BELIEF Trial - LAA Isolation for Long Standing Persistent AFIB

Hi Folks,

Just a update here on a very important international multi-center fully randomized controlled trial (the most rigorous and typically useful kind of study) called the BELIEF Trial of 4 years running on Left Atrial Appendage Isolation that was presented on Monday at the huge European Society of Cardiology 2015 Congress in London. And this seminal trial showed a very powerful impact on successfully ablating even the most challenging class of ablation patients, those with long standing persistent AFIB when including LAA isolation to a standard extended PVAI ablation procedure.

This topic is particularly relevant for many of our readers as it was spearheaded by St David's Medical Center and with Drs. Andrea Natale and Luigi DiBiase at the forefront of structuring the trial. This comes as no surprise, as Dr Natale and his groups have led the charge forward in the early recognition of, and investigation into plus development of, LAA involvement in more advanced AFIB cases and they have pioneered how best to ablate .. in this case isolate ... the LAA and Coronary Sinus as two structures repeatedly found to be key remaining triggering culprit(s) after the standard PVAI portion of an ablation is complete and yet there are still active drivers that need to be addressed.

This carefully conducted trial took place in recruiting and ablating a cohort of 173 long standing persistent AFIB patients spread between Austin, San Francisco, La Jolla, Kansas City and two centers in Italy. 85 patients received the standard 'Extended PVAI', also developed at Cleveland Clinic and St Davids, plus LAA isolation and formed 'Group 1'. 'Group 2' consisted of 88 additional long standing persistent AFIB patients who received only the standard Extended PVAI alone during the index procedure, but not LAA isolation. And up to two procedures were included, as needed, as part of the study end point which is understandable with the extremely high odds of needing more than one procedure in this class of patients.

To accurately appreciate the very robust success achieved in this first randomized control trial examining LAA isolation, it's very important to understand and keep in mind that these were not long standing 'paroxysmal' cases nor were they 'regular persistent' AFIB cases either of less than one year duration. The BELIEF trial included only patients who had been in unbroken AFIB for at least 1 year of 24/7 long standing persistent activity, and a large majority were in non stop AFIB for a good number of years longer than that.

Such long standing persistent AFIB cases have been far more challenging previously to get good durable results with using any method, including catheter ablation, even with a several procedures without addressing these more perimeter key trigger sources such as the CS and LAA.

The net results after two full years in this most challenging class of patients (not just the typical 12 months most ablation studies cut off by in determining success rates) including a maximum standard ablation plus LAA isolation and one touch up ( if needed) in Group 1 ( 85 patients) vs Group 2 ( 88 patients) who received the standard ablation alone in the index procedure but did get an LAA isolation is deemed necessary in any touch up procedure required during this two year window.

At 2 years 76% were AFIB free and off all AAR drugs in Group 1 who all got LAA isolation in the index procedure plus a single touch up if needed ( 27 of 85 - 31.7% needing a touch up), vs a Group 2 number of 56% who were free of arrhythmia and AAR drugs at the 2 year mark. However, importantly, any in this Group 2 needing a touch up were also offered and given LAA isolation when indicated during the 2nd ablation (total of 35 out of 88 (39.7%).

As such, and as noted by discussant Dr. Gerhard Hindricks from Germany who was on the panel presenting the BELIEF trial, that the results would have looked even stronger had the LAA isolation not been given to the control Group 2 in their follow up 2nd ablation. They added the LAA isolation for the control group, if any follow up was needed, because they had already demonstrated such clear efficacy over two years between the two groups even when raising the success rates of the control group more by adding the LAA isolation as part of any touch up as needed, and not to have offered them the best chance for success in the 2nd procedure would have been unethical and not in the patient's best interest by that point in the process.

To put that in perspective, after one year, those who had LAA isolation had a two times greater likelihood of being arrhythmia free at 1 year: 56% compared to 28% who had only the standard extended PVAI during the first year.

These are impressive success rates indeed for such a difficult class of patients who, in past studies on long standing persistent AFIB, typically had 'success' rates only in the range of the mid 20% to low 40% at best.

When LAA isolation is given to those with either long standing paroxysmal AFIB or standard persistent AFIB of less than 1 year duration that show strong active triggering from the LAA during their index or follow up ablation, the success rates will be substantially higher still than reported here for those with long standing persistent cases.

It will no doubt still take a couple more years and another study or two to likely fully open up the doors to wide acceptance of adding LAA isolation for those advanced cases of AFIB that show clear LAA involvement during the ablation ( not all persistent cases, but most long standing persistent cases do have LAA involvement). There has just been so much resistance in the EP community to venture much beyond the PVI into non-PV triggers until fairly recently so we it will take a while yet, but this study is a major step forward toward encouraging far more EPs to learn how to do LAA isolation and better care for more advanced AFIB cases, many of whom were just sent out to pasture on an OAC and maybe some beta blockers for rate control and a wish for good luck.

Also, obviously with the potential for requiring long term anti-coagulation in those with too low LAA mechanical function as a result of successful LAA isolation, that too has added another point of reluctance which will take a bit more time to fully overcome.

