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Atrial fibrillation is the most prevalent sustained cardiac rhythm disorder in adult populations, and accounts for one third of hospitalisations due to cardiac rhythm disturbances. Prevalence in the US and worldwide has been estimated at 2.2 and 5.5 million, respectively, while incidence is reported to be 350,000 per year (US) and 720,000 per year (worldwide). Atrial fibrillation and its associated complications therefore represent a major challenge for drug development. Click continue when you are ready.
Numerous population studies have shown atrial fibrillation prevalence to increase with age, with less than 1% of the population under 50 years and approximately 9% of patients aged over 80 years reported to be affected. Click continue when you are ready.
The total number of patients with atrial fibrillation is steadily increasing with time and is predicted to more than double in the next 40 years. It is estimated that by 2050 there will be almost 3 million Americans aged over 80 years with atrial fibrillation, illustrating the increasing need for effective anticoagulation treatment that is well tolerated in this patient group.
Thus epidemiological studies demonstrate that patients with atrial fibrillation represent one of the largest patient populations in cardiovascular disease, with further growth expected. Novel, effective and safe treatments suitable for a cross-section of patients with thromboembolic complications associated with atrial fibrillation, such as stroke, will therefore become increasingly important.
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Age is the most consistent risk factor, with the risk of developing atrial fibrillation highest in older patients with structural heart disease.
Atrial fibrillation patients were more likely to have cardiovascular risk factors and/or diseases at baseline than patients without atrial fibrillation. For instance, data from the Framingham study showed that congestive heart failure was an independent predictor of atrial fibrillation.
Patients with congestive heart failure may predispose to atrial fibrillation, and atrial fibrillation may likewise predispose to congestive heart failure. Data from the Framingham study showed that congestive heart failure increased the risk of developing atrial fibrillation by a factor of 4.6 in men and 5.4 in women.
Hypertension is another risk factor associated with atrial fibrillation, in some studies increasing the risk of atrial fibrillation almost two-fold. Hypertension is associated with left ventricular hypertrophy, impaired ventricular filling, left atrial enlargement, and slowing of atrial conduction velocity. The high left ventricular pressures in a hypertensive heart result in increased atrial pressures and an increased potential for atrial fibrillation.
The triggers of atrial fibrillation relate to several different conditions, some of which are better understood than others.
One of the factors in developing atrial fibrillation has been thought to relate to stretching the atrium. Little has been demonstrated about whether there are stretch mediated ion channels, which would produce this effect, but it remains an interesting hypothesis. Increased atrial pressure may also enhance fibrosis and contribute to the development of re-entrant circuits.
Increased left atrial pressure occurs in the setting of left ventricular dysfunction, both in congestive heart failure and in hypertension as well as mitral stenosis. Increased right atrial pressure arises from increased pressures in the pulmonary arteries as might occur with pneumonia, pulmonary emboli , hypoxia or chronic obstructive pulmonary disease (COPD).
Increased vagal tone may precipitate atrial fibrillation, probably through acetylcholine mediated ion channels in the atrium. Vagally mediated atrial fibrillation often occurs at night, with slowing of the heart rate, or with vagal stimuli such as pain or drinking a cold beverage. Atrial fibrillation has also been reported in association with diverticulitis and with gastric reflux as vagal stimuli.
Both low thyroid levels (hypothyroidism) and high thyroid levels (hyperthyroidism) are associated with atrial fibrillation. Although thyroid receptors have been reported in the heart, there has not been any direct mechanistic relationship defined.
Although there has long been an association with alcohol use and atrial fibrillation, causing a syndrome called "holiday heart", it is not known why some people are more sensitive to this than others. Other factors, which seem to increase sympathetic tone, such as stimulants, amphetamines, bronchodilators, and stress also have been reported in association with atrial fibrillation.
In a normal heartbeat, activation begins in the sinus node located at the top of the right atrium, near the insertion of the superior vena cava. This sinus node has spontaneous activation, largely driven by calcium ion currents.
From the sinus node, activation spreads to the left atrium via Bachmann's bundle at the tip of the atrial septum, producing the P wave on the electrocardiogram (or ECG ), and causing both atria to contract simultaneously. From the atria, the impulse proceeds via the AV node to the ventricles, causing them to contract and resulting in the QRS complex on the ECG. In this way, normal sinus rhythm produces a coordinated contraction of the atria and ventricles.
