Cardiac Arrhythmias in Women

Differences between the sexes in cardiac electrophysiology were first described in 1919 by Lombard and Cope, who reported a longer length of systole in women than in men.¹ Shortly afterward, in 1920, Bazett found the QT interval to be 6% longer in women than in men.² Several prominent electrophysiologic differences have been noted between the sexes. By 5 years of age, girls have a higher heart rate than do boys, which might be explained by a shorter sinus node refractory time.³ The shorter QT interval in men is noted during puberty, as sex hormone levels rise.⁴ The length of the QT interval in men increases linearly through adulthood until the age of 50, when it becomes similar to that of women, which correlates with the decrease in androgen levels.⁵ Furthermore, QRS amplitude and duration are greater in men, consequent to a higher cardiac mass and thicker left ventricular walls.⁶

Effects of Sex Hormones

Sex hormones contribute to the differences in cardiac electrophysiology between men and women. Testosterone suppresses inward calcium currents and enhances inward rectifying potassium currents, which might explain why the QT interval is shorter in men.⁷ Moreover, the testosterone-mediated increase in repolarization reserve in men might explain their lower susceptibility to drug-induced polymorphic ventricular arrhythmias.^7–9 Testosterone levels are higher in women with polycystic ovary syndrome, and these women have a QTc interval that is about 66 ms shorter than that of women who do not have the syndrome, which provides further evidence that higher levels of testosterone decrease the QTc interval.¹⁰

In contrast to the effects of testosterone, estrogen prolongs the QT interval.¹¹ Progesterone (the electrophysiologic effects of which are opposed by estrogen) may have a reducing effect on QT interval in women similar to that of testosterone in men. The increase in progesterone and the decrease in estrogen levels during the normal menstrual cycle correspond to the increased frequency, symptomatic burden, and duration of supraventricular tachycardia (SVT).¹² Sick sinus syndrome, SVT, atrioventricular nodal re-entry tachycardia (AVNRT), and postural orthostatic tachycardia syndrome are more common in women than in men.^13,14 In fact, AVNRT—the most common type of SVT in women—is twice as common in women as in men; women also tend to be younger at the time of its onset.¹⁵

Atrial Fibrillation

Atrial fibrillation (AF) affects approximately 2.2 million people in the United States each year, and its incidence doubles with each decade of adult life. Atrial fibrillation is more common in men, but after age 75, almost 60% of people with AF are women. Moreover, the mortality rate is higher in women than in men. In women, AF is often caused by valvular heart disease; in men, it is more often associated with coronary artery disease.¹⁶ Furthermore, women have a higher incidence of AF associated with obesity.

The risk of stroke and death associated with AF is higher in women than in men.¹³ When taking sotalol or dofetilide, women have an increased risk of torsades de pointes and a higher risk of bradyarrhythmias.^16,17 In addition, women are exposed to a significantly higher risk of bleeding after taking anticoagulative agents.¹⁶

Women tend to have more symptoms associated with AF. Women who have paroxysmal AF may have faster heart-rate responses (and longer episodes) than do men with paroxysmal AF.¹⁸ Compared with men, women have a higher recurrence rate of AF.¹⁸

The sex of the patient can have an effect on the treatment plan for AF. Women with AF derive the greatest benefit from anticoagulation but fare worse than men when a rhythm-control strategy is used.¹⁹ Outcomes after catheter ablation for AF are similar between the sexes, yet women are referred later and less frequently and often present in a more complex preoperative condition. Ablation of AF appears to be as safe and effective in women as it is in men, and despite the higher risk profile in women, there is no difference in clinical outcome.¹⁶

Pregnancy

Pregnancy increases the risk of new-onset SVT. This risk is higher in pregnant patients with Wolff-Parkinson-White syndrome.²⁰ In the absence of structural heart disease, AF and atrial flutter are rare during pregnancy.²¹ Nonsustained ventricular arrhythmias occur in up to 50% of pregnant women, but the clinical risk of sustained ventricular arrhythmia in the absence of structural heart disease is low.²²

Most antiarrhythmic drugs are classified as category C drugs during pregnancy by the United States Food and Drug Administration (FDA), which indicates that animal studies have revealed the potential for adverse effects to the fetus.²³ Therefore, drug therapy should be used only in patients who have life-threatening arrhythmias or debilitating symptoms. Most β-blockers are classified as category C drugs by the FDA; however, atenolol is classified as a category D drug because it has been implicated in intrauterine growth retardation, and sotalol, pindolol, and acebutolol are classified as category B drugs.²² Other class C drugs include adenosine, digoxin, and heparin, whereas lidocaine and enoxaparin are class B drugs. Enoxaparin is safe for the fetus, but some formulations contain the preservative benzylalcohol, which can be harmful.²⁴ Amiodarone is considered a category D drug, and warfarin (category X) should not be used at all during pregnancy because of its teratogenicity.

Summary

Several specific electrophysiologic parameters are different between men and women. These differences should be considered while caring for patients with AF, because a better understanding of these factors will improve patient care. Pregnancy, although considered a proarrhythmic state, restricts the use of pharmacologic therapy. Nevertheless, effective pharmacologic management of arrhythmias in pregnant women can be achieved.