In the Medscape article summarizing the presentation by Dr Luigi DiBiase of these very encouraging BELIEF trial results, one EP from Brigham and Women's reflected and showed an example of the kind of learning curve many will have to undergo when he clearly did not realize these were only long standing persistent cases and clearly just assumed they were typical regular persistent cases. In addition, his main concern was whether or not a patient can stop OAC drugs and how would they know.

That is an important, but very much secondary issue as no one with long standing persistent AFIB is going to go indefinitely without being put on an OAC for life in any event. The key issue here, is not first and foremost trying to get people off OAC drugs, but to restore NSR long term and then address any OAC issue as needed going forward.

Of interest, in the BELIEF trial the patients who had LAA isolation also had a follow up TEE some 6 months later (85 in Group 1 and in Group 2 there were 8 patients who also had LAA isolation during follow up ablation) 48% had preserved LAA ejection fraction and function and 52% had impaired function and thus would have to either stay in an oral anticoagulant indefinitely or go for an Atriclip, LARIAT or Watchman procedure to offer the possibility of stopping all OAC drugs. This is a bit better odds of potentially being able to stop OAC after LAA isolation than we have assumed recently.

I will be covering this study in more detail in the next AFIB Report hopefully out by end of September or first week of Oct, but I thought it worthwhile to post this news since quite a few of us here who have had LAA isolation, or might require this procedure in the future, should find it all very encouraging and very good to know.

Cheers!
Shannon

PS: Here is the Medscape article link but you will have to register to be able to open it in your browsers : BELIEF Trial - LAA Isolation for Long Standing Persistent AFIB



Edited 5 time(s). Last edit at 09/04/2015 01:20PM by Shannon.

Shannon,

Thank you, my friend. This is indeed welcome and encouraging news!

John

My last ablation and touch up, by Dr. Natale, were LAA and coronary sinus ablations and so far they have worked. Glad to have had the latest and best for my difficult case. But then that's why we go to Dr. Natale.

Nick

That is exciting news Shannon. Thanks for the mssg the other day. You can probably help me with a few questions regarding LAA ablation that I have always wondered about and this looks like a good time to ask given the nice results out of BELIEF. The appendage is probably the most delicate structure in the LA, ie the thinness factor, how does Natale go about deciding whether to go in and do a focal ablation or whether it should be isolated, or is focal never done because it is too high risk to venture into the LAA? How does he do the mapping/pacing, is it FAM merged with CT or MRI.? Any idea on learning curve? Even amongst the high volume centers, I believe there would be formidable reluctance to ventue there based upon past comments from lower skilled EPs about the aggressiveness of Maestro Natale.

I found answers to some of my questions in the Circulation article below -

[circ.ahajournals.org]



Edited 4 time(s). Last edit at 09/05/2015 03:21AM by Shannon.

Shannon, looking at the Circulation article referenced above, the following are the LSPAF stats and LAA firing prevalence.

The total patient population for that study was N=3966

Out of that total, LSPAF population was N=1145 (100%)
Out of the LSPAF population, redo was N=503 (44%)
In those redos, LAA firing was N=149 (13% of original LSPAF population, and 30% of LSPAF redos)

First of all, am I looking at the numbers correctly? If so, it seems that the best possible improvement in BELIEF would be 149/1145 for LAA isolation vs no LAA isolation. I must not be capturing some significant differences somewhere. Any comments appreciated.



Edited 1 time(s). Last edit at 09/04/2015 04:42PM by researcher.

HI Researcher,

In answer to the first post above here is my reply which I first added by mistake to your own post and have since moved it here after realizing I clicked in the wrong box :-).

They use Carto 3D and ICE .. CT, MRI or 3D-TEE is used for LAA morphological classification when needed, such as before any ligation or exclusion device or procedure. .. or also just to type the morphology to help in the decision making process for understanding the degree of risk one may be under with a less friendly LAA shape compared to say the Chicken wing shape which is the most favorable and carries a very low risk of emboli clot formation within the LAA .. OF course, after an ARTICLIP is applied the morphology is a moot point from then on and not a factor as you will have no more LAA.

Also, the LAA tissue is variegated and has some very thin tissue areas, but Dr Natale does not do any focal LAA ablation within the LAA any longer but ablates around the thick mouth area to either delay it in amplitude of the LAA signal, or when after doing an isuprel drug challenge after completing the ablation plus after finishing eh delay of the LAA and the isuprel does not re-excite the LAA trigger again and make it go chaotic once again.

As long as the LAA signal that he has at first delayed and made well-behaved remains that way, even after such intense stimulation as 20mcg/kg/min of drug infusion for 10 to 15 minutes of time, he will end the ablation and see how well that holds long term. If it acts up again and causes late breakthrough of ATachy or A Flutter again after the blanking period, then he will go back in and finish off full LAA isolation at that time.

In the early days of him starting to address the LAA he did try to use LAA focal ablation, as Bordeaux still pretty much uses .. or at least they may still do so, and did use a focal approach up through the last time I heard them present there approach at Orlando AFIB 2014... but they may well have started by now to including full LAA isolation and if not yet, this BELIEF trial will certain add a lot of ammo for them to consider doing so.

