Ablation Of Cardiac Arrhythmias2005: State Of The Art

Roberto De Ponti, MD

Department of Cardiovascular Sciences, Ospedale di Circolo e Fondazione Macchi, Universityof Insubria, Varese, Italy

Address for correspondence: Roberto De Ponti, MD, Department of Cardiovascular Sciences,Ospedale di Circolo e Fondazione Macchi, University of Insubria – Varese, Italy, Viale Borri,57, I-21100 Varese, Italy. E-mail: rdponti@tin.it

Abstract
At the time of antiarrhythmic surgery, cryothermal energy application by a hand-heldprobe was used to complement dissections and resections and permanently abolish thearrhythmogenic substrate. Over the last decade, significant engineering advances allowedpercutaneous cryoablation based on catheters, apparently not very different from standardradiofrequency ablation catheters. Cryothermal energy has peculiar characteristics. In fact, itallows testing in a reversible way the effects of energy application at higher temperature, beforeproducing a permanent lesion at –75°C. Moreover, slow formation of the lesion allows timelydiscontinuation of the application, as soon as inadvertent modifications of normalatrioventricular conduction are observed during ablation in the proximity of atrioventricular nodeand His bundle, avoiding its permanent damage. Over the last years, percutaneous cryothermalablation has been widely used for a variety of cardiac arrhythmias. From the data gathered, it isunlikely that cryoablation will replace standard ablation in unselected cases. Nevertheless, for theabove mentioned peculiarities, cryothermal ablation has proved very effective and safe forablation of arrhythmogenic substrates close to the normal conduction pathways, becoming thefirst choice method to ablate anteroseptal and midseptal accessory pathways. It can be also thebest treatment for ablation of the slow pathway to abolish atrioventricular node reentranttachycardia in pediatrics or when particular anatomy of the Koch’s triangle is observed.Cryothermal ablation of the pulmonary veins for atrial fibrillation, although longer thanradiofrequency ablation, is not associated with pulmonary vein stenosis and is expected to be lessthrombogenic; new catheter designs for cryothermal ablation of this challenging arrhythmia areto be tested to assess their efficacy and clinical usefulness.

Keywords: cryoablation; cardiac arrhythmia

From surgical to catheter-based cryoablation

In the 80’s, epicardial cryoablation was introduced in antiarrhythmic surgery for ablationof accessory pathways by Klein et al1. A hand-held cryoprobe was applied at the site whereintraoperative mapping localized the arrhythmogenic substrate. The probe was refrigerated to–60°C and its effectiveness was evaluated during continuous monitoring of the cardiac electricalactivity. This method, largely used in the past2,3,4for antiarrhythmic surgery and still in use for

the treatment of some forms of ventricular tachycardia5,6, is safe and effective. During surgery,cryomapping allowed precise localization of the arrhythmogenic substrate by monitoring theeffect of a cryothermal energy application with higher temperature (0 to –15°C) for a limitedtime (15-30s), before producing a permanent lesion at –65°C only in the most appropriate site7. In the 90’s, significant engineering advances allowed the development of systems forpercutaneous cryoablation, consisting of a steerable catheter, apparently not very different fromstandard ablation catheters for radiofrequency energy delivery, and a dedicated console (Figure1). Fluid nitrous oxide is delivered under pressure to the catheter tip through a hollow injectiontube, which runs internally for the whole length of the catheter. In a small chamber inside the tipelectrode, nitrous oxide is made expand and a liquid to gas phase change takes place with heatextraction from the electrode-to tissue interface. The gas is constantly removed through a secondcoaxial lumen inside the catheter, under vacuum. The tip temperature is constantly monitored bythe console, which in turn adjust the nitrous oxide flow to obtain and maintain the presettemperature. Two systems for cryoablation are currently available. The first is provided byCryocath Technologies Inc. (Montreal, Canada) and utilizes 7 or 9 F steerable catheters with 4, 6or 8 mm long tip electrode. The ablation catheter is connected to a dedicated console, which hastwo algorithms available: 1) for cryomapping with slow decrease of the temperature to – 30°C upfor 80 s; 2) for cryoablation with faster decrease of the temperature to –75°C for up to 480 s. Inany case, the target temperature can be manually preset on the console at any value between –30and –75°C. The second system (CryoCor Inc., San Diego, California, USA) has 10 F steerablecatheters with 6.5 or 10 mm long tip electrodes. The console has a built-in closed loop pre-coolerfor the fluid nitrous oxide, whose flow at the catheter tip is adjusted during the application tomaintain a temperature of –80°C.
Figure 1.
Scheme of cryoablation system. The steerable catheter and the console areconnected by: 1) a coaxial cable, used both to deliver fluid nitrous oxide to thecatheter and to remove separately the gas from the catheter; 2) electrical cable, whichis connected both to the conventional recording system for electrograms (EGMs)analysis and storage and to the console for reading of the tip temperature. A tank offluid nitrous oxide is located inside the console; the gas removed from the catheter tothe console is evacuated through a scavenging hose into the vacuum line of theelectrophysiology laboratory. The system has several sensors to avoid inadvertentleaks of nitrous oxide into the patient body and to check connections of the differentcables to the console.

