Latest Review Date: October 2023

Category: Laboratory

POLICY:

The use of the Presage® ST2 Assay is considered investigational for all indications, including but not limited to the following:

• to evaluate the prognosis of individuals diagnosed with chronic heart failure;
• to guide management (e.g. pharmacological, device-based, exercise) of individuals diagnosed with chronic heart failure;
• in the post cardiac transplantation period, including but not limited to predicting prognosis and predicting acute cellular rejection

The measurement of volatile organic compounds to assist in the detection of moderate grade 2R (formerly grade 3) heart transplant rejection is considered investigational.

DESCRIPTION OF PROCEDURE OR SERVICE:

Clinical assessment and noninvasive imaging of chronic heart failure can be limited in accurately diagnosing patients with heart failure because symptoms and signs can poorly correlate with objective methods of assessing cardiac dysfunction. For management of heart failure, clinical signs and symptoms (e.g., shortness of breath) are relatively crude markers of decompensation and occur late in the course of an exacerbation. Thus, circulating biomarkers have potential benefit in heart failure diagnosis and management.

In transplant recipients, despite the progress in immunosuppressant therapy, the risk of rejection remains. Diagnosis of allograft rejection continues to rely on clinical monitoring and histologic confirmation by tissue biopsy. However, due to limitations of tissue biopsy, including a high degree of interobserver variability in the grading of results and its potential complications, less invasive alternatives have been investigated. Several laboratory-tested biomarkers of transplant rejection have been evaluated and are commercially available for use. The laboratory tests for heart transplant rejection currently evaluated in this policy include the following: Presage® ST2 Assay kit, which measures the soluble suppression of tumorigenicity-2 (sST2) protein biomarker; Heartsbreath test, which measures breath markers of oxidative stress.

Heart Failure

Heart failure is a major cause of morbidity and mortality worldwide. The term heart failure refers to a complex clinical syndrome that impairs the heart's ability to move blood through the circulatory system. The prevalence of heart failure in the U.S. between 2013 and 2016 was an estimated 6.2 million for Americans ≥20 years old, up from 5.7 million between 2009 and 2012. Heart failure is the leading cause of hospitalization among people older than age 65 years, with direct and indirect costs estimated at $37 billion annually in the U.S. Although survival has improved with treatment advances, absolute mortality rates of heart failure remain near 50% within 5 years of diagnosis.

Physiology

Heart failure can be caused by disorders of the pericardium, myocardium, endocardium, heart valves or great vessels, or metabolic abnormalities. Individuals with heart failure may present with a wide range of left ventricular (LV) anatomy and function. Some have normal LV size and preserved ejection fraction; others have severe LV dilatation and depressed ejection fraction. However, most patients present with key signs and symptoms secondary to congestion in the lungs from impaired LV myocardial function. They include dyspnea, orthopnea, and paroxysmal dyspnea. Other symptoms include weight gain due to fluid retention, fatigue, weakness, and exercise intolerance secondary to diminished cardiac output.

Diagnosis

Initial evaluation of a patient with suspected heart failure is typically based on clinical history, physical examination, and chest radiograph. Because people with heart failure may present with nonspecific signs and symptoms (e.g., dyspnea), accurate diagnosis can be challenging. Therefore, noninvasive imaging procedures (e.g., echocardiography, radionuclide angiography) are used to quantify pump function of the heart, thus identifying or excluding heart failure in patients with characteristic signs and symptoms. These tests can also be used to assess prognosis by determining the severity of the underlying cardiac dysfunction. However, clinical assessment and noninvasive imaging can be limited in accurately evaluating patients with heart failure because symptoms and signs can poorly correlate with objective methods of assessing cardiac dysfunction. Thus, invasive procedures (e.g., cardiac angiography, catheterization) are used in select patients with presumed heart failure symptoms to determine the etiology (i.e., ischemic vs. nonischemic) and physiologic characteristics of the condition.

