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The history of myocardial cryoablation

Open heart surgery for arrhythmias began in the 1960s. In its infancy, this involved sharp surgical dissection of the putative arrhythmia focus/reentrant pathway or palliative resection of the AV conduction system. Although usually definitive, there was little margin for error. The ability of cryogenic energy to create reversible interruption in myocardial function added and additional method of site-specific mapping. Also its ability with more vigorous cooling to create discrete, structurally intact, electrically inert foci in myocardium makes it a potentially useful therapeutic modality in the treatment of a variety of tachyarrhythmias. The technology was originally applied in the construction of rigid metal probes. The application of this technology to cardiac arrhythmias found its origin in open-heart surgery in the 1970s.

Surgical cryoablation of the AV conduction system

Surgical division of the AV conduction for recurrent drug-refractory supraventricular tachycardia SVT and subsequent pacemaker placement was first performed in the 1960s (1-4). In 1977, Gallagher et al. evaluated cryoablation as an alternative to surgical division, using a cryogenic probe to first map and subsequently ablate AV conduction. In their first published report, these investigators studied three patients with severe, life-threatening supraventricular tachyarrhythmias that proved refractory to numerous antiarrhythmic agents (1). Each patient underwent open-heart surgery with cardiopulmonary bypass. The right atrium was opened and intra-operative cryomapping techniques were utilized to identify the AV conduction system. Using a hand-held nitrous oxide-cooled cryogenic probe, the area identified by recording a His bundle potential was cooled to 0°C for 30 seconds, which produced reversible complete heart block with junctional escape in each case, confirming the location of the AV node. Freezing at this area at –60°C for two consecutive 90-second periods caused sustained complete heart block (CHB). In some cases, a third freeze was applied to the area between the first lesion and the coronary sinus. CHB with a subsidiary junctional escape was observed in each patient at up to 37 months of follow-up; one patient had complete heart block confirmed at electrophysiology testing 9 days following cryoablation (5). This group went on to extend this pilot study to a total of 22 patients with a variety of recalcitrant supraventricular tachycardias. Using the protocol described, stable complete heart block was achieved in 17 patients (77%). Sixteen of these patients had a follow-up electrophysiologic testing 7 to 10 days after the procedure. In each case, isoproterenol infusion was noted to increase the junctional rate in a dose-dependent manner, while atropine had no effect, consistent with complete disruption of AV nodal tissue and preservation of junctional tissue presumably from the proximal bundle of His. Two patients developed incomplete right bundle branch block and one patient had new precordial Q waves - the latter had also received ventriculotomy for attempted simultaneous treatment of ventricular tachycardia. This patient died 12 months following the procedure of an unrelated cause at which time autopsy confirmed discrete fibrosis of the common His bundle and the upper right ventricular aspect of the muscular interventricular septum. Post-operative HB electrograms were obtained from 3 patients, which demonstrated AV block with his bundle deflections preceding each QRS. The conclusion of this group was that cryoablation offered a safe and effective alternative to mechanical disruption of the AV node for patients with drug-refractory supraventricular arrhythmias.

Subsequent to these studies, surgical approaches to atrioventricular ablation not requiring bypass have been successfully elaborated. Bredikis and coworkers in Lithuania have published a series of studies in patients in which this was affected through two atriotomy incisions, one for the cryogenic probe and the other for passage of the surgeon’s finger into the atrium to allow digital identification of the anatomic landmarks surrounding the AV node (6). The latter were confirmed by recording His potentials, cryogenic mapping, pressure-induced AV block, or by anatomic definition alone. The success rate in this series of 34 patients was 85%. In a less detailed ensuing report by these authors, they performed the procedure in 72 patients with a success rate of 92% with only one complete failure (7). They reported a single death for which details were not given. Another alternative approach avoiding the need for CPB was reported by Louagie et al. who performed epicardial atrioventricular ablation by application of the cryogenic probe to the right coronary fossa (8). The location of the His bundle was confirmed by cryomapping and subsequent ablation.

Surgical cryoablation for AV Nodal Reentry Tachycardia

The unique ability of the application of cryogenic temperatures to map conduction pathways at moderate temperatures and then to produce irreversible lesions at lower temperatures led to its central role in the current understanding of AV nodal anatomy and the ability to ablate AV nodal reentry tachycardia (AVNRT) while preserving normal anterograde atrioventricular conduction.

