Does exercise cause myocardial fibrosis? Please don't say exercise can cause heart disease

What one treatment in the practice of medicine are you most sure of?

For me, it is absolutely clear: Regular exercise promotes and sustains wellness. Don't call it exercise; that's too clinical. Just say using your body on a regular basis.

Not all, but a large share, of this American College of Cardiology (ACC) 2013 meeting addresses diagnostic tests for and treatments of diseases that could have been prevented or delayed. Excluding genetic disorders and flukes of nature (paroxysmal supraventricular tachycardia and idiopathic cardiomyopathy, for example), much of what a heart doctor treats is avoidable. We can all agree that the human race is suffering through a period of severe underexercise.

This is why it hurts me to even bring up the idea that too much exercise could cause problems. You don't want anything down in print about exercise being bad for the heart.

But why wouldn't exercise have a dose-response curve? Everything does, except, perhaps, love. (Whoa, did I just type that?)

Endurance exercise and its potential to cause heart disease is a compelling narrative. All good stories feature conflict.

On the one hand, exercise is good and vital. But . . . on the other is the endurance-athlete mindset (I know them well). These folks have studied the training modules: You load the muscle with stress. Although this induces short-term inflammation, with adequate rest, the muscle adapts and comes back stronger. Our competitors train like crazy, so to win we must outwork our adversaries. Alas, the problem is that training like Lance does not mean riding like Lance. (That simile is less apropos these days, but you understand.)

There were a number of notable sessions at the 2013 ACC meeting that shed light on this intriguing topic. In the next few paragraphs, I will offer my completely biased views on the matter of chronically inflaming oneself over a lifetime.

Endurance athletics and AF

During a session entitled Turn the beat around: Atrial fibrillation in the active patient and athlete, Dr Brian Olshansky (University of Iowa) made clear that long-term endurance athletics (definitely) increases the risk of atrial fibrillation. There can be no debate on this. He also pointed out that female gender might be protective. Women endurance athletes seem not to have the association with AF. That was interesting. (Are women smarter about training?)

What is the mechanism of AF in athletes?

The short answer is we do not know. In the same session, Dr Rachel Lampert (Yale) offered evidence that there might be something to the interaction between high vagal tone interspersed with bursts of adrenaline. It makes sense because we know both milieus are arrhythmogenic: vagal stimulation decreases action potential duration and enhances electrical heterogeneity, while norepinephrine increases automaticity and ectopy. Add to this the possibility of structural remodeling and inflammation, and you have a good theory of why athletes are susceptible to AF.

The only thing I would add to this story is the possible role of genetics. Clearly, the phenotype of slow-twitch athletes with AF is repetitive—tall, Northern Euro, detail-oriented, measured, determined, etc. Why wouldn't their genotypes be similar as well? We know that AF has a strong genetic basis; it's a good bet that susceptibility to the effects of exercise is, too. What's more, might the same genes that make one think riding six hours in the rain is fun also make one susceptible to AF?

Is there such a thing as the Phidippides cardiomyopathy? It's a relevant question for electrophysiologists, because fibrosis increases the susceptibility to arrhythmia and sudden death. A great deal of observational data suggest that a small but not insignificant minority of endurance exercisers develop myocardial scar, predominantly in the right ventricle and septum. One theory is that short-term inflammation induces injury, and if the heart is never allowed to rest and heal, inflammation leads to scar. Postmarathon and -triathlon studies confirm transient rises in cardiac enzymes and RV dysfunction. And some studies show a correlation between exercise chronicity/intensity with fibrosis. (The above hyperlink takes you to a thorough review article on the subject.)

Not everyone agrees. Dr Kyler Barkley from the University of Texas presented this series of 93 healthy senior citizens for whom an extensive 20-year bank of demographic data were available. They grouped subjects into four strata of exercise ranging from sedentary to competitive athletes. Fitness tests along with MRIs were done in each of the subjects. Their findings were both simple and elegant. Cardiopulmonary fitness, measured by VO₂ max tests, correlated well with training, which isn't surprising, but confirms the validity of the self-reported exercise dose. Most importantly, none of the competitive-level seniors had evidence of scar on MRI scans. The conclusion: long-term endurance exercise does not cause fibrosis.