Treatment

Patients with heart failure may be treated using a number of interventions. Lifestyle factors such as the restriction of salt and fluid intake, monitoring for increased weight, and structured exercise programs are beneficial components of self-management. A variety of medications are available to treat heart failure. They include diuretics (e.g., furosemide, hydrochlorothiazide, spironolactone), angiotensin-converting enzyme inhibitors (e.g., captopril, enalapril, lisinopril), angiotensin receptor blockers (e.g., losartan, valsartan, candesartan), b-blockers (e.g., carvedilol, metoprolol succinate), and vasodilators (e.g., hydralazine, isosorbide dinitrate). Numerous device-based therapies are also available. Implantable cardioverter defibrillators reduce mortality in patients with an increased risk of sudden cardiac death. Cardiac resynchronization therapy improves symptoms and reduces mortality for patients who have disordered LV conduction evidenced by a wide QRS complex on electrocardiogram. Ventricular assist devices are indicated for patients with end-stage heart failure who have failed all other therapies and are also used as a bridge to cardiac transplantation in select patients.

Heart Failure Biomarkers

Because of limitations inherent in standard clinical assessments of patients with heart failure, a number of objective disease biomarkers have been investigated to diagnose and assess heart failure patient prognosis, with the additional goal of using biomarkers to guide therapy. They include a number of proteins, peptides, or other small molecules whose production and release into circulation reflect the activation of remodeling and neurohormonal pathways that lead to LV impairment. Examples include B-type natriuretic peptide (BNP), its analogue N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin T and I, renin, angiotensin, arginine vasopressin, C-reactive protein, and norepinephrine.

BNP and NT-proBNP are considered the reference standards for biomarkers in assessing heart failure patients. They have had a substantial impact on the standard of care for diagnosis of heart failure and are included in the recommendations of all major medical societies, including the American College of Cardiology Foundation and American Heart Association, European Society of Cardiology, and the Heart Failure Society of America. Although natriuretic peptide levels are not 100% specific for the clinical diagnosis of heart failure, elevated BNP or NT-proBNP levels in the presence of clinical signs and symptoms reliably identify the presence of structural heart disease due to remodeling and heightened risk for adverse events. Natriuretic peptides also can help in determining the prognosis of heart failure patients, with elevated blood levels portending a poorer prognosis.

In addition to diagnosing and assessing the prognosis of heart failure patients, blood levels of BNP or NT-proBNP have been proposed as an aid for managing patients diagnosed with chronic heart failure. Levels of either biomarker rise in response to myocardial damage and LV remodeling, whereas they tend to fall as drug therapy ameliorates symptoms of heart failure. Evidence from a large number of randomized controlled trials (RCTs) that have compared BNP- or NT-proBNP-guided therapy with clinically guided adjustment of pharmacologic treatment of patients who had chronic heart failure has been assessed in recent systematic reviews and meta-analyses. However, these analyses have not consistently reported a benefit for BNP-guided management. Savarese et al (2013) published the largest meta-analysis to date–a patient-level meta-analysis that evaluated 2686 patients from 12 RCTs. This meta-analysis showed that NT-proBNP-guided management was associated with significant reductions in all-cause mortality and heart failure-related hospitalization compared with clinically guided treatment. Although BNP-guided management in this meta-analysis was not associated with significant reductions in these parameters, differences in patient numbers and characteristics may explain the discrepancy. Troughton et al (2014) conducted a second patient-level meta-analysis that included 11 RCTs with 2000 patients randomized to natriuretic peptide-guided pharmacologic therapy or usual care. The results showed that, among patients 75 years of age or younger with chronic heart failure, most of whom had impaired left ventricular ejection fraction, natriuretic peptide-guided therapy was associated with significant reductions in all-cause mortality compared with clinically guided therapy. Natriuretic-guided therapy also was associated with significant reductions in hospitalization due to heart failure or cardiovascular disease.

Suppression of Tumorigenicity-2 Protein Biomarker

A protein biomarker, ST2, has elicited interest as a potential aid to predict prognosis and manage therapy of heart failure. This protein is a member of the interleukin-1 (IL-1) receptor family. It is found as a transmembrane isoform (ST2L) and a soluble isoform (sST2), both of which have circulating IL-33 as their primary ligand. ST2 is a unique biomarker that has pluripotent effects in vivo. Thus, binding between IL-33 and ST2L is believed to have an immunomodulatory function via T-helper Type II lymphocytes and was initially described in the context of cell proliferation, inflammatory states, and autoimmune diseases. However, the IL-33/ST2L signaling cascade also is strongly induced through mechanical strain of cardiac fibroblasts or cardiomyocytes. The net result is mitigation of adverse cardiac remodeling and myocardial fibrosis, which are key processes in the development of heart failure. The soluble isoform of ST2 is produced by lung epithelial cells and cardiomyocytes and is secreted into the circulation in response to exogenous stimuli, mechanical stress, and cellular stretch. This form of ST2 binds to circulating IL-33, acting as a “decoy,” thus inhibiting the IL-33 associated antiremodeling effects of the IL-33/ST2L signaling pathway. Thus, on a biologic level, IL-33/ST2L signaling plays a role in modulating the balance of inflammation and neurohormonal activation and is viewed as pivotal for protection from myocardial remodeling, whereas sST2 is viewed as attenuating this protection. In the clinic, blood concentrations of sST2 appear to correlate closely with adverse cardiac structure and functional changes consistent with remodeling in patients with heart failure, including abnormalities in filling pressures, chamber size, systolic and diastolic function.

