Optical Mapping and Gene Targeting for Ventricular Tachycardia
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Solution Overview
Problem
Current technologies are inadequate in diagnosing and treating ventricular tachycardia (VT) due to limited understanding of the underlying cellular and tissue electrophysiology in infarct scar border zones.
Innovation Solution
The method involves measuring action potential durations (APDs) in myocardial tissue to identify VT circuits, using techniques like electrogram mapping and optical mapping, and targeting specific genes such as KCNE3 and KCNE4 with inhibitory nucleic acids or ablating the affected cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current diagnostic and treatment technologies are used for ventricular tachycardia, then treatment can be provided, but the underlying cellular and tissue electrophysiology remains poorly understood limiting effectiveness
Solution Approach 1:
The patent replaces conventional mechanical/electrical mapping systems with optical mapping technology that uses fluorescent dyes and imaging systems to visualize action potential durations and repolarization characteristics in real-time, enabling direct observation of cellular electrophysiology without invasive electrical stimulation
Solution Approach 2:
The patent changes the measurement parameters from traditional ECG electrical signals to optical signals measuring action potential duration, repolarization time, and fluorescence intensity, allowing direct quantification of cellular electrophysiological properties that were previously inaccessible
2Measurement precision
If action potential duration mapping is performed to identify VT circuits, then VT circuits can be identified, but the complexity of measurement and mapping increases
Solution Approach 1:
The patent segments the heart into multiple measurement zones (endocardial, mid-myocardial, epicardial layers) and uses multiple catheter positions to systematically map APD variations, breaking down the complex 3D mapping problem into manageable sequential measurements
Solution Approach 2:
The patent introduces optical dyes and fluorescent imaging as intermediaries between the electrical activity and the detection system, allowing non-contact measurement of action potential characteristics through light emission rather than direct electrical recording
3Reliability
If genes KCNE3 and KCNE4 are targeted with inhibitory nucleic acids, then VT can be treated, but the complexity of molecular therapy increases
Solution Approach 1:
The patent performs preliminary identification of KCNE3/KCNE4 upregulation and APD heterogeneity before administering inhibitory nucleic acids, using optical mapping and gene expression analysis to select patients and determine dosing parameters in advance
Solution Approach 2:
The patent changes the treatment approach from conventional electrical ablation to molecular therapy targeting specific gene expression, using nucleic acid inhibitors to modulate ion channel function and restore normal repolarization characteristics
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 enables effective identification and treatment of VT circuits by addressing repolarization heterogeneity and reducing the expression of genes contributing to VT, thereby improving patient outcomes.
Implementation Method 1
measuring a first action potential duration (APD) of a first tract of myocardial tissue of a subject; measuring a second action potential duration (APD) of a second tract of myocardial tissue that is adjacent to the first tract
Implementation Method 2
the first APD and/or the second APD are measured by optical mapping
Data Source
AI summary
In some aspects, the disclosure relates methods for treating ventricular tachycardia in a subject. In some embodiments, methods of the disclosure comprise measuring action potential durations and/or expression levels of KCNE3 and/or KCNE4 in a subject. In some aspects, the disclosure relates to methods and compositions for reducing or inhibiting the activity of KCNE3 and/or KCNE4, for example, in subjects having ventricular tachycardia.