Lesion formation by cryothermal energy

Since cryothermal energy has been widely used in surgery, the types of cellular lesioncaused by tissue freezing are well known8. The mechanisms underlying lesion formation by

cryoenergy are two-fold: 1) a direct cell injury and 2) a vascular mediated tissue injury.The direct cellular injury is due to ice formation, which has different distributionaccording to temperature reached during cooling. By cooling to mild temperature (0 to –20°C),ice forms only extracellularly. Consequently, extracellular environment becomes hyperosmoticand an intracellular to extracellular water shift occurs. This causes cellular shrinkage and damageto membrane. Cooling to these temperature may result in cellular death, if the application isenough prolonged. Using short applications with limited temperature, the effect produced on thecell is reversible and cellular function recovers, although minimal cellular damage may beproduced. In the clinical use, the option of producing a functionally reversible lesion is quiteattractive to test the effect of cryoablation without producing a permanent lesion. Conversely, bycooling down to –40°C and further, intracellular water freezes and formation of intracellular iceresults in major and irreversible disruption of organelles and cell membrane with cellular death.Intracellular ice may propagate from one cell to another via intercellular channels.The second mechanism underlying lesion formation by cryothermal energy delivery is avascular-mediated mechanism. In fact, the initial tissue response to cooling is vasoconstrictionwith decreased blood flow. As tissue freezes, circulation ceases uniformly in the frozen tissue.The uniformity of cell death in a lesion produced by cryothermal energy has suggested ischemicnecrosis as the main mechanism for tissue death, although it is impossible to distinguish thetissue damage caused by this mechanism from the one produced by intracellular ice formation.Upon re-warming, a hyperemic response is observed with increased vascular permeability andedema formation. Other than producing increased permeability and edema, endothelial damageresults in platelet aggregation and micro-thrombus formation, with stagnation ofmicrocirculation in about 30-45 min.
Especially in the percutaneous closed chest cryoablation, the effect produced by energyapplication is the result of a temperature gradient occurring at the electrode/tissue interface andpossibly influenced by different factors, such as contact or blood flow. At the interface, thecoldest area is the one adjacent to the catheter tip, where functional effects of energy delivery areobserved earlier. Conversely, the less cooled area is the one at the periphery of the cryolesion,whose dimensions may also vary according to the duration of freezing. Due to limited (both intime and temperature) cooling of outer limit of the lesion, reversible tissue damage is more likelyto occur in this area. As a consequence, the effects obtained late during cryothermal energyapplication are likely to revert early upon re-warming and, therefore, any expected functionalmodification induced by cryoenergy should occur early (usually within the first 30 s of theapplication) in order to obtain a successful and permanent ablation of a given arrhythmogenicsubstrate.

Cryothermal vs radiofrequency energy: differences and their clinical implications

In closed chest cryoablation, the effect of cryothermal energy application greatly dependson the minimum temperature reached, the application duration and the temperature timeconstant9. The latter value indicates the course of the descent of temperature to the targettemperature and a shorter value (expressed in seconds) identifies a more effective application.Due to intrinsic characteristics of cryothermal energy at a fixed minimum temperature, the lesionforms more slowly than the one produced by hyperthermic injury. This has two practicalimplications. The first is that the application duration for cryoablation is significantly longer thanfor radiofrequency energy and a lesion produced by cryothermal energy by a 4 mm tip 7 Fcryocatheter at –75°C for 240 s has a comparable depth to the one obtained by radiofrequencyenergy applied in temperature control mode at 50 W, +70°C for 60 s10. Second, the longerestimated time required to create a permanent lesion may be clinically useful to better modulatethe lesion formation in critical areas (i.e. close to the atrioventricular node-His bundle). In thesecases, if inadvertent modifications of conduction over the normal pathways is observed duringthe application, immediate discontinuation of cryothermal energy application results in return to

