How do you diagnose congestive heart failure (CHF) in a patient with a normal brain natriuretic peptide (BNP) level?

Diagnosing Heart Failure with Normal BNP: Understanding False Negatives

While a normal BNP (<100 pg/mL) or NT-proBNP (<400 pg/mL) makes heart failure unlikely in untreated patients with a negative predictive value of approximately 90-94%, false negatives can occur, and the diagnosis must rely on echocardiography combined with clinical assessment, ECG findings, and evaluation of specific conditions that suppress natriuretic peptide levels. 1, 2, 3

When BNP Can Be Falsely Normal Despite Heart Failure

Obesity-Related Suppression

• Obese patients (BMI >30 kg/m²) frequently have falsely low BNP values that mask cardiac dysfunction, requiring a 20-30% reduction in diagnostic thresholds 2, 3
• This represents one of the most common causes of false-negative BNP results in clinical practice 3

Flash Pulmonary Edema

• Acute presentations without sufficient time for BNP elevation can occur, particularly in acute mitral regurgitation or hypertensive crisis 1

Heart Failure with Preserved Ejection Fraction (HFpEF)

• The diagnostic potential of natriuretic peptides is less clear when systolic function is normal, as BNP elevation may be less pronounced in diastolic dysfunction 1
• HFpEF patients may have normal or only mildly elevated BNP despite significant symptoms 1

Diagnostic Algorithm When BNP is Normal

Step 1: Evaluate the ECG

• If the ECG is completely normal, heart failure—especially with systolic dysfunction—is unlikely (<10% probability) 1
• An abnormal ECG warrants further investigation regardless of normal BNP 1
• Look specifically for: pathological Q-waves (prior MI), left ventricular hypertrophy, QRS duration ≥120 ms (dyssynchrony), atrial fibrillation, or ischemic changes 1

Step 2: Perform Echocardiography

• Echocardiography is the diagnostic standard and must be performed to confirm or exclude heart failure when clinical suspicion persists despite normal BNP 1
• Assess left ventricular ejection fraction (LVEF), wall motion abnormalities, valvular disease, and diastolic dysfunction 1, 4
• For HFpEF diagnosis, three conditions must be satisfied: (1) symptoms/signs of heart failure, (2) normal or mildly abnormal LVEF (45-50%), and (3) evidence of abnormal left ventricular stiffness 1

Step 3: Chest X-Ray Evaluation

• Assess for cardiomegaly, pulmonary venous congestion, interstitial edema, or pleural effusions 1
• A displaced cardiac apex, third heart sound, and chest radiography findings of venous congestion or interstitial edema are useful in identifying heart failure 5
• Note that significant LV systolic dysfunction can be present without cardiomegaly on chest X-ray 1

Step 4: Clinical Examination Findings

• Look for elevated jugular venous pressure, peripheral edema, pulmonary rales, S3 gallop, and hepatomegaly 1, 5
• A third heart sound is particularly specific for heart failure 5

Step 5: Laboratory Assessment

• Complete blood count, electrolytes, creatinine/eGFR, liver enzymes, thyroid function, and glucose 1
• Cardiac troponins if acute coronary syndrome is suspected 1, 6

Common Pitfalls and How to Avoid Them

Do Not Rely on BNP Alone in Obese Patients

• Always consider obesity as a cause of falsely low BNP and lower your diagnostic threshold accordingly 2, 3
• In obese patients with clinical signs of heart failure, proceed directly to echocardiography regardless of BNP level 3

Do Not Dismiss HFpEF

• Up to 40-50% of heart failure patients have diastolic heart failure with preserved left ventricular function, and BNP may be less elevated in these patients 5
• Echocardiographic assessment of diastolic function is essential 1

Do Not Skip the ECG

• A completely normal ECG makes heart failure unlikely and should prompt reconsideration of the diagnosis 1
• Conversely, an abnormal ECG in the setting of normal BNP warrants echocardiography 1

Consider the Clinical Context

• In the acute setting, BNP <100 pg/mL has a negative predictive value of 94% for ruling out heart failure, but this applies to untreated patients 2, 3
• Patients already on diuretics or other heart failure therapies may have suppressed BNP levels 1, 2

Summary of False-Negative Scenarios

The most important false-negative scenarios include:

• Obesity (most common) 2, 3
• HFpEF/diastolic dysfunction 1
• Flash pulmonary edema without time for BNP elevation 1
• Patients already on heart failure treatment 1, 2

When clinical suspicion for heart failure remains high despite normal BNP, proceed directly to echocardiography—this is the definitive diagnostic test and should not be delayed. 1, 4