Recent Article From Dr. Mandrola

From March 3, 2015: "A Report from Western AF: The Tide Is Changing

It was an honor to speak at the Eighth Annual Western AF Symposium in Park City, UT. Western AF is always a great meeting, but this year it was special. Something big happened. You could sense it in the room and in the conversations.

Mainstream electrophysiology gets it: AF is a symptom of a systemic disease.

At Western AF, giants in the field of electrophysiology, from Indianapolis, Philadelphia, Salt Lake City, Chicago, Cleveland, Boston, Australia, Germany, and the Netherlands all stressed that doctors who treat patients with AF must first treat cardiovascular risk factors.

You have heard this before, but never from the leaders of the field.

It all fits.

Consider these three questions:

Why have the results of AF ablation—for anything other than the rare case of focal AF—been so dismal?

Why would a panel of eight electrophysiologists describe different techniques for ablation of the same disease—persistent AF?

Why would we see atrial fibrosis and atrial electrical disease progress after successful ablation? (Pause on that one.)

It is simple. Because the atria reflect the health of the human being.

Dr Nassir Marrouche and his team at University of Utah organize Western AF, so the meeting reflects their research interests in fibrosis and imaging. We heard talks on how fibrosis affects the electrical function of the atria. It surely does, but where does the fibrosis come from?

We learned that high left atrial pressure, from, say, hypertension, obesity, sleep apnea, and maybe even endurance exercise, induces myocytes to lay down fibrosis. We heard that a bad night's sleep affects gene expression, and pericardial fat releases profibrotic cytokines.

Dr Kalyanam Shivkumar (University of California Los Angeles) taught us that the heart has its own—intrinsic—nervous system. Our heart feels stuff, is what I heard. (Just typing that feels good.)

We also heard this gem: weight loss and risk-factor management improve atrial electrical function—not just in sheep, in people!

These lessons explain why a procedure that creates more scar will never be the answer for a disease that stems from scar.

The take-home is this: when AF appears, it is sign that the atria is distressed. The answer, therefore, is to treat the problems that cause the distress.

A good doctor sees the problem, and then treats that problem.

Of Course It Is Hard

Now to the response that always arises when I report this news.

Dr Marrouche asked me the standard American-doctor question: "Okay, John, we now know lifestyle factors are critical, but how do we put this into action?"

My answer is leadership. Doctors, especially specialists, should take the lead. It is a top-down message. It is on those of us who wield the catheters. And it is not an easy message.

It is hard to change human behavior. It is hard to tell patients their way of life led to this problem. It is hard to go against market forces that favor procedures. And it is really hard to do all this in a short office visit, one made even shorter by electronic medical records.

Yet we fail, spectacularly so, if we substitute an expensive, risky, and wrong procedure for a symptom of a wider disease. Dr Greg Feld (University of California, San Diego) said it well in a Q&A session. Reflecting on the history of electrophysiology, he noted that we were successful in Wolff Parkinson White and supraventricular tachycardia (SVT) ablation because we understood mechanisms. We were even okay, he said, when we ablated focal AF from the pulmonary veins.

The problem now is we know the mechanism for most forms of AF—it is end-organ damage from systemic disease. And that is precisely why a catheter is not, nor will it ever be, the only answer.

My take is that heart doctors don't have to be lifestyle gurus. We don't need gimmicks. We just have to see the truth, speak the truth, and target the truth with our treatments. We must also enroll help—and convince our employers to see the value of a team approach for people with AF.

If an AF patient gets mad at this message and goes across the street for a second opinion (or to his primary-care doctor) and hears the same message, then there will be progress. But if that patient goes for a second opinion and hears he can be fixed with a procedure or a device, then the problem remains.

JMM"

________________

Dr. M is an EP.

Have enjoyed many of his writings.

/L

Hi Larry,

Thanks for posting this article. I too have been reading Dr. Mandrola's articles and have learned much from him. I am in full agreement with his views on the science of risk management as perhaps providing the major tools for reigning in the Beast. I personally am fully committed to managing risk factors in my own life.

