대한응급의학회지제 24 권제 4 호 Volume 24, Number 4, August, 2013 원 저 혈역학적으로안정된폐색전증환자에서입원후저혈압발생예측을위한심근효소검사소견 울산대학교의과대학서울아산병원응급의학교실, 강릉아산병원응급의학과 1 이종승 정상구 1 손창환 서동우 이재호 오범진 김원영 임경수 Value of Cardiac Biomarkers for Predicting Hypotension in Non-highrisk Patients with Acute Pulmonary Embolism Jong Seung Lee, M.D., Sang Ku Jung, M.D. 1, Chang- Hwan Sohn, M.D., Dong-Woo Seo, M.D., Jae Ho Lee, M.D., Bum-Jin Oh, M.D., Ph.D., Won Young Kim, M.D., Ph.D., Kyoung-Soo Lim, M.D., Ph.D. Purpose: Recent and numerous studies have indicated that cardiac biomarker elevation during acute pulmonary embolism (PE) predicts in-hospital death. However, the role of cardiac biomarkers for predicting the occurrence of hypotension is unknown. The aim of the present study was to evaluate whether increased levels of cardiac biomarkers can predict the occurrence of hypotension (sytolic blood pressure (SBP) <90 mmhg) within 24 hours in non-high-risk patients with acute PE. Methods: Study subjects included all consecutive patients with acute PE, as diagnosed by chest computed tomographic angiography, in the emergency department (ED) from January 2009 through December 2011. All patients underwent tests for troponini (TnI), creatinine kinase-mb isoenzyme (CK-MB), and brain natriuretic peptide (BNP) levels upon ED admission and were divided into two groups based on the occurrence of hypotension within 24 hours. Results: Out of 196 stable patients with acute PE admitted to the ED during the study period, 154 patients were included. Within 24 hours of hospitalization, 13 (8.4%) patients developed hypotension. The mean values for serum TnI, 책임저자 : 김원영서울특별시송파구올림픽로 43길 88 울산대학교의과대학서울아산병원응급의학과 Tel: 02) 3010-3350, Fax: 02) 3010-3360 E-mail: wonpia@yahoo.co.kr 접수일 : 2013년 7월 17일, 1차교정일 : 2013년 7월 20일게재승인일 : 2013년 8월 1일 384 CK-MB, and BNP were significantly higher in patients who developed hypotension than in patients who did not. The TnI value was the most accurate biomarker for predicting the occurrence of hypotension. Moreover, elevated levels of ctni (>0.05 ng/ml) upon admission were an independent predictor for developing hypotension within 24 hours in patients with stable acute PE at the time of ED admission (odds ratio 11.0, 95% confidence interval (CI) 2.8-43.8, p=0.00). Conclusion: