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Fibrosis

Don’t Delay—A-Fib is a Progressive Disease

Quote - Joan Schneider, Ann Arbor, MI, A-Fib free after PV Catheter Abaltion - A-Fib.com

Joan Schneider, Ann Arbor, MI, A-Fib free after PV Catheter Abaltion

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.)

Unless too feeble, there’s no good reason to just leave someone in A-Fib.
Don’t listen to doctors who want to just control your symptoms with drugs. Leaving patients in A-Fib overworks the heart, leads to fibrosis and increases the risk of stroke.

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!

 

2016 AF: Thickening of Left Atrium and Fibrosis Amount Predicts Outcome of A-Fib Ablation

AF Symposium 2016

Thickening of Left Atrium and Amount of Fibrosis Predicts Outcome of A-Fib Ablation

by Steve S. Ryan, PhD

Dr. Nassir F. Marrouche

Dr. Nassir F. Marrouche

Dr. Nassir F. Marrouche, University of Utah (CARMA), is known for ground-breaking, thought-provoking research using MRI. His presentation was entitled “Atrial and Ventricular Myopathy: A Novel risk predictor for stroke and cardiovascular events.”

Amount of Fibrosis Better Predictor of Stroke Risk (and Heart Attack)

Dr. Marrouche began by showing how today’s stroke guidelines (CHADS2 or CHA2DS2-VASc) are mediocre predictive tools overall, according to most studies. Whereas atrial fibrosis detected by Delayed Enhancement-MRI (DE-MRI) is a better predictor of stroke risk.

DE-MRI stands for Delayed Enhancement Magnetic Resonant Imaging.

In Dr. Marrouche’s study, patients with more than 21% fibrosis had a 19.6% risk of stroke while those with under 8.5% fibrosis had only a 1% risk. The more fibrosis, the greater risk of clots forming in the Left Atrial Appendage (LAA).

In a study by King, higher levels of fibrosis were associated with ‘Major Adverse Cardiac Events’ (MACE), not only stroke but heart attack and deep vein thrombosis (a blood clot within a vein).

Cardiomyopathy and Fibrosis

Dr. Marrouche showed slides of normal atrial myocytes (muscle cells) vs. examples with extensive fibrosis where collagen replaced most of the red myocytes (which store oxygen until needed for muscular activity).

This is an important finding which may change the way we look at fibrosis.

This fibrosis correlated with abnormality of the atria (atrial myopathy) and deterioration of the ability of heart muscles to contract (cardiomyopathy). This is an important finding which may change the way we look at fibrosis.

(For further information on Dr. Marrouche’s work, see Higher Fibrosis at Greater Risk of Stroke and Precludes Catheter Ablation.)

Fibrosis/Myopathy Correlates with Atrial Strain

Dr. Marrouche showed slides of how the left atrium of an A-Fib patient with extensive fibrosis worked much harder to pump and had nearly three times more strain than a patient with mild fibrosis. (This may be why the left atrium often stretches and expands in remodeling.)

A-Fib Thickens Left Atrial Shape

In another ground-breaking observation, Dr. Marrouche showed slides of how the shape of the left atrium (LA) gets thicker as one progresses from no-A-Fib to paroxysmal to persistent A-Fib. In fact, in a study by Bieging, LA shape (thickness) is a strong independent predictor of outcome after AF ablation.

Left Atrial Appendage and Stroke Risk

Dr. Marrouche found that the Left Atrial Appendage (LAA) length, thickness and orientation correlate with stroke risk. These findings open up new avenues of research in A-Fib. Just looking at the LAA might produce an indication of stroke risk, which can be combined with other predictive measures.

Left Ventricular Disease Predicts Recurrence after Ablation Therapy

Some A-Fib patients also have a diseased Left Ventricle (LV) which shows up using ‘Late Gadolinium Enhancement- MRI’ (LGE-MRI). In a study by Suksaranjit, the recurrence rate after an ablation was 69% in patients with Left Ventricular LGE-MRI revealed disease, compared to 38% in patients without LV LGE-MRI. These patients also have more major adverse cardiac and cerebrovascular events.

Conclusion

Dr. Marrouche is now using both the amount of fibrosis and left atrial shape to stage and treat A-Fib patients. The main points we can learn from Dr. Marrouche’s research are:

Fibrosis makes the heart stiff, less flexible and weak, overworks the heart, reduces pumping efficiency and leads to other heart problems.

• Fibrosis puts you are greater risk of a stroke and other vascular problems.
• More fibrosis leads to thickened heart tissue, strains the heart and reduces the ability of the heart muscles to contract.
• A-Fib changes the thickness/shape of the left atrium.
• A-Fib can also change the length, thickness and orientation of the Left Atrial Appendage (LAA).
• Left Ventricular disease may accompany or be caused by A-Fib, be measured by MRI, and predict recurrence after catheter ablation..

What Patients Need To Know

Don’t delay! Your A-Fib leads to fibrosis! A-Fib produces fibrosis which is considered permanent and irreversible. Any treatment plan for A-Fib must try to prevent or stop remodeling and fibrosis.

Caveat: After reading Dr. Marrouche’s research and new insights that atrial fibrosis detected by DE-MRI is a better predictor of stroke risk (than CHADS2 or CHA2DS2-VASc), don’t rush into your EPs office asking about using MRI to diagnose your amount of fibrosis. Not every MRI technician and doctor has the special training and experience necessary to perform Dr. Marrouche’s testing. (And insurance companies may not want to pay for this testing. However, that may soon change.)

References for this article

Return to 2016 AF Symposium Reports by Steve Ryan, PhD

If you find any errors on this page, email us. Y Last updated: Monday, February 22, 2016

My 2015 Top Five List: Advancements in the Treatment of A-Fib

Looking back over 2015, I found five significant developments for those ‘living’ with A-Fib and those seeking their ‘cure’. My ‘Top Five List’ focuses on the Watchman device, a Pradaxa antidote and research findings about lifestyle choices, and reducing fibrosis.

1. FDA Approves the Watchman Device

The Watchman occlusion device

The Watchman is positioned via catheter

Anticoagulant Alternative: Because A-Fib patients are at high risk of stroke and clots, a blood thinner (anticoagulant) like warfarin is often prescribed. If you can’t or don’t want to be on blood thinners, you had few options.

That was until March 2015 when the US Food and Drug Administration (FDA) approved the Watchman device. There’s now an option to blood thinners! The Watchman device (Boston Scientific) is inserted to close off the Left Atrial Appendage (LAA), the origin of 90%-95% of A-Fib clots.

To read my complete Top Five List…go to My 2015 Top Five List: A Review of Advancements in the Treatment of A-Fib->.

My 2015 Top Five List: A Review of Advancements in the Treatment of A-Fib

2015 in Review at A-Fib.comWith the beginning of a new year, we often look back and measure how far we’ve come. In 2015, I found five significant advancements in the treatment of Atrial Fibrillation.

1. FDA Approves the Watchman Device

The Watchman occlusion device

The Watchman is positioned via catheter

Anticoagulant Alternative: Because A-Fib patients are at high risk of stroke and clots, a blood thinner (anticoagulant) like warfarin is often prescribed. If you can’t or don’t want to be on blood thinners, you had few options.

That was until March 2015 when the US Food and Drug Administration (FDA) approved the Watchman device. There’s now an option to blood thinners! The Watchman device (Boston Scientific) is inserted to close off the Left Atrial Appendage (LAA), the origin of 90%-95% of A-Fib clots.

It’s not an absolute guarantee you will never have a stroke―but neither is taking warfarin or the newer anticoagulants. For more, see Watchman Device: An Alternative to Blood Thinners.

2. Research: Watchman Better Than a Lifetime on Warfarin

Warfarin - Coumadin tablets various dosages

Warfarin (Coumadin)

The Watchman device isn’t simply an alternative to taking warfarin, clinical trials show it’s actually better. Patients with the Watchman had fewer hemorrhagic strokes and less bleeding compared to patients on warfarin. (Warfarin and other anticoagulants work by causing bleeding and are inherently dangerous.)

