Sex Variation in the Electrocardiogram

In an editorial in the December 2012 issue of Critical Care Nurse, Grif Alspach challenged acute and critical care nurses to recognize, identify, and mitigate gender bias in critical care.1 This challenge is a necessary and urgent call to action. To meet the challenge, we should know more about sex disparities in cardiac conditions. Sex variation related to the electrocardiogram (ECG) is both genetic and sex-steroid linked, and sex-related variations in anatomy and physiology exist beyond the reproductive system.2 The ECG challenge for this issue is to consider the sex-based disparities in the ECG and cardiac rhythms. Entire books are written on cardiac disease in women,3,4 so no claims of comprehensiveness are made in this short column. Rather, I provide a brief overview of the topic to stimulate critical thinking related to a more gender-based cardiac nursing practice.Sex-based morphological differences in the ECG enable clinicians to distinguish the average ECG of a woman from that of a man. Five characteristics of the typical male ECG pattern differ from those of the typical female pattern.5 In men, the amplitude of the ST junction is higher, the ST segment is shorter and more up-sloping, the T-wave ascent is faster, and the T-wave height is greater. Other morphological variations include a shorter PR segment and a narrower QRS with lower voltage in women.2 These variations may be related to small differences in working myocardial cell depolarization and repolarization between men and women. Although distinguishing the average ECG of women from men is possible on the basis of these morphological variations, the differences are so subtle that on a case-by-case basis, individual differences may override sex differences.The heart rate of women is slightly faster than that of men, by about 3 to 5/min according to one source4 and 2 to 7/min according to another,3 with slight variations throughout the lifespan. The proposed mechanisms for this variance include sex differences in sinus node automaticity (shorter sinus node recovery time in females), gender variance in exercise capacity,3 and hormonal influence.4 One source notes that stroke volume in women is 10% less than that of men, but with the heart rate variation taken into account, the cardiac index of men and women is approximately the same.2 Heart rate variability in women, however, is less than that of men during the second and third decades, purportedly as a result of hormonal influence on autonomic regulation.6The condition termed inappropriate sinus tachycardia almost exclusively is seen in women. This diagnosis is made when other causes of tachycardia have been eliminated. Patients with the condition have unexplained rapid sinus rates at rest or with mild activity.7 The proposed mechanisms are altered sinus node automaticity, autonomic disturbance, or a combination of both. The condition most often is seen in women younger than 40 years, and the number of health care workers with this condition is more than expected.6The rate of occurrence of certain supraventricular tachycardias (SVTs) varies between men and women. Atrioventricular nodal reentry tachycardia, the most common regular SVT,8 is characterized by rapid narrow QRS tachycardia related to multiple conduction pathways (slow and fast) between the atria and ventricles. Atrioventricular nodal reentry tachycardia is more common by a 2:1 margin in women.3,6 The proposed mechanism for the disparity is a shorter refractory period of the slow atrioventricular nodal pathway in women, creating more opportunities for reentry.6 Accessory pathway conditions, such as Wolff-Parkinson-White syndrome, occur less often in women than in men.6Atrial fibrillation (AF), the most common SVT overall,6 also occurs less frequently in women than in men, including AF after heart surgery. Although the mechanism for this disparity is unknown, evidence suggests that AF is more likely associated with coronary disease in men, and with heart failure and valve disease in women.3 Although the overall incidence of AF is higher in men throughout the lifespan, the number of men and women with the condition is approximately the same as a result of the longer lifespan of women.3 The incidence of sudden cardiac death in women is about half that of men. This lower incidence is partially, but not fully, explained by the delay in onset of coronary heart disease seen in the female population4 (see Table 1).Sex-based difference in the length of the QT interval is the most important ECG disparity from both a practical and a clinical standpoint. The difference in the corrected QT interval (QTc) between men and women is about 20 milliseconds.3 A longer QT interval in women is associated with a higher incidence of torsade de pointes (TdP), and women are less tolerant than men to the use of QT-prolonging drugs.9 Interestingly, the cause of this disparity is related to shorter QTc in men as opposed to longer QTc in women. Children of both genders have equal QTc measurements until puberty, when the QTc in male adolescents shortens.6 The proposed mechanism for this change is the influence of androgens on the potassium channels involved in myocyte repolarization.The clinical consequence of this variation is that female sex itself is a risk factor when considering any pharmaceutical therapy that is associated with increased QT interval. Indeed, women have a 3-fold greater chance of developing TdP (Figure 1) than men when taking class 3 antiarrhythmic drugs (potassium channel blockers).3 Women also are at higher risk when taking certain non antiarrhythmic drugs. The authoritative website www.crediblemeds.org, associated with the University of Arizona, maintains a regularly updated listing of drugs with the potential for precipitating TdP.10 Of the 35 drugs listed at the time of this publication, 12 of those drugs are designated as high risk for women by a margin of at least 2-fold over men (Table 2).If sex disparities are to make a difference in the way we care for our patients, then those disparities should have clinical significance. Some of the disparities discussed previously currently do not have a known clinical significance. However, variations in frequency of specific arrhythmias and differences in QT interval are clearly important factors to consider when assessing risk for women. Acute and critical care nurses should be especially vigilant in monitoring women for QT prolongation and related tachyarrhythmias. Medication reconciliation in women has increased urgency, because the use of multiple drugs that are associated with QT prolongation and TdP creates an additive effect. Awareness that certain dysrhythmias occur more or less often in women has implications for both emergency treatment and posthospital discharge planning.In this brief review, I have looked at just a small segment of the sex-based variations related to cardiac care. Areas not covered include pregnancy, cyclical hormonal effects on the heart, and variation in the trajectory of valve disease, heart failure, and coronary artery disease. As noted by Alspach,1 one of the causes of gender bias is assuming that the sexes are the same in all areas except the reproductive system. Current evidence shows that they are not, and future research will help unravel the differences in more detail. In the meantime, we can better inform our cardiac nursing practice by being mindful of the sex differences in the ECG.