Canadian Journal of General Internal Medicine

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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.

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.

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.

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.

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.

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.

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).

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.

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:

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.

Paroxysms of rapid, consecutive premature atrial contractions, or

short paroxysms of AF, can promote further functional changes

that can perpetuate AF.

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.

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.

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.

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.”

Possible targets for these are

included in Table 1.

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

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.

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.

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.

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.

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.

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.

Figure 2. Relationship of cardiovascular risk factors to pathogenesis of AF.

Adapted from Van Wagoner et al.

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.

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.

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.

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.

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.

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.

Parkash et al performed a multicenter, randomized trial

examining the effect of an aggressive blood pressure control

strategy on recurrent AF after catheter ablation.

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.

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.

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.

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.

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.

In a recent clinical

trial, there was no benefit of continuous positive airway pressure

therapy on cardiovascular outcomes

; 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).

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).

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.

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.

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.

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,

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.

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.

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