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Mahan VL. Heme oxygenase/carbon monoxide system affects the placenta and preeclampsia. Med Gas Res 2025; 15:276-287. [PMID: 39829164 PMCID: PMC11918472 DOI: 10.4103/mgr.medgasres-d-24-00081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/17/2024] [Accepted: 11/25/2024] [Indexed: 01/22/2025] Open
Abstract
Preeclampsia affects 2% to 8% of pregnancies worldwide and results in significantly high maternal and perinatal morbidity and mortality, with delivery being the only definitive treatment. It is not a single disorder, but rather a manifestation of an insult(s) to the uteroplacental unit -whether maternal, fetal, and/or placental. Multiple etiologies have been implicated, including uteroplacental ischemia, maternal infection and/or inflammation, maternal obesity, sleep disorders, hydatidiform mole, maternal intestinal dysbiosis, autoimmune disorders, fetal diseases, breakdown of maternal-fetal immune tolerance, placental aging, and endocrine disorders. Early- and late-onset preeclampsia are associated with different etiologies: early-onset preeclampsia develops because of poor placentation, while late-onset preeclampsia occurs in women with latent maternal endothelial dysfunction. In preeclamptic placentas, acquired, genetic, and immune risk factors may result in impaired trophoblast invasion and spiral artery remodeling, which affects uteroplacental perfusion. The resulting placental hypoxia affects the heme oxygenase system-a known stress response pathway affected by hypoxia that is important during normal pregnancy and may offer a therapeutic approach in preeclampsia. This review will address the effect of the heme oxygenase/carbon monoxide system on the placenta and preeclampsia.
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Affiliation(s)
- Vicki L. Mahan
- Department of Surgery, Queen Elizabeth Central Hospital, Blantyre, Malawi
- Drexel University Medical School, Philadelphia, PA, USA
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2
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Ghossein‐Doha C, Thilaganathan B, Vaught AJ, Briller JE, Roos‐Hesselink JW. Hypertensive pregnancy disorder, an under-recognized women specific risk factor for heart failure? Eur J Heart Fail 2025; 27:459-472. [PMID: 39563186 PMCID: PMC11955315 DOI: 10.1002/ejhf.3520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 09/26/2024] [Accepted: 10/24/2024] [Indexed: 11/21/2024] Open
Abstract
During pregnancy, the maternal cardiovascular (CV) system undergoes major haemodynamic alterations ensuring adequate placental perfusion and a healthy pregnancy course. Hypertensive disorders of pregnancy (HDP) occur in almost 10% of gestations and preeclampsia, a more severe form, in 3-4%. Women with HDP demonstrated impaired myocardial function, biventricular chamber dysfunction and adverse biventricular remodelling. Shortly after delivery, women who experienced HDP express increased risk of classic CV risk factors such as hypertension, renal disease, abnormal lipid profile, and diabetes. Within the first two decades following a HDP, women experience increased rates of heart failure, chronic hypertension, ischaemic heart and cerebral disease. The mechanism underlying the relationship between HDP in younger women and CV disease later in life could be explained by sharing pre-pregnancy CV risk factors or due to a direct impact of HDP on the maternal CV system conferring a state of increased susceptibility to future metabolic or haemodynamic insults. Racial disparities in CV risk and social determinants of health also play an important role in their remote CV risk. Although there is general agreement that women who suffered from HDP should undertake early CV screening to allow appropriate prevention and timely treatment, a screening and intervention protocol has not been standardized due to limited available evidence. In this review, we discuss why women with hypertensive pregnancy may be disproportionately affected by heart failure with preserved ejection fraction and how cardiac remodelling during or after pregnancy may influence its development.
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Affiliation(s)
- Chahinda Ghossein‐Doha
- Cardiovascular Institute, Thorax Center, Department of CardiologyErasmus Medical CenterRotterdamThe Netherlands
| | - Basky Thilaganathan
- Molecular and Clinical Sciences Research InstituteSt. George's University of LondonLondonUK
- Fetal Medicine Unit, Department of Obstetrics and GynaecologySt George's University Hospitals NHS Foundation TrustLondonUK
| | - Arthur Jason Vaught
- Department of Gynecology and ObstetricsJohns Hopkins University School of MedicineBaltimoreMDUSA
| | - Joan E. Briller
- Division of Cardiology, Department of Medicine and Department of Obstetrics and GynecologyUniversity of Illinois ChicagoChicagoILUSA
| | - Jolien W. Roos‐Hesselink
- Cardiovascular Institute, Thorax Center, Department of CardiologyErasmus Medical CenterRotterdamThe Netherlands
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Vasapollo B, Novelli GP, Maellaro F, Gagliardi G, Pais M, Silvestrini M, Pometti F, Farsetti D, Valensise H. Maternal cardiovascular profile is altered in the preclinical phase of normotensive early and late intrauterine growth restriction. Am J Obstet Gynecol 2025; 232:312.e1-312.e21. [PMID: 38763339 DOI: 10.1016/j.ajog.2024.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 05/01/2024] [Accepted: 05/13/2024] [Indexed: 05/21/2024]
Abstract
BACKGROUND The maternal cardiovascular profile of patients who develop late fetal growth restriction has yet to be well characterized, however, a subclinical impairment in maternal hemodynamics and cardiac function may be present before pregnancy and may become evident because of the hemodynamic alterations associated with pregnancy. OBJECTIVE This study aimed to investigate if maternal hemodynamics and the cardiovascular profile might be different in the preclinical stages (22-24 weeks' gestation) in cases of early and late fetal growth restriction in normotensive patients. STUDY DESIGN This was a prospective echocardiographic study of 1152 normotensive nulliparous pregnant women at 22 to 24 weeks' gestation. The echocardiographic evaluation included morphologic parameters (left ventricular mass index and relative wall thickness, left atrial volume index) and systolic and diastolic maternal left ventricular function (ejection fraction, left ventricular global longitudinal strain, E/A ratio, and E/e' ratio). Patients were followed until the end of pregnancy to note the development of normotensive early or late fetal growth restriction. RESULTS Of the study cohort, 1049 patients had no complications, 73 were classified as having late fetal growth restriction, and 30 were classified as having early fetal growth restriction. In terms of left ventricular morphology, the left ventricular end-diastolic diameter was greater in uneventful pregnancies (4.84±0.28 cm) than in late (4.67±0.26 cm) and in early (4.55±0.26 cm) (P<.001) fetal growth restriction cases, whereas left ventricular end-systolic diameter was smaller in uneventful pregnancies (2.66±0.39 cm) than in late (2.83±0.40 cm) and in early (2.82±0.38 cm) (P<.001) fetal growth restriction cases. The relative wall thickness was slightly higher in early (0.34±0.05) and late (0.35±0.04) fetal growth restriction cases than in uneventful pregnancies (0.32±0.05) (P<.05). In terms of systolic left ventricular function, at 22 to 24 weeks' gestation, cardiac output was higher in uneventful pregnancies (6.58±1.07 L/min) than in late (5.40±0.97 L/min) and in early (4.76±1.05 L/min) (P<.001) fetal growth restriction cases with the lowest values in the early-onset group. Left ventricular global longitudinal strain was lower in appropriate for gestational age neonates (-21.6%±2.0%) and progressively higher in late (-20.1%±2.2%) and early (-18.5%±2.3%) (P<.001) fetal growth restriction cases. In terms of diastolic left ventricular function, the E/e' ratio showed intermediate values in the late fetal growth restriction group (7.90±2.73) when compared with the appropriate for gestational age group (7.24±2.43) and with the early fetal growth restriction group (10.76±3.25) (P<.001). The total peripheral vascular resistance was also intermediate in the late fetal growth restriction group (1300±199 dyne·s·cm-5) when compared with the appropriate for gestational age group (993±175 dyne·s·cm-5) and the early fetal growth restriction group (1488±255 dyne.s.cm-5) (P<.001). CONCLUSION Early and late fetal growth restriction share similar maternal hemodynamic and cardiovascular profiles with a different degree of expression. These features are already present at 22 to 24 weeks' gestation and are characterized by a hypodynamic state. The degree of these cardiovascular changes may influence the timing of the manifestation of the disease; a hypovolemic, high resistance, low cardiac output state might be associated with early-onset fetal growth restriction, whereas a milder hypovolemic state seems to favor the development of the disease in the final stages of pregnancy.
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Affiliation(s)
- Barbara Vasapollo
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy; Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy
| | - Gian Paolo Novelli
- Prehospitalization Unit, Department of Integrated Care Processes, Policlinico di Tor Vergata, Rome, Italy.
| | - Filomena Maellaro
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy; Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy
| | - Giulia Gagliardi
- Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy
| | - Marcello Pais
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy
| | - Marco Silvestrini
- Prehospitalization Unit, Department of Integrated Care Processes, Policlinico di Tor Vergata, Rome, Italy; Department of Sports Medicine, Tor Vergata University, Rome, Italy
| | - Francesca Pometti
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy
| | - Daniele Farsetti
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy; Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy
| | - Herbert Valensise
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy; Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy
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Yerlikaya-Schatten G, Karner E, Heinzl F, Prausmüller S, Kastl S, Springer S, Zilberszac R. Cardiac function in pregnant women with preeclampsia. Front Cardiovasc Med 2024; 11:1415727. [PMID: 39741662 PMCID: PMC11685740 DOI: 10.3389/fcvm.2024.1415727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 11/26/2024] [Indexed: 01/03/2025] Open
Abstract
Introduction Preeclampsia (PE) is thought to be the consequence of impaired placental perfusion leading to placental hypoxia. While it has been demonstrated that PE may be a consequence of maternal cardiovascular maladaptation, the exact role of maternal cardiac function remains to be determined. This study sought to assess cardiac characteristics in pregnant women diagnosed with PE and to determine the possible relationship between PE, maternal cardiac changes/function, and NT-proBNP levels. Methods This was a retrospective analysis of 65 pregnant women diagnosed with PE who had an echocardiographic examination during pregnancy. Where available, NT-proBNP levels were analyzed. All patients underwent a comprehensive echocardiographic examination based on a standardized examination protocol. Results Left ventricular size was within the normal range, and there was normal radial left ventricular function. Longitudinal contractility was impaired with a global longitudinal strain of -17.8% (quartiles -20.2 to -15.4). The cardiac index was in the normal range with a median of 3.2 ml/min/m2 (quartiles 2.6-4.0). The left atrium was of borderline size in longitudinal diameter [50 (44.8-54.3) mm], but within the normal range in volumetric index [27.3 (22.9-37.3) ml/m2]. Furthermore, mild left ventricular hypertrophy [septal thickness 12 (10-13) mm] and at least borderline elevated filling pressures with an E/e' ratio of 10.6 (8.5-12.9) were found. Maximal tricuspid regurgitation velocity [2.9 (2.5-3.3) m/s] and derived systolic pulmonary pressure [38 (29.5-44.5) mmHg] were borderline elevated. Regarding NT-proBNP levels, an increase in NT-proBNP levels correlated with a decrease in gestational age at delivery (p < 0.0002) and maternal cardiac changes. Obstetric characteristics showed a preterm rate of 71.43%, mostly due to maternal aggravation of PE or because of fetal signs of deprivation based on placental insufficiency. Neonatal deaths occurred in five cases (7.69%). Conclusion Changes in cardiac function in the context of hypertensive pregnancy diseases can be observed with regard to various echocardiographic parameters. Furthermore, there is a significant association between NT-proBNP levels and a decrease in gestational age at delivery in women with PE, which thus might be useful as a prognostic factor for the management of women with preeclampsia and changes in maternal cardiac function during pregnancy.
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Affiliation(s)
- Gülen Yerlikaya-Schatten
- Department of Obstetrics and Gynecology, Division of Obstetrics and Feto-maternal Medicine, Medical University of Vienna, Vienna, Austria
| | - Eva Karner
- Department of Obstetrics and Gynecology, Division of Obstetrics and Feto-maternal Medicine, Medical University of Vienna, Vienna, Austria
| | - Florian Heinzl
- Department of Obstetrics and Gynecology, Division of Obstetrics and Feto-maternal Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Stefan Kastl
- Department of Cardiology, Medical University of Vienna, Vienna, Austria
| | - Stephanie Springer
- Department of Obstetrics and Gynecology, Division of Obstetrics and Feto-maternal Medicine, Medical University of Vienna, Vienna, Austria
| | - Robert Zilberszac
- Department of Cardiology, Medical University of Vienna, Vienna, Austria
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Liu J, Dong Y, Zhou Y, Wang W, Li Y, Pei J. Exploring genetic associations between immune cells and hypertensive disorder of pregnancy using Mendelian randomization. BMC Pregnancy Childbirth 2024; 24:756. [PMID: 39548401 PMCID: PMC11566496 DOI: 10.1186/s12884-024-06950-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 11/04/2024] [Indexed: 11/18/2024] Open
Abstract
BACKGROUND Observational epidemiological studies suggested that immunological dysregulation and inflammation play a significant role in the placental and renal dysfunction that leads to maternal hypertension. The immunophenotypes' possible causalities with hypertensive disease of pregnancy remain ambiguous. We performed two-sample Mendelian randomization (MR) analyses to comprehensively investigate the causal effect of immunophenotypes on hypertensive disorder of pregnancy (HDP). METHODS The large-scale genome-wide association studies (GWASs) data on immunological traits was taken from public catalog for 731 immunophenotypes. The summarized GWAS data in 4 types of HDP were retrieved from FinnGen database, including 811,605 Finnish individuals. The primary analysis was the inverse variance weighted (IVW) method, supplemented by conducting sensitivity analysis. To confirm whether cardiovascular proteins mediated the causal effect of immune cells on HDP, we additionally executed a mediation MR study. RESULTS After looking into genetically predicted immunophenotype biomarkers, we discovered 14 highly correlative immunophenotypes and 104 suggestive possible factors. The IVW analysis indicated that HLA DR on myeloid DC, HLA DR on plasmacytoid DC, and HLA DR on DC had a significant association with pre-eclampsia/eclampsia (PE), whereas CD4+ CD8dim AC and CD4+ CD8dim % leukocyte were protective against gestational hypertension (GH). All of HDP in our study had no statistically significant impact on immune cells, according to reverse MR analysis. The mediating role of LOX-1between HLA DR on plasmacytoid DC and chronic hypertension prior to pregnancy was validated. CONCLUSION This study showed that many immunophenotypes are implicated in HDP. Furthermore, the level of LOX-1 mediated the pathophysiology relationship between HLA DR on plasmacytoid dendritic cells and chronic hypertension prior to pregnancy.
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Affiliation(s)
- Jingting Liu
- Maternal and Child Health Care Research Center, Gansu Provincial Maternity and Child Care Hospital, Lanzhou, 730050, China
| | - Yijun Dong
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730000, China
| | - Yawei Zhou
- Maternal and Child Health Care Research Center, Gansu Provincial Maternity and Child Care Hospital, Lanzhou, 730050, China
| | - Wendi Wang
- Maternal and Child Health Care Research Center, Gansu Provincial Maternity and Child Care Hospital, Lanzhou, 730050, China
| | - Yan Li
- Department of Biochemistry and Molecular Biology, Medical College of Northwest Minzu University, Lanzhou, 730030, China.
| | - Jianying Pei
- Maternal and Child Health Care Research Center, Gansu Provincial Maternity and Child Care Hospital, Lanzhou, 730050, China.
