Hypertensive disorders in pregnancy (HDP) are associated with adverse pregnancy outcomes, both for the mother and the newborn. Also, HDP is a risk factor for ischemic heart disease, hypertension, and stroke later in life [1].

During pregnancy, the mother’s heart adapts to the increased volume, usually changing its geometry toward eccentric hypertrophy or concentric remodeling leading to changes in its function [2]. As echocardiographic parameters for assessing geometry and systolic function are volume-dependent they may not entirely reflect left ventricular geometry in pregnant women. The impacts of these changes are more evident in pregnancies affected by gestational hypertension and preeclampsia (PE). Consequently, in addition to physiological changes, these alterations in maternal cardiac geometry in women with HDP are linked to more pronounced adverse remodeling. This remodeling can further influence cardiac function and contribute to the overall risk of adverse pregnancy outcomes, highlighting the importance of thorough cardiac assessment during pregnancy [3]. Three-dimensional (3D) echocardiography has proved to be highly precise for evaluating cardiac chamber geometry [4]. During pregnancy, slight systolic function decline is observed, as indicated by both ejection fraction (EF) and left ventricular global longitudinal strain (LV GLS) [5]. Similar changes were also evident in the 3D assessment of maternal cardiac morphology and left ventricular myocardial deformation, which showed a better correlation with magnetic resonance imaging (MRI) than two-dimensional (2D) assessment [6]. On the other hand, studies have shown that 3D LV GLS is a better predictor of adverse events compared to EF and 2D LV GLS in patients who have experienced a myocardial infarction [7], asymptomatic diabetic patients compared to control [8], as well as in cardio-oncology [9].

There is limited data assessing a mother’s 3D left ventricular systolic function during pregnancy. While 3D echocardiography (3DE) has been used in other clinical scenarios, its application in HDP is still underexplored. 3DE has shown significant advantages in accuracy, reproducibility, and versatility, often serving as a stronger prognostic predictor than two-dimensional echocardiography (2DE). The assessment of chamber volumes using 3DE has been more precise and accurate. Parameters such as ejection fraction and left ventricular hypertrophy are recognized as significant predictors of cardiovascular outcomes. However, despite their importance in cardiovascular pathology, the use of 3DE to assess cardiac geometry during pregnancy has not been extensively utilized or studied.

The aim was to assess the impact of the 3D left ventricle systolic function in women with HDP on pregnancy outcomes.

This prospective cohort study enrolled primiparous women with singleton pregnancies who had no previous comorbidities or risk factors. Pregnant women with any pregnancy-related comorbidities, such as gestational diabetes or thyroid disorders, were excluded from the study.

Conducted from December 2021 to April 2024 at a tertiary care center, the study involved a comprehensive assessment of each participant’s medical history, physical examination, laboratory tests, transthoracic echocardiogram, and 24-hour ambulatory blood pressure monitoring (ABPM). This was done both at baseline (screening) between the 23rd and 41st gestational weeks, with a median of 34.0 (ranging from 31.0 to 36.0 weeks) for the entire cohort, and again six weeks after delivery. The goal was to exclude any cases of chronic (pre-existing) hypertension. Six weeks postpartum, all participants were normotensive; those with still-elevated blood pressure values were excluded from the study.

A total of 321 pregnant women were screened. After excluding 18 subjects due to insufficient image quality for analysis, 22 for incorrectly recorded blood pressure by ABPM, and 43 who were lost to follow-up (as they did not attend check-ups), 174 women with HDP and 64 normotensive healthy pregnant controls were analyzed.

In this study, “HDP” refers to gestational hypertension and PE, defined according to the current guidelines of the European Society of Cardiology [1]. The research received approval from the Institution’s Ethics Committee (number 1189-1/5), and all participants provided informed consent to take part in the study.

Our research revealed that 3D echocardiographic assessment of the mother’s systolic function during pregnancy is a better predictor of pregnancy outcomes compared to 2DE We have shown that 3D evaluation of EF is a good predictor of preterm delivery, while 3D LV GAS is an excellent predictor of IUGR, but also correlates well with the birth weight of the newborn. To the best of our knowledge, this is the first study to assess the influence of the maternal systolic function of the LV assessed by 3DE on pregnancy outcomes.

