Quantitative Assessment of the Physiological Parameters Influencing QT Interval Response to Medication: Application of Computational Intelligence Tools.
Journal:
Computational and mathematical methods in medicine
PMID:
29531576
Abstract
Human heart electrophysiology is complex biological phenomenon, which is indirectly assessed by the measured ECG signal. ECG trace is further analyzed to derive interpretable surrogates including QT interval, QRS complex, PR interval, and T wave morphology. QT interval and its modification are the most commonly used surrogates of the drug triggered arrhythmia, but it is known that the QT interval itself is determined by other nondrug related parameters, physiological and pathological. In the current study, we used the computational intelligence algorithms to analyze correlations between various simulated physiological parameters and QT interval. Terfenadine given concomitantly with 8 enzymatic inhibitors was used as an example. The equation developed with the use of genetic programming technique leads to general reasoning about the changes in the prolonged QT. For small changes of the QT interval, the drug-related IKr and ICa currents inhibition potentials have major impact. The physiological parameters such as body surface area, potassium, sodium, and calcium ions concentrations are negligible. The influence of the physiological variables increases gradually with the more pronounced changes in QT. As the significant QT prolongation is associated with the drugs triggered arrhythmia risk, analysis of the role of physiological parameters influencing ECG seems to be advisable.
Authors
Keywords
Action Potentials
Algorithms
Anti-Arrhythmia Agents
Arrhythmias, Cardiac
Artificial Intelligence
Calcium
Cell Membrane
Clinical Trials as Topic
Electrocardiography
Electrophysiology
Heart
Humans
Ions
Models, Statistical
Myocytes, Cardiac
Observer Variation
Potassium
Programming Languages
Regression Analysis
Reproducibility of Results
Risk
Sodium
Software
Terfenadine