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1 대한내과학회지 : 제 78 권제 1 호 2010 원저 인공심박동기환자에서심실동기이상의관련인자 전남대학교의과대학전남대학교병원순환기내과 김성수 조정관 김현국 장수영 심두선윤남식 윤현주 홍영준 박형욱 김주한안영근 정명호 박종춘 강정채 The factors influencing ventricular dyssynchrony in patients with permanent pacemaker Sung Soo Kim, M.D., Jeong Gwan Cho, M.D., Hyun Kuk Kim, M.D., Soo Young Jang, M.D., Doo Sun Sim, M.D., Nam Sik Yoon, M.D., Hyun Ju Yoon, M.D., Young Joon Hong, M.D., Hyung Wook Park, M.D., Ju Han Kim, M.D., Young Keun Ahn, M.D., Myung Ho Jeong, M.D., Jong Chun Park, M.D., and Jung Chaee Kang, M.D. The Heart Center of Chonnam National University Hospital, Cardiovascular Research Institute of Chonnam National University, Gwangju, Korea Background/Aims: Chronic right ventricular pacing (RVP) can lead to increased risks of ventricular dyssynchrony (VD), heart failure, and mortality. This study examined the factors influencing VD in patients treated with a permanent pacemaker (PPM). Methods: The study enrolled 139 patients (M:F=1:1.35, 66.8±1.0 years) who had permanent pacemaker implanted [AAI (R): 11, VVI (R): 39, VDD (R): 50, DDD: 39]. Their clinical characteristics, 12-lead electrocardiogram (ECG), echocardiography, and laboratory parameters were evaluated. The patients were divided into two groups according to the presence of VD. Results: VD was seen in 71.9% of the patients with a PPM. No significant difference was observed in the clinical characteristics, except for the indications and current action mode of the PPM. VD was more frequently associated with patients with AV block and ventricular pacing. The QRS duration and QTc interval were significantly wider in patients with VD (159.9±3.2 vs ±6.3 ms, p<0.001; 487.7±4.0 vs ±8.0 ms, p<0.05, respectively). On echocardiography, tricuspid regurgitation was more common in patients with VD. The N-terminal B-type natriuretic peptide (NT-proBNP) level was higher in the dyssynchrony group (431.4±66.1 vs ±40.8, p<0.05). Conclusions: Patients with AV block and ventricular pacing developed VD more frequently. A higher serum NT-proBNP level and prolonged QRS duration, QTc, and tricuspid regurgitation might be associated with VD. (Korean J Med 78:59-67, 2010) Key Words: Pacemaker; ECG; Echocardiography Received: Accepted: Correspondence to Jeong Gwan Cho, M.D., The Heart Center of Chonnam National University Hospital, 671 Jaebongro, Dong-gu, Gwangju , Korea chojg@unitel.co.kr

