by Steve S. Ryan, PhD
It’s a bad idea to just live with your Atrial Fibrillation. A-Fib is a progressive disease. It reduces the amount of blood flowing to the rest of your body by about 15%–30% with damaging effects. At the same time, your heart is working progressively harder and harder.
A-Fib is definitely curable. (I was cured of my A-Fib in 1998). If you have A-Fib, no matter how long you’ve had it, you should aim for a complete and permanent cure.
If your doctor is satisfied with just keeping your A-Fib “under control,” I recommend you get a second opinion.
Refer to our Finding the Right Doctor page and related readings. We step you through all you need to know to find the right doctor for you and your treatment goals.
#AtrialFibrillation #afib #Arrhythmia #AtrialTachycardia #Tachycardia
6. What causes Paroxysmal (occasional) A-Fib to turn into Persistent (chronic) A-Fib?
Researchers are still working to find the answer(s) to this question. We do know that 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.)
The main trigger seems to be increased pressures in the left atrium that causes the muscle fibers around the pulmonary vein openings to start beating on their own.
Uncontrolled blood pressure, untreated sleep apnea and diabetes, or a worsening cardiomyopathy seem to be key factors that make people progress from Paroxysmal to Persistent A-Fib. Research tells us that even after a successful ablation for Persistent A-Fib, “the long term success rates depend mostly on treatment of hypertension and obstructive sleep apnea.”
What does this mean to you? The longer you have Atrial Fibrillation, the harder it can be to cure it. Consider working aggressively to stop your A-Fib as with antiarrhythmic meds or with a minimally-invasive Pulmonary Vein Ablation or a Mini-maze surgery. You don’t want to be part of the 54% whose A-Fib becomes permanent.
4. “I’m worried about going into permanent (Chronic) A-Fib which I know is harder to cure. I’ve had Paroxysmal (occasional) A-Fib for a couple of months, but the A-Fib episodes seem to be getting longer and more frequent. How long do I have before I go into permanent A-Fib?”
Worst case scenario, Paroxysmal (occasional) A-Fib can progress to permanent in about one year. In a study of 5,000+ A-Fib patients, 54% of those on rate control meds went into permanent A-Fib in one year. However, there are people who’ve had Paroxysmal A-Fib for years and never progress to permanent A-Fib.
But the odds are against you. You are correct that the longer you have Atrial Fibrillation, the harder it can be to cure it. Consider working aggressively to stop your A-Fib as with antiarrhythmic meds or with a minimally-invasive Pulmonary Vein Ablation or a Mini-maze surgery. You don’t want to be part of the 54% whose A-Fib becomes permanent.1
To learn about various Treatment options for Atrial Fibrillation, see our Treatments page. Think about your treatment goals. Is managing your A-Fib and increased stroke risk with meds okay with you? Or do you prefer to aim for a cure? Discuss the options with your doctor. Take action as soon as practical.
- O’Riordan, M. RECORD AF: Better Success With Rhythm Control, But No Difference in Outcomes. Heartwire/Medscape Medical News. November 17, 2009. Last accessed March 29, 2014. URL: http://www.medscape.com/viewarticle/712576↵
Obesity Strong Predictor of A-Fib Risk and Recurrence
Report by Steve S. Ryan, PhD
Dr. David Wilber of Loyola University Medical Center in Chicago, IL gave a presentation entitled “Obesity, Inflammation and Atrial Fibrillation.”