In stable patients with acute PE, an elevated TnI can predict the in-hospital development of hypotension within 24 hours. This finding is valuable for selecting patients who might benefit from intensive clinical surveillance and escalated treatment. Key Words: Pulmonary embolism, Computed tomography, Troponin Departments of Emergency Medicine, Asan Medical Center, Seoul, Korea, Gangneung Asan Hospital, University of Ulsan College of Medicine, Kangneung 1 서 급성폐색전증은응급의료센터에서흔히관찰되는질환으로심혈관계사망원인의주요한원인질환중하나이다 1). 유럽과북미의다기관연구보고에따르면폐색전증의 3개월사망률은 15.3% 에이르며특히사망환자의 75% 가처음입원시에발생한다고보고되고있어초기에적절한치료의중요성이강조되고있다 2). 급성폐색전증의사망률은환자의임상적상태에따라서 1% 에서 65% 까지다양하다고보고되고있으므로, 환자의임상양상및검사소견에따른위험도평가 (risk stratification) 가필요하며이에따른적절한치료가요구된다 3,4). 최근발표된폐색전증치료지침에서는저혈압 ( 수축기혈압 <90 mmhg) 혹은쇼크의증거가있는경우사망률이 15% 이상이므로급성폐색전증환자에서혈전용해치료가중요한적응증이되며, 이러한 론
이종승외 : 혈역학적으로안정된폐색전증환자에서입원후저혈압발생예측을위한심근효소검사소견 / 385 경우를고위험 (high-risk) 폐색전증으로정의하였다. 그렇지않은환자를비고위험 (non-high-risk) 폐색전증으로분류하였고이들을대상으로추가적인위험도평가를통하여중등도위험의폐색전증을찾아내야한다고권고 (Class IIa, Grade A) 하고있다 5). 이에따라폐색전증환자의예후를결정할수있는예측인자에대한많은연구들이진행되었고, 심초음파검사상우심실부전유무, 폐혈관전산화단층촬영 (Computed tomographic pulmonary angiography, CTPA) 상우심실확대소견, 혈중 brain natriuretic peptide (BNP) 상승, 그리고혈중 troponin I (TnI) 상승등이환자의사망률을결정하는주요한예측인자로보고되었다 6-13). 그러나지금까지폐색전증환자에대한연구들은대부분환자의사망률를예측할수있는소견에집중되어있고환자에게혈전용해제치료의기회를줄수있는병원내저혈압발생의예측에대한연구는거의보고된바가없다. 응급실에서진료의가내원시혈역학적으로안정적이었던폐색전증환자중어떠한환자에서저혈압이발생하는지예측할수있다면환자의분류나적절한처치에큰도움을받을수있다는점에서사망률의예측보다더중요할수있을것이다. 이에저자들은단일응급의료센터에내원하여 CTPA로진단된혈역학적으로안정된폐색전증환자를대상으로, 내원시측정한심장표지자검사값이입원 24시간이내발생하는저혈압 ( 수축기혈압 <90 mmhg) 을예측할수있는지알아보고자본연구를시행하였다. 대상과방법 1. 대상 2009년 7월부터 2011년 12월까지서울소재단일응급의료센터로내원한 18세이상의환자중에서내원시혈역학적으로안정된급성폐색전증 ( 수축기혈압 >90 mmhg 혹은쇼크상태가아닌 ) 으로진단받은 196명의환자를대상으로후향적연구를시행하였다. 이중폐색전증이재발하였거나한번이상입원하였던 21명, 응급실내원시심장표지자검사가시행되지않았던 15명, 투석치료를받는만성신부전환자 4명, 그리고급성관상동맥질환이동반되었던 2명을제외한 154명을최종적으로본연구의대상으로하였다 (Fig. 1). 폐색전증의진단은응급의료센터에서시행된 CTPA에서세분절을포함한폐동맥가지에서관내충만결손 (intraluminal filling defect) 이최소한군데이상확인되었을때로정의하였다. 입원후저혈압의발생은응급실내원시혈역학적으로안정적인급성폐색전증환자가내원이후 24시간안에저혈량성쇼크나패혈증쇼크의증거가없이수축기혈압 <90 mmhg로측정될때로정의하 였다. 입원후저혈압발생유무에따라대상환자를입원후저혈압이발생하였던군과발생하지않았던군으로분류하였고, 심장표지자값을포함함임상적소견및예후를조사하여조사된각각의항목에대해비교분석하였다. 2. 병력, 입원경과, 혈액검사및경흉부심초음파검사모든대상환자의내원당시환자의성별, 연령, 증상, 과거병력 ( 당뇨, 만성폐쇄성폐질환, 심박출량 45% 미만의울혈성심부전, 심부정맥혈전증, 악성종양 ), 초기생체징후, 초기혈액검사, 입원경과및사망유무를전자의무기록과의료보험기록등을통해조사하였다. 