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Radiofrequency ablation vs. cryoablation

Prior to 1981, the only option for treating fast heart rhythms other than antiarrhythmic drugs was open-heart surgery. In the operating room with the heart exposed, the part of the heart that caused the racing could be dissected with a scalpel or frozen with a large metal hand-held probe. In 1981 the first reported cases of percutaneous ablation were published in the New England Journal of Medicine, and a new era began. Initially, however, the energy source for ablation was direct current energy. These procedures involved positioning a non-steerable catheter near the target and then putting the full output of a standard defibrillator through the catheter. Thus 2000 volts of direct current energy was delivered via the catheter to the heart in less than 5 milliseconds. If the catheter could transmit the energy to the heart (not all could), the strong electrical field with associated shock wave of several atmospheres (barotrauma) would disrupt the cells closest to the catheter. Cells farther away were partially affected and remote cells not affected at all. The lesion was not very dense or homogenous and resulted in strands of scar tissue mixed with alive but stunned heart myocardial cells. The only reason this procedure survived was because the only other option to medications was open-heart surgery.

Then in the mid 1980s, animal studies involved radiofrequency (RF) current. This electrical energy, with a frequency of 750 kHz, was what surgeons used for electrocautery in the operating room. RF energy when investigated in animal hearts was found to produce less irregular, more dense/homogenous lesions, and the first successful human cases were reported a few years later. Because the voltage was much lower, barotrauma was eliminated, and the procedure caught on rapidly. RF ablation creates lesions of sufficient size to destroy reentrant circuits as well as abnormal foci and therefore cure most patients of their arrhythmia.

The advantages of RF ablation

Foremost of all is the vast number of RF ablation procedures that have been performed. Because of this, many hospitals offer RF ablation making it available within a reasonable distance to nearly all residents of the US. There are many different catheters for the electrophysiologist to use, and most have good handling characteristics. Once the catheter is in position, it only takes 60 seconds to make a lesion, and this is important to minimize the length of procedures. Therefore, RF ablation has been the mainstay for percutaneous intracardiac ablation.

The drawbacks of RF ablation

RF ablation, however, has some limitations and drawbacks. A large study of RF ablation conducted in 18 very good institutions in the 1990s found an overall success rate of 95%, but about 5% of patients had arrhythmia recurrence (1). Major complications occurred in 3% of patients including death, stroke, and accidental damage to the AV Node requiring a permanent pacemaker, perforation of the heart, myocardial infarction, pneumothorax and thromboembolism. Minor complications occurred in 8% of patients including pleural or pericardial effusion, pulmonary insufficiency, nerve injury, and hypotension. These outcomes may be slightly better today, but not remarkably so. Therefore the search for better energy sources for ablation has continued including microwave, laser, high-frequency ultrasound and cryothermal.

The first drawback of RF ablation stems from the fact that an RF burn disrupts the endothelium – when this happens, thrombus forms. Complications related to this may include stroke, myocardial infarction, pulmonary embolism or peripheral arterial embolism. A review of many studies suggested that thromboembolic complications occur in about 1 out of 200 patients overall (2). However, on the left side of the heart where the risk of stroke is highest, the risk was 2-3% in one study (2).

The second drawback of RF ablation is the inability to assess the effect of heating the tissue at a certain site in the heart without creating an irreversible effect. Although one report in pediatric patients has been published (3), most electrophysiologists do not believe that it is possible to do this with RF energy. Therefore what happens is that the electrophysiologist positions the ablation catheter in the best location and turns on the RF energy. Usually the tissue is rapidly heated to the point that it dies. If the catheter is too close to vital heart structures or if the catheter moves, accidental damage may occur to surrounding normal structures. Although the RF power can be rapidly turned off if an adverse effect is detected, the lethal temperature can persist for up to 12 seconds, and the damage may progress and may become permanent (4). In the aforementioned large study, the risk of accidental damage to the AV node was 3%, and 1% of patients had to have a permanent pacemaker implanted (3). Other structures that can be damaged by RF energy include the phrenic nerve and the pulmonary veins (close to where ablation for atrial fibrillation occurs).

