2014 Boston AF Symposium
Fibrotic Atrial Cardiomyopathy (FACM)
By Steve S. Ryan, PhD
Dr. Hans Kottkamp of the Hirslanden Hospital in Zurich, Switzerland presented the concept of “Fibrotic Atrial Cardiomyopathy (FACM)” in his talk entitled “Fibrotic Atrial Cardiomyopathy – Implications for Catheter Ablation of AF.”
TYPES OF A-FIB substrates
Dr. Kottkamp discussed two types of substrates (or genotypes) of how A-Fib develops:
- “Focal” A-Fib with the trigger as the only driver and with no (or very limited) structural atrial remodeling over time (even decades or “forever”).
- A-Fib due to a severe underlying structural heart disease, e.g., mitral stenosis which causes significant structural remodeling.
Then he proposed a third type:
- A-Fib as a manifestation of a pre-existing “Fibrotic Atrial Cardiomyopathy (FACM)” which can be mild (I), moderate (II), or severe (III). FAMC involves structural remodeling in a potentially progressive disease process. FAMC may explain what was characterized as “Lone” A-Fib with no previously identifiable cause in an otherwise healthy patient.
(Cardiomyopathy is a heart condition or disease in which the heart muscle is weakened and the heart’s ability to pump blood is impaired. For example, fibrous tissue may partially replace the heart muscle, disabling the heart so that it no longer functions properly and blood no longer moves efficiently. Cardiomyopathy is often accompanied by atrial fibrillation. Dr. Kottkamp’s concept of “atrial cardiomyopathy” isn’t the same thing as normal cardiomyopathy in which the ventricles are impaired.)
PREVIOUS STUDIES OF FIBROSIS
At last year’s Boston A-Fib Symposium (see BAFS 2013: A-Fib Produces Fibrosis—Experimental and Real-World Data), Dr. Kottkamp cited several studies which indicated that A-Fib doesn’t seem to always produce fibrosis, where there is a great variability in the degree of fibrosis.1 This is in contrast with Dr. Jose Jalife’s experimental studies of sheep where A-Fib clearly produces fibrosis (see BAFS 2013: A-Fib Produces Fibrosis—Experimental and Real-World Data). In the real, messy world it isn’t always as easy and clear how to isolate the mechanisms that produce or limit fibrosis. As Dr. Kottkamp points out, sheep are not humans. Fibrosis may work differently in humans compared to animal models like sheep. (Of course it would be unethical to experimentally produce A-Fib and fibrosis in humans as one can in animal models.)
Dr. Kottkamp cited his and other researchers’ histological data and showed slides of heart cell tissue which showed in his analysis that:
- The hypothesis that fibrosis progresses systematically from paroxysmal to persistent A-Fib was not confirmed.
- While there was a tendency of increased mean fibrosis level in patients with persistent vs paroxysmal A-Fib, the variation within the two groups was very high.
- No correlation at all could be detected between patient age and increase in the extent of fibrosis or fatty changes in atrial tissue.2
- Atrial samples taken from age-matched A-Fib-free patients contained negligibly low amounts of fibrofatty tissue despite similar clinical high-risk profiles.3
Similar to Dr. Nassir Marrouche’s Utah Stages I-IV, Dr. Kottkamp showed slides of paroxysmal patients with No Fibrosis (no FACM), Mild Fibrosis (FACM I), Moderate Fibrosis (FACM II), Severe Fibrosis (FACM III).
WHAT DR. KOTTKAMP’S RESEARCH MEANS FOR A-FIB PATIENTS
According to Dr. Kottkamp, what FACM means for patients:
- In patients with “Focal” paroxysmal A-Fib (no or almost no fibrosis [No FACM], PV isolation can (almost) be considered curative. Though there are relatively rare cases of extra-PV foci in these cases.
- In patients with FACM I AND II (similar to Utah Stages II and III) the ablation cannot really “cure” the underlying disease FACM. However, in many of these cases, ablation can effectively treat the arrhythmia A-Fib which in many patients is the only clinical manifestation of the FACM disease.
