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Standardized combined Doppler-electrocardiogram assessment was performed longitudinally at three different locations of internal jugular veins between 12 wk of gestation and 6 wk postnatally in 24 uncomplicated pregnancies. All images were classified as typical or non-typical based on the presence of the physiologic deflections A, X, H and C. Linear mixed models with random intercepts of typical images were used to investigate gestational changes in venous pulse transit time and venous impedance index. Unequivocal identification of venous pulse transit time and venous impedance index was possible in 2617 of 3798 (69%) and 2234 of 3798 (59%) images, respectively. The best identification rate (80%, 1018/1266) was at the right distal internal jugular vein. Venous pulse transit time increased with gestational age at all locations; venous impedance index decreased at the right sided internal jugular vein. Maternal jugular venous pulse waveform by combined Doppler-electrocardiogram allows unequivocal identification of A-deflection and calculation of venous pulse transit time and venous impedance index in around two-thirds of assessments, with the highest success rate at the right distal internal jugular vein. Gestational evolutions of venous pulse transit time and venous impedance index are similar to those reported at the level of renal interlobar and hepatic veins.

BACKGROUND: Preeclampsia is strongly associated with left ventricular concentric remodeling (LVCR) and left ventricular hypertrophy (LVH) up to 10 years after delivery. This predisposes to heart failure later in life. Adequate detection and prediction of LVCR or LVH is expected to decrease the risk of developing clinical heart failure within this high-risk female population. Therefore, we developed and internally validated a prediction model for aberrant cardiac remodeling in formerly pregnant women. METHODS: This large cohort study included women with a history of preeclampsia or normotensive pregnancy within a postpartum interval of 6 months to 30 years. Cardiovascular assessment was performed, including echocardiography, 30-minute blood pressure measurements, and circulating biomarkers. Aberrant cardiac remodeling based on echocardiographic findings was defined as either LVCR or LVH. Discriminative performance was evaluated by the area under the receiver operating characteristic curve. RESULTS: A total of 1397 women were included, of which 139 (10%) with LVCR or LVH (mean±SD age, 43±9 years) and 1258 (90%) without LVCR or LVH (40±8 years). The final prediction model was established based on the predictors age, waist circumference, systolic blood pressure, glycated hemoglobin, antihypertensive medication use, and early onset preeclampsia (yes/no). After internal validation, the prediction model showed accurate discriminative ability with an area under the receiver operating characteristic curve of 0.702 (95% CI, 0.657–0.756). CONCLUSIONS: Based on the conventional predictors, we developed a prediction model for women who are on average 8 to 12 years postpartum. Internal validation showed accurate discriminative ability. Upon external validation, this model may aid clinicians to initiate further diagnostic testing or clinical follow-up. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02347540.

Contains fulltext : 293584.pdf (Publisher’s version ) (Open Access) BACKGROUND: The leading global risk factor for cardiovascular-disease-related morbidity and mortality is hypertension. In the past decade, attention has been paid to increase females' representation. The aim of this study is to investigate whether the representation of females and presentation of sex-stratified data in studies investigating the effect of antihypertensive drugs has increased over the past decades. METHODS: After systematically searching PubMed and Embase for studies evaluating the effect of the five major antihypertensive medication groups until May 2020, a scoping review was performed. The primary outcome was the proportion of included females. The secondary outcome was whether sex stratification was performed. RESULTS: The search resulted in 73,867 articles. After the selection progress, 2046 studies were included for further analysis. These studies included 1,348,172 adults with a mean percentage of females participating of 38.1%. Female participation in antihypertensive studies showed an increase each year by 0.2% (95% CI 0.36-0.52), p < 0.01). Only 75 (3.7%) studies performed sex stratification, and this was the highest between 2011 and 2020 (7.2%). CONCLUSION: Female participation showed a slight increase in the past decade but is still underrepresented compared to males. As data are infrequently sex-stratified, more attention is needed to possible sex-related differences in treatment effects to different antihypertensive compounds.

Introduction: Among its effect on virtually all other organs, COVID-19 affects the cardiovascular system, potentially jeopardizing the cardiovascular health of millions. Previous research has shown no indication of macrovascular dysfunction as reflected by carotid artery reactivity, but has shown sustained microvascular dysfunction, systemic inflammation, and coagulation activation at 3 months after acute COVID-19. The long-term effects of COVID-19 on vascular function remain unknown. Materials and Methods: This cohort study involved 167 patients who participated in the COVAS trial. At 3 months and 18 months after acute COVID-19, macrovascular dysfunction was evaluated by measuring the carotid artery diameter in response to cold pressor testing. Additionally, plasma endothelin-1, von Willebrand factor, Interleukin(IL)-1ra, IL-6, IL-18, and coagulation factor complexes were measured using ELISA techniques. Results: The prevalence of macrovascular dysfunction did not differ between 3 months (14.5%) and 18 months (11.7%) after COVID-19 infection (p = 0.585). However, there was a significant decrease in absolute carotid artery diameter change, 3.5% ± 4.7 vs. 2.7% ± 2.5, p—0.001, respectively. Additionally, levels of vWF:Ag were persistently high in 80% of COVID-19 survivors, reflecting endothelial cell damage and possibly attenuated endothelial function. Furthermore, while levels of the inflammatory cytokines interleukin(IL)-1RA and IL-18 were normalized and evidence of contact pathway activation was no longer present, the concentrations of IL-6 and thrombin:antithrombin complexes were further increased at 18 months versus 3 months (2.5 pg/mL ± 2.6 vs. 4.0 pg/mL ± 4.6, p = 0.006 and 4.9 μg/L ± 4.4 vs. 18.2 μg/L ± 11.4, p < 0.001, respectively). Discussion: This study shows that 18 months after COVID-19 infection, the incidence of macrovascular dysfunction as defined by a constrictive response during carotid artery reactivity testing is not increased. Nonetheless, plasma biomarkers indicate sustained endothelial cell activation (vWF), systemic inflammation (IL-6), and extrinsic/common pathway coagulation activation (FVII:AT, TAT) 18 months after COVID-19 infection.

Preeclampsia is often preceded by abnormal hemodynamic changes with heterogeneous patterns in the first half of pregnancy. We assessed the effect of timely tailored correction of nonphysiological hemodynamic changes on preventing preeclampsia in a high-risk population. Primiparous women with a history of preeclampsia were invited to participate in a longitudinal program in their next pregnancy, including repeated hemodynamic assessments at 12-, 16-, 20- and 30-week gestation additional to regular pregnancy checkups. When at least 2 of the hemodynamic variables were not within physiological reference values, the hemodynamic imbalance between cardiac output and peripheral vascular resistance was counteracted with either labetalol, methyldopa, or nifedipine using a simple treatment algorithm. Normogram-guided women (n=157) were matched to 157 women receiving care as usual (power, 80%; α=0.05). Risk of recurrent preeclampsia was analyzed with logistic regression adjusted for daily low-dose aspirin or calcium supplementation. Hemodynamic changes were considered nonphysiological in 90% of women in the normogram-guided group. Twelve percent of these women developed recurrent preeclampsia compared with 22% in the care-as-usual group (adjusted odds ratio, 0.47 [95% CI, 0.25–0.88]). There were no differences between groups in gestational age at delivery (38 1 and 38 2 weeks in the normogram-guided and care-as-usual groups, respectively) and neonatal birth weight (3148 and 3180 g in the normogram-guided and care-as-usual groups, respectively). Tailored circulatory normalization of nonphysiological hemodynamic changes during pregnancy halves the risk of recurrent preeclampsia, without disadvantageous effects on offspring outcome. This simple and innovative treatment strategy may also be beneficial to other women at increased risk for preeclampsia in pregnancy. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04216706.

