To this day, women fight for the legal and social equality of the female sex. In medicine, however, equal treatment oriented toward men can have negative consequences for women. Particularly in gender-sensitive aspects such as in risk assessment, diagnosis and therapy of various clinical pictures related to the heart, experts advocate gender-specific care.
The female heart is not simply a small version of the male heart. Using similar diagnostic criteria for women’s and men’s hearts, heart disease is often overlooked in women and is diagnosed later and with more severe symptoms than in men. Recent studies suggest that this is at least partly due to the lack of gender-specific diagnostic criteria. While it is well known that the female heart is smaller than the male, it has long been ignored that it also has a different microstructural architecture. This has serious implications for a variety of cardiac parameters [2].
Gender differences in cardiac structure and function.
The heart of an adult human being is about the size of a fist and weighs approximately 300 g. While the dimensions of the human heart are often given as fixed values, its size and weight are neither constant throughout life, nor are they similar in women and men, explains Prov.-Doz. Dr. Pascal Bauer, University Hospital Giessen and Marburg GmbH Medical Clinic I – Cardiology and Angiology Giessen [1]. At birth, the human heart has less than one tenth of the maximum mass of an adult. With age, the total number of cardiac muscle cells remains the same, but the cells themselves increase in volume. This allows the heart to grow. On average, the mass of the adult female heart is between 230 and 280 g and is about 26% lighter than that of the male heart, which weighs between 280 and 340 g. When isometrically scaled at -26%, female wall thickness and their ventricular and atrial diameters would be approximately (1.00-0.26)1/3 = 0.90 times that of their male counterparts, meaning they would be -9.0% smaller. In both women and men, heart mass continues to increase with age. In the elderly, women’s hearts with an average mass of 388 g are about -4% smaller than men’s hearts with an average mass of 405 g [2].
However, the female and male heart not only differ in mass and size, but also exhibit a variety of functional, structural, genetic and hormonal differences: for example, women have a higher resting heart rate than men, and their hearts take longer from contraction to relaxation. This is due to the action of testosterone during ventricular repolarization and can be observed by longer QT intervals in the electrocardiogram. This puts women at greater risk for drug-induced arrhythmias. There is growing evidence that both progesterone and testosterone protect against arrhythmias, while estrogen may increase susceptibility to arrhythmias. From a functional perspective, sex hormones are involved in the regulation of calcium homeostasis, leading to sex differences in the excitation-contraction coupling pathway of the heart. Regarding autonomic cardiac function, women have stronger vagal control over sympathetic responsiveness for cardiac function than men. Myocardial metabolism is directly related to cardiac function; sex differences exist in myocardial oxygen consumption and glucose utilization. Estrogen has been shown to decrease glucose utilization, implying that fatty acid oxidation is more responsible for energy production in women than in men [2].
Echocardiography – Gender-specific normal values
In contrast to the male heart, the female heart has a lower cardiac output. With end-diastolic and end-systolic volumes of 124 and 53.53 ml, the female heart has a stroke volume of 69.32 ml, which is 23% smaller than the male heart with end-diastolic and end-systolic volumes of 168.35 and 78.60 ml and a stroke volume of 89.75 ml. Interestingly, the female heart tries to compensate for this difference by having a 6% higher heart rate of 79.1 beats per minute compared to the male heart at 74.3 beats per minute. Nevertheless, cardiac output remained consistently smaller in women than in men, 5.6 vs. 6.7 L/min (-16%), and 4.6 vs. 5.9 L/min (-22%). Nevertheless, the female heart with 0.126 L/[kg-min] has a 21% higher value than the male heart with 0.104 L/[kg-min], when scaled with the female and male lean body mass of 36.5 kg and 56.7 kg, respectively (Table 1) [2].
In addition, the female heart has 10-14% higher contractility than the male heart. Most reported strains in the female heart are significantly greater, with circumferential strains of +11 and +10% and longitudinal strains of +14 and +13% in the left and right ventricles, respectively. Strain rates are more difficult to measure, and sex differences vary from +13 to +49%, yet all female strain rates are consistently greater than males. The reported values in the Tables 1 and 2 can be correlated by a simple backward hemisphere calculation: Based on the reported left ventricular end-diastolic and end-systolic volumes of 168.35 and 78.6 mL, respectively, for the male heart and 124 and 53.53 mL, respectively, for the female heart in Table 1, this estimate would predict male and female left ventricular dilations of -22 and -24%, respectively, and a difference between female and male left dilations of +9%. This estimate is consistent with the differences measured in vivo of +11% in the circumferential direction and +14% in the longitudinal direction in Table 2 [2].
