Restitution properties as a function of activation time (AT), activation-recovery interval (ARI), an established surrogate for APD, and repolarization time (RT).

<p>These intervals were divided in 5 quintiles and restitution slopes grouped accordingly. Markers and bars represent the median and median absolute deviation across restitution protocols (n = 14) of the median restitution slope within each quintile. From top to bottom: , and (rate of change of RT, APD and AT with respect to S1–S2 PI) and the APDR slope <i>α</i>. Right hand column shows the median and median absolute deviation (across protocols) of median slopes within each protocol. P-value of Kruskal Wallis assessing the global difference across quintiles is reported on top of each panel. +: <i>P</i> < 0.05 (Wilcoxon rank sum test) with respect to the first quintile. For example, the upper-left panel shows that decreased with AT. Cardiac sites that activated within the last three quintiles (<i>AT</i> ≥ 46 ms ca) had a significantly lower than that of the cardiac sites that activated within the first quantile (<i>AT</i> ≤ 0.25 ms ca).</p

Influence of the pathway of activation on the APD restitution slope.

<p> is the coefficients of determination between activation times (AT) for two consecutive pacing protocols. Δ|<i>α</i>| is the absolute difference between APDR slopes for the two consecutive protocols. Each marker represent each of the 6 subject for which restitution protocols were repeated twice, pacing from different sites. The higher the degree of similarity between pathways of activation (higher ) the lower the difference between slopes calculated at the same cardiac sites. Markers and bars represent median and median absolute deviation of Δ|<i>α</i>| across cardiac sites. Median Δ|<i>α</i>| was linearly correlated with with a correlation coefficient <i>r</i> = −0.91. Δ|<i>α</i>| was significantly higher for than .</p

APD restitution dispersion contributed to the increase of ARI dispersion and it is due to both repolarization and activation dynamics.

<p>Each point represents a restitution protocol (n = 14). Left: APD restitution dispersion correlated with the increase in the dispersion of ARI between the largest and the shortest pacing intervals (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161765#pone.0161765.g008" target="_blank">Fig 8</a>-middle panel). The dispersion of APDR slope <i>α</i> correlated better with dispersion (middle), i.e. the heterogeneity of AT restitution, than with dispersion (right), i.e. the heterogeneity of the slope between RT and S1–S2 PI.</p

Main cardiac intervals from action potentials (AP) and unipolar electrograms recording at a given cardiac site <i>x</i> during an S1–S2 restitution protocol (schematic).

<p>Sub-index <i>x</i> is omitted for clarity. PI: Pacing interval; AT: Activation time, from pacing stimulus to AP upstroke ; RT: Repolarization time, form pacing stimulus to AP recovery . APD: Action potential duration, ; DI: Diastolic interval, form AP recovery to following AP upstroke, . CL: Local cycle length, from AP upstroke to following AP upstroke, . The APD restitution curve represents <i>APD</i>_<i>n</i> as a function of <i>DI</i>_<i>n</i>−1 for different S1–S2 PI, <i>t</i>₂. See Eqs (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161765#pone.0161765.e001" target="_blank">1</a>)–(<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161765#pone.0161765.e008" target="_blank">5</a>) for a description of their interactions.</p

Contribution of repolarization and activation dynamics to APDR slope <i>α</i>.

<p>The contribution of AT and RT was estimated as the sensitivity of <i>α</i> to changes in (rate of change of RT with respect to S1–S2 PI) and (rate of change of AT with respect to S1–S2 PI), respectively, as in Eqs (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161765#pone.0161765.e037" target="_blank">16</a>) and (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161765#pone.0161765.e038" target="_blank">17</a>). Bar and lines represent the median and median absolute deviation across n = 14 restitution protocols, of median and estimated within each restitution protocol. Differences between and are statistically significant (<i>P</i> < 0.0001, Wilcoxon rank-sum test).</p

Dispersion of AT (left), ARI (middle) and RT (right) increased for short S1–S2 pacing intervals.

<p>Bars represent median and median absolute deviation of the dispersions across different protocols (n = 14). Dispersion was calculated as the difference between 95th and 5th percentile of each distribution.</p

Main cardiac intervals, activation time (AT), activation-recovery interval (ARI), an established surrogate for the APD, repolarization time (RT) and diastolic interval (DI) as a function of pacing interval (PI) during an S1–S2 restitution protocol.

<p>Intervals measured in sites that activated within the first (<i>AT</i> ≤ 44.6 ms), second (44.6 < <i>AT</i> ≤ 62.7 ms) and third (<i>AT</i> > 62.7 ms) terciles are represented with different markers. Changes are commented in the text.</p

APD restitution curves in a representative patient exhibiting high, middle and low APDR slope, <i>α</i>, corresponding to 95th, 50th and 5th percentile of <i>α</i> distribution.

<p>APD restitution curves in a representative patient exhibiting high, middle and low APDR slope, <i>α</i>, corresponding to 95th, 50th and 5th percentile of <i>α</i> distribution.</p