Atrial fibrillation

Endothelial dysfunction due to atherosclerosis is considered to play a vital role, and inflammation and prothrombotic factors are known to be elevated in patients with AF and may contribute to endothelial dysfunction and thrombus formation in the left atrium.

AF may occur because of different pathophysiological conditions that lead to remodeling of the left atrium.

It is a chronic, progressive disorder with increased risk of thromboembolism and heart failure.

It starts as an isolated electrical disorder, but progressive electrical and structural remodeling of the heart leads to longer lasting forms of atrial fibrillation.

About 1/3 of cases of AF start out as a short, self terminating paroxysmal episode that progresses to longer lasting persistent attacks over time.

Once the transition from paroxysmal to persistent, AF occurs, treatment success decreases, and adverse risks increase.

Affects up to 2% of the population.

Accounts for an estimated $6.65 billion in annual expenditures.

Approximately 33.5 million individuals have atrial fibrillation worldwide.

By age 75 years, more than 10% of the population will have developed atrial fibrillation.

Prevalence increasing: expected to increase 3 fold in the next 3 decades.

Lifetime risk for developing AF is 21% – 23% in women and 17 – 26% in men.

Lifetime risk of each fibrillation is estimated about one in three individuals of European ancestry and one in five in those of African ancestry.

In high income countries the development of atrial disease and atrial fibrillation is most often a consequence of hypertension, ischemic heart disease, or advanced stage.

In low and middle income countries rheumatic heart disease is an important cause of atrial enlargement and atrial fibrillation.

Most common cardiac arrhythmia in the elderly.

AF is the most common sustained arrhythmia affecting approximally 1% of the population.

Cardio respiratory fitness is protective of atrial fibrillation , which is the most common arrhythmia worldwide with clinical significance.

Accounts for approximately one third of hospitalizations for cardiac rhythm disturbances.

After age 60 is a marker for increase in cardiovascular events.

Symptoms include, but are not limited to, palpitations, exercise intolerance, and ddyspnea.

Mortality rates among patients with atrial fibrillation remain up to 2 fold higher than mortality rates among individuals without atrial fibrillation, even with anticoagulation.

Patients with AF have stroke, acute coronary syndrome, heart failure, and cardiovascular death at a rate of approximately 5% per year, and 35-50% of patients with AF receive adequate anticoagulation either receive inpattient therapy or die within five years.

Trials have shown that the cessation of anticoagulation given the maintenance of sinus rhythm may be harmful, and the benefit of atrial fibrillation suppression can be achieved when anticoagulation is maintained:an explanation is that atrial fibrillation is aa epiphenomenon, a marker for an underlying atrial myopathy, or atrial cardiopathy, and not necessarily causal of atrial fibrillation.

The prevalence of coronary artery disease and peripheral artery disease among patients with atrial fibrillation ranges from 18-45% and 4-17%, respectively.

Will affect one in six individuals.

Lifetime risk from age 40 years and older is 26%.

Approx 5% of patients with atrial fibrillation have no risk factors for stroke.

Modifiable risk factors include hypertension, obesity, diabetes, sleep apnea, sedentary lifestyles, and alcohol consumption.

Approximately 1/3 of patients with atrial fibrillation at risk for a stroke are not given oral anticoagulants, but instead are treated with antiplatelet monotherapy or left untreated.

Only one and 10 deaths in AF are stroke related, whereas seven in 10 deaths are ucardiovascular related.

Many patients discontinue oral anticoagulation.

BNP and NT-Pro-BNP are associated with atrial fibrillation incidence, post-operative atrial fibrillation incidence, and prognosis in atrial fibrillation.

BNP and NT-BNP associated with diagnosis of heart failure in atrial fibrillation.

Inflammatory biomarkers commonly preceded the onset of atrial fibrillation and heart failure with preserved ejection fraction in the general community.
Atrial fibrillation and heart failure with a preserved ejection fraction are closely intertwined, and atrial fibrillation is the most common harbinger of heart failure with a preserved ejection fraction, and most patients with heart failure with preserved ejection fraction develop atrial fibrillation at some point in their course.

Commonly occurs in heart failure-in greater than 40% of patients with reduced ejection fraction and in greater than 60% with preserved ejection fraction.

Many patients with AF have evidence of latent heart failure on invasive or non-invasive evaluation.
Patients with atrial fibrillation and heart failure with a preserved ejection fraction frequently have evidence of an expansion of epicardial adipose tissue.
Circulating levels of adipocytokine are commonly associated with epicardial fat inflammation and leptin is increase in patients with atrial fibrillation or with heart failure with preserved ejection fraction.

Only half of all eligible patients are prescribed oral anticoagulation in accordance with guidelines (Mazurek M).

28% of high-risk patients defined as CHA2DS2-VASc are not anticoagulated, where as 51% of very low risk patients are inappropriately anticoagulated (Camm AJ).

Non-adherence to atrial fibrillation guidelines is common ranging from 33 – 68% among the high-risk population.

One in 10 patients with atrial fibrillation refuses to take oral anticoagulants, and the same proportion may have contraindications to anticoagulant therapy

In the Framingham study 1.8% of patients had AF.

Strong evidence for heritable relationship in that first degree relatives of individuals younger than 60 years with atrial fibrillation or nearly 5 times more likely to have atrial fibrillation compared with the general population.

Estimated 7 million affected patients in the U.S.

6% of men and 3% of women over the age of 65, and up to 16% of men and 12% of women over the age of 75 have atrial fibrillation.

Incidence of 3.7 per 1000 person-years in 2000 in the US (Miyasaka Y et al).

Direct costs of AF $6.billion annually.

Less frequently seen in Asians.

Atrial fibrillation is a stronger risk factor for stroke, heart disease, heart failure and death in women than it is in men.

Atria are susceptible to fibrosis that results from inflammation of epicardial adipose tissue seen in obesity or diabetes.

Atrial fibrosis results in persistent and long-standing atrial fibrillation.

