Atrial and Ventricular Myopathy: A Novel Risk Predictor for Stroke and Cardiovascular Events

 Nassir Marrouche, MD

Nassir Marrouche, MD

Atrial myopathy is an area we need to focus on—it’s a warning sign and indicator for the risk of stroke, not only in the atrium but the ventricles as well.
 

"I think almost every electrophysiologist or cardiologist will tell you that every atrial fibrillation (AF) patient has some kind of fibrosis or myopathy in their heart, in the atrium at least. The question is, what came first: the chicken or the egg?"

"That is the debate going on,” said Nassir F. Marrouche, MD (executive director, Comprehensive Arrhythmia Research and Management Center [CARMA]; director, Electrophysiology Labs; director, Atrial Fibrillation Program and associate professor of medicine, University of Utah Health Sciences Center, Salt Lake City, Utah) to AF Symposium News in a live interview on site at the meeting. “For the last nine years at the CARMA Center, we have looked at the atrium of the human AF, and we were surprised to find different degrees of fibrosis in patients with AF. Even in 60% of non-AF patients, you will see some degree of significant fibrosis.”

AF is associated with tissue as well as overall atrial chamber structural/shape remodeling as demonstrated in both animal models and humans. This remodeling process is integral to the pathophysiology of the arrhythmia and constitutes the substrate required for its maintenance.

He explained: “What we’re realizing is that fibrosis is happening independent from AF. It doesn’t follow AF, it’s more the other way around. AF is becoming more and more an indicator of something going on in the heart based on the myopathy. To summarize, we knew that fibrosis and AF were intertwined from animal models, but what we’re learning in humans is that fibrosis is there and AF is suddenly ‘parking’ on top of it. The question is how. There are multiple theories, but data has found that the rotational activities seem to anchor on fibrotic tissues.”

He continued: “What’s the value of this fibrosis in terms of going forward and managing AF? We have found over the years in multicenter studies such as DECAAF I that fibrosis predicts failure of procedure and failure of cardioversion. There are four stages, and the higher the fibrosis, the worse the outcome. “We’re realizing that the location of this fibrosis is an important factor.”

In addition, a paper published in JACC a couple of years ago showed patients with stroke have higher amounts of fibrosis: “If you look at quartiles, you have 20% or more fibrosis, your chance is two times or higher than stage 2-3, and 19 times higher than stage 1.”

He noted: "We’re doing a women-only heart research initiative to analyze why women with AF, at any age, have 8-10% more fibrosis than men, and they stroke more. We’re studying this patient population for a three-year period, and are using biometrics as well as looking at their ECGs to see how this is impacting fibrosis.”

Dr. Marrouch stressed that “atrial myopathy or fibrotic change are becoming more important than AF itself. AF is more of an indicator now for an ongoing myopathy process.”

He added that we should also increase the pool of ablation—of all the 6 million AFs today, maybe half of them are in the early stages of fibrosis, and they profit very well as a success story. “How can one say if a ballon or laser or RF is needed? That is what we focus on as Eps, because we know ablation, but what we’re saying at the CARMA Center in Utah is let’s go outside that box,” said Dr. Marrouche. “The DECAAF-II study will be looking at this and evaluating fibrosis and ablating it, versus standard of care. We’re hoping that by ablating and homogenizing fibrosis in the atrium, we have a better outcome.”

Thromboembolism risk stratification tools do not incorporate any measure of the atrial remodeling seen in AF patients. Moreover, the predictive value for the available tools is mediocre, with a c-statistic varying between 0.56-0.67. Delayed enhancement-MRI (DE-MRI) has been shown to detail the severity of atrial and ventricular fibrosis in patients with AF.

Dr. Marrouche associated the severity of atrial and ventricular fibrosis detected using MRI with the severity of AF and AF burden. The incidence of embolic strokes and major cardiovascular events, along with the presence of transesophageal electrocardiography (TEE) abnormalties, were other factors that have been associated with risk of stroke and major cardiovascular events. In these studies advanced atrial and ventricular tissue structural remodeling was shown to be associated with a higher risk of cardiovascular embolic events, including left atrial appendage thrombi and spontaneous echocardiographic contrast in the left atrium. Dr. Marrouche also showed the predictive ability of cardiac fibrosis and a chambers shape-based model to improve the statistical power of currently available models such as CHAD2DS2-VASc.

“DE-MRI helps predict success of cardioversion, success of ablation, it guides me through ablation and where I should be ablating, and last but not least, helps me define which patient should be on blood thinners for eh rest of their lives, and which patients I can stop blood thinners after the ablation.”


We took this even further by adding into account the shape of the heart chamber. We’re finding that the shape of the heart, the shape of the chest and where the heart sits, seems to predict stroke risk.

“We took this even further by adding into account the shape of the heart chamber. We’re finding that the shape of the heart, the shape of the chest and where the heart sits, seems to predict stroke risk. I believe that shape seems to improve prediction for recurrence and success as well. Thus, DE-MRI has given me a lot of data, but the bottom line is that myopathy is an indicator for stroke and even mortality if you see our data. We’re doing multicenter studies to look at this in a prospective fashion.”

“Atrial myopathy is an area we need to focus on—it’s a warning sign and indicator for the risk of stroke, not only in the atrium but the ventricles as well. Atrial myopathy is also a marker for failure of procedure, heart failure, and obviously cardiovascular events as well.”

As a result, Dr. Marrouche believe we’ll begin to see a more tailored, individualized approach to AF based on the association between fibrosis and arrhythmia recurrence.

Tammy Griffin-Kumpey