Abstract
Objectives
The objective of this study was to assess transthoracic echocardiography (TTE) parameters in pregnancy by race and ethnicity.
Methods
We performed a retrospective cohort study of pregnant individuals without cardiovascular disease who underwent a perinatal TTE between October 2017 and May 2022. Demographics and echocardiographic parameters were compared by race/ethnicity. Multivariate regression analysis was performed for TTE parameters after adjusting for age and hypertension.
Results
During the study period, 369 individuals had TTEs with a mean age of 31.8 ± 6.0 years old. Subjects were 55.3% White, 24.7% Hispanic, 14.1% Black, and 6.0% Asian. TTE parameters of left ventricular (LV) ejection fraction and LV mass index differed by race/ethnicity, though no difference was seen in cardiac geometry.
Conclusion
The differences in TTE parameters may not be clinically significant as most values fall within normal clinical ranges. Further prospective studies are needed to better evaluate cardiac outcomes by differences in echocardiographic parameters in pregnancy.
Introduction
Cardiovascular disease (CVD) is the leading cause of pregnancy-related mortality in the United States, with nearly two-thirds of these deaths being deemed preventable.1,2 CVD affects up to 4% of all pregnancies, but accounts for over 25% of maternal deaths and disproportionately affects individuals from racial/ethnic minority backgrounds. 3 Pregnancy may unmask or exacerbate underlying cardiac disease due to the increased cardiac demands in the pregnant state, and accurate diagnosis and detection must be employed to reduce maternal morbidity, mortality, and racial disparities in care.
Due to the numerous physiological adaptations that are normally seen in pregnancy to support the increased metabolic demands of the mother and fetus, it is critical that clinicians understand the normal and abnormal cardiac structural and functional changes seen in pregnancy and in the immediate postpartum period. 4 Transthoracic echocardiography (TTE) is the most commonly used method to assess cardiac function and structure in pregnancy due to its safety and accessibility. A number of prior studies have strived to define normal echocardiographic parameters during pregnancy, however most of the literature is based on small numbers of pregnant patients at varying time points in pregnancy making it difficult to establish general references ranges.5–8 In nonpregnant patients, there is significant variation observed in normative values of echocardiographic parameters by race and ethnicity, yet this variation has not been studied in pregnant populations. 9
Given the paucity of data surrounding normative TTE parameters in pregnancy and by race and ethnicity, this study's objective was to compare TTE parameters and cardiac geometry among pregnant individuals without CVD by race and ethnicity.
Material and methods
Study population and design
This was a retrospectively cohort study of perinatal patients who underwent a TTE as part of their pregnancy care. Inclusion criteria included all patients aged 18 years or older who received prenatal and postpartum care at a single tertiary care center between 1 October 2017 and 1 May 2022 and had a TTE during pregnancy or within 12 weeks postpartum that was considered normal. A normal TTE was defined as any imaging with no evidence of systolic or diastolic dysfunction, congenital cardiac lesions, moderate/severe valvular disease, and/or pericardial effusions classified as larger than trivial. Patients were excluded if: (1) medical records/TTEs were not available for review, (2) TTEs were performed prior to pregnancy and/or more than 12 weeks postpartum, (3) known diagnosis of cardiac disease or abnormal TTE, and/or (4) were of unknown race/ethnicity or identified as multiracial on self-report. Cardiac disease was defined as a history of cardiomyopathy (peripartum or other), valvular heart disease, known connective tissue disease, congenital heart disease, or congestive heart failure. For patients with multiple pregnancies during the five-year eligibility period, only the first pregnancy was used. For patients with multiple TTEs during pregnancy, the first TTE performed in the perinatal period was used.
A query was performed by a biostatistician to identify patients who underwent a TTE as part of their obstetrical care. Data were then extracted from the medical records and transferred to REDCap, a secure database. 10 All methods were approved by the university's institutional review board (STUDY00000111).
Assessment of exposure and outcomes
The primary exposure of interest was race and ethnicity. Both race and ethnicity are self-reported in the medical record and are defined as American Indian/Alaska Native, Asian, Black/African American, Hispanic, or White.
