European Heart Journal doi:10.1093/eurheartj/ehr218 ESC GUIDELINESESC Guidelines on the management ofcardiovascular diseases during pregnancyThe Task Force on the Management of Cardiovascular Diseasesduring Pregnancy of the European Society of Cardiology (ESC)Endorsed by the European Society of Gynecology (ESG), the Association forEuropean Paediatric Cardiology (AEPC), and the German Society for GenderMedicine (DGesGM)Authors/Task Force Members Vera Regitz-Zagrosek (Chairperson) (Germany)*,Carina Blomstrom Lundqvist (Sweden), Claudio Borghi (Italy), Renata Cifkova(Czech Republic), Rafael Ferreira (Portugal), Jean-Michel Foidart† (Belgium),J. Simon R. Gibbs (UK), Christa Gohlke-Baerwolf (Germany), Bulent Gorenek(Turkey), Bernard Iung (France), Mike Kirby (UK), Angela H. E. M. Maas (TheNetherlands), Joao Morais (Portugal), Petros Nihoyannopoulos (UK),Petronella G. Pieper (The Netherlands), Patrizia Presbitero (Italy),Jolien W. Roos-Hesselink (The Netherlands), Maria Schaufelberger (Sweden),Ute Seeland (Germany), Lucia Torracca (Italy).ESC Committee for Practice Guidelines (CPG): Jeroen Bax (CPG Chairperson) (The Netherlands),Angelo Auricchio (Switzerland), Helmut Baumgartner (Germany), Claudio Ceconi (Italy), Veronica Dean (France),Christi Deaton (UK), Robert Fagard (Belgium), Christian Funck-Brentano (France), David Hasdai (Israel),Arno Hoes (The Netherlands), Juhani Knuuti (Finland), Philippe Kolh (Belgium), Theresa McDonagh (UK),Cyril Moulin (France), Don Poldermans (The Netherlands), Bogdan A. Popescu (Romania), Zeljko Reiner (Croatia),Udo Sechtem (Germany), Per Anton Sirnes (Norway), Adam Torbicki (Poland), Alec Vahanian (France),Stephan Windecker (Switzerland).* Corresponding author. Vera Regitz-Zagrosek, Charite Universitaetsmedizin Berlin, Institute for Gender in Medicine, Hessische Str 3 –4, D-10115 Berlin, Germany. Tel: +49 30 450 ´525 288, Fax: +49 30 450 7 525 288, Email: firstname.lastname@example.org† Representing the European Society of Gynecology.‡ Representing the Association for European Paediatric Cardiology.Other ESC entities having participated in the development of this document:Associations: European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA).Working Groups: Thrombosis, Grown-up Congenital Heart Disease, Hypertension and the Heart, Pulmonary Circulation and Right Ventricular Function, Valvular Heart Disease,Cardiovascular Pharmacology and Drug Therapy, Acute Cardiac Care, Cardiovascular Surgery.Councils: Cardiology Practice, Cardiovascular Primary Care, Cardiovascular Imaging. The content of these European Society of Cardiology (ESC) Guidelines has been published forpersonal and educational use only. No commercial use is authorized. No part of the ESC Guidelines may be translated or reproduced in any form without written permission fromthe ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handlesuch permissions on behalf of the ESC.Disclaimer. The ESC Guidelines represent the views of the ESC and were arrived at after careful consideration of the available evidence at the time they were written. Healthprofessionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of healthprofessionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient’sguardian or carer. It is also the health professional’s responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.& The European Society of Cardiology 2011. All rights reserved. For permissions please email: email@example.com.
ESC Guidelines Page 3 of 51 10.2. Risk factors for pregnancy-related venous thrombo- ACC American College of Cardiology embolism and risk stratiﬁcation . . . . . . . . . . . . . . . . 38 ACE angiotensin-converting enzyme 10.3. Prevention of venous thrombo-embolism . . . . . . . . . 38 ACS acute coronary syndrome 10.4. Management of acute venous thrombo-embolism . . . 39 AF atrial ﬁbrillation 10.5. Recommendations for the prevention and management AHA American Heart Association of venous thrombo-embolism in pregnancy and aPTT activated partial thromboplastin time puerperium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 ARB angiotensin receptor blocker11. Drugs during pregnancy and breastfeeding . . . . . . . . . . . . 41 AS aortic stenosis 11.1. General principles . . . . . . . . . . . . . . . . . . . . . . . . 41 ASD atrial septal defect 11.2. Recommendations for drug use . . . . . . . . . . . . . . . 42 AV atrioventricular12. Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 AVSD atrioventricular septal defect13. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 BMI body mass index BNP B-type natriuretic peptide BP blood pressureList of tables CDC Centers for Disease ControlTable 1. Classes of recommendation CHADS congestive heart failure, hypertension, age (.75Table 2. Levels of evidence years), diabetes, strokeTable 3. Estimated fetal and maternal effective doses for various CI conﬁdence intervaldiagnostic and interventional radiology procedures CO cardiac outputTable 4. Predictors of maternal cardiovascular events and risk CoA coarction of the aortascore from the CARPREG study CT computed tomographyTable 5. Predictors of maternal cardiovascular events identiﬁed in CVD cardiovascular diseasecongential heart diseases in the ZAHARA and Khairy study DBP diastolic blood pressureTable 6. Modiﬁed WHO classiﬁcation of maternal cardiovascular DCM dilated cardiomyopathyrisk: principles DVT deep venous thrombosisTable 7. Modiﬁed WHO classiﬁcation of maternal cardiovascular ECG electrocardiogramrisk: application EF ejection fractionTable 8. Maternal predictors of neonatal events in women with ESC European Society of Cardiologyheart disease ESH European Society of HypertensionTable 9. General recommendations ESICM European Society of Intensive Care MedicineTable 10. Recommendations for the management of congenital FDA Food and Drug Administrationheart disease HCM hypertrophic cardiomyopathyTable 11. Recommendations for the management of aortic disease ICD implantable cardioverter-deﬁbrillatorTable 12. Recommendations for the management of valvular heart INR international normalized ratiodisease i.v. intravenousTable 13. Recommendations for the management of coronary LMWH low molecular weight heparinartery disease LV left ventricularTable 14. Recommendations for the management of cardiomyopa- LVEF left ventricular ejection fractionthies and heart failure LVOTO left ventricular outﬂow tract obstructionTable 15. Recommendations for the management of arrhythmias MRI magnetic resonance imagingTable 16. Recommendations for the management of hypertension MS mitral stenosisTable 17. Check list for risk factors for venous thrombo-embolism NT-proBNP N-terminal pro B-type natriuretic peptideTable 18. Prevalence of congenital thrombophilia and the associ- NYHA New York Heart Associationated risk of venous thrombo-embolism during pregnancy OAC oral anticoagulantTable 19. Risk groups according to risk factors: deﬁnition and pre- PAH pulmonary arterial hypertensionventive measures PAP pulmonary artery pressureTable 20. Recommendations for the prevention and management PCI percutaneous coronary interventionof venous thrombo-embolism in pregnancy and puerperium PPCM peripartum cardiomyopathyTable 21. Recommendations for drug use PS pulmonary valve stenosis RV right ventricular SBP systolic blood pressure SVT supraventricular tachycardia TGA complete transposition of the great arteriesAbbreviations and acronyms TR tricuspid regurgitation UFH unfractionated heparinABPM ambulatory blood pressure monitoring VSD ventricular septal defect
