Atrial Electrogram Analysis for ROS-Associated Tissue Detection

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Solution Overview

Problem

Current methods lack effective detection and ablation techniques for reactive oxygen species (ROS)-associated cardiac tissue in atrial fibrillation (AF), which hinders the success of AF ablation procedures, especially in patients with structural heart disease.

Innovation Solution

The method involves analyzing atrial electrograms (EGMs) to identify ROS-associated cardiac tissue using correlations with EGM characteristics before and after ROS blockade, and employing therapeutic DNA, such as dominant negative TGF-β R2 cDNA or NOX2 shRNA, to reduce ROS production, guiding targeted ablation therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional ablation methods are used without ROS detection, then the ablation procedure can be performed, but the precision and success rate of AF ablation is reduced

Engineering Contradiction:
Improvedetection precision of ROS-associated tissueVSAvoidsuccess rate of AF ablation procedure
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent uses EGMs as an intermediary signal to indirectly detect ROS-associated tissue characteristics. By analyzing EGM features (fractionated signals, frequency content, amplitude variations) that correlate with ROS presence, the method enables precision detection without requiring direct ROS measurement tools. This intermediary approach resolves the contradiction by providing sufficient detection precision through electrical signal analysis.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces mechanical/biophysical ROS detection methods with electrical field-based EGM analysis. Instead of using physical probes to measure ROS directly, the invention utilizes the electrical activity already present in cardiac tissue (EGMs) to infer ROS-associated tissue characteristics, thereby achieving precise detection through a non-invasive electrical measurement approach.

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

2Manufacturing precision

If EGM analysis is performed to identify ROS-associated tissue, then the precision of ablation targeting is improved, but the complexity of the procedure increases

Engineering Contradiction:
Improveprecision of ablation targetingVSAvoidcomplexity of EGM analysis system
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent leverages the universality of EGM recording technology, which is already a standard tool in cardiac electrophysiology procedures. By analyzing existing EGM data with advanced signal processing algorithms, the method achieves precise ROS-associated tissue identification without requiring separate dedicated detection devices, thus minimizing procedural complexity while maintaining high targeting precision.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent creates a virtual map of ROS-associated tissue by analyzing and processing EGM signals. Instead of physically marking or directly visualizing ROS tissue, the system generates an electrical signal-based representation (copy) of the tissue characteristics, which guides ablation targeting. This virtual mapping approach simplifies the overall system complexity compared to direct physical detection methods.

Inventive Principle:
Principle #26Copying

3Object-generated harmful factors

If therapeutic DNA is used to reduce ROS production, then ROS-associated tissue activity is reduced, but the treatment protocol becomes more complex

Engineering Contradiction:
ImproveROS production in cardiac tissueVSAvoidcomplexity of gene therapy protocol
Core Design Contradiction:
Object-generated harmful factorsVSDevice complexity

Solution Approach 1:

The patent extracts or suppresses the harmful ROS production pathway by introducing therapeutic DNA (such as siRNA or antisense oligonucleotides) that specifically targets and inhibits ROS-generating enzymes or pathways in cardiac tissue. This extraction of the harmful function (ROS production) directly addresses the contradiction by reducing harmful factors through a targeted molecular approach.

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentUS9907479B2Contribution of oxidative stress to AF electrograms
Publication Date: 2018.03.06 NORTHWESTERN UNIV
  • US9907479B2 patent drawing
  • US9907479B2 patent drawing
  • US9907479B2 patent drawing

AI summary

The invention relates generally to methods of detecting reactive oxygen species (ROS) in cardiac tissue and treatment modalities for ablating ROS-associated tissue in cardiac disease. The methods rely upon targeting ROS-associated cardiac tissue for ablation and/or gene therapy in a subject using analytical tools based upon a plurality of recorded atrial EGMs for a tissue to assess ROS content and underlying AF organization as a function of ROS blockade conditions.