Quantification of left ventricular myocardial strain: Comparison between MRI tagging, MRI feature tracking, and ultrasound speckle tracking.

Ultrasound speckle tracking is frequently used to quantify myocardial strain, and magnetic resonance imaging (MRI) feature tracking is rapidly gaining interest. Our aim is to validate cardiac MRI feature tracking by comparing it with the gold standard method (i.e., MRI tagging) in healthy subjects and patients. Furthermore, we aim to perform an indirect validation by comparing ultrasound speckle tracking with MRI feature tracking. Forty-two subjects (17 formerly preeclamptic women, three healthy women, and 22 left bundle branch block patients of both sexes) received 3-T cardiac MRI and echocardiography. Cine and tagged MRI, and B-mode ultrasound images, were acquired. Intrapatient global and segmental left ventricular circumferential (MRI tagging vs. MRI feature tracking) and longitudinal (MRI feature tracking vs. ultrasound speckle tracking) peak strain and time to peak strain were compared between the three techniques. Intraclass correlation coefficient (ICC) (< 0.50 = poor, 0.50-0.75 = moderate, > 0.75-0.90 = good, > 0.90 = excellent) and Bland-Altman analysis were used to assess correlation and bias; p less than 0.05 indicates a significant ICC or bias. Global peak strain parameters showed moderate-to-good correlations between methods (ICC = 0.71-0.83, p < 0.01) with no significant biases. Global time to peak strain parameters showed moderate-to-good correlations (ICC = 0.56-0.82, p < 0.01) with no significant biases. Segmental peak strains showed significant biases in all parameters and moderate-to-good correlation (ICC = 0.62-0.77, p < 0.01), except for lateral longitudinal peak strain (ICC = 0.23, p = 0.22). Segmental time to peak strain parameters showed moderate-to-good correlation (ICC = 0.58-0.74, p < 0.01) with no significant biases. MRI feature tracking is a valid method to examine myocardial strain, but there is bias in absolute segmental strain values between imaging techniques. MRI feature tracking shows adequate comparability with ultrasound speckle tracking.

Active plasma renin concentration throughout healthy and complicated pregnancy: a systematic review and meta-analysis.

BACKGROUND: Pregnancy is characterized by profound circulatory changes and compensatory adjustments in the renin-angiotensin-aldosterone system (RAAS). Differences in regulatory response may antedate or accompany vascular complicated pregnancy. We performed a systematic review and meta-analysis to delineate the trajectory of active plasma renin concentration (APRC) in healthy pregnancy and compare this to complicated pregnancy. METHODS: We performed a systematic review and meta-analysis on APRC during normotensive and hypertensive pregnancies, using PubMed (NCBI) and Embase (Ovid) databases. We included only studies reporting measurements during pregnancy together with a nonpregnant reference group measurement. Risk of bias was assessed with QUIPS. Ratio of the mean (ROM) and 95% confidence intervals (CI) of APRC values between pregnant and nonpregnant women were estimated for predefined intervals of gestational age using a random-effects model. Meta-regression was used to analyze APRC over time. RESULTS: In total, we included 18 studies. As compared to nonpregnant, APRC significantly increased as early as the first weeks of healthy pregnancy and stayed increased throughout the whole pregnancy (ROM 2.77; 95% CI 2.26-3.39). APRC in hypertensive complicated pregnancy was not significantly different from nonpregnancy (ROM 1.32; 95% CI 0.97-1.80). CONCLUSION: Healthy pregnancy is accompanied by a profound rise in APRC in the first trimester that is maintained until term. In hypertensive complicated pregnancy, this increase in APRC is not observed.

Attenuated cognitive functioning decades after preeclampsia.

