The study included 33 patients with surgical early menopause and 29 control subjects matched for clinical and demographic characteristics. We excluded 4 patients in the surgical early menopause group due to the presence of AF with valvular disease. All participants signed a consent form following the receipt of study information. Patient age, sex, body weight, height, cardiovascular risk factors, current medications, and history of other systemic diseases were recorded in the patient form. The duration and cause of surgical menopause were also recorded. The median time since surgical operation was 2.1 years (range, 1-5 years). Individuals that had had surgery 1-5 years prior to the study were included.

The exclusion criteria included surgical menopause for less than one year, being on estrogen replacement therapy, improper measurement of blood pressure, history of coronary artery disease, heart failure with preserved or reduced ejection fraction (EF), cardiomyopathy, severe valvular heart disease, poor echocardiographic image quality, and presence of AF or history of paroxysmal AF attack. The protocol was approved by the institutional review board of the Faculty of Medicine, Ondokuz Mayis University and adhered to the Declaration of Helsinki.

The echocardiography was performed on each patient in the left lateral decubitus position through the parasternal and apical windows. M-mode, two-dimensional, pulsed and color flow Doppler echocardiographic imaging of all patients was performed by the same operator using a Vivid 7 device (3.5-MHz phased array transducer; GE Medical System, Horten, Norway). Posterior wall thickness, interventricular septum thickness, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and LA anteroposterior diameter were measured using the M-mode technique. The modified Simpson technique was used to measure the left ventricular EF.

Transmitral flow speeds (E and A) were assessed by pulsed wave Doppler in the apical four chamber windows. Pulsed wave tissue Doppler imaging was performed using a low-wall filter setting, a little sample size, and an ideal gain. The Doppler pulse was arranged parallel to the direction of flow. For the tissue Doppler view of the annular movement, the sample volumes were placed at the septal, lateral mitral, and lateral tricuspid annuli in the apical 4-chamber window. Peak early (e′) and late (a′) diastolic velocities and systolic velocities (s′) were calculated. At least three values for each measurement were averaged, and the data are presented as means of three to six consecutive heartbeats.

The tissue Doppler echocardiography was performed with transducer frequencies of 3.5 to 4.0 MHz by regulating the spectral pulsed Doppler signal filters until a Nyquist limit of 15 to 20 cm/s was achieved and by using the minimal ideal gain. The monitor scan velocity was adjusted to 100 mm/s. In the apical four chamber window, the pulsed Doppler sample volume was positioned at the septal annulus, the lateral mitral annulus, and the lateral tricuspid annulus. Atrial electromechanical connection (PA′), the time period from the beginning of the P wave on the superficial electrocardiogram to the beginning of the late diastolic wave (A′), was assessed for the lateral mitral annulus (PA′ lateral), septal mitral annulus (PA′ septum), and lateral tricuspid annulus (PA′ tricuspid) (Figure 1). The PA′ values from three sequential heart pulses were averaged.

The difference between the PA′ lateral and the PA′ tricuspid (PA′ lateral–PA′ tricuspid) represents the inter-atrial EMD. The difference between the PA′ septum and the PA′ tricuspid (PA′ septum–PA′ tricuspid) represents the right atrial EMD. Finally, the difference between the PA′ lateral and PA′ septum (PA′ lateral–PA′ septum) represents the LA EMD.4)5)8)9)10)11)12) Intra-observer coefficients of variation for intra- and inter-atrial EMD were 2.9% and 3.8%, respectively.

An electrocardiogram was recorded during echocardiography. Measurements were taken from the three cardiac cycles by the same operator. Following the collection of data, LA volume measurements were performed by two operators simultaneously and the mean values were averaged. Conventional measurements were conducted using transthoracic echocardiography and LA size and functions were assessed. All atrial volumes were calculated using a uniplanar area–length (apical four-chamber) formula. LA borders were traced using planimetry. The borders included the walls of the LA and excluded pulmonary veins and the LA appendage. Left atrial volume index (LAVI) was calculated by dividing LA volume by body surface area of patients. Maximal LA volume (LAV_max), minimal LA volume (LAV_min), and atrial precontraction LA volume (LAV_preA) were also calculated (Figure 2).4)5)8)9)10)11)12)

The following formulas were used for calculating LA functions:

LA reservoir function is referred to as LA ejection fraction (LA_EF), LA conduit function is referred to as LA passive emptying fraction, and LA pumping function is referred to as LA active emptying fraction.8)9)10)11)12)

All data were evaluated using the SPSS (Statistical Package for Social Sciences) software for Windows 22.0 (SPSS Inc., Armonk, NY, USA). Student's t-tests were performed for independent samples based on previous clinical studies; the power of the test was found to be 80.52% when a total of at least 56 subjects were included in the study. Descriptive statistics are described by the mean ± standard deviation (min-max), the frequency distribution, and the percentage. Pearson's chi-square tests and Fisher's exact tests were used to assess categorical factors. Normally distributed parameters were analyzed using visual (histogram and probability plots) and analytical techniques (Shapiro-Wilk Test). For variables without a normal distribution, Mann-Whitney U-tests were used to compare two independent groups, and Student's t-tests were used for normally distributed parameters. Values of p < 0.05 were considered significant.

The primary restriction of this study was its small sample size. Additionally, AF was evaluated and patients were excluded according to each patient's history. However, none of the patients in this study underwent 24-hour Holter monitoring to further exclude patients with potential AF. Similarly, diabetes mellitus was excluded by patient history, symptoms, and clinical findings, not HgA1c level. Accurate measurement of the diameter, area, and volume in this study were dependent on echocardiographic imaging angles and geometric presumptions, and these parameters are also load-dependent. Pulsed-wave tissue Doppler imaging is restricted by the angle dependency of the technique. Moreover, fine atrial walls are difficult to measure. To reduce these deficits, three sequential cardiac periods were assessed and averaged for each measurement. In addition to volumetric measurements, two-dimensional tension, measured by Doppler-based tension or speckle tracking, is often used to assess LA functions. However, no tension measurements were performed in our study. Finally, we could not assess associations between time since surgery and the echocardiography parameters.

We report a statistically significant impairment in atrial electrical delay and electromechanical functions in surgical early menopause patients. Future clinical trials with larger sample sizes that include patients with other forms of early menopause are necessary to confirm the role of surgical menopause in subclinical cardiac alterations and the onset of AF.