Page 4 of 51 ESC GuidelinesVT ventricular tachycardia evaluation of diagnostic and therapeutic procedures was per-VTE venous thrombo-embolism formed including assessment of the risk–beneﬁt ratio. EstimatesWHO World Health Organization of expected health outcomes for larger populations were included, where data exist. The level of evidence and the strength of recommendation of particular treatment options were weighed and graded according to pre-deﬁned scales, as outlined in1. Preamble Tables 1 and 2.Guidelines summarize and evaluate all available evidence, at the The experts of the writing and reviewing panels ﬁlled in declara-time of the writing process, on a particular issue with the aim of tions of interest forms which might be perceived as real or poten-assisting physicians in selecting the best management strategies tial sources of conﬂicts of interest. These forms were compiledfor an individual patient, with a given condition, taking into into one ﬁle and can be found on the ESC Web Site (http://account the impact on outcome, as well as the risk –beneﬁt ratio www.escardio.org/guidelines). Any changes in declarations of inter-of particular diagnostic or therapeutic means. Guidelines are no est that arise during the writing period must be notiﬁed to the ESCsubstitutes but are complements for textbooks and cover the and updated. The Task Force received its entire ﬁnancial supportEuropean Society of Cardiology (ESC) Core Curriculum topics. from the ESC without any involvement from healthcare industry.Guidelines and recommendations should help the physicians to The ESC CPG supervises and coordinates the preparation ofmake decisions in their daily practice. However, the ﬁnal decisions new Guidelines produced by Task Forces, expert groups, or con-concerning an individual patient must be made by the responsible sensus panels. The Committee is also responsible for the endorse-physician(s). ment process of these Guidelines. The ESC Guidelines undergo A great number of Guidelines have been issued in recent years extensive review by the CPG and external experts. After appropri-by the ESC as well as by other societies and organizations. Because ate revisions it is approved by all the experts involved in the Taskof the impact on clinical practice, quality criteria for the develop- Force. The ﬁnalized document is approved by the CPG for publi-ment of guidelines have been established in order to make all cation in the European Heart Journal.decisions transparent to the user. The recommendations for for- The task of developing Guidelines covers not only the inte-mulating and issuing ESC Guidelines can be found on the ESC gration of the most recent research, but also the creation of edu-website (http://www.escardio.org/guidelines-surveys/esc-guidelines/ cational tools and implementation programmes for theabout/Pages/rules-writing.aspx). ESC Guidelines represent the ofﬁcial recommendations. To implement the guidelines, condensedposition of the ESC on a given topic and are regularly updated. pocket guidelines versions, summary slides, booklets with essential Members of this Task Force were selected by the ESC to rep- messages, and an electronic version for digital applications (smart-resent professionals involved with the medical care of patients phones, etc.) are produced. These versions are abridged and, thus,with this pathology. Selected experts in the ﬁeld undertook a com- if needed, one should always refer to the full text version which isprehensive review of the published evidence for diagnosis, manage- freely available on the ESC website.ment, and/or prevention of a given condition according to ESC The National Societies of the ESC are encouraged to endorse,Committee for Practice Guidelines (CPG) policy. A critical translate, and implement the ESC Guidelines. Implementation Table 1 Classes of recommendation Classes of Deﬁnition Suggested wording to use recommendations Class I Evidence and/or general agreement Is recommended/is that a given treatment or procedure indicated is beneﬁcial, useful, effective. Class II Conﬂicting evidence and/or a divergence of opinion about the usefulness/efﬁcacy of the given treatment or procedure. Class IIa Weight of evidence/opinion is in Should be considered favour of usefulness/efﬁcacy. Class IIb Usefulness/efﬁcacy is less well May be considered established by evidence/opinion. Class III Evidence or general agreement that Is not recommended the given treatment or procedure is not useful/effective, and in some cases may be harmful.
ESC Guidelines Page 5 of 51 they should be managed by interdisciplinary teams; high risk Table 2 Levels of evidence patients should be treated in specialized centres; and diagnostic procedures and interventions should be performed by specialists Data derived from multiple randomized with great expertise in the individual techniques and experience Level of clinical trials Evidence A or meta-analyses. in treating pregnant patients. Registries and prospective studies are urgently needed to improve the state of knowledge. Data derived from a single randomized Level of clinical trial Evidence B or large non-randomized studies. 2.2 Methods The Guidelines are based on a systematic search of the literature Consensus of opinion of the experts and/ Level of of the last 20 years in the National Institutes of Health database or small studies, retrospective studies, Evidence C registries. (PubMed). The publications and recommendations of the Euro- pean and American cardiological societies are also considered: American Heart Association/American College of Cardiology (AHA/ACC),2 the ESC in 2003,3 the Working Group Valvular Heart Disease of the ESC,4 the guidelines of the German Societyprogrammes are needed because it has been shown that the of Cardiology (German Society of Cardiology),5,6 and the ESCoutcome of disease may be favourably inﬂuenced by the thorough Task Force on the Management of Valvular Heart Disease 2007.7application of clinical recommendations. Surveys and registries are needed to verify that real-life dailypractice is in keeping with what is recommended in the guidelines, 2.3 Epidemiologythus completing the loop between clinical research, writing of The spectrum of CVD in pregnancy is changing and differsguidelines, and implementing them into clinical practice. between countries. In the western world, the risk of CVD in preg- The guidelines do not, however, override the individual respon- nancy has increased due to increasing age at ﬁrst pregnancy andsibility of health professionals to make appropriate decisions in the increasing prevalence of cardiovascular risk factors—diabetes,circumstances of the individual patients, in consultation with that hypertension, and obesity. Also the treatment of congenital heartpatient, and, where appropriate and necessary, the patient’s guar- disease has improved, resulting in an increased number ofdian or carer. It is also the health professional’s responsibility to women with heart disease reaching childbearing age.8 In westernverify the rules and regulations applicable to drugs and devices at countries maternal heart disease is now the major cause ofthe time of prescription. maternal death during pregnancy.9 Hypertensive disorders are the most frequent cardiovascular events during pregnancy, occurring in 6–8% of all pregnancies.102. General considerations In the western world, congenital heart disease is the most frequent cardiovascular disease present during pregnancy (75 –82%), with2.1 Introduction shunt lesions predominating (20–65%).11,12 Congenital heart disease represents just 9– 19% outside Europe and NorthAt present, 0.2 –4% of all pregnancies in western industrialized America. Rheumatic valvular disease dominates in non-westerncountries are complicated by cardiovascular diseases (CVD),1 countries, comprising 56 –89% of all cardiovascular diseases inand the number of the patients who develop cardiac problems pregnancy.11,12during pregnancy is increasing. Nevertheless, the number of such Cardiomyopathies are rare, but represent severe causes of car-patients presenting to the individual physician is small. However, diovascular complications in pregnancy. Peripartum cardiomyopa-knowledge of the risks associated with CVD during pregnancy thy (PPCM) is the most common cause of severe complications.13and their management are of pivotal importance for advisingpatients before pregnancy. Therefore, guidelines on disease man-agement in pregnancy are of great relevance. Such guidelines 2.4 Haemodynamic, haemostatic, andhave to give special consideration to the fact that all measures metabolic alterations during pregnancyconcern not only the mother, but the fetus as well. Therefore, Pregnancy induces changes in the cardiovascular system to meetthe optimum treatment of both must be targeted. A therapy the increased metabolic demands of the mother and fetus. Theyfavourable for the mother can be associated with an impairment include increases in blood volume and cardiac output (CO), andof the child, and in extreme cases treatment measures which reductions in systemic vascular resistance and blood pressure (BP).protect the survival of the mother can cause the death of the Plasma volume reaches a maximum of 40% above baseline at 24fetus. On the other hand, therapies to protect the child may weeks gestation. A 30 –50% increase in CO occurs in normal preg-lead to a suboptimal outcome for the mother. Because prospective nancy. In early pregnancy increased CO is primarily related to theor randomized studies are lacking, with a few exceptions, rec- rise in stroke volume; however, in late pregnancy, heart rate is theommendations in this guideline mostly correspond to the evidence major factor. Heart rate starts to rise at 20 weeks and increaseslevel C. until 32 weeks. It remains high 2–5 days after delivery. Systemic Some general conclusions have arisen from these guidelines: BP (SBP) typically falls early in gestation and diastolic BP (DBP)counselling and management of women of childbearing age with is usually 10 mmHg below baseline in the second trimester. Thissuspected cardiac disease should start before pregnancy occurs; decrease in BP is caused by active vasodilatation, achieved