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Vasapollo B, Zullino S, Novelli GP, Farsetti D, Ottanelli S, Clemenza S, Micaglio M, Ferrazzi E, Di Martino DD, Ghi T, Di Pasquo E, Orabona R, Corbella P, Frigo MG, Prefumo F, Stampalija T, Giannubilo SR, Valensise H, Mecacci F. Maternal Hemodynamics from Preconception to Delivery: Research and Potential Diagnostic and Therapeutic Implications: Position Statement by Italian Association of Preeclampsia and Italian Society of Perinatal Medicine. Am J Perinatol 2024; 41:1999-2013. [PMID: 38350640 DOI: 10.1055/a-2267-3994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/15/2024]
Abstract
OBJECTIVE The Italian Association of Preeclampsia (AIPE) and the Italian Society of Perinatal Medicine (SIMP) developed clinical questions on maternal hemodynamics state of the art. STUDY DESIGN AIPE and SIMP experts were divided in small groups and were invited to propose an overview of the existing literature on specific topics related to the clinical questions proposed, developing, wherever possible, clinical and/or research recommendations based on available evidence, expert opinion, and clinical importance. Draft recommendations with a clinical rationale were submitted to 8th AIPE and SIMP Consensus Expert Panel for consideration and approval, with at least 75% agreement required for individual recommendations to be included in the final version. RESULTS More and more evidence in literature underlines the relationship between maternal and fetal hemodynamics, as well as the relationship between maternal cardiovascular profile and fetal-maternal adverse outcomes such as fetal growth restriction and hypertensive disorders of pregnancy. Experts agreed on proposing a classification of pregnancy hypertension, complications, and cardiovascular states based on three different hemodynamic profiles depending on total peripheral vascular resistance values: hypodynamic (>1,300 dynes·s·cm-5), normo-dynamic, and hyperdynamic (<800 dynes·s·cm-5) circulation. This differentiation implies different therapeutical strategies, based drugs' characteristics, and maternal cardiovascular profile. Finally, the cardiovascular characteristics of the women may be useful for a rational approach to an appropriate follow-up, due to the increased cardiovascular risk later in life. CONCLUSION Although the evidence might not be conclusive, given the lack of large randomized trials, maternal hemodynamics might have great importance in helping clinicians in understanding the pathophysiology and chose a rational treatment of patients with or at risk for pregnancy complications. KEY POINTS · Altered maternal hemodynamics is associated to fetal growth restriction.. · Altered maternal hemodynamics is associated to complicated hypertensive disorders of pregnancy.. · Maternal hemodynamics might help choosing a rational treatment during hypertensive disorders..
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Affiliation(s)
- Barbara Vasapollo
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy
- Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy
| | - Sara Zullino
- Department of Obstetrics and Gynecology, Biomedical, Experimental and Clinical Sciences, University Hospital Careggi, Florence, Italy
| | - Gian Paolo Novelli
- Department of Integrated Care Services, Prehospitalization Unit, Policlinico di Tor Vergata, Rome, Italy
| | - Daniele Farsetti
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy
- Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy
| | - Serena Ottanelli
- Department of Obstetrics and Gynecology, Biomedical, Experimental and Clinical Sciences, University Hospital Careggi, Florence, Italy
| | - Sara Clemenza
- Department of Obstetrics and Gynecology, Biomedical, Experimental and Clinical Sciences, University Hospital Careggi, Florence, Italy
| | - Massimo Micaglio
- Department of Anesthesia and Intensive Care, Unit of Obstetric and Gynecologic Anesthesia, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
| | - Enrico Ferrazzi
- Department of Obstetrics and Gynecology, Unit of Obstetrics, Department of Woman, Child, and Newborn, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical and Community Sciences, University of Milan, Milan, Italy
| | - Daniela Denis Di Martino
- Department of Obstetrics and Gynecology, Unit of Obstetrics, Department of Woman, Child, and Newborn, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - Tullio Ghi
- Obstetrics and Gynecology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Elvira Di Pasquo
- Obstetrics and Gynecology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Rossana Orabona
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Paola Corbella
- Maternal Infant Department SC, Obstetrics and Gynecology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Maria Grazia Frigo
- Department of Anesthesia and Resuscitation in Obstetrics, San Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy
| | - Federico Prefumo
- Obstetrics and Gynecology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy
| | - Tamara Stampalija
- Unit of Fetal Medicine and Prenatal Diagnosis, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy
| | - Stefano Raffaele Giannubilo
- Department of Obstetrics and Gynecology, Marche Polytechnic University, Ancona, Italy
- Department of Clinical Sciences, Polytechnic University of Marche Salesi Hospital, Ancona, Italy
| | - Herbert Valensise
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy
- Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy
| | - Federico Mecacci
- Department of Obstetrics and Gynecology, Biomedical, Experimental and Clinical Sciences, University Hospital Careggi, Florence, Italy
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de Chiara M, Montano C, Costanza D, Coluccia P, Auletta L, Greco A, Pasolini MP. Doppler ultrasonographic measurements of the lateral digital palmar artery in pregnant mares. Vet Radiol Ultrasound 2024; 65:279-287. [PMID: 38494832 DOI: 10.1111/vru.13356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 02/20/2024] [Accepted: 02/29/2024] [Indexed: 03/19/2024] Open
Abstract
Cardiovascular changes have been reported in late pregnancy in mares. However, there are no data on changes in peripheral blood flow. Doppler ultrasound represents a sensitive method for assessing the blood flow directed to the hoof. The aims of this study were to evaluate the blood flow parameters of the lateral palmar digital artery (LPDA) in pregnant mares and to assess intra- and interrater agreement between two observers with different levels of experience. The LPDAs of pregnant Italian Standardbred mares were examined. The vessels were located with B-mode ultrasound and analyzed with color and pulsed wave Doppler. The following parameters were recorded by the operators: heart rate (HR), peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI). Measurements were performed between 2 and 3 months of gestation (T1), in the last month of pregnancy (T2) and a week after delivery (T3). Seventeen mares aged 3-18 years met the inclusion criteria. Ultrasound examinations of the LPDA were subjectively easy to perform and well tolerated by the mares. Interrater and intrarater agreement were good and moderate, respectively. The HR was higher at T2 than at T1 and T3. The PSV and RI changed significantly during pregnancy, with higher values at T2 and T3, whereas the EDV remained unchanged throughout the examination. Doppler examination showed that peripheral flow changes were present in mares in late pregnancy. However, the persistence of higher values after delivery invites further investigation to assess the correlation between metabolic/endocrine changes related to pregnancy and Doppler parameters.
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Affiliation(s)
- Mariaelena de Chiara
- Department of Veterinary Medicine and Animal Production, University of Napoli "Federico II", Napoli, Italy
| | - Chiara Montano
- Department of Veterinary Medicine and Animal Production, University of Napoli "Federico II", Napoli, Italy
| | - Dario Costanza
- Interdepartmental Centre of Veterinary Radiology, University of Napoli "Federico II", Napoli, Italy
| | - Pierpaolo Coluccia
- Interdepartmental Centre of Veterinary Radiology, University of Napoli "Federico II", Napoli, Italy
| | - Luigi Auletta
- Department of Veterinary Medicine and Animal Sciences (DIVAS), University of Milano, Lodi, Italy
| | - Adelaide Greco
- Interdepartmental Centre of Veterinary Radiology, University of Napoli "Federico II", Napoli, Italy
| | - Maria Pia Pasolini
- Department of Veterinary Medicine and Animal Production, University of Napoli "Federico II", Napoli, Italy
- Interdepartmental Centre of Veterinary Radiology, University of Napoli "Federico II", Napoli, Italy
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Kornacki J, Olejniczak O, Sibiak R, Gutaj P, Wender-Ożegowska E. Pathophysiology of Pre-Eclampsia-Two Theories of the Development of the Disease. Int J Mol Sci 2023; 25:307. [PMID: 38203478 PMCID: PMC10779413 DOI: 10.3390/ijms25010307] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 12/20/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
Pre-eclampsia (PE) continues to be a leading cause of maternal and fetal mortality and morbidity. While substantial progress has been made in understanding the pathomechanisms of PE, the pathophysiology of the disease is still not fully understood. While the "two-stage model" of the development of PE is the most widely accepted theory, stating that the placenta is the main source of the disease, there are some other pathophysiological models of PE. Among these other theories, the one considering heart dysfunction as serving as the primary cause of PE seems to be gaining increasing prominence. In this review, we aim to elucidate these two divergent concepts concerning the development of PE. Despite some differences in their proposed pathomechanisms, both theories share vital pathophysiological elements in common. A central and critical component in both models is impaired placental perfusion, which appears to be a crucial phenomenon in PE. A comprehensive understanding of the different pathomechanisms involved in PE may be helpful in clinical practice, prompting a more individual approach to care of patients with PE.
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Affiliation(s)
- Jakub Kornacki
- Department of Reproduction, Chair of Reproduction and Perinatal Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (O.O.); (R.S.); (P.G.); (E.W.-O.)
| | - Olga Olejniczak
- Department of Reproduction, Chair of Reproduction and Perinatal Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (O.O.); (R.S.); (P.G.); (E.W.-O.)
| | - Rafał Sibiak
- Department of Reproduction, Chair of Reproduction and Perinatal Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (O.O.); (R.S.); (P.G.); (E.W.-O.)
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-701 Poznan, Poland
- Doctoral School, Poznan University of Medical Sciences, 60-701 Poznan, Poland
| | - Paweł Gutaj
- Department of Reproduction, Chair of Reproduction and Perinatal Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (O.O.); (R.S.); (P.G.); (E.W.-O.)
| | - Ewa Wender-Ożegowska
- Department of Reproduction, Chair of Reproduction and Perinatal Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (O.O.); (R.S.); (P.G.); (E.W.-O.)
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9
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Vasapollo B, Novelli GP, Farsetti D, Pometti F, Frantellizzi R, Maellaro F, Silvestrini M, Pais M, Valensise H. NO donors on top of anti-hypertensive therapy reduces complications in chronic hypertensive pregnancies with hypodynamic circulation. Eur J Obstet Gynecol Reprod Biol 2023; 291:219-224. [PMID: 37924629 DOI: 10.1016/j.ejogrb.2023.10.033] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 10/19/2023] [Accepted: 10/30/2023] [Indexed: 11/06/2023]
Abstract
OBJECTIVES Chronic hypertension is associated with significant adverse maternal and fetal outcomes that appear to be often associated to a hypodynamic circulation. Treatment of hypertensive disorders of pregnancy tailored on maternal hemodynamics might reduce or mitigate these complications. Our purpose was to assess the hemodynamic modifications induced by the addition of NO donors and increased oral fluid intake on top of standard antihypertensive therapy in hypodynamic chronic hypertensive patients. We further evaluated if the possible hemodynamic modification induced by NO donors and increased oral fluid intake might be associated to a reduction of the severity and rate of complications vs. patients on antihypertensive standard treatment. STUDY DESIGN This was a case-control study of 321 chronic hypertensive patients with a hypodynamic circulation at the echocardiographic evaluation at 24 weeks' gestation. We included 160 controls (standard antihypertensive therapy) and 161 cases (standard therapy + NO donor patches + increased oral fluid intake). Student T test for paired and unpaired data, univariate logistic regression analysis, ROC curve analysis, and Cox Hazards Regression analysis were used as appropriate. RESULTS At enrollment the hemodynamic parameters were similar between the two groups. After 3-4 weeks stroke volume (77 ± 19 mL vs. 69 ± 19 mL; p < 0.001), and cardiac output (6.2 ± 1.7 L vs. 5.0 ± 1.6 L; p < 0.001) were higher and total peripheral vascular resistance (1465 ± 469 dyne·s·cm-5 vs. 1814 ± 524 dyne·s·cm-5; p < 0.001) was lower in the cases vs controls. Superimposed preeclampsia, preterm delivery before 34 weeks, abruptio placentae, HELLP Syndrome, fetal growth restriction, and perinatal death were more represented in the standard treatment group vs NO treated patients (81% vs 53%; p < 0.001). In particular, the standard treatment group showed 48% fetal growth restriction vs 34% in the NO treated group (p < 0.011). The Cox proportional-hazards regression showed a lower proportion of event-free pregnancies in controls on standard treatment (HR 2.6; 95% CI 2.0-3.5; p < 0.0001), and a prolongation of pregnancies in CH cases complicated by fetal growth restriction taking NO donors (HR 0.29; 95% CI 0.19-0.43; p = 0.0001). CONCLUSIONS The tailored treatment with NO donors and oral fluids of hypodynamic CH might have positive effects on the reduction or mitigations of adverse outcomes.
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Affiliation(s)
- Barbara Vasapollo
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy; Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy
| | | | - Daniele Farsetti
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy; Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy
| | - Francesca Pometti
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy
| | | | - Filomena Maellaro
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy
| | - Marco Silvestrini
- Pre Hospitalization Unit, Policlinico di Tor Vergata, Rome, Italy; Residency in Sports Medicine, Tor Vergata University, Rome, Italy
| | - Marcello Pais
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy
| | - Herbert Valensise
- Department of Surgical Sciences, Tor Vergata University, Rome, Italy; Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy
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10
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Xiang Q, Wei Y, Feng X, Chen S, Zhao Y. Initial establishment and validation of a predictive model for preeclampsia in twin pregnancies based on maternal characteristics and echocardiographic parameters. Acta Obstet Gynecol Scand 2023; 102:1566-1574. [PMID: 37533238 PMCID: PMC10577616 DOI: 10.1111/aogs.14651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 06/22/2023] [Accepted: 07/12/2023] [Indexed: 08/04/2023]
Abstract
INTRODUCTION The primary objective of this study was to evaluate the association between maternal echocardiographic changes and the occurrence of preeclampsia (PE) in twin pregnancies. Additionally, we established and validated a prediction model for PE in twin pregnancies. MATERIAL AND METHODS The first part of this study was retrospective and included data from 854 twin pregnancies that received antenatal care at Peking University Third Hospital from April 2017 to April 2021 (training cohort). Overall, 159 women who underwent transthoracic echocardiography were included in the analysis. To build a predictive model, cardiac findings were compared between normotensive women and those with PE. The model was then validated in a prospective longitudinal cohort (test cohort) that included 109 women with twin pregnancies who underwent two consecutive transthoracic echocardiography examinations during the second and third trimesters. RESULTS Fifty-four normotensive women and 105 women with PE were analyzed in the retrospective cohort that was used to build the model in which later preeclampsia was associated with higher left ventricular mass index (>61 g/m2 ), interventricular septal thickness (>7.87 mm), left atrial anteroposterior diameter (>33.5 mm), mitral inflow late diastolic velocity (A) (>0.685 m/s), ratio of early diastolic velocity (E) and peak early diastolic myocardial velocity of the lateral mitral annulus (>6.5), and lower peak early diastolic myocardial velocity (<13.1 cm/s). The optimized PE prediction model based on the interventricular septal thickness, left atrial anteroposterior diameter, A, peak early diastolic myocardial velocity and pre-pregnancy bodyweight index was then established (area under the curve [AUC] = 0.840, 95% CI 0.778-0.903, P < 0.001). The model was tested in the prospective cohort including 87 normotensive women and 22 women with PE; the validation test showed that the prediction model in the second (AUC = 0.801) and third (AUC = 0.811) trimesters had high discriminative ability and calibration. CONCLUSIONS Maternal echocardiographic changes in twin pregnancies are associated with the development of preeclampsia. The model constructed, based on the echocardiographic parameters and body mass index, provides novel ideas for the prediction of PE.
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Affiliation(s)
- Qianqian Xiang
- Department of Obstetrics and GynecologyPeking University Third HospitalBeijingChina
- National Clinical Research Center of Obstetrics and GynecologyPeking University Third HospitalBeijingChina
- National Center for Healthcare Quality Management in ObstetricsBeijingChina
| | - Yuan Wei
- Department of Obstetrics and GynecologyPeking University Third HospitalBeijingChina
- National Clinical Research Center of Obstetrics and GynecologyPeking University Third HospitalBeijingChina
- National Center for Healthcare Quality Management in ObstetricsBeijingChina
| | - Xinheng Feng
- Department of CardiologyPeking University Third HospitalBeijingChina
| | - Shaomin Chen
- Department of CardiologyPeking University Third HospitalBeijingChina
| | - Yangyu Zhao
- Department of Obstetrics and GynecologyPeking University Third HospitalBeijingChina
- National Clinical Research Center of Obstetrics and GynecologyPeking University Third HospitalBeijingChina
- National Center for Healthcare Quality Management in ObstetricsBeijingChina
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11
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Sedaghati F, Gleason RL. A mathematical model of vascular and hemodynamics changes in early and late forms of preeclampsia. Physiol Rep 2023; 11:e15661. [PMID: 37186372 PMCID: PMC10132946 DOI: 10.14814/phy2.15661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 03/15/2023] [Accepted: 03/16/2023] [Indexed: 05/17/2023] Open
Abstract
Preeclampsia-eclampsia syndrome is a leading cause of maternal mortality. The precise etiology of preeclampsia is still not well-defined and different forms exist, including early and late forms or preeclampsia, which may arise via distinctly different mechanisms. Low-dose aspirin administered at the end of the first trimester in women identified as high risk has been shown to reduce the incidence of early, but not late, preeclampsia; however, current risk factors show only fair predictive capability. There is a pressing need to develop accurate descriptions for the different forms of preeclampsia. This paper presents 1D fluid, solid, growth, and remodeling models for pregnancies complicated with early and late forms of preeclampsia. Simulations affirm a broad set of literature results that early forms of preeclampsia are characterized by elevated uterine artery pulsatility index (UA-PI) and total peripheral resistance (TPR) and lower cardiac output (CO), with modestly increased mean arterial blood pressure (MAP) in the first half of pregnancy, with elevation of TPR and MAP beginning at 20 weeks. Conversely, late forms of preeclampsia are characterized by only slightly elevated UA-PI and normal pre-term TPR, and slightly elevated MAP and CO throughout pregnancy, with increased TPR and MAP beginning after 34 weeks. Results suggest that preexisting arterial stiffness may be elevated in women that develop both early forms and late forms of preeclampsia; however, data that verify these results are lacking in the literature. Pulse wave velocity increases in early- and late-preeclampsia, coincident with increases in blood pressure; however, these increases are mainly due to the strain-stiffening response of larger arteries, rather than arterial remodeling-derived changes in material properties. These simulations affirm that early forms of preeclampsia may be associated with abnormal placentation, whereas late forms may be more closely associated with preexisting maternal cardiovascular factors; simulations also highlight several critical gaps in available data.
