Download
Canadian Journal of General Internal Medicine
Volume 13, Special Issue 1, 2018 21
Atrial Fibrillation Special Issue
About the Author
Ratika Parkash is with the QEII Health Sciences Center, Halifax, Nova Scotia.
Correspondence may be directed to: Ratika.parkash@nshealth.ca
Does Lifestyle Impact Risk, Burden, and
Symptomatology of Atrial Fibrillation?
Ratika Parkash MD MS
DOI: 10.22374/cjgim.v13iSP1.310
Atrial fibrillation is the most common sustained arrhythmia,
affecting 1-2% of the general population and 8% of patients over
the age of 80 years.
1
The lifetime risk for development of AF is
26% for men and 23% for women. It is associated with significant
morbidity, mortality and cost, but also with an increase in mortality
and a six-fold risk of stroke.
2,3
The Framingham heart study
showed that AF was associated with a 1.5 to1.9 fold mortality risk
after adjustment for the preexisting CV conditions with which
AF was related.
4
The Heart and Stroke Foundation estimates that
350 000 Canadians are living with atrial fibrillation, and that this
is increasing due to Canada’s aging population.
5
The diagnosis of AF may be made fortuitously, such as through
a pulse check, or in the emergency department if the patients
presents with symptoms. Severity of symptoms for AF may range
from a ‘nuisance’ feeling of palpitations to debilitating symptoms
that do not permit performance of activities of daily living, interfere
with normal livelihood and significantly impair exercise tolerance.
The most severe symptoms are those resulting in hemodynamic
compromise and heart failure, which are associated with poor
prognosis and increased mortality.
6
Those that are symptomatic
pose the greatest burden to the health care system, often making
repeated visits to the emergency room for treatment or repeated
hospitalizations due to delayed and limited access to specialist
care, to initiate necessary therapies or undergo crucial cardiac
investigations. Those that are asymptomatic don’t pose as great a
burden, at the time of diagnosis, however, are at risk for deleterious
consequences if not treated appropriately. The mainstay for therapy
for AF is aimed at stroke prevention and control of symptoms due
to the arrhythmia itself. The primary mode of therapy is to use
rate controlling agents, such as calcium channel blockers or beta
blockers, but patients with more symptoms may require rhythm
control. In one study, AF was diagnosed by the family physician
in 63.2% of events, by an office-based cardiologist in 13.2%, and
by hospital-based physicians in 23.9% of cases.
7
Up to a third of
patients with AF will present to an emergency department (ED)
at some time due to symptoms, representing 3-6% of all medical
admissions to hospital.1 Overall, the estimated care costs of
hospitalized AF patients are 9 to 23-fold greater than for those
without AF.
8
Most AF care is delivered through family physicians, eventual
referral to specialists, but many repeated emergency room visits,
or even hospitalizations may have occurred, prior to specialist
assessment. Mcdonald et al. reported an 88% increase in ED visits
with a primary diagnosis of AF over a 12 year period (1993 to
2004).
9
Of these, 64% were admitted to hospital; this proportion
remained constant over the 12 year period. There are few data on
the actual costs to the health care system for AF. Khaykin et al.
estimated a cost of $4840/patient/year of AF.
10
The distribution
of costs are amongst inhospital care, emergency room visits and
family physician visits. There are many aspects of AF management
that are best managed by those specifically trained to manage
AF. It is well documented that there are a number of care gaps
in management of AF at the general practitioner level.
11,12
These
issues relate to which patients to anticoagulate, when to perform
a cardioversion, when to switch from rate to rhythm control, and
when to refer for catheter ablation.
Pathophysiology of AF as it relates to cardiovascular risk factors
AF may be due to one of three mechanisms:
13
the initiation
and perpetuation of atrial fibrillation requires triggers which
start an episode, and an arrhythmogenic substrate which allows
it to continue. The triggers typically consist of ectopy which most
frequently originate in the pulmonary veins, but extra-pulmonary
Canadian Journal of General Internal Medicine
22 Volume 13, Special Issue 1, 2018
vein triggers may also exist in the coronary sinus, superior vena
cava or within the body of the left atrium.
14,15
The maintenance
of AF, once triggered, is due to changes in atrial structural and
electrophysiologic properties. These changes may result from
a wide variety of causes including left atrial stretch, structural
remodeling leading to atrial fibrosis, as in congestive heart failure.