- While patients in FACM III (similar to Utah Stage IV) are very hard or impossible to cure with today’s standard catheter mapping and ablation techniques.
Dr. Kottkamp’s conclusions:
- Circumferential PV isolation is a cornerstone treatment for most patients with paroxysmal A-Fib.
- The concept of FACM as a primary atrial disease explains recurrences of paroxysmal or even persistent A-Fib after a period of stable Sinus Rhythm after a previous PV isolation by the potentially progressive nature of the FACM disease (which is independent of the arrhythmia).
- In patients with A-Fib recurrence after durable PV isolation, the ablation strategy can be targeted to the individual substrate localization.
- In patients with more advanced substrates (FACM II-III), additional substrate modification may be reasonable in patients with persistent A-Fib already in the first ablation session.
Dr. Kottkamp’s concept of Fibrotic Atrial Cardiomyopathy may become important in our understanding of A-Fib, though it needs further studies to determine how it develops and progresses, how it differs from fibrosis measurements like Utah Stages I-IV, how best to quantify and measure it, etc.
Dr. Kottkamp’s concept that Lone A-Fib may come from Cardiomyopathy, that “Lone” A-Fib isn’t really lone or idiopathic but may come from a form of Atrial Cardiomyopathy may be an important thesis for future research. It may explain why some paroxysmal A-Fib patients have extensive fibrosis, while others don’t. (Though there are other factors which may produce fibrosis as well as Cardiomyopathy.)
Dr. Platonov’s finding that age doesn’t relate to fibrosis is certainly good news for patients. It indicates that just because we are getting older, our hearts aren’t automatically developing fibrosis. (Though we do know that A-Fib is associated with aging of the heart. As patients get older, the prevalence of A-Fib increases, roughly doubling with each decade.4 This suggests that A-Fib may be related to degenerative, age-related changes in the heart.)
Contrary to Dr. Jalife’s experimental studies with sheep which showed that A-Fib produces fibrosis, Dr. Kottkamp’s studies indicate that in the real world fibrosis doesn’t progress systematically from paroxysmal to persistent A-Fib. But his studies did show that there was more fibrosis in persistent vs. paroxysmal A-Fib patients. And that people without A-Fib compared to age-matched patients with A-Fib, had “negligibly low amounts of fibrofatty tissue (fibrosis) despite similar clinical high-risk profiles.”
Even though animal models like sheep aren’t perfect, studies like Dr. Jalife’s are scientifically sound and very convincing. Sheep hearts seem very similar to human hearts for all practical purposes. As patients with A-Fib, we have to base our medical decisions on the conclusion that A-Fib produces fibrosis (Dr. Kottkamp disagrees with this conclusion); that if we stay in A-Fib over a significant period of time, we will progressively develop fibrosis which is currently irreversible. However, as Dr. Kottkamp points out, it isn’t inevitable that everyone will develop fibrosis to an equal extent. This is consistent with Dr. Jalife’s studies in which even sheep with the same environment, diet, similar gene pool, etc. did differ in how fast they developed fibrosis.
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Last updated: Wednesday, September 2, 2015
- Mahnkopk, C. et al Evolution of the left atrial substrate in patients with lone atrial fibrillation using delayed-enhanced MRI: implications for disease progression and response to catheter ablation. Heart Rhythm. 2010 Oct. 7(10):1475-81 http://www.ncbi.nlm.nih.gov/pubmed/20601148 doi: 10.1016/j.hrthm.2010.06.030. Epub 2010 Jul 1.↵
- Platonov, PG et al. Structural Abnormalities in Atrial Walls Are Associated With Presence and Persistency of Atrial Fibrillation But Not With Age. J Am Coll Cardiol 2011;58(21):2225-2232. Last accessed 4/1/14 http://content.onlinejacc.org/article.aspx?articleid=1147757. doi:10.1016/j.jacc.2011.05.061↵
- Calkins, H, Berger, R. Atrial Fibrillation: Management Strategies. Scientific American Special Health Reports. Last accessed August 24, 2015. URL: http://tinyurl.com/Calkins-A-Fib-Mgmt-strategies, p. 9.↵
High Fibrosis at Greater Risk of Stroke and Precludes Catheter Ablation: Lessons Learned from the DECAAF Trial
By Steve S. Ryan, PhD
Presenter: Dr. Nassir Marrouche of the Comprehensive Arrhythmia Research and Management Center (CARMA) at the University of Utah Health Sciences gave a presentation entitled “The Ablation Lesion or the Atrial Disease? Lessons Learn from DECAAF.”