Left atrial fibrosis, is  a hallmark of atrial myopathy, and plays an important role in the pathophysiology of AF.

Occurrence of process is common and its prevalence is much higher than the recognized prevalence of AF.

Prolonged atrial distention due to chronic increases in left ventricular filling pressure contributes to the genesis of atrial fibrillation.

Depression and anxiety are common in patients with AF.

Depressive symptoms are associated with increased likelihood of atrial fibrillation, and patients with AF have a higher level of anxiety in patients with hypertension.

Higher risk in patients with metabolic syndrome.

Obesity accounts for a substantial proportion of increasing prevalence.

Fat stores correlated with incident AF.

Classified in a number of ways: Lone atrial fibrillation-typically in patients younger than the age of 60 years without structural heart disease.

Classification systems can distinguish between primary and secondary AF: secondary type may be associated with cardiac surgery, hyperthyroidism or acute alcohol intoxication.

Classification also distinguishes between paroxysmal and non- paroxysmal AF.

Occurs in a paroxysmal, self remitting pattern or may persist.

In acute atrial fibrillation heart rate ranges from 60 beats per minute to 160 beats per minute or more.

The presence of paroxysmal atrial fibrillation has nearly the same risk for thromboembolic events in both the paroxysmal and chronic atrial fibrillation phases.

In contrast, patients with chronic atrial fibrillation the development of a rapid heart rate is more gradual and occurs in response to physical activity or other stresses.

Rate control involves the use of negatively chronotropic drugs such as beta-blockers, or calcium channel blockers to reduce the rapid ventricular rate frequently found in atrial fibrillation.

Heart rate control is an essential element of management and rate control relieves patients of symptoms of palpitations or dyspnea on exertion.

Conversely, Rhythm control involves the use of pharmacological, electrical, or surgical cardioversion to convert atrial fibrillation to normal sinus rhythm.

Early rhythm control therapy is associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with early age atrial fibrillation in cardiovascular conditions.

May be asymptomatic and therefore subclinical.

Subclinical atrial fibrillation describes AF that is asymptomatic or that produces short-lasting, non-specific symptoms/findings that is not readily diagnosed by standard clinical testing, but is diagnosed only with the use of long-term continuous cardiac rhythm monitoring or an implanted, cardiac pacemaker or defibrillator.

Subclinical atrial fibrillation is reported to be present in more than 1/3 of all the patients with hypertension, who had received a pacemaker, and was associated with an increased risk of ischemic stroke with systemic embolism by a factor of 2.5.

Among patients with subclinical atrial fibrillation, anticoagulant therapy results in a lower risk of stroke, or systemic embolism than aspirin, but a higher risk of major bleeding (ARTESIA Investigators).

There is an inverse association between exercise capacity and the likelihood of development of atrial fibrillation.

Autonomic dysregulation has been postulated as an important factor in its initiation.

The autonomic nervous system is associated with increased sympathetic outflow and efferent cardiac sympathetic nerve stimulation enhancing the development of atrial fibrillation.

Asymptomatic AF is associated with older age, more comorbidities, and higher thromboembolic risks.

Outcomes do not differ between asymptomatic and symptomatic  atrial fibrillation presentations as they are comparably reduced by anticoagulation.

Patient with atrial fibrillation have elevated comorbidity  indices compared to non-AF patients.

Asymptomatic AF patients have a 2 fold higher 1 year mortality rate than symptomatic patients (9.4% vs. 4.2%) (Boriani G et al).

Many patients with AF on screening EKG had not previously had a diagnosis of AF.

Since 15% of strokes are attributed to documented AF, 50 to 60% to documented cerebrovascular disease, and 25% patients who have ischemic strokes have no etiologic factor identified.

Approximately 20% of patients who have a stroke associated with atrial fibrillation are first diagnosed with atrial fibrillation at the time of the stroke or shortly thereafter.

Among patients with acute ischemic stroke in the US, 18.2% have atrial fibrillation and this prevalence increases 40% in patients older than 85 years.

Patients with AF and renal dysfunction are at increased risk of systemic embolic events relative to those without chronic kidney disease.

The risk of cardiovascular complications is increased during the first year after atrial fibrillation is diagnosed.

The need for anticoagulation is based on the assessment using CHA2DS2-VAScscore.

Relative stroke risk increases 7% with every 10 mL per minute per 1.73 minutes squared decrease in GFR.

A GFR <60 mL/min/1.73 m2 is associated with a 43% higher risk of incident stroke.

In a cohort study involving nearly 24,000 adults those who had AF at baseline were twice as likely to develop MI during the ensuing 7 years of follow-up.

The increased risk of MI conferred by AF is significantly stronger among women and blacks than among men and whites (Soliman EZ et al).

Associated with dementia.

Increases risk of dementia by 40% independent of the occurrence of clinical stroke.

Dementia associated with AF May be due to hypoperfusion, inflammation, brain atrophy, genetic factors.

Cerebral infarction, including silent stroke, play a central role in dementia.

Subclinical AF Is often suspected to be the cause of unidentified stroke.

Accounts fot 15-20% of all strokes.

Associated with an increased percentage of reticulated platelets which are relatively resistant to antiplatelet treatment.

The prevalence and prognosis of subclinical atrial fibrillation has been difficult to assess.

Associated with autonomic dysregulation as a result of sympathetic/parasympathetic mismatch.

May occur due to sudden shifts between high sympathetic and high vagal tone.

There may be a primary increase in adrenergic tone followed by an abuupt shift toeards vagal predominance.

A heterogeneous process influenced by multiple factors including: neural, structural, hemodynamic and electrical pathology.

Above factors include left atrial size, left atrial stretch in the setting of hypertension or diastolic dysfunction, and varied conduction patterns throughout the atrial myocardium due to fibrosis.

Hypertension is presently end up to 80% of individuals with atrial fibrillation.

Sodium channels control cell depolarization, beginning an action potential, while potassium channels the return the cell to its resting state through depolarization.