16
Paroxysms of rapid, consecutive premature atrial contractions, or
short paroxysms of AF, can promote further functional changes
that can perpetuate AF.
17
The role of the autonomic nervous
system in the maintenance of AF has also been extensively
studied. The ganglionic plexi are located along the great vessels
and in the pericardial fat pads. Scherlag et al. have performed
numerous experimental studies demonstrating that activation of
the ganglionic plexi at the junctions of the pulmonary vein and
atrium may result in conversion of pulmonary vein ectopy to
atrial fibrillation.
18
Kistler et al. studied the effect of chronically
elevated BP in animal models. It was found that elevated BP was
associated with atrial fibrosis, significant conduction abnormalities,
shortening of atrial wavelength and increased AF.
19
In both human
and animal models, obstructive sleep apnea has been shown
to result in increased atrial fibrosis and increased incidence of
extra-pulmonary vein triggers.
20
Other clinical factors have been
implicated in atrial remodeling and consequent AF, including:
increased age, obesity, diabetes and heart failure.
Current Status of Management of AF
Current guidelines suggest that AF treatment should focus on
strategies to prevent stroke, and to manage and control heart rate
and rhythm.
21,22
AF is known to be a chronic disease. Rarely, patients
will have a single episode of AF, but the majority of patients have
progressively more episodes, or present with persistent AF. As
with all chronic diseases, it cannot be cured but can be controlled
with effective treatments, as recommended by the guidelines. Our
current health care system was designed to address acute illness,
rather than chronic disease. AF often occurs in the setting of other
diseases, increasing the complexity in determining appropriate
therapies. Lone atrial fibrillation occurs in a very small proportion of
patients who present with new onset AF and may not even be a real
entity. Most often, AF occurs in the setting of other cardiovascular
disease, obesity, diabetes, sleep apnea or a combination of the
above. In order to effectively manage AF, a ‘holistic’ approach is
necessary. Appropriate management of hypertension, sleep apnea,
obesity etc needs to become part of the mainstay of therapy for
AF. The CCS AF guidelines recommendations state: “Underlying
causes or precipitating factors for AF including hypertension
should be identified and treated.”
23
Possible targets for these are
included in Table 1.
24
Lifestyle Modification in AF
There are several facets of lifestyle modification that can be
addressed to modify AF and its resultant outcomes. Risk factor
modification has been termed the fourth pillar of AF care,
with the first three being rate, rhythm and stroke prevention.
The presence of risk factors that are known to promote AF are
increasing in prevalence in the population: it is likely that the
AF epidemic is greater than predicted. The Framingham study
evaluated the incidence and prevalence of AF and its risk factors
over 50 years.25 In 9511 patients over 50 years of observation,
the incidence of AF increased in both men (3.7 vs 13.4 per 1000
person-years) and women (2.5 vs 8.5 per 1000 person-years).
Conventional Risk Factors Emerging Risk Factors Less Established Risk Factors
Advancing age Subclinical atherosclerosis Chronic obstructive pulmonary disease
male Borderline hypertension Left atrial dilatation
Coronary artery disease Chronic kidney disease Atrial conduction delay/PR interval
hypertension Subclinical hyperthyroidism Left ventricular diastolic dysfunction
Heart failure Inflammation Left ventricular hypertrophy/diastolic dysfunction
Valvular disease Elevated natriuretic peptides Obesity
diabetes Widened pulse pressure Genetic factors
Thyroid disease Excessive endurance exercise
Obstructive sleep apnea syndrome Excessive alcohol intake
Increased height
Increased birth weight
Smoking
Caffeine intake
Ethnicity
Table 1. Potentially Modifiable Risk Markers/Conditions Associated with AF
24
Does Lifestyle Impact Risk, Burden, and Symptomatology of Atrial Fibrillation?
Canadian Journal of General Internal Medicine
Volume 13, Special Issue 1, 2018 23
The population attributable risk over time for AF increased
due to higher body mass index (BMI) and diabetes. In a further
analysis of the Framingham study, the risk profile of patients as
it related to the lifetime risk of atrial fibrillation as assessed.
26
In
this study 4.6% of patients had an optimal risk profile, defined as
no smoking, alcohol consumption within recommended limits,
normal body mass index, normotensive, no diabetes, heart failure
or myocardial infarction. The lifetime risk of AF was 23.4% with
an optimal risk profile, 33.4% with a borderline risk profile and
38.4% with an elevated risk profile (Figure 1).
