Key Points
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Large myocardial lesions can be created in the right and left ventricles in animal models with use of nitrous oxide–powered catheters.
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A 8-mm tip electrode on a 9-French catheter produced transmural lesions at all applications done in an animal model.
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Cryoablation of idiopathic left ventricular tachycardia and of right ventricular outflow tract (RVOT) tachyarrhythmias in humans were reported with success rates comparable with radiofrequency catheter ablation.
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Cryoablation does not trigger focal activity during ablation.
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Cryoablation of RVOT tachyarrhythmias is painless, in contrast with radiofrequency ablation.
Efficacy of cryoablation to treat ventricular tachycardias (VTs) was first proved for open-chest heart surgery in a patient with scleroderma-associated VT in 1978 and in a case of right ventricular outflow tract (RVOT) tachycardia in 1979. During a period between 1980 and 1990 when no implantable defibrillators were available, surgical aneurysmectomy and subendocardial resection after ventriculotomy were the last chance for life-saving in cases of life-threatening ventricular tachyarrhythmias in patients with ischemic heart disease who were resistant to drug treatment. Cryoablation was often used in combination with a scalpel; presumably, it was used for better preservation of postoperative left ventricular function caused by less pronounced stromal effects of cryothermia.
For percutaneous, transluminal cryocatheter ablation, the first success was demonstrated by Paul Gillette and colleagues in Charleston, South Carolina, reported in 1991. They successfully ablated the atrioventricular (AV) node in an animal model. The catheter used had an 11-French (Fr) diameter and was cooled with pressurized nitrous oxide, which is characterized by a nadir temperature of −92°C when being vaporized. This refrigerant is currently used in transvenous cryocatheters as well.
Since 2000, catheter-based cryoablation has been reported in larger patient cohorts, for AV nodal reentrant tachycardia, Wolff–Parkinson–White syndrome, atrial flutter, and atrial fibrillation. These initial promising reports have been confirmed. The cryoablation of supraventricular tachycardias has recently developed into a useful alternative to radiofrequency (RF) ablation with a better safety profile, as outlined in previous chapters.
Concerns about the Role of Cryoablation in Ventricular Tachycardias
Compared with supraventricular tachycardias, the use VT ablation and number of peer-reviewed publications were low. What might be the reasons for this? First, and maybe most important, is the fact that the tip electrode of such a catheter is fixed to the tissue side at one point during the refrigerant delivery. This results in a smaller surface area of coagulation, which is attractive in relation to safety aspects but not with respect to efficacy. In general, an ablation catheter in the ventricles is brushing with the tip electrodes, which are moved by different forces: breathing, valvular opening and closing, and the spiral movement of the ventricles during contraction. Because about 20 seconds after the start of refrigerant to cool the tip down are needed, there are virtually 1 to 2 seconds where the electrode is fixed to endocardial tissue during all the movements described. When it is not frozen very close to the target substrate, ablation will be unsuccessful, because position cannot be corrected during freezing. RF ablation catheters can be repositioned during energy delivery.
Another important issue is the recent strategy of larger substrate modification in patients with multiple scars in the left ventricle after myocardial infarction. Using a three-dimensional electroanatomic mapping system to create a line of block through different scar areas, application of cryoenergy is too time-consuming, because it needs 4 minutes for each freeze.
A third concern may be velocity of surrounding blood flow at the electrode. High blood flow cools the electrode driven with RF energy, which permits higher energy delivery with possible deeper lesions without an increasing risk for thrombus formation or charring. However, high blood flow velocity, which is expected in ventricles, can diminish freezing efficacy and lesion volume because of the warming effect from the surrounding blood.
Last, but not least, the outer dimensions of the sheets available for cryocatheters are large with 10-Fr or more for a large-tip cryocatheter. This can result in more bleeding complications, as well as AV fistulae formation. Although theoretic and somewhat speculative concerns exist, in our experience, they can be circumvented; these concerns and strategies against them are discussed in the following sections.