Yet another drawback of RF ablation is its limited effectiveness in areas of low blood flow. In such areas like the coronary sinus or an atrial appendage, when RF power is turned on, the temperature of the catheter tip gets too hot producing blood clotting. Since energy is titrated by the console depending on temperature, not enough energy is delivered to make a big enough lesion to ablate the target (5). Sometimes a catheter that is irrigated with saline keeping the temperature down can help in this situation (6). However, such catheters tend to make bigger lesions, and this is usually undesirable in such areas.

RF ablation is also associated with myocardial perforation with cardiac tamponade. This potentially life-threatening complication occurred in 2.5% of patients in the large study referred to above (1). This complication may occur because tissue heating with RF ablation is greatest below the endocardium where temperatures can reach 100 degrees Centigrade. When this happens, steam is rapidly formed. If the steam pocket ruptures on the epicardial side of the myocardium, perforation occurs (7). The risk of this complication is less with irrigated catheters (6). Even if steam is not created, RF energy denatures the extracellular tissue matrix (8) weakening ablated tissue and predisposing to cardiac rupture.

Next, RF ablation produces a somewhat irregular lesion that can create the substrate for other arrhythmias (9). Because of this, arrhythmogenic foci can be produced that are proarrhythmic. Conversely, in other cases the full effect of RF ablation may not occur immediately. This delayed effect may produce an arrhythmia after the patient has left the hospital (sometimes requiring a pacemaker).

Lastly, in some cases it may be very difficult for the electrophysiologist to position the ablation catheter and keep it stable at the desired site. If the catheter is not stable, it may be very difficult to make a large enough lesion to ablate the target. In other cases, the moving of the catheter cools the tip allowing a deeper/hotter lesion than the electrophysiologist intends leading to steam formation.

The advantages of cryoablation

Ultimately, the technology of the hand-held surgical probe was able to be made small and flexible enough that catheters were developed (10) that could be used percutaneously just like the RF catheters. When these catheters were used in animals and compared with RF ablation catheters, the cryoablation catheters produced less endocardial irritation and thrombosis (11). The cryoablation catheters could also be used safely and effectively in areas of reduced blood flow. When these catheters were tried in patients, the ability to reversibly cool the intended target to assess efficacy also worked well. Also, the catheter was found to adhere tightly to the intended target and not move around like RF catheters (12). A large study was performed with the first of these cryoablation catheters that had the same metal tip size as the RF catheters. This trial, the “FROSTY Trial” (13) looked at almost 200 total patients with various forms of supraventricular arrhythmias. All patients had attempted cryoablation using this catheter. The immediate success was 93% in AVNRT patients (the most common cause of SVT) - sufficiently high to receive FDA approval of this catheter for this arrhythmia. The success for ablating other reentry circuits as well as targeting the AV Node prior to planned pacemaker insertion was less than that typically achieved with RF ablation. Nevertheless, the catheter performed well. Complications occurred in 4% of patients, significantly less than in RF studies and were thought not to be device-related. There is evidence supporting the claim that cryoablation is safer than RF ablation. In a study of people with atrial fibrillation, cryoablation was found to be less thrombogenic than RF ablation (14).

Disadvantages of cryoablation

The main disadvantage of cryoablation is the fact that with the catheter used in the FROSTY trial, the lesions were too small to have a lasting effect in some patients. In Europe, two trials were performed randomizing patients with AVNRT to either RF or cryoablation. Both the RF and the cryocatheters had 4 mm tip electrodes. These studies (15, 16) showed comparable success rates and safety. Fewer lesions were required in patients having cryoablation than in those receiving RF ablation (16). Success at the end of the procedure was comparable in the groups, but in one of the studies (15) the recurrence rate in patients treated with cryoablation was higher than in patients treated with RF ablation. Higher recurrence rates have also been reported in pediatric patients (17). The reason for this is that the cryocatheter used in these studies makes too small of a lesion to cure some patients. A more recent study of 75 patients who all underwent cryoablation using a catheter with a larger tip electrode was successful at the end of the procedure in 99% of patients with recurrent SVT in 5%. These results are nearly comparable to those of RF ablation. Therefore, the inferior efficacy of cryoablation potentially is solvable by using cryocatheters with larger tip electrodes. A cryoablation catheter with a large (8 mm) distal electrode has been approved by the FDA for use in ablation of atrial fibrillation and flutter. A cryoablation catheter with a medium-sized (6mm) distal ablation electrode is approved in Canada and Europe and is currently under investigation in the US in the ICY-AVNRT Trial.

