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About the Authors
Michael J. Quon is with the Division of General Internal Medicine, Department of Medicine, University of Ottawa, Ottawa, Ontario,
Canada.
Louise Pilote is with the Divisions of General Internal Medicine and of Clinical Epidemiology, Department of Medicine, The Research
Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Address for correspondence: louise.pilote@mcgill.ca
Is Secondary Atrial Fibrillation Different? Or Is
Atrial Fibrillation Just Atrial Fibrillation?
Michael J. Quon MD and Louise Pilote MD MPH PhD
DOI: 10.22374/cjgim.v13iSP1.305
ABSTRACT
Secondary atrial fibrillation (AF) is self-limited AF associated with an acute reversible
precipitant. About 1/3 of all Framingham Heart Study patients with first-detected AF had a
potentially reversible, precipitant. There are limited reports assessing outcomes of secondary
AF and risks to established primary AF remain unclear. Evidence-based recommendations to
guide management of these patients are limited and prior studies suggests practice patterns are
different in secondary AF. In this review, we summarize the current evidence on risks of AF
recurrence, ischemic stroke and outcomes of anticoagulation in secondary AF, compared to
primary AF. We provide an overview and recommend management approach in monitoring
for AF recurrence and thromboembolic prophylaxis in these patients.
Canadian Journal of General Internal Medicine
Volume 13, Special Issue 1, 2018 27
Self-limited or transient atrial fibrillation (AF) occurring
during an acute reversible precipitant has been referred to as
secondary AF,
1
temporary cause of AF,
2
and AF occurring
transiently during stress.
3
Alternatively, it has been classified
as either ‘reversible’ or ‘provoked’ AF, varying in terms of the
underlying cardiac substrate and risk for AF recurrence.
4
Given
it was described in prior American Heart Association / American
College of Cardiology / Heart Rhythm Society guidelines,
1
we
continue using the defining term ‘secondary AF. In this article,
we review prior studies and provide an overview of long-term
management approaches to secondary AF. We will use the term
primary AF’ to describe established AF, without an associated
secondary precipitant.
Potentially reversible precipitants of secondary AF include
surgery (both cardiothoracic and non-cardiothoracic), acute
cardiac pathology (including acute coronary syndrome (ACS),
myocarditis, acute pericardial disease), acute pulmonary pathology
(including influenza, pneumonia, bronchitis, COPD exacerbation,
pulmonary embolism, pneumothorax and bronchoscopy-related),
acute infection (including sepsis and non-pulmonary infections),
acute alcohol consumption, electrocution, thyrotoxicosis, and
other metabolic disorders.
2,5,6
Secondary AF is not an uncommon
clinical scenario faced by clinicians. In fact, the Framingham
Heart Study showed 31% of patients with first-detected AF had a
secondary, potentially reversible, precipitant. The most common
precipitants observed in this study were cardiothoracic surgery
(30%), acute infection (23%), non-cardiothoracic surgery (20%)
and ACS (18%).
5
Despite its prevalence, studies examining outcomes in
secondary AF are limited. Previous retrospective studies also
have used different definitions of secondary AF. Some have
included only transient AF, and excluded persistent AF,
2,7–9
while others have included all types of AF associated with a
secondary precipitant.
10,11
Moreover, it is unclear if the risks
associated with each secondary precipitant is the same. As a result,
there are limited evidence-based recommendations to guide
management of these patients. In our review, we focus on long
term management of secondary AF. We review AF recurrence
and ischemic stroke; we do not describe the approach to acute
management of AF nor rate and rhythm control strategies in
secondary AF. We highlight the existing research, compare
risks to primary AF, and propose treatment recommendations
for secondary AF. We provide an overview of approaches to
monitoring for AF recurrence and thromboembolic prophylaxis
in this patient population.
Guideline Recommendations
Current AF guidelines do not directly address the recommended
management of patients with secondary AF. The most recent
American Heart Association/American College of Cardiology/
Heart Rhythm Society guidelines acknowledge the limited
long-term data in patients with AF occurring with potentially
reversible’ conditions. They state that the AF may recur so these
patients “should receive careful follow-up.