2 - The Korean Journal of Medicine: Vol. 78, No. 1, 서론 Furman 과 Robinson 등 1) 이 1958년최초로인공심박동기를이식한이후, 인공심박동기는서맥성부정맥환자의최종적인치료법으로사용되고있다. 인공심박동기치료는동기능부전증과방실전도차단환자의수명연장및삶의질향상에크게기여하였으나, 인공적인심실조율은심실내자극의전달이정상적인히스퍼킨제계 (His-purkinje system) 를통해일어나지않고조율전극이위치된곳에서조율세포사이를통해서전파되므로이에따른문제가생길수있다. 그러한문제중최근에는심실동기이상 (ventricular dyssynchrony) 에대한관심이높아지고있다. 심실동기이상이란심실의모든부위가동시에수축하지못하고, 서로다른시기에불균일하게수축하는현상을말한다. DAVID trial 2), MOST trial 3), MADIT II trial 4) 등과같은여러다기관연구들에서장기적인우심실조율은심실동기이상을초래하여심부전을악화시키고사망률을증가시킨다고보고되었다 5-7). 그러나국내에서는이러한심실동기이상에대한연구는미미한상태이며, 심실동기이상을예측하는데유용한검사법이없다. 이에저자등은인공심박동기이식환자에서심초음파도를이용하여심실동기이상을평가한후, 조율방식, 조율기간, 조율후심전도및심초음파도소견, 혈청표지자등과의관계를조사하였다. 대상및방법 1. 대상 1991년 1월부터 2008년 3월까지전남대학교병원에서서맥성부정맥으로인공심박동기를이식받은후정기적으로순환기내과외래에서추적관찰중인환자들가운데 139명 ( 남 : 여 =1:1.35, 66.8±1.0년 ) 의환자를대상으로하였다. 제외대상은국소심근운동장애가있는관상동맥질환, 신기능이상 (creatinine>1.5 mg/dl), 선천성심장병등으로하였다. 2. 방법인공심박동기이식당시심전도및심초음파도소견은의무기록을통하여분석하였으며, 추적심전도, 심박동기기능분석및심초음파도와혈청표지자검사는같은날에시행하였다. 심전도및심박동기기능분석을통하여심박동기의현재동작모드를파악하였다. 심초음파도를통하여심 실동기이상이없는환자를대조군, 심실동기이상이있는환자를동기이상군으로분류하여임상적특징, 심전도소견, 혈청표지자, 심초음파도소견등을비교하였다. 1) 심초음파도이면성및 M형심초음파도, 조직도플러영상 (tissue doppler imaging) 은 VIVID 7 (GE, USA) 와 Acuson Sequoia C256 (Siemens, USA) 심초음파기를이용하여좌측앙와위 (left lateral decubitus position) 에서표준방법으로시행하였다. 심장의구조적인이상과기능을평가하였으며, 좌심실구혈률은 Teicholz method 8) 및 Simpson s method 9) 로측정하였다. 삼첨판역류증은정상인에서도잘나타날수있기때문에경도 (mild) 에서중등도 (moderate) 이상을기준으로하였다. 심실동기이상은심초음파도에서 (1) 심실간기계적인지연 (interventricular mechanical delay, IVD) >40 ms, (2) 중격과측벽간운동지연 (septal to lateral wall motion delay, SLWD) >65 ms 등두가지조건가운데하나라도있으면심실동기이상이있는것으로정의하였다 ( 그림 1A, 1B) 10-12). 좌심실유출로에서도플러심초음파도를시행하여 QRS 파시작시점과좌심실유출로혈류의시작사이의시간간격을측정하여대동맥박출전시간을산출하고같은방법으로우심실유출로에서폐동맥박출전시간을산출하여, 두값의차이가 40 ms 이상이면좌우심실간동기이상이있다고판정하였다 ( 그림 1A) 10). 심실내동기이상은좌심실내에서어느한부분이먼저수축하고다른부분이늦게수축함으로써좌심실국소벽이비동기적으로수축하는것을말하며 M형심초음파도또는조직도플러심초음파도를이용하여평가한다. 본연구에서는조직도플러심초음파도로심실중격과측벽의국소심근운동속도곡선을얻어, QRS 파시작에서부터수축기최대속도점까지의시간을구하여두값의차이가 65 ms 이상이면비정상으로판정하였다 ( 그림 1B) 11,12). 2) 심전도표준 12 유도심전도를기록하여조율방식, 조율심전도에서 QRS파폭, 교정 QT 간격을측정하였다. 3) 혈청표지자말초혈액검사, 혈청지질, 섬유소원, 고민감도 C 반응단백질, 혈청 B-type natriuretic peptide (BNP) 등을측정하였다. 혈청 BNP는 NT-proBNP (ECLIA, NT-proBNP kit, Roche

pulmonary and aortic outflow. The interventricular delay is calculated by subtracting the pulmonary pre-ejection time from the aortic pre-ejection time.

