편집자문위원 (가나다순)

고재곤 / 울산의대 곽충환 / 경상의대 김대경 / 인제의대 김대혁 / 인하의대

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김종윤 / 연세의대 김준 / 울산의대 김준수 / 성균관의대 김진배/ 경희의대

남궁준 / 인제의대 노태호 / 가톨릭의대 박경민 / 인제의대 박상원 / 고려의대

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오동진/ 한림의대 오용석 / 가톨릭의대 이경석 / 전북의대 이만영 / 가톨릭의대

이명용 / 단국의대 이문형 / 연세의대 임홍의/ 고려의대 장성원 / 가톨릭의대

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최윤식 / 서울의대 최의근 / 서울의대 최인석 / 가천의대 최종일 / 고려의대

한상진 / 한림의대 허준 / 성균관의대 현명철 / 경북의대

부정맥은 대한심장학회 부정맥연구회가 주관하며 엠엠케이커뮤니케이션즈에서 발행하고 있습니다.

본지와 관련된 문의사항이나 건의사항이 있으시면 발행사인 엠엠케이커뮤니케이션즈로 연락하여 주시기 바랍니다.

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발행일 2015년 3월 30일

The Official Journal of Korean

Heart Rhythm Society

목적과개요

‘부정맥’은부정맥과 관련된 새로운 임상 연구, 진료지침, 증례 등을 소개하여

부정맥연구회 회원 및 개원의의 지속적인 의학교육에 이바지하고자

발행되는 학술지입니다.

‘부정맥’은 부정맥의 진단과 치료, 임상 연구와 관련된 원저, 종설,

논평, 증례 보고 등의 원고를 공모하며, 제출된 원고는

편집위원회의 검토를 거쳐 게재됩니다.

Cover: Contrast dye injection after Watchman™ implantation (Page 34) Amplatzer™ Cardiac Plug device is appropriately compressed and fixed with “tire-like” shape in the lobe of LAA and the disc is fully covering the entrance to the LAA (Page 39)

The Official Journal of Korean Heart Rhythm Society

March 2015Volume 16 l No. 1

Original ArticlesRadiation Dose and Cancer Risk of Cardiac Electrophysiology Procedures Hyun-Ok Cho, Hyoung-Seob Park, Hyun-Chul Choi, Yun-Kyeong Cho, Hyuck-Jun Yoon, Hyungseop Kim, Chang-Wook Nam, Seongwook Han, Seung-Ho Hur, Yoon-Nyun Kim, Kwon-Bae Kim, Dae-Woo Hyun

Calcium Dynamics and the Mechanisms of Ventricular Tachycardia to Ventricular Fibrillation Transition in Cryoablated Rabbit VentriclesGyo-Seung Hwang

Effects of Angiotensin Converting Enzyme Inhibitors and Statins on Endothelial Function, Inflammation, and Coagulation in patients with Hypertension and Atrial FibrillationHyung Wook Park, Min Chul Kim, Kyung Hoon Cho, Cheol Hwan Kim, Kyung Hwan Kim, Seung Jin Jun, Woo Jin Kim, Kyoung Jin Lee, Sung Soo Kim, Hyun Kuk Kim, Hae Chang Jeong, Jae Yeong Cho, Ki Hong Lee, Nam Sik Yoon, Keun-Ho Park, Doo sun Sim, Hyun Ju Yoon, Kye Hun Kim, Young Joon Hong, Ju Han Kim, Youngkeun Ahn, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park

Main Topic Reviews

Left Atrial Appendage Occlusion

좌심방이폐색술의소개와적응증

온영근

Watchman™을이용한경피적좌심방이폐색술

엄재선

Amplatzer™CardiacPlug를이용한경피적좌심방이폐색술

신승용, 임성일, 김진석, 임홍의

LARIAT®Device를이용한경피적좌심방이폐색술남기병

좌심방이절제술:수술치료의역할

정동섭

Article Review뇌졸중의 원인에 심방세동이 관련 있는지 보려면 어떻게 확인하는 것이 좋을까?

오세일

Case ReviewsVentricular Tachycardia with Two Distinct Morphologies Caused by Herbal Medicine Containing Ephedra sinica Seung Yong Shin

Accessory Pathway with Decremental Conduction PropertiesYong Seog Oh

자율학습문제

자율학습문제정답(51호,52호)

04

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Arrhythmia 2015;16(1):4-10

Introduction

Electrophysiology study (EPS) and radiofrequency catheter

ablation (RFCA) are widely used for the diagnosis and treatment

of cardiac arrhythmias. EPS and RFCA are very complicated

procedures, requiring extended periods of time and advanced

technologies that vary according to the disease of the patients.

Fluoroscopy is used during EPS and RFCA to guide the catheter

through the vessels while viewing the fluoroscopy monitor to

reach the desired area to examine and monitor the procedure.

However, fluoroscopy exposes patients and staff members to

radiation, and this can result in possible skin damage, cancer, and

Radiation Dose and Cancer Risk of Cardiac Electrophysiology Procedures

Received: December 15, 2014Revision Received: January 25, 2015Accepted: March 26, 2015Correspondence: Hyoung-Seob Park, MD, Division of Cardiology, Department of Internal Medicine, Keimyung University Dongsan Medical Center, 194 Dongsan-dong, Jung-gu, Daegu, South Korea. 700-712. Fax: +82-53-250-7034E-mail: drparkgyver@gmail.com

Copyright © 2015 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd.

Hyun-Ok Cho*1, Hyoung-Seob Park*2, Hyun-Chul Choi2, Yun-Kyeong Cho2, Hyuck-Jun Yoon2, Hyungseop Kim2, Chang-Wook Nam2, Seongwook Han2, Seung-Ho Hur2, Yoon-Nyun Kim2, Kwon-Bae Kim2, Dae-Woo Hyun1

1 Department of Cardiology, Andong medical group,

Kyungsangbukdo, Korea2 Department of Cardiology, Keimyung University Dongsan

Medical Center, Daegu, Korea

ABSTRACT

Background & Objectives: This study aimed to investigate the effec-

tive dose and organ dose of radiation exposure in patients undergo-

ing cardiac electrophysiology (EP) procedures and to estimate the

risk of cancer by measuring the effective dose in staff members.

Materials and Methods: We calculated the dose by using the value

of the dose-area product (DAP) to check the exposure dose in pa-

tients and staff members during EP procedures. The dose and cancer

risk in staff members were estimated after the procedure by reading

the optically stimulated luminescent dosimeter (OSL) attached to

the radiation protection equipment.

Results: The study duration was 3 months. The total number of pro-

cedures was 89 cases (electrophysiology study [EPS] and catheter

ablation: 62 cases [including 21 atrial fibrillation ablation], and

pacemaker implantations: 27 cases). The mean effective dose in the

primary operator over 3 months was 1.6 mSv, with a 1-year conver-

sion of 6.4 mSv. The lifetime attributable risk of cancer (LAR) for a

male primary operator with an annual exposure dose of 6.4 mSv

who worked from age 18 to 65, assuming continuous exposure, for

all cancers would be an incidence of 1,958 per 100,000 people. In

addition, the calculated mortality rate would be 1 in 92, or 1.08%.

Conclusion: EP procedures are associated with occupational radia-

tion exposure and an increased lifetime attributable risk of cancer.

Efforts should be made to minimize the radiation exposure of pa-

tients and medical staff members.

Key Words: electrophysiology, radiation, cancer

ORIGINAL ARTICLES

05

Radiation Dose and Cancer Risk

genetic effects.1-3

An existing study on radiation exposure during RFCA showed

that the mean equivalent doses to the cardiologist’s left hand and

forehead were 0.24 mSv and 0.05 mSv, respectively, per RFCA

procedure, which was more than twice the mean dose for other

cardiology procedures.4 Another study reported that cardiac

electrophysiologists have high radiation exposure, with a median

of 4.3 mSv per year (range 3.5-6.1 mSv).5 In other studies of

RFCA, when the patients had an effective dose of 8.3 mSv for one

hour of fluoroscopy, they had a cancer risk of 480-650 per million

patients.6 Therefore, radiation exposure during electrophysiology

(EP) procedures is not insignificant for both patients and staff.

According to the European Committee on Radiation Risk,

when adults are exposed to a 10 mSv dose, 1 out of every 1,000

can be at risk for a possible solid tumor or leukemia in their

lifetime.7 Another report showed that if fluoroscopy exposure lasts

for more than 1 hour during an EP procedure, the dosage will

exceed the threshold and result in skin damage.8 However, most

cardiologists who perform procedures are not familiar with

radiation physics or methods to protect against it, or did not

received proper education about the risks of radiation, so

individual cardiologists are subjected to different levels of

exposure.9

Although many existing studies on radiation exposure in EP

procedures have focused on effective doses in patients,2,3,6,10 and

some have examined the radiation dose in both patients and staff

members,2,11,12 few have included cancer risk in their analysis.

Therefore, this study aimed to determine the effective dose and

organ dose from radiation exposure during EP procedures in

patients, as well as to measure the risk of cancer from the effective

dose to staff members.

Materials and Methods

Patients

This study included 89 consecutive patients who received EP

procedures and cardiac implantable electronic device (CIED)

procedures from October 2011 to February 2012. All patients

gave informed consent. Three staff members (one cardiac

electrophysiologist, one radiologic technologist, and one nurse)

were included for the measurement of radiation exposure.

Radiation Dose Measurement

Procedures were performed using Philips Allura Xper FD20

fluoroscopy system (Philips Medical Systems, Eindhoven, The

Netherlands). The procedure was performed with fluoroscopy set

to “normal” and cinematic acquisition imaging frame rates set at

15 frames/sec in cardiac mode.

The tube voltage, tube current, and radiation exposure time

parameters were set at the time of installment with automatic

exposure control (AEC). Tube voltage, which was between

70-120 kV, was applied according to the type and size of the

Table 1. Mean DAP and effective dose in each procedure

Procedure No. PatientWeight, kg

FluoroscopyTime, min DAP (Gy-cm2) Deff (mGy)

Total 89 63 (38-88) 17.9 (0.1-68.4) 112.0 (0.3-519.6) 35.9 (0.1-166.5)

AFIB 21 68 (47-83) 38.0 (14.2-68.4) 262.5 (92.3-519.6) 84.1 (29.6-166.5)

AFL/AT 6 56 (46-66) 13.4 (8.3-13.4) 52.1 (47.9-56.2) 16.6 (15.3-18.0)

AVNRT 23 55 (45-64) 12.5 (7.1-27.4) 64.4 (15.8-203.8) 20.7 (5.1-65.3)

AVRT 9 63 (38-88) 12.8 (5.0-44.2) 60.1 (17.2-198.8) 19.8 (6.0-64.1)

PMK/ICD 27 71 (44-85) 6.3 (0.1-28.4) 31.2 (0.3-92.7) 10.0 (0.1-29.7)

VT 3 68 (64-72) 10.1 (6.0-15.4) 50.9 (24.1-81.4) 16.3 (7.7-26.1)

AFIB, atrial fibrillation; AFL, atrial flutter; AT, atrial tachycardia; AVNRT, atrioventricular nodal reentrant tachycardia; AVRT, atrioventricular reentrant tachy-cardia; CBT, concealed bypass tracts; DAP, dose area product; Deff, Effective dose; EPS, electrophysiology study; ICD, implantable cardioverter defibrillator; PMK, pacemaker; VT, ventricular tachycardia.

06

Arrhythmia 2015;16(1):4-10

patient. A basic 1.5 mm Al and filtration of 0.2 mm Cu was

installed and a 0.1 mm Cu + 1.0 mm Al was applied for the

Selective Fluoro Prefilter.

Calculation of the Effective Dose and Organ Dose in Patients

The dose of radiation exposure to patients during the EP

procedure was measured by a dose area product (DAP) meter

(Diameter PTW, Freiburg, Germany), which was attached to the

collimator on the tube housing. The DAP value was used to

calculate the effective dose and organ dose with the PCXMC

Monte Carlo simulation program (version 1.5). The tube voltage

of the X-ray, tube current, and exposure time parameters were

performed by the AEC without a manual control. The tube

voltage of the AEC was flexible depending upon the size of the

patients and direction of the recording, ranging between 70-120

kV.

Radiation Exposure and Cancer Risk in Staff In order to measure the radiation exposure to staff members, an

optically stimulated luminescent dosimeter (OSL) (Inlight/DSL

NanoDot Dosimeters, Landauer, Glenwood, IL. USA) was

attached to the protective equipment. The potential measurement

of the dose limit by the OSL was 100 ∂ Sv, the range of the energy

was 5 keV-20 MeV, and the accuracy was ± 5% of the standard

deviation. The OSL was attached at several locations: inside and

outside of the gonad area, on the chest area of the apron, on the

lead goggles and thyroid protector of the operator, and also inside

and outside of the nurse's and radiological technologist’s apron.

After staff members had worn the OSL for 3 months, the data

collected from the OSL was sent to a specialist who determined

the radiation dose exposure at each site.

The effective dose of the staff members followed the Niklason

calculation,13 which is calculated as Deff = 0.02 (Hos-Hu) + Hu

(Hos is the dose outside of the lead apron and Hu is the dose

inside the lead apron). The lifetime attributable risk (LAR) of

cancer for the staff member was calculated based on the BEIR VII

study.14 That study showed the occurrence of cancer per every

100,000 people when they were exposed to 10 mGy annually

between the ages of 18 and 65; that data was directly applied to

the calculation of cancer risk to staff members. For example, when

the annual radiation exposure to staff members was 5 mSv, the

LAR was 5/10×3,059/100,000. This study measured the cancer

risk under the assumption that the staff members were

continuously exposed to radiation from the age of 18 to 65.

Results

Radiation Dose in the Patients

The average fluoroscopic duration was 20.8 minutes during the

procedure, the maximum was 68.4 minutes, and the total

fluoroscopic time was 1,040.1 minutes. The DAP value was an

Table 2. Organ dose of the patients in the total EP procedures

OrganOrgan dose in the procedures

Mean (mGy) Minimum (mGy) Maximum (mGy)

Lung 66.22 0.20 306.94

Heart 193.47 1.00 896.53

Breast 143.46 0.40 664.76

Liver 37.29 0.10 172.77

Stomach 72.90 0.20 337.83

Spleen 35.65 0.10 165.19

Pancreas 59.92 0.20 277.66

Thymus 239.48 0.70 1,109.80

EP, electrophysiology.

07

average of 112.0 Gy・cm2, and the maximum value was 519.6

Gy・cm2. Calculating the effective dose with the DAP value using

the PCXMC program resulted in an average of 35.9 mGy with a

maximum value of 166.5 mGy.

The average fluoroscopic time, DAP value, and effective dose

according to each EP procedure are shown in Table 1. The

fluoroscopic duration was the longest during AF ablation at 30.8

minutes, and the highest average effective dose in patients

measured was 84.1 mGy. The organ dose converted with the

DAP value for the entire EP procedure in patients was highest in

the thymus, with an average of 239.48 mGy, followed by the heart

at 193.47 mGy, and breasts at 143.46 mGy (Table 2).

Effective Dose and Cancer Risk to Staff Members

The effective dose in staff members was calculated by reading

the OSL, which was worn for three months during the EP

procedures. The effective dose in the primary operator who was

closest to the patients for three months was 1.6 mSv, which

equates to an annual radiation exposure dose of 6.4 mSv. The

effective dose in the radiologic technologist was 0.98 mSv, and in

the nurse it was 0.75 mSv. The dose outside the apron for the

gonadal gland was 6,930 μSv, the dose in the area of the eyes was

3,200 μSv, and the thyroid was 4,020 μSv. These measurements

suggest that the outside of the apron in the gonadal gland area was

more exposed than the facial area. The attenuation rate, which

compared the readings inside and outside of the protective gear,

was calculated at 83.8% for the apron of 0.5 mm thickness, 77.0%

for the 0.5 mm thyroid protector, and 50.4% for goggles with 0.07

mm lead thickness.

The cancer risk for male primary operators who are exposed to

6.4 mSv of radiation annually from the age of 18 to 65 is 1,958 per

100,000; in other words, 1 in every 51 operators would be at risk

for cancer. For operators consistently exposed to 6.4 mSv per year,

the mortality rate is 1 in every 92 operators (Table 3, 4).

Discussion

This study calculated the radiation dose in patients using the

DAP value in order to identify the radiation exposure dose to staff

members and patients during EP procedures while wearing

protective gear with an OSL attached during the procedure. The

amount of exposure of the patients as well as the risk of cancer was

also calculated. Interventions such as EPS procedures usually use

fluoroscopy. Because fluoroscopy is done by an AEC, there can be

difficulty in measuring the radiation exposure dose in patients.

Radiation can vary during fluoroscopy, and the exposed area of

the body constantly changes; therefore, in these kinds of

measurements, the dose-area product, DAP, is commonly applied.

The DAP value using the DAP meter is known as an effective way

to measure the amount of radiation in cardiac fluoroscopy and the

radiation area during fluoroscopy.15,16

In the previous studies, the DAP value during EPS procedures

was 11.6-251 Gy・cm2,4,17,18 and the effective dose in the patients

OSL, optically stimulated luminescent dosimeter.

Table 3. Effective dose and protector attenuation rate per procedure calculated from the OSL measurements

Primary operator Effective dose (μSv) Attenuation rate (%)

Chest over apron 8,96083.8

Chest under apron 1,450

Eyes over goggle 3,20050.4

Eyes under goggle 1,590

Thyroid over protector 4,02077.9

Thyroid under protector 890

Gonadal over apron 6,93077.6

Gonadal under apron 1,550

Radiation Dose and Cancer Risk

08

was 17 mSv.4 Kovoor stated that it was 6.34 mSv for procedures

lasting 60 minutes,3 while Lickfett reported it was between 1.48-

49.75 Gy・cm2.2

This study showed that the DAP value during EP procedures

was an average of 112.0 Gy・cm2 and the average effective dose in

the patients was 35.9 mSv, with a maximum of 166.5 mSv. This

study showed a higher average effective dose than previous studies.

During EP procedures, if patients are exposed to radiation for

longer than one hour, the threshold amount of radiation that is

critical for the skin will be reached, which has been reported

previously.8 During the AF ablation in this study, the exposure

time was an average of 30.8 minutes, and there was a long

exposure of 68 minutes, so the amount of radiation likely

exceeded the limit for skin damage.

The medical staff who perform electrophysiology procedures

often ignore or underestimate the danger of radiation. However,

the constant exposure to radiation during a few years of work or

life-long practice accumulates, and it can cause physical damage.

Furthermore, cardiologists are exposed to scattered rays, which

provide a fluctuating dose of radiation. In some cases, they are

exposed to direct rays. Because their hands, legs, and head area are

not properly protected, their accumulated dose can significantly

increase. In a study by Lucia Venneri,5 67% of the 5,164 cardiac

catheterization laboratory staff who worked with radiation in a

hospital were exposed to radiation of 6 mSv or more. The study

also showed that staff members who worked at cardiology centers

might be exposed to the highest level of radiation. That study

noted that the annual radiation exposure for interventional

cardiologists averaged 3.3 mSv (2.0-19.6 mSv), and for

electrophysiology cardiologists it was 4.3 mSv (3.5-6.1 mSv),

equating to a fatal cancer risk of 1 in 384. The all-cause cancer risk

is 1 in 192. In the BEIR study,14 staff members exposed to 2 mSv

of radiation annually from the age of 18 to 65 had cancer risks of

612/100,000 for men or 859/100,000 for women. In other

words, the all-cause cancer risk for exposed staff was 1 in 136 and

the mortality rate was 1 in 245. Another study found that the

effective radiation dose in operators during percutaneous

coronary intervention procedures was 0.17-31.2 μSv and 0.24-9.6

μSv during EP and ablation procedures.19

In the present study, the effective radiation dose in staff

members during the EPS procedure was 1.6 mSv over three

months of exposure for primary operators, with an annual

exposure of 6.4 mSv. Extrapolating from this data, the all-cause

cancer incidence is 1 in 51, and the mortality rate is 1 in 92.

Therefore, although radiation exposure during EP procedures is

not immediately harmful in primary operators, over time, the

cumulative exposure can increase cancer risk. Radiation exposure

generally occurs due to scattered rays, except in the instances when

Table 4. LAR of cancer and mortality for the primary operator

OrganIncidence Mortality

LAR (per million) Odds LAR (per million) Odds

Stomach 79 1:1,266 42 1:2,381

Colon 353 1:283 175 1:571

Liver 60 1:1,667 46 1:2,174

Lung 372 1:269 315 1:317

Prostate 105 1:952 205 1:488

Bladder 229 1:437 51 1:1,961

Other 513 1:195 253 1:395

Thyroid 18 1:5,556 - -

All solid 1,727 1:58 902 1:111

Leukemia 230 1:435 186 1:538

Total 1,958 1:51 1,088 1:92

LAR, lifetime attributable risk.

Arrhythmia 2015;16(1):4-10

09

operators put their hands into the fluoroscopic field to operate the

catheter. Fluoroscopy rays scatter in the iris of the radiation tube,

via leakage, and from reflection of patients.20 With the under tube

method, most rays reflected from the patients under the table,

which can directly affect the gonadal glands. In this study the

under tube method was used during EP procedures, and, as a

result, radiation exposure to primary operators appears higher in

the gonadal glands than in the eyes or thyroid gland. The results of

this study showed the same conclusion as the previous study.

Although operators wear aprons, lead shields, and goggles to

protect themselves, during long-term performance of these

procedures, it is impossible to avoid radiation exposure and its

effects. If operators fail to use protective gear or adjust the

exposure time properly, within a few years their eyes, skin, thyroid,

and gonadal glands may have increased cancer risk. The

attenuation rate of the protection equipment identified in this

study was 83.8% for a 0.5 mm lead apron, 77.9% for a 0.5 mm

lead thyroid protector, and 50.4% for 0.07 mm lead goggles. This

means that current equipment does not fully protect workers

from radiation exposure. The attenuation rate varied depending

on the kind. The most effective methods to reduce radiation

exposure during cardiac interventional procedures include

education regarding long-term exposure, developing a program to

decrease exposure to patients, installing proper equipment, and

using appropriate protective gear. Another method for reducing

exposure is in the operation of the machine. By setting a low level

for the fluoroscopy mode, preventing any unnecessary screen

widening, minimizing the source image distance (SID),

maximizing the source object distance (SOD), using a proper

filter, and selecting an image capture instead of spot image,

exposure to radiation for both patients and staff could be reduced.