IntroductionMyocardial infarction with non-obstructive coronary arteries (MINOCA) predominantly affects younger females. Women with a history of gestational hypertension (GH), preeclampsia (PE), and gestational diabetes mellitus (GDM) are subjected to an elevated lifetime risk of cardiovascular disease. However, data on the potential association between these obstetric complications and MINOCA is lacking. Therefore, the current study aimed to provide insight in the prevalence of metabolic and hypertensive pregnancy disorders (MHPD) in MINOCA patients and their clinical characteristics.MethodsIn this observational cohort study conducted at the Zuyderland Medical Center and Maastricht University Medical Center in the Netherlands, patients were enrolled if they were identified as having MINOCA. Data on individual patient characteristics, laboratory results, electrocardiography as well as (non-)invasive imaging procedures were derived from the electronic health record system. Patients were asked to complete a questionnaire about prior MHPD including GDM, GH, and PE. Patients were grouped into those with MHPD and those with prior uncomplicated normotensive pregnancy (or pregnancies; NP).ResultsAfter excluding patients without 1-year follow-up (n = 53), 86 female MINOCA patients remained eligible for analysis. Of the total female population, 25 (29.1%) patients had MHPD, including GH (n = 19; 22.1%), PE (n = 4; 4.7%), and GDM (n = 7; 8.1%). The MHPD patients showed higher rates of chronic hypertension (84.0 vs. 55.7%; p = 0.013), hypercholesterolemia (64.0 vs. 34.4%; p = 0.012), a family history of CVD (84.0 vs. 45.9%; p = 0.001), gout or rheumatic arthritis (16.0 vs. 1.6%; p = 0.024), and were more often non-smokers (45.8 vs. 78.3%; p = 0.004), compared to the NP patients. Moreover, MHPD patients were more likely to use cardiovascular medications at baseline. A trend toward no specific cause found for the MINOCA event was observed in MHPD patients compared to the NP group (64.0 vs. 42.6%, p = 0.072).ConclusionA history of metabolic and hypertensive pregnancy disorders occurred in one-third of female MINOCA patients. In these patients, conventional cardiovascular risk factors were more prevalent compared to NP patients. In most MHPD patients, the specific cause for MINOCA remained unclear.

Myocardial injury in COVID-19 is associated with in-hospital mortality. However, the development of myocardial injury over time and whether myocardial injury in patients with COVID-19 at the intensive care unit is associated with outcome is unclear. This study prospectively investigates myocardial injury with serial measurements over the full course of intensive care unit admission in mechanically ventilated patients with COVID-19. As part of the prospective Maastricht Intensive Care COVID cohort, predefined myocardial injury markers, including high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and electrocardiographic characteristics were serially collected in mechanically ventilated patients with COVID-19. Linear mixed-effects regression was used to compare survivors with nonsurvivors, adjusting for gender, age, APACHE-II score, daily creatinine concentration, hypertension, diabetes mellitus, and obesity. In 90 patients, 57 (63%) were survivors and 33 (37%) nonsurvivors, and a total of 628 serial electrocardiograms, 1,565 hs-cTnT, and 1,559 NT-proBNP concentrations were assessed. Log-hs-cTnT was lower in survivors compared with nonsurvivors at day 1 (β -0.93 [-1.37; -0.49], p

IntroductionPreeclampsia, an endothelial disorder of pregnancy, predisposes to remote cardiovascular diseases (CVD). Whether there is an accelerated effect of aging on endothelial decline in former preeclamptic women is unknown. We investigated if the arterial aging regarding endothelial-dependent and -independent vascular function is more pronounced in women with a history of preeclampsia as compared to women with a history of solely normotensive gestation(s).MethodsData was used from the Queen of Hearts study (ClinicalTrials.gov Identifier NCT02347540); a large cross-sectional study on early detection of cardiovascular disease among young women (≥18 years) with a history of preeclampsia and a control group of low-risk healthy women with a history of uncomplicated pregnancies. Brachial artery flow-mediated dilation (FMD; absolute, relative and allometric) and sublingually administered nitroglycerine-mediated dilation (NGMD; absolute and relative) were measured using ultrasound. Cross-sectional associations of age with FMD and NGMD were investigated by linear regression. Models were adjusted for body mass index, smoking, antihypertensive drug use, mean arterial pressure, fasting glucose, menopausal state, family history of CVD and stress stimulus during measurement. Effect modification by preeclampsia was investigated by including an interaction term between preeclampsia and age in regression models.ResultsOf the 1,217 included women (age range 22–62 years), 66.0% had a history of preeclampsia and 34.0% of normotensive pregnancy. Advancing age was associated with a decrease in relative FMD and NGMD (unadjusted regression coefficient: FMD: −0.48%/10 years (95% CI:−0.65 to −0.30%/10 years), NGMD: −1.13%/10 years (−1.49 to −0.77%/10 years)) and increase in brachial artery diameter [regression coefficient = 0.16 mm/10 years (95% CI 0.13 to 0.19 mm/10 years)]. Similar results were found when evaluating FMD and NGMD as absolute increase or allometrically, and after confounder adjustments. These age-related change were comparable in former preeclamptic women and controls (p-values interaction ≥0.372). Preeclampsia itself was independently associated with consistently smaller brachial artery diameter, but not with FMD and NGMD.ConclusionIn young- to middle-aged women, vascular aging in terms of FMD and NGMD was not accelerated in women after preeclampsia compared to normotensive pregnancies, even though former preeclamptic women consistently have smaller brachial arteries.

Preeclampsia is a maternal hypertensive disease, complicating 2–8% of all pregnancies. It has been linked to a 2–7-fold increased risk for the development of cardiovascular disease, including heart failure, later in life. A total of 40% of formerly preeclamptic women develop preclinical heart failure, which may further deteriorate into clinical heart failure. Noninvasive cardiac imaging could assist in the early detection of myocardial abnormalities, especially in the preclinical stage, when these changes are likely to be reversible. Moreover, imaging studies can improve our insights into the relationship between preeclampsia and heart failure and can be used for monitoring. Cardiac ultrasound is used to assess quantitative changes, including the left ventricular cavity volume and wall thickness, myocardial mass, systolic and diastolic function, and strain. Cardiac magnetic resonance imaging may be of additional diagnostic value to assess diffuse and focal fibrosis and perfusion. After preeclampsia, sustained elevated myocardial mass along with reduced myocardial circumferential and longitudinal strain and decreased diastolic function is reported. These findings are consistent with the early phases of heart failure, referred to as preclinical (asymptomatic) or B-stage heart failure. In this review, we will provide an up-to-date overview of the potential of cardiac magnetic resonance imaging and echocardiography in identifying formerly preeclamptic women who are at high risk for developing heart failure. The potential contribution to early cardiac screening of women with a history of preeclampsia and the pros and cons of these imaging modalities are outlined. Finally, recommendations for future research are presented.

ObjectiveTo assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.DesignRegistry based observational study.Setting74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021ParticipantsAll adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients).Main outcome measuresAny cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.ResultsOf 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).ConclusionsIn patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.

