Boston AF Symposium, January 15-17, 2009 “Atrial Fibrillation: Mechanisms and New Directions in Therapy”

The annual international Boston A-Fib Symposium is one of the most important conferences on A-Fib in the world. It brings together researchers and doctors who share the latest information.  However, if you haven’t read and understood most of A-Fib.com, it may be difficult reading.

OVERVIEW-HIGHLIGHTS

The overall mood of the 14th annual Boston A-Fib Symposium seemed to be one of confident expectation, reflecting perhaps the mood of our country anticipating the presidential inauguration. One might also describe this Symposium’s signature or most prominent concern as the “CFAE (Complex Fractionated Atrial Electrograms) vs. Dominant Frequency Controversy.”

List of Presentations

• Merits of GP (Ganglionated Plexi) Ablation 

CFAEs vs. Dominant Frequency

Several doctors made presentations on Electograms in A-Fib, reflecting the importance and ongoing controversies in the field. According to Dr. Jose Jalife of the Un. of Michigan in Ann Arbor, the areas of Dominant (highest) Frequency found in the atria indicate sites of A-Fib generation. These Dominant Frequency areas do not coincide with areas of CFAEs (Complex Fractionated Atrial Electrograms). Dr Jalife disagrees with Dr. Nademanee (who discovered CFAEs) about the importance of CFAEs in ablation. Dr. Shin-Ann Chen of Veteran’s General Hospital in Taipei, Taiwan found that areas of CFAEs change their location after the Pulmonary Veins are successfully ablated. His current protocol is to first ablate the PVs, then make linear lines, and only then ablate CFAEs. This differs from Dr. Nademanee who first ablates areas of CFAEs. Dr. Moussa Mansour of Massachusetts General in Boston recommended using areas of Dominant Frequency as a target for ablation. Though areas of DF and CFAEs are related, their regions overlap only in about 50% of cases. Dr. Vivek Reddy of the Un. of Miami added yet another term to the current Electrogram lexicon “EGMCL” (Electrogram Mean Cycle Length). He recommended that high density mapping be done after PV ablation in order to identify “pockets” of CFAE sites which he termed “EGMCL.” From a clinical perspective, in order to organize the chaotic electrograms often found in Chronic A-Fib, the Bordeaux group ablates areas of Dominant Frequency first.

Future Alternatives to Warfarin

“Warfarin’s days are numbered!” according to Dr. Michael Ezekowitz of Lankenau Institute for Medical Research in Wynnewood, PA. One could almost hear a collective sigh of relief from the doctors in attendance who cope every day with the dosage and side effects problems of warfarin. Dr. Ezekowitz confidently asserted that there will soon be available more user-friendly anticoagulants. He described seven drugs in advanced clinical trials to replace warfarin, and said that some, if not all of them, may be approved by the FDA within a minimum of five years. (Author’s Note: At the present time, 2 or 3 are close to approval, while the rest are much further out because they are in early trials. Dabigatran may be approved in the next 12-24 months, because its phase 3 trials are far along and look impressive. The next closest is rivaroxiban, but it’s just recruiting for Phase 3. [Thanks to Mallanie True Hills for these insights.])

Robotic vs. Magnetic Navigation/Ablation

Robotic navigation and ablation seemed the clear winner in a debate between Dr. Andrea Natale of the Texas Cardiac Arrhythmia Institute in Austin, TX (Hanson robotic) and Dr. Carlo Pappone of San Raffaele University Hospital in Milan, Italy (Stereotaxis magnetic). From the data presented, the Hanson Robotic system appeared more ergonomically user-friendly and more directly responsive to the operator. While Stereotaxis uses a mouse and click system with what Dr. Natale described as a 5-7 second delay, Hanson uses a motion controller with a flexible guide catheter directly responsive to an operator’s touch that replicates an operator’s natural hand movements. According to data presented by Dr. Natale, the Stereotaxis system is prone to charring which can cause clotting and stroke, while the Hanson system uses a flexible irrigated tip catheter less prone to charring. The Hanson robotic system is pressure sensitive, while Dr. Pappone acknowledged that the Stereotaxis system to date sometimes doesn’t provide enough pressure when making ablations. The Hanson system is portable and easily attaches to a procedure table.

