대한내과학회지 : 제 73 권제 5 호 2007 급성심근경색환자에서재관류방법에따른 P파폭과 P파분산의변화 인하대학교의과대학심장내과학교실 최웅길 김대혁 김기창 안인선 김수현 유형권 권준 박금수 이우형 =Abstract= Change of the P wave duration and P wave dispersion according to treatment strategy in patients with a acute myocardial infarction Woong Gil Choi, M.D., Dae Hyeok Kim, M.D., Gi Chang Kim, M.D., In Sun Ahn, M.D., Soo Hyun Kim, M.D., Hyung Kwon Yu, M.D., Jun Kwan, M.D., Keum Soo Park, M.D. and Woo Hyung Lee, M.D. Division of Cardiology, Department of Internal Medicine, College of Medicine, Inha University Incheon, Korea. Background : P wave dispersion (PWD) and P wave duration have been used to evaluate the discontinuous propagation of sinus impulse and the prolongation of atrial conduction time, respectively. This study was conducted to compare the change of the maximal P wave duration (Pmax) and PWD according to the treatment strategy used in patients with an acute myocardial infarction (AMI). Methods : We retrospectively evaluated 86 patients that experienced an AMI. Patients were classified into three groups according to the treatment strategy: primary percutaneous coronary intervention (PCI), thrombolytic therapy, and delayed PCI. ECGs that were obtained from all patients on admission and on the second day were analyzed. The Pmax and minimum P wave duration (Pmin) were measured from a 12-lead ECG. The PWD was calculated as the difference between the Pmax and Pmin. Result : There was no significant difference in the age, gender, medication, coronary risk factor, ejection fraction, left atrial diameter, basal Pmax and PWD among the groups. However, there were significant differences in P max and PWD between the primary PCI group and the other groups on the second day after hospital admission. In the thrombolytic therapy and delayed PCI groups, the PWD was significantly lower in the patients with a patent infarct-related artery (IRA) than in patients without a patent IRA on the second day after hospital admission. Conclusions : These findings suggest that a primary PCI decreased the Pmax and PWD more than thrombolytic therapy or a delayed PCI.(Korean J Med 73:489-495, 2007) Key Words : P wave duration, P wave dispersion, Acute myocardial infarction Received : 2006. 11. 30 Accepted : 2007. 3. 14 Correspondence to : Dae Hyeok Kim, M.D., Department of Cardiology, Inha University hospital, 7-206, 3ga Sinheung-dong, Jung-gu, Incheon 400-711, Korea E-mail : kdhmd@korea.com, kdhmd@inha.ac.kr - 489 -