Page 6 of 51 ESC Guidelinesthrough the action of local mediators such as prostacyclin and The ﬁnal phenotype will also be determined by incomplete pene-nitric oxide. In the third trimester, the DBP gradually increases trance and pleiotropic effects, and may vary signiﬁcantly. Forand may normalize to non-pregnant values by term. defects that are inherited in a polygenic manner, recurrence risk The heart can increase its size by up to 30%, which is partially is less clearly deﬁned. Autosomal recessive and X-chromosomaldue to dilatation. Data regarding systolic and diastolic function in recessive inheritance are rare.pregnancy are scarce. Systolic function increases ﬁrst but may Genetic testing may be useful:decrease in the last trimester. Reports on diastolic function are † in cardiomyopathies and channelopathies, such as long QTconﬂicting. syndromes17 Pregnancy induces a series of haemostatic changes, with an † when other family members are affectedincrease in concentration of coagulation factors, ﬁbrinogen, and † when the patient has dysmorphic features, developmental delay/platelet adhesiveness, as well as diminished ﬁbrinolysis, which lead mental retardation, or when other non-cardiac congenitalto hypercoagulability and an increased risk of thrombo-embolic abnormalities are present, in syndromes such as in Marfan,events. In addition, obstruction to venous return by the enlarging 22q11 deletion, Williams –Beuren, Alagille, Noonan, anduterus causes stasis and a further rise in risk of thrombo-embolism. Holt–Oram syndrome. Maternal glucose homeostasis may change and cholesterol levelsincrease in adaptation to fetal–maternal needs. For a steadily increasing number of genetic defects, genetic screen- Physiological changes that occur during pregnancy can affect ing by chorionic villous biopsy can be offered in the 12th week ofabsorption, excretion, and bioavailability of all drugs.14 The pregnancy. All women with congenital heart disease should beincreased intravascular blood volume partly explains the higher offered fetal echocardiography in the 19th to 22nd week of preg-dosages of drugs required to achieve therapeutic plasma concen- nancy. Measurement of nuchal fold thickness in the 12th to 13thtrations, and the dose adaptations needed during treatment. More- week of pregnancy is an early screening test for women over 35over, the raised renal perfusion and the higher hepatic metabolism years of age. The sensitivity for the presence of a signiﬁcantincrease drug clearance. The altered pharmacokinetics of drugs heart defect is 40%, while the speciﬁcity of the method is 99%.vary in magnitude during different stages of pregnancy, making The incidence of congenital heart disease with normal nuchalcareful monitoring of the patient and dose adjustments necessary. fold thickness is 1/1000.18 Uterine contractions, positioning (left lateral vs. supine), pain, The inheritance pattern differs among the diseases, and there-anxiety, exertion, bleeding, and uterine involution cause signiﬁcant fore genetic counselling by a geneticist is highly recommendedhaemodynamic changes during labour and post-partum. Anaesthe- for patients and their family members.17 Genetic testing aftersia, analgesia, haemorrhage, and infection may induce additional careful counselling has the rationale of identifying at-risk asympto-cardiovascular stress. SBP and DBP increase 15 –25% and 10 – matic or disease-free relatives and to guide clinical surveillance for15%, respectively, during uterine contractions. Such increases are disease onset, thereby enhancing preventive and treatment inter-associated with a rise in pressure in the amniotic ﬂuid, and in the ventions. It is advocated in patients with known genetic disordersintrathoracic venous, cerebrospinal, and extradural ﬂuids. CO and is more advisable if treatment options are available.17increases by 15% in early labour, by 25% during stage 1, and by50% during expulsive efforts.15 It reaches an increase of 80% 2.6 Cardiovascular diagnosisearly post-partum due to autotransfusion associated with uterine in pregnancyinvolution and resorption of leg oedema. The following procedures are of relevance for the diagnosis and In conclusion, the physiological adaptations to pregnancy inﬂu- management of CVD in pregnancy.ence the evaluation and interpretation of cardiac function and clini-cal status. History and clinical investigation2.5 Genetic testing and counselling Many disorders can be identiﬁed by taking a careful personal andAn important aspect concerning the care of young women with family history, particularly cardiomyopathies, the Marfan syn-CVD is the consultation about the risk of inheritance of cardiac drome, congenital heart disease, juvenile sudden death, longdefects for their descendants. The risk is raised signiﬁcantly in com- QT syndrome, and catecholaminergic ventricular tachycardiaparison with parents without CVD where the risk is 1%. In (VT) or Brugada syndrome. It is important to ask speciﬁcallyaddition, there are large differences between each of the heredi- about possible sudden deaths in the family. The assessment oftary heart disease conditions, and the risk for descendants is dyspnoea is important for diagnosis and prognosis of valvedependent on whether only the mother, only the father, or both lesions and for heart failure. A thorough physical examinationparents suffer from hereditary cardiac defects.16 In general, the considering the physiological changes that occur during preg-risk is higher when the mother is affected rather than the nancy (Section 2.4) is mandatory, including auscultation forfather.16 The recurrence risk varies between 3% and 50% depend- new murmurs, changes in murmurs, and looking for signs ofing on the type of maternal heart disease. heart failure. When dyspnoea occurs during pregnancy or Children of parents with a cardiovascular condition inherited in when a new pathological murmer is heard, echocardiography isan autosomal dominant manner (e.g. Marfan syndrome, hyper- indicated. It is crucial to measure the BP, in left lateral recum-trophic cardiomyopathy, or long QT syndrome) have an inheri- bency (see Section 9) using a standardized method, and totance risk of 50%, regardless of gender of the affected parent. look for proteinuria, especially with a history or family history
