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Editorial: Maternal hemodynamics; a 2017 update
Ghossein-Doha, C.* MD, PhD; Khalil, A. MD, PhD; Lees, C.C. # MD, PhD
* Dept of Obstetrics and Gynaecology, Maastricht University Medical Centre (MUMC) & Cardiology department, Zuyderland Medisch Centrum Heerlen.
FetalMedicine Unit, Department of Obstetrics and GynaecologySt George's University of London
# Department of Surgery and Cancer, Imperial College London and Department of Development and Regeneration, KU Leuven, Belgium
Total word count with references: 5745
Total word count without references: 3214
Background
Haemodynamic assessment is assuming an increasingly significant role for the understanding, prediction and management of a growing range of cardiovascular conditions. Evolving techniques allow for assessment of both the heart and vasculature and have been pioneered in the non-pregnant population. But obstetrics is fast catching up, and these methods are now finding a wide range of applications in the care of pregnant women. They can provide valuable information that help us to understand the physiology of normal pregnancy. Perhaps more importantly, they are shedding light on the pathophysiology of various pregnancy conditions, in particular preeclampsia, fetal growth restriction and gestational diabetes mellitus. On the other hand, understanding the hemodynamic changes during normal and complicated pregnancy, may provide us with a better understanding of the associated increased risk for cardiovascular diseases after complicated pregnancies.
In this regard, there is increasing evidence that they may be used to guide therapeutic management, such as the choice of a particular type of antihypertensive medication in the management of preeclampsia or pregnancy induced hypertension. Moreover, some of these techniques show promise for the prediction of pathology (again, in particular preeclampsia and fetal growth restriction) in the first, second or third trimester. Some studies have even investigated whether it might be possible to predict these conditions even prior to pregnancy, the hypothesis being that at least a proportion of women who develop these pathologies during pregnancy may be predisposed by pre-existing vascular abnormalities.
The levels of angiogenic markers such as placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) have been shown to be related to the development of preeclampsia. The interrelationship between maternal haemodynamics and these angiogenic markers is particularly illuminating when attempting to understand the enigmatic pathophysiology of preeclampsia and/or fetal growth restriction. Validation and cross comparison studies are helping to establish the relative utility and accuracy of the various methodologies.
Why is it important now?
In western countries, more women than men die of cardiovascular diseases (CVD) , ADDIN EN.CITE ADDIN EN.CITE.DATA HYPERLINK \l "_ENREF_1" \o "Mosca, 2011 #27" 1, HYPERLINK \l "_ENREF_2" \o "Perk, 2012 #26" 2 making CVD in women an important public health issue. In addition to the gender-independent classical risk factors seen in both men and women, in women specifically the occurrence of preeclampsia is associated with a 2-7 fold increased risk of CVD. HYPERLINK \l "_ENREF_3" \o "Bellamy, 2007 #28" ADDIN EN.CITE Bellamy200728282817Bellamy, L.Casas, J. P.Hingorani, A. D.Williams, D. J.Imperial College School of Medicine, London.Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysisBMJBmjBMJBmjBMJBmj9743357627Age FactorsCardiovascular Diseases/*etiology/mortalityCause of DeathFemaleFollow-Up StudiesHumansNeoplasms/etiology/mortalityPre-Eclampsia/*mortalityPregnancyRisk Factors2007Nov 101756-1833 (Electronic)
0959-535X (Linking)17975258http://www.ncbi.nlm.nih.gov/pubmed/17975258207204210.1136/bmj.39335.385301.BE3 Though this has been known for a number of years, new methods of assessing maternal haemodynamics offer an opportunity to help answer the age old question whether this is because these women already had cardiovascular pathology prior to pregnancy and that preeclampsia represents an unmasking of this pre-existing condition (analogous to gestational diabetes), or whether preeclampsia arises de novo in otherwise healthy women and damages the cardio vascular system, leading to the long term increase in risk.