It’s too early to say the same about the newer anticoagulants like Pradaxa, Xarelto, Eliquis and Savaysa/Lixiana with their short history but one would expect the same general principles to apply. For more, see Watchman Better Than Warfarin.

3. Antidote for Pradaxa

Praxbind - antidote to Pradaxa

Praxbind: Pradaxa antidote

Up to now, patients on Pradaxa have been bleeding to death in the emergency room while doctors were powerless to stop their bleeding and could only stand by and watch them die. See Stop Prescribing or Taking Pradaxa.

In October 2015, the FDA granted “accelerated approval” to Praxbind, the reversal agent (antidote) to Pradaxa (Boehringer Ingelheim). Praxbind (idarucizumab) is given intravenously to patients and reverses the anticoagulant effect of Pradaxa within minutes.

Note: The reversal agent, Andexanet Alfa, is on FDA fast track and is expected to be approved by mid-2016 as an antidote for Xarelto and Eliquis (Factor Xa inhibitors).

4. Life Style Changes Can Make Some People A-Fib Free

Weightloss

Weightloss

Weight Loss: A weight loss program and counseling in Australia has worked so well that some patients have become A-Fib free.

In his Adelaide clinic, Dr. Prashanthan Sanders convinces his overweight A-Fib patients to buy into the program, lose weight, and keep it off.  This holistic approach to health has also been successfully applied to other A-Fib contributing factors such as diabetes, sleep apnea, hypertension, binge drinking and smoking. See Weight Loss Key to Reverse Atrial Fibrillation, Improve Ablation Success.

Exercise

Exercise

Exercise: But not everyone can lose weight and keep it off. And other risk factors like hypertension and diabetes are more difficult to permanently change.

The same Australian researchers found that exercise improves A-Fib (even obese A-Fib patients benefit from exercise). Supervised aerobic and strength exercises reduced A-Fib by 84%.

Combine for Best Results: Exercise and weight loss together produced the best results. An astounding 94% of obese patients who both lost weight and exercised regularly were A-Fib free after rhythm control therapy (i.e., antiarrhythmic drugs and/or catheter ablation).

Couch Potato Warning: If you don’t exercise regularly, you’re almost guaranteed to stay in A-Fib. Even with rhythm control (antiarrhythmic drugs and/or ablation), 83% of the low-fitness obese patients had A-Fib.

5. Research Studies: Preventing Fibrosis

Fibrotic cells - 2008 Boston A-Fib Symposium Kottkamp

Fibrotic cells

A-Fib produces fibrosis, and up to now, was considered permanent and irreversible. Fibrosis is fiber-like scar tissue that stiffens and weakens the heart muscle which reduces pumping efficiency and leads to other heart problems.  (See Fibrosis and A-Fib).

Dr. Jose Jalife’s experimental studies with sheep found that a Gal-3 inhibitor (GM-CT-01) actually reduced or prevented fibrosis. Better yet, instead of having to wait years for possible FDA approval, a natural supplement, Pecta-Sol C (Modified Citrus Pectin) works like a Galectin-3 inhibitor.

For A-Fib patients, this may provide the means to avoid fibrosis or repair fibrotic heart tissue. (See Galectin-3 Inhibitor Prevents A-Fib).

A Personal Prediction

WATCHMAN device at A-Fib.com

WATCHMAN device

On a personal note, I’m excited about the great potential of the Watchman device to significantly reduce or eliminate the threat of strokes—especially in the elderly―even if they don’t have A-Fib.

Imagine a world where stroke risk could be eliminated by a simple 20-30 minute procedure. The Watchman device (and other occlusion devices) may change the way elderly medicine is practiced.

If you find any errors on this page, email us. Y Last updated: Thursday, January 21, 2016

Should the Left Atrial Appendage (LAA) be Removed in Patients With A-Fib?

Dr. Dhanunjaya Lakkireddy

Dr. Dhanunjaya Lakkireddy

AF Symposium 2015

Should the Left Atrial Appendage (LAA) be Removed in Patients With A-Fib?

by Steve S. Ryan, PhD

Leading doctors and researchers have pointed out the importance of the Left Atrial Appendage (LAA) particularly when ablating persistent A-Fib. In the Bordeaux group’s Five-Step Ablation Protocol for Chronic A-Fib, after isolating the Pulmonary Veins (PVs), their next step is to look for A-Fib signals coming from the LAA. In 2010, Dr. Andrea Natale and his colleagues showed that in 30% of A-Fib patients, the LAA was the only structure that had A-Fib signals. (Circulation 2010.)

In his presentation, Dr. Dhanunjaya Lakkireddy from the Un. of Kansas Hospital in Kansas City, MO, confirmed these findings. After the PVs, “the LAA is the most common source of (A-Fib) focus triggers and other A-Fib signals.”

In Older Patients the PVs Have No A-Fib Signals

He further stated that in patients over 70 years old, especially women, the LAA plays a more important role so much so that the PVs are often silent.

How Removing the LAA Affects Left Atrium Pumping Volume

Removing or closing off the LAA reduces the pumping volume of the left atrium by 15% to 30%. But after the LAA is removed, the overall left atrium volume improves.

Removing The LAA Reduces Natriuretic Peptides―But The Heart Compensates Over Time

The LAA is responsible for neuroharmonal changes such as natriuretic peptide levels (i.e., regulates the amount of sodium in the urine) which are important for bodily functions such as thirst. When the LAA is removed, natriuretic peptide levels go down. But Dr. Lakkireddy’s research shows that over time these levels normalize. Other heart areas such as the right atrium compensate and produce more natriuretic peptides to make up for what the LAA used to produce.

Removing the LAA Lowers Blood Pressure

Removing or closing off the LAA often improves blood pressure by dropping epinephrine (adrenaline) levels and lowering (“down-regulating”) the

renin-angiotensin system (hormone system that regulates blood pressure and fluid balance).

Removing the LAA Improves Recurrence Rates

Dr. Lakkireddy found that removing or closing off the LAA at the same time as a catheter ablation for A-Fib reduces recurrence rates by 29%.

Editor’s Comments:
Why LAA A-Fib Signal Sources in Older People—Why Do PVs Go Silent?
One of the most important findings of Dr. Lakkireddy’s research is that in older people the LAA is the most important source of A-Fib signals, so much so that the PVs are often silent. This is counter-intuitive and hard to understand. If, as we know from years of previous research, A-Fib usually starts and is most often found in the PVs, why do the PVs go silent and A-Fib activity mostly move to the LAA in older people? What is the physical or chemical mechanism that causes this major change?
Sea-Change in Ablation Strategy
Dr. Lakkireddy’s presentation was the most important and ground-breaking for older A-Fib patients. It should change the way ablations are performed on older people. If you are over 70 years old, in persistent A-Fib and aren’t very active, you must seek out EPs and centers who understand and ablate the LAA. Most EPs don’t even look at the LAA as possible A-Fib signal sources. Don’t rely on your local EP to learn about this research and adopt any requisite new ablation strategies.
In Older A-Fib Patients the LAA Should be Removed
It certainly looks like, in the case of older people with A-Fib, the LAA should be removed by an occlusion device (either the Lariat or by surgery [AtriClip]). In addition to the known benefit of reducing A-Fib stroke risk (90%-95% of A-Fib clots come from thee LAA), the LAA is a major and often the only source of A-Fib signals in older people.
Little Downside to Removing the LAA
And according to Dr. Lakkireddy, there is very little downside to removing the LAA.
Blood pressure goes down, over time natriuretic peptide levels return to their pre-LAA levels as the heart compensates, the lost LA pumping volume does improve, and recurrence rates are reduced when the LAA is removed.
Older people who are less active may not even notice the loss of LAA pumping volume or the reservoir or surge effect of the LAA. (On the other hand, an active athletic senior may be affected by the loss of pumping volume if the LAA is removed.)
LAA Can Be Removed Before or After an Ablation
In the case of a catheter ablation for A-Fib, it may not be necessary to remove the LAA at the time of the ablation. Since it is a safer procedure than even an A-Fib ablation, the LAA could be removed three months before or after a catheter ablation.