혈중 TnI, creatinine kinase-mb (CK-MB) isoenzyme, 그리고 BNP 같은심장표지자는응급실내원시채혈된동일한검체를이용하여측정되었다. 혈중 TnI 값은 Chemiluminescence immunoassay (Ortho-Clinical Diagnostics, Rochester, New York, USA) 를이용하여측정되었고측정범위는 >0.01 ng/ml이며정상값은 <0.05 ng/ml, 중등도상승값은 0.05~1.5 ng/ml, 그리고 >1.5 ng/ml 일때심근경색을진단할수있다. 혈중 CK-MB 값은 2-site sandwich immunoassay (AVIA Centaur CK-BM, Deerfield, Illinois, USA) 방법을이용하여측정되었고 <5.0 ng/ml을정상값으로, 혈중 BNP 값은 Immunoradiometric assay (Shinoria, CIS bio international, France) 을이용하여측정되었고측정범위는 2~2000 pg/ml이었다. 심초음파검사는응급의료센터에내원후 24시간안에심장내과전문의에의해시행되어결과를확인할수있었던 125명 (81.2%) 의환자를분석하였다. 좌심실박출률 (ejection fraction) 의측정은 modified Simpson s method를이용하여심첨 4방 /2방단면도상에서측정하고삼첨판역류분사속도는심첨 4방단면도상에서측정하였다. 흉골연단축단면도상에서심실사이막의형태이상유무 (D-shape) 와우심실운동의이상여부도확인하였다. Fig. 1. Selection of patients
386 / 대한응급의학회지 : 제 24 권제 4 호 2013 3. 통계통계검정은 SPSS 12.0 프로그램 (IBM corp., Chicago, IL, USA) 을이용하였다. 연속형변수의경우평균 (± 표준편차 ) 로표시하였고, 범주형변수의경우빈도수 (%) 로표시하였다. 입원후저혈압이발생한군과발생하지않는군을대상으로연속형변수의비교는정규분포를따르는경우 Student s t-test를시행하였고정규분포를따르지않는경우 Mann-Whitney U test 를시행하였다. 범주형변수의비교는 Chi-Square test나 Fisher s exact test를시행하였다. 의미있는인자들을단변량분석을통하여구하였으며다중회귀분석을이용하여유의한인자를확인하였다. 모든분석에있어서 p 값이 0.05 미만인경우통계적으로유의한차이가있다고판정하였다. 결과혈역학적으로안정된폐색전증으로진단된대상환자 154명중입원 24시간이내에저혈압이발생한환자는 13 명으로전체환자의 8.4% 를차지하였다. 대상환자들의평균나이는 63.5±16.0세였으며남자는 69명 (44.8%) 이었다. 대상환자중입원후혈전용해술치료를받은환자는 18명 (11.7%) 이었고혈전절제술은 4명 (2.6%), 하부정맥여과기 (inferior vena cava filter) 처치는 19명 (12.3%) 으로조사되었다. 대상환자의 28일사망률은 5.8% 였으며 6개월사망률은 8.4% 였다. 저혈압이발생하였던환자군과발생하지않았던환자군간의비교시, 환자의나이, 성별에서유의한차이가없었고, 당뇨, 심부전, 심부정맥혈전, 악성종양, 만성폐쇄성폐질환여부등에서도두군간에유의한차이는없었다 (Table 1). 응급의료센터내원당시수축기혈압및이완기혈압에서차이는없었으며, 내원시측정된산소포화도값과초기혈액검사상 creatinine 값과 c-reactive protein 값에서도두군간에유의한차이가없었다. 그러나내원시측정된혈중 TnI 값은저혈압이발생하였던군에서 0.98±1.96 ng/ml로발생하지않았던군의 0.10±0.35 ng/ml보다통계적으로유의하게높았고 (p<0.00) 혈중 TnI 값이상승된경우 (>0.05 ng/ml) 에도저혈압이발생하였던군에서발생하지않았던군보다유의하게많았다 (69.2% vs. 15.6%, p<0.05). 또한혈중 CK-MB 값과 BNP값도저혈압이발생되었던군에서발생하지않았던군보다유의하게높았었다 (5.0 U/L vs. 2.6 U/L, p=0.03; 619.9 ng/ml vs. 284.7 ng/ml, p=0.04). 심초음파검사결과저혈압이발생하였던환자군과발생하지않았던환자군의좌심실박출률에는차이가없었고우심실운동이상여부와좌심실의 D-shape 유무는저혈 압이발생하였던환자군에서더흔히관찰되는경향을보였으나통계적으로유의한차이는없었다 (Table 1). 또한응급실내원시혈역학적으로안정된폐색전증환자였음에도입원후저혈압이발생하였던환자군에서는입원한달이내에혈전용해술을시행받은경우가더많았으며 (46.2% vs. 8.5%, p<0.00), 혈전제거술 (15.4% vs. 1.4%, p=0.04) 및인공환기기처치를시행받은경우도 (76.9% vs. 1.4%, p<0.00) 더많았다 (Table 2). 