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Affiliation(s)
- Farbod Sedaghati
- The George W. Woodruff School of Mechanical EngineeringGeorgia Institute of TechnologyAtlantaGeorgiaUSA
| | - Rudolph L. Gleason
- The George W. Woodruff School of Mechanical EngineeringGeorgia Institute of TechnologyAtlantaGeorgiaUSA
- The Wallace H. Coulter Department of Biomedical EngineeringGeorgia Institute of TechnologyAtlantaGeorgiaUSA
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12
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Ziganshina MM, Muminova KT, Khasbiullina NR, Khodzhaeva ZS, Yarotskaya EL, Sukhikh GT. Characterization of Vascular Patterns Associated with Endothelial Glycocalyx Damage in Early- and Late-Onset Preeclampsia. Biomedicines 2022; 10:2790. [PMID: 36359309 PMCID: PMC9687171 DOI: 10.3390/biomedicines10112790] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/21/2022] [Accepted: 10/28/2022] [Indexed: 11/15/2023] Open
Abstract
This paper provides an assessment of molecular and functional changes in blood vessels, and a description of vascular patterns during preeclampsia (PE). Patients with normal pregnancy, and pregnancy complicated by PE at earlier (20-34 weeks) and later terms (≥34 weeks) underwent a 24 h monitoring of blood pressure, central hemodynamics, arterial stiffness, and myocardial function. The blood levels of the structural components of endothelial glycocalyx (eGC): syndecan-1 (SDC 1), heparan sulfate proteoglycan 2 (HSPG2), and hyaluronic acid (HA) were determined. In early-onset PE, the vascular pattern comprised changes in all structural components of eGCs, including transmembrane proteoglycans levels, and severe disorders of central hemodynamics, arterial stiffness, and myocardial changes, probably leading to more severe course of PE and the formation of morphological grounds for cardiovascular disorders. The vascular pattern in late-onset PE, including changes in HA levels, central hemodynamics, and myocardial function, may be a signal of potential cardiovascular disorder. PE may change adaptive hemodynamic responses to a pathological reaction affecting both arterial elasticity and the left ventricular myocardium, with its subsequent hypertrophy and decompensation, leading to a delayed development of cardiovascular disorders after PE. Further clinical studies of these indicators will possibly identify predictors of PE and long-term consequences of the disease.
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Affiliation(s)
- Marina M. Ziganshina
- National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, Oparina Street 4, Moscow 117997, Russia
| | - Kamilla T. Muminova
- National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, Oparina Street 4, Moscow 117997, Russia
| | - Nailia R. Khasbiullina
- National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, Oparina Street 4, Moscow 117997, Russia
| | - Zulfiya S. Khodzhaeva
- National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, Oparina Street 4, Moscow 117997, Russia
| | - Ekaterina L. Yarotskaya
- National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, Oparina Street 4, Moscow 117997, Russia
| | - Gennady T. Sukhikh
- National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, Oparina Street 4, Moscow 117997, Russia
- Department of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Professional Education, I.M. Sechenov First Moscow State Medical University, Trubetskaya Street 8-2, Moscow 119991, Russia
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13
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Montaguti E, Di Donna G, Youssef A, Pilu G. Hypertensive disorders and maternal hemodynamic changes in pregnancy: monitoring by USCOM ® device. J Med Ultrason (2001) 2022; 49:405-413. [PMID: 35705778 DOI: 10.1007/s10396-022-01225-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 04/13/2022] [Indexed: 11/25/2022]
Abstract
Hypertensive disorders are quite common, complicating about 10% of pregnancies, while preeclampsia occurs in 2-8% of cases. The most recognized etiopathogenetic factor for the development of preeclampsia is deficient remodeling of the spiral arteries during trophoblastic invasion. Recently, some authors speculated about the "cardiovascular origin of preeclampsia"; in particular, they postulate that placental dysfunction is not the primum movens of preeclampsia, but it could be caused by a failure of the maternal cardiovascular system to adapt to the pregnancy itself. Moreover, several studies have also shown that developing preeclampsia in pregnancy is associated with an increased risk of cardiovascular disease later in life. Due to the importance of this pathology, it would be crucial to have an effective screening in order to implement a prophylaxis; for this purpose, it could be useful to have an accurate and noninvasive device for the assessment of maternal hemodynamic variables. USCOM® (Ultrasonic Cardiac Output Monitor) is a noninvasive Doppler ultrasonic technology which combines accuracy, reproducibility, noninvasiveness, and a fast learning curve. Maternal hemodynamic evaluation is important in order to monitor the changes that the maternal organism encounters, in particular a reduction in blood pressure, a decrease in total peripheral resistances, and an increase in cardiac output, resulting in a hyperdynamic circle. These hemodynamic modifications are lacking in pregnancies complicated by preeclampsia. For these reasons, it is crucial to have a tool that allows these parameters to be easily evaluated in order to identify those women at higher risk of hypertensive complications and more severe outcomes.
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Affiliation(s)
- Elisa Montaguti
- Obstetric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 13, 40138, Bologna, Italy.
| | - Gaetana Di Donna
- Obstetric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 13, 40138, Bologna, Italy
| | - Aly Youssef
- Obstetric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 13, 40138, Bologna, Italy
| | - Gianluigi Pilu
- Obstetric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 13, 40138, Bologna, Italy
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14
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Reddy M, Palmer K, Rolnik DL, Wallace EM, Mol BW, Da Silva Costa F. Role of placental, fetal and maternal cardiovascular markers in predicting adverse outcome in women with suspected or confirmed pre-eclampsia. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2022; 59:596-605. [PMID: 34985800 DOI: 10.1002/uog.24851] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 11/14/2021] [Accepted: 12/20/2021] [Indexed: 06/14/2023]
Abstract
OBJECTIVE To assess the performance of placental, fetal and maternal cardiovascular markers in the prediction of adverse perinatal and maternal outcomes in women with suspected or confirmed pre-eclampsia. METHODS This was a prospective prognostic accuracy study of women with suspected or confirmed pre-eclampsia who underwent a series of investigations to measure maternal hemodynamic indices, mean arterial pressure, augmentation index, ophthalmic artery peak systolic velocity (PSV) ratio, uterine artery pulsatility index (UtA-PI), fetal biometric and Doppler parameters, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). The performance of these markers, individually or in combination, in predicting adverse perinatal and maternal outcomes was then assessed using receiver-operating-characteristics (ROC)-curve analysis. Adverse maternal outcome was defined as one or more of severe hypertension, admission to the intensive care unit, eclampsia, placental abruption, HELLP syndrome, disseminated intravascular coagulation, platelets < 100 × 109 /L, creatinine > 90 μmol/L and alanine aminotransferase > 100 U/L. Adverse perinatal outcome was defined as one or more of preterm birth at or before 34 + 0 weeks, neonatal intensive care unit admission for > 48 h, respiratory distress syndrome, intraventricular hemorrhage, hypoxic ischemic encephalopathy, necrotizing enterocolitis, retinopathy of prematurity and confirmed fetal infection. RESULTS We recruited 126 women with suspected (n = 31) or confirmed (n = 95) pre-eclampsia at a median gestational age of 33.9 weeks (interquartile range, 30.9-36.3 weeks). Pregnancies with adverse perinatal outcome compared to those without had a higher median UtA-PI (1.3 vs 0.8; P < 0.001), ophthalmic artery PSV ratio (0.8 vs 0.7; P = 0.01) and umbilical artery PI percentile (82.0 vs 68.5; P < 0.01) and lower median estimated fetal weight percentile (4.0 vs 43.0; P < 0.001), abdominal circumference percentile (4.0 vs 63.0; P < 0.001), middle cerebral artery PI percentile (28.0 vs 58.5; P < 0.001) and cerebroplacental ratio percentile (18.0 vs 46.5; P < 0.001). Pregnancies with adverse perinatal outcome also had a higher median sFlt-1 (8208.0 pg/mL vs 4508.0 pg/mL; P < 0.001), lower PlGF (27.2 pg/mL vs 76.3 pg/mL; P < 0.001) and a higher sFlt-1/PlGF ratio (445.4 vs 74.4; P < 0.001). The best performing individual marker for predicting adverse perinatal outcome was the sFlt-1/PlGF ratio (area under the ROC curve (AUC), 0.87 (95% CI, 0.81-0.93)), followed by estimated fetal weight (AUC, 0.81 (95% CI, 0.73-0.89)). Women who experienced adverse maternal outcome had a higher median sFlt-1 level (7471.0 pg/mL vs 5131.0 pg/mL; P < 0.001) and sFlt-1/PlGF ratio (204.3 vs 93.3; P < 0.001) and a lower PlGF level (37.0 pg/mL vs 66.1 pg/mL; P = 0.01) and estimated fetal weight percentile (16.5 vs 37.0; P = 0.04). All markers performed poorly in predicting adverse maternal outcome, with sFlt-1 (AUC, 0.69 (95% CI, 0.60-0.79)) and sFlt-1/PlGF ratio (AUC, 0.69 (95% CI, 0.59-0.78)) demonstrating the best individual performance. The addition of cardiovascular, fetal or other placental indices to the sFlt-1/PlGF ratio did not improve the prediction of adverse maternal or perinatal outcomes. CONCLUSIONS The sFlt-1/PlGF ratio performs well in predicting adverse perinatal outcomes but is a poor predictor of adverse maternal outcomes in women with suspected or diagnosed pre-eclampsia. The addition of cardiovascular or fetal indices to the model is unlikely to improve the prognostic performance of the sFlt-1/PlGF ratio. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
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Affiliation(s)
- M Reddy
- Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
- Monash Women's, Monash Health, Clayton, Victoria, Australia
| | - K Palmer
- Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
- Monash Women's, Monash Health, Clayton, Victoria, Australia
| | - D L Rolnik
- Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
- Monash Women's, Monash Health, Clayton, Victoria, Australia
| | - E M Wallace
- Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
| | - B W Mol
- Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
- Aberdeen Centre for Women's Health Research, Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK
| | - F Da Silva Costa
- Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
- Maternal Fetal Medicine Unit, Gold Coast University Hospital and School of Medicine, Griffith University, Gold Coast, Queensland, Australia
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15
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Francisco C, Gamito M, Reddy M, Rolnik DL. Screening for preeclampsia in twin pregnancies. Best Pract Res Clin Obstet Gynaecol 2022; 84:55-65. [PMID: 35450774 DOI: 10.1016/j.bpobgyn.2022.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 03/13/2022] [Indexed: 11/02/2022]
Abstract
Twin pregnancies are an important risk factor for preeclampsia, a hypertensive disorder of pregnancy that is associated with a significant risk of maternal and perinatal morbidity. Given the burden of preeclampsia, the identification of women at high risk in early pregnancy is essential to allow for preventive strategies and close monitoring. In singleton pregnancies, the risk factors for preeclampsia are well established, and a combined first-trimester prediction model has been shown to adequately predict preterm disease. Furthermore, intervention with low-dose aspirin at 150 mg/day in those identified as high-risk reduces the rate of preterm preeclampsia by 62%. In contrast, risk factors for preeclampsia in twin pregnancies are less established, the proposed screening models have shown poor performance with high false-positive rates, and the benefit of aspirin for the prevention of preeclampsia is not clearly demonstrated. In this review, we examine the literature assessing prediction and prevention of preeclampsia in twin pregnancies.
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Affiliation(s)
- Carla Francisco
- Department of Obstetrics and Gynaecology, Hospital Beatriz Ângelo, Avenida Carlos, Teixeira 3, 2674-514 Loures, Portugal.
| | - Mariana Gamito
- Department of Obstetrics and Gynaecology, Hospital Beatriz Ângelo, Avenida Carlos, Teixeira 3, 2674-514 Loures, Portugal.
| | - Maya Reddy
- Department of Obstetrics and Gynaecology, Monash University, 246 Clayton Road, Clayton, Melbourne, Victoria, Australia.
| | - Daniel L Rolnik
- Department of Obstetrics and Gynaecology, Monash University, 246 Clayton Road, Clayton, Melbourne, Victoria, Australia.
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16
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Vasapollo B, Novelli GP, Farsetti D, Valensise H. Maternal peripheral vascular resistance at mid gestation in chronic hypertension as a predictor of fetal growth restriction. J Matern Fetal Neonatal Med 2022; 35:9834-9836. [PMID: 35337240 DOI: 10.1080/14767058.2022.2056443] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
We aimed at analyzing the relationship between maternal hemodynamics as expressed by Peripheral Vascular Resistance (PVR) at mid gestation and fetal growth at delivery in chronic hypertension. 152 chronic hypertensive patients were submitted to echocardiography noting PVR at 22-24 weeks' gestation and were followed until delivery noting birthweight centile and the diagnosis of fetal growth restriction (FGR). The logarithmic correlation analysis showed that PVR at mid gestation was strongly related to birthweight at delivery (r = -0.72; p < .001). Moreover, PVR was predictive of both a birthweight <10th centile (PVR >1466 Sensitivity 75.0%, Specificity 93.4%, AUC 0.83, p < .001) and FGR (PVR > 1355 Sensitivity 84.2%, Specificity 93.2%, AUC 0.88, p < .001). This study highlights the importance of maternal hemodynamics as expressed by PVR at mid gestation for the identification of chronic hypertensive patients at risk for developing fetal growth restriction. This observation might open new areas of intervention to treat patients with altered hemodynamics (PVR > 1355 dyne s cm-5).
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Affiliation(s)
- Barbara Vasapollo
- Division of Obstetrics and Gynecology, Policlinico Casilino Hospital, Rome, Italy
| | | | - Daniele Farsetti
- Division of Obstetrics and Gynecology, Policlinico Casilino Hospital, Rome, Italy
| | - Herbert Valensise
- Division of Obstetrics and Gynecology, Policlinico Casilino Hospital, Rome, Italy.,Department of Surgery, Tor Vergata University, Rome, Italy
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17
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A mathematical model of maternal vascular growth and remodeling and changes in maternal hemodynamics in uncomplicated pregnancy. Biomech Model Mechanobiol 2022; 21:647-669. [PMID: 35112224 DOI: 10.1007/s10237-021-01555-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 12/26/2021] [Indexed: 11/02/2022]
Abstract
The maternal vasculature undergoes tremendous growth and remodeling (G&R) that enables a > 15-fold increase in blood flow through the uterine vasculature from conception to term. Hemodynamic metrics (e.g., uterine artery pulsatility index, UA-PI) are useful for the prognosis of pregnancy complications; however, improved characterization of the maternal hemodynamics is necessary to improve prognosis. The goal of this paper is to develop a mathematical framework to characterize maternal vascular G&R and hemodynamics in uncomplicated human pregnancies. A validated 1D model of the human vascular tree from the literature was adapted and inlet blood flow waveforms at the ascending aorta at 4 week increments from 0 to 40 weeks of gestation were prescribed. Peripheral resistances of each terminal vessel were adjusted to achieve target flow rates and mean arterial pressure at each gestational age. Vessel growth was governed by wall shear stress (and axial lengthening in uterine vessels), and changes in vessel distensibility were related to vessel growth. Uterine artery velocity waveforms generated from this model closely resembled ultrasound results from the literature. The literature UA-PI values changed significantly across gestation, increasing in the first month of gestation, then dramatically decreasing from 4 to 20 weeks. Our results captured well the time-course of vessel geometry, material properties, and UA-PI. This 1D fluid-G&R model captured the salient hemodynamic features across a broad range of clinical reports and across gestation for uncomplicated human pregnancy. While results capture available data well, this study highlights significant gaps in available data required to better understand vascular remodeling in pregnancy.