The study had several limitations. First, the amount of indirect

radiation exposure in the patients could differ from the amount of

direct radiation exposure because of the calculation of the

radiation exposure using the PCXMC program with the DAP

value. Second, this study calculated the risk of cancer using the

BEIR VII study, but the potential cancer risk could be higher in

this study. This study ruled out many factors that could influence

the effective dose during the procedure, such as personnel,

mechanical, and environmental factors. Because the procedures

were performed with cardiac mode and a high frame rate setting,

the amount of radiation exposure was higher than we expected.

Recently, the fluoroscopic setting was changed to “low” and

cinematic acquisition imaging frame rates changed to 3.75

frames/sec in cardiac EP mode. Therefore, we assume that the

amount of radiation exposure was much reduced as compared to

the study results.

References

1) Park TH, Eichling JO, Schechtman KB, Bromberg BI, Smith JM,

Lindsay BD. Risk of radiation induced skin injuries from

arrhythmia ablation procedures. Pacing Clin Electrophysiol.

1996;19:1363-1369.

2) Lickfett L, Mahesh M, Vasamreddy C, Bradley D, Jayam V, Eldadah

Z, Dickfeld T, Kearney D, Dalal D, Luderitz B, Berger R, Calkins

H. Radiation exposure during catheter ablation of atrial fibrillation.

Circulation. 2004;110:3003-3010.

3) Kovoor P, Ricciardello M, Collins L, Uther JB, Ross DL. Risk to

patients from radiation associated with radiofrequency ablation for

supraventricular tachycardia. Circulation. 1998;98:1534-1540.

4) McFadden SL, Mooney RB, Shepherd PH. X-ray dose and

associated risks from radiofrequency catheter ablation procedures.

Br J Radiol. 2002;75:253-265.

5) Venneri L, Rossi F, Botto N, Andreassi MG, Salcone N, Emad A,

Lazzeri M, Gori C, Vano E, Picano E. Cancer risk from professional

exposure in staff working in cardiac catheterization laboratory:

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Minguez I. Dosimetric and radiation protection considerations

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protection--the iaea's initiatives. Int J Cardiol. 2007;114:256-260.

Radiation Dose and Cancer Risk

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10) Damilakis J, Theocharopoulos N, Perisinakis K, Manios E,

Dimitriou P, Vardas P, Gourtsoyiannis N. Conceptus radiation

dose and risk from cardiac catheter ablation procedures.

Circulation. 2001;104:893-897.

11) Rosenthal LS, Mahesh M, Beck TJ, Saul JP, Miller JM, Kay N,

Klein LS, Huang S, Gillette P, Prystowsky E, Carlson M, Berger

RD, Lawrence JH, Yong P, Calkins H. Predictors of fluoroscopy

time and estimated radiation exposure during radiofrequency

catheter ablation procedures. Am J Cardiol. 1998;82:451-458.

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Passman RS, Palmer A, Zimmer M, Davidson CJ. Effectiveness of

shielding for patients during cardiac catheterization or

electrophysiologic testing. Am J Cardiol. 2001;88:1320-1323.

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risks from exposure to low levels of ionizing radiation: Beir vii

phase 2. Washington, D.C., National Academies Press. 2006.

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medical x-ray examinations from measurements of the dose-area

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Arrhythmia 2015;16(1):4-10

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Arrhythmia 2015;16(1):11-18

Calcium Dynamics and the Mechanisms of Ventricular Tachycardia to Ventricular Fibrillation Transition in Cryoablated Rabbit Ventricles

Gyo-Seung Hwang, MD, PhD

Department of Cardiology, Ajou University School of

Medicine, Suwon, Korea

Received: December 22, 2014Revision Received: February 4, 2015Accepted: March 26, 2015Correspondence: Gyo-Seung Hwang, MD, PhD, Department of Cardiology, Ajou University School of Medicine, San 5 Wonchon-dong, Yeongtong-gu, Suwon, Korea, 443-721Tel: +82-31-219-4190, Fax: +82-31-219-5708 E-mail: hwanggs@medimail.co.kr

Copyright © 2015 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd.

ABSTRACT

Background and Objectives: An electrical shock applied on the T

wave can induce a brief period of ventricular tachycardia (VT), or

Wiggers’ stage I ventricular fibrillation (VF), which degenerates into

VF through the development of wavebreaks. The role of intracellular

calcium (Cai) dynamics on VT to VF transition remains unclear.

Subjects and Methods: We simultaneously mapped epicardial mem-

brane potential (Vm) and Cai after a T-wave shock in 10 Langendorff-

perfused rabbit ventricles. Optical mapping was performed on the

thin (0.5 mm) layer of the surviving left ventricular epicardium after

endocardial cryoablation. A biphasic waveform shock (117 ± 62 V)

was applied on the T wave with a S1-shock coupling interval of 142

± 25 ms to induce VT.

Results: A total of 145 episodes of new wavebreaks occurred from

within the mapped region, 1122 ± 647 ms after the shock, resulting

in VT to VF transition. In 135 of 145 episodes (93%), the wavebreaks

occurred when a wavefront visited an area with persistent Cai eleva-

tion. In 103 of the 135 episodes, this area was co-localized within

the wavebreak site and appeared to surround part of a Cai sinkhole.

In 4 episodes (3%), the wavebreak occurred when a wavefront vis-

ited an area already depolarized by another wavefront, without con-

comitant Cai elevation. However, 6 (4%) wavebreak episodes devel-

oped spontaneously regardless of the presence of another wavefront

and Cai dynamics.

Conclusion: Wavebreaks occurring in high Cai areas are the most

common phenomenon associated with VT to VF transition and con-

tinuing VF after a T-wave shock.

Key Words: ventricular tachycardia, ventricular fibrillation, calcium

ORIGINAL ARTICLES

12

Arrhythmia 2015;16(1):11-18

Introduction

Ventricular fibrillation (VF) initiates as a well-organized waves

consisting of one or two functionally re-entrant rotating waves

(rotors). This stage, classically defined as Wiggers stage 1 VF,

degenerates within seconds, into a more complex, less organized

activation pattern classically defined as Wiggers stage 2 VF.1 This

process is thought to involve wavebreaks, wherein wavefronts are

split into two or more pieces by a conduction block.

Wavebreaks can occur when wavefronts collide with an

obstacle, which can be either anatomic or functional, but the

occurrence of such events depends on tissue excitability, obstacle

size, and wavefront curvature.2 Previous studies showed that heart

wavebreaks seem to occur when wavefronts encounter zones of

refractoriness created by the passage of the previous activation.2,3

The restitution hypothesis predicts that a small perturbation in

action potential duration (APD) can result in larger APD changes

on a beat-to-beat basis (i.e., alternans), which would increase the

vulnerability to unidirectional conduction block and

wavebreaks.4,5 Furthermore, alternans can be spatially discordant,

when the phase of alternation is out of phase with different

regions of the heart, and tend to increase the dispersion of

refractoriness and the propensity to conduction blocks.6

While intracellular calcium (Cai) cycling is also increasingly

recognized as an important regulator of dynamic wave instability,

Cai dynamics may also contribute independently to initiation and

break of reentry;7,8 however, its role in wavebreak occurrence is still

unclear.

In this study, we aimed to classify the patterns of wavebreak

using dual optical mapping techniques to study membrane

potential (Vm) and Cai during the application of T-wave shocks,

as well as to examine the role of Cai dynamics.

To exclude the possibility that the wavebreak occurred

somewhere beneath the tissue surface, we studied 10 hearts in

which endocardial cryoablation left only a thin (0.5-mm) layer of

surviving epicardial tissue.

Materials & Methods

Surgical Preparation and Cryoablation

New Zealand white rabbits (N=10) weighing 3-5 kg were used

in this study. After general anesthesia, the rabbit hearts were

rapidly excised through midline sternotomy and immersed in cold

Tyrode’s solution (NaCl 125, KCl 4.5, NaH2PO4 1.8, NaHCO3

24, CaCl2 1.8, MgCl2 0.5, dextrose 5.5, and albumin 100 mg/L in

deionized water). The ascending aorta was immediately

cannulated and perfused with warm oxygenated Tyrode’s solution

(36.5ºC ± 0.5ºC, pH 7.4 ± 0.5) at a rate of 30-40 mL/min to

maintain a perfusion pressure between 80 and 95 mmHg. Two

widely spaced bipolar electrodes were used for continuous

pseudo-electrocardiography monitoring. Endocardial

cryoablation was performed by placing a 7-cm SurgiFrost® probe

(CryoCath Technologies Inc., Montreal) into the left ventricle

(LV). The probe temperature was decreased to -135ºC for 5-10

minutes, during which, the epicardium was protected by the

addition of warm (37°C) oxygenated Tyrode’s solution, while the

entire heart was continuously Langendorff-perfused. Bipolar

electrodes for S1 pacing were attached to the LV apex. Right

ventricular (RV) endocardial (cathode) and LV patch electrode

(anode) were placed for direct current (DC) shocks. After the

optical mapping study, we perfused the coronary arteries with 1%

triphenyl tetrazolium chloride (TTC) and sectioned the heart

horizontally into five equally spaced sections to document the

effects of cryoablation.

Optical Mapping

We used 0.5 mg of Rhod-2 AM (Molecular Probes) dissolved

in 1 mL of dimethylsulfoxide containing Pluronic F-127 (20%

wt/vol) to stain Cai. This solution was diluted in 300 mL of

Tyrode’s solution to achieve a final Rhod-2 AM concentration of

1.48 µmol/L, and was infused into the heart over a 10-min period.

After perfusion with dye-free Tyrode's solution for 15-30 min to

achieve Rhod-2 AM de-esterification, the heart was then stained

again by direct injection of a voltage sensitive dye (RH237,

Molecular Probes) into the perfusion system. The double-stained

heart was excited with a laser light at 532 nm. Fluorescence was

collected using two charge-coupled device (CCD) cameras

(Dalsa) covering the same mapped field. The CCD cameras for

Vm and Cai, were fitted with 715-nm long-pass and 580 ± 20 nm

band-pass filters, respectively. The digital images (128 × 128

13

Calcium Dynamics and Wavebreak Mechanisms

pixels) were gathered from the epicardium of the LV (25 x 25 mm2

area), resulting in a spatial resolution of 0.2 x 0.2 mm2 per pixel.

We acquired 1,000 frames continuously with a 12-bit resolution

(260-400 frames/second, or roughly 2.5-4 ms per frame). The

voltage sensitive dye RH237 was used because its emission

bandpass differs from that of Rhod-2, thereby preventing crosstalk

between the two signals. The signal-to-noise ratio of our mapping

system, as estimated from the peak-to-peak time variation in

fluorescence intensity, is 40 to 1 during pacing and about 5 to 1

during VF. Cytochalasin D (cyto-D, 5-10 µmol/L) was added to

the perfusate to minimize motion artifacts.

As two CCD cameras were used, the same anatomical location

may appear at different coordinates on the Vm and Cai maps.

Therefore, we implanted four cactus needles on the epicardium as

registration markers. A software program then used these markers

to match the pixels on the Vm and Cai maps to the same locations.

Data analyses were performed only with aligned maps.

Dual Optical Mapping of VT to VF Transition

After 8 S1 paced beats, biphasic truncated exponential

waveform shocks (117 ± 62 V) of fixed pulse duration (6 ms)

were delivered with a S1-shock coupling interval of 142 ± 25 ms

from a Ventritex HVS-02 defibrillator on the T wave with dual

optical mapping, and data recorded during the induction of VF.

AB

D

C

Vm

Vm

Cai

Cai

0 ms

236 ms

244 ms

Wavebreak

Shock 244 ms300 ms

240 ms

244 ms

-8

-4

0

4

8

3

2

0

-2

-3

(F-F)/F(%)

Figure 1. A wavebreak at a high Cai area. A. There were high (white asterisk) and low (yellow asterisk) Cai areas in the frame (236 ms). The wavefront only propagated (marked by white arrow) at the low Cai area (yellow asterisks on both Vm and Cai maps). B. The black arrow indicates phase singularity on the phase map. C. The surviving ventricular myocardium after endocardial cryoablation was stained brick red by 1% Triphenyl tetrazolium chloride. D. Optical tracing during shock on T. The red and black line segments indicate the time of shock and the time of VT to VF transition, respectively. The yellow and white asterisks on Vm maps indicate the same location as the yellow and white asterisks on the Cai maps, respectively. Cai, intracellular calcium; Vm, membrane potential; VT, ventricular tachycardia; VF, ventricular fibrillation.

14

Data Analysis

The activation maps were used to examine Vm and Cai patterns

during the induction of VF. The average fluorescence level (F) of

the entire data window was calculated first, and the fluorescent

level of each pixel was then compared with this average. We

assigned shades of red to represent above-average fluorescence and

shades of blue to represent below-average fluorescence to generate

the ratio maps. All data are presented as means ± SD.

Results

Patterns of Wavebreak

A total of 145 episodes of new wavebreaks occurred from

within the mapped region 1122 ± 647 ms, resulting in VT to VF

transition, with large and spatially heterogeneous variations of Vm

and Cai occurring shortly after the shock-induced VT. In 135 of

145 episodes (93%), the wavebreaks occurred when a wavefront

visited an area with persistent Cai elevation. The Vm map at that

site showed partial or full repolarization. Figure 1 shows a typical

example of a wavebreak in a high Cai area. Figure 1A shows Vm

and Cai maps at the time of the shock (0 ms) and three additional

snapshots 4 ms apart. In this and other color panels, the right and

left lower corners were outside of the heart and were cropped. The

bright dot observed at 0 ms is a light artifact used to indicate the

time of the shock, after which, the Cai map showed high Cai and

low Cai areas marked with a white and yellow asterisk,

respectively, in the 236-ms frame. In the Vm map, the wavefronts

propagated only from the corresponding low Cai area (yellow

A

B

C

Vm

Vm

Cai

Cai

0 ms

196 ms

244 ms

Shock 244 ms300 ms

208 ms

224 ms

-8

-4

0

4

8

3

2

0

-2

-3

(F-F)/F(%)

Figure 2. A wavebreak in the Cai sinkhole. The white arrow indicates Cai sinkhole like activity. The wavefront arose from the Cai sinkhole and made a wavebreak at the same site. The two black arrows in panel B indicate phase singularities that were developed in the Cai sinkhole. In panel C, the red and black line segments indicate the time of shock (0 ms) and the time of wave break (224 ms), respectively. Cai, intracellular calcium; Vm, membrane potential.

Arrhythmia 2015;16(1):11-18

15

asterisk in the 240-ms frame) and formed a wavebreak (white

arrow in the 244-ms frame). The black arrow shown in the phase

map (Figure 1B) indicates a phase singularity formed at the

boundary between the high and low Cai area, 244 ms after the

shock. Phase singularities are points surrounded by all phases of

activation that occur at the intersection of wavefronts and

wavebacks, formed by wavebreak events.7 Figure 1C shows a

ventricular myocardium after successful endocardial cryoablation.

While the surviving epicardium shows a brick red color after

staining with a 1% TTC solution, TTC-negative tissues show cell

necrosis and contraction bands, compatible with effective

cryoablation.

Figure 1D shows optical signals of Vm and Cai. Red and black

line segments indicate the time of shock, and VT to VF transition,

respectively. In 103 of the 135 episodes, the region of persistent

Cai elevation appeared to surround part of a Cai sinkhole (a low

Cai area surrounded by a high Cai area) which hindered wavefront

propagation, and led to the occurrence of the wavebreak in the Cai

sinkhole. Figure 2 shows a typical pattern of a wavebreak in the

Cai sinkhole that occurred 196 ms after the T-wave shock, shown

by the white arrow on panel A. An electrical activation, marked by

the yellow asterisk on the Vm Map in the 208-ms frame, arose

from the corresponding Cai sinkhole site. The wavefront

propagated (224 ms frame in panel A) and the wavebreak

occurred (black arrows in panel B). However, in 4 episodes (3%), a

wavebreak occurred when a wavefront encountered an area

already depolarized by another wavefront, without concomitant

Cai elevation. This is illustrated in Figure 3A by the lack of Cai

activation observed on the Cai map at the corresponding site of

the Y wavefront (marked by asterisk in the 832-ms frame) when

the X and Y wavefronts met. Nonetheless, the wavebreak then

developed at the edge of the X wavefront (white and black arrows

in the 852-ms frame shown in Figure 3A and 3B). In addition, 6

(4%) wavebreak episodes developed spontaneously regardless of

the presence of another wavefront and Cai dynamics. Figure 4

shows an example of a spontaneous wavebreak, in which the

wavefront (frame 510 ms) spontaneously split to both sides (525-

ms frame), resulting in a wavebreak (528-ms frame, Panel B).

A B

C

Vm

Vm

Cai

Cai

832 ms 852 ms

X

Y

Shock 852 ms

300 ms

852 ms

244 ms

-8

-4

0

4

8

3

2

0

-2

-3

(F-F)/F(%)

Figure 3. A wavebreak by another wavefront. A wavebreak developed (white arrow on panel A) when a wavefront (X) met an area (Y) already depolarized by another wavefront, without concomitant Cai elevation. The black arrow in panel B indicates phase singularity. In panel C, the red and black line segments indicate the time of shock (0 ms) and the time of wave break (852 ms), respectively. Cai, intracellular calcium; Vm, membrane potential.

(F-F)/F(%)

Calcium Dynamics and Wavebreak Mechanisms

16

Discussion

Wiggers first proposed four distinct phases of VF based on

epicardial motion visualized by high-speed cinematography in

canine hearts. The 4 stages are as follows: (1) initial tachysystolic

stage (0-1 s of VF), (2) stage of convulsive incoordination (1-40 s

of VF), (3) stage of tremulous incoordination (40 s-3 min of VF),

and (4) stage of progressive atonic incoordination (>3 min of

VF).1 The wavebreak (VT to VF transition) may occur during

stage 2. The present study showed that the formation of

wavebreaks at high Cai areas is the most common phenomenon

associated with the VT to VF transition and the continuation of

VF after a T-wave shock. These findings indicate that Cai

dynamics play an important role in the VT to VF transition.

Mechanisms of Wavebreak Generation

Tissue heterogeneity, resulting from electrical and structural

remodeling, has been considered a key factor promoting

wavebreaks. Recent evidence indicates that dynamic factors such

as cellular membrane voltage and Cai cycling operate

synergistically with tissue heterogeneity to promote wavebreaks.

Normally, when a wave propagates through tissue, the wavefront

and waveback never touch, but when they do, their point of

intersection defines a wavebreak. This point is sometimes called a

phase singularity,7 around which all phases of activation-recovery

(action potential) converge.9

Moreover, wavebreaks may also occur at anatomic source-sink

mismatches,7 such as pectinate10 and papillary muscle insertions,11

A B

C

Vm

Vm

Cai

Cai

510 ms

525 ms525 ms

Shock 525 ms

300 ms

528 ms

3

2

0

-2

-3

Figure 4. A spontaneous wavebreak. A wavebreak occurred regardless of another wavefront and transient Cai. The wavefront spontaneously divided along both directions (white arrows, 525 ms). The black arrows in panel B indicate phase singularities. In panel C, the red and black line segments indicate the time of shock (0 ms) and the time of wave break (525 ms), respectively. Cai, intracellular calcium; Vm, membrane potential.

-8

-4

0

4

8

(F-F)/F(%)

Arrhythmia 2015;16(1):11-18

17

or at the anterior right ventricular insertion site;12 they may also

occur when electrical excitability is depressed regionally due to

ischemia or drugs. However, a rotor induced by rapid pacing or a

premature stimulus, may spontaneously break up into a

fibrillation-like state despite homogeneous initial conditions.

Furthermore, dynamic factors may also induce fibrillation in

the normal heart.13,14 For instance, as the wavelength is the product

of APD and conduction velocity (CV), a steep APD restitution

slope ( >1)13,15 or a broad CV restitution can drive a wavebreak.16

An alternative possible explanation for the VT to VF transition

is also provided by Keldermann et al., who reported that a

mechanoelectrical feedback via stretch-activated channels could

induce the deterioration of an otherwise stable spiral wave into

turbulent wave patterns similar to that of VF.17

Calcium Dynamics and Wavebreak

The role of Cai cycling as a key factor in dynamic wave

instability is well recognized, and increasing evidence suggests

that, under normal physiological conditions, regulation of the

contractile force of the beating heart by Cai is tightly controlled by

Vm, such that the Cai transient is effectively slaved to the AP.

However, calcium-induced calcium release can exhibit

independent dynamics.7 For instance, Cai transients induce

alternans and highly complex periodicities, despite the fact that

the Vm waveform is fixed,18 and Cai alternans is also the

predominant cause of APD alternans19 and promoter of

wavebreaks.

Moreover, Cai dynamics plays an important role in the

mechanism of ventricular vulnerability and defibrillation. In fact,

we previously showed that the first postshock activation always

occurs from a Cai sinkhole after unsuccessful and type B successful

defibrillation shocks.8 In this study, most wavebreaks originated

around the high Cai area of the Cai sinkhole, as this region of

persistent Cai elevation hindered wavefront propagation,

generating the typical wavebreak pattern seen in Figure 2.

Therefore, the results from this study add to the accumulating

evidence suggesting that Cai dynamics plays an important role in

VT to VF transition and defibrillation.

Study Limitations

This study has a number of limitations. As with all current

optical mapping studies, deeper layers of myocardium could not

be examined for other possible preferential wavebreaks locations.

