A Study of Cardiovascular Hemodynamics in Preeclamptic and Normotensive Pregnancies and its Association with Maternal Outcomes

Abstract

Background

Preeclampsia (PE) leads to substantial changes in maternal cardiac geometry and function such as elevated afterload which leads to elevated end systolic pressure and reduced emptying of the left ventricle. Systolic and diastolic dysfunction both occurs in preeclampsia where diastolic dysfunction precedes systolic dysfunction. The aim of our study was to assess cardiovascular hemodynamic functions in normotensive and preeclamptic women and its association with maternal outcome.

Material and method

It was a prospective cohort study conducted in a tertiary healthcare center over one year. One hundred and fifty-eight women, 79 women with PE (group A) and 79 normotensive women (group B), were selected. Echocardiography was performed in all recruited women for maternal outcome.

Result

The following echocardiographic parameters were higher in preeclamptic subjects as compared to normotensive women: LV ESV (50.40 ± 15.08ml vs. 40.34 ± 5.24ml); LV EDV (103.77±17.78ml vs. 89.23±7.90ml); LV systolic mass(91.28±10.80gm vs 82.90±4.68gm); LV diastolic diameter (4.26 ± 0.35cm vs. 3.93±0.16cm); LV systolic diameter 2.67 ± 0.54cmvs 2.14 ± 0.29cm); E wave (0.86±0.25m/s vs. 0.75±0.07 m/s); and A wave (0.82±0.16m/s vs. 0.64±0.09 m/s). However, parameters such as ejection fraction (55.41 ±11.83% vs. 64.50±3.63%) and E/A ratio (1.06±0.28 vs. 1.17±0.09) were lower in preeclamptic women. Women with abnormal ECHO finding were associated with pulmonary edema, cardiomyopathy, abruptio, eclampsia, and mortality and adverse obstetrical outcomes like abruption, AKI, eclampsia, and HELLP syndrome.

Introduction

Preeclampsia is a specific disorder of pregnancy characterized by new onset hypertension, i.e., systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg developing after 20 week of gestation with the involvement of at least one organ system which completely resolves within 12 weeks postpartum [1]. It constitutes the major reason behind maternal morbidity and mortality and affects 2–8% of pregnant patients [2]. In developing countries, it is just behind anemia as the major cause of maternal mortality and morbidity. In preeclamptic women, as there is elevated afterload it leads to elevated end-systolic pressure and reduced emptying of the left ventricle [3]. In comparison with normal pregnancy, acute preeclampsia is linked to a significantly increased risk of myocardial damage and asymptomatic left ventricular (LV) abnormal function. Systolic and diastolic dysfunction both occurs in pre-eclampsia where diastolic dysfunction precedes systolic dysfunction [4].

Pulmonary failure and cardiac failure are common in preeclamptic women. Peripartum cardiomyopathy is also common in preeclamptic women which increases the risk of developing cardiac problems in future [5]. Thus, if cardiac dysfunction is diagnosed in early pregnancy, it can prevent the progression of disease severity and reduce the incidence of maternal morbidity and mortality in preeclamptic women.

Hence, this study was planned to evaluate cardiovascular parameters using echocardiography in normotensive and preeclamptic women before delivery and to study its association with maternal outcomes.

Material and Methods

The study was conducted in Department of Obstetrics and Gynaecology, in collaboration with Department of Cardiology King George’s Medical University, Lucknow. It is an ongoing prospective cohort study. Women with singleton pregnancy and gestational age ≥ 32 weeks were enrolled in the study. Women with gestational age < 32 weeks, chronic hypertension, preexisting heart disease, renal disease, severe anemia, autoimmune disease, and twin pregnancy were excluded from the study.

A total of 158 women were enrolled in the duration of one year period. Out of these, 79 had preeclampsia (Group 1) and 79 were normotensive (Group II). Subjects were classified as preeclampsia if blood pressure was ≥ 140/90 mmHg with proteinuria more than + 2 on urine dipstick examination. Subjects were categorized into non-severe PE and severe PE based on ACOG 2020 guidelines.

After obtaining proper informed consent, all women underwent detailed history and examination. (Pulse and BP were recorded.) Mean arterial pressure (MAP) was calculated by formula: MAP = diastolic blood pressure + 1/3(systolic blood pressure-diastolic blood pressure).

