What is the rationale for ordering a Brain Natriuretic Peptide (BNP) test and a Bilateral Lower Extremity (BLLE) ultrasound in a patient with symptoms of shortness of breath (dyspnea) and swelling in the lower extremities, but with a normal 2-dimensional echocardiogram (2D echo), normal Ejection Fraction (EF), and normal Right Ventricular Systolic Pressure (RVSP)?

Rationale for BNP Testing and Lower Extremity Ultrasound in Patients with Normal Echocardiogram

BNP testing and bilateral lower extremity ultrasound are recommended in patients with shortness of breath and lower extremity edema despite normal echocardiographic findings to rule out alternative diagnoses and identify conditions that may not be apparent on standard echocardiography. 1, 2

Diagnostic Value of BNP Testing

• BNP testing improves diagnostic accuracy compared to standard clinical judgment alone in patients presenting with dyspnea, with high sensitivity (90%) and moderate specificity (76%) for diagnosing heart failure 1, 2

• BNP levels <100 pg/mL or NT-proBNP <300 pg/mL make acute heart failure syndrome unlikely (approximate negative likelihood ratio of 0.1), which helps rule out heart failure as a cause of symptoms 1, 3

• BNP testing in emergency departments improves evaluation and treatment of patients with acute dyspnea, reducing time to discharge and total treatment costs 1, 2

• BNP testing is particularly valuable when clinical assessment is uncertain, as it can reduce clinical indecision by up to 74% 4

Reasons for BNP Testing Despite Normal Echo

• Normal echocardiographic findings (normal EF, normal RVSP) do not completely exclude heart failure with preserved ejection fraction (HFpEF), which may present with normal systolic function but abnormal diastolic function 1

• Approximately 29% of patients with confirmed HFpEF can have normal BNP levels (≤100 pg/mL) despite elevated pulmonary capillary wedge pressures, making both echo and BNP testing complementary rather than redundant 5

• BNP analysis in association with echocardiographic filling patterns improves diagnostic accuracy, as a normal BNP level along with completely normal diastolic end-filling parameters makes heart failure much less likely 1

• BNP testing helps identify alternative diagnoses such as pulmonary embolism, COPD exacerbation, or other causes of dyspnea when levels are low despite significant symptoms 1, 3

Rationale for Lower Extremity Ultrasound

• Bilateral lower extremity ultrasound is indicated to evaluate for deep vein thrombosis (DVT) as a potential cause of lower extremity edema and possible source of pulmonary embolism, which can present with dyspnea 1

• In unstable patients with suspected pulmonary embolism, bedside cardiac ultrasonography and venous examination of the proximal bilateral lower extremities should be considered prior to CT imaging 1

• Lower extremity ultrasound can identify venous insufficiency or other vascular causes of edema that would not be apparent on echocardiography 1

• The combination of BNP testing and lower extremity ultrasound provides complementary diagnostic information that helps distinguish between cardiac and non-cardiac causes of dyspnea and edema 1, 3

Clinical Algorithm for Patients with Normal Echo but Persistent Symptoms

1. Measure BNP/NT-proBNP levels:

   • If BNP <100 pg/mL or NT-proBNP <300 pg/mL: Heart failure is unlikely; consider alternative diagnoses 1, 2
   • If BNP >500 pg/mL or NT-proBNP >1,000 pg/mL: Heart failure is likely despite normal echo; consider HFpEF with diastolic dysfunction 1, 3

2. Perform bilateral lower extremity ultrasound:

   • To evaluate for DVT as a cause of lower extremity edema and possible source of pulmonary embolism 1
   • To assess for venous insufficiency or other vascular causes of edema 1

3. Consider additional testing based on results:

   • If both tests are negative, consider other causes such as pulmonary disease, anemia, or deconditioning 1, 6
   • If BNP is elevated despite normal echo, consider more detailed assessment of diastolic function or other cardiac conditions 1, 5

Common Pitfalls to Avoid

• Relying solely on echocardiography to rule out heart failure, as it may miss diastolic dysfunction or early stages of heart failure 1

• Failing to consider factors that affect BNP levels such as age, obesity, renal function, and atrial fibrillation when interpreting results 2, 3

• Overlooking non-cardiac causes of dyspnea and edema when echocardiography is normal 1, 6

• Dismissing the possibility of heart failure in obese patients who may have lower BNP levels despite having heart failure 3, 5