6
They do provide recommendations on AF associated with
ACS, hyperthyroidism, acute non-cardiac illness, pulmonary
disease and post-op cardiac and thoracic surgery. For patients
with new onset, transient AF as a complication of ACS, “the need
for OAC and duration of OAC should be based on the patient’s
CHA
2
DS
2
VASC risk score.” For acute non-cardiac illnesses
(reversible precipitants such as hypertension, post-operative
state, pulmonary embolism, viral infection), treatment of the
underlying condition and correction of any contributing factors
is advised. “For many of these patients, AF will spontaneously
terminate with correction of the underlying condition.” In
these non-cardiac illnesses, “the role of OAC is less clear, likely
disease-specific and needs to be addressed on the basis of the
patient risk profile and duration of AF”. In hyperthyroidism
and AF, OAC “should be guided by CHA
2
DS
2
VASC risk score
in thyrotoxicosis. Meanwhile, restoring a euthyroid state often
results in reversion to sinus rhythm, after which, treatment
recommendations with OAC are not provided. In post-operative
cardiothoracic surgery patients, “it is reasonable to administer
antithrombotic medication in patients who develop postoperative
AF, as advised for nonsurgical patients.
6
European and Canadian guidelines make fewer recommendations
regarding secondary AF. Canadian guidelines make recommendations
on concomitant AF in association with NSTEACS and STEMI,
but do not specifically address patients with self-limited AF
in these diagnoses.
12,13
European guidelines recommend that
long term OAC be considered in patients with AF after cardiac
surgery at risk for stroke considering individual stroke and
bleeding risk.
14
Among these most recent guidelines, there are
no recommendations for management of other precipitants of
secondary AF nor any recommendations on monitoring for AF
recurrence in secondary AF.
6,13,14
AF Recurrence
Existing research does not support the concept that patients with
secondary AF are cured of AF after effective treatment of the
potentially ‘reversible’ associated condition. In the Framingham
Heart Study, 5-, 10-, and 15-year incidences of recurrent AF
were determined after retrospective review of subsequent
outpatient and hospital visits. AF recurrence rates were greater
among individuals without a secondary AF precipitant (59–71%)
compared with those with a precipitant (42–62%).
5
In secondary
AF associated with sepsis, 1- to 5-year rates of recurrent AF were
44–55%, compared to 57–64% in individuals with prior AF.
10
Canadian Journal of General Internal Medicine
28 Volume 13, Special Issue 1, 2018
Atrial Fibrillation Special Issue
In new-onset, perioperative AF, 1-year rates of post-discharge
encounters with a recorded diagnosis of AF was 37%.
11
These
studies show that secondary AF often recurs after treatment of
the precipitant, however they suggest that the relative risk of
recurrence may be lower than primary AF.
At present, there is limited data to predict which patients will
develop recurrent AF. Evaluation of a patient with secondary AF
for risk of recurrence is advised following conversion to sinus
rhythm. Establishing a pre-test probability of underlying AF
should include review for patient demographics and established
chronic risk factors for clinical AF including age, male sex,
white race, hypertension, diabetes mellitus, valve disease, left
ventricular dysfunction, obesity, sleep apnea, chronic kidney
disease and alcohol consumption.
15,16
While not well studied,
factors in secondary AF that have been associated with recurrent
AF include higher age, body weight, and valvular heart disease.
5
Similar to primary AF, most patients with first-detected secondary
AF should undergo echocardiography to evaluate cardiac
structure and function.
Following conversion to sinus rhythm, the recommended
rhythm monitoring approach for recurrent AF remains unclear
in secondary AF patients. To our knowledge, there have been no
previous studies that have systematically monitored secondary
AF patients for AF recurrence. Retrospective studies on AF
recurrence often have reviewed administrative claims or clinic
visits and hospitalizations for any detected AF on 12-lead
ECG or Holter monitor. In addition to 24- or 48-hour Holter
monitoring, further monitoring for recurrence can be considered
with extended continuous external ECG monitoring. Rates of
recurrence or cost-effectiveness in these more sensitive, long-term
monitoring strategies has not been evaluated in the secondary
AF population.