Electrical remodeling of the atria occurs such that repolarization is accelerated and the atrial action potential duration and refractory period are shortened with disruption of the normal depolarization/repolarization cycle of atria cells.

Prolonged tachycardia can lead to reduced LV function and clinical heart failure.

Patients converted to sinus rhythm after a number of months have improved left ventricular systolic function and exercise tolerance.

Risk factors include older age, male gender, hypertension, and underlying cardiac disease.

More prevalent in men in all age groups, but women account for over half of atrial fibrillation cases in daily practice as related to their superior survival.

Even brief periods of asymptomatic AF episodes can raise the risk of stroke.

Stroke from atrial fibrillation begins with the development of a left atrial appendage thrombus.

Thrombi in a fibrillating left atrial appendage contains platelet rich regions surrounded by layers of fibrin.

It is  thought that the heightened risk of stroke and systemic thromboemboli occurs due to the stasis of blood in the left atrial appendage, produced by rapid and disorganized fibrillation of atrial tissue.

The platelet count of embolized thrombi is greater than that of thrombi not embolized..

Caused by multiple electrical wavelets appearing in the atrium simultaneously, resembling the waves that would be produced if one drops pebbles in a bucket of water at the same time.

The arrhythmia is acute when it develops spontaneously in a person with a previously normal sinus rhythm.

In all cases of atrial fibrillation the ventricular response is irregular and the rate ranges from 60-220 beats permitted, depending on the patient’s age, whether there is underlying atrioventricular node disease, and where the patient has received drugs that affect the AV node.

The most triggers of AF are ectopic atrial beats that arise from muscle sleeve of the pulmonary veins.

There are a number of potassium channels in the atria and ventricles.

Kur (ultra-rapid delayed rectifier potassium channel) is predominantly active in the atria and not expressed in the ventricles.

Rarely, if ever, a one time event but can be expected to recur in an unpredictable fashion.

Resting cardiac output may improve by 15-43% when sinus rhythm is restored.

Rhythm control does not necessarily reduce the risk of stroke in AF.

An alternative to antiarrhythmic drugs is the Maze procedure involving ligation of the appendages of the atria followed by placement of incisions in locations that prevent the development of AF.

Maze procedure has an 80-90% chance of success and a 2% risk of complications including needing a pacemaker.

Despite therapy with antiarrhythmic drugs, studies report recurrence rates of 50-60% during a mean follow-up of one to two years.

Without preventative treatment, AF will recur in 90% of patients.

In hospitalized patients with AF an increase in comorbidity index is it inversely associated with oral anticoagulant prescriptions during follow-up and is associated with an increased risk of stroke, major bleeding and all-cause death.

The initial recommendation for AF is the use of anti-arrhythmic drugs for the maintenance of the sinus rhythm in symptomatic patients, however these medications have limited effective efficacy and they have substantial side effects.

Antiarrhythmic drugs have cumulative adverse effects over time.

Ablation of the atrioventricular node and permanent pacing are effective in controlling ventricular rate but does not eliminate atrial fibrillation.

Biventricular pacing is recommended for improvements in the quality of life, functional capacity, and left ventricular ejection fraction in patients with atrial fibrillation.

Atrioventricular nodal blockers, such as beta blockers and calcium-channel blockers are routinely used to control the heart rate.

Beta blockers can be given intravenously to control ventricular rate in AF or flutter.

Oral beta blockers are used to control rate long-term.

Beta blockers a preferred over calcium channel channel blockers in patients with coronary artery disease or systolic dysfunction.

In patients with AF related to stress or anxiety may have a better relief of symptoms with beta blockers than calcium-channel blockers due to the anti-adrenergic effects of beta blockers.

The calcium channel blockers diltiazem and verapamil are effective in slowing the ventricular rate in AF or flutter.

IV calcium channel blocker‘s can be complicated by hypertension or bradycardia.

Diltiazem and verapamil a preferred over beta blockers for use in patients with asthma. ardioversion

Catheter ablation of atrial fibrillation is an effective treatment for this arrhythmia, with reported cure rates of 60-70% for a paroxysmal AF after one or more procedures.

Catheter ablation, reduces, arrhythmia, recurrences, produces clinically, meaningful improvements and quality of life and reduces healthcare resource utilization.

Catheter ablation improve quality of life, but not mortality of cardiovascular outcomes.

Catheter ablation is superior to antiarrhythmic drugs in maintaining sinus rhythm improve the quality of life and patients in whom drugs have failed.

Catheter ablation as a first line treatment may be better than antiarrhythmic drugs in preventing the recurrence of atrial tachyarrhythmias, including the EF burden, and improving patient well-being.

Among patients receiving initial treatment for symptomatic, paroxysmal A F there was a significant lower rate of atrial fibrillation recurrence with catheter cryoballoon ablation than with antiarrhythmic drug therapy (Andrade JG).


In a randomized trial cryoballoon ablation as the initial therapy for AF was superior to drug therapy for the prevention of atrial arrhythmia recurrence In patients with paroxysmal atrial fibrillation (Wazni, O).

CABANA Trial showed that among patients with symptomatic atrial fibrillation, catheter ablation, compared with medical therapy, led to clinically important and significant improvement in the quality of life at 12 months.

The use of first line ablation therapy in the course of paroxysmal atrial fibrillation is superior to anti-rhythmic drug therapy at three years with an approximate 50% lower incidence of recurrent atrial tachyarrhythmias.

Initial treatment of paroxysmal atrial fibrillation with catheter cryoablation is associated with a lower incidence of persistent atrial fibrillation or recurrent atrial tachyarrhythmias over three years (Andrade JG).

Control of the ventricular rate by ablation of the atrioventricular node and permanent pacing does not adversely affect long-term survival.

The rate of death among patients with AF is about double that among patients with normal sinus rhythm.

Associated with stroke, heart failure and death.

Usually, a progressive disease that often begins with infrequent episodes of limited duration, paroxysmal atrial fibrillation.