An enzyme-linked immunosorbent ‒based assay is commercially available for determining sST2 blood levels (Presage® ST2 Assay). The manufacturer claims a limit of detection of 1.8 ng/mL for sST2, and a limit of quantification of 2.4 ng/mL, as determined according to Clinical and Laboratory Standards Institute guideline EP-17-A. Mueller and Dieplinger (2013) reported a limit of detection of 2.0 ng/mL for sST2 in their study. In the same study, the assay had a within-run coefficient of variation of 2.5% and a total coefficient of variation less than 4.0%, demonstrated linearity within the dynamic range of the assay calibration curve, and, exhibited no relevant interference or cross-reactivity.

The ST2 biomarker is not intended to diagnose heart failure, because it is a relatively nonspecific marker that is increased in many other disparate conditions that may be associated with acute or chronic manifestations of heart failure. Although the natriuretic peptides (BNP, NT-proBNP) reflect different physiologic aspects of heart failure compared with sST2, they are considered the reference standard biomarkers when used with clinical findings to diagnose, prognosticate, and manage HF and as such are the comparator to sST2.

Heart Transplant Rejection

Most cardiac transplant recipients experience at least a single episode of rejection in the first year after transplantation. The International Society for Heart and Lung Transplantation (2005) modified its grading scheme for categorizing cardiac allograft rejection. The revised (R) categories are listed in Table 1.

Table 1. Revised Grading Schema for Cardiac Allograft Rejection.

Acute cellular rejection is most likely to occur in the first 6 months after transplantation, with a significant decline in the incidence of rejection after this time. Although immunosuppressants are required on a life-long basis, dosing is adjusted based on graft function and the grade of acute cellular rejection determined by histopathology. Endomyocardial biopsies are typically taken from the right ventricle via the jugular vein periodically during the first 6 to 12 months post transplant. The interval between biopsies varies among clinical centers. A typical schedule is weekly for the first month, once or twice monthly for the following 6 months, and several times (monthly to quarterly) between 6 months and 1-year post transplant. Surveillance biopsies may also be performed after the first postoperative year (eg, on a quarterly or semiannual basis). This practice, although common, has not been demonstrated to improve transplant outcomes. Some centers no longer routinely perform endomyocardial biopsies after 1 year in patients who are clinically stable.

While the endomyocardial biopsy is the criterion standard for assessing heart transplant rejection, it is limited by a high degree of interobserver variability in the grading of results and potential morbidity that can occur with the biopsy procedure. Also, the severity of rejection may not always coincide with the grading of the rejection by biopsy. Finally, a biopsy cannot be used to identify patients at risk of rejection, limiting the ability to initiate therapy to interrupt the development of rejection. For these reasons, an endomyocardial biopsy is considered a flawed criterion standard by many. Therefore, noninvasive methods of detecting cellular rejection have been explored. It is hoped that noninvasive tests will assist in determining appropriate patient management and avoid overuse or underuse of treatment with steroids and other immunosuppressants that can occur with false-negative and false-positive biopsy reports. Two techniques are commercially available for the detection of heart transplant rejection.

Noninvasive Heart Transplant Rejection Testing

Presage ST2 Assay

In addition to its use as a potential aid to predict prognosis and manage therapy of heart failure, elevated serum ST2 levels have also been associated with increased risk of antibody-mediated rejection following heart transplant. For this reason, ST2 has also been proposed as a prognostic marker post heart transplantation and as a test to predict acute cellular rejection (graft-versus-host disease). The Presage ST2 Assay, described above, is a commercially available sST2 test that has been investigated as a biomarker of heart transplant rejection.

