원저 Korean Circulation J 04;34(2):159-169 만성승모판폐쇄부전증환자에서의안지오텐신전환효소억제제의장기투여효과 서울대학교의과대학내과학교실, 1 한림대학교의과대학내과학교실 2 김대희 1 이명묵 1 이해영 1 조현재 1 박승정 1 서재빈 1 서정원 1 양한모 1 윤창환 1 조상호 1 이준희 2 김용진 1 김명아 1 손대원 1 오병희 1 박영배 1 Long-Term Effect of Angiotensin Converting Enzyme Inhibitor on Chronic Mitral Regurgitation Dae-Hee Kim, MD 1, Myung-Mook Lee, MD 1, Hae-Young Lee, MD 1, Hyun-Jai Cho, MD 1, Seung-Jung Park, MD 1, Jae-Bin Seo, MD 1, Jung-Won Suh, MD 1, Han-Mo Yang, MD 1, Chang-Hwan Yun, MD 1, Sang-Ho Cho, MD 1, Jun-Hee Lee, MD 2, Yong-Jin Kim, MD 1, Myoung-A Kim, MD 1, Dae-Won Sohn, MD 1, Byung-Hee Oh, MD 1 and Young-Bae Park, MD 1 1 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 2 Department of Internal Medicine, Hanlym University College of Medicine, Seoul, Korea ABSTRACT Background and Objectives:Angiotensin converting enzyme inhibitors (ACEI) have been suggested to be beneficial in regurgitant valvular heart disease by reducing both preload and afterload. Moreover their benefits have also been proven in acute mitral regurgitation (MR). However the role of long term administration of ACEI in chronic MR remains in dispute. Subjects and Methods:One hundred patients with more than moderate degree MR (rheumatic MR or Mitral valve prolapse [MVP] MR) were identified from patients undergoing cardiac echocardiography between April 1984 and July 02. Patients with co-morbid valvular heart disease more than mild degree were excluded from the study. The subjects were divided into the study group (who took ACEI) and the control group. Medical records and echocardiographic reports were reviewed and the etiology of MR, left ventricular end-diastolic dimensions (LVEDD), end-systolic dimensions (LVESD), left atrial dimensions, and ejection fraction (EF) changes were studied serially for both groups. Results:The mean duration of follow-up was 5.0± 3.2 years. There were no significant differences in age, blood pressure, or basal echocardiographic parameters between the rheumatic MR and MVP MR groups. In the MVP MR patients, the ACEI group showed a statistically significant increase in EF (p=0.007), decrease in LVESD (p=0.0014) and decrease in left atrial dimensions (p=0.01). However, in the rheumatic MR patients, the ACEI group showed no significant changes compared to those of the non-acei group. Conclusion:Long term ACEI therapy seems to be beneficial in mildly symptomatic MR due to mitral valve prolapse. (Korean Circulation J 04;34 (2):159-169) KEY WORDS:Mitral valve regurgitation;mitral valve prolapse;angiotensin-converting enzyme inhibitor. 