Background: In his BAFS 2011 presentation, (see BAFS 2011: MRI [Magnetic Resonant Imaging) Applied to A-Fib), Dr. Marrouche described the data enhancement (also called “delayed-enhancement”) MRI process which uses a metallic Gadolinium contrast dye to see in 3D and identify collagen fibrotic areas in the heart. Dr. Marrouche uses MRI to separate A-Fib patients by their degree of fibrosis into four “stages:” In addition to other factors, the amount of fibrosis in the left atrium is key to ablation treatment success.
• “Utah Stage 1” low scarring or fibrosis
• “Utah Stage 2” 5%-20% fibrosis
• “Utah Stage 3 20%-35% fibrosis
• “Utah Stage 4: greater than 35% fibrosis
Detecting Fibrosis with the DE-MRI
To begin, Dr. Marrouche showed slides of how the delayed-enhancement MRI (DE-MRI) is used to detect fibrosis.1 Using “Masson trichome” staining, he showed slides of how normal myocytes (heart muscle) appear normal and red, while areas of collagen (fibrosis) appear blue and almost blot out the red myocytes in someone with extensive A-Fib.
DECAFF Study Findings
The Delayed Enhancement-MRI Determinant of Successful Catheter Ablation of Atrial Fibrillation trial (DECAAF) was conducted at 15 different centers worldwide between 2010 and 2011. The degree of fibrosis in patients with atrial fibrillation was followed before and after their catheter ablation.2
The DECAFF study showed that patients with more fibrosis (Utah Stage III and IV) had less successful ablation outcomes. They also had a greater risk of stroke. MRI was also used to detect ablation scarring and gaps in ablation lesions. (The various centers used different types of catheter ablation such as PVI with RF or with Cryo.) In a somewhat controversial statement, Dr. Marrouche had previously stated, “encircling the (pulmonary) veins with lesions as seen on the MRI was not important in terms of treatment success.”3
These findings support Dr. Marrouche’s previous presentation at the Boston A-Fib Symposium (see BAFS 2011: MRI [Magnetic Resonant Imaging] Applied to A-Fib).
The only predictor of atrial fibrosis was hypertension (p=0.004).
The predictors of recurrence after ablation were:
- Left atrial fibrosis (p<0.0001) Each 1% increase in fibrosis was associated with a 6% increased risk of recurrence.
- Mitral valve disease (p<0.0001)
- Left Ventricular Ejection Fraction (p<0.05)
Dr. Marrouche discussed what he called residual fibrosis “fibrotic tissue not covered with ablation lesions.” Residual fibrosis is measured by subtracting ablated scar area from pre-ablation DE-MRI. The more residual fibrosis, the more there is an increased risk of recurrence.
DECAFF Conclusions: Utah Stage III & IV Fibrosis Levels Not Recommended For Catheter Ablation
Dr. Marrouche concluded from the DECAFF study that “Atrial fibrosis detected using DE-MRI is a strong and independent predictor of procedural outcome in patients undergoing ablation of atrial fibrillation.” For all patients in Utah Stage IV and for many in Utah Stage III, they are not recommended for catheter ablation but should be put on life-long medication instead. Because of the extent of their fibrosis, they have less successful ablation outcomes.
