Atrial fibrillation (AF) is the most common heart rhythm disorder in the world and is associated with stroke and peripheral embolism.¹ Nearly 2.5 million people in the US alone have AF and those with AF are five times more likely to suffer a stroke as compared to those without AF. As we age, the incidence of AF increases and risk factors for AF include advancing age, diabetes, hypertension CHF, valvular heart disease and myocardial infarction.² It has been long proven that AF is an independent risk factor for stroke and confers a three-to-five-fold increased risk that increases with age.³ Data from the Framingham Heart Study demonstrates a nearly two-fold increase in death in patients with AF as compared to those without AF and this risk was present in both men and women.⁴ Other trials such as the RACE study (RAte Control versus Electrical cardioversion) have demonstrated a higher mortality and lower quality of life in women with AF as compared to men.5

Pathophysiology, causes and symptoms of AF

AF occurs when the atria no longer participate in a coordinated electrical systole resulting in contraction. In AF, the cells in the atria rapidly depolarize and fire in a disordered fashion, resulting in the absence of P-waves on electrocardiography (EKG) and a variable R-R interval with fibrillatory oscillations on a rhythm strip. Symptoms of AF may be quite variable and may involve no symptoms whatsoever in some patients. In other individuals, there may be significant fatigue, shortness of breath, exercise intolerance or palpitations.

AF is associated with a number of toxic, metabolic, endocrine and genetic abnormalities and the incidence increases with age.⁶ Thyroid disease is commonly identified as a precipitating factor. Some of the more common cardiac-related causes of AF include coronary artery disease, cardiothoracic surgery, hypertension and valvular heart disease. In addition, congenital heart disease can predispose patients to the development of AF at earlier ages. The etiologies of AF seem to differ in population studies of men and women. Men are more likely to have coronary artery disease and women are more likely to have hypertension and valvular heart disease as a predisposing factor for AF.

The causes of AF are multi-factorial and can be both primary and secondary to other medical problems.

In AF, the goal of therapy is the prevention of stroke and the relief of symptoms. In many patients, most of the symptoms are related to poorly controlled, irregular ventricular rates.7 Interestingly, the rates of death in patients with a history of AF is doubled — although this finding appears to be an association rather than a case of cause and effect. The treatment strategies for AF include either control of rate versus control of rhythm. However, a key component to either strategy is stroke prevention through anticoagulation. Data from the AFFIRM trial makes it abundantly clear that it is safe and effective to treat AF with either a rate control or rhythm control strategy with similar outcomes.⁸ In patients in which a strategy of rhythm control is chosen, therapy most often includes initiation of antiarrhythmic drugs followed by electrical cardioversion.⁹ Many clinicians argue that the rhythm control strategy offers the advantages of fewer symptoms, reduced risk of stroke (because of a presumed less time spent in AF), and eventual discontinuation of anticoagulation therapy. A potential disadvantage to a rhythm control strategy is the fact that antiarrhythmic therapy includes a higher risk of side effects (all antiarrhythmic drugs have the potential for pro-arrhythmia).¹⁰ Alternatively, a strategy of rate control focuses on the use of drug therapy with AV (atrio-ventricular) nodal blocking agents to control ventricular response during AF. With this strategy, less toxic drugs may be utilized but chronic anticoagulation is a must. In addition, in refractory cases of rate control in AF, an ablation of the AV node along with pacemaker implantation may be utilized in order to definitively control ventricular rates.

Over the last 15 years, newer, more advanced therapies for AF have been developed that can be utilized in conjunction with both the rate control and rhythm control strategies. Radiofrequency ablation is an invasive technique that focuses on eliminating the electrical triggers for AF in the left atrium and pulmonary veins.11 In this procedure, catheters are taken to the left atrium via a percutaneus approach with a trans-septal puncture of the intra-atrial septum. The pulmonary veins are then carefully mapped and electrical triggers are eliminated through the application of radiofrequency energy. In many patients the cure rates for AF with this technique can approach 85% or more. Other invasive techniques have been utilized for rate control. In patients with chronic, refractory AF, many cardiologists will implant a pacemaker (or biventricular pacemaker) and subsequently ablate the AV node. In this procedure, the ablation of the AV node will eliminate all rapid ventricular response and will make the patient pacemaker-dependent. Because of the data surrounding right-ventricular-only pacing and increased incidence of congestive heart failure (CHF), many clinicians will implant a biventricular device in order to maintain ventricular synchrony and pace both the left and right ventricles — thus avoiding pacing-related CHF.^12,13 This technique can be incredibly effective and can produce patient responses and outcomes similar to those with rhythm control. However, in patients with chronic AF and AV node ablation, it is essential that lifelong anticoagulation is maintained in order to prevent stroke. In those who have successfully undergone AF ablation, it is possible to discontinue anticoagulation after a long period of proven maintenance of normal sinus rhythm (NSR).

