Coverage Policy Manual
Policy #: 2015007
Category: Medicine
Initiated: January 2015
Last Review: August 2018
  ST2 Assay for Chronic Heart Failure

Heart Failure
HF is one among many cardiovascular diseases that comprises a major cause of morbidity and mortality worldwide. The term “heart failure” (HF) refers to a complex clinical syndrome that causes impairment of the heart’s ability to move blood through the circulatory system (Yancy, 2013). In the United States, approximately 600,000 individuals are estimated to be living with chronic HF (Roger, 2011). HF is the leading cause of hospitalization among people older than age 65 years, with direct and indirect costs estimated at about $37 billion annually in the U.S (Roger, 2011). Although survival has improved with treatment advances, the absolute mortality rates of HF remain at about 50% within 5 years of diagnosis.
Heart failure can be caused by disorders of the pericardium, myocardium, endocardium, heart valves or great vessels, or metabolic abnormalities, Individuals with HF may exhibit a wide range of LV anatomy and function. Some have normal LV size and preserved ejection fraction (EF); others have severe LV dilatation and depressed EF. However, most patients present with key signs and symptoms that are secondary to congestion in the lungs from impaired LV myocardial function (Yancy, 2013). These include dyspnea, orthopnea, and paroxysmal dyspnea. Other symptoms include weight gain due to fluid retention, fatigue, weakness and exercise intolerance that also are secondary to diminished cardiac output.
Initial evaluation of a patient in whom HF is suspected is typically based on clinical history, physical examination, and chest radiograph. Because people with HF may present with signs and symptoms that are relatively nonspecific, for example dyspnea, an accurate diagnosis can be a challenge. Therefore, noninvasive imaging studies, such as echocardiography and radionuclide angiography, are used to quantify to pump function of the heart, thus identifying or excluding HF 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 (Yancy, 2013).  However, clinical assessment and noninvasive imaging methods can be limited in accurately evaluating patients with HF because symptoms and signs can be poorly correlated with objective methods of assessing cardiac dysfunction (Rohde, 2004; Marcus, 2005; Stevenson, 1989). Thus, invasive procedures such as cardiac angiography or catheterization are used in selected patients with presumed HF symptoms to determine the etiology (ie, ischemic vs non-ischemic) and physiologic characteristics of the condition.
Patients with HF 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 as components of self-management. A variety of medications are available to treat HF. These include diuretics (eg, furosemide, hydrochlorothiazide, spironolactone, etc.), angiotensin converting enzyme inhibitors (eg, captopril, enalapril, lisinopril, etc.), angiotensin receptor blockers (eg, losartan, valsartan, candesartan), beta blockers (eg, carvedilol, metoprolol succinate, etc.), and vasodilators (eg, hydralazine, isosorbide dinitrate)]. Numerous device-based therapies also are 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 EKG. Ventricular assist devices are indicated for patients with end-stage HF who have failed all other therapies and are also used as a bridge to cardiac transplantation in selected patients (Yancy, 2013).
HF Biomarkers
Because of limitations inherent to usual assessment of suspected HF patients, a number of objective disease biomarkers have been investigated to diagnose HF and assess patient prognosis, with the additional goal of using biomarkers to guide therapy (Gaggin, 2013). They include a number of proteins, peptides, or other small molecules whose production and release into the circulation reflect the activation of remodeling and neurohormonal pathways that lead to LV impairment. Examples include BNP, its analog - NT-proBNP, troponin T and I, renin, angiotensin, arginine vasopressin, C-reactive protein, and norepinephrine . (Yancy, 2013; Gaggin, 2013).  
BNP and NT-proBNP are considered the reference standard for biomarkers in assessing HF patients. They have had substantial impact on the standard of care for the diagnosis of HF and are included in the recommendations of all major societies including the American College of Cardiology, (Yancy, 2013) European Society of Cardiology,(McMurrayy, 2012) and the Heart Failure Society of America (Heart Failure Society, (Lindenfeld, 2010). Although natriuretic peptide levels are not 100% specific for the clinical diagnosis of HF, elevated values for either BNP or NT-proBNP in the presence of clinical signs and symptoms reliably identifies the presence of structural heart disease due to remodeling and heightened risk for adverse events. Natriuretic peptides also can help in determining prognosis of HF patients, with elevated blood levels portending poorer prognosis.