Cardio vascular function and adverse pregnancy outcomes
Classic studies from the early 1990s have suggested that cardiac output is higher in women that develop pre-eclampsia compared to those that are normotensive. HYPERLINK \l "_ENREF_4" \o "Easterling, 1990 #409" ADDIN EN.CITE Easterling199040940940917Easterling, T. R.Benedetti, T. J.Schmucker, B. C.Millard, S. P.Department of Obstetrics and Gynecology, University of Washington, Seattle.Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal studyObstet GynecolObstetrics and gynecologyObstet GynecolObstetrics and gynecologyObstet GynecolObstetrics and gynecology1061-9766AdultBlood Pressure/physiologyCardiac Output/physiologyFemaleGestational AgeHemodynamics/*physiologyHumansLongitudinal StudiesPre-Eclampsia/*physiopathologyPregnancy/*physiologyStroke Volume/physiologyVascular Resistance/physiology1990Dec0029-7844 (Print)
0029-7844 (Linking)2234714http://www.ncbi.nlm.nih.gov/pubmed/22347144 By contrast, in those pregnancies that are destined to be complicated by poor fetal growth very early first trimester cardiac output changes are less marked compared to those in women that go on to have normal sized babies. HYPERLINK \l "_ENREF_5" \o "Duvekot, 1993 #408" ADDIN EN.CITE ADDIN EN.CITE.DATA 5 Later studies-from the 2000s-have lent further credence to this hypothesis, suggesting that fetal growth restriction is associated with high total peripheral vascular resistance and low cardiac output and pre-eclampsia with the opposite. ADDIN EN.CITE ADDIN EN.CITE.DATA HYPERLINK \l "_ENREF_6" \o "Valensise, 2008 #411" 6, HYPERLINK \l "_ENREF_7" \o "Vasapollo, 2008 #410" 7 From this has developed the concept-still not fully investigated-that therapy targeted at HYPERLINK \l "_ENREF_8" \o "Savu, 2012 #414" vasodilatation and increasing intravascular volume might lead to a better outcome and increased fetal growth in early growth restriction. HYPERLINK \l "_ENREF_6" \o "Valensise, 2008 #411" ADDIN EN.CITE ADDIN EN.CITE.DATA 6
The key to these functional changes may be in the way that the heart adapts structurally to the increased demands that the mothers circulation faces in pregnancy. In contrast to the physiological eccentric left ventricular (LV) remodeling seen in healthy pregnancies, preeclamptic pregnancies are characterized by the less favorable concentric LV remodeling. HYPERLINK \l "_ENREF_8" \o "Melchiorre, 2011 #33" ADDIN EN.CITE ADDIN EN.CITE.DATA 8 The additional increase in left ventricular mass (LVM) in women with PE may not always resolve after delivery. HYPERLINK \l "_ENREF_9" \o "Simmons, 2002 #364" ADDIN EN.CITE ADDIN EN.CITE.DATA 9-11 In fact, Melchiorre et al, have shown that up to one year postpartum, 40% of former PE patients have structural or functional cardiac abnormalities, consistent with Heart Failure (HF) stage-B. HYPERLINK \l "_ENREF_11" \o "Melchiorre, 2011 #36" ADDIN EN.CITE ADDIN EN.CITE.DATA 11 Recently, (published in this issue) Ghossein-Doha et al studied in a cross-sectional cohort the magnitude to which preeclampsia (PE) and conventional, but modifiable cardiovascular risk factors, are associated with asymptomatic structural and functional cardiac abnormalities postpartum. They found that after adjusting for conventional risk factors, preeclampsia remained independently associated with a 4 times increased risk for having subclinical HF stage-B. Moreover, after PE, prehypertension aggravates the risk for HF stage-B 4 times, while other constitutions of the metabolic syndrome did not.
Pregnancy and cardiac remodelling
Normotensive and hypertensive pregnancies provide two very different models to study cardiac remodelling in response to different patterns of change in both preload and afterload. Cardiac remodelling is defined as the change in size, shape and/or structure of the heart HYPERLINK \l "_ENREF_12" \o "Gaasch, 2011 #416" ADDIN EN.CITE Gaasch201141641641617Gaasch, W. H.Zile, M. R.Department of Cardiovascular Medicine, Lahey Clinic, 14 Mall Road, Burlington, Massachusetts 01805, USA. william.h.gaasch@lahey.orgLeft ventricular structural remodeling in health and disease: with special emphasis on volume, mass, and geometryJ Am Coll CardiolJournal of the American College of CardiologyJ Am Coll CardiolJournal of the American College of CardiologyJ Am Coll CardiolJournal of the American College of Cardiology1733-405817Cardiac VolumeHeart/anatomy & histology/*physiologyHumansHypertrophy, Left Ventricular/*classification/pathology/physiopathology*Ventricular Remodeling2011Oct 181558-3597 (Electronic)
0735-1097 (Linking)21996383http://www.ncbi.nlm.nih.gov/pubmed/2199638310.1016/j.jacc.2011.07.02212 and serves as an important compensatory mechanism to maintain the pumping capacity of the heart in response to either volume or pressure overload. Cardiac remodelling can be divided geometrically in either eccentric or concentric remodelling based on the ratio of LV wall thickness and end diastolic volume, the so called relative wall thickness (RWT). HYPERLINK \l "_ENREF_13" \o "Cantor, 2005 #417" ADDIN EN.CITE ADDIN EN.CITE.DATA 13 Eccentric remodelling as seen in healthy athletes and normal pregnancy, which is defined as a RWT <0.43, i s p r i m a r i l y d e t e r m i n e d b y v o l u m e o v e r l o a d a n d i s i n m o s t c a s e s p h y s i o l o g i c a l . C o n c e n t r i c r e m o d e l l i n g , a s s e e n i n h y p e r t e n s i v e h e a r t d i s e a s e a n d p r e e c l a m p s i a , w h i c h i s d e f i n e d a s a R W T e"0 . 4 3 , i s m a i n l y d e t e r m i n e d b y p r e s s u r e o v e r l o a d a n d i n m o s t c a s e s i s maladaptive and detrimental. HYPERLINK \l "_ENREF_14" \o "Rohini, 2010 #418" ADDIN EN.CITE Rohini201041841841817Rohini, A.Agrawal, N.Koyani, C. N.Singh, R.JSS College of Pharmacy(1) (Off campus of JSS University, Mysore), Ooty, Tamilnadu, India. ahuja rohini@yahoo.co.inMolecular targets and regulators of cardiac hypertrophyPharmacol ResPharmacological researchPharmacol ResPharmacological researchPharmacol ResPharmacological research269-80614Cardiomegaly/genetics/*metabolism/*physiopathologyCardiovascular Agents/*administration & dosage*Drug Delivery SystemsGenetic VariationHeart Failure/metabolismHumansModels, BiologicalMyocytes, Cardiac/metabolism/physiologyNeovascularization, Physiologic/physiologySignal Transduction/*physiology2010Apr1096-1186 (Electronic)
1043-6618 (Linking)19969085http://www.ncbi.nlm.nih.gov/pubmed/1996908510.1016/j.phrs.2009.11.01214 Pressure and volume overload-induced stresses stimulate various signalling pathways essential for the induction of a hypertrophic response of the cardiomyocyte. HYPERLINK \l "_ENREF_15" \o "Heineke, 2006 #419" ADDIN EN.CITE ADDIN EN.CITE.DATA 15 Not only volume and pressure load determine cardiac remodelling, but also neurohormonal factors.