Two points were raised in the Q and A. The first addressed this study's differences from prior observational data on fibrosis. Dr Barkley hinted at the possibility that occult heart diseases might have accounted for the discordance. Their cohort was well measured and followed closely over two decades. The second issue was whether his study's subjects represented a survivor cohort. Were they just a self-selected group that tolerated the chronic exercise? The answer here is unknown.

My take

Please don't ask where the upper limit of exercise is. I don't think there is just one threshold. Individuals differ in their tolerance for stress. As physicians, though, we can emphasize to our patients what we know:

It is possible to exercise enough to harbor an increased risk of arrhythmia and maybe even induce fibrosis. It's worth noting that "superfitness" does not inoculate against heart disease. Do not judge a book by its cover. The engine should not be assumed healthy because the chassis looks sleek.

A final note: Good luck getting this cohort to modify their lifestyle.

JMM

Your comments

	Does exercise cause myocardial fibrosis? Please don't say exercise can cause heart disease
	# 1 of 18	March 11, 2013 03:44 (EDT)
	Harold Baird	Weight training also does it. I have a long term history of weight training. I also have been abladed for AFIB and AFLUTTER. My Atria is enlarged a little, 45mm, with no high blood pressure at rest. Heavy lifting gives a short term increase in blood pressure. 1.5 to 2.0 grams of Potasium supliment daily for the last eight months has completely stopped the PAC's I had since the AFIB ablation in JAn 2009. Author's disclosure (Mar 11, 2013) I have no relevant disclosures to make in connection with this topic.
	# 2 of 18	March 11, 2013 04:24 (EDT)
	Paul Demjanenko	Too much exercise is harmful I am convinced that too much exercise is harmful. I have a handfull of friends-competitive male athletes, all in their 50s, who have either Afib, flutter or cardiomyopathy. These people have exercised at a high level for 30+ years(marathons, triathlons). They are all otherwise very healthy. It is interesting to hear them talk about their meds and ablations. There must be some dose response relationship. How much exercise is too much? Author's disclosure (Mar 11, 2013) I have no relevant disclosures to make in connection with this topic.
	# 3 of 18	March 12, 2013 04:43 (EDT)
	nancy croteau	Women, bodies, and exercise I was in really great shape from lots of swimming, running, and dance. Then came the heart attack. I am convinced that one cause was too much swimming, running, and dance and too fast swimming, running, and dance. I did it to look beautiful. It will be hard to convince younger women not to overdo in the current climate of beauty and femininity. Author's disclosure (Mar 12, 2013) I have no relevant disclosures to make in connection with this topic.
	# 4 of 18	March 13, 2013 06:27 (EDT)
	EFTHIMIOS ANAGNOSTOU	everything in excess is against nature Walking is man's best medicine. Hippocrates Author's disclosure (Mar 13, 2013) I have no relevant disclosures to make in connection with this topic.
	# 5 of 18	March 14, 2013 03:15 (EDT)
	Barbara Zimich	correlation with any other factors? As a long time ETT (exercise tolerance test) Tech, athlete, clinical exercise specialist and coach, I've seen many arrhythmias in athletes. Anecdotally in long distance, long time runners more than bikers. As in the general population, heredity does its part. And, I hesitate to say, a correlation with drinking. Fine wines and good beer are preferred in the "cohort" I've "studied", but there it is. Author's disclosure (Mar 14, 2013) I have no relevant disclosures to make in connection with this topic.
	# 6 of 18	March 21, 2013 01:22 (EDT)
	Mike smith	Resistance training is an issue Many wonderful papers by Miyachi and Tanaka et al have found increased arterial stiffness as related to resistance training performed absent an aerobic training program. The performance of the heart is determined by the blood vessels. Like anything, balance is key. I doubt that 50 years from now we will see a huge spike in the prevalence of AF due to "over exercising", where we will continue to see diabetes, metabolic syndrome and other comorbidities skyrocket as people will cherry pick studies like this to say "see, exercise is bad for you! I knew it all along! supersize my happy meal nom nom nom" Author's disclosure (Mar 21, 2013) I have no relevant disclosures to make in connection with this topic.
	# 7 of 18	March 21, 2013 01:48 (EDT)
