The Longer You Have A-Fib, the Greater the Risk
A-Fib begets A-Fib. The longer you have A-Fib, the greater the risk of your A-Fib episodes becoming more frequent and longer, often leading to continuous (Chronic) A-Fib. (However, some people never progress to more serious A-Fib stages.)
Fibrosis makes the heart stiff, less flexible and weak, reduces pumping efficiency and leads to other heart problems. The abnormal rhythm in your atria causes electrical changes and enlarges your atria (called remodeling) making it work harder and harder over time.
Don’t let your doctor leave you in A-Fib. Educate yourself. Any treatment plan for A-Fib must try to prevent or stop remodeling and fibrosis. And always aim for a Cure!
To learn more, read my editorial, Leaving the Patient in A-Fib—No! No! No!
Educate Yourself—and Always Aim for a Cure!
“I’m getting by with my Atrial Fibrillation. With the recent improvements in Pulmonary Vein ablation techniques, should I wait until a better technique is developed?”
A-Fib is a progressive disease. The longer you have it, in general the worse it gets. In a process called “remodeling” your heart may change physically and electrically if you have A-Fib long enough. The longer you have A-Fib, the harder it is to cure.
For instance, a patient can be diagnosed with paroxysmal A-Fib initially and then transition to persistent, and eventually to long-standing persistent A-Fib. This progressive nature of atrial fibrillation is why doctors say, “A-Fib begets A-Fib”.
So, it’s important to be cured as soon as reasonably possible. See our Overview of A-Fib.
With today’s current Pulmonary Vein Ablation (Isolation) procedures using Pulmonary Vein Potentials, you have an 70%-85% chance of becoming A-Fib-free (in cases of Paroxysmal A-Fib). (The other 15% though not cured are often significantly improved; meds that didn’t work before may now work.) With a second ablation the success rate is 90% or greater.
So don’t wait. Your odds aren’t going to get much better than that.
¤ Haïssaguerre M. “Electrophysiological End Point for Catheter Ablation of Atrial Fibrillation Initiated From Multiple Pulmonary Venous Foci,” Circulation. 2000;101:p. 1409.
¤ Jaïs, P. NASPE Convention presentation, San Diego, CA, May 8, 2002.
Return to FAQ Catheter Ablations
2014 Boston AF Symposium
Cellular Remodeling and Mapping of A-Fib
Report by Dr. Steve S. Ryan, PhD
Dr. Sanjiv Narayan of the University of California, San Diego gave a presentation entitled “Cellular Remodeling and Spatial Mapping of Human AF.” Dr. Narayan is known for inventing the FIRM mapping/ablation system (Topera). (For a discussion of the FIRM system, see BAFS 2013: FIRM [Focal Impulse and Rotor Modulation] for Catheter Ablation of A-Fib by Dr. Narayan of UC San Diego).
Background: Understanding the Firm System. Because the FIRM system uses a proprietary, patented algorithm to identify A-Fib producing spots in the heart, it’s hard to understand and evaluate it. (In a private conversation with someone from Topera, this algorithm is a closely guarded secret like the secret recipe for Coca Cola.) If you’re the type of person who likes to look under the hood of your car and understand the mechanics of how it operates, the FIRM system may be very frustrating. (Continued below)1
SUSTAINING MECHANISMS, SUBSTRATES, CFAES
Dr. Narayan began his presentation by discussing Sustaining Mechanisms (Substrate, CFAEs). (CFAEs are Complex Fractionated Atrial Electrograms [an electrogram is a picture of the electrical activity of the heart as sensed by a pacemaker or catheter in the heart]. They are low voltage electrical signals with very short cycle lengths used to identify areas in the heart that need to be ablated.) (For an in-depth discussion of CAFEs, see BAFS 2011: Using CAFEs in Ablating Persistent A-Fib )
Dr. Narayan identified four different types of non-localized sustaining mechanisms―Collision, Block, Pivot Point and Slow Conduction (see graphic online). But these CFAEs have no discrete target. “Localized ablation can’t work.”
Whereas what Dr. Narayan described as Spatially Localized (”Drivers”) are identifiable A-Fib targets. When one ablates these “(true) sources,” A-Fib is eliminated.