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18
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Melchiorre K, Giorgione V, Thilaganathan B. The placenta and preeclampsia: villain or victim? Am J Obstet Gynecol 2022; 226:S954-S962. [PMID: 33771361 DOI: 10.1016/j.ajog.2020.10.024] [Citation(s) in RCA: 116] [Impact Index Per Article: 38.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 09/28/2020] [Accepted: 10/19/2020] [Indexed: 12/20/2022]
Abstract
Preeclampsia is a disease whose characterization has not changed in the 150 years since the cluster of signs associated with the disorder were first described. Although our understanding of the pathophysiology of preeclampsia has advanced considerably since then, there is still little consensus regarding the true etiology of preeclampsia. As a consequence, preeclampsia has earned the moniker "disease of theories," predominantly because the underlying biological mechanisms linking clinical epidemiologic findings to observed organ dysfunction in preeclampsia are far from clear. Despite the lack of cohesive evidence, expert consensus favors the hypothesis that preeclampsia is a primary placental disorder. However, there is now emerging evidence that suboptimal maternal cardiovascular performance resulting in uteroplacental hypoperfusion is more likely to be the cause of secondary placental dysfunction in preeclampsia. Preeclampsia and cardiovascular disease share the same risk factors, preexisting cardiovascular disease is the strongest risk factor (chronic hypertension, congenital heart disease) for developing preeclampsia, and there are now abundant data from maternal echocardiography and angiogenic marker studies that cardiovascular dysfunction precedes the development of preeclampsia by several weeks or months. Importantly, cardiovascular signs and symptoms (hypertension, cerebral edema, cardiac dysfunction) predominate in preeclampsia at clinical presentation and persist into the postnatal period with a 30% risk of chronic hypertension in the decade after birth. Placental malperfusion caused by suboptimal maternal cardiovascular performance may lead to preeclampsia, thereby explaining the preponderance of cardiovascular drugs (aspirin, calcium, statins, metformin, and antihypertensives) in preeclampsia prevention strategies. Despite the seriousness of the maternal and fetal consequences, we are still developing sensitive screening, reliable diagnostic, effective therapeutic, or improvement strategies for postpartum maternal cardiovascular legacy in preeclampsia. The latter will only become clear with an acceptance and understanding of the cardiovascular etiology of preeclampsia.
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Affiliation(s)
- Karen Melchiorre
- Department of Obstetrics and Gynaecology, Spirito Santo Tertiary Level Hospital of Pescara, Pescara, Italy
| | - Veronica Giorgione
- Molecular and Clinical Sciences Research Institute, St George's University of London, London, United Kingdom
| | - Basky Thilaganathan
- Molecular and Clinical Sciences Research Institute, St George's University of London, London, United Kingdom; Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St George's University Hospitals NHS Foundation Trust, London, United Kingdom.
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19
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Gibbone E, Huluta I, Wright A, Nicolaides KH, Charakida M. Maternal Cardiac Function at Midgestation and Development of Preeclampsia. J Am Coll Cardiol 2022; 79:52-62. [PMID: 34991789 DOI: 10.1016/j.jacc.2021.10.033] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 10/06/2021] [Accepted: 10/12/2021] [Indexed: 01/22/2023]
Abstract
BACKGROUND Preeclampsia (PE) is an independent risk factor for adverse maternal cardiovascular outcomes. The role of maternal cardiac function in the pathophysiology of PE remains unclear. OBJECTIVES This study sought to describe differences in cardiac function at midgestation between women who develop PE and those with uncomplicated pregnancy and to establish whether routine cardiac assessment at midgestation can improve performance of screening for PE achieved by established biomarkers. METHODS Mean arterial pressure was measured, medical history was obtained, and left ventricular (LV) systolic and diastolic functions were assessed using standard echocardiography and speckle tracking imaging. Uterine artery pulsatility index and serum placental growth factor and soluble fms-like tyrosine kinase-1 were measured. RESULTS In 4,795 pregnancies, 126 (2.6%) developed PE. Following multivariable analysis, peripheral vascular resistance was significantly higher and LV global longitudinal systolic strain, ejection fraction, cardiac output, and left atrial area were mildly lower in women who developed PE compared to those who did not. There was a weak association between maternal cardiovascular indices and biomarkers of placental perfusion and function. Cardiac indices did not improve the performance of screening for PE on top of maternal risk factors, mean arterial pressure, and biomarkers of placental perfusion and function. CONCLUSION Women who develop PE have an increase in peripheral vascular resistance and a mild reduction in LV functional cardiac indices long before PE development. However, cardiac indices do not improve the performance of screening for PE; thus, their routine clinical use is not advocated.
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Affiliation(s)
- Elena Gibbone
- Harris Birthright Research Centre for Fetal Medicine, King's College London, London, United Kingdom
| | - Iulia Huluta
- Harris Birthright Research Centre for Fetal Medicine, King's College London, London, United Kingdom
| | - Alan Wright
- Institute of Health Research, University of Exeter, Exeter, United Kingdom
| | - Kypros H Nicolaides
- Harris Birthright Research Centre for Fetal Medicine, King's College London, London, United Kingdom.
| | - Marietta Charakida
- Harris Birthright Research Centre for Fetal Medicine, King's College London, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom
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20
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Mecacci F, Avagliano L, Lisi F, Clemenza S, Serena C, Vannuccini S, Rambaldi MP, Simeone S, Ottanelli S, Petraglia F. Fetal Growth Restriction: Does an Integrated Maternal Hemodynamic-Placental Model Fit Better? Reprod Sci 2021; 28:2422-2435. [PMID: 33211274 PMCID: PMC8346440 DOI: 10.1007/s43032-020-00393-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 11/09/2020] [Indexed: 11/25/2022]
Abstract
In recent years, a growing interest has arisen regarding the possible relationship between adverse pregnancy outcomes (APOs) and inadequate maternal hemodynamic adaptations to the pregnancy. A possible association between "placental syndromes," such as preeclampsia (PE) and fetal growth restriction (FGR), and subsequent maternal cardiovascular diseases (CVD) later in life has been reported. The two subtypes of FGR show different pathogenetic and clinical features. Defective placentation, due to a poor trophoblastic invasion of the maternal spiral arteries, is believed to play a central role in the pathogenesis of early-onset PE and FGR. Since placental functioning is dependent on the maternal cardiovascular system, a pre-existent or subsequent cardiovascular impairment may play a key role in the pathogenesis of early-onset FGR. Late FGR does not seem to be determined by a primary abnormal placentation in the first trimester. The pathological pathway of late-onset FGR may be due to a primary maternal cardiovascular maladaptation: CV system shows a flat profile and remains similar to those of non-pregnant women. Since the second trimester, when the placenta is already developed and increases its functional request, a hypovolemic state could lead to placental hypoperfusion and to an altered maturation of the placental villous tree and therefore to an altered fetal growth. Thus, this review focalizes on the possible relationship between maternal cardiac function and placentation in the development of both early and late-onset FGR. A better understanding of maternal hemodynamics in pregnancies complicated by FGR could bring various benefits in clinical practice, improving screening and therapeutic tools.
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Affiliation(s)
- F Mecacci
- Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology, University of Florence, Viale Morgagni 44, 50134, Florence, Italy
| | - L Avagliano
- Department of Health Sciences, San Paolo Hospital Medical School, University of Milano, Milan, Italy
| | - F Lisi
- Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology, University of Florence, Viale Morgagni 44, 50134, Florence, Italy
| | - S Clemenza
- Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology, University of Florence, Viale Morgagni 44, 50134, Florence, Italy
| | - Caterina Serena
- Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology, University of Florence, Viale Morgagni 44, 50134, Florence, Italy.
| | - S Vannuccini
- Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology, University of Florence, Viale Morgagni 44, 50134, Florence, Italy
- Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy
| | - M P Rambaldi
- Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology, University of Florence, Viale Morgagni 44, 50134, Florence, Italy
| | - S Simeone
- Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology, University of Florence, Viale Morgagni 44, 50134, Florence, Italy
| | - S Ottanelli
- Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology, University of Florence, Viale Morgagni 44, 50134, Florence, Italy
| | - F Petraglia
- Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology, University of Florence, Viale Morgagni 44, 50134, Florence, Italy
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21
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Gibbone E, Wright A, Vallenas Campos R, Sanchez Sierra A, Nicolaides KH, Charakida M. Maternal cardiac function at 19-23 weeks' gestation in prediction of pre-eclampsia. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2021; 57:739-747. [PMID: 33294998 DOI: 10.1002/uog.23568] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 11/29/2020] [Accepted: 11/30/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVES First, to examine the factors from maternal characteristics and medical history that affect maternal cardiovascular indices, and, second, to examine the potential value of maternal cardiovascular indices at 19-23 weeks' gestation, on their own and in combination with maternal factors and the established biomarkers of pre-eclampsia (PE), including uterine artery pulsatility index (UtA-PI), mean arterial pressure (MAP), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1), in the prediction of subsequent development of PE. METHODS This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, assessment of maternal E/A ratio, E/e' ratio, myocardial performance index, global longitudinal systolic strain, left ventricular ejection fraction, peripheral vascular resistance, left ventricular cardiac output and left ventricular mass indexed for body surface area, and measurement of MAP, UtA-PI, serum PlGF and serum sFlt-1. The measurements of the eight maternal cardiac indices were standardized to remove the effects of maternal characteristics and elements from the medical history. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE and determine the detection rate, at a 10% false-positive rate, in screening by a combination of maternal demographic characteristics and medical history with biomarkers. RESULTS The study population of 2853 pregnancies contained 76 (2.7%) that developed PE. In pregnancies that subsequently developed PE, there was evidence of altered cardiac geometry, impaired myocardial function and increased peripheral vascular resistance. All maternal cardiovascular indices were affected significantly by maternal demographic characteristics and elements of medical history known to be associated with an increased risk for subsequent development of PE. After adjustment for maternal demographic characteristics and medical history, the only cardiovascular index that was affected significantly by subsequent development of PE was peripheral vascular resistance. Peripheral vascular resistance multiples of the median (MoM) was correlated with MAP MoM, which is not surprising because blood pressure is involved in the estimation of both. There were weak correlations between several cardiovascular indices and MAP MoM, but none was correlated with MoM values of UtA-PI, PlGF or sFlt-1. The performance of screening for delivery with PE at < 37 weeks' gestation or delivery with PE at any gestational age in screening by maternal demographic characteristics and medical history or combinations of maternal factors with MAP, UtA-PI, PlGF and sFlt-1 was not improved by the addition of peripheral vascular resistance. CONCLUSION Assessment of maternal cardiovascular function provides information on the pathophysiology of PE but is not useful in the prediction of PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
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Affiliation(s)
- E Gibbone
- Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK
| | - A Wright
- Institute of Health Research, University of Exeter, Exeter, UK
| | - R Vallenas Campos
- Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK
| | - A Sanchez Sierra
- Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK
| | - K H Nicolaides
- Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK
| | - M Charakida
- Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK
- School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
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22
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Quesada O, Shandhi MMH, Beach S, Dowling S, Tandon D, Heller J, Etemadi M, Roy S, Gonzalez Velez JM, Inan OT, Klein L. Use of Ballistocardiography to Monitor Cardiovascular Hemodynamics in Preeclampsia. WOMEN'S HEALTH REPORTS 2021; 2:97-105. [PMID: 33937907 PMCID: PMC8080913 DOI: 10.1089/whr.2020.0127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 03/08/2021] [Indexed: 11/29/2022]
Abstract
Objective: Pregnancy requires a complex physiological adaptation of the maternal cardiovascular system, which is disrupted in women with pregnancies complicated by preeclampsia, putting them at higher risk of future cardiovascular events. The measurement of body movements in response to cardiac ejection via ballistocardiogram (BCG) can be used to assess cardiovascular hemodynamics noninvasively in women with preeclampsia. Methods: Using a previously validated, modified weighing scale for assessment of cardiovascular hemodynamics through measurement of BCG and electrocardiogram (ECG) signals, we collected serial measurements throughout pregnancy and postpartum and analyzed data in 30 women with preeclampsia and 23 normotensive controls. Using BCG and ECG signals, we extracted measures of cardiac output, J-wave amplitude × heart rate (J-amp × HR). Mixed-effect models with repeated measures were used to compare J-amp × HRs between groups at different time points in pregnancy and postpartum. Results: In normotensive controls, the J-amp × HR was significantly lower early postpartum (E-PP) compared with the second trimester (T2; p = 0.016) and third trimester (T3; p = 0.001). Women with preeclampsia had a significantly lower J-amp × HR compared with normotensive controls during the first trimester (T1; p = 0.026). In the preeclampsia group, there was a trend toward an increase in J-amp × HR from T1 to T2 and then a drop in J-amp × HR at T3 and further drop at E-PP. Conclusions: We observe cardiac hemodynamic changes consistent with those reported using well-validated tools. In pregnancies complicated by preeclampsia, the maximal force of contraction is lower, suggesting lower cardiac output and a trend in hemodynamics consistent with the hyperdynamic disease model of preeclampsia.
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Affiliation(s)
- Odayme Quesada
- Women's Heart Center, The Christ Hospital Heart Vascular and Lung Institute, Cincinnati, Ohio, USA.,Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, California, USA
| | - Md Mobashir Hasan Shandhi
- School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA
| | - Shire Beach
- Division of Cardiology, Department of Internal Medicine, University of California San Francisco, San Francisco, California, USA
| | - Sean Dowling
- Division of Cardiology, Department of Internal Medicine, University of California San Francisco, San Francisco, California, USA
| | - Damini Tandon
- Division of Cardiology, Department of Internal Medicine, University of California San Francisco, San Francisco, California, USA
| | - James Heller
- Department of Obstetrics and Gynecology, University of California San Francisco, San Francisco, California, USA
| | - Mozziyar Etemadi
- Department of Obstetrics and Gynecology, University of California San Francisco, San Francisco, California, USA
| | - Shuvo Roy
- Division of Cardiology, Department of Internal Medicine, University of California San Francisco, San Francisco, California, USA
| | | | - Omer T Inan
- School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA
| | - Liviu Klein
- Division of Cardiology, Department of Internal Medicine, University of California San Francisco, San Francisco, California, USA
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23
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Angsubhakorn N, Benditt D. Relative Sinus Bradycardia: An Unexpected Finding in Preeclampsia With Acute Pulmonary Edema. Cureus 2021; 13:e13262. [PMID: 33728199 PMCID: PMC7948310 DOI: 10.7759/cureus.13262] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Preeclampsia is a multifactorial pregnancy-specific syndrome, which can result in significant alterations in cardiovascular hemodynamics. We report an observation of unexpected relative bradycardia in a previously healthy woman who presented with postpartum preeclampsia and acute pulmonary edema. We observed an increase in heart rate following normalization of blood pressure, which suggested that the initial slower than expected heart rate may reflect a baroreceptor response to hypertension. Whether this finding should be regarded as a severe aspect of the disease spectrum needs further study.
