AT THE ESC CONGRESS 2015
LONDON (FRONTLINE MEDICAL NEWS) – Atrial fibrillation in the elderly general population was independently associated with accelerated losses of brain volume and cognitive function in a major longitudinal study.
These findings from the population-based Age, Gene/Environment Susceptibility–Reykjavik Study (AGES-Reykjavik) have the potential to change the management of atrial fibrillation (AF), Dr. David O. Arnar said at the annual congress of the European Society of Cardiology.
“I think these data potentially suggest it’s better for the brain to remain in sinus rhythm than to pursue rate control in AF. We also have other studies, postablation studies, that show doing an ablation procedure to restore sinus rhythm delays the onset of cognitive dysfunction. So I think we have more and more data that are suggesting AF may be bad for the brain in more ways than just causing cerebral infarcts. That possibility needs to be considered as an endpoint in future studies of treatment strategies,” asserted Dr. Arnar, a cardiologist at Landspítali–The National University Hospital of Iceland, Reykjavik.
The AGES-Reykjavik Study is an ongoing project designed to investigate the genetic and environmental factors that contribute to clinical and subclinical diseases in older-age individuals.
The new data Dr. Arnar presented are an outgrowth of an earlier report from AGES-Reykjavik, which concluded that AF was associated with smaller brain volume and diminished cognitive performance independent of cerebral infarcts. The observed deficits were smallest in subjects with no history of AF, larger in those with paroxysmal AF, and largest of all in participants with persistent/permanent AF ( Stroke. 2013 Apr;44:1020-5 ). However, this was a cross-sectional analysis, which by definition doesn’t permit drawing conclusions regarding cause and effect.
That earlier report was the impetus for the new study featuring a mean of 5.2 years of longitudinal follow-up. The study included 2,472 elderly, nondemented subjects with a mean baseline age of 76 years who underwent brain MRIs and structured cognitive function testing, with repeated assessments roughly a half-decade later.
A total of 121 subjects had ECG-confirmed AF or a history of AF at entry. Another 132 developed new-onset AF during follow-up. Since the participants with prevalent or incident AF had significantly higher levels of cardiovascular risk factors, alcohol consumption, history of cerebral infarcts, and other potential confounders, extensive multivariate statistical adjustments were required in analyzing the data, according to the cardiologist.
During the follow-up period, the AF-free subjects experienced a mean 1.8% reduction in gray matter volume, compared with a 2.7% decrease in individuals with prevalent AF and a 3.88% reduction in those with incident AF. All differences were statistically significant.
Loss of white matter volume over time followed a similar pattern: a mean loss of 5.35% in the no-AF group, compared with a 5.5% drop in those with prevalent AF and a 6.56% decrease in individuals with incident AF.
The volume of white matter lesions rose by 31.6% in the elderly no-AF group, 26.9% in those with prevalent AF, and 43.5% in subjects with new-onset AF during follow-up.
“It surprised us that the changes were most pronounced in those with incident AF rather than prevalent AF,” Dr. Arnar confessed. “How do we explain that? Well, I don’t know, but you wonder if the effect of AF on the brain could be most pronounced initially and then as AF goes on, an adaptation process occurs so that the rate of change in the brain becomes less pronounced as the AF becomes more chronic.”
Turning to the results of cognitive function testing, a composite measure of processing speed declined over time by 10% in the no-AF group, 12.7% with prevalent AF, and 13.9% with incident AF. All differences were statistically significant.
The rate of decline in executive function was 8% in the no-AF subjects, 10.2% with prevalent AF, and 11.8% with incident AF.
Similarly, scores on memory testing dropped by 9.3% in the no-AF group, 9.9% with prevalent AF, and 11.9% with incident AF.
The mechanism by which AF accelerates brain aging is unknown. Dr. Arnar strongly suspects it is multifactorial, with candidate processes including altered autonomic regulation of blood flow, microemboli causing brain atrophy, and most assuredly AF-induced diminution of cerebral blood flow.
He presented cerebral blood flow data obtained via phase contrast MRI on 2,125 study participants. Those with no history of AF averaged a total cerebral blood flow of 540 mL/min. Subjects with a history of AF who were in sinus rhythm at the time of the brain scan averaged 520 mL/min. And subjects in AF when they were scanned averaged less than 480 mL/min.
Dr. Arnar also presented preliminary results from an ongoing brain perfusion imaging study conducted in AF patients before and after direct current cardioversion. Among 17 patients who responded to cardioversion by going into sinus rhythm and staying there for at least 10 weeks until their follow-up MRI, total cerebral blood flow improved by a mean of 70 mL/min from a precardioversion figure of 557 mL/min. Both white and gray matter perfusion improved by a mean of 16%.
In contrast, the 10 patients who remained in AF despite the cardioversion attempt showed no improvement in any of these three endpoints over the 10 weeks.
Audience members wondered whether being on warfarin or beta blocker therapy affected the rate of brain volume loss or cognitive function. Not in the cross-sectional study published in Stroke, Dr. Arnar replied. However, those analyses have yet to be conducted in the new longitudinal study.
The AGES-Reykjavik Study is funded by the U.S. National Institutes of Health, Icelandic Heart Association, and the Icelandic Parliament. Dr. Arnar reported having no financial conflicts.