The reason they and at first Natale tried to avoid the LAA isolation of course was to prevent the roughly 50% risk of LAA functional velocity slowing to the point of requiring OAC long term of going for an ligation or occlusion procedure.

However, Dr Natale found over the first few years of experimentation that LAA focal ablation simply does not work very well at all, and as you noted it does bring a bit more risk for perforation, though he said it is more a matter of learning and mastering correct technique to greatly minimize that risk even in the thin and variegated LAA wall tissue.

He tried an LAA focal ablation in me too during my index procedure, but when my LAA did not behave under the Isuprel challenge he started to finish my index ablation with a full LAA isolation. Alas, that is when that unfortunately Infrahisian Left Bundle Branch Block that was totally unrelated to AFIB triggered at an inopportune time and forced a quick end to that first ablation for me forcing Dr Natale to caridovert me into NSR rather than complete the LAA isolation in that first ablation due to my BP crashing from my rate dependent LBBB activation when my AFIB converted to an elongated flutter at just the precise rate of 188bpm to trigger that LBBB.

So we had to stop that index procedure just a few burns shy of achieving what in hindsight would clearly have been a 'one and done' procedure for me even with as aggressive of symptomatic persistent AFIB as I had then! He said right after that first ablation that we have to be content with having ended all AFIB at that point, but knowing too I would need to return so he could finish up the LAA isolation to really put the genie back in the bottle long term, which as you all know I did some 4 years later in 2012 and the rest is history including all arrhythmia since then.

But after that first ablation I was free of all arrhythmia for 11 months and then had a flutter in Holland that was cardioverted and then went another 14 months with zero arrhythmia before the next LAA based flutter/tachy appeared after I had returned to Hawaii, and got same day EVC then too. Then 9 more months of total quiet went by before the next breakthrough of LAA Tachy/Flutter. after which it started triggering like clock work every 3 to 4 weeks and resulting in a total of 14 more ECV ( a total of 16 ECV all together) over the next 14 months before finally making it back to Dr Natale's table again to finish up full LAA isolation.. After that last ablation, I felt solid as a rock and have remained so for over 3 years now, and have had zero AFIB of even 1 second duration for over 7 years.

In any event, you mention that some less experienced EPs may well still be reluctant to learn LAA isolation even after the strong results from BELIEF trial, and that may well be true, especially for those who have always been reticent to move beyond a simple anatomical approach to Straight forward paroxysmal and some early stage persistent cases with generally small LA dimensions. But you really don't want an EP like that on your team in any event, if you have even a more complex paroxysmal case, much less a persistent or an LSPAF case.

And while some poorly informed EPs might still wrongly refer to Dr Natale as 'aggressive', those that really follow his work and have worked closely with him clearly realize he is plowing the cutting edge of this field, and has been for years now.

And in fact, as we have seen time and again here on out forum, Natale is singularly selective in what he ablates in various patients and does not at all use a 'cookie cutter one size fits all with that size always being a maximum ablation' as some EPs or Cardios who mostly have their own agenda might sometimes comment on from a position of pure speculation and ignorance about what the nature of Natale's practice really is.

What Natale does, and teaches to his proteges, is to be skillful in addressing any and all scenarios that might arise in any given patient, and not just settle for limiting ones tool kit to doing anatomical-only ablation because that is the easiest to pull off, as the majority of EPs still do, unfortunately.

Natale does press EPs at conferences to learn to do more and spread their wings and go to wherever they must to learn more advanced techniques. Some more confident young EPs take him ( and other top EPs like U Penn, Bordeaux and a handful of other elite centers, up on the challenge and will help themselves become the next generation of leaders in the field as a result. Some other EPs resent the big boys pressing then to spread their wings even after getting their EP fellowships and thus and a good number seemingly don't want to feel forced to take on more than they feel comfortable with, and that is certainly their right and prerogative too ... its just as a patient you want to try to avoid partnering with such folks unless perhaps you are sure you have a very basic and simple paroxysmal case.

Even then, why would anyone want to gamble on landing an EP who 'ought' to be just good enough!?

The thing with elite-level EPs like Natale and 30 or so others I know of in that general realm of excellence, they will typically only do as much as is required to give each patient their best chance for the minimal amount of total ablation burden over a one, two to occasionally three over all procedures. With Natale he truly is doing the least amount of total work for challenging cases with all of his touch ups being truly just that .. generally no more than a true touch up ... with each one having progressively less total added ablation burden on the heart than the index procedure ... and that is a very big deal to understand and take into consideration.

Anyway, researcher, I will address your very good question on the percentages of LAA isolation required in LSPAF patients as raised in St David's first seminal study on that issue which first announced that the LAA is an Under-reconized source of arrhythmia, in my next reply below.

Be well,
Shannon



Edited 2 time(s). Last edit at 09/16/2015 01:49AM by Shannon.

researcher Wrote:
-------------------------------------------------------
> Shannon, looking at the Circulation article
> referenced above, the following are the LSPAF
> stats and LAA firing prevalence.
>
> The total patient population for that study was
> N=3966
>
> Out of that total, LSPAF population was N=1145
> (100%)
> Out of the LSPAF population, redo was N=503
> (44%)
> In those redos, LAA firing was N=149 (13% of
> original LSPAF population, and 30% of LSPA
> redos)
>
> First of all, am I looking at the numbers
> correctly? If so, it seems that the best possible
> improvement in BELIEF would be 149/1145 for LAA
> isolation vs no LAA isolation. I must not be
> capturing some significant differences somewhere.
> Any comments appreciated.


