Metabolite Factor Panel for HFpEF Risk Stratification
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Solution Overview
Problem
Current biomarkers for heart failure with preserved ejection fraction (HFpEF) are incomplete, failing to effectively discriminate between HFpEF and risk prediction, leading to inadequate diagnostics and treatment strategies.
Innovation Solution
The method involves determining the levels of specific metabolites such as medium-chain acylcarnitines, short-chain dicarboxylacylcarnitines, long-chain acylcarnitines, ketone-related metabolites, glycine, ornithine, tiglyl-carnitine, 3-hydroxy-linoleyl-carnitine, and docosanoyl-carnitine in patient samples, using techniques like mass spectrometry, to assess the risk of death or major adverse cardiac events (MACE) and develop targeted treatment plans.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current biomarkers are used for HFpEF diagnosis, then the diagnostic process is simple, but the diagnostic accuracy is insufficient
Solution Approach 1:
The patent segments the diagnostic approach by categorizing metabolites into distinct factors (Factor 1: medium-chain acylcarnitines, Factor 3: short-chain dicarboxylacylcarnitines, Factor 4: long-chain acylcarnitines, Factor 5: ketone-related metabolites, Factor 10: glycine/ornithine/tiglyl-carnitine, Factor 12: 3-hydroxy-linoleyl-carnitine, Factor 14: docosanoyl-carnitine). This segmentation allows comprehensive metabolic profiling while organizing complexity into manageable, clinically interpretable groups, thereby improving diagnostic accuracy without overwhelming clinical utility.
2Reliability
If comprehensive metabolic profiling is performed, then risk stratification accuracy is improved, but the complexity of the method increases
Solution Approach 1:
The patent creates a universal metabolite factor panel that serves multiple functions: (1) diagnosing HFpEF, (2) stratifying risk for death or MACE, and (3) guiding treatment decisions. The same set of metabolite factors is used across different clinical scenarios, making the complex metabolic profiling method broadly applicable and clinically versatile, thereby improving reliability without proportionally increasing operational complexity.
3Measurement precision
If multiple metabolite factors are measured, then the ability to discriminate HFpEF is improved, but the cost and time of analysis increase
Solution Approach 1:
The patent performs preliminary organization of metabolite data into predefined factors (Factors 1, 3, 4, 5, 10, 12, 14) based on established metabolic pathways and clinical relevance. This preliminary structuring of the metabolome allows rapid interpretation of complex metabolic profiles, enabling high-resolution HFpEF discrimination without proportionally increasing analysis time, as the framework is prepared in advance rather than requiring de novo analysis of each metabolite.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach provides improved diagnostic accuracy and risk stratification for HFpEF, enabling more effective management and prognosis of cardiovascular events by identifying specific metabolic biomarkers associated with HFpEF.
Implementation Method 1
using techniques like mass spectrometry, to assess the risk of death or major adverse cardiac events (MACE)
Data Source
AI summary
Disclosed herein are compositions and methods for targeted metabolomics profiling to provide absolute quantification of a broad array of metabolic intermediates of fatty acids, amino acids, and carbohydrate metabolism for HFpEF. In an aspect, the disclosure relates to a method for assessing risk of death or a major adverse cardiac event (MACE) in a subject diagnosed with heart failure with preserved ejection fraction (HFpEF). The method may include (a) determining in a sample from the subject the level of each metabolite in at least one factor, wherein the factor is selected from the group consisting of factor 1, factor 3, factor 4, factor 5, factor 10, factor 12, and factor 14; and (b) comparing the level of each metabolite in the sample to a standard, wherein the level of the metabolite in the subject relative to a standard is indicative of the risk of death or MACE in the subject.