Abstract
Background
Distinctions between electrocardiograms of female and male subjects have been recognized for many years. Due to these differences, arrhythmias in each gender have a tendency to differ. In our study, we aimed to compare electrocardiography intervals between men and women with short QRS durations.
Methods
Subjects with a QRS interval of ≤80 ms were included in the study. Patients were grouped by gender and the parameters were compared. Patients with diseases that might affect QRS interval and/or who were on medications were excluded. The electrocardiogram intervals of the subjects were measured, Holter monitors were placed, and parameters of time‐based heart rate variation were analyzed.
Results
A total of 100 patients (55% female) were included in the study. According to statistical analysis, no significant difference between the genders was observed in the heart rate or in the parameters, such as QT, JT, JTp, and TpTe intervals or heart rate‐corrected QTc, JTc, JTpc, and TpTec intervals, which affect repolarization and are known to be arrhythmia precursors by shortening or elongation. No statistically significant difference was found between the two groups for the parameters of heart rate variability time measures (SDNN, SDANN, rMSSD, and pNN50).
Conclusion
We observed that when the QRS interval gets shorter, repolarization differences between the genders disappear. New studies are required on this subject.
Keywords: shortened QRS, accelerated depolarization, gender, repolarization parameters
The fact that there are differences between the electrocardiograms (ECGs) of female and male subjects was first recognized in Bazett's study1 in 1920, which showed that the female QT interval was longer than the male QT interval. In the following years, the ECG parameters of both genders were investigated in detail and gender differences were shown for many ECG parameters, along with QT interval.2, 3, 4, 5, 6, 7 These differences were supposed to be related to sex hormones.8, 9
Repolarization takes place more slowly in females than in males, which makes women more prone to arrhythmias, such as torsades de pointes, and they are also more affected by the arrhythmogenic adverse events of antiarrhythmic, antipsychotic, gastrokinetic, and antihistaminic drugs.10, 11
Studies on gender‐related ECG parameters have mostly focused on changes in repolarization. However, depolarization and depolarization‐repolarization interactions have not been thoroughly investigated. An indicator of ventricular depolarization is the QRS interval, which is known to be shorter in women.12 More importantly, it is widely accepted that the duration of the QRS complex affects repolarization and leads to arrhythmogenic events.13, 14 Shortening of the QRS duration is an indicator of the acceleration of depolarization.15 It is well‐recognized that both shorter and longer QRS intervals lead to syndromes that cause arrhythmias due to ion channel defects of mirror‐image character.16 Wolpert et al.14 suggested that as a wider QRS might lead to arrhythmia, a shortened QRS interval might also cause arrhythmia via the same mechanism. Their study showed that shortening of the QRS interval affected repolarization and therefore caused arrhythmogenic events. However, the reason for this arrhythmia could not be completely clarified. Elongation of repolarization is one of the well‐recognized arrhythmia predictors.
Based on the fact that women have a slower repolarization and faster depolarization, this study aimed to investigate which gender was more prone to arrhythmia when depolarization accelerated by doing a comparison between the genders for ECG parameters such as QT, QTc, JTp, JTpc, TpTe, and TpTec, which show repolarization in subjects with accelerated depolarization and shortened QRS.
MATERIAL AND METHODS
This study was performed between January 1, 2011 and April 1, 2012 at a tertiary health center. Patients who were admitted to the cardiology clinic with a QRS interval of ≤80 ms on ECG, and who underwent K+, lipid profile, thyroid function, and echocardiography (ECHO) testing the same day, were included in the study. For each patient, 24‐hour ECG Holter data within the first 5 days were prospectively collected. Female and male subjects older than 18 years of age and with a QRS interval of ≤80 ms on ECG were included in the study. The exclusion criteria were: QRS interval of >80 ms; temporary or permanent heart pacemaker; use of medications that may affect the QT interval (antiarrhythmics, antipsychotics, antidepressants, antibiotics, and similar drugs); clinically significant hypothyroidism, hyperthyroidism or hypopotassemia; epilepsy‐like seizures that may affect 24‐hour ECG Holter registry; malignant disease; pregnancy; and autonomous neuropathy. Since a previous study7 concluded that menstrual periods have an effect on the QT interval, women having their menstrual periods were excluded. Age, gender, hypertension (HT), diabetes mellitus (DM), coronary artery disease (CAD), smoking, medications, and gynecological history were recorded. Weights and heights were measured and body mass indices (BMIs) were calculated. This study was approved by the Trakya University Medical Faculty Ethical Board (prot Vr. 2011/107) and all patients signed informed consent forms.
