Athletes and AF: Connecting the Lifestyle Dots

John Mandrola


February 26, 2015

The only way to begin an essay about athletes and atrial fibrillation is to say exercise is good.

It is no surprise, then, that in the Cardiovascular Health Study,[1] older subjects who walked the most enjoyed the lowest risk of AF. Likewise, Dr Peter Ofman (Brigham and Women's Hospital, Boston, MA) and colleagues performed a meta-analysis[2] of four studies with more than 95 000 subjects and found no significant association between regular physical activity and increased AF risk.

I repeat: Regular exercise is good.

But there is little regular about the long-term endurance sportsman or -woman. Here we speak more of an addiction than a healthy habit. I have firsthand knowledge of this phenotype because I was once afflicted.

The Endurance Athlete

The endurance athlete is special. These are not the people who run a marathon; they are the types who ride their bike to the marathon, run the 26.2 miles, then ride home.

The normal exerciser sweats, breathes hard, and occasionally pushes his heart rate close to maximum. The competitive chronic endurance athlete pushes well past that threshold on a regular basis—for years and decades. Going over the limit—in dose and intensity—is what defines these individuals.

Endurance athletes endure fluid shifts, changes in pH and electrolytes, and fluctuations in blood pressure. Their atria are exposed to chronic volume and pressure overload. Athletes live in a disordered autonomic milieu—spikes of sympathetic outflow interrupt a persistently high parasympathetic tone. The athletic heart is exposed to extreme tachycardia and long periods of profound bradycardia.

And it is not only the physical effects. Endurance athletes who compete may also develop mental and emotional stressors. Although the incidence is not known, some athletes use substances to enhance performance or promote rest—many of which are arrhythmogenic. In addition, those who exercise as a vocation rather than a hobby may endure self-esteem issues, which have been correlated[3] with greater inflammatory responses to stress.

AF Incidence in the Athlete

Numerous investigators have addressed the incidence of AF in sportspersons. These studies enrolled orienteerers, marathon runners, elite cyclists, and cross-country skiers. Drs Jawdat Abdulla and Jens Nielsen (Glostrup University, Copenhagen) did a meta-analysis[4] of six case-control studies of 655 athletes and 895 control subjects. They found AF in 23% of athletes and 12.5% in controls. The odds ratio for AF in the athlete group was 5.29 (95% CI 3.57–7.85).

A complete literature search yields many small studies that correlate long-term sports activity and AF. When considered individually, each of these retrospective, longitudinal, case-control, or observational trials suffer from weaknesses. Small numbers of subjects, varying types of exercise, and selection bias are the main issues. What's more, women are underrepresented.

That said, when these studies are taken together, you can see a pattern: younger patients with lower cumulative dose of exercise have lower AF risk. Older patients with higher dosages of exercise have higher AF risk.

Potential Mechanisms of AF

Triggers. Atrial fibrillation involves triggers and substrate. The triggers most often involve focal discharges from the sleeves of myocardium in the area of the pulmonary veins. These areas lie adjacent to autonomic ganglia.

In an elegant study, Dr Eugene Patterson (University of Oklahoma, Norman) and colleagues demonstrated triggered firing within canine pulmonary veins with combined parasympathetic and sympathetic stimulation.[5] Their key finding was the interplay between the properties of the pulmonary-vein (PV) cells and autonomic activity.

Here is how their results may apply to the endurance athlete: PV cells have inherently short action potential (AP) duration. Vagal stimulation further shortens AP duration, then sympathetic stimulation enhances Ca-current, which has a net depolarizing effect and can lead to rapid repetitive firing. Voilà, an endurance athlete now has the triggers for AF.

Abnormal Substrate in Lone AF. Multiple authors of a recent white paper in the Journal of the American College of Cardiology argue that "lone" AF mostly does not exist.[6] The presence of paroxysmal AF suggests the likelihood of atrial structural disease.

Dr Martin Stiles (University of Adelaide, Australia) and colleagues set out to determine whether patients with paroxysmal AF have an abnormal substrate. The stimulus for the work came from the observation (made initially by Dr Maurits Allessie's group[7]) that a second factor—beyond AF alone—may be responsible for the development and progression of AF.

The Australian research team did electrophysiology studies on 25 patients referred for ablation of paroxysmal AF and 25 with left-sided accessory pathways and no AF. [8] The differences were striking. Compared with the control group, AF patients had larger left atria, longer atrial refractory periods, longer intra-atrial conduction time, slower conduction velocity, more fractionated electrograms, and longer sinus-node recovery time.