TTE (Transthoracic echocardiography) was done using GE ultrasound machine with a 2.5 MHz transducer at the time of enrolment. Two-dimensional echocardiography facilitated M-mode recording and color flow mapping facilitated Doppler measurements were performed. The probe was placed on patient’s chest in left lateral position in 3 different views, i.e., parasternal long axis, apical 4 chamber, and parasternal short axis view. Systolic parameters studied were left ventricular end-diastolic volume (LV EDV), left ventricular end-systolic volume (LV ESV), left ventricular systolic mass (LV SM), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), and ejection fraction (EF). Diastolic parameters included E wave, A wave, and E/A ratio.

All recruited women were followed till discharge for any cardiovascular dysfunction such as cardiomyopathy, pulmonary edema/cardiac failure, stroke, and adverse obstetric outcomes like abruption, eclampsia, HELLP, AKI, and maternal death.

The statistical analysis was done using SPSS (Statistical Package for Social Sciences) version 21.0 statistical Analysis Software. Student’s t test was used as a test of significance.

The p value of <0.05 was considered to be statistically significant.

Results

A total of 158 pregnant women were enrolled in the study after fulfilling the inclusion criteria. Out of these, 79(50%) women were noted as preeclamptic and 79(50%) women were noted as normotensive. The demographic profiles of study population were noted and are illustrated in Table 1. No difference in maternal age, BMI, gestational age at enrolment was observed between two groups. However, the difference in heart rate, systolic BP, diastolic BP, and mean arterial pressure (MAP) and gestational age at delivery were statistically significant (p value < 0.001).

Table 1.

Baseline characteristics of two study groups

SN	Parameters	Group I (n = 79)		Group II (n = 79)		Student’s t test
		Mean	SD	Mean	SD	‘t’	‘p’
1-	Mean age (years)	29.33	4.47	28.21	4.12	1.630	0.105
2-	Mean BMI(kg/m2)	21.70	1.77	21.79	2.22	1.359	0.176
3-	Mean SBP(mmHg)	153.22	15.02	120.84	8.73	17.206	< 0.001
4-	Mean DBP(mmHg)	101.87	11.42	80.10	5.55	15.260	< 0.001
5-	MAP(mmHg)	118.99	11.42	93.68	5.28	18.849	< 0.001
6-	Mean gestational at time of admission(in weeks)	34.53	1.97	34.87	1.93	− 1.090	0.278
7-	Mean gestational at time of delivery(in weeks)	35.36	2.42	38.14	1.56	− 6.445	< 0.001

The systolic echocardiographic parameters such as LV EDV, LV ESV, LV systolic mass,

LVIDs, and LVIDd were found to significantly higher in preeclamptic women than normotensive women, (p < 0.001). Ejection fraction in the preeclamptic women (55.41 ± 11.83%) was found to be significantly lower (p < 0.001.) than that of normotensive women (64.50 ± 3.63%). The diastolic parameters such as E wave and A wave were significantly higher (p < 0.001) in preeclamptic women. However, the E/A ratio was significantly lower in preeclamptic women in comparison with normotensive women (Table 2).

Table 2.

Comparison of Echocardiographic Parameters between two study groups

SN		Group I (n = 79)		Group II (n = 79)		Statistical significance
		Mean	SD	Mean	SD	‘t’	‘p’
I	Systolic parameters
1-	LV ESV (ml)	50.40	15.08	40.34	5.24	5.599	< 0.001
2-	LV EDV (ml)	103.77	17.78	89.23	7.90	6.639	< 0.001
3-	LV Dias diam (cm)	4.26	0.35	3.93	0.16	7.733	< 0.001
4-	LV Sys diam (cm)	2.67	0.54	2.14	0.29	7.792	< 0.001
5-	LV Sys Mass (gm)	91.28	10.80	82.90	4.68	6.329	< 0.001
6-	Ejection fraction (%)	55.41	11.83	64.50	3.63	− 6.529	< 0.001
II	Diastolic parameters
7	E wave (m/s)	0.86	0.25	0.75	0.07	4.005	< 0.001
8	A wave (m/s)	0.82	0.16	0.64	0.09	9.074	< 0.001
9	E/A ratio	1.06	0.28	1.17	0.09	− 3.504	0.001

In our study, out of 79 preeclamptic women, 41(51.9%) women had normal ECHO finding, whereas 38 (48.1%) women had significant ECHO changes. In the current study, systolic and diastolic echocardiographic parameters (except E/A ratio) were significantly higher (p < 0.001) among preeclamptic women with abnormal echocardiographic findings than that of with normal echocardiographic findings (Table 3). Out of 79 preeclamptic women, 53 (67%) had normal outcome, whereas 26 (32.9%) had abnormal cardiovascular outcome. Cardiomyopathy (17.7%) was the most common cardiovascular complication, followed by pulmonary edema (13.9%), whereas none of the patient had stroke. No cardiac dysfunction was observed in preeclamptic women having normal echocardiographic findings at the time of enrolment, and the difference was statistically significant (p < 0.001) (Table 4).