I continue to loose weight so that I may walk around as a really slender person in blissful nsr. I have been tested in a sleep study and have learned that I do not suffer from sleep apnea. I precisely control my hypertension with my own 'cocktail' of BP meds I have developed over the years with the co-operation of my primary doc. I am expecting that as my weight drops to a BMI in the low 20's my hypertension will come into the normal range. (it has happened before) I eat no processed foods, no wheat, no sugar (except for fruits), eat healthy fats (fish oil, coconut oil, extra virgin olive oil, nuts), lots of veggies and some animal protein. As I continue to heal from my February 26th ablation in Austin I will begin slowly to implement an exercise program. For now I am walking and doing some "planks". At the 6-8 week mark I will ramp up somewhat, but still not pedal to the metal. Cross training will have to wait for at least 3 months.

I have been sharing this information to all who will listen. I am fortunate to have a Primary Doc. who is receptive to these ideas.

However, Dr. Mandrola sometimes veers into the minimalist camp in discussing ablation. He simply really doesn't seem to like it as a treatment, as you can read above. Of course, ablation is not the whole answer, we here know that. Where I differ with Dr. Mandrola is in his not emphasizing the importance of choosing a truly top tier EP for one's ablation procedure. In my opinion, it is only with the aggressive risk factor management, outlined above, AND the choice of an EP who has achieved prominence through research, writing, the training of hundreds of other EPs, and most important having performed thousands of successful afib ablations.

For me, as a former persistant afibber (three years in constant afib, no treatment) I chose to research and find the best EP I could find. TA DA! Dr. Andrea' Natale.

JohnB

Larry ~ Thanks for posting Dr. M's comments. I certainly agree that more should be done formally to investigate the underlying cause behind LAF….and also, I certainly agree that a reasonable amount daily of exercise is good.

What Dr. Mandrola (and so many others) fails to address is the knowledge that prolonged and intense exercise produces large amounts of oxidative stress that results in fibrosis which is found to underlie arrhythmia…and also that fibrosis formation is promoted by a magnesium deficiency. Fibrosis interferes with electrical conduction. These points have been posted in various threads here on our forum.

I was particularly interested in the work by William Rowe regarding fibrosis referenced in the Conference Room reports on the link to fibrosis and arrhythmia. There are numerous study references in both Conference Room Sessions 24 and 75 on Cardiac Fibrosis and Magnesium deficiency…

Jackie: AFib caused by endurance exercise (studies)
October 07, 2012

Exercise and Arrhythmia

I’d like to direct you to a report titled “Correcting Magnesium May Prolong Life” by William J. Rowe, MD, that was referenced in a magnesium thread (General Health Forum) not long ago and to share with you excerpts from several of many very important observational articles by Dr. Rowe.

Last February, when that observational report first circulated, I began following the various related links related not only to that report but to the many exercised-induced, heart-related problems reported Dr. Rowe which then link to a wider scope of other informative links.
[www.femsinspace.com]

Since so often we have new readers looking for arrhythmia help who also report they are endurance runners or exercisers, Dr. Rowe’s research reports investigating magnesium deficiencies in world-class athletes are highly informative and relevant to this thread as well.

Dr. Rowe is a physician involved in research studying the detrimental effects of space travel for both humans and animals and is not only an MD, but a Fellow British Interplanetary Society (FBIS) member. (Bio link follows)

The entire original report is definitely worth reading since, once again, it confirms the important role of magnesium and which segues right into all the previous Conference Room discussions on fibrosis formation being the result of magnesium deficiency and a cause for not only arrhythmia but other heart function problems as well.

Dr. Rowe says, “Since microgravity accelerates the aging process, the loss of the functional capacity of the cardiovascular system in open space flight is over ten times faster which not only means specific care and attention to space travelers, but also a type of ‘fast forward’ look at what eventually happens to us here on Earth at a much slower, but inevitable pace. It takes a huge amount of effort and medical detail to ensure that those in space remain healthy.”

