Catheter Ablation

[ed]

Have been bothered by A-Fib now for several years.  Started with Dig and worked way up the med ladder to Betapace which has worked very well for the past three years.  However, recently reg dose of 120 mgs twice daily is no longer controlling the condition.  Doseage increased to 160, if no positive result an ablation is being suggested.  I am told Amiodarone might do the trick, but MD's seem to feel not the way to go.
Have tried to obtain information re ablation but there does not seem to be to much available.  Any first hand comments would be appreciated.

[Cleveland Clinic, MD]

Dear Ed,
Afib ablation is still a new procedure so there is still not a lot written about it out there.  In certain well selected individuals I think it is a good procedure to try.  It is only successful in about 60% of people over the long run.  I'm sure these numbers will improve as new technology comes along.  I've attached a paper that gives quite a bit of information about afib ablation and a review of the medical literature.  It's somewhat technical but you may find it helpful.

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ATRIAL FIBRILLATION ABLATION, WHICH APPROACH IS BEST - LINEAR, FOCAL, SEGMENTAL OR CIRCUMFERENTIAL?
Christopher R. Cole,M.D. Andrea Natale, M.D.
Cleveland Clinic Foundation,  Cleveland, Ohio, USA

Introduction
   Over the past 5 years there has been a paradigm shift in the treatment of atrial fibrillation (AF).  Advances in the understanding of the initiating triggers of AF and in ablation technique have changed the treatment of AF from one of chronic control to acute cure.   The question of the ability to cure AF has been answered; what remains to be answered is what technique is best suited to achieve this end.  
  
There are currently 3 main approaches to AF ablation: atrial linear lesions to interrupt AF wavelet propagation, focal ablation of foci that trigger AF, and circumferential ablation of the pulmonary vein ostium to achieve electrical isolation of triggering foci.  We will explore the advantages and disadvantages of each of these 3 techniques and discuss potential future directions of AF ablation.

Background
The magnitude of the problem of AF is well known.   By age 65 upwards of 5% of the population have had an episode of AF and over a third of hospitalizations for arrhythmias are due to AF.   It is a major cause of morbidity, with over 200,000 strokes a year attributed to AF.  In the United States the cost to treat AF is $3.6 billion annually of which $400 million is for drugs alone (1, 2).

Until recently, pharmacotherapy with antiarrhythmic drugs or rate control agents with anticoagulation was the only treatment option for patients with AF.   Although better than placebo at maintaining sinus rhythm (3) antiarrhythmic drugs are relatively ineffective over the long run.  The retention rate for SR at 6 months after cardioversion is only 60% in patients on antiarrhythmic therapy (4).  In addition, antiarrhythmic drugs confer a small but added pro-arrhythmic risk to the patient, particularly those with structural heart disease.  For these reasons investigators have been looking for better treatment options for AF including ablation.

Overview of the Approaches to Atrial Fibrillation Ablation
As the understanding of the mechanisms of arrhythmias progresses, so does the ability to treat arrhythmias with catheter-based interventions (5). As we have seen in the past few years, each change in the mechanistic understanding of AF corresponded to advancement in the treatment options.

The hypothesis of a critical mass needed to sustain atrial fibrillation (6, 7) and the multiple wavelet theory of atrial fibrillation (8-10) led to the development of the surgical maze procedure (11, 12).   By making multiple linear scars in the atrium, the  atrial chambers are compartmentalized in smaller regions unable to sustain AF. This technique, although successful, requires general anesthesia and open heart surgery.  These important limitations have fueled interest in the development of catheter-based ablation procedures.

