Non-OperatedMildand SevereRheumaticMitralValveDisease DuringPregnancy

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1 ORİJİNAL ARAŞTIRMA Non-OperatedMildand SevereRheumaticMitralValveDisease DuringPregnancy Ahmet Cem İyİbozkurt, MD, a Süleyman Engin AkhAn, MD, a Samet topuz, MD, a İbrahim kalelioğlu, MD, a tülay ÖzkAn, MD, b recep has, MD, a lem i İbrAhİMoğlu, MD a Departments of a obstetrics and Gynecology, b Anesthesiology and reanimation, İstanbul university İstanbul Faculty of Medical, İStAnbul Ge liş ta ri hi/received: ka bul ta ri hi/accepted: Thisarticlewaspresentedasaposteratthe FIGOChiliWorldin2003. ya zış ma Ad re si/correspondence: Ahmet Cem İyİbozkurt, MD İstanbul university İstanbul Faculty of Medicine, Department of obstetrics and Gynecology, İStAnbul, turkey cemiyi@yahoo.com ABSTRACT Objective:Comparisonofmaternalandfetaloutcomesinalargegroupofpregnant womenwithmildandsevererheumaticmitralvalvediseasethatweredeliveredinourclinic.materialandmethods:among18553deliveriesofsevenconsecutiveyears,209womenwithnonoperated rheumatic mitral valve disease were retrospectively analyzed: 189 New York Heart AssociationcriteriaclassI-IIand20classIII-IVpatientswerecompared.Allpatientshadtheircardiaclesionsconfirmedbyanechocardiogramduringthethirdtrimester.Peripartummeasureslike methodofdelivery,gestationalweekatdelivery,birthweight,apgarscoreswererecorded.fetal andmaternaloutcomemeasuresincludedmaternalandfetalmortality,complicationsintheperipartumandpostpartumperiod,thedurationofhospitalizationandrequirementofintensivecare inthepostpartumperiod.allparameterswerecomparedbyeitherusingfischer sexact,chi-squared andstudent-ttests.results:therewasnosignificantdifferencebetweentwogroupsintermsofage, parity,typeofdelivery,birthweights,andpresenceofintrauterinegrowthretardation.maternal andfetalmortalitywassignificantlyincreasedinclassiii-ivpatients(p=0.003,p=0.018respectively).intensivecarerequirement,presenceofpulmonaryhypertension,anddevelopmentofany maternalcomplicationwerealsomorecommoninthesepatients.conclusion:maternalandfetal mortalityissignificantlyincreasedinpregnantwomenwithnewyorkheartassociationclassiii andivrheumaticmitralvalvedisease.toidentifythesepregnantwomenandprovidetheirantenatalfollow-upafterproperwork-upinspecializedcentersisimportant,sincemostarelacking properantenatalcare. KeyWords:Maternalmortality,mitralvalve,perinatalmortality,pregnancy,rheumaticfever ÖZETAmaç:Kliniğimizdedoğumyaptırılanhafifveağırromatizmalmitralkapakhastalığıolan vebüyükbirgrupoluşturangebelerdematernalvefetalsonuçlarınkarşılaştırılması.gereçve Yöntemler: Yediyıliçindekliniğimizdeyaptırılan18553doğumiçinderomatizmalmitralkapak hastalığıolanveopereedilmemiş209geberetrospektifolarakdeğerlendirildi: NewYorkHeart Association (NYHA)kriterlerinegöre189I-II.sınıfve20III-IV.sınıfhastaçalışmadakarşılaştırıldı. Bütünolgulardamitralkapakhastalığıvarlığıüçüncütrimesterdeyapılanekokardiyografiile doğrulandı.tümkadınlardadoğumşekli,doğumdagestasyonelhafta,doğumağırlığıveapgar skorlarıilematernalvefetalmortalite,peripartumvepostpartumdönemdekomplikasyongelişimi, hastanedeyatışsüresiilepostpartumdönemdeyoğunbakımihtiyacıgibifetomaternalparametreler çalışmadadeğerlendirildi.buparametrelerfischerexact,ki-karevestudent-ttestkullanılarak analizedildi.bulgular:gruplararasındayaş,parite,doğumşekli,doğumağırlığıvegelişmegeriliği açısından anlamlı bir fark bulunamadı. Ancak