What is atrial fibrillation?

Atrial fibrillation (AF) is a type of cardiac arrhythmia. An arrhythmia is when the heartbeat becomes irregular or changes its rate inappropriately. An arrhythmia can occur for a number of reasons, but in cases of AF it happens when another part of the heart (often located at the pulmonary veins) tries to take over as the pacemaker. Many parts of the right and left upper chambers (atria) try to signal the heart to beat with rapid, irregular impulses. These impulses cause the upper heart to contract very rapidly, often so fast that the chambers “quiver” instead of “really” pumping. This fibrillation, or rapid contracting, of the atria interrupts the heart’s normal efficient pumping.

What are the potential problems resulting from atrial fibrillation?

A person with AF is more than 3 to 5 times as likely to have a stroke than the general population. When the quivering atria no longer pumps blood efficiently, some blood may stay in the atria with each heartbeat. The pooled blood may eventually clot, increasing the risk of stroke from a dislodged clot. About 15% of all strokes occur in people with AF.

AF may prevent the heart from pumping enough blood and oxygen to meet a person's needs. The quivering atria fail to efficiently pump blood. The rapid ventricular heart rate fails to efficiently pump blood to the rest of the body. Patients often complain of a lack of energy and significantly reduced quality of life.

The disease incidence increases with age. As a patient grows older, the risk of AF seems to increase, especially after age 60.

Further Information

Atrial Fibrillation, The Disease

Definition

Atrial Fibrillation (AF) is a supraventricular tachyarrhythmia (an abnormal rapid, chaotic heart beat arising in the atria) characterized by uncoordinated atrial activation with consequent deterioration of atrial mechanical function. In effect, the atria quiver and fail to perform their pumping function of filling the ventricles. The lack of atrial pumping action and the resultant pooling of blood presents opportunities for the formation of thrombi leading to embolic stroke. AF also affects the pumping rhythm of the ventricles by increasing heartbeat and thus lowering pumping efficiency.

On an electrocardiogram (ECG), AF is described by the replacement of consistent P waves by rapid oscillations or fibrillatory waves that vary in size, shape and timing, associated with an irregular, frequently rapid ventricular response when atrioventricular (AV) conduction is intact.

Underlying Mechanisms

There is recently developed evidence that, in addition to the substrate needed for multiple macro reentrant circuits, AF is triggered by one or more rapidly firing foci in a majority, if not all cases. In a landmark study published in 1998, Hassaguerre and coworkers described their experience with 45 patients. In these patients, a single point of origin of ectopic beats was found in 29 patients (64%), two points in 9 patients (20%) and three or four in the remaining 7 patients (15%). Of the 69 ectopic points, 65 (94%) originated in the pulmonary veins, 3 in the right atrium and 1 elsewhere in the left atrium. Among the ectopic points originating in the pulmonary veins, about half were in the left superior pulmonary vein and another one third in the right superior pulmonary vein. This study and other related studies have been important in focusing many programs in the medical community to develop catheter or surgical devices to electrically isolate the pulmonary veins as a therapy to treat or cure AF.

Related Arrhythmias

AF may occur in isolation or in association with other arrhythmias, most commonly atrial flutter or atrial tachycardia.

Atrial flutter may arise during treatment with antiarrhythmic agents prescribed to prevent recurrent AF. Atrial flutter may initiate AF, may degenerate into AF or the ECG pattern may alternate between atrial flutter and AF, reflecting changing activation of the atria.

Other atrial tachycardias, AV reentrant tachycardias, and AV nodal reentrant tachycardias may also trigger AF. A unique type of atrial tachycardia has recently been identified that commonly originates in the pulmonary veins, but may arise elsewhere, and often degenerates into AF.

Classifications

AF has a heterogeneous clinical presentation, occurring in the presence or absence of detectable heart disease or related symptoms. The classification scheme recommended in the Guidelines follows:

The clinician records a first-detected episode of AF, whether or not it is symptomatic or self-limited, recognizing that there may be uncertainty about the duration of the episode or about previous episodes. When a patient has had 2 or more episodes, AF is considered recurrent.

If the AF terminates spontaneously, recurrent AF is designated paroxysmal.

When sustained, recurrent AF (not self-terminating) is designated persistent. Persistent AF is still designated persistent even if terminated by electrical cardioversion or pharmacological therapy.

AF also includes long-standing AF when cardioversion failed or was not indicated or attempted usually leading to permanent (or continuous) AF.

The classification system applies to episodes lasting longer than 30 seconds and that are unrelated to a reversible cause. Secondary AF that occurs in the setting of acute myocardial infarction, cardiac surgery, pericarditis, myocarditis, hyperthyroidism, pulmonary embolism, pneumonia, or acute pulmonary disease is considered separately.

In addition, “lone AF” generally applies to AF patients under 60 years of age without clinical or echocardiographic evidence of cardiopulmonary disease.

Prevalence Atrial Fibrillation

United States

Based on the combined results of four patient population studies in the United States, including the well regarded Framingham Heart Study as reported in the Treatment Guide, the estimated number of patients in the United States in 2003 who suffer from Atrial Fibrillation is 2,463,000. The 1995 population, prevalence and prevalence rate per age group in the US population and the prevalence projected for 2003 are detailed in Chart 1.