Electrocardiographic Parameters
ECGs were performed with the Nihon Kohden Cardiofax GEM ECG‐9020K (Tokyo, Japan). Patients whose QRS intervals were calculated automatically by ECG as ≤80 ms were included in the study. Heart rate was the time between two R waves. QT interval was the time between the Q wave start and the T wave end. The JT interval was the time between the J wave start and the T wave end. The JTp interval was the interval between the J wave start and the T wave tip. TpTe interval was the time between the T wave tip and the T wave end (Fig. 1). Corrected QT (QTc = QT/√RR), JT (JTc = JT/√RR), JTp (JTpc = JTp/√RR), and TpTe (TpTec = TpTe/√RR) were calculated by correcting the QT, JT, JTp, and TpTe intervals (according to RR intervals, using Bazett's formula). For each patient, QT, JT, JTp, and TpTe levels were measured in milliseconds. These values were converted to sec and the sec square root of the RR interval was divided to this value. The obtained value was converted to milliseconds, and the QTc, corrected JT (JTc), corrected JTp (JTpc), and corrected TpTe (TpTec) were obtained.
Figure 1.
The points and intervals of electrocardiographic parameters.
Laboratory Data
Blood analysis was done using the Siemens Advia 1800 autoanalyser (Siemens Healthcare Diagnostics, Tarrytown, NY, USA). Potassium (K), triiodothyronine (T3), thyroxine (T4), thyroid‐stimulating hormone (TSH), total cholesterol, low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), and triglyceride (TG) levels of the patients were evaluated. Patients with thyroid function disorders were excluded.
Heart Rate Variability (HRV) Parameters
Each patient underwent 24‐hour Holter ECG follow‐up to evaluate HRV, using the DMS 300–3A Holter Recorder (Los Angeles, CA, USA). For analysis of HRV, the Holter records of all cases were evaluated manually to exclude artifacts, and were then automatically calculated using DMS Serials Holter Software Premier 11. For the time‐based HRV parameters, SDANN (standard deviation of averages of NN intervals calculated over 5‐minute periods of the entire recording), rMSSD (square root of mean squared differences of successive normal‐to‐normal intervals), and pNN50 (proportion derived from dividing NN50 by the total number of all NN intervals) were evaluated. Parameters for HRV were evaluated according to recommendations of European Society of Cardiology the North American Society of Pacing Electrophysiology.17
Statistical Analysis
Statistical analysis was done using the SPSS 19.0 statistics program. Compliance of measurable data with normal distribution was checked with a single‐sample Kolmogorov‐Smirnov test. For the cases with normal distribution, t‐test for independent groups for intergroup comparisons was done. For the cases without normal distribution, the Mann‐Whitney U test was performed. Additionally, two‐way variant analysis was done. For qualitative data, Pearson chi‐square and Fisher precise chi‐square analyses were used. For descriptive statistics, median (minimum‐maximum) values and arithmetic mean ± standard deviations were presented. For all statistics, the significance limit was P < 0.05.
RESULTS
The mean QRS interval of 100 patients (55% female) included in the study was 75.24 ± 3.92 ms (74.44 ± 4.10 ms for females and 76.22 ± 3.49 ms for males). Demographic, clinical, and laboratory data of the patients are presented in Table 1.
Table 1.