Our findings regarding the impaired systolic and diastolic function of the left ventricle in hypertensive pregnant women, along with the increased mass of the LV compared to normotensive individuals, align with numerous previous studies [16]. Significantly lower birth weight, higher prevalence of IUGR and preterm delivery in HDP compared to normotensive pregnant women is also previously known [17]. Our research supports these findings. While changes in diastolic function and left ventricle geometry during hypertensive pregnancy have been recognized in previous decades [18, 19, 20, 21, 22, 23], data regarding systolic function remain limited and somewhat contentious [23, 24]. As mentioned in the introduction, changes in the geometry of the LV during pregnancy, necessitate a more accurate assessment of its function and morphology of the LV which can be achieved through 3DE. Cong et al. [6] demonstrated that both 2DE and 3DE parameters representing the function and morphology of the LV in healthy pregnant women change throughout pregnancy. They found that systolic function parameters are at their lowest during the third trimester, while the LV mass notably increases. After delivery, there is a significant improvement in systolic function parameters and LV mass decreases [6]. Our results coincide with the mentioned research for normotensive pregnant women, but also for pregnant women with HDP, where these changes were even more pronounced. Women with HDP exhibited statistically significant impairments in both 2D and 3D parameters of systolic and diastolic function of the LV, with decreases in absolute values of 2D LV GLS and 3D strain in all directions, as well as significantly higher values ​​of the LV mass index compared to normotensive pregnant women. After delivery, all the mentioned parameters showed improvement across the entire cohort, as well as distinctly in both hypertensive disorders of pregnancy groups and controls. Interestingly women who were hypertensive during pregnancy, despite being normotensive after delivery, still had statistically significant higher LV mass values compared to those who were normotensive during pregnancy.

In terms of LV systolic function, the difference in EF values was no longer significant, when assessed using both 2D and 3D methods. This change can likely be attributed to the normalization of BP during the postpartum period. Unlike LV EF, both the 2D and 3D strain values remained statistically significantly worse in women with HDP both at baseline and six weeks after delivery. This finding may imply that the assessment of the systolic function of women with HDP using the speckle tracking method may provide a more accurate indication of the subendocardial damage in the LV compared to the ejection fraction.

Company Calabuig et al. [25] analyzed 3D echocardiographic parameters in women with PE and showed that women with PE had lower LV diastolic function and increased LV mass index compared with controls. Notably, there was a postpartum improvement in these indices, attributed to an improvement of their risk factor profiles [25]. Pregnant women with underlying risk factors (e.g., smoking) and all other comorbidities were excluded from our research. The only exception was obesity, which was not used as an exclusion criterion. This decision was made because pregnant women were primarily screened during the third trimester, and factors such as swelling and increased volume load made BMI a less reliable exclusion metric. After delivery, we obtained the anamnestic information that some participants had actually gained more weight compared to their pre-pregnancy state, which indicates that the observed improvements in the aforementioned parameters cannot be solely attributed to the reduction of obesity as a risk factor. Although there are limited studies on the use of 3DE in pregnant women, particularly those with HDP, existing research in the non-pregnant population has demonstrated that 3D strain analysis (3D STE) offers greater accuracy and objectivity than 2D STE when assessing cardiac systolic dysfunction or dysregulation, without relying on geometric assumptions [26, 27]. Also, 3DE provides higher accuracy and reproducibility as compared to cardiac magnetic resonance both in pregnant women and in the non-pregnant population [6, 28].

The GAS, a parameter uniquely obtainable through 3D STE analysis, combines the evaluation of longitudinal and circumferential deformations. This makes it particularly sensitive to detecting anomalies without geometric assumptions, especially in the subendocardial layer, which is often one of the first areas affected in various cardiac conditions [29].

Our study showed that 3D echocardiographic assessment of the mother’s systolic function during HDP is a better predictor of pregnancy outcomes than 2D. We have shown that the strongest predictor for the occurrence of intrauterine growth retardation is a decrease in the absolute value of the GAS. Specifically, a reduction of 1 unit in GAS increases the possibility of IUGR by 77%. The cut of value of LV GAS is –26.75. Furthermore lower GAS correlates with lower birth weight. Taking into account the changes in the geometry of the LV during pregnancy, especially in hypertensive pregnant women, we may conclude that such results are expected when taking into account the volume and the geometrically independent assessment of the systolic function by the GAS.

Since similar analyzes have not been conducted in pregnant women before, we can compare them with the research demonstrating that 3D LV GLS and 3D LV GCS provide better predictive capability regarding ejection fraction and adverse events in patients with a history of myocardial infarction [30]. Additionally, LV GAS has been independently associated with an increased risk of death or heart failure following acute myocardial infarction [30]. Also, a recently published meta-analysis showed that 3D myocardial strain was reduced in all directions in asymptomatic diabetic patients compared to controls, as well as hemoglobin A1c was associated with worse 3D LV GLS and 3D LV GSC [8]. Besides that, the early change to abnormal values of 3D LV GAS was associated with a subsequent decrease in LV EF, representing a promising technique to predict chemotherapy-induced cardiomyopathy in patients with breast cancer [9].

Absolute LV GAS values ​​in our study were statistically significantly lower in hypertensive pregnant women compared to normotensive ones and remained significantly lower even after delivery, although previously hypertensive participants became normotensive. The relationship of LV GAS with BP values has been shown in a previous study [31], as well as 3D LV GLS, GCS and GRS.

Therefore we can assume that GAS, as a comprehensive parameter of myocardial systolic deformation in all three dimensions, is the most sensitive parameter for detecting occult myocardial dysfunction in HDP, as it was shown for the association with exercise time and predictive value on E/e’ for exercise capacity in participants undergoing a treadmill exercise test [32] and with common LV systolic function parameters [33].

Our study also revealed another advantage of 3D assessment of LV systolic function in pregnant women by the significant association of 3D LV EF with preterm delivery, with a cut-off value of 62.05%. The decrease of 1% in 3D LV EF increases the risk of preterm delivery by 22%. We have previously shown that 2D deterioration of LV systolic function is associated with preterm delivery [34], while a recent study showed that 3D LV EF has superior predictive ability over 2D LV EF [35]. The cut-off value of 62.05 for 3D LV EF offers valuable insights for predicting preterm delivery. However, there is a need for further clarification on its clinical application and a comparison with existing methods and established markers, such as cervical length measurement and maternal clinical factors (e.g., history of preterm birth, infections) [36]. When comparing this cut-off to other clinical methods for predicting preterm delivery, it is essential for future studies to focus on refining these predictions by considering various clinical contexts and potential combinations with other established predictors.

While traditional echocardiographic methods have been utilized to assess cardiac function in pregnancy, there is a notable scarcity of studies focusing on the specific contributions of 3DE in understanding cardiac changes in women with HDP. Our study aims to fill this knowledge gap by providing a comprehensive evaluation of 3DE parameters and their clinical relevance in this population. The application of 3DE allows for more precise and reproducible measurements of LV function without relying on geometric assumptions inherent in 2DE methods. This advancement is particularly crucial in the context of HDP, where alterations in cardiac structure and function can be subtle yet clinically significant. By utilizing 3DE , we can detect early changes that may not be apparent with conventional techniques. Our findings not only support previous research indicating cardiac dysfunction in HDP but also extend this knowledge by highlighting the utility of 3DE as a valuable tool for early detection and monitoring. The identification of specific cut-off values, such as the one we established for 3D LV EF, could be the way to integrate this into routine clinical practice.

In addition to HDP as a risk factor for cardiovascular morbidity later in life [1], a recently published study showed that preterm delivery, low birth weight of the newborn, and intrauterine growth retardation are also risk factors for future adverse maternal cardiovascular events [37]. We have shown that deterioration of the systolic function of the mother’s left ventricle during HDP obtained by 3DE assessment, is significantly related to the mentioned pregnancy outcomes. Therefore, 3D assessment of LV function during HDP, especially LV GAS, as a comprehensive parameter of myocardial systolic deformation in all three dimensions, and because of that the most sensitive parameter for detecting subclinical myocardial dysfunction in HDP, could be a good screening tool for detecting women at increased risk of developing cardiovascular complications. In that context, more frequent checks of those women are very important, as well as advising them to change their lifestyle habits.

To the best of our knowledge, this is the first study to investigate the impact of 3DE assessment of LV systolic function in pregnant women on pregnancy outcomes.

In our view, studying 3D LV GAS is particularly significant because it combines both 3D LV GLS and 3D LV GCS. We believe this method provides a more accurate assessment of LV systolic function in pregnant women, especially those with hypertension, due to changes in LV geometry.

It is a single-center study. Future multicenter research assessing the impact of 3D LV GAS on maternal cardiovascular events is needed to confirm our results. Also, we believe that future studies are needed to assess these parameters in earlier pregnancy (e.g., in the first trimester) in order to confirm the use of these echocardiographic measures as early markers for obstetric complications, or to potentially guide clinical decisions during the prognosis of pregnancy complications, both in terms of IUGR and preterm delivery.

3DE assessment of the mother’s systolic function during pregnancy is a good predictor of pregnancy outcomes. The strongest predictor of preterm delivery is 3D LV EF, while the LV GAS is the strongest predictor of the intrauterine growth retardation, but also correlates well with the birth weight.

All data reported in this paper will be shared by the lead contact upon request.

Conceptualization, AI, MP; methodology, MBje; validation, DJI; formal analysis, ST, MS and DD; investigation, TM, SS, MS; resources, writing—original draft preparation, AI, AM; writing—review and editing, AM; interpretation, MBač, ASM, AM; supervision, MBač, ASM. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The research protocol was approved by the Ethics Committee of the Institute of Cardiovascular Diseases of Vojvodina (Ethic Approval Number: 1189-1/5), and all of the participants provided signed informed consent. The study was carried out in accordance with the guidelines of the Declaration of Helsinki.

This study was supported by Provincial Secretariat for Health of the Autonomous Province of Vojvodina (Serbia) – the “Early detection of changes in maternal cardiac function and pattern of blood pressure during ABPM in hypertensive pregnancies” project. The preparation of this paper was supported by the Provincial Secretariat for Higher Education and Scientific Research of the Autonomous Province of Vojvodina (Serbia), grant number (0032710122024 09418 003 000 000 001 04 003).

The authors declare no conflict of interest.