maternal ve fetal mortalitenin NYHA III-IV sınıfındakihastalardaanlamlıolarakarttığısaptandı(sırasıylap=0.003vep=0.018).yoğunbakım ihtiyacıvepulmonerhipertansiyonvarlığınındabugebelerdedahasıkolduğugörüldü.sonuç: NYHAIIIveIVsınıfındakiromatizmalmitralkapakhastalığıolupçoğunluğutakipsizolanbu gebelerdematernalvefetalmortaliteanlamlıolarakartmıştır.buhastalarınöncedensaptanarak takipvedoğumlarınıgereğindekardiyakaçıdandestekverebilecekyoğunbakımimkanıolan hastanelerdeyapmalarıuygunolacaktır. AnahtarKelimeler: Maternalmortalite,mitralkapak,perinatalmortalite,gebelik,romatizmalateş Cop yright 2008 by Tür ki ye Kli nik le ri TurkiyeKlinikleriJGynecolObst2008;18(5): TurkiyeKlinikleriJGynecolObst2008;18(5)

2 nthedevelopingworld,rheumaticheartdisease(rhd)isstillthemostcommoncauseof valvular heart disease in pregnant women. Arisingsecondarytorheumaticfever,groupAβhemolyticstreptococciareinvolvedintheprocess, but the pathogenic mechanism remains obscure. Acuterheumaticfevermostoftenoccursin children;thepeakage-relatedincidenceisbetween5and15years.approximately3%ofindividuals with untreated group A streptococcal pharyngitisdeveloprheumaticfever.fortytosixty percentofpatientswithacuterheumaticfeverhavecarditisandasignificantnumberdeveloprhd. ThemostcommonlesionassociatedwithRHDis mitralstenosis,occurringin75%ofthecases.mitralstenosiscombinedwithregurgitationisalsorelativelycommon,makinguparound30%ofthe patientswithcarditis. Inourinstitution,rheumaticmitralvalvediseaseisresponsibleforthemajorityofcardiacdiseaseinpregnantwomen.Frequently,thesewomen haveacomplication-freepregnancyandpuerperium. However, in New York Heart Association (NYHA,1964)functionalstatusClassIII-IVwomen,pregnancyposesagreatthreattowell-being ofbothmotherandthefetus.althoughcomplicationsincludingpulmonaryedemaanddeathmay occurduringpregnancy,manyoftheseyoungwomenareasymptomatic,andarediagnosedtohave RHDduringpregnancy.Thepresentstudywasdesignedtoevaluatetheeffectsofseverityofnon-operatedrheumaticmitralvalvedisease(RMVD)on maternal and fetal outcome in a relatively large groupofpatientscaredinauniversity-clinicsetting. MA te ri Al AnD MEt hods Thepatientpopulationconsistedofretrospectively analyzed209pregnantwomenwithnon-operated rheumaticmitralvalvediseasewhodeliveredin ourlaborunitin7consecutiveyearsstartingfrom 1996.Amongthe18.553deliveries,431pregnant womenhadcardiacdisease (2.3%);and299ofthem (69.3%)hadvalvularheartdisease.Themostfrequentlyaffectedvalvewasthemitralvalve(277 women).afterexcluding47patientsdiagnosedto havemitralvalveprolapse,and22patientswith prosthetic mitral valves, maternal and perinatal outcomeof209patientswerestudied. Age,parity,preliminarydiagnosisatadmittance,frequencyandplaceofantenatalvisitsofall womenwererecorded.then,womenwereassignedtoagradeaccordingtotheassessmentoffunctional status of the cardiac disease by NYHA criteriaandhadtheircardiaclesionsconfirmedby anechocardiogramduringthethirdtrimester.the type of mitral valve disease, diagnostic method used, presence of pulmonary hypertension, and currentlyprescribeddrugswerealsonoted. Information about peripartum events like themethodofdelivery,gestationalweekatdelivery,thebirthweightofthenewborn,1-minute and 5-minute Apgar scores were recorded. All womenreceivedendocarditicprophylaxisduring delivery. Maternalandfetaloutcomemeasuresincluded maternalandfetalmortality,complicationsinthe