The second disadvantage of cryoablation is that the current catheters do not handle as well as RF ablation catheters. It is more difficult to make tight turns, loops and other advanced maneuvers.

Thirdly, compared with RF ablation’s ability to make a lesion in 60 seconds, a comparable lesion with cryoablation takes 8 minutes if done correctly. This difference is magnified if insurance lesions are to be placed to minimize the chance that the heart rhythm problem will recur.

Lastly, the cryoablation catheters are more complicated and must be built by hand and therefore are more expensive.

Fewer centers doing cryoablation

There are several reasons why fewer EP centers are performing cryoablation. First of all, most electrophysiologists doing RF ablation believe that it is good enough so that cryoablation is not essential. So what if 1 in 200 patients end up with a permanent pacemaker? We all tend to think that this will not happen to us – only to less experienced operators. Why should we take the extra time it takes to do cryoablation for this unlikely event? The other side effects also are rare and the safety of cryoablation for them has not been proven beyond a shadow of a doubt. There is not as much known about cryoablation when compared with the vast knowledge base for RF ablation. Secondly, most electrophysiologists that I speak to around the country tell me that they are unwilling to take the extra time required to perform cryoablation. Thirdly, many of the academic electrophysiologists who are training the next generation of physicians seem very close-minded toward cryoablation. Therefore many of our newest doctors are unfortunately not being trained in this technique.

New ablation technologies

Microwave energy is also being developed for use in cardiac ablation (18). Microwave energy works by making water molecules vibrate producing heat. It is capable of making larger and deeper lesions than those of RF or cryo. Like cryo, it irritates the endocardium less than RF and should therefore cause less thrombosis. Unfortunately, microwave, like RF, can damage adjacent structures like the coronary arteries leading to damage of the myocardium, the esophagus or the lung. Microwave ablation has been used successfully to cure atrial fibrillation during open-heart surgery. There are also microwave catheters that can be used percutaneously just like RF and cryo catheters. These are being used in investigational studies in patients with atrial flutter and atrial fibrillation.

Ultrasound also can be used to oscillate and heat water molecules. Ultrasound, like microwave, can create deeper lesions. Another advantage of ultrasound is that it can be focused beneath the endocardial surface if the target is deep within the muscle. However as with RF and microwave, there is a risk of injury to adjacent structures. An ultrasound balloon catheter was developed for use in pulmonary vein isolation in patients with atrial fibrillation. Unfortunately, only 30% of patients were cured owing to difficulties in delivering the energy in a circular fashion and the handling characteristics of the catheter (19).

Laser is yet another energy source being developed for ablation. Like the others it causes oscillation of water molecules and heats tissue. Laser can make deeper lesions and does not predispose to blood clot formation. Making linear lesions is a potential strength of laser ablation. Yet there still is a risk of damaging surrounding structures. There is very limited experience with laser even during open-heart surgery. A laser balloon catheter has been developed for use in pulmonary vein isolation but thus far has been used only in animals (20).

Reviews

Skanes A, Klein G, Krahn A, and Yee R. Cryoablation: potentials and pitfalls. Journal of Cardiovascular Electrophysiology. 2004; 15: S28-S34
A good in-depth discussion of cryoablation

Perry J. State-of-the-art pediatric interventional electrophysiology: transvenous cryoablation establishes its niche. Heart Rhythm. 2006; 3: 259-260
An editorial of the value of cryoablation from an experienced center

McDaniel G, Van Hare G. Catheter ablation in children and adolescents. Heart Rhythm. 2006; 3: 95-101
A balanced review of ablation in younger people

References

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  2. Zhou L, Keane D, et al. Thrombogenic complications of cardiac radiofrequency catheter ablation. Journal of Cardiovascular Electrophysiology. 1999; 10: 611-620
  3. Cole J, Epstein M, Triedman J, etal. Low temperature mapping predicts site of successful ablation while minimizing myocardial damage. Circulation. 1996; 94: 253-257
  4. Bunch T, Bruce K, Johnson S etal. Analysis of Catheter-Tip (8-mm) and Actual Tissue Temperatures Achieved During Radiofrequency Ablation at the Orifice of the Pulmonary Vein. Circulation. 2004; 110: 2988-2995
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