IGFBP7-to-BNP Ratios for HFpEF Versus HFrEF Detection

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Solution Overview

Problem

Current biomarker-based methods are cumbersome and ineffective for reliably differentiating between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF, as existing markers like NT-proBNP show stronger associations to systolic dysfunction rather than diastolic abnormalities, and there is a lack of established biomarkers for HFpEF diagnosis.

Innovation Solution

The use of the ratio of IGFBP-7 to a BNP-type peptide (such as NT-proBNP) and the ratio of the sum of IGFBP-7+CRP to the amount of a BNP-type peptide for calculating and comparing with reference ratios to differentiate between HFpEF and HFrEF, aided by automation and computer-implemented calculations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If BNP-type peptides (NT-proBNP) are used as biomarkers for heart failure diagnosis, then the ability to detect systolic dysfunction is improved, but the ability to differentiate HFpEF from HFrEF deteriorates

Engineering Contradiction:

Improvedetection of systolic dysfunctionVSAvoiddifferentiation between HFpEF and HFrEF

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent changes the biomarker parameters from using BNP-type peptides alone to using a combination of IGFBP-7 and BNP-type peptides. IGFBP-7 shows stronger associations with diastolic dysfunction and HFpEF, while BNP-type peptides remain useful for detecting systolic dysfunction. This parameter change enables reliable differentiation between HFpEF and HFrEF by leveraging the complementary strengths of both biomarkers.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If multiple biomarkers are combined for HFpEF diagnosis, then the diagnostic accuracy is improved, but the complexity of the diagnostic method increases

Engineering Contradiction:

Improvediagnostic accuracy for HFpEFVSAvoidcomplexity of biomarker-based method

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and focuses on the most discriminatory biomarker combination for HFpEF diagnosis: IGFBP-7 and BNP-type peptides. By selecting this specific pair of biomarkers that show complementary patterns in HFpEF versus HFrEF, the method achieves high diagnostic accuracy without the need to measure numerous biomarkers, thereby reducing diagnostic complexity while maintaining reliability.

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS12461113B2IGFBP7 ratio for HFpEF

Publication Date: 2025.11.04 ROCHE DIAGNOSTICS OPERATIONS INC

AI summary

The present invention relates to a method for differentiating between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) in a subject suffering from heart failure, said method comprising the steps of determining the amounts of IGFBP7 (Insulin-like growth factor-binding protein 7), of a BNP-type peptide, and optionally of CRP (C-reactive protein) in a sample from the subject, calculating (i) a ratio of the amount of IGFBP7 and the amount of the BNP-peptide or (ii) a ratio of the sum of the amounts of IGFBP7 and CRP and the amount of the BNP-type peptide, comparing the ratio calculated with a reference ratio, and differentiating between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). The present invention further concerns a method for the diagnosis of HFpEF.