Results from Animal Studies
Reek et al reported results of cryoablation in the right and left ventricles of sheep with chronic myocardial infarction with inducible VT. In three sheep, they produced 12 left and 9 right ventricular lesions with a 10-Fr cryocatheter at a mean temperature of −84.1°C. The respective mean lesion volume was 175.8 ± 170.3 mm 3 . Lesion depth was found with 4.2 ± 2.5 mm. However, only 5 of 21 lesions were transmural. In the postmyocardial infarction model, they could induce VT in three of six sheep, from which five were targeted. With 6 ± 3 applications, they were successful to ablate the responsible tissue side without reproducible induction by programmed ventricular stimulation. The authors could prove that, after myocardial infarction, VT ablation is possible with a cryocatheter. However, insufficient transmurality in the majority of applications was also demonstrated.
D’Avila et al reported about whether linear epicardial cryoablation was capable of creating large, homogenous lesions in regions of the myocardium, including scarred ventricles in a chronic porcine postinfarction model and healthy animals. Eighty focal endocardial and 28 focal epicardial cryolesions were compared with regard to lesion characteristics in normal animals. Average lesion depth was 4.8 ± 0.2 mm in epicardial lesions and 4.6 ± 0.9 mm in endocardial lesions. The length and width of epicardial lesions were significantly larger compared with endocardial ones. This can result from the lack of blood flow at the epicardial location. Lesions at the borderline zone of infarction scars were not different from those at healthy myocardium.
Both studies proved that large and deep lesions can be obtained at the endocardial site either in healthy or infracted myocardium using large-tip cryocatheters, and that postinfarction VT can be successfully ablated in animal models.
An important question in regard to importance of size of the cryocatheter to create a high-volume lesion in the ventricles was addressed by Hashimoto et al. in 2009. A 7-Fr catheter with a 6-mm tip electrode was compared with an 9-Fr catheter with an 9-mm electrode. Lesions were produced at the endocardial and epicardial aspects in an animal model. Time for cryoenergy delivery was chosen with 240 seconds at one place at a temperature between −70°C and −80°C measured at the electrode. In acute experiments in the 7-Fr group, endocardial lesion volume was 144.1 ± 86.0 mm 3 and lesion depth was 5.1 ± 1.6 mm, and epicardial lesion volume was 205.6 ± 157.8 mm 3 and lesion depth was 4.7 ± 2.2 mm. In the 9-Fr group, endocardial lesion volume was 301.5 ± 177.4 mm 3 ( P < 0.001 vs. 7-Fr group) and lesion depth was 8.4 ± 1.9 mm ( P < 0.001 vs. 7F group), and epicardial lesion volume was 375.3 ± 167.6 mm 3 ( P < 0.01 vs. 7-Fr group) and lesion depth was 5.0 ± 2.3 mm. All applications with the 9-mm tip electrodes were transmural. In summary, larger catheters produce significantly deeper lesions, but require diameters of 9-Fr.
Cryoablaton of Ventricular Tachyarrhythmias in Humans
In pediatric patients, treatment of right VTs was reported from an international multicenter registry published in 2005. Three of 66 patients reported suffered from VT, which was successfully ablated in 2 of 3. Cryomapping with a first attempt of only −30°C was used in patients of this registry before final ablation attempt. With limitation regarding the small number of patients with VT, success rate was lower compared with patients with SVT.
A successful cryoablation in a child with a VT origin from the proximal right bundle brunch has been reported from Children’s Hospital Boston. Roberts-Thomson et al. reported few cases with epicardial approaches to VT out of more than 4000 ablations. The main goal was the analysis of complications caused by injury of coronary arteries. They reported a serious injury of a branch of the right coronary artery after epicardial cryoablation. Although total complication rate at coronary arteries was very low with 0.09% of all cases of different arrhythmogenic targets, that demonstrated that complications of a serious nature can occur independent of a used technology, which was thought to be highly safe.