Episodes of paroxysmal atrial fibrillation tend to become more frequent and longer in time and progress to persistent atrial fibrillation, which fails to terminate spontaneously with in seven days, or permanent atrial fibrillation if it lasts longer than one year.

First-line ablation of pulmonary vein isolation is associated with improved clinical outcomes compared with initial antiarrhythmic drugs.

In a prospective, multicenter randomized trial of 167 patients that did not respond to at least one antiarrhythmic drug and who experienced at least 3 AF episodes within 6 months of randomization, to catheter ablation or to antiarrhythmic drug therapy: at the end of 9 months 66% of patients treated in the catheter group remained free from protocol treatment failure, compared to 16% of antiarrhythmic drug patients (Wilber DJ).

Associated with organic heart disease in about 90% of patients.

Fewer than 20% have rheumatic heart disease.

Hypertension single most common risk factor.

Stroke, heart failure are common complications of AF, are both related to hypertension.

Risk of cognitive dysfunction increased in AF.

Overt hyperthyroidism is a well known risk factor.

Subclinical hyperthyroidism with a serum TSH levels below normal and a free T4 within the normal rage is also predictor of atrial fibrillation.

In a cross sectional population based study the free serum T4 concentration is independently associated with atrial fibrillation in euthyroid patients with serum TSH levels in the normal range (Gammage).

A prospective study of patients with normal thyroid function and the risk of AF participants in the lowest quartile of the normal range of serum TSH had an almost 2 fold increased risk of AF compared to those in the highest quartile (Heeringa).

In the above study there was a graded association between free T4 levels and risk of AF.

Majority originates within the orifices of one or more of the pulmonary veins.

Incidence approximately doubles with each decade of adult life and ranges from 2 or 3 new cases per 1000 population per year between the ages of 55 and 64 to 35 new cases per 1000 population per year between ages of 85 and 94 years.

Found in 0.1% of adults younger than 55 years and in more than 9% of individuals over he age of 80 years.

Associated with increased long-term risk of stroke, congestive heart failure and mortality rate, especially in women.

May be an independent risk factor for death, with a relative risk of about 1.5 for men and 1.9 for women after adjustment for known risk factors.

AF in Framinham Heart Study most increased death risk ascribed to individuals dying within 30 days after a first AF episode.

Thromboembolism originates from the left atrial appendage in the vast majority of cases.

90% thrombi atrial fibrillation related strokes arise from the left atrial appendage.

Minimally invasive closure of the left atrial appendage has reduced the risk of stroke without warfarin.

Among patients with AF who had undergone cardiac surgery, most of whom continued to receive ongoing anti thrombotic therapy, the risk of ischemic stroke or systemic embolism was lower with concomitant left atrial appendage occlusion  performed during surgery than  without it (LAAOS III investigators).

Patients receiving anticoagulation for atrial fibrillation and have a history of falling have a higher risk of major bleeding, including intracranial bleeding and death but similar rates of stroke or systemic embolism and hemorrhagic stroke.

Novel oral anticoagulants have benefits over warfarin with a 50 to 80% reduction in intracranial bleeding and these drugs are a better alternative than Warfarin for anticoagulation in patients with a history of falls.

Compared with vitamin K antagonist, non-vitamin K antagonists oral anticoagulants (NOAC) use is associated with better net clinical benefit in elderly patients with atrial fibrillation due to lower rates of major bleeding.

Direct oral anticoagulants-Dabigatran, rivaroxaban, apixaban and edoxaban are recommended for stroke/system embolism prevention among patients with non-valvular atrial fibrillation and are associated with lower stroke/myocardial infarction and all-cause mortality rates compared with warfarin.

Among individuals 65 years or older with atrial fibrillation treatment with  rivaroxaban compared with apixaban was associated with significant increased risk of major ischemic or hemorrhagic events.

Among patients with AF and stage four or five chronic kidney disease or undergoing hemodialysis, rivaroxaban appears it associated with significantly less major bleeding compared to warfarin.

The concomitant use of direct oral anticoagulants with antiplatelet agents is associated with a similar risk of G.I. bleeding, and a lower risk of intracranial hemorrhage and other major bleeding than concomitant warfarin-antiplatelet use (Douros A).

A single ECG recording of atrial fibrillation in a middle-aged female increased the risk of a cardiovascular event by fivefold in the next 2 decades: for men the risk is twofold.

Transthoracic echocardiography is indicated in the management of atrial fibrillation to define cardiac structure and anatomy.

Uncommon in patients with chronic, stable coronary artery disease occurring in only 0.6% of such patients.

Approximately 75% of individuals with atrial fibrillation in middle age will die or be hospitalized for a cardiovascular reason within 20 years, a 2-3 fold increase compared to those who do not have atrial fibrillation.

From 10-13% of patients with acute MI have AF and portends a worse prognosis.

Patients with severe obstructive sleep apnea and AF may have a decreased response to antiarrhythmic drug therapy, and may yet be at higher risk for atrial fibrillation ablation failure.

Alcohol has a dose-dependent relationship with AF, with higher amounts associated with increased risk and some increase in risk even at low levels of alcohol.

There is a dose independent relationship between alcohol intake and incident atrial fibrillation, left atrial dilatation, atrial fibrosis, and recurrence of arrhythmia after ablation.

Abstinence from alcohol reduces arrhythmia recurrence in regular drinkers with atrial fibrillation.

Moderate-to-heavy alcohol consumption is strongly associated with atrial fibrillation in both men and women.

There is a dose dependent effect with one drink per day associated with the reported 8% increase risk of atrial fibrillation.

Alcohol is a common trigger for episodes of paroxysmal atrial fibrillation.

Excessive alcohol causes increased atrial activity, increased sympathetic tone or parasympathetic tone, or both, shortens atrial refractoriness, and reduces sodium channel expression: excessive exposure  triggers and maintains atrial fibrillation.
Regular moderate alcohol consumption is associated with clinically significant atrial activity and structural remodeling including left atrial dilatation atrial fibrosis and slowing of conduction.