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Return to: AF Symposium: Steve’s In-Depth Reports Written for Patients

Last updated: Friday, March 6, 2015

 

Obesity Produces Fibrosis, But Getting Lean Reverses Fibrosis (in Sheep)

AF Symposium 2015

Dr. Prashanthan Sanders 150 pix at 96 res

Dr. Prashanthan Sanders

Obesity Produces Fibrosis, But Getting Lean Reverses Fibrosis (in Sheep)

by Steve S. Ryan, PhD

In a fascinating experimental study with sheep, Dr. Prashanthan Sanders from Royal Adelaide Hospital in Australia, overfed sheep so that they developed sustained obesity for 72 weeks. Their fibrosis increased. Their atria were damaged by fibrotic tissue replacing normal atria muscle. As the sheep moved from being overweight to obese, it was progressively easier to induce A-Fib.

Then Dr. Sanders made the sheep lose weight. With a 30% weight reduction, the fibrosis was no longer present! The sheep were similar to the lean sheep controls.

Dr. Sanders used activation mapping to show that in the obese sheep there was an increased delay in activation suggesting delayed conduction. It took a longer time to activate the atria. But when the obese sheep lost weight, conduction became normal. Also there were improvements in left atrial pressure, inflammatory cell counts and fibrosis, atrial TGf beta 1 and reversal of connexin-43 and ETR-beta (which contribute to fibrosis).

Hypertension and A-Fib in Sheep

Dr. Sanders also stimulated sheep into progressive hypertension for 15 weeks. As with the obese sheep above, these hypertensive sheep developed fibrosis. And activation mapping again showed delayed and abnormal conduction.

Sleep Apnea and A-Fib in Animals

Citing other research, including from Dr. Andrea Natale’s group, repetitively blocking off breathing as in sleep apnea developed increased fibrosis as well as slowed atrial conduction, increased atrial size, and induced more atrial fibrillation.

More Risk Factors Lead to Persistent A-Fib

Dr. Sanders pointed out that A-Fib patients with cardiovascular risk factors like obesity, hypertension, and sleep apnea are more likely to progress to persistent A-Fib than individuals with few or no risk factors.

Fibrosis Produces More Fibrosis

Fibrosis (interstitial fibrosis) is the main factor in changing the atrial substrate. Voltage maps of fibrotic atria show large areas of low voltage, increased areas of scarring, and a more complex electrogram resulting in abnormal conduction. According to Dr. Sanders, fibrosis produces more fibrosis. “There is clear evidence that A-Fib feeds back on itself to remodel this process, and there is even a suggestion that it may induce further atrial fibrosis.”

Editor’s Comments:
(Readers of this report may also want to read Dr. Jose Jalife’s similar experimental sheep studies where, among other findings, he proved that pacing sheep into A-Fib produces fibrosis. See Experiments in Atrial Remodeling in Sheep and the Transition From Paroxysmal to Persistent A-Fib.)
In a previous report Dr. Sanders described the great results he is achieving by having his overweight A-Fib patients lose weight, buy into the program and keep the weight off. Sometimes this life style change alone makes them A-Fib free. But not everyone can lose weight and keep it off. Other risk factors like hypertension and diabetes are more difficult to permanently change. And once A-Fib is well established, life style changes aren’t as effective. Though life style changes certainly do improve overall health and heart health.
Fibrosis is Usually Permanent and Irreversible
Unlike some of Dr. Sanders results with sheep, fibrosis in general is considered permanent and irreversible.
Life Style Changes Usually Not Effective in Lone A-Fib
Approximately half of people with A-Fib have no risk factors or co-morbidities (which used to be called “Lone A-Fib.”) I, for example, developed A-Fib at age 54 when I was in perfect health, running track and 5ks, lifting weights, etc. Life style changes aren’t always effective in cases of Lone A-Fib.
Risk Factors lead to persistent A-Fib
Why do some people with A-Fib stay Paroxysmal for years while others progress rapidly to Persistent A-Fib? Perhaps Dr. Sanders has discovered the reason. Risk factors or co-morbidities like obesity, sleep apnea, hypertension, diabetes, etc. make people more likely to transition from paroxysmal to persistent A-Fib. Patients with A-Fib risk factors should be warned of this danger.
Fibrosis Produces More Fibrosis
Here’s yet another scary thought for anyone with A-Fib. According to Dr. Sanders, fibrosis may feed upon itself producing yet more fibrosis.
Though this isn’t normally done today, anyone diagnosed with A-Fib ought to have a heart MRI to measure exactly how much fibrosis has developed in their heart and how much and how fast it is progressing.
This danger of fibrosis progression is yet another incentive to consider a catheter ablation in order to be A-Fib free with no further progression of fibrosis.

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Last updated: Friday, March 6, 2015

AF Symposium 2015 Brief Reports by Steve S. Ryan, PhD

20th Annual AF Symposium

by Steve S. Ryan, PhD

This overview should give you a sense of the topics floating through the three days in Orlando and the over sixty presentations by fifty A-Fib experts and researchers. (Most recent brief reports listed first)

AF Symposium: My Brief Reports

 The Novel Oral Anticoagulants: Xarelto Best Seller; Dr. Daniel Singer
 Stimulating the Front Ear Flap Inhibits A-Fib—Research by Dr. Warren Jackman
 Dr. Ruskin Asked: Can Anyone in A-Fib Really Be Asymptomatic?
 The Rhythmia 3-Dimensional Mapping System (Live from Leipzig via Satellite) 
 LAA Occlusion Devices: Is the Watchman Device Dead in the Water?
 FDA ‘Easy Feasibility Study’ (EFS 
 Reversal Agents for the New Anticoagulants (NOACs)? 
 Female Gender: Is it a Risk Factor for Stroke?
 Living in A-Fib More Dangerous Than Having an Ablation
 Rotors! Rotors! Rotors! Sizzling Topic but No Consensus
 Holistic Approach to Health: Great Results Dealing with Obesity
 Atrial Esophageal Fistula: A Case Study
 Anticoagulation Case Study: Dilemma for 92-year-old With Paroxysmal A-Fib
 Ablation Without X-Ray or Fluoroscopy (Live via Satellite)
 From Beijing: Strange Chinese Case (Live via Satellite)
 Ablation & Closing Off the Left Atrial Appendage in the Same Procedure (Live via Satellite)
 Contact Force Sensing and Jet Ventilation (Live Satellite Presentation)
 Non-Invasive Electrocardiographic Imaging—ECGI—CardioInsight
 Fibrosis and A-Fib: Continuing Research on Sheep

The Rhythmia 3-Dimensional Mapping System (Live from Leipzig via Satellite)

Rhythmia 3-Dimensional Mapping image

Image from Rhythmia 3-Dimensional Mapping system by Medtronic

Live Via Satellite TV icon(Please be advised that the Symposium organizers go to great lengths not to identify or unfairly publicize one device over another. When writing these reports I often have to do a good deal of research to correctly identify and describe particular devices that are demonstrated, as a service to readers. But this in no way implies or suggests that one device is superior to another.)

Dr. Gerhard Hindricks of the University of Leipzig in Germany gave a dynamic presentation of a catheter ablation of a 46-year-old female with paroxysmal A-Fib using the Rhythmia 3-dimensional multipolar mapping system by Boston Scientific. Along with his colleagues Drs. Andreas Bollmann and Jedrzej Kosiuk, they used the Rhythmia special basket catheter to generate a 3-D map of electrogram voltages and activation times. To me it seemed amazingly fast. The eight-splined bidirectional catheter produced 1,000 data points per minute. In what seemed like only a few passes, they produced a 3-D color reconstruction of the patient’s left atrium.