	John Hagan	Too much exercise is too much: over-dosing can be hazardous I got the below e-mail today from the son of a close friend. The young man (mid-late 30’s) is an elite athlete as is his wife. He is a swift runner also a long distance bicyclist and has biked across several states including Colorado. I think he and his wife want to run marathons. I have sent them all growing literature on cardiovascular toxicity of excessive endurance exercise. Both he and his wife resisted. He sent me this e mail with a link to a video in which two time Iron Man Triathlon winner and top world triathlon champion Normann Stadler, age 38 describes his diagnosis of aortic valve dilation and insufficiency. Note that in this interview the commentator never asks about the relationship of Stadler’s over the top work outs for years on end and the development of the heart valve disorder. Note also near the end that Stadler says he has heard from athletes all over the world who had the same problem. This is one aspect of the cardiology literature I have not researched. Is there an established or putative relationship to the types of excessive endurance cases you’ve been reporting with valvular heart disease? If not could this not be the nidus for collection of a series like the ones demonstration high CAC scores and Pheidippides Cardio-myopathy. Could this close the circle? Historically remember there was a huge resistance to linking smoking with lung cancer, especially in the studies funded by big tobacco and physicians that advertised smoking ‘to soothe the throat”. Once it was established smoking causes lung cancer it was again a reach to tie tobacco with heart disease, after that physicians and research “got it” that tobacco was bad multi-system for the human body and a whole cascade of diseases across many body systems were tied to tobacco use. Could not the same thing happen when physicians/cardiology “gets it” that going flat out red line endurance exercise over years and years may cause lots of other CV problems. Ultrasound studies of carotids in endurance athletes I believe are abnormal. Could not all this pounding also destroy the circular structure of the heart valve especially the aortic? What do you think?. COPY e-mail to Dr. Hagan. PLEASE FOLLOW LINKS TO TWO TIME WORLD IRON MAN CHAMPION NORMANN STADLER TALK ABOUT HIS HEART AORTIC VALVE SURGERY. Dr. Hagan, I hope you are doing well! I stumbled upon the below video this past weekend, and thought of you. It’s been on mind a lot. Normann is a two time Ironman world champion. The title says it all, “Breakfast with Bob: Normann Stadler talks about his heart surgery”. Many of his comments are exactly what you have said in the past, “I never thought I would have a heart problem”. He talks about his “open Aortic valve problem”. You will not surprised to hear when he talks about the many emails he gets from athletes all over the world who share in the same problems. I look forward to your comments. or John C. Hagan III, MD, FACS, FAAO, Editor, Missouri Medicine medical journal Author's disclosure (Mar 21, 2013) 1. I am an ophthalmologist by way of general practice; I am age 69 and have been for 43 years an excessive endurance exerciser. (4 marathons, 25 half marathons, 2 Half Iron-Man's; I have had exercised induced "lone AF", and an extremely high CAC score with negative heart work up. I personally believe excessive exercise can cause CV disease and have published on same. I think moderate exercise is the best medicine physicians can prescribe; just don't "overdose".
	# 8 of 18	March 21, 2013 01:54 (EDT)
	John Hagan	Omited hyperlinks to Iron Man Champion has heart surgery http://triathlon.competitor.com/2011/10/features/breakfast-with-bob-normann-stadler-talks-about-his-heart-surgery_41437 or http://on.aol.com/video/ironman-world-champion-normann-stadler-on-his-heart-surgery-517414378 Author's disclosure (Mar 21, 2013) 1. I am an ophthalmologist by way of general practice; I am age 69 and have been for 43 years an excessive endurance exerciser. (4 marathons, 25 half marathons, 2 Half Iron-Man's; I have had exercised induced "lone AF", and an extremely high CAC score with negative heart work up. I personally believe excessive exercise can cause CV disease and have published on same. I think moderate exercise is the best medicine physicians can prescribe; just don't "overdose".
	# 9 of 18	March 21, 2013 06:49 (EDT)