Alcohol is an important modifiable risk factor in the management of atrial fibrillation and abstinence is related to prolonged recurrent free disease.

Extreme exercise is linked to potential cardiotoxicity, including an increased risk of AF.

Incidental irradiation of the sinoatrial node during chemo, radiotherapy, may be associated with development of  atrial fibrillation and increased mortality.

Vitamin D intake of greater than 100 mg per mL may be associated with increased risk.

Associated with congestive heart failure, stroke and renal insufficiency.

AF associated with syncope and falls in older adults.

1/3 of atrial fibrillation j patients have mild moderate renal dysfunction, and up to 3% have severe renal dysfunction.

The presence of atrial fibrillation represents a sixfold increased risk of stroke.

Patients with chronic kidney disease and AF have a 3-fold higher risk for stroke.

New onset atrial fibrillation in severe sepsis associated with an increased risk of and hospital stroke and death, compared with patients with no atrial fibrillation and patients with pre-existing atrial fibrillation (Walkey AJ et al).

Among older patients the recent diagnosis of atrial fibrillation is associated with increased risk for stroke in women rather than men regardless of warfarin use (Tsadok MA et al).

This suggests that current day anticoagulant management to prevent stroke in older women may not be adequate.

Higher risk of stroke in women vs men with AF.

In a large Danish study of AF patients switching to

Dabigatran from warfarin increased the risk of myocardial infarction compared to continued warfarin usage in the early period after switching (Larsen TB et al).

In a VA study of patients with atrial fibrillation switched from warfarin to dabigatran

There was an increased likelihood of gastrointestinal bleeding (Vaughan Sarrazin M).

Consumption of up to 2 drinks per day not associated with increased risk of atrial fibrillation among initially healthy, middle aged women (Conen), however in women with a greater consumption of 2 or more alcoholic beverages per day has a 1.6 fold greater risk relative to non-drinking women.

Digoxin linked with a significant increase in mortality in patients with atrial fibrillation (AF), according to results from a study of 4060 AF patients in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial: digoxin was associated with a 41% increase in deaths from any cause. associated with a 35% increase in cardiovascular deaths and a 61% increase in deaths from arrhythmias.

The AFFIRM trial compared to the effects of rhythm control with the rate control and showed no group difference in overall mortality.

In the AFFIRM. trial anti-arrhythmic drugs were not effective at maintaining sinus rhythm in almost half the patients in the rhythm control group

In the AFFIRM trial patients randomized to rhythm control or to ventricular rate control had similar rates of all-cause mortality, but the patient in the rhythm control group exhibited a trend towards increased ischemic strokes after the discontinuation of anticoagulation therapy.

The above study suggested that patients with a history of atrial fibrillation should continue anticoagulation indefinitely based on their underlying stroke risk profile.

A metaanalysis of five randomized trials of rhythm control as compared with rate control showed no significant differences with respect to all cause mortality and stroke, although the results appeared to favor rate control.

Comparing warfarin in atrial fibrillation in real world studies versus clinical trials reveals that in the real world there is a higher risk of major bleeding, ischemic stroke, and mortality (Murcia AF Project).

Lone atrial fibrillation describes AF in the absence of demonstrable underlying cardiac disease or a history of hypertension.

Lone atrial fibrillation occurs in approximately 3%-11% of patients with AF.

Lone atrial fibrillation in patients younger than 60 years old has a benign prognosis.

Lone atrial fibrillation have a lower risk of thromboembolism than other patients with AF.

All-cause mortality rates with lone atrial fibrillation similar to those of age and sex matched controls without AF after 30 years of observation.

New onset AF in healthy women is independently associated with all cause, cardiovascular, and non-cardiovascular mortality, with some of the risk potentially explained by nonfatal cardiovascular events: 34,722 women older than 45 years and free of atrial fibrillation and cardiovascular disease at baseline in the Women’s Health Study were prospectively followed (Conon D et al).

New onset atrial fibrillation doubles the risk of mortality.

The Woman’s Health Study showed that the risk of all cause death was doubled and cardiovascular death quadrupled by new onset AF in initially healthy women.

Patients who have experienced a myocardial infarction or those with heart failure that is atrial fibrillation associated, are at increased risk of sudden cardiac death.

Since AF and sudden cardiac death share many risk factors, it is unknown whether AF is independently associated with increased risk of sudden cardiac death in general population.

In the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study incident AF was associated with increased risk of sudden cardiac death and non sudden cardiac death Chen LY et al).

Women with AF have an increased risk for cardiovascular events, including stroke.

Studies have suggested annualized rate of stroke is 3% in women compared to 1.6% in men.

In the above study it is suggested that the risk of death is increased (2.1%) even in populations with a low burden of comorbidities and low short-term mortality rate with atrial fibrillation.

In the above study by Conen atrial fibrillation developed in 2.9% of patients, and 65% of the cases were paroxysmal, self terminating and lasting less than seven days, and 7.3% were lone, occurring in those younger than 60 years of age without hypertension or heart failure at the time of diagnosis.

In the above study, hypertension was strongly associated with incident AF with 44% of women who went on to develop AF had hypertension at baseline, compared to 26% of those who did not develop AF.

Associated with a mortality rate 1.5 to 1.9 higher than expected in the general population.

Lone atrial fibrillation in patients older than 61 years of age there is an increased risk of stroke and AF.

As a complication of myocardial infarction is a poor prognostic process.

Postoperative atrial fibrillation is the most common complication after heart surgery with a reported incidence, on average, about 35%.

Incidence ranges between 20-40% after coronary artery bypass surgery and higher after valve and combined valve and bypass surgery.

In association with heart surgery increases morbidity, increased risk of stroke and prolonged hospitalization.

Intravenous hydrocortisone reduces the relative risk of postoperative AF by 37% compared with placebo in patients undergoing CABG surgery, aortic valve replacement or combined CABG and aortic valve replacement.