3 - Sung Soo Kim, et al. Ventricular dyssynchrony in patients with permanent pacemaker - A B Figure 1. (A) To measure the interventricular delay on Doppler echocardiography, the right and left ventricular pre-ejection intervals are measured from the onset of the QRS on the ECG to the onset of pulmonary and aortic outflow. The interventricular delay is calculated by subtracting the pulmonary pre-ejection time from the aortic pre-ejection time. (B) To measure the septal to lateral wall delay from tissue Doppler images, in the apical four chamber view, the end diastolic still frame image is drawn with the left ventricular endocardial contour tracing. Left ventricular wall motion displacement between end-diastole and end-systole is determined for 100 endocardial segments with the centerline method. The average septal and lateral motion from 40 adjacent septal and lateral segments and three to seven cardiac cycles is displayed as displacement over time. The shift between the curves indicates the septal to lateral wall delay. Table 1. Baseline clinical characteristics Normal Dyssynchrony (n=39) (n=100) p Age (years) 67.3± ± Sex (%) 0.86 Male 17 (43.6) 42 (42.0%) Female 22 (56.4) 58 (58.0%) Diabetes mellitus (%) 6 (15.4) 14 (14.0) 0.83 Hypertension (%) 7 (17.9) 10 (10.0) 0.81 Angina pectoris (%) 4 (10.2) 3 (3.0) 0.08 Atrial fibrillation (%) 2 (2.5) 2 (2.0) 0.06 Smoking (%) 7 (17.9) 19 (19.0) 0.88 Indication (%) Sick sinus syndrome 20 (51.2) 25 (25.0) Atrioventricular block 19 (48.7) 75 (75.0) Type of pacemaker (%) 0.22 AAI (R) 4 (36.3%) 7 (63.4) VVI (R) 8 (20.5%) 31 (79.5) VDD (R) 10 (20.0%) 40 (80) DDD (R) 17 (43.5%) 22 (56.5) Current acting mode of pacemaker Atrial pacing 19 (59.33%) 15 (44.1) Ventricular pacing 20 (18.7%) 85 (81.0) Duration (months) 96.1± ± Diagnostics, Mannheim, Germany) 로측정하였다. 4) 통계통계분석은 SPSS 12.0 (SPSS, Inc., Chicago, II, USA) 을이용하였으며, 모든측정값은평균 ± 표준편차로표시하였다. 연속형변수의평균간차이분석에는독립표본 T 검정이사용되었으며, 환자의기본적인특성과연관성평가에는카이제곱검정및 Fisher s extact test가사용되었다. p 값이 0.05 미만일경우에의미있는것으로간주하였다. 결과 1. 일반적인특성전체환자의평균연령은 66.8±1.1세였으며남녀비는 1 : 1.4이었다. 시술된인공심박동기는 AAI (R) 11명 (7.9%), V (D) DD (R) 89명 (64.1%), VVI (R) 39명 (38.0%) 이었다. 관찰대상 139명가운데심실동기이상은 100명 (71.9%) 에서관찰되었다 ( 표 1). 좌우심실간동기이상 (interventricular dyssynchrony) 은 52명 (38%) 에서관찰되었으며, 심실내동기이상 (intraventricular dyssynchrony) 인중격과측벽간운동지연은 77 명 (59%) 에서관찰되었다 ( 표 2). 심실동기이상이없는대조군은 39명 (28.1%) 이었다 ( 표 1). 나이, 남녀비, 동반질환등은두군사이에통계학적으로유의한차이가없었다. 인공심