peri-andpostpartumperiod(presenceofpulmonaryedema,cardiacfailure,etc.),presenceofcongenitalmalformations,thedurationofhospitalization and requirement of intensive care in the postpartumperiod. Thedataobtainedfrompatients fileswasregisteredinadatabaseformedbyusingmicrosoft Access.ClassI-II(mild)andClassIII-IV(severe) patientswereseparatedintotwogroupsandthedatawascomparedaccordingtothisclassification. Therewere 189mildand20severewomenwith RMVD. Quantitative and qualitative data were comparedbyspss12.0usingindependent-twovariablet-test, Fishers exacttestand chi-squaretest, respectively.statisticalsignificancewasaccepted atp<0.05. re SultS MeanmaternalageofsevereRMVDpatientswere slightlyhigherthanmildrmvdgroup(30.3±5.1 vs.28.4±5.2),butthedifferencewasnotsignificant(p=0.128).only37.8%ofthepatientsreceived prenatal care in our university clinic. Data TurkiyeKlinikleriJGynecolObst2008;18(5) 307

3 TABLE 1: Comparison of age, parity and frequency of perinatal care between the two groups. Values were expressed as mean ± SD and n (%) when applicable. Parameters Class I-II Class III-IV (n= 189) (n= 20) p Age (years) number of nulliparous patients 117 (61.9%) 8 (40%) patients without prenatal care 104 (55%) 14 (70%) 0.24 aboutage,parityandfrequencyofperinatalcare weredetailedintable1. Thetwomostcommonmitralvalvediseasesin themildrmvdgroupwereisolatedmitralregurgitation(51patients,26.9%)andisolatedmitralstenosis (48 patients, 25.3%). However, the most commonmitralvalvediseaseintheseverermvd groupwascombined mitralvalvedisease(stenosis andregurgitation)(35%).distributionofvalvular pathologieswasdetailedintable2. Meangestationalageatthetimeofdelivery wasnotdifferentbetweenthetwogroups(37.2± 4.3 and37.0±3.4weeksinmildandseverermvd groups,respectively).theratesofcesareansection werealsosimilar(table3).themostcommonindicationforcesareandeliverywas elective cesare- aninbothgroups(table4).intheseverermvd group,secondmostcommonindicationwasfetal distress(30%). Maternalcomplicationsweremorecommon intheseverermvdgroup[11%mildvs.65%severe,(p=0.0001)](table5).numberofwomenhavingpre-orpostpartumcardiacfailurewasalso significantlymorecommonintheseverermvd group(p=0.0023).presenceofpulmonaryhypertension was much more frequent (p=0.0001) in ClassIII-IVwomenwhencomparedtoclassI-II women [(5.8% class I-II vs. 55% class III-IV, (p=0.0001)].womenintheseverermvdgroup requiredintensivecaresignificantlymorethanthe othergroup(p=0.0002)andhadsignificantlylonger hospitalstay(p=0.0012). Maternalmortalityoccurredin3/20(15%)of severermvdcasesandin1/189(0.5%)ofthemild RMVDcases(Table5).ThematernalmortalityrateinthesevereRMVDgroupwassignificantlyincreased(p=0.0029). Intermsoffetaloutcomeparameters,birthweightwasestimatedtobelowerinthesevereRMVD group(2918±727vs. 2742±753g),butitdidnot reachstatisticalsignificance(p=0.31)(table6).the meanapgarscoreswere7.96±1.53and7.55±1.87 at1minute,and9.38±0.99and8.95±1.76at5mi- TABLE 2: Distribution of valvular pathologies (a CM: Combined mitral valve disease [CM: Mitral stenosis + Mitral regurgitation]). Data are expressed as n(%). Class I-II (n= 189) Class III-IV (n= 20) Mitral stenosis 48 (25.3) 5 (25) Mitral stenosis +Aortic regurgitation 12 (6.3) 2 (10) Mitral stenosis + Aortic regurgitation + Aortic stenosis 4 (2.4) Mitral stenosis + Aortic regurgitation +tricuspid regurgitation 1 (0.5) Mitral regurgitation 51 (26.9) 3 (15) Mitral regurgitation + Aortic regurgitation 14 (7.4) 2 (10) Mitral regurgitation + Aortic regurgitation + tricuspid regurgitation 4 (2.4) Mitral regurgitation + tricuspid regurgitation 2 (1) Mitral regurgitation + Aortic stenosis + tricuspid regurgitation 1 (0.5) Mitral regurgitation + pulmonary regurgitation 1 (0.5) CMa 41 (21.6) 7 (35) CM+ Aortic regurgitation 9 (4.7) 1 (5) CM + tricuspid regurgitation 1 (0.5) total TurkiyeKlinikleriJGynecolObst2008;18(5)