Dr. Wilber described the findings of several studies on obesity and A-Fib:
1. Obese Patients Are at Greater Risk of Developing A-Fib.
In the Framingham Heart Study of 5,282 patients followed for 13.7 years, obese patients had a 1.5 greater risk of developing A-Fib. (Wang et al. JAMA 2004; 2022:2474)
In studies involving 68,000 people, obese patients had a 49% increased risk of new onset A-Fib (Wanahita et al. AHJ 2008; 155:310-315)
Increase In BMI (Body Mass Index) Is associated with a risk of developing A-Fib
♦ 16% for a BMI increase of 5-15%
♦ 46% for a BMI increase of 16-35%
♦ 90% for a BMI increase of over 35%
2. Obesity Produces Left Atrium Volume Changes and Overload
In the MONICA study of 1212 patients followed for ten years, 36% had hypertension, 34% were obese. Only obesity predicted Left Atrium volume changes and produced volume overload. (Hypertension produced pressure overload.) (Stritzke et al. JACC 2009; 54:1982-9)
3. Predictably Progress to Permanent A-Fib
In the Olmstead County study of 3,248 patients with Paroxysmal A-Fib (1980-2000), BMI greater than 35 (obese) predicted progression to permanent A-Fib independent of age, gender and clinical variables.
Obesity Factors Influencing or Responsible for A-Fib
Dr. Wilber then examined what factors or elements of obesity were responsible for affecting A-Fib.
1. Epicardial fat had more local chemokines, cytokines, and cellular infiltrates (fibrosis) than subcutaneous fat. He described an experimental study where epicardial and subcutaneous fat were added to atrial rat tissue. (Epicardial fat had higher levels of activin A and other biomarkers of fibrosis.)
2. In the Framingham Offspring study, only pericardial fat volume was significantly associated with A-Fib risk. 13% increased risk of A-Fib per 10 ml volume of pericardial fat.
3. In sheep experiments, obesity was profibrotic (increase in interstitial and cytoplasmic TGF-B1, PDGF-BB, and CTGF levels). Increasing weight produced significant increase in A-Fib burden (more and longer A-Fib episodes)
4. Risk of recurrence increases with obesity (Guijian et al, PACE 2013; 36:748-756). Left Atrium fat volume was the only significant predictor of recurrence (Tsao et al 2011)
5. A 19% decrease in weight significantly decreases A-Fib burden.
Dr. Wilber’s Conclusions
• Obesity is a strong independent predictor of A-Fib risk
• Obesity produces cardiac structural remodeling, notably LA volume and diastolic dysfunction
• Local direct effects which promote Left Atrium fibrosis through inflammatory and profibrotic cytokines
• Epicardial fat volume may be a useful way to measure or be a marker for local direct effects like fibrosis. Epicardial fat is independently associated with A-Fib risk relative to BMI, Left Atrial Volume, and other risk factors
• Obesity significantly impacts A-Fib recurrence after ablation
• Weight lost reduces the risk of new onset A-Fib, and subsequent progression/recurrence after A-Fib onset
Obesity is a major problem particularly in the US, so we can expect to see an increased number of the obese developing A-Fib (along with a host of other problems like hypertension, diabetes, coronary disease and sleep apnea).
The most startling statistic Dr. Wilber cited was that a BMI increase of 35% in men from age 25 to 50 increased the risk of developing A-Fib by 90%. Practically speaking, almost everyone who becomes obese in their lifetime will develop A-Fib. That’s a really scary statistic with enormous public health consequences.
And paroxysmal A-Fib patients who are obese will predictably progress to persistent (chronic) A-Fib.
“Is it a waste of time to perform a catheter ablation on someone who is obese? Aren’t they more at risk of recurrence?” They certainly are more at risk of recurrence. But a successful catheter ablation will change their lives and improve their quality of life. However, EPs should insist that obese patients who have a successful ablation must lose weight. But that should be easier to do if the obese person is in normal sinus rhythm and isn’t plagued by A-Fib symptoms like being unable to exercise because of a racing heart.
As Dr. Wilber suggests, measurement of epicardial fat volume should become a routine part of a yearly physical. For example, if a patient has a certain amount of epicardial fat volume, they should be told they are at a greater risk of developing A-Fib (and other health problems).
The good news is that weight loss both reduces the risk of developing A-Fib and reduces A-Fib burden (how badly A-Fib affects us). And it lowers the risk of recurrence after a successful catheter ablation.
