General Overview

Unraveling the LAF mystery is a tall order, even assuming the certitude of Coumel's three critical ingredients - arrhythmogenic substrate, autonomic dysfunction, and trigger. I believe that the interplay between these three inputs is relatively straightforward, but that there is tremendous intra- and inter- individual variation in all three. It is not a question of whether or not you have X,Y, or Z, but how much of each do you have, as more of one requires less of the others.

Arrhythmogenic substrate
Required for all AF (physiologic and pathologic).
Abnormal atrial activation in young patients with lone atrial fibrillation
[www.ncbi.nlm.nih.gov]
Atrial fibrillation, atrial flutter, and atrial tachycardia seem to thrive in all AFers. This is why an antiflutter ablation (cavo-tricuspid-isthmus line) is routinely undertaken during PVI. This arrhythmogenicity can't be explained on the basis of just some abnormality in the pulmonary veins cured by PVI.
This arrhymogenicity is genetic and beyond our control. It is even beyond the control of the ablationist, who only impacts the trigger component. LAFers must remember this, as they age. AF begets AF and this would appear to be thru the development of additional trigger foci secondary to atrial stretch. Indeed the talented ablationists in Bordeaux only routinely search for extra pulmonary trigger foci in cases of persistent or permanent AF. Removal of triggers in the PVs via PVI, undercutting the required critical mass of triggers, doesn't preclude subsequent creation over time of new extra pulmonary triggers required to reach critical mass. AF really is akin to a nuclear bomb exploding in our chest as World War III.
Cause of Very Late Recurrence of Atrial Fibrillation or Flutter After Catheter Ablation for Atrial Fibrillation
[www.ncbi.nlm.nih.gov] (extra pulmonary triggers)
Even in those without frequent episodes the steady increase in cardiac fibrosis with age must add to abnormal conduction vulnerability. Those on "the List" probably have low arrhythmogenic potential and can exercise sufficient control over the other two inputs. The only list for those with more significant arrhythmogenic potential is the ablationist's list. I am convinced that my LAF was/is predominantly due to strong arrhythmogenic potential. My history of endurance sports frame shifted onset two decades earlier, as both parents developed AF in their 70s.

Autonomic Dysfunction
Adrenergic (e.g., stress) or vagal (e.g., endurance sports) tone extremes appear to potentiate the substrate in LAF, but pathologic AF is only adrenergic. Undoubtedly some of this autonomic tone is genetic. The differences between physiologic and pathological AF in age at onset and BMI suggest at least to me that LAFers carry more arrhymogenic substrate. Low blood volume due to dehydration or MVPS (mitral valve prolapse syndrome) clearly aggravates autonomic dysfunction.

Triggers
Virtually all triggering (LAF and AF) starts in the pulmonary veins with PACs. A critical mass of such foci is required and this is probably determined by the pulmonary venous sleeves, which, when sufficiently stretched, create sufficient foci. This stretching of the pulmonary veins probably precedes any measurable increase in left atrial size (usually normal in LAF). Whether this stretching is due to genetic causes related to the mitral valve, e.g., mild regurgitation, or develops later is unclear.
LAFers think of potassium, magnesium, stress, alcohol, coffee, tyramine, glutamate, dehydration, etc., as triggers, but IMHO these impact either autonomic dysfunction or electrolyte imbalance or both. Electrolyte imbalance then potentiates the firing of these rogue cells, as Hans calls them, and autonomic dysfunction via shortening of the AERP (atrial effective refractory period) sustains these chaotic "rogue" waves and the resulting AF.

With the above in mind, perhaps a personal analysis of ones own ongoing battle with the beast might lead to a better path of attack.

Anyway, that's my story and I'm sticking with it.

Anyone out there whose experience is discordant with this understanding of the process, don't be shy.

CRAPOPHILE IN CHIEF

It's so good to have you back on the board, PC. I have learned a lot from you over the years.

Gill

Aloha Pat,

Arrhythmogenic substrate

Not much to do here unless Jackie & Erling are correct that proteolytic enzymes will help remove fibrosis. I tried a 3 month course of 3x5/day Vitalizm tabs during my recent afib progression with negative results. It is hard to get dosing info on this stuff for afib.

