Paroxysmal atrial fibrillation (PAF) has typically been diagnosed in a patient with cardiac symptoms seeking care for episodic symptoms which ultimately- by either office EKG or some monitoring device shown to have atrial fibrillation ( AF).
The medical literature is conflicted in regard to the risk of PAF versus permanent or persistent AF. It is not surprising that expert opinion in that regard is conflicted as well, While opinions may differ current US guidelines recommend oral anticoagulation( OAC) for PAF patients based on their risk assessment score. Usually the CHA2DS2-VASc score is used and a value of 2 or more would lead to recommendation of OAC.In other words. the same recommendation for persistent or permanent AF applies to PAF.Note this refers to what I will call "clinical PAF" subclinical PAF (SCAF) has become an clinical management issue as huge amounts of data has become available from the rate and rhythm recordings of pace maker patients.
A 2014 report by Vanassche which analyzed data from 6563 AF patients not treated with oral anticoagulants (OAC) determined that stroke risk in permanent AF was roughly twice that of PAF.
They reported that AF pattern ( PAF versus non PAF ) was the second strongest predictor of stroke second only to previous history of stroke. If their data are conclusive in this regard that does not necessarily mean that OAC not be used . Even though the risk of stroke is lower, still the stroke risk may overwhelm the risk of serious bleeding from OAC leading to a positive clinical benefit or trade-off and a reasonable recommendation for OAC.
A new and expanding data base has emerged from the experience of
pacemaker (PM) patients. The ability of PMs to store and analyze large
amounts of rate and rhythm data has lead to the realization that
typically asymptomatic bursts or runs of subclinical atrial fibrillation are very common in PM
patients, values from several studies reporting an incidence of 30-55%.
The questions arises-is the risk of these SCAFs equivalent to that of the classically diagnosed PAF. Further, is there value to quantitative the SCAF perhaps in terms of duration or frequency . The literature has adopted the concept of atrial fibrillation burden ( AFB) and several studies have attempted to determine if there is a correlation between PAF ( as in minutes per day) and stroke risk). More importantly is it possible to find an AFB threshold associated with a clinically important risk of stroke or how much SCAF is necessary to warrant OAC.
In general ,reports of these attempts indicate there is a correlation between PM detected AFB and stroke risk , however the reports differ in regards to finding burden levels that demonstrate an increase hazard ratio- usually in the range of 2 or under (and sometimes statistically significant and sometimes not). The small number of events of interest-stroke and peripheral emboli- in various duration based subgroups lead to wide confidence intervals and HR values that fluctuate as burden levels increase-sometime being statistically significant at lower levels but surprisingly not at higher which was the case, for example in the SOS-AF project.
Some of the of AF burden levels at which a increased hazard ratio (HR) for stroke or other embolic events) have been reported from various studies are shown here: ( note with one exception runs of SCAF less than five or six minutes-depending of the particular study-are not analyzed.) So to date with one recent exception there is essentially no data on the risk of SCAF events of less than 5 minutes
ASSERT six minutes
TRENDS -5.5 hours
SOS AF - one hour
CARELINK/VA 5.5 hours
These studies were reviewed by Chen-Scarabelli et al in 2015 and also by Camm et al in 2016 and they reached opposing conclusions. Camm's review concluded that data were insufficient to recommend OAC in SCAF while Chen-Scarabelli and Kenneth Ellenbogen said that OAC should be initiated on the basis of stroke risk assessment using the CHA2DS2-VASc score regardless of the mechanism of detection of the atrial fibrillation.
In the observational TRENDS project, data from 3035 PM patients were analyzed. Those characterized as a "low" AF burden (AFB) ( low is defined as less than or equal to 5.5 hours on an single day) gave a risk estimate similar to having zero AF. An AF burden of greater than 5.5 hours doubled the thromboembolism risk.
Also a sub-study of the TRENDS project showed that 29 of the 40 patients who had a embolic event had no AF detected in the 30 day period preceding the event suggesting that the relationship between AF and stroke may not be a simple as the former invariably causing the latter.
As Glotzer and his co-authors in the TRENDS project emphasized, the available data-even combining data from several studies as was done in the SOS AF project- do not necessarily make it possible define a "safe "AFB that confers no risk greater than observed with no AFB. The event rates ( i.e stroke and other embolism events) are low in all of these studies, lower than predicted based on a widely accepted 4% per year rate in atrial fibrillation patients) and this limits statistical precision and produces wide confidence limits as well as limits the number of threshold ranges that can be analyzed with the expectation of statistical significance.
Small numbers in each duration subgroup lead to results that sometimes seem
counter intuitive- for example : In the SOS AF a statistically increased
HR was found for the five minutes cutoff and the one hour cutoff but not
the six hours or 12 hour or 23 hour. A long duration would have been thought to impair a higher HR.
The RATE RHYTHM study was designed to determine if there is a definable burden of AFIB that will be predictive of thromboembolic events. At this writing I have only access to an abstract of the findings. I believe that the investigators found there were no risk for bursts of atrial fibrillation less than 20 seconds. .
The data indicate that the risk of PM detected SCAF is lower than the clinically detected classical PAF but there is a correlation between SCAF and stroke risk and SCAF is an independent risk factor for or predictor of stroke. ( An independent risk factor is not necessarily causal- see here) . Of course the question is with the variable coarse- grain risk values derived from any of these studies is anticoagulation for these SCAF warranted and in that regard there is not unanimity of expert opinion.
Guidelines ,with the exception of the Canadian Cardiovascular Society guidelines, do not recommend specifically to give OAC for device-detected AF. The Canadians suggested that OAC could be given to patients 64 and older with a CHADS score one or more who have SCAF episodes lasting a day or more or for those with a shorter interval if they have recently had a cryptogenic stroke. ( ref 1)
A number of researchers have argued that randomized trials are needed to determine the clinical benefit for OAC in PM detected PAF. Two such trials are now in progress The ARTESIA project aims to enroll 4000 patients and randomize patients with at least one episode equal to or greater than 6 minutes of AF to either apixaban or aspirin. 2019 is the projected end date. Note even after this trial is complete there will still not be any RCT level evidence about what to do with patients with AF burdens of less than 6 minutes per day. The NOAH project will compare edoxaban or aspirin/placebo in patients over 65 years of age with one additional CHA2DS2VASc risk factor.
RCTs do seem to be needed, I believe we have learned all we can from the type the observational trials mentioned above and expert opinion differs regarding the management of SCAAF detected by PM recordings. An optimistic view is that these 2 RCTS may allow recommendations regarding OAC and device detected to move past battling expert opinion and trying to tease clinical truth from conflicting observational data.
1.Verma A et al 2014 Focused update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial fibrillation. Can J Cardiol. 2014 30 114-1130
update 12/16/16 A paragraph inadvertently omitted was added.
addendum 1/18/17 and 2/4/17 several minor changes made in syntax and typos corrected.
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