-The Korean Journal of Medicine : Vol. 73, No. 5, 2007 - 서론심방세동은치료방법의발전에도불구하고급성심근경색의비교적흔한합병증으로남아있다. 심근경색후발생한심방세동은심기능을더욱악화시키며입원기간내 (in-hospital) 및장기사망률 (long-term mortality) 의증가와연관되어있다 1, 2). 심방세동발생에는동성흥분파의비균질전도와심방내및심방간전도장애가중요한역할을하는데 3), 심전도에서 P파폭과 P파분산이이와밀접히연관된것으로알려져있다. P파분산과심방세동에대한연구는고혈압환자, 발작성심방세동, 안정형협심증환자, 관상동맥우회술환자등을대상으로한연구외에도최근급성심근경색환자에서보고되고있다 4, 5). 하지만급성심근경색환자에서일차적관상동맥중재술, 혈전용해요법, 지연관상동맥중재술간의치료방법이 P파폭과 P파분산에미치는영향에대한연구는국내에서아직보고되지않았다. 이연구의목적은급성심근경색환자의치료전략에따른최대 P파폭과 P파분산의변화를알아보고자하였다. 대상및방법 1. 연구대상 2005년 5월부터 2006년 5월까지인하대병원에서급성심근경색을진단받고치료를시행한환자 86명을대상으로하였다. 급성심근경색은 30분이상지속되는흉통, 내원당시심전도에서 2개이상의연속된사지유도또는흉부유도에서의 1 mm 이상의 ST절의변화와 creatine kinase-mb 의수치가 2배이상상승하는경우세가지항목중두가지이상의항목을만족할경우로정의하였다. 과거의심방세동, 심방조동의과거력이있거나심전도에서각차단이있는경우, 심박동기삽입이필요한심실내전도지연, 심전도에서조기흥분파가관찰되는경우, 비후성심근병증, 확장성심근병증, 판막대치술이나동맥류절제등의수술을함께받은경우, 항부정맥제를받은환자들은제외하였다. 2. 방법 1) 임상양상 86명의환자들의본원심장혈관센터데이터베이스 와의무기록을분석하여환자들의병력, 이학적소견, 기초임상병리검사, 투여약물, 심초음파검사, 관상동맥촬영결과를확인하였다. 86명의환자는각각일차적관상동맥중재술군, 혈전용해요법군, 지연관상동맥중재술군으로분류하였다. 일차적관상동맥중재술군은내원당시응급실에서아스피린 300 mg과 clopidogrel 300 mg을복용하고헤파린 5000 unit을정주한후심도자실로옮겨관동맥중재술이시행되었으며, 혈전용해요법군은 TNK-tPA를체중에따라조정된용량을 10초간빠르게정주하였고, 3~7일이경과된후관상동맥조영술이시행되었다. 지연관상동맥중재술을받은환자는대부분시간이경과됐거나흉통이가라앉아서아스피린을경구투여하였고, 헤파린과니트로글리세린을정주하며보존적치료후 3~7일이경과된후관상동맥조영술이시행되었다. 2) 12유도표면심전도의분석 12유도표면심전도는 Marquette electronics 사의 MAC VU 003A (U.S.A) 측정하였고, 응급실내원당시의모든환자의심전도와일차적관상동맥중재술, 혈전용해요법을시행받은환자군은치료 2일후에지연관상동맥중재술로예정된환자는입원 2일후의심전도를분석하였다. P파폭은 P파의최초시작부위와마지막끝나는부위의폭을 20 msec 단위의자를이용하여두사람이수동식으로측정하였다. P파의최초시작부위는등전압선과 P파가편향하는시작부위의경계로정의하였고, P파의마지막부위는 P 파의마지막편향부위와등전압선의경계로정의하였다. 최대 P파폭은여러유도에서측정된 P파폭중가장긴폭으로정의하였고, P파분산은 12유도의 P파폭중최대값과최소값을측정하여두값의차이로정의하였다. 대부분의유도에서 P파폭을측정할수있었으며 P파폭의측정이애매한유도의거의대부분에서 P파의폭은그환자의 P파폭의최대값과최소값사이였으며 4개의유도에서 P파의진폭이작아측정불가능한경우측정값에서제외하였다. 3) 심방세동발생의확인급성심근경색으로내원하여퇴원전까지의입원기간동안집중치료실에서의심전도모니터링, 심전도검사를통해확인된자료를통해심방세동의발생여부를결 - 490 -
- Woong Gil Choi, et al : P wave duration and P wave dispersion in acute myocardial infarction patients - Table 1. Clinical characteristic of the patients Characteristics Primary PCI Thrombolytic therapy Delayed PCI (n=28) (n=27) (n=31) p value Age (years) Gender (M/F) DM Smoking Hypertension Stroke AF ACE inhibitor or ARB CCB Statin Beta blocker LA dimension LV EF (%) 50.36±10.6 25/3 8 (29%) 22 (78%) 3 (11%) 0 (0%) 3 (11%) 26 (92%) 1 (3%) 19 (68%) 14 (50%) 36.8±3.2 47.9±8.0 53.15±12.3 24/3 11 (40%) 24 (88%) 6 (22%) 1 (3%) 4 (15%) 20 (74%) 2 (7%) 22 (81%) 12 (44%) 