High-Resolution Measurement of Local Activation Time Differences From Bipolar Electrogram Amplitude

FIGURE 1. DELTA method calculation of inter-electrode LAT difference using clinical EGMs. (A) A representative pair of unipolar electrograms recorded from 2 mm center-to-center spaced electrodes (blue and red) and their calculated bipolar electrogram (black). Using the timing of their maximum negative dV/dt (the standard activation time annotation method) their activation time difference is 2 ms. (B) The same unipolar electrograms (blue and red) after amplitude normalization to a range of 0 to 1 mV. The period of the unipolar downstrokes (gray) is isolated in the inset. The peak amplitude of the resulting bipolar electrogram (black) occurs during the phase of simultaneous unipolar downstrokes, and by DELTA predicts a –2.191 ms time delay between the two unipolar signals.

FIGURE 2. Unipolar amplitude normalization corrects for differences in EGM morphology due to electrode-tissue distance or CV. (A) Simulated unipolar EGMs with electrode- tissue distances of 1.5, 2.25, 3.25, 4.25, and 5.25 mm before (top) and after (bottom) amplitude normalization. (B) Simulated unipolar electrograms from model locations with CV of 70.0, 62.9, 56.0, 50.9, and 46.8 cm/sec before (top) and after (bottom) amplitude normalization.

FIGURE 3. After unipolar amplitude normalization, peak bipolar voltage amplitude more closely encodes inter-electrode LAT differences. The peak to peak (A) and peak (B) voltage amplitude of each clinically recorded bipolar EGM is correlated with the LAT difference between its component unipolar EGMs. (C) After normalizing unipolar EGMs to 1 mV amplitude (peak to peak), the peak voltage of the resulting bipolar EGMs more closely encodes the unipolar LAT differences (bottom). n = 18740. Error bars represent the standard deviation.

FIGURE 4. Example LAT difference calculation by standard and DELTA methods using simulated EGMs. (A) Unipolar electrograms (U) and calculated bipolar electrogram (B) recorded from simulated electrodes with inter-electrode distance of 1 mm. (B) Transmembrane voltage (V) of simulated cells at the site of unipolar electrograms in (A) (top). Local activation times calculated by threshold crossing of the action potential upstroke (dashed lines) reveal ground truth inter-electrode time delay of 1.400 ms. This same inter-electrode time delay is found by the standard method (maximum negative dV/dt timing) using the 200 kHz sampled unipolar electrograms (bottom). (C) When these unipolar signals are sampled at 1 kHz, the inter-electrode time delay calculated by the standard method is 1 ms (dashed lines, top). If instead, the inter-electrode time delay is calculated by DELTA using the amplitude normalized signals (bottom), an inter-electrode time delay of 1.404 ms is found.

FIGURE 5. LAT differences measured by DELTA are accurate in a computational model. (A) LAT differences measured by DELTA (triangles) more closely reproduce ground truth measurements (dashed line) compared to standard technique (circles) in the computational model. (B) Focusing on LAT differences of 2 ms or less (corresponding to dashed box in Panel A) it is seen that in spite of using the same 1 ms sampled EGMs, by using the higher resolution voltage data the DELTA method avoids the 1 ms discretization of measured LAT differences measurements produced by the standard LAT annotation technique.

FIGURE 6. CV calculation using DELTA-derived LAT differences improves accuracy at small spatial scales in a 1D computational model. (A) In the setting of linearly decreasing tissue conductivity, CV decreases along the length of the simulated sheet. Results are shown for CV calculation by inter-electrode time delays between 1 mm separated simulated electrodes. When compared to CV calculated using time delays found by action potential upstroke time (green), CV calculated with time delays found by timing of unipolar maximum negative dV/dt (purple) are inaccurate due to only 1 ms temporal resolution (resulting in only time delays of 1 or 2 ms in this example). If instead time delays are calculated by the DELTA method (green), the resulting calculated CV closely recreates the ground truth.

FIGURE 7. Measuring LAT differences using DELTA improves the accuracy of 2D CV measurement in the computational model compared to standard LAT measurement technique. (A) Example of 2D CV triangulation from a triad of electrodes in the model, with planar wavefront propagation from the inferior edge. When compared to the ground truth CV (white arrow), CV calculated using DELTA-derived LAT differences (red arrow) is more accurate than that calculated using LAT differences found by standard technique (black arrow). See text for additional details. CV angles (B) and speeds (C) calculated from triads rotated by 15 degree increments through 360 degrees (n = 25). When compared to ground truth (dashed lines), CV angle and speeds calculated using DELTA-derived LAT differences are more accurate than using standard LAT measurement technique (maximum negative dV/dt timing). Shown are means with error bars representing ranges.

FIGURE 8. LAT differences calculated by the DELTA method correlate with gold standard time domain measurements. Comparing standard LAT difference measurement (by maximum negative dV/dt timing) to LAT differences calculated by the DELTA method reveals a close 1:1 correlation for time delays within approximately ± 5 ms. Shown are the mean (circles) and standard deviation (error bars). Data shown is the collection of all bipole combinations (including all inter-electrode spacings). The identity line (dashed) is included for clarity.