Patients with High Levels of Fibrosis More at Risk of Stroke
One of the most important findings for patients from Dr. Marrouche’s studies is that patients with high levels of fibrosis are more at risk of stroke. Utah Stage IV patients were four times more likely to have a stroke than patients with a low level of atrial fibrosis. In his previous work, Dr. Marrouche found that even patients in simple early-onset paroxysmal A-Fib can have high levels of fibrosis. (Many other factors besides A-Fib can produce fibrosis in the heart.) Anyone in A-Fib should probably have an MRI to measure their level of fibrosis. Instead of the less empirical CHADS2 score, an MRI would quantify whether or not a person needs to be on anticoagulants. MRIs to measure fibrosis should become a routine diagnostic tool.
Hypertension Produces Fibrosis
In Dr. Marrouche’s studies, hypertension was the only guaranteed predictor of developing fibrosis. We already knew that hypertension was a cause or trigger of A-Fib. Thanks to Dr. Marrouche, we also now know that hypertension causes or triggers fibrosis. If you have real hypertension, do what you can to lower it (diet, exercise, medications, etc.) Though sometimes this is very hard to do.
More research needs to be done on the link(s) between hypertension, fibrosis and A-Fib. If we induce hypertension, for example in animal studies, does it produce both fibrosis and A-Fib at the same time? Or does the A-Fib develop first, then produce fibrosis?
High Fibrosis Precludes Catheter Ablation
Sad news for patients? According to Dr. Marrouche’s studies, high levels of fibrosis preclude having a catheter ablation, that catheter ablation has a poor success rate in cases of high fibrosis (Utah Stages III and IV). Dr. Marrouche recommends that these high fibrosis patients reconcile themselves to living the rest of their lives on meds, that they can’t be cured of their A-Fib by catheter ablation. (It must be devastating for a patient to hear this.)
But many centers and doctors specialize in ablating patients with persistent and long-standing persistent A-Fib. For example, in a live case ablation at the 2014 Boston A-Fib Symposium at Orlando, Dr. Mélèze Hocini from the Bordeaux Group using ECGI successfully ablated a patient with persistent A-Fib and a fibrosis score of 22% (Utah Stage III) who also had a huge dilated left atrium. Fibrotic heart tissue doesn’t preclude or prevent making catheter burns in the heart. Rather, high levels of fibrosis are usually associated with more difficult-to-ablate cases where there are more A-Fib signals sources than just in the pulmonary veins. But some doctors and centers do these kinds of ablations all the time with high success rates.
If someone tells you that you have too much fibrosis to have a successful catheter ablation, get a second opinion. But you probably shouldn’t go to your local EP. Instead you need to go to more experienced doctors and centers like the Bordeaux group who specialize in tracking down, mapping and isolating A-Fib signal sources coming from other spots in the heart than the pulmonary veins. (See my list of EPs specializing in Persistent and Long-standing Persistent A-Fib.)
“encircling the (pulmonary) veins with lesions as seen on the MRI was not important in terms of treatment success.”
Practically all the centers in the study started by isolating the PVs. But success (freedom from recurrence) in the DECAAF study was dependent on the previous amount of fibrosis. However, the PVs usually do need to be isolated for treatment success.
“Residual Fibrosis”, from the perspective of A-Fib patients, isn’t all that different from ablation burns. Catheter ablation doesn’t change fibrotic heart tissue to normal tissue. In both cases the heart tissue is scarred, dead, immobile, with little or no blood flow and transport function. That’s why most EPs try to keep catheter ablation burns to a minimum.
Stuart, C. MRI may help identify best candidates for ablation. Cardiovascular Business. Feb 05, 2014. Last accessed March 16, 2014, URL: http://tinyurl.com/DECAAFTrial
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Last updated: Thursday, January 26, 2017
- VIDEO: 3D Model of Left Atrium Demonstrating Left Atrial Fibrosis in a Patient with Atrial Fibrillation. Last accessed March 16, 2014. URL: http://tinyurl.com/DECAAF3DModel↵
- Marrouche NF, et al. Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study. JAMA. 2014 Feb 5;311(5):498-506. doi: 10.1001/jama.2014.3. PubMed PMID: 24496537.↵
- O’Riordan, Michael. DECAFF Published: MRI Aids in AF Ablation Success. Heartwire, February 5, 2014. http:”//www.medscape.com/viewarticle/820230↵