Ischemic Stroke
Limited studies have examined the risk of ischemic stroke in patients
with secondary AF. Understanding relative stroke risk compared to
primary AF patients is important to determine optimal treatment of
these patients. With inclusion of all secondary AF precipitants, the
Framingham Heart Study observed the risk of stroke in patients with
secondary AF was similar to those with primary AF.
5
Meanwhile,
another retrospective study found a secondary AF cohort had
lower stroke risk when compared to a similar primary AF cohort
(1.1 - 1.6 compared to 1.6 - 2.5 per person-years).
17
In ACS, secondary AF has been associated with an increased
risk of in-hospital stroke
18
and post-hospitalization stroke.
5
Annual
risks of stroke following hospitalization with AF in ACS have
been variable, reported from 0.4–10%.
7–9,19
A meta-analysis of 14
studies of new-onset AF complicating ACS, AF was associated
with an increased risk of stroke, after adjustment of ischemic
stroke risk factors. This association persisted in patients with
transient, secondary AF.
20
In sepsis, secondary AF has also been associated with
higher rates of both in-hospital stroke
21
and stroke following
discharge,
10
when compared to patients without AF. Within 5
years of hospitalization, stroke risk in sepsis patients with new
onset AF (5.3%) was increased compared to patients without AF
(4.7%) but lower compared to patients with prior AF (5.9%).
10
Understanding the relative risk of ischemic stroke in secondary
AF requires further study.
Anticoagulation
Given the poor quality of evidence and limited treatment
recommendations, practice patterns are variable on thromboembolic
stroke prevention in secondary AF. On one side of the spectrum,
secondary AF could be considered like primary AF with OAC
initiated based on current guideline recommendations.
6,13,14
On
the other side, secondary AF could be considered a reversible
event unlikely to recur after the precipitant is removed without
OAC initiation. Overall, it seems clinicians are initiating OAC
less frequently in secondary AF compared to primary AF. In
a retrospective study, one third of patients who developed
secondary AF were discharged on OAC,
17
compared to rates
of 46–60% in similar studies examining primary AF.
22–24
In
another retrospective study the OAC prescription rates observed
(36%) were similar in secondary AF patients.
2
To our knowledge, there are no studies examining benefits of
OAC in secondary AF compared to primary AF. In secondary AF
associated with ACS, OAC has been associated with a decreased
incidence of stroke in some reports.
8,19
While it may have been
underpowered to detect a significant benefit, no trends towards
benefit of OAC in stroke reduction were observed in secondary
AF associated with ACS, acute pulmonary disease, and sepsis.
17
It has been further hypothesized that benefits of OAC may vary
depending on the associated precipitant.
4
In addition, there is minimal data on bleeding risks in
secondary AF patients that are prescribed OAC. Secondary
AF is frequently observed in patients with high bleeding risks,
including older patients with multiple comorbidities, taking
other anti-thrombotic medications.
5,17
OAC was associated with
higher bleeding risks in secondary AF patients (3.6–6.2 per 100
person-years)
17
compared to primary AF patients in similar
cohort studies (1.5–4.3 per 100 person-years).
22–24
The benefits and risks of OAC in secondary AF require
further research. At present, it is unclear if the benefits of stroke
reduction and risks of bleeding apply equally in secondary AF
patients compared to primary AF. It remains unknown if current
OAC recommendations for thromboembolic prophylaxis in
primary AF should apply directly to patients with secondary
Canadian Journal of General Internal Medicine
Volume 13, Special Issue 1, 2018 29
Quon and Pilote
AF. Careful individual assessment is warranted while we await
randomized trials assessing OAC in secondary AF.