OBJECTIVES: To investigate healthcare system-driven variation in general characteristics, interventions, and outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the ICU within one Western European region across three countries. DESIGN: Multicenter observational cohort study. SETTING: Seven ICUs in the Euregio Meuse-Rhine, one region across Belgium, The Netherlands, and Germany. PATIENTS: Consecutive COVID-19 patients supported in the ICU during the first pandemic wave. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline demographic and clinical characteristics, laboratory values, and outcome data were retrieved after ethical approval and data-sharing agreements. Descriptive statistics were performed to investigate country-related practice variation. From March 2, 2020, to August 12, 2020, 551 patients were admitted. Mean age was 65.4 ± 11.2 years, and 29% were female. At admission, Acute Physiology and Chronic Health Evaluation II scores were 15.0 ± 5.5, 16.8 ± 5.5, and 15.8 ± 5.3 (p = 0.002), and Sequential Organ Failure Assessment scores were 4.4 ± 2.7, 7.4 ± 2.2, and 7.7 ± 3.2 (p < 0.001) in the Belgian, Dutch, and German parts of Euregio, respectively. The ICU mortality rate was 22%, 42%, and 44%, respectively (p < 0.001). Large differences were observed in the frequency of organ support, antimicrobial/inflammatory therapy application, and ICU capacity. Mixed-multivariable logistic regression analyses showed that differences in ICU mortality were independent of age, sex, disease severity, comorbidities, support strategies, therapies, and complications. CONCLUSIONS: COVID-19 patients admitted to ICUs within one region, the Euregio Meuse-Rhine, differed significantly in general characteristics, applied interventions, and outcomes despite presumed genetic and socioeconomic background, admission diagnosis, access to international literature, and data collection are similar. Variances in healthcare systems' organization, particularly ICU capacity and admission criteria, combined with a rapidly spreading pandemic might be important drivers for the observed differences. Heterogeneity between patient groups but also healthcare systems should be presumed to interfere with outcomes in coronavirus disease 2019. ispartof: CRITICAL CARE MEDICINE vol:50 issue:4 pages:595-606 ispartof: location:United States status: published

Contains fulltext : 229383.pdf (Publisher’s version ) (Open Access) Obesity leads to an amplified risk of disease and contributes to the occurrence of type 2 diabetes, fatty liver disease, coronary heart disease, stroke, chronic kidney disease and various types of cancer. MicroRNAs (miRNAs), small non-coding RNA molecules of 20-25 nucleotides, can remain stable in plasma and have been studied as potential (predictive) biomarkers for obesity and related metabolic disorders. The aim of this study was to identify circulating miRNAs as biomarkers for obesity status and metabolic alterations in women. Circulating miR-216a and miR-155-5p were selected by miRNA expression profiling and validated by real time quantitative PCR in a validation cohort of 60 obese women and 60 normal weight-age-matched control women. This was supplemented by correlation analysis of the candidate miRNA and anthropometric variables, blood biochemistry and lipid profile markers. Circulating miR-216a was validated as a biomarker of obesity status with significantly reduced levels in obese women. Interestingly, this was associated with a negative correlation between the plasma miR-216a content and body mass index (BMI), waist circumference, mean arterial pressure (MAP), triglycerides, ratio of total cholesterol/high density lipoprotein (HDL)-cholesterol and high sensitivity-C reactive protein (hs-CRP).Taken together, we provide evidence for an abnormally expressed circulating miRNA, miR-216a, with additive value as a predictive marker for obesity that correlates with metabolic alterations presented by lipid profile and inflammatory markers.

Objectives Pregnancy complicated by pre-eclampsia (PE) and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is associated with an increased risk of cardiovascular (CV) diseases later in life. Subclinical cardiac alterations precede eminent CV diseases. Speckle-tracking echocardiography (STE) is an effective method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to investigate the prevalence of subclinical myocardial dysfunction in former PE patients (with and without HELLP syndrome) compared to normotensive women affected by HELLP syndrome. Methods In this cross-sectional retrospective study, women with a history of normotensive HELLP (n = 32), PE without HELLP (n = 59), and PE with HELLP (n = 101) underwent conventional and STE as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity. Results Women with a history of PE with HELLP syndrome were characterized by a higher prevalence of altered left ventricular circumferential and global longitudinal two-dimensional (2D) strain (74 and 20%, respectively), altered right ventricular longitudinal 2D strain (37%), and left atrial (LA) 2D strain (57%). Moreover, a higher proportion of alterations of biventricular and LA strains was also present in former PE without HELLP as well as in the normotensive HELLP group. Conclusions In the first years after a pregnancy complicated by HELLP syndrome, irrespective of whether there was concomitant PE, a higher rate of abnormal STE myocardial function is observed. Therefore, these women may benefit from CV risk management.

Contains fulltext : 238866.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To meta-analytically determine the adaptation of left ventricular diastolic function (LVDF)-indices to singleton normotensive pregnancies. METHODS: Literature was retrieved from PubMed and Embase. We included studies that reported a nonpregnant reference measurement and LVDF indices (mitral inflow signals, left atrial volume and tissue Doppler measurements). Mean differences between pregnant and reference measurements and weighted means of absolute values were calculated using a random-effects model. RESULTS: We included 34 eligible studies. Normotensive pregnancies were characterized by an initially larger increase in the passive left ventricular filling (E-wave peak velocity, 13%) compared to active left ventricular filling during diastole (A-wave peak velocity, 6%) resulting in a 16% increase of the E/A ratio in the first trimester. The E/A ratio progressively decreased during advancing gestation to -18% at term, resulting from stabilizing E-wave peak velocity and increased A-wave peak velocity. The E/e' ratio was increased between 22 and 35 weeks (a maximal increase of 13%) in normotensive pregnancy. Left atrial volume (LAV) progressively increased from 15 weeks onwards with a maximal increase of 30% between 36 and 41 weeks. CONCLUSION: LVDF in normotensive pregnancy was improved in the first trimester after which LVDF progressively worsened. Large-scale studies in normotensive and hypertensive complicated pregnancies are needed for a more precise insight into LVDF changes during pregnancy.

Objective To evaluate the association between deferred delivery in early‐onset pre‐eclampsia and offspring outcome and maternal cardiovascular, renal and metabolic function in the postpartum period. Design Observational study. Setting Tertiary referral hospital. Population Nulliparous women diagnosed with pre‐eclampsia before 34 weeks’ gestation who participated in a routine postpartum cardiovascular risk assessment programme. Women with hypertension, diabetes mellitus or renal disease prior to pregnancy were excluded. Methods Regression analyses were performed to assess the association between pregnancy prolongation and outcome measures. Main outcome measures Offspring outcome and prevalence of deviant maternal cardiovascular, renal and metabolic function. Results The study population included 564 women with a median pregnancy prolongation of 10 days (interquartile range [IQR] 4–18) who were assessed at on average 8 months (IQR 6–12) postpartum. Pregnancy prolongation after diagnosis resulted in a decrease in infant mortality (adjusted odd ratio [aOR] 0.907, 95% CI 0.852–0.965 per day prolongation). This improvement in offspring outcome was associated with an elevated risk of moderately increased albuminuria (aOR 1.025, 95% CI 1.006–1.045 per day prolongation), but not with aberrant cardiac geometry, cardiac systolic or diastolic dysfunction, persistent hypertension or metabolic syndrome. Conclusion Pregnancy prolongation in early‐onset pre‐eclampsia is associated with improved offspring outcome and survival. These effects do not appear to be deleterious to short‐term maternal cardiovascular and metabolic function but are associated with a modest increase in risk of residual albuminuria. Tweetable abstract Pregnancy prolongation in pre‐eclampsia has only a limited effect on postpartum maternal cardiovascular function., Tweetable abstract Pregnancy prolongation in pre‐eclampsia has only a limited effect on postpartum maternal cardiovascular function.