예후에있어서도저혈압이발생하였던환자군은발생하지않았던환자군에비해유의하게재원기간이길었으며 28일사망률이 23.1% 로저혈압이발생하지않았던군의사망률 4.3% 에비해유의하게높음을확인할수있었다 (Table 2). 단변량분석에서통계적으로유의하였던인자들을성별, 연령을보정하여다변량로지스틱회귀분석을시행하였을때심장표지자검사중혈중 TnI 값의상승 (>0.05 ng/ml) 만이입원후 24시간이내저혈압의발생을예측할수있는독립된예측인자였다 (odds ratios (OR) 11.0, 95% confidence intervals (CI) 2.8-43.8, p<0.00) (Table 3). 고찰저자들은응급의료센터로내원하여 CTPA 검사로진단되었던혈역학적으로안정된폐색전증환자를대상으로, 내원시측정한심장표지자검사값이입원 24시간이내발생하는저혈압 ( 수축기혈압 <90 mmhg) 을예측가능한지확인하고자하였고, 혈중 TnI 값의상승 (>0.05 ng/ml) 만이입원후 24시간내저혈압의발생을예측할수있는독립된예측인자 (OR 11.0, 95% CI 2.8-43.8, p<0.00) 임을확인할수있었다. 이전의관련연구들에서는혈역학적으로안정된폐색전증환자중에서혈전에의해폐혈관의막힘과이로인한이차적혈관수축으로폐혈관의저항이증가되어발생되는우심실부전이사망률과관련된중요한예후인자로알려져이러한우심실부전을찾고자하는연구가대부분이었었다 14-16). 특히우심실부전을확인할수있는가장민감한검사방법으로알려진심장초음파검사법이일차적검사로권고되어왔으나, 환자의상태나검사자의숙련도에따라많은차이를보일수있으며응급의료센터내에서언제나시행될수없다는한계점이있어, 최근에는 CTPA 검사를통하여진단과동시에우심실부전여부를확인하고자하는연구들이진행되었다 6,17). 저자들도선행연구에서 CTPA 상 RV/LV ratio >1.3가입원한달이내주요유해사건 (Major adverse events) 발생을예측할수있는유용한예측인자 (OR 8.0, 95% CI 2.7-23.2, p<0.00) 임을확인
이종승외 : 혈역학적으로안정된폐색전증환자에서입원후저혈압발생예측을위한심근효소검사소견 / 387 하였다 12). 이연구에서정의된주요유해사건은응급센터를통해입원후 1달이내에폐색전증과관련된쇼크, 기도삽관, 혈압유지를위한승압제정주, 심폐소생술, 사망, 혈전용해술, 혈전제거술등을시행한경우였다. 그러나대부분의이전연구들에서확인하고자하였던환자의사망률를예측할수있는인자도중요하겠으나응급실진료의의입장에서는내원시혈역학적으로안정적이었던폐색전증환자중에서어떠한환자에서저혈압이발생하는지예측할수있다면집중감시가가능한구역에서관찰하면서필요시적절한처치가가능하다는점에서사망률예측보다더 중요할것이다. 그러나지금까지보고된저혈압발생에대한국내연구는없었고환자에게혈전용해제치료의기회를줄수있는병원내저혈압발생예측에대해진행된외국연구도거의보고된바가없다. 최근 Gallotta 등 18) 이 TnI (>0.03 μg/l) 이면입원기간중에혈역학적불안전성이발생할수있다고보고하였는데이문헌이이러한주제에대한유일한문헌이다. 그러나저자들의연구와달리 Gallotta 등 18) 의연구는 90명의환자를대상으로한소수의연구이며, 대부분의폐색전증환자가사망하는초기에발생하는저혈압의예측하고자하였던저자들과는달리단 Table 1. Baseline clinical characteristics and laboratory findings of the study patients on admission to the emergency department. Variables Developing hypotension (n=13) No-developing hypotension (n=141) p value Demographic factor Age, years 62.0±13.3 63.7±16.2 0.72* Male 04 (030.8) 066 (42.9) 0.18* Comorbidity DM 02 (015.4) 018 (12.8) 0.40* COPD 01 (07.7)0 010 (07.1) 1.00* Cardiovascular disease 01 (07.7)0 010 (07.1) 1.00* Heart failure (EF<45%) 01 (07.7)0 008 (05.7) 1.00* Deep vein thrombosis 02 (015.4) 024 (17.0) 1.00* Malignancy 05 (038.5) 056 (39.7) 1.00* Stroke 02 (015.4) 010 (07.1) 0.27* Dyspnea (NYHA class) 13 (100.0) 125 (89.6) 0.22* I 00 (00.0)0 002 (01.4) II 02 (15.4) 036 (25.5) III 03 (23.1) 053 (37.6) IV 08 (61.5) 034 (24.1) Initial vital sign Systolic BP, mmhg 123.4±23.40 126.8±22.60 0.72* Diastolic BP, mmhg 79.7±17.8 83.0±15.0 0.59* SaO 2, % 93.1±8.40 93.0±7.10 0.96* Laboratory findings Troponin I, ng/ml 0.98±1.96 0.10±0.35 0.00* Troponin I > 0.05 ng/ml 09 (69.2) 022 (15.6) 0.00* CK-MB, U/L 5.0±2.0 2.6±3.7 0.03* CK-MB> 5 U/L 04 (30.8) 018 (12.8) 0.09* BNP, pg/ml 619.9±606.3 284.7±495.7 0.04* BNP > 350 pg/ml 06 (46.2) 032 (22.7) 0.09* Creatinine, mg/dl 1.2±0.7 1.0±0.8 0.83* CRP, mg/dl 5.0±7.2 4.8±6.2 0.93* Echocardiographic findings (n=125) (n=12) (n=113) EF 57.3±10.3 57.7±9.4 0.90* RV dysfunction 08 (66.7) 059 (52.2) 0.38* D-shaped LV 09 (75.0) 048 (42.5) 0.12* IVC plethora 04 (33.3) 052 (46.4) 0.13* Values are expressed as mean±sd or n (%). * Statistical significance test was done by Mann-Whitney U-test. DM: diabetes mellitus, COPD: chronic obstructive pulmonary disease, NYHA: New York Heart Association, BP: blood pressure, SaO 2: arterial oxygen saturation, CK-MB: creatinine kinase-mb isoenzyme, BNP: brain natriuretic peptide, CRP: C- reactive protein, EF: ejection fraction, RV: right ventricle, LV: left venticle, IVC: inferior vena cava
388 / 대한응급의학회지 : 제 24 권제 4 호 2013 순히입원기간중에발생할수있는혈역학적불안정성에대해서만확인하였던점이큰차이점이다. 또한비교적소수의환자를대상으로하여서인지 TnI의상승이입원기간중의혈역학적불안정을예측할수있었으나 28일사망률과는관련성을찾을수없었다는점도본연구결과와차이점일것이다. 최근발표된폐색전증치료지침에따르면혈역학적으로안정된급성폐색전증환자들을비고위험 (non-highrisk) 폐색전증으로분류하고우심실부전여부와심근손상여부를파악하여위험도를보다세분화하는것이필요하다고제시하고있고이러한위험도분류에심장표지자를사용한결과를제시하고있다 5). 이렇듯급성폐색전증환자에서위험도분류를위한심장표지자검사는보편적인검사방법이며본연구결과심장표지자검사중혈중 TnI 값의상승 (>0.05 ng/ml) 만이입원후 24시간내저혈압의발생을예측할수있는독립된예측인자였다. 즉우심실부전의민감한지표로제시된 BNP보다도폐혈관압과우심실압의증가로인한관상동맥관류의감소로인해발현되는 TnI의증가가 24시간이내의저혈압발생가능성을예측할수있는보다나은지표임을확인할수있었다. 그러므로급성폐색전증환자가내원시 troponin 검사결과를확인하여상 승이관찰되는환자에서는보다주의깊은관찰이필요할것이다. 본연구의제한점으로는단일응급의료센터에서진행된후향적연구인점과연구기간동안전체환자를대상으로하지못하고응급실내원시심장표지자검사가시행되지않았던 15명이제외되었다는점, 그리고병원특성상연구대상자중악성종양환자가 61명 (40.0%) 로관련연구들과비교해서많은비율을차지하였던점을들수있다. 또한혈중 TnI 값이증상발현 1~3시간에는상승되지않을수있기에응급실내원후 TnI 값을주기적으로측정하였어야하겠으나후향적연구의특성상내원시측정된 TnI 값만제시한것이제한점이다. 결론응급의료센터내원시혈역학적으로안정되었던폐색전증환자에서혈중 TnI 값의상승 (>0.5 ng/ml) 은입원후 24시간내저혈압의발생을예측할수있는독립된예측인자이다. 