Approach to Management
Due to limited evidence-based recommendations, there are various
approaches to management of secondary AF. After resolution
of a transient episode of new-onset AF with an associated
precipitant, clinicians are often faced with assessment of stroke
risk, similar to treatment of primary AF. Unlike established
primary AF, secondary AF decisions may additionally depend on
the patient’s risk of AF recurrence, in addition to balancing the
risks of ischemic stroke, bleeding and the patient’s goals of care.
Risk factors for secondary AF being a presentation of
underlying, unmasked sub-clinical AF should be identified.
Patient characteristics and risk factors to develop AF including age,
hypertension and structural heart disease should be considered.
Echocardiogram could identify further structural risk factors
of primary AF, such as severe LA dilation,
25
mitral stenosis or
mod-severe mitral regurgitation.
The impact on stroke risk from the secondary AF and
characteristics of each precipitant has been minimally studied.
While not previously validated in a secondary AF population,
the CHADS2 score could be used to further stratify stroke risk.
The CHADS2 score would be similarly used in patients who
have underlying sub-clinical AF.
13
In addition to structural
heart disease, echocardiogram could identify further stroke risk
factors such as left atrial spontaneous echo contrast, thrombus
or complex aortic plaque.
26
While not studied in all precipitants,
longer duration of AF was shown to increase stroke risk in
secondary AF associated with ACS.
8
After conversion of secondary AF to sinus rhythm, we
recommend rhythm monitoring for sub-clinical paroxysmal AF.
At minimum, routine diagnostic screening techniques, such as
inpatient cardiac telemetry and outpatient 24- or 48-hour Holter
monitoring, should be performed. While widely available, these
strategies are limited by their modest sensitivity in detecting
paroxysmal AF. Should decisions on antithrombotic therapy
warrant further investigation for management decisions, further
longer-term monitoring, such as external event monitor (e.g.,
ECG patch) can be considered.
Secondary AF patients should be evaluated for risk for
underlying AF and recurrence of AF in addition to risks of
stroke and bleeding. Given the frequently observed recurrence
of secondary AF and its association with ischemic stroke, we
recommend careful consideration of an antithrombotic strategy
in these patients. Unless low stroke risk (e.g. CHADS2 = 0 with
age < 65 years), high bleeding risk, or not in congruence with
the patient’s goals of care, it seems reasonable to initiate an
antithrombotic therapy, until results from echocardiogram and
rhythm monitoring for paroxysmal AF are available.
Recommendations on ischemic stroke prevention can
include the following:
Initiation of long term OAC indefinitely
Initiation of OAC while awaiting results from
echocardiogram and monitoring strategy for sub-clinical AF
Initiation of ASA while awaiting results from echocardiogram
and monitoring strategy for sub-clinical AF
After rhythm monitoring and echocardiogram results are
obtained, all patients should have clinical follow-up with re-
assessment of stroke and bleeding risks. While 24-hour Holter
monitoring is not sufficiently sensitive in detecting AF, observation
of paroxysmal AF could provide a clear diagnosis of primary
AF. Similarly, echocardiogram showing left atrial spontaneous
contrast, thrombus or rheumatic mitral disease would offer
clear evidence-based treatment recommendations with OAC.
Conclusions
While not extensively studied, secondary AF is not infrequently
observed in patients with first-detected AF. Studies show that
secondary AF frequently recurs, yet there is limited data to
predict which patients will develop recurrent AF. Stroke rates are
elevated following episodes of secondary AF. When compared
to primary AF, both risks of AF recurrence and ischemic stroke
require further study in secondary AF patients. Randomized
trials of OAC in secondary AF are needed to understand the
optimal approach to antithrombotic therapy in these patients.
Until then, patients should be assessed for risks of pre-existing
AF and AF recurrence in addition to stroke and bleeding risks.
After conversion to sinus rhythm and treatment of the associated
precipitant, further monitoring for AF recurrence and careful
individual assessment of antithrombotic therapy are warranted.
Funding
There is no relationship with industry. Research was funded by
a grant from the Canadian Institutes of Health Research. Dr.
Pilote holds a James McGill chair at McGill University.
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