Heart Failure

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Pediatrics
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Clinical diagnosis compatible with congestive heart failure (CHF); Framingham criteria may be helpful

Criteria for Diagnosis

Laboratory Testing

  • Diagnosis may be difficult due to overlapping symptoms common in many diseases
  • Natriuretic peptides – B-type (BNP) and N-terminal proBNP (NT-proBNP)
    • High sensitivity and specificity for differentiating between cardiac and noncardiac etiologies
      • Considered gold standard for clinical heart failure biomarker testing (Januzzi, 2015)
      • Negative predictive value (>98%) – normal values essentially without CHF
      • Concentrations expected to exceed diagnostic cutoff in 90% of patients with CHF
    • Best documented use is emergency testing in patients presenting with acute dyspnea and a clinical scenario suggesting CHF (Anwarrudin, 2006)
      • Single cutoff point strategy BNP <100 pg/mL or NT-proBNP <900 pg/mL – CHF is unlikely
      • BNP <100 pg/mL or NT-proBNP <300 pg/mL – CHF unlikely
        • Cutoff of 100 pg/mL provides maximal combination of sensitivity, specificity, and negative predictive value for contributing to diagnosis of CHF
      • BNP 100-400 pg/mL or NT-proBNP 300-449 pg/mL (<50 years of age) or 300-899 pg/mL (50-75 years) – CHF possible
      • BNP >400 pg/mL or NT-proBNP ≥450 pg/mL (<50 years); ≥900 pg/mL (50-75 years); ≥1,800 pg/mL (>75 years) – CHF likely
    • Performance slightly better in men versus women  and in younger (<70 years) versus older patients
    • May not be as useful in patients >75 years, shock (cardiogenic or septic)
    • Cutoff point values for renal failure
      • In renal failure (glomerular filtration rate [GFR] <60 mL/min/1.73 m2) and BNP ≥200 pg/mL or NT-proBNP ≥1,200 pg/mL; CHF likely
    • Referral to specialist within 2 weeks is suggested for suspected CHF with elevated levels of BNP (see NICE 2010 chronic heart failure guideline)
  • Troponin testing
    • Troponin I or T should be assessed in patients presenting with acutely decompensated CHF (ACCF /AHA, 2013)
  • Other laboratory testing

Imaging Studies

  • Chest x-ray – bilateral interstitial infiltrates, cephalization of vessels, cardiomegaly, Kerley B lines, effusions
  • Ventilation/perfusion (V/Q) scan, pulmonary angiography – rule out pulmonary embolism

Other Testing

  • Electrocardiogram (EKG) – Q waves, ventricular hypertrophy, heart block, atrial fibrillation
  • Echocardiogram – frequently reduced ejection fraction
    • Role in excluding valvular disease
    • Test of choice before natriuretic peptides if patient has recent urinary infection (within 2 weeks) (NICE, 2012)
  • Sleep study

Prognosis

  • Natriuretic peptides
    • Secreted from cardiomyocytes in response to pressure and volume overload
    • Several recent studies suggest BNP value at time of discharge may be a reliable predictor of morbidity and recurrent hospital admission
      • <300 pg/mL associated with benign course
    • Reduction of NP during therapy – associated with improved clinical outcome
    • BNP >125 pg/mL or NT-proBNP >1,000 pg/mL with rising values – predictive of adverse outcome
  • Soluble suppression of tumorigenicity-2  (ST-2)
    • Marker of fibrosis – assesses a different biochemical pathway from BNP
    • Recommend baseline and posttreatment measurements
    • Several recent studies (eg, PRIDE Study; Mueller, 2008) suggest that higher levels (>0.20 ng/mL) are associated with mortality and morbidity at 1 year
      • Increased risk with rising levels
    • Additive risk stratification when combined with NT-proBNP (AHA, 2013)
    • May be useful in risk stratification and assessment in patients with known cardiovascular disease
    • Uninfluenced by renal insufficiency, age, sex, body mass (Heil, 2015)
  • Emerging Markers
    • Galectin-3
      • Soluble protein secreted by macrophages, which leads to fibrosis
      • May be useful in stratification, particularly combined with NT-proBNP
        • May not offer any better prognostication than NT-proBNP singularly
      • Affected by renal function (relationship with GFR is highly correlated)
    • Cystatin C
      • Protease inhibitor, which is a marker for GFR
      • May be useful when combined with NT-proBNP, especially in elderly patients (Yancy, 2013)
        • Elevated levels appear to correlate with worse hospital morbidity (Manzano-Fernandez, 2011)
    • NGAL
      • Increased expression in epithelial damage
      • Participates in inflammatory reactions during heart failure

Differential Diagnosis

  • National Academy of Clinical Biochemistry Laboratory Medicine Practice guidelines state that screening is reasonable in high-risk patients (eg, diabetic patient with history of myocardial infarction)
    • Use B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP)
  • Serial use of natriuretic peptide (NP) measurements to guide titration of therapy
    • Small and underpowered studies suggest benefit (Shah, 2014)
    • Low target value must be selected (eg, b-type NP [BNP] of 100 ng/L or NT-proBNP of 1,000 ng/L)

Heart failure is a clinical syndrome resulting from impaired function of the ventricular myocardium. It is often referred to as congestive heart failure.

