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1 종설 Korean Circulation J 2003;33(12): 임신중판막질환의치료 가톨릭대학교의과대학내과학교실 윤호중 Treatment of Valvular Heart Disease during Pregnancy Ho-Joong Youn, MD Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea ABSTRACT The evaluation and management of valvular heart disease in the pregnant patient requires an understanding of the normal physiological changes associated with gestation, labor, delivery and the early postpartum period. On average, there is a 50% increase in the circulating blood volume during pregnancy, accompanied by a commensurate increase in cardiac output, which usually peaks between the midportion of the second and third trimesters. An obstruction of the inferior vena caval, from a gravid uterus, leads to hypotension with weakness. Valvular heart disease is associated with increased maternal and fetal risks during pregnancy, including NYHA functional Class III to IV symptoms, mitral stenosis, with NYHA functional Class II to IV symptoms, valvular disease resulting in severe pulmonary hypertension, valvular disease, with severe left ventricular dysfunction, mechanical prosthetic valves requiring anticoagulation and aortic regurgitation in Marfan syndrome. Pregnancy should be discouraged for some conditions, such as cyanotic heart disease, Eisenmenger syndrome or severe pulmonary hypertension. Patients with severe mitral stenosis, who develop NYHA functional class III-IV symptoms during pregnancy, should undergo a percutaneous balloon mitral valvotomy, provided the valve is anatomically suitable. Individual counseling usually requires a multidisciplinary approach, and should include information about contraception, the maternal and fetal risks of pregnancy and any expected long-term outcomes. However, many patients with valvular heart disease can be successfully managed throughout pregnancy, and during labor and delivery, with conservative medical measures that are designed to optimize the intravascular volume and systemic loading conditions. (Korean Circulation J 2003;33 (12): ) KEY WORDS:Pregnancy;Valvular heart disease. 서 임신중정상적으로일어나는혈액양의증가와그에따른심박출량의증가는승모판협착증이나대동맥판막협착증에서는심잡음을증가시키지만한편승모판이나대동맥판막폐쇄부전증에서는임신중체순환 교신저자 : 윤호중, 서울영등포구여의도동 62 가톨릭대학교의과대학내과학교실전화 :(02) 전송 :(02) younhj@catholic.ac.kr 론 저항의감소로오히려심잡음을감소된다. 판막질환은임신중심장에다양한혈류역학적변화를일으킴으로서, 심기능을악화시킬수있으며, 임신전정상적인기능을보였던심장에서도경우에따라서는치명적인비가역적인손상을줄수있다. 대부분의건강한산모들에서도임신말기에는공통적으로피로감, 운동능력의감소, 호흡곤란등을호소하기때문에임신으로인한심혈관계의정상적인생리학적및해부학적변화를병적인상태와구별하는것이중요하며임신중판막질환을평가하고치료하기위해 1071