Although, this is the reason why we performed experiments using

cryoablated ventricles, the myocardial ischemia caused by

subendocardial cryoablation could have affected the results of this

study. It is possible that 10 wavebreak episodes were the result of

subepicardial wavebreaks, regardless of Cai dynamics, because

wavebreaks that occurred in the subepicardium could not be

detected by the epicardial mapping techniques used. In addition,

all experiments were performed with rabbit hearts (New Zealand

white rabbits), and mechanisms underlying wavebreaks may differ

in different species, as well as in ischemic and failing hearts.

Conclusion

Wavebreaks occurring in high Cai areas appears to be the most

common phenomenon associated with VT to VF transition and

continuing VF after a T-wave shock. These findings indicate that

Cai dynamics play an important role in the mechanisms of VT to

VF transition.

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Arrhythmia 2015;16(1):19-24

Effects of Angiotensin Converting Enzyme Inhibitors and Statins on Endothelial Function, Inflammation, and Coagulation in Patients with Hypertension and Atrial Fibrillation

Hyung Wook Park, MD, Min Chul Kim, MD, Kyung Hoon Cho, MD, Cheol Hwan Kim, MD, Kyung Hwan Kim, MD, Seung Jin Jun, MD, Woo Jin Kim, MD, Kyoung Jin Lee, MD, Sung Soo Kim, MD, Hyun Kuk Kim, MD, Hae Chang Jeong, MD, Jae Yeong Cho, MD, Ki Hong Lee, MD, Nam Sik Yoon, MD , Keun-Ho Park, MD, Doo sun Sim, MD, Hyun Ju Yoon, MD, Kye Hun Kim, MD, Young Joon Hong, MD, Ju Han Kim, MD, Youngkeun Ahn, MD, Myung Ho Jeong, MD, Jeong Gwan Cho, MD, Jong Chun Park, MD

Department of Cardiovascular Medicine, Chonnam

National University Hospital, Gwangju, Korea

Received: January 21, 2015Revision Received: March 16, 2015Accepted: March 26, 2015Correspondence: Hyung Wook Park, MD, Division of Cardiology, Department of Internal Medicine, Chonnam National University Hospital, Gwangju, KoreaTel: +82-62-220-6415, Fax: +82-62-223-3105, E-mail: mdhwp@chol.com

Copyright © 2015 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd.

ABSTRACT

Introduction: The renin-angiotensin-aldosterone system has been reported to affect the endothelial function, prothrombotic and hy-percoagulable state, and maintenance of atrial fibrillation (AF). Whether angiotensin converting enzyme inhibitors (ACEIs) and statins improve the prothrombotic condition of patients with hyper-tension and AF is unclear.Materials & Methods: Patients with hypertension and AF were di-vided into four groups: Group I (N=15; M:F, 10:5; age, 49±6 years) received no ACEI or statin, group II (N=17; M:F, 11:6; age, 48±6 years) received cilazapril 5 mg without statin, group III (N=18; M:F, 9:9; age, 49±7 years) received cilazapril 5 mg and atorvastatin 10 mg, and group IV (N=16; M:F, 10:6; age, 45±3 years) received cila-zapril 5 mg and atorvastatin 40 mg. Serum markers of endothelial function (von Willebrand factor [vWF]), inflammation (quantitative and high-sensitivity C-reactive protein, erythrocyte sedimentation rate), and coagulation (fibrinogen, fibrinogen degradation product, d-dimer) were measured at baseline and 6 months. Results: There were no thromboembolism cases in any group during the 6-month follow up. There were no significant differences in the levels of each marker at baseline. There were no significant changes in vWF at 6 months in group I and II; however. it was significantly re-duced at 6 months (172±43%, vs. 110±41%, p=0.001) in group III. vWF and fibrinogen levels were significantly reduced at 6 months in group IV (184±52% vs. 150±68%, p=0.021 and 331±73 mg/dL vs. 275±57 mg/dL, p=0.047, respectively). Other markers were not changed significantly in any group.Conclusion: High doses of statin and ACEI may have a beneficial ef-fect on endothelial function and coagulation, which may contribute to the reduction of thromboembolism risk in patients with hyperten-sion and AF.

Key Words: atrial fibrillation, thromboembolism, angiotensin con-

verting enzyme inhibitor, statin

ORIGINAL ARTICLES

20

Arrhythmia 2015;16(1):19-24

IntroductionAtrial fibrillation (AF) is a common cardiac arrhythmia

associated with a substantial risk of stroke and thromboembolism.1

Although the mechanism of stroke and thromboembolism in AF

patients is incompletely understood, the increased risk is mainly

due to the embolization of thrombus formed within the left atrial

appendage.2 There is increasing evidence that the increased risk of

stroke and thromboembolism in AF patients is facilitated by

increased thrombogenesis, with changes in the left atrial wall, a

prothrombotic or hypercoagulable state (including abnormalities

of hemostasis, thrombosis, and platelet and endothelial function),

and AF-related inflammation, leading to the fulfillment of

Virchow's triad.3-8

The renin-angiotensin-aldosterone system and inflammation

have been reported to affect the endothelial function,

prothrombotic and hypercoagulable state, and maintenance of

AF. It is not certain whether angiotensin converting enzyme

inhibitors (ACEIs) and statins improve the prothrombotic

condition in hypertension patients and reduce thromboembolism

in patients with persistent and permanent AF.

Material and Methods

All patients enrolled had hypertension, more than one known

risk factor for thromboembolism, and no prior history of taking

ACEIs, angiotensin receptor blockers, or statins. The enrolled

patients were randomly assigned to four groups. Group I (N=15;

M:F, 10:5; age, 49±6 years) received no ACEI or statin, group II

(N=17; M:F, 11:6; age, 48±6 years) received cilazapril 5 mg

without statin, group III (N=18; M:F, 9:9; age, 49±7 years)

received cilazapril 5 mg and atorvastatin 10 mg, and group IV

(N=16; M:F, 10:6; age, 45±3 years) received cilazapril 5 mg and

atorvastatin 40 mg.

Serum markers of endothelial function (von Willebrand factor

[vWF]), inflammation (quantitative and high sensitive C-reactive

protein [CRP], erythrocyte sedimentation rate [ESR]), and

coagulation (fibrinogen, fibrinogen degradation product [FDP],

d-dimer) were measured at baseline and 6 months. Blood samples

were obtained by atraumatic venipuncture in the morning, after

fasting for >12 hours. Blood was drawn without stasis into a tube

preloaded with trisodium citrate. vWF was measured by the

enzyme-linked immunosorbent assay technique using commercial

reagents (R & D systems, MN, USA). CRP was measured by the

latex agglutination method (quantitative CRP, Behring

nephelometer analyzer; high-sensitivity CRP, Olympus AU

5400). Measurements of fibrinogen, FDP, and d-dimer were

performed with chromogenic assay (Sysmex CA1500, Sysmex

Corporation, Kobe, Japan).

All patients received antithrombotic therapy according to the

American College of Cardiology/American Heart Association

guideline. Drugs for heart rate control were prescribed equally

among all groups. Those who received anti-inflammatory drugs

such as steroids were excluded. Previously established and widely

accepted epidemiologic risk factors for thromboembolism

including old age (≥65 years), hypertension, diabetes mellitus,

heart failure, and history of embolism were investigated, and

echocardiographic parameters including left ventricular ejection

fraction (LVEF) and left atrial dimension were measured. Left

ventricular dysfunction was defined as LVEF less than 40%.

Exclusion criteria were recent (<6 months) myocardial infarction

or acute coronary syndrome, stroke, infection or inflammatory

disease, surgery, malignancy, thyrotoxicosis, and renal or liver

impairment.

Results are expressed as mean ± standard deviation.

Comparison of serum markers between groups were analyzed

using the paired t-test and analysis of variance. All statistical

calculations were performed using commercially available

statistical package software (SPSS version 12.0; IBM

Corporation, IL, USA). A P value <0.05 was considered

statistically significant.

Results

Clinical and demographic characteristics of the study

population are shown in Table 1. There were no significant

changes at 6 months or between-group differences in total

cholesterol, low-density lipoprotein cholesterol, high-density

lipoprotein cholesterol, and triglyceride levels at baseline and 6

months (Figure 1).

21

Markers of Endothelial Dysfunction

The vWF (factor 8-related antigen) level was significantly

decreased from baseline to 6 months in groups III and IV which

received statin (group III, 172% to 110%, p<0.001; group IV,

184% to 125%, p=0.021). There were no significant changes in

the vWF (ristocetin cofactor) level at 6 months or between-group

differences at baseline and 6 months (Figure 2).

Markers of Inflammatory Activity

There were no significant changes at 6 months or between-

group differences in ESR and CRP (quantitative and high-

sensitivity) levels at baseline and 6 months (Figure 3).

Coagulation Markers

Fibrinogen levels were significantly decreased in group IV

(331±73 mg/dL vs. 275±57 mg/dL, p=0.047). However, there

were no significant changes in the other coagulation markers

(Figure 4).

Discussion

Endothelial dysfunction may lead to increased endothelial

adhesiveness to leukocytes and the production of procoagulant

and vasoactive molecules, cytokines, and growth factors.9 The

vWF is a multifunctional plasma protein that plays a very

important role in hemostasis following vascular injury. Circulating

platelets adhere to the injured site and initiate the process of

thromobosis, and subendothelial vWF mediates platelet adhesion

to the injured site. The vWF is secreted not only from the vascular

endothelium but also from the atrial endocardium in response to

vascular injury and vascular disease. Raised plasma levels of vWF

were reported to be associated with widespread endothelial

damage/dysfunction, atherothrombosis, left atrial endothelial

damage, and left atrial appendage thrombosis.10,11 Also,

thrombomodulin (TM), a transmembrane spanning protein

which can also be cleaved from the membrane to circulate in a

soluble form, is one of the major anticoagulant components of the

endothelial surface.12,13 Thrombin bound to TM consequently

loses its procoagulant and proinflammatory functions. It cannot

cleave fibrinogen or activate platelets and factor XIII.14 The

present study results suggest that markers of endothelial

dysfunction, especially the vWF, are associated with known

epidemiologic risk factors for thromboembolism in Korean AF

patients. Furthermore, ACEI and statin use could improve the

endothelial function after 6 months, regardless of the statin dose.

There is an apparent link between thrombogenesis and

Hypertension and Atrial Fibrillation

Table 1. Clinical characteristics of patients

Group I (n=15) Group II (n=17) Group III (n=18) Group IV (n=16) P value

Age (y) 49±6 48±6 49±7 45±3 NS

Men, n 10 11 9 10 NS

Echocardiography

LVEF (%) 66±9 68±4 63±4 61±7 NS

LAD (mm) 34±8 37±8 37±14 39±12 NS

Risk factors for TE, n (%) NS

Hypertension 15 (100) 17 (100) 18 (100) 16 (100)

Diabetes mellitus 3 (15) 4 (24) 5 (28) 5 (31)

Age (≥65 years) 8 (53) 9 (53) 10 (56) 9 (56)

LV failure (EF <40%) 3 (20) 2 (12) 5 (28) 4 (24)

History of TE 0 0 1 (7) 1 (6)

EF, ejection fraction; LAD, left atrial dimension; LVEF, left ventricular ejection fraction; TE, thromboembolism.

22

inflammation. An established index of inflammation is

interleukin-6 (IL-6), which is a circulating cytokine produced by

monocytes, macrophages, T-lymphocytes, and endothelial cells.

IL-6 can induce a prothrombotic state by increasing the

expression of fibrinogen, tissue factor, factor VIII, and von

Willebrand factor, as well as by activating endothelial cells and

increasing platelet production.3-5 Elevated CRP levels have been

reported in AF patients, reflecting an inflammatory state, which

could promote the persistence of AF.15 Although the CRP level

was increased and correlated with some known risk factors for

thromboembolism in previous studies, the use of ACEI or statin

did not affect these markers or composite endpoint even with

high doses. These results suggested the lesser role of inflammation

in terms of thromboembolic risks in Korean AF patients.

The level of hemostatic activation may also reflect the

underlying mechanism of thromboembolism, especially

pronounced in cardioembolic stroke.16 Fibrin D-dimer assay is

based on the production of cross-linked fibrin by thrombin,

making it a sensitive marker of fibrin turnover, and allows the

recognition of activated coagulation.17 Coagulation markers were

substantially increased and associated with some risk factors for

thromboembolism, and the use of high-dose atorvastatin at 40 mg

could reduce fibrinogen levels after 6 months. Further well-

controlled studies are required to evaluate the clinical effect of this

dose and treatment duration.

There were no remarkable lipid profile changes even after 6

months of treatment with high-dose statin therapy. This result

may have been associated with patient compliance. The

mechanism of the pleiotropic effect of statins which involves an

improvement in endothelial function and coagulation is unclear.

While the benefits of antithrombotic therapy in preventing

stroke in AF patients are being increasingly recognized, further

developments in thromboprophylaxis are needed, especially as

warfarin confers the inconvenience of regular monitoring of

Figure 1. Total cholesterol (A), low-density lipoprotein cholesterol (B), high-density lipoprotein cholesterol (C), and triglyceride levels (D) at baseline and 6 months.

A

C

B

D

Arrhythmia 2015;16(1):19-24

23

Figure 3. Levels of inflammation markers (erythrocyte sedimentation rate (A), quantitative C-reactive protein (B), high-sensitivity C-reactive protein (C)) at baseline and 6 months.

Figure 2. Von Willebrand factor (%) at baseline and 6 months (factor 8-related antigen (A), ristocetin cofactor (B)).

Figure 4. Levels of coagulation markers (fibrinogen (A), fibrinogen degradation product (B), fibrin D-dimer (C)) at baseline and 6 months.

A

A

A

C

C

B

B

B

Hypertension and Atrial Fibrillation

24

prothrombin time (PT) and the benefits of aspirin are

inconsistent. Current clinical practice for prevention of

thromboembolic stroke in AF patients is limited not only by the

low efficacy of antiplatelet therapy but also by the hemorrhagic

complications and the inherent need for PT monitoring with

warfarin therapy.18

In conclusion, the present study showed some beneficial effects

of ACEI and high-dose statin on endothelial function and

coagulation. The use of these drugs in addition to the

conventional treatment with anticoagulation drugs may be useful

for the prevention of thromboembolic events in high-risk patients

or for secondary prevention of thromboembolism. The present

study findings should be verified in further randomized

controlled studies.

References

1) Wolf PA, Abbot RD, Kannel WB. Atrial fibrillation as an

independent risk for stroke: the Framingham Study. Stroke.

1991;22:983-988.

2) Hart RG, Halperin JL. Atrial fibrillation and stroke: concepts and

controversies. Stroke. 2001;32:803-808.

3) Lip GYH, Lowe GDO, Rumley A, Dunn FG. Increased markers of

thrombogenesis of chronic atrial fibrillation: effects of warfarin

therapy. Br Heart J. 1995;73:527-533.

4) Lip GYH. Does atrial fibrillation confer a hypercoagulable state?

Lancet. 1995;346:1313-1314.

5) Kumagai K, Fukunami M, Ohmori M, Kitabatake A, Kamada T,

Hoki N. Increased cardiovascular clotting in patients with chronic

atrial fibrillation. J Am Coll Cardiol. 1990;16:377-380.

6) McEver RP. Adhesive interactions of leukocytes, platelets, and the

vessel wall during hemostasis and inflammation. Thromb Haemost.

2001;86:746-756.

7) Kerr R, Stirling D, Ludlam CA. Interleukin 6 and haemostasis. Br J

Hematol. 2001;115:3-12.

8) Joseph L, Fink LM, Hauer-Hensen M. Cytokines in coagulation

and thrombosis: a preclinical and clinical review. Blood Coagul

Fibrinol. 2002;13:105-116.

9) Blann AD. Endothelial cell activation, injury, damage and

dysfunction: separate entities or mutual terms. Blood Coagul

Fibrinolysis. 2000;11:623-630.

10) Conway DSG, Pearce LA, Chin BSP, Hart RG, Lip GYH.

Prognostic value of plasma von Willebrand factor and soluble

P-selectin as indices of endothelial damage and platelet activation

in 994 patients with nonvalvular atrial fibrillation. Circulation.

2003;107:3141-3145.

11) Roldan V,Marin F, Garcia-Herola A, Lip GYH. Correlation of

plasma von Willebrand fator levels, an index of endothelial

damage/dysfunction, with two point-based stroke risk

stratification scores in atrial fibrillation. Thromb Res.

2005;116:321-325.

12) Califano F, Giovanniello T, Pantone P, Campana E, Parlapiano F.

Clinical importance of thrombomodulin serum levels. Eur Rec

Med Pharmacol Sci. 2000;4:59-66.

13) Maruyama I. Thrombomodulin, an endothelial anticoagulant; its

structure, function and expression. Jpn Circ J. 1992;56:187-191.

14) Fuentes-Prior P, Iwanaga Y, Huber R, Pagila R, Rumennik G, Seto

M, et al. Structural basis for the anticoagulant activity of the

thrombin-thrombomodulin complex. Nature. 2000;404:518-525.

15) Chung MK, Martin DO, Sprecher D, Wazni O, Kanderian A,

Carnes CA, et al. C-reactive protein elevation in patients with

atrial arrhythmias. Inflammatory mechanisms and persistence of

atrial fibrillation. Circulation. 2001;104:2886-2891.

16) Feinberg WM, Erickson LP, Bruck D, Kittelson J. Hemostatic

markers in acute ischemic stroke. Association with stroke type,

severity, and outcome. Stroke. 1996;27:1296-1300.

17) Lip GYH, Lowe GDO. Fibrin D-dimer turnover;a useful clinical

marker of thrombogenesis? Clin Sci. 1995;89:205-214.

18) Levine MN, Raskob G, Landefeld S, Kearon C: Hemorrhagic

complications of anticoag ulant treatment. Chest.

2001;119:108S-121S.

Arrhythmia 2015;16(1):19-24

25

Arrhythmia 2015;16(1):25-29

서론

심방세동은심장부정맥중에서가장흔한부정맥으로

비판막성심방세동환자의경우혈전색전증에의한뇌졸중의

빈도가약5배증가하고,매년약5%의뇌졸중이발생하는

것으로알려져있다. 심방세동에의한혈전색전증으로

뇌졸중이발생하는경우의90%가좌심방이에서유발된

혈전색전증에의한것으로알려져있고,다른원인에의한

경우보다뇌손상의범위가크며,신경학적장애가심하여

사망이나중증장애로이어질위험이높다.따라서심방세동

환자에서항응고제치료를통한혈전색전증예방은매우

중요한치료전략중하나이다.

그렇지만 이러한 항응고제 치료는 출혈 위험도를

증가시키는문제점이있다.최근에새로운항응고제를이용한

여러 연구에서도 추적관찰 결과 20-30%의 환자에서

항응고제를중단하는것으로보고되었고,이렇게항응고제

투여를중단한경우에혈전색전증의위험성이증가하였다.

하지만심방세동환자에서항응고제의사용에문제가있는

경우좌심방이폐색술이항응고제를대체할수있을것으로

생각된다.현재경피적좌심방이폐색기구로서Watchman™

과Amplatzer™CardiacPlug(ACP)두가지기구가시술에

사용되고있으며,비교적좋은결과가발표되고있다.이에

비판막성심방세동환자에서좌심방이폐색술치료에대한

소개및적응증에대해기술하고자한다.

비판막성심방세동환자에서뇌졸중위험도평가

2012년ESC(EuropeanSocietyofCardiology)심방세동

치료권고안및2014년AHA/ACC/HRS(AmericanHeart

Association/American College of Cardiology/Heart

RhythmSociety)심방세동치료권고안에서CHA2DS2-

VASc점수(Table1)를뇌졸중위험도평가를위해추천하고

있다. 심부전(Congestive heart failure), 고혈압

(Hypertension),연령(Age:75세이상2점,65-74세1점),

좌심방이 폐색술의 소개와 적응증

Received: November 7, 2014Revision Received: February 23, 2015Accepted: March 26, 2015Corresponding author: Young Keun On, MD, PhD, FHRS, Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, #81 Irwon-ro Gangnam-gu, Seoul, Korea, 135-710Tel: +82-2-3410-3420, Fax: +82-2-3410-3849E-mail: yk.on@samsung.com, oykmd123@gmail.com

Copyright © 2015 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd.

Young Keun On, MD, PhD, FHRS

Division of Cardiology, Department of Medicine, Samsung

Medical Center, Sungkyunkwan University School of

Medicine

ABSTRACT

Atrial fibrillation (AF), whether paroxysmal, persistent, or perma-

nent, and whether symptomatic or silent, significantly increases the

risk of thromboembolic ischemic stroke. Non-valvular AF increases

the risk of stroke by 5 times. Thromboembolism occurring with AF

is associated with a greater risk of recurrent stroke, more severe dis-

ability, and mortality. Most strokes in patients with AF result from

thrombus formation in the left atrial appendage (LAA). Occlusion of

the LAA by means of a device could be an alternative to oral antico-

agulation, mainly in patients who cannot tolerate the latter therapy

because of a high bleeding risk.

Key Words: atrial fibrillation, thromboembolism, anticoagulation,

left atrial appendage

MAIN TOPIC REVIEWS

26

당뇨병(Diabetes mellitus), 뇌졸중(Stroke), 혈관질환

(Vasculardisease)과성별(여성1점)의종합점수로비판막성

심방세동환자에서의뇌졸중위험도를평가한다.CHA2DS2-

VASc점수2점이상인뇌졸중고위험군환자에서는반드시

항응고제를사용하도록권고하고,CHA2DS2-VASc점수1

점에서도 뇌졸중 위험도와 출혈 위험도를 비교하여

항응고제의사용을고려하도록권고하고있다.

비판막성심방세동환자에서항응고제치료에따른

출혈위험도평가

항응고제사용에따른출혈위험도를임상에서쉽게

평가하기위해HAS-BLED출혈위험점수(HAS-BLED

bleedingriskscore,Table2)의사용을추천하고있다.이는

고혈압(Hypertension),신장혹은간기능이상(Abnormal

renal/liverfunction),뇌졸중(Stroke),출혈의병력이나성향

(Bleedinghistoryorpredisposition),불안정한INR(Labile

INR[internationalnormalizedratio]),고령(Elderly,65세

이상)및출혈성향을증가시키는약제나과량의술(Drug/

alcohol)등의복용을출혈위험인자로고려한점수이다.