The idea that atrial fibrillation could be triggered from a rapidly firing single focus was first suggested by Scherf in the 1940's (13). However, it was not until recently that this idea was more fully explored.  It is now believed that in addition to the substrate needed for multiple wavelets, AF is triggered by a rapidly firing focus in the majority, if not all, cases.  The recognition of this mechanism is based on the pioneering work of  Haissaguerre et. al. (14, 15) who first demonstrated that atrial ectopic beats within the pulmonary veins are responsible for the initiation of spontaneous paroxysms of AF.  This finding paved the way to different catheter-based treatment approaches.  Focal ablation of the ectopic focus was initially considered.  However, since detailed mapping and ablation within the pulmonary veins is technically challenging and carries the risks of pulmonary vein stenosis, circumferential lesions to electrically isolate the pulmonary vein from the atrium has been considered more recently.

Patient Selection
As with any procedure one of the keys to success is proper patient selection.  In a patient who has planned open-heart surgery for another reason the surgical maze procedure may be the best approach.   If the patient has infrequent episodes of AF and infrequent APCs, a focal AF ablation may be difficult to perform.

While there are no hard age cutpoints, a younger individual with paroxysmal AF and no other serious health problems would be a more ideal candidate for ablation than an older individual with chronic AF and other major illnesses.  Generally a trial of at least 2 antiarrhythmic drugs is given before proceeding to ablation.  If the left atrium is greatly enlarged (>4.5cm) on transthoracic echocardiogram, ablation may be less likely to succeed. Currently patients with a low EF (<40%) are excluded from ablation procedures; As the field progresses, the exclusion criteria will probably change.  

Linear Lesions (Atrial Segmentation, Maze Procedure)
The first catheter-based approach to ablation of AF was designed to mimic the surgical maze procedure (11).   The catheter-based maze has been performed by using a variety of catheters to make linear lesions in the atrium and interrupt the propagation of the wavelets of AF (16-20).   Several different approaches have been used including epicardial linear lesions generated by hand-held probes (21), the creation of right sided only linear lesions (17, 20, 22, 23), both right and left sided linear lesions (16, 18, 19), and the use of different proprietary catheters (24). The use of three-dimensional electroanatomical mapping has been suggested to facilitate line placement and to insure continuity of the lesions as well (25, 26).  

In a pioneering work, Swartz created 3 right atrial linear lesions, 4 left atrial linear lesions and one septal linear lesion using standard 7F ablation catheters and specialized coaxial long sheaths (16).  All 30 of his patients required both right and left sided lesions for termination of fibrillation and there was an 80% success rate.  There were two strokes following left-sided ablation in his series.

Due to the stroke risk of left-sided ablation right-sided only ablation appeared more appealing (17, 20, 22, 23). Haissaguerre et. al. described the first successful right-sided ablation case report (17).  Using specially designed catheters with closely spaced ring electrodes the investigators made two geometric linear lesions in the right atrium with successful cure of AF.  

Natale et. al. performed  right-sided only linear ablations in 18 patients with a 22 month success rate of 50% (20).  Of those who remained in sinus rhythm, 5 subjects did not require medication and 4 subjects responded to antiarrhythmic drugs that were previously ineffective.   Garg had a similar success rate in a series of  12 patients (23). Interestingly, although right atrial lesions may decrease the atrial defibrillation thresholds they seem to create the substrate for more incessant arrhythmias.

Subsequently Haissaguerre et. al. explored the addition of left-sided linear lesions for patients who failed right-sided only lesions in a series of 45 patients (18).   Patients were divided into 3 groups of 15 subjects with a different right-sided ablation pattern used in each group.  Those who failed right-sided ablation only proceeded on to left-sided ablation.  The success rate of the right-sided only approach was low- only a success rate of 13% without drugs to 40% with medications.  The addition of left-sided linear lesions in 10 patients increased the success rate with medication to 60% and decreased the number of episodes of AF in 70% of the patients.  Complications included 3 sinus node dysfunctions and 1 case of hemopericardium.

