Heart Failure

Indications for Testing

Clinical diagnosis compatible with CHF; Framingham criteria may be helpful

Criteria for Diagnosis

Framingham criteria to establish clinical diagnosis of congestive heart failure

At least 1 major and 2 minor criteria must be met
- Major criteria
  - Paroxysmal nocturnal dyspnea
  - Neck vein distention
  - Rales
  - Cardiomegaly
  - Acute pulmonary edema
  - S3 gallop
  - Increased venous pressure (>16 cm H₂0)
- Minor criteria
  - Extremity edema
  - Nocturnal cough
  - Dyspnea on exertion
  - Hepatomegaly/splenomegaly
  - Pleural effusion
  - Cardiac output reduced by one-third from normal
  - Tachycardia (≥120 bpm)
- Major or minor criteria
  - Weight loss ≥4.5 kg over 5 days of treatment

Laboratory Testing

Initial testing – CBC, urinalysis, electrolytes, BUN, creatinine, transaminases

Natriuretic peptides – B-type (BNP) and N-terminal proBNP (NT proBNP)

High sensitivity and specificity for differentiating between cardiac and noncardiac causes
- Useful to rule out CHF due to high negative predictive value (>98%)
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
- BNP <100 pg/mL or NT proBNP <300 pg/mL – heart failure unlikely
  - Cutoff of 100 pg/mL provides maximal combination of sensitivity, specificity and negative predictive value for contributing to diagnosis of CHF
- BNP 100-500 pg/mL or NT proBNP 300-450 pg/mL (<50 years) or 300-900 pg/mL (50-75 years) – heart failure possible
- BNP >500 pg/mL or NT proBNP >450 pg/mL (<50 years) or >900 pg/mL (≥50 years) – heart failure likely
Performs slightly better in men than in women and in younger (<70 years) rather than older patients; may not be as useful in the very aged (>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 not useful in patients with shock – elevated in both septic and cardiac shock
In renal failure (GFR <60 mL/min/1.73 m²) – BNP 200 pg/mL or NT-proBNP 1,200 pg/mL
- Cut points change (BNP and NT-proBNP are cleared renally)

Other possible testing
- TSH – rule out hyper- or hypothyroidism
- Fasting transferrin in patients of northern European descent – rule out hemochromatosis
- Lipid studies
- Glycosylated hemoglobin – rule out DM

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

EKG – Q waves, ventricular hypertrophy, heart block, atrial fibrillation
Echocardiogram – frequently reduced ejection fraction
Sleep study

Prognosis

BNP
- Several recent studies suggest BNP value at discharge may be reliable indicator of recurrent admission and morbidity
- <300 pg/mL associated with benign course
- Reduction of NPs during therapy associated with improved clinical outcome
Soluble ST2
- Several recent studies suggest that higher levels are associated with mortality and morbidity at 1 year
- Complements prognostic value of NT-proBNP
- Useful in risk stratification and assessment in patients with known CVD
- Not yet approved by FDA

Differential Diagnosis

Cardiac
- Acute myocardial infarction
- Cardiomyopathy
- Valvular disease
- Pericarditis
- Arrhythmias (atrial fibrillation)
Pulmonary
- COPD
- Asthma
- Restrictive lung disease
- Hereditary lung disease
- Pneumothorax
- Pulmonary embolism
Other
- Septic shock
- Metabolic conditions
- Thyrotoxicosis
- Anxiety
- Neuromuscular disorders
- Obesity
- Anemia

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)
- BNP or NT proBNP

Serial use of NP measurements to guide titration of therapy
- No randomized studies prove risk vs. benefit ratio is acceptable

Heart failure is a clinical syndrome in which the heart muscle is unable to pump enough blood to meet tissue demands. It is often referred to as congestive heart failure (CHF).