The primary outcomes of interest were TTE parameters and cardiac geometry. All TTE parameters were generated by clinical echocardiography attendings using standard cardiac views and extracted by trained research assistants. Parasternal long view was utilized to measure the left ventricular (LV) internal diameter diastole, LV internal end-diastolic diameter, interventricular septum (IVS), and posterior wall (PW). Apical four-chamber view was used to measure left atrial (LA) volume, tricuspid annular plane systolic excursion (TAPSE), E/A ratio, septal e’, and lateral e’. E/A ratio, septal e’, and lateral e’ are measures used to assess cardiac diastolic function. LV mass index, LA volume index, and LV diastolic volume index were each calculated by their respective value divided by body surface area. If a reference range for ejection fraction was reported, the mid-point of the range was selected for abstraction. Reference means were obtained from the normative values provided by the American Society of Echocardiography. Cardiac geometry was calculated from the relative wall thickness and LV mass index, and classified as normal, eccentric hypertrophy, concentric remodeling, and concentric hypertrophy. 11
Additional covariates and demographics of interest included age, parity, pregravid body mass index (obtained from initial prenatal visit measurements), alcohol use in pregnancy, tobacco use in pregnancy, history of or current diagnosis of gestational or pregestational diabetes mellitus, history of chronic hypertension, and history of or current diagnosis of hypertensive disorders of pregnancy including gestational hypertension, preeclampsia with and without severe features, HELLP syndrome, or eclampsia. 12
Statistical analysis
All data were summarized using raw numbers and percentages for categorical data and means (standard deviations) for continuous data. Analyses were then performed to compare patient demographics by race/ethnicity. Categorical variables were compared with chi-square or Fisher exact test where appropriate, and continuous variables were compared with ANOVA. For echocardiographic parameter comparisons, subsequent Sidak correction for post-hoc analysis of statistically significant findings given multiple comparisons was performed with a significant p-value established as p < .005. Multivariate regression analysis was then performed for the TTE parameters significantly different after univariate analysis by race and ethnicity after adjusting for age and history of chronic hypertension. Data was analyzed using STATA SE (College Park, TX) software.
Results
During the study period, 369 subjects had a normal TTE in the perinatal period with a mean age of 31.8 ± 6.0 years and a pregravid body mass index of 29.0 ± 7.0 kg/m2. Subjects identified as 55.3% White, 24.7% Hispanic, 14.1% Black/African American, 6.0% Asian, and 0.5% American Indian/Alaska Native. The TTEs were most commonly performed for complaints of palpitations or dyspnea in pregnancy.
The racial/ethnic groups varied slightly by age (Asian 34.2 years, Black 34.4 years, Hispanic 28.2 years, and White 32.1 years, p = .01) and nulliparity (range 21.2–45.6%, p = .004). History of chronic hypertension was also different by group (Table 1). There was no statistically significant difference in pregravid body mass index, alcohol or tobacco use in pregnancy, history of pregestational or gestational diabetes mellitus, history of hypertensive disorders of pregnancy, or perinatal timing of TTE by race/ethnicity (Table 1). The majority of TTEs were performed in the third trimester.
Demographics of perinatal subjects compared by race and ethnicity a .
All data are reported as n (%) or mean (standard deviation).
History of or current diagnosis.
With respect to TTE parameters, there was a slight difference in LV function by LV ejection fraction by race/ethnicity (range 60.8–64.4%, p < .001, Table 2), though all values were in the normal reference range. Additionally, there were statistically significant differences in LV mass index, LA volume index, tricuspid regurgitation peak gradient, and lateral e’ by race/ethnicity (Table 2). However, on multivariate analysis, we found that only LV ejection fraction and LV mass index remained statistically different by race and ethnicity (Table 3). Patients identifying as Asian and Black/African American had higher ejection fractions compared to White patients after adjusting for age and history of chronic hypertension (Table 3). With the same adjustments, patients identifying as White had a lower LV mass index compared to patients identifying as Asian (Table 3).
Echocardiography parameters in perinatal subjects by race and ethnicity.
Abbreviations: LA: left atrium; LV: left ventricle; RA: right atrium; RV: right ventricle; TR: tricuspid regurgitation.
All data are reported as mean (standard deviation) or n (%).
Multivariate regression analysis evaluating racial/ethnic differences in left ventricular ejection fraction and mass index.
Abbreviation: LA: left atrium.
Analyses are adjusted for age and chronic hypertension.
Of the sample cohort, 74.3% had normal geometry, 17.6% had concentric remodeling, 4.3% had concentric hypertrophy, and 3.8% had eccentric remodeling. There was no statistically significant difference in cardiac geometry by race/ethnicity (Table 4).