논문접수일 :03 년 08 월 13 일수정논문접수일 :03 년 9 월 22 일심사완료일 :03 년 10 월 06 일교신저자 : 이명묵, 110-744 서울종로구연건동 28 서울대학교의과대학내과학교실전화 :(02) 7-3285 전송 :(02) 3673-2913 E-mail:mmlee@snu.ac.kr 159
서론 승모판폐쇄부전증은심장판막질환중가장높은유병률을보이는질환으로중증환자에서는수술적교정이표준적치료로인정되고있으나경증환자및무증상환자에서의내과적치료방침은정해져있지않다. 급성승모판폐쇄부전증환자에서 nitroprusside 나 hydralazine 과같은혈관확장제의투여는후부하의감소를통해승모판막을통한역류분율의감소, 심박출량의증가및좌심실용적의감소를가져올수있음이알려져있고, 1-3) 이에따라만성승모판폐쇄부전증환자의장기적내과치료에안지오텐신전환효소억제제의사용이시도되고있으나아직그장기효과에대해서는논란이있는실정이다. 만성승모판폐쇄부전증환자에서의안지오텐신전환효소억제제투여효과에대한연구로많이인용되는것이 Wisenbaugh 등 4) 과 Schon 등 5) 에의한두개의논문이다. Wisenbaugh 등 4) 은뉴욕기능분류 2도이하의만성승모판폐쇄부전증환자에서 Captopril 투여 6개월후좌심실수축말기내경, 이완말기내경및박출계수의유의한변화를관찰할수없다고보고한반면, Schon 등 5) 은뉴욕기능분류 2도이상의환자가다수포함된 (9/ 12) 환자군에대해 Quinapril 투여 12개월후좌심실수축말기내경, 이완말기내경이유의하게감소한다고보고하였다. 국내에서는연등 6) 이뉴욕기능분류 2도이하환자를대상으로안지오텐신전환효소억제제 3년간투여한결과기저좌심실내경이증가되어있던군에서좌심실수축말기내경, 이완말기내경이감소함을보고하였다. 종래이들연구에대한고찰에서는각환자군간증상의경중이중점적으로거론되었고이들환자군간의승모판폐쇄부전증의병인에대해서는충분한고려가이루어지지않았으나, 최근연구결과들은승모판폐쇄부전증의병인에따라안지오텐신전환효소억제제의투여효과가다르게나타날수있음을시사하고있다. 7) 이에저자들은증상이없거나경미한만성승모판폐쇄부전증환자에서병인에따른안지오텐신전환효소억제제의장기투여가좌심실용적및수축기능에미치는효과를비교분석하고자하였다. 대상및방법 본연구는 1984 년 4월에서 02 년 7월까지서울대 1 학병원내과를방문하여신체검사및심초음파검사를통해만성승모판폐쇄부전증으로진단받은환자중, 경도이상의다른판막질환이동반되어있지않으며, 노작성호흡곤란증상의정도가뉴욕기능분류 (NYHA) 상 2 도이하이고, 도플러심초음파에서중등도이상의승모판폐쇄부전 8) 을보이며 ( 승모판역류의제트면적이좌심방면적의 % 이상일때 ), 이후 2회이상주기적심초음파검사를시행한환자를대상으로하였다. 경흉부심초음파검사상승모판소엽의석회화나비후, 승모판경계부융합이동반된군을류마티스성승모판폐쇄부전증으로, 수축기에좌심방내로승모판소엽이탈출되며편측성역류혈류가관찰되는경우를승모판탈출증에의한승모판폐쇄부전으로규정하였으며, 두가지원인중어느것에도해당되지않는환자및원인이불분명한환자는대상에서제외하였다. 또한, 심초음파도로측정한승모판막내경이 2.0 cm 2 이하인승모판협착증이동반된경우, 혹은도플러심초음파도에서중등도이상의대동맥판폐쇄부전이나경대동맥판막압력차가 25 mmhg 이상의대동맥판협착증이동반된경우에도대상에서제외하였다. 이렇게해서선정된 100 명의대상환자를안지오텐신전환효소억제제를사용한군과약물투여를하지않았거나안지오텐신전환효소억제제이외의약제를사용한군으로나누었고이후시행한경흉부심초음파에서미국심초음파학회 (American Society of Echocardiography) 의기준 8) 에의거하여폐쇄부전의정도를비교후좌심실의수축말기내경, 이완말기내경, 좌심방내경및박출계수를측정하였고, 각환자에서진단당시의기저치와비교한변화량을비교하였다. 각측정치는 ( 평균 ± 표준편차 ) 의형식으로표현하였으며, 각군간의변화량의비교를위해선형회귀분석법을이용하였고, 시간에따른각개인의변화를비교하기위해 SAS 8.2 version의 Random effect model 을이용해분석하였다. 결과 대상환자군의특성대상환자 100명의평균추적관찰기간은 5.0±3.2년 ( 범위 1~16 년 ) 이었다. 류마티스성승모판폐쇄부전증 / 안지오텐신전환효소억제제투여군 (Rheumatic MR/ Korean Circulation J 04;34(2):159-169