baseline conduction properties, with no permanent damage to normal conduction. Recently, ithas been demonstrated in a canine model10 that cryolesions are associated with significantly lessendothelial disruption and overlying thrombus formation as compared to lesion produced byradiofrequency energy, regardless of the preventive use of aspirin. This characteristic could bevery important, especially when multiple and prolonged energy applications are required to treatatrial arrhythmias in the left atrium. Unlike lesions produced by a hyperthermic injury,cryolesions show both in open chest11and closed chest10,12models, a well demarcated borderzone and preservation of the extracellular collagen matrix with no collagen denaturation, norcontracture related to hyperthermic effects. These histologic observations combine with theclinical evidence that cryothermal energy application adjacent to coronary arteries, as well as invenous vessels (coronary sinus, middle cardiac vein and pulmonary veins)12,13,14,15, does notresults in damage nor chronic stenosis of their lumen.
In the already mentioned study10, it has been pointed out that lesions by radiofrequencyenergy have a comparable depth of those produce by cryoablation. Nevertheless, radiofrequencyenergy ablation resulted in a highly significantly greater area and a nearly significantly largervolume when compared to cryolesions. Moreover, colder temperatures were associated withdeeper lesions and greater area and volume were associated with use of 9 F as compared to 7 Fcatheters. It is not clear why cryothermal energy produces a lesion with similar depth, but smallerarea and volume, when compared to the one produced by a “similar” radiofrequency energyapplication. One plausible explanation could be the “cryoadherence” effect, which is a tightadherence of the catheter tip to the adjacent tissue caused by cooling. Due to this effect, thelesion produced is very focal, since the “brushing” of the tip electrode, usually observed duringradiofrequency ablation, is missing. On the other hand, the advantage of this effect is two-fold. First, below the critical temperature of –20°C it allows good tip electrode to tissue contact,which persists throughout the whole application and it is not dependent on the torsion/deflectionmanoeuvres applied to the catheter. It is well known that a fixed and stable contact during thewhole application is essential, especially for ablation in proximity of critical areas, such asatrioventricular node and His bundle. Second, the cryoadherence effect allows safe continuationof the application, even when sudden changes in heart rhythm that usually displace the ablationcatheter (such as tachycardia termination or pacing) occur. Moreover, cryoadherence does notcompromise safety, since, upon discontinuation of cryothermal energy delivery, the defrost phaseis very fast (within 3 s) and the catheter can be immediately disengaged from the ablationposition.

Finally, another peculiarity of cryothermal energy is the complete absence of patientsymptoms in almost every case, in spite long-lasting applications. In our experience, we haveevaluated patient perceptions during cryothermal energy application in a series of non-sedatedcases. In almost all cases, the absolute absence of perception was demonstrated by the fact thatthe patient was unable to tell when the application was started and discontinued. Only in somecases, when multiple and prolonged applications are delivered in the left heart, a light sense ofcold or headache is perceived as minor discomfort. Although the full explanation of the absenceof symptoms is not completely clear, this characteristic can be particularly useful in young aswell as in paediatric patients.

Clinical use in ablation of cardiac arrhythmias

Over the last five yeas, the world-wide experience in catheter ablation of cardiacarrhythmias by using cryothermal energy has increased unabated. Based on this experience,cryoablation should not be viewed as a replacement for radiofrequency energy, which willcontinue to be the method of choice in many clinical situations. Nevertheless, ablation bycryothermal energy should be rather considered as a useful addition to the electrophysiologist’sarmamentarium. In fact, different types of arrhythmias are now successfully treated bycryoablation and in some cases, especially in proximity to normal conduction pathways,

treatment by this energy source is considered the first choice therapy for its safety and efficacy.The following is a brief analysis of the experience in cryoablation for each of the consideredarrhythmias.

