore (the FMD %) within 15 minutes, administered in the physician office or hospital. Low scores indicate the need for medical attention, whereas a higher score may assist in making further medical assessment decisions by the physician. (3)

Regulatory Status

The Endo PAT 2000™ device developed by Itamar Medical, Ltd, Israel, as a non-invasive diagnostic test for coronary artery endothelial dysfunction. The U.S. Food and Drug Administration (FDA) cleared the Endo PAT 2000™ device on November 13, 2003 as a 510(k) that uses a reactive hyperemia (presence of blood flow to a body part or organ) procedure measuring the peripheral arterial tonometry or tone (PAT). This device is a next generation version of Itamar’s PAT 1000Rd™ (representing peripheral artery tonometer) FDA cleared on February 21, 2001. (2) FDA Product Code: DQK.

Rationale:

The medical policy was developed based on a MedLine search of peer-reviewed scientific literature completed through June 2016. The following is a summary of the key literature to date.

The U.S. Food and Drug Administration (FDA) clearance process reviewed the one clinical study supplied to the FDA from the manufacturers of the Endo PAT 2000™. The clinical study reported the safety and effectiveness of the Endo PAT 2000™ as an aiding tool in the diagnosis of coronary artery endothelial dysfunction. The device was evaluated against a gold standard for endothelial dysfunction evaluation, the Intracoronary Acetylcholine (Ach) Challenge method. The reference method is an intracoronary procedure, which incorporates measurements of endothelium-dependent and endothelium-independent coronary flow reserve, calculated as the percentage change in coronary blood flow (CBF) and coronary artery diameter in response to the Ach challenge. Study population included intent to treat patients, who had been referred to the cardiac catheterization laboratory for diagnostic angiography secondary to signs or symptoms of ischemic heart disease and suspected coronary endothelial dysfunction, but who showed no angiographic evidence of obstructive coronary artery disease (CAD), and who underwent Ach challenge test. Patients were then evaluated using the Endo PAT 2000™, which measures peripheral arterial tone changes at the fingertip, to a reactive hyperemia challenge. Study results demonstrated that the Endo PAT 2000™ is safe and effective for its intended use, as a statistical analysis of the study results showed acceptable sensitivity and specificity in a comparative study to a gold standard procedure, and no adverse events related to the device were reported. (3)

The majority of the literature regarding endothelial function (EF) assessment consisted of small, non-randomized controlled, case series. Approximately half of the five clinical studies reviewed were undertaken in Europe. (4-8) The number of patients enrolled in the studies varied from as few as 18 to 270, with three studies having less than 60. There was no consistency in the methods used for the clinical trials: peripheral arterial tonometry (PAT) comparison to varied levels of arm occlusion (4); documentation of adverse events tracked during a 7-year follow-up period after upper-arm occlusion (5); comparison of 3 different techniques revealing varied and individual outcomes: flow-mediated dilation (FMD), acetylcholine-mediated dilation, and PAT (6); assessment of EF using FMD and peripheral artery tone (7); and, evaluation of two peripheral vascular beds before and during PAT. (8)

A recent 2016 review from UpToDate concluded that endothelial dysfunction plays an important role in the pathogenesis and clinical course of atherosclerotic CAD, cardiac transplant vasculopathy, microvascular obstruction in ST-elevation myocardial infarction (STEMI), and microvascular angina. (9) EF testing, using direct or indirect methods is not a method of testing currently used in clinical practice. In 2015, Matsuzawa et al. concluded peripheral EF testing has the potential for identifying the 118 patients studied who were at high-risk for CAD. (10) In contrast, the 2015 U.K. study of 25 clinically healthy patients from Brolin et al. questioned the reliably of this testing to predict coronary plaque burden. (11)

Ongoing and Unpublished Clinical Trials

A search of ClinicalTrials.gov in June 2016 did not identify any ongoing or unpublished trials that would likely influence this review.

Professional Guidelines and Position Statements

There are no professional guidelines and position statements that would likely influence this review.

Summary of Evidence

The available evidence published in the peer-reviewed literature is inadequate to conclude that EF testing of endothelial dysfunction as a technique to assess risk of CAD in symptomatic or asymptomatic individuals. Therefore, the use of EF assessment or testing is considered experimental, investigational and/or unproven as a method to evaluate coronary artery disease (CAD).

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:

This procedure should not be reported with codes 93922 and 93923.

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

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

[Deleted 1/2019: 0337T]

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. ECRI Institute. Coronary Artery Disease. Plymouth Meeting (PA): ECRI Institute; 2012 August. 1 p. (Health Technology Forecast).

2. FDA – 510K Summary for Endo PAT 2000. U.S. Food and Drug Administration – Center for Devices and Radiologic Health (2003 November 12). Available at <http://www.fda.gov> (accessed on October 9 2013).

3. Endothelial function assessment (Endo PAT) Trachea button – Product information. Israel: Itamar Medical Ltd. Available at <http://www.itamar-medical.com> (accessed on October 9 2013).

4. Faizi AK, Kornmo DW, Agewell S. Evaluation of endothelial function using finger plethysmography. Clin Physiol Func Imaging. Sep 2009; 29(5):372-5. PMID 19552735

5. Rubinshtein R, Kuvin JT, Soffler M, et al. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Euro Heart J. May 2010; 31(9):1142-8. PMID 20181680

6. Lind, L. Relationships between three different tests to evaluate endothelium-dependent vasodilation and cardiovascular risk in a middle-aged sample. J Hypertens. Aug 2013; 31(8):1570-4. PMID 23625114

7. Onkelinx S, Cornelissen V, Goetschalckx K, et al. Reproducibility of different methods to measure the endothelial function. Vasc Med. Apr 2012; 17(2):79-84. PMID 22402933

8. Kuvin JT, Mammen A, Mooney P, et al. Assessment of peripheral vascular endothelial function in the ambulatory setting. Vasc Med. Feb 2007; 12(1):13-6. PMID 17451088

9. Widmer RJ, et al. Coronary artery endothelial dysfunction: clinical aspects. In: UpToDate, Kaski JC (Ed), UpToDate, Waltham, MA. Available at <http://www.uptodate.com> (accessed on June 29 2016).

10. Matsuzawa Y, Li J, Aoki T, et al. Predictive value of endothelial function by noninvasive peripheral arterial tonometry for coronary artery disease. Coron Artery Dis. May 2015; 26(3):231-8. PMID 25503420

11. Brolin EB, Agewall S, Brismar TB, et al. Neither endothelial function nor carotid artery intima-media thickness predicts coronary computed tomography angiography plaque burden in clinically healthy subjects: a cross-sectional study. BMC Cardiovasc Disord. Jul 7 2015; 15:63. PMID 26148508

Policy History:

Date Reason
8/15/2017 Reviewed. No changes.
9/1/2016 Document updated with literature review. Coverage unchanged.
11/1/2015 Reviewed. No changes.
1/1/2014 New medical document. Endothelial function (EF) assessment is considered experimental, investigational and/or unproven as a method to evaluate coronary artery disease (CAD).

Archived Document(s):

Title:Effective Date:End Date:
Endothelial Function (EF) Assessment01-01-202208-14-2022
Endothelial Function (EF) Assessment11-15-202012-31-2021
Endothelial Function (EF) Assessment04-01-201911-14-2020
Endothelial Function (EF) Assessment08-15-201703-31-2019
Endothelial Function (EF) Assessment09-01-201608-14-2017
Endothelial Function (EF) Assessment11-01-201508-31-2016
Endothelial Function (EF) Assessment01-01-201410-31-2015
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