Heartsbreath Test

The Heartsbreath™ test, a noninvasive test that measures breath markers of oxidative stress, has been developed to assist in the detection of heart transplant rejection. In heart transplant recipients, oxidative stress appears to accompany allograft rejection, which degrades membrane polyunsaturated fatty acids and evolving alkanes and methylalkanes that are in turn, excreted as volatile organic compounds in breath. The Heartsbreath test analyzes the breath methylated alkane contour, which is derived from the abundance of C4 to C20 alkanes and monomethylalkanes and has been identified as a marker to detect grade 3 (clinically significant) heart transplant rejection.

KEY POINTS:

The most recent literature update was performed through August 21, 2023.

Summary of Evidence

For individuals who have chronic heart failure who receive the sST2 assay to determine prognosis and/or to guide management, the evidence includes correlational studies and two meta-analyses. Relevant outcomes are OS, quality of life, and hospitalization. Most of the evidence is from reanalysis of existing RCTs and not from studies specifically designed to evaluate the predictive accuracy of sST2, and prospective and retrospective cross-sectional studies made up a large part of one meta-analysis. Studies have mainly found that elevated sST2 levels were statistically associated with elevated risk of mortality. A pooled analysis of study results found that sST2 significantly predicted overall mortality and cardiovascular mortality. Several studies, however, found that sST2 test results did not provide additional prognostic information compared with or N-terminal pro B-type natriuretic peptide levels. Moreover, no comparative studies were identified on the use of the sST2 assay to guide management of patients diagnosed with chronic heart failure. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have heart transplantation who receive sST2 assay to determine prognosis and predict acute cellular rejection, the evidence includes a small number of retrospective studies on the Presage ST2 Assay. Relevant outcomes are OS, morbid events, and hospitalization. No prospective studies were identified that provide high-quality evidence on the ability of sST2 to predict transplant outcomes. One retrospective study (n=241) found that sST2 levels were associated with acute cellular rejection and mortality; another study (n=26) found that sST2 levels were higher during an acute rejection episode than before rejection. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have a heart transplant who receive a measurement of volatile organic compounds to assess cardiac allograft rejection, the evidence includes a diagnostic accuracy study. Relevant outcomes are OS, test validity, morbid events, and hospitalizations. The published study found that, for identifying grade 3 (now grade 2R) rejection, the NPV of the breath test the study evaluated (97.2%) was similar to endomyocardial biopsy (96.7%) and the sensitivity of the breath test (78.6%) was better than that for biopsy (42.4%). However, the breath test had a lower specificity (62.4%) and a lower PPV (5.6%) in assessing grade 3 rejection than a biopsy (specificity, 97%; PPV, 45.2%). The breath test was also not evaluated for grade 4 rejection. This single study is not sufficient to determine the clinical validity of the test measuring volatile organic compounds and no studies on clinical utility were identified. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Positions Statements

American College of Cardiology et al

In 2022, the American College of Cardiology, American Heart Association, and Heart Failure Society issued updated a guideline for the management of heart failure. The 2022 guideline replaced a 2013 guideline and a 2017 focused guideline update. The guideline states measurement of natriuretic peptide levels may be useful for diagnosis, risk stratification, and prognosis of heart failure. The use of soluble suppression of tumorigenicity-2 is not discussed specifically, though the guideline notes that "a widening array of biomarkers including markers of myocardial injury, inflammation, oxidative stress, vascular dysfunction, and matrix remodeling have been shown to provide incremental prognostic information over natriuretic peptides but remain without evidence of an incremental management benefit."

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Heart Failure, Heart transplant, HF, Presage® ST2 Assay, ST2 (suppression of tumorigenicity), soluble suppression of tumorigenicity-2 (sST2), Heartsbreath test

APPROVED BY GOVERNING BODIES:

The U.S. Food and Drug Administration (FDA) has cleared multiple biomarker tests for the detection of heart and renal allograft rejection. Table 2 provides a summary of the biomarker tests currently included in this policy that have FDA clearance.

Table 2. Select Biomarkers for Detection of Heart or Renal Allograft Rejection Cleared by the U.S. Food and Drug Administration

FDA: Food and Drug Administration

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan. 