Comparison of Baseline Characteristics between Female and Male Groups
| Variables | Female (n:55) | Male (n:45) | P |
|---|---|---|---|
| Median age years (Min‐Max) | 57 (23–79) | 60 (24–84) | 0.180a |
| BMI kg/m2± SD | 27.80 ± 3.71 | 27.19 ± 2.90 | 0.359b |
| Diabetes mellitus n (%) | 9 (9) | 6 (6) | 0.673c |
| Hypertension n (%) | 21 (21) | 12 (12) | 0.223c |
| CAD n (%) | 2 (2) | 3 (3) | 0.489c |
| Smoking n (%) | 3 (3) | 6 (6) | 0.292d | |
| Family history of SCD n (%) | 0 (0) | 1 (1) | 0.450d |
| ARB/ACE‐I n (%) | 19 (19) | 37 (37) | 0.073d |
| CCB n (%) | 6 (6) | 2 (2) | 0.289d |
| Antiaggregant n (%) | 4 (4) | 5 (5) | 0.728d |
| Anticoagulant n (%) | 2 (2) | 2 (2) | 1.000d |
| OAT n (%) | 7 (7) | 6 (6) | 0.929c |
| Insülin n (%) | 4 (4) | 0 (0) | 0.125d |
| Statin n (%) | 5 (5) | 2 (2) | 0.453d |
| Median K+ mg/dL (min‐max) | 4.80 (3.70—5.60) | 4.70 (3.80–5.70) | 0.550a |
| Median TG mg/dL (min‐max) | 141 (56–890) | 161 (52–666) | 0.291a |
| Median TC mg/dL (min‐max) | 191 (117–290) | 171 (87–332) | 0.032a |
| Median LDL mg/dL (min‐max) | 128 (33–357) | 122 (43–357) | 0.292a |
| Median HDL mg/dL (min‐max) | 53 (26–101) | 78 (24–68) | <0.001a |
Mann‐Whitney U test;
Independent t‐test;
Pearson's chi‐square;
Fisher's exact test; Continuous data are expressed as mean ± SD and median (minimum‐maximum). Categorical data are expressed as n (%). Statistical significance level is P < 0.05.
BMI = body mass index; SD = standard deviation; CAD = coronary artery disease; SCD = sudden cardiac death; ACE‐I = angiotensin converting enzyme inhibitors; ARB = angiotensin receptor blocker; CCB = calcium channel blockers; K = potassium; min = minimum; max = maximum; OAD = oral antidiabetic treatment; HDL = high density lipoprotein; LDL = low density lipoprotein; FPG = fasting plasma glucose; TG = triglycerides.
The patients included in the study were grouped by gender. The median age was 57 years for female patients and 58 years for male patients, with no significant difference between the groups (P = 0.178). BMI was 27.80 ± 3.70 kg/m2 for the females and 27.19 ± 2.88 kg/m2 for the males, with no statistically significant difference between the groups (P = 0.359; Table 1).
The two groups were compared for DM, HT, CAD, smoking, and family history. No significant differences were observed between the groups for DM, HT, CAD, and smoking (P = 0.673, P = 0.273, P = 0.292, and P = 0.292, respectively), and family history of sudden cardiac death was also not significantly different between the groups (P = 0.450; Table 1).
When the groups were assessed for medication history, they did not differ for angiotensin receptor blockers/angiotensin‐converting enzyme blockers, dihydropyridine calcium channel blockers, antiaggregants and anticoagulant usage (P = 0.073, P = 0.289, P = 0.728, and P = 1.000, respectively). No statistically significant difference was present between the groups for oral antidiabetic drugs, insulin and statin usage (P = 0.929, P = 0.125, and P = 0.453, respectively; Table 1).
Total cholesterol, LDL, HDL, and TG levels of the patients were assessed and no significant difference was observed between the groups for median TG, total cholesterol, and LDL values (P = 0.291, P = 0.032, and P = 0.292, respectively). The median HDL level was statistically significantly higher in male than in female patients (P < 0.001; Table 1).