Normotensive pregnancy is a state primarily of increased volume load driven by the need for the developing fetus to receive adequate blood, oxygen and nutrient supply. HYPERLINK \l "_ENREF_16" \o "Poppas, 1997 #412" ADDIN EN.CITE Poppas199741241241217Poppas, A.Shroff, S. G.Korcarz, C. E.Hibbard, J. U.Berger, D. S.Lindheimer, M. D.Lang, R. M.Department of Medicine, University of Chicago Medical Center, IL 60637, USA.Serial assessment of the cardiovascular system in normal pregnancy. Role of arterial compliance and pulsatile arterial loadCirculationCirculationCirculationCirculationCirculationCirculation2407-159510AdultAorta/physiology/ultrasonographyArteries/*physiologyBlood Flow Velocity*Blood Volume*Cardiovascular Physiological PhenomenaComplianceEchocardiographyFemaleHumansModels, CardiovascularPregnancy/*physiologyPulsatile FlowReference ValuesVasomotor System/*physiology1997May 200009-7322 (Print)
0009-7322 (Linking)9170404http://www.ncbi.nlm.nih.gov/pubmed/917040416 During the first trimester, cardiac output already increases by around 40% in concert with a fall in total peripheral vascular resistance and a rise in cardiac preload. HYPERLINK \l "_ENREF_13" \o "Hibbard, 2004 #413" HYPERLINK \l "_ENREF_17" \o "Hibbard, 2004 #413" ADDIN EN.CITE Hibbard200441341341317Hibbard, J. U.Shroff, S. G.Lang, R. M.Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL, USA.Cardiovascular changes in preeclampsiaSemin NephrolSeminars in nephrologySemin NephrolSeminars in nephrologySemin NephrolSeminars in nephrology580-7246Blood CirculationCardiovascular System/*physiopathologyFemaleHeart/physiopathologyHemodynamicsHumansPre-Eclampsia/*physiopathologyPregnancyVentricular Function, Left2004Nov0270-9295 (Print)
0270-9295 (Linking)15529293http://www.ncbi.nlm.nih.gov/pubmed/1552929317 During normal pregnancy, indicators of preload, such as ventricular volumes, left atrial size and plasma volume, increase progressively while determinants of afterload, such as the fall in vascular resistance and heart rate augmentation, can be observed. HYPERLINK \l "_ENREF_5" \o "Duvekot, 1993 #408" ADDIN EN.CITE ADDIN EN.CITE.DATA 5 As a response to the physiological haemodynamic demand that accompanies normal pregnancy, morphological changes leading to eccentric hypertrophy are triggered. These morphological changes in cardiac remodelling are reversible with no long term adverse effects on cardiac function. ADDIN EN.CITE ADDIN EN.CITE.DATA HYPERLINK \l "_ENREF_9" \o "Simmons, 2002 #364" 9, HYPERLINK \l "_ENREF_18" \o "Savu, 2012 #414" 18
However, not every pregnancy results in a physiological adaptation of the maternal cardiovascular system. In contrast to the physiological eccentric left ventricular (LV) remodeling seen in healthy pregnancies, pregnancy related hypertensive disorders such as preeclampsia are characterized by LV concentric remodelling which is often paralleled by a subnormal, poorly expanding plasma volume, elevated cardiac afterload and cardiovascular sympathetic over-activity. HYPERLINK \l "_ENREF_10" \o "Melchiorre, 2011 #118" ADDIN EN.CITE ADDIN EN.CITE.DATA 10 This aberrant cardiac geometry and function triggered by preeclampsia may persist postpartum, especially after preterm preeclampsia. HYPERLINK \l "_ENREF_19" \o "Sattar, 2002 #415" ADDIN EN.CITE Sattar200241541541517Sattar, N.Greer, I. A.Glasgow Royal Infirmary University NHS Trust, Glasgow G31 2ER. nsattar@clinmed.gla.ac.ukPregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening?BMJBmjBMJBmjBMJBmj157-603257356Coronary Disease/etiologyDiabetes, Gestational/etiologyFemaleForecastingHumansInfant, Low Birth WeightInfant, NewbornMass Screening/methodsMetabolic Syndrome XObstetric Labor, Premature/etiologyPre-Eclampsia/etiologyPregnancyPregnancy Complications, Cardiovascular/*etiologyPrenatal Diagnosis/methodsRisk Factors2002Jul 201756-1833 (Electronic)
0959-535X (Linking)12130616http://www.ncbi.nlm.nih.gov/pubmed/12130616112367819 Melchiorre et al. have shown that at 1 year postpartum, the proportion of patients with aberrant LV geometric remodelling was significantly higher in the preeclampsia group compared to the control group (72% versus 24%). HYPERLINK \l "_ENREF_11" \o "Melchiorre, 2011 #36" ADDIN EN.CITE ADDIN EN.CITE.DATA 11 In particular, early-onset preeclampsia (developing before 34 weeks of gestation) relates to persistent residual postpartum concentric LV remodelling, HYPERLINK \l "_ENREF_11" \o "Melchiorre, 2011 #36" ADDIN EN.CITE ADDIN EN.CITE.DATA 11 aand up to one year postpartum, 40% of former preeclampsia patients have structural or functional cardiac abnormalities, consistent with Heart Failure (HF) stage-B.