Shannon's Reply

Good questions and insight Researcher, you earned your nickname there with sleuthing out the old numbers from that breakthrough study from May 2010 Circulation out of St Davids in which the LAA was first really defined as an under-recognized trigger source of arrhythmia in certain classes of AFIB patients.

Keep in mind that that first study was really from 2009 but was only published in May of 2010, so it was in the early couple of years of LAA isolation work to begin with when they were still learning a tremendous amount about how to detect and ferret out true LAA active sources and such.

The reason for the relatively low number of those with actively sustained arrhythmia firing straight from the LAA is that at that time and in that first study they relied on documentation of actual firing from the LAA that would initiate sustained arrhythmias as the criteria for listing a patients and 'LAA firing'. Since then they have learned how to place the the lasso mapping catheter inside the Left Superior Pulmonary Vein (RSPV) and the ablation catheter within the right superior PV (RSPV) and take a distal view of the LAA from the Lasso in the LSPV to get more accurate and reliable detection of LAA trigger sources, compared to just making and detection from the ostium of the LAA itself which is less robust a view point for detection than is the distal view from the LSPV.

From the added research and large database of ongoing experience they learned that when it comes to LSPAF cases, even detection of a specific series of PACs-only firing from the LAA, or even when there is no firing detected from the LAA, are very important signals in these LSPAF cases.

As you know in LSPAF, its not uncommon for the intensity of arrhythmia to lessen over time and become less symptomatic as a result and as such it can be less obvious in detecting these triggers as well as you might imagine.

This is why in the BELIEF trial , and also implied in the first study from 2010, they designed the study with an empirical arm and in the other arm in which LAA isolation was only allowed to be done on those with actively documented LAA firing, only 10 patients had LAA isolation from that arm as a result!

Now fast forward to the real world results from this carefully designed and well laid out randomized control trial in BELIEF we see the larger numbers of the LSPAF patients who had success in the standard 'extended PVAI plus LAA isolation' Group 1 compared to those LSPAF patients in Group 2 who only had the standard extended PVAI alone! thus this new study really underscores the major importance of the LAA in arrhythmia-genesis this case of Long standing persistent AFIB patients.

And we have correlation with this finding in the large literature from the Cox-Maze and Mini Maze history in which they achieve a very solid level of AFIB reduction for sure. At the recent ISLAA (International Symposium on Left Atrial Appendage 2015) Dr Cox himself and several other cardiac surgeon and Maze operators noted that no doubt a significant portion of their robust success rates were due to all of these procedures including full ligation with Atriclip or amputation of the LAA as a matter of routine in each MAZE or Mini-Maze, and its clear now that the impressive success rates in these surgical ablation procedures that also include removing the LAA from the equation are now finding a corollary in the catheter ablation field too for such challenging cases as are LSPAF cases, now that they are also addressing the LAA as well.

ALso, keep in mind that a fair number of regular persistent cases as well as longer standing paroxysmal cases can and often do have LAA involvement as well and many of those can benefit from LAA isolation as well.

Dr Natale does not automatically do LAA isolation on these patients but rather will try to delay any LAA trigger sources and see if it hold and behaves during Isuprel challenge, and if so he would usually not do full LAA isolation in that same ablation and just see how well the patient does going forward.

We have seen a growing number of such cases in which I would have fully expected him to have to do a full LAA isolation on a patient from our forum and he winds up just delaying it at first and often it has help for a good while and continues too in many cases. It others, there has been a flair up of the flutter or tachy after 4 to 6 months indiciating a stronger likelihood of needing to finish up that full LAA isolation.

In any event, this is the step by step approach Natale takes which insuring the patient will only have the minimal amount of ablation needed to put the genie well locked up in the bottle again for the long term and he is actually the most conservative of those very skilled elite level operators I know of in getting the most bang for his ablation buck in the long run that we have seen so far. Hence our ongoing enthusiastic recommendation for his services, especially for long term afibbers.

Cheers!
Shannon

PS researcher, I will not be able to answer any more questions this week on the forum until I return from the World AFIB Day event in KC where I have to give a little talk too at the dinner this coming week. Im putting all that together now as well as starting the next AFIB Report layout and simply have no more time until a week from this Monday when I'll be able to answer any more questions you are any others here might have on this topic.



Edited 2 time(s). Last edit at 09/16/2015 01:52AM by Shannon.

Thanks for mssg and replies. Have a nice time in KC.

This is all well and good, but the research that is really needed is research to uncover the root cause of afib.

I believe the research into LAA firing adds to the understanding of AF development so it is an important piece of the puzzle just as PV firing is of principal importance. My sister in law in her early 60's just had two right sided accessory pathways ablated. She lived with WPW ever since she remembered. I suspect she has a genetic predisposition to having those two circuits. Her episodes were getting longer and longer and she finally decided to do something about it before retirement and while still under excellent medical coverage. Her last episode lasted 4 hrs and HR hovered around 300. Now she wonders why see hasn't taken care of the problem sooner. Saw her Sunday and she looks 10 yrs younger.