2 서는복합적인요인들이고려되어야한다. 정상임신이심장에미치는영향 정상임신중혈류역학적변화정상적으로임신중에는혈장용적, 적혈구의양및심박출량이기준치이상으로증가한다 (Fig. 1). 1) 임신중에발생하는혈류역학적변화에대한기존의연구들은심도자검사를이용하였기때문에, 소수의임산부를대상으로임신기간중단지제한된시점에서만측정할수있었다. 2) 최근 Doppler 심초음파를이용한심박출량의평가는임신중심박출량의변화정도와변화시점에대한많은이해를갖게해주었다. 심박출량은임신중기준치의 45% 까지증가하게되는데임신 10주에이미심박출량의증가를관찰할수있으며, 24주경에최대에도달하여임신후반기까지는더이상증가하지않는다는보고와, 임신말기까지지속적으로증가한 Percentage change from prepregnancy value Fig. 1. Changes in plasma volume, erythrocyte volume, and hematocrit during pregnancy. Total blood volume SVR wks LVEDV LVESV LV SV 8 20 HR Plasma volume Erythrocyte volume (iron supplements) Erythrocyte volume (no iron supplements) Hematocrit (iron supplements) Hematocrit (no iron supplements) Duration of pregnancy (weeks) CO 45% Fig. 2. Cardiovascular effects during pregnancy. SVR: systemic vascular resistance, LVEDV:left ventricular enddiastolic volume, LVESV:left ventricular end-systolic volume, HR:heart rate, CO:cardiac output. 40 다는보고가있는데후자에서는임신후반부에심박동수의증가가심박출량의증가에관여하기때문으로보고있다 (Fig. 2)(Table 1). 실제로임신중에는심박동수가기준치보다 25~30% 정도증가한다. 임신중심박출량이증가하는기전은호르몬과관련이있고일부연구에서는혈류역학적변화가체순환저항 (systemic vascular resistance) 의일차적인감소에의한다는가설을제시하였다. 3) 심박출량의증가에도불구하고체순환저항의감소는혈압을약간감소시킨다. 그러나심박출량의증가의많은부분은심박수의증가에의해서일어난다. 폐동맥압은또한임신중정상을유지하는데이것은혈류량의증가에대한균형을유지하기위하여폐순환저항 (pulmonary vascular resistance) 이감소됨을시사한다. 4) 정상임신중심장의형태학적및기능적변화임신중심박출량의증가는좌심실크기, 용적및형태의변화에서반영된다. M형심초음파를이용한연구에서임신중이완기말좌심실폭이약간증가되고수축기말폭은변화가없기때문에, 분획단축률 (Fractional shortening) 은약간증가하는것으로나타났다. 또한좌심실벽두께가증가하여좌심실무게는증가한다. 이면성심초음파를이용한연구에서좌심실의이완기말용적과좌심실구혈률 (Ejection Fraction) 은약간증가하였다. 5) 이러한소견들은좌심실이완기용적의증가로인한부하상태의변화또는체순환저항의감소때문인지는완전히밝혀져있지않다. 임신중좌심실형태의변화에대한일부연구가있었지만극적인 Table 1. Hemodynamic changes during normal pregnancy Parameters 1st trimester 2nd trimester 3rd trimester Blood volume Cardiac output to to Stroke volume, or Heart rate or Systolic Bp Diastolic Bp Pulse pressure Systemic vascular resistance 1072 Korean Circulation J 2003;33(12):