Atrial fibrillation is a rapid, disorganized rhythm of contraction in the atrium. Instead of normal contractions, there is a series of tiny contractions (or fibrillations), and the ventricles do not fill and contract properly. The impulses leading to these contractions originate in regions of the atria other than the sinus node, and are considered abnormal.
Many cases of atrial fibrillation can begin with abnormal impulses generated in the pulmonary veins. These impulses are conducted to the left atrium and set up multiple micro-re-entrant circuits producing the chaotic, irregular atrial activation characteristic ofatrial fibrillation.
During atrial fibrillation, different areas of the atrium are being excited at different times, generating a “spiral wave" of conduction. Atrial tissues from these areas show an increased variability in length of the effective refractory period often with a shortened ERP, resulting in a rapid atrial rate.
The re-entry wavelength may also have an important role in determining susceptibility to re-entrant atrial arrhythmias, including atrial fibrillation.
A Dutch pharmacologist, Maurits Alessie, has described the atrial remodelling that occurs with atrial fibrillation as “Atrial fibrillation begets atrial fibrillation". As atrial fibrillation occurs, there is shortening of the action potential duration, facilitating micro-re-entry and facilitating continuation of atrial fibrillation. Mechanical remodelling also occurs with reduced atrial contractility after prolonged episodes of atrial fibrillation.
Atrial flutter is a related condition that can occur and is treated together with atrial fibrillation. It is characterised by a regular, rapid heart rhythm with an atrial rate of 250-350 beats per minute, resulting in a “saw-toothed" ECG pattern.
A macro-re-entry circuit encompassing the entire right atrium is responsible for the generation of atrial flutter. This macro-re-entrant circuit involves the isthmus area between the tricuspid valve and the inferior vena cava.
How atrial flutter and atrial fibrillation are interrelated is not precisely understood, and both types of arrhythmia may occur in the same patient.
Atrial fibrillation and atrial flutter are independent predictors of increased morbidity and mortality in general, and both are associated with significant symptoms that diminish the quality of life. Patients with either of these arrhythmias were also more likely to suffer from heart failure, diabetes mellitus, and stroke.
Compromised haemodynamics leads to three kinds of problems. Roll your cursor over any of the table headings to review the details of that section.
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A disturbance of the rhythm and loss of atrial systolic function results also in abnormal blood flow in stasis in the atria, factors that predispose to the formation of intra-atrial blood clots, or
thrombi . The left atrial appendage ( LAA ) is the most common site of intracardiac thrombus formation in patients with atrial fibrillation (anatomical reasons).
During episodes of atrial fibrillation, echocardiography can detect spontaneous echo contrast as a result of the formation of thrombus in the atria. Stasis within the left atria has been related to haemostatic abnormalities that are suggestive of a hypercoagulable state and that involve coagulation factors and endothelial and platelet function. When confined to the heart, a thrombus is typically asymptomatic. Part or all of the thrombus may become dislodged and subsequently ejected out of the heart at high pressure. This embolus , which is carried through the arterial system, then becomes lodged in small blood vessels, commonly small blood vessels in the brain. Occlusion of an artery in the brain results in an ischaemic stroke, one of the most severe complications of atrial fibrillation. Rarely, emboli from the left atrium entering arterial circulation may lodge in renal or other arteries resulting in systemic embolic event.
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Match each statement to the appropriate consequence of atrial fibrillation.
The American College of Cardiology/American Heart Association/ European Society of Cardiology has published practice guidelines for the management of patients with atrial fibrillation . First, physicians are recommended to distinguish a first-detected episode of atrial fibrillation from recurrent atrial fibrillation. A patient is considered to have recurrent atrial fibrillation after suffering two or more episodes.
Once established as a first-detected episode of atrial fibrillation, the condition is classified according to its duration. There may be some uncertainty regarding the exact duration but generally it can be determined whether it is non self-terminating, lasting greater than 7 days, or self-terminating, lasting less than 7 days. Self-terminating atrial fibrillation and non-self terminating and are classified as paroxysmal and persistent, respectively. Recurrent atrial fibrillation is also classified as persistent or paroxysmal according to duration. Termination by pharmacological therapy or electrical cardioversion does not change the classification of either persistent or paroxysmal atrial fibrillation. Cases of long-term atrial fibrillation in which repeated attempts to convert to normal sinus rhythm have failed or it is judged inappropriate to attempt conversion are classified as permanent atrial fibrillation. Paroxysmal and persistent atrial fibrillation can occur in the same patients at different times.