As a result of the analysis, the median value for QT interval was 390 ms in female patients and 390 ms in male patients, with no statistically significant difference observed between the groups (P = 0.431). The mean QTc interval was 423.53 ± 33.37 ms for women and 417.00 ± 28.80 ms for men, with no statistically significant difference between the groups (P = 0.137; Table 2).
Table 2.
Comparison of Electrocardiographic Parameters between Female and Male Groups
| Variables | Female (n:55) | Male (n:45) | P |
|---|---|---|---|
| Median QT ms (min‐max) | 390 (315–472) | 390 (128–460) | 0.431a |
| QTc ms ± SD | 423.53 ± 33.37 | 417.00 ± 28.80 | 0.304b |
| Median JT ms (min‐max) | 315 (214–384) | 326 (262–419) | 0.330a |
| Median JTc ms (min‐max) | 342 (247–413) | 326 (262–419) | 0.137a |
| Median JTp ms (min‐max) | 226 (70–284) | 227 (76–289) | 0.163a |
| Median JTpc ms (min‐max) | 253 (148–307) | 237 (187–290) | 0.155a |
| Median TpTe ms (min‐max) | 75 (52–96) | 75 (50–107) | 0.658 a |
| Median TpTec ms (min‐max) | 83 (50–107) | 82 (53–109) | 0.903a |
Mann‐Whitney U test;
Independent t‐test; Continuous data are expressed as mean ± SD and median (minimum‐maximum). Statistical significance level is P < 0.05.
ms = millisecond; SD = standard deviation; min = minimum; max = maximum; QT interval is considered as time between Q wave start and T wave end; JT intervals is considered as time between J wave (the junction between the S wave and the ST segment) and T wave end; JTp interval is the interval between J wave (the junction between the S wave and the ST segment) and T wave tip; TpTe interval is time between T wave tip and T wave end; corrected QT (QTc= QT/√RR), JT (JTc= JT/√RR), JTp (JTpc= JTp/√RR) and TpTe (TpTec= TpTe/√RR) are calculated by correcting QT, JT, JTp, TpTe intervals (according to RR intervals, using Bazett's formula).
The median level for JTp interval was 226 ms for females and 227 ms for males, and the JTpc interval median was 253 ms for females and 237 ms for males. For JTp and JTpc interval median values, no statistically significant difference was observed between the groups (P = 0.163 and P = 0.155, respectively; Table 2).
In both the female and male groups, the median for TpTe interval was 75 ms, with no significant difference between the groups (P = 0.658). The median TpTec interval was 83 ms for females and 82 ms for males, with no statistically significant difference observed between the groups (P = 0.903; Table 2).
The parameters for HRV (SDNN, SDANN, rMSSD, and pNN50) were compared and there was no significant difference between the male and female groups (P = 0.693, P = 0.396, P = 0.530, and P = 0.920, respectively; Table 3).
Table 3.
Comparison of Heart Rate Variability (HRV) Parameters between Female and Male Groups
| Variables | Female (n:55) | Male (n:45) | P |
|---|---|---|---|
| Median SDANN ms (min‐max) | 99 (48–187) | 101 (34–184) | 0.693a |
| Median SDNN ms (min‐max) | 42 (22–97) | 31 (11–137) | 0.396a |
| Median rMSSD ms (min‐max) | 28 (7–94) | 31 (11–197) | 0.530 a |
| Median pNN50 ms (min‐max) | 4 (0–55) | 5 (0–49) | 0.920 a |
Mann‐Whitney U test; Continuous data are expressed as median (minimum‐maximum). Statistical significance level is P < 0.05.
min = minimum; max = maximum; SDANN = standard deviation of averages of NN intervals calculated over 5‐minute periods of entire recording; SDNN = the standard deviation of NN intervals; rMSSD = square root of mean squared differences of successive normal‐to‐normal intervals; pNN50 = proportion derived from dividing NN50 by total number of all NN intervals.
DISCUSSION
When the ECGs of female and male patients are investigated, differences are observed between genders. For example, the QT intervals of women are longer than those of men, which makes women more prone to the arrhythmic effects of medications that elongate the QTc interval, such as antipsychotics and antibiotics. Another ECG parameter that currently interests investigators due to possible influences on repolarization and arrhythmia is shortened QRS interval. In this study, we evaluated the differences between ECGs of female and male patients whose QRS intervals were below the normal percentile.