In addition to diagnosing and assessing prognosis of HF patients, blood levels of BNP or NT-proBNP have been proposed as an aid for managing patients diagnosed with chronic HF (Yancy, 2013; Savarese, 2013; Troughton, 2014). Levels of either biomarker rise in response to myocardial damage and LV remodeling, whereas they tend to fall as drug therapy ameliorates symptoms of HF. Evidence from a large number of randomized clinical trials (RCTs) that compared BNP- or NT-proBNP-guided therapy to clinically guided adjustment of pharmacologic treatment of patients with chronic HF has been compiled in recent systematic reviews and meta-analyses (MA). However, these analyses have not consistently reported a benefit for BNP-guided management. The largest meta-analysis to date was a patient-level MA that included 2686 patients from 12 RCTs (Savarese, 2013). This MA showed that NT-proBNP-guided management was associated with significant reductions in all-cause mortality and HF-related hospitalization compared with clinically-guided treatment. Although BNP-guided management in this MA was not associated with significant reductions in these parameters, differences in patient numbers and characteristics may explain the discrepancy. A second patient-level MA included 11 RCTs and 2000 patients randomized to natriuretic peptide-guided pharmacologic therapy or usual care (Troughton, 2014). These results show that among patients 75 years of age or younger with chronic HF, most of whom had impaired LVEF, 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 HF or cardiovascular disease.
ST2 protein biomarker
A new protein biomarker, referred to as ST2 (suppression of tumorigenicity-2) has elicited interest as a potential aid to predict prognosis and manage therapy of chronic HF (Bhardwaj, 2010; Chowdhury, 2013; Ciccone, 2013; Daniels, 2014; Dieplinger, 2014; Mueller, 2013; Shah, 2010). 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 IL33 and ST2L is believed to have an immunomodulatory function via T-helper type 2 lymphocytes and was initially described in the context of cell proliferation, inflammatory states, and autoimmune diseases (Xu, 1998). 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 HF (Weinberg, 2002). 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 anti-remodeling effects of the IL33-ST2L signaling pathway. Thus, on a biologic level, IL33- 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 HF, including abnormalities in filling pressures, chamber size, systolic and diastolic function (Gaggin, 2013; Ciccone, 2013; Dieplinger, 2014).
An enzyme-linked immunosorbent (ELISA)-based assay is commercially available for determining sST2 blood levels (Presage® ST2 Assay, Critical Diagnostics, San Diego, CA, USA) (Mueller, 2013). 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. In one published study, a limit of detection of 2.0 ng/mL for sST2 was reported.16 In the same study, the assay had a within-run coefficient of variation (CV) of 2.5% and a total CV less than 4.0%; demonstrated linearity within the dynamic range of the assay calibration curve; and, exhibited no relevant interference or cross-reactivity.
ST2 is not intended for use in diagnosis of HF, 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 HF (Dieplinger, 2014; Mueller, 2013). Although the natriuretic peptides, BNP and NT-proBNP, reflect different physiologic aspects of HF compared with sST2, they are considered to be the reference standard biomarker when used with clinical findings to diagnose, prognosticate, and manage HF and as such are the comparator to sST2.
Regulatory Status
The Presage® ST2 Assay kit received 510(k) marketing clearance from FDA in December 2011. The assay also received Conformite Europeenne (CE) Mark in January 2011. According to the FDA 510(k) Summary, the Presage® ST2 Assay is to be used in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic HF.
The Presage® ST2 Assay kit is provided in a microplate configuration. The kit contains a ready-to-use 96-well microtiter plate coated with mouse monoclonal antihuman sST2 antibodies; a recombinant human sST2 standard calibrator (lyophilized); a standard diluent; an anti-ST2 biotinylated antibody reagent (mouse monoclonal antihuman sST2 antibodies) in phosphate-buffered saline; a sample diluent; a tracer concentrate and tracer diluent; a wash concentrate; a tetramethylbenzidine reagent; a stop solution; and 2 levels of controls provided in a sealed, lyophilized format (high and low control).
Two other research products are available to assay sST2: the MBL ST2 ELISA kit (Medical and Biological Laboratories, MA, USA and the Human ST2/IL-1 R4 DuoSet® (R&D Systems, MN, USA). They use different standards, different antibodies, different reagents and buffers and thus, results are not comparable between them and the Presage® ST2 Assay.16 Furthermore, neither the MBL ST2 ELISA nor the Human ST2/IL-1 R4 DuoSet® assay has received FDA marketing approval. These assays are not considered in this Policy.
There is a specific CPT code for this test:
83006 Growth stimulation expressed gene 2 (ST2, Interleukin 1 receptor like-1).