ACEI), 류마티스성승모판폐쇄부전증 / 안지오텐신전환효소억제제비투여군 (Rheumatic MR/non-ACEI), 승모판탈출증에의한승모판폐쇄부전 / 안지오텐신전환효소억제제투여군 (MVP MR/ACEI), 승모판탈출증에의한승모판폐쇄부전 / 안지오텐신전환효소억제제비투여군 (MVP MR/non-ACEI) 4군간관찰기간의유의한차이는없었다. ACEI 군은모두 56명으로 Enalapril (10~ mg/ 일 ) 을투여한환자가 44명이었고 Captopril (37.5~75 mg/ 일 ) 을투여한환자는 12명이었다. 이들중 Rheumatic MR/ACEI 군 (n=25) 에서안지오텐신전환효소억제제만을투여한군은 18명이었으며이뇨제와디곡신을동시에투여한환자는 2명디곡신만을동시에투여한군은 2명, 이뇨제만을동시에투여한군은 3명이었다. Rheumatic MR/non-ACEI 군 (n=11) Table 1. Main clinical features of patients with rheumatic mitral regurgitation (MR)(A) and mitral valve prolapse (MVP)(B) (A) Rheumatic MR/non-ACEI Rheumatic MR/ACEI p* Number 11 25 Age (year) 33±17 38±16 NS Male:Female 4:7 8:17 NS Duration of F/U (yr) 6.3±4.1 4.5±2.4 NS F/U results F/U continued 07 13 NS F/U loss 02 06 NS Operation 01 03 NS Mx change 01 03 NS Systolic BP (mmhg) 122± 134±27 NS Diastolic BP (mmhg) 076±13 083± NS Heart rate (BPM) 073±07 079±18 NS AF 02 04 NS LVH 02 02 NS HT 02 03 NS (B) MVP/non-ACEI MVP/ACEI p Number 33 31 Age (year) 37±17 41±15 NS Male:Female 12:21 11: NS Duration of F/U (yr) 5.6±3.7 4.4±2.6 NS F/U results F/U continued 21 23 NS F/U loss 08 04 NS Operation 03 03 NS Mx change 01 01 NS Systolic BP (mmhg) 135± 137±24 NS Diastolic BP (mmhg) 082±12 085±14 NS Heart rate (BPM) 075±09 075±21 NS AF 02 05 NS LVH 06 04 NS HT 09 12 NS *: univariate analysis, NS: not significant, ACEI: angiotension converting enzyme inhibitor, AF: atrial fibrillation, LVH: left ventricular hypertrophy, HT: hypertension 161
에서는이뇨제와디곡신을동시에투여한환자는 2명, 으며이들의자료는마지막추적관찰된심장초음파디곡신만을투여한군은 2명, 이뇨제만을투여한군은측정치까지를기준으로하였다. 1명이었고베타차단제만을복용하는군은 1명, 5명은투약에변화가있었던사람들은 ACEI 군에서는 ACEI 아무약도복용하지않았다. 에서안지오텐신수용체차단제로바꾼환자들로, 바꾸 MVP MR/ACEI 군 (n=31) 에서안지오텐신전환효소기직전까지의 echo data 만을사용하였고, Non-ACEI 억제제만을투여한군은 18명이었으며이뇨제와디곡군에서는전립선비대증으로인해베타차단제를알파신을동시에투여한환자는 3명, 디곡신을동시에투여차단제로바꾼사람이 1명씩있었으나통계적으로영향한군은 5명, 이뇨제만을투여한군은 5명이었다. MVP 을미치지않아분석에그대로사용하였으며수술을시 MR/non-ACEI 군 (n=33) 에서는이뇨제와디곡신을동행받은환자들은수술전경도의증상을가지고있을시에투여한환자는 4명, 디곡신을동시에투여한군은때까지의자료만을사용하였다. 3명, 이뇨제를동시에투여한군은 3명이었고, 2명은베타차단제를복용하였으며 21명은아무약도복용하지승모판폐쇄부전증의병인에따른안지오텐신전환효소억제제않았다. 의투여효과 Rheumatic MR과 MVP MR군에서각각 ACEI 군과류마티스성승모판폐쇄부전증환자군과승모판탈출 non-acei군사이에는안지오텐신전환효소억제제외증에의한승모판폐쇄부전증환자군에서투여군과대의약제복용에대해서는통계적으로차이가없었다. 