Autonomic Dysfunction

In my case, if the autonomic dysfuntion does not happen, NSR is the result.

Triggers

Question: "Electrolyte imbalance then potentiates the firing of these rogue cells, as Hans calls them, and autonomic dysfunction via shortening of the AERP" How does electrolyte imbalance potentiate "autonomic dysfunction via shortening of the AERP." Unless you mean because the AERP is short that autonomic dysfunction allows the rogue cells to fire. I don't understand how electrolyte balance is related to ANS funtion.

In my case, during my 7 year relative quiecence period, as long as the electrolyte levels were fine, I could be "as vagal as I wanna be." With no afib consequences. Today, if get very vagal (HR in the high 30's or low 40's) and if I get prone and go to bed that way, I'm almost guaranteed afib.

My current solution is bedtime flec, but I don't think I've exhausted the electrolyte tools yet. The flec does buy time to play with the electrolytes.

George

Hi George,
I guess I wasn't using the best grammar. What I was trying to propose was that
1) electrolyte imbalance., i.e., low Mg or low K or both, of whatever etiology triggers these rogue cells to fire (PACs)
2) autonomic tone, either adrenergic or vagal, of whatever etiology kicks in and causes widespread shortening of the AERP, enabling the triggered-rogue-cell-originating waves to create/spread chaos/fibrillation in the adjacent atrium.
Some subscribe to the wavelet theory and others to the rotor theory, but whatever floats your boat.
I was trying (poorly) to implicate two separate but simultaneous developments and didn't mean to imply that one caused the other.
Also, IMHO If autonomic tone is strong, only a few PAC couplets might tip the scale. If PACs are frequent, only a little tone might tip the scale. This is just my simplistic overview of LAF.

Fellow crampophiles,
IMHO, unless an LAFer has just a touch of arrhythmogenic substrate, frustration tends to be a constant companion when battling the beast. Many eventually end up on the ablationist's table. Nonetheless, the truly dedicated seem consumed with the search for some universal yet to be discovered culprit, the removal of which will lead to NSR. While the search often leads to more healthful living, IMHO LAF is much more complicated than that.

Aloha Pat,

My experience agrees with your electrolyte imbalance/autonomic tone analysis. If electrolytes are good, then ANS doesn't matter. If electrolytes are imbalanced, then ANS matters alot.

I've always felt that to be successful with a non-medical approach to afib, the arrhythmogenic substrate level must be low and generally the non-medical approach started very early in the progression of afib. There are always cases that are exceptions, however. My correspondent who used the vagolytic, propantheline bromide, successfully to keep afib at bay had awful afib for many years prior. Flec also failed him. His sister in the UK had an early ablation with disasterous results. He therefore is very anti-ablation. More recently, he discovered that just the right amount of D3 kept him in rhythm with no PACs or PVCs when monitoring on his Polar (without using the P. As an aside, he used swimming pool water test strips for calcium hardness (CaCO3) on his urine. He found that when his serum D3 was too low, urine calcium hardness was 1000 ppm. When just right it was 500 ppm. Just right for him was around 50 ng/ml, lower than the frequently quoted 70-100 ng/dl ideal range. At levels above this, he gets large numbers of PACs. At too low of levels, he gets afib.

George

Hi again George,

I've often wondered why the rogue cells in AF that comprise the trigger component seem to prefer the pulmonary veins (90%), conveniently enabling their isolation and often subsequent NSR. Are these ganglionic plexi (GPs), which seems most likely? In session 35 of the Conference Room proceedings we speculated that these might possibly represent P cells (pole cells) and Hans suggested an inflammatory component by free radicals produced in the lungs might induce their "participation."

These probable GPs appear to be vagal in origin. The Bordeaux group showed no difference in AERP (atrial effective refractory period) between 20 paroxysmal AFers and 20 controls. However, the pulmonary venous effective refractory periods were SHORTER than AERP in these AFers but were LONGER than AERP in the controls. Why is that? Is it due to inflammation? IMHO it is due to mild stretching. The sites most susceptible to stretching would seem to be the venous points of entry into the atria, precisely the extra pulmonary ablation sites that most often trigger AF. Why do the Bordeaux ablationists routinely search for extraulmonary foci in persistent but not paroxysmal AF? Could this be due to greater mild atrial stretching over time in those with a greater AF burden? Pappone has called these extra pulmonary foci vagal reflex foci, because when stimulated bu the electrophysiologist, they induce immediate hypotension or bradycardia. He also states that ablation success goes to the high 90s, again suggesting a critical mass of rogue cell sites is required to sustain AF.