Return to Index of Articles: AF Symposium: Steve’s Summary Reports
Last updated: Tuesday, February 9, 2016
Atrial Remodeling and the Transition From Paroxysmal to Persistent AF by Dr Jose Jalife-2014 Boston AF Symposium
2014 Boston AF Symposium
Experiments in Atrial Remodeling in Sheep and the Transition From Paroxysmal to Persistent A-Fib
By Steve S. Ryan, PhD
Dr. Jose Jalife of the Center for Arrhythmia Research of the University of Michigan described his experiments inducing A-Fib in sheep by pacing their hearts. He is trying to discover the mechanisms underlying the transition from paroxysmal to persistent A-Fib.
Background: Some patients remain paroxysmal (usually with anti-arrhythmic therapy), while a large proportion progress to persistent A-Fib. (In a study of 5,000+ A-Fib patients, 54% of those on rate control meds went into permanent A-Fib in one year.)1
Previous presentation summary: This talk was a continuation of Dr. Jalife’s 2013 Boston A-Fib Symposium presentation on his experimental studies with sheep. (See A-Fib Produces Fibrosis—Experimental and Real-World Data.) He implanted pacemakers in the hearts of sheep; then induced A-Fib by pacing for 6-30 seconds, then stopped, then paced again, etc. He continued this sequence until the sheep were in persistent A-Fib. He left them in A-Fib for about a year. Dr. Jalife also had a control group of sheep who were monitored but not paced into A-Fib.
Pacing Sheep into A-Fib
Once pacing started in the sheep, it took around 5.5 days to produce the first A-Fib episode. It took around 7-9 weeks of pacing for the sheep to move from Paroxysmal to Persistent A-Fib. At that point the sheep stayed in Persistent A-Fib without any further need of pacing. Dr. Jalife’s sheep developed two major types of atrial remodeling:
- Structural Remodeling (Fibrosis)
- Electrical Remodeling (ion channel expression changes)
(In humans, remodeling usually also results in atrial dilation. Dr. Jalife’s sheep once in A-Fib also developed significant Atrial Dilation compared to a control group of sheep.)
Unlike humans, the sheep didn’t develop heart failure, left ventricle dilation and dysfunction, or tachycardia-induced cardiomyopathy despite being in A-Fib for more than a year. This is possibly because sheep have a very good AV Node (unlike most humans) which filters the A-Fib pulses from affecting the ventricles and keeps the ventricular rate low.
Genetic Differences in Sheep
But there were differences in the sheep. Some sheep transitioned into persistent A-Fib fast (<40 days) while others needed more pacing to transition into persistent A-Fib (>40 days). Sheep from the same herd would have the same diet, environment, etc. But genetically they must have been different in their ability to hold out from transitioning into persistent A-Fib.)
All ventricular parameters remained normal in the paced sheep, except for atrial dilation and the markers of fibrosis which increased progressively as the sheep went from paroxysmal to persistent A-Fib. Fibrosis appeared in the right atrium, left atrium and the posterior left atrium. This fibrosis was the result of collagen deposition in the atria which is a permanent remodeling effect of A-Fib.
Dr. Jalife showed slides of a normal pig’s heart compared to a pig in persistent A-Fib. Well over ½ the atria seemed fibrotic.
Mechanisms of Electrical Remodeling
As expected, sustained A-Fib shortened the atrial action potential duration and refractory period. Also, rotor frequencies were increased. For example, in one sheep the dominant frequency of the first episode of paroxysmal A-Fib was 7.3 Hz, but increased progressively to 10.3 Hz during the transition to persistent AF. When AF in that sheep became persistent, the dominant frequent had stabilized at 11.3 Hz and remained constant for up to a year.
In perhaps the most important findings of Dr. Jalife’s experiments, the rate of increase in dominant frequency correlated strongly with the time at which AF stabilized. In other words, although the progression from paroxysmal to persistent A-Fib varied from one animal to another, the rate of dominant frequency increase could be used to forecast the time at which AF became persistent.