Cardiac surgery and extracorporeal circulation associated with systemic inflammatory response which may increase incidence of AF.

After cardiac surgery complement, CRP levels, white blood cell count are increased in patients that develop AF.

The most common arrhythmia encountered in the early postoperative period, affecting 10% of patients undergoing major noncardiothoracic operations, 29% after noncardiac thoracic operations, and up to 50% after cardiac valve procedures.

Affects more than 1 million Americans/year.

Can cause or exacerbate heart failure.

Doubles all-cause and cardiovascular mortality risk.

Lone atrial fibrillation (AF) describes isolated episodes of AF, and when occurs in the perioperative period has previously presumed to be benign cardiac arrhythmias in response to physiologic stress.

However, a recent study published in the Journal of the American Medical Association evaluating patients without pre-existing AF who were hospitalized for surgery in an observational retrospective cohort study: results of this large observational study established that perioperative AF associated with non-cardiac surgery is definitely a risk factor for ischemic stroke in the future.

Larger left atrial volume associated with a higher risk of atrial fibrillation.

Results in 75,000 cases of stroke each year.

Approximately 5% of patients with AF will develop a stroke.

There is a steep age-related increase the risk of strokes in patients with atrial fibrillation, ranging from 1.5% at age 50-59 years to 23.5% at age 80-89 years.

Annual risk of stroke estimated to be as high as 23.5% in patients with atrial fibrillation age of 80-90 years.

Responsible for 15% of all strokes and nearly 35% of patients over the age of 80 years.

Non-valvular AF responsible for 15-20% of all ischemic strokes.

Risk of stroke increased by a factor of 5.

2-5% annual rate of developing in individuals older than 65 years.

Risk factors for developing emboli are history of prior emboli, hypertension, history of CHF, diabetes, left ventricular dysfunction, left atrial size greater than 2.5 cm/m and women over the age of 75 years.

Patients with type two diabetes are at increased risk of developing atrial fib relation, and patients with the combination of atrial fibrillation and diabetes are at high risk for stroke.

Patients with no risk factors have a risk of 1%/year for emboli.

Patients with 1 or 2 risk factors have a 6% embolic rate per year.

Patients with 3 or more risk factors have a 19% embolic rate per year.

The use of nonsteroidal anti-inflammatory drugs and the use of steroidal anti-inflammatory drugs are associated with an increased risk of chronic atrial fibriilation (De Caterina R et al).

Among patients with paroxysmal AF 24 weeks of Omega-3 fatty acids compared with placebo did not reduce recurrent episodes of atrial fibrillation over six months (Kowey PR et al).

Current use of nonsteroidal anti-inflammatory drugs is associated with a statistical 44% increase in the risk of chronic atrial fibrillation, but not with paroxysmal AF (De Caterina R et al).

Corticosteroids associated with chronic atrial fibrillation.

African-Americans have a paradoxically low prevalence of AF.

Hypotheses to explain the association of atrial fibrillation: high dose corticosteroids mediate potassium efflux via a direct affect on cell membranes inducing arrhythmias, mineral corticosteroid effect can cause salt and fluid retention, hypertension, left atrial enlargement, and congestive heart failure, all known risk factors for atrial fibrillation, may favor development of late potentials and cause peripheral vasodilatation and anaphylactic reactions ( Freedman MD et al, Ozen S et al).

Rate of ischemic stroke among patients with nonvalvular atrial fibrillation is 5% without the use of anticoagulation.

Patients without risk factors should receive aspirin 325 mg per day.

Anticoagulation is the cornerstone of preventing strokes in AF.

A meta-analysis of trials comparing warfarin with placebo in nonvalvular AF in stroke prevention demonstrated a significant reduction in in stroke and all cause mortality in patients treated with warfarin (Hart RG et al).

Patients with one or more risk factors should receive anticoagulation with warfarin raising the INR between 2 and 3. Levels below 1.8 do not protect patients from emboli.

For patients on oral anticoagulation there are 16.5 bleeding episodes per 100 treatment-years with 2.7 major bleeding episodes and 0.64 episodes resulting in death over a 1-year period.

Warfarin therapy reduces the risk of embolic stroke vs. aspirin or placebo in patients with AF and two or more CHADS2 risk factors.

Patients with AF at highest risk of stroke, those wth previous stroke or TIA with nonvalvular AF derive the greatest risk reduction of stroke with warfarin compared with aspirin or no antithrombotic treatment (Hart RG et al).

Current use (2012) of warfarin in nonvalvular AF is associated with a low rate of residual stroke or systemic embolism of an estimated rate of 1.66 per year (Agarwal S et al).

The decision utilize warfarin in atrial fibrillation using the CHADS2 score should be driven more by the patient’s risk of stroke than by the risk of bleeding (Chen WT et al).

Long term anticoagulation lowers the risk of stroke approximately 68% per year in patients with nonvalvular AF and even more in patients with valvular AF.

Warfarin prevents 64% of strokes (Hart RG).

Warfarin used in only two thirds of appropriate candidates.

Suboptimal use of warfarin related to diet and drug interactions, need to monitoring with INR and risk of hemorrhage,

Between 15% and 44% of eligible patients are treated with anticoagulants.

Cardioversion related risk of embolization in patients with AF for longer than 48 hours is approximately 5.5% but falls to less than 1% if anticoagulated.

The treatment of choice for urgent conversion of symptomatic unstable atrial fibrillation is DC cardioversion.

Anti-arrhythmic drugs particularly amiodarone are used to restore and maintain normal sinus rhythm.

No anticoagulation is required for cardioversion if AF has been present for less than 48 hours.

If AF is present for more than 48 hours the patient should receive anticoagulants for 3 weeks before and at least 4 weeks after cardioversion.u

It is estimated that after stopping warfarin in a patient with atrial fibrillation for an operative procedure the risk of embolization is 0.012-.3% assuming the INR is subtherapeutic for 4-6 days.