3 변화는관찰되지않았다. 임신중좌심실유출로및대동맥의직경이지속적으로증가하며그정도는평균 1~2 mm에불과하지만이러한작은변화가정확한심박출량의측정을위해서는중요할수있다. 6) 또한좌심방의전후직경이약 4 mm 정도증가하고승모판륜및삼첨판륜직경의작은증가가일어나는데이로인하여폐쇄부전의소견이흔하게관찰된다. 5) 출산후심장의변화대부분의임산부들에게서출산전의검사수치들을얻기는어렵지만일부연구에서는임신전부터시작한전향적연구를통하여, 임신전, 임신중및임신후의혈류역학적및해부학적변화를관찰하였다. 7) 이들의연구에따르면임신중일어나는일부의변화들은출산후까지지속되거나때로는영구적인경우도있다. 출산후혈류역학적및해부학적변화가 6~12 주에걸쳐서빠르게기준치로돌아온다고하더라도임신전과는차이를보일수있다. 특히대동맥및좌심실직경은정상성인에서의범위에들어있더라도임신전에비하여증가된상태로남아있을수있다. 7) 주산기의혈류역학적변화주산기에일어나는부하상태의극적인변화는 1) 자궁수축, 2) 출산과관련된통증, 3) 마취약제, 4) 출산시실혈등과관련이있다. 건강한산모는임신과관련된정상생리학적변화들에적응하지만심질환을갖고있는산모들은이러한변화들에대하여적응이어려울수있다. 출산과관련된급성실혈에도불구하고태반방출후에심박출량이실제적으로 10% 정도증가하여 24시간가량지속된다. 그후수일에서 2주간에걸쳐서임신전과비교하여 25~30% 정도로감소하는데이것은심박수의감소및혈관내용적의감소와관련이있다. 8)9) 출산도중자궁수축은심박수와혈관내용적의증가를일으켜심박출량을증가시킨다. 또한출산도중폐동맥압및좌심실압의증가가일어나는데, 좌심실의탄성이감소되어있는환자-대동맥판막협착증또는좌심실비대증-에서는이러한증가가더욱가중된다. 제왕절개시에는정상분만에비하여용적의변화가더욱커지기때문에, 심질환을갖고있는환자에서는불리할수있다. 출산시의통증은심박수및체혈관 저항을증가시키기때문에심혈관질환을갖고있는산모에서는심박출량의감소를초래할수있다. 마취약제는통증이완화또는제거에도움이될수있지만전부하, 후부하및심기능에영향을미칠수있다. 10)11) 임신과관련된혈액학적변화들임신은단백질 S 활성도의상대적감소, 울혈및정맥고혈압등으로인한과응고상태와관련이있다. 에스트로젠은중간이상크기의동맥의중막안에교원질의침착을방해할수있다. 혈액내순환하는에라스타제 (elastase) 는임신중대동맥의탄력성층판 (elastic lamellae) 과중막을약화시킬수있으며이로인하여교원성질환의기왕력이없이도대동맥박리의선행원인이될수있다. 12) 임신중판막질환의치료 임신과관련된판막질환의일반적인치료지침으로서청색증, Eisenmenger 증후군, 심한폐동맥고혈압이있는상태에서는임신을피할것을권한다. 또한 1) 증상을동반하거나동반하지않는중증의대동맥판협착증, 2) NYHA 기능분류상 Ⅲ 또는 Ⅳ의증상을갖는승모판및대동맥판막폐쇄부전증, 3) NYHA 기능분류상 Ⅱ에서 Ⅳ의증상을갖는승모판협착증, 4) 심한폐동맥고혈압을초래한판막질환 ( 폐동맥압이체동맥압의 75% 이상인경우 ), 5) 심한좌심실기능부전을동반한판막질환 ( 좌심실구혈률 <40%), 6) 항응고제를필요로하는기계적인공판막, 7) Marfan 증후군에서동반된대동맥폐쇄부전증등은모성및태아의위험도를증가시키므로주의를요한다. 승모판협착증임신중의승모판협착증은대부분에서만성류마티스판막질환이그원인이다. 대부분의중등도, 중증의승모판협착증환자는임신기간동안 NYHA 기능단계가 1단계혹은 2단계정도악화진다 ) 승모판협착증에서승모판역류가자주동반되지만, 혈역학적인문제는협착과더관련이많다. 임신중생리적인심박수및혈액량의증가는좁아진승모판을통한압력차를더욱증가시키게되고증가된좌심방압력은심방 1073

4 조동이나심방세동을유발하고, 심실박동수를증가시켜좌심방압을더올리게된다. 14) 또한임신기간동안의감소된혈청삼투압과출산전후기의과도한정맥내수액치료는폐부종을일으키기가쉽다. 모체의부정맥, 19) 외과적중재를요하는심낭압전, 색 전증 20) 등의심각한합병증이일부에서보고되었으며 태아를방사선에노출시킬수있기때문에임신1기동안에는가능하면피해야한다. 15) 일반적인치료원칙승모판협착증이있는환자의치료는심박수를줄이고혈액량을감소시키는것을목표로한다. 일상활동을제한하고, 베타차단제를투여하는것으로심박수와증상을효과적으로조절할수있고, 15-17) 심방세동이있는환자에서는심실박동수를조절하기위해디곡신이사용될수있으며염분섭취를제한하고이뇨제를복용함으로써혈액량을줄일수있다. 그러나저혈량증과자궁태반의혈류부전을방지하기위해과도한이뇨제의사용은피해야한다. 대부분의승모판협착증환자에서는질식분만이가능하다. 증상이있는환자, 중등도또는중증의협착 ( 승모판면적 <1.5 cm 2 ) 환자에서는분만중집중적인혈역학적관찰이요구된다. 