조군간에서심초음파지표기저치와최종검사시의측초진시연령, 수축기및이완기혈압, 맥박수는 Rheumatic MR/ACEI, Rheumatic MR/non-ACEI, MVP 수없었으나 (Table 2A, B), SAS의 Random effect 정값을단순비교하였을때에는유의한차이를발견할 MR/ACEI, MVP MR/non-ACEI 4군간에유의한차이 model을이용해각군에서의각개인의변화량을추적는없었다. 좌심실의수축말기내경, 이완말기내경, 좌비교하고이것을회귀분석을시행하였을때, 류마티스성심방내경및박출계수모두 4군간에유의한차이는관승모판폐쇄부전증환자군에서는안지오텐신전환효소찰되지않았다 (Table 1, 2). 억제제투여군과대조군간에구출율 (ejection fraction), 추적검사에서제외된환자는각군에서차이가없었심방내경, 좌심실수축말기내경, 좌심실이완말기내경 Table 2. Serial changes of echocardiographic parameters of patients with rheumatic mitral regurgitation (A) and mitral valve prolapse (B) (A) Rheumatic MR/non-ACEI Rheumatic MR/ACEI p* Parameters changed Basal Last F/U Basal Last F/U LVESD (mm) 39±5 38±6 41±8 41±8 NS LVEDD (mm) 58±7 59±8 61±9 61±10 NS LA demension (mm) 42±8 45±9 45±9 48±13 NS EF (%) 53±9 57±6 56±4 56±9 NS (B) MVP/non-ACEI MVP/ACEI p* Parameters changed Basal Last F/U Basal Last F/U LVESD (mm) 35±5 36±6 37±6 35±5 NS LVEDD (mm) 55±8 56±9 58±6 57±5 NS LA demension (mm) 39±8 41±10 44±9 46±10 NS EF (%) 59±6 59±7 58±9 ±8 NS *: univariate analysis. NS: not-significant, MR: mitral regurgitation, ACEI: angiotension converting enzyme inhibitor, MVP: mitral valve prolapse, LVEDD: left ventricle end diastolic dimension, LVESD: left ventricular end systolic dimension, EF: ejection fraction 162 Korean Circulation J 04;34(2):159-169
의변화추이에있어통계적으로유의한차이는관찰되지않았다 (Fig. 1, 2, 3, 4 상단 ). 승모판탈출증환자군에서는안지오텐신전환효소억제제투여군에서대조군에비해구출률이유의하게상승하였으며 (Fig. 1, p=0.007), 회귀분석의평균기울기는 (the mean estimates of slope) 0.89±0.24% vs 0.07±0.%/year 로이로부터추정한 10년간의예상변화량은평균적으로 8.9±2.4% 로호전되는양상이었다 (Fig. 1). 좌심실수축말기내경의경우안지오텐신전환효소억제제투여군에서 -0.59±0.16 mm로대조군 (0.05± 0. mm/year) 에비해유의하게감소하였으며 (Fig. 2, p=0.0014), 분석하였을때 10년간변화량으로추정하였을때평균적으로 5.9±1.6 mm 감소하여대조군의 0.5±2 mm 확장에비해호전되는양상이었다 (Fig. 2). 좌심방내경의경우안지오텐신전환효소억제제투여군에서 -0.27±0.37 mm로대조군 (-0.02±0.47 mm/ 0.8 ACEI (-) 0.8 ACEI (+) 0.7 0.7 0.6 0.6 0.5 0.5 0.4 0.4 0.3 0.3 years Rheumatic mitral regurgitation 0.9 0.9 0.8 0.8 0.7 0.7 0.6 0.6 0.5 0.5 0.4 0.4 0.3 0.3 0.2 0.2 years Mitral valve prolapse regurgitation Fig. 1. Effects of ACE inhibitors on left ventricular ejection fraction. Thick lines illustrate mean values of the slopes. In MVP MR patients, the mean estimate of slopes of the EF changes in ACEI group is +0.89±0.24%/year, while that for the control group is +0.07±0.