It is likely that the high prevalence of structural and functional cardiac abnormalities postpartum are at least in part a result of unfavourable cardiac adaptation in response to haemodynamic changes during preeclampsia, although baseline differences cannot be excluded. Therefore, it is likely that preventing unfavourable cardiac adaptation during pregnancy by modifying aberrant hemodynamics may decrease the prevalence of unfavourable cardiac profiles postpartum. Insight into cardiac adaptation and the related molecular profiles during complicated pregnancy may provide opportunities to improve clinical approaches, in order to predict and prevent preeclampsia related LV concentric remodelling.
Identifying the pre-stage of cardiovascular disease
Although using the term HF stage-B is subject to debate, this definition aids in clustering and identifying asymptomatic structural and cardiac abnormalities in these relatively young women. This is particularly relevant because there is an increasing understanding that cardiovascular diseases are generally progressive, proceeding through asymptomatic to symptomatic stages, and that the progression from the asymptomatic HF stage-B to the symptomatic stage-C increases mortality 5-fold. HYPERLINK \l "_ENREF_20" \o "Jessup, 2009 #37" ADDIN EN.CITE ADDIN EN.CITE.DATA 20 Since therapeutic interventions during the asymptomatic phase of cardiac impairment can improve the long-term prognosis more effectively than when initiated at a symptomatic stage, identifying this stage in relatively young subpopulations may have major population clinical benefits. ADDIN EN.CITE ADDIN EN.CITE.DATA HYPERLINK \l "_ENREF_20" \o "Jessup, 2009 #37" 20, HYPERLINK \l "_ENREF_21" \o "Ammar, 2007 #46" 21
One of the primary determinants for heart failure is blood pressure. It has been suggested that the cardiac effect of blood pressure follows a J-curve. HYPERLINK \l "_ENREF_22" \o "Mancia, 2013 #47" ADDIN EN.CITE ADDIN EN.CITE.DATA 22 This may suggest that mildly increased blood pressure, high enough to diagnose prehypertension after preeclampsia yet below the threshold for diagnosing hypertension, may play an important role in the increased prevalence of structural abnormalities in this young female population. Prehypertension, defined as systolic BP between 120 and 139 mmHg and/or a diastolic blood pressure between 80 and 89 mmHg, has been identified as a potent predictor of chronic hypertension. HYPERLINK \l "_ENREF_23" \o "Parikh, 2008 #406" ADDIN EN.CITE Parikh200840640640617Parikh, N. I.Pencina, M. J.Wang, T. J.Benjamin, E. J.Lanier, K. J.Levy, D.D'Agostino, R. B., Sr.Kannel, W. B.Vasan, R. S.Framingham Heart Study, Framingham, Massachusetts 01702-5803, USA.A risk score for predicting near-term incidence of hypertension: the Framingham Heart StudyAnn Intern MedAnn Intern MedAnnals of internal medicine102-101482AdultAge FactorsAgedBlood PressureBody Mass IndexFemaleHumansHypertension/*epidemiology/geneticsIncidenceLongitudinal StudiesMaleMiddle AgedParentsRisk AssessmentRisk FactorsSex FactorsSmoking/adverse effects2008Jan 151539-3704 (Electronic)
0003-4819 (Linking)18195335http://www.ncbi.nlm.nih.gov/pubmed/1819533523 Data from the Framingham Heart study indicated that, compared to a blood pressure below 120/80 mmHg, prehypertension was associated with an increased risk of myocardial infarction (RR 3.5) and coronary artery disease (RR1.7). HYPERLINK \l "_ENREF_24" \o "Qureshi, 2005 #407" ADDIN EN.CITE ADDIN EN.CITE.DATA 24 Ghossein-Doha et al found that two thirds of women initially identified as normotensive at one year after preeclampsia and who went on to develop hypertension fulfilled the criteria for prehypertension. HYPERLINK \l "_ENREF_25" \o "Ghossein-Doha, 2014 #6" ADDIN EN.CITE ADDIN EN.CITE.DATA 25 Earlier studies showed that prehypertension accelerates the development of LV hypertrophy and cardiac diastolic dysfunction. ADDIN EN.CITE ADDIN EN.CITE.DATA HYPERLINK \l "_ENREF_26" \o "Markus, 2008 #48" 26, HYPERLINK \l "_ENREF_27" \o "Ghossein-Doha, 2013 #7" 27 HYPERLINK \l "_ENREF_26" \o "Ghossein-Doha, 2013 #7" Certain antihypertensive medication (mainly angiotensin converting enzyme inhibitors and angiotensin receptor blockers) have a protective and inhibitory effect on adverse cardiac remodeling. HYPERLINK \l "_ENREF_20" \o "Jessup, 2009 #37" ADDIN EN.CITE ADDIN EN.CITE.DATA 20 Whether treating prehypertension with blood pressure lowering medication intervenes in the progressive increase in LVMi and RWT, resulting in a decreased prevalence of HF, remains to be elucidated.
