Atrial Arrhythmias: Localization and Role for Cryosurgery

Doug L. Jones^{1,2, 3}, Allan Skanes^2,3, Gerard M. Guiraudon⁴, Colette M. Guiraudon⁵ Domenic Santoianni⁶

Departments of ¹Physiology, ²Medicine, ⁴Surgery, and ⁵Pathology
The University of Western Ontario, London, Ontario, CANADA, N6A 5C1
³The Lawson Health Research Institute, London, Ontario, N6A 4G5
⁶CryoCath Technologies Inc.Kirkland, Québec H9H 5H3

Abstract: Arrhythmias arising from the atrium, are the most common rhythm disturbance seen in general practice. The most widely used ablative therapy presently involves Radio Frequency (RF) ablation. Recent studies have explored the utility and feasibility of cooling for mapping of regions involved in arrhythmia and cryotherapy for ablation of arrhythmic or zones critical for arrhythmia propagation.  Here we describe some experience with cryotherapy in the atria and utilization of the coronary sinus to access regions of left-sided accessory pathways.

INTRODUCTION

Atrial arrhythmias are the most commonly seen arrhythmias in general practice. With the exception of symptom alleviation through ablation of the A-V node, there continues to be extensive effort directed at localizing the initiation sites within the atrium and either ablating or electrically isolating them. To date the most widely used technique for minimally invasive ablation is catheter based Radio Frequency (RF) ablation of offending heart tissue, usually guided by electrical mapping. There remains concern with RF procedures as significant charring and loose thrombus as well as stenosis of pulmonary veins can accompany RF ablations. We have been exploring the utility of cryoablative procedures to accomplish isolation or ablation of atrial arrhythmic zones. Our original experience  was with rigid probes applied to the beating heart for accessory pathway ablation [1]. Subsequently we have used the rigid probes for “proof of principle” and then followed up with flexible catheter-based cryoprobes from CryoCath Technologies Inc., which are more readily applicable to minimally invasive and robotic surgery, including ablations of the beating heart.

The studies described in this presentation are separated into two broad categories: ablations aimed at the regions of the pulmonary veins, and ablations aimed via the coronary sinus for ablation of left-sided accessory pathways. With both regions, cooling (ice mapping) can also be used to identify critical pathways or regions prior to lesioning.

Pulmonary Vein Lesions

We have explored both an epicardial and endocardial approach to isolating potential arrhythmic zones in the pulmonary veins. Our initial experiments with conventional mapping indicated that the region of the posterior-superior left atrium had the most rapid cycle lengths during atrial fibrillation [2]. Cooling of a 5 mm cryoprobe (Frigitronics, Shelton, CT – ice mapping) applied to this region, abolished atrial fibrillation, suggesting that the region around the pulmonary veins was important for the initiation of atrial fibrillation. Subsequent studies by Haissaguerre and colleagues [3] have also suggested that this region, particularly the superior pulmonary veins were the sites of the initiation of the majority of atrial fibrillation identified in their patients (see fig. 1).

Figure 1: Diagrammatic representation of localization of initiating zones in the atrium modified Haissageurre et al., 1998 [3]. The numbers indicate the location and numbers of initiation sites.

This led to several recent attempts to either ablate these zones or provide an encircling lesion. Our initial experiments in 8 dogs with an epicardial approach to the pulmonary vein region using a flexible cryoprobe (CryoCath Technologies, Inc., Kirkland, Qué), and halocarbon 502 as a refrigerant fluid, met with limited success [4]. Although lesions penetrated 3-4 mm into the atrial tissue, the large heat capacity of the blood pool, coupled with the irregular contour superior and posterior on the left atrium left regions in which lesions failed to achieve transmural ablation.

More recent experiments using expanding gas nitrous oxide or argon resulted in transmural lesions and sometimes transcavitary lesions, in many free wall areas, (see fig. 2). However, overlying fat and blood volume heat load prevented continuous transmural lesions with encircling lesions. Nevertheless, with the cooling  of argon these results showed promise for open heart procedures such as accompanying valve replacement.

Figure 2: Malleable SurgiFrost® catheter. The sheath can be extended or retracted to expose from 1 – 6 cm.

Endocardial Cryolesions

An alternate approach to the pulmonary veins is with encircling catheters placed trans-septally into the  pulmonary veins. A new cryocatheter, (Arctic Circlerä - see fig. 3) was positioned into the pulmonary veins of 6 pigs and cryolesions were generated. Encircling cryolesions were produced in the ampulla of the right and left pulmonary veins. Cryolesions were applied in 9 patients with recent onset atrial fibrillation, 4.4 ± 1.6 lesions per vein in 1-3 (mean 2.4) pulmonary veins per patient. Seven of the 9 patients have been symptom free with the remaining 2 requiring previously unsuccessful antiarrhythmic drugs over 1-3 months of follow up.