BACKGROUND: Preeclampsia, a hypertensive pregnancy disorder, is a leading cause of maternal and fetal morbidity and mortality, with remote cardio- and cerebrovascular implications. After preeclampsia, women may report serious disabling cognitive complaints, especially involving executive function, but the extent and time course of these complaints are unknown. OBJECTIVE: This study aimed to determine the impact of preeclampsia on perceived maternal cognitive functioning decades after pregnancy. STUDY DESIGN: This study is part of a cross-sectional case-control study named Queen of Hearts (ClinicalTrials.gov Identifier: NCT02347540), a collaboration study of 5 tertiary referral centers within the Netherlands investigating long-term effects of preeclampsia. Eligible participants were female patients aged ≥18 years after preeclampsia and after normotensive pregnancy between 6 months and 30 years after their first (complicated) pregnancy. Preeclampsia was defined as new-onset hypertension after 20 weeks of gestation along with proteinuria, fetal growth restriction, or other maternal organ dysfunction. Women with a history of hypertension, autoimmune disease, or kidney disease before their first pregnancy were excluded. Attenuation of higher-order cognitive functions, that is, executive function, was measured with the Behavior Rating Inventory of Executive Function for Adults. Crude and covariate-adjusted absolute and relative risks of clinical attenuation over time after (complicated) pregnancy were determined with moderated logistic and log-binomial regression. RESULTS: This study included 1036 women with a history of preeclampsia and 527 women with normotensive pregnancies. Regarding overall executive function, 23.2% (95% confidence interval, 19.0-28.1) of women experienced clinically relevant attenuation after preeclampsia, as opposed to 2.2% (95% confidence interval, 0.8-6.0) of controls immediately after childbirth (adjusted relative risk, 9.20 [95% confidence interval, 3.33-25.38]). Group differences diminished yet remained statistically significant (P < .05) at least 19 years postpartum. Regardless of history of preeclampsia, women with lower educational attainment, mood or anxiety disorders, or obesity were especially at risk. Neither severity of preeclampsia, multiple gestation, method of delivery, preterm birth, nor perinatal death was related to overall executive function. CONCLUSION: After preeclampsia, women were 9 times more likely to experience clinical attenuation of higher-order cognitive functions as opposed to after normotensive pregnancy. Despite overall steady improvement, elevated risks persisted over decades after childbirth.

Differences and Similarities Among COVID-19 Patients Treated in Seven ICUs in Three Countries Within One Region: An Observational Cohort Study.

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.

Spiral artery blood flow during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Downstream remodeling of the spiral arteries (SpA) decreases utero-placental resistance drastically, allowing sustained and increased blood flow to the placenta under all circumstances. We systematically evaluated available reports to visualize adaptation of spiral arteries throughout pregnancy by ultra-sonographic measurements and evaluated when this process is completed. METHODS: A systematic review and meta-analysis of spiral artery flow (pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV)) was performed. English written articles were obtained from Pubmed, EMBASE and Cochrane Library and included articles were assessed on quality and risk of bias. Weighted means of Doppler indices were calculated using a random-effects model. RESULTS: In healthy pregnancies, PI and RI decreased from 0.80 (95% CI: 0.70-0.89) and 0.50 (95% CI: 0.47-0.54) in the first trimester to 0.50 (95% CI: 0.45-0.55, p < 0.001) and 0.39 (95% CI: 0.37-0.42, p < 0.001) in the second trimester and to 0.49 (95% CI: 0.44-0.53, p = 0.752) and 0.36 (95% CI: 0.35-0.38, p = 0.037) in the third trimester, respectively. In parallel, PSV altered from 0.22 m/s (95% CI: 0.13-0.30 m/s) to 0.28 m/s (95% CI: 0.17-0.40 m/s, p = 0.377) and to 0.25 m/s (95% CI: 0.20-0.30 m/s, p = 0.560) in the three trimesters. In absence of second and third trimester Doppler data in complicated gestation, only a difference in PI was observed between complicated and healthy pregnancies during the first trimester (1.49 vs 0.80, p < 0.001). Although individual studies have identified differences in PI between SpA located in the central part of the placental bed versus those located at its periphery, this meta-analysis could not confirm this (p = 0.349). CONCLUSIONS: This review and meta-analysis concludes that an observed decrease of SpA PI and RI from the first towards the second trimester parallels the physiological trophoblast invasion converting SpA during early gestation, a process completed in the midst of the second trimester. Higher PI was found in SpA of complicated pregnancies compared to healthy pregnancies, possibly reflecting suboptimal utero-placental circulation. Longitudinal studies examining comprehensively the predictive value of spiral artery Doppler for complicated pregnancies are yet to be carried out.

Study protocol for the randomized controlled EVA (early vascular adjustments) trial: tailored treatment of mild hypertension in pregnancy to prevent severe hypertension and preeclampsia.