Vascular Function
Though perhaps not studied as comprehensively as the heart, vascular function has been assessed in relation to established disease or its prediction. Various characteristics of vascular function can be assessed using measures of arterial stiffness, wave reflection, microcirculation and endothelial function [either by flow mediated dilation (FMD) or carotid intima-media thickness (CIMT)]. A range of blood vessels have been studied using one or more of these methodologies, including the aorta, brachial artery, carotid artery, ophthalmic artery and uterine artery (uteroplacental circulation). In addition, the maternal microcirculation can now be assessed reproducibly, as can retinal vascular responses. HYPERLINK \l "_ENREF_28" \o "Kane, 2016 #422" ADDIN EN.CITE Kane201642242242217Kane, S. C.Brennecke, S. P.da Silva Costa, F.The University of Melbourne, Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Parkville, Victoria, Australia.
Pregnancy Research Centre, Department of Maternal Fetal Medicine, The Royal Women's Hospital, Parkville, Victoria, Australia.
Perinatal Services, Monash Health, Clayton, Victoria, Australia.
Monash Ultrasound for Women, Clayton, Victoria, Australia.Ophthalmic Artery Doppler Analysis: A Window into the Cerebrovasculature of Women with Pre-EclampsiaUltrasound Obstet GynecolUltrasound Obstet GynecolUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and GynecologyDoppler ultrasonographyEclampsiaHypertensionOphthalmic artery ultrasonographyPre-eclampsiaPregnancy2016Aug 31469-0705 (Electronic)
0960-7692 (Linking)27485824http://www.ncbi.nlm.nih.gov/pubmed/2748582410.1002/uog.1720928
Arterial endothelial function has been classically assessed by FMD. HYPERLINK \l "_ENREF_29" \o "Verma, 2003 #421" ADDIN EN.CITE Verma200342142142117Verma, S.Buchanan, M. R.Anderson, T. J.Department of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada. Subodh.Verma@Sympatico.caEndothelial function testing as a biomarker of vascular diseaseCirculationCirculationCirculation2054-910817Biomarkers/analysisC-Reactive Protein/analysisCardiovascular Diseases/*diagnosis/*physiopathologyEndothelium, Vascular/*physiopathologyHumansPredictive Value of TestsPrognosisVasomotor System/physiopathology2003Oct 281524-4539 (Electronic)
0009-7322 (Linking)14581384http://www.ncbi.nlm.nih.gov/pubmed/1458138410.1161/01.CIR.0000089191.72957.ED29 The technique, though reproducible, takes several minutes and proxy methods include augmentation index (AIx) and pulse wave velocity (PWV). Stiffer arteries measured in the first trimester are associated with a higher risk of preeclampsia and small for gestational age babies. HYPERLINK \l "_ENREF_30" \o "Savvidou, 2011 #428" ADDIN EN.CITE Savvidou201142842842817Savvidou, M. D.Kaihura, C.Anderson, J. M.Nicolaides, K. H.Department of Maternal Fetal Medicine, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, UK. msavvidou@dsla.ndo.co.ukMaternal arterial stiffness in women who subsequently develop pre-eclampsiaPLoS OnePLoS OnePloS onee1870365AdultCardiovascular System/physiopathologyDiastoleFemaleHumansMothersPre-Eclampsia/*physiopathologyPregnancyPregnancy Complications, Cardiovascular/diagnosis/physiopathologyPregnancy Trimester, SecondRiskSystoleUltrasonography, DopplerUterine Artery/*diagnostic imaging/*physiopathologyVascular Resistance2011May 031932-6203 (Electronic)
1932-6203 (Linking)21559278http://www.ncbi.nlm.nih.gov/pubmed/21559278PMC308690310.1371/journal.pone.001870330 Established preeclampsia is also associated with stiffer arteries as measured by AIx and uterine artery impedance. ADDIN EN.CITE ADDIN EN.CITE.DATA HYPERLINK \l "_ENREF_31" \o "Khalil, 2010 #430" 31, HYPERLINK \l "_ENREF_32" \o "Everett, 2011 #429" 32 This raises the intriguing possibility that uterine artery impedance is as much related to a mothers systemic arterial function as to the downstream placental bed.