37.4±5.8 46.8±4.4 50.83±12.1 28/3 9 (29%) 28 (90%) 10 (32%) 1 (3%) 5 (16%) 23 (74%) 4 (13%) 22 (71%) 7 (23%) 37.7±3.1 50.6±11.6 0.984 0.983 0.548 0.376 0.138 0.606 0.825 0.124 0.419 0.489 0.071 0.729 0.245 PCI, percutaneous coronary intervention; AF, atrial fibrillation; ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; LA, left atrial; LVEF, left ventricle ejection fraction; M/F, male/female; DM, diabetes mellitus 정하였다. 3. 통계적분석통계분석에는윈도우용 SPSS (Statistical Package for Social Science) version 10.0 프로그램 (Microsoft Corporation, U.S.A) 을사용하였으며연속형변수는평균 ± 표준편차로표시하였고, 범주형변수는빈도로표시하였다. 두군간의연속형변수의비교에는 unpaired t-test 를두군이상의비교에는 ANOVA 분석을이용하였고, 각군간차이는사후검정 (post-hoc analysis) 를이용하였다. 범주형변수비교는 Chi-square test를이용하였다. 동일군에서입원당시및 2일후의최대 P파폭과 P파분산의비교는 paired t-test를시행하였다. p 값이 0.05미만의경우를통계적으로의미가있다고보았다. 본연구에서는 P파폭의측정에있어측정자내, 측정자간신뢰도를평가하기위해진단검사방법의일치도를이용하였다. 결과 1. 대상환자의특징심근경색환자중일차적관상동맥중재술, 혈전용해요법, 지연관상동맥중재술을시행한환자는각각 28명, 27명, 31명이었다. 환자군중평균나이는각군별로유의한차이가없었으며기타성별, 고혈압, 당뇨병, 베타차단제와칼슘차단제복용여부는각군간통계적인차이가없었다. 심초음파검사에서좌심방직경, 좌심실구혈률역시각군간통계적인차이가없었다 ( 표 1). 관상동맥조영술에서 1혈관질환이 46명, 2혈관질환이 31명, 3혈관질환이 9명이었으며각치료군간통계적인차이가없었다. 경색관련혈관역시치료군간통계적인차이는없었다 ( 표 2). 입원기간중발작성심방세동이발생한환자는 12명이었으며일차적관상동맥중재술군은경우 3 명, 혈전용해요법군의경우 4명, 지연관상동맥중재술군의경우 5명으로치료군별로통계학적차이는없었다. 2. P파폭과분산내원시 12유도표면심전도에서최대 P파폭, 최소 P 파폭과 P파분산은각치료군간에유의한차이는없었으나 2일후시행한심전도에서일차적관상동맥중재술군이다른치료군과비교하여최대 P파폭과 P파분산이의미있게작게관찰되었다 ( 표 3, 그림 1). 또한일차적관상동맥중재술군에서만입원당시비교하여입원 2일후에시행한심전도에서최대 P파폭과 P파분산의의미있는감소를나타내었으며혈전용해요법치료군과지연관상동맥중재술군에서는통계학적으로의 - 491 -
- 대한내과학회지 : 제 73 권제 5 호통권제 567 호 2007 - Table 2. Coronary angiographic characteristic of the patients CAOD 1-vessel disease 2-vessel disease 3-vessel disease Infarct related vessel LAD LCX RCA Primary PCI (n=28) 18 9 1 15 6 7 Thrombolytic therapy (n=27) 14 10 3 12 6 9 Delayed PCI (n=31) 14 12 5 13 6 12 p value PCI, percutaneous coronary intervention; CAOD, coronary artery obstruction disease; LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery 0.410 0.843 Table 3. Comparison of the P wave duration on admission and on the second day according to the treatment strategy Primary PCI Delayed PCI Thrombolytic therapy p value Pmax (ms) on admission Pmin (ms) on admission PWD (ms) on admission Pmax (ms) after 2 day Pmin (ms) after 2 day PWD (ms) after 2 day 111.0±8.5 61.9±7.1 49.9±7.5 98.2±7.7 64.3±9.9 33.6±7.3 111.4±7.3 64.5±7.4 46.5±7.6 112.1±13.1 61.5±8.1 49.9±16.6 112.7±12.1 66.2±9.22 47.3±10.3 113.2±11.9 61.7±8.82 51.3±12.7 