Heart Failure

Heart failure (HF), a common clinical syndrome with high morbidity and mortality, results from a structural or functional cardiac issue that leads to impaired ventricular filling or ejection.   The incidence of HF increases with age.  Symptoms and signs of HF are nonspecific, which presents a diagnostic challenge. These symptoms include dyspnea, fatigue, exercise intolerance, fluid retention, and edema.  Measurement of natriuretic peptides, particularly B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), may be used to support a diagnosis of HF, inform prognosis, guide therapy, and monitor disease progression and therapeutic response.   Additional laboratory testing may be used to identify possible HF etiologies or alternative diagnoses,  inform prognosis, and monitor treatment and the development of comorbidities.

Quick Answers for Clinicians

What are the risk factors for heart failure, and what are the important comorbidities in heart failure?

Risk factors for heart failure (HF) include hypertension, diabetes mellitus, metabolic syndrome, and atherosclerotic disease.  Several cardiomyopathies may also lead to the development of HF.  Important comorbidities include atrial fibrillation, anemia, hypertension, ischemic heart disease, hyperlipidemia, diabetes mellitus, and chronic kidney disease.  A thorough laboratory workup including a CBC and urinalysis, as well as electrolyte, blood urea nitrogen (BUN), creatinine, glucose, hemoglobin A1c, liver enzyme, lipid, and thyroid function tests is recommended to evaluate for risk factors and comorbidities in HF.    

What are special considerations for laboratory testing in pediatric patients with suspected heart failure?

Most heart failure (HF) in children is related to congenital heart disease.  Recommended initial testing in children includes a CBC, along with electrolyte, glucose, acid-base status, blood urea nitrogen (BUN), creatinine, liver enzyme, and thyroid function tests.  Natriuretic peptide measurement is also recommended to distinguish and confirm HF.  Due to the congenital nature of pediatric HF, genetic testing may be useful. 

What are emerging biomarkers in heart failure?

Several emerging biomarkers are currently being researched in heart failure (HF). The measurement of myocardial injury and fibrosis markers (eg, soluble ST2 receptor [sST2], galectin-3 [Gal-3], and GDF-15) has demonstrated utility in risk models for new-onset HF.  Furthermore, these markers may provide additional prognostic value when used in conjunction with natriuretic peptide measurement in acute and chronic HF.    Markers of renal function may also add value.  The use of a multiple-marker strategy (ie, several of these markers tested in conjunction) may improve risk stratification. 

Indications for Testing

Laboratory testing for HF may be used to:

  • Assess risk of developing new-onset HF
  • Support a diagnosis of HF in adult patients who present with signs and symptoms of HF or a history of cardiac disease
  • Establish prognosis in adult patients diagnosed with HF
  • Monitor disease progression and the effects of treatment

Laboratory Testing

Careful clinical evaluation (including imaging) and patient history are the primary ways to assess patients for HF; however, laboratory testing plays an important role in risk assessment, diagnosis, prognosis, and monitoring. A laboratory workup for renal, liver, and thyroid function, as well as anemia and diabetes mellitus, is recommended in suspected or newly diagnosed HF.    

Risk Assessment

Biomarkers may be useful for risk stratification in patients considered to be at increased risk for HF (eg, after myocardial infarction). Natriuretic peptides, particularly BNP and NT-proBNP, are nonspecific markers of cardiac stretch  that have been demonstrated to have predictive value for certain types of new-onset HF.  Appropriate care after natriuretic peptide-based screening may prevent the development of HF.  Serial measurement of troponin levels has also been demonstrated to have predictive value. 

Diagnosis

Natriuretic Peptides

Measurement of BNP and NT-proBNP also aids in HF diagnosis    and helps to identify patients who require further assessment.  Lower values of natriuretic peptides exclude HF,   whereas elevated natriuretic peptide values support an HF diagnosis, although natriuretic peptides may be elevated in a number of cardiac and noncardiac conditions.    ,  Natriuretic peptide levels may be reduced in individuals with obesity or in individuals of African or African-Caribbean descent.  Levels may also be reduced in those taking diuretics, angiotensin-converting enzyme inhibitors, beta blockers, angiotensin II receptor blockers, or mineralocorticoid receptor antagonists. 