The maternal venous system must not be forgotten. Though it is more difficult to assess, and venous assessment is less reproducible than arterial, there are distinct differences between healthy and preeclamptic pregnancies. ADDIN EN.CITE ADDIN EN.CITE.DATA HYPERLINK \l "_ENREF_33" \o "Gyselaers, 2015 #434" 33, HYPERLINK \l "_ENREF_34" \o "Mesens, 2015 #432" 34
What we learn from the studies in this issue of the journal
This special issue of the journal brings together some of the cutting edge research in this field which we hope will excite clinicians and academics about the future potential of these new and evolving techniques. The studies included can be broadly considered under five categories: physiology, therapeutics, prediction, postpartum, and validation/cross-comparison.
Physiology
Guy et al studied the effect of maternal posture on maternal cardiac function at 35 to 37 weeks gestation in over 3000 normal pregnancies. Paradoxically, the change from the supine to the upright position and passive leg raising may result in an increase in preload and consequent increase in cardiac index and stroke volume index with a fall in total peripheral resistance index (Guy 2017). These changes were similar but less marked in women that went on to develop preeclampsia or gestational hypertension. Guy et al also reported that maternal cardiac function (cardiac output, stroke volume and total peripheral resistance) is influenced by maternal characteristics and proposed the use of multiple of medians (MoMs) to adjust for these correlations. HYPERLINK \l "_ENREF_35" \o "Guy, 2016 #435" ADDIN EN.CITE Guy201643543543517Guy, G. P.Ling, H. Z.Garcia, P.Poon, L. C.Nicolaides, K. H.Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK. liona.poon@cuhk.edu.hk.
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong. liona.poon@cuhk.edu.hk.Maternal cardiovascular function at 35-37 weeks' gestation: Relation to maternal characteristicsUltrasound Obstet GynecolUltrasound Obstet GynecolUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and GynecologyCardiac outputMaternal cardiovascular functionMaternal characteristicsThird-trimester screeningTotal peripheral resistance2016Sep 271469-0705 (Electronic)
0960-7692 (Linking)27671837http://www.ncbi.nlm.nih.gov/pubmed/2767183710.1002/uog.1731135 Moreover, Iacobaeus et all, have demonstrated in a longitudinal study that During normal pregnancy, the volume expansion necessary for sufficient fetal growth is accommodated by early and marked changes of the maternal vascular system. These hemodynamic changes seem to be dependent on normal adaptive endothelial and vascular function. HYPERLINK \l "_ENREF_36" \o "Iacobaeus, 2016 #450" ADDIN EN.CITE ADDIN EN.CITE.DATA 36
Therapeutic
Stott et al suggest that the assessment of individual maternal haemodynamics may be useful when selecting the type of antihypertensive drug to be used in pregnancy at different stages of treatment. In women starting antihypertensive drug therapy, they could predict those women that would respond to labetalol and those who would require additional vasodilator treatment. HYPERLINK \l "_ENREF_37" \o "Stott, 2016 #437" ADDIN EN.CITE Stott201643743743717Stott, D.Papastefanou, I.Paraschiv, D.Clark, K.Kametas, N. A.Antenatal Hypertension Clinic, Division of Women's Health, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
Leto Maternity Unit, Athens, Greece.
Antenatal Hypertension Clinic, Division of Women's Health, King's College Hospital, Denmark Hill, London, SE5 9RS, UK. nick.kametas@kcl.ac.uk.
Harris Birthright Research Centre for Fetal Medicine, Division of Women's Health, King's College Hospital, Denmark Hill, London, SE5 9RS, UK. nick.kametas@kcl.ac.uk.Serial haemodynamic monitoring to guide treatment of maternal hypertension leads to a reduction in severe hypertension ratesUltrasound Obstet GynecolUltrasound Obstet GynecolUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology2016Oct 311469-0705 (Electronic)
0960-7692 (Linking)27800645http://www.ncbi.nlm.nih.gov/pubmed/2780064510.1002/uog.1734137 Similarly, during the acute phase of labetalol therapy, they used maternal haemodynamic measurements to identify women whose hypertension was unlikely to be controlled using labetalol alone and so were likely to require additional vasodilator therapy. The use of serial haemodynamic monitoring to guide treatment in these women significantly reduced the rates of severe hypertension and allowed women to be triaged into those with low vascular resistance who could be successfully treated with labetalol alone and those with a high vascular resistance who would need additional vasodilator therapy. HYPERLINK \l "_ENREF_38" \o "Stott, 2016 #449" ADDIN EN.CITE Stott201644944944917Stott, D.Bolten, M.Paraschiv, D.Papastefanou, I.Chambers, J. B.Kametas, N. A.Antenatal Hypertension Clinic, Division of Women's Health, King's College Hospital, Denmark Hill, London, UK.
Leto Maternity Unit, Athens, Greece.
Cardiothoracic Centre, Guy's and St Thomas Hospital, London, UK.
Antenatal Hypertension Clinic, Division of Women's Health, King's College Hospital, Denmark Hill, London, UK. nick.kametas@kcl.ac.uk.