Table 3.

Comparison of normal and abnormal echocardiographic parameters in Preeclamptic women (Group I)

SN	Parameters	Normal Echocardiographic findings (n = 41)		Abnormal Echocardiographic findings (n = 38)		Statistical significance
		Mean	SD	Mean	SD	‘t’	‘p’
I-	Systolic parameters
1-	LV ESV (ml)	41.89	4.92	59.57	16.92	− 6.406	< 0.001
2-	LV EDV (ml)	94.19	7.99	114.09	19.66	− 5.975	< 0.001
3-	LV Dias diam (cm)	4.06	0.15	4.49	0.37	− 6.824	< 0.001
4-	LV Sys diam (cm)	2.43	0.44	2.94	0.52	− 4.695	< 0.001
5-	LV Sys Mass (gm)	85.81	4.11	97.19	12.59	− 5.485	< 0.001
6-	Ejection fraction (%)	62.45	2.80	47.82	13.12	6.975	< 0.001
II-	Diastolic parameters
7-	E wave (m/s)	0.74	0.12	1.00	0.28	− 5.481	< 0.001
8-	A wave (m/s)	0.74	0.14	0.92	0.13	− 6.199	< 0.001
9-	E/A ratio	1.02	0.22	1.10	0.33	− 1.174	0.244

Table 4.

Association of Echocardiographic abnormality at the time of enrolment with adverse Cardiovascular outcome in Preeclamptic women (Group I)

SN	Outcome	Total (N = 79)	Normal Echocardiographic (n = 41)		Abnormal Echocardiographic (n = 38)		Statistical significance
			No	%	No	%	χ2	‘p’
1-	Pulmonary edema	11	0	0.0	11	28.9	13.788	< 0.001
2-	Cardio-myopathy	14	0	0.0	14	36.8	18.359	< 0.001
3-	Mortality	1	0	0.0	1	2.6	1.093	0.296

All the 79 normotensive women had normal obstetrical outcome, while in 79 preeclamptic women only 45 (57%) had normal outcome, whereas 34 (43%) had abnormal obstetrical outcome. Most common adverse obstetric outcome was eclampsia (17.7%) followed by abruption (13.9%), AKI (7.6%), and HELLP (3.8%), and this was seen in higher proportion in women with abnormal echocardiographic findings (Table 5).

Table 5.

Association of Echocardiographic abnormality with Adverse Obstetric Outcome in Preeclamptic women (Group I)

SN		Total (N = 79)	Normal Echocardiography (n = 41)		Abnormal Echocardiography (n = 38)
			No	%	No	%
1-	Abruption	11	4	45.5	6	54.4
2-	AKI	6	1	16.7	5	83.3
3-	Eclampsia	14	2	14.3	12	85.7
4-	HELLP	3	0	0.0	3	100.0
5-	No adverse outcome	45	33	73.3	12	26.7

χ² = 22.619; p < 0.001

In the present study, the predictive accuracy of ejection fraction to predict cardiovascular dysfunction in preeclamptic women was determined by the ROC (receiver operator curve) analysis (area under curve: 0.838, with 95% confidence level). The value of EF < 62.8% was found to be 70.9% sensitive and 83.5% specific. At this cutoff value, the calculated positive predictive value and negative predicted value were 81.2 and 74.2%, respectively (Fig. 1).

Fig. 1.

ROC curve depicting sensitivity and specificity of ejection fraction to predict cardiovascular dysfunction in preeclamptic women

Discussion

The circulatory system undergoes a variety of changes during pregnancy. These changes are heavily influenced by various maternal factors such as the stage of gestation, the patient’s physical stature, their anxiety/stress levels, socioeconomic status, and food habits. The period of gestation marks different stages of cardiovascular adaptation. With increasing gestational age, there is increase in cardiac output, plasma volume, and heart rate. There is slight decrease in blood pressure in the first and second trimester. These cardiovascular changes are more pronounced in women with smaller body size, high BMI. Chronic stress and anxiety can also exacerbate the cardiovascular changes. Poor socioeconomic status and salt rich diet can also negatively influence the overall cardiovascular changes.