The actual ablation was routine. They terminated the A-Fib into sinus rhythm without having to use Electrocardioversion. But they found that the PV isolation was incomplete. Using the same Rhythmia 3-D mapping catheter, they were easily and quickly able to locate the gap in the Left Superior PV and ablate it.

LAA Occlusion Devices: Is the Watchman Device Dead in the Water?

Dr. Vivek Reddy from Mount Sinai School of Medicine in New York City gave a very well referenced and persuasive presentation on the Watchman device which closes off the Left Atrial Appendage to prevent clots and strokes. The theory behind the Watchman device is that most A-Fib clots originate in the Left Atrial Appendage (LAA). The Watchman closes off the LAA where 90-95% of A-Fib strokes come from. It’s a very low risk procedure that takes as little as 20 minutes to install. Afterward, you would usually not need to be on blood thinners. (For more, see my article, The Watchman Device: The Alternative to Blood Thinners).

Dr. Reddy certainly persuaded me that the FDA should approve the Watchman device. Dr. Reddy, earlier in Washington, had made the same persuasive arguments before the FDA.

Dr. Andrew Farb from the FDA took the bull by the horns and gave his perspective on the various LAA Closure (Occlusion) Devices. But as one would expect, he didn’t indicate how the FDA would rule on the Watchman device, since deliberations were still ongoing.

After his presentation, I asked him several pointed questions about this, but he was, of course, careful not to comment about current FDA deliberations. My guess? If body language, momentum, mood of the presentations, and more importantly recent research indicate anything, the Watchman device probably will not be approved by the FDA.

There was a palpable sense of sadness at the end of these presentations. The attendees realized that the game may be over for the Watchman device. I hope I am wrong, since the Watchman device would be an important tool to help A-Fib patients. Once the FDA rules and the current clinical trials of the Watchman device end, you will probably have to go to Canada or overseas to get a Watchman device installed.

(Happily I was wrong on this prediction. Update: The U.S. Food and Drug Administration (FDA) approved Boston Scientific’s WATCHMAN™ LAA closure technology for use in the U.S. on March 13, 2015. It has been available internationally since 2009. The FDA approval of the WATCHMAN device is based on the clinical program which consists of numerous studies, with more than 2,400 patients and nearly 6,000 patient-years of follow-up. The Watchman device will be available first at U.S. centers where it has been used in clinical studies.)

Watchman May Win FDA Approval

In my earlier brief reports on the Orlando AF Symposium, based on the recent research and the FDA presentation, I said the Watchman device probably won’t be approved in the US. I’m happy to say that I am most likely wrong.

At the LAA Symposium 2015 in Marina del Rey, CA, it was suggested that the Watchman device may be approved by the middle of this year. One presenter described how the FDA chairman talked with several people who were going to Canada to have the Watchman device installed. He seemed embarrassed that the Watchman was available everywhere in the world but not in the US and said that it has to be approved.

Other doctors I talked with at the LAA Symposium were of the same opinion. Presenters described how clinical trials for other LAA closure devices were on hold so that they could get approved in comparison to the Watchman (Non-Inferiority Trials). Dr. Dhanunjaya Lakkireddy of the University of Kansas Medical Center said that we are at a “tipping point” for the (A-Fib) industry.

FDA ‘Easy Feasibility Study’ (EFS)

As everyone, including the FDA, is well aware, A-Fib innovations usually start in Europe where they are more easily approved. Then only later do they move to the US for FDA approval, since the FDA generally requires more data than European regulators.

Drs. Jun Dong and Andrew Farb from the FDA described the FDA’s ‘Easy Feasibility Study’ (EFS) program where medical device innovations could be evaluated  in the US without having to go to Europe first. He encouraged researchers and attendees to take advantage of the new EFS program. This is major news and may make the development of A-Fib innovations much easier to accomplish in the US.

For further information, contact: Andrew Farb, Email: Andrew.farb@fda.hss.gov. 301-796-6317

Reversal Agents for the New Anticoagulants (NOACs)?

Dr. Luigi Di Biase from the Albert Einstein College of Medicine in the Bronx, NY and Dr. Daniel Singer from Massachusetts General Hospital in Boston each described potentially great developments in reversal agents for apixaban (Eliquis) and rivaroxaban (Xarelto).

Dr. Di Biase described studies where leaving people on uninterrupted rivaroxaban and apixaban before, during and after an ablation dramatically reduced the amount of silent thromboembolic lesions and were as safe as warfarin with regards to stroke and TIAs. (This didn’t work with dabigatran [Pradaxa].) But if patients develop bleeding or effusion during the ablation, they are in trouble because there is no direct reversal agent as there is for warfarin. He has used Factor IV as an indirect reversal agent. Dr. Singer also described how Factor IV was used as a reversal agent for apixaban.

But there are new reversal agents for apixaban and rivaroxaban which promise to completely reverse the effects of these two drugs in less than four minutes. The FDA is speeding up studies on these reversal agents. But one never knows when or if the FDA will approve them.

Female Gender: Is it a Risk Factor for Stroke?

Dr. John Day of the Intermountain Heart Institute in Murray, UT (and recently elected president of the Heart Rhythm Society) may be the first A-Fib leader to publicly question whether women should be given one point on the stroke risk CHA2DS2-VASc scale just because of their gender. Many doctors have said this in a circumspect way. Dr. Eric Prystowsky in a presentation at last year’s AHS meeting thought that most doctors would agree with Dr. Day, “as long as there wasn’t a camera focused on them.” He gave the example of a 45-year-old woman in good health and a 45-year-old man with hypertension who according to current guidelines should both be given one point on the stroke risk CHA2DS2-VASc score.

Editor’s Comments:
As readers of A-Fib.com, you know that’s been my opinion ever since the original European guidelines came out. Women in their child-bearing years are much less at risk of stroke because of the blood-thinning effect of losing blood each month. And even after menopause women have less risk of stroke. But eventually they do have more strokes. But not because of an innate inferiority, but because women live longer than men. Stroke is age related. An observational Danish registry study documents this.
For more, see The Denmark Study: Women in A-Fib Not at Greater Risk of Stroke Contrary to CHA2DS2-VASc Guidelines!) (Be advised that the original European guidelines were written by doctors with major conflicts of interest.) These guidelines may be a not so very subtle form of gender bias.

Living in A-Fib More Dangerous Than Having an Ablation

Living in A-Fib is more dangerous than having an ablation, according to Dr. Josef Kautzner from Prague, the Czech Republic. Studies have documented that the adverse effects of living in A-Fib, having to take A-Fib drugs and anticoagulants for life are both pragmatically and statistically worse than having an ablation. Dr. Kautzner discussed how A-Fib can cause or is associated with silent brain lesions and dementia. Any time you go into a hospital is a risk. And no one would say that a catheter ablation is a walk in the park. But an ablation is a low risk procedure, though not risk free. The risk is similar to having your tubes tied. The possible adverse effects of an ablation procedure (like bleeding at the groin) are generally temporary, unlike the lasting, permanent damage you can do to your heart, body and brain by living in A-Fib for years.

Rotors! Rotors! Rotors! Sizzling Topic but No Consensus

The most hotly discussed topic at this year’s symposium was rotors. The opinions expressed about rotors were at times very heated, more than I had ever seen at an AF Symposium. Dr. Shih-Ann Chen of Taipei, Taiwan disagreed with Dr. Sanjiv Narayan of Stanford, CA about the basic concepts of rotors and how they should be defined. Dr. Ravi Mandapati of UCLA and Loma Linda University disagreed with Dr. Narayan which was all the more striking in that he had worked with Dr. Narayan when he was at UCLA. Dr. Pierre Jais of Bordeaux, France said that the FIRM mapping system misses 40% of the atrium area.