4 - 대한내과학회지 : 제 78 권제 1 호통권제 593 호 Table 2. Comparison of IVD and SLWD Dyssynchrony (n=100) IVD (n=52) SLWD (n=77) Age (years) 65.3± ± ±1.31 Sex (%) Male (46.0) 33 (42.9) Female (53.8) 44 (57.1) Diabetes mellitus (%) 14 7 (13.5) 11 (14.3) Hypertension (%) 10 6 (11.5) 7 (9.1) Angina pectoris (%) 3 1 (1.9) 2 (2.6) Atrial fibrillation (%) 2 1 (1.9) 1 (1.3) Smoking (%) (25) 14 (18.2) Indication (%) Sick sinus syndrome (19.2) 19 (24.7) Atrioventricular block (80.8) 58 (75.3) Type of pacemaker (%) AAI (R) 7 2 (3.8) 6 (7.8) VVI (R) (30.7) 23 (29.9) VDD (R) (42.3) 31 (40.3) DDD (R) (23.1) 17 (22.1) Current action mode Atrial pacing 15 2 (3.8) 14 (18.2) Ventricular pacing (96.2) 63 (81.8) Duration (months) 73.6± ± ±5.0 IVD, interventricular delay; SLWD, septal to lateral wall delay. 박동기적응증으로동기능부전보다방실전도차단이심실동기이상군에더흔하게동반되었다 (p=0.003). 인공심박동기의종류에따른차이는없었으나, 심방조율에비해심실조율이심실동기이상군에서유의하게많았다 (p=0.001, 표 1). 인공심박조율기간은대조군에서 96.1±32.5개월, 동기이상군에서 73.6±47.1개월로서두군간통계학적으로유의한차이가없었다 (p=0.497). 2. 혈청표지자말초혈액검사및간기능검사, 지질대사, 고민감도 - C반응단백에서의미있는차이는보이지않았다. 전해질중나트륨수치와혈중요소질소와크레아틴이동기이상군에서높은소견을보였으며, 혈청 NT-proBNP는동기이상군에서유의하게높았다 (202.7±40.8 vs ±66.1 pg/ml, p=0.004, 표 3). 3. 심전도소견심전도에서인공심박동기이식직후의 QRS파폭은동기 이상군에서더넓었으며 (136.2±6.8 vs ±3.6 ms, p=0.04), 추적심전도에서도동기이상군에서 QRS파폭 (129.4±6.3 vs ±3.2, p<0.001) 및보정 QT 간격 (470.9±8.1 vs ±4.0, p<0.05) 이의미있게넓었다 ( 표 4). 추적심전도에서 QRS 폭은 IVD와 SLWD와의미있는상관관계를보였다 ( 그림 2A, 2B). ROC 곡선에서조율성 QRS파폭이 170 ms 이상일경우심실동기이상을예측하는데민감도 44%, 특이도 90% 였다 ( 그림 2C). 4. 심초음파도소견인공심박동기이식직후심초음파도측정값에는두군사이에통계학적으로유의한차이가없었다. 그러나추적심초음파도에서삼첨판막역류증이심실동기이상군에서의미있게많았다 (22.3% vs. 66.9%, p<0.05, 표 4). 고찰본연구에서는심실동기이상은인공심박동기를삽입한

5 - 김성수외 13 인. 심실동기이상의관련인자 - Table 3. Laboratory findings No dyssynchrony (n=39) Dyssynchrony (n=100) p WBC (10 3 /mm 3 ) 6.91± ± Hemoglobin (g/dl) 15.28± ± Platelet count (10 3 /mm 3 ) ± ± Aspartate aminotransferase (U/L) 28.27± ± Alanine aminotransferase (U/L) 21.97± ± Blood Urea Nitrogen (mg/dl) 16.47± ± Creatinine (mg/dl) 0.77± ± Na + (meq/l) ± ± K + (meq/l) 4.28± ± Glucose (mg/dl) ± ± Total cholesterol (mg/dl) ± ± Triglyceride (mg/dl) ± ± LDL cholesterol (mg/dl) ± ± HDL cholesterol (mg/dl) 55.89± ± hscrp (mg/l) 0.79± ± NT probnp (pg/ml) ± ± LDL cholesterol, low-density lipoprotein cholesterol; HDL cholesterol, high-density lipoprotein cholesterol; hscrp, high-sensitivity