The use of the Presage® ST2 Assay does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness:
    • to evaluate the prognosis of patients diagnosed with chronic heart failure;
    • to guide management (pharmacological, device-based, exercise, etc.) of patients diagnosed with chronic heart failure;
    • in the post cardiac transplantation period, including but not limited to predicting prognosis and predicting acute cellular rejection;
    • for any other indication.
For members with contracts without primary coverage criteria, the use of the Presage® ST2 Assay is considered investigational:
    • to evaluate the prognosis of patients diagnosed with chronic heart failure;
    • to guide management (pharmacological, device-based, exercise, etc.) of patients diagnosed with chronic heart failure;
    • in the post cardiac transplantation period, including but not limited to predicting prognosis and predicting acute cellular rejection;
    • for any other indication.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.

This Policy was based on a literature review of the National Library of Medicine PubMed database and EMBASE, with an electronic search on October 22, 2014 with no date restrictions. Evidence was sought on clinical use of the Presage® ST2 Assay to predict outcomes of patients who were diagnosed with chronic heart failure (HF), and to guide therapeutic management of such patients.
ST2 can be used as both a prognostic marker and as an aid in management. Assessment of a prognostic tool typically focuses on 3 categories of evidence: (1) technical performance; (2) clinical validity (ie, statistically significant association between the test result and health outcomes); and (3) clinical utility (ie, demonstration that use of the prognostic information clinically can alter clinical management and/or improve health outcomes compared with patient management without use of the prognostic tool). In some cases, it is important to evaluate whether the test provides incremental information above the standard workup in order to determine whether the test has utility in clinical practice. Assessment of efficacy for therapeutic intervention involves a determination of whether the intervention improves health outcomes. The optimal study design for this purpose is a randomized controlled trial (RCT) that includes clinically relevant measures of health outcomes. Intermediate outcome measures may also be adequate if there is an established link between the intermediate outcome and true health outcomes. Nonrandomized comparative studies and uncontrolled studies can sometimes provide useful information on health outcomes but are prone to biases such as noncomparability of treatment groups, placebo effect, and variable natural history of the condition.
Use of sST2 Levels for Establishing Prognosis of Chronic Heart Failure
A number of clinical studies in which sST2 blood levels were determined using the Presage® ST2 Assay have reported that there is an association between ST2 levels and adverse outcomes in patients who were diagnosed with chronic HF. A substantial body of biomarker evidence has been reported retrospectively from subsets of patients who were enrolled in RCTs of HF interventions. These RCTs include Val-HeFT (Valsartan Heart Failure Trial) (Cohn, 2001); HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) (O’Connor, 2009); CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) (Kjekshus, 2007); and, PROTECT (ProBNP Outpatient Tailored Chronic Heart Failure study) (Januzzi, 2011).  Although the patients in these RCTs were well-characterized and generally well-matched between study arms, the trials were neither intended nor designed to specifically evaluate biomarkers as risk predictors. At present, no prospectively gathered evidence is available from an RCT in which sST2 levels were compared with levels of a natriuretic peptide (BNP or NT-proBNP) to predict risk for adverse outcomes among well-defined cohorts of patients with diagnosed chronic HF.
Summary of Evidence on Use of sST2 for Establishing Prognosis of Chronic HF
Evidence is available from clinical studies in which the Presage® ST2 Assay was used to quantify sST2 levels in chronic HF patients and determine whether they are associated with disease prognosis. In general, it appears that elevated sST2 levels predict higher risk of poor outcomes compared with lower levels. However, the available evidence is limited by interstudy inconsistency and differences in patient characteristics, particularly the severity of HF, its etiology, duration, and treatment. Furthermore, most of the evidence was obtained from retrospective analyses of sST2 levels in subsets of larger patient cohorts within RCTs, potentially biasing the findings. The evidence primarily shows associations between elevated sST2 levels and poor outcomes but does not go beyond that in demonstrating a clinical connection between biomarker status, treatment received, and clinical outcomes. Further, sST2 levels were not properly compared with the reference standard natriuretic peptides in any biomarker study.  
Use of sST2 Levels for Guidance of Chronic HF Therapy
No evidence is available from a clinical study of any design in which outcomes were compared between groups of well-matched patients who were managed according to serial changes in sST2 blood levels versus reference standard BNP or NT-proBNP levels.
Use of sST2 in post-cardiac transplantation patients
Serum ST2 levels have been proposed as a prognostic marker post-cardiac transplantation and as a test to predict acute cellular rejection (graft versus host disease). There is very little evidence available for these indications. Januzzi et al performed a retrospective study in which sST2 levels were measured in 241 patients post-heart transplant (Januzzi, 2013). Over a follow-up period of up to seven years, sST2 levels were predictive of total mortality (HR = 2.01; 95% CI 1.15-3.51; p = 0.01). sST2 levels were also associated with risk of acute cellular rejection, with a significant difference between the top and bottom quartiles of sST2 levels in the risk of rejection (p=0.003).
In another study by Pascual-Figal et al, 26 patients were identified who were post-cardiac transplantation and had an acute rejection episode (Pascual-Figal, 2011).  sST2 levels were measured during the acute rejection episode and compared to levels that were measured when acute rejection was not present. sST2 levels were higher during the acute rejection episode compared to the non-rejection period (130ng/ml versus 50ng/ml, p=0.002). Elevated sST2 levels greater than 68ng/ml had a positive predictive value of 53% and a negative predictive value of 83% for the presence of acute cellular rejection. The addition of sST2 levels to serum BNP resulted in incremental improvement in identifying rejection episodes.
Summary of Evidence
Evidence on the prognostic use of the Presage® ST2 Assay to predict clinical outcomes in patients diagnosed with chronic heart failure (HF) consists of studies that report a correlation between ST2 (suppression of tumorigenicity-2) levels and poor clinical outcomes. In some cases, but not all, ST2 provided incremental prognostic information above that of standard clinical exam and BNP levels. There is no evidence that ST2 provides clinically actionable information that can be used to improve outcomes. As a result, there is insufficient evidence to conclude that ST2 improves outcomes compared with standard care using either BNP or NT-proBNP measurements.
No evidence was identified on the use of the Presage® ST2 Assay to guide management of patients diagnosed with chronic HF. Therefore, the use of this assay for guiding management decisions for patients with HF is considered investigational. There is also very little evidence on the use of this test in the post-transplantation period, including its use for predicting prognosis and predicting acute cellular rejection, as a result sST2 is also considered investigational for use in the post- cardiac transplantation period.
Practice Guidelines and Position Statements
The American College of Cardiology/American Heart Association (ACC/AHA) has published evidence-based guidelines based on a systematic review of the literature on the management of HF. In the review, ACC/AHA state that sST2 is a biomarker for myocardial fibrosis that predicts hospitalization and death in patients with HF and provides additive prognostic information to natriuretic peptide levels.1 In the ambulatory HF setting, ACC/AHA applies a IIb Class of Recommendation and assigns a B level of evidence for the use of sST2 as an option to provide additive prognostic information to established clinical evaluation and biomarkers. The guidelines are silent on other uses of sST2.
2017 Update
A literature search conducted through July 2017 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
Findings of studies on the prognostic value of sST2 for chronic heart failure were pooled in a 2017 meta-analysis by Aimo and colleagues (Aimo, 2017). The meta-analysis included 7 studies, including post hoc analyses of RCTs, and calculated the association between the Presage ST2 Assay and health outcomes. A pooled analysis of 7 studies found that sST2 was a statistically significant predictor of overall mortality (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.37 to 2.22). Moreover, a pooled analysis of 5 studies found that sST2 was a significant predictor of cardiovascular mortality (HR=1.79; 95% CI, 1.22 to 2.63).
Ongoing and Unpublished Clinical Trials
A search of in April 2017 did not identify any ongoing or unpublished trials that would likely influence this review.
2018 Update
A literature search was conducted through July 2018.  There was no new information identified that would prompt a change in the coverage statement.  