Recommended Natriuretic Peptide Values to Exclude HFa,b
Clinical Setting BNP NT-proBNP
Nonacute <35 pg/mL <125 pg/mL 

<400 ng/Lc 

Acute <100 pg/mL <300 pg/mL

aEither BNP or NT-proBNP measurements may be used to support the diagnosis of HF, as long as their absolute values and cut points are not used interchangeably.  

bSpecific cutoff values are not addressed by guidelines from the American College of Cardiology, American Heart Association, and Heart Failure Society of America. 

cThe NICE 2018 guideline  recommends urgent referral for specialist assessment if NT-proBNP is >2,000 ng/L, and nonurgent referral if NT-proBNP is between 400 and 2,000 ng/L.

NICE, National Institute for Health and Care Excellence

Sources: Ponikowski, 2016 ; NICE, 2018 ; NICE, 2014 

Although BNP levels are commonly used in HF evaluation, there is substantial diversity in BNP assays, and reference materials to calibrate BNP assays are lacking.  Furthermore, the biology of the natriuretic peptides is complex, which results in variation between patients.  Therefore, the American Association for Clinical Chemistry suggests using age- and sex-specific reference and clinical decision limits and interpreting results in context.  Repeat tests should be performed using the same assay and laboratory to ensure consistency.

Cardiac Troponins​

Cardiac troponins I or T can also be tested in patients who present with suspected chronic ambulatory or acutely decompensated HF.   In addition to acute coronary syndrome, troponins may indicate cardiac ischemia and myocyte damage related to HF.  

Prognosis

Measurement of BNP or NT-proBNP is useful for establishing disease severity and prognosis in chronic HF   and for prognosis in the acute setting.   Cardiac troponins may add additional prognostic value. 

Monitoring

Natriuretic Peptides

Serial natriuretic peptide measurements can be used to evaluate the effect of diuretic therapy and monitor volume status in anticipation of hospital discharge, although the usefulness of natriuretic peptide levels to reduce hospital stay or mortality has not been well established.  In certain euvolemic patients, BNP or NT-proBNP levels can be used to achieve optimal guideline-directed medical therapy; however, the use of natriuretic peptide-guided therapy in acutely decompensated HF is not well established.   Recent guidelines recommend consideration of NT-proBNP measurement for treatment optimization only in a specialist care setting for patients <75 years of age who have HF with reduced ejection fraction and an estimated glomerular filtration rate of >60 mL/min/1.73m2.  BNP may not be a suitable biomarker of HF in patients treated with sacubitril/valsartan; NT-proBNP may be more suitable.

Renal Function Monitoring

Serum electrolyte and renal function tests are recommended for serial monitoring in HF, both in the acute and chronic settings, because worsening renal function is associated with a poor prognosis.  The frequency of renal function monitoring depends on the clinical status of the patient.   Serum electrolytes and renal function tests are also recommended in patients on angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and diuretics.  

Additional Treatment Monitoring

Measurement of serum digoxin at 8-12 hours following a dose can be used to assess suspected toxicity or nonadherence to digoxin therapy.  Liver and thyroid function tests should be offered as part of a routine clinical review in patients taking amiodarone. 

Pediatrics

Pediatric patients with HF require special consideration because pediatric HF may present differently from adult HF and, unlike adult HF, is primarily linked to congenital heart disease.  Recommended initial testing in pediatric patients consists of measuring electrolytes, glucose, blood urea nitrogen (BUN), creatinine, and thyroid hormone levels, along with liver function tests and a CBC.  These tests may be repeated as needed to monitor clinical status.  Natriuretic peptides have demonstrated value as confirmatory tests for acute HF in children; NT-proBNP may be more useful due to its longer half-life and higher stability relative to BNP.  Cardiac troponins and other biomarkers are of limited utility in pediatric patients.  Genetic testing may be useful, as the majority of pediatric cases are thought to have a genetic basis; early identification of a genetic etiology of HF may enable disease-specific treatment and identification of at-risk family members and could guide reproductive counseling. 

ARUP Laboratory Tests

Natriuretic Peptides

Aids in diagnosis, prognosis, and management of acute and chronic HF

Cardiac Troponins

Complements prognostic value of natriuretic peptides and aids in risk stratification

Emerging Markers

Complements prognostic value of natriuretic peptides and aids in risk stratification

Treatment Monitoring

Use to monitor blood levels of digoxin

Medical Experts

Contributor

Genzen

Jonathan R. Genzen, MD, PhD
Associate Professor of Clinical Pathology, University of Utah
Chief Operations Officer, Medical Director of Automated Core Laboratory, ARUP Laboratories

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®