Epidemiology

  • Prevalence – 5-7 million in U.S. (ACCF/AHA, 2013)
    • ~550,000 annual new cases in U.S. (Januzzi, 2015)
  • Age – ≥65 years
  • Sex – M>F (difference narrows as women age)

Etiology (numerous)

Risk Factors

Categorization

  • Diastolic vs. systolic with reduced ejection fraction dysfunction
  • Low-output vs. high-output
  • Acute vs. chronic
  • Left-sided vs. right-sided

Clinical Presentation

  • Spectrum of clinical signs and symptoms
    • Ascites
    • Dyspnea, orthopnea, paroxysmal nocturnal dyspnea, rales, tachypnea
    • Fatigue and weakness
    • Hepatomegaly
    • Jaundice
    • Nausea, anorexia, cachexia
    • Pedal edema
    • Pulsus alternans, tachycardia
    • S3/S4

Clinical Background

Epidemiology

  • Incidence – cardiomyopathy occurs in 8/100,000 infants

Etiology

  • Most chronic heart failure (CHF) in children is related to congenital heart disease
    • Increased systolic output with pulmonary over-circulation
      • Large patent ductus arteriosus
      • Persistent aorta pulmonary connections
      • Ventricular septal defect
    • Low cardiac output
      • Critical aortic stenosis
      • Hyperplastic left heart
      • Severe coarctation of the aorta
    • Acquired disorders

Clinical Presentation

  • Neonates
    • Irritability
    • Poor feeding
    • Respiratory difficulty
  • Children
    • Abdominal pain
    • Anorexia
    • Dyspnea, cough
    • Fatigue

Diagnosis

Indications for Testing

  • Clinical diagnosis compatible with CHF; Framingham criteria may be helpful (refer to Diagnosis tab)

Laboratory Testing

  • Initial testing – CBC, urinalysis, electrolytes, blood urea nitrogen (BUN), creatinine, transaminases
  • Natriuretic peptides (B-type natriuretic peptide [BNP] or N-terminal pro B-type natriuretic peptide [NT-pro BNP])
    • Natriuretic cutoff points must be age- and gender-related in children
      • Cutoffs also vary by type of test

Imaging Studies

  • Refer to Diagnosis tab

Other Testing

  • Refer to Diagnosis tab

Prognosis

  • Natriuretic peptides (NP) –not enough literature is available to suggest use is helpful in pediatric populations (as opposed to adult population)
    • Single study indicated b-type NP (BNP) ≥300 pg/mL was prognostic for poorer outcome (Price, 2006)

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

proBrain Natriuretic Peptide, NT 0050083
Method: Quantitative Electrochemiluminescent Immunoassay

Limitations

In patients with renal insufficiency, NT-proBNP may accumulate to concentrations that no longer correlate with New York Heart Association functional classifications

Do not use as a stand-alone test; assess clinical presentation and other evaluation (eg, chest x-ray, echocardiogram)

B-Type Natriuretic Peptide 0030191
Method: Quantitative Chemiluminescent Immunoassay

Limitations

Blood concentrations of natriuretic peptides may be elevated in patients with myocardial infarction and in patients who are candidates for or are undergoing renal dialysis

False-positive results more common in females >75 years

Do not use as a stand-alone test; assess clinical presentation and other evaluation (eg, chest x-ray, echocardiogram)

ST2, Soluble 2002270
Method: Quantitative Enzyme Immunoassay

Limitations

Possibility of interference with anti-reagent antibodies and patient sample

Biological variability – 30% for healthy adults

Galectin-3, Serum 2007138
Method: Quantitative Enzyme Immunoassay

Cystatin C, Serum 0095229
Method: Quantitative Nephelometry

Related Tests

Guidelines

Chronic heart failure in adults: management. National Institute for Health and Care Excellence. London, England [Reviewed Jan 2015; Accessed: Nov 2015]

Hunt SAnn, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LWarner, Yancy CW. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: develope Circulation. 2009; 119(14): e391-479. PubMed

Januzzi JL, Mebazaa A, Di Somma S. ST2 and prognosis in acutely decompensated heart failure: the International ST2 Consensus Panel. Am J Cardiol. 2015; 115(7 Suppl): 26B-31B. PubMed

Lambert M. NICE Updates Guidelines on Management of Chronic Heart Failure. 85(8): 832-834. Am Fam Physician. Leawood, KS [Accessed: Nov 2015]

