ESC Guidelines On The Management Of Cardiovascular Diseases During .

3149ESC Guidelines10.2. Risk factors for pregnancy-related venous thromboembolism and risk stratification . . . . . . . . . . . . . . . .318410.3. Prevention of venous thrombo-embolism . . . . . . . . .318410.4. Management of acute venous thrombo-embolism . . .318510.5. Recommendations for the prevention and managementof venous thrombo-embolism in pregnancy andpuerperium . . . . . . . . . . . . . . . . . . . . . . . . . . . . .318711. Drugs during pregnancy and breastfeeding . . . . . . . . . . . .318711.1. General principles . . . . . . . . . . . . . . . . . . . . . . . .318711.2. Recommendations for drug use . . . . . . . . . . . . . . .318812. Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . .319113. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3191List of tablesTable 1. Classes of recommendationTable 2. Levels of evidenceTable 3. Estimated fetal and maternal effective doses for variousdiagnostic and interventional radiology proceduresTable 4. Predictors of maternal cardiovascular events and riskscore from the CARPREG studyTable 5. Predictors of maternal cardiovascular events identified incongential heart diseases in the ZAHARA and Khairy studyTable 6. Modified WHO classification of maternal cardiovascularrisk: principlesTable 7. Modified WHO classification of maternal cardiovascularrisk: applicationTable 8. Maternal predictors of neonatal events in women withheart diseaseTable 9. General recommendationsTable 10. Recommendations for the management of congenitalheart diseaseTable 11. Recommendations for the management of aortic diseaseTable 12. Recommendations for the management of valvular heartdiseaseTable 13. Recommendations for the management of coronaryartery diseaseTable 14. Recommendations for the management of cardiomyopathies and heart failureTable 15. Recommendations for the management of arrhythmiasTable 16. Recommendations for the management of hypertensionTable 17. Check list for risk factors for venous thrombo-embolismTable 18. Prevalence of congenital thrombophilia and the associated risk of venous thrombo-embolism during pregnancyTable 19. Risk groups according to risk factors: definition and preventive measuresTable 20. Recommendations for the prevention and managementof venous thrombo-embolism in pregnancy and puerperiumTable 21. Recommendations for drug useAbbreviations and acronymsABPMambulatory blood pressure CDCCHADSAmerican College of Cardiologyangiotensin-converting enzymeacute coronary syndromeatrial fibrillationAmerican Heart Associationactivated partial thromboplastin timeangiotensin receptor blockeraortic stenosisatrial septal defectatrioventricularatrioventricular septal defectbody mass indexB-type natriuretic peptideblood pressureCenters for Disease Controlcongestive heart failure, hypertension, age(.75 years), diabetes, strokeCIconfidence intervalCOcardiac outputCoAcoarction of the aortaCTcomputed tomographyCVDcardiovascular diseaseDBPdiastolic blood pressureDCMdilated cardiomyopathyDVTdeep venous thrombosisECGelectrocardiogramEFejection fractionESCEuropean Society of CardiologyESHEuropean Society of HypertensionESICMEuropean Society of Intensive Care MedicineFDAFood and Drug AdministrationHCMhypertrophic cardiomyopathyICDimplantable cardioverter-defibrillatorINRinternational normalized ratioi.v.intravenousLMWHlow molecular weight heparinLVleft ventricularLVEFleft ventricular ejection fractionLVOTOleft ventricular outflow tract obstructionMRImagnetic resonance imagingMSmitral stenosisNT-proBNP N-terminal pro B-type natriuretic peptideNYHANew York Heart AssociationOACoral anticoagulantPAHpulmonary arterial hypertensionPAPpulmonary artery pressurePCIpercutaneous coronary interventionPPCMperipartum cardiomyopathyPSpulmonary valve stenosisRVright ventricularSBPsystolic blood pressureSVTsupraventricular tachycardiaTGAcomplete transposition of the great arteriesTRtricuspid regurgitationUFHunfractionated heparinVSDventricular septal defect

3150VTVTEWHOESC Guidelinesventricular tachycardiavenous thrombo-embolismWorld Health Organization1. PreambleGuidelines summarize and evaluate all available evidence, at thetime of the writing process, on a particular issue with the aim ofassisting physicians in selecting the best management strategiesfor an individual patient, with a given condition, taking intoaccount the impact on outcome, as well as the risk –benefit ratioof particular diagnostic or therapeutic means. Guidelines are nosubstitutes but are complements for textbooks and cover theEuropean Society of Cardiology (ESC) Core Curriculum topics.Guidelines and recommendations should help the physicians tomake decisions in their daily practice. However, the final decisionsconcerning an