Angiotensin 1 receptors (AT1s), which reflect stretching and mediate AERP shortening, are increased in the left atrium, but not the right atrium in LAFers v. normal. So, is mild stretching over time at the root of our problem, at least insofar as the trigger component is concerned?

This does not even address the role stretching might play in facilitation of the arrhythmogenic substrate. We already know that a shortened AERP enhances dispersion and the likelihood of circus movements, which involves the substrate.

We'll reserve that for some future discussion, when others are more likely to be in brain cramp withdrawal

CIC (CRAPOPHILE in CHIEF)

Hi PC,

Boy, you know how to start an argument. Regarding the GPs, it is worth noting that during the Five Box procedure practiced by Dr. Sirak at Ohio State, he strips the GPs right off (he calls it "autonomic ablation.") Essentially he is removing the dysfunctional ANS and making the body re-establish it. Sounds extreme, but his success rate is very good (90%+)

EB

Hi EB,

Yes, the GPs are key.

The first ablation breakthrough came with the discovery that the PVs were the source of AF triggering ectopics 90% of the time. Then came the discovery that ganglionic plexi were also intimately involved in the AF process. These appear to be predominantly located on the epicardial surface and are easily stripped as in your case. I have no doubt that the PV triggers represent ganglionic plexi and that the extra pulmonary sites are as well. They probably correspond to the vagal reflex sites on the endocardial surface that result in bradycardia or hypotension when stimulated.

The question is: Are GPs more critical to juicing up autonomic tone or to triggering PACs or both?

Very good question- in my case, I am 11 months post op and I rarely have PACs. During the blanking period (first 6 months) I did have runs of PACs, however my resting heart rate was much higher, usually 80-90 bpm. Prior to the surgery my resting rate was always in the 50s.

A couple of months ago, almost instantaneously, my resting rate dropped and it is now mid-60s. And as I said, the PACs pretty much stopped about that same time.

I attribute all of this to healing from the ANS ablation-

EB

EB,

IMHO these GPs function more in the trigger domain than in the dysfunctional ANS domain.

I've often wondered why ablationists like Nadamanee in LA have been so successful with focal ablation without any PVI component. Why is the pulmonary vein ERP shortened in paroxysmalers (rather than lengthened in normals) compared to the AERP? If autonomic tone were involved the nearby left atrium should also exhibit a shortened AERP. I'm presuming that the PV cells responsible for this are GPs. Furthermore, why does Pappone state that ablation success rate approach 100% if vagal reflex sites are identified and abated?

Therefore, it seems entirely plausible to suspect that these GPs, especially those that develop outside the PVs, play a very integral role in initiation.

You claim that your HR dropped simultaneously with your PAC frequency 6 months post surgery. This was presumably due to reconnection of vagal nerve fibers, which has been well documented after the blanking period. One would expect the PACs to increase not decrease with this increasing vagal tone. I think you are now triggerless.

This then brings up several questions: Are the GPs more critical than the arrhythmogenic substrate? Do you believe that LAFers have an arrhythmogenic substrate over and above any element of autonomic dysfunction?

PC,

You should call Dr. Sirak, he is available for telephone consultation. I had a very interesting 45 minute conversation prior to scheduling my surgery. Your questions are much better than mine.

Regarding arrhythmogenic substrate, in my case he noted myocardial fibrosis in my LA, in fact he took multiple ablative passes to achieve electrical isolation. FWIW I am one of those (former) lifetime runners. He commented that the fibrosis was not unusual in exercise fanatics-

He did comment to me that in vagal affibers, the ANS ablation was a most important step-

So I still have the fibrotic heart, however I have the multiple ablative "boxes" that he put in place. That address Coumel's #1, arrhythmogenic substrate.