Epidemiology

Prevalence
- >10% in patients >80 years (NHANES:2005-2006)
- 1% in patients <60 years
Age – ≥65 years
Sex – M>F (difference narrows as women age)

Etiology – numerous

Cardiac
- Myocardial infarction/ischemic heart disease
- Arrhythmias (atrial fibrillation is most common)
- Hypertension
- Myocarditis
- Congenital heart disease
- Valvular disease (aortic stenosis)
Infectious
- Sepsis
- Endocarditis
Pulmonary
- Embolism
- Hypertension
- Chronic obstructive pulmonary disease (COPD)
High-output forms
- Anemia
- Thyrotoxicosis

Risk Factors

Categorization

Diastolic vs. systolic dysfunction
Low-output vs. high-output
Acute vs. chronic
Left-sided vs. right-sided

Clinical Presentation

Dyspnea, orthopnea, paroxysmal nocturnal dyspnea
Fatigue and weakness
Nausea and anorexia
Physical examination includes tachycardia, S3/S4, pulsus alternans, pulmonary rales, ascites, hepatomegaly, jaundice, pedal edema, cachexia

Clinical Background

Epidemiology

Incidence – cardiomyopathy occurs in 8/100,000 infants

Etiology

Most chronic heart failure in children is related to congenital heart disease
- Increased systolic output with pulmonary over-circulation
  - Ventricular septal defect (VSD)
  - Large patent ductus arteriosus (PDA)
  - Persistent aorta pulmonary connections
- Low cardiac output
  - Hyperplastic left heart
  - Critical aortic stenosis
  - Severe coarctation of the aorta
- Acquired disorders
  - Rheumatic heart disease
  - Acute myocarditis
  - Anti-neoplastic drugs
  - Nutritional cardiomyopathy

Clinical Presentation

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

Diagnosis

Indications for Testing

Clinical diagnosis compatible with congestive heart failure; Framingham criteria may be helpful (refer to Diagnosis tab)

Laboratory Testing

Initial testing – CBC, urinalysis, electrolytes, BUN, creatinine, transaminases
Natriuretic peptides (BNP and NT-proBNP)
- Different optimal diagnostic cutoff values necessary
  - Higher concentrations of natriuretic peptides that decrease rapidly
- Natriuretic cutpoints 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 – unlike adults, not enough literature available to suggest use is helpful
- Single study indicated BNP ≥300 pg/mL was prognostic for poorer outcome (Price, et al, Circulation, 2006)

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Rule out sepsis

Test name: Urinalysis, Complete

ARUP #: 0020350

Methodology: Reflective Photometry/Microscopic by Yellow IRIS

Use:

Rule out infection and hematuria

Test name: Electrolyte Panel

ARUP #: 0020410

Methodology: Quantitative Ion-Selective Electrode/Enzymatic

Use:

Rule out electrolyte abnormalities

Test name: Hepatic Function Panel

ARUP #: 0020416

Methodology: Refer to individual components.

Use:

Rule out hepatic involvement

Test name: Creatinine, Serum or Plasma

ARUP #: 0020025

Methodology: Quantitative Enzymatic

Use:

Rule out renal failure

Test name: proBrain Natriuretic Peptide, NT

ARUP #: 0050083

Methodology: Quantitative Electrochemiluminescent Immunoassay

Use:

Aid in assessing severity of CHF in symptomatic and asymptomatic patients

Pro-BNP is generally more sensitive but less specific than BNP

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)

Test name: ST2, Soluble

ARUP #: 2002270

Methodology: Quantitative Enzyme Immunoassay

Use:

Aid in assessing severity of CHF in symptomatic and asymptomatic patients

Test complements prognostic value of NT-proBNP

Limitations:

Results not intended to be used as sole means for clinical diagnosis or patient management decisions

Test name: B-Type Natriuretic Peptide

ARUP #: 0030191

Methodology: Quantitative Chemiluminescent Immunoassay

Use: Aid in assessing severity of CHF in symptomatic and asymptomatic patients

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)

Additional Tests Available

Test name: Digitoxin

ARUP #: 0090085

Methodology: Quantitative CEDIA Immunoassay

Comments:

Test name: Digoxin

ARUP #: 0090080

Methodology: Enzyme Immunoassay

Comments: