Study Population
The study was approved by the Ethics Committee of Harbin Medical University. From October 2020 to January 2021, we prospective recruited 109 consecutively women (47 GDM and 62 healthy controls) with a singleton pregnancy who underwent comprehensive transthoracic echocardiography (TTE) assessment. All the patients have signed the informed consent before echocardiography.
The International Association of Diabetes and Pregnancy Study Groups (IADPSG) defined GDM as any degree of low glucose tolerance first diagnosed during pregnancy(9). The diagnose criteria includes fasting plasma glucose (FPG) ≥ 5.1 mmol/l (92 mg/dL), 1-hour plasma glucose ≥ 10.0 mmol/l (180 mg/dL), and 2-hour plasma glucose ≥ 8.5 mmol/l (153 mg/dL). In this study, GDM patients should have normal LVEF (≥ 54%), no history of relevant cardiovascular diseases or other metabolic diseases.
Clinical Information
The age, body mass index (BMI), blood pressure (BP), heart rate (HR), gestational weeks, and blood glucose level of the study population were queried at their enrollment. BP was measured three times and averaged after at least ten minutes of rest. BP was measured in a silent room 5 to 10 minutesbefore echocardiography with an aneroid sphygmomanometer twice in a seated position,with the right arm at the level of the heart, after 5 minutes of rest.
Ultrasound Protocol
Conventional Echocardiography
Echocardiography was performed by two senior sonographers (Ziyao Li and Wei Li) on GE Vivid E9 and E95 (GE Medical Systems, Milwaukee, WI, USA) with an M5S probe (2.5~4.0 MHz). All data were averaged from three consecutive cardiac cycles. Patients with poor image quality were excluded before recruitment. Images were recorded and studied according to the recommendations of the American Society of Echocardiography(10).
In the parasternal long-axis view, LV end-diastolic diameter (LVEDd), interventricular septum (IVS) thickness, posterior wall thickness (PWT), and LV end-systolic diameter (LVESd) were measured by M-mode echocardiography. LV mass (LVM) was calculated by using the Devereux formula(11): LVM = 0.8×{1.04×[(LVEDd+IVS+PWT)3–LVEDd3]}+0.6g. Relative wall thickness (RWT) was calculated using the formula RWT = 2×(PWT/LVEDd). LVEF and LA volume (LAV) were measured using the biplane Simpson method. LVM, LAV, and stroke volume (SV) were indexed for body surface area (BSA) to get LV mass index (LVMI), LA volume index (LAVI), and stroke volume index (SVI), respectively. In the apical four-chamber view, pulse Doppler and tissue Doppler were performed to measure early diastolic mitral inflow velocity (E), and early diastolic annular velocity (e′). And mean e′ was the averaged velocity of the septal and lateral mitral annulus (12).
Two-Dimensional Speckle Tracking Echocardiography
LV global longitudinal strain (LV-GLS) and LA phasic strain were analyzed offline using EchoPAC software (version 203, GE Healthcare, Horten, Norway). Allow the patient to hold their breath to get ultimate images of three consecutive cardiac cycles at a frame rate ≥ 60 frames per second. The 2D-STE measurements were performed by two physicians in a double-blinded manner for intraclass correlation coefficients (ICC) testing.
To measure LV-GLS, 2D-STE was performed by tracing the LV endocardial boundary in the apical three-chamber, four-chamber, and two-chamber views(13). We use the apical three-chamber view to identify the aortic valve closure and then mark the mitral annulus points and apex in each apical view. The software can track the endocardial border and automatically generate six segments of longitudinal strain from each apical view separately, and then LV-GLS is averaged from all those 18 segments.
The biplane (4-chamber and 2-chamber) views were accepted for LA strain evaluation, according to the consensus from the European Association of Cardiovascular Imaging (EACVI)/American Society of Echocardiography (ASE)/Industry Task Force (14). When tracing the LA endocardial border, the atrial appendage and pulmonary veins were eliminated. Then six segmental LA longitudinal strain curves were automatically presented by the software. An R-R gating protocol was applied to get the LA phasic strain, which including reservoir strain (LA-Sr), conduit strain (LA-Scd), and contractile strain (LA-Sct) (15).
Statistical Analysis
Continuous variables were expressed as mean ± standard deviation (SD) and compared by the Student t-test. We firstly performed the univariate logistic regression to assess the crude correlations between clinical/echocardiographic characteristics and GDM. Variables with a p-value less than 0.05 in univariate regression entered into the multivariate models, and a forward “likelihood ratio” selection approach was applied to identify parameters that were independently associated with GDM. The current study conducted two multivariate models which separately included either LV-GLS or LA phasic strain, to better identify their associations with GDM. ICC was examined by the Bland-Altman plot. We used SPSS version 25.0 (IBM Corporation, Armonk, NY) statistical software. A p-value less than 0.05 was considered statistically significant.