Congestive Heart Failure (CHF) Risk Testing

CHF – A Major Health Problem

•	Affects almost 4.8 million Americans1
•	550,000 new cases diagnosed every year1
•	Leading cause of hospitalization in the elderly1
•	50% of CHF patients are asymptomatic and difficult to diagnose2
•	Primary symptoms of CHF such as dyspnea, edema and fatigue may also be indicative of pulmonary disease3

Benefits of BNP and proBNP Testing

•	Strong negative predictive value - 98% or greater - allows BNP and proBNP to rule out CHF3,4,5
•	Help triage possible CHF patients by determining whether symptoms such as dyspnea, edema, and fatigue are due to heart or lung disease3,6
•	Can detect asymptomatic left ventricular dysfunction in post-MI patients7,8
•	Help optimize treatment in individuals with heart failure
•	Aid in the prognosis of existing CHF patients - BNP and proBNP levels increase proportionally with severity of disease3,5,9
•	Track the course of CHF: Levels correlate with the New York Heart Association classification of CHF7,10

Clinical Summary

•	B-type, or brain, natriuretic peptide (BNP) was first isolated from brain tissue, but is synthesized primarily in the ventricles of the heart. Cleavage of the 108-amino acid precursor of BNP (proBNP) produces two molecules: (1) BNP, the active C-terminal, 77 to 108-amino acid molecule; and (2) N-terminal proBNP (NT-proBNP), the inactive 1 to 76-amino acid molecule. Studies indicate that NT-proBNP testing has the same clinical utility as BNP.11,12,13
•	BNP increases glomerular filtration rate, decreases sodium retention, and inhibits renin and aldosterone secretion. It is a marker of cardiac dysfunction that correlates with the severity of symptomatic and asymptomatic left ventricular hypertrophy14 and CHF15 (including the NYHA classification16). Since NT-proBNP levels also correlate strongly with heart failure, either can be used to triage symptomatic patients (eg, patients with dyspnea). For example, BNP can be used to differentiate cardiac failure from primary lung disease in patients with acute dyspnea17 and to indicate increased left ventricular mass in patients with essential hypertension.18 When levels are within the normal reference range, the patient's symptoms are probably not due to heart failure. Conversely, when levels are elevated, there is an increased probability of heart failure and further cardiac assessment is warranted.
•	The degree of BNP or NT-proBNP elevation can be used to predict future cardiac events and survival. For example, BNP levels predicted heart failure and death after myocardial infarction.19 Similarly, the relative risk of death based on baseline NT-proBNP levels in patients presenting with chest pain and no ST-segment elevation was 4.2, 10.7, and 26.6 for NT-proBNP quartiles 2, 3, and 4, respectively (relative to the 1st quartile).20
•	If early studies are confirmed and clinical cut-points are established, these markers may assist in maximizing therapy. Troughton, et al showed improved treatment outcomes when a specific NT-proBNP level (<200 pmol/L) was used as the therapeutic target rather than clinical criteria.21 Richards, et al showed that NT-proBNP levels above the median predicted response to carvedilol therapy in a group of patients with chronic ischemic (LV) dysfunction.22
•	Investigation into the utility of BNP testing for heart disease screening in a primary care setting (high-risk individuals and/or the general population) is also on-going.23

Individuals Suitable for Testing

•	Patients with suspected heart failure
•	Patients with diagnosed heart failure

	Reference Range
				BNP (pg/mL)		ProBNP (pg/mL)
		Healthy males		< 100		≤ 60
		Healthy females		< 100		12 – 150

Test Ordering Information

•	CPT Code* 83880
•	BNP Specimen requirements:
	–	1 mL frozen EDTA plasma (lavender-top plastic tube)
	–	Do not use glass tubes or transfer pipets. (Can original specimen be collected in glass EDTA tube then transferred to plastic?)
•	ProBNP Specimen requirements:
	–	1 mL refrigerated EDTA plasma (lavender-top tube)
	–	Separate plasma as soon after collection as possible. Keep refrigerated or frozen after separation.
•	For complete specimen requirements and other ordering information, contact your local Quest Diagnostics laboratory, or visit our online Test Menu

Interpretive Information

•	Symptomatic patients who present with a BNP or NT-proBNP level within the normal reference range are highly unlikely to have CHF. Conversely, an elevated baseline level indicates the need for further cardiac assessment and indicates the patient is at increased risk for future heart failure and mortality.
•	BNP is increased in CHF, left ventricular hypertrophy, acute myocardial infarction, atrial fibrillation, cardiac amyloidosis, and essential hypertension. Elevations are also observed in right ventricular dysfunction, pulmonary hypertension, acute lung injury, subarachnoid hemorrhage, hypervolemic states, chronic renal failure, and cirrhosis.
•	NT-proBNP levels are increased in CHF, left ventricular dysfunction, myocardial infarction, valvular disease, hypertensive pregnancy, and renal failure, even after hemodialysis.
•	Although levels of BNP and NT-proBNP are similar in normal individuals, NT-proBNP levels are substantially greater than BNP levels in patients with cardiac disease due to increased stability (half-life) of NT-proBNP in circulation. Thus, results from the two tests are not interchangeable.