%/year, and there was statistically significant difference between the slopes of the ACEI group and the control group (p=0.007). But in rheumatic mitral regurgitation patients, no significant difference was observed. EF: ejection fraction, MVP: mitral valve prolapse, MR: mitral regurgitation, ACEI: angiotensin converting enzyme inhibition. 163
year) 에비해통계적으로유의하게시간의경과에따라감소되는양상이었고 (Fig. 4, p=0.01), 10년간변화량으로추정하였을때투여군에서 10 년간평균적으로 2.7± 3.7 mm 감소가예상되었다 (Fig. 4). 그러나이완기말좌심실용적의변화에서는투여군과대조군간에유의한차이는관찰되지않았다 (Fig. 3). 고찰 만성승모판폐쇄부전증환자에서좌심실용적의점 진적증가는좌심실기능부전이시작됨을의미하며, 증상이없는상태에서도비가역적인좌심실의기능부전이오기전에수술적교정을시행하는것이추천되고있다. 9) 이러한방침은심초음파도상좌심실수축말기내경이 45 mm 이상인만성승모판폐쇄부전증환자에서개심술후좌심실의기능회복이되지않거나예후가불량하다는보고에기인하는데, 10) 이에따라좌심실용적특히수축말기좌심실용적은만성승모판폐쇄부전증환자의예후에중요한인자로생각되며, 수술전환자의내과적치료역시폐동맥쐐기압의감소, 역류분율의감소와 mm ACEI (-) ACEI (+) Rheumatic mitral regurgitation years Mitral valve prolapse regurgitation Fig. 2. Effects of ACE inhibitors on the left ventricular end-systolic dimension. Thick lines illustrate mean values of the slopes. In MVP MR patients, the mean estimate of slopes of the end-systolic dimension changes in ACEI group is -0.59± 0.16 mm/year, while that for the control group is 0.05±0. mm/year, and there was statistically significant difference between the slopes of the ACEI group and the control group (p=0.0014). But in rheumatic mitral regurgitation patients, no significant difference was observed. EF: ejection fraction, MVP: mitral valve prolapse, MR: mitral regurgitation, ACEI: angiotensin converting enzyme inhibition. 164 Korean Circulation J 04;34(2):159-169
함께좌심실용적의감소를목표로하며이를경과관찰의중요한지표로삼고있다. 11) 심근병증에의한승모판폐쇄부전증에서혈관확장제의사용은질병의경과에호전을가져오는것으로알려져있는데, 이는심실확장에따른승모판소엽접합장애와판막륜의확장에의한기능성폐쇄부전증에서혈관확장제의사용이좌심실용적의감소와, 역류되는판구면적을감소시켜효과를나타내는것으로생각된다. 12-14) 또한급성승모판폐쇄부전증환자에서 nitroprusside 나 hydralazine 과같은혈관확장제의투여효과역시같은기전에의할것으로생각된다. 그러나실제임상에서가장문제가되는정상심박출량을보이며경도의좌심실확장이관찰되는무증상혹은경증의대상기 (compensated stage) 에서승모판폐쇄부전증환자에대해서는안지오텐신전환효소억제제등혈관확장제를이용한내과적치료가폭넓게시도되고있는것이현실이나이의장기투여효과에대한무작위연구 (randomized trial) 는없는실정이며여러연구의결과도상반되게나타나고있다. Wisenbaugh 등 4) 은뉴욕기능분류 2도이하의만성승모판폐쇄부전증환자 32명에서 Captopril 을하루 75 mg 투여하여 6개월후좌심실수축말기내경, 이완말기내경및박출계수의유 90 mm ACEI (-) 90 ACEI (+) Rheumatic mitral regurgitation years Mitral valve prolapse regurgitation Fig. 3. Effects of ACE inhibitors on left ventricular end-diastolic dimension. ACE inhibitor did not decrease end-diastolic dimension in both MVP MR rheumatic mitral regurgitation patients. MVP: mitral valve prolapse, MR: mitral regurgitation, ACEI: angiotensin converting enzyme inhibition. 165