Comments added June 20, 2009: A correspondent who wishes to remain anonymous pointed out that the Hansen robotic system does require extensive manual skill, whereas the Stereotaxis magnetic system is automated. (To this author, this is a major difference between the two systems. Even with skilled, experienced operators it is still possible with a robotic system to have misplaced ablation burns or accidents such as perforations. Whereas the magnetic system using a mouse to make the ablations seems safer, ultimately more efficient, and more capable of being used by new operators.

The Stereotaxis system now uses an irrigated-tip catheter which is less prone to charring.)

(Before each presentation, doctors disclose any potential conflict of interest. Dr. Natale disclosed he is a partner with Dr. Burckhardt, the CMO of Stereotaxis.)

Merits of GP (Ganglionated Plexi) Ablation

In another dramatic debate Dr. Eric Prystowsky of the Care Group in Indianapolis, IN (Con) and Dr. Warren Jackman of the Un. of Oklahoma in Oklahoma City, OK (Pro) argued the merits of GP (Ganglionated Plexi) ablation. Dr. Prystowsky agreed with Dr. Jackman that GPs contain nerve systems that affect the Pulmonary Veins, and that Pulmonary Vein Ablation works perhaps because it cuts across and disrupts these nerve pathways to the PVs. However, Dr. Prystowsky seemed to carry the day by pointing out that GPs not only affect the Pulmonary Veins but also contain nerves that extend to the ventricles of the heart and also affect the GI (Gastro Intestinal) system. Surgeons who have ablated the GPs while doing a Mini Maze operation have found that the GI has been compromised. Dr. Prystowsky cautioned that ablating the GPs with nerves leading to the ventricles may possibly produce ventricular electrical instability with possible sudden cardiac death. (This is a cautionary hypothesis. Further research is necessary to establish how ablating the GPs affects the ventricles.) The previous presenter, Dr. Dainius Pauza, described in detail how nerves in the GPs extend to the ventricles in his talk on the “Neural Anatomy of the Heart and Pulmonary Veins. (Author’s Note: Dr. Prystowsky raised a serious question for A-Fib patients. Does ablating the GPs risk damaging the nerve electrical system which affects the ventricles, and which may even lead to future sudden cardiac death? Until more research establishes how these GP nerves actually affect the ventricles, we should be cautious about having our GPs operated on or ablated.)

Moving from Conscious Sedation to General Anesthesia

In the U.S. a trend may be developing to use General Anesthesia during ablation (in Conscious Sedation the patient is lightly sedated rather than completely unconscious during General Anesthesia). Dr. Andrea Natale of the Texas Cardiac Arrhythmia Institute and Dr. David Packer of the Mayo Clinic in Rochester, MN said that they have moved to General Anesthesia because:

• there is less patient movement which helps decrease re-conduction problems,
• the esophagus doesn’t move,
• patients like it better because they don’t experience any discomfort or pain.

In a later presentation Dr. Pierre Jaïs said that the Bordeaux group uses Conscious Sedation. One reason is that with General Anesthesia doctors can’t tell if a patient develops a thrombus or clotting which might cause a stroke. Of the attendees 42% indicated they use General Anesthesia, while 58% use Conscious Sedation. (Symposium attendees used a touchpad audience feedback system to answer questions from the presenters, making the Symposium more of an interactive process. Though not a scientific survey, this interaction system gave a sense of the general attitudes and practices of the attendees.)

The Dronedarone Symposium

The 14th Boston A-Fib Symposium was unusual in that it featured a debate on dronedarone, a drug not currently in use and not yet approved by the FDA. Dr. Albert Waldo of University Hospital of Cleveland (Pro) and Dr. Douglas Packer of the Mayo Clinic in Rochester, MN (Con) debated whether all A-Fib patients should be treated with dronedarone. The debate moderator, Dr. Peter Kowey of Lankenau Hospital in Wynnewood, PA, said the ATHENA study of dronedarone is a model for antiarrhythmic drug trials. (Dronedarone is intended to replace amiodarone.) The ATHENA clinical trial found that dronedarone wasn’t quite as effective as amiodarone, but was much safer. Dr. Packer acknowledged the positive results of the ATHENA study, but argued that catheter ablation may be better for an A-Fib patient than an antiarrhythmic drug like dronedarone. He also pointed out that the ATHENA trial didn’t specify what dosage of dronedarone to use. A very high dosage may produce GI (Gastro Intestional) problems. Dr. Waldo presented a sobering statistic that in 2050 16 million people in the US will have A-Fib vs. about 3 million today. It is predominately older people who get A-Fib. For people over 80, for whom catheter ablation may not be possible, dronedarone may become their only option.