Expanding on this work, Jais and colleagues used biatrial linear lesions in 44 patients (19).  Using two right-atrial lines (1 septal and 1 cavotricuspid) and 3-4 left-atrial lines they were able to achieve a success rate of 57% with medications.  There were improvements in an additional 27% of the patients and 16% were considered treatment failures.   There were 5 pericardial effusions and 1 each of a pulmonary embolism, inferior myocardial infarction and a reversible cerebral ischemic event.  An average of 2.7 ± 1.3 procedures were needed with mean cumulative duration of procedure, fluoroscopy, and radiofrequency applications of 615±345, 171±94, and 104±56 min.  Based on this experience, the authors concluded that despite a relatively high success rate, this procedure is too long, and the safety and efficacy need to be improved by the development of appropriate tools before it is applied to a broader range of patients (19).

Focal AF Ablation
The initial description of rapidly firing foci within the pulmonary veins was made in patients undergoing linear lesions in the left atrium. In these patients Haissaguerre and his coworkers observed fast and irregular "focal" atrial tachycardias that acted as triggers for the development of AF (14).  Of clinical significance, ablation of these foci resulted in cessation of the AF.  

The early experience in patients with paroxysmal AF was reported in a landmark study published in 1998 (15). Of the 45 patients, a single point of origin of atrial ectopic beats was found in 29 patients, two points in 9 patients and 3 or 4 points in 7 patients, for a total of 69 foci.  One of the foci was in the posterior left atrium, 3 were in the right atrium, but the majority (94%) originated from the pulmonary veins (PV).   Of those originating from the PV about half were from the left superior vein, a third from the right superior vein and the rest from the inferior veins with the predominance coming from the left inferior vein. 62% of the patients had no recurrence of their AF in the 8±6 months of follow-up after ablation (15).  These findings were subsequently confirmed by other investigators (29).

The early series included patients with frequent paroxysms of AF. Recently Natale et. al. reported their results with 48 patients with  persistent or chronic (23%) drug-refractory AF lasting for a median of 3 years (range 1 to 6 years) (27).   In nearly 2/3 of the patients, the site of earliest activation of the atrial ectopic beats was from the pulmonary veins, with the left superior PV the most common.  However, in 37% of the patients the earliest activation was in the right atrium, predominantly in the high and mid crista terminalis.  During follow-up, sinus rhythm was successfully maintained in 40 patients (83%), but only 4 patients (8%) maintained sinus rhythm without any drug therapy.

One shortcoming of focal AF ablation is the necessity to localize the earliest point of activation of the atrial ectopic beats.  This however requires the presence of frequent atrial ectopic beats and can be technically challenging in the patient with persistent AF.  In the first situation a variety of protocols can be used to elicit PACs and AF including infusion of isoproterenol, aminophylline or adenosine and induction of AF by rapid pacing followed by transvenous atrial defibrillation (TADF), using low energy shocks administered between electrodes in the right atrium and coronary sinus (28).   This eliminates the need to use higher energy transthoracic shocks and could facilitate mapping and subsequent ablation of triggering foci.

An important potential side effect and limitation of focal AF ablation is pulmonary vein (PV) stenosis.  Chen et. al. (29) obtained follow-up transesophageal echocardiograms on 79 patients who had undergone focal AF ablation.  After 6±2 months 42% of the patients had focal stenosis of the ablated PV.  However, only two patients had symptoms:  One patient had mild exertional dyspnea following the ablation that resolved 3 months later and the other had onset of mild exertional dyspnea 5 months after the ablation.

Isolation of the Pulmonary Veins by Circumferential or Segmental Lesions
The understanding that many cases of AF are triggered by foci in the PVs and the recognition of the limitations with the focal approach has generated interest in anatomical approaches geared to electrically isolate the pulmonary veins.   There are many theoretical advantages to an anatomic approach as opposed to a focal approach.  First, the trigger does not need to be firing at the time of ablation.  Second, detailed mapping is not required. Third, persistent AF does not prevent the procedure.  Fourth, the lesion need not be precise, and lastly, the length of the procedure and fluoroscopic time maybe potentially shorter.

