BNP <100 pg/mL in Sepsis Does NOT Reliably Rule Out Heart Failure
In septic patients, a BNP below 100 pg/mL cannot be used to exclude heart failure because sepsis itself elevates BNP independent of cardiac dysfunction, markedly reducing the test's diagnostic accuracy. 1
Why the Standard Rule-Out Threshold Fails in Sepsis
Sepsis Independently Elevates BNP
Sepsis is explicitly listed by the European Society of Cardiology as a non-cardiac cause of elevated natriuretic peptides, appearing alongside conditions like renal dysfunction, liver cirrhosis, and severe infections as confounders that can raise BNP without heart failure being present. 2
In patients with severe sepsis or septic shock, BNP levels are highly elevated and comparable to those found in acute heart failure patients (median 572 ng/L in sepsis vs 581 ng/L in HF), despite significant hemodynamic differences between the two conditions. 3
BNP increases with sepsis severity (sepsis < severe sepsis < septic shock) and correlates with Sequential Organ Failure Assessment scores (r² = 0.74), functioning more as a marker of overall illness severity than cardiac dysfunction. 4, 5
The Mechanism Behind BNP Elevation in Sepsis
Sepsis causes upregulation of proinflammatory cytokines that directly damage cardiomyocytes and produce cardiac contractile dysfunction, triggering BNP release even without traditional heart failure. 5
Sepsis-associated myocardial dysfunction occurs through inflammation-mediated mechanisms distinct from volume overload or chronic heart failure, yet still stimulates BNP secretion. 3
Guideline-Based Approach to Cardiac Assessment in Sepsis
Do Not Rely on BNP Thresholds
Current guidelines advise that BNP results be interpreted together with clinical examination and imaging studies to exclude non-cardiac causes such as sepsis. 1
The standard BNP <100 pg/mL rule-out threshold should not be used to exclude heart failure in sepsis; clinicians should proceed directly to cardiac imaging for definitive assessment. 1
Proceed Directly to Echocardiography
When evaluating a septic patient for possible heart failure, echocardiography is recommended to assess: 1
Left ventricular ejection fraction to identify systolic dysfunction (low EF <50% is associated with higher BNP and increased mortality in sepsis, with odds ratio = 3.03). 4
Diastolic function parameters to detect heart failure with preserved ejection fraction. 1
Right ventricular function, as RV dysfunction from sepsis-related pulmonary hypertension can elevate BNP. 1
Valvular abnormalities that may contribute to hemodynamic compromise. 1
Clinical Context: Hemodynamic Differences Despite Similar BNP
In one study comparing sepsis and heart failure patients monitored with pulmonary artery catheters, mean pulmonary artery occlusion pressure was 16 mm Hg in sepsis vs 22 mm Hg in HF (p=0.02), and cardiac index was 4.6 L/min/m² in sepsis vs 2.2 L/min/m² in HF (p=0.03)—yet BNP and NT-proBNP levels were not statistically different between groups. 3
This demonstrates that sepsis produces a hyperdynamic state with elevated BNP despite fundamentally different cardiac physiology compared to traditional heart failure.
Prognostic Value in Sepsis
In septic patients, elevated BNP should be regarded primarily as a marker of overall illness severity and prognosis rather than as a definitive indicator of heart failure. 1
BNP elevation in septic shock prognosticates survival and correlates with organ failure scores, making it useful for risk stratification but not for ruling out cardiac dysfunction. 5
Critical Pitfall to Avoid
Do not assume that a "normal" or low BNP in a septic patient excludes significant cardiac dysfunction. The inflammatory milieu of sepsis alters BNP kinetics unpredictably, and early systolic dysfunction may be present even with BNP levels that would typically exclude heart failure in non-septic patients. 4, 3