FDA a Big Hit

One of the most interesting and anticipated sessions featured Dr. Randell Brockman of the FDA who moderated a panel and audience discussion of A-Fib ablation. The panel featured some of the most well known doctors in A-Fib. Dr. Brockman had many questions for the panel and audience, and used the audience feedback system to tabulate responses. This session provided an opportunity for regulators and A-Fib doctors to share their concerns and to understand each other’s different perspectives. One concern raised at this session was the problem of relapse after a successful ablation. Is one year of monitoring enough? Dr. Pierre Jaïs said there was a 25% relapse rate after five years, while Dr. Prystowsky said most patients remain clear of A-Fib after one year. Dr. Wyn Davies of St. Mary’s Hospital in England said that successfully ablated A-Fib patients should be followed and monitored throughout their lifetime. Dr. Carlo Pappone said catheter ablation should not be a first line therapy for A-Fib patients, that drug therapy should be tried first before moving to catheter ablation. While the complication rate for catheter ablation is low and the complications are anticipated and normally well handled, still complications do occur and are a somewhat harrowing experience that doctors would rather avoid. Dr. Pierre Jaïs in a later panel echoed Dr. Pappone.

Dublin, Ireland and Mass. General Live Satellite Ablations

In a live satellite transmission form Dublin, Ireland (a ‘first” for the Boston A-Fib Symposium), Dr. David Keane of St. Vincent’s University Hospital in Dublin performed an ablation on a patient with Paroxysmal (occasional) A-Fib using the new Bard Mesh catheter (not yet approved in the US). The Mesh catheter is both a mapping and an ablation catheter. Thirty-six strands of variable braded wire meshwith an electrode array can be expanded into a balloon-like shape to map and ablate the Pulmonary Vein openings. These wire strands also contain 36 bipoles to record electrogram (electronic A-Fib signals) info in the heart. The Mesh catheter can ablate in a complete circle or in any one of four color coded quadrants for a partial burn. The Mesh catheter burns at 100 Watts for 180-300 seconds. Dr. Douglas Packer commented that multi-array catheters can get very hot. In point of fact, in the ablation from Dublin, Dr. Keane had to make 11 burns to completely isolate one vein. The second live satellite transmission was the ablation of a Persistent A-Fib patient at Massachusetts General by Dr. Moussa Mansour. He was able to successfully ablate the patient’s A-Fib, but an Atrial Tachycardia remained. Speakers throughout the Symposium commented on how difficult it is to find and ablate these Atrial Tachycardia which often remain after A-Fib is ablated. Dr. Mansour later reported that he was never able to find and ablate his patient’s Atrial Tachycardia. He instead had to perform an Electrical Cardioversion to restore her to Sinus Rhythm.

Major Medical Breakthrough in imaging—3D Rotational Angiography

At a luncheon sponsored by Phillips several presenters described 3-D Rotational Angiography which appears like a 3-D fluoroscopic (X-ray) image of the heart made while the camera rotates around the body. Electrogram (electronic information such as the location of A-Fib sources) can be superimposed over these live 3-D images. Real time image integration will be available shortly.

To this author 3-D Rotational Angiography is a major medical breakthrough in imaging and mapping the heart.

Non-Invasive Ablation

The last presenter of the Symposium, Dr. Wyn Davies of St. Mary’s Hospital in London, described what may become another medical breakthrough—a non-invasive method of performing ablations using focused-beam X-Ray. The CyberKnife system can focus X-Ray beams on precise spots in the heart without damaging adjacent areas. Similar systems have already been used in many patients to ablate cancer tumors without damaging other tissues. A robotically controlled linear accelerator can track and compensate for respiratory and heart beat motion. However, unlike RF or Cryo ablation, the results of these X-Ray ablations will not be known till 30 to 60 days after the ablation. A system with this much delay may never become suitable for complicated cases of A-Fib (Persistent or Chronic A-Fib) where there are often many different sources of A-Fib pulses not easily mapped and ablated.

The Atrial Selective Drug Ranolazine

The medicine ranolazine, recently approved by the FDA, is of great interest to A-Fib doctors, because it is atrial selective (it only affects the atrium and not the ventricles). Though it has not been approved by the FDA to treat A-Fib, panelists said that it is being used off-label* combined with amiodarone (also atrial selective. This combination seems to reduce the excitability of A-Fib areas of the heart. *”Off-label” means outside of licensed indication—the clinical application of prescribed drugs for indications other than those approved by the FDA. Off-label uses are legal and may be in the best interests of patients. But they have not received the same degree of independent scrutiny through randomized clinical trials as have approved indications. One can not advertise or market a drug for something other than what has been approved by the FDA.