0.488 0.089 0.995 < 0.01 0.267 < 0.01 PCI, percutaneous coronary intervention; Pmax, maximal P wave duration; Pmin, minimum P wave duration; PWD, P wave dispersion Figure 1. Comparison of maximum P wave duration and P wave dispersion on 2nd day among all three groups according to the treatment strategy; P max and PWD were significantly lowed in the primary PCI group than other groups. P max, maximum P wave duration; PWD, P wave dispersion; PCI, percutaneous coronary intervention. 미있는감소를나타내지못했다 ( 표 4). 지연관상동맥중재술과혈전용해요법을시행한환자군에서입원 3~7일후에시행한관상동맥조영술상지연관상동맥중재술군의경우 22명 (71%), 혈전용해 요법군의경우 20명 (74%) 에서경색관련혈관 (infarctrelated artery) 의개존성 (patency) 및 TIMI (Thromobolysis in myocardial infarction) III flow가관찰되었고, 이경우그렇지않은군보다입원 2일후심전도에 - 492 -
- 최웅길외 8 인 : 급성심근경색환자에서 P 파폭과 P 파분산의변화 - Table 4. Comparison of the P wave duration and PWD on admission and the second day Admission 2nd day p value P max (ms), primary PCI P min (ms), primary PCI PWD (ms), primary PCI P max (ms), thrombolytic therapy P min (ms), thrombolytic therapy PWD (ms), thrombolytic therapy P max (ms), delayed PCI P min (ms), delayed PCI PWD (ms), delayed PCI 111.0±8.5 61.9±7.1 49.9±7.5 112.7±12.1 66.2±9.22 47.3±10.3 111.4 ±7.3 64.5±7.4 46.5±7.6 98.21±7.7 64.3±9.9 33.57±7.3 113.2±11.9 61.7±8.82 51.3±12.7 112.1±13.1 61.5±8.1 49.9±16.6 0.0001 0.213 0.0001 0.767 0.072 0.065 0.827 0.118 0.338 PCI, percutaneous coronary intervention; Pmax, maximal P wave duration; PWD, P wave dispersion Table 5. Comparison of the maximum P wave duration and P wave dispersion between the patent IRA group and the occluded IRA group in the non-primary PCI group Pmax (ms) on admission Patent IRA (n=42) Occluded IRA (n=15) p value 113.2±10.3 108.5±7.7 PWD (ms) on admission Pmax (ms) on 2nd day PWD (ms) on 2nd day 46.5±8.8 110.8±12.7 47.3±13.6 47.6±9.6 117.5±11.3 59.5±15.1 0.693 0.081 0.005 PCI, percutaneous coronary intervention; IRA, Infarct related artery; Pmax, maximal P wave duration; PWD, P wave dispersion 0.114 서 P파분산이의미있게작게관찰되었다 ( 표 5). 3. 측정자내, 측정자간신뢰도의평가진단검사방법의일치도를이용하여평가한측정자재, 측정간신뢰도의평가에서측정자내신뢰도는최대 P파폭이 0.86이며최소 P파폭이 0.79이었다. 측정자간신뢰도는최대 P파폭이 0.72이며최소 P파폭이 0.62으로모든값의일치도가우수하였다. 고찰심방세동은급성심근경색에서가장흔한부정맥중하나로급성심근경색환자중 5~18% 에서발생한다 6). 일반적으로심방세동은어떤종류의심장질환에서도발생할수있으며울혈성심부전이있을때가장흔하게관찰된다. 심방세동의위험인자는주로류마티스성심질환, 고혈압성심혈관질환, 모든원인에의한심부전, 관상동맥질환등으로알려져있다. 급성심근경색에서는동결절및심방의허혈, 울혈성심부전, 심낭염, 우실심의심근경색이심방세동의발생에관여하게되며노인환자와수축 기심부전이중요한위험인자로알려져있다 7). 