분만시의혈역학적관찰을함으로써이뇨제의정맥투여, 디곡신, 베타차단제, 니트로글리세린을사용함으로써혈역학적으로안정화시키고, 좌심방압의상승을예방할수있다. 분만과함께임신자궁에의한대정맥폐쇄가줄어정맥유입량이즉시증가하게됨으로서, 폐동맥쐐기압력이상당히증가하게된다. 그러므로출산후최소수시간동안은집중적인혈역학적관찰을해야한다. 경막외마취는질식혹은복부분만을하는승모판협착환자모두에게가장적절한마취방법이지만체혈관의확장을일으켜서폐동맥압과좌심방압을심각하게떨어뜨리기도한다. 이러한접근을통하여승모판협착증이있는대부분의환자에서중증일지라도비교적합병증없이분만할수있다. 풍선판막성형술임신중 NYHA 기능분류상 Ⅲ에서 Ⅳ의증상이있는중증의승모판협착증에서는풍선판막성형술을시행하는것을권하고있다. 임신기간동안의승모판협착환자에서경피적풍선판막성형술이증가하고있으며 18-20) 많은증례에서모체와태아에좋지않은영향없이혈역학적, 증상적호전을보였다. 그러나동시에종종자궁수축의시작, 18) 태아가사를일으킬수있는 승모판재건술과치환술임신중의승모판재건술과치환술은내과적치료에반응하지않는중증의판막협착 ( 승모판면적 <1 cm 2 ) 이나임신, 분만중에경과관찰이불가능한경우에만고려되어야한다. 21)22) 임신한환자에서의승모판막경계절개술 ( 폐쇄혹은개방 ) 과승모판막치환술의위험은임신하지않은환자와비슷하지만 21) 유산률을증가시킨다. 22) 승모판역류증승모판탈출증의전체유병률은 2.4% 이며임신여성에서는 1.2% 로보고되었으며, 임신중승모판폐쇄부전증을일으키는가장흔한원인이다. 임신기간동안에기능적수축기심잡음의빈도가증가하고, 제 1심음의분리음간격이넓어지기때문에승모판탈출증은잘못진단될수도있기때문에, 심초음파적진단기준에의해서확진되어야한다. 23)24) 승모판역류증환자는생리적으로체혈관저항의감소로인해좌심실부하를줄임으로써임신에비교적잘견딘다. 증상이있는환자에서이뇨제를포함한약물치료가적응이되며, 좌심실수축기기능이저하된환자에서는디곡신이사용될수있다. 임신시하이드랄라진은안전하기때문에, 25) 좌심실후부하를줄이고, 분만기동안의등척성운동과관련된혈역학적악화를예방하기위해서사용될수있다. 26) 흉통이나부정맥이있는승모판탈출증환자에서임신기간동안약물의사용은피해야하지만베타차단제는적응이될때는권장된다. 특히승모판이두꺼워졌거나승모판역류가있는승모판탈출증환자는감염성심내막염의위험이증가한다. 일반적으로합병증이없는질식분만의경우예방적항생제를권장하지는않지만, 질식분만과제왕절개동안폐혈증의발생을항상예측할수는없기때문에, 승모판이두꺼워졌거나역류가있는경우에서분만중예방적항생제의사용이정당화될수있다. 승모판탈출증과관련된폐쇄부전은일반적으로내과적치료를 1074 Korean Circulation J 2003;33(12):

5 시행하는데, 건삭파열, 폐쇄부전병변의급성악화등의경우에서는승모판막수술을시행할수있다. 특히젊은여성에서는항응고제의사용을피하기위하여승모판막성형술이선호된다. 대동맥판협착증가임여성에서가장흔한대동맥판협착증의원인은선천성대동맥이첨판이다. 경증및중등도협착과정상좌심실구혈률을보이는환자는전임신기간을통하여내과적인치료를받을수있다. 심한협착 ( 평균압력교차 >50 mmhg) 이나증상이있는환자에서는증상이완화될때까지임신을연기할것을권장한다. 대동맥이첨판과낭포성중막괴사 (cystic medial necrosis) 사이에연관성이있으며, 특히임신 3기에는자발적대동맥박리가일어날수있다. 임신기간중류마티스성대동맥판협착은비교적드물며, 류마티스판막질환을가진임신환자의 5% 에서는승모판질환과관련하여발생한다. 15) 판막면적이 1.0 cm 2 이상인대동맥판협착환자는임신을잘견디지만, 더중증의협착이있는환자는노작성호흡곤란, 실신등의임상소견과폐부종이악화될수있다. 14)27) 임신기간동안내과적치료에반응하지않는심각한증상이발생한경우, 임신을종결하거나외과적 ( 판막치환술 ), 또은경피적풍선판막성형술이필요할경우도있다. 21)28) 대동맥판역류증승모판역류와비슷하게, 대동맥판역류또한임신에잘견딘다. 증상이있는환자는좌심실후부하를줄여주기위해이뇨제, 디곡신, 하이드랄라진등이안전하게사용될수있다. 폐동맥판협착증독립적인폐동맥판협착증은성공적인출산에거의장애가되지않는다. 필요하다면심초음파유도하에풍선판막성형술을시도할수있다. Marfan 증후군 Marfan 증후군환자에서의임신은 1) 심혈관계합병증, 2) Marfan 증후군의높은유전율 29)30) 이라는두가지문제점을고려하여야한다. 상행대동맥확장에 의한심혈관계합병증은대동맥판역류증, 울혈성심부전, 관상동맥을포함한대동맥박리를유발할수있다. 대동맥확장이있거나, 이전에박리의과거력이있는환자에서는대동맥박리의위험률이현저히증가한다. 심혈관계침범이적고, 대동맥직경이 40 mm 미만인 Marfan 증후군환자는임신에의한심혈관계의악화없이임신을잘견딜수있다. 