CT-proET-1 Biomarker for Syncope Therapy Stratification

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Solution Overview

Problem

Current diagnostic methods for syncope are inadequate, lacking a gold standard for diagnosis and consensus on underlying mechanisms, making it challenging to accurately diagnose and treat specific types of syncope, which is crucial for preventing recurrence and associated injuries.

Innovation Solution

A method involving the determination of CT-proET-1 levels in bodily fluids to stratify patients for cardiac pacemaker therapy, where levels above a threshold indicate orthostatic hypotension and levels below indicate cardioinhibitory reflex, guiding the need for cardiac pacemaker treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current diagnostic methods (ECG monitoring, autonomic tests, head-up tilt test) are used for syncope diagnosis, then the diagnostic process can identify potential causes, but the diagnostic accuracy is insufficient and there is no gold standard for diagnosis

Engineering Contradiction:
Improvediagnostic accuracyVSAvoiddiagnosis reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention changes the diagnostic parameter from functional tests (ECG, tilt test) to a biochemical parameter (CT-proET-1 concentration). This biomarker provides a quantitative measure that directly reflects the pathophysiological state, enabling more precise and reliable differentiation between syncope subtypes without relying on subjective test interpretations.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

CT-proET-1 serves as an intermediary biomarker that mediates between the complex physiological processes of syncope and the diagnostic assessment. This single measurable parameter translates complex autonomic and cardiovascular responses into a straightforward diagnostic indicator, resolving the uncertainty in current diagnostic methods.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If ECG monitoring and autonomic tests are performed to diagnose syncope, then potential arrhythmias and autonomic dysfunction can be detected, but the diagnostic process is time-consuming and not always successful

Engineering Contradiction:
Improvediagnosis reliabilityVSAvoiddiagnostic time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The invention performs preliminary biochemical assessment by measuring CT-proET-1 levels before proceeding to more time-consuming functional tests. This upfront biomarker measurement provides immediate diagnostic direction, reducing the overall diagnostic time by eliminating unnecessary extended monitoring and repetitive testing in many cases.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention extracts the essential diagnostic information into a single biomarker measurement (CT-proET-1), separating the critical diagnostic function from the complex battery of tests. This extraction provides rapid diagnostic insight without requiring the full time investment of comprehensive functional testing for every patient.

Inventive Principle:
Principle #2Taking out (Extraction)

3Measurement precision

If head-up tilt test is used to reproduce neurally-mediated reflex, then the diagnostic sensitivity for vasovagal syncope increases, but the test is not always successful and can be invasive

Engineering Contradiction:
Improvediagnostic sensitivityVSAvoidtest invasiveness
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

CT-proET-1 serves as a non-invasive intermediary marker that reflects the same pathophysiological mechanisms targeted by the tilt test but without requiring physical provocation. This biomarker provides equivalent diagnostic information about neurally-mediated reflex dysfunction without the discomfort, risk, or failure associated with active tilt testing.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention replaces the mechanical/physical provocation system (tilt table, active standing) with a biochemical measurement system. Instead of mechanically stressing the cardiovascular system to elicit symptoms, the biomarker measurement passively detects the underlying physiological state, eliminating test-related harm while maintaining diagnostic sensitivity.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

4Adaptability or versatility

If current classification methods based on efferent pathway (sympathetic or parasympathetic) are used, then the syncope type can be categorized, but the differential diagnosis between orthostatic hypotension and neurally-mediated reflex syncope remains difficult

Engineering Contradiction:
Improveclassification capabilityVSAvoiddifferential diagnosis accuracy
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The invention introduces a new biochemical parameter (CT-proET-1 concentration) that differentiates between syncope subtypes based on distinct pathophysiological mechanisms. Orthostatic hypotension shows elevated CT-proET-1 due to chronic sympathetic impairment, while neurally-mediated syncope shows normal or reduced levels, providing a clear biochemical distinction that resolves the diagnostic overlap.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention segments the syncope population into distinct biochemical groups based on CT-proET-1 levels, creating clear diagnostic categories. This segmentation separates patients with orthostatic hypotension from those with neurally-mediated reflex syncope, enabling tailored therapeutic approaches and eliminating the uncertainty of overlapping clinical presentations.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP2841949B1Biomarkers for the therapy stratification of syncope
Publication Date: 2017.11.22 BRAHMS GMBH
  • EP2841949B1 patent drawingFigure 1
  • EP2841949B1 patent drawingFigure 2~3
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AI summary

The present invention relates to a method for the diagnosis and/or prognosis and/or assessment and/or therapy stratification of syncope in a patient the method comprising: determining the level of at least one biomarker selected from the group consisting of proADM, proANP, proBNP, proAVP, proET-1 and PCT or a fragment of at least 12 amino acids thereof, in a sample of a bodily fluid of said patient, correlating said level of at least one biomarker or fragments thereof with the diagnosis and/or prognosis and/or assessment and/or therapy stratification of syncope.