Update on the Watchman Device

Dr. Zoltan Turi of Cooper University Hospital in Camden, NJ, in discussing mechanical devices to prevent stroke, indicated that the Watchman Deviceshowed the most promise, had completed its clinical trials, and was close to getting FDA approval.

Catheter Ablation Survey

Up to this time the last comprehensive survey of the methods, safety and efficacy of catheter ablation for A-Fib was completed in 2002. Dr. Riccardo Cappato of the Istituto Policlinico San Donator in Milan, Italy reported on an updated survey of 2003-2006. This survey showed there was a larger success rate of ablated patients free of antiarrhythmic drugs in 2006 than in 2002, the overall success rate of ablations was similar in 2002 and 2006, but the complications rate for 2006 was lower.

Surgery for A-Fib

Dr. Ni Ad of the Inova Heart and Vascular Institute in Washington, DC described his Full Maze minimally invasive operation using Cryotherm energy with a 93% success rate. He recommends that patients with Paroxysmal A-Fib have a Catheter Ablation procedure. Dr. James Edgerton of the Heart Hospital in Plano, TX uses the Wolf Mini Maze bipolar clamp combined with an extended lesion line set, and staples shut the Left Atrial Appendage. Dr. Ralph Damiano, Jr. of Barnes Jewish Hospital in St. Louis uses Body Surface Mapping and Dominant Frequency Mapping while ablating with the bipolar clamp.He stresses tailoring the operation to the needs and structural geometry of each patient. A typical Cox Maze lesion set may be too much for some patients and not enough for others. He mentioned that the Mini Maze operation is less successful in patients with large atriums. Also, a Mini Maze can not be re-done or touched up, because of the scarring from the operation. He said that the bipolar clamp lesions do not disrupt or impede circulation or nerve paths in the heart.

A-Fib Induces Fibrosis

Dr. Stanley Nattel of the Un. of Montreal, Canada reported that lone A-Fib may induce fibrosis and collagen formation in the heart.

(Author’s Note: Dr. Nattel’s research may help resolve the chicken and the egg controversy of whether A-Fib induces fibrosis or vice versa.

This is an important finding for A-Fib patients who face the choice of staying in controlled A-Fib by taking medications or having a Pulmonary Vein Ablation. It seems the more one stays in A-Fib, the more fibrosis and collagen are formed in the atrium [the remodeling effect]. Fibrosis is most likely permanent, whereas other effects of A-Fib can often be reversed. For patients considering a PVA(I), it’s probably better to get an ablation and cure one’s A-Fib sooner rather than later.)

However, Dr. Nicholas Peters of St. Mary’s Hospital and Imperial College in London, England stated that, even though A-Fib is a progressive disease which tends to get worse over time, some patients never progress from Paroxysmal (occasional) A-Fib to Persistent or Chronic (permanent) A-Fib.

Visually Measuring the Success of a PVA(I)

Dr. Andre d’Avila of the Un. of Miami proposed a novel way of assessing the success of a Pulmonary Vein Ablation. He showed that, before a successful PV ablation, the Pulmonary Vein sheaths expand and contract as the heart beats. But after a successful PVA(I), these PV sheaths no longer change in volume. Imaging or visualizing PV contraction would be a non-invasive and relatively easy method of  confirming PV isolation.

Genetics may play a significant role in the development of A-Fib

Dr. Dan Roden of Vanderbilt University described how genetic research may become important to A-Fib patients. He predicted that within five years research may identify what genes predispose a patient to A-Fib. Then personalized therapy can be developed based on the patient’s genes. “Lone A-Fib” (A-Fib without a known cause) may actually be caused by genetics. Technology Update For those of you interested in new A-Fib therapy products showcased at the Symposium, see http://www.jafib.com/published/webFormat/Khaykin/khaykin.pdf (Thanks to Dick Inglis for this reference.)

PRESENTATIONS

Dr. Dan Roden of the Vanderbilt University School of Medicine discussed how genetics may play a important role in a patient’s development of A-Fib. The title of his presentation was “AF as part of the spectrum of monogenic cardiac diseases (HCM, LQTS, Brugada, sodium channel mutations & SA function, HCN Mutations and SN Dysfunction).” (These medical terms and abbreviations are described in the footnote at the end of this report.)