BACKGROUND: In contrast to severe gestational hypertension, it is questioned whether antihypertensive medication for mild to moderate gestational hypertension prevents adverse maternal and offspring outcomes. Hypertensive drugs halve the risk of severe hypertension, but do not seem to prevent progression to preeclampsia or reduce the risk of complications in offspring. In fact, beta-blockers, a first line therapy option, are suspected to impair foetal growth. Disappointing effects of antihypertensive medication can be anticipated when the pharmacological mode of action does not match the underlying haemodynamic imbalance. Hypertension may result from 1) high cardiac output, low vascular resistance state, in which beta blockade is expected to be most effective, or 2) low cardiac output, high vascular resistance state where dihydropyridine calcium channel blockers or central-acting alpha agonists might be the best corrective medication. In the latter, beta-blockade might be maternally ineffective and even contribute to impaired foetal growth by keeping cardiac output low. We propose a randomized controlled trial to determine whether correcting the haemodynamic imbalance in women with mild to moderate hypertension reduces the development of severe hypertension and/or preeclampsia more than non-pharmacological treatment does, without alleged negative effects on foetal growth. METHODS: Women diagnosed with mild to moderate hypertension without proteinuria or signs of other organ damage before 37 weeks of pregnancy are invited to participate in this randomized controlled trial. Women randomized to the intervention group will be prescribed tailored antihypertensive medication, using a simple diagnostic and treatment algorithm based on the mean arterial pressure/heart rate ratio, which serves as an easy-to-determine proxy for maternal circulatory state. Women randomized to the control group will receive non-pharmacological standard care according to national and international guidelines. In total, 208 women will be randomized in a 1:1 ratio. The primary outcome is progression to severe hypertension and preeclampsia and the secondary outcomes are adverse maternal and neonatal outcomes. DISCUSSION: This trial will provide evidence of whether tailoring treatment of mild to moderate gestational hypertension to the individual haemodynamic profile prevents maternal disease progression. TRIAL REGISTRATION: NCT02531490 , registered on 24 August 2015.

Early-Pregnancy Circulating Antioxidant Capacity and Hemodynamic Adaptation in Recurrent Placental Syndrome: An Exploratory Study.

BACKGROUND/AIMS: Placental syndromes (PS) refer to pregnancy complications that include gestational hypertension, (pre)eclampsia, HELLP syndrome, and/or placental insufficiency-induced fetal growth restriction. These disorders are characterized by increased oxidative stress. This study aims to test the hypothesis that the abnormal hemodynamic adaptation to pregnancy, typical for early PS pregnancy, is accompanied by abnormal maternal levels of antioxidants relative to those in normal pregnancy. METHODS: Before, and at 12, 16, and 20 weeks pregnancy, we measured trolox equivalent antioxidant capacity (TEAC), uric acid (UA), and TEACC (TEAC corrected for UA) in maternal serum of former PS patients, who either developed recurrent PS (rPS; n = 16) or had a normal next pregnancy (non-rPS; n = 23). Concomitantly, we also measured various hemodynamic variables. RESULTS: rPS differed from non-rPS by higher TEACC levels before pregnancy (178 vs. 152 µM; p = 0.02) and at 20 weeks pregnancy (180 vs. 160 µM; p = 0.04). Only non-rPS responded to pregnancy by significant rises in hemodynamic measures. CONCLUSION: These data indicate that rPS pregnancies are preceded by an increase in antioxidant capacity, presumably induced by subclinical vascular injury and low-grade chronic inflammation.

Circulating Fibronectin and Plasminogen Activator Inhibitor-2 Levels as Possible Predictors of Recurrent Placental Syndrome: An Exploratory Study.

BACKGROUND/AIM: Placental syndromes (PS) are characterized by endothelial dysfunction complicating placental dysfunction. Possible markers for endothelial dysfunction and amount of trophoblast are fibronectin and plasminogen activator inhibitor-2 (PAI-2), respectively. We aimed (1) to determine whether in women with recurrent PS (rPS), this complication is preceded by deviating fibronectin- and PAI-2-levels, and (2) whether this is dependent on pre-pregnant plasma volume (PV). METHODS: In 36 former patients, we determined fibronectin- and PAI-2-levels in blood-samples collected preconceptionally and at 12-16 weeks in their next pregnancy. Differences were analyzed between pregnancies with rPS (n = 12) and without rPS (non-rPS, n = 24) using linear mixed models, with subanalyses based on pre-pregnant normal or subnormal PV. RESULTS: We observed higher fibronectin-levels at 12-16 weeks (p < 0.05 and p < 0.01, respectively) and lower PAI-2-levels at 16 weeks (p < 0.01) in the rPS subgroup, the intergroup differences being larger in women with subnormal PV. CONCLUSION: We showed that former PS patients who developed rPS have raised fibronectin- and reduced PAI-2-levels already in early/mid pregnancy. These deviations are even more prominent in women with subnormal pre-pregnant PV, supporting development of a 2-step screening program for former patients to identify the high-risk subgroup of women who may benefit from closer surveillance.