The diagram in Figure 2 demonstrates the inter-relationship
of these facets.
Exercise in AF
Exercise and physical activity have been shown to improve outcomes
in patients with cardiac health conditions such as ischemic heart
disease, myocardial infarction and congestive heart failure but its
effects on AF remain somewhat unclear.
28
Exercise has numerous
cardiac effects including reducing heart rate and increasing stroke
volume. Chronic exercise can further help protect the myocardium
from acute ischemia and improve function in response to cardiac
insults such as hypertension, myocardial infarction and general
wear and tear associated with aging.
29
The effects of exercise training on health benefits in AF
have been evaluated in two systematic reviews. These studies
have demonstrated that exercise can increase exercise capacity,
improve quality of life, and provide a mechanism of rate control
in AF patients.
30,31
An increase in exercise capacity in AF patients
who exercised was demonstrated with increased distances in
six-minute walk tests, and increased muscular strength, power
and work. Exercise has been shown in some studies to lower
resting heart rate by 7 beats per minute and improve heart rate
reserve by 15 beats per minute. It should be noted that there are
many important parameters to consider when evaluating health
outcomes with exercise in AF patients. More work is needed to
establish appropriate values for these parameters to maximize
beneficial health outcomes.
While many studies have enrolled AF patients in different
exercise regimens, only a handful to our knowledge have reported
adverse events.
31
An estimated life-threatening adverse event rate
of 1 per 209 752 minutes of exercise has been calculated in AF
patients. Similarly for non-life-threatening adverse events (e.g.,
ischemic chest pain, exercise-induced AF), the adverse event
rate is estimated to increase to 1 per 9756 minutes of exercise.
These studies suggest that exercise is a safe therapy that can be
further investigated in AF patients. The significance of this work
is highlighted by the fact that patients with AF often present with
symptoms of dyspnea, fatigue, palpitations, and decreased exercise
capacity. These symptoms not only make it more difficult for
patients to exercise, but also reduces their quality of life. Exercise
intolerance and sedentary behaviour specifically can drive weight
gain and lead to a variety of health issues. The effects of physical
activity, as well as physical inactivity ie sedentary behaviour, is
unknown in this population. The FIT project examined 64 561
adults without AF from 1991 to 2009 and found that one higher
metabolic equivalent during treadmill testing was associated with a
7% lower risk of incident AF, with a stronger relationship amongst
obese patients.
32
The CARDIO FIT study found an association
between a gain of ≥2 METS pre and post a tailored exercise program
to be associated with improvements in AF burden and symptom
severity in a single center cohort study. Malmo et al. performed
a single center randomized trial in 50 patients demonstrating
a positive effect of intense aerobic interval training to reduce
Figure 1. Cumulative risk (%) for development of AF according to risk-factor
burden: optimal, borderline or elevated. Shading=95% confidence intervals.
26
Figure 2. Relationship of cardiovascular risk factors to pathogenesis of AF.
Adapted from Van Wagoner et al.
27
Parkash et al
Canadian Journal of General Internal Medicine
24 Volume 13, Special Issue 1, 2018
recurrent AF in a population of patients with nonpermanent
AF.
33
Although none of these studies provide definitive evidence
regarding the benefits of exercise in AF, they do demonstrate
that it is reasonable to have patients with AF perform moderate
exercise, without the danger of deleterious effects.
Obesity and AF
Two randomized trials have shown reduction of AF and improved
quality of life in patients with obesity and in patients with heart
failure.
34,35
Abed et al. examined the effect of weight reduction and
cardiometabolic risk factor treatment in patients with AF.34 Abed
et al. examined the effect of weight reduction and cardiometabolic
risk factor treatment in patients with AF and found an improvement
in AF-related quality of life in the experimental arm. The LEGACY
study was a cohort study that demonstrated weight reduction
of ≥ 10% to be associated with a six-fold greater probability of
arrhythmia-free survival compared with the those who loss less
weight or did not lose weight at all.
36
Blood Pressure and AF
Hypertension is the most prevalent, independent and potentially
modifiable risk for atrial fibrillation.
37,38
The Framingham study
revealed that an electrocardiographic diagnosis of LVH increases
the risk of AF by more than 3 fold.
39
These changes may be a
direct result of increased left atrial stretch resulting from increased
pressures on the left side of the heart.
Recent studies have found a direct relationship between the
risk of AF and systolic and diastolic BP. Conen et al. evaluated the
risk of incident AF in healthy, middle-aged women as it pertains
t o B P.