Number 2 is the dyfunctional ANS; stripping the GPs rebooted that.

Number 3 is the trigger, stripping the GPs make me triggerless.

It would appear that Dr. Sirak's procedure addresses all three. Does that make sense?

Thanks,

EB

EB,

I'm not quite sure how Dr. Sirak can make the statement "fibrosis is not unusual in exercise fanatics". As a retired pathologist, I know that the only way to demonstrate fibrosis is by biopsy and neither he nor anyone else has done this on endurance athletes. I'm sure he also subscribes to the inflammatory origin of LAF, equating association with causation, very much in vogue with lame stream medicine. LAF episodes demonstrably elevate inflammatory markers and to prove causation would require a very large prospective study. Again, such will never be done. My post ablation inflammatory markers crashed by almost 90%, hardly consistent with a pre existing causative inflammatory condition. H ans had a similar experience.

There are many excellent physicians/ablationists/Maze guys out there. But don't believe everything they say. They often don't have time to properly explain things and resort to more simple minded remarks.

Before my last ablation (second) in Bordeaux for I was reviewing my ER EKG diagnostic of atrial flutter. Normally the atrial contractions in flutter are obscured by the QRS complex and IV adenosine is used to suppress conduction thru the AV node. I noticed that I had down going F waves in my inferior leads, which is 90% diagnostic of right sided origin. However, during my initial ablation for fibrillation nearly 7 years prior I'd had preventative CTI (cavo tricuspid isthmus) ablation for flutter. Bordeaux boasts a 99% efficiency on this. When I raised this question to Dr. Jais preablation, he didn't answer the question. I assume he was just too busy. Anyway, the flutter was right side in origin.

Your post otherwise makes a lot of sense.

It was my assumption that his fibrosis diagnosis was based on the multiple ablative passes that were required to achieve electical isolation. The surgical report stated "myocardial fibrosis in the LA etc"

He is looking at the heart through a scope but he didn't do any biopsies. I took his comment to mean that it was not unusual for cardio fanatics to require multiple passes which equals fibrosis. And he may have been simplying for the layperson-

Very interesting information, I really appreciate the comments.

EB

Hi PC - A comment on the flutter issue... In the earlier years when many of us had ablations using older techniques, it was often noted that flutter often surfaced after the initial procedure and the reason given was that the right side flutter was there all along but the left-side afib masked or covered up the symptoms; plus, the mapping procedures were less perfected. Often, since the flutter was intermittant, it didn't show up during the initial ablation but definitely was evident eventually, post-ablation... requiring the second procedure for the right-side flutter.

Now, it seems that when flutter crops up later post-ablation in a selected few individuals after an initially successful procedure it can sometimes be traced to areas in and around the LAA -- as mentioned frequently in Shannon's post on that topic. It's also been mentioned that cardiac fibrosis formation not related to ablation scars can be one of the left atrial flutter sources. I recently talked with an EP who said that left-side flutter occurred from new potentials and had nothing to do with ablation scars...rather the signals just found new routes around the original scars.

Has anything turned up in your research in that regard?

Jackie

Hi Jackie,

Thank you for your post.

My understanding of atrial flutter is as follows:
Typical flutter involves the right atrium, specifically the cavo-tricuspid isthmus, and the reentrant circuit is always counter clockwise.
Atypical atrial flutter is predominantly right sided, but the circuit is clockwise. Left sided flutter is also classified within the atypical category.
Type I v. Type II flutter is based on some specific electrophysiologic characteristics.
Most flutter arises in the right atrium and is typical, unless there has been a previous left atrial ablation, in which case the odds highly favor left atrial origin.
Therefore, I suspect that left sided flutter in the absence of a prior ablation occurs but is decidedly rare, although data on this is hard to come by.

If fibrosis unrelated to a prior LA ablation for afib were responsible for post ablation left atrial flutter, I would expect to see much more left sided flutter in the general population. After all, LAFers seem to be a proactive, healthier group in general. Most of the usual causes of cardiac fibrosis would seem less likely amongst LAFers. Again IMHO the fibrosis/inflammatory hand is overplayed in explaining LAF, especially in those less than 60). I'm putting my money on atrial stretch as the primary culprit.