4 TABLE 3: Comparison of gestational week at delivery and type of delivery between the two groups. Values were expressed as mean ± SD and n (%) when applicable. Parameters Class I-II Class III-IV (n= 189) (n= 20) P Gestational age (week) 37.2 ± ± type of Delivery 1. Vaginal 101 (53.4) 7 (35) Vacuum extraction 14 (7.4) 3 (15) Cesarean section 74 (39.2) 10 (50) 0.35 TABLE 4: Indications of cesarean section. Indications of Class I-II Class III-IV Cesarean Section (C/S) (n= 74) (n= 10) Electivea 27 (36.4) 5 (50) prior C/S 16 (21.6) 1 (10) Fetal distress 7 (9.5) 3 (30) Failed Induction 5 (6.7) 1 (10) breech presentation 8 (10.8) --- breech + nulliparous 2 (2.7) --- Arrest of labor 7 (9.5) --- Cephalopelvic Disproportion 1 (1.4) --- IuGrb + oligohydramnios 1 (1.4) --- (a: Elective includes cases in which C/S indication is favored by cardiologists and anesthesiologists. C/S is recommended by cardiologists and anesthesiologists in 17 patients in Class I-II, and all patients in Class III-IV and hence performed. b: Intrauterine growth retardation). Data are expressed as n(%). nutesinthemildandintheseverermvdpatients, respectively(inbothp=ns).therewasnostatisticallysignificantdifferencebetweenthetwogroups intheincidenceofintrauterinegrowthretardation (IUGR).However,therewasasignificantdifferenceintheperinatalmortalityratebetweenthetwo groups[2.1%(4/189)classi-iivs.20%(4/20)class III-IV(p<0.01)].InthemildRMVDgroup,twofetusesofpreeclampticmothersat29 th weekofgestation had no fetal cardiac activity on admission. Otherperinataldeathsinthisgroupweredueto complicationsofprematuredeliveries:oneintraventricular bleeding and one respiratory distress syndromeduetomeconiumaspiration.therewere 4perinataldeathsinthesevereRMVDgroup.These died due to complications of prematurity in this groupofpatients.thereweretwomaternaldeaths inthisgroupofpatients. SixfetusesinthemildandonefetusinthesevereRMVDgrouphadcongenitalmalformations. Thesemalformationswereisolatedhydrocephaly (twopatientsinthemildandtheonlypatientwith malformationintheseverermvdgroup),hydronephrosis(2cases),andmesentericcyst(1case). Onefetuswithmultiplecongenitalmalformations (gastrointestinalsystemobstruction,ambiguousgenitalia,cleftlipandpalate)wasmedicallyaborted at22weeksofgestation. TABLE 5: Maternal outcome parameters in both groups. Values were expressed n (%). Maternal Outcome Parameters Class I-II (n= 189) Class III-IV (n= 20) p patients who develop maternal complications 21 (11) 13 (65) Maternal death 1 (0.5) 3 (15) number of patients having pre- or postpartum cardiac failure 11 (5.8) 6 (30) pulmonary hypertension 11 (5.8) 11 (55) patients in need of intensive care 9 (4.7) 7 (35) Duration of hospital stay (days) TABLE 6: Fetal outcome parameters in both groups. Values were expressed as mean ± SD and n (%) when applicable. Fetal Outcome Parameters Class I-II (n= 189) Class III-IV (n= 20) p birth weight (g) minute ApGAr minute ApGAr IuGr 13 (6.8) 3 (1.5) perinatal death 4 (2.1) 4 (20) TurkiyeKlinikleriJGynecolObst2008;18(5) 309