Cardiac geometry in perinatal subjects by race and ethnicity.
All data are reported as n (%).
Discussion
In this retrospective cohort study, LV ejection fraction and LV mass index differed by race and ethnicity after adjusting for baseline differences in demographics including age and a history of chronic hypertension. Given that the mean values of these parameters were within the normal reference range, these differences may not be clinically significant.
Commonly accepted TTE reference ranges are derived from population studies that have predominately used European/North American populations, which may affect the extrapolation to other racially and ethnically diverse patient samples. 13 Other literature has shown differences in TTE parameters by race with Asian nonpregnant patients having higher a’ velocities, lower E wave, and smaller RA end-systolic volumes compared with White subjects, while other studies have shown no differences in LV ejection fraction by race.14–16 The differences in TTE parameters seen in our study between Asian subjects compared to other races is likely due to the small sample size as is evidenced by the wide confidence intervals seen in adjusted analyses.
Variations in cardiac geometry are commonly seen by race with Black/African American patients having higher prevalence of concentric remodeling/hypertrophy even when controlling for the presence of hypertension. 17 There was a trend toward patients identifying as Black/African American having higher prevalence of concentric remodeling and hypertrophy compared to other races, but it was not statistically significant. While the current study did not find this difference, it is possibly due to the sample size and warrants further investigation in populations with and without chronic hypertension.
Minor differences in LV ejection fraction and LV mass index by race and ethnicity were identified in this study, however, these parameters were predominately within the normal reference ranges. There is no clear physiologic explanation to justify this change, given the overall similar end diastolic volumes in the study sample. While differences in chamber size by race and ethnicity have been noted in other studies, there is no data on variation in ejection fraction by race.14–16 Given the increasing morbidity and mortality seen with CVD in pregnancy, it will be critically important to understand if slight variations in TTE parameters may signify underlying CVD or increase risk of adverse perinatal and cardiac outcomes. Based on our current study findings, abnormalities in TTE parameters uncovered during pregnancy should not be attributed to race/ethnicity differences and should be of concern for unmasking of CVD.
This study was a first step to examine a large and diverse cohort of pregnancies to determine if there were race/ethnicity-based differences in cardiac structure and function. Future studies of diverse patients with larger populations of perinatal patients identifying as Black/African American, Asian, and Native American should be performed to further assess the racial/ethnic differences in TTE parameters and cardiac geometry.
Strengths and limitations
The strengths of this study include the in-depth retrospective review of records and TTE measurements and the importance of the topic given the paucity of data in the perinatal population. There is little data regarding normative TTE parameters in perinatal subjects and no literature examining differences by race and ethnicity in pregnant subjects to the best of our knowledge.
This study has limitations including the sample size and small categories of Asian and Native American participants and the variation in timing of TTE obtainment. TTEs were performed at various time points in pregnancy and in the postpartum period, which may alter TTE parameters due to the cardiovascular changes in pregnancy. However, there was no statistically significant difference in TTE timing in pregnancy by race and ethnicity. There was no a priori sample size calculation performed, which may have underpowered the current study's ability to detect true differences in primary outcomes. Finally, this study did not collect information on myocardial strain parameters, which may provide more information on subclinical myocardial dysfunction in pregnant women.18,19 Future studies are needed to evaluate difference in global longitudinal strain among pregnant patients of difference races and ethnicities.
Conclusions
Our data suggest that while there were differences in TTE parameters by race and ethnicity, these differences may not be clinically significant as most mean values fall within the normal clinical ranges. As maternal morbidity and mortality due to CVD increases, reliance on TTE to evaluate for underlying CVD will be critically important for diagnosis and disease monitoring. Establishment of references ranges in pregnancy and an understanding that out-of-range TTE parameters should not be solely attributed to race and ethnicity will be important in working to reduce maternal morbidity and mortality.
Footnotes
Authorship/contributorship
All authors were involved in the manuscript write up and all approved of this submission.
Disclosure statement
The authors report no conflicts of interest.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethical approval/consent
This report was IRB approved.
Funding
Dr Kovell is supported by the National Institutes of Health through the National Center for Advancing Translational Sciences (Grant No. KL2TR001455) and the National Heart, Lung, and Blood Institute (Grant No. K23HL163450). Dr Wilkie is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Grant No. K23HD111526-01A1).
IRB approval
IRB approval was obtained from UMASS Chan IRB.
