Evolution of Atrial Fibrillation Ablation at Sequoia Hospital

Example AF Case

The patient is a 29-year-old female student who was first diagnosed with atrial fibrillation (AF) in 2005. Her first episode was persistent, requiring cardioversion. She is physically active and runs on a regular basis. She continued to have paroxysmal AF with dizziness after running. In 2009, the frequency of her arrhythmias dramatically increased, to the point that she was having daily episodes. Ambulatory ECG monitoring showed both a rapid, regular SVT approaching 200 bpm and AF. She was treated with flecainide and metoprolol, but again returned in persistent atypical atrial flutter requiring cardioversion. She was then admitted for further antiarrhythmic drug trials and spent 10 days as an inpatient. Propafenone was initiated, but she developed symptomatic post-AF termination pauses of up to 7 seconds.

A pacemaker was recommended so that she could safely take another antiarrhythmic such as dofetilide. At that point she sought a second opinion with our group — expressing both a strong desire to become pregnant and to avoid long-term medications and/or a pacemaker. We felt she would be a reasonable candidate for pulmonary vein (PV) isolation.

She was taken to Sequoia Hospital’s electrophysiology (EP) lab in December 2009. A complete diagnostic electrophysiology study revealed no evidence of any reentry supraventricular tachycardia, bypass tracts, or atrial tachycardia at baseline, on isoproterenol or during washout. All 4 pulmonary veins were isolated (Figure 1), and a right atrial cavotricuspid isthmus line was ablated with documented bidirectional block. Total AF procedure time was 75 minutes.

Post-ablation, she has had no further arrhythmias, completed a successful pregnancy, and recently ran in the Boston Marathon. Ultimately, the solution to her problem was a curative procedure that took only 75 minutes with an overnight observation, compared with her 10-day hospital stay for drug loading that failed to maintain sinus rhythm. The case sounds simple, but as many electrophysiologists know, the evolution of electrophysiological advances leading to her successful ablation was long and complex.

Discussion

In this article, we will discuss the evolution of our AF ablation program at Sequoia Hospital in Redwood City, California. We have performed over 2,000 AF ablation procedures since 2003. Our case mix includes many patients referred by outside electrophysiologists after a failed ablation or Maze procedure; only 30% of our patients have paroxysmal AF. Our current AF ablation procedure is the result of refinements of our techniques through the assimilation of technology, experience, and continued reflection upon our previous results. We will discuss several aspects of our current technique that we consider to be innovative and that have given us excellent results despite being a bit different than other centers.

Early Years

Our very first procedures used a wide area circumferential ablation (WACA) technique without a circular mapping catheter, utilizing a 3D electroanatomic system with conscious sedation and an 8mm non-irrigation ablation catheter. Initial procedures were long (averaging over 4 hours), presented a struggle with conscious sedation, and were associated with a major complication rate of 4.6% and a low single procedure success rate (30–40%). We made several immediate changes that paid high dividends:

1. We used a circular mapping catheter to confirm entrance block, and in more recent years, to confirm both entrance and exit block.
2. The circular mapping and ablation catheters were introduced via a single transseptal puncture, eliminating the complexities and inherent risks associated with two separate transseptal punctures. 
3. General anesthesia became standard, to improve both patient and physician comfort. We now realize that general anesthesia likely also plays a role in improving the single procedure success rate by improving catheter stability. In 2011, Di Biase et al showed a significant decrease in procedure and fluoroscopy times with general anesthesia, which concurs with our experience.¹ 
4. When the importance of repeat AF ablation procedures in improving our ultimate success rate became clear, we began to counsel patients regarding this at initial consultation in an attempt to create appropriate expectations. Published data from our lab eventually confirmed the importance of this strategy.²
5. Reports of atrial-esophageal fistulas began to surface, and we introduced esophageal temperature monitoring and empiric periprocedural proton pump inhibitor therapy for prophylaxis.
6. We limited all vascular access to one groin to minimize potential sites for hematoma.