40
Over a followup period of 12.4 years, the longer term risk
of AF increased as the systolic and diastolic BP increased. Only a
systolic BP < 120 mmHg was not associated with an increased HR of
developing AF. The primary prevention of AF with antihypertensive
therapy has been reported previously. A post-hoc analysis of
the Losartan Intervention for Endpoint reduction (LIFE) study
found that losartan reduced the incidence of new-onset AF from
10.1 to 6.8 per 1000 patient-years, as compared to atenolol alone;
a meta-analysis examining the effect of angiotensin converter
enzyme inhibition or angiotensin II receptor blockade on primary
prevention of AF in patients with structural heart disease showing
similar findings, providing support for the pleotropic effects of
these medications.
41,42
Whether aggressive BP control is of benefit in prevention of
AF once it develops remains elusive. Secondary prevention of AF,
has not been found to be of benefit using angiotensin converter
enzyme inhibition or angiotensin II receptor blockade. The Gruppo
Italiano per lo Studio della Sopravvivenza nell’Insufficienza cardiac
Atrial Fibrillation (GISSI-AF) study failed to show any benefit in
preventing recurrent AF in a population of AF with paroxysmal
or persistent AF.
43
The Atrial Fibrillation Clopidogrel Trial with
Irbesartan to Prevent Vascular Events (ACTIVE I) trial also failed to
show that the pleotropic effects of angiotensin II receptor blockade
had any effect on cardiovascular outcomes in patients with AF.
44
Parkash et al performed a multicenter, randomized trial
examining the effect of an aggressive blood pressure control
strategy on recurrent AF after catheter ablation.
45
This study
did not find a benefit to reduction in AF with targeting this risk
factor in isolation. The study did however demonstrate that
patients whose baseline blood pressure was < 140 mm Hg, had a
significantly lower recurrence of AF after ablation, as compared
to those whose blood pressure was elevated at baseline (45%
recurrence for SBP<140 compared to 86% recurrence for SBP>150,
p=0.03). Patients older than the age of 61 had a significant benefit
to aggressive BP lowering, as compared to younger patients (pfor
interaction =0.011).
These studies did not find direct benefits to aggressive BP
lowering in AF; it remains important, however, to treat this risk
factor using the current recommendations from the Canadian
Hypertension Education Program guidelines as the target for BP
control in AF patients.
46
Sleep Apnea and AF
Sleep apnea is a disorder of breathing resulting in hypoventilation,
hypopneas and apnea during sleep. It is associated with deleterious
outcome when left untreated, particularly from a cardiovascular
viewpoint.
47
It is known to affect 4% of middle-aged men and 2%
of middle-aged women, as a whole. In the setting of concomitant
AF, sleep apnea has been found to occur in up to 1 in 5 patients in
the ORBIT AF registry.
48
The ORBIT registry also demonstrated
in reduction in progression to AF, with no effect on mortality
or cardiovascular hospitalization. Obstructive sleep apnea and
AF are known to coexist; the risk of AF recurrence is higher in
patients who have undergone catheter ablation in patients with
obstructive sleep apnea, compared to those patients who do not
have it.
49
Systematic reviews have pooled data from cohort studies
that support the beneficial effect of sleep apnea treatment on AF,
in combination with catheter ablation of AF.
49
In a recent clinical
trial, there was no benefit of continuous positive airway pressure
therapy on cardiovascular outcomes
50
; the effect of CPAP in AF has
been shown to be of benefit in cohort studies but no randomized
studies have been performed.
Multifactorial Risk Factor Management
There have been a few studies that have examined the effect of
multifactorial risk factor management in patients with AF. The
concept here is that treating a single risk factor in isolation may be
ineffective, that many patients have multiple risk factors that coexist
and overlap to result in further maintenance of AF. Rienstra et al.
examined the optimization of heart failure medications, cardiac
rehabilitation and aggressive blood pressure control in patients
Does Lifestyle Impact Risk, Burden, and Symptomatology of Atrial Fibrillation?
Canadian Journal of General Internal Medicine
Volume 13, Special Issue 1, 2018 25
with AF and heart failure, and demonstrated maintenance of sinus
rhythm as measured on a 7 day Holter at one year pf 75% in the
intervention group, as compared to 63% in the control group (OR
1.77, p=0.042).