Maternal metabolic syndrome, preeclampsia, and small for gestational age infancy.

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.

DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia (DECONNECT): research protocol for a cross-sectional pilot study.

INTRODUCTION: Pre-eclampsia is a hypertensive disorder affecting up to 8% of pregnancies. After pre-eclampsia, women are at increased risk of cognitive problems, and cerebrovascular and cardiovascular disorders. These sequelae could result from microvascular dysfunction persisting after pre-eclampsia. This study will explore differences in cerebral and myocardial microvascular function between women after pre-eclampsia and women after normotensive gestation. We hypothesise that pre-eclampsia alters cerebral and myocardial microvascular functions, which in turn are related to diminished cognitive and cardiac performance. METHODS AND ANALYSIS: The cross-sectional 'DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia' (DECONNECT) pilot study includes women after pre-eclampsia and controls after normotensive pregnancy between 6 months and 20 years after gestation. We recruit women from the Queen of Hearts study, a study investigating subclinical heart failure after pre-eclampsia. Neuropsychological tests are employed to assess different cognitive domains, including attention, processing speed, and cognitive control. Cerebral images are recorded using a 7 Tesla MRI to assess blood-brain barrier integrity, perfusion, blood flow, functional and structural networks, and anatomical dimensions. Cardiac images are recorded using a 3 Tesla MRI to assess cardiac perfusion, strain, dimensions, mass, and degree of fibrosis. We assess the effect of a history of pre-eclampsia using multivariable regression analyses. ETHICS AND DISSEMINATION: This study is approved by the Ethics Committee of Maastricht University Medical Centre (METC azM/UM, NL47252.068.14). Knowledge dissemination will include scientific publications, presentations at conferences and public forums, and social media. TRIAL REGISTRATION NUMBER: NCT02347540.

Peripartum and Long-Term Maternal Cardiovascular Health After Preeclampsia.

There is widespread acceptance of the increased prevalence of cardiovascular diseases occurring within 1 to 2 decades in women following a preeclamptic pregnancy. More recent evidence suggests that the deranged biochemical and echocardiographic findings in women do not resolve in the majority of preeclamptic women following giving birth. Many women continue to be hypertensive in the immediate postnatal period with some exhibiting occult signs of cardiac dysfunction. There is now promising evidence that with close monitoring and effective control of blood pressure control in the immediate postnatal period, women may have persistently lower blood pressures many years after stopping their medication. This review highlights the evidence that delivering effective medical care in the fourth trimester of pregnancy can improve the long-term cardiovascular health after a preeclamptic birth.

Prediction Model Based on Easily Available Markers for Aberrant Cardiac Remodeling in Women After Pregnancy.

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.

Sex Differences in the Anti-Hypertensive Effect of Calcium-Channel Blockers: A Systematic Review and Meta-Analysis.

Cardiovascular disease (CVD) is the number one cause of death worldwide, with hypertension as the leading risk factor for both sexes. As sex may affect responsiveness to antihypertensive compounds, guidelines for CVD prevention might necessitate divergence between females and males. To this end, we studied the effectiveness of calcium channel blockers (CCB) on blood pressure (BP), heart rate (HR) and cardiac function between sexes. We performed a systematic review and meta-analysis on studies on CCB from inception to May 2020. Studies had to present both baseline and follow-up measurements of the outcome variables of interest and present data in a sex-stratified manner. Mean differences were calculated using a random-effects model. In total, 38 studies with 8202 participants were used for this review. In females as compared to males, systolic BP decreased by -27.6 mmHg (95%CI -36.4; -18.8) (-17.1% (95%CI -22.5;-11.6)) versus -14.4 mmHg (95%CI -19.0; -9.9) (-9.8% (95%CI -12.9;-6.7)) (between-sex difference p < 0.01), diastolic BP decreased by -14.1 (95%CI -18.8; -9.3) (-15.2%(95%CI -20.3;-10.1)) versus -10.6 mmHg (95%CI -14.0; -7.3) (-11.2% (95%CI -14.8;-7.7)) (between-sex difference p = 0.24). HR decreased by -1.8 bpm (95%CI -2.5; -1.2) (-2.5% (95%CI -3.4; -1.6)) in females compared to no change in males (0.3 bpm (95% CI -1.2; 1.8)) (between-sex difference p = 0.01). In conclusion, CCB lowers BP in both sexes, but the observed effect is larger in females as compared to males.