Your comments about the connection between flutter and fibrillation are well made. LAFers are well advised to watch for flutter post fib ablation and for afib post flutter ablation.

My view on afib/flutter is that trigger spots, potentiated by mild but chronic cell stretching, produce PACs that result in reentry (v on the basis of automaticity). The reentry is enabled by excess but unequal autonomic tone with differentiall AERP shortening in adjacent cells. This reentrant closed loop (circus movement) then results in rapid firing (mimicking automaticity). The product is sustained tachycardia, flutter, or afib, depending on the "fertility" of the involved atrium. This "fertility" is dependent not only on AERP but also on the presence of a critical mass of other trigger foci that can be enticed into participation.

When one reviews the usual post ablation report, one often encounters phrases such as, "when the left atrial roof line was made cycle length dropped 15 milliseconds" or "after isolating the LSPV (left superior pulmonary vein) cycle length dropped 10 ms." In other words when a contributing trigger focus was eliminated (decreasing critical mass) HR decreased. Once the critical mass threshold was broken, fibrillation episode terminated.

For years prior to diagnosis of afib and later flutter, I noticed short (5 second or so) bursts of tachycardia. One preablation 24 hour Holter demonstrated 133 very brief episodes of tachycardia. IMHO when other trigger foci are more numerous => atrial fibrillation, when they are absent => tachycardia, when intermediate in number => atrial flutter.

The coronary sinus (right atrium) is quite prone to producing trigger foci. During my two Bordeaux afib ablations (about 5 days apart) in 2005 the coronary sinus required additional attention. Perhaps there remained a trigger focus that eventually expressed itself in flutter 7 years later. Jais told me post flutter ablation that the flutter circuit involved a thin rim of tissue on the epicardial surface that bypassed the previous CTI cut. The deeper one cuts in this area, the more risk to perforation thru to the esophagus. That's one of the many reasons to select the most experienced and successful ablationist.

Two preablation echocardiograms demonstrated normal size left atrium but mild right atrial enlargement. Could some pressure due to mild mitral regurgitation have been transmitted from my left atrium to my right via my patent foramen ovale? Could this have caused my typical atrial flutter (right sided)?

This then leads to the question:
Are atrial septal defects more common in those with right sided atrial flutter, even amongst non LAFers?

Obviously many of my comments and conclusions are based on anecdotal evidence and are unavoidably subjective and speculative.

Hi Pat

"This does not even address the role stretching might play in facilitation of the arrhythmogenic substrate. We already know that a shortened AERP enhances dispersion and the likelihood of circus movements, which involves the substrate. "

I presume you ment circular.

I do find the postulated reconnection of EB's vagaus nerve fibers correlating with a reduction of PAC's curious.

My own case is likewise curious. If I solve the ANS puzzle, I don't have afib. I'm now one month into successfully using flec prophylactically. The week prior to starting this, I'd had afib every morning around 3AM, converted with 300 mg flec. I started using the flec in advance of going to bed initially at 300 mg, but after one night dropped it to 200 mg. Subsequently, I've titrated it back to 50 mg. What is really curious is the action of my ANS. Why it acts differerently at one time than another is the curious issue. Not only am I now down to 50 mg/day of flec, but I can have sex and an orgasm 10 hours later without as much as one missed beat in the vagal aftermath. I can, and have been drinking a few glasses of wine in the evening (though alcohol has not historically been a trigger for me). In the last week, I did start taking a heaping spoonful of ginger powder 2x/day My heart seems to be even more stable since doing this. No ANS aberations - like dropping to 38 BPM upon eating cold (frozen) food. Also getting prone does not cause ANS aberations.

The Bordeaux group would consider my case persistent as I had a 75 day episode in 2004.

Assuming flec half lives from 12 to 24 hours (the stated half life is 12-27 hours), I did rough calculations on the effective dosage and it worked out to between 1.33 and 2 times the daily dose. At 300 mg/day, this would mean the flec in my system was like a 400 to 600 mg dose. Now, at 50mg/day it is like a 65 to 100 mg dose. A 6 times reduction, no matter how you look at it. That it is effective is absolutely amazing to me - I'm happy and puzzled.

George