Risk of stroke with nonvalvular AF is 5-fold and the risk with valvular AF is 17-fold.

The restoration and maintenance of a sinus rhythm correlates with an improved quality of life for these patients.

Antiarrhythic drugs are effective in maintaining sinus rhythm for 1 year in 50-65% of patients and amiodarone is the most effective of these drugs.

The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Trial of 4000 patients 66 years or older and with at least one other risk factors for stroke, and the Rate Control versus Electric Cardioversion (RACE) trial of 522 patients with a history of recurrent AF after electrical cardioversion: both investigations failed to a demonstrate mortality benefit with rhythm control.

The initial strategy of rhythm control has been associated with a reduced risk of death from cardiovascular causes and with reduced rates of stroke.

In patients with acute onset AF and with impaired left ventricular function, amiodarone or digoxin have been recommended because of minimal inotropic effect (Iqbal).

Among patients with permanent AF and heart failure treated with low-dose digoxin or a beta blocker revealed no statistical difference in quality of life at six months (Kotecha D).
Among hospitalized older patients with heart failure and reduced or preserved ejection fraction and atrial fibrillation digoxin  utilization was not associated with all cause mortality, and was associated with lower risk of heart failure readmission (Singh S).

In patients with persistent AF amiodarone is effective in achieving and maintaining sinus rhythm in 50-70% of cases.

Conversion to sinus rhythm and maintaining that rhythm is the cornerstone of management.

The AFFORD trial demonstrated that high-dose omega-3 fatty acids does not reduce AF recurrence or inflammation or oxidative stress markers.

Surgical therapy is most appropriate in patients who require open-heart surgery for another indication.

Present in approximately 50% of all patients undergoing surgery for the treatment of mitral valve disease.

Dual chamber or atrial pacing decreases the risk of atrial fibrillation in patients with sinus node impairment and who require permanent pacing.

The prevalence of atrial fibrillation among dialysis patients is as high as 11.6%.

Atrial pacing decreases symptomatic atrial fibrillation with patients with sick sinus syndrome and with paroxysmal atrial fibrillation.

Atrial pacing is more protective compared to ventricular pacing.

Class Ic agents flecainide and propafenone are used to convert patients with atrial fibrillation of recent onset with a success rate of 58-95%.

Therapy that reduces blood pressure, blocks the renin-angiotensin-converting enzyme by ACE inhibitors or angiotensin II receptor antagonists can decrease incidence of AF in patients with hypertension, congestive heart failure and after myocardial infarction.

ARBs, specifically Irbesartan, does not reduce cariovascular enents in patients with atrial fibrillation in patients with atrial fibrillation (ACTIVE I Investigators).

ARBs have no effect in preventing atrial fibrillation in patients with intermittent atrial fibrillation(The GISSI-AF Invest a Tors).

The priority of treatment is to first control the heart rate with a ventricular rate of 60-80 per minute at rest and between 90 and 115 per minute during moderate exercise, secondly, to prevent thromboembolism and finally, if possible, correct the rhythm disturbance.

Conversion to sinus rhythm associated with improved exercise capacity and quality of life, so its restoration and maintenance is a major therapeutic goal.

The therapeutic armamentarium includes rate controlled drugs, antiarrhythmic drugs, and catheter ablation.

Goals of treatment is to improve the quality of life and decrease atrial fibrillation related morbidity and mortality.

Random assignment of 614 patients with AF to undergo lenient rate control (<110 beats/min), vs strict rate control(<80 beats/min): Primary outcome of death from cardiovascular causes, hospitalization for CHF, stroke, systemic embolism, bleeding and life-threatening arrhythmias: rate 12.9% in lenient group vs. 14.9% in the strict control group-lenient rate control as effective as strict rate control and is easier to achieve (Van Gelder IC).

6-20% of patients with severe sepsis develop new onset atrial fibrillation.

New onset atrial fibrillation in severe sepsis is associated with higher mortality and prolonged hospitalization.

Radiofrequency catheter ablation effective treatment with paroxysmal atrial fibrillation.

Radio frequency catheter ablation can restore sinus rhythm and may be superior to anti-arrhythmic drugs in maintaining sinus rhythm and improving symptoms.

Effective therapy in patients with recurrent episodes of arrhythmia despite anti arrhythmic drug therapy.

Fibrosis and myolysis common in atria when AF becomes persistent.

Extensive atrial fibrosis detected by magnetic resonance imaging predicts a poor outcome after ablation.

In a random assignment of 294 patients with paroxysmal AF to antiarrhythmic drug therapy or radiofrquency catheter ablation as first line therapy: no significant difference between treatment groups in cumulative burden of AF over 2years(Nielsen JC et al).

In a randomized trial of 1504 patients with atrial fibrillation and cardioversion this agent was safe and effectively prevented the risk of stroke (Cappato R et al).

In the above study Rivaroxaban’s 2-4 hour action allows for a more rapid conversation than vitamin K antagonists.

In atrial fibrillation patients with a history of stroke/TIA who are vitamin K antagonist naïve, dabigatran provides similar protection to warfarin against the current stroke/TIA.

Warfarin experienced patients with AF and a history of stroke or transient ischemic attack who are switched to dabgatran therapy may have an increased rate of recurrent stroke compared to patients persisting with vitamin K antagonist treatment: caution required when switching prior warfarin experienced atrial fibrillation patients to dabigatran.

The cumulative incidence risk in the above study for composite outcome of stroke, non-CNS embolism, TIA, myocardial infarction, and all- cause mortality was 0.61% with Rivaroxaban and 1.22% in patients receiving vitamin K antagonists.

In patients with atrial fibrillation and bioprosthetic mitral valve, rivaroxaban is not inferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months (RIVER trial investigators).

In a trial of patients with atrial fibrillation who stopped taking warfarin before elective surgery or an invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin to prevent arterial thromboembolism(Douketis JD et al).