Objective To evaluate the association between different pre-eclampsia (PE) phenotypes and the development of metabolic syndrome postpartum, in order to identify the subgroup of formerly pre-eclamptic women with a worse cardiovascular risk profile requiring tailored postpartum follow-up. Methods This was a cohort study of 1102 formerly pre-eclamptic women in whom cardiovascular and cardiometabolic evaluation was performed at least 3 months postpartum. Women were divided into four subgroups based on PE resulting in delivery before 34 weeks (early-onset (EO)) or at or after 34 weeks (late onset (LO)) of gestation and whether they delivered a small-for-gestational-age (SGA) neonate. Metabolic syndrome was diagnosed as the presence of hyperinsulinemia along with two or more of: body mass index >= 30 kg/m(2); dyslipidemia; hypertension; and microalbuminuria or proteinuria. Data were compared between groups using ANOVA after Bonferroni correction. Odds ratios (OR) were calculated using logistic regression to determine the association between metabolic syndrome and the four subgroups. We constructed receiver-operating characteristics curves and computed the area under the curve (AUC) to quantify the ability of different obstetric variables to distinguish between women who developed metabolic syndrome and those who did not. Results The prevalence of metabolic syndrome was higher in women with EO-PE and SGA (25.8%) than in those with EO-PE without SGA (14.7%) (OR 2.01 (95% CI, 1.34-3.03)) and approximately five-fold higher than in women with LO-PE with SGA (5.6%) (OR 5.85 (95% CI, 2.60-13.10)). In women with LO-PE, the prevalence of metabolic syndrome did not differ significantly between women with and those without SGA. Multivariate analysis revealed that a history of SGA, a history of EO-PE and systolic blood pressure at the time of screening are the best predictors of developing metabolic syndrome postpartum. The AUC of the model combining these three variables was 74.6% (95% CI, 70.7-78.5%). The probability of the presence of metabolic syndrome was calculated as: P = 1/(1 + e(-LP)), where LP is linear predictor = -8.693 + (0.312 x SGA (yes = 1)) + (0.507 x EO-PE (yes = 1)) + (0.053 x systolic blood pressure). Conclusions The incidence of metabolic syndrome postpartum was associated more strongly with EO-PE in combination with SGA as compared with LO-PE or EO-PE without SGA. Both time of onset of PE and fetal growth affect the risk of metabolic syndrome after a pre-eclamptic pregnancy. Copyright (c) 2018 ISUOG. Published by John Wiley & Sons Ltd.

Objectives Pre-eclampsia (PE) is associated with both postpartum endothelial dysfunction and asymptomatic structural heart alterations consistent with heart failure stage B (HF-B). In this study we assessed the relation between endothelial function, by means of flow-mediated dilation (FMD), and HF-B at 4 years postpartum. Methods In 67 formerly PE women and 37 healthy parous controls, we ultrasonographically assessed cardiac function, geometry and FMD. HF-B was diagnosed as left ventricular hypertrophy (left ventricular mass index (LVMi) >95 g/m2), concentric remodelling (relative wall thickness (RWT) >0.42 and LVMi ≤95 g/m2), mild systolic dysfunction (left ventricular ejection fraction (LVEF) >40 and

Objectives Pre-eclampsia (PE) is associated with both postpartum endothelial dysfunction and asymptomatic structural heart alterations consistent with heart failure Stage B (HF-B). In this study, we assessed the relationship between endothelial function, measured by flow-mediated dilation (FMD), and HF-B in women with a history of PE. Methods This was an observational study in which 67 formerly pre-eclamptic women (>= 4 years postpartum) and 37 healthy parous controls were assessed ultrasonographically for cardiac function and geometry, as well as for endothelial function by means of brachial artery FMD. HF-B was diagnosed as left ventricular hypertrophy (left ventricular mass index (LVMi) > 95 g/m(2)), concentric remodeling (relative wall thickness> 0.42 and LVMi 40% and < 55%) or asymptomatic valvular disease. Cardiovascular and metabolic syndrome variables were compared between women with history of PE and controls, as well as between those in the formerly pre-eclamptic group who had HF Stage A, HF-B or no HF. Logistic regression analysis was performed to assess the associations of FMD with PE, metabolic syndrome risk factors and obstetric parameters. Results The prevalence of HF-B amongst formerly pre-eclamptic women was three-fold higher than that observed for controls (25% vs 8%, P < 0.05), while FMD was lower in formerly pre-eclamptic women compared with controls (6.12% vs 8.22%, P < 0.01); history of PE remained associated independently with lower FMD after adjusting for metabolic syndrome risk factors and obstetric parameters (beta, -1.88; 95% CI, -3.59 to -0.18). However, HF-B did not relate to low FMD in formerly pre-eclamptic women. Conclusions Years after pregnancy, formerly preeclamptic women have lower FMD and have HF-B more often compared with healthy parous controls. Nonetheless, HF-B was not related to reduced FMD. Copyright c (C) 2017 ISUOG. Published by John Wiley & Sons Ltd.

Contains fulltext : 229328.pdf (Publisher’s version ) (Open Access) BACKGROUND: Many studies investigate the role of pharmacological treatments on disease course in Corona Virus Disease 2019 (COVID-19). Sex disparities in genetics, immunological responses, and hormonal mechanisms may underlie the substantially higher fatality rates reported in male COVID-19 patients. To optimise care for COVID-19 patients, prophylactic and therapeutic studies should include sex-specific design and analyses. Therefore, in this scoping review, we investigated whether studies on pharmacological treatment in COVID-19 were performed based on a priori sex-specific design or post-hoc sex-specific analyses. METHODS: We systematically searched PubMed, EMBASE, UpToDate, clinical trial.org, and MedRxiv for studies on pharmacological treatment for COVID-19 until June 6th, 2020. We included case series, randomized controlled trials, and observational studies in humans (≥18 years) investigating antiviral, antimalarial, and immune system modulating drugs. Data were collected on 1) the proportion of included females, 2) whether sex stratification was performed (a priori by design or post-hoc), and 3) whether effect modification by sex was investigated. FINDINGS: 30 studies were eligible for inclusion, investigating remdesivir (n = 2), lopinavir/ritonavir (n = 5), favipiravir (n = 1), umifenovir (n = 1), hydroxychloroquine/chloroquine (n = 8), convalescent plasma (n = 6), interleukin-6 (IL-6) pathway inhibitors (n = 5), interleukin-1 (IL-1) pathway inhibitors (n = 1) and corticosteroids (n = 3). Only one study stratified its data based on sex in a post-hoc analysis, whereas none did a priori by design. None of the studies investigated effect modification by sex. A quarter of the studies included twice as many males as females. INTERPRETATION: Analyses assessing potential interference of sex with (side-)effects of pharmacological therapy for COVID-19 are rarely reported. Considering sex differences in case-fatality rates and genetic, immunological, and hormonal mechanisms, studies should include sex-specific analyses in their design to optimise COVID-19 care. FUNDING: None.

