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non-localized sustaining mechanisms

Cellular Remodeling and Mapping – 2014 Boston AF Symposium

Sanjiv Narayan

Sanjiv Narayan MD

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’.

Editor’s Comments:
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.

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Last updated: Wednesday, September 2, 2015 

 

References    (↵ returns to text)

  1. 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.)

  2. 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.

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