Author + information
- Received November 9, 2017
- Revision received December 20, 2017
- Accepted December 21, 2017
- Published online February 28, 2018.
- Koji Miyamoto, MD,
- Suraj Kapa, MD,
- Siva K. Mulpuru, MD,
- Abhishek J. Deshmukh, MBBS,
- Samuel J. Asirvatham, MD,
- Thomas M. Munger, MD,
- Paul A. Friedman, MD∗ ( and )
- Douglas L. Packer, MD
- Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
- ↵∗Address for correspondence:
Dr. Paul A. Friedman, Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905.
Objectives This study aimed to assess the outcome of cryoablation in patients with ventricular arrhythmias (VAs) originating from the para-Hisian region.
Background There are few data regarding the outcome of cryoablation in patients with VAs originating from the para-Hisian region, where there is the risk of injury to the conduction system.
Methods The study analyzed all patients undergoing cryoablation at the Mayo Clinic (Rochester, Minnesota) as part of an ablation for VAs originating from the para-Hisian region.
Results The study population consisted of 10 patients (64 ± 15 years of age, 7 men). Cryoenergy was applied after an unsuccessful radiofrequency (RF) ablation in 8 (80%) patients. The VAs were successfully ablated with cryoablation in 7 (70%) patients; RF ablation after an unsuccessful cryoablation eliminated the VAs at almost the same location with careful monitoring in 1 patient. The authors could not ablate the actual focus because a transient atrioventricular block developed during cryo- and RF energy applications, which led to an unsuccessful ablation in the remaining 2 patients. A complete atrioventricular block occurred during the cryoenergy application in 1 patient, who needed a permanent pacemaker implantation. There were no VA recurrences in 4 of 8 (50%) patients with procedural success during a median follow-up period of 122 days (interquartile range: 43 to 574 days).
Conclusions Cryoablation is clinically effective in some patients with VAs originating from the para-Hisian region, where there is the risk of injury to the conduction system, and therefore should be considered as an alternative to or in addition to RF ablation in these cases. Cryoablation requires care because it can also lead to major complications.
Radiofrequency (RF) ablation is the gold standard for the catheter-based ablation of ventricular arrhythmias (VAs) and supraventricular arrhythmias due to its larger and deeper lesion creation (1,2). However, cryoablation is considered as an alternative energy source when there is the risk of injury to critical structures such as the His bundle (3,4). In addition, cryoablation has been used to improve catheter stability and energy delivery in cases in which RF ablation fails (3,5).
There are, however, few data regarding the safety and efficacy of cryoablation with respect to VAs originating from the para-Hisian region, where there is the risk of injury to the conduction system. This study aimed to assess the outcome of cryoablation in patients with VAs originating from the para-Hisian region.
We retrospectively analyzed all patients undergoing cryoablation as part of an ablation for VAs origination from the para-Hisian region between April 1, 2008, and February 28, 2017, at the Mayo Clinic (Rochester, Minnesota). Cryoablation was performed in patients with VAs originating from the para-Hisian region due to the potential risk of injury to the His bundle. The study was approved by the Institutional Review Board, and written informed consent was obtained from all patients before the procedure. Patients who underwent cryoablation for other reasons, such as for VAs originating from a non–para-Hisian region, or supraventricular tachycardia ablation, were excluded. We assessed the clinical characteristics, procedural success, complications, and clinical success.
Steerable multielectrode catheters were positioned in the coronary sinus, His bundle region, and right ventricular (RV) apex for recording and pacing. Intracardiac echo and fluoroscopy were used as a means to locate the cardiac structures and assess the pericardial space during the procedures.
Programmed ventricular extrastimulation of up to 3 extrastimuli and burst pacing from the RV or left ventricle (LV) was performed at baseline and after an isoproterenol infusion. The 3-dimensional geometry, voltage map, or activation map of the chamber of interest were depicted by the CARTO version 3, XP (Biosense Webster, Diamond Bar, California) mapping system. Pace mapping was also used to determine the origin of the VA. It was performed with a pacing cycle of 600 ms, pulse width of 2 ms, and at twice the diastolic threshold. The location of the His bundle electrograms was assessed in both the RV and LV. A retrograde transaortic approach was used to access the LV.