Use of the Irrigated Tip Catheter at 50 Watts with Perpetual Motion

The next major improvement in our AF ablation outcomes came from our early adoption of the open irrigated tip catheter (OITC) for left atrial ablation and the use of 50W power with this catheter. Our first 42 cases using the OITC were performed with maximum power of 30–40 watts, which is what many labs still utilize. Although extremely safe, our results revealed a single procedure success rate of roughly 40%, likely due to inadequate lesions with low power. Over time we cautiously accumulated experience with increasing power to 50 watts, and now routinely perform ablation in all areas of the left atrium with 50 watts utilizing a technique of “perpetual motion.” Perpetual motion refers to the technique of sweeping the ablation catheter over the left atrial tissue while keeping the time of ablation in any one spot limited to 5–10 seconds, which is crucial to safely and effectively creating radiofrequency (RF) lesions using 50 watts in the left atrium. With this technique, we improved procedural success rates, decreased fluoroscopy times and time spent with catheters in the left atrium, and decreased overall procedure time with no increase in complication rates utilizing 50 watts.³ We have never experienced an atrial-esophageal fistula in over 2,000 AF ablations despite the use of 50 watts in the posterior left atrium.

Lower Target Activated Clotting Times of 200–250 Seconds

Early in our experience, we had occasional bleeding problems associated with keeping the activated clotting times (ACT) at 350 seconds. Open irrigated tip catheters have less catheter-related char and thrombus associated with constant irrigation of the tip in animal studies.⁴ Based on this lower incidence of catheter tip thrombus in animals, we decreased our target ACT over time as we developed experience and confidence with the OITC. Our current target ACT is between 200 and 250 msec. By utilizing lower target ACTs, we have shown an overall lower complication rate with less vascular and hemorrhagic complications related to PV ablation and a stroke risk that is nearly zero (Figure 2).⁵ We strongly emphasize that when using a lower target ACT, one must use a single transseptal puncture with two catheters through the single puncture, use an OITC catheter, and infuse the maintenance heparin through the transseptal sheath.

Radiofrequency Transseptal Needle

In early 2009 we began using the NRG^™ RF transseptal needle (Baylis Medical, Montreal, Quebec, Canada) for left atrial access, and were immediately impressed with its ease of use. Aneurysmal/mobile septa and thickened/scarred septa on redo procedures have increased risk due to the excessive force required with a standard transseptal needle to access the left atrium. This excessive force can result in damage to surrounding structures. The RF needle requires significantly less force on the septum to access the left atrium, as the RF energy does much of the work. Using this RF needle, we have been able to show a significantly lower tamponade risk and a lower failure to cross rate compared to the standard transseptal needle.⁶ We performed more than 750 consecutive AF ablations without a tamponade using this needle. The RF needle has become standard equipment for our AF ablation procedure.

Direct Thrombin Inhibitors and Post-Ablation Anticoagulation

Prior to November 2010, our lab’s anticoagulation protocol pre- and post-ablation included warfarin with enoxaparin for bridging. All patients were on warfarin for 3 months post-ablation. Pre-ablation anticoagulation was generally determined by CHADS₂ score and chronicity of AF. Warfarin was discontinued for the ablation. We have not embraced the strategy of full oral anticoagulation during ablation. Initial reports showed no advantage to the current strategy of bridging with enoxaparin;⁷ however, subsequent non-randomized reports suggest a decreased risk of thromboembolism, bleeding complications, and cost.⁸ Although these results are potentially enticing, we have only had 3 intraprocedural strokes in over 2,000 AF ablations using interrupted anticoagulation, and have been unwilling to trade the risks/complications of increased bleeding that might occur with uninterrupted warfarin. More importantly, uninterrupted anticoagulation will likely prove less practical in the future given the superior results of the direct thrombin inhibitors apixaban (Eliquis, Pfizer/Bristol-Myers Squibb) and dabigatran (Pradaxa, Boehringer Ingelheim) compared with warfarin. It is likely that warfarin’s days are numbered and, in fact, most of our new consults for AF ablation arrive on dabigatran. It seems impractical to take a patient off dabigatran to place them on warfarin in order to do their ablation procedure on uninterrupted systemic anticoagulation. Similarly, it seems dangerous to perform an AF ablation on a direct thrombin inhibitor given the current lack of a specific antidote. Certainly, this may change in the future if the pharmaceutical industry can develop an antidote. More widespread use of these drugs will occur as insurance coverage improves and patient costs come down.