HAS-BLED출혈위험점수가0-1점이면중증출혈의

빈도가약1%,5점이면12.5%정도로알려져있고,3점

이상이면중증출혈의빈도가3.74%정도로고위험군에

해당된다.그러나출혈고위험군환자라도항응고제의사용을

금기하는것은아니며,항응고제치료시교정이가능한출혈

위험인자를적극적으로교정하도록권고하고있다.

좌심방이의해부학적이해

비판막성심방세동에의한혈전색전증으로발생하는

뇌졸중의약90%는좌심방이에서유발된혈전색전증에의한

것으로알려져있다.좌심방이는방실구(atrioventricular

sulcus)의앞쪽에위치하고있고,주위에좌회선동맥(left

circumflexartery),좌측횡격막신경(leftphrenicnerve),

좌측폐동맥(left pulmonary artery),좌측폐정맥(left

pulmonaryvein)등이분포하고있다.좌심방이의모양은

매우다양하고,크게4가지형태로분류한다.선인장(cactus)

형태,닭날개(chickenwing)형태,풍향계(windsock)형태,

양배추(cauliflower)형태로나뉘어진다.

혈전색전성뇌졸중을예방하기위해좌심방이폐색술및

절제술이시행되고있고,이러한치료법에는심장수술과

동시에시행하는좌심방이절제술,흉강경을통한좌심방이

절제술,심외접근을통한경피적좌심방이폐색술,혈관을

통한 경피적 심내 접근 좌심방이 폐색술 등이 있다.

혈전색전성뇌졸중을예방하기위한좌심방이폐색술을

시행하기위해서는좌심방이및주위구조물에대한정확한

해부학적인이해가필요하다.시술전및시술중좌심방이

구조물에대한경식도심초음파,CT,X-선투시검사,

조영술등을포함한다양한영상검사의이해및적절한

좌심방이폐색술기구의선택이필요하며,시술후에도

Arrhythmia 2015;16(1):25-29

Table 1. CHA2DS2-VASc score

Letter Risk factor Score

C Congestive heart failure/LV dysfunction 1

H Hypertension 1

A2 Age ≥75 2

D Diabetes mellitus 1

S2 Stroke/TIA/thromboembolism 2

V Vascular disease* 1

A Age 65-74 1

S Sex category (i.e. female sex) 1

Maximum score 9

* Prior myocardial infarction, peripheral artery disease, aortic plaque LV, left ventricular; TIA, transient ischemic attack.

27

좌심방이 폐색술의 소개와 적응증

좌심방이구조물에대한경식도심초음파검사등의영상

추적관찰이필요하다.

좌심방이폐색술의기존연구

심방세동환자에서항응고제의사용에문제가있는경우

좌심방이폐색술이항응고제를대체하여사용될수있을

것으로생각되고,현재경피적좌심방이폐색기구로서

Watchman™device(BostonScientific,MapleGrove,MN,

USA)와ACP(St.JudeMedical,Minneapolis,MN,USA)두

가지기구가국내에서시술되고있다.

현재까지좌심방이폐색술에대한대규모임상은부족한

실정이며,Watchman™device에대한소규모무작위배정

연구및Watchman™device와ACPdevice에대한몇몇

관찰연구에서좋은결과가발표되고있다.

PROTECTAF (Watchman™LeftAtrialAppendage

SystemforEmbolicProtection inPatientsWithAF)1는

좌심방이폐색술에대한최초의무작위배정연구로항응고제

치료에비하여Watchman™device의비열등성을보고자한

연구이다.연구대상자의기준은 18세이상의비판막성

심방세동환자로CHADS2점수1점이상으로하였고,제외

기준은warfarin금기환자,좌심방이내에혈전,심방중격류

(septalaneurysm)를동반한난원공개존증(patentforamen

ovale),움직이는대동맥죽종,증상이있는경동맥질환

등이었다. 좌심방이 폐색술 이후 warfarin을 45일간

사용하였고,경식도심초음파검사후에warfarin을중단하고

aspirin과clopidogrel병합요법을6개월까지투여하였으며,

이후aspirin단독으로진행하였다.Warfarin군은6개월

동안2주간격으로INR을2-3으로유지하였고,이후한달

간격으로검사하였다.

1년추적관찰결과warfarin군66%에서INR2-3의

범위를보였고,Watchman™device군과warfarin군에서

혈전색전의차이는없었다.Watchman™device군에서주로

시술과관련된합병증이약 10%로보고되었다.이러한

시술과관련된합병증은시술자의경험이쌓임에따라

감소하여이후발표된CAP(continuousaccessprotocol)

registry2에서는약3.7%로보고되었다.

ASAP(ASAPlavixFeasibilityStudyWithWatchman™

LeftAtrialAppendageClosureTechnology)연구3는

warfarin금기환자를대상으로CHADS2점수1점이상(평균

2.8)으로하였고,좌심방이폐색술이후aspirin과clopidogrel

병합요법을6개월까지투여하였으며,이후aspirin단독으로

진행하였다.95%에서성공적으로Watchman™device를

시술하였고, 1년추적관찰결과허혈성뇌졸중이 1.7%

발생하여유사한CHADS2점수의심방세동환자군에비해

Table 2. HAS-BLED bleeding risk score

Letter Risk factor Score

H Hypertension 1

A Abnormal renal and liver function (1 points each) 1 or 2

S Stroke 1

B Bleeding 1

L Labile INRs 1

E Elderly (e.g. age >65 years) 1

D Drugs or alcohol (1 point each) 1 or 2

Maximum score 9

* 'Hypertension' is defined as >systolic blood pressure 160 mmHg, ‘Abnormal kidney function’ is defined as the presence of chronic dialysis or renal transplantation or serum creatinine ≥200 mmol/L. ‘Abnormal liver function’ is defined as chronic hepatic disease (cirrhosis) or biochemical evidence of significant hepatic derangement (bilirubin >2 x upper limit of normal, in association with aspartate aminotransferase/alanine aminotransferase/alkaline phosphatase >3 x upper limit normal, etc.). ‘Bleeding’ refers to previous bleeding history and/or predisposition to bleeding, e.g. bleeding diathesis, anemia, etc. ‘Labile INRs’ refers to unstable/high INRs or poor time in therapeutic range (<60%). Drugs/alcohol use refers to concomitant use of drugs, such as antiplatelet agents, non-steroidal anti-inflammatory drugs, or alcohol abuse, etc.

INR, international normalized ratio.

28

77%의뇌졸중감소율,aspirin과clopidogrel병합요법군에

비해64%의뇌졸중감소율을보였을것으로보고하였다.

ACPdevice에대한유럽의관찰연구4에의하면152명의

환자에서시술되었으며,15명(9.8%)에서시술관련부작용이

관찰되었고,10년간추적관찰하였을때1.3%의혈전색전증

관련사건이발생하였다.

ACP device에 대한 캐나다의 관찰 연구5에 의하면

비판막성심방세동환자로warfarin금기증인평균CHADS2

점수 3점인 환자를 대상으로 98%의 환자에서시술에

성공하였고,1.9%에서기구색전,1.9%에서심낭삼출의

합병증이관찰되었다.시술이후 3개월까지 aspirin과

clopidogrel 병합요법을 시행하고, 이후 단독

항혈소판제요법을시행하였다.평균20개월추적관찰에서

3.4%의뇌졸중및색전증을보여기대치10%에비해낮은

수치를보고하였고,주된출혈도3.4%로기대치8.7%에비해

낮은수치를보였다.

좌심방이폐색술의적응증

2012년ESC권고안에는비판막성심방세동환자에서

뇌졸중발생위험이높고,장기간의항응고제사용이금기인

경우에좌심방이폐색술을고려할수있다고언급하였다

(Figure1).

기존에발표된연구들을참고하여비판막성심방세동환자

중에서1)CHA2DS2-VASc점수2이상이고HAS-BLED

출혈위험점수3이상인고위험군에서항응고제사용후에

반복적인출혈로항응고제를사용할수없는경우, 2)

항응고제의과민증등의금기증이있는경우,3)항응고제를

Figure 1. Evaluation scheme for considering left atrial appendage occlusion.LAAC, left atrial appendage closure, TIA, transient ischemic attack.

Prior stroke/TIA while on anticoagulant

therapy

Unwilling to take anticoagulant

therapy

Persistent non-compliance with

anticoagulant therapy

Non-valvular atrial fibrillation

LAAC therapy

Thromboembolic risk (CHA2DS2-VASc≥2)but no effective anticoagulation

Recurrent bleeding on

anticoagulant therapy

Intolerant to anticoagulant

therapy

Contraindicationto anticoagulant

therapy

Thromboembolic risk (CHA2DS2-VASc≥2)AND Bleeding risk (HAS-BLED≥3)

Arrhythmia 2015;16(1):25-29

29

사용하기어려운경우에좌심방이폐색술을고려할수있고,

또한 4) CHA2DS2-VASc점수 2이상인고위험군에서

항응고제사용후에도뇌졸중이발생하거나5)항응고제

사용의순응도가낮은경우,6)항응고제의사용을거부하는

경우에좌심방이폐색술을고려할수있다.6

현재까지 좌심방이 폐색술의 대규모 임상은 부족한

실정으로좌심방이폐색술의효과에대한좀더장기적인

연구결과및새로운항응고제에대한비교연구등이

필요하므로무차별적인좌심방이폐색술에대한시도보다는

가장효과적일수있는적응증에대한연구가필요하리라

생각된다.

결론

심방세동의치료전략에는혈전색전증에의한뇌졸중

예방을위한항응고요법이매우중요하며,뇌졸중위험도와

항응고제사용에따른출혈위험도를평가하여환자개인별로

맞춤 치료를 해야 한다. CHA2DS2-VASc 점수 2점

이상에서는반드시항응고제를사용하도록권고하고있지만,

비판막성심방세동환자에서항응고제의사용에문제가있는

경우는좌심방이폐색술이항응고제를대체하여사용될수

있을 것으로 기대한다. 또한 좌심방이 폐색술이 가장

효과적인적응증에대한연구도필요할것이다.

References

1) Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H,

Buchbinder M, Mullin CM, Sick P; PROTECT AF Investigators.

Percutaneous closure of the left atrial appendage versus warfarin

therapy for prevention of stroke in patients with atrial fibrillation: a

randomised non-inferiority trial. Lancet. 2009;374:534-542.

2) Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of

percutaneous left atrial appendage closure: results from the

Watchman Left Atrial Appendage System for Embolic Protection

in Patients with AF (PROTECT AF) clinical trial and the

Continued Access Registry. Circulation. 2011;123:417-424.

3) Reddy VY, Mobius-Winkler S, Sievert H, Miller MA, Neuzil P,

Schuler G, Wiebe J, Sick P, Sievert H. Left atrial appendage closure

with the Watchman device in patients with a contraindication for

oral anticoagulation: ASA Plavix Feasibility Study with Watchman

Left Atrial Appendage Closure Technology (ASAP Study). J Am

Coll Cardiol. 2013;61:2551-2556.

4) Nietlispach F, Gloekler S, Krause R, Shakir S, Schmid M, Khattab

AA, Wenaweser P, Windecker S, Meier B. Amplatzer left atrial

appendage occlusion: single center 10-year experience. Catheter

Cardiovasc Interv. 2013;82:283-289.

5) Urena M, Rodes-Cabau J, Freixa X, Saw J, Webb JG, Freeman M,

Horlick E, Osten M, Chan A, Marquis JF, Champagne J, Ibrahim

R . Percutaneous left atrial appendage closure with the

AMPLATZER cardiac plug device in patients with nonvalvular

atrial fibrillation and contraindications to anticoagulation therapy. J

Am Coll Cardiol. 2013;62:96-102.

6) John CA, Colombo A, Corbucci G, Palletized L. Left atrial

appendage closure: a new technique for clinical practice. Heart

Rhythm. 2014;11:514-521.

좌심방이 폐색술의 소개와 적응증

30

Arrhythmia 2015;16(1):30-36

서론

심방세동은가장흔한지속성부정맥이며,심인성뇌경색의

주된원인이다.심방세동환자에서심방의효과적인수축이

없기때문에좌심방내에혈액의저류가형성되고,이것으로

인하여혈전생성이촉진된다.주로혈전이형성되는부위는

좌심방이로알려져있다.1심방세동환자의관리에있어서

뇌경색의예방이가장중요한부분이다.유의한판막질환이

없는심방세동환자의뇌경색예방을위한표준지침은

CHA2DS2-VASc 점수를 이용하여 뇌경색의 위험도를

평가하고경구항응고제를투여하는것이다.2,3 그러나

항응고제의출혈위험성때문에좌심방이폐색술이등장하게

되었다.여기서는좌심방이폐색기구의하나인Watchman™

에대하여알아보고자한다.

Watchman™을 이용한 경피적 좌심방이 폐색술

Received: November 25, 2014Revision Received: March 2, 2015Accepted: March 26, 2015Correspondence: Jae-Sun Uhm, MD, Department of Cardiology, Severance Cardiovascular Hospital, 50 Yonsei-ro Seodaemun-gu, Seoul, Korea, 120-752Tel: +82-2-2228-8441, Fax: +82-2-2227-7732E-mail: jason@yuhs.ac.kr

Copyright © 2015 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd.

Jae-Sun Uhm, MD

Department of Cardiology, Arrhythmia Center, Severance

Cardiovascular Hospital, Yonsei University College of

Medicine

ABSTRACT

It is well known that atrial fibrillation (AF) is the most important

cause of cardioembolic stroke, while the left atrial appendage (LAA)

is a common source of thrombus in patients with AF. The Watch-

man™ is an umbrella-shaped LAA occlusion device that can be im-

planted transvenously in the LAA via a delivery sheath for stroke

prevention in patients with non-valvular AF. Warfarin can be dis-

continued 45 days after Watchman™ implantation. The PROTECT

AF (Watchman™ Left Atrial Appendage System for Embolic Protec-

tion in Patients With AF) trial was the first prospective randomized

trial to show that the Watchman™ was not inferior to warfarin for

stroke prevention in patients with non-valvular AF. CAP (continuous

access protocol) registry data, ASAP (ASA Plavix Feasibility Study

With Watchman™ Left Atrial Appendage Closure Technology) reg-

istry data, and the PREVAIL (Watchman™ LAA Closure Device in

Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy)

trial have confirmed this non-inferiority. The Watchman™ is expect-

ed as an alternative to oral anticoagulation therapy. Long-term data

from the Watchman™ and from comparisons between the Watch-

man™ and new oral anticoagulants (NOACs) need to be evaluated.

Great attention should be paid to the selection of patients for the

Watchman™ implantation.

Key Words: atrial fibrillation, left atrial appendage, Watchman™

MAIN TOPIC REVIEWS

31

Watchman™을 이용한 경피적 좌심방이 폐색술

좌심방이의해부발생학

좌심방이는진도개의귀모양으로생겼고,좌심방과좌심실

사이의고랑위에위치한다.좌상폐정맥,좌회선지관상동맥,

대심장정맥등이인접하여위치한다.좁은기저부와예각의

첨부를 가지고 있다는 점에서 우심방이와 구분된다.

좌심방이의입구의지름은10-40mm이며,길이는16-51

mm이다.4좌심방이의내부를살펴보면빗살모양근육이

발달하여있고,두개이상의엽으로구성되어있는경우가

종종있다. 발생학적으로좌심방이를제외한좌심방의

대부분은폐정맥에서기원한조직으로구성되어있어빗살

모양근육이없고,좌심방이는원시심장조직에서기원하기

때문에빗살무늬근육이뚜렷하다.좌심방이의모양은

사람마다차이가커서닭날개모양(50.9%),바람자루모양

(29.0%),선인장모양(14.9%),콜리플라워모양(5.2%)등으로

구분하기도한다.5,6또한좌심방이의입구의모양도다양하여

타원형(68.9%),발모양(10.0%),삼각형(7.7%),물방울모양

(7.7%),원형(5.6%)등이있다.5

Watchman™의구조

Watchman™은낙하산모양이며,스스로펼쳐지는니티놀

(nitinol)뼈대구조와투과성폴리에스터막으로구성되어

있다(Figure1).좌심방이에위치시켰을때좌심방쪽으로

폴리에스터막이위치하며,좌심방이쪽으로니티놀구조가

노출되어있다.Watchman™의중간부위에방사형으로

좌심방이에고정시키기위한미늘이있다.폴리에스터막은

혈액투과가가능하여,Watchman™삽입후내피화하는데

걸리는 45일 동안은 warfarin 투여가 필요하다.

Watchman™은21,24,27,30,33mm의다섯가지크기가

있으며,장치의안착을위하여가장크게측정된좌심방이

입구의지름보다약 2-4mm큰장치를삽입할것을

권유한다(Table1).Watchman™을체외에서좌심방이까지

전달하기위한유도관은길이75cm,내부지름12Fr.,외부

지름14Fr.이며,원위부가한번구부러진것과두번

구부러진것의두가지모양이있다(Figure2).

Watchman™의삽입방법

Watchman™삽입전경식도심초음파및심장CT등을

시행하여좌심방내에혈전이없는지확인하고,좌심방이의

지름을적어도4개이상의다양한각도에서측정한다.시술은

대개전신마취하에서X-선투시시설이있는심도자실에서

이루어진다.시술과정을영상화하기위한경식도심초음파

탐촉자를삽입하고,경식도심장초음파로0,45,90,135도의

각도에서좌심방이입구의지름을측정한다(Figure 3).

대부분의 경우 135도에서 측정한 지름이 가장 크며,

Watchman™의크기를선택하는데중요하다.기구를

삽입하기위하여우측대퇴정맥을천자한다.Brockenbrough

바늘및Swartz유도관을이용하여중격천자를한다.

Watchman™삽입을위한천자부위는난원와의뒤쪽이

적절하다.중격천자직후 heparin을적절히투여하여

활성응고시간(activation clotting time)을250-300초로

유지한다.Swartz유도관을통하여Amplatzer™와이어또는

Inoue와이어를좌상폐정맥에넣고Watchman™전달용

유도관으로교체한다.Watchman™전달용유도관의첨부를

좌심방에위치시킨후유도관을통하여pigtail카테터를

좌심방내로삽입한다.유도관을반시계방향으로돌려서

pigtail카테터를좌심방이첨부까지부드럽게삽입한다.이후

Watchman™전달용유도관을 pigtail 카테터를따라

Table 1. Watchman™ device selection according to the left atrial appendage (LAA) orifice size

LAA orifice (mm) Watchman™ diameter (mm)

17-19 21

20-22 24

23-25 27

26-28 30

29-31 33

32

좌심방이깊숙한곳까지천천히삽입한다.

Pigtail카테터를통하여우전두향경사투영(RAO[right

anterioroblique]cranialprojection)및우전미향경사투영

(RAOcaudalprojection)의두방향으로좌심방이조영술을

시행하고,좌심방이입구의지름을측정한다(Figure4A).

경식도심초음파및좌심방이조영술에서측정한좌심방이

입구의지름중큰것을채택하여,Watchman™의크기를

선택하는데기준으로삼는다.적절한크기의Watchman™을

선택한후장치를꺼내어멸균된생리식염수안에서장치

내에있는공기를털어내고전달용와이어를연결하고전달용

카테터안으로밀어넣는다.전달용카테터근위부에있는

측부주입구로생리식염수를강한힘으로주입하여전달용

카테터및Watchman™내의공기를다시한번제거한다.

전달용와이어에연결된Watchman™을전달용유도관의

첨부까지 이동시킨다. 우전미향경사투영으로 좌심방이

조영술을시행하여장치의안착부위를다시한번확인한후

Watchman™을천천히전진시켜장치를조심스럽게펼친다.

전달용와이어를풀기전에다음의기준을만족하는지X-

선투시및경식도심초음파영상으로확인해야한다.(1)장치

주변으로 혈류의 흐름이 유의하게 남아 있는지, (2)

좌심방이의모든엽을덮었는지, (3)장치가좌심방으로

튀어나와있지않은지,(4)장치가10-20%이상눌려있는지,

(5)전달용와이어로장치를흔들어보아안정성이있는지,(6)

장치가좌회선지관상동맥및좌폐정맥을막지않았는지

확인한다.위의기준을모두만족하면전달용와이어를풀고

유도관을통하여좌심방이방향으로조영제를쏘아장치의

삽입위치를다시한번확인하고시술을마친다(Figure4B).

Watchman™의삽입후관리

Watchman™삽입술관련합병증은약5-10%에서발생할

수있는데,혈심낭,뇌경색,장치의색전증,장치관련혈전

생성,접근혈관관련합병증등이발생할수있다.7시술중

이러한합병증이발생하지않도록적절한활성응고시간을

유지하는 것, 좌심방이 입구의 지름을 여러 각도에서

측정하는것,카테터를교체할때마다세심하게생리식염수를

Figure 1. Watchman™ device (Courtesy of Boston Scientific).

Arrhythmia 2015;16(1):30-36

33

관류하는것,조심스럽게장치를펼치는것등이필요하다.

또한시술직후이러한합병증또는전신마취관련합병증이

발생하는지주의깊은관찰이필요하며,가능하면시술후

하루정도는중환자실에서관찰할것을권유한다.

Watchman™삽입후내피화가이루어지는데약45일이

걸리므로8Watchman™삽입후적어도45일동안warfarin

을 투여하여 INR을 2-3 수준으로 유지해야 한다.

Watchman™삽입45일후경식도심초음파를시행하여

장치가안정적인지,장치주변으로유의하게혈류가새는지,

장치주변으로혈전이발생하지는않았는지확인해야한다.