The indicator of ventricular depolarization is the QRS interval.12 On human ECG, QRS interval elongation is related to cardiac mortality and recurrent VT attacks.12 Similarly, shortening of the QRS interval may cause arrhythmia, syncope, and sudden cardiac death.13 Arrhythmia due to QRS interval shortening is not yet completely understood. Wolpert et al.14 observed that in patients with shortened QRS intervals, there were syncope attacks and ST, T alterations during physical effort. These J point changes and ST, T alterations observed during exercise, as well as ST, T changes observed with the ajmaline test, suggest that QRS shortening has an influence on repolarization.
The QRS interval is known to be shorter in females than in males.12 Although a shorter QRS complex with a lower voltage in females was attributed to small heart sizes in females, the difference was maintained when QRS duration was adjusted for BMI and heart mass.3 In our study, the QRS interval of females was 74.44 ms and of males was 76.22 ms, which complies with the data in the literature.
Another difference between female and male ECG is related to heart rate.1 In a large population study with 5116 subjects, the mean heart rate of women was found to be 3–5 beats/minute faster than in men.7 The reason for this difference can be attributed to variations in daily activities, the different habits of men and women, and exercise tolerance. Another important reason for this difference is considered to originate from variations in the sinus knot and autonomous nervous system activity. Sinus knot recovery time is shorter in women and although rare, sinus tachycardia is a more common syndrome in females.3 In our study, the heart rate of female patients was faster than that of male patients (the RR interval was 851.65 ms in women and 861.27 ms in men). However, no statistically significant difference was observed.
The sum of depolarization and repolarization is considered the QT interval, and alterations in QT interval duration are used frequently in daily practice as an indicator for arrhythmias. Since this interval is affected by the heart rate, QTc is used in daily practice. The QTc of women is longer than in men,1, 18 by nearly 10–20 ms, and the difference becomes more prominent during the menstrual period.7 This ECG difference between females and males makes women more prone to fatal arrhythmias, such as torsades de pointes and Brugada syndrome. Several mechanisms are responsible for the difference between genders. Among these, the major ones are differences in flows of Na, K, and Ca++ and variations in male and female sex hormones.14
In our study, we evaluated the QT and QTc levels of subjects from both genders who had shortened QRS intervals (in other words, fast depolarization). Also, we investigated the JT, JTp, and TpTe parameters, which are known as ECG findings of repolarization. We measured the mean QTc interval of women at 423.53 ms and of men at 410.00 ms. Women in our study had a nearly 6.5 ms longer QTc interval than did men. This was somewhat shorter than the 10–29 ms difference found in normal population studies and there was no statistically significant difference between the groups. Since no significant difference was observed between the groups, we did not do additional investigations, such as evaluation of menstruation or hormone‐level status.