Drs. Haissaguerre and Jais from Bordeaux and Dr. Sebastien Knecht of Brussels, Belgium gave presentations on how they were using the CardioInsight body surface mapping vest to perform ablations of “drivers” at many different centers, while Dr. Karl-Heinz Kuck from Hamburg, Germany using a different body surface mapping system said that he couldn’t ablate rotors. Dr. Narayan says the FIRM system finds a maximum of 2-3 rotors in the atria, while other systems find as many as seven. The FIRM system says rotors are usually relatively stable and can last as long as 30 seconds while others say they rotate in one fixed spot for only one or two rotations, that they tend to migrate within a certain area.

The presenters obviously didn’t share a consensus of basic concepts of what rotors are, how they work, their importance in A-Fib, how they should be correctly identified, used, and ablated. (It seems to me the Bordeaux group has the best understanding and pragmatic use of rotors. They refer to “rotors” and focal sources as “drivers.”) But the CardioInsight system Bordeaux uses isn’t currently available or isn’t being tested in the US.

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Holistic Approach to Health: Great Results Dealing with Obesity

Obesity was one of the most often discussed topics. There is a growing consensus among EPs that it isn’t enough to just give obese patients a catheter ablation while not dealing with their obesity. If the obesity isn’t dealt with, their A-Fib is very likely to re-occur. A-Fib will develop in other spots that haven’t been ablated. The condition (obesity) that triggered or caused the A-Fib will trigger or cause it again, if it isn’t taken care of.

Dr. Prashanthan Sanders of Adelaide, Australia described the great results he is getting in his clinic which includes a weight loss program and counseling. He convinces his overweight patients to buy into the program, lose weight, and keep it off. The program works so well that just by losing weight patients become A-Fib free. This program is a holistic approach to health and also is developed to work for diabetes, sleep apnea, hypertension, binge drinking and smoking.

Dr. Sanders foresees a world where some patients become A-Fib free simply by changing their life style, where they don’t have to have a catheter ablation to become A-Fib free.

Many other doctors commented that A-Fib treatment at many centers today includes or should include much more than A-Fib ablation and drugs. A-Fib centers should have nutritionists, exercise therapists, sleep apnea specialists, etc. as part of their A-Fib program.

Atrial Esophageal Fistula: A Case Study

Dr. John Day of the Intermountain Heart Institute in the Challenging Cases Discussion described his experience with the dreaded Atrial Esophageal Fistula. Though very rare, this is one of the few possible complications of a catheter ablation that can kill you. An ablation, if not done with caution, can irritate and damage the esophagus which often lies right next to the heart. Over 2-3 weeks stomach acid can eat through this damaged area to produce a hole or fistula from the esophagus into the heart.

As soon as Dr. Day saw this patient, he knew it was a fistula and immediately called surgeons and a GI doctor. All the surgeons were doing operations and didn’t want to do the surgery in the EP lab. Dr. Day described how he and his colleagues ran down the hospital hallway to the operating room while giving the patient a transfusion and at the same time pumping out the blood escaping from his heart.

The GI doctor got there first and put in a stent in the esophagus to plug the hole. There was lots of discussion as to whether this was the best approach, but it worked. The patient survived but had to spend a month in the hospital.

This cautionary and very dramatic tale certainly got the attention of all the attendees. No matter how rare a fistula is, every EP and A-Fib center must have an established protocol in place to deal with it. I remember Dr. Hugh Calkins in a previous Symposium advising, “There are only two kinds of EPs—those who have not had an Atrial Esophageal Fistula and those who have!” (Dr. Calkins’ patient with fistula also survived.)

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Anticoagulation Case Study: Dilemma for 92-year-old With Paroxysmal A-Fib

Dr. Peter Kowey of Lankenau Hospital in Winnewood, PA described a case that illustrates the kind of dilemma both doctors and patients often have to face. A 92-year-old woman with paroxysmal A-Fib who had been treated for many years with warfarin had some bruising and nuisance bleeding, but never anything major.

Dr. Kowey thought that ethically he should tell her about the different new anticoagulants which may be superior to warfarin, then see if she wanted to change. She went with apixaban (Eliquis), then six months later had a stroke even though she was taking apixaban properly and conscientiously. Happily, she made an almost full recovery. She returned to warfarin which had worked for her in the past and which she was comfortable using.

Editor’s Comments:
One of the reasons Dr. Kowey discussed the new anticoagulants with his 92-year-old patient was because warfarin is considered more apt to cause bleeding in older patients. The newer anticoagulants in clinical trials caused less bleeding. But we don’t have much data from the clinical trials on people over 90 years old.
Can we say that apixaban didn’t work or was ineffective? No. Anticoagulants reduce but do not totally eliminate the risk of an A-Fib stroke. Just because she had a stroke doesn’t mean apixaban didn’t work.
Dr. Jeremy Ruskin pointed out that there has never been and probably never will be a head-to-head comparison of the three new anticoagulants. But in my opinion apixaban (Eliquis) appears to have tested better and is safer than the others
For more, see my 2013 BAFS articles, The New Anticoagulants (NOACs) and Warfarin vs. Pradaxa and the Other New Anticoagulants.

Ablation Without X-Ray or Fluoroscopy (Live via Satellite)

Live Via Satellite TV iconIn the satellite case live presentations, Drs. Rodney Horton and Amin Al-Ahmad from the Texas Cardiac Arrhythmia Institute in Austin, TX surprised us by doing an ablation without wearing the standard lead aprons to prevent fluoroscopy exposure. Even more surprising was one of the lab assistants who was pregnant. She could work on the ablation because no fluoroscopy was used. The doctors did the whole ablation using ICE (Intracardiac Echo) and 3D mapping. They showed for example how ICE can be used to thread the catheter up into the heart and into the left atrium. Dr. Horton said that not having to wear those heavy lead aprons would probably add 5-10 years to his ablation career.

(They didn’t wear surgical masks during the ablation which was surprising to me. I will write them for an explanation.)

From Beijing: Strange Chinese Case (Live via Satellite)

Live Via Satellite TV iconThe live satellite case from Beijing, China was technically flawless and probably a first of its kind. But it wasn’t much of a learning experience for the attendees. The Chinese EPs only used one catheter and had to frequently pull out the mapping catheter and replace it with the ablation catheter, etc. When the expert panel asked them questions, the Chinese EPs either didn’t understand or simply didn’t answer them. They seemed very uncomfortable. It seemed like a throwback to ablation techniques of 20 years ago.

Ablation and Closing Off the Left Atrial Appendage in the Same Procedure (Live via Satellite)

Live Via Satellite TV iconDrs. Claudio Tondo, Gaetano Fassini, Massimo Moltrasio, and Antonio Dello Russo from Milan, Italy showed how they do a catheter ablation for A-Fib and install the Watchman device in the same procedure, when it’s needed. They do the ablation procedure first. Then when the patient is in sinus rhythm, they install the Watchman device. (This can’t be done in the US, because the Watchman device hasn’t received FDA approval. In later discussions including representatives of the FDA, there was an all too real possibility that the Watchman will never receive FDA approval.)

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Contact Force Sensing and Jet Ventilation (Live Satellite Presentation)

Image of the TactiCath Quartz irrigated ablation catheter with EnSite Contact Force Module (Photo St. Jude Medical, Inc.)

TactiCath Quartz irrigated ablation catheter with EnSite Contact Force Module (Photo St. Jude Medical, Inc.)

Live Via Satellite TV icon Drs. Kevin Heist and Moussa Mansour from Massachusetts General in Boston showed in a live case how they used a Contact Force Sensing catheter combined with Jet Ventilation. (There are two Contact Force Sensing catheters approved by the FDA—the ThermoCool Smart Touch device by Biosense Webster (approved Feb. 24, 2014) and the TactiCath Quartz Contact Force Ablation Catheter by St. Jude Medical (approved Oct. 27, 2014). This live case used the TactiCath catheter but didn’t imply or suggest it is superior to the ThermoCool catheter. For a description of each, see my 2014 AF Symposium report The New Era of Catheter Ablation Technology: Force Sensing Catheters.