But A-Fib remodeling often leads to ‘substrates’ (CFAEs) that are spatially localized.
ROLE OF PACS
Dr. Narayan discussed the role of PACs (Premature Atrial Contractions) in A-Fib remodeling (‘Substrate’, CFAEs). In describing the findings from his own studies of fibrosis and Stiles’ “Reduced Voltage areas”2, PACs trigger A-Fib. But they don’t in patients without A-Fib.
Advanced or cellular remodeling may be due to APD (Action Potential Duration) Oscillations at slow rates in a rotor pattern, and they enable PACs to trigger A-Fib. In mapping these signals, A-Fib is sustained by spatially reproducible rotors.
DR. NARAYAN’S CONCLUSIONS
• Remodeling is the “rosetta stone” linking basic science with clinical observations of A-Fib.
• Remodeling is spatially non-uniform and regional, that explains clinical observations, A-Fib ‘substrates’.
We still don’t understand how the FIRM system algorithms actually work. We can only speculate that the FIRM mapping system identifies Sustaining Mechanisms (Substrate, CFAEs) that produce rotors and filters out others that don’t. However, unless someone “leaks” the algorithms, we’ll probably never know and be able to compare and evaluate the FIRM system.
Dr. Narayan’s findings about PACs (Premature Atrial Contractions) is most important for A-Fib patients. Doctors tend to dismiss PACs because everyone gets them. But as many people with A-Fib know all too well, PACs often precede an A-Fib attack. Dr. Narayan’s studies show that PACs trigger A-Fib attacks, but they don’t in people without A-Fib. And PACs can be very disturbing, even if they don’t trigger A-Fib, particularly in people who’ve had a successful catheter ablation and are A-Fib free.
Can ablation techniques or meds be developed to eliminate PACs and thereby eliminate going into A-Fib? Should EPs ablate for PACs even without A-Fib? (I know of one EP who does ablate for PACs, even in the absence of A-Fib/Flutter.)
Many EPs map and ablate CAFEs (Sustained Mechanisms, Substrates) when trying to “cure” patients in Persistent A-Fib. But according to Dr. Narayan, ablating these areas is ineffective “Localized ablation can’t work,” because there is no discrete target as there is for areas producing rotors. (The ECGI system also seems to identify foci and rotors as compared to CFAEs.) For patients, Dr. Narayan’s observations may result in much less unnecessary burning and scarring of the heart during an ablation procedure.
Return to Index of Articles: AF Symposium: Steve’s Summary Reports
Last updated: Wednesday, September 2, 2015
- But here’s a possible way the FIRM system could possibly be evaluated. Take a standard Lasso mapping catheter or a system like ECGI and meticulously identify every possible A-Fib producing spot in, for example, an animal or human heart in long-term persistent A-Fib. Such a heart usually has many different A-Fib producing spots. Carefully mark the exact location of every foci, rotor, potential, CFAE or any spot producing possible A-Fib signals. Then immediately afterwards, use the FIRM mapping system on the same heart and compare the results. The FIRM system usually finds only one or two A-Fib signal sources in each atria. The FIRM algorithm probably filters out a lot of other A-Fib signal sources as noise. What does the FIRM system filter out? What does it select?
In the live satellite case presented at the 2014 Boston A-Fib Symposium in Orlando, the Bordeaux group using the ECGI system found many different foci and rotors in a patient in persistent A-Fib. But these were clustered in predominantly three areas. Would they show up in the FIRM system as only three foci/rotors?