In 1979, the serendipitous surgical cure of AVNRT with preservation of anterograde AV nodal conduction in a single patient by Pritchett et.al. during routine dissection of the His bundle region prompted Holman and Cox to evaluate the area of the triangle of Koch using handheld cryogenic probes in dogs (9, 10). In these elegant studies, cryolesions were placed encircling the triangle of Koch. If AV nodal block occurred during the application of cryogenic temperatures, the probe was immediately shut off and the area warmed with saline. Anterograde and retrograde conduction studies were performed acutely and chronically: AV nodal conduction delay and refractory period prolongation were present acutely, but had resolved by 14 weeks. AV nodal echo beats present prior to ablation were no longer inducible, suggesting that the anatomical substrate for AVNRT had been ablated. Consistent with this observation, dual AV nodal physiology that had been noted in three dogs at baseline electrophysiologic (EP) testing was uniformly eliminated by the procedure (10). In light of these findings, Cox et al. (11) and other investigators (12) went on to perform similar procedures in patients with drug-refractory AVNRT. The procedure proved to be 100% effective with no patient requiring pacemaker placement or continued drug therapy. Right bundle branch block was reported in 3 of the first 8 patients studied (11). This was presumed on the basis of histologic studies in the canine model (12) to represent extension of the cryolesion either into the right bundle itself, or to fibers in the His bundle destined to feed the right bundle branch.

Surgical cryoablation of accessory pathways

The application of cryogenic temperatures to accessory pathway (AP) ablation was initially explored as an alternative to surgical treatment, in view of the considerable mortality rate (3.6-5.4%) associated with conventional surgery (13, 14). The potential for the formation of a more stable lesion and, with the advent of handheld probes, a relatively less invasive procedure requiring less bypass time made a cryogenic approach an appealing alternative. Several clinical series and case reports of cryoablation for APs have been published. None of the trials were designed prospectively. The earliest report of cryoablation AP ablation was a pilot evaluation of two patients, one with a left posterior AP, and the other with an anterior septal AP (15). Confirmation of the former was done by direct electrical recording of the AP and resolution of the delta wave by applying pressure to the putative AP site. In the latter situation, the presence of a septal AP capable of only retrograde conduction was confirmed by cryomapping that demonstrated reversible block of the AP. The pathways identified in both cases were then ablated endocardially with the patients on bypass, using a hand-held cryogenic probe freezing the tissue to -60°C for 90 seconds with two sequential applications. Both patients remained free of arrhythmia at follow up.

With a view toward further minimization of morbidity and mortality associated with surgical open heart ablation, an epicardial (“closed heart”) approach was first employed by Guiraudon and colleagues (16) who ultimately reported a series of 105 patients with left lateral, posteroseptal, and right ventricular free wall APs (17). Depending on the AP location and mapping results, some patients had procedures performed without bypass. Efficacy was excellent, with only four patients requiring reoperation, one of whom required a third procedure. There was a single failure, but the patient’s arrhythmia became easily controlled with procainamide. Morbidity was minimal - the patient requiring 3 procedures developed a post-surgical coagulopathy that resolved. There were no deaths. Using the closed heart approach, Watanabe et al. avoided the use of bypass in a series of 28 patients who had a total of 31 APs (18). Only three patients had to be converted to an endocardial procedure, two because of failure to achieve ablation epicardially, and one because of a surgical atrial wall tear unrelated to the cryoablation. Morbidity was otherwise limited to conversion to an open-heart procedure in one patient, and efficacy was 100%.

The approach to left lateral and left posterior APs is limited anatomically. Bredikis and Bredikis surmounted this limitation by introducing a specially designed cryogenic probe into the coronary sinus, allowing cryoablation of left sided APs without the need for bypass. Nineteen of 21 patients were successfully managed by this approach. In two cases, the coronary sinus was torn and required surgical ligation (19). There were no reports of left circumflex coronary artery complications. Patients with septal APs have also been successfully treated with cryoablation. Lee et al. described a series of 18 patients, 11 with classic Wolff-Parkinson-White (WPW) syndrome and 7 with permanent junctional reciprocating tachycardia who underwent surgical endocardial cryoablation (20). After tricuspid valve annulus endocardial mapping, lesions were produced at the site of earliest activation. Overlapping endocardial lesions were subsequently applied toward the AV node and across the septum opposite the initial lesion.