35
Another single center study examined the role
of risk factor management concomitantly with catheter ablation
for AF. Pathak et al. performed a single center, cohort study that
demonstrated that patients who chose to undergo aggressive risk
factor modification had a reduction in AF compared to those
who did not with an odds ratio of 4.8 (95% confidence interval
2.04-11.4).
51
Delivery of Lifestyle Modification: Use of SpecializedClinics
How best to deliver lifestyle modification to this population
remains an unanswered question. The use of cardiac rehabilitation
programs has been traditionally reserved for those with acute
coronary syndromes. Expansion of these programs to include
AF patients could result in an overload of this resource, required
for a different cardiac population. In addition, ensuring delivery
of care across geographic boundaries, particularly in Canada is
important. Using ‘bricks and mortar’ programs, this becomes
difficult. Specialized AF clinics have garnered significant attention
recently. The studies that have been performed are discussed below.
Gillis et al. published their preliminary data from this type of
clinic, which showed encouraging results.
52
The clinic accepted
20–40 patients per week for assessment. The time for specialist
assessment was brought to 38+/-31 days, as compared to 221+/-
774 days in the year prior to the formation of the clinic. The
number of emergency department visits and hospitalizations
were dramatically reduced, 82% and 56% respectively. Gillis et
al. first established their clinic through an innovative fund from
their health care region. The results were so positive that funds to
permanently establish this clinic were allocated. The Integrated
Management to AF study (ICAT-AF) demonstrated that a nurse-
led, physician supervised program providing education and
management of risk factors (before-after study; n=433) could
improve guideline adherence, and improve health outcomes
(decreased AF-related ED visits and hospitalizations by 29% in
new onset AF.
53
The largest study examining this model of care
was performed in the Netherlands. Hendriks et al. demonstrated
a reduction in CV mortality in a randomized controlled trial of
a nurse-led, physician supervised AF clinic in the Netherlands,
as compared to usual care.
54
Cardiovascular death occurred at a
rate of 1.1% in the nurse-led care vs. 3.9% in the usual care group
(hazard ratio: 0.28; 95% CI: 0.09–0.85; P= 0.025); cardiovascular
hospitalization was reduced to 13.5 from 19.1% in the usual care
group (hazard ratio: 0.66; 95% CI: 0.46–0.96, P=0.029). The
Hendriks study utilized a computer-based algorithm to assist the
nurse with the AF care. This computer-based algorithm is costly
to apply widely and as such the outcomes observed by the study
may not be generalizable.
Multiple prior studies have demonstrated the effectiveness
of multidisciplinary care in peri-procedural management. Recent
reviews have emphasized the importance of integrated care for
heart rhythm disorders. Greater coordination of care with nursing
interventions has demonstrated more efficient use of resources,
55
and better coordination of heart rhythm procedures,
56,57
as well
as better implementation of other cardiac therapies.
58,59
In these studies, the observed reduction in primary outcome
events may be attributable to several factors including consistency
of patient education delivered by a nurse, repeated encounters,
improved guideline adherence, particularly in OAC use, as well
as risk factor management, resulting in the observed reduction in
cardiovascular events. Significant delays in receiving guideline-
indicated therapies, specifically appropriate anticoagulation, could
lead to adverse cardiovascular outcomes. Based on previously
published data, the monthly incidence of stroke with non-valvular
AF ranges from 0.23% to 1.5%, depending on CHADS2 score.
60
Given wait times for specialist assessment, whether through a
specialized AF clinic or specialist usual care, the incidence of
stroke could be reduced by improving anticoagulation at the
time of AF diagnosis.
Conclusion
The difficulty arises in how patients with AF and its associated
risk factors should be managed. The use of specialized clinics
may result in patients receiving care from various specialists,
that may lead to multiple and potentially conflicting treatment
recommendations. As the complexity of medical problems
plaguing an individual patient increases, so does the number
of specialty clinics that he/she may be exposed to. This results
in greater need for centralization of a patient’s care with their
family physician. Risk factor management may be improved by
a form of integrated care. Using a combination of pharmacologic
and non-pharmacologic treatments (ie focus on lifestyle), risk
factors that aggravate and trigger AF likely need to become a
part of our usual armamentarium of care in AF patients. The
most expeditious model of care for AF remains a challenge in
our resource-constrained environment, but remains an important
focus to improve outcomes associated with AF.
References
1. Lip GY, Tse HF. Management of atrial fibrillation. Lancet 2007;370:604–618.
2.