CURRENT CODING:

CPT Codes:

PREVIOUS CODING:

CPT Codes:

REFERENCES:

1. Aimo A, Vergaro G, Passino C, et al. Prognostic value of soluble suppression of tumorigenicity-2 in chronic heart failure: a meta-analysis. JACC Heart Fail. Apr 2017; 5(4):280-286.
2. Anand IS, Rector TS, Kuskowski M, et al. Prognostic value of soluble ST2 in the Valsartan Heart Failure Trial. Circ Heart Fail. May 2014; 7(3):418-426.
3. Bayes-Genis A, de Antonio M, Galan A, et al. Combined use of high-sensitivity ST2 and NTproBNP to improve the prediction of death in heart failure. Eur J Heart Fail. Jan 2012; 14(1):32-38.
4. Bhardwaj A, Januzzi JL, Jr. ST2: a novel biomarker for heart failure. Expert Rev Mol Diagn. May 2010; 10(4):459-464.
5. Broch K, Ueland T, Nymo SH, et al. Soluble ST2 is associated with adverse outcome in patients with heart failure of ischemic etiology. Eur J Heart Fail. Mar 2012; 14(3):268-277.
6. Chowdhury P, Kehl D, Choudhary R, et al. The use of biomarkers in the patient with heart failure. Curr Cardiol Rep. Jun 2013; 15(6):372.
7. Ciccone MM, Cortese F, Gesualdo M, et al. A novel cardiac bio-marker: ST2: a review. Molecules. 2013; 18(12):15314-15328.
8. Cohn JN, Tognoni G, Valsartan Heart Failure Trial I. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. Dec 2001; 345(23):1667-1675.
9. Daniels LB, Bayes-Genis A. Using ST2 in cardiovascular patients: a review. Future Cardiol. Jul 2014; 10(4):525-539.
10. Dieplinger B, Mueller T. Soluble ST2 in heart failure. Clin Chim Acta. Sep 2014.
11. Dupuy AM, Curinier C, Kuster N, et al. Multi-marker strategy in heart failure: combination of st2 and crp predicts poor outcome. PLoS One. 2016; 11(6):e0157159.
12. Felker GM, Fiuzat M, Thompson V, et al. Soluble ST2 in ambulatory patients with heart failure: Association with functional capacity and long-term outcomes. Circ Heart Fail. Nov 2013; 6(6):1172-1179.
13. Gaggin HK, Januzzi JL, Jr. Biomarkers and diagnostics in heart failure. Biochim Biophys Acta. Dec 2013; 1832(12):2442-2450.
14. Gaggin HK, Motiwala S, Bhardwaj A, et al. Soluble concentrations of the interleukin receptor family member ST2 and beta-blocker therapy in chronic heart failure. Circ Heart Fail. Nov 2013; 6(6):1206-1213.
15. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. May 03 2022; 145(18): e895-e1032.
16. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
17. Januzzi JL, Horne BD, Moore SA, et al. Interleukin receptor family member ST2 concentrations in patients following heart transplantation. Biomarkers. May 2013; 18(3):250-256.
18. Januzzi JL, Jr., Rehman SU, Mohammed AA, et al. Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction. J Am Coll Cardiol. Oct 2011; 58(18):1881-1889.
19. Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. Nov 2007; 357(22):2248-2261.
20. Ky B, French B, McCloskey K, et al. High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure. Circ Heart Fail. Mar 2011; 4(2):180-187.
21. Lindenfeld J, Albert NM, Boehmer JP, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail. Jun2010; 16(6): e1-194.
22. Marcus GM, Gerber IL, McKeown BH, et al. Association between phonocardiographic third and fourth heart sounds and objective measures of left ventricular function. JAMA. May 2005; 293(18):2238-2244.
23. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. Aug 2012; 14(8):803-869.
24. Mueller T, Dieplinger B. The Presage ((R)) ST2 Assay: analytical considerations and clinical applications for a high-sensitivity assay for measurement of soluble ST2. Expert Rev Mol Diagn. Jan 2013; 13(1):13-30.
25. O'Connor CM, Whellan DJ, Lee KL, et al. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. Apr 2009; 301(14):1439-1450.
26. Pascual-Figal DA, Garrido IP, Blanco R, et al. Soluble ST2 is a marker for acute cardiac allograft rejection. Ann Thorac Surg. Dec 2011; 92(6):2118-2124.
27. Phillips, M., Boehmer, J.P., Cataneo, R.N., et al. Heart allograft rejection:  Detection with breath alkanes in low levels (the HARDBALL study). J Heart Lung Transplant 2004; 23(6): 701-708.
28. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. Feb 2011; 123(4):e18-e209.
29. Rohde LE, Beck-da-Silva L, Goldraich L, et al. Reliability and prognostic value of traditional signs and symptoms in outpatients with congestive heart failure. Can J Cardiol. May 2004; 20(7):697-702.
30. Savarese G, Trimarco B, Dellegrottaglie S, et al. Natriuretic peptide-guided therapy in chronic heart failure: a meta-analysis of 2,686 patients in 12 randomized trials. PLoS One. 2013; 8(3):e58287.
31. Shah RV, Januzzi JL, Jr. ST2: a novel remodeling biomarker in acute and chronic heart failure. Curr Heart Fail Rep. Mar 2010; 7(1):9-14.
32. Stevenson LW, Perloff JK. The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. JAMA. Feb 1989; 261(6):884-888.
33. Troughton RW, Frampton CM, Brunner-La Rocca HP, et al. Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: an individual patient meta-analysis. Eur Heart J. Jun 2014; 35(23):1559-1567.
34. Virani SS, Alonso A, Benjamin EJ, et al. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. Mar 03 2020; 141(9): e139-e596.
35. Weinberg EO, Shimpo M, De Keulenaer GW, et al. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation. Dec 2002; 106(23):2961-2966.
36. Xu D, Chan WL, Leung BP, et al. Selective expression of a stable cell surface molecule on type II but not type 1 helper T cells. J Exp Med. Mar 1998; 187(5):787-794.
37. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Card Fail. Aug 2017; 23(8): 628-651.
38. Zhang R, Zhang Y, An T, et al. Prognostic value of sST2 and galectin-3 for death relative to renal function in patients hospitalized for heart failure. Biomark Med. 2015; 9(5):433-441.