Patent Law: The algorithms to analyze MRI slices, such as used by Dr. Marrouche, or the algorithms to map electrophysiology, such as used by Topera, have to be kept secret. Dr. Marrouche and Topera really have no choice. According to current US patent law (which I highly disagree with), you can’t enforce a patent on a medical technique. But you can for a surgical technique. For you legal types, the statute reads “35 USC 287(c) (1) With respect to a medical practitioner’s performance of a medical activity that constitutes an infringement under section 271(a) or (b) of this title, the provisions of sections 281 , 283 , 284 , and 285 of this title shall not apply against the medical practitioner or against a related health care entity with respect to such medical activity.” This law effectively makes any patent on a medical technique worthless. (Thanks to David Pressman, Patent Attorney for this important observation.)↵
- Stiles MK, John B, Wong CX, et al. Paroxysmal Lone Atrial Fibrillation Is Associated With an Abnormal Atrial Substrate: Characterizing the “Second Factor”. J Am Coll Cardiol. 2009;53(14):1182-1191. doi:10.1016/j.jacc.2008.11.054.↵
Atrial Remodeling and the Transition From Paroxysmal to Persistent AF by Dr Jose Jalife-2014 Boston AF Symposium
2014 Boston AF Symposium
Experiments in Atrial Remodeling in Sheep and the Transition From Paroxysmal to Persistent A-Fib
By Steve S. Ryan, PhD
Dr. Jose Jalife of the Center for Arrhythmia Research of the University of Michigan described his experiments inducing A-Fib in sheep by pacing their hearts. He is trying to discover the mechanisms underlying the transition from paroxysmal to persistent A-Fib.
Background: Some patients remain paroxysmal (usually with anti-arrhythmic therapy), while a large proportion progress to persistent A-Fib. (In a study of 5,000+ A-Fib patients, 54% of those on rate control meds went into permanent A-Fib in one year.)1
Previous presentation summary: This talk was a continuation of Dr. Jalife’s 2013 Boston A-Fib Symposium presentation on his experimental studies with sheep. (See A-Fib Produces Fibrosis—Experimental and Real-World Data.) He implanted pacemakers in the hearts of sheep; then induced A-Fib by pacing for 6-30 seconds, then stopped, then paced again, etc. He continued this sequence until the sheep were in persistent A-Fib. He left them in A-Fib for about a year. Dr. Jalife also had a control group of sheep who were monitored but not paced into A-Fib.
Pacing Sheep into A-Fib
Once pacing started in the sheep, it took around 5.5 days to produce the first A-Fib episode. It took around 7-9 weeks of pacing for the sheep to move from Paroxysmal to Persistent A-Fib. At that point the sheep stayed in Persistent A-Fib without any further need of pacing. Dr. Jalife’s sheep developed two major types of atrial remodeling:
- Structural Remodeling (Fibrosis)
- Electrical Remodeling (ion channel expression changes)
(In humans, remodeling usually also results in atrial dilation. Dr. Jalife’s sheep once in A-Fib also developed significant Atrial Dilation compared to a control group of sheep.)
Unlike humans, the sheep didn’t develop heart failure, left ventricle dilation and dysfunction, or tachycardia-induced cardiomyopathy despite being in A-Fib for more than a year. This is possibly because sheep have a very good AV Node (unlike most humans) which filters the A-Fib pulses from affecting the ventricles and keeps the ventricular rate low.
Genetic Differences in Sheep
But there were differences in the sheep. Some sheep transitioned into persistent A-Fib fast (<40 days) while others needed more pacing to transition into persistent A-Fib (>40 days). Sheep from the same herd would have the same diet, environment, etc. But genetically they must have been different in their ability to hold out from transitioning into persistent A-Fib.)
All ventricular parameters remained normal in the paced sheep, except for atrial dilation and the markers of fibrosis which increased progressively as the sheep went from paroxysmal to persistent A-Fib. Fibrosis appeared in the right atrium, left atrium and the posterior left atrium. This fibrosis was the result of collagen deposition in the atria which is a permanent remodeling effect of A-Fib.
Dr. Jalife showed slides of a normal pig’s heart compared to a pig in persistent A-Fib. Well over ½ the atria seemed fibrotic.
Mechanisms of Electrical Remodeling
As expected, sustained A-Fib shortened the atrial action potential duration and refractory period. Also, rotor frequencies were increased. For example, in one sheep the dominant frequency of the first episode of paroxysmal A-Fib was 7.3 Hz, but increased progressively to 10.3 Hz during the transition to persistent AF. When AF in that sheep became persistent, the dominant frequent had stabilized at 11.3 Hz and remained constant for up to a year.