	James O'Keefe	Interaction between alcohol and excessive endurance exercise and AFIB The risks of CV disease from smoking is a straight line linear relationship, the more you smoke the worse your risk for many adverse CV outcomes. The exercise--CV health relationship is U shaped and bidirectional, none is bad, too much is bad. Moderate is just right. Like alcohol that way. The devil is in the details: not sure exactly where the safety threshold is with exercise when a good thing becomes less good, or even harmful. BTW, the interaction between moderate (or higher) alcohol intake with excessive exercise for increased risk of atrial fibrillation is almost certainly real and important. I know it has been something I have personally seen is several patients, colleagues, etc. Author's disclosure (Mar 21, 2013) I have no relevant disclosures to make in connection with this topic.
	# 10 of 18	March 22, 2013 01:12 (EDT)
	Sid Nelson	Strenuous exercise dose-response: No added CHD benefits (& probable harm) Asking for the dose-response curve for exercise is practicing evidence-based medicine, instead of faith-based medicine. Unfortunately, though, the actual evidence for significant CVD benefits with exercise is really not too good. In the recent “Dose Response Between Physical Activity and Risk of Coronary Heart Disease A Meta-Analysis,” Sattelmair, et al. aggregated the data from 9 studies which allowed for quantitative estimates of leisure-time physical activity in order to build a composite dose-response curve. For men, there was no CHD improvement past about 800 kcal/week worth of exercise and, for women, no added benefit between about 500 and 2000 kcal/week. The curves just flattened out. At these activity levels, the average hazard ratio for CHD, compared to those with zero physical activity, was only about 0.80 for men and 0.75 for women. For the resulting dose-response curves, see Circulation, 2011; 124:789-795. According to the recent Aerobics Center Longitudinal Study, one of the largest single exercise/running analyses performed to date, with more than 52,000 men and women participating (and being later, not included in the above meta-analysis), if you ran modestly at less than 5 miles per hour or if you ran 6 or 7 times per week for years and years, your all-cause mortality rate, compared to sitting on the couch, over 15 years dropped by only about 10%. Worse, in this analysis the dose-response curve was definitely U-shaped. According to the researchers: "The fact that it reached its plateau at such a low level is surprising, as is the fact that it didn't level off but actually went the other way. We never had a point where runners did worse than nonrunners, but really, if you put it in almost a joking way, it showed that if you ran enough you got yourself back to the level of a couch potato. You lost the survival advantage." See: Lee DC, Pate RR, Lavie CJ, et al. “Running and all-cause mortality risk—is more better?” American College of Sports Medicine 2012 Annual Meeting; June 2, 2012; San Francisco, CA. Presentation 3471 and O'Keefe JH, Patil HR, Lavie CJ, et al. “Potential adverse cardiovascular effects from excessive endurance exercise,” Mayo Clin Proc 2012; 87:587-595. The quote comes from where this had been previously reported on by TheHeart.org: Google “The not-so-long run: Mortality benefit of running less than 20 miles per week”. (Note also that it is not uncommon for even modest exercise to negatively affect intermediate cardiovascular risk factors. See Bouchard C, Blair SN, Church TS, et al. “Adverse metabolic response to regular exercise: Is it a rare or common occurrence?” PLoS ONE 2012: “Th[is] new publication is thus the culmination of findings from six [exercise] studies... Using the above definitions, 12% of participants had an adverse response for SBP, 13% for HDL-C, 10% for triglycerides, and 8% for insulin. About 7% of participants experienced adverse responses for two or more risk factors.” Exercise also didn’t help diabetics any in the recent Early ACTID randomized control trial: Andrews, et al., “Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes,” Lancet 2011; 378: 129–39.) The fact is, if you stress any organ over an extended period, you ultimately harm the organ. The heart and vascular system are not somehow special in this regard. Unfortunately, we have a multi-multi-billion-dollar exercise industry now vested in this country, so you will have to be satisfied with being inundated with faith. Evidence be damned. Author's disclosure (Mar 22, 2013) I have no relevant disclosures to make in connection with this topic.
	# 11 of 18	March 22, 2013 01:27 (EDT)