Lynn,

The good news is that there truly IS a tremendous amount of in-depth basic metabolic and biochemical science being done at large centers around the world focused on uncovering the many contributions towards different people getting AFIB at different times, circumstances, genetics, environmental and life style influences and from various triggers etc etc.

This idea that no one out there is really looking for the core cause ... or better yet .. a myriad of cause(s) with a capital plural 'S' on the end, is simply not true! That very focus you wish for is very much a key driver in research centers from the US, Canada to Europe, Australia and Asia.

That there is also a lot of practical real world in the 'here and now' research on ablation methods as well and also a good deal of investigation regarding life style risk factor contributors are on-going as well in several areas of the world, and all for better controlling AFIB while an ultimate cure for the masses still escapes us ...

And before anyone jumps in with a laundry list of out of context quotes from various disparate articles trying to claim magnesium is that holy grail 'Cure' ... lets just move past that limited and not well supported claim at long last. Magnesium is a very useful and even critical element in biochemistry and overall good health as well as cardio health ... no question, but there has just not be enough real world long term true success from using magnesium as a true cure, or magnesium and potassium balance as the basis for a universal cure, as yet .. If it was such a cure, we would have been the one's to have seen it long ago by now.

Instead, we've had only a few people who actually have claimed very long term over 5 consecutive years success with Magnesium alone are as the prime element of a total cure, as one example.

And yet there truly are many combinations of natural and dietary protocols that can and do, indeed, help grant long term remission for sure to a fair number of afibbers, and we have seen a good number of such cases as in Conference room 61 for example.

But then again, these success stories largely reflect the common sense reality that there are different strokes for different folks and while they point to some common ground between these methods, most such approaches can only be offered as good suggestions for people to really try and see if they work for them, and if so, then fantastic for as long as it continues to work at a high level of success. But that scenario, too, is not on par with a universal true cure, if you appreciate the distinction.

A proper electrolyte balance including that of magnesium, potassium, sodium and calcium, including repletion of depleted magnesium stores ... may very well be one of the key cogs in the management cascade for many afibbers, but at best, it is only a mid-level player in this complex and highly elusive search for core causes and fundamental elements that run through all forms of AFIB.

It may well be that AFIB is not really a disease and as such, and will never have a formal and straight forward 'Cure' that is universally applicable and works reasonably well for nearly every Afibbers ... like Vitamin C does for instance with scurvy .. and in mention of that Vitamin C/Scurvy true cure example its important to underscore that the analogy that was bantered about a while back here comparing the relationship of AFIB and magnesium to that of Vitamin C and scurvy simply has no relevance or comparison at all to one another.

And that lack of association between magnesium/AFIB and Vitamin C/ with scurvy .. in no way undermines the very real value magnesium can bring to not only helping quieten down to various degrees and unruly heart. It is no less valuable than it has always been, in spite of it not being the holy grail cure.

No doubt continued progress will be made with big jumps in our knowledge and treatment methods about and for AFIB along the way .. just like this BELIEF trial heralds a significant step forward for that most difficult class of patients who were very difficult to treat by any means previously, and yet now have real hope for regaining their lives with a strong percentage of success via LAA isolation when that source of ongoing arrhythmia remains a key trigger in a given case.

The point being Lynn, that there really is a ton of fundamental research going on right now, and has been for many years by some very bright and dedicated scientist and all looking at core issues on the cellular, intracellular and genetic levels. At the same time, research into how AFIB works in its many manifestations via pioneers like Dr Natale, Kansas University, Univ. of Penn, the group at Bordeaux and a number of other top centers are all pressing the state of the art in how to actually improve treatments for patients while we are waiting for some 'all time cure' to manifest from basic science. And this real world practical patient treating 'in the now' research may very well reveal insights that move the whole field closer to a more universal functional cure as well, just through increasing our understanding of how this beast lives and progresses over time.

In any event, just take heart that there is no paucity of real fundamental core cause research going on around AFIB, but in the meantime the demand for better treatments is ongoing as well and that is what we normally hear most about as patients are most interested in what can help them now and on secondarily what 'might' pan out theoretically much further down the road.

Cheers!
Shannon



Edited 1 time(s). Last edit at 09/11/2015 03:39AM by Shannon.

Dr. John has posted his doubts about the BELIEF trial.

For myself, having already had extensive ablation of the left and right atrium and LAA and waiting for the follow-up TEE, this was a little disconcerting to read. I am in the group of CHAD score = 1 and was never in persistent AFIB. But I had a good diet and lifestyle (well, except for job stress and a commute from hell), all of my efforts at supplements appeared to have little or no effect. I am now in NSR, though a little fast. Hoping for the best in the future and am optimistic. I don't know where I would be if I'd decided against the ablations with Dr. Natale. Probably would have retired and still had intermittent episodes and the resulting anxiety. I haven't read anything that Dr. John has written that I haven't already tried.