Atrioventricular nodal reentrant tachycardia. So far, slow pathway ablation for atrioventricularnodal reentrant tachycardia by cryothermal energy represents the numerically larger experiencein the clinical application of this new technology. Unlike radiofrequency energy, acceleratedjunctional rhythm is not observed during cryothermal energy application on the slowatrioventricular node pathway. Therefore, the only marker of effective ablation is suppression oftachycardia inducibility during initial cooling (Figure 2A-B). Accordingly, baseline noninducibility of the arrhythmia may be a limitation to the application of this technique. From theearly report16, several papers have contributed to accumulating experience in slow pathwayablation, with a satisfactory success rate and a recurrence rate varying from 6 to 9.7%17,18,19,20,21,22. In the “Frosty” trial19, a multicentric prospective trial performed in the UnitedStates, 103 patients with atrioventricular nodal reentrant tachycardia were enrolled. On anintention-to-treat basis, the acute procedural success was 91% with no device-relatedcomplications and a recurrence rate of 6% in a 6 month follow-up. Cryomapping proved usefulto predict the site of successful ablation. Nine patients had inadvertent modifications of theconduction over normal atrioventricular conduction pathways, including first to third degreeatrioventricular block and right bundle branch block. These all resolved completely, usuallywithin a minute or less and had no sequelae. A database gathering the worldwide experience andbased on a combination of registry and prospective trial data reports no case of permanentatrioventricular block following cryothermal ablation of the slow pathway in more than 300patients with atrioventricular nodal reentrant tachycardia20. Temporary first degree or higheratrioventricular block, observed in 15 cases (4.3%) during cryomapping at –30°C or duringcryoablation at –75°C, was always reversible. Recently, the results of the first two prospectiverandomized trials on transvenous cryoablation versus radiofrequency ablation of the slowpathway for treatment of atrioventricolar nodal reentrant tachycardia have been published21,22. Inthese studies, cryoablation proved as effective and safe for the cure of atrioventricular nodalreentrant tachycardia as radiofrequency ablation. The higher recurrence rate that may beobserved in the cryoablation group21suggests that, unlike radiofrequency ablation, prolongedenergy applications and postablation waiting time are necessary when cryothermal ablation isused to minimize recurrence in the follow-up. In our own experience, we treat atrioventricularnodal reentrant tachycardia by slow pathway cryoablation in patients with particular anatomiccharacteristics, refractory to standard radiofrequency energy ablation or in pediatrics. Especiallyin cases with difficult anatomy, such as a small or distorted Koch’s triangle, the characteristics ofcryothermal energy allow test of the ablation effect in particularly risky sites without producingirreversible damage to atrioventricular conduction, if the application is timely interrupted. Insome complex cases, we found it necessary to resort to longer cryothermal energy applications(up to 480 s) and to prolong postablation observation up to 60 min. In a patient withatrioventricular nodal reentrant tachycardia, who underwent multiple unsuccessful ablation of theslow pathway, we decided to target the fast pathway by cryothermal energy23. In this particularcase, selective and safe ablation of the fast pathway at the apex of the Koch’s triangle wasaccomplished and this resulted in permanent cure of the arrhythmia.

According to the presented data, cryothermal energy is a valuable and useful alternativeto radiofrequency energy to treat patients with atrioventricular nodal reentrant tachycardia.Absence of permanent inadvertent damage of atrioventricular conduction makes this newtechnology particularly useful in cases with difficult anatomy, unsuccessful prior standardablation procedure, in pediatrics and in all cases, in whom even the lower risk of atrioventricularblock still possible with radiofrequency energy, is considered unacceptable.

Figure 2A-B. Example of suppression of inducibility of atrioventricular nodalreentrant tachycardia during cooling of the slow pathway. Form top to bottom, lead I,II, III, V1, V6, bipolar recordings from the coronary sinus catheter (from distal toproximal; CS4 is used for stimulation and not visualized) and from the distal (HBEd)and proximal (HBEp) electrode pairs of the the His bundle catheter are displayed. Inpanel A, programmed atrial stimulation (p=400, 260/240) from the coronary sinusreproducibly induces typical sustained atrioventricular nodal reentrant tachycardia. Inpanel B, also bipolar recordings from the distal (ABLd) and the proximal (ABLp)electrode pairs of the cryoablation catheter are displayed. Now, during cooling at–30°C on the slow pathway, S3 beat is blocked even at a longer coupling interval(S3= 290 ms) and tachycardia is no longer inducible. Artefacts in the ABLd are dueto ice formation on the tip electrode.

