Heart Failure

Heart failure (HF) is a clinical syndrome with an increasing prevalence and a high morbidity and mortality rate. It is classified by the location (right or left side) and degree of functional impairment, either with preserved ejection fraction (HFpEF), midrange EF (HFmrEF), or with reduced EF (HFrEF). On presentation, patients may have new onset or acute HF, or they may have acutely decompensated congestive heart failure (ADCHF).

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

Indications for Testing

  • Dyspnea
  • Signs and symptoms of volume overload
    • Displaced cardiac apical impulse
    • Third or fourth heart sound
    • Extremity edema
    • Elevated jugular venous pulse
  • Fatigue/weakness
  • Weight loss
  • Radiographic findings of volume overload such as venous congestion, pulmonary infiltrates, and cardiomegaly
  • History of cardiac disease (coronary artery disease, myocardial infarction)

Criteria for Diagnosis

  • Framingham criteria
    • May assist in establishing congestive heart failure (CHF) in conjunction with
      • Medical history
      • Laboratory test results
      • Imaging and diagnostic studies
    • Simultaneous presence of at least 2 major criteria or 1 major criterion in conjunction with 2 minor criteria

Laboratory Testing

  • Natriuretic peptides
    • B-type (BNP) and N-terminal proBNP (NT-proBNP)
      • Best used to rule out heart failure – low concentrations essentially rule out heart failure
      • Useful in conjunction with overload physical exam
      • Nonspecific marker of damage or stretch – can be seen in a multitude of clinical scenarios
        • NT-proBNP may be more consistent/stable marker compared to BNP
      • Elevations in BNP may be due to reasons other than heart failure
    • Midregional pro A-type natriuretic peptide (MR-proANP) (not offered at ARUP Laboratories)
      • Promising independent predictor of major adverse cardiovascular events (Lindberg, 2015)
  • Additional laboratory testing
    • Renal function studies – evaluate for kidney disease
    • Troponin I or T should be assessed in patients presenting with acutely decompensated congestive heart failure (American College of Cardiology Foundation [ACCF]/AHA, 2013)
      • Can be used to evaluate for acute coronary syndrome – does not necessarily indicate acute coronary syndrome
      • May be indicative of cardiac ischemia and myocyte damage related to heart failure mechanism
    • Thyroid stimulating hormone (TSH) – rule out thyroid dysfunction
    • Glycosylated hemoglobin – rule out diabetes mellitus
    • Iron studies – consider in suspected iron overload cases
    • Lipid studies – rule out coronary artery disease
      • Avoid ordering expanded lipid panels (particle sizing, nuclear magnetic resonance) to screen for cardiovascular disease (Choosing Wisely: Fifteen Things Physicians and Patients Should Question, 2016; American Society for Clinical Pathology)

Imaging Studies and Procedures

  • Chest x-ray
    • Signs of heart failure
      • Bilateral interstitial infiltrates
      • Cephalization of vessels
      • Cardiomegaly
      • Kerley B lines
      • Effusion
    • Also use to evaluate for infection
  • Electrocardiogram
    • Evaluate for arrhythmia as evidence of previous myocardial infarction
  • Echocardiogram
    • Use to confirm diagnosis and to classify heart failure (heart failure with preserved ejection fraction [HFpEF], heart failure with reduced EF [HFrEF])
    • Assist with determining etiology – evaluate for ventricular hypertrophy, valvular pathology, wall motion changes
    • Test of choice before natriuretic peptide testing if patient has had urinary tract infection within 2 weeks (National Institute for Health and Clinical Excellence [NICE], 2010)
  • Computed tomographic pulmonary angiography (CTPA) scan or ventilation/perfusion (V/Q) scan
    • Evaluate for pulmonary embolism as alternative diagnosis to heart failure
  • Polysomnogram
    • Identify sleep apnea


  • Acute heart failure – worse prognosis associated with
    • Systolic BP <115 mm Hg
    • High blood urea nitrogen (BUN) (>43 mg/dL)
    • Elevated creatinine (>2.75 mg/dL)
    • Elevated troponin (≥0.01 ng/mL)
    • BNP >500 pg/mL
    • Hyponatremia (<135 mmol/L)
  • Prognostic biomarkers
    • Use of multiple biomarkers may improve risk stratification (Bayes-Genis, 2015)

Differential Diagnosis

  • Cardiac
    • Acute myocardial infarction
    • Arrhythmias (atrial fibrillation)  
    • Cardiomyopathy
    • Pericarditis/pericardial effusion
    • Myocarditis
    • Valvular disease
  • Pulmonary
    • Asthma
    • Chronic obstructive pulmonary disease (COPD)
    • Pleural effusion
    • Hereditary lung disease
    • Pneumothorax
    • Pulmonary embolism
    • Restrictive lung disease
    • Aspiration
    • Foreign body
    • Malignancy
  • Other


  • Currently there are no screening recommendations for heart failure
    • Heart failure should be considered in individuals with previous myocardial infarction or other previous cardiac damage (National Academy of Clinical Biochemistry [NACB], 2007)
  • Natriuretic peptides – use serial measurements to evaluate
    • Effect of diuretic therapy
    • Volume status in anticipation of hospital discharge
  • Digoxin – heart failure treatment in select cases
    • Monitor blood levels due to narrow therapeutic index
  • Renal function – worsening renal function associated with worse prognosis