Dr. Rowe’s microgravity observations confirm the strong need for magnesium’s protective properties as an antioxidant and calcium channel blocker against the adverse effects in space; i.e., oxidative stress, insulin resistance, inflammatory conditions in space with animals showing significant endothelial injuries and mitochondrial damage…..not all that different from what we encounter here in everyday life.

Following are a few quotes/clips from many of the very interesting observational reports. Hopefully, you’ll be inspired to continue reading.

Jackie

Each Marathoner is Different
William J. Rowe M.D.
Daily Progress, Charlottesville, Virginia, Jan. 25, 2012

The recent encouraging article in the Sunday issue (Jan 15, 2012) citing a New England J. of Medicine paper, I believe, is somewhat misleading with the concluding statement that since the incidence of sudden death is very low among those participating in marathons, it follows that this is a reasonably safe proposition.

My concern is this: although the incidence of sudden death during this single event is extremely low, might there not be recurring asymptomatic injuries, during or immediately after such events? “ Silent ischemia “ (an imbalance between oxygen supply and demand ) is a huge problem in Cardiology and provides a rationale for example for performing exercise stress and invasive tests.

Granted we have the genes for long distance running based on the fact that the Navajo, Tarahumara Indians, Bushmen of the Kalahari desert, and the Aborigines all have the capability of chasing an antelope for up to 2 days until the animal drops from exhaustion. But with my having published in 1992 a LANCET study of Sy Mah, the Guinness Book of Records holder for having completed 524 marathons, free of any cardiac symptoms despite findings at autopsy consistent with permanent injury to the normal heart , I am concerned that prospective marathoners will develop a false sense of security.
Continue: [femsinspace.com]

Extraordinary unremitting endurance exercise and permanent injury to normal heart
WILLIAM J. ROWE, MD
The Lancet, Vol 340 VOL 340: SEPT 19, 1992, pp. 712-714

(selected quotes)
This hypothesis is that permanent cardiac injury could develop in some endurance athletes despite the absence of coronary atherosclerosis and ventricular hypertrophy. The proposed mechanism by which this injury could arise involves two physiological "vicious cycles". The first vicious cycle would occur between severe ischaemia and high catecholamines, the second would be between coronary vasospasm (induced by high catecholamines) and endothelial injury. The likelihood of the injury becoming permanent might increase if there is insufficient time between bouts of endurance exercise for regression of ischaemia and endothelial repair. Furthermore, magnesium ion deficiency, which can be induced by exercise, could exacerbate these vicious cycles and also contribute to catecholamine-induced thrombogenesis. In addition to ischaemia, there are several mechanisms, including the effect of free fatty acids liberated by the lipolytic effect of high catecholamines, that could cause direct myocardial injury.

Introduction
Early man's survival before the development of even the crudest of weapons probably depended on his capacity for great endurance. This capacity is exemplified today by the Tarahumara Indians of northern Mexico who can chase a deer for up to 2 days until the animal drops from exhaustion.[1] Primitive hunting societies follow a "Palaeolithic rhythm" of 1 or 2 days of hunting, 6 to 8 hours a day, followed by 1 or 2 days of rest.[2] Could some endurance athletes benefit by this restraint? In the past 2 decades, there has been a sharp increase in the number of extremely challenging endurance events. Such events include the world's longest annual ultramarathon (over 1000 km) in Australia, and in the USA the most arduous yearly marathon, to Pike's Peak (4300 m). The cavalier attitude to the potential cardiac risk may result partly from the popular belief promulgated by Karvonen and cited in a widely circulated textbook of the heart,[3] that there is no evidence that strenuous athletic activity in a trained individual with a normal heart increases the risk of early death or morbidity from cardiovascular disease.