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A patient may or may not be aware of his or her arrhythmia. The symptoms vary with each patient, and include palpitations, a rapid heartbeat, or a sudden pounding in the chest, dizziness, syncope , chest discomfort, or shortness of breath. The impact that symptoms have on functional status or quality of life is a major factor in determining how soon a normal rhythm needs to be restored. The patient's history is critical for eliciting what factors are associated with the occurrence of the arrhythmia and whether those factors need to be addressed before proceeding with treating the arrhythmia.
Physicians often suspect atrial fibrillation when patients describe its symptoms.
Patients with atrial fibrillation may be exquisitely sensitive to the change in rhythm, while others do not notice it at all. Often patients are aware of “palpitations, a sensation that the heart is skipping beats or being inappropriately fast or slow.
Some patients with atrial fibrillation notice a reduced exercise tolerance. Some of this may relate to the loss of atrial kick, others may have an inappropriate heart rate response to exercise, either too slow or too fast.
Identifying triggers of the arrhythmia may be useful in preventing recurrences. Having a glass of wine or eating chocolates may precipitate atrial fibrillation in susceptible individuals. Others may describe onset after drinking a cold beverage, with heartburn or with having a sensation of bloating. Identifying and preventing triggers may be an option for preventing atrial fibrillation in some patients. Click continue when you are ready.
Documentation of the arrhythmia is the most definitive diagnostic tool. Diagnosis of atrial fibrillation is relatively straightforward if the arrhythmia can be captured on an electrocardiogram ( ECG ) or rhythm strip. If the arrhythmia is intermittent (or paroxysmal), diagnosis can be more problematic, requiring more sustained recording techniques. The presence and severity of symptoms may also influence treatment decisions.
A routine ECG while the patient is having atrial fibrillation is the definitive diagnostic tool. While there are several rhythms, which may cause an irregular rhythm, the 12-lead ECG is a recording of the actual rhythm and can document the atrial activity.
In a normal sinus rhythm, the ECG demonstrates a discrete P wave, which reflects regular atrial depolarisation, with each P wave followed by a QRS produced by ventricular activation.
Atrial fibrillation is characterised by a rapid, irregular atrial activation without discrete P waves on an ECG. The ventricular response rate is irregular and has no discrete relationship to atrial activity.
In atrial fibrillation, the atrial activity is very irregular giving the multiple, low amplitude signals across the baseline of the ECG. The irregular conduction to the ventricle is reflected in the irregularity of the ventricular activation (QRS complexes).
With a Holter monitor, every heartbeat is recorded over a 24-hour interval. With this technique, paroxysmal episodes of atrial fibrillation could be recorded even if the patient is not having any symptoms. Additional information can be provided about the heart rate preceding the event to assess whether autonomic function may be a factor in the arrhythmia. Having only 24 hours of information is the major limitation of this technique, as there is often a low probability of someone having an event in the 24-hour period being recorded. Click continue when you are ready.
An echocardiogram, which uses ultrasound to image the heart, provides important information for the initial evaluation of most patients with atrial fibrillation. Either transthoracic echocardiography or transoesophageal echocardiography or a combination of the two may be appropriate. The initial goal of the echocardiography evaluation should be to establish the presence or absence of structural heart disease including valvular abnormalities, congenital anomalies, chamber distensions, pericardial thickening or effusions, ventricular function and presence of thrombus .
Left atrial size is an important predictor of outcome in patients with atrial fibrillation. Left atrial enlargement may increase the risk of stroke, owing to a greater potential for stasis in the dilated chamber. Although transthoracic echocardiography is adequate for assessing chamber size, detection of thrombi or the assessment of left atrial appendage anatomy and function requires the transoesophageal approach.
The left slide shows a view of the left atrial appendage and the arrow points at a thrombus in the appendage. In the right slide the movements of the thrombus is seen in the appendage during atrial contraction.
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Match the appropriate statement to the most appropriate symptom or type of atrial fibrillation.
Most patients with atrial fibrillation have significant symptoms, particularly reduced exercise tolerance, with some even being able to tell the exact time the arrhythmia occurs. For these patients, restoration and maintenance of normal sinus rhythm offers a marked improvement in symptoms. Benefits of normal sinus rhythm are less certain in patients who have noted no impairment of their functional capacity.