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Affiliation(s)
| | - David Benditt
- Cardiac Arrhythmia Center, Cardiovascular Division, University of Minnesota, Minneapolis, USA
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24
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Dobrowolski P, Kosinski P, Prejbisz A, Szczepkowska A, Klisiewicz A, Januszewicz M, Wielgos M, Januszewicz A, Hoffman P. Longitudinal changes in maternal left atrial volume index and uterine artery pulsatility indices in uncomplicated pregnancy. Am J Obstet Gynecol 2021; 224:221.e1-221.e15. [PMID: 32717256 DOI: 10.1016/j.ajog.2020.07.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/10/2020] [Accepted: 07/22/2020] [Indexed: 11/26/2022]
Abstract
BACKGROUND Data on the relationship between longitudinal changes in maternal volume-dependent echocardiographic parameters and placentation in uncomplicated pregnancy are limited. OBJECTIVE This study aimed to evaluate changes in volume-dependent echocardiographic parameters in uncomplicated pregnancy to test the hypothesis of the existence of an association between volume-dependent echocardiographic parameters and Doppler ultrasound parameters of fetal circulation and the uterine artery in uncomplicated pregnancy and to establish which of the volume-dependent echocardiographic parameters best depicts volume changes and correlates best with Doppler ultrasound of fetal circulation and the uterine artery in healthy pregnancy. STUDY DESIGN Data from 60 healthy pregnant women were analyzed. A complete echocardiographic study was performed at 11 to 13, 20 to 22, and 30 to 32 weeks' gestation: left ventricular end-diastolic volume, early diastolic peak flow velocity, late diastolic peak flow velocity, left atrial area, and left atrial volume index were assessed. Obstetrical assessment was performed including fetal growth and uterine artery pulsatility index. Fetal well-being was assessed by umbilical and middle cerebral artery blood flow. Serum pregnancy-associated plasma protein A and free β-human chorionic gonadotropin were assessed during the routine first-trimester scan (11-13 weeks' gestation). RESULTS Left ventricular end-diastolic volume and left atrial area increased significantly between 11 to 13 and 20 to 22 weeks' gestation but not between 20 to 22 and 30 to 32 weeks' gestation. Left atrial volume index measured at 30 to 32 weeks' gestation correlated with uterine artery pulsatility indices in 3 trimesters. Changes in the left atrial volume index between the third and first trimesters correlated significantly with the uterine artery pulsatility index measured at 20 to 22 weeks' gestation (r=-0.345; P=.020) and at 30 to 32 weeks' gestation (r=-0.452; P=.002). Changes in the left atrial volume index between the second and first trimesters significantly correlated with the uterine artery pulsatility index measured in the first trimester (r=-0.316; P=.025). CONCLUSION Our study showed that in an uncomplicated pregnancy, among volume-dependent echocardiographic parameters, left atrial volume index increased between both the first and second trimesters and the second and third trimesters and correlated with parameters of Doppler ultrasound of the fetal circulation and the uterine artery. Our results expand on the previous observation on the relationship between maternal cardiovascular adaptation and placentation in women with heart diseases to the population of healthy women with uncomplicated pregnancy.
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25
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Ormesher L, Higson S, Luckie M, Roberts SA, Glossop H, Trafford A, Cottrell E, Johnstone ED, Myers JE. Postnatal Enalapril to Improve Cardiovascular Function Following Preterm Preeclampsia (PICk-UP):: A Randomized Double-Blind Placebo-Controlled Feasibility Trial. Hypertension 2020; 76:1828-1837. [PMID: 33012200 PMCID: PMC7610547 DOI: 10.1161/hypertensionaha.120.15875] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 08/19/2020] [Indexed: 12/16/2022]
Abstract
Hypertensive disease in pregnancy is associated with future cardiovascular disease and, therefore, provides an opportunity to identify women who could benefit from targeted interventions aimed at reducing cardiovascular morbidity. This study focused on the highest-risk group, women with preterm preeclampsia, who have an 8-fold risk of death from future cardiovascular disease. We performed a single-center feasibility randomized controlled trial of 6 months' treatment with enalapril to improve postnatal cardiovascular function. Echocardiography and hemodynamic measurements were performed at baseline (<3 days), 6 weeks, and 6 months postdelivery on 60 women. At randomization, 88% of women had diastolic dysfunction, and 68% had concentric remodeling/hypertrophy. No difference was seen in total vascular resistance (P=0.59) or systolic function (global longitudinal strain: P=0.14) between groups at 6 months. However, women treated with enalapril had echocardiographic measurements consistent with improved diastolic function (E/E'[the ratio of early mitral inflow velocity and early mitral annular diastolic velocity]: P=0.04) and left ventricular remodeling (relative wall thickness: P=0.01; left ventricular mass index: P=0.03) at 6 months, compared with placebo. Urinary enalapril was detectable in 85% and 63% of women in the enalapril arm at 6 weeks and 6 months, respectively. All women responded positively to taking enalapril in the future. Our study confirmed acceptability and feasibility of the study protocol with a recruitment to completion rate of 2.2 women per month. Importantly, postnatal enalapril treatment was associated with improved echocardiographic measurements; these early improvements have the potential to reduce long-term cardiovascular disease risk. A definitive, multicenter randomized controlled trial is now required to confirm these findings. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT03466333.
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Affiliation(s)
- Laura Ormesher
- From the Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine (L.O., E.C., E.D.J., J.E.M.), University of Manchester, United Kingdom
- St Mary's Hospital (L.O., H.G., E.D.J., J.E.M.), Manchester University NHS Foundation Trust, United Kingdom
| | - Suzanne Higson
- Manchester Heart Centre (S.H., M.L.), Manchester University NHS Foundation Trust, United Kingdom
| | - Matthew Luckie
- Manchester Heart Centre (S.H., M.L.), Manchester University NHS Foundation Trust, United Kingdom
| | - Stephen A Roberts
- Centre for Biostatistics (S.A.R.), University of Manchester, United Kingdom
| | - Heather Glossop
- St Mary's Hospital (L.O., H.G., E.D.J., J.E.M.), Manchester University NHS Foundation Trust, United Kingdom
| | - Andrew Trafford
- Division of Cardiovascular Sciences (A.T.), University of Manchester, United Kingdom
| | - Elizabeth Cottrell
- From the Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine (L.O., E.C., E.D.J., J.E.M.), University of Manchester, United Kingdom
| | - Edward D Johnstone
- From the Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine (L.O., E.C., E.D.J., J.E.M.), University of Manchester, United Kingdom
- St Mary's Hospital (L.O., H.G., E.D.J., J.E.M.), Manchester University NHS Foundation Trust, United Kingdom
| | - Jenny E Myers
- From the Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine (L.O., E.C., E.D.J., J.E.M.), University of Manchester, United Kingdom
- St Mary's Hospital (L.O., H.G., E.D.J., J.E.M.), Manchester University NHS Foundation Trust, United Kingdom
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26
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Non-invasive cardiovascular assessment of pregnancy in healthy female cats. J Vet Cardiol 2020; 33:25-33. [PMID: 33279770 DOI: 10.1016/j.jvc.2020.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Revised: 10/06/2020] [Accepted: 10/26/2020] [Indexed: 11/23/2022]
Abstract
INTRODUCTION The aim of this study was to evaluate cardiac morphology, indices of systolic and diastolic function, systolic blood pressure (SBP), and uterine artery resistance index (RI) during normal feline pregnancy. ANIMALS; MATERIALS AND METHODS: Twenty domestic short-hair pregnant queens, weighing 2.4-3.9 kg. Animals were assessed by two-dimensional, M-mode, and Doppler echocardiography, non-invasive SBP measurement, and uterine Doppler ultrasound every 10 days from mating to parturition. RESULTS Interventricular septal thickness at end-diastole and end-systole, left ventricular internal dimension at end-diastole, left ventricular free wall thickness at end-diastole and end-systole, fractional shortening, stroke volume, cardiac output (CO), heart rate, and peak velocities of early and late diastolic transmitral flow increased during the second half of gestation, while SBP and RI decreased during the same period (p < 0.01). DISCUSSION AND CONCLUSIONS Cardiac structure and function varied during normal pregnancy in these queens. Eccentric hypertrophy, increased indices of systolic function, and increased measurements of CO seem to be the consequences of the hemodynamic modifications occurring during pregnancy. The assessment of maternal cardiovascular function may prove a useful screening tool to detect pregnancy complications in feline species.
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27
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Melandri M, Spalla I, Fanciullo L, Alonge S. Pregnancy Effect on Echocardiographic Parameters in Great Dane Bitches. Animals (Basel) 2020; 10:ani10111992. [PMID: 33138153 PMCID: PMC7694152 DOI: 10.3390/ani10111992] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/24/2020] [Accepted: 10/27/2020] [Indexed: 12/03/2022] Open
Abstract
Simple Summary In women, as well as in bitches, pregnancy is associated with the adaptation of the left ventricular function. Pregnancy mainly represents a status of increased volume load of the maternal heart driven by the need to supply an adequate blood flow through an augmented uterine perfusion to the developing fetuses. Consequently, cardiac morpho-functional changes are expected. Cardiac morphology and function in pregnant bitches that would develop complications may differ from those with a normal outcome. Thus, the assessment of the maternal cardiovascular function may be a useful screening tool to detect pregnancy complications in dogs. Few studies investigated the cardiac maternal adaptation in different gestational ages in dogs. Breed is a known source of variation in echocardiographic values; hence, the cardiac performance during pregnancy may also be prone to a breed-related variation. For these purposes, due to possible breed-related variations in cardiac parameters and function, and to the specific predisposition for myocardial diseases, echocardiographic changes along pregnancy in healthy Great Dane bitches were evaluated. A significant effect of the age of gestation on the increase of functional and diastolic parameters and on the decrease of systolic parameters was reported. Abstract Pregnancy is associated with adaptation of the left ventricular (LV) function. Due to differences between breeds in baseline echocardiographic values and specific predispositions for myocardial diseases, breed-specific echocardiographic parameters may be helpful to evaluate whether the systolic function varies during pregnancy. This study enrolled nine healthy Great Dane bitches with uncomplicated pregnancy. Echocardiographic M-mode and B-mode data were collected before ovulation and within 7 days of the predicted parturition term. Evaluated parameters were: LV dimension in diastole (LVd) and systole (LVs), end-diastolic (EDVI) and end-systolic (ESVI) volumes indexed to body surface area (BSA), end-diastolic (EDV) and end-systolic (ESV), end-point-septal-separation (EPSS), left atrium to aortic root ratio (LA/Ao), sphericity index (SI), ejection fraction (EF), fractional shortening (FS), stroke volume (SV), heart rate (HR), and cardiac output (CO). The ANOVA showed a statistical effect of the age of gestation (p < 0.01) on the increase of diastolic dimensions and functional parameters and on the decrease of systolic dimensions. The CO increase parallels the rise in SV and HR (p < 0.01). No statistical differences were observed for EPSS, LA/Ao, and SI. The changes in cardiac chambers and function are likely to reflect maternal adaptation to allow the fetal development in uncomplicated pregnancy. The present study provides specific echocardiographic values in uncomplicated pregnancy of Great Danes, showing that the systolic function is enhanced and that the increase in preload, observed during gestation, is the likely mechanism.
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28
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Valensise H, Farsetti D, Pisani I, Tiralongo GM, Gagliardi G, Lo Presti D, Novelli GP, Vasapollo B. Hemodynamic maladaptation and left ventricular dysfunction in chronic hypertensive patients at the beginning of gestation and pregnancy complications: a case control study. J Matern Fetal Neonatal Med 2020; 35:3290-3296. [PMID: 32933343 DOI: 10.1080/14767058.2020.1818206] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
OBJECTIVE The aim of this study was to evaluate early pregnancy differences in maternal hemodynamics, cardiac geometry and function, between chronic hypertensive (CH) patients with and without the development of feto-maternal complications later in pregnancy. METHODS We performed a case-control study on nulliparous CH treated patients. From a group of CH patients referred to our outpatient clinic at 4-6 weeks for a clinical evaluation the first consecutive 30 patients with subsequent complications (superimposed PE, abruptio placentae, uncontrolled severe hypertension with delivery <34 weeks, HELLP syndrome, FGR, perinatal death) were enrolled; the first 2 CH women with uneventful pregnancy referred after the case were enrolled as controls for a total of 60 patients. All patients were shifted to alpha-methyl dopa at the beginning of pregnancy and were submitted to an echocardiographic evaluation to assess the maternal hemodynamics, cardiac geometry, diastolic and systolic function. RESULTS Patients developing complications had a lower early pregnancy heart rate (73 ± 11 vs. 82 ± 11 bpm), cardiac output (5.23 ± 1.2 vs. 6.5 ± 1.3 L/min, p<.01) and cardiac index (3.0 ± 0.7 vs. 3.6 ± 0.7 L/min/m2, p<.01); higher total vascular resistance (1554 ± 305 vs. 1248 ± 243 d.s.cm-5, p<.01) and total vascular resistance index (2666 ± 519 vs. 2335 ± 431, d.s.cm-5/m2, p<.01); higher left ventricular mass index (42.1 ± 8.6 vs. 36.9 ± 8.3 g/m2, p<.01) and relative wall thickness (0.40 ± 0.05 vs. 0.36 ± 0.05, p<.01) of the left ventricle, resulting in a higher prevalence of altered cardiac geometry vs. uneventful CH controls. Diastolic and systolic dysfunction were also present with a higher E/e' ratio (10.50 ± 3.56 vs. 7.22 ± 1.91, p<.01) and a lower stress corrected midwall mechanics (89 ± 21 vs. 100 ± 22, p=.02) of the left ventricle. CONCLUSION CH treated patients developing maternal and/or fetal complications show early pregnancy altered cardiac geometry, diastolic and systolic dysfunction, and impaired hemodynamics with a high resistance circulation.
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Affiliation(s)
- Herbert Valensise
- Division of Obstetrics and Gynecology, Policlinico Casilino Hospital, Rome, Italy.,Department of Surgery, Tor Vergata University, Rome, Italy
| | - Daniele Farsetti
- Division of Obstetrics and Gynecology, Policlinico Casilino Hospital, Rome, Italy.,Department of Surgery, Tor Vergata University, Rome, Italy
| | - Ilaria Pisani
- Division of Obstetrics and Gynecology, Policlinico Casilino Hospital, Rome, Italy
| | | | - Giulia Gagliardi
- Division of Obstetrics and Gynecology, Policlinico Casilino Hospital, Rome, Italy
| | - Damiano Lo Presti
- Division of Obstetrics and Gynecology, Policlinico Casilino Hospital, Rome, Italy
| | | | - Barbara Vasapollo
- Division of Obstetrics and Gynecology, Policlinico Casilino Hospital, Rome, Italy
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Vasapollo B, Novelli GP, Gagliardi G, Farsetti D, Valensise H. Pregnancy complications in chronic hypertensive patients are linked to pre-pregnancy maternal cardiac function and structure. Am J Obstet Gynecol 2020; 223:425.e1-425.e13. [PMID: 32142824 DOI: 10.1016/j.ajog.2020.02.043] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 02/21/2020] [Accepted: 02/21/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Chronic hypertension complicates around 3% of all pregnancies and is associated with an increased risk for pregnancy complications such as superimposed preeclampsia, fetal growth restriction, preterm delivery, and stillbirth, reaching a rate of complications of up to 25-28%. OBJECTIVE We performed an echocardiographic study to evaluate pre-pregnancy cardiac geometry and function, along with the hemodynamic features of treated chronic hypertension patients, searching for a possible correlation with the development of feto-maternal complications and with pre-pregnancy therapy. MATERIALS AND METHODS This was a prospective observational cohort study of 192 consecutive patients receiving treatment for chronic hypertension (calcium channel blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, α1-adrenoceptor antagonists, and/or diuretics). Patients underwent echocardiography before pregnancy, assessing left ventricular morphology and function, cardiac output, and total vascular resistance. Pre-pregnancy therapy was noted, patients were shifted to α-methyldopa right before pregnancy, and were followed until delivery, noting major early (<34weeks' gestation) and late (≥34 weeks' gestation) complications. Comparisons among the 3 groups (ie, those with no complications, early complications, and late complications) were performed with 1-way analysis of variance with Student-Newman-Keuls correction for multiple comparisons. The Mann-Whitney U test was used for non-normally distributed data. Comparison of proportions was used as appropriate. Receiver operating characteristic curve analysis was used to identify cutoff values of diastolic dysfunction in this population using the E/e' ratio, and separate cutoff of values for total vascular resistance for the prediction of early and late complications of pregnancy. Binary univariate and multivariate logistic regression as well as Cox proportional hazards regression were used to evaluate the possible correlation among angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and/or calcium channel blocker pre-pregnancy therapy, cardiovascular features, and the risk for subsequent early and late complications of pregnancy. RESULTS Of 192 patients, 141 had no complications, and 51 had a complicated pregnancy (24 had early complications and 27 had late complications). Concentric geometry was more frequent in those women with early versus late and no complications (50% vs 13.5% and 11.1%, respectively; P < .05), whereas eccentric hypertrophy was more represented in women with late versus early and no complications (32% versus 12.5% and 1.4%, respectively; P < .05). The receiver operating characteristic curve showed an E/e' ratio value >7.65 (sensitivity, 59.6%; specificity, 68.6%) as a predictor of subsequent complications of pregnancy, whereas total vascular resistance <1048 (sensitivity, 83.7%; specificity, 55.6%) was predictive for late complications and total vascular resistance >1498 (sensitivity, 87.5%; specificity, 78.0%) for the early complications of pregnancy. Univariate analysis showed that the following parameters were predictive for complications of pregnancy: altered geometry of the left ventricle (odds ratio, 5.94; 95% confidence interval, 2.90-12.19), diastolic dysfunction (odds ratio, 3.22; 95% confidence interval, 1.63-6.37), altered total vascular resistance (odds ratio, 3.52; 95% confidence interval, 1.78-6.97), and pre-pregnancy therapy without calcium channel blockers/angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (odds ratio, 2.73; 95% confidence interval, 1.37-5.42). These parameters, except for altered total vascular resistance, were independent predictors in the multivariate analysis corrected for body mass index, heart rate, parity, and mean arterial pressure. CONCLUSION Chronic hypertension patients with pre-pregnancy cardiac remodeling and dysfunction more often develop early and late complications of pregnancy. Pre-pregnancy therapy for chronic hypertension patients with calcium channel blockers and/or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers may positively influence cardiac profiles and the outcome of a future pregnancy with a reduced rate of complications.
