How do you diagnose congestive heart failure (CHF) and can a brain natriuretic peptide (BNP) test result in a false negative?

Diagnosing Congestive Heart Failure and BNP False Negatives

Congestive heart failure is diagnosed through a combination of clinical assessment, ECG, natriuretic peptides (BNP/NT-proBNP), and echocardiography, with BNP levels <100 pg/mL making heart failure unlikely—however, false negatives can occur in flash pulmonary edema, obesity, and early acute presentations before peptide release. 1

Diagnostic Algorithm

Initial Assessment in Acute Presentations

For patients presenting emergently with suspected heart failure:

• ECG is mandatory first-line testing - A completely normal ECG makes heart failure, especially with systolic dysfunction, unlikely (<10% probability) and should prompt reconsideration of the diagnosis 1, 2, 3
• Chest X-ray should be obtained to assess for cardiomegaly, pulmonary congestion, and pleural effusions 1
• Immediate echocardiography is recommended for shocked or severely hemodynamically compromised patients 1
• BNP/NT-proBNP measurement with high exclusion cut-off points: BNP <100 pg/mL or NT-proBNP <300 pg/mL makes heart failure unlikely 1, 3

Non-Acute Presentations (Outpatient/Primary Care)

For patients with gradual symptom onset:

• ECG first - If completely normal AND natriuretic peptides are normal, heart failure is essentially excluded 2, 3
• Natriuretic peptide testing as initial screening:
  • BNP <100 pg/mL: heart failure unlikely 1, 3
  • BNP 100-400 pg/mL: uncertain diagnosis, requires echocardiography 1
  • BNP >400 pg/mL: heart failure likely 1, 3
  • NT-proBNP <400 pg/mL: heart failure unlikely 1
  • NT-proBNP 400-2000 pg/mL: uncertain diagnosis 1
  • NT-proBNP >2000 pg/mL: heart failure likely 1

Confirmatory Testing

Echocardiography is essential to evaluate:

• Left ventricular ejection fraction (LVEF <40% = HFrEF; ≥50% = HFpEF if heart failure present) 3
• Regional and global ventricular function 1
• Valvular abnormalities 1
• Diastolic dysfunction parameters 1
• Right ventricular function and pulmonary artery pressures 1

BNP False Negatives: Critical Clinical Scenarios

When BNP Can Be Falsely Normal or Low

"Flash" pulmonary edema represents the most important false negative scenario:

• During acute flash pulmonary edema, BNP levels may remain normal at the time of admission because insufficient time has elapsed for peptide synthesis and release 1
• BNP release occurs in bursts and may lag behind acute clinical changes 4, 5

Obesity systematically lowers BNP values:

• Obese patients have lower BNP levels for any given cardiac condition, possibly due to increased clearance or suppression by sex hormones 1, 6
• Consider lowering diagnostic thresholds by 20-30% in patients with BMI ≥30 kg/m² 6

Heart failure with preserved ejection fraction (HFpEF):

• BNP levels tend to be less elevated in HFpEF compared to HFrEF 1, 6
• Normal or mildly elevated BNP does not exclude HFpEF 1

Early acute presentations:

• In the initial hours of acute decompensation, BNP may not yet be elevated despite severe hemodynamic compromise 5
• One case report documented low BNP on admission that rapidly increased after diuretic therapy despite clinical improvement 5

Factors That Lower BNP Independent of Heart Failure Status

• Treatment effects: ACE inhibitors, ARBs, and diuretics can decrease BNP levels 6
• Obesity: Results in 20-30% lower values 6
• Certain demographics: Black patients may have lower baseline values 6

Conditions That Elevate BNP Without Heart Failure

Cardiac causes:

• Acute coronary syndromes 1, 6
• Atrial fibrillation 1, 6
• Left ventricular hypertrophy 1, 6
• Valvular heart disease 6

Non-cardiac causes:

• Renal failure (decreased clearance) 1, 6
• Pulmonary embolism 1, 6
• Severe COPD with elevated right heart pressures 1
• Sepsis 1
• Advanced age (>75 years) 1, 6

Critical Pitfalls to Avoid

Do not rely on BNP alone in isolation - It should always be interpreted with clinical context, ECG, and imaging 1, 6, 5

Do not dismiss heart failure in flash pulmonary edema with normal BNP - Clinical presentation and chest X-ray findings take precedence; repeat BNP in 6-12 hours if initial value is unexpectedly low 1

Do not use standard BNP cut-offs in obese patients - Lower thresholds by 20-30% for BMI ≥30 kg/m² 6

Do not assume normal BNP excludes HFpEF - Diastolic dysfunction may present with only mildly elevated or normal BNP; echocardiographic assessment of diastolic function is required 1

Do not overlook the "grey zone" (BNP 100-400 pg/mL or NT-proBNP 300-900 pg/mL) - These patients require echocardiography for definitive diagnosis 1, 6

In patients on neprilysin inhibitors, use NT-proBNP instead of BNP for monitoring, as BNP levels are artificially elevated by these medications 6

Additional Diagnostic Tests

Routine laboratory evaluation should include:

• Complete blood count (anemia can mimic or exacerbate heart failure) 1
• Serum electrolytes, creatinine, glucose 1
• Liver enzymes 1
• Thyroid function tests (TSH) 1, 6
• Urinalysis 1

Consider coronary angiography in patients with angina, known coronary disease, or unexplained heart failure to identify reversible ischemic causes 1