We began the use of dabigatran pre- and post-ablation in November 2010. Several properties of this drug make it well suited for ablation. Unlike warfarin, it has a rapid onset of action with full anticoagulation within 1–2 hours of oral intake. Based on its elimination half-life in patients with normal glomerular filtration rate (GFR), we are comfortable stopping this medication 36 hours (roughly 3 half lives) prior to ablation. This has allowed us to eliminate enoxaparin as an outpatient both pre- and post-ablation, which has greatly improved patients’ acceptance of the procedure. Although dabigatran was initially expensive with poor insurance coverage, patients have accepted the cost given their short financial exposure, the fact that they do not need to purchase enoxaparin, and that the long-term goal is to cure their AF and potentially relieve them of all anticoagulation. Our initial experience in 123 patients has been published,⁹ and we have now performed over 450 ablations with dabigatran post-ablation with no CVA/TIA or hemorrhagic complications. We have developed an algorithm for dabigatran discontinuation pre-ablation based on GFR (Figure 3). Patients will receive a 0.5 mg/kg dose of enoxaparin immediately post-ablation (in the cath lab), with a second dose 12 hours later. Dabigatran is then started 22–24 hours post-ablation, and is continued for 3 months as an outpatient (Figure 3). At present, the role of rivaroxaban (Xarelto, Bayer) for periprocedural anticoagulation remains unclear, as it has only recently become available, and given its single-day dosing and longer half-life in the absence of a reversal agent, may create more complex anticoagulation scenarios and/or bleeding complications.

Vascular Access

Various strategies we have used in the EP lab to decrease the risk of groin complications include vascular ultrasound to allow direct visualization of femoral vein puncture, small gauge needles to access, and avoidance of femoral artery access. The use of these three strategies has assisted us in keeping an extremely low groin complication rate with similar effect shown by others in a recent publication.¹⁰

Current Status

We have devoted considerable resources to tracking our procedural and long-term AF ablation outcomes. Several members of our staff work full time to follow our patients. We currently do an AF ablation in less than 2 hours. Our risk of major complications in 2009 and 2010 were 0.9% and 0.6%, respectively. Our 5-year AF-free rates for patients either rendered AF-free by the initial ablation or undergoing a repeat ablation are 94% for paroxysmal AF, 77.3% for persistent AF, and 74.4% for longstanding persistent AF.²

Future Directions

Fortunately, major efforts have been devoted to AF ablation technology development, and we are likely to have better tools to perform this procedure over the next 5-10 years. Below are some areas of interest:

1. Ablation earlier in the disease course – It is clear that patients with persistent or longstanding persistent AF have poorer outcomes than patients with paroxysmal AF.² One of the most important factors that could improve AF ablation success may be to consider ablation earlier in the disease process and before patients have languished in AF for months or years — often having failed multiple antiarrhythmic drugs. Evaluation of our AF ablation outcomes shows that persistent AF patients who always have their AF terminated in less than one week by drugs or cardioversion have better ablation outcomes than those who are left in AF for more than a week at a time.¹¹ We have also shown that both paroxysmal and persistent AF patients who have never failed antiarrhythmic drug therapy have better ablation outcomes than those who fail drugs, and that the number of drugs failed before ablation is an independent predictor of AF ablation outcome.¹² Each time we allow patients to remain in AF for long periods of time or delay ablation by trying serial antiarrhythmic drugs, we appear to be lowering their chance of a successful AF ablation. Given the poor efficacy, significant toxicity, and frequent intolerance of the available antiarrhythmic drugs, we hope the next iteration of the AF management guidelines will upgrade AF ablation to first line therapy for the most symptomatic patients whose AF has progressed to the point where long-term therapy is necessary.
2. PV reconnection – This is the “Achilles heel” of AF ablation and very likely the main cause of repeat procedures. OITC at 50 watts has helped in decreasing redo rates, but more guidance/tools are clearly needed.