Morbidity related to endurance exercise
The case of a fatal myocardial infarction in the absence of significant coronary atherosclerosis reported by Green et al[4] in a runner nearing the end of a marathon was complicated since the athlete probably also had heat stroke.[5] Acute pulmonary oedema developed in 2 apparently healthy participants near the end of the 90 km Comrades Ultramarathon in South Africa. Follow-up studies revealed that the athletes' coronary arteries were angiographically normal and that there were no other apparent confounding factors[6]
With regard to a permanent cardiac injury, Sy Mah, who set a world record of 524 marathons, was shown by stress tests to have probable exercise-induced coronary vasospasm with circadian variation 9 months before death from lymphoma at age 62 years. There was no history of heat stroke,[4,5] nor were any other confounding factors found at necropsy, which revealed focal fibrosis of the left ventricular papillary muscles. It was postulated[7] that these findings were related to exercise induced high concentrations of catecholamines.[8]

Magnesium deficiency and thrombogenesis
Magnesium ion deficiency is a further possible complication of long exercise,[18-20] some deficiency may still be present 3 months later.[18] The mechanism is not clear, but may be partly due to removal of free magnesium ions from the circulation by chelation with catecholamine-induced free fatty acids.[19]

Exposure to heat also contributes to magnesium ion deficiency.[20] This deficiency increases release of catecholamines,[21] increases the potential for coronary vasospasm,[22] potentiates the vasoconstrictor action of catecholamines,[22] and—in combination with catecholamine infusions or stress—sensitises animals to myocardial necrosis.[23]

Magnesium ion deficiency may precipitate a hypercoagulable state,[23] which may be aggravated by residual increased catecholamines (conducive to platelet aggregation and thrombin generation),[24] the increase in catecholamine concentration may persist until the second day after a marathon.[25] It is noteworthy that in a group of 20 patients with vasospastic (variant) angina Goto et al [26] showed that almost half had magnesium ion deficiency that is often unrecognised.[19,21,26]
Continue reading: [www.femspace.com] for this report and the many other related articles at these links: [www.femsinspace.com]

A World Record Marathon Runner with Silent lschemia without
Coronary Atherosclerosis*
William Rowe, M.D.
A 62-year-old world record marathon runner was found to
have silent ischemia manifested by a very abnormal stress
test, whereas at autopsy nine months later, there was
virtually no coronary atherosclerosis nor other disease of
the coronary microvasculature. However, there was focal
fibrosis of the papillary muscles consistent with remote
ischemia secondary to possible CV. It is postulated that
endurance-related high catecholamine levels might have
been responsible.
(the pdf version of this article has a graphic color photo of fibrosis in the ventricle.) [journal.publications.chestnet.org]

American J. Cardiology 86:256, 2000
Our Ancestors Had It Right
William J. Rowe, MD
Swanton, Ohio 28 March 2000
The absorption of just the right amount of iron through the intestine (duodendum) might have provided significant cardiovascular advantages to early man, the Masai of today, and conceivably has been advantageous to an extraordinary urban athlete. Excess iron may be more detrimental than iron deficiency, because high iron levels can lead to the formation of highly reactive hydroxyl radicals and lipid peroxidation, conducive to early atherosclerosis. Furthermore, there must be enough protein in the diet to sequester iron.(1)
But can we, with our modem diet and often iron supplements, establish a proper balance?
Continue: [www.femsinspace.com]

Potential Myocardial Injuries to Normal Heart with Prolonged Space Missions
Selected quotes:
(Animal) Studies by the Russians, of experimental animals in space, demonstrated pronounced impaired microcirculation and serious myocardial pathology, even on space flights of only a few weeks. Edema of the endothelium was demonstrated, with altered endothelial permeability, and some of the coronary vessels were completely occluded. There was also noted atrophy of the cardiac muscle. Other studies suggested the possibility that some of these changes were stress-related, since there was significant increase in the concentration of norepinephrine in cardiac tissue. Finally, in addition to decreased activity of enzymes with injury of the mitochondria, there was evidence of impairment in the repair mechanism.5 These animal studies suggest that even relatively brief space missions, may predispose to a myocardial infarction in the absence of coronary artery disease prior to the space flight.