In addition, the female heart has a greater ejection fraction than the male heart. The end-diastolic volume of women and men differs in the left and right ventricles by -26 and -23%, respectively, which is consistent with the difference in total female and male heart mass of -26%. At the same time, the end-systolic volume of women and men differs by -32 and -35% for the left and right ventricles, respectively. These numbers suggest that the female systolic heart is disproportionately smaller than the male systolic heart. These volume differences result in a greater ejection fraction of +7 and +11% for the left and right ventricles of women compared with men [2].
ECG diagnostics – gender differences
Anatomical differences between male and female patients not infrequently present challenges in electrode placement and accurate ECG acquisition. Unfortunately, anatomical misplacement of ECG electrodes is common and has a significant impact on clinical diagnosis, explains Prof. Dr. Carsten Jungbauer, University Hospital Regensburg Clinic and Polyclinic for Internal Med. II, Cardiology Regensburg (D) [3].
Causes of misplacement include both modifiable and non-modifiable patient factors such as body habitus, body position, lack of anatomical awareness, lack of confidence, competence, or even overconfidence. Only 50% of nurses and <20% of cardiologists correctly placed precordial V1 and V2 electrodes [4]. The Society for Cardiological Science and Technology ( SCST ) guidelines and recommendations state that the V4, V5, and V6 electrodes should be placed under the breast in women when the breast tissue covers the correct anatomic positions (Fig. 1) [5,6]. In addition, when lifting the chest to place the electrodes, a certain amount of caution and dexterity is required [6]. The breast should be lifted only with the back of the hand. In a study conducted, it was found that 52% of women preferred electrodes placed on the breast tissue as they considered it less intrusive, 38% were indifferent, and 10% preferred placement under the breast [5].
ECG Basics – Man vs. Woman
The QRS complex (ventricular complex) is characterized with some variability. Table 3 [7] shows differences between gender as well as age-related differences and differences between ethnicities. Furthermore, a close look at the individual values, shows a continuous QRS duration <100 ms. In clinical practice, a QRS duration of >120 ms is rather abnormal in men and women. The amplitude of the QRS complex also shows sex differences. Men show significantly higher values in the mean amplitude of V2, which decrease with age. While in women the values remain relatively constant. The whole corresponds to the left ventricular mass (LV mass index), which decreases with aging in men but remains constant in women [7].
The ST-section elevations show a comparable picture concerning the sex differences. Here, too, a decrease with age is seen in men, whereas the values in women remain relatively constant [7]. This is also reflected in the ST-segment elevation myocardial infarction guidelines. In the proper clinical context, ST-segment elevation (measured at the J point) is considered indicative of acute coronary artery occlusion in the following cases: at least two contiguous leads with ST-segment elevation ≥2.5 mm in men <40 Jahre und ≥2 mm bei Männern>40 years. In women, ≥1.5 mm in leads V2-V3 and/or ≥1 mm in other leads (in the absence of left ventricular hypertrophy or left bundle branch block) [8].
QT time prolongation is usually associated with hypokalemia, hypocalcemia, or medications (e.g., antibiotics). The mean difference between men and women is 10 ms. The QTc upper limit of the norm is 460 ms in women and 450 ms in men [7]. Which is also reflected in the guidelines where men receive a point in the QT calculator if the QT time is between 450-460 ms [7]. Interestingly, prolongation by a class III antiarrhythmic drug in women is associated with progesterone levels during the menstrual cycle. Many women therefore predispose to a higher arrhythmia risk during menstruation and the ovulatory phase compared with the luteal phase [9].
Gender adaptations in cardiovascular disease.
Epidemiological studies have shown that women make up the majority of patients with HFpEF (heart failure with preserved ejection fraction) and that female sex is one of the strongest differentiators between HFpEF and heart failure with reduced ejection fraction (HFrEF). LV ejection fraction (EF) increases with age in both sexes, although to a greater extent in women. However, despite their overall higher EF, women show a greater reduction in longitudinal systolic contraction velocity with age. At the cellular level, the number of cardiomyocytes at birth is similar between the sexes, but in aging women, the decline in cardiomyocyte number and mass is relatively smaller, and there is less tendency for cardiomyocyte hypertrophy and eccentric LV remodeling than in men [10].
Cardiac aging predisposes older women to HFpEF because concentric LV remodeling and diastolic dysfunction are hallmarks of HFpEF and are more pronounced in women with HFpEF than in men with HFpEF. On exertion, an increased increase in LV diastolic elasticity in women compared with men, together with reduced chronotropic and contractile reserve, contributes to exercise intolerance, a defining clinical feature of HFpEF. In particular, the smaller LV chamber size in women results in a greater reliance on an increase in heart rate to meet the cardiac output demands of exercise; therefore, chronotropic incompetence may contribute more to the reduction in maximal oxygen consumption in women with HFpEF than in men [10].