31) 대부분의 Marfan 증후군과관련된합병증은임신후반기에발생한다. Marfan 증후군은또한자궁경부무력증, 태반위치의이상, 산후출혈합병증의원인이된다. 32) Marfan 증후군환자의임신관리는모체와태아의위험에대한상담을포함시켜야한다. 29) 심각한심혈관침범이있는여성- 특히대동맥확장이나대동맥박리의과거력-은임신시합병증의위험이높기때문에임신하지않는것이좋으며, 이미임신을했다면조기유산하는것이낫다. 반대로심혈관합병증이없고, 대동맥직경이정상인경우위험률은유의하게낮지만정상크기의대동맥을가진환자에서도종종대동맥박리가생길수있다는보고가있으므로 29) 대동맥직경이 40 mm보다큰경우에는고위험군에포함시켜야되며임신전및임신중에심초음파검사를포함한주기적경과관찰은필요하다. 31) 대동맥직경이 50 mm 이상일때에는임신전대동맥에대한선택적복원의적응증이된다. 하행대동맥을침범하는대동맥박리나동맥류가있을수있기때문에이러한경우에는경식도심초음파가경흉부심초음파보다많은정보를제공한다. 33) 임신중격심한신체활동은피해야하며대동맥확장과합병증의위험률을줄이기위해베타차단제를사용해야한다. 34) 임신중에상당한대동맥확장이관찰되는경우에는치료적유산과함께외과적치료가고려되어야한다. 29) 대동맥확장, 대동맥박리와그외심혈관합병증이있는경우에는질식분만과관련된혈역학적변화를최소화하기위해제왕절개에의한복식분만이더선호된다. 29)31) 임신과관련된판막질환에서의고려되어야될그밖의문제점들 심내막염의예방 The Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the American Heart 1075

6 Association 에서는감염이의심되는상태가아니라면, 판막질환이있는환자라도합병증이없는자연분만이나제왕절개수술을할경우에는예방적항생제의사용을권장하고있지않는다. 예방적항생제사용은인조혈관을가지고있거나, 이전에심내막염의과거력이있거나복잡한선천적심질환이있는경우, 또는수술적으로폐혈관과전신혈관사이의통로 (systemicpulmonary conduit) 를만든경우에선택적으로예방적항생제를투여할수있다. 35) 임신중판막수술과가임기여성에서의인공심장판막의선택임신한환자에서의심장판막수술은이상적인상태라하더라도수술시심폐우회로가유발하는혈류속도의증가와순환혈류온도의증가로인하여태아절박가사와태아성장지연, 또는유산의발병율이높아진다. 만약가능하다면태아가충분히성숙하여생존이가능하고, 제왕절개를동시에시행할수있을때까지수술을연기하는것이좋다. 수술은내과적으로치료가불가능한상태이거나 ( 폐부종 ) 저심박출량으로인한증상이있을경우에만시행하여야한다. 36) 가임기여성에서의인공심장판막의선택은매우어려운문제이다. 37) 신세대의인공판막은지속성, 낮은재수술위험성, 혈역학적우위를제공하지만항응고요법의필요성은산모의출혈과태아소실의위험성의증가와연관되어있다. 젊은환자들에게서조직판막은판막손상의빈도가높으며이것은임신시더욱가속화되어 38) 10년이내에약 30% 에서판막교환이필요하며특히대동맥위치의작은판막인경우에혈역학적지수가좋지않다. 39) 동종판막과새로운심장판막들이혈역학적으로우세한것으로나타났지만임신한여성에대한정보는제한적이다. 40) 2세대인공판막은지속성과혈역학적우수성, 그리고항응고요법시혈전색전증의낮은위험성및낮은출혈합병증때문에판막교환이필요하고모니터가가능한모든가임기의여성에게우선순위로생각되고있다. 인공판막을가진여성에서임신과관련된위험성은주로혈역학적부담의증가, 혈전색전증의증가및심혈관계약물과항응고제에의한태아에의좋지않은영향과관련되어있다. 1000예이상의경험으로보아임신전에증상이없거나적었던환자들은대부분임신에의한혈역학적부담을잘견디는반면에기능적감소와함께약물치료의 1076 시작또는용량의증가가필요할때도드물지않다. 40) 임신중혈전색전증의발생빈도는약 10~15% 증가하는것으로보고되어있다. 이러한환자들의 2/3 에서판막혈전이나타나며이들중 40% 가사망에이른다. 39) 혈전색전증은대부분구세대의인공승모판막에서나타나는것으로보고되어있다. 38)41) 임신중사용되는항응고제 ( 와파린과헤파린 ) 의문제점인공판막을가진임산부의경우항응고제의투여는불가피하지만와파린이나헤파린의사용은산모와태아에게출혈이나혈전같은중요한문제를일으킬수있다. 임신중에는환자와태아에대한안정성때문에헤파린이와파린보다우선순위로여겨지고있다. 42) 와파린과같은경구용항응고제는기형유발효과, 태아출혈성합병증의증가, 중추신경계손상의위험때문에임신시에는금기로생각되어왔는데, 임신중피하헤파린사용시인공판막혈전의발생률이증가할수있다는보고는 38)41) 인공심장판막을가진임신한여성에서헤파린의효율성에대한의문을제기시켰다. 43) 이에따라인공판막을가진환자에서임신 35주까지는항응고제로서와파린을사용하는방법이제안되었다. 