  • Prevalence – 5-7 million afflicted and >1 million hospitalized in U.S. (American College of Cardiology Foundation [ACCF]/American Heart Association [AHA], 2013)
    • ~550,000 new cases in U.S. annually (Januzzi, 2015)
    • Estimated >60% of heart failure (HF) in U.S. is likely a consequence of coronary heart disease (He, 2001)
  • Age – typically ≥65 years
  • Sex – M>F (difference diminishes as women age)


  • Cardiac
    • Myocardial infarction/coronary artery disease
    • Valvular disease (aortic stenosis)
    • Cardiomyopathy (idiopathic, hypertrophic, postpartum, restrictive, toxic)
    • Hypertension
    • Arrhythmias (atrial fibrillation is most common)
    • Congenital heart disease
    • Myocarditis
    • Cardiotoxic medications
  • Infectious
  • Pulmonary
  • High-output cardiac failure

Risk Factors

  • Coronary artery disease
  • Increased age
  • Male sex
  • Physical inactivity
  • Cigarette smoking
  • Obesity
  • Diabetes
  • Hypertension
  • Valvular heart disease
  • Alcoholism
  • Thyroid disease


  • Terminology of HF with preserved, midrange, and reduced ejection fraction (EF) (Ponikowski, European Society of Cardiology, 2016)
    • HF with preserved EF (HFpEF) – signs and symptoms of HF with left ventricular EF remaining >50%
    • HF with reduced EF (HFrEF) – signs and symptoms of left ventricular EF <40%
    • HF with midrange EF (HFmrEF) – gray zone for individuals with an EF between 40% and 50% who have signs and symptoms of HF (controversial concept – applied more in Europe)

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
    • Congenital heart disease – 8/100,000 infants
    • Cardiomyopathy – 12/million children per year (Children’s Cardiomyopathy Foundation, 2017)


  • Most chronic heart failure (CHF) in children is related to congenital heart disease
    • Increased systolic output with pulmonary overcirculation
      • 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 section)

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-proBNP])
    • Cutoff points in children are dependent on age and sex

Imaging Studies

Refer to Diagnosis section


  • NP – not enough literature is available to suggest use is helpful in pediatric (as opposed to adult) populations
    • Single study indicated 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

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 are more common in women >75 years

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

ST2, Soluble 2002270
Method: Quantitative Enzyme Immunoassay


Possibility of interference with antireagent antibodies in patient specimen

Biological variability or reference change value for healthy adults is 30%

Galectin-3, Serum 2007138
Method: Quantitative Enzyme Immunoassay

Cystatin C, Serum 0095229
Method: Quantitative Nephelometry


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

Chow SL, Maisel AS, Anand I, Bozkurt B, de Boer RA, Felker M, Fonarow GC, Greenberg B, Januzzi JL, Kiernan MS, Liu PP, Wang TJ, Yancy CW, Zile MR, et al. Role of Biomarkers for the Prevention, Assessment, and Management of Heart Failure: A Scientific Statement From the American Heart Association. Circulation. 2017; 135(22): e1054-e1091. PubMed

Chronic heart failure in adults: management. National Institute for Health and Care Excellence. London, England. Published August 2010 [Reviewed: Jan 2014; Accessed: Nov 2017]

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 ACCF/AHA Task Force on Practice Guidelines: developed in collaboration with the ISHLT. 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

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

Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola V, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Authors/Task Force Members. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016; 37(27): 2129-200. 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

Cantinotti M, Law Y, Vittorini S, Crocetti M, Marco M, Murzi B, Clerico A. The potential and limitations of plasma BNP measurement in the diagnosis, prognosis, and management of children with heart failure due to congenital cardiac disease: an update. Heart Fail Rev. 2014; 19(6): 727-42. PubMed

Classes of Heart Failure. American Heart Association. Dallas, TX [Updated: May 2017; Accessed: Nov 2017]

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

He J, Ogden LG, Bazzano LA, Vupputuri S, Loria C, Whelton PK. Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med. 2001; 161(7): 996-1002. 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

Kuo DC, Peacock F. Diagnosing and managing acute heart failure in the emergency department. Clin Exp Emerg Med. 2015; 2(3): 141-149. 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: Nov 2017]

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

Lindberg S, Jensen JS, Pedersen SH, Galatius S, Goetze JP, Mogelvang R. MR-proANP improves prediction of mortality and cardiovascular events in patients with STEMI. Eur J Prev Cardiol. 2015; 22(6): 693-700. 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

McCullough PA, Nowak RM, McCord J, Hollander JE, Herrmann HC, Steg PG, Duc P, Westheim A, Omland T, Knudsen CW, Storrow AB, Abraham WT, Lamba S, Wu AH, Perez A, Clopton P, Krishnaswamy P, Kazanegra R, Maisel AS. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation. 2002; 106(4): 416-22. PubMed

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

Potter LR. Natriuretic peptide metabolism, clearance and degradation. FEBS J. 2011; 278(11): 1808-17. 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

Teerlink JR, Alburikan K, Metra M, Rodgers JE. Acute decompensated heart failure update. Curr Cardiol Rev. 2015; 11(1): 53-62. 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

Wicks EC, Davies LC. Heart failure - what the general physician needs to know. Clin Med (Lond). 2016; 16(1): 25-33. 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

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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

Content Reviewed: 
November 2017

Last Update: December 2017