Background During uncomplicated pregnancy, left ventricular remodeling occurs in an eccentric way. In contrast, during preeclamptic gestation, the left ventricle hypertrophies concentrically, concurrent with loss in circulatory volume and increased blood pressure. Concentric cardiac structure persists in a substantial proportion of women and may be associated with pressure and volume load after preeclampsia. We hypothesize that low volume load, as indicated by plasma volume (PV) after preeclampsia and increased pressure load, is associated with remote concentric remodeling. Methods and Results In this longitudinal cohort study, we included 100 formerly preeclamptic women. Two visits were performed: at 0.8 years postpartum and at 4.8 years postpartum. During visit 1, we measured blood pressure and PV (I 125 dilution technique, low PV ≤48 mL/kg lean body mass). During the second visit, we assessed cardiac geometry by cardiac ultrasound. Concentric remodeling was defined as relative wall thickness >0.42 and left ventricular mass index ≤95 g/m 2 . We adjusted multivariable analysis for primiparity, systolic blood pressure, PV mL/kg lean body mass, and antihypertensive medication at visit 1. Low PV is associated with remote concentric remodeling (odds ratio [OR], 4.37; 95% CI, 1.06–17.40; and adjusted OR, 4.67; 95% CI, 1.02–21.42). Arterial pressure load (systolic, diastolic, and mean arterial pressure) is also associated with development of concentric remodeling (OR, 1.15 [95% CI, 0.99–1.35]; OR, 1.24 [95% CI, 0.98–1.58]; and OR, 1.20 [95% CI, 0.98–1.47], respectively). Conclusions In former preeclamptic women, development toward left ventricular concentric remodeling is associated with low volume load and increased pressure load.

Background: The prothrombotic phenotype has been extensively described in patients with acute coronavirus disease 2019 (COVID-19). However, potential long-term hemostatic abnormalities are unknown.Objective: To evaluate the changes in routine hemostasis laboratory parameters and tissue-type plasminogen activator (tPA) rotational thromboelastometry (ROTEM) 6 months after COVID-19 intensive care unit (ICU) discharge in patients with and without venous thromboembolism (VTE) during admission.Methods: Patients with COVID-19 of the Maastricht Intensive Care COVID cohort with tPA ROTEM measurement at ICU and 6-month follow-up were included. TPA ROTEM is a whole blood viscoelastic assay that illustrates both clot development and fibrinolysis due to simultaneous addition of tissue factor and tPA. Analyzed ROTEM parameters include clotting time, maximum clot firmness (MCF), lysis onset time (LOT), and lysis time (LT).Results: Twenty-two patients with COVID-19 were included and showed extensive hemostatic abnormalities before ICU discharge. TPA ROTEM MCF (75 mm [interquartile range, 68-78]-59 mm [49-63]; P

Objective To describe the physiological pattern of gestational plasma volume adjustments in normal singleton pregnancy and compare this with the pattern in pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction. Methods We performed a meta-analysis of the current literature on plasma volume adjustments during physiological and complicated pregnancies. Literature was retrieved from PubMed (NCBI) and EMBASE (Ovid) databases. Included studies reported both reference plasma volume measurements (non-pregnant, prepregnancy or postpartum) and measurements obtained during predetermined gestational ages. Mean differences bet ween the reference and pregnancy plasma volume measurements were calculated for predefined intervals of gestational age using a random-effects model described by DerSimonian and Laird. Results Thirty studies were included in the meta-analysis with publication dates ranging from 1934 to 2007. Plasma volume increased in the first weeks of pregnancy, with the steepest increase occurring during the second trimester. Plasma volume continued to increase in the third trimester with a pooled maximum increase of 1.13 L (95% CI, 1.07–1.19 L), an increase of 45.6% (95% CI, 43.0–48.1%) in physiological pregnancies compared with the reference value. The plasma volume expansion in gestational hypertensive and growth-restricted pregnancies was 0.80 L (95% CI, 0.59–1.02 L), an increase of 32.3% (95% CI, 23.6–41.1%) in the third trimester, a smaller increase than in physiological pregnancies (P

Objectives Pre-eclampsia (PE) is associated with both postpartum structural asymptomatic heart disease (i.e. heart failure Stage B (HF-B)) and conventional cardiovascular (CV) risk factors. We aimed to evaluate the extent to which PE, adjusted for conventional CV risk factors, is associated independently with asymptomatic cardiac abnormalities postpartum. Methods In this cross-sectional cohort study, 107 formerly pre-eclamptic women and 41 women with uneventful previous pregnancy (controls) were invited for CV risk assessment 4–10 years postpartum. This included cardiac ultrasound, blood pressure (BP) measurement and evaluation of metabolic syndrome determinants. Asymptomatic structural and functional cardiac abnormalities were classified as HF-B, according to the American Heart Association guidelines. Prehypertension was defined as systolic BP of 120–139 mmHg and/or diastolic BP of 80–89 mmHg. Univariate and multivariate regression analyses were performed to calculate associations of PE and conventional risk factors with HF-B. Results The prevalence of asymptomatic HF-B was approximately 3.5-fold higher in the PE group compared with controls (25% vs 7%, P < 0.01); 67% of this group had concentric remodeling and 22% had mildly impaired ejection fraction. After adjustment for postpartum interval, hypertension and high-density lipoprotein, PE was significantly associated with HF-B (adjusted odds ratio, 4.4 (95% CI, 1.0–19.1)). Moreover, in the formerly pre-eclamptic group, prehypertension was associated significantly with HF-B (odds ratio, 4.3 (95% CI, 1.4–12.7)), while metabolic syndrome determinants were not. Conclusion PE is associated with a four-fold increased female-specific risk of asymptomatic cardiac abnormalities. Prehypertension apparently increases this risk significantly, while metabolic syndrome determinants do not. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Objectives After pre-eclampsia (PE), the prevalence of structural heart disease without symptoms, i.e. heart failure Stage B (HF-B), may be as high as one in four women in the first year postpartum. We hypothesize that a significant number of formerly pre-eclamptic women with HF-B postpartum are still in their resolving period and will not have HF-B during follow-up. Methods In this prospective longitudinal cohort study, we included 69 formerly pre-eclamptic women who underwent serial echocardiographic measurements at 1 and 4 years postpartum. HF-B was diagnosed as left ventricular hypertrophy (left ventricular mass index (LVMi) > 95 g/m2), concentric remodeling (relative wall thickness > 0.42 and LVMi ≤ 95 g/m2), mild systolic dysfunction (left ventricular ejection fraction > 40% and < 55%) or asymptomatic valvular disease. Women were subdivided and analyzed according to HF-B outcome: no HF-B at either visit; HF-B at first visit only; HF-B at second visit only; HF-B at both visits. Results The prevalence of HF-B in formerly pre-eclamptic women was 23% in the first year postpartum and 23% after 4 years. At the second visit, HF-B had resolved in 62.5% of affected women but was newly developed in 19% of initially unaffected women. At the first visit, 56% of women diagnosed with HF-B had reduced systolic function whereas at the second visit 69% of women with HF-B had concentric remodeling with mostly normal ejection fraction, consistent with diastolic dysfunction. Conclusions The prevalence of HF-B can be considered consistently high (1 in 4) amongst formerly pre-eclamptic women at follow-up. Nonetheless, at an individual level, more than 60% of women found initially to be affected by HF-B will recover, whilst about 20% of formerly pre-eclamptic women with normal echocardiography in the first year postpartum will develop HF-B over the following years. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

OBJECTIVE: To evaluate subsequent rate of thrombosis among obstetric antiphospholipid syndrome (Ob-APS) women in a multicenter database of antiphospholipid antibody (aPL)-positive patients; and clinical utility of adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. DESIGN: Retrospective study. SETTING: APS Alliance For Clinical Trials & International Networking (APS ACTION) Clinical Database And Repository. POPULATION: Women with Ob-APS. METHODS: Comparison of clinical and laboratory characteristics; measurement of aGAPSS of Ob-APS women with or without thrombosis after initial pregnancy morbidity (PM). MAIN OUTCOME MEASURES: Risk factors for thrombosis, aGAPSS. RESULTS: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented thrombosis, and 47 (63%) of them developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had higher aGAPSS compared to those with Ob-APS alone ([median 11.5 [4-16] vs 9 [4-13], P = 0.0089]). CONCLUSION: Based on retrospective analysis of our multicenter aPL database, 63% of Ob-APS women developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased risk. Women with subsequent thrombosis after Ob-APS had higher aGAPSS score at registry entry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. There was no funding for this study.

Objective: Monitoring hemodynamic status throughout pregnancy may help in identifying women with maladaptation predisposing to hypertensive complications. The Ultrasonic Cardiac Output Monitor (USCOM) is an easy-to-operate device for measuring cardiac output (CO) quickly. Our aim was to assess agreement between USCOM and transthoracic echocardiography (TTE) in: 1) non-pregnant women to correct for possible sources of discrepancy; 2) women longitudinally over the course of the pregnancy.Study design: High-risk women admitted for cardiovascular risk factor evaluation before pregnancy and multiple times during pregnancy, were included. CO was measured by TTE directly followed by USCOM measurements.Main outcome measures: Bias, limits of agreement (LOA) and percentage error between the two methods by Bland-Altman analysis.Results: Despite comparable non-pregnant CO levels (4.6 L/min), LOA and percentage error between the two methods improved moderately by optimizing the measurements using only the highest quality USCOM recordings in 132 non-pregnant women (percentage error of 39% and 30%, respectively). During pregnancy, in total 83, 106, 96 and 77 measurements were evaluated at respectively 12, 16, 20 and 30 weeks gestational age. Mean CO in USCOM was about 0.6 L/min higher compared to TTE in all trimesters; percentage error ranged from 35% to 45%. Linear mixed model analysis showed no association between bias and moment of measurement.Conclusion: Agreement between USCOM and TTE in pregnancy was outside our a priori determined level of acceptability and therefore absolute values of USCOM and TTE cannot be used interchangeably. Future research should focus on the agreement of USCOM and TTE in clinical decision-making.

Contains fulltext : 208669.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To review systematically current literature on kidney function changes during pregnancy, in order to estimate the extent of adaptation over the course of both healthy physiological and complicated singleton pregnancies, and to determine healthy pregnancy reference values. METHODS: PubMed (NCBI) and EMBASE (Ovid) electronic databases were searched, from inception to July 2017, for studies on kidney function during uncomplicated and complicated pregnancies. Included studies were required to report a non-pregnant reference value of kidney function (either in a non-pregnant control group or as a prepregnancy or postpartum measurement) and a pregnancy measurement at a predetermined and reported gestational age. Kidney function measures assessed were glomerular filtration rate (GFR) measured by inulin clearance, GFR measured by creatinine clearance and serum creatinine level. Pooled mean differences between pregnancy measurements and reference values were calculated for predefined intervals of gestational age in uncomplicated and complicated pregnancies using a random-effects model described by DerSimonian and Laird. RESULTS: Twenty-nine studies met the inclusion criteria and were included in the analysis. As early as the first trimester, GFR was increased by up to 40-50% in physiological pregnancy when compared with non-pregnant values. Inulin clearance in uncomplicated pregnancy was highest at 36-41 weeks, with a 55.6% (53.7; 95% CI, 44.7-62.6 mL/min) increase when compared with non-pregnant values, and creatinine clearance was highest at 15-21 weeks' gestation, with a 37.6% (36.6; 95% CI, 26.2-46.9 mL/min) increase. Decrease in serum creatinine level in uncomplicated pregnancy was most prominent at 15-21 weeks, with a 23.2% (-0.19; 95% CI, -0.23 to -0.15 mg/dL) decrease when compared with non-pregnant values. Eight studies reported on pregnancies complicated by a hypertensive disorder. Meta-regression analysis showed a significant difference in all kidney function parameters when comparing uncomplicated and hypertensive complicated pregnancies. CONCLUSIONS: In healthy pregnancy, GFR is increased as early as the first trimester, as compared with non-pregnant values, and the kidneys continue to function at a higher rate throughout gestation. In contrast, kidney function is decreased in hypertensive pregnancy. (c) 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Introduction Recurrence rates of preeclampsia vary based on severity of disease in the complicated pregnancy together with presence of risk factors consistent with the metabolic syndrome. Several efforts to reduce recurrent disease have been implemented in clinical practice in the past decades. Objective To assess whether recurrence rates of preeclampsia and related foetal complications decreased in the past 20 years in women who received tailored preventive advices after an extensive non-pregnant assessment on cardiovascular risk factors. Methods In this observational cohort study, we included 752 women who had their first pregnancy complicated by preeclampsia between 1996 and 2012, and who participated in a non-pregnant cardiovascular and metabolic assessment at least 4 months after delivery. A questionnaire was sent to women to follow-up on their next pregnancy outcome. We divided the study population in three groups based on year of their second delivery (1) 1996–2004; (2) 2005–2009; and (3) 2010–2016. We compared recurrence rates of preeclampsia and related foetal complications between the groups with the chi-square test. Results In total, 467 (62%) women responded to the questionnaire of which two-thirds had a subsequent ongoing pregnancy. The overall recurrence rate of preeclampsia was 24%. Preeclampsia recurred in 29% (29/99) of women who delivered between 1996 and 2004, compared to recurrence rates of 20% (20/99) in 2005–2009 and 24% (28/119) in 2010–2016 (p-value .319). Related offspring complications, including small for gestational age, decreased significantly over time (p-value .016). Discussion Recurrence rates of preeclampsia did not decrease over the past 20 years in women who have been extensively assessed on cardiovascular risk factors. In the same period, foetal and neonatal outcomes improved substantially. Efforts to extend and improve strategies to reduce recurrence risk of preeclampsia still seem to be necessary.

Introduction: Women with former preeclampsia (exPE) develop chronic hypertension 4 times more often than healthy parous controls. Women, destined to develop remote chronic hypertension, had increased left ventricular mass index (LVMI) and diastolic blood pressure (BP) prior to the onset of hypertension as compared to those remaining normotensive. However, longitudinal data on the progress of this increased LVMI in women destined to develop hypertension are lacking. Methods: We included 20 women with exPE and 8 parous controls. At both 1- and 14-year postpartum (pp), we performed cardiac ultrasound and determined circulating levels of the metabolic syndrome variables. Of 14-year pp, 7 (35%) former patients had developed chronic hypertension. We compared these 7 former patients with both the 13 former patients who remained normotensive and the 8 parous controls using the Mann-Whitney U test and Kruskal-Wallis analysis. Results: Women with hypertensive exPE differed from their normotensive counterparts by a higher incidence of early-onset preeclampsia (PE) in their index pregnancy and a higher rate of recurrence in next pregnancies. At 1-year pp, they also had high/normal BP and higher fasting insulin levels. At 14 years pp, the relative left ventricular wall thickness was higher, and the E/A ratio was lower, in the hypertensive group relative to those remaining normotensive. Conclusion: Women with exPE are at increased risk of developing chronic hypertension, when (1) the PE in the index pregnancy had an early-onset and/or recurred in next pregnancies and (2) the 1-year pp. Blood pressure was high normal. We also noticed that at 14 years pp, the hypertensive group showed signs of concentric left ventricular remodeling along with a decreased E/A ratio.