Cryoenergy or RF energy were delivered at myocardial sites exhibiting the earliest ventricular activation, a local unipolar QS pattern, or perfect pace mapping. For cryoablation, we used a 4-mm or 6-mm-tip cryoablation catheter (Freezor, Medtronic, Minneapolis, Minnesota). At first, cryomapping at –30°C was performed to assess the electrical conductivity by a cryoenergy application when using 4-mm-tip catheter. Only when the cryomapping was safe, a 4-min ablation freeze with a target temperature of –70 to –80°C was applied while monitoring the conduction system. For RF ablation, we used an open irrigated tipped catheter (Thermocool, Biosense Webster). RF energy was delivered for up to 2 min in a power-controlled mode as follows: a power of 30 to 50 W and an irrigation rate of 17 to 30 ml/min.
After the ablation, programmed RV stimulation was repeated to induce the VAs. The endpoint of the catheter ablation was the elimination and subsequent noninducibility of VAs during an isoproterenol infusion, programmed ventricular extrastimulation, and burst pacing.
Definitions of the procedural and clinical outcomes
Procedural and clinical success was defined as follows.
1. Procedural outcome: defined as successful if there was an elimination and noninducibility of the clinical VA. A procedure was deemed as failed if the clinical VA was not eliminated, or if it was inducible with isoproterenol or programmed stimulation.
2. Clinical outcome: defined as successful if the VA burden with Holter recordings was reduced by more than 80% when compared with a pre-procedure recording, and there was the absence of arrhythmia symptoms at the last follow-up, either on or off antiarrhythmic drugs (6). Clinical failure was defined as the presence of symptoms or clinical VAs despite antiarrhythmic drugs, requiring a repeat procedure, and/or no significant reduction in the VA burden with follow-up Holter recordings (<80% burden reduction).
All patients underwent at least 24 h of continuous monitoring of their electrocardiograms after the ablation procedure. Patients underwent serial physical examinations, complete blood counts, and recording of the electrocardiogram and transthoracic echocardiogram. After hospital discharge, patients were followed via telephone interviews at 30 days in addition to the follow-up recommended by their primary cardiologist. A 24-h Holter recording was obtained before and 1 to 3 months after the ablation. When patients had symptoms, additional Holter recordings were performed at our institute or the outpatient clinic.
The data are expressed as means ± SD for the continuous variables and as numbers and percentages for the categorical variables.
The study population consisted of 10 patients who underwent cryoablation for VAs originating from the para-Hisian region (Table 1). Seven (70%) patients were men. The mean age was 64 ± 15 years. The LV ejection fraction was reduced (<50%) in 4 (40%) patients, and the mean LV ejection fraction was 47 ± 12%. Five (50%) patients had underlying heart disease with tachycardia-induced cardiomyopathy in 2 patients, dilated cardiomyopathy in 2 patients, and aortic valve replacement in 1 patient. Four (40%) patients had undergone a prior RF ablation session. The total number of VAs per day assessed by Holter recordings before the procedure was 23,226 ± 13,303.
The site of the earliest ventricular activation was found in the RV in 6 (60%) patients and in the LV in 4 (40%) patients. Cryoablation was attempted after an unsuccessful RF ablation in 8 (80%) patients, and without a previous RF ablation in the remaining 2 (20%) patients. The VAs were successfully ablated with cryoablation in 7 (70%) patients; however, 1 patient developed complete atrioventricular block (AVB). The cryo- and RF ablation procedures were performed from both the RV and LV in another 2 patients. However, transient AVB developed during cryo- and RF energy applications, and we could not ablate the actual focus, which led to an unsuccessful ablation in these 2 patients. The remaining patient was ablated successfully with an RF application after a failed cryoablation at almost the same location while carefully monitoring the electrograms during the ablation. A 4-mm tip cryoablation catheter was used in 5 patients, and a 6-mm tip in the remaining 5 patients. The procedure time, fluoroscopic time, and radiation exposure were 359 ± 67 min, 52 ± 18 min, and 1,073 ± 965 mGy, respectively (Table 2). Figure 1 shows a flow chart of the ablation results.
Figure 2 shows a representative case of a VA originating from the para-Hisian region in a 33-year-old man. The earliest ventricular activation site of the premature ventricular contractions (PVCs) was at an RV anteroseptal position near the His bundle. We elected to proceed with cryoablation rather than RF ablation. Although a His bundle electrogram was recorded at the earliest site, cryomapping had no influence on the conduction system. The VA was eliminated by cryoablation at that site without any disturbance of the conduction system.