I think the article is only disconcerting to the extent that Dr. John is still too inexperienced to treat LSPAF patients, the toughest class of AF ablation patients. The success rate presented in the BELIEF trial is outstanding. Probably the best that has ever been published. It is a little silly to argue facts (BELIEF results) with feelings (Dr. John). That's my take coming from a physical science background and I agree that more research trials need to done as suggested by Hindricks to see if the results can be replicated by other top centers that ablate LSPAF patients.



Edited 1 time(s). Last edit at 09/15/2015 03:35PM by researcher.

Dr. John Mandrola's current Newsletter:

In AF ablation, ask tough questions about left atrial appendage isolation

Posted: 14 Sep 2015 05:54 AM PDT

A study presented recently at the 2015 European Society of Cardiology meeting promoted electrical isolation of the left atrial appendage as a useful strategy for the ablation of long-standing persistent AF. The study came from an influential research group. ESC increased the influence of this trial by making it a “Hot-Line” session presentation.

The BELIEF study had serious flaws. I think LAA isolation is a bad idea, a dangerous idea. I’m not alone. Professor Gerhard Hindricks from Leipzig gave a cordial but robust rebuttal of the trial after its presentation. A prominent ablation doctor in the US called me this weekend to express his concern over the promotion of this trial.

I am not saying isolation of the appendage is always a bad idea. Sometimes it happens because of ablation of other areas; sometimes a trigger of AF comes from within the appendage. In my experience, these occasions are uncommon, almost rare.

The BELIEF study considered empiric isolation of the appendage. Empiric being medical speak for doing it in all comers– or just because.

Proceeding on with extensive ablation strategies is curious because the best evidence in AF ablation favors a less-is-more approach. The STAR AF II trial shocked the EP community because it showed less ablation was superior–even in patients with advanced (persistent) AF. And whether or not you believe in rotor ablation, the concept points to focal ablation of areas of rotors rather than empiric ablation of swaths of the left atrium.

In last week’s opinion column over at theheart.org on Medscape, I wrote five reasons why I thought this was a bad idea. The link and title are here: Doubting the BELIEF Trial on LAA Isolation

JMM

Perfectly well said Researcher, right on the mark!

I am just back home from Kansas City and returned home last night and am reviewing both this article, and a follow up shorter one on the same topic that Dr. Mandrola put out yesterday that is even more in need of rebuttal in my view.

I am writing a formal rebuttal to both right now and will post them here too in this thread likely tomorrow, in place of this ad hoc dictated response on my iPhone that I wanted to at least get out even though its a longer rough draft and off the cuff,.. once I hone it down and edit it some to read a bit more concisely I will send copies directly to Dr Mandrola and to Medscape as well.

In my view, on this BELIEF Trial issue Dr John is clearly letting his feelings and convictions about 'Less must equal more' color his judgement and from a number of his comments on a the topic of LAA isolation its apparent that he clearly has far more limited experience with than area than do the authors of BELIEF ... Not even in the same universe.

Alas, with his bully pulpit and his very good writing style (and he is a good communicator for sure) he is also inadvertently doing a big disservice by trying to use his personal opinions, born of his far more limited personal experience, to shout down the results from the BELIEF trial presented as a very well vetted and very strongly structured and carried out peer-reviewed randomized control trial as empirical scientific findings!

In spite of there being zero deaths, no PV stenosis, no esophageal fistulas or no strokes/TIAs in the study arm with standard extended PVAI and full LAA isolation ... Dr John calls it all 'dangerous and a bad idea' ... based on what Dr John?? ... your 'gut feel' or reading the bones of of ancient ancestors?? Certainly there is risk in all cardiac procedures and LAA isolation does require more skill and experience to perform reliably, safely and in an expert fashion, but that is no reason to brand it especially dangerous in the face of very good safety shown in this expert centers experience or try to dissuade this whole class of LSPAF patients who this study examined who have had so little real long term hope previously and now have very good odds of restoring long term NSR and regaining a large part of quailty of life left for them.

I find it odd too that he complains even that BELIEF was granted (and fully deserved) unanimous approval for 'Hot Line' presentation status at ESC Congress 2015 in London two weeks ago. The last time I looked getting such a prestigious presentation status doesn't just arbitrarily fall off a tree!

It is voted by the full expert committee membership at ESC who carefully review and debate the merits and structure of every randomized controlled trial being presented that year, and only those few deemed most significant, ground breaking and SOLID get Hot Line status ... so he is basically insulting the whole ESC committee by so cavalierly, and irresponsibly, in my view, assuming they were wrong in granting such an important recognition and status to a full randomized controlled prospective trial by the largest AFIB research center in the world, simply because it does only seems to run counter to Dr Johns 'Less is always more' personal belief system..

I think Dr John really means well and his heart may be in the right place and we all here fully support his relatively new found belief in life style risk factor (RFM) modification that for the last 16 years has been our cornerstone foremost recommendation for all newly diagnosed Afibbers to adopt with real dedication. Though its hardly a novel idea nor did this very good and common sense idea get started in Adelaide Australia, by any means. There have been a host of prior studies pointing to the very helpful impact of RFM modification too by other large centers before these two Aussie study's of ARREST-AF and CARDIOFIT. And I give Prash Sanders and his group credit for laying out a specific and rigorous protocol for patients to follow to help maximize their RFM improving efforts. That is all well and good.