Harris Birthright Research Centre for Fetal Medicine, Division of Women's Health, King's College Hospital, Denmark Hill, London, UK. nick.kametas@kcl.ac.uk.Longitudinal hemodynamics in the acute phase of treatment to predict the need for vasodilatory therapy in pregnant women treated with labetalolUltrasound Obstet GynecolUltrasound Obstet GynecolUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology2016Oct 201469-0705 (Electronic)
0960-7692 (Linking)27762457http://www.ncbi.nlm.nih.gov/pubmed/2776245710.1002/uog.1733538
Moreover, Ambrozic et al evaluated lung and cardiac ultrasound for assessment of fluid tolerance and fluid responsiveness in severe preeclamptic patients before and after delivery. HYPERLINK \l "_ENREF_39" \o "Ambrozic, 2016 #451" ADDIN EN.CITE Ambrozic201645145145117Ambrozic, J.Brzan Simenc, G.Prokselj, K.Tul, N.Cvijic, M.Lucovnik, M.Department of Cardiology, University Medical Center Ljubljana, Slovenia.
Department of Perinatology, Division of Obstetrics and Gynecology, University Medical Center Ljubljana, Slovenia.
Department of Perinatology, Division of Obstetrics and Gynecology, University Medical Center Ljubljana, Slovenia. miha.lucovnik@kclj.si.Lung and cardiac ultrasound for hemodynamic monitoring of patients with severe preeclampsiaUltrasound Obstet GynecolUltrasound Obstet GynecolUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecologydiastolic dysfunctionechocardiographyfluid responsivenessfluid tolerancelung ultrasoundpassive leg raisingpreeclampsia2016Oct 131469-0705 (Electronic)
0960-7692 (Linking)27736042http://www.ncbi.nlm.nih.gov/pubmed/2773604210.1002/uog.1733139 They found that severe preeclampsia is associated with an increase in extravascular lung water, which could in part be caused by disturbed diastolic left ventricular function. Excess lung water can be identified in severe preeclamptic patients before appearance of clinical signs by using lung ultrasound. The role of these findings in clinical practice, still need to be determined. HYPERLINK \l "_ENREF_39" \o "Ambrozic, 2016 #451" ADDIN EN.CITE Ambrozic201645145145117Ambrozic, J.Brzan Simenc, G.Prokselj, K.Tul, N.Cvijic, M.Lucovnik, M.Department of Cardiology, University Medical Center Ljubljana, Slovenia.
Department of Perinatology, Division of Obstetrics and Gynecology, University Medical Center Ljubljana, Slovenia.
Department of Perinatology, Division of Obstetrics and Gynecology, University Medical Center Ljubljana, Slovenia. miha.lucovnik@kclj.si.Lung and cardiac ultrasound for hemodynamic monitoring of patients with severe preeclampsiaUltrasound Obstet GynecolUltrasound Obstet GynecolUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecologydiastolic dysfunctionechocardiographyfluid responsivenessfluid tolerancelung ultrasoundpassive leg raisingpreeclampsia2016Oct 131469-0705 (Electronic)
0960-7692 (Linking)27736042http://www.ncbi.nlm.nih.gov/pubmed/2773604210.1002/uog.1733139
Prediction
Initial studies focused predominantly on the first and second trimester prediction of preeclampsia and fetal growth restriction. ADDIN EN.CITE ADDIN EN.CITE.DATA HYPERLINK \l "_ENREF_40" \o "Khalil, 2012 #424" 40, HYPERLINK \l "_ENREF_41" \o "Khalil, 2012 #423" 41 More recently, however, more studies have assessed third trimester (34 to 37 weeks gestation) prediction of later development of preeclampsia. HYPERLINK \l "_ENREF_42" \o "Guy, 2016 #439" ADDIN EN.CITE Guy201643943943917Guy, G. P.Ling, H. Z.Garcia, P.Poon, L. C.Nicolaides, K. H.Harris Birthright Research Centre for Fetal Medicine, King's College, London, UK.
Harris Birthright Research Centre for Fetal Medicine, King's College, London, UK. liona.poon@cuhk.edu.hk.
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong. liona.poon@cuhk.edu.hk.Maternal cardiac function at 35-37 weeks' gestation: prediction for preeclampsia and gestational hypertensionUltrasound Obstet GynecolUltrasound Obstet GynecolUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and GynecologyCardiac outputGestational hypertensionMaternal cardiovascular functionPreeclampsiaThird-trimester screeningTotal peripheral resistance2016Sep 131469-0705 (Electronic)
0960-7692 (Linking)27619066http://www.ncbi.nlm.nih.gov/pubmed/2761906610.1002/uog.1730042 Other studies have attempted to predict these pregnancy pathologies even prior to conception! HYPERLINK \l "_ENREF_43" \o "Mahendru, 2016 #441" ADDIN EN.CITE Mahendru201644144144117Mahendru, A. A.Foo, F. L.McEniery, C. M.Everett, T. R.Wilkinson, I. B.Lees, C. C.Fetal Medicine Department, Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Department of Surgery and Cancer, Imperial College London, London, UK.
Experimental Medicine and Immunotherapeutics, ACCI, Level 3 Addenbrooke's, Cambridge, UK.
Department of Development and Regeneration, KU Leuven, Leuven, Belgium.Change in maternal cardiac output from pre-conception to mid-pregnancy is associated with birth weight in healthy pregnanciesUltrasound Obstet GynecolUltrasound Obstet GynecolUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecologybirth weightcardiac outputhemodynamicspregnancyvascular resistance2016Nov 181469-0705 (Electronic)
0960-7692 (Linking)27859800http://www.ncbi.nlm.nih.gov/pubmed/2785980010.1002/uog.1736843
In a cohort of around 3000 pregnancies, Guy et al assessed the prediction of preeclampsia/pregnancy induced hypertension using maternal cardiac function at 35 to 37 weeks gestation. HYPERLINK \l "_ENREF_42" \o "Guy, 2016 #439" ADDIN EN.CITE Guy201643943943917Guy, G. P.Ling, H. Z.Garcia, P.Poon, L. C.Nicolaides, K. H.Harris Birthright Research Centre for Fetal Medicine, King's College, London, UK.
