John Mandola


March 17, 2015

It is hard to believe the cardiology community missed it for so long—and at so much expense.

Dr Richard Fogel is the president of the Heart Rhythm Society. He pulled me aside during the American College of Cardiology (ACC) 2015 Scientific Sessions to say the LEGACY trial is the most important study of this meeting. "It changes the entire approach to patients with AF . . . And you can quote me on that," he said.

You could see the look of epiphany on his face. Dr Fogel went on. "Let me put my clinician's hat on for a second," he said. "Maybe instead of talking about drugs or ablation, I should tell my patients with AF about weight loss."

The LEGACY trial provides something that is increasingly rare at medical meetings. That is, it causes a change in an approach to patients with a common disease. The key word here is approach. LEGACY was not just about a treatment. It does far more. It gets us closer to understanding AF. And when we understand a malady, we are better able to help people.

The Study

LEGACY investigators analyzed consecutive patients who presented to the Adelaide University hospital electrophysiology service. Their hypothesis was that weight loss, if sustained and linear (not fluctuating), would reduce AF burden. They were also interested in the long-term effects of weight loss on cardiovascular risk factors such as blood pressure, diabetes, lipids, left atrial (LA) volume, and inflammation.

The primary end point was AF burden. The secondary outcomes were measures of cardiac structure, CV risk factors, and inflammation. The trial included 355 patients with body-mass index (BMI) >27; researchers separated them into three groups based on the amount of weight loss—those with >10% weight loss (n=135), 3% to 9% weight loss (n=103), and <3% weight loss (n=117). The groups were similar in baseline characteristics.

Recall that in Adelaide, all overweight and obese patients with AF are encouraged to be seen in a separate physician-led goal-directed clinic for weight loss and risk-factor treatment.

Here are nine summary statements of the results (see full coverage here):

  • Sustained weight lost associated with a dose-dependent reduction in AF burden.

  • Patients with long-term weight loss were six times more likely to be free of AF.

  • Nearly half (46%) of overweight patients who lost 10% of their body weight were AF-free without drugs or ablation.

  • Weight loss also benefited patients who were treated with medications and/or ablation (similar to the ARREST-AF trial).

  • Patients with linear (gradual and steady) weight loss did better than those whose weight fluctuated.

  • Participation in a separate goal-directed, physician-led weight-loss clinic increased the odds of durable weight loss and decreased the likelihood of weight fluctuation.

  • Weight loss induced favorable structural remodeling. LA volume and CRP levels were lower in the group with >10% weight loss.

  • Durable weight loss resulted in marked improvement in blood pressure—with less medication. (That is not a typo. BP improved with fewer pills.)

  • Weight loss lowered the number of patients with HbA1c>7 and decreased insulin and LDL levels.

Q&A with Dr Sanders

I had the pleasure of interviewing senior researcher Dr Prash Sanders after the late-breaking trial presentation. Here are highlights of our chat.

Can you explain the role of the physician-led clinic?

"This is important," Sanders said. It is separate from the electrophysiology clinic. In this encounter, patients meet with a doctor who focuses only on weight loss and risk factors. The other key is that patients are given achievable goals and a plan. Patients are not just told to lose 20 kg.

And here is something I had not heard before: This is not a fancy clinic. There are no waterfalls or soft music. It is just one patient and one doctor in a simple room with no props. Two people working together toward an achievable goal.

What did you learn about the durability of weight loss?

Two-thirds of patients who lost >10% of their BMI maintained the loss. But again, Sanders emphasized the value of the separate clinic. Of the patients who sustained >10% weight loss, 85% of them were enrolled in the clinic, while only two of 18 patients who did not lose weight were in the clinic. The clinic provides the support and tools that patients need to maintain healthy living.

What about the decreased benefit in patients with weight fluctuation?

This was a notable finding, because it points to the need for continued follow-up and support. We must keep patients engaged in the process of healthy living. If they lose weight and then gain it back, they don't benefit as much.

What do the changes in cardiac structure tell you?

Sanders said the reduction in LA volume and decrease in CRP with weight parallel their findings in animal studies. These structural changes provide a biologic link or mechanism as to how weight loss decreases AF burden. Less atrial stretch means less dilation, fibrosis, and electrical delay. And these things make the atria less likely to fibrillate.

How should these findings change our approach to patients with AF?

A strategy to address risk factors in patients with AF is not extra. It should be part of the process. Sanders used the word team when it comes to the care of patients with AF. This team includes cardiologists, generalists, nurse practitioners, and most important, the patient.

What do you say to the legions of caregivers in North America who say this cannot be done? Or we cannot afford team AF care?

Dr Sanders answer was simple. "How we can afford not to do it?"



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