그러므로급성폐색전증환자에서 TnI 값의상승이관찰될경우집중적인환자감시를통해 24시간내발현 Table 2. Comparison of management and outcomes of acute pulmonary embolism between in patients with developing hypotension within 24 h and in patients did not. Variables Developing hypotension (n=13) Non-HI group (n=141) p value Management Thrombolysis 06 (46.2) 12 (08.5) 0.00* Thrombectomy 02 (15.4) 02 (01.4) 0.04* Inferior vena cava filter 04 (30.8) 29 (20.6) 0.48* Ventilation support 10 (76.9) 02 (01.4) 0.00* Cardiopulmonary resuscitation 06 (28.6) 02 (01.6) 0.00* Outcomes Length of stay, day 24.9±27.1 14.2±16.0 0.02* 28 day mortality 03 (23.1) 06 (04.3) 0.03* 6 month mortality 03 (23.1) 12 (08.5) 0.08* Values are expressed as n (%). * Statistical significance test was done by Mann-Whitney U test. Table 3. Factors associated with occurrence of hypotension by multiple logistic regression analysis in stable patients with acute pulmonary embolism. Adjusted OR Multivariate analysis 95% CI p value Gender 02.60 0.61-11.09 0.20 Age 00.99 0.94-1.030 0.50 Troponin I > 0.05 ng/ml 11.03 2.78-43.81 0.00 CK-MB > 5 UL 00.93 0.20-4.280 0.93 BNP > 350 ng/ml 01.83 0.48-6.930 0.37 OR: odds ratio, CI: confidence interval, CK-MB: creatinine kinase-mb isoenzyme, BNP: brain natriuretic peptide
이종승외 : 혈역학적으로안정된폐색전증환자에서입원후저혈압발생예측을위한심근효소검사소견 / 389 될수있는저혈압에대해조기에적절한처치를받을수있도록하여야할것이다. 참고문헌 01. Laporte S, Mismetti P, Décousus H, Uresandi F, Otero R, Lobo JL, et al. Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous thromboembolism: findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry. Circulation. 2008;117:1711-6. 02. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353:1386-9. 03. Kasper W, Konstantinides S, Geibel A, Olschewski M, Heinrich F, Grosser KD, et al. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol. 1997;30:1165-71. 04. White RH. The epidemiology of venous thromboembolism. Circulation. 2003;107(Suppl 1):14-8. 05. Guidelines on diagnosis and management of acute pulmonary embolism. Task Force on Pulmonary Embolism, European Society of Cardiology. Eur Heart J. 2000;21: 1301-36. 06. Schoepf UJ, Kucher N, Kipfmueller F, Quiroz R, Costello P, Goldhaber SZ. Right ventricular enlargement on chest computed tomography: a predictor of early death in acute pulmonary embolism. Circulation. 2004;110:3276-80. 07. Kreit JW. The impact of right ventricular dysfunction on the prognosis and therapy of normotensive patients with pulmonary embolism. Chest. 2004;125:1539-45. 