Wolf PA, Dawber TR, Thomas HE, Jr., Kannel WB. Epidemiologic assessment
of chronic atrial fibrillation and risk of stroke: the Framingham study.
Neurology 1978;28:973–977.
3. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor
to stroke in the elderly. The Framingham Study. ArchInternMed
1987;147:1561–1564.
4. Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D.
Impact of atrial fibrillation on the risk of death: the Framingham Heart Study.
Circulation 1998;98:946–52.
5. Stroke. Heart and Stroke Foundation of Canada 2013.
Parkash et al
Canadian Journal of General Internal Medicine
26 Volume 13, Special Issue 1, 2018
6. Parkash R, Maisel WH, Toca FM, Stevenson WG. Atrial fibrillation in heart
failure: high mortality risk even if ventricular function is preserved. AmHeart
J 2005;150:701–706.
7.
Kirchhof P, Schmalowsky J, Pittrow D et al. Management of patients with
atrial fibrillation by primary-care physicians in Germany: 1-year results of
the ATRIUM registry. Clin Cardiol 2014;37:277–84.
8.
Wolf PA, Mitchell JB, Baker CS, Kannel WB, D’Agostino RB. Impact of
atrial fibrillation on mortality, stroke, and medical costs. Arch Intern Med
1998;158:229–34.
9.
McDonald AJ, Pelletier AJ, Ellinor PT, Camargo CA, Jr. Increasing US
emergency department visit rates and subsequent hospital admissions for
atrial fibrillation from 1993 to 2004. AnnEmergMed 2008;51:58–65.
10.
Khaykin Y, Morillo CA, Skanes AC, McCracken A, Humphries K, Kerr
CR. Cost comparison of catheter ablation and medical therapy in atrial
fibrillation. Journal of cardiovascular electrophysiology 2007;18:907–13.
11.
Gladstone DJ, Bui E, Fang J et al. Potentially preventable strokes in high-risk
patients with atrial fibrillation who are not adequately anticoagulated. Stroke
2009;40:235–240.
12.
Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GY. Underuse of
oral anticoagulants in atrial fibrillation: a systematic review. Am J Med
2010;123:638–645.
13.
Nattel S. New ideas about atrial fibrillation 50 years on. Nature 2002;415:219–226.
14.
Haissaguerre M, Jais P, Shah DC et al. Spontaneous initiation of atrial
fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med
1998;339:659–666.
15.
Dixit S, Marchlinski FE, Lin D et al. Randomized ablation strategies for
the treatment of persistent atrial fibrillation: RASTA study. Circ Arrhythm
Electrophysiol 2012;5:287–94.
16.
Saygili E, Rana OR, Saygili E et al. Losartan prevents stretch-induced
electrical remodeling in cultured atrial neonatal myocytes. Am J Physiol
Heart Circ Physiol 2007;292:H2898-H2905.
17.
Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation
begets atrial fibrillation. A study in awake chronically instrumented goats.
Circulation 1995;92:1954–1968.
18.
Scherlag BJ, Patterson E, Po SS. The neural basis of atrial fibrillation. J
Electrocardiol 2006.
19. Kistler PM, Sanders P, Dodic M et al. Atrial electrical and structural
abnormalities in an ovine model of chronic blood pressure elevation after
prenatal corticosteroid exposure: implications for development of atrial
fibrillation. Eur Heart J 2006;27:3045–3056.
20. Anter E, Di Biase L, Contreras-Valdes FM et al. Atrial Substrate and Triggers
of Paroxysmal Atrial Fibrillation in Patients With Obstructive Sleep Apnea.
Circ Arrhythm Electrophysiol 2017;10.
21.
Gillis AM, Verma A, Talajic M, Nattel S, Dorian P. Canadian cardiovascular
society atrial fibrillation guidelines 2010: rate and rhythm management.
CanJCardiol 2011;27:47–59.
22.
Cairns JA, Connolly S, McMurtry S, Stephenson M, Talajic M. Canadian
cardiovascular society atrial fibrillation guidelines 2010: prevention of stroke
and systemic thromboembolism in atrial fibrillation and flutter. CanJCardiol
2011;27:74–90.
23. Healey JS, Parkash R, Pollak PT, Tsang TS, Dorian P. Canadian
Cardiovascular Society 2010 Atrial Fibrillation Guidelines: Chapter 2 - Atrial
Fibrillation: Etiology and Initial Investigations. CanJCardiol 2011.
