EXPERT ANALYSIS FROM AF SYMPOSIUM 2018

ORLANDO (FRONTLINE MEDICAL NEWS) Accumulation of fibrotic deposits within the left atrium has gained currency as an apparent trigger of adverse cardiovascular events, particularly strokes, and has also become the target for ablative strategies by some operators for more effective rhythm control in patients with atrial fibrillation.

“A strong and graded association exists between the severity of left atrial fibrosis severity and major cardiovascular adverse events, primarily due to stroke, transient ischemic attack, and heart failure, Nassir F. Marrouche, MD , said at the annual International AF Symposium.

As a result of this link, “atrial fibrosis should be considered in assessing cardiovascular risk,” said Dr. Marrouche, professor of medicine and director of the electrophysiology laboratories at the University of Utah, Salt Lake City.

Atrial fibrosis is quantified noninvasively by Dr. Marrouche and his associates with late gadolinium enhancement MRI. They published results of a retrospective study in 2017 showing that, during follow-up of 1,228 patients from their center with atrial fibrillation, the 5% of patients who had the highest level of left atrial fibrosis – 30% or more of left atrial tissue – had a significantly increased rate of cardiovascular events during follow-up, compared with the 35% of studied patients with fibrosis constituting less than 10% of their left atrium. The remaining 60% of studied patients had fibrotic tissue that formed 10%-29% of their total left atrial area.

This relationship was strongest when the analysis focused exclusively on the incidence of strokes or transient ischemic attacks. These events occurred nearly fourfold more often among patients with the highest amount of fibrosis, compared with those with the least (J Amer Coll Cardiol. 2017 Sep; 70[11]:311-21 ).

Given that the finding came from a retrospective, single-center study, the clinical implication of fibrosis remains too uncertain to apply to current routine practice. But Dr. Marrouche strongly suspects that fibrotic tissue in the left atrium serves as a potent trigger of thrombosis.

“We think that even patients with a CHA2DS2-VASc score of zero who have a high level of fibrosis may need treatment with an anticoagulant, but we need a prospective study” to validate this, Dr. Marrouche said.

Another area for further research is to explore agents that may be able to prevent or reverse fibrosis in the left atrium. One candidate class of drugs are the angiotensin-converting enzyme inhibitors, he said in an interview.

Atrial fibrosis can have a variety of causes, including hypertension, inflammation, genetics, frequent high-intensity exercise, or other histories that produce regular intervals of extreme atrial stretch, he noted.

Dr. Marrouche is leading a multicenter trial that will test the efficacy of an ablation method for patients with atrial fibrillation tailored to isolating heavily fibrotic regions of the atria. The Efficacy of Delayed Enhancement MRI-Guided Ablation vs. Conventional Catheter Ablation of Atrial Fibrillation ( DECAAFII ) trial is comparing ablation aimed at fibrotic regions against conventional ablation in about 900 patients. Results are expected in another 2-3 years.

Although the usefulness of ablation aimed at isolating areas of fibrosis in the atrium remains unproven, this approach has already been embraced by some operators, including Hans Kottkamp, MD , a professor and electrophysiologist at Hirslanden Hospital in Zurich.

Dr. Kottkamp developed an ablation method he calls “box isolation of fibrotic areas,” or BIFA, and he routinely uses this approach in selected patients in combination with standard pulmonary vein isolation (J Cardiovasc Electrophysiol. 2016 Jan; 27[1]:22-30 )(JACC Clin Electrophysiol. 2017 Jul; 3[7]:643-53 ).

“Fibrosis is the fundamental histologic finding and the key pathophysiologic player in atrial fibrillation,” Dr. Kottkamp said in a separate talk at the meeting. “We suggest doing ablation based on the substrate, and not based on whether the atrial fibrillation is paroxysmal or persistent.” His group uses voltage mapping instead of MRI as their tool for quantifying the amount of fibrosis and pinpointing its location.

“The fibrosis is usually regionalized; it’s not everywhere” in the left atrium, Dr. Kottkamp noted, and the location is very individualized. “You need to look for it in each patient.”

In his experience, about 20% of patients with paroxysmal AF have enough atrial fibrosis to warrant using BIFA along with pulmonary vein isolation. “Among patients with persistent AF, the percentage with significant fibrosis rises to about two-thirds,” Dr. Kottkamp said in an interview. Combining BIFA with pulmonary vein isolation in these patients with higher fibrosis substantially boosts procedural success.

In a recent report, Dr. Kottkamp and his associates presented their experience using BIFA on 92 patients with AF and fibrotic atrial cardiomyopathy. The outcomes showed a relatively high level of success in resolving the AF after an average follow-up of 16 months, with a 69% success rate after a single procedure and an 83% success rate when selected patients received a second BIFA.

Overall, each patient in the series received an average of 1.2 BIFA ablations (J Cardiovasc Electrophysiol. 2017 Sep; 28[9]:971-83 ).

Currently, a limited number of other groups uses BIFA or a similar fibrosis-based ablation approach, and these strategies have not yet undergone prospective assessment in a multicenter study. Despite that, Dr. Kottkamp said he was “confident it will become standard of care.”

Dr. Marrouche has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Cardiac Design, Marreck, Medtronic, Preventice, VytronUS, and Wavelet Health, and he has received research support from Abbott, Biosense Webster, Biotronik, Boston Scientific, GE Sciences, and VytronUS. Dr. Kottkamp has been a consultant to Biosense Webster and has been a consultant to and has an equity interest in Kardium.

mzoler@frontlinemedcom.com

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