In preeclampsia, cardiovascular changes include elevated blood pressure, increased systemic vascular resistance, and endothelial dysfunction. These lead to impaired blood flow, increased cardiac workload, and potential organ damage. Placental ischemia exacerbates hypertension, increasing the risk of left ventricular dysfunction, thrombosis, and short- and long-term cardiovascular complications.

Till date cardiovascular assessment in pregnant women using echocardiography was indicated only in women with heart disease or in women presenting with breathlessness. Our study highlights the role of ECHO in prediction of adverse cardiovascular and obstetrical outcomes in preeclamptic women.

The current study infers that echocardiography can detect structural, hemodynamic, and functional changes in the cardiovascular system in preeclampsia, and these can be used to predict adverse cardiovascular and obstetrical outcomes in these women. Preeclampsia women showed reduced cardiac output (CO), left ventricular mass, and higher carotid intima-media thickness and peak mitral filling early diastole/atrial contraction ratio [6].

The difference in the echocardiographic systolic parameters was found to be statistically significant in our study (p < 0.001) similar to the study conducted by Shivananjiah et al. [7] showing that due to increased afterload in preeclampsia, there is elevated end-systolic volume.

The mean LV diastolic diameter, LV systolic diameter, and LV systolic mass was found to be statistically significant (p value < 0.001), showing left ventricular hypertrophy. Mostafavi et al. [8] carried out a cross-sectional study to assess alterations in the diastolic and systolic functions of the left ventricle (LV) in preeclamptic patients. The LV end-diastolic diameter (47.43 ± 4.94 mm vs 44.84 ± 4.30 mm; P = 0.008), LV end-systolic diameter (31.16 ± 33.3 mm vs 29.20 ± 3.75 mm; P = 0.008), and right ventricular diameter (27.93 ± 1.71 mm vs 24.53 ± 23.3; P = 0.001) were all significantly higher in the preeclampsia group.

Therefore, it suggests that in preeclampsia, due to increase in systemic blood pressure, there is adaptation through a proportional increase in left ventricular mass which maintains normal left ventricular performance despite the pathologic increase in ventricular afterload.

In our study, the mean ejection fraction in preeclampsia was found to be 55.41 ± 11.83% in comparison with 64.50 ± 3.63% in normotensive women which was statistically significant (p value < 0.001). In the studies done by Nandhini C et al. [4] and Muthyala et al. [9], the mean ejection fraction was also found to be above 50% in all cases and the value of EF was slightly less in preeclamptic women than normotensive women.

The echo diastolic parameters such as the mean E wave, A wave, and E/A ratio were found to be statistically significant (p value < 0.001). Sengodan et al. [5] showed that compared to normotensives, preeclamptic patients had a mean A wave velocity of 0.497–1.053 m/s, indicating the importance of diastolic dysfunction. Vaught et al. [10] study also focused on right ventricular (RV), systolic pressure (RVSP), and echocardiographic-derived diastolic and systolic parameters and found that preeclampsia women developed grade 2 diastolic function and pulmonary edema.

In preeclamptic women, the elevated E wave velocities indicate changes in the hypertrophic ventricle’s passive myocardial compliance and a larger transmittal pressure gradient during early passive filling. The increased peak A wave velocity indicates that atrial systole plays a more significant role in the hypertrophied ventricular filling in these women. Compared to a normal pregnancy, acute preeclampsia is linked to a significantly increased prevalence of myocardial damage and asymptomatic left ventricular (LV) abnormal function. Within the population with severe preeclampsia, left ventricular systolic function is within normal limits, whereas left ventricular diastolic dysfunction is more common in preeclampsia.

The study done by Castleman et al. [11] also shows that cardiac function and structure using echocardiography are altered in preclinical preeclampsia and also that diastolic dysfunction and increased peripheral vascular resistance have strong correlation with the disease severity.

Preeclamptic women had more diastolic dysfunction in comparison with normotensive women as the left ventricle becomes stiff due to increase in afterload causing impaired relaxation of ventricles, and it usually precedes the systolic dysfunction [12].

Alhuneafa et al. [13] in their recent study examine the echocardiographic differences in biventricular structure and function in 3 HDP groups (gestational hypertension, non-severe, and severe preeclampsia of women in comparison with normotensive pregnant controls) and observed echocardiographic parameters demonstrated a graded difference in left ventricular (LV) mass index, relative wall thickness, mitral inflow E, mitral inflow A, left atrial volume index, tricuspid velocity with the most profound findings noted in the SPE group. Specifically, adjusted LV mass index (adjusted β = 14.45, 95% CI: 9.00-19.90) was highest in the SPE group in comparison with controls (P < 0.001).