5 DIS CuS SI on Thereareafewpublicationsonpregnantpatients withrhdinthelastdecade.in1998,tanandde Swiet have examined 73 pregnant women with cardiacdiseaseinwestlondonandonly12%of thesewomenhadrheumaticvalvedisease. 1 Inmost ofthedevelopedcountries,theincreasinglyimportantandmostcommoncardiacprobleminyoung pregnantwomeniscongenitalheartdisease. 2 On thecontrary,rheumaticvalvediseaseisstillthe mostcommoncauseofcardiacdiseaseencounteredinpregnantwomeninourclinic.mitralvalve isthemostfrequentlyaffectedvalve.itisofnote thatmostofthesewomen(around85%)areliving inruralareas. Despitelimitationbysmallnumberofpatients ineachsubgroupoftypeofvalvularpathology,the presenceofcombinedmitralvalvediseasewasassociatedwithahighernyhaclass.thefrequency ofisolatedmitralstenosiswascomparableinboth groups.ourfindingoftherelativelyincreasedfrequencyofmitralregurgitationinthemildrmvd groupwasnotsurprisingbecausemitralregurgitationiswelltoleratedinpregnancy,probablydueto decreasedsystemicvascularresistance;andhence associatedwithalowernyhaclass. 3 It is well known that women with severe RMVDhaveasignificantlyhigherrateofcomplicationsincludingpre-andpostpartumcardiacfailure.IntheseriesofDesaietalfromSouthAfrica, 51%ofthe128patientswithmitralstenosishad complicationsandmostwererelatedtopulmonary edema. 4 Inourseries,theoverallcomplicationrate was 11% in the mild and %65 in the severe RMVDgroup.Siuetalpublishedaseriesof221 pregnantwomenwithcardiacdiseaseandtheratio ofpatientswhodevelopedheartfailurewas18%. 5 Incidenceofheartfailureinourstudywas5.8% and30%inthemildandtheseverermvdpatientsrespectively. Ourstudyalsosupportstheviewthatpulmonaryhypertensionisanimportantoperatingfactor affectingprognosisinpatientswithvalvularheart disease, despiterecentdatashowsthatthematernal mortalityduetopulmonaryhypertensionisdecreasing. 6,7 Mortalityrateinpatientswithpulmonary hypertensioninourserieswasaround18%(4/22) andsupportstherecentliterature.however,pulmonaryhypertensionwaspresentinallofthefour maternaldeathsinourstudy.allofthesepatients werereferredtoourclinicduetounstablematernal status,andnonehadreceivedaproperantenatalcare.theonlypatientlostinthemildrmvdgroup hadcombinedmitralvalvedisease,pulmonaryhypertensionandatrialfibrillation.shediedpostpartumduetocardiacfailureandshock.likewise,in theseverermvdgroupallthreepatientsdieddue to cardiogenic shock. One of these patients had combinedmitralvalvediseaseandpulmonarystenosis,anddiedaftertwohoursofadmittancedueto cardiogenicshock.theothertwopatientshadseveremitralstenosisandpulmonaryhypertension.one ofthemdevelopedcardiacfailureaftervaginaldelivery,anddiedduetopulmonaryembolismonthe seventhpostpartumday.thelastpatientwasadmittedincardiogenicshock.shewasdeliveredimmediatelybycesareansectionduetofetaldistress, butdiedonthesecondpostpartumday. Inaddition,ourdatashowsthatinclassIII-IV patientswithrmvd,theneedofintensivecare andthedurationofhospitalstayaresignificantly increased,whichwouldleadtoamarkedincrease inhealthcarecostsofthesepatients.theseresults suggestarationaleforclosehemodynamicmonitoringinpatientswithseverermvd. Thehighrateofcesareansectioninthepresentstudyreflectsthedecisionsofamultidisciplinaryteamincludingacardiologist,aneonatologist, ananesthetist,andanobstetrician.althoughobstetriciansinourinstitutionareinfavorofvaginal delivery,doctorsfromotherspecialtiesarerecommendingsectioninthesehighriskwomen. Thepresentstudydemonstratesanadverseeffectonfetalmortality.Althoughbirthweight,presenceofintrauterinegrowthrestriction,incidence ofprematuredeliveryandapgarscoreswerenot affectedbytheseverityofthefunctionalstatusof RMVD,perinatalmortalitywasincreasedincases withclassiii-ivmitralvalvedisease.theseresults arenotinaccordancewithsomeotherpublished data.inthestudyofshawneyetal.pretermbirth 310 TurkiyeKlinikleriJGynecolObst2008;18(5)