A complication occurred in 1 patient (a 77-year-old man) who developed complete AVB during the cryoablation (Figure 3). At baseline, the patient had first-degree AVB with a PR interval of 204 ms. We identified the earliest ventricular activation site near the His bundle. We elected to use cryoablation with a 4-mm tip to reduce the risk of AVB. We carefully mapped the area adjacent to the His bundle. The initial cryoapplication was 1 cm below the His bundle. PVCs were quickly eliminated when the cryotemperature dropped down to −80°C. However, when the cryoapplication was discontinued, the PVCs recurred. A cryoapplication to a superior location to the His bundle did not have any effect on the PVCs. We applied the cryoapplication 1 cm below the His bundle again, where a far-field His bundle electrogram was recorded and the local electrogram was 16 ms before the onset of the QRS complex. PVCs were eliminated during the mapping mode at −30°C, and the AV conduction was intact. Then the temperature was lowered to −80°C. In 5 s, complete AVB developed, and the cryoablation was stopped. We observed the AVB for 1 h during the procedure and 24 h after that; however, complete AVB persisted with a junctional escape rate between 30 to 50 beats/min and a permanent pacemaker was implanted.
There were no VA recurrences in 4 of 8 (50%) patients with procedural success (4 of 7 patients that were successfully ablated with cryoablation) during a median follow-up period of 122 days (interquartile range: 43 to 574 days). The VAs were successfully ablated in 4 of 6 patients with nonsustained ventricular tachycardia and in all 4 patients with PVCs. In those 8 patients that were successfully ablated, there were no VA recurrences in 1 of 4 patients with nonsustained ventricular tachycardia and 3 of 4 patients with PVCs. The LV ejection fraction normalized in 2 patients that were successfully ablated with cryoablation and had no VA recurrences (47% to 54% and 45% to 61%, respectively). In 6 patients with an unsuccessful procedure (2 patients) or a clinical VA recurrence (4 patients), 2 patients underwent a subsequent ablation session with RF ablation; however, RF ablation could not eliminate the VAs in both patients.
Reduced risk of damage to the conduction system
Cryoablation is frequently considered in patients with VAs originating from the para-Hisian region, where there is the risk of injury to the conduction system. RF ablation near the conduction system can cause complete AVB (7). The “reduced risk of damage to surrounding structures” in cryoablation is thought to be attributed to its feature of creating reversible and smaller lesions with a well demarcated border zone as compared with RF ablation (8,9). Cryomapping at less severe temperatures has been used to assess the electrical conductivity by a cryoenergy application before the formation of a permanent lesion. If the electrical conductivity was impaired, it would recover after the cessation of energy application. Only when cryomapping is safe, cryoenergy with a target temperature of −70°C to −80°C is applied while monitoring the conduction system. That is why no permanent AVB had been reported with cryoablation thus far; however, variable degrees of transient AVB have been reported during cryoablation in 2% to 23% of procedures (3,10,11).
The degree of irreversible damage created by freezing is, however, controversial and early acute irreversible effects with fatal changes in the subcellular organelle structure and mitochondrial destruction have also been reported (9,12). In addition, it remains unclear whether the cryothermal effect by cryomapping with a temperature of −30°C always implies that by cyroablation with a target temperature of −70°C to −80°C. Kimman et al. (13) reported that 2 cases had temporary complete AVB by cyroablation with a temperature of −75°C, whereas this was not observed during cryomapping with a temperature of −30°C. Furthermore, the size of the ice ball is often larger than the tip of the catheter, and it may lead to damage to unanticipated sites. In our series, injury to the conduction system did not recover, and an implantation of a permanent pacemaker was required in 1 case. That case already had an impaired conduction system (first-degree AVB) at baseline. This highlights the need for extreme caution when ablating near the conduction system, even when using cryoenergy. To the best of our knowledge, this is the first report that has described complete AVB requiring a permanent pacemaker implantation as a complication of cryoablation.
When mapping and ablating near a critical structure, it may be reasonable to precisely map with a closely spaced bipolar catheter and we should ablate with a small-tipped catheter starting slightly away accounting for the increase in the ice ball compared with the tip of the catheter. In addition, detailed pace mapping would provide a more precise mapping as Rivera et al. (5) reported. Unlike RF ablation, we lose electrical information from the tip electrode during cryoablation without any conduction system ectopy so careful attention is needed.