mm ACEI (-) ACEI (+) Rheumatic mitral regurgitation Mitral valve prolapse regurgitation Fig. 4. Effects of ACE inhibitors on left atrial dimension. Thick lines illustrate mean values of the slopes. In MVP MR patients, the mean estimate of slopes of the left atrial dimension changes in ACEI group is -0.27±0.37 mm/year, while that for the control group is -0.02±0.47 mm/year, and there was statistically significant difference between the slopes of the ACEI group and the control group (p=0.01). But in rheumatic mitral regurgitation patients, no significant difference was observed. EF: ejection fraction, MVP: mitral valve prolapse, MR: mitral regurgitation, ACEI: angiotensin converting enzyme inhibition. 의한변화를관찰할수없었다고보고한반면, Schon 등 5) 은뉴욕기능분류 2도이상의환자가다수포함된 (9/ 12) 환자군에대해 Quinapril 을일일 10 mg 혹은 mg 투여하여 3개월및 12개월후, 방사선핵종좌심실조영술에서의수축말기용적지수, 이완말기용적지수와역류분율및심초음파도에서의좌심실수축말기내경, 이완말기내경이기저치와비교하여유의하게감소한다고보고하였다. 종래이들연구에대한분석에서는각환자군들간의증상의경증이중점적으로거론되었고이들환자군간의승모판폐쇄부전증의병인에대해서는충 분한고려가이루어지지않아서실제로는대상환자군간의병인의차이가결과에영향을미칠가능성을배재할수없다. 이에따라이들연구를분석해보면 Wisenbaugh 등 4) 의환자군의경우대부분 (29/32 명 ) 이류마티스성심질환이었다. 또한 Rothlisberger 등 15) 의연구에서는뉴욕기능분류 2도이상의증상을보이며주로류마티스성심질환자로이루어진 (12/16 명 ) 환자군을대상으로 Captopril 또는 Nifedipine의 1회투여후에심도자상좌심실수축말기내경이증가하고, 좌심실박출분획이감소함을보고하였다. 반면, Schon 등 5) 의연구에 166 Korean Circulation J 04;34(2):159-169
서의환자군은뉴욕기능분류 2도이상의증상을나타낸환자들이다수 (75%) 를차지하며다양한질환군 ( 승모판탈출증 5, 확장성심근증 3, 류마티스성심질환 2, 심내막염의과거력 2) 을포함하고있다. 이들연구에대한분석에서 Levine 과 Gaasch 등 16) 은 Rothlisberger 등 15) 과 Wisenbaugh 등 4) 의연구결과가환자군의대부분이고정된판구면적을가지는류마티스성승모판폐쇄부전증이었던것에기인할가능성을재기하였다. 또이러한가설은 Jeang 등 7) 의연구에서지지받고있는데, Jeang 등은류마티스성승모판폐쇄부전증환자군과승모판탈출증환자군에서의경구 isosorbide dinitrate 의투여효과를비교한연구에서류마티스성승모판폐쇄부전증환자군에서는역류분율의유의한증가가관찰된반면승모판탈출증환자군에서는유의한감소가관찰됨을보고하였다. 이론상으로혈관확장제에의한후부하감소는좌심실에서대동맥으로의혈류구출시의저항을감소시켜역류용적을감소시킬것으로생각된다. 그러나이러한영향은후부하증가가주된병인인대동맥판폐쇄부전증에서는큰효과를나타내지만, 후부하자체가크지않으며좌심실질량 / 용적비의감소가주된병인인승모판폐쇄부전증에서는큰효과를나타내지못할가능성이있고, 17)18) 또한 Tischler 등 19) 은승모판폐쇄부전증환자에서 Enalapril 을 6개월간투여한결과좌심실질량 / 용적비의감소가관찰되었음을보고하여이의사용이좌심실질량의감소를통해승모판폐쇄부전증을악화시킬가능성을재기하였다. 