And we here at afibbers.org all know and support fully adding first RFM modification (which includes dietary and nutritional supplementation when warranted in our recommendations) along with CV risk mitigating strategies (included in the overall RFM acronym) with support from their EPs from the outset of one's formal AFIB treatment. And then we also strongly recommend that when, and if, less than near total remission is achieved after a full year of dedicated effort, that such patients who in spite of those efforts are still suffering with too many AFIB episodes to by all means add in that 'expert ablation process' after carefully choosing the most experienced operator you can find even if you have to travel to find the most experienced operator within your reach, if necessary, for the best combined overall results and to earn the greatest degree of robust continuous NSR long term via such a combined team effort.

Dr. Mandrola in my view, is simply being too idealistic to the point of becoming a bit of an ideologue at times, which can be a well-intentioned though when overblown, a self-deceptive space to operate from. He assumes from one modest group of studies from Australia that these results are sufficient to rewrite global ablation recommendation status ad hoc, and that these steps will automatically mean ablations will now become 'rare' occurrences as such a large majority of Afibbers supposedly will find their AFIB go into remission from weight loss and RFM efforts alone.

On this point, I could not disagree with him more, not with our long experience that if their group is anything like the legions who have come to our site over the years and applied these many of the same RFM improving principles as well, and even with their well done weight loss studies that verify what we have been saying from day one here at afibbers.org since the year 2000... they will very likely find, as we have, that the initial good reductions in AFIB burden will often themselves go into remission too after a year or two, or even five years down the road, and even with continued dedication to all the RFM protocols and methods that will not be enough for the majority of these same people to keep the lid on the AFIB kettle from boiling over again with a vengeance.

I'd be willing to bet Dr John a cold Heineken at one of the AFIB conferences, that as time goes along he too will find both further confirmation of the wisdom of including such natural and allopathic methods together as a combined approach for improving RFM and CVRF issues, when those factors are key issues for given patients. But that he will also discover that over time AFIB itself, and its progression, is rather relentless and resilient and in the majority of those who initially benefit it will very often return .. possibly underscoring a likely genetic component as well as life style issues. It could be that the later to these two influences may simply accelerate the progression of the disease and make AFIB more likely to manifest earlier than it possibly would have had the person always taken very good care of themselves physically, as a well-supported hypothesis from our long and impressive anecdotal history.

As such, our experience indicates that the very best program includes adding, at the right time, that 'expert ablation process' along with a life long dedication to RFM reduction to achieve the most robust and durable freedom from arrhythmia for the long term for the majority of Afibbers.

Dr John, in my view, just goes too far here on this issue, beyond what even the Aussie researchers, including Dr. Prash Sanders, convey in their study. And he presumes that those results represent a more or less full replacement for catheter ablation for the vast majority of people. Granted, he does acknowledge that CA will still have a very limited role in some cases in his speculative projection. But he also presumes that RFM reduction and weight loss, based on this single set of studies, will render catheter ablation to a "rarely needed adjunct in a relatively few cases".. a lovely idea that simply has veryr little support from our long collective history in the trenches of this lousy condition.

To me, as well as to many others in the Cardio/EP world well above my pay grade, this view is far too indealistic and most docs I know in this field strongly feel that we would need at least a couple more large randomized control trials from larger centers in other parts of the world as well, fully confirming long term remission of AFIB via Risk Factor reducing protocols alone in paroxysmal and persistent cases ( not to mention LSPAF cases) before even considering the idea of relagating ablations to more or less a little used after thought.

Even in the Aussie studies, it was the obese afibbers that benefited most from the aggressive life style and CV risk reduction protocols, as expected, and only those that were able to prevent ANY fluctuation of more than a modest narrow range of weight change over time, were able to maintain that hard won anti-arrhythmia burden-reducing benefit of those stringent RFM modifying protocols ... as worthy and recommendable as they are.

Not surprisingly, from our collective experience over the years and as a possible glimpse of the shelf life on the initial AFIB remissions often possible with RFM efforts, the Aussie group also have reported increasing difficulty being able to still once again recruit enough of those same weight loss/AFIB free people from the initial study, beyond two years or so in order to be able to continue and extend the study time frame much further.

No doubt, a fair number of the subjects in the study will be successful in keeping the weight off, but even still, I can safely bet my bottom dollar that a good percentage of those who do will still not have heard the last from AFIB ... at least not without also adding in an expert ablation process to the equation.

Indeed, the most impressive stats from Adelaide, and which conform very well with our long experience, shows that the combination of dedicated long term RFM reducing methods plus an expert CA, are most often the winning formula for the majority of afibbers long term and this is especially true for persistent and LSPAF who also do much better, in our experience, with more extended expert ablation including LAA isolation when indicated.

What Dr John will almost certainly find out as well, based on our long experience, is that life style and weight loss for all its major benefits, does not rise to the level of a robust core cure-all for AFIB for the majority .. it can be a big help for sure, and even for a few years up to around five years in some cases it can indeed help trigger a relatively long and very worthwhile mostly quiet remission period .. and even longer for a much smaller lucky group of afibbers, and is highly recommended wholeheartedly in any event .. but it is not a long term panacea for the majority.