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Garcia-Gonzalez C, Georgiopoulos G, Azim SA, Macaya F, Kametas N, Nihoyannopoulos P, Nicolaides KH, Charakida M. Maternal Cardiac Assessment at 35 to 37 Weeks Improves Prediction of Development of Preeclampsia. Hypertension 2020; 76:514-522. [PMID: 32564692 DOI: 10.1161/hypertensionaha.120.14643] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Preeclampsia at term accounts for half of maternal deaths from hypertensive disorders. We aimed to assess differences in maternal cardiac indices at 35+0 to 36+6 weeks' gestation between women who subsequently developed preeclampsia at term compared with those with uncomplicated pregnancy and to evaluate whether cardiac indices offer incremental prognostic value to the available screening algorithm for preeclampsia. We recruited 1602 women with singleton pregnancies who attended for a routine hospital visit at 35+0 to 36+6 weeks' gestation between April and November 2018. We recorded maternal characteristics and preeclampsia-risk-score derived from a competing risks model and measured cardiac indices. Preeclampsia developed in 3.12% (50/1602) of participants. Women with preeclampsia, compared with those without, had increased mean arterial pressure (97.6, SD, 5.53 versus 87.9, SD, 6.82 mm Hg), systemic vascular resistance (1500, interquartile range, 1393-1831 versus 1400, interquartile range, 1202-1630 PRU) and preeclampsia-risk-score (23.4, interquartile range, 9.13-40 versus 0.9, interquartile range, 0.32-3.25). Multivariable analysis demonstrated independent association between the incidence of preeclampsia and E/e' (hazard ratio, 1.19/unit [95% CI, 1.03-1.37]; P=0.018) as well as left ventricular mass indexed for body surface area (hazard ratio, 1.03/[g·m2] [95% CI, 1.003-1.051]; P=0.029). Women with E/e' ≥7.3 and left ventricular mass indexed for body surface area ≥63.2 g/m2 had an increased risk for developing preeclampsia, despite low preeclampsia-risk-score <5% (hazard ratio, 20.1 [95% CI, 10.5-38.7], P<0.001). Increased left ventricular mass and E/e' offer incremental information to available scoring systems and better stratify women at risk of developing preeclampsia at term.
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Affiliation(s)
- Coral Garcia-Gonzalez
- From the Harris Birthright Research Centre for Fetal Medicine, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom; and Cardiology Unit, Hammersmith Hospital, Imperial College London, United Kingdom
| | - Georgios Georgiopoulos
- From the Harris Birthright Research Centre for Fetal Medicine, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom; and Cardiology Unit, Hammersmith Hospital, Imperial College London, United Kingdom
| | - Samira Abdel Azim
- From the Harris Birthright Research Centre for Fetal Medicine, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom; and Cardiology Unit, Hammersmith Hospital, Imperial College London, United Kingdom
| | - Fernando Macaya
- From the Harris Birthright Research Centre for Fetal Medicine, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom; and Cardiology Unit, Hammersmith Hospital, Imperial College London, United Kingdom
| | - Nikos Kametas
- From the Harris Birthright Research Centre for Fetal Medicine, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom; and Cardiology Unit, Hammersmith Hospital, Imperial College London, United Kingdom
| | - Petros Nihoyannopoulos
- From the Harris Birthright Research Centre for Fetal Medicine, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom; and Cardiology Unit, Hammersmith Hospital, Imperial College London, United Kingdom
| | - Kypros H Nicolaides
- From the Harris Birthright Research Centre for Fetal Medicine, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom; and Cardiology Unit, Hammersmith Hospital, Imperial College London, United Kingdom
| | - Marietta Charakida
- From the Harris Birthright Research Centre for Fetal Medicine, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom; and Cardiology Unit, Hammersmith Hospital, Imperial College London, United Kingdom
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McLaughlin K, Nadeem L, Wat J, Baczyk D, Lye SJ, Kingdom JC. Low molecular weight heparin promotes transcription and release of placental growth factor from endothelial cells. Am J Physiol Heart Circ Physiol 2020; 318:H1008-H1017. [PMID: 32196359 DOI: 10.1152/ajpheart.00109.2020] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Circulating levels of placental growth factor (PlGF) are significantly reduced in women who develop preeclampsia. Low molecular weight heparin (LMWH) has been shown to acutely elevate circulating PlGF levels in pregnant women at increased risk of preeclampsia. The objective of the current investigation was to determine the mechanisms by which LMWH mediates the extracellular release of PlGF from endothelial cells. Cultured human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs) were exposed to LMWH; PlGF transcription, translation, mobilization, and secretion were then assessed. LMWH significantly increased the release of PlGF from both HAECs and HUVECs. LMWH treatment promoted a significant increase of PlGF-1 mRNA expression in HAECs, accompanied by the intracellular transport and release of PlGF into the conditioned media. LMWH-mediated release of PlGF from HAECs was not directly mediated by extracellular mobilization, synthesis, or stability of PlGF mRNA/protein. LMWH exposure promotes the release of PlGF from endothelial cells through the upregulation of PlGF-1 mRNA expression. Stimulation of circulating PlGF levels by LMWH may be an important mechanism by which LMWH could reduce the risk of preeclampsia or minimize disease severity.NEW & NOTEWORTHY There are few therapeutic options available for the prevention of preeclampsia, a serious hypertensive disorder of pregnancy. Women who subsequently develop preeclampsia exhibit significantly reduced circulating levels of the proangiogenic placental growth factor protein. Low molecular weight heparin (LMWH) has previously been investigated as a preventative therapy against the development of preeclampsia; however, its mechanism of action is not known. The current study determined that LMWH promotes the transcription and release of placental growth factor protein from endothelial cells, providing a mechanistic basis by which LMWH could reduce the risk of preeclampsia or minimize disease severity.
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Affiliation(s)
- Kelsey McLaughlin
- Division of Cardiology, Department of Medicine, Sinai Health System, University of Toronto, Toronto, Canada.,The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Lubna Nadeem
- The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Jovian Wat
- The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Dora Baczyk
- The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Stephen J Lye
- The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.,Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Sinai Health System, University of Toronto, Toronto, Canada.,Department of Physiology, University of Toronto, Toronto, Canada
| | - John C Kingdom
- The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.,Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Sinai Health System, University of Toronto, Toronto, Canada
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32
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Blood pressure changes during twin pregnancies: the Japan Environment and Children's Study. J Hypertens 2020; 37:206-215. [PMID: 30015758 DOI: 10.1097/hjh.0000000000001846] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Although a twin pregnancy is a risk factor for hypertensive disorders of pregnancy, studies investigating longitudinal blood pressure changes during twin pregnancies are uncommon. The aims of this study were to evaluate the longitudinal blood pressure changes during twin pregnancies and to compare blood pressure levels between twin and singleton pregnancies. METHODS Five hundred dichorionic diamniotic twin, 240 monochorionic diamniotic twin, and 80 775 singleton pregnancies were included in this Japanese prospective birth cohort study. A marginal model was applied to evaluate the SBP, DBP, and mean arterial pressure levels during early gestation, mid-gestation, and late gestation. RESULTS The blood pressure levels fell from early-to-mid-gestation and rose after mid-gestation in the dichorionic and monochorionic diamniotic twin pregnancies. The SBP and mean arterial pressure levels during early gestation and the DBP and mean arterial pressure levels during late gestation were higher in the dichorionic diamniotic twin pregnancies than those in the singleton pregnancies. The blood pressure levels in the monochorionic diamniotic twin pregnancies were higher than those in the singleton pregnancies at each gestational stage, except for the SBP during late gestation. CONCLUSION Although the longitudinal blood pressure changes during twin pregnancies were similar to those during singleton pregnancies, the blood pressure levels during twin pregnancies were higher. Further studies that examine the associations between the longitudinal blood pressure changes during pregnancy and the perinatal outcomes in twin pregnancies are necessary.
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Gungoren F, Tanriverdi Z, Besli F, Barut MU, Tascanov MB. The evaluation of diastolic function and myocardial performance index during pregnancy: A tissue Doppler echocardiography study. Echocardiography 2019; 36:2152-2157. [PMID: 31755585 DOI: 10.1111/echo.14537] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 10/16/2019] [Accepted: 10/25/2019] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND The pregnancy process is characterized by several changes in the cardiovascular system, especially in left ventricle (LV) systolic and diastolic function. Tissue Doppler imaging (TDI) is a useful tool to evaluate global LV function. This study investigated changes in LV functions using TDI in third-trimester pregnant women. METHODS A total of 86 consecutive third-trimester healthy pregnant women and 40 age-matched nonpregnant healthy women (control group) were enrolled in this cross-sectional study. LV diameter, standard Doppler and tissue Doppler parameters, and myocardial performance index (MPI) were measured for all patients. RESULTS There was no significant difference in baseline characteristics between the pregnant and control groups. However, the cardiac chamber diameter was larger, the Am velocity was higher, and the E velocity, Em velocity, and E/A ratio were lower in the pregnant group. In addition, the MPI was significantly higher in the pregnant group compared to the control group (0.57 ± 0.11 vs 0.42 ± 0.02, P < .001). Correlation analysis showed that gestational week was positively correlated with the MPI (r = .407, P = .003). CONCLUSIONS Detailed assessment of cardiac function is important during pregnancy. We demonstrated that pregnancy was associated with a significantly increased MPI, as well as structural and functional changes.
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Affiliation(s)
- Fatih Gungoren
- Department of Cardiology, Harran University School of Medicine, Sanliurfa, Turkey
| | - Zulkif Tanriverdi
- Department of Cardiology, Harran University School of Medicine, Sanliurfa, Turkey
| | - Feyzullah Besli
- Department of Cardiology, Harran University School of Medicine, Sanliurfa, Turkey
| | - Mert Ulas Barut
- Department of Gynecology and Obstetrics, Harran University School of Medicine, Sanliurfa, Turkey
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Mostafavi A, Tase Zar Y, Nikdoust F, Tabatabaei SA. Comparison of left ventricular systolic function by 2D speckle-tracking echocardiography between normal pregnant women and pregnant women with preeclampsia. J Cardiovasc Thorac Res 2019; 11:309-313. [PMID: 31824613 PMCID: PMC6891035 DOI: 10.15171/jcvtr.2019.50] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Accepted: 08/25/2019] [Indexed: 01/17/2023] Open
Abstract
Introduction: In light of previous studies reporting the significant effects of preeclampsia on cardiac dimensions, we sought to evaluate changes in the left ventricular (LV) systolic and diastolic functions in patients with preeclampsia with a view to investigating changes in cardiac strain.
Methods: This cross-sectional study evaluated healthy pregnant women and pregnant women suffering from preeclampsia who were referred to our hospital for routine healthcare services. LV strain was measured by 2D speckle-tracking echocardiography.
Results: Compared with the healthy group, echocardiography in the group with preeclampsia showed a significant increase in the LV end-diastolic diameter (47.43 ± 4.94 mm vs 44.84 ± 4.30 mm; P = 0.008), the LV end-systolic diameter (31.16 ± 33.3 mm vs 29.20 ± 3.75 mm; P = 0.008), and the right ventricular diameter (27.93 ± 1.71 mm vs 24.53 ± 23.3; P = 0.001). The mean global longitudinal strain was -18.69 ± 2.8 in the group with preeclampsia and -19.39 ± 3.49 in the healthy group, with the difference not constituting statistical significance (P = 0.164). The mean global circumferential strain in the groups with and without preeclampsia was -20.4 ± 12.4 and -22.68 ± 5.50, respectively, which was significantly lower in the preeclampsia group (P = 0.028).
Conclusion: The development of preeclampsia was associated with an increase in the right and left ventricular diameters, as well as a decrease in the ventricular systolic function, demonstrated by a decline in global circumferential strain.
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Affiliation(s)
- Atoosa Mostafavi
- Shariati Hospital, Tehran University of Medical Science, Tehran, Iran
| | - Yaser Tase Zar
- Shariati Hospital, Tehran University of Medical Science, Tehran, Iran
| | - Farahnaz Nikdoust
- Shariati Hospital, Tehran University of Medical Science, Tehran, Iran
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35
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Vaught AJ, Kovell LC, Szymanski LM, Mayer SA, Seifert SM, Vaidya D, Murphy JD, Argani C, O'Kelly A, York S, Ouyang P, Mukherjee M, Zakaria S. Acute Cardiac Effects of Severe Pre-Eclampsia. J Am Coll Cardiol 2019; 72:1-11. [PMID: 29957219 DOI: 10.1016/j.jacc.2018.04.048] [Citation(s) in RCA: 123] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2018] [Revised: 03/23/2018] [Accepted: 04/07/2018] [Indexed: 01/19/2023]
Abstract
BACKGROUND Pre-eclampsia with severe features (PEC) is a pregnancy-specific syndrome characterized by severe hypertension and end-organ dysfunction, and is associated with short-term adverse cardiovascular events, including heart failure, pulmonary edema, and stroke. OBJECTIVES The authors aimed to characterize the short-term echocardiographic, clinical, and laboratory changes in women with PEC, focusing on right ventricular (RV) systolic pressure (RVSP) and echocardiographic-derived diastolic, systolic, and speckle tracking parameters. METHODS In this prospective observational study, the authors recruited 63 women with PEC and 36 pregnant control patients. RESULTS The PEC cohort had higher RVSP (31.0 ± 7.9 mm Hg vs. 22.5 ± 6.1 mm Hg; p < 0.001) and decreased global RV longitudinal systolic strain (RVLSS) (-19.6 ± 3.2% vs. -23.8 ± 2.9% [p < 0.0001]) when compared with the control cohort. For left-sided cardiac parameters, there were differences (p < 0.001) in mitral septal e' velocity (9.6 ± 2.4 cm/s vs. 11.6 ± 1.9 cm/s), septal E/e' ratio (10.8 ± 2.8 vs. 7.4 ± 1.6), left atrial area size (20.1 ± 3.8 cm2 vs. 17.3 ± 2.9 cm2), and posterior and septal wall thickness (median [interquartile range]: 1.0 cm [0.9 to 1.1 cm] vs. 0.8 cm [0.7 to 0.9 cm], and 1.0 cm [0.8 to 1.2 cm] vs. 0.8 cm [0.7 to 0.9 cm]). Eight women (12.7%) with PEC had grade II diastolic dysfunction, and 6 women (9.5%) had peripartum pulmonary edema. CONCLUSIONS Women with PEC have higher RVSP, higher rates of abnormal diastolic function, decreased global RVLSS, increased left-sided chamber remodeling, and higher rates of peripartum pulmonary edema, when compared with healthy pregnant women.