individual patient must be made by the responsiblephysician(s).A great number of Guidelines have been issued in recent yearsby the ESC as well as by other societies and organizations. Becauseof the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make alldecisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESCwebsite idelines/about/Pages/rules-writing.aspx). ESC Guidelines represent the officialposition of the ESC on a given topic and are regularly updated.Members of this Task Force were selected by the ESC to represent professionals involved with the medical care of patientswith this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for diagnosis, management, and/or prevention of a given condition according to ESCCommittee for Practice Guidelines (CPG) policy. A criticalevaluation of diagnostic and therapeutic procedures was performed including assessment of the risk–benefit ratio. Estimatesof expected health outcomes for larger populations were included,where data exist. The level of evidence and the strength ofrecommendation of particular treatment options were weighedand graded according to pre-defined scales, as outlined inTables 1 and 2.The experts of the writing and reviewing panels filled in declarations of interest forms which might be perceived as real or potential sources of conflicts of interest. These forms were compiledinto one file and can be found on the ESC Web Site (http://www.escardio.org/guidelines). Any changes in declarations of interest that arise during the writing period must be notified to the ESCand updated. The Task Force received its entire financial supportfrom the ESC without any involvement from healthcare industry.The ESC CPG supervises and coordinates the preparation ofnew Guidelines produced by Task Forces, expert groups, or consensus panels. The Committee is also responsible for the endorsement process of these Guidelines. The ESC Guidelines undergoextensive review by the CPG and external experts. After appropriate revisions it is approved by all the experts involved in the TaskForce. The finalized document is approved by the CPG for publication in the European Heart Journal.The task of developing Guidelines covers not only the integration of the most recent research, but also the creation of educational tools and implementation programmes for therecommendations. To implement the guidelines, condensedpocket guidelines versions, summary slides, booklets with essentialmessages, and an electronic version for digital applications (smartphones, etc.) are produced. These versions are abridged and, thus,if needed, one should always refer to the full text version which isfreely available on the ESC website.The National Societies of the ESC are encouraged to endorse,translate, and implement the ESC Guidelines. ImplementationTable 1 Classes of recommendationClasses ofrecommendationsDefinitionClass IEvidence and/or general agreementthat a given treatment or procedureis beneficial, useful, effective.Class IIConflicting evidence and/or adivergence of opinion about theusefulness/efficacy of the giventreatment or procedure.Suggested wording to useIs recommended/isindicatedClass IIaWeight of evidence/opinion is infavour of usefulness/efficacy.Should be consideredClass IIbUsefulness/efficacy is less wellestablished by evidence/opinion.May be consideredEvidence or general agreement thatthe given treatment or procedureis not useful/effective, and in somecases may be harmful.Is not recommendedClass III

3151ESC GuidelinesTable 2Levels of evidenceLevel ofEvidence AData derived from multiple randomizedclinical trialsor meta-analyses.Level ofEvidence BData derived from a single randomizedclinical trialor large non-randomized studies.Level ofEvidence CConsensus of opinion of the experts and/or small studies, retrospective studies,registries.programmes are needed because it has been shown that theoutcome of disease may be favourably influenced by the thoroughapplication of clinical recommendations.Surveys and registries are needed to verify that real-life dailypractice is in keeping with what is recommended in the guidelines,thus completing the loop between clinical research, writing ofguidelines, and implementing them into clinical practice.The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in thecircumstances of the individual patients, in consultation with thatpatient, and, where appropriate and necessary, the patient’s guardian or carer. It is also the health professional’s responsibility toverify the rules and regulations applicable to drugs and devices atthe time of prescription.2. General considerations2.1 IntroductionAt present, 0.2 –4% of all pregnancies in western industrializedcountries are complicated by cardiovascular diseases (CVD),1and the number