	Sid Nelson	Actually, it’s worse than that It’s actually, worse than the meager 15-to-20% CHD benefits noted above. There are two critical flaws in all of the many observational exercise trials that I’ve seen. First, none of the exercise trials explicitly test for the possibility of reverse causality. They all just compute their hard-outcome rate-ratios relative to couch-potatoes at a zero or low activity level. But it is not that high exercise or activity-levels cause better health; it’s that healthier people will be more willing and able to have higher exercise or activity-levels. The no/low exercise cohort automatically contains many already-unhealthy people in it who can’t/don’t exercise and it is their hard-outcomes that drive the differences between the first few cohort divisions. Unfortunately, we can’t adequately control for this in our regression equations. We need high-adherence, long-term, hard-outcome RCTs--which, unfortunately, aren’t going to happen. But if we could do these, then we’d likely see no gains--most likely net harms--from exercise, particularly strenuous exercise. So that initial, quick 15-20% risk reduction is likely just an artifact of unaccounted-for confounders and reverse causality. Second, and perhaps even more important, these trials never control for plasma vitamin D (and they could...). If there are any actual beneficial CVD effects from higher exercise/activity levels, it’s likely not from stressing the heart or vascular system itself, but rather from the body’s inevitable added exposure to sunshine and requisite higher vitamin D production and plasma levels and their consequent biologic effects. It is self-evident that those who exercise or are more active will, on average, spend more time outdoors exposed to sunshine. It is well established that the higher the activity level, the higher the measured serum 25-Hydroxyvitamin D levels. See, for example, Scagg et al., “Serum 25-hydroxyvitamin D3 is related to physical activity and ethnicity but not obesity in a multicultural workforce,” Aust N Z J Med. 1995 Jun;25(3):218-23: “Conclusions: ... [P]eople who are inactive, have decreased body levels of vitamin D; this might partly explain their increased risk of cardiovascular disease.” It is also well established that those with higher 25(OH)D have significantly fewer CVD events and lower mortality. See, e.g., Arch Intern Med. 2008;168(11):1174-1180. "After adjustment for matched variables, men deficient in 25(OH)D (<15 ng/mL ) were at increased risk for MI compared with those considered to be sufficient in 25(OH)D (>30 ng/mL) (relative risk ... 2.09)"; also Clin Endocrinol (Oxf). 2009 Nov;71(5):666-72. "After adjustment ... the hazard ratios [for the first 25(OH)D quartile when compared with the upper three] remained significant for all-cause [HR=1.97] and for cardiovascular mortality [HR=5.38]"; or, for a meta-analysis, Wang, et al., “Circulating 25-Hydroxy-Vitamin D and Risk of Cardiovascular Disease A Meta-Analysis of Prospective Studies,” Circulation Cardiovasc Qual Outcomes 2012 [with 19 studies with composite low/high relative risks for various CVD outcomes of 1.40 to 1.60]. Note how much higher these 25(OH)D associations are compared to those for exercise--and these vitamin D analyses control for activity level, while the exercise studies don’t control for 25(OH)D. Conclusion: The evidence so far appears to me to say that popping a few D3 pills each day would provide far greater benefits, and at far less costs, than exercise. See, e.g., Vacek et al., "Vitamin D Deficiency and Supplementation and Relation to Cardiovascular Health," Am J Cardiol. 2012 Feb 1;109(3):359-63. There the difference in hard outcomes was dramatic: "Vitamin D supplementation conferred substantial survival benefit (odds ratio for death 0.39). Author's disclosure (Mar 22, 2013) I have no relevant disclosures to make in connection with this topic.
	# 12 of 18	March 22, 2013 01:29 (EDT)
	Sid Nelson	Finally... Commenters above have given a lot of anecdotes where strenuous exercise ultimately causes AF. In addition to cardio effects, just about every strenuous exerciser that I have known eventually had to stop or scale down their regimes due to an orthopedic or other injury. (How about you?) In other words, if you are a long-time exerciser, you eventually seriously hurt yourself. Close to 100% of the time. Now how is that “healthy”? Maybe it isn’t so absolutely clear that regular exercise promotes and sustains wellness after all... Author's disclosure (Mar 22, 2013) I have no relevant disclosures to make in connection with this topic.
	# 13 of 18	March 24, 2013 03:55 (EDT)
