Adenosine in human atrial fibrillation modulates and re-distributes atria-wide dominant frequencies and directs to reentry ablation sites with improved outcome

Figures

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  Fig. 1. Flow chart of actions and data prior, during, and following the mapping-ablation procedure. Yellow squares correspond to ECGi data acquisition and processing. Black arrows, work flow; Blue arrows, data flow; Green squares, intracardiac data acquisition, processing, and navigation; B1, basal 1 mapping; B2, basal 2 mapping; Ado, Adenosine mapping.

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  Fig. 2. Rotational domains in ECGi mappings. (A) ECGi atrial maps showing density of rotations (composite maps; CardioInsight;) in the Basal 1 (top), Basal 2 (middle) and Adenosine infusion (bottom) mappings in a representative patient. Numbers on maps are number of reentries and colors indicate total number of rotations, regardless of belonging to the same reentry. High number of rotations were consistently observed in the lateral-high RA in this patient (red). Maps are from case N° 7. (B) Cumulative mean ± std of total number of reentries (left), average reentry duration (middle) and average reentry cycle length (right) during Basal 1, Basal 2 and Adenosine (Ado) mapping in each patient (N = 25). Reentry cycle length shows a variation across mapping stages (See also Table 1).

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  Fig. 3. DF maps of TQ segments and their Welch’ average power spectra during Basal 1. Basal 2 and Ado mapping in a representative patient. (A) DF maps of representative sequential TQ segments in temporal order from early (top) to late (bottom) during Basal 1, Basal 2 and Ado mappings. DF is calculated for each TQ segment using SFFT. Highest DF domains (orange-red) are visible in DF maps during Ado mapping. (B) Cumulative DF maps of all TQ segments during Basal 1 (n = 15), Basal 2 (n = 14) and Ado (n = 8) based on SFFT-Welch’s averaged power spectra. Maps are from case N° 24.

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  Fig. 4. Baseline stability of DF measurements from virtual EGMs. (A) A posterior view of an ECGi-based DF bi-atrial map and sample virtual EGMs obtained during Basal 1 (DFB1, left) and Basal 2 (DFB2, right) mapping in a representative patient. Maps show stability at 6.1 Hz at the right atrium appendage and a reduction from 6.1 in DFB1 to 5.4 Hz in DFB2 near the pulmonary veins. (B) A map of the DF differences (ΔDF) between DFB1 and DFB2 maps in panels A and B. Note: values in the color bar are downward from zero (red) to 1 (blue). (C) Cumulative histogram of absolute DF differences (|ΔDF|) between Basal 1 and Basal 2 across all nodes and maps (N = 25). (D) 2D histograms of normalized DFB1 (left) and DFB2 (right) versus |ΔDF| (N = 25). DF values were normalized between 0 and 1 based on each patient’s minimal and maximal DF values. Maps in panels A and B are from case N° 21.

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  Fig. 5. Adenosine effect on DFs in a representative patient. (A) Anterior (top) and posterior (bottom) views of DF maps during Basal 1 mapping with sample virtual EGMs signal segments and corresponding DFs. (B) DF maps with same view as in A during Adenosine mapping showing areas with increased DFs (red areas) relative to Basal 1 mapping. (C) Histograms of DFs during Basal 1 mapping shown in A (DFB1, left) and during Adenosine mapping shown in B (DFAdo, right). The distribution during Adenosine is showing a marked band split relative to the distribution during Baseline 1. Data are from case N° 20.

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  Fig. 6. Cumulative analysis of the DFs in 21 patients during B1, B2 and Ado mappings. (A) Histogram of DFs during B1 (DFB1, left) and B2 (DFB1, right) mappings with superimposed single-mode Gaussian best fit (green) and fitting parameters. (B) Left: Histogram of DFs during Ado (DFAdo) mapping with superimposed single-mode Gaussian best fit (green) showing broadening of distribution relative to A and reduced Adjusted R2. Right: Histogram of same data in left graph transformed to have DFAdo = 0 at the specific band splitting DF of each patient (see Fig. 5C). A superimposed bi-modal Gaussian best fit (green) with low (red arrow) and high (blue arrow) bands shows a greater Adjusted R2 value than in left graph. (C) 2D histogram of DFAdo transformed to have 0 value at the band split frequency for each patient separately and |ΔDF| for Adenosine mapping (N = 21). Peak distributions at low and high bands (yellow bins) are visible at |ΔDF|≤ 0.4 Hz. (D) Temporal behavior of DFs in all ECGi nodes belonging to low (red) and high (blue) frequency DFAdo bands. Nodes during B1 and B2 mappings were assigned to the low and high frequency bands based on the DFAdo values at the nodes during Ado mapping.

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  Fig. 7. Atrial distributions of high DFAdo, stable basal DFs and rotational domains. (A) A normalized DFAdo map from a representative patient. (B) A map of the stability in DFs during the 2 basal DF mappings in the same patient as in A. High stability regions are in red and low stability in blue. (C) Map of the DFAdo map in panel A weighted by the basal Stability map in panel B results in a normalized DFAdo-Stability index (DFASI) map. Red arrow points to highest DFASI value domain in the lateral RA. (D) Rotational domains maps during basal mapping of the same patient. Red arrows point to a stable reentry domain with maximal number of rotations correlating with the high DFASI domain in panel C. Maps in A–D are from case N° 18. (E) Distribution of stable CardioInsight rotational domain (green) and DFASI ≥ 0.8 (red) across the atria of all patients. Numbers in parenthesis indicate the number of those occurring in the same patient. DFASI, DFAdo stability index; ILA, inferior LA; SLA, superior LA; LAA, LA appendage; IRA, inferior RA; SRA, superior RA; RAA, RA appendage.

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  Fig. 8. Ablation at High DFASI domains and freedom of arrhythmias. (A) A representative DFASI map (left) with high value domain (black arrow) at an area which was ablated (red arrow in right panel). Maps are from case N° 20. (B) A representative DFASI map with high value DFASI domain (black arrow) which was not ablated (blue arrow in right panel). Maps are from case N° 25. (C) Survival probability for all arrhythmia freedom for all patients. Traces are for patients in which ablation included all domains with DFASI ≥ 0.8 (red, (+)) and those in which ablation did not include all such domains (blue, (−)). Number of patients at risk in the 2 groups are indicated below graph.