C-reactive protein; NT-proBNP, N-terminal B-type natriuretic peptide. Table 4. Electrocardiography and echocardiography findings No dyssynchrony Dyssynchrony p Electrocardiography Insertion time QRS duration (msec) 136.2± ±3.6 <0.05 Corrected QT (msec) 462.2± ± Present time QRS duration (msec) 129.4± ±3.2 <0.001 Corrected QT (msec) 470.9± ±4.0 <0.05 Echocardiography Insertion time Ejection Fraction (%) 65.7± ± LVEDd (mm) 52.5± ± TR (%) 6 (28.6) 15 (71.4) Present time Ejection Fraction (%) 63.0± ± LVEDd (mm) 50.7± ± TR (%) 31 (22.3%) 93 (66.9%) <0.05 Diastolic dysfunction (%) 32 (23.0%) 81 (58.3%) 0.88 LVEDd, left ventricular end-diastolic diameter; TR, tricuspid regurgitation

6 - The Korean Journal of Medicine: Vol. 78, No. 1, A B C Figure 2. (A) A correlation exists between the QRS duration and the interventricular delay (IVD). (B) A correlation is observed between the QRS duration and the septal to lateral wall delay (SLWD) on tissue Doppler images (TDI). (fuqrsd=follow-up QRS duration). (C) The area under the receiver operation characteristic (AUC) curve of QRS duration and ventricular dyssynchrony was A value of 170 msec predicted the development of ventricular dyssynchrony with a sensitivity of 44% and specificity of 90%. 환자의 71.9% 에서나타났으며, 나이와성별, 기저질환, 조율기간과의상관관계는보이지않았으나방실전도차단및심실조율환자에서더흔하게동반되었다. 심전도의 QRS파폭의연장, 교정 QT간격의연장및심초음파도검사의삼첨판막역류증그리고높은혈청 NT pro-bnp 가심실동기이상과관련이있었다. 인공심박동기의장기적인우심실조율은심실의동기이상을유발하여, 심기능을저하시키고, 입원및사망률을증가시키는것으로알려져있다 1-6). 또한심근의조직학적변화를유발하여심근섬유크기의변화, 섬유화, 지방축적및병적인관류장애까지초래하게된다 13-16). 심실동기이상은좌우심실간동기이상 (interventricular dyssynchrony), 심실내 동기이상 (intraventricular dyssynchrony) 으로구별된다. 본연구에서심실동기이상을평가한결과, 총 139명중에좌우심실간동기이상이 52명 (38%) 에서심실내동기이상은 77명 (59%) 에서관찰되어심실내동기이상이더많았다 ( 표 2). 심실동기이상유무는동기능부전보다는방실전도차단에서더흔하게동반되었으며, 심방조율보다는심실조율에서더유의하게많았다 ( 표 1). 방실전도차단에의한심실조율시 QRS파는심실의탈분극이히스- 퍼킨제전도계를이용하지않고심실근세포사이의느린전도에의해일어나기때문에심실내전도시간이연장되고탈분극의진행방향도바뀌어좌각차단형으로변한다 17). 따라서우심실조율은심실이비동기적으로수축하므로심실동기이상을악화시킨다

7 - Sung Soo Kim, et al. Ventricular dyssynchrony in patients with permanent pacemaker - 고생각되었다. 그러나본연구결과에서는인공심박동기타입에따라서는심실동기이상의차이를관찰할수없었다. 이는 DDD형인공심박동기에서심방조율과심실조율양을정확하게측정하지못한것에기인한것으로보여추가적인연구가필요할것으로생각되었다. 또한 AAI (R) 형인공심박동기는심방조율을하는박동기이기때문에심실동기이상이적을것으로판단되었으나 7예의환자에게있어서발견되었다. 이는진행된심부전및심근경색의벽운동이상등에서도심실동기이상이올수있는것처럼심실동기이상이단순히조율방법의차이에서만결정되지않음을보여준다. 심실조율기간이길어질수록심실동기이상이많아질것으로생각되었으나본연구에서는유의한차이를보이지않았다. 