of the patients who develop cardiac problemsduring pregnancy is increasing. Nevertheless, the number of suchpatients presenting to the individual physician is small. However,knowledge of the risks associated with CVD during pregnancyand their management are of pivotal importance for advisingpatients before pregnancy. Therefore, guidelines on disease management in pregnancy are of great relevance. Such guidelineshave to give special consideration to the fact that all measuresconcern not only the mother, but the fetus as well. Therefore,the optimum treatment of both must be targeted. A therapyfavourable for the mother can be associated with an impairmentof the child, and in extreme cases treatment measures whichprotect the survival of the mother can cause the death of thefetus. On the other hand, therapies to protect the child maylead to a suboptimal outcome for the mother. Because prospectiveor randomized studies are lacking, with a few exceptions, recommendations in this guideline mostly correspond to the evidencelevel C.Some general conclusions have arisen from these guidelines:counselling and management of women of childbearing age withsuspected cardiac disease should start before pregnancy occurs;they should be managed by interdisciplinary teams; high riskpatients should be treated in specialized centres; and diagnosticprocedures and interventions should be performed by specialistswith great expertise in the individual techniques and experiencein treating pregnant patients. Registries and prospective studiesare urgently needed to improve the state of knowledge.2.2 MethodsThe Guidelines are based on a systematic search of the literatureof the last 20 years in the National Institutes of Health database(PubMed). The publications and recommendations of the European 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 ValvularHeart Disease of the ESC,4 the guidelines of the German Societyof Cardiology (German Society of Cardiology),5,6 and the ESCTask Force on the Management of Valvular Heart Disease 2007.72.3 EpidemiologyThe spectrum of CVD in pregnancy is changing and differsbetween countries. In the western world, the risk of CVD in pregnancy has increased due to increasing age at first pregnancy andincreasing prevalence of cardiovascular risk factors—diabetes,hypertension, and obesity. Also the treatment of congenital heartdisease has improved, resulting in an increased number ofwomen with heart disease reaching childbearing age.8 In westerncountries maternal heart disease is now the major cause ofmaternal death during pregnancy.9Hypertensive disorders are the most frequent cardiovascularevents during pregnancy, occurring in 6–8% of all pregnancies.10In the western world, congenital heart disease is the most frequentcardiovascular disease present during pregnancy (75 –82%), withshunt lesions predominating (20–65%).11,12 Congenital heartdisease represents just 9– 19% outside Europe and NorthAmerica. Rheumatic valvular disease dominates in non-westerncountries, comprising 56 –89% of all cardiovascular diseases inpregnancy.11,12Cardiomyopathies are rare, but represent severe causes of cardiovascular complications in pregnancy. Peripartum cardiomyopathy (PPCM) is the most common cause of severe complications.132.4 Haemodynamic, haemostatic, andmetabolic alterations during pregnancyPregnancy induces changes in the cardiovascular system to meetthe increased metabolic demands of the mother and fetus. Theyinclude increases in blood volume and cardiac output (CO), andreductions in systemic vascular resistance and blood pressure (BP).Plasma volume reaches a maximum of 40% above baseline at 24weeks gestation. A 30 –50% increase in CO occurs in normal pregnancy. In early pregnancy increased CO is primarily related to therise in stroke volume; however, in late pregnancy, heart rate is themajor factor. Heart rate starts to rise at 20 weeks and increasesuntil 32 weeks. It remains high 2–5 days after delivery. SystemicBP (SBP) typically falls early in gestation and diastolic BP (DBP)is usually 10 mmHg below baseline in the second trimester. Thisdecrease in BP is caused by active vasodilatation, achieved