08. Giannitsis E, Katus HA. Risk stratification in pulmonary embolism based on biomarkers and echocardiography. Circulation. 2005;112:1520-1. 09. Binder L, Pieske B, Olschewski M, Geibel A, Klostermann B, Reiner C, et al. N-terminal pro-brain natriuretic peptide or troponin testing followed by echocardiography for risk stratification of acute pulmonary embolism. Circulation. 2005;112:1573-9. 10. Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation. 2007;116:427-33. 11. Yoon JC, Kim WY, Choi SS, Jung SK, Sohn CH, Kim W, et al. D-dimer as a Prognostic Tool in Patients with Normotensive Pulmonary Embolism. Tuberc Respir Dis. 2010;68:87-92. 12. Jung SK, Kim WY, Lee CW, Seo DW, Lee YS, Lee JH, et al. Chest CT Parameters to Predict the Major Adverse Events in Acute Submassive Pulmonary Embolism. Tuberc Respir Dis. 2010;69:184-90. 13. Kim HW, Kim WY, Sohn CH, Seo DW, Lee JH, Kim W, et al. Clinical Outcome Related to Diagnosis of Saddle Pulmonary Embolism using Computed Tomographic Angiography in an Emergency Department. J Korean Soc Emerg Med. 2012;23:229-34. 14. Ribeiro A, Lindmarker P, Juhlin-Dannfelt A, Johnsson H, Jorfeldt L.. Echocardiography Doppler in pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate. Am Heart J. 1997;134:479-87. 15. Kasper W, Konstantinides S, Geibel A, Tiede N, Krause T, Just H. Prognostic significance of right ventricular afterload stress detected by echocardiography in patients with clinically suspected pulmonary embolism. Heart. 1997;77:346-9. 16. Burgess MI, Bright-Thomas RJ, Ray SG. Echocardiographic evaluation of right ventricular function. Eur J Echocardiogr. 2002;3:252-62. 17. van der Meer RW, Pattynama PM, van Strijen MJ, van den Berg-Huijsmans AA, Hartmann IJ, Putter H, et al. Right ventricular dysfunction and pulmonary obstruction index at helical CT: prediction of clinical outcome during 3-month follow-up in patients with acute pulmonary embolism. Radiology. 2005;235:798-803. 18. Gallotta G, Palmieri V, Piedimonte V, Rendina D, De Bonis S, Russo V, et al. Increased troponin I predicts inhospital occurrence of hemodynamic instability in patients with sub-massive or non-massive pulmonary embolism independent to clinical, echocardiographic and laboratory information. Int J Cardiol. 2008;124:351-7.