In perhaps the most important findings of Dr. Jalife’s experiments, the rate of increase in dominant frequency correlated strongly with the time at which AF stabilized. In other words, although the progression from paroxysmal to persistent A-Fib varied from one animal to another, the rate of dominant frequency increase could be used to forecast the time at which AF became persistent.
In other words, although the progression from paroxysmal to persistent A-Fib varied from one animal to another, the rate of dominant frequency increase could be used to forecast the time at which AF became persistent.
Dr. Jalife and his team also identified the mechanisms of electrical remodeling in sheep, which ion channels in the heart are responsible for transitioning sheep from paroxysmal to persistent A-Fib. Sodium and calcium heart electrical currents were lowered, while potassium and IK1 currents were increased. These electrical changes were associated with gene expression changes “in the alpha subunits of the L-type calcium (CACNA1C) and sodium (SCNSA) channel protein.”
- “Sustained AF reduces L-type calcium (Caᵥ1.2) and sodium (Naᵥ1.5) protein expression”
- “Sustained AF reduces the rapid sodium inward (INa) and L-type calcium (ICaL) currents”
- “Sustained AF reduces the transient outward current (Ito)”
- “Sustained AF increases the inward rectifying potassium current (IK1) and protein expression of the Kir2.3 channel”
The sheep model explains the structural and electrical remodeling that occurs in humans.
As in humans, there is a variable progression in time from paroxysmal to persistent A-Fib.
The rate of dominant frequency increase during such a progression predicts the time at which AF stabilizes and becomes persistent, reflecting changes in Action Potential Duration and densities of ICaL, IK1, INa and Ito.
Predicting the transition from paroxysmal to persistent A-Fib is feasible, at least in some patients, by measuring the increase in dominant frequency over time.
No one seeing Dr. Jalife’s presentation could doubt that A-Fib produces fibrosis. (Though even among sheep in the same environment, diet, etc. and with a similar gene pool, there were differences in how fast the individual sheep progressed to persistent A-Fib.) As patients with A-Fib, we have to base our medical decisions on the conclusion that A-Fib produces fibrosis; that if we stay in A-Fib over a significant period of time, we will progressively develop fibrosis which is currently irreversible and can lead to a host of other heart problems.
A common strategy today…is to leave you in A-Fib but control your heart rate by the use of beta-blockers, etc. But leaving you in A-Fib produces fibrosis which is irreversible and very damaging to the heart.
A common strategy today for treating A-Fib is to leave you in A-Fib but control your heart rate by the use of beta-blockers, calcium-channel blockers, etc. But leaving you in A-Fib produces fibrosis which is irreversible and very damaging to the heart. If your doctor wants to leave you in A-Fib, Dr. Jalife’s experiments would recommend that you get a second opinion, and ASAP.
One of the major advantages of a successful catheter ablation (and surgery) is it probably reverses the electrical remodeling effect of A-Fib. This makes intuitive sense. A heart beating in normal sinus rhythm (NSR) doesn’t usually produce those weird ion channel currents. But more research needs to be done before we can conclude this. However, a successful catheter ablation does not reverse fibrosis (structural remodeling), though it may reduce atrial dilation.
By identifying the actual mechanisms of electrical remodeling, Dr. Jalife’s ground-breaking experiments may lead to new therapies and drugs to combat not only the transition from paroxysmal to persistent A-Fib, but how to prevent patients from developing A-Fib in the first place. And using dominant frequency to predict when a patient is transitioning to persistent A-Fib, can be an invaluable tool for doctors (and reassuring for patients).
One of the scariest parts of Dr. Jalife’s presentation was how fast he could pace those sheep into persistent A-Fib. Obviously sheep aren’t people. But we know that for most people, there is a relatively short window of time when they progress from paroxysmal to persistent A-Fib (about a year). When you have A-Fib, you can’t count on genetics, diet, life style, environment, etc. to protect you from progressing to persistent A-Fib. Right now we just don’t know why some people stay paroxysmal for years, while most become persistent after a relatively short time. Worst case scenario, you have about a year. Act accordingly.
- Peykar, S. Atrial Fibrillation. Cardiac Arrhythmia Institute/Sarasota Memorial Hospital website. Last accessed Jan 5 2013. URL:http://caifl.com/arrhythmia-information/atrial-fibrillation/↵