1. We await with interest the development of ablation catheters capable of more durable lesions and the potential of contact force sensor technology to optimize tissue contact, and therefore, ensure the creation of lesion transmurality, which may lower rates of PV reconnection.
2. Also of interest are the development of effective protocols to guide ablation endpoints, including post-RF intraprocedural wait times and optimal use of isoproterenol and adenosine for evaluation of extrapulmonary trigger points and PV reconnection.
3. Additional data/studies are needed to assess whether the addition of pulmonary vein exit block isolation offers benefit over entry block isolation alone.

3. Cryoablation – It is unclear that cryoablation technology offers any significant advantage over RF ablation, and may be associated with increased complication rates and costs. The Freeze AF trial will randomize 244 paroxysmal AF patients to cryoballoon vs. OITC ablation, and may offer some insights.
4. Esophageal temperature monitoring – Better methods to monitor and evaluate the esophageal temperature during ablation on the posterior left atrial wall are under development (Figure 4).

Conclusions

The evolution of AF ablation has been rapid and has occurred in little more than 10 years. The next decade should lead to solutions for some of the current problems with AF ablation. It is remarkable that all of these developments to date permit electrophysiologists to restore many patients, such as our example case, to sinus rhythm and to useful, happy, and productive lives.

References

1. Di Biase L, Conti S, Mohanty P, et al. General anesthesia reduces the prevalence of pulmonary vein reconnection during repeat ablation when compared with conscious sedation: Results from a randomized study. Heart Rhythm 2011;8:368-372.
2. Winkle RA, Mead RH, Engel G, et al. Long-term results of atrial fibrillation ablation: The importance of all initial ablation failures undergoing a repeat ablation. Am Heart J 2011;162:193-200.
3. Winkle RA, Mead RH, Engel G, et al. Atrial fibrillation ablation: “Perpetual motion” of open irrigated catheters at 50 W is safe and improves outcomes. Pacing Clin Electrophysiol 2011;34:531-539.
4. Yokoyama K, Nakagawa H, Wittkampf FH, et al. Comparison of electrode cooling between internal and open irrigation in radiofrequency ablation lesion depth and incidence of thrombus and steam pop. Circulation 2006;113:11-19.
5. Winkle RA, Mead RH, Engel G, et al. Safety of lower activated clotting times during atrial fibrillation ablation using open irrigated tip catheters and a single transseptal puncture. Am J Cardiol 2011;107:704-708.
6. Winkle RA, Mead RH, Engel G, et al. The use of a radiofrequency needle improves the safety and efficacy of transseptal puncture for atrial fibrillation ablation. Heart Rhythm 2011;8:1411-1415.
7. Wazni OM, Beheiry S, Fahmy T, et al. Atrial fibrillation ablation in patients with therapeutic international normalized ratio: Comparison of strategies of anticoagulation management in the periprocedural period. Circulation 2007;116:2531-2534.
8. Di Biase L, Burkhardt JD, Mohanty P, et al. Periprocedural stroke and management of major bleeding complications in patients undergoing catheter ablation of atrial fibrillation: The impact of periprocedural therapeutic international normalized ratio. Circulation 2010;121:2550-2556.
9. Winkle RA, Mead RH, Engel G, et al. The use of dabigatran immediately after atrial fibrillation ablation. J Cardiovasc Electrophysiol 2011 Sept 28. Epub ahead of print.
10. Abhishek F, Heist EK, Barrett C, et al. Effectiveness of a strategy to reduce major vascular complications from catheter ablation of atrial fibrillation. J Interv Card Electrophysiol 2011;30:211-215.
11. Winkle RA, Mead RH, Engel G, et al. Relation of early termination of persistent atrial fibrillation by cardioversion or drugs to ablation outcomes. Am J Cardiol 2011;108:374-379.
12. Winkle RA, Mead RH, Engel G, et al. Prior antiarrhythmic drug use and the outcome of atrial fibrillation ablation. Europace 2011 (In press).