And to posit that it will, and should, render ablation a moot point for the majority based on such skimpy projections and lack of long term evidence is the height of misleading and irresponsible reporting in my view.

At this stage of the game, it still requires using all of the best tools in the tool shed at the right and appropriated time for the majority of afibbers to earn the best and most truly durable freedom from the beast that we can win for ourselves long term.

As worthwhile as the Australia obesity/AFIB studies are, they would not have been the first revelation to Dr John of that common sense approach had he had the chance to visit our website many years ago during his early EP days. Likewise, I hope he will benefit from, and take to heart, our long experience too with these protocols, and perhaps temper his proclamations now that he has found, in essence, the holy grail for the vast majority of afibbers who, thus, will not need an ablation after all based on these still rather preliminary but encouraging and very predictable results from Australia (at least predictable to us at afibbers.org).

Doing so, might save him having to issue another self-directed retraction to his own admittedly premature overly enthusiastic endorsement of another 'less must be more' concept as with his mia culpa shared some months back on his blog space concerning his early unbridled support for FIRM-only ablation after a spate of more independent studies were recently released being unable to conFIRM that the emperor indeed is wearing a full set of clothes at this stage of our understanding. While the jury is still out on FIRM, at the very least Dr Johns immediate and enthusiastic embrace of that technology to us all in the public from the moment it was first revealed as a new potentail mapping and ablation tool some years ago, has proven entirely premature at this point in time.

STAR -II has some interesting lessons to tell for sure, and could easily be a subject for another thread indeed, but suffice it to say in the interest of brevity that STAR-II was investigating a very different population base than is the LSPAF cohort investigated in BELIEF Trial. And as a result, to arbitrarily try to superimpose what he presumes is the only take home message from STAR II study onto the Long standing persistent AFIB group in BELIEF, is truly a non-starter! Indeed, its hard to believe that anyone with intimate familiarity with both persistent and LSPAF ablation would ever consider results from a study of one class of patients to be fully applicable to the other, out of hand.

The reason I'm addressing what I see as clearly some misplaced, potentially misleading and at the very least very premature comments about the BElIEF trial, even though no doubt inadvertently so, is that I have spoken to a handful of people over the last few years who had postponed timely ablations when a few of which were even set to go with one of the top experts in the world. But after they had read Dr Johns what now seems to have been equally premature and overly exuberant endorsement of an ablation system that promised a small handful of burns to cure AFIB when it first came out. All of these folks had canceled out of their ablations from riding the wave of that enthusiastic promise they heard from Dr Johns column.

And several cancelled in spite of having severe symptoms and increasing episode frequency with the hope that just around the corner would be this new easy panacea. A few of these then went on to develop full persistent AFIB from the continued remodeling from waiting on that promised dream they heard about on the blog, if only it would pan out soon enough. That constitutes real harm to me, and now I see the potential for even more harm from some similar well-intentioned but out-of-line personal opinion comments on BELIEF Trial that might also result in some premature and possibly harmful decisions by real patients. That is my main concern here.

This is not an 'either/or' debate between ablation or life-style risk reduction, in any way shape or form either! Both aspects are the two cornerstones of our prime recommendation as a complete winning formula we have validated over the years to work the best.

And the best thing too, is that when followed as we lay it out beginning with the RFM methods up front, all those who will be able to put the genie back in the bottle for the long term with RFM modification alone will certainly be able to discover that fact during the first 6 months to one full year of truly dedicated adoption or all the recommended RFM reducing protocols for them (including those that overlap with Dr. Sanders' group excellent recommendations)..

However, when following our regimen, the patient who is less than fully successful in that first year of RFM effort will not be left out to dry due to being deemed too 'unworthy' of rescue because they didn't have enough 'will power' or perhaps are considered 'too far gone already' by less experienced ablationist not so familiar and experienced with more advanced ablation methods and nuances. And thus, some of this folks deemed too far gone for an ablation are relegated to the unlucky exit wing of the ablation allocation triage list. Next, they are put on OAC drugs for life, loaded up with energy and libido-robbing rate control drugs ... and, in effect, are shoved out on the ice flow with the eskimos.

Ongoing long standing persistent AFIB does not have to lead directly to death either to effectively ruin one's life!

Anyway, you get the picture and Ive got to get back to the main response and will return later tomorrow ...

Be well Shannon



Edited 9 time(s). Last edit at 10/12/2015 03:23PM by Shannon.

The BELIEF trial involved primarily male patients with mean body-mass index (BMI) of approximately 33 kg/m2. I'ld like to see a similar study involving female patients who would probably have a lower mean BMI.

Betty

Hi Betty,

I'm sure there will be more women in future LAA isolation trials now that this important first randomized control trials on LAA ISO will crack open the door to more research in this field. And the BELiEF trial authors ended the presentation at ESC calling for more trials and also more physiopathology studies to help better define the physiological reasons for the impressive success shown with a previously most difficult class of patients to treat.

As women get older too they are even more likely than men to have LAA involvement ... Alas women do get the shorter end of the stick with a lot of these CVD issues.

Shannon

Shannon,
As always, well stated!
Thanks for your dedicated work to this board and community. We are lucky to have you!
Ken