In the above study bridging nearly tripled the risk of major bleeding without providing benefits in preventing myocardial infarction, venous thromboembolism, or death when compared with no bridging.

The above study suggests that the risk of arterial thromboembolism in patients with atrial fibrillation who temporarily stop warfarin may have been overstated.

In the above BRIDGE study- Bridging Anticoagulation in Patients Who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgical clinical trial2000 patients randomly signed to bridging protocol with low molecular weight heparin or foregoing anticoagulation bridging when undergoing a procedure- A strategy of foregoing in the anti coagulation bridging was non inferior to bridging with low molecular weight heparin in terms of preventing arterial thrombotic events and there was improvement in both major and blood minor bleeding events.

Dabigatran in atrial fibrillation has a more predictable anticoagulation response and warfarin and may be recommended for patients who are unable to maintain stable INR values on warfarin.

Edoxanan versus warfarin reduces the disease mortality by reducing fatal intracranial bleeding and also reduces non-fatal bleeding.

In elderly Japanese patients with AF who were not appropriate candidates for standard oral anticoagulants, a once daily 15 mg dose of edoxaban was superior to placebo in preventing stroke with systemic embolism and did not result in a significantly higher incidence of major bleeding than placebo (Akao K).

Studies demonstrate that there is no significant reduction in total mortality in the treatment of atrial fibrillation with warfarin compared to antiplatelet therapy, nor is there differences in dual antiplatelet therapy.

Warfarin is superior in reducing embolic events in patients with AF as compared with dual antiplatelet therapy with aspirin and clopidogrel.

Antiplatelet therapy is frequently used instead of oral anticoagulants in patients with AF particularly in the elderly and other high-risk patients.

Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis

Risk of outcomes associated with atrial fibrillation: specifically, all cause mortality, cardiovascular mortality, major cardiovascular events, any stroke, ischaemic stroke, haemorrhagic stroke, ischaemic heart disease, sudden cardiac death, congestive heart failure, chronic kidney disease, and peripheral arterial disease.

Atrial fibrillation was associated with an increased risk of all cause mortality, cardiovascular mortality, major cardiovascular events, stroke, ischemic stroke, ischemic heart disease, sudden cardiac death, heart failure, chronic kidney disease and peripheral arterial disease but not hemorrhagic stroke.

The use of novel oral anticoagulant or warfarin is not more effective than using no anticoagulants at all in reducing the risk of ischemic stroke or systemic embolism in patients with atrial fibrillation in stages 4-5 chronic kidney disease (Chang S-H).

The highest absolute risk increase was for heart failure.

It is increasing in prevalence in both developing and developed countries and is associated with an increased risk of all cause mortality and stroke, as well as higher medical costs and a reduced quality of life.

Although the prevention and management of stroke in atrial fibrillation has been the primary focus of treatment.

Can be associated with a range of different cardiovascular diseases, including ischemic heart disease and chronic kidney disease.

Stroke studies involving 6 143 925 patients, 7.0% adults had atrial fibrillation.

The absolute risk increase of stroke associated with atrial fibrillation was 3.6 events/1000 participant years.

The relation between atrial fibrillation and ischemic stroke is consistent, irrespective of baseline demographics and clinical characteristics.

Atrial fibrillation is not associated with a higher risk of hemorrhagic stroke.

The absolute risk increase in chronic kidney disease associated with atrial fibrillation is 6.6 events/1000 participant years.

In the association between atrial fibrillation and peripheral arterial disease, the relative risk is 1.31.

Atrial fibrillation is associated with an increased risk of all cause mortality ,cardiovascular mortality, major cardiovascular events, ischaemic heart disease stroke and ischemic stroke.

Heart failure is the most common non-fatal cardiovascular event among older adults with atrial fibrillation.

The RE-LY trial in patients with atrial fibrillation, cardiac deaths—sudden cardiac death and progressive heart failure—accounted for 37.4% of all deaths, whereas deaths related to stroke and hemorrhage accounted for 9.8% of all deaths.

The relative risk of all cause mortality is lower in participants receiving anticoagulation.

Hypertension is diagnosed in up to 90% of patients with atrial fibrillation.

Novel oral anticoagulants reduce mortality in CHF related to stroke, with little reduction in mortality related to congestive heart failure and sudden cardiac death.

Pharmacological control of atrial fibrillation and the restoration of sinus rhythm has shown no benefit over rate control for sudden cardiac death, worsening heart failure,or mortality.

Interventions are needed to reduce the risk of non-stroke cardiovascular outcomes in adults with atrial fibrillation.


Anti-coagulant treatment reduces the risk of thromboembolic stroke with AF, but can cause intracranial and other serious bleeding.

The decision to use oral anticoagulants in nonvalvular AF should be based on the CHA 2DS 2-VASc score: for a man with a score of two or greater than women with a score of three or greater, treatment with an oral anticoagulant is recommended.

Use of oral anticoagulant is considered in men with a score of one and in women with a score of two, and may be omitted in men with a score of zero and women with a score of one.

Call patient with atrial fibrillation who have moderate to severe mitral stenosis or a mechanical valve should be anticoagulated.

Direct oral anticoagulants or non-vitamin K oral anticoagulants are now recommended over the vitamin K antagonist warfarin in patients with nonvalvular atrial.fibrillation.

Patient with moderate-severe mitral stenosis or a mechanical valve should take warfarin.

A percutaneous implant that closes off the left atrial appendage is considered for a non-surgical patient with atrial fibrillation at increased risk of stroke who have contraindications to long-term anticoagulation.

Ventricular rate control is an alternative to rhythm control for first line management of chronic AF.

Anti-arrhythmic drugs are associated with toxicity, and rhythm control with these drugs is not showing to be more effective in preventing complications then rate control alone.

Drugs most commonly used for rate control: beta blockers are preferred for rate control.

Verapamil or diltiazem may be preferred in patients with asthma,

Amiodarone may be effective when other drugs have failed to control ventricular rate.

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