Contains fulltext : 182443.pdf (Publisher’s version ) (Closed access) OBJECTIVE: The aim of this systematic review and meta-analysis was to describe comprehensively the pattern of cardiac remodeling during normotensive human singleton pregnancy and to compare it with that of pregnancy complicated by hypertension. METHODS: We performed a meta-analysis of the current literature on cardiac remodeling during normotensive and complicated pregnancies. Literature was retrieved from PubMed (NCBI) and EMBASE (Ovid) databases. Included studies needed to report a reference measurement (matched non-pregnant control group, prepregnancy or postpartum) and measurements made during predetermined gestational-age intervals. Mean differences between reference and pregnancy data were calculated using the random-effects model described by DerSimonian and Laird. RESULTS: Forty-eight studies were included in the meta-analysis, with publication dates ranging from 1977 to 2016. During normotensive pregnancy, most geometric indices started to increase in the second trimester. Left ventricular mass (LVM) increased by 28.36 (95% CI, 19.73-37.00) g (24%), and relative wall thickness (RWT) increased by 0.03 (95% CI, 0.02-0.05) (10%) compared with those in the reference group. During hypertensive pregnancy, LVM and RWT increased more than during normotensive pregnancy (92 (95% CI, 75.46-108.54) g (95%) and 0.14 (95% CI, 0.09-0.19) (56%), respectively). CONCLUSIONS: During normotensive pregnancy, most cardiac geometric indices change from the second trimester onwards. Both LVM and RWT increase, by 20% and 10%, respectively, consistent with concentric rather than eccentric remodeling. Cardiac adaptation in hypertensive pregnancy deviates from that in healthy pregnancy by a greater change in LVM (95% increase from reference) and RWT (56% increase from reference). Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

Introduction During pregnancy, left ventricular (LV) diastolic function is of utmost importance to accommodate the increased preload in order to maintain increased cardiac output without triggering excessive sympathetic-tone-regulated reliance on heart rate. Insight in the physiological adaptation of diastolic function during pregnancy may enable the identification of women with impaired cardiac compliance, maladaptive to the pregnancy associated volume overload. Objective To meta-analytically determine the pattern of diastolic function indices during singleton normotensive pregnancies and hypertensive complicated pregnancies. Methods We performed a systematic review and meta-analysis on diastolic function during pregnancy using PubMed and Embase. We included studies that reported a non-pregnant reference measurement. Indices of interest were: mitral E-wave velocity, mitral A-wave velocity, E/A ratio, and left atrial volume (LAV). Mean differences between pregnant and reference measurements were calculated for predefined gestational age intervals using a random-effects model. Results We included 29 eligible studies. Normotensive pregnancies were characterized by a larger increase in passive LV filling (E-wave, 12%) compared to active LV filling during diastole (A-wave, 5%) resulting in a 17% increase of the E/A ratio in the first trimester. The E/A ratio progressively decreased during advancing gestation with 18%, resulting from normalized E-waves and increased A-waves. Hypertensive complicated pregnancies had a tendency of a larger decrease of the E/A ratio although not statistically significant (31%, p = 0.74). LAV increased more in hypertensive pregnancies compared to normotensive pregnancies (30% vs. 112% respectively, p Discussion Diastolic function in normotensive pregnancy is mainly dominated by passive filling in the first trimester while more by active filling later on in pregnancy. The E/A ratio therefore increases in the first trimester, to eventually progressively decrease in the second half of pregnancy. Stronger decline in E/A ratio along with concomitant increase in LAV in hypertensive pregnancies suggest fortified loss in cardiac diastolic function.

Introduction Insights in the adaptation of cardiac output (CO) and peripheral systemic vascular resistance in normal pregnancy may aid in identifying women with deviant adaptation. These women are thought to be at risk for hypertensive related complications during pregnancy. Objectives First, to describe the pattern of CO and peripheral resistance changes in normotensive singleton pregnancies. Second, to explore the adaptation of these variables in pregnancies complicated by hypertension, pre-eclampsia and/or foetal growth restriction. Methods We performed a meta-analysis of systematically reviewed literature on CO and peripheral resistance throughout normotensive and complicated pregnancies, using PubMed (NCBI) and Embase (Ovid) databases. Only studies reporting measurements during pregnancy and non-pregnant reference values were included. Pooled mean differences between pregnant and non-pregnant women were calculated for predefined intervals of gestational age using a random-effects model. Results In total, 92 studies were included in this meta-analysis. In uncomplicated pregnancies, CO progressively increased from the first weeks on. After peaking in the early third trimester (+1.47 L/min, over 30% increase as compared to the non-pregnant reference group), CO declined slightly until term. Next to that, peripheral resistance decreased progressively until early third trimester (−316 dyn · s · cm−5, −24% as compared to the non-pregnant group), after which it increased a little. In the first trimester of complicated pregnancies, an augmented increase in CO was observed (+1.36 L/min versus +0.73 L/min in the uncomplicated pregnancies, p Discussion During normal pregnancy, CO increases and peripheral resistance decreases by 30% and 24% respectively, reaching their maximum measure in the second half of pregnancy. Deviant hemodynamic adaptations showing an initial augmented increase with a cross-over to a low cardiac output might identify pregnancies that will be complicated by hypertension and/or growth restriction.

Introduction One out of four former preeclamptic women shows aberrant cardiac remodelling consistent with subclinical heart failure (HF). These women are prone for the development of remote symptomatic HF, stressing the need to develop a predictive multimarker model for persistent aberrant cardiac geometry postpartum. Objective To develop a potential predictive multimarker model for aberrant cardiac remodelling in former PE patients. Methods In this cross-sectional study, we included 752 women with a history of PE. These women underwent cardiovascular screening between 6 months and 5 years postpartum consisting of echocardiography, systolic and diastolic blood pressure (sys- and diasBP), plasma volume (PV) measurements and venapunction to assess uric acid, C-reactive protein (CRP) and fibrinogen. Determinants for cardiac geometry (left ventricular mass (LVM) and relative wall thickness (RWT)) where assessed with cardiac ultrasound. We used ANCOVA to perform univariate and multivariate analysis. Results Multivariable analysis showed that both SysBP and PV were independently correlated with RWT and LVMi ((b = 0.06, 95% CI 0.03–0.08 and b = 26.24, 95%CI18.07–34.41, P Discussion This study shows a potential role for SysBP, PV, CRP, and uric acid as markers to predict persistent aberrant cardiac remodelling in former preeclamptic women. Future studies should evaluate the predictive value of this model prospectively.