Biochemical Evidence of Fibrosis in Elite Athletes. Drs Mitchell Lindsay and Francis Dunn (Western Infirmary, Glasgow, Scotland) measured markers of collagen equilibrium[9] in elite athletes and normal controls. Compared with sedentary controls, the athletes had higher levels of plasma carboxyterminal propeptide of collagen type I (PICP), carboxyterminal telopeptide of collagen type I (CITP), and tissue inhibitor of matrix metalloproteinase type 1 (TIMP‐1). Athletes with left ventricular hypertrophy (LVH) had higher levels of TIMP-1.

Endurance-Exercise-Induced AF in Rats. The most influential study on mechanisms of AF in athletes comes from the laboratory of Dr Stanley Nattel (Montreal Heart Institute and University of Montreal, Quebec). This group has previously shown that exercise training induced electrical and structural remodeling of the rat ventricle.

In this paper,[10] lead author Dr Eduard Guasch (University of Montreal) and colleagues studied the effects of endurance exercise on the atria. They trained male rats to run 1 hour per day, 5 days per week, for up to 16 weeks.

Compared with sedentary controls, exercised rats displayed evidence of enhanced vagal tone, atrial dilation, atrial fibrosis, and vulnerability to pacing-induced AF. Atropine blocked AF inducibility. Detraining resulted in rapid reversibility of vagal enhancement and AF vulnerability, but not structural changes. Fibrosis and left atrial (LA) dilation remained after the rats stopped exercising.

The research team then explored the mechanisms for enhanced vagal effects. They found exercised rats had both greater baroreflex sensitivity (phenylephrine challenge) and greater end-organ vagal response—manifested by enhanced acetylcholine-dependent potassium currents.

Going further, the investigators considered molecular reasons for enhanced vagal sensitivity. They reported altered mRNA expression levels of several regulators of G-protein signaling (RGS) that could have contributed to increased cardiomyocyte sensitivity to cholinergic stimulation.

This was an important study that not only confirms (and replicates) the effects of exercise training on the heart but also explains how AF could afflict athletes. It is hard to observe these findings—even in a rat model—and not think that chronic exposure to endurance exercise could be the "second factor" that leads to the delayed-onset structural and electrical changes in the atria of athletic patients previously thought to have "lone" AF.

Other experts, however, urge caution. Drs Jonatan Ruiz (University of Granada, Spain), Michael Joyner (Mayo Clinic, Rochester, MN) and Alejandro Lucia (European University, Madrid, Spain) argued in a CrossTalk feature in the Journal of Physiology[11] that the training program was "far higher than values sustained by elite endurance athletes." Translated to human terms, they estimated that the rat training regimen would equate to a human exercising several hours per day at 85% to 90% of maximum heart rate for 5 days per week for 10 years—a high dose even by Ironman standards. In addition, Ruiz et al contend the shocks delivered to the rat's tails to keep them running might have confounded the results.

Of Rats and Men. Dr Matthias Wilhelm (University of Bern, Switzerland) and colleagues[12] studied a random sample of 60 runners during after a 10-mile running race in Switzerland. They did echocardiograms and signal-averaged ECGs in this middle-aged cohort of runners and controls. The groups were stratified based on lifetime training hours and included marathoners and casual runners. The Swiss team found that LA volume, parasympathetic tone, numbers of premature atrial contractions (PACs), and signal-averaged P-wave duration increased in parallel with lifetime training hours. Although this was a small nonrandomized study with self-reported training hours, the relationship of LA volume (structure) and signal-averaged P wave (electrical) moved in the same direction as the rat training model.

Implications for Treatment

The more we learn about the disease atrial fibrillation, the more obvious it becomes that therapy must be directed at the underlying cause.

AF happens for a reason—and that reason is the therapeutic target.

When AF occurs because of sleep apnea, we treat the sleep apnea. When AF occurs because of excess alcohol intake, we prescribe less alcohol. When AF occurs because of hypertension and obesity, we treat those primary diseases.

Now consider the endurance athlete who presents with atrial fibrillation without other cardiac risk factors: In the past, we would shrug our shoulders and say, "oh well, you have lone AF. . . . It is just bad luck. No worries. We can isolate your pulmonary veins."

And it is true—studies with small numbers of patients and short follow-up show this nontargeted strategy[13] might work as well in athletes as it does in normal people, which is hardly a cause for joy.

But then what? Do we send the endurance athlete back out to the track or trail? Or do we tell them the truth?

I cannot see how you could review the evidence outlined above and believe that medications, burns, or freezes are the best (or only) strategies for the human athlete with AF.

Oh. . . . And one more thing: Regular exercise is good for you.


[Editor's note: An earlier version of this article incorrectly stated that athletes have a persistently low parasympathetic tone.]


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