6 andsmallforgestationalagenewbornswerefound tobeincreasedinnyhafunctionalclassiii-ivpatients. 8 Hameedandcolleaguesreportedanincreased incidence of preterm delivery, intrauterine growthrestrictionandreducedbirthweightinpatientswithvalvularheartdiseasewhenmatched withcontrols. 9 Duetotherelativelysmallnumber ofpatientswithfunctionalclassiii-ivinourpresentstudy,theresultscannotbeconclusive. Animportantlimitationofourstudyisthat, allofourresultsarevalidforourtertiarycarecenterandtheyshouldnotbeextrapolatedtoother pregnantwomenwithmitralvalvedisease. Overall,thepresentstudydemonstratesanimportanteffectofseverityofRMVDonfetaland maternaloutcomeofpregnancy,especiallyifitis neglected.ourdatasupportsthecurrentliterature thatmaternalmortalityisrareinnon-operatedpatientswithmitralvalvediseaseatnyhafunctionalclassiandii. 10 However,increasedmaternal complicationsandfetalmortalityinnon-operated pregnant women with mitral valve disease at NYHAclassIII-IVmandateclosematernalandfetalfollow-upinthesepatientswithspecialemphasis on the presence of pulmonary hypertension. Closedmitralcommissurotomyincaseofsevere stenosisduringpregnancyisreportedtobesafeto performespeciallyinpatientswhoarenotrespondingtomedicaltherapyifappropriate. 11 Women especiallywithseveremitralvalvediseaseshould beidentifiedbeforepregnancyandshouldbefollowedbyspecializedcentersinordertoimprovefetalandmaternaloutcome. 1. tan J, de Swiet M. prevalence of heart disease diagnosed de novo in pregnancy in a West london population. br J obstet Gynaecol 1998;105: lupton M, oteng-ntim E, Ayida G, Steer pj. Cardiac disease in pregnancy. Curr opin obstet Gynecol 2002;14: Cunningham EG, Gant nf, leveno kj, III.Gillstrap lc, hauth JC, Wenstrom kd. Cardiovascular diseases. In: Cunningham EF, ed. Williams obstetrics. 21st eds. new york, usa: McGraw-hill; p Desai Dk, Adanlawo M, naidoo Dp, Moodley J, kleinschmidt I. Mitral stenosis in pregnancy: references a four-year experience at king Edward VIII hospital, Durban, South Africa. bjog 2000; 107: Siu SC, Sermer M, harrison DA, Grigoriadis E, liu G, Sorensen S,et al. risk and predictors for pregnancy-related complications in women with heart disease. Circulation 1997; 96: Almange C. pregnancy and congenital heart disease. Arch Mal Coeur Vaiss 2002;95: Valdés G, Matthei r, Fernández MS, Schacht C, Corthorn J, Germaín AM. pulmonary hypertension and pregnancy. rev Med Chil 2002;130: Sawhney h, Aggarwal n, Suri V, Vasishta k, Sharma y, Grover A. Maternal and perinatal outcome in rheumatic heart disease. Int J Gynaecol obstet 2003;80: hameed A, karaalp IS, tummala pp, Wani or, Canetti M, Akhter MW, et al J Am Coll Cardiol 2001;37: brady k, Duff p. rheumatic heart disease in pregnancy. Clin obstet Gynecol 1989;32: yavaş S, İşcan hz, Mavioğlu l, Ünal u, Akgül A, birincioğlu Cl. Closed Mitral Commissurotomy In Mitral Stenosis And pregnancy: long term results. turkiye klinikleri J Cardiovasc Sci 2007;19: TurkiyeKlinikleriJGynecolObst2008;18(5) 311