심방심근의불균질한변화와비등방성의전도성질은동성흥분파의비균질전도 (inhomogenous conduction) 와비연속적전도를야기하며이러한심방의불균질한구조와전기생리학적특징은조기흥분파의단방향전도장애를증가시켜심방세동의발생과유지에중요한회귀가발생하는데중요한역할을하는것으로생각되고있다. 이러한전기생리학적특성이심전도에서 P파분산의증가로반영되며 P파분산이발작성심방세동의발생의예후인자로인정되고있다 8, 9). 이는고혈압환자 10, 11) 를대상으로발작성심방세동의발생을예측한연구 와관상동맥우회술을시행받은환자에서심방세동의발생을예측하기위한연구 12) 로확대되었다. 이러한 P파폭과분산을측정하는방법은 12유도표면심전도에서측정한방법과 P파신호가산평균심전도법을이용한여과 P파분산측정이유용한검사방법 13-15) 으로알려져있다. 하지만후자의방법은안정된상태의환자의경우비교적용이하게시행할수있지만급성심근경색환자가응급실로내원할경우표면심전도에비 - 493 -
-The Korean Journal of Medicine : Vol. 73, No. 5, 2007 - 해 20분정도의시간소비가필요하며비용이많이들어임상적으로적용하기힘든면이존재한다. 본연구에서는 12유도표면심전도를이용하여전벽심근경색을포함한다른심근경색환자를대상으로일차적관상동맥중재술, 혈전용법요법및지연관상동맥중재술의치료방법에따른 P파간격과 P파간격분산의차이를살펴보았다. 허혈성심장질환에서 P파간격의변화는이전부터논의되어왔는데 Dilaveris 등 16) 은협심증환자를대상으로심근허혈이 P파폭과 P파분산에미치는영향을보고하였으며 Baykan 등 17) 은급성전벽심근경색환자를대상으로 P파의폭을관찰하여 P파의폭이향후심방세동발생의중요한예후인자임을예증하였다. 또한 Akedemir 등 5) 은급성전벽심근경색환자를대상으로일차적관상동맥중재술을시행한경우가혈전용해요법을시행한경우와비교하여 P파간격분산이의미있게감소하였다고보고하였다. 본연구에서도앞의언급된연구와마찬가지로일차적관상동맥중재술을시행한군이다른치료전략을시행한경우와비교하여시술후최대 P파폭과 P파간격분산이유의하게감소하였으나, 혈전용해요법과지연관상동맥중재술을시행한군에서는약물치료후유의한차이는없었다. 이러한결과는일차적관상동맥중재술에의해즉각적인재관류및허혈로부터빠른회복을기대할수있으며이를통해 P파폭과분산의의미있는감소를가져왔다고추론할수있다. 혈전용해요법과지연관상동맥중재술을시행한경우관상동맥조영술에서개존성이관찰되었던군에서개존성이없었던군에비해치료후 P파분산이의미있게감소하였다. 이는심근경색이발생후경색연관동맥의재관류정도에따라최대 P파폭과 P파분산이영향을받는것으로생각되며, 심근허혈이있는경우 P파분산과최대 P파폭이늘어나는 Dilaveris 등의연구 16) 와상응하는결과라고생각된다. 본연구에서는 12명의환자에서심방세동이발생하였다. 각치료군간심방세동의발생이의미있는통계학적의미를가지지못했는데경색관련혈관별로분류하면우측관상동맥폐쇄가 6명에서발생하여가장많은경우를차지하였다. Sakata 등 18) 이발표한연구에서는심근경색후 24시간이내에발생한심방세동의경우우측관상동맥의폐쇄가가장많았으며 24시간이후에발생한 심방세동의경우좌전하행동맥의폐쇄가다수였다. 또한 Crenshaw 등 19) 의경우심근경색후심방세동의발생에서우측관상동맥의폐쇄가많은경향을보여본연구와상응하는결과를나타냈다. 본연구의제한점은연구에포함된환자수가적고후향적연구라는점이라하겠으며추후더많은환자를대상으로한전향적연구가필요하리라생각된다. 또한본연구에서는 12유도표면심전도의 P파간격을 20 msec 단위의자를이용하여측정하였는데이는판독자간측정결과의차이로인해재현성이제한될가능성이있을것으로생각된다. 본연구에서는공동연구자와의교차검정과반복측정을통해이러한오차를줄이고자노력하였는데측정자내신뢰도와측정자간신뢰도의일치도가모두우수한일치도를보였다. 요약목적 : 급성심근경색증환자에서심방세동은 10~ 20% 의빈도로발생되는흔한부정맥이다. 최대 P파폭과 P파분산은심방세동의전기생리학적특성과연관된동성흥분파의비균질전도, 심방내전도장애와밀접히연관된것으로알려져있다. 이연구의목적은급성심근경색증환자의재관류치료방법이최대 P파의폭과 P파분산에대해미치는효과를비교분석하였다. 방법 : 2005년 5월부터 2006년 5월까지급성심근경색으로본원에내원한 86명의환자를대상으로응급실내원당시의모든환자의심전도와일차적관상동맥중재술, 혈전용해요법을시행받은환자군은치료 2일후에지연관상동맥중재술로예정된환자는입원 2일후의심전도에서최대 P파폭과 P파분산을측정하여각군간의차이를분석하였다. 결과 : 일차적관상동맥중재술, 혈전용해요법, 지연관상동맥중재술을시행한환자는각각 28명, 27명그리고 31명이었다. 일차적관상동맥중재술을시행한군이다른치료전략을시행한군에비해시술후최대 P파폭과 P파간격분산이다른군에비해유의하게감소하였으나, 혈전용해요법과지연관상동맥중재술간의치료후유의한차이는없었다. 혈전용해요법과지연관상동맥중재술을시행한경우경색관련관상동맥의개존성이있었던군에서개존성이없었던군에비해 2일후 P 파분산이의미있게감소하였다. 결론 : 급성심근경색증환자에서일차적관상동맥 - 494 -
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