Pulmonary hypertension (PH) is a major pathophysiological and clinical feature of HFpEF. Although increased LV filling pressures and LA pressures are fundamental to the cause of PH in HFpEF, it is likely that there are other precipitating factors affecting the pulmonary circulation, particularly in women. Combined pre- and post-capillary PH develops in a subset of HFpEF patients and is favored by advancing age and valvular heart disease, particularly mitral regurgitation, which is more common in women. Women are also more susceptible to idiopathic pulmonary arterial hypertension with increased pulmonary vasoconstriction and intrinsic pulmonary artery remodeling, which affects four times as many women as men. This may indicate underlying sex differences in pulmonary vascular remodeling and reactivity [10].
This association between pulmonary vascular function, women, and HFpEF is highlighted in a study that found that 82% of patients with HFpEF and PH were female, compared with 58% of patients without PH. The underlying pathophysiology is complex. During rapid saline loading, there is a greater increase in pulmonary capillary wedge pressure in older women than in men, which is associated with a greater increase in right atrial pressure, which may indicate relatively impaired left atrial diastolic function and greater pericardial restraint in women. Interestingly, the slope of the ratio of mean pulmonary artery pressure to volume of saline infused is steeper in both young and elderly women, suggesting a lower reserve for flow-mediated dilatation of the pulmonary artery compared with men [10].
Hypertension is more common in female patients with heart failure (HF) than in males, 50% and 40%, respectively. In addition, hypertension increases the risk of HF threefold in women compared with twofold in men. This could be explained by a higher augmentation index between peripheral and central blood pressure in women compared with men, which contributes to greater end-organ damage including LV hypertrophy. A direct relationship between carotid augmentation index and diastolic dysfunction is observed in women but not in men. Women adapt to pressure overload differently than men, with more pronounced remodeling of a concentric rather than eccentric nature and a more profound response to hypertension and obesity than men [10].
Coronary artery disease: although men are more likely to have obstructive coronary lesions, women are more prone to microvascular and endothelial dysfunction, thicker arterial walls with nonobstructive coronary disease, and vascular spasm. Higher rates of angina attributable to coronary microvascular dysfunction in women result in hypertrophy and fibrosis. Recent data from theAtherosclerosis Risk in Communities (ARIC) study have shown that retinal microvasculature characterization by retinal photography adds value to current practice guidelines in predicting coronary artery disease events in women but not in men. Microvascular rarefaction and ischemia have been shown to play an important role in the pathophysiology of HFpEF [10].
Cardiac Arrhythmias: Figure 2 [11] shows that atrioventricular reentry tachycardias are more common in men, whereas AV nodal reentry tachycardias are more likely to develop in women. Looking at idiopathic ventricular arrhythmias, it is apparent that women are more likely to have a right ventricular outflow tract of ventricular arrhythmias, whereas men are more likely to have a left ventricular outflow tract of ventricular arrhythmias or ventricular arrhythmias from deep within the left ventricle. In women, the symptoms and frequency of arrhythmias depend on the menstrual cycle. Women also have a higher risk of being underserved with an ICD, as well as a higher risk of adult-onset long-QT syndrome malignant events and a higher incidence of uncoupling, whereas men are more likely to develop ventricular fibrillation [11].
Atrial fibrillation: Women have a greater LA volume index and lower LA efficiency than men in atrial fibrillation. In addition, atrial fibrillation appears to increase the risk of HF in women. They are more likely to suffer from palpitations and anxiety, as well as high blood pressure, valvular heart disease, and lower quality-of-life scores. In an analysis of the TOPCAT trial (Treatment of Preserved Cardiac Function HF With an Aldosterone Antagonist Trial), AF was associated with a higher risk of hospitalization in women compared with men with HFpEF, suggesting that AF plays a greater role in women with HFpEF [10]. Women diagnosed later in the course of the disease are less likely to be referred to specialized centers or clinics. Female sex is further associated with a higher risk of thromboembolic events, and women continue to have a higher recurrence rate after pulmonary vein isolation with more complications [11].
Congress: 89th Annual Meeting of the DGK
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- Jungbauer C: Geschlechterunterschiede in der EKG-Diagnostik. 89. Jahrestagung der DGK, 12.04.2023, Sitzung: Geschlechtersensible Diagnostik in der Kardiologie.
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