This combination of Force Sensing Catheter with Jet Ventilation for RF ablation probably represents the most advanced RF ablation strategy available today. Jet Ventilation doesn’t stop the heart from beating as in bypass surgery. But to this observer it seemed to put the heart in a type of slow motion with a lot less movement than when the heart is beating in normal sinus rhythm. You could really see a difference when they turned the Jet Ventilation off and on. Slowing down the heart like this helps the ablation doctor make lesions in hard-to-access areas and makes it easier to hold the catheter steady and apply the right contact pressure.

Non-Invasive Electrocardiographic Imaging—ECGI—CardioInsight

Drs. Michel Haissaguerre and Pierre Jais from Bordeaux/LYRIC gave presentations on the ECGI system. The day before their ablation, the patient lies down on his/her back and a technician places a vest-like device with 256 electrodes over his/her chest and stomach. These electrodes combine with rapid CT (Computed Tomography) scans to produce a very detailed 3D color map of the heart. (For a detailed description and discussion of the ECGI system, see 2013 BAFS: Non-Invasive Electrocardiographic Imaging [ECG]) The system automatically detects rotors and foci and computes them into a “Cumulative Map” or movie. These driver regions are ranked, based on statistical prevalence.

Then, Dr. Sebastien Knecht from CHU Brugmann, Brussels, Belgium, described the AFACART trial design and preliminary results using the CardioInsight ECGI system. Many centers in Europe including four in Germany are now using the CardioInsight. Requiring very little training, technicians and EPs using the CardioInsight system are getting similar great results like the Bordeaux group. Though these studies just started, it looks like the CardioInsight ECGI mapping and ablation system is poised to revolutionize the way EPs map and perform ablations.

Fibrosis and A-Fib: Continuing Research on Sheep

Dr. Jose Jalife of the University of Michigan in Ann Arbor, MI, continued his exciting research on fibrosis and A-Fib. In previous Symposiums Dr. Jalife demonstrated how A-Fib produces fibrosis. When he paced sheep into A-Fib, their hearts became fibrotic within a very short time. The markers of fibrosis (collagen and scarring) increased progressively as the sheep went from paroxysmal to persistent A-Fib. (See A-Fib Produces Fibrosis—Experimental and Real-World Data.)

Fibrosis is tissue that has fiber-like characteristics which develop in place of the normal smooth walls of the heart. Fibrotic tissue is scarred, immobile, basically dead tissue with reduced or no blood flow and no transport function. It results in a loss of atrial muscle mass. Over time it makes the heart stiff, less flexible and weak, overworks the heart, reduces pumping efficiency and leads to other heart problems. Fibrosis, up to now, was considered permanent and irreversible. But Dr. Jalife gave his sheep a Gal-3 inhibitor GM-CT-01 that actually prevented and reduced fibrosis! (For his previous presentations, see 2014 BAFS: The Holy Grail: Preventing A-Fib by a GAL-3 Inhibitor.)

In his continuing studies of sheep, Dr. Jalife found that fibrosis predicts recurrence, and that fibrosis can not be reversed if it is well established, even with GAL-3 Inhibitors.

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Last updated: Friday, November 18, 2016 

FAQs Understanding A-Fib: Questions from Patients

FAQs Understanding Your A-Fib A-Fib.comFAQs: Understanding Atrial Fibrillation

Atrial Fibrillation patients often have loads of “Why?” and “How?” questions. Here are answers to the most frequently asked questions by patients and their families. (Click on the question to jump to the answer.)

1. Why does so much Atrial Fibrillation come from the Pulmonary Vein openings?

2. Is my Atrial Fibrillation genetic? Will my children get A-Fib too? Updated!

3. Why do older people get Atrial Fibrillation more than younger people?

4. Is Atrial Fibrillation (A-Fib) different from what doctors call Paroxysmal Supraventricular Tachycardia?

5. What is the difference between “Adrenergic” and “Vagal” Atrial Fibrillation? How can I tell if I have one or the other? Does it really matter? Does Pulmonary Vein Ablation (Isolation) work for Adrenergic and/or Vagal A-Fib?

6. What causes Paroxysmal (occasional) A-Fib to turn into Persistent (Chronic) A-Fib?

7. I’ve heard about ‘stiff heart’ or diastolic dysfunction. When you have A-Fib, do you automatically have diastolic heart failure? What exactly is diastolic dysfunction?

8. A-Fib and Flutter—I have both. Does one cause the other?” 

9. “My surgeon wants to close off my LAA during my Mini-Maze surgery. Should I agree? What’s the role of the Left Atrial Appendage?” 

10. “I’ve read about stem cells research to regenerate damaged heart tissue. Could this help cure A-Fib patients?”

11. What is the heart’s ejection fraction? As an A-Fib patient, is it important to know my EF? 

12. “I read that the local anesthesia my dentist uses may trigger my A-Fib. Why is that?”

13. “How can I determine or measure how much fibrosis I have? Can something non-invasive like a CT scan measure fibrosis?

14. “I have paroxysmal A-Fib with “pauses” at the end of an event. Will they stop if my A-Fib is cured? My cardiologist recommends a pacemaker. I am willing, but want to learn more about these pauses first.

15. “I have paroxysmal A-Fib and would like to know your opinion on which procedure has the best cure rate”

16. “I am 69 years old, in permanent A-Fib for 15 years, but non-symptomatic. My left atrium is over 55mm and several cardioversions have failed. My EP won’t even try a catheter ablation. I exercise regularly and have met some self-imposed extreme goals. What more can I do? NEW!

Last updated: Friday, December 9, 2016

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FAQs Understanding A-Fib: Measuring Fibrosis

 FAQs Understanding A-Fib: Fibrosis

FAQs Understanding Your A-Fib A-Fib.com13.  “How can I determine or measure how much fibrosis I have? I’ve had A-Fib for several years and have read that it may produce fibrosis and collagen deposits in the atrium. Can something non-invasive like a CT scan measure fibrosis?”

The more one stays in A-Fib, the more fibrosis and collagen are formed in the atrium [the remodeling effect]. Electrophysiologists (EP) can measure fibrosis by going inside the heart and mapping fibrosis with a voltage monitoring catheter. Recent research indicates that Fibrosis can be measured by an MRI.

Dr. Nassir Marrouche, University of Utah School Of Medicine, is pioneering the use of magnetic resonance imaging (MRI) to measure fibrotic heart tissue. MRI is better than fluoroscopy and CAT scans because it reveals damaged, fibrotic tissue due to atrial fibrillation. In addition to other factors, Dr. Marrouche considers the amount of fibrosis in the left atrium is key to ablation treatment success. (To learn more, see my report from the 2014 Boston AF Symposium: High Fibrosis at Greater Risk of Stroke and Precludes Catheter Ablation: Lessons Learned from the DECAAF Trial.)

Anyone in A-Fib might want to consider an MRI to measure their level of fibrosis.

To the best of my current knowledge, a Computerized tomography (CT scan) does not measure Fibrosis.

Thanks to Stewart Stafford for this question.

Resources:
¤ Spragg, D., et al. Role of Magnetic Resonance Imaging of Atrial Fibrosis in Atrial Fibrillation Ablation. Arrhythmia & Electrophysiology Review 2013;2(2):124-7.
¤  Breakthrough: Use of MRI in Catheter Ablation for Atrial Fibrillation. StopAfib.org website. November 7, 2008 Last accessed March 29, 2014 URL: http://www.stopafib.org/newsitem.cfm/NEWSID/120

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High Fibrosis Precludes Catheter Ablation DECAAF Trial-2014 Boston AF Symposium

2014 Boston AF Symposium

Nassir Marrouche MD

Nassir Marrouche MD

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.

Editor’s Comments:
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
“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.