38)41)44) 임신중와파린의사용은와파린에의한배아병증 (warfarin embryopathy) 과뇌출혈위험성의증가와관련이있다. 42) 와파린에의해유발된배아병증의발생률은 5~9% 이며 43) 이러한위험도는임신 6주에서 12주사이에노출될경우에그용량과연관이있는것으로보이고, 진통과출산의과정에서, 특히난산의경우태아의대뇌출혈이합병될수도있다. 36)45) 헤파린은태반을통과하지않기때문에상대적으로안전하다고여겨져왔지만장기간사용할경우무균성농양, 골다공증, 혈소판감소증, 출혈등의합병증이발생할수있다. 여러연구에서고위험산모에서헤파린을피하주사할경우, 태아판막혈전을포함한혈전색전성합병증의위험도가받아들이기어려울정도 (12%~ 24%) 로높게나타났음에도불구하고적절한피하헤파린의용량조절방법은아직확립되지않았다. 36) 임신중항응고제의선택은신중해야하며산모와태아에대한위험이비슷하다고하더라도, 산모가선호하는방법을고려하여야한다. 많은여성에서와파린에의한 4~10% 정도의태아기형이발생할수있는위험도는받아들일만하다. 이러한이유때문에여성들은임신초 Korean Circulation J 2003;33(12):

7 기또는임신전기간을통해서와파린투여를원치않을수도있다. 그러나산모들이헤파린을선택할경우에도산모의출혈이나인공판막혈전이발생할위험성이증가할수있다. 그러므로이러한문제점에대한충 분한토의가임신전에있어야한다 (Table 2, 3). 46) 저분자량헤파린은태반을통과하지않으며, 비분할헤파린 (unfractionated heparin) 보다생체이용율이월등히높으며, 투여가쉽고, 검사실검사로관찰이필요 Table 2. Recommendations for anticoagulation during pregnancy:weeks 1 through 35 in patients with mechanical prosthetic valves 46) Indication Class 1 The decision whether to use heparin during the first trimester or to continue oral anticoagulation *I throughout pregnancy should be made after full discussion with the patient and her partner; if she chooses to change to heparin for the first trimester, she should be made aware that heparin is less safe for her, with a higher risk of both thrombosis and bleeding, and that any risk to the mother also jeopardizes the baby 2 High-risk women (a history of thromboembolism or an older-generation mechanical prosthesis in the I mitral position) who choose not to take warfarin during the first trimester should receive continuous unfractionated heparin intravenously in a dose to prolong the midinterval (6 hours after dosing) aptt to 2 to 3 times control. Transition to warfarin can occur thereafter 3 In patients receiving warfarin, INR should be maintained between 2.0 and 3.0 with the lowest possible IIa dose of warfarin, and low-dose aspirin should be added 4 Women at low risk (no history of thromboembolism, newer low-profile prosthesis) may be managed with adjusted-dose subcutaneous heparin (17,500 to 20,000 U BID) to prolong the midinterval (6 hours after dosing) aptt to 2 to 3 times control IIb 1 From the european society of cardiology guidelines for prevention of thromboembolic