Although QTc, one of the parameters of repolarization, is a common and conventional method for determining prearrhythmias, it cannot be used in cases in which the QRS interval exceeds 120 ms or in cases of branch blocks, since it may give false results. In such cases, since the QRS interval is not added to the measurement, the JT interval, a valuable indicator of repolarization that gives more reliable information, is preferred. Furthermore, many investigators suggest that the JT interval is better than QT at measuring specific repolarization duration.19 The JT interval alters depending on rate, so the JT interval corrected by rate (JTc) is used.20 In our study, we also first measured the JT interval and then calculated the JTc interval according to heart rate. We showed that in subjects with shortened QRS, JTc intervals were not significantly different between the genders. In previous studies, the JTc in women was longer than in men.20, 21 In women, the JTc interval does not alter before and after menopause.22 The reason for the longer JTc in women depends on slower repolarization in female subjects. This is a disadvantage since it makes women more prone to arrhythmias due to medications that elongate repolarization, but meanwhile it brings an advantage by protecting them from tachyarrhythmias.21
The TpTe value on human ECG shows transmural (global) dispersion of repolarization, and its elongation is a predictor of malignant arrhythmias.22, 23, 24 Especially in long‐QT syndrome, short‐QT syndrome, hypertrophic cardiomyopathy, postacute myocardial infarction and Brugada syndrome, the elongation of the TpTe value increases the risk of malignant arrhythmias.18, 23 TpTe is affected by age, gender, QT interval, heart rate, and previous myocardial infarction.24 Erikssen et al.,24 in a study on 1484 acute myocardial infarction patients, found that TpTe elongation in the first year was related to high mortality and that TpTe could be used as a prognostic criterion in myocardial infarction follow‐up. In our study, groups were matched according to age distribution, which affects TpTe values. In addition, both women and men with CAD were evaluated statistically within groups. Studies that evaluate TpTe differences between the genders have presented conflicting results. A study25 on 1081 healthy subjects showed no differences between male and female patients. In one study, TpTe durations in women were longer than in men21; however, in another study, the TpTe duration in men was longer.20 In our study, both TpTe and rate‐corrected TpTec values were longer in men but the difference was not statistically significant.
In our investigation on QT, JT, JTp, and TpTe and their rate‐corrected ECG parameters in subjects with shortened QRS intervals, we observed that the repolarization differences between the two genders disappeared when depolarization accelerated. This indirectly showed that when depolarization accelerates, the two genders have similar arrhythmia potentials. This supports the idea that depolarization has an effect on repolarization, and this should be further investigated.
One of the factors that influences repolarization, and essentially the QT interval, is the autonomous nervous system activity of the heart. HRV is a parameter that reflects autonomous nervous system activity of the heart. HRV and efferent cardiac sympathetic‐parasympathetic modulation can be measured at sinus node level. SDNN is considered an indicator of global HRV and it represents total neurocardiac input. A decrease in SDNN reflects an abnormal interaction between the sympathetic and parasympathetic systems. In our study, no significant difference was observed in global HRV (SDNN) between genders. In addition, no significant difference was observed for RMSSD and pNN50, which are indicators of parasympathetic tonus increase.
In subjects with accelerated depolarization, when gender differences were matched for age, BMI, drugs, autonomous activity of the heart, and concomitant diseases, all of which are factors known to affect repolarization, no significant difference was observed between the genders for the ECG parameters that influence repolarization.
The most important limitation of our study was being unable to compare these groups to subjects with normal QRS intervals. Therefore, it is not totally clear whether the argument, which is that repolarization times of women are longer and women are more prone to arrhythmia with acceleration of depolarization, is invalidated due to our selected population.
In conclusion, previous studies suggested that QRS intervals in women were shorter than in men, while parameters that affect repolarization were longer in women than in men and therefore women were more prone to arrhythmias, such as Brugada syndrome and torsades de pointes. We included subjects from both genders with accelerated depolarization, and observed no significant differences between the genders in heart rate and QT, JT, JTp, and TpTe, which are parameters that affect repolarization and their shortening or elongation are indicators of arrhythmia. Therefore, we showed that the conventional knowledge that repolarization parameters are normally prolonged in women was not valid when depolarization accelerated. It can be hypothesized that when depolarization accelerates, both genders may have similar arrhythmia potentials; however, it is obvious that more studies are required on this subject.
CONCLUSION
In our study, when depolarization accelerated, no significant differences were observed between the genders for heart rate and QT, JT, JTp, and TpTe, which are parameters that affect repolarization and are arrhythmia precursors (either by shortening or elongation). We showed that the conventional knowledge that repolarization parameters are normally prolonged in women is not valid when depolarization accelerates.
LIMITATIONS
We compared ECG parameters between the genders in patients with short QRS durations. The wide QRS group was not included in the study, and the mean age of the patients was partially elderly. We think that a study comparing the genders using young, healthy groups, and according to short and wide QRS duration, could give more valuable data.
A cross‐sectional, single‐center study
No authors have any financial or other conflict of interest in regard to the present work.
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