Accessory pathways. In Table 1, published data on cryothermal ablation of anteroseptal (parahissian) and midseptal accessory pathways are reported17,19,24-29. As shown, this techniquein anterospetal and midseptal areas, both at high risk of complete permanent atrioventricularblock when standard radiofrequency energy in performed, is highly safe and successful. In thelarger series, success rate is above 90%. Although transient modifications of the normalatrioventricular nodal conduction pathways are observed during cooling, no permanentmodifications is observed with the only exception of right bundle branch block in 2 cases in asingle centre. In fact, immediate discontinuation of cryothermal energy application at anytemperature upon observation of modification of conduction over normal pathways results inreturn to baseline condition, soon after discontinuation. Resumption of accessory pathwayconduction with palpitation recurrences may occur in the follow up to 20%, but, especially inyoung healthy individual, a recurrence is by far more acceptable than permanent completeatrioventricular block requiring pacing, which was invariably the case in many series ofradiofrequency ablation of these pathways. In our experience, we have treated 18 patients withanteroseptal or midseptal accessory pathways, so far, age ranging 11-51 years. No patient wasexcluded from the study for proximity of the accessory pathway to the normal conductionpathways (Figure 3). Successful ablation was obtained in all, but 1 pediatric and asymptomaticpatient, in whom conduction properties over the accessory pathway indicated ablation, whichwas eventually postponed. Cryoadherence effect proved very useful in every case, but especiallywhen energy delivery was performed during orthodromic atrioventricular tachycardia, to bettervisualize the His bundle electrogram and to monitor conduction over normal pathways. Nocomplication or palpitation recurrences were observed during a 17±10 month follow-up. Inapproaching anteroseptal and midseptal accessory pathways, instead of performing“cryomapping” at –30°C in the selected site, we found it useful to test cryothermal energyapplications with a step-by-step method to decrease temperature. In fact, in the most suitable sitewith the best contact (sometimes, a superior vena cava approach via a subclavian or a brachialvein is useful to stabilize contact), test applications are applied for 30 s, initially with atemperature of –30°C. If this test application is successful with no modification of normalconduction, then transition to ablation at –75°C up to 480 s is made. If the test application isunsuccessful, after re-warming, further 30s applications are tested, decreasing for eachapplication the temperature by 10°C every step, up to the last application at –70°C. This isbecause we observed that the amount of cryothermal energy required for permanent ablation isquite individual (ranging from an application of –40°C for 40s to an application of –75°C for480 s) and limiting test applications to only –30°C may limit the applicability of cryoablation inthese patients. On the other hand, the use of cryothermal energy at temperatures lower than –30°C should be considered safer than radiofrequency energy in these critical sites.

Cryoablation can be also successfully and safely used to ablate selected cases ofepicardial left-sided accessory pathways within the coronary sinus, well beyond the middlecardiac vein, once attempts by using both transseptal and transaortic approach have failed20,30.Similarly, safe and successful cryothermal energy ablation of permanent junctional reciprocatingtachycardia has been reported in children, in the midseptal region, at the coronary sinus os or inthe middle cardiac vein31.

The experience of cryoablation in unselected accessory pathways is more limited and lesssatisfactory20. Of 51 accessory pathways with various locations, only 69% were successfullyablated and this value is considerably lower than the one reported for radiofrequency ablation.There are many possible explanations for this including the learning curve and the smaller size ofthe lesion produced by cryoablation10. In any case, all the peculiarities of cryothermal energy,which are optimal for septal ablation, are less important or even useless for ablation of accessorypathways located elsewhere. Indian Pacing and Electrophysiology Journal (ISSN 0972-6292), 5(1): 12-24 (2005)


Roberto De Ponti, “Cryothermal Energy Ablation Of Cardiac Arrhythmias 2005:19State Of The Art”Table 1. Review of cryoablation of anteroseptal or midseptal accessory pathwaysAbbreviations: No.pts: number of patients; AntSept: number of patients withanteroseptal accessory pathways; MidSept: number of patients with midseptalaccessory pathways; RBBB: right bundle branch block; n.r.: not reported

Focal atrial tachycardia and isthmus-dependent atrial flutter. Occasionally, successfulcryoablation of focal atrial tachycardia has been reported and its safety has been confirmed alsofor ablation of atrial foci located close to the atrioventricular node32.
Several papers have reported cryoablation of the cavotricuspid isthmus for typical atrialflutter with an acute and long-term success comparable to the one of radiofrequencyablation33,34,35,36. The use of larger catheter and longer electrode for ablation in this area isassociated with a lower number of applications and a shorter procedural time. As forradiofrequency ablation, a case of transient ST segment elevation in the inferior leads wasobserved during cryo application at the septal isthmus, with wall irregularities in the rightcoronary artery without significant stenosis35. The major advantage of using cryothermal energyto produce bidirectional conduction block of the cavo-tricuspid isthmus is the absence of painperception related to energy application. In a prospective randomized trial in which a visualanalogue scale to evaluate pain was used, pain perception was by far lower if not existent in thecryothermal as compared to radiofrequency energy group34.