83006Growth stimulation expressed gene 2 (ST2, Interleukin 1 receptor like-1)

References: Aimo A, Vergaro G, Passino C, et al.(2017) Prognostic Value of Soluble Suppression of Tumorigenicity-2 in Chronic Heart Failure: A Meta-Analysis. JACC Heart Fail. Apr 2017;5(4):280-286. PMID 27816512

Anand IS, Rector TS, Kuskowski M, et al.(2014) Prognostic value of soluble ST2 in the Valsartan Heart Failure Trial. Circ Heart Fail. May 2014;7(3):418-426. PMID 24622243

Bayes-Genis A, de Antonio M, Galan A, et al.(2012) 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. PMID 22179033

Bhardwaj A, Januzzi JL, Jr.(2010) ST2: a novel biomarker for heart failure. Expert Rev Mol Diagn. May 2010;10(4):459-464. PMID 20465500

Broch K, Ueland T, Nymo SH, et al.(2012) Soluble ST2 is associated with adverse outcome in patients with heart failure of ischaemic aetiology. Eur J Heart Fail. Mar 2012;14(3):268-277. PMID 22302661

Chowdhury P, Kehl D, Choudhary R, et al.(2013) The use of biomarkers in the patient with heart failure. Curr Cardiol Rep. Jun 2013;15(6):372. PMID 23644993

Ciccone MM, Cortese F, Gesualdo M, et al.(2013) A novel cardiac bio-marker: ST2: a review. Molecules. 2013;18(12):15314-15328. PMID 24335613