Using this method, Lee reported 16 definitive cures. One patient who had both an anteroseptal and a posteroseptal AP was noted to have recurrence of a delta wave on surface electrogram at 10 months, but had no recurrence of tachycardia off medication. Another patient who did not have return of his delta wave did have recurrences of poorly documented tachycardias requiring medical treatment. Morbidity was limited to one case of postoperative pancreatitis. There were no deaths. Five patients had depressed left ventricular ejection fractions preoperatively, all of which normalized post-operatively, consistent with a diagnosis of resolved tachycardiomyopathy (20).

Surgical cryoablation of bundle branches

Andress etal. reported the use of cryoablation in the setting of a patient with bundle branch reentry that proved recalcitrant to medical treatment, radiofrequency (RF) and DC energy (21). The patient was a 30 year old woman with Ebstein’s anomaly who presented with a sustained left bundle branch block morphology tachycardia and who was found to have inducible bidirectional bundle branch reentry on electrophysiology testing. Despite receiving 23 RF applications, and four 200-300J DC shocks to her right bundle branch, the patient returned to her baseline incomplete right bundle branch block pattern, and bundle branch reentry was still inducible 48 hours following her procedure. Subsequently, the patient had open-heart surgery and received extensive cryoablation over the entire length of her right interventricular septum. Postoperatively she developed stable right bundle branch block and ventricular tachycardia was no longer inducible. The patient remained symptom free over 10 months of follow-up (21).

Surgical cryoablation of ventricular tachycardia

In 7 patients undergoing operative subendocardial resection for ventricular tachycardia, cryomapping was used to identify the site of origin of the ventricular tachycardia that was then resected (22). Other surgeons have used cryoablation of the putative site of ventricular tachycardia origin to attempt to cure it (23).

Surgical cryoablation of atrial flutter

The first report of atrial flutter (AFl) successfully treated surgically by cryoablation was first described by Klein and colleagues in 1986 (24). At that time there was question over the exact mechanism of AFl. Based on the proposed mechanism of isthmus-dependent conduction, Klein described two patients successfully treated with surgical cryoablation of the right atrial subeustacian isthmus through an epicardial approach. The procedures were performed on CPB with 15 mm cryo lesions overlapping cooled to -60C for two minutes (25). This layed the groundwork for cryoablation treatment of typical AFl via an epicardial approach. The most recent report of correction of AFl with cryoablation comes from Yamauchi in Tokyo, Japan (26). They reported their experience with a patient treated surgically for atypical left AFl through an epicardial approach. The details of cryoablation were not detailed in their description. cryoablation lines were made through the left atrial appendage as well as around both sets of pulmonary vein openings. This essentially created an epicardial Maze procedure for the treatment of atypical left AFl with single success. Subsequent published literature details the transition of cryo treatment for AFl using an endocardial approach (27).

Surgical cryoablation of atrial fibrillation

The use of cryoablation to simplify the traditional cut-and-sew Maze III procedure was initially reported in 62 patients with chronic atrial fibrillation (AF) undergoing surgical repair of mitral valve disease (28). Comparable to results with the classic Maze procedure (29-33) 52 (84%) of these patients regained sinus rhythm. The 10 patients who remained in AF had a significantly longer duration of preoperative AF. Subsequently, cryoablation has become one of several alternate energy sources commonly used to replace surgical incisions as lines of conduction block in the surgical management of AF (34) No systematic comparisons of cryoablation and other energy sources in this setting have been reported.

cryoablation is a particularly safe modality for endocardial ablation during open cardiac surgical procedures. In 32 patients with chronic AF undergoing valvular heart surgery, concomitant linear cryoablation connecting the four pulmonary veins (PVs) and mitral annulus effectively restored and maintained sinus rhythm over a 9-month minimum follow-up (35). The addition of limited left atrial cryoablation to valve surgery added only 20 minutes to the procedure time, potentially reducing myocardial ischemic time as well as the bleeding risk (35). Similarly, replacing surgical incisions with cryoablation for PV isolation resulted in significantly reduced CPB time, aortic cross-clamp time and chest tube drainage among case matched patients undergoing the maze procedure in association with mitral valve surgery (36). The rate of sinus rhythm restoration in the cryoablation group was 85% and comparable to the group which isolated the PVs by incision and suture (36).