특히Watchman™의좌심방쪽면에있는전달용와이어를

연결하는나사장치에혈전이생길가능성이있다.9만약장치

주변으로유의하게새는혈류가있거나장치주변혈전이

있다면 warfarin을 유지해야 한다. PROTECT AF

(Watchman™LeftAtrialAppendageSystemforEmbolic

Protection in PatientsWith AF)연구에서는경식도

심초음파에서컬러도플러로본장치주변의혈류지름이5

mm 이하이면 유의하지 않다고 간주하였다.7 그러나

심초음파의컬러범위설정에따라혈류제트의지름은변할

수 있어서어느정도새는혈류를유의하다고간주할

것인가에대한기준은아직논란이많다.장치주변으로

유의하게새는혈류가없고장치관련혈전이없다면

warfarin을중단하고,aspirin100mg또는clopidogrel75

mg을평생투여한다.그러나환자의CHA2DS2-VASc점수가

높다면warfarin을중단하는데있어서더욱신중을기해야

할것이다.

Watchman™의성적

2009년Lancet에발표된PROTECTAF연구10는비판막성

Figure 2. Delivery sheaths: single-curved and double-curved (Courtesy of Boston Scientific).

Watchman™을 이용한 경피적 좌심방이 폐색술

34

Figure 3. Sizing of the left atrial appendage orifice diameter, landing zone diameter, and length on multi-angle transesophageal echocardiographic images.

Figure 4. (A) Left atrial appendage orifice sizing from a fluoroscopic image in the right anterior oblique caudal projection. (B) Contrast dye injection after Watchman™ implantation.

A B

Arrhythmia 2015;16(1):30-36

35

심방세동 환자를 대상으로 warfarin과 비교하여

Watchman™의뇌경색예방효과와안전성을보고자한

전향적무작위비열등성연구였다.707명의환자를대상으로

하였으며,평균CHADS2점수는2.2점이었고, 18개월을

추적관찰하였다.그결과Watchman™군에서warfarin

군보다뇌경색발생률이29%줄어들어Watchman™이

warfarin보다열등하지않다는것을보여주었다.2013년

Circulation에발표된추적관찰기간을2.3년으로연장한

PROTECTAF연구결과에서는warfarin군에비하여

Watchman™군에서뇌경색의발생률이32%줄어들었을

뿐만아니라전체사망률도34%감소하여Watchman™이

warfarin보다열등하지않음을보여주었다.11

2011년Circulation에발표된Watchman™삽입환자를

대상으로한PROTECTAF연구및CAP(continuousaccess

protocol)registry연구7는혈심낭,시술관련뇌경색,장치

색전증및출혈합병증등을종결점으로하였다.이연구에는

PROTECTAF연구에등록된환자542명및새로등록된460

명이포함되었으며,평균나이74세,평균CHADS2점수2.4

점이었다.초기PROTECTAF군,말기PROTECTAF군,

가장최근인registry군의세시기별로결과를보면시술의

경험이축적될수록시술시간,삽입성공률,삽입후warfarin

중단비율,혈심낭및뇌경색과같은장치삽입관련합병증이

줄어드는것으로나타났다.

2013년JournalofAmericanCollegeofCardiology에

발표된 ASAP (ASA Plavix Feasibility Study With

Watchman™LeftAtrialAppendageClosureTechnology)

연구12는warfarin의금기증인비판막성심방세동환자에서

Watchman™의안전성및타당성을알아보고자한다기관

전향적비무작위타당성registry연구이다.150명의환자를

대상으로하였으며,평균나이72.5세,평균CHADS2점수

2.8점이었다.연구종결점은뇌경색,뇌출혈,전신색전증,

사망으로정하였고, 14.4개월동안추적관찰하였다.이

연구에서는Watchman™삽입후warfarin을투여하지

않고,aspirin과clopidogrel(또는ticlopidine)을투여하였다.

그결과CHADS2점수에따른뇌경색의위험도에비하여

Watchman™을넣은환자에서뇌경색의발생률이77%

감소하였다.

2014년JournalofAmericanCollegeofCardiology에

발표된PREVAIL(Watchman™LAAClosureDevice in

PatientsWithAtrialFibrillationVersusLongTerm

Warfarin Therapy) 연구13는 Watchman™의효과와

안전성을 확인하는 전향적 무작위 연구이다. 연구에

참여하였던41개기관중18개기관은Watchman™을삽입한

경험이없는기관이었다.461명을대상으로하였고,평균

나이74.3세,평균CHADS2점수2.6점이었다.연구종결점은

7일이내와이후뇌경색,전신색전증등으로하였다.7일

이내 및 이후 뇌경색, 전신 색전증의 발생률에서

Watchman™군이warfarin군에비하여열등하지않음을

보였다.

결론

비판막성심방세동환자에서Watchman™을이용한

좌심방이폐색술을통하여뇌경색의발생을낮출수있었다.

Watchman™이장기항응고요법을대체할수있을것으로

기대된다.그러나아직은Watchman™의장기성적및

뇌경색예방효과에있어서새로운항응고제와의비교결과를

주의깊게지켜보아야하겠다.항응고제사용및시술에따른

위험성,비용및환자의선호도등을고려하여대상환자의

선택에신중을기해야한다.

References

1) Thambidorai SK, Murray RD, Parakh K, Shah TK, Black IW,

Jasper SE, Li J, Apperson-Hansen C, Asher DR, Grimm RA, Klein

AL. Utility of transesophageal echocardiography in identification of

thrombogenic milieu in patients with atrial fibrillation (an ACUTE

ancillary study). Am J Cardiol. 2005;96:935-941.

2) January CT, Wann LS, Alpert JS, Calkins H, Cleveland JC Jr,

Cigarroa JE, Conti JB, Ellinor PT, Ezekowitz MD, Field ME,

Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy

CW. 2014 AHA/ACC/HRS guideline for the management of

patients with atrial fibrillation: a report of the American College of

Cardiology/American Heart Association Task Force on Practice

Guidelines and the Heart Rhythm Society. Circulation.

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3) Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser

SH, Hindricks G, Kirchhof P. 2012 focused update of the ESC

guidelines for the management of atrial fibrillation. Eur Heart J.

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2012;33:2719-2747.

4) Ernst G, Stollberger C, Abzieher F, Veit-Dirscherl W, Bonner E,

Bibus B, Schneider B, Slany J. Morphology of the left atrial

appendage. Anatom Record. 1995;242:553-561.

5) Yang Y, Di Biase L, Horton RP, Nguyen T, Morhanty P, Natale A.

Left atrial appendage studied by computed tomography to help

planning for appendage closure device placement. J Cardiovasc

Electrophysiol. 2010;21:973-982.

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Corsinovi L, Pianelli M, Cesarani F, Faletti R, Righi D, Natale A,

Gaita F. Left atrial appendage morphology and silent cerebral

ischemia in patients with atrial fibrillation. Heart Rhythm.

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7) Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of

percutaneous left atrial appendage closure: results from the

Watchman left atrial appendage system for embolic protection in

patients with AF (PROTECT AF) clinical trial and the continued

access registry. Circulation. 2011;123:417-424.

8) Schwartz RS, Holmes DR, Van Tassel RA, Hauser R, Henry TD,

Mooney M, Matthews R, Doshi S, Jones RM, Virmani R. Left

atrial appendage obliteration: mechanisms of healing and

intracardiac integration. JACC Cardiovasc Interv. 2010;3:870-877.

9) Gasparini M, Ceriotti C, Bragato R. Huge left atrial thrombus after

left atrial appendage occlusion with a Watchman device. Eur Heart

J. 2012;33:1998.

10) Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H,

Buchbinder M, Mullin CM, Sick P. Percutaneous closure of the

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stroke in patients with atrial fibrillation: a randomised non-

inferiority trial. Lancet. 2009;374:534-542.

11) Reddy VY, Doshi SK, Sievert J, Buchbinder M, Neuzil P, Huber

K, Halperin JL, Holmes D. Percutaneous left atrial appendage

closure for stroke prophylaxis in patients with atrial fibrillation;

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Wiebe J, Sick P, Sievert H. Left atrial appendage closure with the

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Arrhythmia 2015;16(1):37-42

서론

뇌졸중은우리나라성인의주요사망원인중하나로

인구의고령화가진행됨에따라환자가급격하게증가하고

있다.대부분의선진국과비슷하게우리나라도뇌출혈보다는

뇌경색이대부분을차지하고있으며,이중 1/6이상이

심방세동과연관된것으로밝혀졌다.1심방세동은가장흔한

부정맥으로유병률이꾸준히증가하고있고,80대에서는

유병률이 7.3-13.7%에 이르는 것으로 알려졌다.2,3

심방세동과연관된혈전에의한뇌경색은동맥경화에의한

뇌경색보다광범위한뇌손상을일으키거나,재발위험이

높고,단기사망률이높기때문에심방세동환자에서는

뇌경색예방을위한항응고요법이무엇보다도중요하다고할

수 있다. 환자의 위험도에 따라 적절한 항응고요법이

이루어질경우에는뇌경색위험도를60%까지감소시킬수

있다.4

그러나전통적인표준치료법으로받아들여지고있는

warfarin은사용시잦은혈액검사로인한불편함,다양한

약제간상호작용,심각한출혈합병증위험성등의이유로

실제처방률은높지않다.5,6몇년전부터도입되어사용중인

새로운경구항응고제들이이와같은warfarin의단점들을

많이극복하였다.하지만다양한동반질환으로여러약제를

복용중이거나,간,신장등주요장기의기능이저하된고령

환자에서는출혈위험성이함께증가하기때문에여전히

Amplatzer™ Cardiac Plug를 이용한 경피적 좌심방이 폐색술

Received: November 1, 2014Revision Received: February 23, 2015Accepted: March 26, 2015Corresponding Author: Hong Euy Lim, M.D, Ph.D, Division of Cardiac Electrophysiology, Korea University Guro Hospital, 148, Gurodong-ro, Guro-gu, Seoul, Republic of Korea 152-703Tel: +82-2-2626-1046, Fax: +82-2-867-9093E-mail: hongeuy@korea.ac.kr, h3lim@medimail.co.kr

Copyright © 2015 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd.

Seung Yong Shin, MD,1 Sung Il Im, MD,2 Jin-Seok Kim, MD,3 and Hong Euy Lim, MD.3

1 Division of Cardiology, Cardiovascular and Arrhythmia

Center, Chung-Ang University Hospital, College of

Medicine, Chung-Ang University, Seoul, Korea 2 Division of Cardiology, Kosin University Gospel Hospital,

Pusan, Korea3 Division of Cardiology, Cardiovascular Center, Korea

University Ansan Hospital, Korea University College of

Medicine, Ansan, Korea4 Division of Cardiology, Cardiovascular Center, Korea

University Guro Hospital, Korea University College of

Medicine, Seoul, Korea

ABSTRACT

Atrial fibrillation (AF) is one of the major causes of ischemic stroke,

and its incidence increases with age. Although oral anticoagulation

is the standard therapy for stroke prevention in AF patients who have

risk factors for thromboembolism, many of these patients do not

receive anticoagulation therapy for various reasons, such as drug

side effects and complications, even though new oral anticoagu-

lants (NOACs) have now been introduced in clinical practice. In an

attempt to overcome these limitations, specially designed devices

with a transcatheter delivery system have been used to occlude the

left atrial appendage (LAA), which has been proved to be the ma-

jor source of thrombus formation in patients with non-valvular AF.

Many clinical studies have demonstrated that occlusion of the LAA

with devices can prevent ischemic stroke and systemic thromboem-

bolism more safely and effectively than standard warfarin therapy.

Prospective multicenter studies including AF patients with various

medical conditions will be needed to prove the efficiency of LAA

occlusion with devices in comparison with NOACs.

Key Words: atrial fibrillation, device, left atrial appendage

MAIN TOPIC REVIEWS

38

항응고요법을적절하게유지하는것이어렵거나위험한

경우가 많다.7-9 뿐만 아니라 항응고요법유지 중에도

뇌경색이발생하는경우가있어현재사용중인예방법으로는

충분하지않은경우도있음을알수있다.

이와같은문제점에대한보완책으로혈전의주요생성

부위인좌심방이(left atrial appendage)를수술적으로

절제하거나,최근에는경피적중재술을통해좌심방이를

막아주어 혈전을 예방하는 술식이 도입되어 일반적인

항응고요법이어려운환자들에게선택적으로사용되고

있다.10현재국내에는Watchman™과Amplatzer™Cardiac

Plug(ACP)2가지경피적좌심방이폐색술(percutaneousleft

atrialappendageocclusion)도구가도입되어사용중인데,

그중하나인ACP를중심으로기구의특징과장단점,

현재까지의안전성,유효성에관한연구결과들에대해서

살펴보고자한다.

좌심방이의해부학적구조

좌심방이는배아좌심방(embryonic leftatrium)의흔적

기관으로임신3주에좌심방이생기면서흔적으로남아있다.

좌심방이의입구는좌상폐정맥(left superiorpulmonary

vein)과승모판륜(mitralannulus)사이에위치하며,모양과

크기는매우다양하나일반적으로타원형모양(ellipticalor

ovalshape)이다.삼각형이며,아랫부분이넓은깔때기모양

(funnelshape)인우심방이와달리입구가좁은경우가많다.

좌심방이에는잔기둥형성(trabeculation)이많고빗살근

(pectinatemuscle)이존재하므로내면이주름진모양을하고

있어좌심방몸체(body)와구분이가능하다.11220명의부검

(necropsy)연구에따르면좌심방이의용적은0.7-19.2mL

이며,가장좁은부분의직경은5-27mm,가장넓은부분의

직경은10-40mm,길이는16-51mm로매우다양한것으로

나타났으나,모양에있어서는70%가량이낚시바늘처럼

구부러지거나나선형을하고있는것으로밝혀졌다.그중

심방세동환자의좌심방이는입구의직경과부피가더크고,

가지의개수가적은것으로나타났다.12

좌심방이의혈류

좌심방이는좌심방보다강하게수축하며,동율동일때

좌심방이의혈류는4상성(quadriphasic)인것으로밝혀졌다.13

이것은좌심방이의능동적인수축과좌심방및좌심실의수축

또는이완에따른수동적인움직임의종합적인결과이다.첫

번째좌심방이에서나가는혈류는좌심실의이완기초반에

늘어난좌심실이좌심방이를눌러주면서발생하게되고(1st

outflow),이후좌심방으로유입되는혈류가좌심방이로

들어오게된다(1st inflow).두번째좌심방이에서나가는

혈류는좌심방과좌심방이가함께수축하면서일어나며(2nd

outflow),좌심방이의회복/이완기에좌심방이로두번째

혈류가들어오게된다(2ndinflow).14

이처럼좌심방이의혈류는리듬뿐만아니라좌심실의이완

기능변화에영향을받으므로심방세동환자에서심부전이

동반될경우혈전이더욱쉽게발생할것을예상할수있다.

Arrhythmia 2015;16(1):37-42

Figure 1. (A) The Amplatzer™ Cardiac Plug (ACP), (B) An example of left atrial appendage occlusion using the ACP device.

A B

39

Amplatzer™ Cardiac Plug를 이용한 경피적 좌심방이 폐색술

실제로 심방세동이 발생하면 동율동일 때보다 혈류가

느려지고좌심방이가커지므로혈전이생기기쉬워진다.

경식도심초음파를통해서살펴본결과비판막성심방세동

환자에서는혈전의90%이상이좌심방이에서발견되었다.15,16

초기좌심방이폐색술

이와같이좌심방이가혈전발생의주요병소라는것이

널리알려지면서승모판수술시좌심방이를제거하는수술적

절제술을함께시도하게되었으나,수술적절제술시약1/3-

1/2은 좌심방이가 완전히 제거되지 못하고 남아 있는

부분에서혈전이재차발생하는것을알게되었다.17-19

수술적인치료법에따른위험성과불만족스러운결과의

문제점을 보완하기 위해 비판막성 심방세동 환자에서

카테터를 이용한 경피적 좌심방이 폐색술이 시도되기

시작하였고,그첫번째시도는PLAATO®(percutaneousleft

atrialappendagetranscatheterocclusion)도구를이용한

시술이었다.20비록2006년에생산이중단되면서현재는

사용되지 않고 있으나, 초창기의 연구 결과들은 매우

고무적인것을볼수있다.총113명에서시술했으며,시술의

성공률은97%이상이었고,이중87%에서주변구조물에

영향을미치지않고좌심방이의혈류를완전히차단시키는

결과를얻을수있었다.

연구대상은항응고제의금기에해당하며,CHADS2점수는

2점이상인환자였는데,PLAATO®를이식한환자군에서

뇌졸중발생은매년2.2%로CHADS2점수가2점이상인

환자에서예상되는뇌졸중위험도인6.3%보다낮은것으로

나타났다.좌심방이폐색술이항응고제의금기에해당하는

환자들에게뇌졸중예방효과가있으며,경구항응고제의

대안이될수있음을처음으로보여주었다.21,22그후이와

유사한형태를가진Watchman™도구가개발되어현재까지

사용중이며,일반적인항응고제로는적절한뇌졸중예방이

어려운환자들에게효과적이라는연구결과들이보고되고

있다.23-25

Amplatzer™ Cardiac Plug를 이용한 좌심방이

폐색술

좌심방이의해부학적인구조상70%이상에서장축이

구부러져있고,여러개의엽(lobe)으로나뉘어져있다.또한

좌심방이입구에서부터초기에두개이상의엽들이분리되기

때문에 앞서 개발된 PLAATO®와 Watchman™처럼

일체형으로만들어진도구로는상당수에서좌심방이입구를

완전히막을수없다는한계를보여주었다.이와같은

불완전한좌심방이폐색술은새로운혈전생성의장소를

제공하게되어뇌졸중예방의기대효과를감소시키는단점이

있다.이를개선하기위해심방중격결손증치료에사용되던

Amplatzer®septaloccluder를변형한기구가ACP이다.

ACP는Figure1에서보는바와같이장치의고정을위한

lobe와좌심방이의입구를완전히막기위한disc의두

부분으로구성되어있고,두부분을연결하는허리부분은잘

구부러질수 있게디자인되어있어장축이구부러진

Figure 2. (A) Fluoroscopic image to measure the entrance of the left atrial appendage (LAA) (B) Amplatzer™ Cardiac Plug device is appropriately compressed and fixed with “tire-like” shape in the lobe of LAA and the disc is fully covering the entrance to the LAA.

A B

40

좌심방이모양에서도고정과폐쇄효과를동시에거둘수

있는큰장점이있다.Figure2는ACPlobe가좌심방이엽

안에서타이어모양으로적절하게압박고정되어있고ACP

disc가좌심방이입구를완전폐색시키고있는실제시술

장면이다.디자인상의장점이실제임상에서결과를개선시킬

수있는지살펴보기위한여러연구들이진행중이며,그중

초기 적합성과 안전성을 살펴본 연구가 각각 유럽과

캐나다에서진행되었다.

Amplatzer™CardiacPlug연구결과

ACP에대한첫연구는유럽에서진행되었으며,143명의

환자를대상으로하였다.26대상환자들의평균연령은74

세였으며,96%에서성공적으로ACP를이식하였다.시술과

연관되어발생한주요합병증은뇌경색(3명),기구의색전

(embolization, 2명), 심낭삼출(5명)등이었다.경미한

합병증으로는심낭천자가필요없는정도의심낭삼출(4명),

공기 색전증에 의한 일시적인 심근허혈(2명) 등이

보고되었다.

다음 연구는 캐나다에서 52명의 환자를 대상으로

진행되었다.27이들의평균나이는74세였고,평균CHADS2

점수는 3점이었다. 98.1%의 환자에서 성공적으로

시술하였고, 기구의 색전과 심낭삼출이 각각 1.9%

발생하였다.시술과연관된뇌경색은없었으며,6개월후

경식도심초음파로살펴본결과16.2%에서기구주변으로

경미한 혈류가 관찰되었으나, 1-2가지 항혈소판제를

복용하면서20개월까지추적해보았을때기구의색전이나

심각한 출혈 합병증은 발생하지 않았다. 다른 곳에서

진행되었던유사연구에서도비슷한정도의안전성,효율성을

확인할수있었다.28,29

경피적좌심방이폐색술이점차늘어나고,시술방법,

도구의개선이이루어지면서최근발표된추적관찰연구

결과들을살펴보면도입초기보다향상된안정성과낮은

합병증발생,대상환자들의CHADS2점수로예측할수있는

뇌경색위험도에비해서낮은뇌경색발생,삶의질향상등의

결과들이보고되었다.22,25,29-32이처럼다양한연구결과들을

종합하여시도된메타분석결과는다음과같다. 17개의

연구에포함된1,107명의환자에게1,052개의좌심방이폐색

도구가이식되었으며,전체시술의성공률은95.1%였고,

7-29개월간추적관찰하였다.환자들의평균CHADS2점수는

2.7점이었고,이들에서예상되는뇌경색발생률은2.5-

5.3/100인・년(person-year)이었는데실제관찰된뇌경색

발생률은0.7/100인・년이었다.33

이와같은수치는warfarin이나다른경구항응고제보다

우월한예방효과이다.비록전향적인비교연구를통해

얻어진결과가아니므로추가적인연구를통한확인이필요할

것이다. 그러나지금까지경구항응고제로는적절하게

치료하지 못하던 환자군에서 치료의 새로운 돌파구를

찾았다는점과앞으로기구와시술방법이더욱발전된다면

경구항응고제보다더안전하고효과적으로뇌경색을예방할

수있을것이라는데에서큰의미를찾을수있다.

결론

지금까지항응고제를장기적으로사용하기어렵거나,

적절한항응고제복용중에도혈전생성에의한뇌졸중이

발생한비판막성심방세동환자들에서경피적좌심방이

폐색술의탄생배경과현주소에대해서자세히살펴보았다.

아직까지는다양한심방모양에맞춰줄수있는다양한

디자인과크기의기구가개발되지않아시술이불가능하거나,

기대한만큼의효과를기대하기어려운경우도있을수있다.

하지만이와같은문제들은좌심방이에대한해부학적인

이해의향상,장기적추적관찰결과에따른시술방법의수정

및보완,경피적좌심방이폐색술도구의과학적개선을

통해서점차나아지고있다.뿐만아니라최근발표된

메타분석의결과를통해서예측해보았을때많은연구와

개선이이루어진다면경피적좌심방이폐색술은약물치료의

단점을보완해줄수있는가장좋은치료법으로자리매김할

것이라기대된다.