ESC Guidelines Page 7 of 51of hypertension or pre-eclampsia. Oximetry should be per- disease with borderline or mildly reduced LVEF. Nuclear scintigra-formed in patients with congenital heart disease. phy should be avoided during pregnancy because of radiation exposure.ElectrocardiographyThe great majority of pregnant patients have a normal electrocar-diogram (ECG). The heart is rotated towards the left and on the Radiation exposuresurface ECG there is a 15–20 left axis deviation. Common ﬁndings The effects of radiation on the fetus depend on the radiation doseinclude transient ST segment and T wave changes, the presence of and the gestational age at which exposure occurs. If possible, pro-a Q wave and inverted T waves in lead III, an attenuated Q wave in cedures should be delayed until at least the completion of thelead AVF, and inverted T waves in leads V1, V2, and, occasionally, period of major organogenesis (.12 weeks after menses). ThereV3. ECG changes can be related to a gradual change in the position is no evidence of an increased fetal risk of congenital malformations,of the heart and may mimic left ventricular (LV) hypertrophy and intellectual disability, growth restriction, or pregnancy loss at dosesother structural heart diseases. of radiation to the pregnant woman of ,50 mGy22,23 (www.bt.cdc. Holter monitoring should be performed in patients with known gov/radiation/prenatalphysician.asp; accessed 31 October 2007).previous paroxysmal or persistent documented arrhythmia [VT, There may be a small increase in risk (1:2000 vs. 1:3000) of childhoodatrial ﬁbrillation (AF), or atrial ﬂutter] or those reporting symp- cancer. The threshold at which an increased risk of congenital mal-toms of palpitations. formations occurs has not been deﬁnitely determined. Some evi- dence suggests that risk of malformations is increased at dosesEchocardiography .100 mGy, whereas the risk between 50 and 100 mGy is lessBecause echocardiography does not involve exposure to radiation, clear. During the ﬁrst 14 days after fertilization, intact survivalis easy to perform, and can be repeated as often as needed, it has without fetal abnormality or death are the most likely outcomes ofbecome an important tool during pregnancy and is the preferred radiation exposure .50 mGy. After the ﬁrst 14 days, radiationscreening method to assess cardiac function. exposure .50 mGy may be associated with an increased risk of con- genital malformations, growth restriction, and intellectual disability.Transoesophageal echocardiography Most medical procedures do not expose the fetus to such highMultiplane transducers have made transoesophageal echocardio- levels of radiation (Table 3). For the majority of diagnostic medicalgraphy a very useful echocardiographic method in the assessment procedures, involving doses to the fetus of up to 1 mGy, theof adults with, for example, complex congenital heart disease. associated risks of childhood cancer are very low. (DocumentsTransoesophageal echocardiography, although rarely required, is of the Health Protection Agency. Radiation, Chemical and Environ-relatively safe during pregnancy. The presence of stomach con- mental Hazards March 2009. RSE-9 Protection of pregnant patientstents, risk of vomiting and aspiration, and sudden increases in during diagnostic medical exposures to ionising radiation. Adviceintra-abdominal pressure should be taken into account, and fetal from the Health Protection Agency, The Royal College of Radiol-monitoring performed if sedation is used. ogists, and the College of Radiographers.)Exercise testingExercise testing is useful to assess objectively the functionalcapacity, chronotropic and BP response, as well as Table 3 Estimated fetal and maternal effective dosesexercise-induced arrhythmias. It has become an integral part of for various diagnostic and interventional radiologythe follow-up of grown up congenital heart disease patients as procedureswell as patients with asymptomatic valvular heart disease.19,20 Itshould be performed in patients with known heart disease, prefer- Maternalably prior to pregnancy to assist in risk assessment. Procedure Fetal exposure exposure This Committee recommends performing submaximal exercisetests to reach 80% of predicted maximal heart rate in asympto- Chest radiograph <0.01 mGy <0.01 mSv 0.1 mGy 0.1 mSvmatic pregnant patients with suspected CVD. There is no evidence (PA and lateral)that it increases the risk of spontaneous abortion.21 Semi- CT chest 0.3 mGy 0.3 mSv 7 mGy 7 mSvrecumbent cycle ergometry appears to be the most comfortablemodality, but treadmill walking or upright cycle ergometry may Coronaryalso be used. Dobutamine stress should be avoided. If respiratory 1.5 mGy 1.5 mSv 7 mGy 7 mSv angiographyagas analysis is used, the limit is a respiratory exchange ratio of 1.0.Stress echocardiography using bicycle ergometry may add to the PCI ordiagnostic speciﬁcity in detecting the presence and extent of radiofrequency 3 mGy 3 mSv 15 mGy 15 mSv catheter ablationaischaemia in high risk patients with possible coronary arterydisease. This can also be useful prior to conception to assess myo- acardial reserve in patients with prior PPCM and recovered LV func- Exposure depends on the number of projections or views. CT ¼ computed tomography; PA ¼ postero-anterior; PCI ¼ percutaneoustion [left ventricular ejection fraction (LVEF)], and also in patients coronary intervention.with other cardiomyopathies, with valvular or congenital heart
Page 8 of 51 ESC Guidelines As a general rule, according to the principle ‘as low as reason- this timing is appropriate to start screening for congential heartably achievable’ (ALARA), all radiation doses due to medical disease. A review of the accuracy of ﬁrst-trimester ultrasoundsexposures must be kept as low as reasonably achievable.24 for detecting major congenital heart disease showed a sensitivity and speciﬁcity of 85% [95% conﬁdence interval (CI) 78 –90%]Chest radiograph and 99% (95% CI 98– 100%), respectively. Early examination inThe fetal dose from a chest radiograph is ,0.01 mGy.25 Neverthe- pregnancy allows parents to consider all options, including termin-less, a chest radiograph should only be obtained if other methods ation of pregnancy, if there are major malformations.33fail to clarify the cause of dyspnoea, cough, or other symptoms.23 The optimum time for screening of normal pregnancies for con- If the required diagnostic information can be obtained with an genital heart diseases34 is 18– 22 weeks of gestation when visual-imaging modality that does not use ionizing radiation, it should ization of the heart and outﬂow tracts is optimal. It becomesbe used as a ﬁrst-line test. If a study that uses ionizing radiation more difﬁcult after 30 weeks since the fetus is more crowdedhas to be performed, the radiation dose to the fetus should be within the amniotic cavity. Second-trimester screening (18– 22kept as low as possible (preferably ,50 mGy). The risks and weeks) for detection of fetal anomalies should be performed bybeneﬁts of performing or not performing the examination should experienced specialists, particularly in pregnancies with riskbe communicated. Documentation of the radiation dose to the factors for congenital heart anomalies.35mother in the medical records, particularly if the fetus is in the Cardiac anatomy and function, arterial and venous ﬂow, andﬁeld of view, is highly recommended.26,27 rhythm should be evaluated. When a fetal cardiac anomaly is sus- pected, it is mandatory to obtain the following.Magnetic resonance imaging and computed tomographyMagnetic resonance imaging (MRI) may be useful in diagnosing (1) A full fetal echocardiography to evaluate cardiac structure andcomplex heart disease or pathology of the aorta.28 It should only function, arterial and venous ﬂow, and rhythm.be performed if other diagnostic measures, including transthoracic (2) Detailed scanning of the fetal anatomy to look for associatedand transoesophageal echocardiography, are not sufﬁcient for anomalies (particularly the digits and bones).complete diagnosis. Limited data during organogenesis are avail- (3) Family history to search for familial syndromes.able, but MRI is probably safe, especially after the ﬁrst trimester.29 (4) Maternal medical history to identify chronic medical disorders, Gadolinium can be assumed to cross the fetal blood–placental viral illnesses, or teratogenic medications.barrier, but data are limited. The long-term risks of exposure of (5) Fetal karyotype (with screening for deletion in 22q11.2 whenthe developing fetus to free gadolinium ions30 are not known, conotruncal anomalies are present).and therefore gadolinium should be avoided. (6) Referral to a maternal–fetal medicine specialist, paediatric car- Computed tomography (CT)31 is usually not necessary to diag- diologist, geneticist, and/or neonatologist to discuss prognosis,nose CVD during pregnancy and, because of the radiation dose obstetric, and neonatal management, and options.involved, is therefore not recommended. One exception is that (7) Delivery at an institution that can provide neonatal cardiacit may be required for the accurate diagnosis or deﬁnite exclusion care, if needed.of pulmonary embolism. For this indication it is recommended if Doppler velocimetry (uterine, umbilical, fetal renal, and cerebralother diagnostic tools are not sufﬁcient (see Section 10). Low radi- arteries, and descending aorta) provides a non-invasive measureation CT 1 –3 mSv can be used in these situations. of the fetoplacental haemodynamic state. Abnormality of the Doppler index in the umbilical