Additional Reading:

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: Saturday, February 13, 2016 

References    (↵ returns to text)

  1. 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
  2. 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.
  3. O’Riordan, Michael. DECAFF Published: MRI Aids in AF Ablation Success. Heartwire, February 5, 2014. http:”//www.medscape.com/viewarticle/820230

Preventing A-Fib by a Gal-3 Inhibitor -2014 Boston AF Symposium

Jose Jalife, MD

Jose Jalife, MD

2014 Boston AF Symposium

The Holy Grail: Preventing A-Fib by a GAl-3 Inhibitor

By Steve S. Ryan, PhD

Dr. Jose Jalife from the Center for Arrhythmia Research at the University of Michigan gave a second presentation aptly titled “Searching for the Holy Grail: Upstream Therapy to Prevent AF Progression.” Briefly summarizing his previously described experimental studies of pacing sheep into A-Fib, it took about seven weeks of pacing to push sheep into persistent self-sustaining A-Fib. (See BAFS 2014: Experiments in Atrial Remodeling in Sheep and the Transition From Paroxysmal to Persistent A-Fib.)

Dr. Jalife asked the question “What if I treat my sheep with a drug that prevents fibrosis? Would I be able to effectively prevent, or at least delay the transition to persistent A-Fib?”

How Fibrosis Develops

In the fibrotic sheep a marker of cardiac fibrosis, pro-collagen type III (PIIINP), was found in their serum. Explaining how sheep develop fibrosis, Dr. Jalife described how a normal heart has what are called “Fibroblasts” which make up 50-70% of cells in the heart. They provide the heart’s structural and mechanical support to the myocytes (muscle cell or muscle fiber). But in fibrosis these Fibroblasts turn into “Myofibroblasts” (activated fibroblasts) which:

  • Are unexcitable (do not contract in response to electrical stimuli)
  • Secrete profibrotic cytokines (cell signaling proteins) (e.g., TGF-ß1, PDGF)
  • Express cell adhesion proteins (e.g., n-cadherin)
  • Replace myocytes in the remodeled myocardium

Fibrosis is tissue that has fiber-like characteristics which develop in place of the normal smooth walls of the heart. Fibrotic tissue is scarred, immobile, basically dead tissue with reduced or no blood flow and no transport function. It results in a loss of atrial muscle mass. Over time it makes the heart stiff, less flexible and weak, overworks the heart, reduces pumping efficiency and leads to other heart problems. Fibrosis, up to now, was considered permanent and irreversible.

Dr. Jalife described Galectin-3 (Gal-3), a protein that produces (“mediates”) tissue fibrosis. (It’s also involved in inflammation, immune response, cancer, heart disease and stroke.) For you technical types, “Gal-3 pentamers bind to poly N-acetyl lactosamine (LNac) residues on TGF receptors of myofibroblasts causing cell surface retention and promoting signaling through Smad and AKT pathways and leading to fibrosis.” (For us non-technical types, all we need to know is that Gal-3 promotes fibrosis.)

When sheep are paced into A-Fib, this also produces more galectin-3. Gelactin-3 in turn promotes structural remodeling (TGF-ß1-induced atrial structural remodeling—fibrosis) and electrical remodeling, which leads to persistent A-Fib.

The Holy Grail of A-Fib—Gal-3 Inhibitors

But the Gal-3 inhibitor GM-CT-011 by Galectin Therapeutics prevents Gal-3 from producing fibrosis!!! This means it’s “a potential new upstream therapy for the prevention of persistent AF.”

To test whether the Gal-3 inhibitor worked or not, Dr. Jalife gave some sheep the Gal-3 inhibitor and other sheep saline twice per week. The inhibitor:

  1. Lessened A-Fib-induced atrial dilation
  2. Reduced fibrosis by 50%!!!
  3. Reduced the increase in dominant frequency
  4. Prevented the shortening of action potential duration in both atria
  5. Increased the percentage of sheep spontaneously terminating their persistent A-Fib during treatment

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Dr. Jalife’s General Conclusions:

  1. Persistent A-Fib remodeling in sheep isn’t caused by other heart problems like altered LV function or other heart illnesses. (In his first presentation Dr. Jalife previously demonstrated that sustained A-Fib leads to progressive atrial dilation but doesn’t alter LV function.)
  2. Atrial remodeling results in part “from proliferation of myofibroblasts expressing α-SMA and secreting cytokines like TGF-ß1, as well as Gal-3.”
  3. Sustained A-Fib leads to atrial dilation, increased atrial collagen and fibrosis, which correlates with increased α-SMA, TGF-ß1 and Gal-3.
  4. Remodeling can be measured by the progressive increase in Dominant Frequency during the transition from paroxysmal to persistent A-Fib. This results from “differential changes in the expression and function of Naᶧ, Ca²ᶧ, and Kᶧ channels.”
  5. “Gal-3 inhibition reduces both A-Fib induced structural and electrical remodeling in the sheep model of persistent A-Fib.” Inhibiting Gal-3 by GM-CT-01 is a new, potentially powerful upstream therapy to prevent persistent A-Fib. [And the most important conclusion!]

Dr. Jalife’s last slide captured the importance of his experimental work:

There is hope for A-Fib prevention.

Added 9/15/15: The natural supplement, Pecta-Sol C (Modified Citrus Pectin), binds to Galectin-3 and is a Galectin-3 inhibitor. It may reduce or prevent structural and electrical A-Fib remodeling.3It is known as a natural detoxifier.

Editor’s Comments:
Throughout this web site I warn about the dangers of developing fibrosis (by for example leaving people in A-Fib while only controlling the heart rate). Up to now fibrosis was permanent and irreversible, and caused irreparable damage to one’s heart. There were no proven and approved therapies to reverse fibrosis. But this may no longer be the case. Dr. Jalife showed that Gal-3 inhibitors reverse fibrosis! This is tremendous news for patients and is certainly the most important finding of this year’s Boston A-Fib Symposium.
Dr. Jalife’s work demonstrated that sheep can be prevented from going from Paroxysmal to Persistent A-Fib by using Gal-3 inhibitors. This is also wonderful news for patients. All too often someone develops A-Fib and, within a year, progresses to persistent A-Fib which is harder to cure and produces more fibrosis and remodeling. But Gal-3 inhibitors stop this progression!
Let’s imagine it’s a couple of years from now. Gal-3 has been approved by the FDA (this obviously isn’t a certainty, but it looks promising). You develop paroxysmal A-Fib (as easily determined by the Dominant Frequency of your A-Fib). Your EP gives you a Gal-3 inhibitor which both keeps you from going into persistent A-Fib and reduces the amount of fibrosis in your heart.
Let’s take this a step further. Some of the sheep taking Gal-3 inhibitors went back into sinus rhythm, possibly because their fibrosis was reduced. Can Gal-3 inhibitors “cure” A-Fib? Is a Gal-3 inhibitor the magic pill we’ve been waiting for? If you develop paroxysmal A-Fib, can you simply take a Gal-3 inhibitor and be A-Fib free? This is probably an overly hopeful speculation. But perhaps this could be Dr. Jalife’s next experiment.
Even if GAl-3 inhibitors are successful and approved by the FDA, in all likelihood there will still be a need for catheter ablation (and surgery). A 50% reduction in fibrosis is great, but there’s still that other 50% which may still be permanent. In private comments to the editor, Dr. Jalife thinks fibrosis might be irreversible once it develops.
The Galectin-3 inhibitor GM-CT-01 (and GR-MD-02) by Galectin Therapeutics (Nasdaq: GALT) is moving toward FDA approval. In studies with rats these Gal-3 inhibitors “led to significantly reduced fibrosis, reversal of cirrhosis and a significant reduction in portal hypertension (cirrhosis is basically fibrosis of the liver).” GR-MD-02 is in Phase 1 clinical trial with the first human patients. It received Fast Track designation from the FDA for fatty liver disease with advanced fibrosis.2
If you are an investor, Galectin Therapeutics (Nasdaq: GALT) might be something worth looking into while it’s still relatively cheap.