In 105 patients with permanent AF, left atrial dilatation, and valvular heart disease, adding linear lesions in the posterior left atrium to PV isolation was more effective than PV isolation alone in achieving sinus rhythm off antiarrhythmic drugs at 2-year follow-up (86% vs. 25%)(37). Postoperative electroanatomic mapping was performed in the first 17 patients from each group and revealed that the surgical intent was fulfilled in only 65% of the patients. These findings question the ability of cryoablation to create transmural lesions when applied to the endocardium of the left atrium during open-heart surgery in these more difficult cases.

Review articles

  1. Harrison L, etal. Cryosurgical ablation of the A-V node-His bundle: a new method for producing A-V block. Circulation. 1977; 55: 463-70
  2. Cole J, etal. The Wolff-Parkinson-White syndrome: problems in evaluation and surgical. Circulation. 1970; 42: 111-21
  3. Slama R, etal. Surgical creation of an auriculoventrical block and implantation of a stimulator in 2 cases of irreducible rhythm disorders. Archives des Maladies du Coeur et des Vaisseaux. 1967; 60: 406-22
  4. Garcia R. and Arciniegas E. Recurrent atrial flutter. Treatment with a surgically induced. Archives of Internal Medicine. 1973; 132: 754-42
  5. Klein G, etal. Cryosurgical ablation of the atrioventricular node-His bundle: long-term follow-up and properties of the junctional pacemaker. Circulation. 1980; 61: 8-15
  6. Bredikis J, Cryosurgical ablation of atrioventricular junction without extracorporeal circulation. Journal of Thoracic and Cardiovascular Surgery. 1985; 90: 61-7
  7. Bredikis J and Bredikis A. Surgery of tachyarrhythmia: intracardiac closed heart cryoablation. Pacing and Clinical Electrophysiology. 1990; 13: 1980-4
  8. Louagie Y, etal. Closed heart cryoablation of the His bundle using an anterior septal approach. Annals of Thoracic Surgery. 1991; 51: 616-9
  9. Holman L., et.al. Cryosurgical modification of retrograde atrioventricular conduction. Implications for the surgical treatment of atrioventricular nodal reentry tachycardia. Journal of Thoracic and Cardiovascular Surgery. 1986. 91(6): 826-34
  10. Holman W, etal. Cryosurgical ablation of atrioventricular nodal reentry: histologic localization of the proximal common pathway. Circulation. 1988; 77: 1356-62
  11. Cox J, Holman W, Cain M. Cryosurgical treatment of atrioventricular node reentrant tachycardia. Circulation. 1987; 76: 1329-1336
  12. Holman W, etal. Cardiac cryosurgery: regional myocardial blood flow of ventricular cryolesions. Journal of Surgical Research. 1986; 41: 524-8
  13. Sealy W, etal. Surgical treatment of Wolff-Parkinson-White syndrome. Annals of Thoracic Surgery. 1969; 8: 1-11
  14. Iwa T, etal. Radical surgical cure of the WPW syndrome: the Kazawa experience. Journal of Thoracic and Cardiovascular Surgery. 1986; 91: 225-33
  15. Gallagher J, etal. Cryosurgical ablation of accessory atrioventricular connections: a method for correction of the pre-excitation syndrome. Circulation. 1977; 55: 471-9
  16. Guiraudon G, etal. Surgical repair of Wolff-Parkinson-White syndrome: a new closed-heart. Annals of Thoracic Surgery. 1984; 37: 67-71
  17. Guiraudon G, etal. Closed-heart technique for Wolff-Parkinson-White syndrome: further. Annals of Thoracic Surgery. 1986; 42: 651-7
  18. Watanabe S, etal. Cryosurgical ablation of accessory atrioventricular pathways without cardiopulmonary bypass: an epicardial approach for Wolff-Parkinson-White syndrome. Annals of Thoracic Surgery. 1989; 47: 257-64
  19. Bredikis J and Bredikis A. Cryosurgical ablation of left parietal wall accessory atrioventricular connections through the coronary sinus without the use of extracorporeal circulation. Journal of Thoracic and Cardiovascular Surgery. 1985; 90: 199-205