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Affiliation(s)
- Arthur Jason Vaught
- Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
| | - Lara C Kovell
- Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
| | - Linda M Szymanski
- Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Susan A Mayer
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sara M Seifert
- Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Dhananjay Vaidya
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Jamie D Murphy
- Department of Anesthesiology & Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Cynthia Argani
- Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Anna O'Kelly
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sarah York
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Pamela Ouyang
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Monica Mukherjee
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sammy Zakaria
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Arterial stiffness in normal pregnancy as assessed by digital pulse wave analysis by photoplethysmography – A longitudinal study. Pregnancy Hypertens 2019; 15:51-56. [DOI: 10.1016/j.preghy.2018.11.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 10/14/2018] [Accepted: 11/12/2018] [Indexed: 11/23/2022]
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Novelli GP, Vasapollo B, Valensise H. Hemodynamic Prediction and Stratification of Hypertensive Disorders of Pregnancy: A Dream That Is Coming True? J Am Heart Assoc 2018; 7:JAHA.118.010084. [PMID: 30007938 PMCID: PMC6064850 DOI: 10.1161/jaha.118.010084] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Affiliation(s)
- Gian Paolo Novelli
- Department of Cardiology, Ospedale San Sebastiano Martire, Frascati, Rome, Italy
| | - Barbara Vasapollo
- Department of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy
| | - Herbert Valensise
- Department of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy.,Department of Obstetrics and Gynecology, Tor Vergata University, Rome, Italy
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McLaughlin K, Zhang J, Lye SJ, Parker JD, Kingdom JC. Phenotypes of Pregnant Women Who Subsequently Develop Hypertension in Pregnancy. J Am Heart Assoc 2018; 7:JAHA.118.009595. [PMID: 30007936 PMCID: PMC6064839 DOI: 10.1161/jaha.118.009595] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Hypertensive disorders complicating pregnancy are a major cause of maternal death. Our objective was to evaluate maternal clinical, hemodynamic, and placental prognostic indicators in a consolidated manner to identify women who develop hypertension in pregnancy. METHODS AND RESULTS Twenty-six normotensive pregnant women from a specialized Placenta Clinic at increased risk of developing de novo hypertension and 20 normotensive healthy pregnant controls were recruited at 22 to 26 weeks' gestation. Fourteen maternal clinical, hemodynamic, and placental characteristics were assessed in the second trimester and aggregated. Principal component analysis of this combined data set determined that 3 dimensions accounted for 56% of the cohort variability. The first dimension accounted for 31% of the cohort variability, with significant contributions from total peripheral resistance, endoglin, and cardiac output. The second dimension was predominantly influenced by body mass index and mean arterial pressure, while uric acid and myeloperoxidase mainly contributed to the third dimension. Unsupervised clustering identified 3 groups within this combined data set. Total peripheral resistance was the most significant distinguishing parameter between these groups (P<0.0001), followed by placental growth factor, endoglin, and cardiac output (P<0.0001). Using these 4 parameters, a receiver operating curve was constructed with an area under the curve of 0.975 (95% confidence interval 0.93-1) for the prediction of developing hypertension in pregnancy. CONCLUSIONS Consolidated assessment of prognostic indicators in the second trimester of pregnancy may be useful to characterize and distinguish pathways by which women may develop hypertension in pregnancy. This approach could contribute to the development of pathway-specific preventative and antihypertensive treatment strategies.
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Affiliation(s)
- Kelsey McLaughlin
- Division of Cardiology, Department of Medicine, Sinai Health System University of Toronto, Canada.,The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute Sinai Health System, Toronto, Canada
| | - Jianhong Zhang
- The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute Sinai Health System, Toronto, Canada
| | - Stephen J Lye
- The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute Sinai Health System, Toronto, Canada.,Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Sinai Health System University of Toronto, Canada
| | - John D Parker
- Division of Cardiology, Department of Medicine, Sinai Health System University of Toronto, Canada
| | - John C Kingdom
- The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute Sinai Health System, Toronto, Canada .,Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Sinai Health System University of Toronto, Canada
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Nagarajappa C, Rangappa SS, Suryanarayana R, Balakrishna S. Urinary congophilia in preeclampsia: Experience from a rural tertiary-care hospital in India. Pregnancy Hypertens 2018; 13:83-86. [DOI: 10.1016/j.preghy.2018.05.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 03/28/2018] [Accepted: 05/13/2018] [Indexed: 12/13/2022]
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40
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Dallmann A, Ince I, Meyer M, Willmann S, Eissing T, Hempel G. Gestation-Specific Changes in the Anatomy and Physiology of Healthy Pregnant Women: An Extended Repository of Model Parameters for Physiologically Based Pharmacokinetic Modeling in Pregnancy. Clin Pharmacokinet 2018; 56:1303-1330. [PMID: 28401479 DOI: 10.1007/s40262-017-0539-z] [Citation(s) in RCA: 85] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND In the past years, several repositories for anatomical and physiological parameters required for physiologically based pharmacokinetic modeling in pregnant women have been published. While providing a good basis, some important aspects can be further detailed. For example, they did not account for the variability associated with parameters or were lacking key parameters necessary for developing more detailed mechanistic pregnancy physiologically based pharmacokinetic models, such as the composition of pregnancy-specific tissues. OBJECTIVES The aim of this meta-analysis was to provide an updated and extended database of anatomical and physiological parameters in healthy pregnant women that also accounts for changes in the variability of a parameter throughout gestation and for the composition of pregnancy-specific tissues. METHODS A systematic literature search was carried out to collect study data on pregnancy-related changes of anatomical and physiological parameters. For each parameter, a set of mathematical functions was fitted to the data and to the standard deviation observed among the data. The best performing functions were selected based on numerical and visual diagnostics as well as based on physiological plausibility. RESULTS The literature search yielded 473 studies, 302 of which met the criteria to be further analyzed and compiled in a database. In total, the database encompassed 7729 data. Although the availability of quantitative data for some parameters remained limited, mathematical functions could be generated for many important parameters. Gaps were filled based on qualitative knowledge and based on physiologically plausible assumptions. CONCLUSION The presented results facilitate the integration of pregnancy-dependent changes in anatomy and physiology into mechanistic population physiologically based pharmacokinetic models. Such models can ultimately provide a valuable tool to investigate the pharmacokinetics during pregnancy in silico and support informed decision making regarding optimal dosing regimens in this vulnerable special population.
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Affiliation(s)
- André Dallmann
- Department of Pharmaceutical and Medical Chemistry, Clinical Pharmacy, Westfälische Wilhelm-University Münster, Münster, Germany
| | - Ibrahim Ince
- ET-TD-ET Systems Pharmacology CV, Bayer AG, Leverkusen, Germany.
| | - Michaela Meyer
- DD-CS Clinical Pharmacometrics, Bayer AG, Wuppertal, Germany
| | - Stefan Willmann
- DD-CS Clinical Pharmacometrics, Bayer AG, Wuppertal, Germany
| | - Thomas Eissing
- ET-TD-ET Systems Pharmacology CV, Bayer AG, Leverkusen, Germany
| | - Georg Hempel
- Department of Pharmaceutical and Medical Chemistry, Clinical Pharmacy, Westfälische Wilhelm-University Münster, Münster, Germany
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Vasapollo B, Lo Presti D, Gagliardi G, Farsetti D, Tiralongo GM, Pisani I, Novelli GP, Valensise H. Restricted physical activity in pregnancy reduces maternal vascular resistance and improves fetal growth. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2018; 51:672-676. [PMID: 28397385 DOI: 10.1002/uog.17489] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2016] [Revised: 01/29/2017] [Accepted: 03/31/2017] [Indexed: 06/07/2023]
Abstract
OBJECTIVES To test the efficacy of maternal activity restriction for reducing peripheral vascular resistance in normotensive pregnant women with raised total vascular resistance (TVR) and to evaluate its effect on fetal growth. METHODS This was a prospective case-control study of 30 women enrolled between 27 and 29 weeks' gestation. All patients met the following criteria: normal blood pressure before and during pregnancy, TVR between 1300 and 1400 dynes × s/cm5 at enrolment, normal fetal Doppler parameters at enrolment and abdominal circumference between the 10th and 25th centiles. Patients were assigned to activity restriction (activity-restriction group; n = 15) or no treatment (control group; n = 15) and were assessed after 4 weeks for TVR and fetal growth. RESULTS TVR at enrolment and estimated fetal weight centile were similar in the activity-restriction group vs controls (1358 ± 26 vs 1353 ± 30 dynes × s/cm5 ; 18th ± 4 vs 19th ± 4 centile; P = NS). After 4 weeks, the activity-restriction group compared with controls showed significantly lower TVR (1165 ± 159 vs 1314 ± 190 dynes × s/cm5 ; P < 0.05), which was associated with higher estimated fetal weight centile (25th ± 5 vs 20th ± 5 centile; P < 0.05). TVR was lower and estimated fetal weight centile higher for the activity-restriction group after 4 weeks compared with at enrolment. CONCLUSIONS In normotensive pregnant women with raised TVR, maternal activity restriction appears to be effective in reducing TVR and therefore enhancing fetal growth. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
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Affiliation(s)
- B Vasapollo
- Department of Biomedicine, Obstetrics and Gynaecology, Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - D Lo Presti
- Department of Biomedicine, Obstetrics and Gynaecology, Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - G Gagliardi
- Department of Biomedicine, Obstetrics and Gynaecology, Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - D Farsetti
- Department of Biomedicine, Obstetrics and Gynaecology, Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - G M Tiralongo
- Department of Biomedicine, Obstetrics and Gynaecology, Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - I Pisani
- Department of Biomedicine, Obstetrics and Gynaecology, Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - G P Novelli
- Department of Cardiology, San Sebastiano Martire Hospital, Frascati, Rome, Italy
| | - H Valensise
- Department of Biomedicine, Obstetrics and Gynaecology, Policlinico Casilino, Tor Vergata University, Rome, Italy
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Valensise H, Tiralongo GM, Pisani I, Farsetti D, Lo Presti D, Gagliardi G, Basile MR, Novelli GP, Vasapollo B. Maternal hemodynamics early in labor: a possible link with obstetric risk? ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2018; 51:509-513. [PMID: 28236342 DOI: 10.1002/uog.17447] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Revised: 02/08/2017] [Accepted: 02/15/2017] [Indexed: 06/06/2023]
Abstract
OBJECTIVE To determine if hemodynamic assessment in 'low-risk' pregnant women at term with an appropriate-for-gestational age (AGA) fetus can improve the identification of patients who will suffer maternal or fetal/neonatal complications during labor. METHODS This was a prospective observational study of 77 women with low-risk term pregnancy and AGA fetus, in the early stages of labor. Hemodynamic indices were obtained using the UltraSonic Cardiac Output Monitor (USCOM® ) system. Patients were followed until the end of labor to identify fetal/neonatal and maternal outcomes, and those which developed complications of labor were compared with those delivering without complications. RESULTS Eleven (14.3%) patients had a complication during labor: in seven there was fetal distress and in four there were maternal complications (postpartum hemorrhage and/or uterine atony). Patients who developed complications during labor had lower cardiac output (5.6 ± 1.0 vs 6.7 ± 1.3 L/min, P = 0.01) and cardiac index (3.1 ± 0.6 vs 3.5 ± 0.7 L/min/m2 , P = 0.04), and higher total vascular resistance (1195.3 ± 205.3 vs 1017.8 ± 225.6 dynes × s/cm5 , P = 0.017) early in labor, compared with those who did not develop complications. Receiver-operating characteristics curve analysis to determine cut-offs showed cardiac output ≤ 5.8 L/min (sensitivity, 81.8%; specificity, 69.7%), cardiac index ≤ 2.9 L/min/m2 (sensitivity, 63.6%; specificity, 76.9%) and total vascular resistance > 1069 dynes × s/cm5 (sensitivity, 81.8%; specificity, 63.6%) to best predict maternal or fetal/neonatal complications. CONCLUSIONS The study of maternal cardiovascular adaptation at the end of pregnancy could help to identify low-risk patients who may develop complications during labor. In particular, low cardiac output and high total vascular resistance are apparently associated with higher risk of fetal distress or maternal complications. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
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Affiliation(s)
- H Valensise
- Department of Biomedicine - Obstetrics and Gynecology Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - G M Tiralongo
- Department of Biomedicine - Obstetrics and Gynecology Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - I Pisani
- Department of Biomedicine - Obstetrics and Gynecology Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - D Farsetti
- Department of Biomedicine - Obstetrics and Gynecology Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - D Lo Presti
- Department of Biomedicine - Obstetrics and Gynecology Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - G Gagliardi
- Department of Biomedicine - Obstetrics and Gynecology Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - M R Basile
- Department of Biomedicine - Obstetrics and Gynecology Policlinico Casilino, Tor Vergata University, Rome, Italy
| | - G P Novelli
- Department of Cardiology, San Sebastiano Martire Hospital, Frascati, Rome, Italy
| | - B Vasapollo
- Department of Biomedicine - Obstetrics and Gynecology Policlinico Casilino, Tor Vergata University, Rome, Italy
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McLaughlin K, Scholten RR, Kingdom JC, Floras JS, Parker JD. Should Maternal Hemodynamics Guide Antihypertensive Therapy in Preeclampsia? Hypertension 2018; 71:550-556. [DOI: 10.1161/hypertensionaha.117.10606] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Kelsey McLaughlin
- From the Division of Cardiology, Department of Medicine (K.M., J.S.F., J.D.P.) and Maternal-Fetal Medicine Division, Department of Obstetrics and Gynaecology (R.R.S., J.C.K.), Sinai Health System, University of Toronto, ON, Canada; and Centre for Women’s and Infant’s Health, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada (K.M., J.C.K.)
| | - Ralph R. Scholten
- From the Division of Cardiology, Department of Medicine (K.M., J.S.F., J.D.P.) and Maternal-Fetal Medicine Division, Department of Obstetrics and Gynaecology (R.R.S., J.C.K.), Sinai Health System, University of Toronto, ON, Canada; and Centre for Women’s and Infant’s Health, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada (K.M., J.C.K.)
| | - John C. Kingdom
- From the Division of Cardiology, Department of Medicine (K.M., J.S.F., J.D.P.) and Maternal-Fetal Medicine Division, Department of Obstetrics and Gynaecology (R.R.S., J.C.K.), Sinai Health System, University of Toronto, ON, Canada; and Centre for Women’s and Infant’s Health, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada (K.M., J.C.K.)
| | - John S. Floras
- From the Division of Cardiology, Department of Medicine (K.M., J.S.F., J.D.P.) and Maternal-Fetal Medicine Division, Department of Obstetrics and Gynaecology (R.R.S., J.C.K.), Sinai Health System, University of Toronto, ON, Canada; and Centre for Women’s and Infant’s Health, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada (K.M., J.C.K.)
| | - John D. Parker
- From the Division of Cardiology, Department of Medicine (K.M., J.S.F., J.D.P.) and Maternal-Fetal Medicine Division, Department of Obstetrics and Gynaecology (R.R.S., J.C.K.), Sinai Health System, University of Toronto, ON, Canada; and Centre for Women’s and Infant’s Health, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada (K.M., J.C.K.)
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De Haas S, Ghossein-Doha C, Geerts L, van Kuijk SMJ, van Drongelen J, Spaanderman MEA. Cardiac remodeling in normotensive pregnancy and in pregnancy complicated by hypertension: systematic review and meta-analysis. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2017; 50:683-696. [PMID: 28078751 DOI: 10.1002/uog.17410] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 12/27/2016] [Accepted: 01/03/2017] [Indexed: 06/06/2023]
Abstract
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 © 2017 ISUOG. Published by John Wiley & Sons Ltd.