Different strategies to anatomical isolation of the PV have been proposed.  One approach is to apply multiple focal lesions guided by either intracardiac echo or a non-fluroscopic mapping system or both to create a circle around the ostium of the PV responsible for triggering AF.  This approach has drawbacks in terms of time and still carries the risk of PV stenosis following the procedure.  More recently, mapping and ablation guided by the use of circular multielectrode or basket catheters (figure 1) have suggested that at least distal isolation could be achieved with segmental lesions delivered at sites with earlier activation.  Whether this approach is beneficial for the majority of patients requires further testing.

An alternative approach to isolation uses balloon-based technologies (figure 2) to deliver lesions in a circumferential pattern to the pulmonary vein ostium (30-33).   The lesion may be created using conventional radiofrequency power or alternative sources such as cryoablation and ultrasound.   Ultrasound energy has the advantage over radiofrequency power of being able to heat the entire depth of the tissue to a relatively uniform temperature (34) and therefore theoretically have less chance of creating PV stenosis.   Cryoablation has the potential of providing the same advantage therefore avoiding stenosis of the PVs.

We have recently reported on the first patients in whom a circumferential ultrasound vein ablation (CUVA) catheter was used (35, 36).    20 patients with AF resistant to drug therapy underwent AF ablation using CUVA catheters.  The mean age of the population was 57 ± 12 with a slight majority of women.   Sixteen of the patients had paroxysmal AF and 4 patients had persistent AF.   After 36 weeks of follow-up, 11 of the 20 patients (55%) had no recurrent episodes of AF.   An additional 6 patients (30%) had their AF controlled with previously ineffective drugs.  Three patients were considered treatment failures.  

Recurrence of AF was attributed to the following reasons: PV ostium larger than the size of the balloon;  very proximal PV ostial foci; and triggers outside the PVs (e.g. Ligament of Marshall).  None of the patients had any evidence of PV stenosis as documented by the pre ablation and 3 month post-ablation spiral computerized tomography.  

Another challenge to the circumferential ablation approach is the anatomy of the pulmonary veins.    The location of the true ostium of the pulmonary vein may be difficult to determine, particularly when multiple branches arise from a funnel shaped opening.  In addition, the shape of the PV may result in eccentric orientation of the ultrasound transducer.  This may render lesions ineffective and prevent isolation of the PV.   Newer intracardiac ultrasound imaging systems (37) may help in defining the anatomy for optimal lesion placement. As many recurrences appear related to deficiencies of the initial system design, it is conceivable that this device may become more effective once these technical limitations are addressed.

Verification of true electrical isolation of the PV following the ablation is of paramount importance.  To facilitate assessment of isolation, the PV electrical activity and the far-field atrial activity recorded from inside the PV must be differentiated prior to the ablation (figure 3). Once ablation lesions are applied this may be difficult because both components may become very small.  Pacing maneuvers from the coronary sinus and the right atrium may help in this process.

Despite the current limitations, the anatomic approach to pulmonary vein isolation using circumferential lesions has great potential. The preliminary experience in humans is quite encouraging.  The use of power sources other than RF appears to greatly reduce, or perhaps eliminate,  the risk of pulmonary vein stenosis.  The next generation of balloon catheters should increase the ease of the procedure and help to overcome some of the technical issues such as vein size and location.   Circumferential ablation of the PV is a promising approach  for the treatment of patients with drug-refractory AF.  Whether lesions limited to segments of the pulmonary veins would represent an alternative to cure the majority of patients is unclear.  It must be remembered that foci triggering AF might originate from sources other that the PVs.  The clinical relevance of such mechanisms is presently unknown and could be under-recognized.



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[Colin]

Dear Sir

I have had Atrial Fibrillation for 4 years, and after 2 1/2 years of amiodarone, which worked well, have had hyperthyroidism and was in bad shape. This is caused by the iodine in amiodarone.After 6 bad months and hospitalisation, my thyroid has finally recovered.
I am now considering catheter ablation of the pulmanory focus, and likewise would appreciate any contacts with anyone who has had this treatment.

Best Regards

[C. Bays]

A most informative article.