Advantages of cryoablation as compared with RF ablation
The potential advantages of cryoablation as compared with RF ablation are: 1) a reduced risk of damage to surrounding structures such as the conduction system, coronary arteries, and phrenic nerves; 2) increased stability of the ablation catheter due to adhesion of the ablation catheter to the tissue; and 3) improved delivery of energy where RF energy cannot be delivered due to an impedance rise or adipose tissue.
Cryoablation of VAs arising from the coronary cusp and coronary venous system has been reported to be suitable to avoid injury to the coronary arteries (3,4,14). The injury to the coronary arteries may lead to life-threatening complications (15). McDonnell et al. (4) reported the safety and efficacy of cryoablation for VAs arising from the coronary cusp. The cryoablation for VAs arising from the coronary venous system has been reported to be suitable although the efficacy is limited (approximately 50%) (3). Aoyama et al. (14) compared cryo- and RF ablation within the canine coronary sinus, and showed that the risk of cryoablation in the coronary sinus has a lower risk of coronary stenosis than RF ablation.
Cryoablation is considered in patients with Vas to address catheter instability at sites where maintaining catheter contact is challenging due to constant motion of a contracting muscular structure, unstable force vector orientation of the catheter tip in the epicardial space, and ablation triggered VAs (5,16). Rivera et al. (5) compared cryoablation and RF ablation in VAs arising from papillary muscles of the LV, and reported a 100% success rate with cryoablation.
Cryoablation is also considered in patients with VAs to address insufficient RF energy deliveries because of impedance rises or adipose tissue in the epicardial space. The presence of epicardial fat prevents thermal conductivity by RF energy, leading to an incomplete lesion creation. Although the influence of epicardial fat on the cryothermal energy is controversial, cryoablation holds the potential of creating a deeper lesion compared with RF ablation (17,18).
Although we used a 24-h Holter recording and the presence of symptoms to define the outcome of the ablation, a longer and more frequent monitoring may be preferable because of the day-to-day variability in the VA frequency. This study was a retrospective analysis performed at a single center with a high procedural volume. Cryoablation has the potential advantage to reduce the risk of damage to surrounding structures; however, it is difficult to accurately set the threshold of the distance to avoid injury to critical structures. Further investigation with a larger patient population is required to confirm our results and the broader applicability.
Cryoablation is clinically effective in some patients with ventricular arrhythmias originating from the para-Hisian region, where there is the risk of injury to the conduction system, and therefore it should be considered as an alternative to RF ablation in these cases. Cryoablation requires careful attention because it can also lead to major complications.
COMPETENCY IN MEDICAL KNOWLEDGE: Because of the inability of RF energy to achieve safe and adequate lesions in some cases due to the risk of injury to the conduction system, cryoablation may be helpful. Cryoablation is clinically effective in some patients with ventricular arrhythmias originating from the para-Hisian region. However, caution is still required to avoid major complications.
TRANSLATIONAL OUTLOOK: More studies are needed to assess the efficacy and safety of a variety of energy sources such as cryoablation for ventricular and supraventricular arrhythmias. Particular focus should be placed on ventricular and supraventricular arrhythmias originating from critical structures such as the coronary arteries and phrenic nerves.
Dr. Packer has served as a consultant for Abbott, Aperture Diagnostics, Biosense Webster, Boston Scientific, CardioFocus, Johnson & Johnson Healthcare Systems, Johnson & Johnson, MediaSphere Medical, Medtronic, St. Jude Medical, Siemens, and Spectrum dynamics; has received research funding from Abbott, Biosense Webster, Boston Scientific/EPT, CardioInsight, CardioFocus, Endosense, Hansen Medical, Medtronic, the National Institutes of Health, Robertson Foundation, St. Jude Medical, Siemens, and Thermedical; and has received royalties from Wiley & Sons, Oxford, and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Abbreviations and Acronyms
- atrioventricular block
- left ventricle/ventricular
- premature ventricular contraction
- right ventricle/ventricular
- ventricular arrhythmia
- Received November 9, 2017.
- Revision received December 20, 2017.
- Accepted December 21, 2017.
- 2018 American College of Cardiology Foundation
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