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Affiliation(s)
- S De Haas
- Department of Obstetrics and Gynaecology, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands
| | - C Ghossein-Doha
- Department of Obstetrics and Gynaecology, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands
| | - L Geerts
- Department of Obstetrics and Gynaecology, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands
| | - S M J van Kuijk
- Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands
| | - J van Drongelen
- Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | - M E A Spaanderman
- Department of Obstetrics and Gynaecology, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands
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Gagliardi G, Tiralongo GM, LoPresti D, Pisani I, Farsetti D, Vasapollo B, Novelli GP, Andreoli A, Valensise H. Screening for pre-eclampsia in the first trimester: role of maternal hemodynamics and bioimpedance in non-obese patients. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2017; 50:584-588. [PMID: 27925328 DOI: 10.1002/uog.17379] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2016] [Revised: 11/09/2016] [Accepted: 11/25/2016] [Indexed: 06/06/2023]
Abstract
OBJECTIVE To test if maternal hemodynamics and bioimpedance, assessed at the time of combined screening for PE, are able to identify in the first trimester of gestation normotensive non-obese patients at risk for pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR). METHODS One hundred and fifty healthy nulliparous non-obese women (body mass index < 30 kg/m2 ) in the first trimester of pregnancy underwent assessment by UltraSonic Cardiac Output Monitor (USCOM) to detect hemodynamic parameters, bioimpedance analysis to characterize body composition, and combined screening for PE (assessment of maternal history, biophysical and maternal biochemical markers). Patients were followed until term, noting the appearance of PE and/or IUGR. RESULTS One hundred and thirty-eight patients had an uneventful pregnancy (controls), while 12 (8%) developed complications (cases). USCOM showed, in cases compared with controls, lower cardiac output (5.6 ± 0.3 vs 6.7 ± 1.1 L/min, P < 0.001), lower inotropy index (1.54 ± 0.38 vs 1.91 ± 0.32 W/m2 , P < 0.001) and higher total vascular resistance (1279.8 ± 166.4 vs 1061.4 ± 179.5 dynes × s/cm5 , P < 0.001). Bioimpedance analysis showed, in cases compared with controls, lower total body water (53.7 ± 3.3% vs 57.2 ± 5.6%, P = 0.037). Combined screening was positive for PE in 8% of the controls and in 50% of the cases (P < 0.001). After identification of cut-off values for USCOM and bioimpedance parameters, forward multivariate logistic regression analysis identified as independent predictors of complications in pregnancy the inotropy index (derived by USCOM), fat mass (derived from bioimpedance analysis) and combined screening. CONCLUSIONS Combined screening for PE and assessment of bioimpedance and maternal hemodynamics can be used to identify early markers of impaired cardiovascular adaptation and body composition that may lead to complications in the third trimester of pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
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Affiliation(s)
- G Gagliardi
- Department of Obstetrics and Gynaecology, Casilino Hospital, Rome, Italy
| | - G M Tiralongo
- Department of Obstetrics and Gynaecology, Casilino Hospital, Rome, Italy
- Department of Biomedicine, Tor Vergata University, Rome, Italy
| | - D LoPresti
- Department of Obstetrics and Gynaecology, Casilino Hospital, Rome, Italy
- Department of Biomedicine, Tor Vergata University, Rome, Italy
| | - I Pisani
- Department of Obstetrics and Gynaecology, Casilino Hospital, Rome, Italy
- Department of Biomedicine, Tor Vergata University, Rome, Italy
| | - D Farsetti
- Department of Obstetrics and Gynaecology, Casilino Hospital, Rome, Italy
- Department of Biomedicine, Tor Vergata University, Rome, Italy
| | - B Vasapollo
- Department of Obstetrics and Gynaecology, Casilino Hospital, Rome, Italy
| | - G P Novelli
- Department of Cardiology, San Sebastiano Martire Hospital, Frascati, Italy
| | - A Andreoli
- Department of Physiology, Tor Vergata University, Rome, Italy
| | - H Valensise
- Department of Obstetrics and Gynaecology, Casilino Hospital, Rome, Italy
- Department of Biomedicine, Tor Vergata University, Rome, Italy
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Influence of non-dipping pattern of blood pressure in gestational hypertension on maternal cardiac function, hemodynamics and intrauterine growth restriction. Pregnancy Hypertens 2017; 10:34-41. [DOI: 10.1016/j.preghy.2017.05.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Revised: 05/05/2017] [Accepted: 05/12/2017] [Indexed: 11/21/2022]
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Non-invasive cardiac output monitoring (NICOM®) can predict the evolution of uteroplacental disease—Results of the prospective HANDLE study. Eur J Obstet Gynecol Reprod Biol 2017; 216:116-124. [DOI: 10.1016/j.ejogrb.2017.07.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Accepted: 07/10/2017] [Indexed: 11/21/2022]
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Pisani I, Tiralongo GM, Lo Presti D, Gagliardi G, Farsetti D, Vasapollo B, Novelli GP, Andreoli A, Valensise H. Correlation between maternal body composition and haemodynamic changes in pregnancy: different profiles for different hypertensive disorders. Pregnancy Hypertens 2017; 10:131-134. [PMID: 29153665 DOI: 10.1016/j.preghy.2017.07.149] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 07/12/2017] [Accepted: 07/25/2017] [Indexed: 10/19/2022]
Abstract
OBJECTIVES To assess and correlate changes in body composition and haemodynamic function during pregnancy. To identify different haemodynamic profiles based on the onset of hypertensive diseases such as gestational hypertension and preeclampsia. METHODS We enrolled 265 healthy, normotensive pregnant women throughout pregnancy (from 6+0 to 36+0weeks). They were subjected to assessment of body composition and haemodynamic function using non-invasive methods. We divided our population in three groups: group A with physiological pregnancy, group B with gestational hypertension and group C with preeclamptic patients. RESULTS In patients who developed gestational hypertension we found lower total body water (TBW) percentage, higher Fat Mass (FM), associated with lower Cardiac Output (CO) and higher Total Vascular Resistance (TVR) during the second trimester. In the third trimester we didn't find haemodynamic differences, but a significative increase in extracellular water (ECW) percentage. In patients who developed preeclampsia we found since the first trimester significative higher TVR and hypodynamic circulation, associated with lower FM percentage. CONCLUSIONS Assessment of body composition and maternal cardiac function may help to identify earlier in pregnancy, patients with different (mal) adaptations to pregnancy. Women with high TVR, hypodynamic circulation and low fat mass during the first trimester, might be at higher risk to develop preeclampsia. Patients with higher BMI and FM percentage, and increased TVR in the second trimester, might be at risk of gestational hypertension and excessive fluid retention at the end of pregnancy.
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Affiliation(s)
- I Pisani
- Department of Obstetrics and Gynaecology, University of Rome ''Tor Vergata'', Rome, Italy.
| | - G M Tiralongo
- Department of Obstetrics and Gynaecology, University of Rome ''Tor Vergata'', Rome, Italy
| | - D Lo Presti
- Department of Obstetrics and Gynaecology, University of Rome ''Tor Vergata'', Rome, Italy
| | - G Gagliardi
- Department of Obstetrics and Gynaecology, Policlinico Casilino, Rome, Italy
| | - D Farsetti
- Department of Obstetrics and Gynaecology, University of Rome ''Tor Vergata'', Rome, Italy
| | - B Vasapollo
- Department of Obstetrics and Gynaecology, Policlinico Casilino, Rome, Italy
| | - G P Novelli
- Department of Cardiology, San Sebastiano Martire Hospital, Frascati (Rome), Italy
| | - A Andreoli
- Department of Physiology, University of Rome ''Tor Vergata'', Rome, Italy
| | - H Valensise
- Department of Obstetrics and Gynaecology, Policlinico Casilino, Rome, Italy; Department of Obstetrics and Gynaecology, University of Rome ''Tor Vergata'', Rome, Italy
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Stott D, Papastefanou I, Paraschiv D, Clark K, Kametas NA. Longitudinal maternal hemodynamics in pregnancies affected by fetal growth restriction. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2017; 49:761-768. [PMID: 27854379 DOI: 10.1002/uog.17340] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2016] [Revised: 10/17/2016] [Accepted: 10/21/2016] [Indexed: 06/06/2023]
Abstract
OBJECTIVE Fetal growth restriction (FGR) is a powerful determinant of poor perinatal outcome. From our previous work in pregnancies at high risk of development of hypertension we found impaired cardiovascular adaptation early in gestation in those destined to deliver growth-restricted infants. In this study, we monitored serially maternal hemodynamics from the first to third trimester in a similar high-risk cohort, in order to determine whether this distinct hemodynamic profile found at presentation persisted throughout pregnancy in those complicated by FGR. METHODS This was a prospective observational study based at a specialist antenatal hypertension clinic at a tertiary hospital in London. Maternal hemodynamics were evaluated serially using a non-invasive bioreactance method in pregnant women referred to the clinic with a history of chronic hypertension or a history of hypertensive disorder in a previous pregnancy. Differences in maternal hemodynamic parameters were compared between women who delivered a baby with a birth weight ≥ 10th vs < 10th percentile and ≥ 5th vs < 5th percentile. RESULTS Eighty-four pregnant women were included in the study. Mean gestational age at presentation was 14.3 weeks. Sixteen women delivered babies with a birth weight < 10th percentile and 11 with a birth weight < 5th percentile. In pregnancies with a birth weight ≥ 10th percentile, longitudinal maternal hemodynamics showed a pattern consistent with well-established physiological changes in pregnancy, i.e. a reduction in vascular resistance and an increase in cardiac output with advancing gestation until mid-pregnancy. However, women who delivered babies with a birth weight < 10th percentile showed a static pattern with no change during gestation and lower cardiac output and higher peripheral vascular resistance. Similar differences were seen when the 5th percentile was used to discriminate between appropriately-grown and growth-restricted babies. CONCLUSION Serial assessment of maternal hemodynamics in high-risk women identifies distinctive trends associated with pregnancies destined to deliver babies with birth weights < 10th and < 5th percentiles. These pregnancies have a suppressed and static maternal cardiac output and stroke volume, and have consistently raised peripheral vascular resistance. This suggests that, in women with chronic hypertension or a history of hypertensive disorder in a previous pregnancy, FGR is associated with a primary and persistent failure of maternal cardiovascular adaptation in pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
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Affiliation(s)
- D Stott
- Antenatal Hypertension Clinic, Division of Women's Health, King's College Hospital, London, UK
| | | | - D Paraschiv
- Antenatal Hypertension Clinic, Division of Women's Health, King's College Hospital, London, UK
| | - K Clark
- Antenatal Hypertension Clinic, Division of Women's Health, King's College Hospital, London, UK
| | - N A Kametas
- Antenatal Hypertension Clinic, Division of Women's Health, King's College Hospital, London, UK
- Harris Birthright Research Centre for Fetal Medicine, Division of Women's Health, King's College Hospital, London, UK
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Stott D, Papastefanou I, Paraschiv D, Clark K, Kametas NA. Serial hemodynamic monitoring to guide treatment of maternal hypertension leads to reduction in severe hypertension. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2017; 49:95-103. [PMID: 27800645 DOI: 10.1002/uog.17341] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 10/20/2016] [Accepted: 10/24/2016] [Indexed: 06/06/2023]
Abstract
OBJECTIVES To examine whether treatment for hypertension in pregnancy that is guided by serial monitoring of maternal central hemodynamics leads to a reduction in the rate of severe hypertension, defined as blood pressure ≥ 160/110 mmHg; and to assess the distinct longitudinal hemodynamic profiles associated with beta-blocker monotherapy, vasodilator monotherapy and dual agent therapy, and their relationships with outcomes, including fetal growth restriction. METHODS This was a prospective observational study at a dedicated antenatal hypertension clinic in a tertiary UK hospital. Fifty-two untreated women presenting with hypertension were recruited consecutively and started on treatment, either with a beta-blocker or a vasodilator. The choice of initial antihypertensive agent was determined according to a model constructed previously to predict the response to the beta-blocker labetalol in pregnant women needing antihypertensive treatment. At presentation, the demographic and maternal hemodynamic variables associated with a therapeutic response to labetalol, defined as blood pressure control < 140/90 mmHg with labetalol monotherapy throughout pregnancy, were ascertained and analyzed with logistic regression to create a model to predict sustained blood pressure control as described above. The women were reviewed regularly until delivery and underwent serial hemodynamic monitoring throughout pregnancy. If their blood pressure was elevated, the prediction model was referred to again to determine if alternative antihypertensive therapy, either with additional beta-blocker or a vasodilator, should be added. RESULTS Treatment by referring to results of serial hemodynamic monitoring reduced the rate of severe antenatal hypertension from 18% to 3.8%. Seventy-seven percent of women were initially prescribed a beta-blocker and 23% a vasodilator. The group that maintained good blood pressure control with beta-blocker monotherapy had the best fetal and maternal outcomes. They had lower blood pressures at presentation and throughout gestation, demonstrated well-maintained cardiac output and had the lowest rates of fetal growth restriction. The groups that required dual therapy to control their blood pressure had persistently higher blood pressure and rate of fetal growth restriction. The groups that required vasodilator therapy due to high levels of peripheral vascular resistance, either at presentation or later in pregnancy, accounted for 81% of cases with fetal growth restriction. CONCLUSION Using serial hemodynamic monitoring in pregnancy to guide treatment of hypertension significantly reduces the rate of severe hypertension and allows identification of high-resistance, low-output hypertensive pregnancies that are associated with an increased rate of fetal growth restriction. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. RESUMEN OBJETIVOS Examinar si el tratamiento para la hipertensión en el embarazo guiado por un seguimiento en serie de las principales constantes hemodinámicas de la madre conduce a una reducción en la tasa de hipertensión grave, definida como presión arterial ≥ 160/110 mmHg; y evaluar los diferentes perfiles hemodinámicos longitudinales asociados a la monoterapia con beta-bloqueantes, la monoterapia con vasodilatadores y la terapia dual, y su relación con los resultados, como la restricción del crecimiento fetal. MÉTODOS: Se realizó un estudio observacional prospectivo en una clínica especializada en hipertensión prenatal de un hospital de atención terciaria del Reino Unido. Se reclutaron consecutivamente a cincuenta y dos mujeres no tratadas que presentaban hipertensión y se comenzó a tratarlas, bien con un beta-bloqueante o bien con un vasodilatador. La elección del agente antihipertensivo inicial se determinó de acuerdo con un modelo elaborado previamente para predecir la respuesta al beta-bloqueante labetalol en mujeres embarazadas que necesitaban tratamiento antihipertensivo. Al inicio se registraron las características demográficas y las variables hemodinámicas maternas asociadas con una respuesta terapéutica al labetalol, definida como un control de la presión arterial < 140/90 mmHg con monoterapia de labetalol durante todo el embarazo que se analizó mediante regresión logística para crear un modelo con el que pronosticar un control sostenido de la presión arterial, como se describe arriba. Las mujeres fueron sometidas a revisiones regulares hasta el momento del parto y se les hizo un seguimiento hemodinámico en serie durante todo el embarazo. Si la presión arterial era elevada, se empleó de nuevo el modelo de predicción para determinar si se debería añadir un tratamiento antihipertensivo alternativo, ya sea con un beta-bloqueante adicional o con un vasodilatador. RESULTADOS El tratamiento que tuvo en cuenta los resultados del seguimiento hemodinámico en serie redujo la tasa de hipertensión prenatal grave del 18% al 3,8%. Al 77% de las mujeres se les recetó inicialmente un y al 23% un vasodilatador. El grupo que mantuvo un buen control de la presión arterial con monoterapia de beta-bloqueantes logró mejores resultados fetales y maternos. Este grupo tuvo menor presión arterial al inicio y durante toda la gestación, mostró un gasto cardíaco en buen estado y tuvo las tasas más bajas de restricción del crecimiento fetal. Los grupos que requirieron terapia dual para controlar su presión arterial mostraron persistentemente una mayor presión arterial y un mayor ritmo de restricción del crecimiento fetal. Los grupos que requirieron tratamiento vasodilatador debido a los altos niveles de resistencia vascular periférica, tanto al inicio como durante el embarazo, representaron el 81% de los casos con restricción del crecimiento fetal. CONCLUSIÓN: El uso de un seguimiento hemodinámico en serie en el embarazo como guía para el tratamiento de la hipertensión reduce significativamente la tasa de hipertensión severa y permite la identificación de embarazos con hipertensión de alta resistencia y malos resultados, asociados con una mayor tasa de restricción del crecimiento fetal. : (≥ 160/110 mmHg);β、,()。 : 。52、,β。β。,(<140/90 mmHg),logistic,。,。,(β)。 : ,18%3.8%。77%β,23%。β。,,。,。,81%。 : ,,、。.
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Affiliation(s)
- D Stott
- Antenatal Hypertension Clinic, Division of Women's Health, King's College Hospital, London, UK
| | | | - D Paraschiv
- Antenatal Hypertension Clinic, Division of Women's Health, King's College Hospital, London, UK
| | - K Clark
- Antenatal Hypertension Clinic, Division of Women's Health, King's College Hospital, London, UK
| | - N A Kametas
- Antenatal Hypertension Clinic, Division of Women's Health, King's College Hospital, London, UK
- Harris Birthright Research Centre for Fetal Medicine, Division of Women's Health, King's College Hospital, London, UK
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