이러한결과는좌심실용적의변화가역류판구면적에영향을미치지못하는류마티스성승모판폐쇄부전증에서혈관확장제의장기투여가효과를나타내지못하는것으로나타난연구결과들과일치하는현상이다. 그러나좌심실내경과압력의변화가역류판구면적에역동적변화를가져올수있는승모판탈출증의경우에는안지오텐신전환효소억제제에의한후부하감소의효과가크게나타날수있고이를통한역류량의감소와나아가승모판폐쇄부전증자체의호전을가져올수있을것으로생각된다. 본연구에서는뉴욕기능분류 2도이하로증상이현저하지않은만성승모판폐쇄부전증환자를류마티스성승모판폐쇄부전증과승모판탈출증의병인에따라나눈후안지오텐신전환효소억제제투여효과를비교하였고, 그결과류마티스성승모판폐쇄부전증환자군에서는투 여군과대조군간에유의한차이를보이지않았으나, 승모판탈출증환자군에서는투여군에서대조군에비해좌심실수축말기내경의유의한감소와구출률유의한증가가있음을관찰할수있었다. 따라서이러한소견은비록증상이경미하더라도좌심실의유의한확장이관찰되는승모판탈출증에의한승모판폐쇄부전증환자에서안지오텐신전환효소억제제의장기간투여가좌심실확장의진행을둔화시키는데효과가있을가능성을제시하고있다. 본연구의제한점으로는첫째역류량자체에대한정량적평가가이루어지지않았다는점을들수있다. 본연구에서는심초음파검사상역류량에대한정량적평가가검사자간, 검사장비간오차가심하며특히승모판탈출증에서의편측성역류에대해서는그오차의정도가더욱크기에초음파상역류량의정성적평가와함께좌심방내경의변화로서역류량의변화를간접평가하였으나, 심도자술이나방사선핵종을이용한좌심실조영술에의한역류량의정량적추적관찰이이루어지지않았다는제약점이있다. 둘째, 후향적인연구로서무작위연구가아니었다는점을들수있는데, 따라서환자들의심초음파검사횟수와기간이일정하지않으며추적관찰에서제외되는경우에는추적관찰에서제외된시점까지의자료만을기준으로하였으므로환자들간의추적관찰기간이서로상이하여통상적인 fixed effect model 을적용할수없었으며, random effect model 을적용하여통계적으로유용한결과를얻어내었다. 또한안지오텐신전환효소억제제외의다른약제로이뇨제와디곡신에대한고려를할수가있는데, 디곡신을사용한사람의대부분은심방세동환자로서심박수조절을위해사용되었다고생각되나이뇨제의경우는 thiazide 계통의이뇨제가대부분으로고혈압약제로서혹은경도의증상조절을위해사용되었을가능성이제일높지만증상이심해서이뇨제를복용하고있는환자가차트상의정보부족으로인해경증의환자로잘못분류되었을가능성도완전히배제할수없으며이는후향적연구의한계라하겠다. 이미우리나라도선진국형질병양상으로변화하여일차성고립성승모판폐쇄부전증의유병률이감소하고있는현실에서다수환자에대한장기추적연구를위해서는불가피했다고생각되나앞으로의전향적인추적관 167
찰을통한연구가필요하리라고생각된다. 요약 배경및목적 : 안지오텐신전환효소억제제는전부하및후부하의감소작용을통해많은심질환에서의치료효과가알려져있으며, 급성승모판폐쇄부전증에있어서도그효과가입증되어있으나만성승모판폐쇄부전증환자에서장기투여시의효과에대해서는논란이있는실정이다. 방법 : 1984년 4월에서 02년 7월까지본원에서심초음파검사를시행받은승모판폐쇄부전증환자중류마티스성승모판폐쇄부전증과승모판탈출증에의한승모판폐쇄부전증환자 100 명을대상으로승모판폐쇄부전증의병인에따른안지오텐신전환효소억제제의장기투여효과를알아보았다. 중등도이상의승모판폐쇄부전증환자를대상으로하였고경도이상의동반판막질환을지닌환자는제외하였으며의무기록과심초음파기록을검토하여안지오텐신전환효소억제제투여군과대조군간에폐쇄부전증의병인과투여기간에따른수축기및이완말기좌심실내경, 좌심방내경, 구출율의변화를관찰하였다. 결과 : 평균관찰기간은 5.0±3.2 년이었고류마티스성승모판폐쇄부전증환자군과승모판탈출증환자군에서투여군과대조군간에연령, 혈압, 심초음파지표기저치, 안지오테신전환효소억제제를제외한다른복용약제에유의한차이는없었다. 류마티스성승모판폐쇄부전증환자군의경우안지오텐신전환효소억제제투여군과대조군간에좌심실수축말기내경및이완말기내경의변화에있어유의한차이는관찰되지않았다. 구출률의변화역시투여군과대조군간에유의한차이는관찰되지않았으며, 좌심방내경의변화역시유의하지않았다. 반면승모판탈출증에의한승모판폐쇄부전증환자군의경우안지오텐신전환효소억제제투여군과대조군간에좌심실이완말기내경의유의한차이는관찰되지않았으나, 수축말기내경의경우안지오텐신전환효소억제제투여군에서대조군에비해유의하게감소하는양상이었다 (p=0.0014). 이에따라구출율역시투여군에서 유의하게증가하는양상이관찰되었으며 (p=0.007), 좌심방내경도투여군에서유의하게감소하였다 (p=0.01). 결론 : 안지오텐신전환효소억제제는승모판탈출증에의한경도이하의증상을가진승모판폐쇄부전증환자에서장기투여시질병경과의호전을가져올수있을것으로생각된다. 