  20. Lee A, etal. Cryoablation of septal pathways in patients with supraventricular tachyarrhythmias. Annals of Thoracic Surgery. 1989; 47: 566-8
  21. Andress J, Vander Salm T, and Huang S. Bidirectional bundle branch reentry tachycardia associated with Ebstein's anomaly: cured by extensive cryoablation of the right bundle branch. Pacing and Clinical Electrophysiology. 1991; 14: 1639-47
  22. Gallagher J, etal. Cryothermal mapping of recurrent ventricular tachycardia in man. Circulation. 1985; 71: 732-9.
  23. Gallagher J, Anderson R, Kassel J, etal. Cryoablation of drug resistant ventricular tachycardia in a patient with a variant of scleroderma. Circulation 1978; 57: 190
  24. Klein G, Guiraudon G, Sharma A and Milstein S. Demonstration of Macroreentry and Feasibility of Operative Therapy in the Common Type of Atrial Flutter. American Journal of Cardiology. 1986; 57: 587-591
  25. Klein G, Harrison L, Ideker R etal. Reaction of the myocardium to cryosurgery: electrophysiology and arrhythmogenic potential. Circulation. 1979; 59: 364-372
  26. Yamauchi S, Imura H, Bessho R, Yamada K and Tanaka S. Simultaneous Surgical Correction of a Common Atrium and Impure Flutter. Annals of Thoracic Surgery. 1997; 64: 548-552
  27. Manusama R, Timmermans C, Limon F, Philippens S, Crijns H, Rodriguez L. Catheter-based cryoablation permanently cures patients with common atrial flutter. Circulation. 2004; 109: 1636-9
  28. Kosakai Y, Kawaguchi A, Isobe F, Sasako Y, Nakano K, Eishi K, Tanaka N, Kito Y, Kawashima Y. Cox maze procedure for chronic atrial fibrillation associated with mitral valve disease. Journal of Thoracic and Cardiovascular Surgery. 1994; 108:1049-1054
  29. Cox J, Schuessler R, D’Agostino H, Stone C, Chang B, Cain M, Corr P, Boineau J. The surgical treatment of atrial fibrillation. III. Development of a definitive surgical procedure. Journal of Thoracic and Cardiovascular Surgery. 1991; 101: 569–583
  30. Cox J, Schuessler R, Boineau J. The development of the Maze procedure for the treatment of atrial fibrillation. Seminars in Thoracic and Cardiovascular Surgery. 2000; 12: 2–14
  31. Cox J, Boineau J, Schuessler R, Kater K, Ferguson T, Cain M, Lindsay B, Smith J, Corr P, Hogue C etal. Electrophysiologic basis, surgical development, and clinical results of the Maze procedure for atrial flutter and atrial fibrillation. Advances in Cardiac Surgery. 1995; 6: 1–67
  32. Sundt T, Camillo C, Cox J. The Maze procedure for cure of atrial fibrillation. Cardiology Clinics. 1997; 15: 739–748
  33. Cox J, Ad N, Palazzo T, Fitzpatrick S, Suyderhoud J, DeGroot K, Pirovic E, Lou H, Duvall W, Kim Y. Current status of the Maze procedure for the treatment of atrial fibrillation. Seminars in Thoracic and Cardiovascular Surgery. 2000; 12: 15-19
  34. Gillinov A. Surgical ablation of atrial fibrillation. Journal of Interventional Cardiac Electrophysiology. 2005; 13: 115-24
  35. Gaita F, Galloti R, Calo L, Manasse E, Riccardi R, Garberoglio L, Nicolini F, Scaglione M, Di Donna P, Caponi D, Franciosi G. Limited posterior left atrial cryoablation in patients with chronic atrial fibrillation undergoing valvular heart surgery. Journal of the American College of Cardiology. 2000; 36: 159-66
  36. Nakajima H, Kobayashi J, Bando K, Niwaya K, Tagusari O, Sasako Y, Nakatani T, Kitamura S. The effect of cryo-maze procedure on early and intermediate term outcome in mitral valve disease: case matched study. Circulation. 2002; 106[supp I]: I-46-I-50
  37. Gaita F, Riccardi R, Caponi D, Shah D, Garberoglio L, Vivalda L, Dulio A, Chiecchio A, Manasse E, Gallotti R. Linear cryoablation of the left atrium versus pulmonary vein cryoisolation in patients with permanent atrial fibrillation and valvular heart disease. Circulation. 2005; 111:136-142