The Amplitude-Normalized Area of a Bipolar Electrogram as a Measure of Local Conduction Delay in the Heart

Background: Re-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.

Aim: To develop and validate a novel metric of local conduction delay in the heart, the amplitude-normalized electrogram area (norm_EA).

Methods: A 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.

Results: In 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 (r ² = 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.

Conclusion: norm_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.

Keywords: bipolar electrogram; cardiac arrhythmia; cardiac mapping; conduction delay; electrophysiology; substrate mapping.