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

  • Framingham criteria to establish clinical diagnosis of congestive heart failure
  • Simultaneous presence of at least two major criteria or one major criterion in conjunction with two minor criteria

      Laboratory Testing

      • Diagnosis may be difficult due to overlapping symptoms common in many diseases (eg, dyspnea)
      • 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


      • Use of multiple markers may improve risk-stratification (Bayes-Genis, 2015)

      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.


      • Prevalence – 5-7 million afflicted and >1 million hospitalized 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


      • 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


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


      • 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


      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


      • 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


      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


      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


      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


      Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Jan 2017]

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

      Hunt SA, 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 LW, 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 [Published Apr 2012; Accessed: Dec 2016]

      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

      Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després J, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB, American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2015 update: a report from the American Heart Association Circulation. 2015; 131(4): e29-322. PubMed

      Tang WH, Francis GS, Morrow DA, Newby K, Cannon CP, Jesse RL, Storrow AB, Christenson RH, Apple FS, Ravkilde J, Wu AH, 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, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, 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, Ordonez-Llanos J. Multiple biomarker strategies for risk stratification in heart failure. Clin Chim Acta. 2015; 443: 120-5. 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

      de Boer RA, Daniels LB, Maisel AS, Januzzi JL. State of the Art: Newer biomarkers in heart failure. Eur J Heart Fail. 2015; 17(6): 559-69. 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

      Kim H, Januzzi JL. Natriuretic peptide testing in heart failure Circulation. 2011; 123(18): 2015-9. PubMed

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

      Lin DC, 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 JC, 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

      Price JF, Thomas AK, Grenier M, Eidem BW, Smith EO, Denfield SW, Towbin JA, Dreyer WJ. B-type natriuretic peptide predicts adverse cardiovascular events in pediatric outpatients with chronic left ventricular systolic dysfunction. Circulation. 2006; 114(10): 1063-9. PubMed

      Shah RV, Januzzi JL. Soluble ST2 and galectin-3 in heart failure. Clin Lab Med. 2014; 34(1): 87-97, vi-vii. 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

      Ueland T, Gullestad L, Nymo SH, Yndestad A, Aukrust P, Askevold ET. Inflammatory cytokines as biomarkers in heart failure. Clin Chim Acta. 2015; 443: 71-7. PubMed

      Wettersten N, Maisel AS. Biomarkers for Heart Failure: An Update for Practitioners of Internal Medicine Am J Med. 2016; 129(6): 560-7. PubMed

      References from the ARUP Institute for Clinical and Experimental Pathology®

      Jasuja GK, 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

      Javan H, Szucsik AM, Li L, Schaaf CL, Salama ME, Selzman CH. Cardiomyocyte p65 nuclear factor-κB is necessary for compensatory adaptation to pressure overload Circ Heart Fail. 2015; 8(1): 109-18. 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

      Shibayama J, Yuzyuk TN, Cox J, Makaju A, Miller M, Lichter J, Li H, Leavy JD, Franklin S, Zaitsev AV. Metabolic remodeling in moderate synchronous versus dyssynchronous pacing-induced heart failure: integrated metabolomics and proteomics study PLoS One. 2015; 10(3): e0118974. PubMed

      Medical Reviewers

      Last Update: February 2017