Interestingly, as with coronary artery disease, there does appear to be stark differences in the treatment of men versus women. Data from the Euro Heart Survey on Atrial Fibrillation was analyzed and researchers found that women with AF were much less likely to be adequately anticoagulated (even though women seem to have a higher risk of AF-related stroke) and tended to be treated with a more conservative rate-control-only strategy.14 In addition, women in this database were much less likely to undergo transesophogeal echocardiography to exclude a left atrial thrombus prior to electrical cardioversion and were also less likely to undergo stress testing as compared to men with similar clinical characteristics. Just as we have seen with the treatment of coronary artery disease, women with AF were also much less likely to undergo invasive procedures for AF such as catheter ablation.

AF and stroke

Stroke is the most common reason for the increased morbidity and mortality associated with AF and women at risk for stroke are often overlooked. In AF, the non-effective mechanical systole associated with the arrhythmia predisposes patients to form clots in the left atrial appendage. In many cases these thrombi will dislodge and produce stroke by occluding a cerebral artery. There is a great deal of data to suggest that anticoagulation can reduce the risk of stroke to that of patients without AF. Yet, many women with AF are not treated with proper anticoagulation.

Anticoagulation has been shown to be highly efficacious in the prevention of stroke — meta-analysis of several different trials demonstrated a 61% reduction in the incidence of stroke in patients treated with warfarin.15 While bleeding complications are a real concern, the target anticoagulation level must balance risk of bleeding with stroke prevention. Bleeding complications increase with advanced age but anticoagulation is still indicated. There are several types of anticoagulation available including aspirin, warfarin and the newer direct thrombin inhibitors. Aspirin provides only modest stroke risk reduction as compared to the other agents but does appear to be more effective in patients with hypertension or diabetes.¹⁶ Several trials over the last 20 years have shown that warfarin is clearly superior to aspirin in the prevention of stroke in AF and warfarin anticoagulation has become the standard of care for the prevention of thromboembolism.¹⁷ Warfarin therapy requires frequent blood testing to monitor levels and effective blood levels can be affected by changes in diet and the use of certain concomitant drugs. Newer anticoagulants have been developed and FDA approved in the last several years that provide alternatives to warfarin therapy and have been shown to be either equivalent to warfarin or superior in terms of efficacy and safety.^18–20 The advantages of the newer anticoagulation agents are the fact that they do not require blood testing to monitor levels and they are not affected by diet. Drawbacks include the fact that there are no available reversal agents for these drugs.

Most clinicians utilize the CHADS2 score to determine the need for anticoagulation.21 The CHADS2 score considers CHF, hypertension, age, diabetes and prior stroke in order to determine thromboembolic risk. With the CHADS2 score, a clinician is able to quickly calculate the lifetime risk for stroke in a patient with AF based on certain risk factors. By calculating this score, the healthcare provider is able to determine which anticoagulant regimen is best indicated for the individual patient.

Women and AF: future directions to improve outcome

Just as with the treatment of coronary artery disease, women with AF are often undertreated and underserved and therapy often falls below standard of care. Data from the European Heart Journal has indicated that as a group, women with AF are more likely to not be anticoagulated and seem to have higher rates of bleeding complication and debilitating stroke.²² In addition, women with AF are not treated as aggressively and represent a minority of patients undergoing advanced procedures such as AF ablation and other device-based therapy. As healthcare providers, we must work diligently to ensure that women with AF are treated according to well-published guidelines. While it is true that women are more likely to suffer procedural-related complications, this should not preclude therapy for those who are indicated. Even though women with AF are more likely to suffer complications and excess morbidity, we must strive to individualize therapy and provide the best available treatments. Just as with coronary artery disease, we must work diligently to educate women about their risk for AF and how to prevent devastating consequences such as stroke. Educating the public as to the etiologies, symptoms and risks associated with atrial fibrillation must play a bigger role in public health policy. Particularly in the era of healthcare reform and cost containment, working to prevent disease must be of paramount importance.

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⁵ Rienstra, M., van Veldhuisen D. J., Hagens, V. E. et al. (2005). Gender-related differences in rhythm control treatment in persistent atrial fibrillation. J Am Coll Cardiol, Volume 46, 1298–1306.

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⁷ Krahn, A. D., Manfreda, J., Tate, R. B. et al. (1995). The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study. Am J Med, Volume 98, 476–484.

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⁹ Falk, R . H. (2001). Atrial fibrillation. N Engl J Med, Volume 344, 1067–1078.

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²² Gomberg-Maitland, M. (2006). Anticoagulation in women with nonvalvular atrial fibrillation in the stroke prevention using an oral thrombin inhibitor (SPORTIF) trials. European Heart Journal, Volume 27, 1947–1953.