Introduction Data on blood pressure (BP) adaptation in pregnancy show conflicting results on the occurrence of a mid-pregnancy BP drop. These inconsistent findings may contribute to delayed recognition of maladaptation in women at risk for a hypertensive complicated pregnancy. Objective To meta-analytically describe the pattern of BP adaptation in singleton normotensive pregnancies and hypertensive pregnancies. Methods We performeda systematic review and meta-analysis using PubMed and Embase. Studies included, needed to report a reference non-pregnant measurement. Mean differences between pregnant and reference measurements were calculated for systolic BP (SBP) and diastolic BP (DBP) in predefined gestational intervals using a random-effects model. Results In total, 110 studies were included (23079 BP readings). In normotensive pregnancy, both SBP and DBP started to decrease early in pregnancy, reaching their maximum reduction of −3.3% (−3.7 mmHg, (95% CI, −5.1 to −2.3)) and −5.6% (−3.9 mmHg, (95% CI, −4.8 to −3.0)) respectively in the late second trimester. In the third trimester, SBP and DBP gradually increased to reference values. In hypertensive complicated pregnancies, SBP did not decrease, while DBP initially decreased with −7.2% (−5.8 mmHg, (95% CI, −8.3 to −3.4)) in the early second trimester. From the second half of pregnancy onwards, BP increased to values higher than reference. SBP and DBP increased with 35% (38.2 mmHg, (95% CI, 27.3–49.2)) and 37% (26.1 mmHg, (95% CI, 18.4–33.8)) respectively in the hypertensive group, statistically significantly higher than normotensive pregnancies (p Discussion This is the first meta-analysis on BP adaptation during pregnancy. In normotensive pregnancy, both SBP and DBP initially decrease, reaching their nadir in the late second trimester showing a clinically moderate, but statistically significant mid-pregnancy drop. Hypertensive complicated pregnancies lack a SBP decrease in early pregnancy which might reflect impaired vascular compliance in these women.

Objective We sought to explore to what extent the presence of cardiometabolic and cardiovascular risk constitutions differ between pregnancies complicated by small-for-gestational-age (SGA) infancy, preeclampsia (PE), or a combination of both. Study Design We conducted a cohort study in women after pregnancies complicated by placental syndrome with fetal manifestations (SGA infancy [n = 113]), maternal manifestations (PE [n = 729]), or both (n = 461). Independent sample t test was used to compare cardiometabolic and cardiovascular risk factors between groups. Logistic regression was used to calculate odds ratios and adjusted odds ratios of the prevalence of the metabolic syndrome and its constituents between groups. Adjustments were made for maternal age, parity, smoking, interval between delivery and measurements, and intrauterine fetal demise. Results The metabolic syndrome was present in 7.5% of women who delivered SGA infants, 15.6% of former PE women, and 19.8% of women after pregnancy complicated by both SGA and PE. Hypertension was observed in 25% of former PE women and 15% of women with solely SGA. Women who delivered a SGA infant had lower global vascular compliance compared to former PE women without SGA. Conclusion Cardiometabolic risk factors consistent with metabolic syndrome relate to the maternal rather than to the fetal presentation of placental syndrome. Nonetheless, highest incidence of metabolic syndrome was observed in women with both PE and SGA. PE relates to chronic hypertension, whereas increased arterial stiffness seems to be associated with women who deliver a SGA infant.

To study the relationship between volume and pressure load on the one hand and relative wall thickness (RWT) on the other hand in former preeclamptic women.In 654 former PE women, blood pressure (BP) and PV (iodine 125 albumin indicator dilution technique) where measured. PV was indexed for body surface area (BSA). Echocardiography was performed to calculate RWT. The study population was divided in 4 subgroups consisting of women with either normal- or high-systolic BP (sysBP) (140 versus ≥140mmHg, respectively) and normal- or low-PV index (1373 versus ≤1373 ml/m2 respectively). Differences between the four subgroups where analyzed with ANOVA. Pearson's rho is calculated for the correlation between PV and sysBP on the one hand and RWT on the other hand.RWT was the lowest in the group with normal sysBP and normal PV and the highest in the subgroup with high sysBP and low PV subgroup (Table 1). Moreover, PVindex correlated negatively with RWT in the setting of both normal sysBP and high sysBP (Figure 1a and b) while systolic BP correlated positively with RWT in the setting of normal sysBP but not in the setting of high sysBP (Figure 1c and d).Raised RWT, as a measure for concentric remodelling, relates to both decreased volume load and increased pressure load.

Objectives Directly measuring the spiral arteries instead of the uterine arteries could better reflect the pathological process underlying placenta insufficiency related diseases collectively known as placenta syndrome (PS). The purpose of this study is to examine if the blood flow velocity of spiral arteries in placenta syndrome-pregnancies is higher compared to healthy pregnancies and can be affected by location of spiral arteries. Methods A cross sectional study was conducted in woman between 24 and 42 weeks of gestation reporting at the department of obstetrics in the MUMC+. Using a Voluson E8TM abdominal transducer with predefined settings, spiral artery flow velocity indices were measured in women with PS (preeclampsia, preterm delivery, pregnancy induced hypertension and intra uterine growth restriction) and compared to women with uncomplicated pregnancies. Results Spiral artery Dopplers were successfully obtained in 32 PS- and 14 control pregnancies. Both groups were comparable in characteristics, except for diastolic blood pressure (73.4 ± 12.1 vs. 62 ± 6.8 mmHg, p = 0.02). Mean peak systolic velocity (PSV) in spiral arteries showed a linear decrease with advancing gestational age in both groups (0.94 ± 0.5 cm/s/week), but was significant higher in PS-group (32.5 ± 8.7 cm/s) compared to control group (24.5 ± 7.1 cm/s, p = 0.03). As expected, the mean PSV of the centrally localized spiral arteries was lower compared to the peripherally localized spiral arteries in the control group (24.5 ± 7.1 cm/s vs. 34.1 ± 14.6 cm/s, p = 0.14). No such difference was found in the PS-group (34.3 ± 8.7 vs. 34.6 ± 23.4 cm/s, p = 0.87). Conclusions Mean blood flow velocity of spiral arteries in placental syndrome pregnancies is higher compared to healthy pregnancies, suggesting that inadequate conversion of the spiral arteries can lead to placental syndrome. These promising findings need to be tested in a prospective cohort to determine the predictive value of spiral artery Dopplers in high risk pregnancies.

Preeclampsia is thought to be preceded by first trimester circulatory maladaptation. Early and late onset PE may exhibit two different cardiac and hemodynamic states. Moreover, early PE relates to postpartum impaired cardiac function. Incomplete resolved or impaired cardiac function may influence the pattern of cardiac adaptation in the next pregnancy and may relate to recurrent disease. We postulate that in women with a history of early PE, the pattern of early cardiac adaptation differs between those that do and those that do not develop recurrent disease.We hypothesize that after early onset PE, in the subsequent gestation, the pattern of cardiac adaptation differs between those that do and those that do not develop recurrent disease.In this cohort study, we included 84 women with a history of early-onset PE. Former PE patients who concomitantly experienced HELLP-syndrome, fetal growth restriction and/or fetal demise, were excluded. The remaining 51 women underwent serial cardiac ultrasound and automated blood pressure and heart rate recordings, once before, and again at gestational age 12, 16 and 20 weeks. Post hoc, women were subdivided into those who did (RECUR) or did not develop recurrent PE (CONTR). We analyzed data using repeated measures analysis of variance.14/51 (27%) women developed recurrent PE. Pre-pregnant heart rate was higher (71 vs 64 bpm, p0.05) and stroke volume lower (68 vs 77mL, p0.05) in RECUR as compared to CONTR. Even though LVM index was consistently lower in the RECUR group, the two subgroups responded to the next pregnancy with a comparable pattern of cardiac adaptation.Despite consistently lower LVM and SV and higher HR, after early onset PE, the pattern of subsequent early pregnancy cardiac adaptation is comparable in those that do and do not develop recurrent disease.