events in valvular heart disease 46) Table 3. Recommendations for anticoagulation during pregnancy : after the 36th week in patients with mechanical prosthetic valves 46) Indication Class 1 Warfarin should be stopped no later than week 36 and heparin substituted in anticipation of labor Iia 2 If labor begins during treatment with warfarin, a cesarean section should be performed Iia 3 In the absence of significant bleeding, heparin can be resumed 4 to 6 hours after delivery and warfarin IIa begun orally Pregnancy in a patients with mechanical heart valve Higher risk first-generation prosthesis (e.g., Starr-Edwards, Bjork-Shiley) in the mitral position Lower risk second-generation prosthesis (e.g., St.Jude medical,medtronic hall) and any mechanical prosthesis in the aortic position Coumadin to INR for 36 weeks followed by IV heparin to APTT of > SC or IV heparin- APTT for 12 weeks Coumadin (NR ) IV heparin (APTT>2.5) SC heparin- (APTT ) for 12 weeks Coumadin (INR ) SC heparin (APTT ) SC heparin- (APTT ) for 12 weeks throughout pregnancy Fig. 3. Suggested algorithm for the management of the anticoagulation in patients with mechanical prosthetic valves during pregnancy. 1077

8 하지않고, 혈소판감소증이나, 골다공증등합병증의유병율이낮다는장점이있다. 저분자량헤파린은심부정맥혈전증의치료에이용되기는하지만, 인공심장판막을가진환자의치료에사용을권장할만한연구결과는아직없는실정이다. 47) Dipyridamole은태아에게유해하기때문에아스피린대용으로권장할수없다. 와파린이나헤파린모두, 모유수유를하는산모에게는사용해서는안된다. 48) 임신중권장되고있는항응고제투여방법 1세대인공승모판막을가진여성에서혈전색전의예방을위해서임신첫 35주동안하루 5 mg 이하의와파린으로치료용량에도달하는경우에 (INR 3.0~4.5) 경구용항응고제로서는가장잘이루어진것으로보고있다. 임신제 1기동안와파린치료를원하지않는환자를위한대안으로서제 1기동안적극적으로모니터하면서적절히용량조절을하여헤파린을경정맥또는피하로투여하고 43) 13~36 주까지는와파린을투여하며그이후분만시까지경정맥또는피하로헤파린을쓰는것이다 (Fig. 3). 고위험군의환자에서는 antifactor Xa가 0.55~0.8 U/mL 또는 aptt가 2.5~3.5에도달하도록고농도의헤파린을사용해야한다. 인공판막을가진환자에서는조산의빈도가높기때문에 41) 35~36 주에는와파린사용중의분만을피하기위해와파린을헤파린으로대체해야하며그전환은병원에서이루어지는것이좋다. 인공대동맥판막과승모판부위의 2 세대인공판막등을가진저위험군환자에서는임신기간내내피하헤파린치료가권장된다 (aptt 2.0~ 3.0). 42) 13주에서 35~36 주까지와파린을사용하는것은헤파린을환자가자가주사하는것이바람직하지않거나부작용이있을때대안이된다. 승모판부위의인공판막이나 1개이상의인공판막을가진경우, 심방세동이있는경우, 전신적혈전색전의기왕력이있는경우에는더고농도의항응고치료가필요할수있다. 항응고치료의강도는자주모니터되어야하며필요할경우즉시교정되어야한다. 요약 임산부는비교적젊고건강한여성으로서, 임신전 에심혈관계의특별한이상이없었던경우가대부분이기때문에산전및임신중심혈관계에대한사전진찰에소홀하기쉬운것이사실이다. 그러나임신기간동안에일어나는생리학적인변화들은심혈관계에많은부담을줌으로서, 기왕의심혈관계질환을악화시킬수있다. 