Worldwide

Applying the US overall prevalence rate to populations in the economically developed world (defined as countries with a per capita GDP equal to or greater than $15,000) indicates that the 2003 AF prevalence within the defined regions is estimated at 8.2 million patients. Prevalence of AF in major world regions is summarized (along with additional data) in Chart 2 in the supporting Excel spreadsheet. Note that there are no large-scale AF prevalence studies available for regions ouPRIde the US and therefore the US AF prevalence rates have been applied to the populations of the economically developed countries of Western Europe, Japan, and the Rest of the World (ROW). The economically developed countries and their populations and per capita GDPs that are included in the world regions are detailed in Appendix A.

There are also significant additional populations of AF patients in the prosperous middle and upper classes (that have substantial wealth and access to world-class medical care) of countries whose overall population does not meet the criteria for classification as an economically developed country. Latin America is a primary example of a major world region that has significant additional prevalence within its economically developed middle and upper classes. These AF patients will have access to and be capable of paying for advanced therapies.

Absent the wide use of curative AF therapies, the prevalence of AF is projected to increase as the population ages in most of the economically developed world.

This AF prevalence provides a substantial reservoir of AF patients to support the market potential for AF therapies.

Incidence

Based on a US large-scale epidemiological study (the Framingham Study), the estimated incidence of new onset (non-rheumatic) AF in 2002 will be greater than 396,000 cases in the US. This estimate is based on the reported incidence per age cohort in 1995 adjusted only for 2002 population projections. The incidence of new onset AF approximately doubles with advancing decades of age independent of any changes in the prevalence of the predisposing conditions. No estimate or adjustment was made in incidence for the underlying trend of increasing incidence of AF after adjustment for age. Estimates based on the reported incidence in the CHS study would predict a higher AF incidence.

Based on the US incidence rate (at 396,000 new onset AF patients per year) applied to population only, the incidence of non-rheumatic AF in the economically developed world (as defined in the prevalence estimates) would be greater than 1,310,000 in 2002.

The age adjusted incidence of AF increased over a thirty year period in the Framingham Study. This trend, if continued, will increase the AF market opportunity but have serious implications for the future impact of AF on the elderly population and on the health care system.

Medical Consequences of Atrial Fibrillation

The medical prognosis (consequences) for patients with AF is very unfavorable.

Mortality Rates

The mortality rate for patients with AF is approximately double the mortality rate for patients in normal sinus rhythm.

The increased mortality in AF is not solely the result of associated and predisposing conditions since, even after these factors are taken into account by means of a multi-variate analysis, mortality is still increased by approximately two-fold.

In 1999, the number of deaths in the US due to Atrial Fibrillation and Flutter was 8,338. In reports of mortality, the total mentions of AF and Flutter as an underlying or contributing cause of death was more than 61,500.

AF and Stroke

The prevalence of AF among stroke victims in the Framingham Study was 15% overall. The distribution was not uniform and increased significantly with age.

The mortality rate from strokes associated with AF is approximately double the mortality rate from strokes without AF involvement.

The attributable risk of stroke in AF represents an estimate of the percentage of stroke events that could be specifically attributed to AF and the proportion of stokes that would prevented if the effect of AF were eliminated. The attributable risk of stroke with AF increased significantly with age, from 1.5% in men and women aged 50 to 59 to 23.5% in those aged 80 to 89. For example, this suggests that in persons over the age of 80 approximately 25% of strokes could be prevented by ideal management of AF. Thus AF is a major factor in the risk of stroke that increases significantly with age.

Prospective data from the Framingham Study demonstrated a 5.6 fold increase in the incidence of stroke in persons with chronic AF resulting from non-rheumatic heart disease after adjustment for age and hypertensive status.

Note that the risk of stoke can be significantly reduced by anticoagulant therapy and that protective levels of anticoagulation could be achieved with an increased, but acceptably low, risk of serious hemorrhage. However, anticoagulant therapy does not cure AF and presents other difficulties. See Alternative Therapies

Hospital Discharges

In 1999, AF and Flutter was the first listed diagnosis in 384,000 hospital discharges from short stay hospitals. While this hospital base does not represent all hospitals, this discharge data is indicative of the magnitude of the health care resources required to treat these arrhythmias. From 1985 through 1999, hospitalizations with atrial fibrillation among men and women 35 years of age and older increased from 154,086 to 376,487 for a first-listed diagnosis and from 787,750 to 2,283,673 for any diagnosis.

Quality of Life

AF may be symptomatic or asymptomatic, even in the same patient. The arrhythmia may present for the first time in an embolic event or exacerbation of heart failure. However, most patients with AF complain of palpitations, chest pain, dyspnea (difficult or labored breathing), fatigue lightheadedness, or syncope (temporary suspension of consciousness due to generalized cerebral ischemia).

In AF, the loss of the atrial contribution to ventricular filling (characterized as the “atrial kick”) can result in as much as a 30% loss of cardiac output. In critically ill or compromised patients this 30% loss can mean the difference between life and death. Regaining the atrial contribution to the heart’s pumping function by curing AF can mean a much more functional quality of life in less severe patients.

Summary

The above is necessarily a very brief summary of the body of evidence that has established AF as a very debilitating, widespread and expensive medical condition that, when treated and cured, can return substantial benefits to patients and to the health care system.

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