Cryoablation of Left Ventricular Tachycardias
Of great interest is a study published in 2010 by Timmermans et al. from the Netherlands. The authors described the attempt to ablate VT originating from the left ventricle. Postinfarction VT is the most common VT, besides outflow tract tachyarrhythmias and much more seldom idiopathic VT. In their study, the authors included 10 patients with postinfarction VT and 7 patients with idiopathic VT. They used a 10-Fr 6.5-mm tip cryocatheter for ablation. The ablation site was selected using entrainment mapping techniques for postinfarction VT. The site of the earliest activation time with optimal pace mapping was used for ablation of idiopathic VT. All targeted VTs were acute and successfully ablated after a median number of two applications of 5 minutes with an average temperature of −82 ± 4°C. Mean procedure and fluoroscopy times were 204 ± 52 and 52 ± 20 minutes for postinfarction VT and 203 ± 24 and 38 ± 15 minutes for idiopathic VT. During a follow-up of 6 months, 40% of patients with myocardial infarction–based VT had a recurrence of the arrhythmia, and only 1 in 7 in the group of idiopathic VT. Although this study had a small number of patients, this is the first report about successful ablation of both infarctions, scar-related VT and bundle brunch reentry VT.
Cryoablation of Right Ventricular Outflow Tract Tachycardias
With the earlier discussed concerns in mind, we attempted to ablate ventricular tachyarrhythmias with focal origin in the RVOT. Results of our group’s early publication from Kurzidim et al. and later experience are discussed in this section.
This type of ventricular arrhythmia has typical electrocardiographic characteristics, which allows for estimation of the location within the RVOT. In general, it has an inferior axis in inferior leads. Negative R wave in V 1 -V 3 is common. Early R-wave progression in V 1 -V 3 is helpful for differentiation from left ventricular outflow arrhythmias.
This group of patients is often symptomatic because of a large amount of premature ventricular contractions (PVCs), periods of bigeminal PVCs, and no sustained VTs. RVOT arrhythmias share a common characteristic: In virtually all patients, this abnormality is unrelated to underlying structural heart disease. The arrhythmia can usually be cured by focal RF ablation within the RVOT, at or just below the pulmonary valve, as it was described early in 1992 with RF energy.
Earlier attempts of our group to ablate with a 7-Fr, 6-mm tip electrode cryocatheter in the RVOT were unsuccessful. However, the introduction of a 9-Fr cryocatheter with an 8-mm tip electrode (Freezor MAX; CryoCath Technologies, Montreal, Quebec, Canada) offered new opportunities. This catheter was proved to have an increase of 60% more refrigerant flow capacity in comparison with smaller catheters.
Meanwhile we have successfully ablated 28 of 31 patients using this technique. Results do not differ from a publication after early experience of our group in 2005. Female sex was largely predominant (25/31). Age was between 30 and 68, with a median of 46 years. Most common symptoms were palpitations with severe anxiety that something dangerous can happen. Further symptoms were sweating, reduction in exercise capacity, and dizziness. Three patients suffered from presyncope; only one patient had syncope. β-blockers were administered in 34 patients and class 1C in 6 patients before ablation without success. Before the procedure, we obtained informed written consent for cryoablation from the patients. It should be mentioned that prescription of β-blockers increased symptoms and number of PVCs in about 50% of patients pretreated with this class 2 medication. The underlying mechanisms, which we can only speculate about here, are delayed afterpotentials from the Purkinje fibers, increasing in number at lower heart rates.
In general, we use RF energy ablation for RVOT arrhythmias. The group of patients reported here was selected because of a high degree of fear related to the ablation procedure. We know from our and others’ experiences with cryoablation of supraventricular tachycardias that application of cryoenergy is without pain. RF energy application at the RVOT often produces discomfort to severe pain, which makes analgesia and sedation necessary. From this point of view, cryoablation is especially helpful in patients who are afraid of the procedure.
In patients with dizziness, presyncope, or syncope, we used the Freezor MAX for mapping and ablation in the RVOT, and an additional 7-Fr steerable catheter for programmed atrial and/or right ventricular stimulation to exclude other arrhythmias. In two patients with different morphologies from RVOT, we used an additional 20-mm Lasso catheter placed a few millimeters below the pulmonary valve for a more rapid and precise identification of different exit locations of PVCs. An example of catheter position for this approach is given in Figure 16–1 . In the majority of patients, only Freezor MAX was used as a single-catheter approach.