Figure 3:  20 mm Arctic Circler® extended and stretched to show the freezing coil loop

Coronary Sinus Lesions

Left-sided accessory pathways are routinely approached for RF ablation either trans-septally or retrogradely from the femoral artery across the aortic valve. Although both approaches are effective, they are not without complications. For several left-sided pathways, potentials can be recorded from catheters inserted into the coronary sinus and these mapped potentials are useful to guide ablation. RF energy delivery within the coronary sinus carries with it the risk of acute thrombosis within the coronary sinus or adjacent circumflex artery and its branches, which may produce arterial thrombosis and myocardial infarction post-ablation. Cryothermal techniques have been found to induce less endothelial disruption and thrombus formation [5]. Also, it is likely that the heat source of blood flowing in the coronary arteries might provide some additional cryoprotection. Proof of principle was initially tested using a rigid Frigitronics 5 mm cryoprobe insulated  with several coats of Insl-X® except for the final 3 mm at the tip. In 5 pigs, the probe was inserted 3-5 cm past the Os of the coronary sinus. Lesions created acutely were well demarcated and without significant disruption of the lining of the coronary sinus, often sparing large and medium sized coronary arteries within the cryolesion zone [6].

Figure 4: Ice cap on the Freezor® flexible and steerable catheter placed for 15 sec in a saline bath.

Subsequent studies using the flexible Freezorä flexible and steerable catheter from CryoCath technologies, Inc. (see fig. 4), inserted through a cut-down to the femoral vein and passed retrogradely to the right atrium to place lesions ~2 and ~3-4 cm from the coronary sinus Os in 13 pigs weighing 30 ± 5 kg [7]. Lesions of 2 and 4 min duration were produced with 25 lesions (7-two min & 18-four min) delivered using the maximum cooling of the system to approximately -70 ºC. Lesion catheter position was verified fluoroscopically and in 5 pigs, coronary arterial flow was monitored via a Doppler flow wire (Cardiometrics, Mountainview, CA), placed as distally as possible in the circumflex artery adjacent to the ablation catheter. Since lesion depth was limited on the lateral region of the coronary sinus, a scale of 0 to +++ was used to evaluate lesions depth and/or lesion breadth. The results of such lesions assessed four days post-surgery were as follows.

TABLE I: Lesion grading based on cryoablation duration.

Duration	Lesion  Grade
	0	+	++	+++
2 min	1	0	1	5*
4 min	0	3	2	13**

* 4 of 7 lesions were transmural
** 14 of 18 lesions were transmural

Four lesions had thin, well adherent thrombus on microscopic examination. One had thrombus evident on gross examination. Angiographic screening indicated no arterial spasm or major thrombus following cryoablation and Doppler measurements (5 pigs) remained unchanged. Coronary flow reserve averaged 1.7 ± 0.8 pre-ablation (see fig. 5) and 1.7 ± 1.0 post-ablation (see fig. 6) (P=0.6). Several adjacent larger and medium coronary arteries were found to be histologically normal, even within the region of myocardial necrosis.

Figure 5: Records of doppler flow taken from the circumflex artery before any lesions. Average Perfusion Velocity (APV) was 10-14 before adenosine and 33 following infusion of 12ug of adenosine in 2 mL, yeilding a Coronary Flow Reserve (CFR) of 3.0

Figure 6: Records of doppler flow taken from the circumflex artery after Cryolesion delivery for 120 seconds.  The APV before adenosine had decreased slightly to 9.4 but the maximum APV was 33, yeilding a slightly increaced CFR of 3.5.

CONCLUSIONS

These studies indicate the potential utility of cryothermal ablation for several atrial arrhythmias. Cryoablative procedures are feasible and appear to be safe, as little risk of thrombus was observed in any of the studies. The optimum placements and pattern of lesions for atrial fibrillation remain to be determined. In addition, the ability to ablate left-sided accessory pathways via the coronary sinus, eliminating trans-septal or retrograde arterial approaches, while enticing, require clinical assessment.

Acknowledgments: Supported by Trust funds of the Department of Medicine and  CryoCath Technologies Inc.

REFERENCES

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[6] D. L. Jones, F. D. Murgatroyd, A. Skanes, et al. “Coronary sinus cryoablation: a minimally invasive approach to posterior AV accessory pathways.” Can. J. Cardiol. Vol 16: (Suppl F) 173F, 2000.

[7] A. C. Skanes, D. L. Jones, P. J. Teefy, et al. Cryothermy within the coronary sinus: feasibility for arrhythmia ablation. PACE (in press), 2002.