Heart Failure

Diagnosis

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
      • Major criteria
        • Paroxysmal nocturnal dyspnea/orthopnea
        • Neck vein distention (in other than supine position)
        • Rales
        • Cardiomegaly determined by x-ray
        • Acute pulmonary edema determined by x-ray
        • Ventricular S3 gallop
        • Increased venous pressure (>16 cm H2O)
        • Hepatojugular reflux
        • Weight loss ≥4.5 kg over 5 days of treatment
        • Pulmonary edema, visceral congestion, cardiomegaly shown on autopsy
      • Minor criteria
        • Bilateral ankle edema
        • Nocturnal cough
        • Dyspnea on exertion
        • Hepatomegaly
        • Pleural effusion determined by x-ray
        • Cardiac output reduced by one-third from normal
        • Tachycardia (≥120 beats per minute)
        • Pulmonary vascular engorgement determined by x-ray

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
      • 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)
      • 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
    • Single cutoff point strategy BNP <100 pg/mL or NT-proBNP <900 pg/mL – CHF is unlikely
    • Performance slightly better in men versus women  and in younger (<70 years) versus older patients
    • May not be as useful in patients >75 years
    • Clinical sensitivity and specificity of NT-proBNP

       Clinical Sensitivity and Specificity of NT-proBNP

      Age (years)

      <45

      45-54

      55-64

      65-74

      ≥75

      Diagnostic cutoff (pg/mL)

      <125

      <125

      <125

      <125

      <450

      Males, clinical sensitivity

      82

      88

      90

      92

      87

      Males, clinical specificity

      96

      93

      88

      87

      89

      Females, clinical sensitivity

      87

      91

      89

      94

      82

      Females, clinical specificity

      85

      86

      80

      58

      88

    • BNP is not useful in patients with shock – levels are elevated in both septic and cardiac shock
    • 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

  • BNP
    • 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
    • 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
    • Appears to be uninfluenced by renal insufficiency
  • Galectin-3
    • Emerging prognostic biomarker – 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
  • Cystatin C
    • Emerging marker of risk in CHF – 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)

Differential Diagnosis

Screening

  • 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)

Monitoring

  • 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)

Clinical Background

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)
  • 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

Pediatrics

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)

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
proBrain Natriuretic Peptide, NT 0050083
Method: Quantitative Electrochemiluminescent Immunoassay

Aids in diagnosis, prognosis, and management of acute and chronic heart failure

ProBNP is generally more sensitive but less specific than BNP

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

Aids in diagnosis, prognosis, and management of acute and chronic heart failure

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

Aids in prognostication in patients with acute and chronic heart failure

Test complements prognostic value of NT-proBNP

Possibility of interference with anti-reagent antibodies and patient sample

Biological variability – 30% for healthy adults

 
Galectin-3, Serum 2007138
Method: Quantitative Enzyme Immunoassay

Use for prognostication in heart failure

Test complements prognostic value of NT-proBNP

   
Cystatin C, Serum 0095229
Method: Quantitative Nephelometry

Use for prognostication in heart failure

Test complements prognostic value of NT-proBNP

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Rule out sepsis

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Rule out infection and hematuria

Electrolyte Panel 0020410
Method: Quantitative Ion-Selective Electrode/Enzymatic

Rule out electrolyte abnormalities

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Rule out hepatic involvement

Creatinine, Serum or Plasma 0020025
Method: Quantitative Enzymatic

Rule out renal failure

Digitoxin 0090085
Method: Quantitative CEDIA Immunoassay
Digoxin 0090080
Method: Immunoassay