Mechanisms for Endothelial Injury
Too much or too little exercise may damage the endothelium through similar mechanisms.4

High shear stress and turbulence, precipitated by catecholamine-induced coronary vasospasm may injure the endothelium and in turn lead to further vasospasm by a vicious cycle. High catecholamines, with release of high levels of free fatty acids, which bind magnesium ions, may persist by ongoing vicious cycles as well. A third vicious cycle can be precipitated by elevations of catecholamines related to ischemia. These mechanisms can injure the normal heart from extraordinary unremitting endurance exercise.2,3
Continue:[www.bad-radkersburg-online.at]
William J. Rowe, M.D.
Former Clinical Assistant
Professor of Medicine
Medical College of Ohio at Toledo

(as reported in CR 74 on fibrosis)
Fibrosis in heart disease: understanding the role of transforming growth factor-beta in cardiomyopathy, valvular disease and arrhythmia.
Khan R, Sheppard R.
Source Immunology. 2006 May;118(1):10-24.
McGill University, Faculty of Medicine, Montreal, Quebec, Canada.
Abstract
The importance of fibrosis in organ pathology and dysfunction appears to be increasingly relevant to a variety of distinct diseases. In particular, a number of different cardiac pathologies seem to be caused by a common fibrotic process. Within the heart, this fibrosis is thought to be partially mediated by transforming growth factor-beta1 (TGF-beta1), a potent stimulator of collagen-producing cardiac fibroblasts. Previously, TGF-beta1 had been implicated solely as a modulator of the myocardial remodelling seen after infarction. However, recent studies indicate that dilated, ischaemic and hypertrophic cardiomyopathies are all associated with raised levels of TGF-beta1. In fact, the pathogenic effects of TGF-beta1 have now been suggested to play a major role in valvular disease and arrhythmia, particularly atrial fibrillation. Thus far, medical therapy targeting TGF-beta1 has shown promise in a multitude of heart diseases. These therapies provide great hope, not only for treatment of symptoms but also for prevention of cardiac pathology as well. As is stated in the introduction, most reviews have focused on the effects of cytokines in remodeling after myocardial infarction. This article attempts to underline the significance of TGF-beta1 not only in the post-ischaemic setting, but also in dilated and hypertrophic cardiomyopathies, valvular diseases and arrhythmias (focusing on atrial fibrillation). It also aims to show that TGF-beta1 is an appropriate target for therapy in a variety of cardiovascular diseases.
PMID:16630019
[www.ncbi.nlm.nih.gov]


REFERENCES:

Original Report:
Correcting magnesium deficiencies may prolong life.
Rowe WJ.
Clin Interv Aging. 2012;7:51-4. Epub 2012 Feb 16.
Source: Medical University of Ohio at Toledo, Ohio, USA.
[www.ncbi.nlm.nih.gov]

Short Biography of Dr Rowe
William J. Rowe M.D. FBIS (Fellow British Interplanetary Society ) is a board certified specialist in Internal Medicine. He received his M.D. at the University of Cincinnati and was in private practice in Toledo, Ohio for 34 years. During that time he supervised over 5000 symptom – limited maximum hospital-based treadmill stress tests. He is a former Assistant Clinical Professor of Medicine at the University of Ohio, School of Medicine at Toledo. He studied 3 world class extraordinary endurance athletes and published their exercise –related magnesium deficiencies. This triggered an 18 year pursuit of the cardiovascular complications of Space flight. He has published in LANCET that extraordinary, unremitting endurance exercise can injure a perfectly normal heart and in CIRCULATION a description of only the second Space-related Syndrome. He has been listed in the Marquis Who’s Who of the World from 2002-2009, 2013. [www.femsinspace.com]


A review of these links is timely in light of Dr. Mandrola’s comments.

Afib and Cardiac Fibrosis
[www.afibbers.org]

Cardiac Fibrotic Remodeling
[www.afibbers.org]

Jackie,

Not much chance that I would engage in "Extraordinary unremitting endurance exercise", marathons, or "prolonged and intense exercise", even after I completely heal from my recent ablation.