	D Hackam	regular exercise, regular nutrition I believe in a balanced approach. Try to mimic the conditions of mother nature. Doing a few hours of vigorous gardening, or less time in wood chopping, taking brisk walks, or hitting the gym for brief, even intense periods of time is likely to be safer and healthier than overexertion during marathons and similar endurance exercise situations. The body is like a tool - don't overuse it, or it will break. Second, we have ignored the importance of healthy diets for far too long and focused on minimizing fat intake, to the detriment of our insulin resistance. The modern US diet now has far too much carbohydrate in it. Hence obesity and diabetes rates are quadruple what they were in the 1960's. Sorry, but this is not due to lack of exercise. What you put into the system is as important as how you take it out. Now we are dealing with a tidal wave of processed carbohydrate foods. This is going to catch up to us. In all things, moderation is the golden rule. Follow the middle way and you cannot go wrong. Author's disclosure (Mar 24, 2013) I have no relevant disclosures to make in connection with this topic.
	# 14 of 18	March 25, 2013 06:26 (EDT)
	James O'Keefe	Moderation--the Sweet Spot for Exercise Regular exercise is perhaps the best way to preserve youthful capabilities and appearance, in addition to relieving stress, improving sleep, augmenting energy level, maintaining normal weight, keeping blood pressure down etc. The last thing we want to do is to discourge them from staying physically active, or give the average sedentary American another excuse to be sitting around all day. We are just making the point that urban myth about marathons and other forms of extreme endurance exercise being good for one's heart is almost certainly not true. A more moderate approach to exercise is better, especially beyond age 45. Author's disclosure (Mar 21, 2013) I have no relevant disclosures to make in connection with this topic.
	# 15 of 18	March 26, 2013 04:56 (EDT)
	D Hackam	question Is there any evidence that the new passion among exercisers and gym members - namely high-intensity interval training (HIIT), a.k.a. turbulence training - is good or bad for the heart? This is doing extremely intense but brief bouts of exertion interspersed with much more moderate "baseline", in order to cause sudden HR acceleration. What does this do to BP, LV function, LA modelling, risk of arrhythmias, etc? Author's disclosure (Mar 24, 2013) I have no relevant disclosures to make in connection with this topic.
	# 16 of 18	March 27, 2013 06:30 (EDT)
	James J. King	CAC’s don’t lie 1. CAC-Coronary Artery Calcification is almost university elevated in Ultra-marathoner’s and those that regularly run marathons. 2. This finding on Cardiac CT forced me to re-think exercise. 3. Very long runs deplete cellular energy. Cells are forced to allow intracellular Calcium to maintain balance as the Sodium-Potassium pump is overwhelmed by ATP depletion. If you run be aware of the incidence of sudden death in older marathoners. This abuse is probably OK only once in the young. Exercise is best in HIIT, with diet with antioxidants and ‘earthing’ to deal with the free radical oxygen species. Author's disclosure (Mar 27, 2013) I have no relevant disclosures to make in connection with this topic.
	# 17 of 18	April 26, 2013 09:50 (EDT)
	Jeffrey Patten	It's time to face it. You must consider the case of the Tarahumara Indians of Mexico who run not only days on end, but often weeks, in sandals, over their native rocky landscape. It's a running culture, a way of life. Do they shorten that life getting AF? Does anyone know? It's time to discover if they don't and why that might be. Author's disclosure (Apr 26, 2013) I have no relevant disclosures to make in connection with this topic.
	# 18 of 18	May 2, 2013 07:37 (EDT)
	baron cosimo	Non-exerciser to exerciser changed AFIB symptoms As someone who was diagnosed with afib last October, and has been trying to understand and manage it, I've paid very close attention to what my body tells me since my first heart flippy-flop. I stopped drinking, ate better, started supplementing vitamins and minerals, tried acupuncture...basically following suggestions that had worked for others. The afib only got worse, though, to the point that I was having it every day. Then, a couple of months ago, I decided (for reasons having nothing to do with afib) that I wanted to start walking more. Since that day I have walked 5-6 miles, six days a week, and have not had so much as a flip or flutter. What a pleasant surprise! But my doctor can't explain it to me. Still, you can't argue with results, even unintended results. Author's disclosure (May 2, 2013) I have no relevant disclosures to make in connection with this topic.

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