특히고위험군에속하는판막질환을갖고있는환자들은개별적인카운셀링을통하여가능한임신을사전에방지하고, 임신과관련된모성및태아의위험도및장기적예후에대한정보를주지시켜야된다. 그러나판막질환을갖고있는대부분의환자들은혈관내용적과전체적인심혈관내부하상태를적절히조절하여주는내과적치료를통하여임신기간중, 그리고분만과출산을성공적으로유도할수있으므로내과와산부인과의사들간의보다긴밀한유대관계가필요하다. 중심단어 : 임신 ; 판막질환. REFERENCES 1) Pitkin RM. Nutritional support in obstetrics and gynecology. Clin Obstet Gynecol 1976;19: ) Katz VL. Physiologic changes during normal pregnancy. Curr Opin Obstet Gynecol 1991;3: ) Duvekot JJ, Cheriex EC, Pieters FA, Menheere PP, Peeters LH. Early pregnancy changes in hemodynamics and volume homeostasis are consecutive adhustments triggered by a primary fall in systemic vascular tone. Am J Obstet Gynecol 1993;169: ) Robson SC, Hunter S, Boys RJ, Dunlop W. Serial changes in pulmonary hemodynamics during human pregnancy: a non-invasive study using Doppler echocardiography. Clin Sci 1991;80: ) Sadanianz A, Kocheril AG, Emaus SP, Garber CE, Parisi AF. Cardiovascular changes in pregnancy evaluated by twodimensional and Doppler echocardiography. J Am Soc Echocardiogr 1992;5: ) Easterling TR, Benedetti TJ, Schmucker BC, Carlson K, Millard SP. Maternal hemodynamics and aortic diameter in normal and hypertensive pregnancies. Obstet Gynecol 1991; 78: ) Hunter S, Robson SC. Adaptation of the maternal heart in pregnancy. Br Heart J 1992;68: ) Robson SC, Dunlop W, Hunter S, Boys R, Bryson M. Hemodynamic changes associated with caesarean section under epidural anesthesia. Br J Obstet Gynecol 1989;96: ) Ronson SC, Dunlop W, Boys RJ, Hunter S. Cardiac output during labour. Br Med J 1987;295: ) Strickland RA, Oliver WC Jr, Chantigian RC, Ney JA, Danielson GK. Anesthesia, cardiopulmonary bypass, and the pregnant patient. Mayo Clin Proc 1991;66: ) Lee HJ, Youn HJ, Chon JY, Choi YW, Moon SH. Anesthesia for cesarean section in a patient with peripartum cardiomyopathy. Korean J Anesthesiol 2000;39: Korean Circulation J 2003;33(12):

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<4D F736F F F696E74202D20BFA1C4DA5FC0D3BBF3C3CAC0BDC6C42E BC8A3C8AF20B8F0B5E55D> 심장 (Heart) 심초음파 서울대병원내과 김용진 심장은평생몇번이나뛸까요? 1) 3 백만번 2) 3 천만번 3) 3 억번 4) 30 억번 30 억박동, 2 억리터의혈액 Cause 심장질환 6.2 12.4 11.1 16.2 뇌졸중 4.3 8.5 7.7 11.3 기타심혈관질환 2.6 5.1 6.0 8.8 심혈관질환 13.1 26.0 24.8 36.3 총사망 50.4