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When a patient arrives in the emergency department struggling to breathe, clinicians face a critical question: Is this heart failure? For millions of patients each year, the answer hinges on the N-terminal brain natriuretic protein (NT-proBNP) biomarker test. But what happens when the patient's body chemistry doesn't follow the standard playbook?
New research from the PRECISE-HF study challenges long-held assumptions about natriuretic peptide thresholds, suggesting that a more personalized diagnostic approach could prevent heart failure from being missed in patients with obesity.
Two Epidemics on a Collision Course
The numbers tell a sobering story. Heart failure currently affects 6.7 million Americans over age 20, with projections showing that figure will climb to 11.4 million by 2050.1 Meanwhile, obesity prevalence is expected to approach 50% of all American adults by 2030.2 These intersecting trends create a diagnostic blind spot that clinicians are only beginning to address.
"Obesity is associated with lower natriuretic peptide levels, which potentially reduces the sensitivity for diagnosing heart failure in patients coming to the emergency department with symptoms," explains Dr. Brandon Allen, an emergency physician and cardiac biomarkers researcher at the University of Florida. "We wanted to know: what if we lowered those thresholds based on elevated BMI?"
The Case for NT-proBNP
Before diving into the research findings, it's worth understanding why NT-proBNP has become an essential tool in the heart failure diagnostic workup.
Both BNP and NT-proBNP serve as markers of cardiac stress, released when the heart is under strain. However, they behave quite differently in clinical practice. BNP is less sensitive for early detection, with a shorter half-life and lower bloodstream concentrations. Conversely, NT-proBNP is more sensitive for early detection with a longer half-life and higher bloodstream concentration.
There's another critical distinction for today's patients. Modern heart failure therapeutics, specifically angiotensin receptor neprilysin inhibitors (ARNIs) like sacubitril/valsartan (Entresto), inhibit the breakdown of BNP, leading to artificially high BNP levels in the bloodstream. NT-proBNP remains unaffected by these medications, making it a more reliable marker for patients on contemporary treatment regimens.
"When we think about precision and accuracy, there's a lot of trust that goes into that," Dr. Allen notes. "We all want high accuracy and high precision with our assays, because that's what allows clinicians to make sound decisions."
Uncovering the Diagnostic Gap
The PRECISE-HF study enrolled nearly 2,400 patients across 17 U.S. sites, providing a robust dataset to examine how obesity affects diagnostic performance. Dr. Allen presented a sub-analysis of these findings at the European Society of Cardiology Congress, focusing specifically on patients with a BMI of 30 or greater.
The standard NT-proBNP rule-out threshold, the level below which heart failure can be confidently excluded, is 300 pg/mL. The research team asked a simple but consequential question: What happens to diagnostic performance in obese patients if that threshold is lowered to 150 pg/mL?
The findings were striking. Among patients in the study who were adjudicated to have heart failure but had NT-proBNP values below the standard 300 pg/mL cutoff, 91% were obese (BMI > 30). In other words, obesity was the primary driver of false negatives. Patients with genuine heart failure might be sent home without appropriate treatment.
"I think we identified a real opportunity here," Dr. Allen reflects. "That 91% figure was pretty telling."
Maintaining Performance at a Lower Threshold
The encouraging news: lowering the threshold didn't compromise diagnostic accuracy. When the cutoff was adjusted to 150 pg/mL for patients with obesity, the test maintained its clinical utility:
- Sensitivity remained high at approximately 96%
- Negative predictive value stayed robust, preserving the test's ability to safely rule out heart failure
- Area under the curve held steady at 0.87, indicating strong overall diagnostic performance
These results suggest that a BMI-adjusted approach could capture heart failure cases that would otherwise be missed, without generating a flood of false positives that burden the healthcare system.
Looking Toward Precision Diagnostics
While these findings are promising, Dr. Allen emphasizes that more work remains. Future research should examine patients with more severe obesity (BMI ≥ 40) and explore how machine learning might enable automated, individualized threshold adjustments.
"The possibilities are endless in this space," he observes. "We're moving toward a world where we can use precision medicine to really adjust these things for individual patients."
For now, the clinical takeaway is clear: a lower NT-proBNP threshold of 150 pg/mL maintains diagnostic safety and accuracy for ruling out heart failure in patients with obesity. As guidelines evolve to reflect this evidence, laboratories and clinicians alike will be better equipped to catch heart failure in a population where it has historically been overlooked.
The Bigger Picture
At its core, this research represents what diagnostic innovation should accomplish: identifying gaps in current practice, generating evidence to address them, and ultimately improving outcomes for patients who might otherwise fall through the cracks.
For laboratory professionals navigating the dual challenges of operational efficiency and clinical excellence, studies like PRECISE-HF underscore why assay selection and interpretation guidelines matter. The test itself is only as valuable as the clinical framework surrounding it, and that framework must evolve alongside our understanding of patient populations.
As obesity rates continue to climb and heart failure prevalence grows, the diagnostic decisions made in emergency departments today will shape patient outcomes for decades to come. Research like this ensures those decisions are informed by sound clinical evidence.
The PRECISE-HF study was conducted across 17 U.S. sites with sponsorship from Beckman Coulter. Dr. Brandon Allen presented these findings at the European Society of Cardiology Congress.