심실동기이상은단순히심박동기차이및심장조율기간에의해서만결정되지않고여러복합적인인자에의해서결정됨을알수있었다. 심전도에서심실동기이상유무에따라 QRS파폭, 교정 QT 간격에차이가있었다. 우심실조율시 QRS파폭의증가는심실내전도지연을의미하며, 인공심박동기환자에서부전으로인한입원의독립적인위험인자라고알려져있다 18-20). 본연구에서는조율성 QRS파폭과심실동기이상이의미있는상관관계를보였다 ( 그림 2A, 2B). 또한 ROC 곡선에서조율성 QRS파폭이 170 ms 이상일경우심실동기이상을예측하는데민감도 44%, 특이도 90% 였다 ( 그림 2C). 조율성 QRS파폭이 190 ms 이상이면심기능저하를동반할위험이높다고보고한 Miyoshi 등 21) 의연구처럼조율성 QRS파폭을측정하는것은심실동기이상을예측하는데유용한방법이될수있을것으로생각되었다. QT 간격은주로심실의재분극시간을반영하나탈분극의이상에의해서도영향을받으며 440 ms 이하가정상으로알려져있다. 본연구에서는보정 QT 간격이심실동기이상유무에따라유의한차이가있음을보여주었으며이는심실동기이상이심실조율에따른심실탈분극의이상과이로인한재분극시간의증가와관련이있음을시사한다. 좌심실구혈률, 좌심실이완기말내경, 이완기기능이상은심실동기이상유무에따라차이가없었으나심초음파추적시에삼첨판막역류가심실동기이상군에서유의하게많았다. 인공심박동기의우심실조율은우심실일부벽이먼저수축하기때문에세개판막엽이긴장도를유지하는시점이달라져서삼첨판막역류가초래될것으로생각된다. 삼첨판막역류가폐동맥압의증가에의해서초래될수도있지만본연구에서는두군에서폐동맥압의차이가없었기때문에 우심실국소벽운동이상이주된기전으로생각되었다. 따라서심초음파도에서삼첨판막역류는심실동기이상을시사하는지표가될수있을것으로보인다. 혈청 NT-proBNP 는심실동기이상군에서통계학적으로유의하게높아서인공심박동기환자에서심실동기이상의동반여부를예측하는데이용될수있을것으로생각되었다. 혈청 NT-pro BNP 는심근스트레스를반영해주는혈청지표인데심부전과급성심근경색증에있어서예후인자로알려져있다. NT-proBNP 는여성, 고령, 신장기능저하, 당뇨병조절불량환자에서도상승할수있는것으로알려져있다 22). 본연구에서는다른영향인자들의차이가없었음에도심실동기이상이있는군에서의미있게높아, 이는심실동기이상이있을경우에심근스트레스가증가하기때문에 NTproBNP 가증가한것으로생각되었다. 혈청 hs-crp는심실동기이상유무에따른차이를보이지않아, 심실동기이상과심근의염증반응과의관계는적을것으로판단된다. 결론적으로영구형인공심박동기이식환자에서심실동기이상은 71.9% 에서관찰되었으며, 방실전도차단및심실조율을하고있는환자에서주로관찰되었다. 따라서영구형인공심박동기삽입시술시에심장내전도계에서동기능부전및전도차단부위를정확히판단하여심실조율을줄여가능한심방조율을하는것이필요할것이다 23). 또한우심실조율시에서도우심실첨단에서만위치하는것이아니라우심실유출로주변의장소에서조율하는방법및양심방심실조율을고려하는것도하나의방법으로생각된다 24). 심전도상에서조율 QRS파의폭, QT 간격과심초음파도의삼첨판막역류증, 혈청 NT pro-bnp 상승이심실동기이상의관련인자로이용할수있을것으로생각되었다. 요약목적 : 최근여러연구에서장기적인우심실조율은심실동기이상을야기하여심기능을저하시키고사망률을증가시키는것으로알려져있다. 심실동기이상은기저질환, 조율방식, 조율장소등에의해서달라질것으로생각되어본연구에서는조율방식, 심실조율정도, 조율심전도 (QRS 형태, 폭, 재분극이상 ), 심실조율기간, 혈청학적표지자등과심실동기이상과의관계를규명하고자하였다. 방법 : 1991년 1월부터 2008년 3월까지인공심박동기를이식받은후정기적으로외래에서추적관찰중인환자들가운데 139명 ( 남 : 여 =1:1.35, 66.8±1.0년 ) 을대상으로시행하였

8 - 대한내과학회지 : 제 78 권제 1 호통권제 593 호 다. 심전도, 심초음파도, 심박동기기능분석과혈청표지자검사를같은날에시행하였다. 심장초음파로심실동기이상을평가하여, 심실동기이상이없는환자를대조군있는환자를동기이상군으로분류하여임상적특징및심전도, 혈청표지자를비교하였다. 결과 : 심실동기이상은인공심박동기를삽입한환자의 71.9% 에서나타났으며, 나이와성별, 기저질환, 조율기간과의관계는보이지않았으나방실전도차단및심실조율환자에서더흔하게동반되었다. 심전도에서 QRS폭의연장, 교정 QT간격의연장등과연관이있었다. 심초음파도검사에서삼첨판막역류증과연관이있었고, 혈청 NT pro-bnp 가유의하게높았다. 결론 : 영구형인공심박동기이식환자에서심실동기이상은주로방실전도차단및심실조율환자에게심박동기를삽입하였을때주로나타났다. 심전도상의조율 QRS파의폭, 교정 QT 간격의증가및심초음파도에서삼첨판막역류증, 혈청 pro-bnp 상승이관련인자로사용할수있을것으로생각되었다. 