NT-proBNP, the go-to peptide biomarker for heart failure, often gives misleading results in HFpEF patients, and this review proposes a structured pathway combining adjusted thresholds with imaging to improve diagnosis.
~50% of heart failure casesHFpEF accounts for roughly half of all heart failure globally but remains one of the most underdiagnosed cardiovascular conditions
What the researchers found
NT-proBNP is a widely used biomarker for heart failure, but its diagnostic accuracy in HFpEF (heart failure with preserved ejection fraction) is compromised by age, obesity, atrial fibrillation, and kidney dysfunction. This review proposes a structured clinical pathway that combines adjusted NT-proBNP thresholds, clinical scoring systems like the H2FPEF and HFA-PEFF scores, and multimodal imaging to improve diagnosis of this commonly missed condition.
HFpEF accounts for approximately 50% of all heart failure cases globally but remains one of the most underdiagnosed cardiovascular conditions because its symptoms mimic those of other age-related conditions.
Why it matters
Half of all heart failure patients have HFpEF, yet many go undiagnosed because the standard biomarker (NT-proBNP) can be misleading in the very populations most affected — older adults with obesity, kidney problems, or irregular heart rhythms. A structured diagnostic approach could catch thousands of missed cases and connect patients to treatment earlier.
The numbers in context
~50% of global HF cases are HFpEF · Evidence compiled from 2022-2025 · Confounders: age, obesity, atrial fibrillation, renal dysfunction
How the study worked
Narrative review critically analyzing recent evidence from 2022-2025 on NT-proBNP's diagnostic role in HFpEF. The authors propose a stepwise clinical pathway integrating adjusted biomarker thresholds, validated scoring systems, and imaging modalities.
Who was studied
Not applicable (review article focused on HFpEF diagnosis in clinical populations, particularly older adults with comorbidities)
What this study cannot tell us
As a narrative review published in Cureus (an open-access journal with lighter peer review), the evidence synthesis may not be as rigorous as a systematic review. The proposed clinical pathway has not been prospectively validated. The abstract doesn't detail how studies were selected or assessed for quality.
How to read the evidence
This is a narrative review compiling evidence from 2022-2025. It proposes a clinical pathway but does not present new clinical data or use systematic review methodology. Published in Cureus, which has a less rigorous peer review process than top cardiology journals.
When this study was published
Published in 2025, this review incorporates the most recent evidence (2022-2025) on NT-proBNP utility in HFpEF, making it highly current.
The bigger picture
NT-proBNP is one of the most important peptide biomarkers in medicine, used millions of times annually to diagnose heart failure. But as the understanding of HFpEF has evolved, it's become clear that a single biomarker cutoff isn't sufficient. This review reflects a broader trend in peptide biomarker research toward context-dependent interpretation rather than one-size-fits-all thresholds.
Questions still open
- Would prospective validation of the proposed clinical pathway show improved HFpEF detection rates compared to standard NT-proBNP interpretation?
- Could machine learning algorithms that integrate NT-proBNP with patient demographics and comorbidities outperform fixed adjusted thresholds?
- Are there emerging peptide biomarkers that could complement NT-proBNP specifically for HFpEF diagnosis?
Common questions
What is NT-proBNP and why is it tested?
Why does NT-proBNP miss so many HFpEF cases?
Read the original research
Optimizing the Use of N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) in the Diagnosis of Heart Failure With Preserved Ejection Fraction (HFpEF): A Clinical Pathway Approach to an Underdiagnosed Entity.
Cureus, 17(12), e99161
Citation
Gupta, Mukulesh; Kumar, Dinesh; Gupta, Tuhina. (2025). Optimizing the Use of N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) in the Diagnosis of Heart Failure With Preserved Ejection Fraction (HFpEF): A Clinical Pathway Approach to an Underdiagnosed Entity.. Cureus, 17(12), e99161. https://doi.org/10.7759/cureus.99161