In this study, normal echocardiographic findings were observed in 41 preeclamptic women in comparison with 79 in normotensive patients. The abnormal echocardiographic findings were present in 38 (48%) preeclamptic women, whereas there was no abnormal echocardiographic finding in normotensive women, and this difference was found to be highly significant statistically (p < 0.001). Out of 38 abnormal echo findings in preeclamptic patients, 23 (60.5%) had grade 1 diastolic dysfunction, 13(34.2%) had grade 2 diastolic dysfunction, and 2(5.3%) patients had grade 3 diastolic dysfunction. It was comparable with the study done by Nandhini C et al. [4] in which 46 patients had grade 1 dysfunction and 4 had grade 2 dysfunction; however, no patient had grade 3 dysfunction. Patients with grade 2 or more diastolic dysfunction had a stormy postoperative period.

In our study, adverse cardiovascular outcome in the form of cardiomyopathy, pulmonary edema, and maternal death was observed in women with preeclampsia having abnormal echocardiographic finding at the time of enrollment. We observed that cardiovascular complications such as pulmonary edema and cardiomyopathy were associated with only abnormal ECHO finding, which was statistically significant and was consistent with the study done by Zaman N et al. [14] concluding that cardiac dysfunction plays a major risk factor for development of life-threatening cardiovascular complications.

Adverse obstetrical outcome in the form of abruption, HELLP, eclampsia, and acute kidney injury in group 1 (preeclamptic women) was associated with both abnormal and normal echocardiographic finding with higher percentage seen in women with abnormal echocardiography, and the difference was statistically significant (p < 0.001).

Adu-Bonsaffoh K et al. [15] also reported eclampsia to be the most common complication.

In our study, the cutoff value of ejection fraction < 62.8% could fairly predict adverse maternal outcome in cases of preeclampsia. It was predicted to be 70.9% sensitive and 83.5% specific, with a negative predicted value of 74.2% and positive predictive value of 84.2%.

Limitations: Serial echocardiography during antenatal and postpartum period to assess whether altered cardiovascular hemodynamics reverts to normal in postpartum would have given deeper insight into the subject.

The pulmonary function, drugs used for the treatment, disease progression, and compliance of patient could also influence the outcome in these women and needs to be studied along with cardiovascular hemodynamics.

Our study shows that in addition to giving real-time insights into maternal cardiovascular parameters, echocardiography in preeclamptic women can be used as a readily applicable tool to give a patient’s specific risk for cardiovascular complications with greater precision than currently possible.

However, accurate interpretation of echocardiographic parameters requires specialized expertise. To ensure precise readings and optimal patient management, it is crucial to establish online platforms that connect primary and tertiary healthcare centers with experienced professionals for expert analysis.

Large multicenter studies are required to gather a broader evidence base and enhance the cost-effectiveness of these recommendations to enable the policy makers to formulate guidelines for integration of maternal ECHO as a component of routine antenatal screening in women with preeclampsia. We suggest collaborating with cardiology specialists to ensure more reliable, actionable insights.

Conclusion

We propose that echocardiography could serve as a versatile, feasible, noninvasive, and readily applicable, and acceptable tool to predict adverse maternal outcomes in cases of preeclampsia thus identifying women at higher risk. Introducing echocardiography in clinical practice has fair accuracy in improving the evaluation of preeclampsia cases and can guide the health care providers in planning delivery at tertiary center equipped with advanced critical care unit with availability of multidisciplinary team consisting of obstetrician, cardiologist, cardiac anesthetist, and critical care specialist.

In this way, echocardiography may play a significant role in mitigating the potentially catastrophic short- and long-term cardiovascular and other complications of preeclampsia and can improve pregnancy outcomes.

Author Contribution

Dr Sneha Agarwal was involved in data collection. Prof Seema Mehrotra contributed to concept and design of study. Dr Vandana Solanki laid out of study and writing. Prof Rishi Sethi contributed to data analysis. Dr Manju Lata Verma was involved in formal analysis of study. Prof Pushpa Shankhwar contributed to hypothesis. Prof S P Jaiswar was involved in concept.

Funding

This study was not funded by any individual or agency.

Declarations

Conflicts of interest

There are no conflicts of interest in the study.

Compliance with Ethical Standards

Ethical Clearance—Institutional ethical committee clearance was obtained for study(ethical XIV-PGTSC-IIA/P22). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from every individual participant included in the study.