중심단어 : 승모판폐쇄부전증 ; 승모판탈출증 ; 안지오텐신전환효소억제제. REFERENCES 1) Goodman DJ, Rossen RM, Holloway EL, Harrison DC. Effect of nitroprusside on left ventricular dynamics in mitral regurgitation. Circulation 1974;:1025-32. 2) Greenberg BH, Massie BM, Brundage BH, Botvinick EH, Parmly WW, Chatterjee K. Beneficial effects of hydralazine in severe mitral regurgitation. Circulation 1978;58:273-9. 3) Greenberg BH, de Mots H, Murphy E, Rahimtoola SH. Arterial dilators in mitral regurgitation: effects on rest and exercise hemodynamics and long term clinical follow-up. Circulation 1982;65:181-7. 4) Wisenbaugh T, Sinovich V, Dullabh A, Sareli P. Six month pilot study of captopril for mildly symptomatic, severe isolated mitral and isolated aortic regurgitation. J Heart Valve Dis 1994;3:197-4. 5) Schon HR, Schroter G, Barthel P, Schomig A. Quinapril therapy in patients with chronic mitral regurgitation. J Heart Valve Dis 1994;3:3-12. 6) Yeon TJ, Oh BH, Cho YS, Hwhng KG, Park DG, Chae IH, Kim HS, Shon DW, Kim CH, Lee MM, Park YB, Choi YS, Shu JD, Lee YW. Effects of long-term angiotensin converting enzyme inhibitor administration in chronic mitral regurgitation. Korean Circ J 1996;26:978-84. 7) Jeang M, Petrovich L, Adyanthaya A, Alexander J. Effects of isosorbide dinitrate on rheumatic and non-rheumatic mitral regurgitation. J Texas Heart Inst 1986;13:453-7. 8) Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD, Levine RA, Nihoyannopoulos P, Otto CM, Quinones MA, Rakowski H, Stewart WJ, Waggoner A, Weissman NJ. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 03;16:777-2. 9) Braunwald E. Heart disease-a textbook of cardiovascular medicine. 5th ed. Philadelphia: WB Saunders; 1997. p.1026-9. 10) Wisenbaugh T, Skudicky D, Sareli P. Prediction of outcome after valve replacement for rheumatic mitral regurgitation in the era of chordal preservation. Circulation 1994;89:191-7. 11) Carabello BA. Mitral valve regurgitation. Curr Probl Cardiol 1998;23:2-41. 12) Kizilbash AM, Willett DL, Brickner ME, Heinle SK, Grayburn PA. Effects of afterload reduction on vena contracta width in mitral regurgitation. J Am Coll Cardiol 1998;32: 427-31. 13) Yoran C, Yellin EL, Becker RM, Gabbay S, Frater RW, Son- 168 Korean Circulation J 04;34(2):159-169
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