24.
Wyse DG, Van Gelder IC, Ellinor PT et al. Lone atrial fibrillation: does it
exist? J Am Coll Cardiol 2014;63:1715–23.
25. Schnabel RB, Yin X, Gona P et al. 50 year trends in atrial fibrillation
prevalence, incidence, risk factors, and mortality in the Framingham Heart
Study: a cohort study. Lancet 2015;386:154–62.
26. Staerk L, Wang B, Preis SR et al. Lifetime risk of atrial fibrillation according
to optimal, borderline, or elevated levels of risk factors: cohort study based on
longitudinal data from the Framingham Heart Study. BMJ 2018;361:k1453.
27. Van Wagoner DR, Piccini JP, Albert CM et al. Progress toward the prevention
and treatment of atrial fibrillation: A summary of the Heart Rhythm Society
Research Forum on the Treatment and Prevention of Atrial Fibrillation,
Washington, DC, December 9-10, 2013. Heart Rhythm 2015;12:e5-e29.
28.
Belardinelli R, Georgiou D, Ginzton L, Cianci G, Purcaro A. Effects of
moderate exercise training on thallium uptake and contractile response to
low-dose dobutamine of dysfunctional myocardium in patients with ischemic
cardiomyopathy. Circulation 1998;97:553–561.
29. Osbak PS, Mourier M, Kjaer A, Henriksen JH, Kofoed KF, Jensen GB. A
randomized study of the effects of exercise training on patients with atrial
fibrillation. AmHeart J 2011;162:1080–1087.
30.
Reed JL, Mark AE, Reid RD, Pipe AL. The effects of chronic exercise
training in individuals with permanent atrial fibrillation: a systematic review.
CanJCardiol 2013;29:1721–1728.
31.
Giacomantonio NB, Bredin SS, Foulds HJ, Warburton DE. A systematic
review of the health benefits of exercise rehabilitation in persons living with
atrial fibrillation. CanJCardiol 2013;29:483–491.
32.
Qureshi WT, Alirhayim Z, Blaha MJ et al. Cardiorespiratory Fitness and Risk
of Incident Atrial Fibrillation: Results From the Henry Ford Exercise Testing
(FIT) Project. Circulation 2015;131:1827–34.
33.
Pathak RK, Elliott A, Middeldorp ME et al. Impact of CARDIOrespiratory
FITness on Arrhythmia Recurrence in Obese Individuals With Atrial
Fibrillation: The CARDIO-FIT Study. J Am Coll Cardiol 2015;66:985–96.
34.
Abed HS, Wittert GA, Leong DP et al. Effect of weight reduction and
cardiometabolic risk factor management on symptom burden and severity
in patients with atrial fibrillation: a randomized clinical trial. JAMA
2013;310:2050–2060.
35. Rienstra M, Hobbelt AH, Alings M et al. Targeted therapy of underlying
conditions improves sinus rhythm maintenance in patients with persistent
atrial fibrillation: results of the RACE 3 trial. Eur Heart J 2018.
36.
Pathak RK, Middeldorp ME, Meredith M et al. Long-Term Effect of Goal
Directed Weight Management in an Atrial Fibrillation Cohort: A Long-term
Follow-Up StudY (LEGACY Study). J Am Coll Cardiol 2015.
37.
Parkash R, Verma A, Tang AS. Persistent atrial fibrillation: current approach
and controversies. Curr Opin Cardiol 2010;25:1–7.
38. Healey JS, Connolly SJ. Atrial fibrillation: hypertension as a causative agent,
risk factor for complications, and potential therapeutic target. Am J Cardiol
2003;91:9G-14G.
39.
Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis,
and predisposing conditions for atrial fibrillation: population-based
estimates. Am J Cardiol 1998;82:2N-9N.
40.
Conen D, Tedrow UB, Koplan BA, Glynn RJ, Buring JE, Albert CM.
Influence of systolic and diastolic blood pressure on the risk of incident atrial
fibrillation in women. Circulation 2009;119:2146–2152.
41.
Wachtell K, Lehto M, Gerdts E et al. Angiotensin II receptor blockade reduces
new-onset atrial fibrillation and subsequent stroke compared to atenolol:
the Losartan Intervention For End Point Reduction in Hypertension (LIFE)
study. J Am Coll Cardiol 2005;45:712–719.