artery correlates to fetoplacentalCardiac catheterization vascular maldevelopment, fetal hypoxia, acidosis, and adverse peri-During coronary angiography the mean radiation exposure to the natal outcome. The most ominous pre-terminal ﬁndings of theunshielded abdomen is 1.5 mGy, and ,20% of this reaches the umbilical artery Doppler waveform are absent end-diastolic vel-fetus because of tissue attenuation. Shielding the gravid uterus ocity and reversed end-diastolic velocity. Reversed end-diastolicfrom direct radiation and especially shortening ﬂuoroscopic time velocity beyond 28 weeks should prompt immediate delivery bywill minimize radiation exposure. The radial approach is preferable caesarean delivery. Absent end-diastolic velocity should promptand should be undertaken by an experienced operator. Most elec- immediate consideration of delivery beyond 32 completedtrophysiological studies aiming for ablation should only be per- weeks.36formed if arrhythmias are intractable to medical treatment and Fetal biophysical proﬁle testing is indicated in pregnancies at riskcause haemodynamic compromise. If undertaken, electroanatomi- of fetal compromise. Testing should be performed one or morecal mapping systems should be used to reduce the radiation times per week, depending upon the clinical situation. Four echo-dose.32 graphic biophysical variables (fetal movement, tone, breathing, and General recommendations for diagnostic and therapeutic man- amniotic ﬂuid volume) and results of non-stress testing are usedagement during pregnancy are listed in Table 9. for scoring. Their presence implies absence of signiﬁcant central nervous system hypoxaemia/acidaemia. A compromised2.7 Fetal assessment fetus exhibits loss of accelerations of the fetal heart rate, decreasedFirst trimester ultrasound allows accurate measurement of gesta- body movement and breathing, hypotonia, and, less acutely,tional age and early detection of multiple pregnancy and of malfor- decreased amniotic ﬂuid volume. From 70% to 90% of late fetalmations. Diagnosis of congenital cardiac malformations can be deaths display evidence of chronic and/or acute compromise.made as early as 13 weeks, and, in families with heart disease, Sonographic detection of signs of fetal compromise can allow
ESC Guidelines Page 9 of 51appropriate intervention that ideally will prevent adverse fetal 2.9 Timing and mode of delivery: risk forsequelae.37,38 mother and child High risk delivery2.8 Interventions in the mother during Induction, management of labour, delivery, and post-partum sur-pregnancy veillance require speciﬁc expertise and collaborative management2.8.1 Percutaneous therapy by skilled cardiologists, obstetricians, and anaesthesiologists, inThe same restrictions which apply for diagnostic coronary angio- experienced maternal –fetal medicine units.45,46graphy (see Section 2.6) are relevant. If an intervention is absol-utely necessary, the best time to intervene is considered to be Timing of deliveryafter the fourth month in the second trimester. By this time orga- Spontaneous onset of labour is appropriate for women withnogenesis is complete, the fetal thyroid is still inactive, and the normal cardiac function and is preferable to induced labour forvolume of the uterus is still small, so there is a greater distance the majority of women with heart disease. Timing is individualized,between the fetus and the chest than in later months. Fluoroscopy according to the gravida’s cardiac status, Bishop score (a scoreand cineangiography times should be as brief as possible and the based upon the station of the presenting part and four character-gravid uterus should be shielded from direct radiation. Heparin istics of the cervix: dilatation, effacement, consistency, and pos-has to be given at 40–70 U/kg, targeting an activated clotting ition), fetal well-being, and lung maturity. Due to a lack oftime of at least 200 s, but not exceeding 300 s. prospective data and the inﬂuence of individual patient character- istics, standard guidelines do not exist, and management should therefore be individualized. In women with mild unrepaired conge-2.8.2 Cardiac surgery with cardiopulmonary bypass nital heart disease and in those who have undergone successfulMaternal mortality during cardiopulmonary bypass is now similar cardiac surgical repair with minimal residua, the management ofto that in non-pregnant women who undergo comparable labour and delivery is the same as for normal pregnant women.cardiac procedures.1 However, there is signiﬁcant morbidityincluding late neurological impairment in 3–6% of children, and Labour inductionfetal mortality remains high.39 For this reason cardiac surgery is Oxytocin and artiﬁcial rupture of the membranes are indicatedrecommended only when medical therapy or interventional pro- when the Bishop score is favourable. A long induction timecedures fail and the mother’s life is threatened. The best period should be avoided if the cervix is unfavourable. While there isfor surgery is between the 13th and 28th week.40,41 Surgery no absolute contraindication to misoprostol or dinoprostone,during the ﬁrst trimester carries a higher risk of fetal malfor- there is a theoretical risk of coronary vasospasm and a low riskmations, and during the third trimester there is a higher inci- of arrhythmias. Dinoprostone also has more profound effects ondence of pre-term delivery and maternal complications. We BP than prostaglandin E1 and is therefore contraindicated inknow from previous studies that gestational age has a large active CVD. Mechanical methods such as a Foley catheter wouldimpact on neonatal outcome.42 Recent improvement in neonatal be preferable to pharmacological agents, particularly in thecare has further improved survival of premature infants. At 26 patient with cyanosis where a drop in systemic vascular resistanceweeks, survival is generally 80%, with 20% having serious and/or BP would be detrimental.47neurological impairment. For this reason, caesarean deliverymay be considered before cardiopulmonary bypass if gestational Vaginal or caesarean deliveryage is .26 weeks.43 Whether or not delivery is advantageous The preferred mode of delivery is vaginal, with an individualizedfor the baby at this gestational age depends on several factors: delivery plan which informs the team of timing of delivery (spon-gender, estimated weight, prior administration of corticosteroids taneous/induced), method of induction, analgesia/regional anaes-before delivery, and the outcome statistics of the neonatal unit thesia, and level of monitoring required. In high risk lesions,concerned. When gestational age is 28 weeks or more, delivery delivery should take place in a tertiary centre with specialistbefore surgery should be considered. Before surgery a full multidisciplinary team care. Vaginal delivery is associated withcourse (at least 24 h) of corticosteroids should be administered less blood loss and infection risk compared with caesarean deliv-to the mother, whenever possible. During cardiopulmonary ery, which also increases the risk of venous thrombosis andbypass, fetal heart rate and uterine tone should be monitored thrombo-embolism.48 In general, caesarean delivery is reservedin addition to standard patient monitoring. Pump ﬂow .2.5 L/ for obstetric indications. There is no consensus regarding absolutemin/m2 and perfusion pressure .70 mmHg are mandatory to contraindications to vaginal delivery as this is very much dependentmaintain adequate utero-placental blood ﬂow; pulsatile ﬂow, on maternal status at the time of delivery and the anticipatedalthough controversial, seems more effective for preserving uter- cardiopulmonary tolerance of the patient. Caesarean deliveryoplacental blood ﬂow. Maternal haematocrit .28% is rec- should be considered for the patient on oral anticoagulantsommended to optimize the oxygen delivery. Normothermic (OACs) in pre-term labour, patients with Marfan syndrome andperfusion, when feasible, is advocated, and state of the art pH an aortic diameter .45 mm, patients with acute or chronicmanagement is preferred to avoid hypocapnia responsible for aortic dissection, and those in acute intractable heart failure.uteroplacental vasoconstriction and fetal hypoxia. Cardiopulmon- Cesarean delivery may be considered in Marfan patients with anary bypass time should be minimized.44 aortic diameter 40 –45 mm.7,49,50 (see also Section 4.3).