POLICY HISTORY:

Medical Policy Panel, January 2015

Medical Policy Group, March 2015 (3): Adopting as new medical policy

Medical Policy Administration Committee, March 2015

Available for comment March 3 through April 17, 2015

Medical Policy Group, June 2016 (3): Updates to Title, Description, Key Points, Key Words & References; clarified policy statement to be able to add to list of investigational indications – no change in policy intents – remains investigational

Medical Policy Panel, May 2017

Medical Policy Group, May 2017 (3): 2017 Updates to Description, Key Points, & References. No change in policy statement.

Medical Policy Panel, May 2018

Medical Policy Group, May 2018 (4): Updates to Description and Key Points. No change to policy statement.

Medical Policy Group, July 2018: Quarterly coding update. Added new CPT code 0055U to Current Coding. Added Key Words myTAIHEART, TAI

Medical Policy Panel, May 2019

Medical Policy Group, May 2019 (9): 2019 Updates to Description and Key Points. No change to policy statement.

Medical Policy Group, March 2020 (9): Removed CPT code 0055U from policy. Added CPT codes 0085T and 86849 to current coding section. Removed key words: myTAIHEART, TAI. Added key word: Heartsbreath test. Added policy statement regarding volatile organic compounds to this policy (moved from MP 212). No change to coverage intent, testing remains investigational. Changed name of this policy to: Laboratory Tests for Chronic Heart Failure and Heart Transplant Rejection.

Medical Policy Administration Committee, April 2020

Medical Policy Panel, May 2020

Medical Policy Group, May 2020 (9): 2020 Updates to Description, Key Points, and References related to ST2. No change to policy statement.

Medical Policy Panel, October 2020

Medical Policy Group, October 2020 (9): Updates to Description, Approved By Governing Bodies. No change to policy statement.

Medical Policy Group, October 2020:  2021 Annual Coding Update. Added 84999 to Current Coding. Moved CPT code 0085T from Current coding section. Created Previous CPT coding section to include code 0085T.

Medical Policy Group, February 2021 (9): Policy statement updated to remove “not medically necessary,” no change to policy intent.

Medical Policy Panel, November 2021

Medical Policy Group, December 2021 (9): Updates to Description, Key Points, References. No change to policy statement. Moved CPT code 86849 from current coding section to previous coding section.

Medical Policy Panel, October 2022

Medical Policy Group, October 2022 (9): Annual updates to Description, Key Points, References. Minor editorial refinement to policy statement, no change to policy intent.

Medical Policy Panel, October 2023

Medical Policy Group, October 2023 (5): Updates to Description, Key Points, Benefit Application, and References. No change to Policy Statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.