42. Healey JS, Baranchuk A, Crystal E et al. Prevention of atrial fibrillation with
angiotensin-converting enzyme inhibitors and angiotensin receptor blockers:
a meta-analysis. J Am Coll Cardiol 2005;45:1832–1839.
43. Disertori M, Latini R, Barlera S et al. Valsartan for prevention of recurrent
atrial fibrillation. N Engl J Med 2009;360:1606–1617.
44.
Yusuf S, Healey JS, Pogue J et al. Irbesartan in patients with atrial fibrillation.
N Engl J Med 2011;364:928–38.
45. Parkash R, Wells GA, Sapp JL et al. Effect of Aggressive Blood Pressure
Control on the Recurrence of Atrial Fibrillation After Catheter Ablation:
A Randomized, Open-Label Clinical Trial (SMAC-AF [Substrate
Modification With Aggressive Blood Pressure Control]). Circulation
2017;135:1788–1798.
46. Leung AA, Daskalopoulou SS, Dasgupta K et al. Hypertension Canada’s 2017
Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of
Hypertension in Adults. Can J Cardiol 2017;33:557–576.
47. Marini C, De SF, Sacco S et al. Contribution of atrial fibrillation to incidence
and outcome of ischemic stroke: results from a population-based study.
Stroke 2005;36:1115–1119.
48. Holmqvist F, Guan N, Zhu Z et al. Impact of obstructive sleep apnea and
continuous positive airway pressure therapy on outcomes in patients with
atrial fibrillation-Results from the Outcomes Registry for Better Informed
Does Lifestyle Impact Risk, Burden, and Symptomatology of Atrial Fibrillation?
Treatment of Atrial Fibrillation (ORBIT-AF). American heart journal
2015;169:647–654 e2.
49.
Li L, Wang ZW, Li J et al. Efficacy of catheter ablation of atrial fibrillation in
patients with obstructive sleep apnoea with and without continuous positive
airway pressure treatment: a meta-analysis of observational studies. Europace
2014;16:1309–14.
50. McEvoy RD, Antic NA, Heeley E et al. CPAP for Prevention of Cardiovascular
Events in Obstructive Sleep Apnea. N Engl J Med 2016;375:919–31.
51.
Pathak RK, Middeldorp ME, Lau DH et al. Aggressive risk factor reduction
study for atrial fibrillation and implications for the outcome of ablation: the
ARREST-AF cohort study. J Am Coll Cardiol 2014;64:2222–2231.
52.
Gillis AM, Burland L, Arnburg B et al. Treating the right patient at the right
time: an innovative approach to the management of atrial fibrillation. Can J
Cardiol 2008;24:195–198.
53.
Carter L, Gardner M, Magee K et al. An Integrated Management Approach to
Atrial Fibrillation. J AmHeart Assoc 2016;5.
54.
Hendriks JM, de WR, Crijns HJ et al. Nurse-led care vs. usual care for
patients with atrial fibrillation: results of a randomized trial of integrated
chronic care vs. routine clinical care in ambulatory patients with atrial
fibrillation. Eur Heart J 2012;33:2692–2699.
55. Gross PA, Patriaco D, McGuire K, Skurnick J, Teichholz LE. A nurse
practitioner intervention model to maximize efficient use of telemetry
resources. Jt Comm J Qual Improv 2002;28:566–573.
56.
Shelton RJ, Allinson A, Johnson T, Smales C, Kaye GC. Four years experience
of a nurse-led elective cardioversion service within a district general hospital
setting. Europace 2006;8:81–85.
57.
Boodhoo L, Bordoli G, Mitchell AR, Lloyd G, Sulke N, PatelN. The safety
and effectiveness of a nurse led cardioversion service under sedation. Heart
2004;90:1443–1446.
58.
Andersen MK, Markenvard JD, Schjott H, Nielsen HL, Gustafsson F. Effects
of a nurse-based heart failure clinic on drug utilization and admissions in a
community hospital setting. Scand Cardiovasc J 2005;39:199–205.
59.
Andersson B, Kjork E, Brunlof G. Temporal improvement in heart failure
survival related to the use of a nurse-directed clinic and recommended
pharmacological treatment. Int JCardiol 2005;104:257–263.
60.
Olesen JB, Lip GY, Hansen ML et al. Validation of risk stratification
schemes for predicting stroke and thromboembolism in patients with atrial
fibrillation: nationwide cohort study. BMJ 2011;342:d124.
Parkash et al