Harris Birthright Research Centre for Fetal Medicine, King's College, London, UK. liona.poon@cuhk.edu.hk.
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong. liona.poon@cuhk.edu.hk.Maternal cardiac function at 35-37 weeks' gestation: prediction for preeclampsia and gestational hypertensionUltrasound Obstet GynecolUltrasound Obstet GynecolUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and GynecologyCardiac outputGestational hypertensionMaternal cardiovascular functionPreeclampsiaThird-trimester screeningTotal peripheral resistance2016Sep 131469-0705 (Electronic)
0960-7692 (Linking)27619066http://www.ncbi.nlm.nih.gov/pubmed/2761906610.1002/uog.1730042 In women who developed term preeclampsia, total peripheral resistance and mean arterial pressure were increased, and the cardiac output was decreased, compared to those who remained normotensive throughout pregnancy. However, the assessment of maternal cardiac function at 35 to 37 weeks gestation is unlikely to improve the performance of screening for preeclampsia provided by maternal factors and mean arterial pressure alone. HYPERLINK \l "_ENREF_42" \o "Guy, 2016 #439" ADDIN EN.CITE Guy201643943943917Guy, G. P.Ling, H. Z.Garcia, P.Poon, L. C.Nicolaides, K. H.Harris Birthright Research Centre for Fetal Medicine, King's College, London, UK.
Harris Birthright Research Centre for Fetal Medicine, King's College, London, UK. liona.poon@cuhk.edu.hk.
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong. liona.poon@cuhk.edu.hk.Maternal cardiac function at 35-37 weeks' gestation: prediction for preeclampsia and gestational hypertensionUltrasound Obstet GynecolUltrasound Obstet GynecolUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and GynecologyCardiac outputGestational hypertensionMaternal cardiovascular functionPreeclampsiaThird-trimester screeningTotal peripheral resistance2016Sep 131469-0705 (Electronic)
0960-7692 (Linking)27619066http://www.ncbi.nlm.nih.gov/pubmed/2761906610.1002/uog.1730042 This group found similar results when assessing pregnancies with small for gestational age (SGA) or large for gestational age (LGA) fetuses. In SGA, cardiac output and heart rate were reduced while total peripheral resistance was increased; on the other hand, in LGA, cardiac output and heart rate were increased while total peripheral resistance was reduced compared to women with normal sized babies. However, again, maternal haemodynamic assessment is unlikely to increase the prediction of SGA or LGA over and above a combination of maternal characteristics and fetal ultrasound biometry. HYPERLINK \l "_ENREF_44" \o "Guy, 2016 #440" ADDIN EN.CITE Guy201644044044017Guy, G. P.Ling, H. Z.Machuca, M.Poon, L. C.Nicolaides, K. H.Harris Birthright Research Centre for Fetal Medicine, King's College, London, UK.
Harris Birthright Research Centre for Fetal Medicine, King's College, London, UK. liona.poon@cuhk.edu.hk.
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong. liona.poon@cuhk.edu.hk.Maternal cardiac function at 35-37 weeks' gestation: relation with birthweightUltrasound Obstet GynecolUltrasound Obstet GynecolUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and GynecologyCardiac outputLarge for gestational age neonatesMaternal cardiovascular functionSmall for gestational age neonatesThird-trimester screeningTotal peripheral resistance2016Oct 51469-0705 (Electronic)
0960-7692 (Linking)27706864http://www.ncbi.nlm.nih.gov/pubmed/2770686410.1002/uog.1731644
Moreover, Dragan et al evaluated whether a cutoff of 38 for the soluble fms-like tyrosine kinase 1 (sFLT-1) to placental growth factor (PLGF) ratio is of predictive value for preeclampsia (PE) in singleton pregnancies, at 30-37 weeks' gestation. HYPERLINK \l "_ENREF_45" \o "Dragan, 2016 #452" ADDIN EN.CITE Dragan201645245245217Dragan, I.Georgiou, T.Prodan, N.Akolekar, R.Nicolaides, K. H.Harris Birthright Research Centre for Fetal Medicine, King's College, London, UK.
Department of Fetal Medicine, Medway Maritime Hospital, Gillingham, UK.
Harris Birthright Research Centre for Fetal Medicine, King's College, London, UK. kypros@fetalmedicine.com.Screening for preeclampsia by the sFLT to PLGF ratio cut-off of 38 at 30-37 weeks' gestationUltrasound Obstet GynecolUltrasound Obstet GynecolUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and GynecologyPlacental growth factorPreeclampsiaPyramid of antenatal caresoluble fms-like tyrosine kinase-12016Sep 131469-0705 (Electronic)
0960-7692 (Linking)27619203http://www.ncbi.nlm.nih.gov/pubmed/2761920310.1002/uog.17301