Pulmonary vein ablation for atrial fibrillation. When radiofrequency energy is applied at the osof the pulmonary veins to prevent atrial fibrillation recurrences, a heat-induced contraction of thepulmonary vein wall can be observed early or during the follow-up, which results in a variabledegree of lumen reduction and a wide spectrum of clinical presentations37. This reaction istypical of hyperthermic injury and results from a combination of edema, endothelial disruptionand collagen denaturation and shrinkage38. The occurrence and the degree of stenosis correlatewith the amount of energy delivered39and lesion extension40. As mentioned above, cryothermalenergy ablation causes less or minimal endothelial disruption, maintenance of extracellularcollagen matrix and no collagen contracture related to thermal effects. Moreover, lowerincidence of thrombus formation is reported with cryoenergy as compared to radiofrequencyenergy ablation. For these characteristics, cryothermal energy ablation can be considered an idealand safer energy source also for pulmonary vein ablation and the incidence of both pulmonary

veins stenosis and thromboembolic events is expected to be dramatically reduced by usingcryoablation. On the other hand, the presence of high blood flow in the pulmonary vein mayrepresent a considerable heat load, which may limit the size and depth of the lesion produced bycryothermal energy at the os of the pulmonary vein. Moreover, the longer time required toproduce a permanent lesion may relevantly reflect on procedure duration, limiting the clinicaluse of this theoretically optimal energy source. Initial experiences of electrophysiologically-guided segmental ostial ablation of the pulmonary vein by using cryothermal energy applicationwith 10 or 7 F catheters20,41have been reported. These experiences show that pulmonary veinisolation is feasible with a comparable number of applications and clinical outcome with regardto radiofrequency ablation; longer procedural times, observed for both the 10 F and the 7 Fcatheter, correlate with longer application times required when cryothermal energy is used.

Figure 3. Example of disappearance of ventricular preexcitation in a case ofparahissian accessory pathway. Surface ECG and bipolar recordings from the distal(ABLd) and proximal (ABLp) electrode pairs of the cryoablation catheter aredisplayed. The relative position of His bundle and the accessory pathway has beenidentified during accurate mapping, also during orthodromic atrioventricularreentrant tachycardia. Accessory pathway turned out to be located at the same sitewhere a high amplitude His bundle potential was recorded. In this figure, the tipelectrode temperature is –23°C and minor artefacts in ABLd suggest that ice isforming on the tip electrode. In the first sinus beat, ventricular preexcitation is stillpresent with optimal A-V and V-delta interval recorded at this site. In the secondbeat, conduction over the accessory pathway is interrupted with disappearance ofventricular preexcitation; now a high amplitude His bundle potential is well evidentin the distal electrode pair of the ablation catheter. Permanent ablation of thisparahissian pathway could be accomplished by limited cryothermal energy deliveryin this site with no modification of conduction over the normal atrioventricularconduction pathway.

Importantly, the early cryoablation experience has not evidenced, so far, development ofpulmonary veins stenosis following ablation. Technologic evolution is now aimed to developnew catheter designs for circumferential ostial ablation of the pulmonary veins, with the optionof deploying in the pulmonary veins an inflatable balloon to reduce the heat load related to bloodflow20. These devices are to be tested in a large patient cohort to assess whether thesetechnological improvements will lead to optimization of the use of cryothermal energy,maximizing the advantages of this new technology and limiting the drawbacks encountered in itsclinical use.

Ventricular arrhythmias. Although clinical data on cryothermal ablation of ventriculararrhythmias are missing, preliminary experimental evidence shows that percutaneouscryoablation in several sites of normal ventricular myocardium is feasible with lesion deeper inthe left than in the right ventricle, probably due to better contact in the former than in the latter42.In the same study, cryothermal energy has been also tested to ablate sustained ventriculartachycardias in a post-infarction sheep model. A limited number of applications was effective insuppressing the inducibility of ventricular arrhythmias, producing a transmural lesion in themajority of the cases with no acute complication.

Interestingly, cryothermal energy could be used to target ventricular tachycardias ofepicardial origin, once the epicardial space has been reached by the non surgical transpericardialapproach, originally described by Sosa43. As compared to radiofrequency energy, cryothermalenergy seems to be safer in the epicardium, due to less probable damage to epicardial coronaryarteries. The reduced heat load in the pericardial space related to the absence of blood flow couldbe to the advantage of cryoablation in these cases, with the possibility to produce largertransmural lesions.

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