The Elephant in the Clinic: EPs Can't Ignore Risk-Factor Management

John Mandrola, MD


May 12, 2017

On the second day of the Heart Rhythm Society (HRS) Scientific Sessions 2017, I attended a late-afternoon session entitled "Treatable cardiovascular risk factors and atrial fibrillation: A new wave of understanding and management."

Despite the less-than-ideal time slot, this session drew my eye because the four lectures came from leaders in the field. I took notes and offer some short highlights.

Basic Mechanisms

Dr Stanley Nattel from the Montreal Heart Institute, QC, the chief justice of basic science in atrial fibrillation (AF), presented a review of basic mechanisms linking cardiovascular risk factors to AF.

Obesity, hypertension (or their combination), obstructive sleep apnea, and diabetes have all been shown to produce atrial fibrosis and conduction slowing in experimental models. These changes increase vulnerability to AF.

As for reversibility of a risk-factor–induced AF substrate, Nattel cited two studies from the Adelaide group that showed normalization of fibrosis in animal models of obesity and hypertension.

In the Q&A, Nattel was asked about his thoughts on reversal of fibrosis. (Remember, cardiac scar is supposed to be permanent.)

He said something I have never heard before: reversal of fibrosis may depend on the type of fibrosis.

He proposes that irreversible fibrosis is seen in conditions like heart failure, in which collagen moves into muscle bundles to replace dead cells. He called this replacement fibrosis—which likely involves very mature collagen.

The kind of fibrosis that is seen with obesity and hypertension may be more interstitial and reactive. The collagen in the interstial spaces may be more susceptible to active turnover.

He did add that interstial fibrosis alone should not produce conduction slowing, because the myocyte bundles are not being infiltrated. He cautioned that these proposed differences were speculative—and needed to be proven scientifically.

Clinical Evidence

Dr Jonathan Kalman from the Royal Melbourne Hospital in Australia discussed the clinical evidence for risk-factor contributions to the AF substrate.

Sadly, he began with the obvious: one of the leading clinical risk factors for AF substrate is aging.

He then noted the breakdown of the concept of lone AF. To summarize, most of the evidence suggests AF is a manifestation of atrial disease.[1]

Two specific nuggets of information I learned in his lecture were:

  • Sleep-disordered breathing may be present at a surprisingly high frequency in nonoverweight AF patients with normal ventricular function.[2]

  • Animal and clinical data show that mitral regurgitation unleashes a potent and perhaps specific damaging effect on AF substrate.[3]

After going through the literature on risk factors, he concluded with this gem:

"Long before the clinical phenotype of AF is manifest," Kalman said, "we have the risk factors and progression of remodeling. I think, for interventionalists, it is important for us to think that our ablation in isolation is not going to be dealing with this problem." (There, my friends, is a pause moment.)

In the final moments of his talk he explored the notion that AF itself progresses the atrial-remodeling process.

Kalman noted that there are very little clinical data on this question. There are data showing patients with more advanced forms of AF have more advanced substrate, but whether this relationship is cause or effect is unclear, he said.

This is an important concept because one of the prevailing theories in EP now is the idea that early ablation reverses the AF substrate. (My bet is that it will not—treating a disease from scar by creating scar makes little sense.)

Treating Risk Factors

Dr Prashanthan Sanders from the University of Adelaide addressed the treatment of these risk factors. Of course he did.

I could write a book detailing the many studies from this group on the value of a physician-led risk-factor management clinic. Sanders elegantly presented the timeline of his work—a story I tell often in my clinic.

It starts with the obese sheep, who, like humans, when given extra food, eat it, and gain weight. The obese sheep develop an AF substrate and then AF. When fed less food, the sheep, like humans, lose weight. Remarkably their AF substrate resolves.

Sanders and colleagues have demonstrated this same process in both randomized trials[4] and large observational studies[5]. (I have written about these studies numerous times.)

The best part of Sanders' talk came in the Q&A when program chair Dr Laurent Macle (Montreal Heart Institute) pressed him on the impossibility that an electrophysiologist could address things like obesity, sleep apnea, high blood pressure, and diabetes. Macle wondered whether risk factors should be handled by internal medicine or primary care.

Sanders nailed it: "The patient's problem is their rhythm. They don't see risk factors as the problem. So the person who can influence patients most is the EP guy."

That statement echoes the wisdom of the late Dr Mark Josephson who more than once said from the podium: "You are not proceduralists; you are doctors."

Risk Factors and AF Ablation

Dr Jason Andrade from the University of British Columbia, Vancouver, discussed risk-factor intervention to improve AF ablation outcomes.

He also offered an elegant literature review, again highlighting work from the Adelaide group[6,7] among others.

Andrade spent time reviewing a recent paper from the Sequoia Hospital group in California.[8] This observational study of more than 2700 patients found that obesity not only is associated with worse efficacy outcomes but also increased the rate of procedural complications.

I get the sense that the Canadian perspective on improving AF outcomes is significantly influenced by the single-payer system. Namely, for cost-conscious Canadians, unlike Americans, it's easier to see the mountain of data that show that treating AF risk factors is a crucial target.

Andrade described their experience with five provincial AF clinics in British Columbia. At first, these clinics were simply periablation clinics, but now have turned into multidisciplinary AF treatment clinics.

Here is a gem of a quote:

"From my perspective, as someone who undertakes these procedures, it would be remiss not to target all the interventions that you can provide to the patient. Because if you solely focus on the interventional approach, you will only get outcomes half as good as you would otherwise."


While hundreds of abstracts and posters at this meeting chronicle the minutia of destroying atrial tissue in an effort to suppress AF episodes, these four lectures describe the need for a new frame to understand AF.

Yes, AF ablation can have a role in AF treatment. But it is a role. Not the role.

You may not believe me, but here are four respected leaders in the field urging you to see the obvious: treatment of people with AF means addressing the root causes of the dysrhythmia.


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