John Mandrola


June 23, 2015

Big news from an electrophysiology meeting usually involves technology.

The European Heart Rhythm Association (EHRA) EUROPACE-CARDIOSTIM 2015 meeting bucked that trend. It turns out that the device required to help millions of people afflicted with atrial fibrillation is a pair of sneakers—for exercise.

The intervention that led to marked improvements in AF burden, lower blood pressure, better glycemic control, lower LDL-C and hs-CRP levels, and favorable structural changes in the heart: cardiovascular fitness.

Medical stories rarely get better than this one.

In a late-breaking-trials session, Dr Rajeev Pathak (University of Adelaide, Australia) presented his team's results of the Cardiorespiratory Fitness on Arrhythmia Recurrence in Obese Individuals with Atrial Fibrillation (CARDIO-FIT) study[1]. This was a registry study involving the same group of patients used in the LEGACY study[2]. Recall that in LEGACY, overweight patients who lost more than 10% of their body weight were six times more likely to be arrhythmia free.

The questions asked in CARDIO-FIT were whether cardiorespiratory fitness in obese AF patients offset some of the detrimental effects of obesity and whether gains in fitness have synergistic effects with weight loss.

The approach to treating patients with AF in Adelaide is to offer all overweight or obese (body-mass index [BMI] >27) patients consultation in a physician-directed risk-factor-management (RFM) clinic. In this "clinic," which is actually just two people (doctor and patient) working together to achieve healthy-living goals, structured exercise is one of the basic recommendations.

The Study

Full details of CARDIO-FIT are covered by heartwire from Medscape. Here is the short story: 825 patients were enrolled in the RFM clinic. Of those, 308 patients had two serial treadmill tests. First, the researchers separated that cohort into those with low (n=95), adequate (n=134), and high (n=79) age-predicted cardiovascular fitness. They then advised patients on age- and ability-matched regular exercise. The three groups were well-matched. Follow-up was 4 years.


Baseline fitness mattered.

  • Two-thirds of patients with high baseline fitness remained free of AF without drugs or ablation, while only 12% of patients with low fitness remained free of AF.

  • When rhythm-control treatment was considered, 84% of patients with high baseline fitness were free of AF. Again, only 17% of those with low fitness were without AF. (That sentence warrants a pause. Said another way, at 4 years, 83% of low-fitness patients had AF even with drugs and ablation.)

Next, researchers split the 308-patient cohort into those with less than 2-MET gains (n=181) and those with greater than 2-MET gains (n=127) on serial exercise tests.

Gains in fitness really mattered.

  • Those patients who gained fitness enjoyed statistically (and clinically) significant improvements in weight loss, blood pressure, number of BP-lowering drugs, glycemic control, and insulin, LDC-C, and hs-CRP levels. Fitness also associated with drops in LA volume and better LV diastolic function. (Imagine if this were a drug.)

  • Fitness gainers reported lower AF symptom burden and better scores on global well-being.

  • Without AF drugs or ablation, 61% of fitness gainers vs 18% of those without gains in fitness remained free of AF.

  • With AF drugs or ablation, 85% of fitness gainers vs 44% of those without gains in fitness were free of AF.

  • In a multivariate analysis, every 1-MET gain in fitness associated with a 12% decrease in AF recurrence.

To assess synergy between fitness and weight loss, the research team split each of the fitness-gained or no-fitness-gained groups into those with or without 10% weight loss.

  • With both weight loss and fitness gain, the odds of AF-free survival without drugs or ablation was 76%, vs only 13% in those with neither weight loss nor fitness gain.

  • With AF drugs or ablation, the weight-loss and fitness-gained group had a 94% chance of being free of AF, while only 34% of those who did not lose weight or gain fitness were free of AF.

The researchers concluded increased fitness associates in a dose-dependent way with a reduction in AF burden and that gains in fitness independently add to the proven benefits of weight loss. This seminal finding argues for a prescriptive role of exercise as part of a rhythm-control strategy.

Expert Comments

Dr Claudia Siklódy (Klinikum Ludwigsburg, Germany) discussed the paper during the late-breaking session. She noted that previous population studies have shown physical activity and fitness correlate with overall mortality benefit, and she made special mention of the striking (but underused) benefits of cardiac rehabilitation in patients with ischemic heart disease.

She then moved to plausibility. How could fitness have done this? She said exercise is known to modulate autonomic function and reduce blood pressure and levels of inflammatory markers—all important factors in the pathogenesis of AF

Siklódy was not surprised by the finding that baseline fitness correlated with better AF control, either with or without rhythm-control strategies. She was, however, surprised by the antiarrhythmic effects of fitness gains alone, without drugs or ablation. She called these findings "spectacular."

She also pointed the packed room to the fact that the number of procedures in both groups were comparable. That meant the role of lifestyle management has an important role in limiting AF disease progression. "We should tell our patients that this disease [AF] doesn't end with an ablation. We must do better with our patients. We can't tell them that we will ablate them and things will be okay."

My Take-home

These observations will change my advice to overweight AF patients. I used to emphasize calorie restriction. I will still do that, but I will also help patients set goals on improving fitness—which is not rocket science. Patients don't need an Apple Watch or a coupon for boot camp; they only need to know that regular exercise is being prescribed because it has health benefits. And to get those benefits, they must make time in their life for exercise.

I agree with Dr Pathak. We must think of regular exercise as a drug. Put the CARDIO-FIT graphs up in your exam room. Show them to patients. Write it on prescription pad if you must.

These observations also add to the understanding of AF mechanisms. Think of the basic science of atrial electrophysiology. If "normal" (not Ironman-type) exercise reduces blood pressure, improves sleep, lowers inflammation, modulates autonomic function, and improves LV elasticity, it makes perfect sense that it would confer antiarrhythmic effects. And the converse is true: it makes little sense to treat a disease caused by stretch-induced conduction abnormalities and scar by laying down more conduction delay and scar in the form of ablation.

Let's end on a soft note. One of the less-discussed benefits of exercise is its effect on our minds. Any exerciser will tell you of its soothing benefits. Mark my words down; as we learn more about how the brain and heart are connected, we will better understand the observation that a calm mind often leads to a calm rhythm. And what better means is there to calm the mind than a spirited session moving our bodies?



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