Page 10 of 51 ESC Guidelines In some centres, caesarean delivery is advocated for women with also be given, but it takes 4–6 h to inﬂuence the INR. If thesevere aortic stenosis (AS) and in patients with severe forms of pul- mother was on OACs at the time of delivery, the anticoagulatedmonary hypertension (including Eisenmenger syndrome), or acute newborn may be given fresh frozen plasma and should receiveheart failure.7,46 (see speciﬁc sections). Caesarean delivery may be vitamin K. The fetus may remain anticoagulated for 8 –10 daysconsidered in patients with mechanical heart valve prostheses to after discontinuation of maternal OACs.prevent problems with planned vaginal delivery. In such patients, a Ventricular arrhythmias during pregnancy and labourprolonged switch to heparin/low molecular weight heparin Arrhythmias are the most common cardiac complication during preg-(LMWH) may indeed be required for a long time before vaginal nancy in women with and without structural heart disease.12,56,57birth, particularly, when the obstetrical situation is unfavourable. They may manifest for the ﬁrst time during pregnancy, or pregnancyThis would increase the maternal risk (see also Sections 5.5 and 5.6). may exacerbate pre-existing arrhythmias.58 – 60 The 2006 ACC/AHA/ ESC guidelines for management of patients with ventricular arrhyth-Haemodynamic monitoring mias and the prevention of sudden cardiac death recommend thatSystemic arterial pressure and maternal heart rate are monitored, pregnant women with prolonged QT syndrome who have had symp-because lumbar epidural anaesthesia may cause hypotension. Pulse toms beneﬁt from continued b-blocker therapy throughout preg-oximetry and continuous ECG monitoring are utilized as required. nancy, during delivery, and post-partum unless there are deﬁniteA Swan – Ganz catheter for haemodynamic monitoring is rarely if contraindications. Use of b-blockers during labour does notever indicated due to the risk of arrhythmia provocation, bleeding, prevent uterine contractions and vaginal delivery.61and thrombo-embolic complications on removal.51 Post-partum careAnaesthesia/analgesia A slow i.v. infusion of oxytocin (,2 U/min), which avoids systemicLumbar epidural analgesia is often recommendable because it hypotension, is administered after placental delivery to preventreduces pain-related elevations of sympathetic activity, reduces maternal haemorrhage. Prostaglandin F analogues are useful tothe urge to push, and provides anaesthesia for surgery. Continuous treat post-partum haemorrhage, unless an increase in pulmonarylumbar epidural analgesia with local anaesthetics or opiates, or artery pressure (PAP) is undesirable. Methylergonovine is contra-continuous opioid spinal anaesthesia can be safely administered. indicated because of the risk (.10%) of vasoconstriction andRegional anaesthesia can, however, cause systemic hypotension hypertension.62,63 Meticulous leg care, elastic support stockings,and must be used with caution in patients with obstructive valve and early ambulation are important to reduce the risk oflesions. Intravenous (i.v.) perfusion must be monitored carefully.52 thrombo-embolism. Delivery is associated with important haemo- dynamic changes and ﬂuid shifts, particularly in the ﬁrst 12 –24 h,Labour which may precipitate heart failure in women with structuralOnce in labour, the woman should be placed in a lateral decubitus heart disease. Haemodynamic monitoring should therefore beposition to attenuate the haemodynamic impact of uterine con- continued for at least 24 h after delivery.64tractions.53 The uterine contractions should descend the fetalhead to the perineum, without maternal pushing, to avoid the Breastfeedingunwanted effects of the Valsalva manoeuvre.54,55 Lactation is associated with a low risk of bacteraemia secondary to Delivery may be assisted by low forceps or vacuum extraction. mastitis. In highly symptomatic/unwell patients, bottle-feedingRoutine antibiotic prophylaxis is not recommended. Continuous should be considered.electronic fetal heart rate monitoring is recommended. 2.10 Infective endocarditisDelivery in anticoagulated women with prosthetic valves Infective endocarditis during pregnancy is rare, with an estimatedOACs should be switched to LMWH or unfractionated heparin overall incidence of 0.006% (1 per 100 000 pregnancies)65 and(UFH) from the 36th week. Women treated with LMWH should an incidence of 0.5% in patients with known valvular or congenitalbe switched to i.v. UFH, at least 36 h before the induction of heart disease.66 The incidence is higher in drug addicts. Patientslabour or caesarean delivery. UFH should be discontinued 4–6 h with the highest risk for infective endocarditis are those with abefore planned delivery, and restarted 4–6 h after delivery if prosthetic valve or prosthetic material used for cardiac valvethere are no bleeding complications (see also Section 5.5). repair, a history of previous infective endocarditis, and someUrgent delivery in a patient with a mechanical valve taking thera- special patients with congenital heart disease.peutic anticoagulation may be necessary, and there is a high riskof severe maternal haemorrhage. If emergent delivery is necessary 2.10.1 Prophylaxiswhile the patient is still on UFH or LMWH, protamine should be The same measures as in non-pregnant patients with recent modi-considered. Protamine will only partially reverse the anticoagulant ﬁcations of guidelines apply.67 Endocarditis prophylaxis is now onlyeffect of LMWH. In the event of urgent delivery in a patient on recommended for patients at highest risk of aquiring endocarditistherapeutic OACs, caesarean delivery is preferred to reduce the during high risk procedures, e.g. dental procedures. During deliveryrisk of intracranial haemorrhage in the fully anticoagulated fetus. the indication for prophylaxis has been controversial and, given theIf emergent delivery is necessary, fresh frozen plasma should be lack of convincing evidence that infective endocarditis is related togiven prior to caesarean delivery to achieve a target international either vaginal or caesarean delivery, antibiotic prophylaxis is notnormalized ratio (INR) of ≤2.4 Oral vitamin K (0.5 –1 mg) may recommended during vaginal or caesarean delivery.67,68
ESC Guidelines Page 11 of 512.10.2 Diagnosis and risk assessmentThe diagnosis of infective endocarditis during pregnancy involves Table 4 Predictors of maternal cardiovascular eventsthe same criteria as in the non-pregnant patient.67 In spite of pro- and risk score from the CARPREG study12gress in the diagnosis and treatment of infective endocarditis,maternal morbidity and mortality remain high, reportedly 33% in Prior cardiac event (heart failure, transient ischaemic attack, stroke before pregnancy or arrhythmia).one study (mainly due to heart failure and thrombo-embolic com-plications).69 Fetal mortality is also high at 29%. Heart failure due Baseline NYHA functional class >II or cyanosis.to acute valve regurgitation is the most common complication, Left heart obstruction (mitral valve area <2 cm2, aortic valve arearequiring urgent surgery when medical treatment cannot stabilize <1.5 cm 2, peak LV outßow tract gradient >30 mmHg bythe patient.67 Cerebral and peripheral embolizations are also fre- echocardiography).quent complications. Reduced systemic ventricular systolic function (ejection fraction <40%).2.10.3 TreatmentInfective endocarditis should be treated the same way as in the CARPREG risk score: for each CARPREG predictor that is present a point isnon-pregnant patient, bearing in mind the fetotoxic effects of anti- assigned. Risk estimation of cardiovascular maternal complicationsbiotics (see Section 11). If infective endocarditis is diagnosed, anti- 0 point 5%biotics should be given guided by culture and antibiotic sensitivity 1 point 27% .1 point 75%results and local treatment protocols. Antibiotics that can be given LV ¼ left ventricular; NYHA ¼ New York Heart Association.during all trimesters of pregnancy are penicillin, ampicillin, amoxi-cillin, erythromycin, mezlocillin, and cephalosporins.70 All