I really am curious, if there are folks here at afibbers.net that place themselves in that group of ultra extreme exercisers.

It is interesting information, though. Moderation in all things, I guess. It seems that there is, in fact, too much of a good thing.

Thank you, Jackie.



Edited 1 time(s). Last edit at 03/12/2015 09:27PM by JohnB.

John,

"I really am curious, if there folks here at afibbers.net that place themselves in that group of ultra extreme exercisers."

and from Jackie's post: "and in the USA the most arduous yearly marathon, to Pike's Peak (4300 m)."

Well I was only moderately nuts as I would only compete in the race up Pike's Peak (considered a half marathon) not the marathon which goes back down, too. I did it for 10 years. I quit training for or entering endurance races two years after I was diagnosed with afib - I'm a slow learner.

I'm sure chronic fitness was my ticket into the afib club.

I'm still pretty active, but don't do endurance training and generally avoid endurance activities. For example, I'll downhill ski, hard, all day, and on the steepest slopes. However, I'll decline to hike or skin up on cross country or AT skis then ski down, foregoing the endurance portion. I also avoid competing so I don't feel I have to push myself to the max. One friend in his 20's wanted us to be a team in an all day competition to see how many laps skiing the steeps we could do. I declined as I knew I'd push myself very hard so as not to let him down.

My question to myself is how much is too much? There is no set answer, but the balance point I've chosen has worked for 10 years. for me. I'm guessing the answer is different for everybody.

The board has morphed from mostly lone afib people in the early years to more general afibbers now. In the early years, it was very common for heavy endurance athletes to show up. These included former olympians.

George

John and George -

Other than extreme endurance exercisers and marathoners, probably most afibbers here don't get to the ischemic stage. Since fibrosis is reversible and magnesium deficiency is real... as found in the reports by Dr. Rowe.. I wanted to emphasize the the importance of always considering that afibbers are typically found to be deficient in magnesium. If they do a lot of aerobic exercise, the fibrosis/ischemic tissue is all but a guaranteed certainty.

I posted what I did to point out that the underlying negative effects of prolonged aerobic exercise... and the unavoidable damage from ROS.. (oxidative stress) resulting in not only fibrosis but the ischemic tissue that can also accompany and which is not reversible.

I don't recall that has been addressed by Dr. Mandrola.


Fibrosis – a substrate for atrial fibrillation
Apart from electrical remodeling and contractile dysfunction, alterations in atrial tissue structure, namely atrial fibrosis, have been shown to increase the susceptibility to AF and may serve as a critical substrate in the formation of the arrhythmia. Additionally, atrial fibrosis is hard to reverse and has therefore been considered as a major contributor in the progression from paroxysmal to persistent or permanent AF (Xu et al., 2004). [www.ncbi.nlm.nih.gov]

Jackie

George and Jackie,

Thank You both for your comments. They do help me to understand and continue my education on this complex and mysterious malady.

I, for one, was probably born with a couch potato gene or two. In my life, I have exercised regularly only intermittently. My way to afib was probably marked by obesity, too little exercise, too much alcohol, and a few years of untreated hypertension. That sentence now shocks me with its obviousness. Ah, youthful ignorance!

Thankfully, I have been taking many of the right vitamins and mineral supplements for more than 35 years. Nutrition has been a field of study for me for another 25 years. So far, it is only hypertension and afib that have plagued me.

I actually do now feel confident that I am finally on the right track. By aggressively addressing the known risk factors, eating right, becoming slender, exercising, keeping my stress levels low and following the insights afforded by studying Functional Medicine, I hope to be able to enjoy, for many years, the Blissful NSR that Dr. Natale has given me.

My belief in the fundamental good will of the Multiverse has certainly led me to this wonderful Forum where I have learned the way back to health.

Thank You All
JohnB

"...Exposure to heat also contributes to magnesium ion deficiency.[20..."

This little gem of a quote can, i think, explain why hot weather or even an overheated room makes me extra vulnerable to afib.

PeggyM