The Role of Genetics in the Development of A-Fib

Dr. Roden pointed out that most discussion of A-Fib is concerned with the downstream aspects of A-Fib such as treatment options. But we should be as concerned with the upstream triggers of A-Fib such as genetics.

Genetic Research

Genetic research is important to A-Fib patients, because genetic variants may predispose people to A-Fib. Dr. Rogan suggested that within five years current genetic research may identify what properties in a patient predispose them to A-Fib. Once this has been determined, a personalized therapy can be developed for each patient based on their underlying genetic predisposition.

Genetic Types of A-Fib

Genetic studies indicate there are different types of A-Fib diseases or A-Fib provokers, such as those mentioned in the above title. According to Dr. Roden, telling someone, “You have A-Fib,” is like saying, “You have cancer,” without indicating what type of cancer.A-Fib is part of the spectrum of “channel-opothy diseases,” particularly of Sodium Channel diseases. (“Channel-opothy” refers to the various chemical and electrical currents that are irregular in a diseased heart.) For example, Dr. Roden pointed out that a Sodium Channel deficiency or genetic mutation on gene SCN5A can lead to “Sodium Channel Deficiency A-Fib” and may be responsible for familial A-Fib. In another example Dr. Roden described how people with Hypertrophic Cardiomyopathy tend to also develop “HCM A-Fib” (22%). The bigger their left atrium and the more severe their heart functions, the more they tend to get HCM A-Fib. Also, people with both Hypertrophic Cardiomyopathy and HCM A-Fib are more likely to develop heart failure.

Lone A-Fib

Lone A-Fib” is usually described as a type of A-Fib without any known causes. But Dr. Roden theorizes that Lone A-Fib is really a genetic disease. He recommended that young people with Lone A-Fib be referred to Dr. Patrick Ellinor at Massachusetts General or to Dr. Dawood Darbar at Vanderbilt for genetic testing, in order to sort out what their genes are and what makes them susceptible to A-Fib.

(Editor’s Note: It may be of great help to both patients and doctors to know what kind of A-Fib one has. Genetic research may make this possible.)

Footnote: “monogenic” controlled by a single gene “HCM” Hypertrophic Cardiomyopathy “LQTS” Long QT Syndrome “SA” Sinoatrial “HCN” Hyperpolarization-activated Cyclic Nucleotide Gated Ion Channel “SN” Sinus Node

Dr. Pierre Jaïs described how the French Bordeaux group ablates atrial tachycardias that often occur after A-Fib has been eliminated. “Advances in the Management of Atrial Tachycardia after AF Ablation.” One of the major problems for doctors performing Pulmonary Vein Ablation procedures is Atrial Tachycardia which remain after A-Fib has been ablated. These Atrial Tachycardia signals are often elusive and difficult to map and ablate. The Bordeaux group currently terminates A-Fib in 84% of cases. But only 13% of these patients return to Sinus Rhythm. While 71% still have Atrial Tachycardias. Instead of using 3-D mapping which can be time consuming and impractical (3-D systems often generate system noise which can mask Atrial Tachycardia signals), the Bordeaux group uses a conventional mapping system using only a multi polar mapping catheter in the Coronary Sinus and an ablation catheter. If the Atrial Tachycardia are regular, they move to Step 3 in the flow chart below and do a focal ablation. If the Atrial Tachycardia are irregular, they move to Step 2 below and check for Macroreentrant circuits (Perimitral, Roof, and Peritricuspid) and perform linear ablations. If the circuits are not Macroreentrant, they move to Step 3. (In the slides below “CL” is the abbreviation for Cycle Length, “PPI” refers to Post Pacing Interval, a method of pacing the atria to find arrhythmias.)

(Editor’s Note: Atrial Tachycardias that remain after an ablation can be a significant problem for A-Fib patients. Often their sources are not found, and a patient is cardioverted hoping the healing process will eventually eliminate these Atrial Tachycardias. But they may come back and lead to more A-Fib or A-Flutter. The Bordeaux Group, by developing a simple, step-wise approach to eliminating Atrial Tachycardias, may significantly improve Catheter Ablation procedures. Another important finding of this study is that so many ablations (71% of “successful” ablations) develop Atrial Tachycardias which can persist after an ablation.)

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Last updated: Wednesday, July 6, 2016

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