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Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC,

Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M,

Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH,

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Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC,

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14) Mikael Kortz RA, Delemarre BJ, van Dantzig JM, Bot H, Kamp

O and Visser CA. Left atrial appendage blood flow determined by

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Doherty RM, Munson JT and Douglas PS. Impaired left atrial

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16) Leung DY, Black IW, Cranney GB, Hopkins AP and Walsh WF.

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762.

17) Katz ES, Tsiamtsiouris T, Applebaum RM, Schwartzbard A,

Tunick PA and Kronzon I. Surgical left atrial appendage ligation is

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Am Coll Cardiol. 2000;36:468-471.

18) Blackshear JL, Johnson WD, Odell JA, Baker VS, Howard M,

Pearce L, Stone C, Packer DL and Schaff HV. Thoracoscopic

extracardiac obliteration of the left atrial appendage for stroke risk

reduction in atrial fibrillation. J Am Coll Cardiol. 2003;42:1249-

1252.

19) Healey JS, Crystal E, Lamy A, Teoh K, Semelhago L, Hohnloser

SH, Cybulsky I, Abouzahr L, Sawchuck C, Carroll S, Morillo C,

Kleine P, Chu V, Lonn E and Connolly SJ. Left Atrial Appendage

Occlusion Study (LAAOS): results of a randomized controlled

pilot study of left atrial appendage occlusion during coronary

bypass surgery in patients at risk for stroke. Am Heart J.

2005;150:288-293.

20) Nakai T, Lesh MD, Gerstenfeld EP, Virmani R, Jones R and Lee

RJ. Percutaneous left atrial appendage occlusion (PLAATO) for

preventing cardioembolism: first experience in canine model.

Circulation. 2002;105:2217-2222.

21) Ostermayer SH, Reisman M, Kramer PH, Matthews RV, Gray

WA, Block PC, Omran H, Bartorelli AL, Della Bella P, Di Mario

C, Pappone C, Casale PN, Moses JW, Poppas A, Williams DO,

Meier B, Skanes A, Teirstein PS, Lesh MD, Nakai T, Bayard Y,

Billinger K, Trepels T, Krumsdorf U and Sievert H. Percutaneous

left atrial appendage transcatheter occlusion (PLAATO system) to

Amplatzer™ Cardiac Plug를 이용한 경피적 좌심방이 폐색술

42

prevent stroke in high-risk patients with non-rheumatic atrial

fibrillation: results from the international multi-center feasibility

trials. J Am Coll Cardiol. 2005;46:9-14.

22) Block PC, Burstein S, Casale PN, Kramer PH, Teirstein P,

Williams DO and Reisman M. Percutaneous left atrial appendage

occlusion for patients in atrial fibrillation suboptimal for warfarin

therapy: 5-year results of the PLAATO (Percutaneous Left Atrial

Appendage Transcatheter Occlusion) Study. JACC Cardiovasc

Interv. 2009;2:594-600.

23) Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H,

Buchbinder M, Mullin CM, Sick P and Investigators PA.

Percutaneous closure of the left atrial appendage versus warfarin

therapy for prevention of stroke in patients with atrial fibrillation: a

randomised non-inferiority trial. Lancet. 2009;374:534-542.

24) Reddy VY, Mobius-Winkler S, Miller MA, Neuzil P, Schuler G,

Wiebe J, Sick P and Sievert H. Left atrial appendage closure with

the Watchman device in patients with a contraindication for oral

anticoagulation: the ASAP study (ASA Plavix Feasibility Study

With Watchman Left Atrial Appendage Closure Technology). J

Am Coll Cardiol. 2013;61:2551-2556.

25) Alli O, Doshi S, Kar S, Reddy V, Sievert H, Mullin C, Swarup V,

Whisenant B and Holmes D, Jr. Quality of life assessment in the

randomized PROTECT AF (Percutaneous Closure of the Left

Atrial Appendage Versus Warfarin Therapy for Prevention of

Stroke in Patients With Atrial Fibrillation) trial of patients at risk

for stroke with nonvalvular atrial fibrillation. J Am Coll Cardiol.

2013;61:1790-1798.

26) Park JW, Bethencourt A, Sievert H, Santoro G, Meier B, Walsh K,

Lopez-Minquez JR, Meerkin D, Valdes M, Ormerod O and

Leithauser B. Left atrial appendage closure with Amplatzer cardiac

plug in atrial fibrillation: initial European experience. Catheter

Cardiovasc Interv. 2011;77:700-706.

27) Urena M, Rodes-Cabau J, Freixa X, Saw J, Webb JG, Freeman M,

Horlick E, Osten M, Chan A, Marquis JF, Champagne J and

Ibrahim R. Percutaneous left atrial appendage closure with the

AMPLATZER cardiac plug device in patients with nonvalvular

atrial fibrillation and contraindications to anticoagulation therapy.

J Am Coll Cardiol. 2013;62:96-102.

28) Lam YY, Yip GW, Yu CM, Chan WW, Cheng BC, Yan BP,

Clugston R, Yong G, Gattorna T and Paul V. Left atrial appendage

closure with AMPLATZER cardiac plug for stroke prevention in

atrial fibrillation: initial Asia-Pacific experience. Catheter

Cardiovasc Interv. 2012;79:794-800.

29) Nietlispach F, Gloekler S, Krause R, Shakir S, Schmid M, Khattab

AA, Wenaweser P, Windecker S and Meier B. Amplatzer left atrial

appendage occlusion: single center 10-year experience. Catheter

Cardiovasc Interv. 2013;82:283-289.

30) Holmes DR, Jr., Kar S, Price MJ, Whisenant B, Sievert H, Doshi

SK, Huber K and Reddy VY. Prospective randomized evaluation

of the Watchman Left Atrial Appendage Closure device in patients

with atrial fibrillation versus long-term warfarin therapy: the

PREVAIL trial. J Am Coll Cardiol. 2014;64:1-12.

31) Reddy VY, Holmes D, Doshi SK, Neuzil P and Kar S. Safety of

percutaneous left atrial appendage closure: results from the

Watchman Left Atrial Appendage System for Embolic Protection

in Patients with AF (PROTECT AF) clinical trial and the

Continued Access Registry. Circulation. 2011;123:417-424.

32) Danna P, Proietti R, Sagone A, Arensi A, Viecca M, Rago A and

Russo V. Does left atrial appendage closure with a cardiac plug

system reduce the stroke risk in nonvalvular atrial fibrillation

patients? A single-center case series. Pacing Clin Electrophysiol.

2013;36:347-353.

33) Bajaj NS, Parashar A, Agarwal S, Sodhi N, Poddar KL, Garg A,

Tuzcu EM and Kapadia SR. Percutaneous left atrial appendage

occlusion for stroke prophylaxis in nonvalvular atrial fibrillation: a

systematic review and analysis of observational studies. JACC

Cardiovasc Interv. 2014;7:296-304.

Arrhythmia 2015;16(1):37-42

43

Arrhythmia 2015;16(1):43-47

서론

LARIAT®는Watchman™,Amplatzer™CardiacPlug

(ACP)device와함께좌심방이폐쇄에이용되는장치이며,

Watchman™,ACP등이심장내에기기(이물질)가남는데

비하여,LARIAT®는심외막에서좌심방이를봉합,결찰하는

방식이어서위의두기기와는차별점이있다.Lariat혹은

lasso는스페인어‘lareata’에서기원하였으며,소몰이를하는

카우보이들이사용하는로프를지칭하는데,본장치의시술이

마치소의목에로프올가미를걸어잡아채는카우보이의

방식과유사하여이러한이름을붙인것으로생각된다.

본고에서는LARIAT®device의간략한소개및최근의임상

적용결과에대하여기술하고자한다.

기기의구성

본기기의구성부품들을제조사인SentreHEART사의

제품설명서에나온그림을인용하여소개하였다(Figure1).

가장핵심이되는부분은LARIAT®suturedeliverydevice로

심외막으로접근하여좌심방이를감아죄는올가미형태로

생겼다(Figure 1A). 심장 박동마다 심하게 움직이는

좌심방이에 대한 접근이 쉽지 않으므로, 이 장치는

FindrWIRZ® guidewire system을이용하여좌심방이로

접근하게되어있다(Figure 1B).FindrWIRZ®guidewire

system은심내막과심외막에위치시키는유도철선인데,양

끝이자석으로이루어져있어서심내/외막을통하여두

철선이마주보는형태로안정적으로유지될수있도록

고안되었다.FindrWIRZ®guidewiresystem이좌심방이를

안정적으로잡고유지시켜주는동안 LARIAT®suture

deliverydevice를통하여suture가이루어지는데,이때

TenSURE™suturetightner가이용된다(Figure1C).시술중

LARIAT®의작동방식에대한이해는유투브동영상(http://

www.youtube.com/watch?v=Ua40eHrSBQ0)을참조하면

편리하다.

시술방법

전신마취하에식도내시경을통하여좌심방이의혈전

유무를확인한다.심외막접근법(epicardial approach)은

통상적인 방법으로 시행하되, 가급적 전방(anterior

LARIAT® Device를 이용한 경피적 좌심방이 폐색술

Received: November 12, 2014Revision Received: February 11, 2015Accepted: March 26, 2015Correspondence: Gi-Byoung Nam, MD, PhD, Heart Institute, Asan Medical Center, 43 Olympic-Ro, Songpa-Gu, Seoul, Korea 138-736Tel: +82-2-3010-3159, Fax: +82-2-486-5918 E-mail: gbnam@amc.seoul.kr

Copyright © 2015 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd.

Gi Byoung Nam, MD

Heart Institute, Asan Medical Center, Division of

Cardiology, Department of Internal Medicine, University of

Ulsan College of Medicine

ABSTRACT

The LARIAT® is a new suture device used for closure of the left atrial

appedndage (LAA). It is distinct from the Watchman™ or ACP de-

vices in that no foreign body remains in the left atrium, and that

a combined endocardial and epicardial approach is used. A brief

summary of the device configuration, procedure methods, and re-

cent clinical results of the LARIAT® device are given below.

Key Words: left atrial appendage, atrial fibrillation, stroke, device

MAIN TOPIC REVIEWS

44

Arrhythmia 2015;16(1):43-47

LARIAT® suture delivery device

FindrWIRZ® guidewire system

TenSURE™ suture tightner

Figure 1. Configuration of the LARIAT® device.(A) The left atrial appendage (LAA) is sutured by the suture delivery device introduced via the epicardial approach. (B) To avoid instability of the LAA before delivery of the suture device, a combined endocardial and epicardial guidewire system is introduced and the two heads of the guide-wires are joined and aligned by magnetic force. (C) Finally, suturing of the LAA neck is achieved using the suture tightener.

Source: product brochure from SentreHEART, Inc (http://www.sentreheart.com/us/products/lariat)

A

B

C

45

LARIAT® Device를 이용한 경피적 좌심방이 폐색술

approach)을 향하도록한다. 조영제를통하여바늘이

심외막을통과한것이감지되면유도철선을넣어서심외막

내로진입한다.이후sheath를통과시키되,점차큰사이즈를

통과시켜서최종적으로는14Fr.구경의LARIAT®장치가

들어갈수있도록점진적으로구멍을넓혀나간다.

심외막경로가확보된이후에는heparin을주입하고SL1

sheath를이용하여중격천자를시행한다.좌심방조영술을

LAO,RAOcaudalview에서시행하여좌심방이의형태를확

인한다.이후0.025”magnettipFindrWIRZ®guidewiresys-

tem(SentreHEART,Inc,CA)의유도철심을SL1sheath를

통하여좌심방이에위치시킨다.이때wire는좌심방이의가장

앞쪽lobe에위치시키는것이유리하다.이후0.035”magnet

tipFindrWIRZ®guidewire를LARIAT®system에장착하여

심외막sheath를통하여집어넣고,심내막의wire와축이맞

도록(coaxial)끝을맞추어위치시킨다(Fiugure2A).이두유

도철선의축이맞는것이확인되면심외막sheath를통하여

LARIAT®snare를집어넣고좌심방이의목에서snare를조

여서좌심방이를막는다(Figure2B).결찰이잘되어있는지

는balloonangiogram을통하여확인할수있고,이후Ten-

SURE™suturetightner(SentreHEART,Inc.,CA)를이용하

여좌심방이를봉합한다(Figure2C).이후LARIAT®suture

deliverysystem을통하여남은실끝을잘라내고delivery

system을심외막에서뽑아내어제거한다(Figure2D).봉합후

새는결찰의누출(leakage)여부를좌심방조영술및경식도초

음파를통하여다시확인한다.

시술결과

최근LARIAT®를이용한좌심방이폐색술의임상결과가

보고되기시작하고있다.2013년Bartus,Lee등이보고한

자료에서는89명의환자중최종85명에서성공적인시술이

이루어졌으며,1심한심낭염2례,퇴원후나타난심낭액이1

례에서관찰되어합병증이비교적많지않았다고주장하고

있으나퇴원후급사가1례에있어서안전성에의문을갖게

Figure 2. LARIAT® implantation technique.The left atrial appendage (LAA) is approached via endocardial and epicardial puncture. Two guidewires are held tight by the magnetic force between the wire tips. (A) After the wires have been secured, the suture delivery system is introduced through the epicardial wire. The endocardial balloon is then inflated before the epicardial snare catches the neck of the LAA. (B) The snare is advanced to the LAA base and tightens the LAA neck. The LAA is sutured and occluded completely by the suture tightener. (C) The suture delivery system is withdrawn into the epicardial space and the suture material is cut after confirmation of complete closure of the LAA.

Source: http://www.youtube.com/watch?v=Ua40eHrSBQ0

A

C D

B

46

하였다.이어서2014년Price등의보고에서는154명의환자

중86%에서성공적인시술이이루어지기는했으나10%에

가까운14명의환자에서주요출혈성부작용이나타났고,16

명에서심낭출혈이있었다고보고하고있다.2더구나이들의

연구에서도 1례의 급사가 있었다고 하는데, 아마도

심낭출혈이급사로표현되었을가능성이높아서출혈성

부작용이중요한문제점으로부각되었다.또한추적관찰중

사망/심근경색/뇌졸중이3%환자에서,심낭출혈이2%의

환자에서 관찰되었고, 약 5%의 환자에서 좌심방이를

제거하고남은부분(stump)에서혈전이형성되었으며,약6%

의환자에서5mm이상의큰누출공(leak)이발견되어시술

후주의깊은추적관찰및합병증에대한평가가필요함을

지적하였다.2

2014년HeartRhythm에발표된Miller,Reddy등의보고

에의하면,전체41명의환자중38명(93%)의환자에서성공적

인시술이이루어졌지만,24%의환자에서누출공이발생하였

고,8명(20%)의환자에서심낭출혈이있었으며,4명(9%)의환

자에서좌심방이천공이발생하였다고보고하여현재의시스

템으로는안전한시술결과를기대하기어렵고추가적인개선

이필요함을시사하였다.3다행히시술후발생한누공에대해

서는Amplatzer™septaloccludedevice를이용하여막아주거

나LARIAT®를이용하여재시술을할수있음이보고되었다.4,5

하지만시술후13개월후에뒤늦게LARIAT®시술부위에서

발생한혈전의예도있어서,6,7시술후적절한기간동안의항

응고치료필요성에대한검토,혈전발생을찾기위한추적

검사프로토콜확립등이추가로정립되어야할사항들이다.

기타LARIAT®효과

LARIAT®는 Watchman™이나 ACP 기기와 달리

좌심방이를결절함으로써 1/3의환자에서는좌심방이의

전기적활성이완전히없어지고,90%이상의환자에서는

좌심방이를조율하여도좌심방으로전기적흥분이전달되지

않는다는것이보고되었다.8이러한결과는LARIAT®가

단순히혈전/색전증의예방효과만갖는것이아니라,

좌심방이에위치하는rotor혹은focaltrigger를제거하여

심방세동의유발/유지를억제할수있을것이라는추정이

가능케하며,아울러criticalmass reduction의효과도

기대할수있음을시사한다.실제로LARIAT®시술후

심방세동의발생빈도가줄어들었다는흥미로운보고도

있어서,9LARIAT®시술이심방세동도자절제술과같이

시행될경우시술의성공률을높이는데기여할수있을

가능성도제시되었다.

결론

LARIAT®시술은움직임이많은좌심방이를심내막-

심외막양방향에서자성을띤두유도철선의도킹시스템을

이용하여좌심방이를안정적으로고정한후심외막을통하여

올가미씌우듯좌심방이를결찰하는방법으로이제까지는

수술적인방법으로만해결할수있었던좌심방이결찰을

비수술적인방법으로가능하게한획기적인시도이다.심장

내에이물질이남지않는다는점에서기존의좌심방이

고립술과는차별되는우수한기법이나,최근의임상적용

결과에서는심낭출혈,좌심방이천공,누출공등의심각한

합병증이문제가되었고,또한시술후뒤늦게나타날수있는

심방혈전형성,급사의발생등이향후해결해야할숙제로

남아있다.현재진행되고있는Watchman™ device와

LARIAT®를직접(head-to-head)비교하는연구(Safetyand

EfficacyofLeftAtrialAppendageOcclusionDevices,

NCT01695564)의 결과는 향후 좌심방이 시술에 있어

LARIAT®의임상적용에큰영향을미칠수있을것으로

예상되어그귀추가주목된다.

References

1) Bartus K, Han FT, Bednarek J, Myc J, Kapelak B, Sadowski J,

Lelakowski J, Bartus S, Yakubov SJ, Lee RJ. Percutaneous left atrial

appendage suture ligation using the LARIAT device in patients with

atrial fibrillation: initial clinicalexperience. J Am Coll Cardiol.

2013;62:108-118.

2) Price MJ, Gibson DN, Yakubov SJ, Schultz JC, Di Biase L, Natale

A, Burkhardt JD, Pershad A, Byrne TJ, Gidney B, Aragon JR,

Goldstein J, Moulton K, Patel T, Knight B, Lin AC, Valderrabano

M. Early safety and efficacy of percutaneous left atrial appendage

suture ligation: results from the U.S. transcatheter LAA ligation

consortium. J Am Coll Cardiol. 2014;64:565-572.

3) Miller MA, Gangireddy SR, Doshi SK, Aryana A, Koruth JS,

Sennhauser S, d'Avila A, Dukkipati SR, Neuzil P, Reddy VY.

Arrhythmia 2015;16(1):43-47

47

Multicenter study on acute and long-term safety and efficacy of

percutaneous left atrial appendage closure using an epicardial suture

snaring device. Heart Rhythm. 2014;11:1853-1859.

4) Guerrero M, Greenbaum A, O'Neill W. First-in-man late partial

recanalization after LARIAT suturing of the left atrial appendage

successfully treated with an AMPLATZER™ septal occluder device.

Euro Intervention. 2014;10:1126.

5) Pillai AM, Kanmanthareddy A, Earnest M, Reddy M, Ferrell R,

Nath J, Pillarisetti J, Vallakati A, Lakkireddy D. Initial experience

with post Lariat left atrial appendage leak closure with Amplatzer

septal occluder device and repeat Lariat application. Heart Rhythm.

2014;11:1877-1883.

6) Truesdell AG, Patel CP, Maini BS. Late-occurring left atrial

appendage thrombus after ligation using LARIAT. J Interv Card

Electrophysiol. 2014;41:101.

7) Koranne KP, Fernando RR, Laing ST. Left atrial thrombus after

complete left atrial appendage exclusion with LARIAT device.

Catheter Cardiovasc Interv. 2015;85:E54-7.

8) Han FT, Bartus K, Lakkireddy D, Rojas F, Bednarek J, Kapelak B,

Bartus M, Sadowski J, Badhwar N, Earnest M, Valderrabano M, Lee

RJ. The effects of LAA ligation on LAA electrical activity. Heart

Rhythm. 2014;11:864-870.

9) Afzal MR, Kanmanthareddy A, Earnest M, Reddy M, Atkins D,

Bommana S, Bartus K, Rasekh A, Han F, Badhwar N, Cheng J,

Dibiase L, Ellis CR, Dawn B, Natale A, Lee RJ, Lakkireddy D.

Impact of left atrial appendage exclusion using an epicardial ligation

system (LARIAT) on atrial fibrillation burden in patients with

cardiac implantable electronic devices. Heart Rhythm. 2014;12:52-

59.

LARIAT® Device를 이용한 경피적 좌심방이 폐색술

48

Arrhythmia 2015;16(1):48-52

서론

만성심방세동을치료하는수술적방법은메이즈(maze)

술식이대표적이다.메이즈술식은심방세동의유발부위를

전기적으로차단하고,심방내존재하는거대재진입로를

예방적으로차단함과동시에좌심방이를절제함으로써재발

후에도혈전으로인한뇌졸중의유병률을낮춘다.1,2하지만

매우 침습적이어서 단독 심방세동 환자들에서는 거의

시행되고있지않다.최근에는흉강경을이용한메이즈

술식이 개발되어 좌심방이의 수술적 절제가 비교적

비침습적으로가능하게되었다.흉강경을이용한수술적절제

방법은여러가지가시도되고있으며,그결과들이주목받고

있다.3,4

메이즈술식에동반된좌심방이차단술

개흉하여메이즈술식을하는경우좌심방이를쉽게차단

혹은제거할수있다.그방법은아래와같다.

•Internalobliteration

•Epicardialligation

•Resectionandclosure

•Staplingexclusion

•Leftatrialclipping

이중가장많이사용되는전통적인방법은좌심방이

입구를내부에서봉합하여막는방법이다.하지만최근에는

좌심방이의내부와좌심방사이가개통되는경우가종종

보고되고있어그안정성에의문점이제기되고있다.5

좌심방이제거술과차단술중에서는차단술보다는제거술이

좌심방이 절제술: 수술 치료의 역할

Received: November 3, 2014Revision Received: February 27, 2015Accepted: March 26, 2015Correspondence: Dong Seop Jeong, MD, PhD, Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, KoreaTel: + 82-2-3410-3488, Fax: +82-2-3410-0089E-mail: opheart1@gmail.com

Copyright © 2015 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd.