ofthem are included in group B of the Food and Drug Administration(FDA) classiﬁcation. Vancomycin, imipenem, rifampicin, and teico- Table 5 Predictors of maternal cardiovascular eventsplanin are all group C, which means risk cannot be excluded and identiﬁed in congential heart diseases in the ZAHARAtheir risk –beneﬁt ratio must be carefully considered. There is a and Khairy studydeﬁnite risk to the fetus in all trimesters of pregnancy withgroup D drugs (aminoglycosides, quinolones, and tetracyclines) ZAHARA predictors57and they should therefore only be used for vital indications.71Valve surgery during pregnancy should be reserved for cases History of arrhythmia event.where medical therapy has failed as per guidelines in non-pregnant Baseline NYHA functional class >II.patients.67 A viable fetus should be delivered prior to surgery Left heart obstruction (aortic valve peak gradient >50 mm Hg).where possible (see Section 2.8.2). Mechanical valve prosthesis.2.11 Risk estimation: contraindications Moderate/severe systemic atrioventricular valve regurgitation (possiblyfor pregnancy related to ventricular dysfunction).2.11.1 Pre-pregnancy counselling Moderate/severe sub-pulmonary atrioventricular valve regurgitationThe risk of pregnancy depends on the speciﬁc heart disease and (possibly related to ventricular dysfunction).clinical status of the patient. Individual counselling by experts is rec- Use of cardiac medication pre-pregnancy.ommended. Adolescents should be given advice on contraception,and pregnancy issues should be discussed as soon as they become Repaired or unrepaired cyanotic heart disease.sexually active. A risk assessment should be performed prior to Predictors from Khairy76pregnancy and drugs reviewed so that those which are contraindi-cated in pregnancy can be stopped or changed to alternatives Smoking history.where possible (see Section 11.2, Table 21). The follow-up plan Reduced subpulmonary ventricular function and/or severe pulmonaryshould be discussed with the patient and, if possible, her partner. regurgitation.Women with signiﬁcant heart disease should be managed jointlyby an obstetrician and a cardiologist with experience in treating NYHA ¼ New York Heart Association.pregnant patients with heart disease from an early stage. Highrisk patients should be managed by an expert multidisciplinaryteam in a specialist centre. All women with heart disease should sections dealing with speciﬁc diseases. In general, the risk of com-be assessed at least once before pregnancy and during pregnancy, plications increases with increasing disease complexity.56,72and hospital delivery should be advised. Disease-speciﬁc series are usually retrospective and too small to identify predictors of poor outcome. Therefore, risk estimation can2.11.2 Risk assessment: estimation of maternal and be further reﬁned by taking into account predictors that have beenoffspring risk identiﬁed in studies that included larger populations with various dis-To estimate the risk of maternal cardiovascular complications, eases. Several risk scores have been developed based on these predic-several approaches are available. Disease-speciﬁc risk can be tors, of which the CARPREG risk score is most widely known andassessed, and is described in these guidelines in the respective used. This risk score has been validated in several studies and
Page 12 of 51 ESC Guidelines Table 6 Modiﬁed WHO classiﬁcation of maternal Table 7 Modiﬁed WHO classiﬁcation of maternal cardiovascular risk: principles cardiovascular risk: application Risk class Risk of pregnancy by medical condition Conditions in which pregnancy risk is WHO I No detectable increased risk of maternal mortality and ¥ Uncomplicated, small or mild I no/mild increase in morbidity. - pulmonary stenosis - patent ductus arteriosus Small increased risk of maternal mortality or moderate - mitral valve prolapse II increase in morbidity. ¥ Successfully repaired simple lesions (atrial or ventricular septal SigniÞcantly increased risk of maternal mortality defect, patent ductus arteriosus, anomalous pulmonary venous or severe morbidity. Expert counselling required. drainage). III If pregnancy is decided upon, intensive specialist cardiac and obstetric monitoring needed throughout ¥ Atrial or ventricular ectopic beats, isolated pregnancy, childbirth, and the puerperium. Conditions in which pregnancy risk is WHO II or III Extremely high risk of maternal mortality or severe morbidity; pregnancy contraindicated. If pregnancy WHO II (if otherwise well and uncomplicated) IV occurs termination should be discussed. If pregnancy ¥ Unoperated atrial or ventricular septal defect continues, care as for class III. ¥ Repaired tetralogy of Fallot Modiﬁed from Thorne et al. 72 ¥ Most arrhythmias WHO ¼ World Health Organization WHO II–III (depending on individual) ¥ Mild left ventricular impairmentappears valuable to predict maternal risk, although overestimation ¥ Hypertrophic cardiomyopathycan occur.57,73 The CARPREG risk score is described in Table 4. Inwomen with congenital heart disease, the CARPREG score12 may ¥ Native or tissue valvular heart disease not considered WHO I or IValso be associated with a higher risk of late cardiovascular events post- ¥ Marfan syndrome without aortic dilatationpregnancy.74 The predictors from the ZAHARA study57 (Table 5) ¥ Aorta <45 mm in aortic disease associated with bicuspid aortic valvehave not yet been validated in other studies. It should be noted that ¥ Repaired coarctationpredictors and risk scores from the CARPREG and ZAHARAstudies are highly population dependent. Important risk factors WHO IIIincluding pulmonary arterial hypertension (PAH) and dilated aorta ¥ Mechanical valvewere not identiﬁed because they were under-represented in these ¥ Systemic right ventriclestudies. The CARPREG study included acquired and congenitalheart disease, while the ZAHARA study investigated a population ¥ Fontan circulationwith congenital heart disease only. ¥ Cyanotic heart disease (unrepaired) The Task Force recommends that maternal risk assessment iscarried out according to the modiﬁed World Health Organization ¥ Other complex congenital heart disease(WHO) risk classiﬁcation.72 This risk classiﬁcation integrates all ¥ Aortic dilatation 40Ð45 mm in Marfan syndromeknown maternal cardiovascular risk factors including the underlying ¥ Aortic dilatation 45Ð50 mm in aortic disease associated with bicuspidheart disease and any other co-morbidity. It includes contraindica- aortic valvetions for pregnancy that are not incorporated in the CARPREG Conditions in which pregnancy risk is WHO IVand ZAHARA risk scores/predictors. The general principles of (pregnancy contraindicated)this classiﬁcation are depicted in Table 6. A practical application ¥ Pulmonary arterial hypertension of any causeis given in Table 7. In women in WHO class I, risk is very low,and cardiology follow-up during pregnancy may be limited to ¥ Severe systemic ventricular dysfunction (LVEF <30%, NYHA IIIÐIV)one or two visits. Those in WHO II are at low or moderate risk, ¥ Previous peripartum cardiomyopathy with any residual impairment ofand follow-up every trimester is recommended. For women in left ventricular functionWHO class III, there is a high risk of complications, and frequent ¥ Severe mitral stenosis, severe symptomatic aortic stenosis(monthly or bimonthly) cardiology and obstetric review duringpregnancy is recommended. Women in WHO class IV should be ¥ Marfan syndrome with aorta dilated >45 mm ¥ Aortic dilatation >50 mm in aortic disease associated with bicuspidadvised against pregnancy but, if they become pregnant and will aortic valvenot consider termination, monthly or bimonthly review is needed. Neonatal complications occur in 20 –28% of patients with heart ¥ Native severe coarctationdisease12,56,57,75,76 with a neonatal mortality between 1% and4%.12,56,57 Maternal and neonatal events are highly correlated.57 Adapted from Thorne et al.73Predictors of neonatal complications are listed in Table 8. LVEF ¼ left ventricular ejection fraction; NYHA ¼ New York Heart Association; WHO ¼ World Health Organization.