Vascular Function, Systemic Inflammation, and Coagulation Activation 18 Months after COVID-19 Infection: An Observational Cohort Study.

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.

Exploring Sex Differences of Beta-Blockers in the Treatment of Hypertension: A Systematic Review and Meta-Analysis.

AIMS: In the prevention of cardiovascular morbidity and mortality, early recognition and adequate treatment of hypertension are of leading importance. However, the efficacy of antihypertensives may be depending on sex disparities. Our objective was to evaluate and quantify the sex-diverse effects of beta-blockers (BB) on hypertension and cardiac function. We focussed on comparing hypertensive female versus male individuals. METHODS AND RESULTS: A systematic search was performed for studies on BBs from inception to May 2020. A total of 66 studies were included that contained baseline and follow up measurements on blood pressure (BP), heart rate (HR), and cardiac function. Data also had to be stratified for sex. Mean differences were calculated using a random-effects model. In females as compared to males, BB treatment decreased systolic BP 11.1 mmHg (95% CI, -14.5; -7.8) vs. 11.1 mmHg (95% CI, -14.0; -8.2), diastolic BP 8.0 mmHg (95% CI, -10.6; -5.3) vs. 8.0 mmHg (95% CI, -10.1; -6.0), and HR 10.8 beats per minute (bpm) (95% CI, -17.4; -4.2) vs. 9.8 bpm (95% CI, -11.1; -8.4)), respectively, in both sexes' absolute and relative changes comparably. Left ventricular ejection fraction increased only in males (3.7% (95% CI, 0.6; 6.9)). Changes in left ventricular mass and cardiac output (CO) were only reported in males and changed -20.6 g (95% CI, -56.3; 15.1) and -0.1 L (95% CI, -0.5; 0.2), respectively. CONCLUSIONS: BBs comparably lowered BP and HR in both sexes. The lack of change in CO in males suggests that the reduction in BP is primarily due to a decrease in vascular resistance. Furthermore, females were underrepresented compared to males. We recommend that future research should include more females and sex-stratified data when researching the treatment effects of antihypertensives.

Biomarkers of sustained systemic inflammation and microvascular dysfunction associated with post-COVID-19 condition symptoms at 24 months after SARS-CoV-2-infection.

Introduction: Comprehensive studies investigating sustained hypercoagulability, endothelial function, and/or inflammation in relation to post-COVID-19 (PCC) symptoms with a prolonged follow-up are currently lacking. Therefore, the aim of this single-centre cohort study was to investigate serum biomarkers of coagulation activation, microvascular dysfunction, and inflammation in relation to persisting symptoms two years after acute COVID-19. Methods: Patients diagnosed with acute SARS-CoV-2 infection between February and June 2020 were recruited. Outcome measures included the CORona Follow-Up (CORFU) questionnaire, which is based on an internationally developed and partially validated basic questionnaire on persistent PCC symptoms. Additionally, plasma biomarkers reflecting coagulation activation, endothelial dysfunction and systemic inflammation were measured. Results: 167 individuals were approached of which 148 (89%) completed the CORFU questionnaire. At 24 months after acute infection, fatigue was the most prevalent PCC symptom (84.5%). Over 50% of the patients experienced symptoms related to breathing, cognition, sleep or mobility; 30.3% still experienced at least one severe or extreme (4 or 5 on a 5-point scale) PCC symptom. Multiple correlations were found between several PCC symptoms and markers of endothelial dysfunction (endothelin-1 and von Willebrand factor) and systemic inflammation (Interleukin-1 Receptor antagonist). No positive correlations were found between PCC symptoms and coagulation complexes. Discussion: In conclusion, this study shows that at 24 months after acute COVID-19 infection patients experience a high prevalence of PCC symptoms which correlate with inflammatory cytokine IL-1Ra and markers of endothelial dysfunction, especially endothelin-1. Our data may provide a rationale for the selection of treatment strategies for further clinical studies. Trial registration: This study was performed in collaboration with the CORona Follow-Up (CORFU) study (NCT05240742, https://clinicaltrials.gov/ct2/show/ NCT05240742).

The Representation of Females in Studies on Antihypertensive Medication over the Years: A Scoping Review.

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.

Characteristics of the Maternal Jugular Venous Pulse Waveform by Combined Doppler-Electrocardiogram Assessment.

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.

Noninvasive Cardiac Imaging in Formerly Preeclamptic Women for Early Detection of Subclinical Myocardial Abnormalities: A 2022 Update.

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.