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In the remodelled atrium in atrial fibrillation, there may be alterations in ion channel function. Antiarrhythmic drugs block atrial fibrillation by blocking various ion channels, and increasing the refractory period in the atrium, thereby extinguishing the micro-re-entrant circuits that trigger atrial fibrillation.
The Vaughan-Williams Classification of antiarrhythmic drugs is based on their electrophysiological properties.
Class IA drugs predominantly block the sodium ion channels. Class IA drugs also have some effect on potassium ion channels. Due to their relatively high level of side effects, including the risk of life-threatening ventricular arrhythmias, they are used infrequently today.
Class IC drugs cause the most marked depression of sodium ion current, often resulting in a prolonged QRS duration at therapeutic concentrations. The amount of ion channel inhibition increases with increasing heart rate, making them particularly useful drugs for the treatment of tachyarrhythmias such as atrial fibrillation.
Class III drugs block the potassium ion current responsible for repolarization in atrial fibrillation and prolong the action potential duration, increasing the refractoriness of the tissue and making it more difficult to sustain micro-re-entry.
Proarrhythmic adverse events are related to occasional excessive QT prolongation the early period after starting the drug, especially in the presence of electrolyte disturbances like hypokalemia.
For persistent or highly symptomatic paroxysmal atrial fibrillation, normal sinus rhythm can be restored with drugs (pharmacological cardioversion) or with an electrical shock (electrical cardioversion). Electrical cardioversion involves the use of an electrical current through the chest wall to convert the abnormal rhythm back to normal, while the patient is under short-acting anaesthesia.
Antiarrhythmic drugs are often used to maintain normal sinus rhythm in the early period after electrical cardioversion, and may be needed on a chronic basis to prevent recurrences of atrial fibrillation. Three to four weeks before a planned electrocardioversion, oral anticoagulant and antiarrhythmic drugs are commonly prescribed. Other recommendations in connection with this procedure are also listed here.
A number of pharmacologic and alternative treatment methods are being developed to maintain normal sinus rhythm.
Prospective data has shown that the annual maintenance of normal sinus rhythm after one cardioversion is less than 20% in the absence of antiarrhythmic drugs. With antiarrhythmic drugs, sinus rhythm can be maintained in about 50 to 65% of atrial fibrillation cases. Thus, chronic antiarrhythmic drug therapy is the current standard for the maintenance of normal sinus rhythm. The choice of antiarrhythmic drug relates to underlying heart disease and a balance of the potential toxicities with the benefit of maintaining normal sinus rhythm.
The principal disadvantage of all forms of cardioversion is a small risk of thromboembolism, which appears to be greatest when Atrial Fibrillation has persisted for over 48 hours. Anticoagulation therapy is therefore recommended in the majority of patients when cardioversion is performed. Shown here is a table summarising the ACCP guidelines. Click continue when you are ready.
Shown here is a summary of the landmark clinical studies comparing rate control with rhythm control (cardioversion) in the treatment of Atrial Fibrillation. Use the bar to scroll through the table. They showed that the number of strokes was significantly greater in patients receiving rhythm control than patients receiving rate control. This was suggested to be due to the common practice of discontinuing anticoagulation therapy after 3-4 weeks of successful restoration of normal sinus rhythm - in contrast to the continued anticoagulation that is recommended with rate control. These trials showed that, because current antiarrhythmic drugs do not effectively prevent relapses of AF, to reduce stroke risk, anticoagulation should be continued the current 3-4 week clinical practice. An alternative anticoagulant, with a superior risk:benefit profile to warfarin is also likely to be beneficial in achieving more effective long term coagulation and therefore reduce the long term risk of stroke. Click continue when you are ready.
While drug therapy is the most common approach to maintain normal sinus rhythm, implantable devices capable of detecting and treating atrial arrhythmias at the earliest possible moment provide one option for controlling atrial arrhythmias for certain patients.
Click on the options to review these different devices for maintaining normal sinus rhythm. Click the continue button to proceed.
Surgical options are also available for prevention of atrial fibrillation. Click on the options to learn more. Click continue when you are ready.
The non-drug therapies are suitable only for a subsection of atrial fibrillation patients who may still require combinations of therapies, including antiarrhythmic drugs, pacemakers, ablation, or surgery. With any single therapy, there is still a real risk of recurrence of arrhythmia. Though the notion is still theoretical, the preferred option for treatment of atrial fibrillation may someday be a combination of therapies, typically an antiarrhythmic drug in addition to other therapies.
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