Cohn JN, Tognoni G, Valsartan Heart Failure Trial I.(2001) A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. Dec 6 2001;345(23):1667-1675. PMID 11759645

Daniels LB, Bayes-Genis A.(2014) Using ST2 in cardiovascular patients: a review. Future Cardiol. Jul 2014;10(4):525-539. PMID 25301315

Dieplinger B, Mueller T.(2014) Soluble ST2 in heart failure. Clin Chim Acta. Sep 28 2014. PMID 25269091

Dupuy AM, Curinier C, Kuster N, et al.(2016) Multi-marker strategy in heart failure: combination of st2 and crp predicts poor outcome. PLoS One. 2016;11(6):e0157159. PMID 27311068

Felker GM, Fiuzat M, Thompson V, et al.(2013) 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. PMID 24103327

Gaggin HK, Januzzi JL, Jr.(2013) Biomarkers and diagnostics in heart failure. Biochim Biophys Acta. Dec 2013;1832(12):2442-2450. PMID 23313577

Gaggin HK, Motiwala S, Bhardwaj A, et al.(2013) 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. PMID 24114865

Heart Failure Society of A, Lindenfeld J, Albert NM, et al.(2010) HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail. Jun 2010;16(6):e1-194. PMID 20610207

Januzzi JL, Horne BD, Moore SA, et al.(2013) Interleukin receptor family member ST2 concentrations in patients following heart transplantation. Biomarkers. May 2013;18(3):250-256. PMID 23557127

Januzzi JL, Jr., Rehman SU, Mohammed AA, et al.(2011) 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 25 2011;58(18):1881-1889. PMID 22018299

Kjekshus J, Apetrei E, Barrios V, et al.(2007) Rosuvastatin in older patients with systolic heart failure. N Engl J Med. Nov 29 2007;357(22):2248-2261. PMID 17984166

Ky B, French B, McCloskey K, et al.(2011) High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure. Circ Heart Fail. Mar 2011;4(2):180-187. PMID 21178018

Marcus GM, Gerber IL, McKeown BH, et al.(2005) Association between phonocardiographic third and fourth heart sounds and objective measures of left ventricular function. JAMA. May 11 2005;293(18):2238-2244. PMID 15886379

McMurray JJ, Adamopoulos S, Anker SD, et al.(2012) ESC guidelines for the diag and treatment of acute and chronic heart failure 2012: The Task Force for the Diag and Treatment of Acute and Chronic Heart Failure 2012 of the European Soc of Cardio. Developed in collaboration with the HFA of the ESC Eur J Heart Fail. Aug 2012;14(8):803-869. PMID 22828712

Mueller T, Dieplinger B.(2013) 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. PMID 23256700

O'Connor CM, Whellan DJ, Lee KL, et al.(2009) Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. Apr 8 2009;301(14):1439-1450. PMID 19351941

Pascual-Figal DA, Garrido IP, Blanco R, et al.(2011) Soluble ST2 is a marker for acute cardiac allograft rejection. Ann Thorac Surg. Dec 2011;92(6):2118-2124. PMID 22035779

Roger VL, Go AS, Lloyd-Jones DM, et al.(2011) Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. Feb 1 2011;123(4):e18-e209. PMID 21160056

Rohde LE, Beck-da-Silva L, Goldraich L, et al.(2004) Reliability and prognostic value of traditional signs and symptoms in outpatients with congestive heart failure. Can J Cardiol. May 15 2004;20(7):697-702. PMID 15197422

Savarese G, Trimarco B, Dellegrottaglie S, et al.(2013) 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. PMID 23472172

Shah RV, Januzzi JL, Jr.(2010) ST2: a novel remodeling biomarker in acute and chronic heart failure. Curr Heart Fail Rep. Mar 2010;7(1):9-14. PMID 20425491

Stevenson LW, Perloff JK.(1989) The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. JAMA. Feb 10 1989;261(6):884-888. PMID 2913385

Troughton RW, Frampton CM, Brunner-La Rocca HP, et al.(2014) 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 14 2014;35(23):1559-1567. PMID 24603309

Weinberg EO, Shimpo M, De Keulenaer GW, et al.(2002) Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation. Dec 3 2002;106(23):2961-2966. PMID 12460879

Xu D, Chan WL, Leung BP, et al.(1998) Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells. J Exp Med. Mar 2 1998;187(5):787-794. PMID 9480988

Yancy CW, Jessup M, Bozkurt B, et al.(2013) 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. Oct 15 2013;62(16):e147-239. PMID 23747642

Zhang R, Zhang Y, An T, et al.(2015) 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. PMID 25985174

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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