In other words, although the progression from paroxysmal to persistent A-Fib varied from one animal to another, the rate of dominant frequency increase could be used to forecast the time at which AF became persistent.
Dr. Jalife and his team also identified the mechanisms of electrical remodeling in sheep, which ion channels in the heart are responsible for transitioning sheep from paroxysmal to persistent A-Fib. Sodium and calcium heart electrical currents were lowered, while potassium and IK1 currents were increased. These electrical changes were associated with gene expression changes “in the alpha subunits of the L-type calcium (CACNA1C) and sodium (SCNSA) channel protein.”
- “Sustained AF reduces L-type calcium (Caᵥ1.2) and sodium (Naᵥ1.5) protein expression”
- “Sustained AF reduces the rapid sodium inward (INa) and L-type calcium (ICaL) currents”
- “Sustained AF reduces the transient outward current (Ito)”
- “Sustained AF increases the inward rectifying potassium current (IK1) and protein expression of the Kir2.3 channel”
The sheep model explains the structural and electrical remodeling that occurs in humans.
As in humans, there is a variable progression in time from paroxysmal to persistent A-Fib.
The rate of dominant frequency increase during such a progression predicts the time at which AF stabilizes and becomes persistent, reflecting changes in Action Potential Duration and densities of ICaL, IK1, INa and Ito.
Predicting the transition from paroxysmal to persistent A-Fib is feasible, at least in some patients, by measuring the increase in dominant frequency over time.
No one seeing Dr. Jalife’s presentation could doubt that A-Fib produces fibrosis. (Though even among sheep in the same environment, diet, etc. and with a similar gene pool, there were differences in how fast the individual sheep progressed to persistent A-Fib.) As patients with A-Fib, we have to base our medical decisions on the conclusion that A-Fib produces fibrosis; that if we stay in A-Fib over a significant period of time, we will progressively develop fibrosis which is currently irreversible and can lead to a host of other heart problems.
A common strategy today…is to leave you in A-Fib but control your heart rate by the use of beta-blockers, etc. But leaving you in A-Fib produces fibrosis which is irreversible and very damaging to the heart.
A common strategy today for treating A-Fib is to leave you in A-Fib but control your heart rate by the use of beta-blockers, calcium-channel blockers, etc. But leaving you in A-Fib produces fibrosis which is irreversible and very damaging to the heart. If your doctor wants to leave you in A-Fib, Dr. Jalife’s experiments would recommend that you get a second opinion, and ASAP.
One of the major advantages of a successful catheter ablation (and surgery) is it probably reverses the electrical remodeling effect of A-Fib. This makes intuitive sense. A heart beating in normal sinus rhythm (NSR) doesn’t usually produce those weird ion channel currents. But more research needs to be done before we can conclude this. However, a successful catheter ablation does not reverse fibrosis (structural remodeling), though it may reduce atrial dilation.
By identifying the actual mechanisms of electrical remodeling, Dr. Jalife’s ground-breaking experiments may lead to new therapies and drugs to combat not only the transition from paroxysmal to persistent A-Fib, but how to prevent patients from developing A-Fib in the first place. And using dominant frequency to predict when a patient is transitioning to persistent A-Fib, can be an invaluable tool for doctors (and reassuring for patients).
One of the scariest parts of Dr. Jalife’s presentation was how fast he could pace those sheep into persistent A-Fib. Obviously sheep aren’t people. But we know that for most people, there is a relatively short window of time when they progress from paroxysmal to persistent A-Fib (about a year). When you have A-Fib, you can’t count on genetics, diet, life style, environment, etc. to protect you from progressing to persistent A-Fib. Right now we just don’t know why some people stay paroxysmal for years, while most become persistent after a relatively short time. Worst case scenario, you have about a year. Act accordingly.
- Peykar, S. Atrial Fibrillation. Cardiac Arrhythmia Institute/Sarasota Memorial Hospital website. Last accessed Jan 5 2013. URL:http://caifl.com/arrhythmia-information/atrial-fibrillation/↵