Added: 9/15/15: Instead of having to wait years for possible FDA approval, you can take a natural supplement, Pecta-Sol C (Modified Citrus Pectin), that works like a Galectin-3 inhibitor to prevent and reduce the development of fibrosis and A-Fib. (Thanks to Mary LaPorte for alerting us to Modified Citrus Pectin.)


Additional reading: Martins, RP et al. Dominant Frequency Increase Rate Predicts Transition from Paroxysmal to Long-Term Persistent Atrial Fibrillation. Circulation, published online January 24, 2014. http://www.ncbi.nlm.nih.gov/pubmed/24463369

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Last updated: Tuesday, September 29, 2015 

References    (↵ returns to text)

  1. former brand name Davanat
  2. Brechka, Nicole (2009). “Putting the Squeeze on Cancer”. Better Nutrition. August 2011. http://www.betternutrition.com/citrus-pectin-cancer-fighter/
  3. Traber PG et al. Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease. Plus One, 2013 Oct.9;8(10):e75361 http://www.ncbi.nlm.nih.gov/pubmed/24130706;  doi: 10.1371/journal.pone.0075361. eCollection 2013.

Atrial Remodeling and the Transition From Paroxysmal to Persistent AF by Dr Jose Jalife-2014 Boston AF Symposium

Jose Jalife, MD

Jose Jalife, MD

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.)

Structural Remodeling

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.

Dr. Jose Jalife 2014 Boston AFib Symposium

Graphic used with permission

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.”

  1. “Sustained AF reduces L-type calcium (Caᵥ1.2) and sodium (Naᵥ1.5) protein expression”
  2. “Sustained AF reduces the rapid sodium inward (INa) and L-type calcium (ICaL) currents”
  3. “Sustained AF reduces the transient outward current (Ito)”
  4. “Sustained AF increases the inward rectifying potassium current (IK1)  and protein expression of the Kir2.3 channel”

Conclusions

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.

Editor’s Comments:
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.

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Last updated: Wednesday, September 2, 2015 

References    (↵ returns to text)

  1. Peykar, S. Atrial Fibrillation. Cardiac Arrhythmia Institute/Sarasota Memorial Hospital website. Last accessed Jan 5 2013. URL:http://caifl.com/arrhythmia-information/atrial-fibrillation/

Stem Cells Reverse Heart Damage—(And May Repair Fibrosis and Scarring in A-Fib)

Stem Cells Reverse Heart Damage—May Repair Fibrosis and Scarring in A-Fib

Stem Cells Reverse Heart Damage

Stem Cells Reverse Heart Damage—May Repair Fibrosis and Scarring in A-Fib

Steve S. Ryan, PhD, Updated October 2014

Dr. M (John Mandrola) in his excellent blog described fascinating research using stem cells to regenerate damaged heart tissue.

Patients who had suffered a heart attack or who had advanced heart failure and heart muscle damage received infusions of stem cells grown from cells taken from a biopsy of their own heart.

Heart Stem Cells Harvested, Purified Then Grow

Dr. Robert Bolli of the University of Louisville and Dr. Piero Anversa at Brigham and Women’s Hospital/Harvard Medical School took the heart stem cells harvested from patients during coronary artery bypass surgery and sent them to Boston where they were purified and allowed to grow.

Cells Infused Back into The Patient’s Heart

Once there were about 1 million of the stem cells per patient, Dr. Bolli’s team in Louisville reintroduce them into the region of the patient’s heart that had been scarred by a heart attack. The purified batch of cardiac stem cells was infused into the patients’ hearts approximately 4 months after their bypass surgery, allowing time for the bypass surgery to heal.

Amazing Results: Heart Damage Reversed!

The results were beyond their wildest expectations. Ejection fraction increased and the amount of scarring and damaged cells decreased. Heart damage was reversed without dangerous side effects. At the start of the study Dr. Bolli’s patients had an average ejection fraction of 30.3%. Four months after receiving stem cells, their ejection fraction was 38.5%. Some patients followed for a full year improved to an an astounding 42.5%. A control group given nothing but standard maintenance medications showed no improvement at all.

Similar Research Studies

Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute, developed a similar stem cell procedure. He found that not only did scar tissue decrease—shrinking between 30% and 47% in patients—but the patients actually generated new heart tissue. On average, the stem cell recipients grew the equivalent of 600 million new heart cells, according to Dr. Marban, who used MRI imaging to measure changes. (A major heart attack might kill off 1 billion heart cells.)

Dr. Anversa found that the heart contains a type of stem cell that can develop into either heart muscle or blood vessel components—whatever the heart needs depending on its injury. But there usually aren’t enough of these heart stem cells available after a heart attack. To provide a patient more of these heart stem cells, the doctors removed heart stem cells by a biopsy and then made millions of copies in a laboratory.

Different Strategies

Drs. Bolli and Anversa and Dr. Marban both used cardiac stem cells, but Drs. Bolli and Anversa  “purified” the cardiac stem cells so that more than 90% of the infusion was actual stem cells. Dr. Marban, on the other hand, used a mixture of stem cells and other types of cells extracted from the patient’s heart. “We found that the mixture is more potent than any subtype we’ve been able to isolate,” he says.

The additional cells may help by providing a supportive environment for the stem cells to multiply. Other scientists have produced improvements in cardiac patients using stem cells derived from bone marrow, though the results aren’t as spectacular as the above studies.

Dr. Bolli’s study (called “SCIPIO’) was the first reported human study of heart derived stem cells. Patients who received these stem cells had significant improvements in heart function, physical capacity and scored better on quality-of-life questionnaires. MRI and ultrasound imaging revealed that areas where stem cells were infused showed major improvement which continued over a year.

Editor’s Comments:
Though this study was not directed to A-Fib patients, let’s fantasize a bit. This study shows that heart stem cells can replace scar tissue and fibrosis with normal beating heart muscle fibers, thereby restoring heart function. Fibrosis and scarring, which are normally considered irreversible heart damage, may no longer be permanent.
Though the jury is still out on this, some studies indicate that fibrosis is associated with A-Fib. (see 2013 BAFS: A-Fib Produces Fibrosis—Experimental and Real-World Data). And fibrosis is linked to the threat of an A-Fib stroke (see BAFS 2014:High Fibrosis at Greater Risk of Stroke and Precludes Catheter Ablation: Lessons Learned from the DECAAF Trial). if injected stem cells somehow signal the heart to repair itself, this may turn fibrosis and scarring back into normal heart muscle.
In the near future a patient with A-Fib, instead of having to undergo catheter ablation (or surgery), may instead receive an injection of their own heart stem cells and be cured of A-Fib and the threat of an A-Fib stroke.
The only risk would be getting a biopsy inside the heart to get a sampling of heart tissue stem cells, then months later another procedure to insert the purified and multiplied heart stem cells. Though not simple procedures, they would probably involve less or at least an equal amount of risk as a catheter ablation but with no permanent scarring through ablation.
(This strategy probably couldn’t be used in someone who has already had a catheter ablation [or surgery]. The heart stem cells might heal the scarring created by the ablation, thereby causing reconnection or regrowth. Though it’s unlikely that stem cells would heal the structural scarring of ablation burns.)
Right now the costs of standard (non-heart) stem cell injection is around $4,000-$5,000 per injection. But currently very few doctors around the US do it.
Prediction: 
The author predicts that heart stem cells injection will rapidly become a standard treatment option, even for A-Fib patients. There shouldn’t be any political or religious objections to this heart stem cell therapy, since it doesn’t rely on embryonic stem cells.
Cardiac stem cell injection is probably a major medical breakthrough for A-Fib patients. Heart stem cell injection regenerates heart muscle. In Dr. Bolli’s words, “if a phase 3 study confirm this, it would be the biggest advance in cardiology in my lifetime. We would possibly be curing heart failure. It would be a revolution.” And this revolution will probably work in patients with A-Fib.
References for this Article

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Last updated: Sunday, February 15, 2015

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