Dong Seop Jeong, MD, PhD

Department of Thoracic and Cardiovascular Surger y,

Cardiovascular Imaging Center, Samsung Medical Center,

Sungkyunkwan University School of Medicine

ABSTRACT

Atrial fibrillation (AF) is present in 1% to 2% of the general popula-

tion, and its prevalence has been predicted to increase more than

five-fold within the next 40 years. Patients with AF are at least five

times more likely to have a stroke than patients without AF. Ap-

proximately 90% of all strokes are ischemic, and 15% to 20% of all

ischemic strokes are associated with AF. More than 90% thrombi

are located at the left atrial appendage (LAA) in patients with AF.

Since the recent development of potentially safer and more effective

percutaneous devices and minimally invasive surgical techniques

for closing the LAA, interest has been renewed in the potential for

using these mechanical approaches to decrease the incidence of

stroke in patients with AF. This review summarizes the current status

regarding surgical approaches to LAA exclusion.

Key Words: atrial fibrillation, left atrial appendage, stroke

MAIN TOPIC REVIEWS

49

좌심방이 절제술: 수술 치료의 역할

성공률이높고안전하다는쪽이우세한실정이다(Table1).6

흉강경하부정맥수술과좌심방이제거술

경피적전극도자절제술이약물요법에비해월등히정상

리듬유지율이높은것으로알려졌으나,여전히환자의1/3

에서는재발을경험하고있을뿐아니라재발에의한뇌졸중

발생위험으로뇌졸중예방을위한항응고제를끊지못하는

환자들이매우많다.반면수술적요법은그침습성으로인해

한계가있어거의시행되지못하는실정이다.이에위험하지

않으면서(최소 침습) 정상 리듬 유지율이 높으며,

재발하더라도좌심방이입구를막거나차단하여뇌졸중을

예방할수있는치료법이절실해졌고,흉강경하부정맥

수술이그역할을시작하게되었다.

양쪽겨드랑이아래에3개씩5mm의포트를뚫어중앙은

흉강경카메라,나머지2개는흉강경수술도구및양극성

고주파절제기구를위해사용한다.흉강경하부정맥수술은

아래와같은술식으로구성되어있다.

•Pulmonaryveinisolation(폐정맥주위차단):

심방세동의주된원인차단

•Ganglionatedplexiablation(신경절차단):

재발의원인이되는부분제거

•Resectionofleftatrialauricle(좌심방이제거):

혈전이가장흔한장소제거

•Posteriorandsuperiorlineablation(추가차단술):

장기성적향상도모

•DivisionofligamentofMarshall(마샬밴드절제):

심방세동재발의드문원인이됨

이중좌심방이제거는심방세동에서혈전의 90%가

발생하는 부위인 좌심방이(left atrial appendage)를

외과적으로절제하고,수술장내에서경식도심초음파를

이용하여잔존좌심방이의여부를확인하게된다.좌심방이를

제거하기위해서는Figure 1과같이흉강경수술용자동

봉합기(stapler)를사용하거나좌심방이클립적용혹은

수술적봉합등의방법을사용한다.6 그중가장많이

사용되는 방법은 자동 봉합기를 사용하는 방법이다.

좌심방이를 외과적으로 제거하여 혈전 발생은 물론

전기적으로도 재발을 예방할 수 있다는 장점이 있기

때문이다.클립을사용하는경우는좌심방이의입구는막을

수있으나자체를제거하는것이아니기때문에장기적으로

재개통될위험이있고,전기적차단효과가증명되어있지

않아추적결과가필요하다.수술적봉합은술식이어려워

출혈,좌심방이파열등의치명적합병증이발생할수있다는

단점이있다.

최근경향

최근에는좌심방이차단용클립이발전하여좌심방이의

크기에따라맞춤형클립이고안되었을뿐만아니라차단시

잔존좌심방이가남지않도록좌심방이클립용수술도구가

진화하여점점더많은관심을받고있다(Figure2).장기

개통을방지하기위해지속적인압박이가해지는재질을

사용하여장기성적이주목된다.Emmert등에의하면가장

최근의결과는매우고무적이다.7모든환자들에서잔존

좌심방이는없었고,재개통도없었으며,미끄러진증례도

없었다.하지만3년의결과이기때문에임상적으로안심하고

사용하기위해장기간연구가필수적이라고생각한다.

Table 1. Success of different techniques for left atrial appendage (LAA) closure

Type Number Patent LAA Remnant LAA Persistent flow Success

Excision, n (%) 52 0 14 (27) 0 38 (73)

Suture exclusion, n (%) 73 6 (8) 6 (8) 44 (61) 17 (23)

Stapler exclusion, n (%) 12 2 (17) 7 (58) 3 (25) 0

Total, n (%) 137 8 (6) 27 (20) 47 (34) 55 (40)

50

Arrhythmia 2015;16(1):48-52

Figure 2. Before and after resection of left atrial auricle: bioglue was applied to stop residual bleeding.

Figure 1. Thoracoscopic resection of left atrial appendage: Left atrial auricle can be safely removed using 60 mm length stapling device after pericardial open.

51

좌심방이 절제술: 수술 치료의 역할

Figure 3. Clip for left atrial appendage closure.

AtriClip PRO

• Quick deploy feature• Head articulation 60˚ side-to-side and up / down w/lock feature• Rigid shaft

AtriClip long

• Head articulation 180˚ side-to-side• Thumb control• Malleable shaft (25 mm)

AtriClip standard

• Head articulation• Plunger grip• Stiff shaft (6 mm)

52

결론

수술적좌심방이절제혹은차단술은가장확실한방법이긴

하지만침습적이기때문에관심을받지못하였다.최근

흉강경하 부정맥 수술이 도입되면서 좌심방이 제거가

안전하고도비침습적으로시행되기시작하였다.자동봉합기

혹은클립을이용한최소침습좌심방이제거및차단술은

아직장기결과가필요하지만단독심방세동환자들에서

뇌졸중을 예방하는 또 하나의 대표적인 옵션으로서

자리매김할것으로기대한다.

References

1) Prasad SM, Maniar HS, Camillo CJ, Schuessler RB, Boineau JP,

Sundt TM 3rd, Cox JL, Damiano RJ Jr. The Cox maze III

procedure for atrial fibrillation: long-term efficacy in patients

undergoing lone versus concomitant procedures. J Thorac

Cardiovasc Surg. 2003;126:1822-1828.

2) Raanani E, Albage A, David TE, Yau TM, Armstrong S. The

efficacy of the Cox/maze procedure combined with mitral valve

surgery: a matched control study. Eur J Cardiothorac Surg.

2001;19:438-442.

3) Piston L, La Meir M, van Opstal J, Blaauw Y, Maessen J, Crijns HJ.

Hybrid thoracoscopic surgical and transvenous catheter ablation of

atrial fibrillation. J Am Coll Cardiol. 2012;60:54-61.

4) Muneretto C, Bisieri G, Bontempi L, Cumis A. Durable staged

hybrid ablation with thoracoscopic and percutaneous approach for

treatment of long-term atrial fibrillation: A 30-month assessment

with continuous monitoring. J Thorac Cardiovasc Surg.

2012;144:1460-1465.

5) Schneider B, Stollberger C, Sievers HH. Surgical closure of the left

atrial appendage - a beneficial procedure? Cardiolog y.

2005;104:127-132.

6) Lee HM, Chung SR, Jeong DS. Initial experience with total

thoracoscopic ablation. Korean J Thorac Cardiovasc Surg.

2014;47:1-5.

7) Emmert M, Puippe G, Baumuller S, Alkadhi H, Landmesser U,

Plass A, Bettex D, Scherman J, Grunenfelder J, Genoni M, Falk V,

Salzerg S. Safe, effective and durable epicardial left atrial appendage

clip occlusion in patients with atrial fibrillation undergoing cardiac

surgery: first long-term results a prospective device trial. Eur J

Cardiothorac Surg. 2014;45:126-131.

Arrhythmia 2015;16(1):48-52

53

Arrhythmia 2015;16(1):53-54

배경

현재가이드라인들은허혈성뇌졸중후에적어도24시간의

심전도모니터링을해서심방세동의존재를확인하도록

권고하고있다.하지만모니터링의가장효율적인기간과

방법에대해서는아직정립된바가없고,진단과정을마친

후에도허혈성뇌졸중의원인이불명확한경우가20-40%에

이른다.원인불명뇌졸중후심방세동의진단은치료계획

설정에중요하다.

방법

연구자들은총441명의원인불명뇌졸중환자를대상으로

무작위배정대조군연구를수행하여삽입형심장모니터

(insertable cardiacmonitor, ICM)를이용한장기간의

모니터링이전통적인추적관찰방법(대조군)보다심방세동을

진단하는데에더효과적임을평가하였다.적어도24시간의

심전도모니터링에서심방세동의증거가없는40세이상의

환자들을사건후 90일내에무작위배정하였다.일차

종말점은6개월내에심방세동(30초이상지속)이처음

발견될때까지의시간으로하였으며,이차종말점은12개월

내에심방세동이처음발견될때까지의시간이었다.데이터는

치료의도원칙에따라분석하였다.

결과

6개월까지 심방세동은 ICM 군에서 8.9% (19명),

대조군에서1.4%(3명)의환자에서발견되었다(위험비6.4;

95%CI 1.9-21.7;p<0.001). 12개월까지는ICM군에서

12.4%(29명),대조군에서2.0%(4명)의환자에서심방세동이

발견되었다(위험비7.3;95%CI2.6-20.8;p<0.001)(Figure

1).

뇌졸중의 원인에 심방세동이 관련 있는지 보려면 어떻게 확인하는 것이 좋을까?

Received: December 1, 2014Revision Received: March 1, 2015Accepted: March 26, 2015Correspondence: Seil Oh, MD, PhD, FHRS, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, KoreaTel: +82-2-2072-2088, Fax: +82-2-762-9662 E-mail: seil@snu.ac.kr

Copyright © 2015 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd.

Seil Oh, MD, PhD, FHRS

Department of Internal Medicine, Seoul National University

College of Medicine and Seoul National University Hospital

Cardiovascular Center

Cryptogenic stroke and underlying atrial fibrillation.

Sanna T, Diener HC, Passman RS, Di Lazzaro V, Bernstein RA, Mo-

rillo CA, Rymer MM, Thijs V, Rogers T, Beckers F, Lindborg K, Brach-

mann J; CRYSTAL AF Investigators.

N Engl J Med. 2014;370:2478-2486.

ARTICLE REVIEW

54

Arrhythmia 2015;16(1):53-54

Figure 1. Time to first detection of atrial fibrillation by 12 months.Red bar, ICM; Blue bar, control; CI, confidence interval; HR, hazard ratio; ICM, insertable cardiac monitor.

HR 7.3; 95% CI 2.6-20.8; p<0.001

0

5

10

15

20

Control ICM

2.0%

12.4%

Atria

l fib

rilla

tion

dete

cted

(%

of p

atie

nts)

ControlICM

55

Arrhythmia 2015;16(1):55-58ECG & EP CASES

Ventricular Tachycardia with Two Distinct Morphologies Caused by Herbal Medicine Containing Ephedra sinica

Seung Yong Shin, MD, PhD.

Division of Cardiology, Department of Internal Medicine,

College of Medicine, Chung-Ang University, Seoul, Korea

Received: November 2, 2014Revision Received: February 21, 2015Accepted: March 26, 2015Correspondence: Seung Yong Shin, MD, PhD, Heart Research Institute, Cardiovascular and Arrhythmia Center, Chung-Ang University Hospital, College of Medicine, Chung-Ang University, 102, Heukseok Ro, Dongjak Gu, Seoul, 156-755, KoreaTel: +82-2-6299-2871, Fax: +82-2-823-0160 E-mail: theshin04@naver.com, theshin@cau.ac.kr

Copyright © 2015 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd.

ABSTRACT

A 77-year-old man presented to the emergency department with dizziness and a fluttering sensation in the chest. Electrocardiography demonstrated sustained monomorphic ventricular tachycardia with two different morphologies (right bundle branch block, left bundle branch block). The patient had taken herbal medicine containing Ephedra sinica for two days. Based on the findings of a thorough work up, I concluded that both of the ventricular tachycardias might have been caused by this herbal medicine.

Key Words: Tachycardia, ventricular, Herbal medicine, Ephedra si-

nica

Introduction

Ephedra alkaloids are a group of sympathomimetic compounds

derived from the shrubs of the Ephedra genus. These alkaloids are

structurally similar to amphetamines and catecholamines, and

possess both α- and β-adrenergic activity.1 Ephedra alkaloids have

been used in traditional folk remedies, particularly in China, for

millennia. The principle alkaloid ephedrine was first isolated in

1885, and has been used in modern medicine as a bronchodilator,

decongestant, and vasopressor.2 Ephedra extracts are also

commonly taken to enhance weight loss and athletic performance.

Ephedra-containing dietary supplements were banned by the

American Food and Drug Administration in 2004 because of

significant adverse effects.3 Between 1995 and 1997, 37 cases of

adverse effects were reported and predominantly involved serious

cardiovascular events (e.g., stroke, myocardial infarction, sudden

cardiac death), despite no underlying cardiovascular disease.3

Here, I report a case of ventricular tachycardia (VT) with two

distinct morphologies caused by the consumption of herbal

medicine containing Ephedra sinica (Ma Huang).

Case

A 77-year-old man presented to the emergency department

with a fluttering sensation in the chest and sudden onset dyspnea.

On initial presentation, the vital signs were as follows: heart rate,

208 beats per minute (bpm); respiratory rate, 22 breaths per

minute; and body temperature, 36.6°C. Although the patient had

weak femoral pulses and a blood pressure of 60/40 mmHg, he

seems to be mentally alert when in a supine position. Breath

sounds were clear, and no evidence of wheezing or crackling.

However, the heart sound was distorted because of tachycardia.

Twelve-lead electrocardiography (ECG; Figure. 1A) initially

showed sustained monomorphic VT (208 bpm), a right bundle

branch block (RBBB) pattern in the precordial leads, and left axis

deviation. Biphasic electrical cardioversion (200 J) successfully

terminated the VT through conversion to atrial fibrillation

(Figure. 1B). After 1 hour, a further sustained monomorphic VT

56

Arrhythmia 2015;16(1):55-58

Figure 1. Twelve-lead electrocardiograms (ECG).(A) The initial ECG shows fast monomorphic ventricular tachycardia (208 bpm), a right bundle branch block in the precordial leads, and left axis

deviation. VT was inferred based on the interpretation of the ECG with the captured beat (arrow).(B) Atrial fibrillation is observed following electrical cardioversion.(C) The ECG of the second VT (210 bpm) shows a left bundle branch block pattern and superior axis deviation.(D) The ECG shows restored sinus rhythm after additional electrical cardioversion.

B

C

D

A

57

Ventricular Tachycardia by Ephedra sinica

(210 bpm) developed spontaneously, with a QRS morphology

that was indicative of left BBB (LBBB) and superior axis

deviation (Figure. 1C). Biphasic electrical cardioversion (200 J)

was reattempted, and sinus rhythm was successfully restored

(Figure. 1D).

After the treatment, the possible causes of the VT were

considered, including anemia, electrolyte imbalance, hypoxemia,

coronary artery disease, cardiomyopathy, congenital heart disease,

or drug effects. Laboratory result revealed normal serum

creatinine levels, electrolyte levels, and arterial blood gases.

Similarly, ECG showed a normal left ventricular ejection fraction

(65%) with no significant valve degeneration or structural

abnormalities. Although coronary angiography revealed a stenosis

of 70% in both the proximal part of the left circumflex coronary

artery and the posterior descending artery, I decided to administer

pharmacologic treatment based on the presence of normal blood

flow and absence of angina.

The patient had been diagnosed with chronic obstructive

pulmonary disease 30 years prior to admission. He had a history

of smoking (one half-pack per day for 50 years) but had ceased

this habit one year previously. The current medication included

methylprednisolone (2 mg/day) and the β2-agonist fenoterol (2.5

mg/day). The patient reported no history of alcohol or

intravenous drug abuse, and had no remarkable family history of

cardiovascular disease or sudden cardiac death. He reported

taking herbal medicine containing E. sinica over the course of two

days (total four doses) for abdominal discomfort and indigestion.

I concluded that the consumption of the herbal medicine was the

cause of the VT with two distinct QRS morphologies.

The patient was prescribed clopidogrel, warfarin, an

angiotensin-converting enzyme inhibitor, a β-blocker, and a statin,

and was advised against resuming the herbal medication prior to

discharge. No recurrences of VT occurred during more than 6

months of follow-up.

Discussion

Ephedrine and related alkaloids have been associated with

numerous adverse cardiovascular events, including acute

myocardial infarction, severe hypertension, myocarditis,4,5 and

lethal cardiac arrhythmias.6,7 This development of adverse

cardiovascular events is largely attributable to the

sympathomimetic activity of these alkaloids.1 That is, these

compounds directly stimulate α1, β1, and β2 adrenergic receptors

and can thereby result in vasoconstriction, bronchodilation,

increased heart rate, enhanced myocardial contractility, and

increased automaticity. Such compounds also shorten cardiac

refractory periods and can therefore facilitate the development of

cardiac arrhythmogenesis.8 The long-term use of ephedrine may

lead to the cardiomyopathy typically observed during

catecholamine excess.7

To date, there has been no report of VT with two distinct QRS

morphologies (RBBB and LBBB) caused by E. sinica in patients.

The present case is also distinct from previously reported cases of

VT6,7 in several additional respects: 1) the sustained distinct

monomorphic VTs originated from different ventricles; 2) the

patient had taken unknown but small doses of E. sinica (four in

total); and 3) the ingestion of the herbal medication had been of a

relatively short duration (two days).

Recently, the molecular mechanisms underlying E. sinica

activity have been demonstrated, in vivo, to involve the activation

of the slowly activating KCNQ1 potassium channel and other

members of the KCNE protein family.9 Although this activation

could be expected to precipitate ventricular arrhythmia, further

investigation is required to confirm this. Nonetheless, because

even short-term, low-dose intake of E. sinica is associated with the

risk of life-threatening ventricular arrhythmias, its use should be

closely monitored and tightly regulated.

References

1) Dulloo AG. Herbal simulation of ephedrine and caffein in

treatment of obesity. Int J Obes Relat metab Disord. 2002;26:590-

592.

2) Haller CA, Benowitz NL. Adverse cardiovascular and central

nervous system events associated with dietary supplements

containing ephedra alkaloids. N Engl J Med. 2000;343:1833-1838.

3) Greenway FL. The safety and efficacy of pharmaceutical and herbal

caffein and ephedrine use as a weight loss agent. Obes Rev.

2001;2:199-211.

4) Mark PB, Watkins S, Dargie HJ. Cardiomyopathy by performance

enhancing drugs in a competitive bodybuilder. Heart. 2005;91:888.

58

5) Samenuk D, Link MS, Homoud MK, Contreras R, Theoharides

TC, Wang PJ, Estes NA 3rd. Adverse cardiovascular events

temporally associated with ma huang, an herbal source of

ephedrine. Mayo Clin Proc. 2002;77:12-16.

6) Makaryus JN, Makaryus AN. Cardiac arrest in the setting of diet

pill consumption. Am J Emerg Med. 2008;26:732.e1-3.

7) Casella M, Dello Russo A, Izzo G, Pieroni M, Andreini D, Russo E,

Colombo D, Bologna F, Bolognese L, Zeppilli P, Tondo C.

Ventricular arrhythmias induced by long-term use of ephedrine in

two competitive athletes. Heart Vessels. 2015;30:280-283.

8) Maughan RJ. Contamination of dietary supplements and positive

drug tests in sport. J Sports Sci. 2005;23:883-889.

9) Jing H, Luo L, Li H, Sun J, Yi H, Wu Y, Wang C, He G. Ephedrine

controls heart rhythms by activating cardiac I (IKs) currents. J

Cardiovasc Pharmacol. 2010;55:145-152.

Arrhythmia 2015;16(1):55-58

59

Received: December 25, 2014Revision Received: February 18, 2015Accepted: March 26, 2015Correspondence: Yong-Seog Oh, MD, PhD, Director of Electrophysiology, Division of Cardiovascular Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, College of Medicine, 505 Banpo-Dong, Seocho-Ku, Seoul, 137-040, Republic of KoreaTel: +82-2-2258-6031, Fax: +82-2-592-3810 E-mail: oys@catholic.ac.kr

Copyright © 2015 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd.

Accessory Pathway with Decremental Conduction Properties

Yong Seog Oh, MD, PhD

Division of Cardiology, Depeartment of Internal Medicine,

Catholic University of Korea

ABSTRACT

Permanent junctional reciprocating tachycardia (PJRT) is an ortho-dromic atrioventricular tachycardia mediated by a concealed acces-sory pathway with slow conduction and decremental property. The accessory pathway in PJRT is most often located in the posteroseptal region, especially around the coronary sinus ostium. Here I describe a case of clinical tachycardia with a long RP interval due to slow retrograde conduction.

Key Words: supraventricular tachycardia, accessory pathway

Introduction

Narrow-QRS tachycardia with a long RP interval presents interesting

diagnostic challenges. A correct diagnosis is essential for performing safe

and effective catheter ablation. The differential diagnosis of

narrow-QRS tachycardia with a long RP interval includes atypical

atrioventricular nodal reentrant tachycardia (AVNRT), ectopic

atrial tachycardia, and atrioventricular reentrant tachycardia (AVRT)

with a decremental property. I present a case of permanent junctional

reciprocating tachycardia (PJRT) with a long RP interval that exhibited a

decremental property.

Case

A 65-year-old woman was referred to our hospital for sustained

palpitations and general weakness. The electrocardiogram (ECG)

showed narrow QRS tachycardia of ~120 /min, with an inverted

P wave in leads II, III, aVF, and a long RP interval in all precordial

leads (Figure 1). She had normal left ventricular function on

echocardiography, with an ejection fraction of 62%. Twenty-four-

hour Holter monitoring showed repeated induction of

supraventricular tachycardia (SVT), with intervening periods of

sinus rhythm lasting a few minutes. I administered IV adenosine,

verapamil injection, and DC cardioversion several times in an

attempt to terminate the tachycardia, but after few seconds in

sinus rhythm the tachycardia was reinduced and sustained. To

maintain sinus rhythm I prescribed 240 mg of verapamil or 150

mg of atenolol per os; however, the patient continued to exhibit

the same drug-refractory tachycardia.