중심단어 : 심박동기 ; 심전도 ; 심초음파도 ; 뇌나트륨이뇨펩타이드 REFERENCES 1) Furman S, Robinson G. The use of an intracardiac pacemaker in the correction of total heart block. Surg Forum 9: , ) Wilkoff BL, Cook JR, Epstein AE, Greene HL, Hallstrom AP, Hsia H, Kutalek SP, Sharma A. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 288: , ) Glotzer TV, Hellkamp AS, Zimmerman J, Sweeney MO, Yee R, Marinchak R, Cook J, Paraschos A, Love J, Radoslovich G, Lee KL, Lamas GA. Atrial high rate episodes detected by pacemaker diagnostics predict death and stroke: report of the Atrial Diagnostics Ancillary Study of the MOde Selection Trial (MOST). Circulation 107: , ) Dhar R, Alsheikh-Ali AA, Estes NA 3rd, Moss AJ, Zareba W, Daubert JP, Greenberg H, Case RB, Kent DM. Association of prolonged QRS duration with ventricular tachyarrhythmias and sudden cardiac death in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II). Heart Rhythm 5: , ) Barold SS, Stroobandt RX. Harmful effects of long-term right ventricular pacing. Acta Cardiol 61: , ) O'Keefe JH Jr, Abuissa H, Jones PG, Thompson RC, Bateman TM, McGhie AI, Ramza BM, Steinhaus DM. Effect of chronic right ventricular apical pacing on left ventricular function. Am J Cardiol 95: , ) Freudenberger RS, Wilson AC, Lawrence-Nelson J, Hare JM, Kostis JB. Permanent pacing is a risk factor for the development of heart failure. Am J Cardiol 95: , ) Teichholz LE, Cohen MV, Sonnenblick EH, Gorlin R. Study of left ventricular geometry and function by B-scan ultrasonography in patients with and without asynergy. N Engl J Med 291: , ) Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 2: , ) Rouleau F, Merheb M, Geffroy S, Berthelot J, Chaleil D, Dupuis JM, Victor J, Geslin P. Echocardiographic assessment of the interventricular delay of activation and correlation to the QRS width in dilated cardiomyopathy. Pacing Clin Electrophysiol 24: , ) Pitzalis MV, Iacoviello M, Romito R, Massari F, Rizzon B, Luzzi G, Guida P, Andriani A, Mastropasqua F, Rizzon P. Cardiac resynchronization therapy tailored by echocardiographic evaluation of ventricular asynchrony. J Am Coll Cardiol 40: , ) Bax JJ, Bleeker GB, Marwick TH, Molhoek SG, Boersma E, Steendijk P, van der Wall EE, Schalij MJ. Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy. J Am Coll Cardiol 44: , ) Prinzen FW, Augustijn CH, Arts T, Allessie MA, Reneman RS. Redistribution of myocardial fiber strain and blood flow by asynchronous activation. Am J Physiol 259:H300-H308, ) Adomian GE, Beazell J. Myofibrillar disarray produced in normal hearts by chronic electrical pacing. Am Heart J 112:79-83, ) Tse HF, Lau CP. Long-term effect of right ventricular pacing on myocardial perfusion and function. J Am Coll Cardiol 29: , ) Karpawich PP, Rabah R, Haas JE. Altered cardiac histology following apical right ventricular pacing in patients with congenital atrioventricular block. Pacing Clin Electrophysiol 22: , ) Andersen HR, Nielsen JC, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T, Pedersen AK. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet 350: , ) Vassallo JA, Cassidy DM, Miller JM, Buxton AE, Marchlinski FE, Josephson ME. Left ventricular endocardial activation during

9 - 김성수외 13 인. 심실동기이상의관련인자 - right ventricular pacing: effect of underlying heart disease. J Am Coll Cardiol 7: , ) Sweeney MO, Hellkamp AS. Heart failure during cardiac pacing. Circulation 113: , ) Shukla HH, Hellkamp AS, James EA, Flaker GC, Lee KL, Sweeney MO, Lamas GA. Heart failure hospitalization is more common in pacemaker patients with sinus node dysfunction and a prolonged paced QRS duration. Heart Rhythm 2: , ) Miyoshi F, Kobayashi Y, ItouH, Onuki T, Matsuyama T, Watanabe N, Liu C, Kawamura M, Asano T, Miyata A, Nakagawa H, Tanno K, Baba T, Katagiri T. Prolonged paced QRS duration as a predictor for congestive heart failure in patients with right ventricular apical pacing. Pacing Clin Electrophysiol 28: , ) Raymond I, Groenning BA, Hildebrandt PR, Nilsson JC, Baumann M, Trawinski J, Pedersen F. The influence of age, sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population. Heart 89: , ) Albertsen AE, Nielsen JC, Poulsen SH, Mortensen PT, Pedersen AK, Hansen PS, Jensen HK, Egeblad H. DDD(R)-pacing, but not AAI(R)-pacing induces left ventricular desynchronization in patients with sick sinus syndrome: tissue-doppler and 3D echocardiographic evaluation in a randomized controlled comparison. Europace 10: , ) McGavigan AD, Mond HG. Selective site ventricular pacing. Curr Opin Cardiol 21:7-14,

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<B0E6C8F1B4EBB3BBB0FA20C0D3BBF3B0ADC1C E687770> 심전도연수강좌 : 처음시작하는사람들을위한심전도 연세대학교원주의과대학순환기내과학교실 안민수 Cardiac Electrophysiology I : Automaticity : 60-100 회 /min, His bundle : 40-60 회 /min Bundle branch : 20-40 회 /min Purkinje fiber : 20 회 /min Cardiac Electrophysiology