Abstract
BackgroundRe-entrant ventricular tachycardia may be non-inducible or haemodynamically compromising, requiring assessment of the electrophysiological properties of the myocardium during sinus rhythm (i.e., substrate mapping). Areas of heart tissue with slow conduction can act as a critical isthmus for re-entrant electrical excitation and are a potential target for ablation therapy.AimTo develop and validate a novel metric of local conduction delay in the heart, the amplitude-normalized electrogram area (norm_EA).MethodsA computational model of a propagating mouse action potential was used to establish the impact of altering sodium channel conductance, intracellular conductivity, fibrosis density, and electrode size/orientation on bipolar electrogram morphology. Findings were then validated in experimental studies in mouse and guinea pig hearts instrumented for the recording of bipolar electrograms from a multipolar linear mapping catheter. norm_EA was calculated by integrating the absolute area of a bipolar electrogram divided by the electrogram amplitude. Electrogram metrics were correlated with the local conduction delay during sodium channel block, gap junction inhibition, and acute ischemia.ResultsIn computational simulations, reducing sodium channel conductance and intracellular conductivity resulted in a decrease in signal amplitude and increase in norm_EA (reflecting a broadening of electrogram morphology). For larger electrodes (3 mm diameter/7.1 mm2 area), the change in norm_EA was essentially linear with the change in local conduction delay. Experimental studies supported this finding, showing that the magnitude of change in norm_EA induced by flecainide (1–4 μM), carbenoxolone (10–50 μM), and low-flow ischemia (25% of initial flow rate) was linearly correlated with the local conduction delay in each condition (r2 = 0.92). Qualitatively similar effects were observed in guinea pig hearts perfused with flecainide. Increasing fibrosis density in the computational model also resulted in a decrease in signal amplitude and increase in norm_EA. However, this remains to be validated using experimental/clinical data of chronic infarct.Conclusionnorm_EA is a quantitative measure of local conduction delay between the electrode pair that generates a bipolar electrogram, which may have utility in electrophysiological substrate mapping of non-inducible or haemodynamically compromising tachyarrhythmia.
Highlights
Substrate mapping of the ventricular myocardium is an electrophysiological mapping modality that is commonly applied when the culprit arrhythmia cannot be induced or is hemodynamically compromising (Pedersen et al, 2014; Priori et al, 2015)
Decreasing either gNa or σi resulted in a reduction in bipolar electrogram amplitude and a broadening of electrogram morphology
Altering gNa exerted a greater effect on electrogram duration vs amplitude and altering σi had a greater effect on electrogram amplitude vs duration
Summary
Substrate mapping of the ventricular myocardium is an electrophysiological mapping modality that is commonly applied when the culprit arrhythmia cannot be induced or is hemodynamically compromising (Pedersen et al, 2014; Priori et al, 2015) It is typically performed during electrical pacing or in sinus rhythm (Pedersen et al, 2014). This may reflect the ambiguity in defining the start and end of the electrogram complexes, which is relevant for low-amplitude-signals, as well as the fact that automated measurements of electrogram duration are susceptible to errors caused by signal artifacts To address these limitations, we sought to develop an alternative, algorithmically calculable and quantitative metric of conduction delay with potential application in electrophysiological substrate mapping procedures. Areas of heart tissue with slow conduction can act as a critical isthmus for re-entrant electrical excitation and are a potential target for ablation therapy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
