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. 2018 Nov 9:10.1109/TBME.2018.2880408.
doi: 10.1109/TBME.2018.2880408. Online ahead of print.

Permanent and Transient Electrophysiological Effects During Cardiac Cryoablation Documented by Optical Activation Mapping and Thermal Imaging

Greg Morley, Scott Bernstein, Laura Kuznekoff, Carolina Vasquez, Phil Saul, Dieter Haemmerich

Permanent and Transient Electrophysiological Effects During Cardiac Cryoablation Documented by Optical Activation Mapping and Thermal Imaging

Greg Morley et al. IEEE Trans Biomed Eng. .

Abstract

Objective: Cardiac catheter cryoablation is a safer alternative to radiofrequency ablation for arrhythmia treatment, but electrophysiological (EP) effects during and after freezing are not adequately characterized. The goal of this study was to determine transient and permanent temperature induced EP effects, during and after localized tissue freezing.

Methods: Conduction in right (RV) and left ventricles (LV) was studied by optical activation mapping during and after cryoablation in paced, isolated Langendorff-perfused porcine hearts. Cryoablation was performed endocardially (n=4) or epicardially (n=4) by a cryoprobe cooled to -120 °C for 8 minutes. Epicardial surface temperature was imaged with an infrared camera. Viability staining was performed after ablation. Motion compensation and co-registration was performed between optical mapping data, temperature image data, and lesion images.

Results: Cryoablation produced lesions 14.9 +/- 3.1 mm in diameter and 5.8 +/- 1.7 mm deep. A permanent lesion was formed in tissue cooled below -5 +/- 4 °C. Transient EP changes observed at temperatures between 17 and 37 °C during cryoablation surrounding the frozen tissue region directly correlated with local temperature, and include action potential (AP) duration prolongation, decrease in AP magnitude, and slowing in conduction velocity (Q10=2.0). Transient conduction block was observed when epicardial temperature reached <17 °C, but completely resolved upon tissue rewarming, within 5 minutes.

Conclusion: Transient EP changes were observed surrounding the permanent cryo lesion (<-5 °C), including conduction block (-5 to 17 °C), and reduced conduction velocity (>17 °C).

Significance: The observed changes explain effects observed during clinical cryoablation, including transient increases in effective refractory period, transient conduction block, and transient slowing of conduction. The presented quantitative data on temperature dependence of EP effects may enable the prediction of the effects of clinical cryoablation devices.

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Figures

Fig. 1.
Fig. 1.
Registration of three image data sets. (A) Activation map, (B) Epicardial temperature profile after 8 min cryoablation, and (C) Endocardial lesion boundary data are geometrically transformed and registered. Endocardial lesion image is shown flipped horizontally (i.e. as if viewed from the epicardial side) to match the viewing direction of data sets (A) and (B). Original data sets are shown in (A) – (C), with black rectangle (having gray line at top) indicating the region and orientation corresponding between the data sets. (D) Visualization of the registered data sets, where isochrones extracted from (A) are shown at 2.5 ms intervals, endocardial lesion boundary from (C) is shown in blue, and epicardial temperature profile from (B) after 8 min cryoablation is shown as color map. All results are shown from the lesion Endo1.
Fig. 2.
Fig. 2.
Cryo lesion gross pathology. Left ventricular lesion Endo1 (not transmural) in (A) Cross section, and (B) Endocardial view. Right ventricular lesion Endo2 (transmural) in (C) Cross section, and (D) Endocardial view. Protruding fiducials are visible in (B) and (D). Both lesions were created by endocardial cryoablation. Dotted lines mark lesion border. Scale bar indicates 5 mm.
Fig. 3.
Fig. 3.
Conduction changes during non-transmural and transmural cryoablation. Non-transmural lesion (Endo1): Epicardial activation map (A) before, (B) at end of 8 min cryoablation applied endocardially, (C) 2 min after cryo, and (D) 5 min after cryo (see also Suppl. Movie 1). Permanent lesion on the opposite side of the myocardium, i.e. the endocardial side, shown as gray shaded region; isochrones shown at 2.5 ms intervals. Arrow in (B) marks region of conduction block. Epicardial temperature profile is shown (E) at end of 8 min cryoablation, and (F) 2 min after cryo. Coronary vessel (arrow), and fiducial marker (arrowhead) are visible in (E). Tissue was paced from a location at the lower left corner, outside the field of view. Scale bar in (A) indicates 10 mm. Transmural lesion (Endo2): Epicardial activation map (G) before, (H) after 1 min cryoablation applied endocardially (black arrow indicates area of conduction block), (I) at the end of 8 min cryoablation, and (J) 5 min after cryoablation (activation map did not change further after 5 min). (K) Temperature time course in epicardial lesion center (gray marker in (L)), with arrows marking time points of tissue freezing and thawing. (L) Epicardial temperature profile at end of cryoablation (see also Suppl. Movie 2). Permanent lesion (epicardial side) is marked in black in (I) and (J), and by gray outline in (L). Scale bar in (A) indicates 10 mm.
Fig. 4.
Fig. 4.
Temperature dependence of (A) conduction velocity, and of (B) action potential duration (APD90). The temperature coefficient for conduction velocity is Q10=2.0. Standard deviation is indicated by bars in (A),(B). (C) Temperature dependence of conduction velocity was used to estimate temperature of conduction block (defined where conduction velocity reaches zero). Blue dashed line indicates linear fit of data (red circles), and intersects with velocity=0 at 17 °C. Based on these data, we estimate transient conduction block to occur at temperatures below 17 °C.
Fig. 5.
Fig. 5.
Temperature dependent changes in action potential morphology. Lesion Endo2: (A) Bright field image, (C) action potential magnitude, and (E) optical signal at indicated locations (corresponding locations indicated by color markers in (A) and (C)). (A), (C) and (E) are shown at the end of the cryoablation. Iceball is visible in (A) and marked by arrow. (B), (D) and (F) show bright field image, action potential magnitude, and optical signal after thawing (5 min after ablation). Permanent lesion is visible in (B) and marked by arrows, coinciding with prior ice ball location in (A). Double arrow in (E) indicates AP magnitude. White dotted curve in (E) and (F) indicates signal before ablation (average signal from all 5 locations). Three fiducial markers are visible in (A) and (B). Before ablation, signals at all locations were equivalent to yellow signal in (F). Scale bar in (A) indicates 10 mm. Action Potential Duration (APD90) map, shown (G) before, (H) at the end of 8 min cryoablation, and (I) 5 min after cryoablation (right). Permanent lesion at epicardial side shown in black in (H) and (I).
Fig. 6.
Fig. 6.
Tissue effects in proximity of a cryo probe. Three temperature ranges with specific tissue effects have been identified and are simultaneously present. The regions where specific effects occur change dynamically as the cryo probe is cooled down, and heats up again after the end of cryoablation.
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