3152through the action of local mediators such as prostacyclin andnitric oxide. In the third trimester, the DBP gradually increasesand may normalize to non-pregnant values by term.The heart can increase its size by up to 30%, which is partiallydue to dilatation. Data regarding systolic and diastolic function inpregnancy are scarce. Systolic function increases first but maydecrease in the last trimester. Reports on diastolic function areconflicting.Pregnancy induces a series of haemostatic changes, with anincrease in concentration of coagulation factors, fibrinogen, andplatelet adhesiveness, as well as diminished fibrinolysis, which leadto hypercoagulability and an increased risk of thrombo-embolicevents. In addition, obstruction to venous return by the enlarginguterus causes stasis and a further rise in risk of thrombo-embolism.Maternal glucose homeostasis may change and cholesterol levelsincrease in adaptation to fetal–maternal needs.Physiological changes that occur during pregnancy can affectabsorption, excretion, and bioavailability of all drugs.14 Theincreased intravascular blood volume partly explains the higherdosages of drugs required to achieve therapeutic plasma concentrations, and the dose adaptations needed during treatment. Moreover, the raised renal perfusion and the higher hepatic metabolismincrease drug clearance. The altered pharmacokinetics of drugsvary in magnitude during different stages of pregnancy, makingcareful monitoring of the patient and dose adjustments necessary.Uterine contractions, positioning (left lateral vs. supine), pain,anxiety, exertion, bleeding, and uterine involution cause significanthaemodynamic changes during labour and post-partum. Anaesthesia, analgesia, haemorrhage, and infection may induce additionalcardiovascular stress. SBP and DBP increase 15 –25% and 10 –15%, respectively, during uterine contractions. Such increases areassociated with a rise in pressure in the amniotic fluid, and in theintrathoracic venous, cerebrospinal, and extradural fluids. COincreases by 15% in early labour, by 25% during stage 1, and by50% during expulsive efforts.15 It reaches an increase of 80%early post-partum due to autotransfusion associated with uterineinvolution and resorption of leg oedema.In conclusion, the physiological adaptations to pregnancy influence the evaluation and interpretation of cardiac function and clinical status.2.5 Genetic testing and counsellingAn important aspect concerning the care of young women withCVD is the consultation about the risk of inheritance of cardiacdefects for their descendants. The risk is raised significantly in comparison with parents without CVD where the risk is 1%. Inaddition, there are large differences between each of the hereditary heart disease conditions, and the risk for descendants isdependent on whether only the mother, only the father, or bothparents suffer from hereditary cardiac defects.16 In general, therisk is higher when the mother is affected rather than thefather.16 The recurrence risk varies between 3% and 50% depending on the type of maternal heart disease.Children of parents with a cardiovascular condition inherited inan autosomal dominant manner (e.g. Marfan syndrome, hypertrophic cardiomyopathy, or long QT syndrome) have an inheritance risk of 50%, regardless of gender of the affected parent.ESC GuidelinesThe final phenotype will also be determined by incomplete penetrance and pleiotropic effects, and may vary significantly. Fordefects that are inherited in a polygenic manner, recurrence riskis less clearly defined. Autosomal recessive and X-chromosomalrecessive inheritance are rare.Genetic testing may be useful:† in cardiomyopathies and channelopathies, such as long QTsyndromes17† when other family members are affected† when the patient has dysmorphic features, developmental delay/mental retardation, or when other non-cardiac congenitalabnormalities are present, in syndromes such as in Marfan,22q11 deletion, Williams –Beuren, Alagille, Noonan, andHolt –Oram syndrome.For a steadily increasing number of genetic defects, genetic screening by chorionic villous biopsy can be offered in the 12th week ofpregnancy. All women with congenital heart disease should beoffered fetal echocardiography in the 19th to 22nd week of pregnancy. Measurement of nuchal fold thickness in the 12th to 13thweek of pregnancy is an early screening test for women over 35years of age. The sensitivity for the presence of a significantheart defect is 40%, while the specificity of the method is 99%.The incidence of congenital heart disease with normal nuchalfold thickness is 1/1000.18The inheritance pattern differs among the diseases, and therefore genetic counselling by a geneticist is highly recommendedfor patients and their family members.17 Genetic testing aftercareful counselling has the rationale of identifying at-risk asymptomatic or disease-free relatives and to guide clinical surveillance fordisease onset, thereby enhancing preventive and treatment interventions. It is advocated in patients with known genetic disordersand is more advisable if treatment options are available.172.6 Cardiovascular diagnosisin pregnancyThe following procedures are of relevance for the diagnosis andmanagement of CVD in pregnancy.History and clinical investigationMany disorders can

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