Mant J, Al-Mohammad A, Swain S, Laramée P, Guideline Development Group. Management of chronic heart failure in adults: synopsis of the National Institute For Health and clinical excellence guideline. Ann Intern Med. 2011; 155(4): 252-9. PubMed

Tang WH Wilson, Francis GS, Morrow DA, Newby K, Cannon CP, Jesse RL, Storrow AB, Christenson RH, Apple FS, Ravkilde J, Wu AH B, National Academy of Clinical Biochemistry Laboratory Medicine. National Academy of Clinical Biochemistry Laboratory Medicine practice guidelines: Clinical utilization of cardiac biomarker testing in heart failure. Circulation. 2007; 116(5): e99-109. PubMed

Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ V, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH Wilson, Tsai EJ, Wilkoff BL, American College of Cardiology Foundation, American Heart Association Task Force on Practice Guidelines. 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. 2013; 62(16): e147-239. PubMed

General References

Anwaruddin S, Lloyd-Jones DM, Baggish A, Chen A, Krauser D, Tung R, Chae C, Januzzi JL. Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study. J Am Coll Cardiol. 2006; 47(1): 91-7. PubMed

Bayes-Genis A, Zhang Y, Ky B. ST2 and patient prognosis in chronic heart failure. Am J Cardiol. 2015; 115(7 Suppl): 64B-9B. PubMed

Gaggin HK, Januzzi JL. Natriuretic peptides in heart failure and acute coronary syndrome. Clin Lab Med. 2014; 34(1): 43-58, vi. PubMed

Heil B, Tang WH. Biomarkers: Their potential in the diagnosis and treatment of heart failure. Cleve Clin J Med. 2015 Dec;82(12 Suppl 2):S28-35. Review. PubMed

Helanova K, Spinar J, Parenica J. Diagnostic and prognostic utility of neutrophil gelatinase-associated lipocalin (NGAL) in patients with cardiovascular diseases--review. Kidney Blood Press Res. 2014; 39(6): 623-9. PubMed

Jarolim P. Overview of cardiac markers in heart disease. Clin Lab Med. 2014; 34(1): 1-14, xi. PubMed

King M, Kingery J, Casey B. Diagnosis and evaluation of heart failure. Am Fam Physician. 2012; 85(12): 1161-8. PubMed

Lin DC C, Diamandis EP, Januzzi JL, Maisel A, Jaffe AS, Clerico A. Natriuretic peptides in heart failure. Clin Chem. 2014; 60(8): 1040-6. PubMed

Manzano-Fernández S, Januzzi JL, Boronat-Garcia M, Bonaque-González JCarlos, Truong QA, Pastor-Pérez FJ, Muñoz-Esparza C, Pastor P, Albaladejo-Otón MD, Casas T, Valdés M, Pascual-Figal DA. β-trace protein and cystatin C as predictors of long-term outcomes in patients with acute heart failure. J Am Coll Cardiol. 2011; 57(7): 849-58. PubMed

Patel RB, Secemsky EA. Clinical features of heart failure and acute coronary syndromes. Clin Lab Med. 2014; 34(1): 15-30, xi. PubMed

Siasos G, Tousoulis D, Oikonomou E, Kokkou E, Mazaris S, Konsola T, Stefanadis C. Novel biomarkers in heart failure: usefulness in clinical practice. Expert Rev Cardiovasc Ther. 2014; 12(3): 311-21. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Jasuja GKaur, Travison TG, Davda M, Murabito JM, Basaria S, Zhang A, Kushnir MM, Rockwood AL, Meikle W, Pencina MJ, Coviello A, Rose AJ, D'Agostino R, Vasan RS, Bhasin S. Age trends in estradiol and estrone levels measured using liquid chromatography tandem mass spectrometry in community-dwelling men of the Framingham Heart Study. J Gerontol A Biol Sci Med Sci. 2013; 68(6): 733-40. PubMed

La'ulu SL, Apple FS, Murakami MM, Ler R, Roberts WL, Straseski JA. Performance characteristics of the ARCHITECT Galectin-3 assay. Clin Biochem. 2013; 46(1-2): 119-22. PubMed

McMillin GA, Owen WE, Lambert TL, De BK, Frank EL, Bach PR, Annesley TM, Roberts WL. Comparable effects of DIGIBIND and DigiFab in thirteen digoxin immunoassays. Clin Chem. 2002; 48(9): 1580-4. PubMed

Mongia SK, La'ulu SL, Apple FS, Ler R, Murakami MM, Roberts WL. Performance characteristics of the Architect brain natriuretic peptide (BNP) assay: a two site study. Clin Chim Acta. 2008; 391(1-2): 102-5. PubMed

Rawlins ML, Owen WE, Roberts WL. Performance characteristics of four automated natriuretic peptide assays. Am J Clin Pathol. 2005; 123(3): 439-45. PubMed

Medical Reviewers

Last Update: February 2016