Supporting Technical Information

•	"Published Support for the Use of BNP to Diagnose or Rule Out Congestive Heart Failure"
•	"Published Support for the Use of proBNP to Diagnose or Rule Out Congestive Heart Failure"

Online Resources for Healthcare Professionals

•	Contact a sales representative to learn more about our testing services or to become a Quest Diagnostics client
•	Access our online Test Menu, to obtain test ordering codes and specimen requirements
•	Visit our Interpretive Guide, for information relating to cardiovascular testing test selection, utilization, and interpretation

Online Test Information for Your Patients
Your patients can learn about health conditions and laboratory tests in our online Patient Health Library. The library is founded on evidence-based information, and includes topics such as:

•	B-type Natriuretic Peptide
•	Ask-the-Doctor Checklist
•	Work in Partnership with Your Doctor
•	Share in Every Medical Decision
•	Healthwise Self-Care Checklist
•	Making Wise Health Decisions

Contact a Quest Diagnostics Sales Representative, learn more about our testing services, and become a client

•	Contact a physician sales representative
•	Contact a hospital sales representative or learn about our complete hospital offerings

* The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed.

References
¹ American Heart Association. 2002 Heart and Stroke Statistical Update. Dallas, Texas: American Heart Association. 2000.
² Gheorghiade M, Bonow R, Goldman L, et al. Use of beta-blocker therapy for mild-to-moderate chronic heart failure. Am J Med 2001; 110 (Suppl 7A).
³ Maisel A. B-Type Natriuretic Peptide Measurements in Diagnosing Congestive Heart Failure in the Dyspneic Emergency Department Patient. Rev Cardiovascular Med (2002;3(suppl 4):S10-S17).
⁴ proBNP proBrain Natriuretic Peptide Package Insert Elecsys® Systems 1010/1020/Modular Analytics E170.
⁵ Kelly R, Struthers AD. Are natriuretic peptides clinically useful as markers of heart failure? Ann Clin Biochem (2001;38:94-102).
⁶ Kucher N, Printzen G, et al. Low Pro-Brain Natriuretic Peptide Levels Predict Benign Clinical Outcome in Acute Pulmonary Embolism. Circulation. (2003; 107:1576-1578).
⁷ Wieczorek SJ. et al. A rapid B-type natriuretic peptide assay accurately diagnoses left ventricular dysfunction and heart failure: A multicenter evaluation. No ST-Segment Elevation. J Am Coll Cardiol (2002;40:437-445).
⁸ Jernberg T. et al. N-Terminal Pro Brain Natriuretic Peptide on Admission for Early Risk Stratification of Patients With Chest Pain and No ST-Segment Elevation. J Am Coll Cardiol (2002;40:437-445).
⁹ Groenning BA. et al. Detection of left ventricular enlargement and impaired systolic function with plasma N-terminal pro brain natriuretic peptide concentrations. Am Heart J (2002; 143:923-929).
¹⁰ Luether M. Why Do We Need Another Test For Congestive Heart Failure? Laboratory Medicine. (2003;34:185-189).
¹¹ Cowie MR and Mendez GF. BNP and congestive heart failure. Prog Cardiovasc Dis. 2002;44:293-321.
¹² Richards AM, Nicholls MG, Yandle TG, et al. Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin. New neurohormonal predictors of left ventricular function and prognosis after myocardial infarction. Circulation.1998:97:1921-1929.
¹³ Hammerer-Lercher A, Neubauer E, Muller S, et al. Head-to-head comparison of N-terminal pro-brain natriuretic peptide, brain natriuretic peptide and N-terminal pro-atrial natriuretic peptide in diagnosing left ventricular dysfunction. Clin Chim Acta. 2001;310:193-197.
¹⁴ McDonagh TA, Robb SD, Murdoch DR, et al. Biochemical detection of left-ventricular systolic dysfunction. Lancet. 1998;351:9-13
¹⁵ Mukoyama Y, Nakao K, Hosoda K, et al. Brain natriuretic peptide as a novel cardiac hormone in humans: Evidence for an exquisite dual natriuretic peptide system, ANP and BNP. J Clin Invest. 1991;87:1402-1412.
¹⁶ Hunt PJ, Richards AM, Nicholls MG, et al. Immunoreactive amino-terminal pro-brain natriuretic peptide (NT-PROBNP): a new marker of cardiac impairment. Clin Endocrinol. 1997;47:287-296.
¹⁷ Davis M, Espiner E, Richards G, et al. Plasma brain natriuretic peptide in assessment of acute dyspnoea. Lancet. 1994;343:440-444.
¹⁸ Kohno M, Horio T, Yokokawa K, et al. Brain natriuretic peptide as a cardiac hormone in essential hypertension. Am J Med. 1992;92:29-34.
¹⁹ Bettencourt P, Ferreira A, Pardal-Oliveira N, et al. Clinical significance of brain natriuretic peptide in patients with postmyocardial infarction. Clin Cardiol. 2000;23:921-927.
²⁰ Jernberg T, Stridsberg M, Venge P, et al. N-terminal pro brain natriuretic peptide on admission for early risk stratification of patients with chest pain and no ST-segment elevation. J Am Coll Cardiol. 2002;40:437-445.
²¹ Troughton RW, Frampton CM, Yandle TG, et al. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancets. 2000;355:1126-1130.
²² Richards AM, Doughty R, Nicholls MG, et al. Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin. Prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. J Am Coll Cardiol. 2001;37:1781-1787.
²³ Smith H, Pickering RM, Struthers A, et al. Biochemical diagnosis of ventricular dysfunction in elderly patients in general practice: observational study. BMJ. 2000;320:906-908.

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