ESC Guidelines Page 13 of 51 inﬂation, it is, however, not without risk in patients with PAH, cya- Table 8 Maternal predictors of neonatal events in nosis, and Fontan circulation. The risk may be lower with the mini- women with heart disease mally invasive hysteroscopic techniques such as the Essure device. Hysteroscopic sterilization is performed by inserting a metal 1. Baseline NYHA class >II or cyanosis12 micro-insert or polymer matrix into the interstitial portion of 2. Maternal left heart obstruction 12,76 each fallopian tube. Three months after placement, correct device placement and bilateral tubal occlusion are conﬁrmed 3. Smoking during pregnancy12,57 with pelvic imaging. Advantages of hysteroscopic sterilization 4. Multiple gestation12,57 include the ability to perform the procedure in an outpatient setting and without an incision. A disadvantage is the 3 month 5. Use of oral anticoagulants during pregnancy12 waiting period until tubal occlusion is conﬁrmed.80 Vasectomy 6. Mechanical valve prosthesis 57 for the male partner is another efﬁcacious option, but the long- term prognosis of the female partner must be taken into Modiﬁed from Siu et al. 12 (CARPREG investigators); Khairy et al. 76; Drenthen/ account as the male partner may outlive her for many years. Pieper et al. 57 (ZAHARA investigators). Given the lack of published data about contraception in heart NYHA ¼ New York Heart Association. disease, advice should be provided by physicians or gynaecologists with appropriate training.2.12 Methods of contraception andtermination of pregnancy, and in vitro 2.12.3 Methods of termination of pregnancyfertilization Pregnancy termination should be discussed with women in whom2.12.1 Methods of contraception gestation represents a major maternal or fetal risk. The ﬁrst trime-Contraceptive methods include combined hormonal contracep- ster is the safest time for elective pregnancy termination, whichtives (oestrogen/progestin), progestogen-only methods, intrauter- should be performed in hospital, rather than in an outpatient facil-ine devices, and emergency contraception. Their use needs to be ity, so that all emergency support services are available. Thebalanced against the risk of pregnancy. method, including the need for anaesthesia, should be considered In 2010, the Centers for Disease Control (CDC) modiﬁed the on an individual basis. High risk patients should be managed in anWHO suggestions for medical eligibility criteria for contraceptive experienced centre with on-site cardiac surgery. Endocarditis pro-use in women with CVD. [http://www.cdc.gov/Mmwr/preview/ phylaxis is not consistently recommended by cardiologists,81 butmmwrhtml/rr59e0528a13.htm]. Monthly injectables that contain treatment should be individualized. Gynaecologists routinelymedroxyprogesterone acetate are inappropriate for patients with advise antibiotic prophylaxis to prevent post-abortal endometritis,heart failure because of the tendency for ﬂuid retention. Low which occurs in 5–20% of women not given antibiotics.82,83dose oral contraceptives containing 20 mg of ethinyl estradiol are Dilatation and evacuation is the safest procedure in both thesafe in women with a low thrombogenic potential, but not in ﬁrst and second trimesters. If surgical evacuation is not feasiblewomen with complex valvular disease.77,78 in the second trimester, prostaglandins E1 or E2, or misoprostol, Apart from barrier methods (condom), the levonorgestrel- a synthetic prostaglandin structurally related to prostaglandin E1,releasing intrauterine device is the safest and most effective contra- can be administered to evacuate the uterus.84 These drugs areceptive that can be used in women with cyanotic congenital heart absorbed into the systemic circulation and can lower systemic vas-disease and pulmonary vascular disease. It reduces menstrual cular resistance and BP, and increase heart rate, effects that areblood loss by 40–50% and induces amenorrhoea in a signiﬁcant pro- greater with E2 than with E1.85portion of users.79 It should be borne in mind that 5% of patients Up to 7 weeks gestation, mifepristone is an alternative toexperience vasovagal reactions at the time of implant; therefore, for surgery. When prostaglandin E compounds are given, systemicthose with highly complex heart disease (e.g. Fontan, Eisenmenger) arterial oxygen saturation should be monitored with a transcu-intrauterine implants are indicated only when progesterone-only taneous pulse oximeter and norepinephrine infused at a rate thatpills or dermal implants have proved unacceptable and, if used, supports the DBP, which reﬂects systemic vascular resistance.they should only be implanted in a hospital environment. A copper Prostaglandin F compounds should be avoided because they canintrauterine device is acceptable in non-cyanotic or mildly cyanotic signiﬁcantly increase PAP and may decrease coronary perfusion.85women. Antibiotic prophylaxis is not recommended at the time of Saline abortion should be avoided because saline absorption caninsertion or removal since the risk of pelvic infection is not increased. cause expansion of the intravascular volume, heart failure, and clot-If excessive bleeding occurs at the time of menses, the device should ting abnormalities.be removed. It is contraindicated in cyanotic women with haemato-crit levels .55% because intrinsic haemostatic defects increase therisk of excessive menstrual bleeding. 2.12.4 In vitro fertilization In vitro fertilization may be considered where the risk of the pro-2.12.2 Sterilization cedure itself, including hormonal stimulation and pregnancy, is low.Tubal ligation is usually accomplished safely, even in relatively high Thrombo-embolism may complicate in vitro fertilization when highrisk women. Because of the associated anaesthesia and abdominal oestradiol levels may precipitate a prothrombotic state.86