The patient was scheduled for electrophysiological study and

catheter ablation. In the electrophysiology lab she showed SVT

with intermittent short periods of sinus rhythm. The SVT could

be easily induced by one premature ventricular contraction

(PVC), and was also inducible in sinus rhythm without any AH

jump (Figure 2). For the differential diagnosis, I applied a PVC

during SVT. In contrast to orthodromic AVRT without a

decremental property, after the PVC the AA interval was

prolonged from 467 ms to 494 ms (Figure 3). To ablate the

Arrhythmia 2015;16(1):59-64ECG & EP CASES

60

Arrhythmia 2015;16(1):59-64

accessory pathway, I identified the earliest activation site of A in

the right posteroseptal area (Figure 4, Figure 5). After 4 seconds of

radiofrequency application, the SVT terminated and showed

ventriculoatrial dissociation (Figure 6). The patient remained in

hospital for two days after the catheter ablation and was

discharged in sinus rhythm.

Discussion

In this case, no preexcitation was observed. During the

tachycardia, the earliest atrial activation was observed around the

coronary sinus ostium. The critical finding for the differential

diagnosis was the atrial response to a PVC during the His

refractory period. Since the atrial activation was delayed by the

PVC, AVNRT could be excluded.1

PJRT is an orthodromic AVRT mediated by a concealed and

slow-conducting accessory pathway. The clinical course of PJRT is

not always benign. Many patients try multiple antiarrhythmic

drugs and ultimately require catheter ablation. Radiofrequency

catheter ablation is a safe and effective therapy.2 However, the

higher recurrence rate of PJRT, compared with that of reentry

with no decremental property, may be explained by the long,

tortuous course of the accessory pathway. The most important

complication of incessant PJRT is tachycardia-induced

Figure 1. (A) Electrocardiogram in tachycardia, (B) Electrocardiogram in sinus rhythm.

A

B

61

Accessory Pathway with Decremental Conduction Properties

Figure 2. (A) Electrocardiogram showing induction of supraventricular tachycardia (SVT) by a premature ventricular contrac-tion (PVC), (B) Electrogram showing SVT induction by PVC.

A

B

62

A

B

Figure 3. (A) Electrocardiogram showing induction of supraventricular tachycardia (SVT) in sinus rhythm, (B) Electrogram showing SVT induction in sinus rhythm.

Arrhythmia 2015;16(1):59-64

63

Figure 4. The earliest atrial activation site in supraventricular tachycardia.

Figure 5. Catheter in fluoroscopic view. RAO, right anterior oblique projection; LAO, left anterior oblique projection.

RAO LAO

Accessory Pathway with Decremental Conduction Properties

64

cardiomyopathy, which has been observed in 18% of patients with

PJRT.3 Slower conduction through the accessory pathway has a

wider excitable gap. In most cases of PJRT, the accessory pathway

is located in the posteroseptal region.

References

1) Ho RT, Frisch DR, Pavri BB, Levi SA, Greenspon AJ. Greenspon.

Electrophysiological features differentiating the atypical

atrioventricular node- dependent long RP supraventricular

tachycardias. Circ Arrhythm Electrophysiol. 2013;6:597-605.

2) Meiltz A, Weber R, Halimi F, Defaye P, Boveda S, Tavernier R,

Kalusche D, Zimmermann M. Permanent form of junctional

reciprocating tachycardia in adults: peculiar features and results of

radiofrequency catheter ablation. Europace. 2006;8:21-28.

3) Bensler JM, Frank CM, Razavi M, Rasekh A, Saeed M, Haas PC,

Nazeri A, Massumi A. Tachycardia-mediated cardiomyopathy and

the permanent form of junctional reciprocating tachycardia. Tex

Heart Inst J. 2010;37:695-698.

Figure 6. (A) Electrogram showing termination of supraventricular tachycardia, (B) Electrogram showing ventriculoatrial dissociation.

A

B

Arrhythmia 2015;16(1):59-64

자율 학습 문제

부정맥에서는매호자율학습문제를수록합니다.해당호에실린원고를바탕으로출제된문제로선생님들의

자기계발에도움이되시길바랍니다.많은참여부탁드립니다.

1. 좌심방이 폐색술의 적응증으로 적당하지 않은 것은 무엇인가?

① 항응고제사용후에반복적인출혈이있는경우

②항응고제과민증이있는경우

③항응고제사용후에도뇌줄중이발생한경우

④항응고제사용후추가적인항혈전제사용이필요한경우

2. 좌심방이 폐색술 시 전달용 와이어를 풀기 전에 확인해야 할 사항으로 적당하지 않은 것은 무엇인가?

① 장치주변에서혈류의흐름이유의하게남아있는지

②장치가30%이상눌려있는지

③전달용와이어로장치를흔들어보아안정성이있는지

④좌심방이의모든엽을덮었는지

3. 좌심방이 결찰을 위한 LARIAT® device에 대한 설명으로 적당하지 않은 것은 무엇인가?

① 심외막에서좌심방이를봉합,결찰하는방식이다.

②심외막접근법(epicardialapproach)은통상적인방법으로시행하되,

가급적전방(anteriorapproach)을향하도록한다.

③출혈성부작용은다른기기에비해크지않다.

④1/3의환자에서는좌심방이의전기적활성이없어짐이보고되었다.

4. 흉강경하 부정맥 수술 시 시행되는 시술이 아닌 것은 무엇인가?

① Pulmonaryveinisolation

②Carvotricuspidisthmusablation

③Ganglionatedplexiablation

④DivisionofligamentofMarshall

모범 답안은 가장 마지막 페이지에 수록되어 있습니다.

투고 및 윤리 규정

목적과개요

부정맥(TheOfficialJournalofKoreanHeartRhythmSociety)

은대한심장학회부정맥연구회의주관으로발행되며,부정맥과관

련된새로운임상연구,진료지침,증례등을소개하여부정맥연

구회회원및개원의의지속적인의학교육에이바지하고자발행

되는최신학술지이다.본지는부정맥의진단과치료,임상연구

와관련된원저,종설,논평,증례보고등을편집위원회에서검토

후게재한다.

연구및출판윤리규정

본규정은대한심장학회부정맥연구회회원들의학술활동중연

구윤리를확보하는데필요한역할과책임에관하여기본적인원

칙과방향을제시하기위하여제정되었으며,각회원은연구활동

중정직성,진실성,정확성이연구결과의신뢰성확보를위한필

수조건임을인식하고모든연구활동을수행함에있어이규정을

준수하도록한다.

1.저자들은UniformRequirementsforManuscripts

SubmittedtoBiomedicalJournals(http://www.icmje.

org/)에서규정한윤리규정을준수해야한다.

2.본학술지에투고하는원고의연구대상이사람인경우는헬

싱키선언(DeclarationofHelsinki[www.wma.net])의윤

리기준에일치해야하며,기관의윤리위원회또는임상시험심사

위원회(InstitutionalReviewBoard)의승인을받고,필요한경

우에연구대상자의동의서를받았음을명시해야한다.

3.동물실험연구는실험과정이연구기관의윤리위원회의규정

이나NIHGuide for theCareandUseofLaboratory

Animals의기준에합당해야한다.

4.간행위원회는필요시환자동의서및윤리위원회승인서의

제출을요구할수있다.

5.이해관계명시(Disclosureofconflictofinterest):연구에

소요된연구비수혜내용은감사의글에필히기입해야한다.

연구에관계된주식,자문료등이해관계가있는모든것은표지

하단에밝혀져야하며,이를모두명시했음을원고의저자전원

의자필서명이있어야한다.

6.원칙적으로타지에이미게재된같은내용의원고는게재

하지않으며,본지에게재된것은타지에게재할수없다.단,독

자층이다른타언어로된학술지에게재하기위한경우등의중

복출판은양측간행위원장의허락을받고,중복출판원고표지에

각주로표시하는등,다음문헌에서규정한요건을갖춘경우에만

가능하다(AnnInternMed1997;126:36-47).

7.윤리규정및표절/중복게재/연구부정행위등모든연구윤리와

연계되는사항에대한심사및처리절차는대한의학학술지편집

인협의회에서제정한'의학논문출판윤리가이드라인(http://

kamje.or.kr/publishing_ethics.html)'을따른다.

원고범위

1.원저(OriginalArticle)는인간을대상으로한연구(임상적조사

및보고서)와동물을이용한실험및생체외실험에대한연구(

기초과학보고서)로한다.

2.종설(ReviewArticle)은특정분야나주제에관해간결하고

포괄적으로평가한논문으로위촉된종설에한하여게재하는것

을원칙으로하나편집진의재량에따라위촉되지않은종설도게

재가능하다.

3.논평(Editorial)은타학술지에게재된논문에대한저자의

견해를기술한것으로,편집진의의뢰하에쓰여진다.

4.증례보고(CaseReport)의요건은국내첫증례또는희귀

증례로제한한다.

집필규정

1.원저와증례보고는영어,종설과논평은한글을사용하여맞춤법에

맞게작성하며모든학술용어는대한의사협회에서발간한의학용

어집의최신판에수록된용어를사용한다.

2.한글로작성하는원고는원어의적당한한글용어가없는경우한

글뒤()안에원어는표기할수있다.부득이외국어를사용할때

는대소문자의구별을정확히해야한다(예：고유명사,지명,인

명은첫글자를대문자로하고그외에는소문자로기술함을원칙

으로한다).적절한번역어가없는의학용어,고유명사,약품명,단

위등은원어를그대로사용한다.

3.번역어가있으나의미전달이명확하지않은경우에는그용어

가최초로등장할때번역어다음소괄호속에원어로표기하고

그이후로는번역어만사용한다.

4.검사실검사수치의단위는SI단위(InternationalSystemof

Units)를사용하고,편집위원회의요구나필요에따라괄호안에

비SI단위수치를첨부할수있다.

5.약자는가능한한사용하지않는것이좋지만,본문에일정용어

가반복사용됨으로인해부득이약자를사용해야하는경우

에는그용어가처음나올때괄호안에약자를함께표기하고

다음부터약자를사용할수있다.

6.원고는컴퓨터문서작성프로그램(MS워드또는한글)을사용

하여작성한다.글자의크기는명조계통의10point,정렬은좌측

정렬을하며,줄간은한글의경우160%,워드의경우1줄간격

으로하며좌우및위아래여백은3cm로한다.원고면의번호

는제목쪽부터시작하여차례대로중앙하단에표시한다.

원고의형식

1. 원저(Original Article)

표지,초록과키워드,본문,감사문,참고문헌,도표,그림/사진

설명,그림및사진의순으로하며,제목쪽과초록및참고문

헌은각각분리된쪽으로작성한다.

1) 표지(Title Page)

①제목,소속,저자명,영문제목및영문소제목(빈칸을포함

하여50자이내),영문저자명,영문소속순으로하며,표지

하단에교신저자(correspondingauthor)의이름,주소,소속,

전화번호,팩스번호,E-mail주소등을명시해야한다.

②저자들의소속이다수인경우소속명을같은행에연이어

나열하며,아라비아숫자의어깨번호로소속과저자명을

일치시킨다.영문저자명뒤의MD나PhD등에는글자다

음에구두점을찍지않는다.

2) 초록과 키워드(Abstracts and Key Words)

모든원고에는영문초록을첨부해야하며,초록은250단어이

내로한다.BackgroundandObjectives,Subjects(Materials)

andMethods,Results,Conclusion의순으로구분하여소제

목에따라줄바꿈없이작성한다.증례보고인경우소제목없

이가능하며,초록은150단어이내로한다.단논평의경우초

록과keywords를첨부하지않는다.그리고각초록의말미에

Indexmedicus에등재된용어5개이내로영문keywords를

삽입한다.

3) 본문(Text)

서론,대상(재료)및방법,결과,고찰,요약,중심단어순으로

작성한다.

①서론에는연구와관련된간략한배경과연구의목적이언급

되어야한다.

②대상(재료)및방법은매우상세히기재해야하며결과의통

계적검증방법도밝혀야한다.

③고찰은연구결과와연관된새롭고중요한측면에대한내용

으로제한한다.

④요약은결과와고찰로부터유도되고,서론에서언급한연구

목적과부합되어야하며,결과의단순한요약은금한다.

요약의구성은배경및목적,방법,결과,결론의순으로구

분하여소제목에따라줄바꿔작성한다.그리고국문논문은

요약다음에한글중심단어를초록의영문중심단어와일치

시켜삽입한다.

4) 감사문(Acknowledgments)

감사문에는본연구의연구비지원기관,본연구를수행하는데

여러가지로도움을주었던분들에대한사항을기술한다.

5) 참고문헌(References)

①원저는30개이하,증례보고는20개이하로제한한다.종설

은참고문헌수를제한하지않는다.

②참고문헌은본문에나타난것만인용한다.본문에서는인용

순서에따라아라비아숫자로저자명뒤또는문장끝에어

깨번호로표시한다.참고문헌의배열도인용한순서대로작

성한다.동일저자의경우연도순으로나열하며,국내문헌도

영문표기를원칙으로한다.

③참고문헌의저자는모두기재한다.저자표기는lastname은

다쓰고,firstname과secondname은첫글자를대문자로

붙이고initial에마침표(.)는사용하지않는다.저자명사이

에는쉼표(,)로구분하고,마지막저자명뒤에는마침표(.)

를찍는다.

④잡지명은‘ListofJournalsIndexMedicus’에의거약어로

기재하며,인용학술지명뒤에는마침표를찍는다.인용논문

의제목중첫글자는대문자로하고,부제목이있는경우

쌍점(：)을붙인후소문자로기재하며제목뒤에는마침표

(.)로표시하며,연도를표시한후쌍반점(；)으로붙여서구

분후,권：시작쪽-끝쪽의전체페이지를기재하며,마지막

에마침표를찍는다.

예)SmithHJ,AllenS,YuW,FardS.Thisisthetitle.

Circulation.2004;104:276-308.

6) 표(Table)

①표는영문과아라비아숫자로기록하며표의제목을명료하게

절혹은구의형태로기술한다.문장의첫자를대문자로한다.

②분량은4줄이상의자료를포함하여1쪽을넘지않는다.

③본문에서인용되는순서대로번호를붙인다.

④약어를사용할때는해당표의하단에알파벳순으로풀어서

설명한다.

⑤기호를사용할때는*,†,‡,§,‖,¶,**,††,‡‡의

순으로하며이를하단각주에설명한다.

⑥표의내용은이해하기쉬워야하며,독자적기능을할수있

어야한다.

⑦표를본문에서인용할때는영문(Table1과같이)을사용한다.

7) 그림 및 사진(Figure)

①그림및사진은‘ppt’파일형식으로원문과별도의파일을만

들어서제출한다.

②동일번호에서2개이상의그림이필요한경우에는아라비아

숫자이후에알파벳글자를기입하여표시한다(예:Figure

1A,Figure1B).

③그림을본문에서인용할때에는한글(Figure1과같이)을사

용한다.

④최종통과시그림및사진은‘jpg’파일형식으로1장씩10메

가이내로파일을만들어서제출한다.

8) 그림 및 사진 설명(Figure Legends)

①본문에인용된순으로아라비아숫자로번호를붙인다.

②모든그림및사진은설명이있어야하며,별지에영문으로

구나절이아닌문장형태로기술한다.

③현미경사진의경우배율을기록한다.

2. 원저 이외의 원고

일반사항은원저에준한다.

1) 종설(Review Article)

종설은특정제목에초점을맞춘고찰로서편집위원회에서위촉

혹은투고에의하여게재한다.단,투고된원고는심사를거쳐게

재여부를결정한다.

2) 증례 보고(Case Report)

①전체분량이A4용지10매이내로작성한다.

②영문초록은항목구분없이150단어이내로한다.

③고찰은증례가강조하고있는특정부분에초점을맞추며

장황한문헌고찰은피한다.

④참고문헌의수는20개이내,그림은5장이내로한다.

⑤저자수는7명이내로한다.

3) 논평(Editorial)

학회지에출판된특정논문에대한논평을의뢰받아집필되는부

문으로학회의의견을반영하는것은아니다.원고는A4용지4

매이내로작성하고참고문헌은10개이내로제한한다.

기타사항

1.본학회지는연간4회(3,6,9,12월말일)발간한다.

2.필요할경우원문에영향을미치지않는범위내에서자구와

체제를편집방침에따라편집위원이수정할수있다.

3.원고의게재여부는원고심사후편집위원회에서결정하며

본규정에맞지않는원고는개정을권유하거나게재를보류할

수있다.

4.학회지의게재는원고의저작권이저자로부터학회지로이양

되는것을저자가승인한것으로인정한다.

5.원고제출처

•부정맥연구회온라인논문투고사이트

http://arrhythmia.medimedia.co.kr

•엠엠케이커뮤니케이션즈(주)

E-mail:jhkim@mmk.co.kr

주소:서울시강남구논현로523,노바빌딩3층

(135-909)

전화:82-2-2007-5435팩스:82-2-3452-5984

저자 점검표

•저자(소속): •논문제목:

다음은귀하가본부정맥(TheOfficialJournalofKoreanHeartRhythmSociety)에투고하는논문이투고규정에맞도록각항목별

로충실히작성되어있는지점검하는저자점검표입니다.논문투고시해당칸에표시하여논문과함께반드시제출하여주십시오.

일반사항

1.본논문의내용은다른학회지에게재되지않았고,게재예정도없다 ☐2.원고는A4용지10포인트크기로여백상,하,좌,우3.5,3,3,3cm,줄간격1기준으로작성하였다 ☐3.원저는표지,영문초록,서론,본론,결론,참고문헌,Table,Figure순서의양식으로구성하며,본론은소제목으로구분한다 ☐4.증례는표지,영문초록,서론,증례,고찰,참고문헌,Table,Figure순서의양식으로구성한다 ☐5.일련쪽수를하단에기재하였다 ☐

표지

1.논문제목 ☐2.저자소속,이름 ☐3.영문제목,영어저자명,영어소속 ☐4.요약제목(Runningtitle)-국문제목30자이상,영문제목12단어이상 ☐5.책임저자이름,주소,전화,Fax,전자우편주소 ☐6.연구비에대한사항을각주에적었다(해당되는경우) ☐

영문 초록

1.영문제목이한글제목과일치하도록작성,영문성명,영문소속의올바른기재 ☐2.원저는내용을Background,Objective,Method,Result,Conclusion으로규정된형식으로작성하였다 ☐3.증례는내용을한단락(paragraph)으로작성하였다 ☐4.KeyWords3-5개를MeSH에맞게작성하였다 ☐

본문

1.한글로사용가능한용어는한글로기재하였다 ☐2.본문중해당참고문헌의어깨번호를표시하였다 ☐

참고문헌

1.투고규정준수에맞게모두영문으로작성하여PubMed와KorMed에서확인하였다 ☐2.참고문헌의모든공저자를기재하였다 ☐3.학술지표기는IndexMedicus의공인된약어를사용하였다 ☐4.학술지를이탤릭체로표기하였다 ☐

Table과 Figure

1.Table과Figure는중복되지않도록작성하였다 ☐2.Table과Figure는투고규정에맞도록작성하였다 ☐3.제목및설명모두영문으로기재하였다 ☐4.제목에서약자를사용하지않으며,Table과Figure에사용된약자는하단에설명을기재하였다 ☐

본논문의저자(들)은부정맥(TheOfficialJournalofKoreanHeartRhythmSociety)의투고규정에따른

위의사항들을확인하였으며,논문게재를요청합니다.

20년월일

저자대표________________________(서명)

저작권 이양 동의서

논문 제목

•국 문

•영 문

본 논문의 저자(들)은 본 논문의 부정맥(The Official Journal of Korean Heart Rhythm Society) 게재를 바라며, 이에 다음 사

항들에 대하여 동의합니다.

1.본논문의저자(들)은본논문이창의적이며,다른논문의저작권침해,비방,혹은사적침해등내포하지않음을확인합니다.

2.본논문의저자(들)은본논문에실제적이고지적인공헌을하였으며,본논문의내용에대하여공적인책임을공유합니다.

3.본논문은과거에출판된적이없으며,현재다른학술지에게재를목적으로제출되었거나제출할계획이없습니다.

4.본논문의저자(들)은본논문이부정맥(TheOfficialJournalofKoreanHeartRhythmSociety)에게재될경우,저작권에

관한모든권리,이익및저작권에대한모든권한행사등을대한심장학회부정맥연구회에이양하기로동의합니다.이는저자(들)이

향후다른논문에본논문의자료를사용할경우대한심장학회부정맥연구회로부터서면허가를받아야하며,이경우자료가발표된

원논문을밝혀야하다는것을의미합니다.

년월일

저자 성명 서명 저자 성명 서명

책임저자 제5저자

제1저자 제6저자

제2저자 제7저자

제3저자 제8저자

제4저자 제9저자

Vol.15 No.4 |통권51호 |자율 학습 문제 [모범 답안]

1. 심방세동 환자에서 증상 관리를 위한 안정 시 심박수의 목표치는 분당 몇 회인가?

① 60회/분 ②70회/분

③80회/분 ④110회/분

☞정답:③

2. 심부전 환자에서 발작성과 지속성 심방세동의 동율동 유지를 위해 사용할 수 있는 약제는 무엇인가?

① Dronedarone

②Amiodarone

③Propafenone

④Flecainide

☞정답:②심부전이동반되어있는경우amiodarone과dofetilide를사용하여동율동을유지할수있다.

3. 다음 중 HAS-BLED 출혈 위험 점수 계산에 포함되는 인자로 옳지 않은 것은 무엇인가?

① Chronicdialysis

②Timeintherapeuticrange65%

③Hypertensionhistorywithsystolic/diastolicBPof135/75mmHg

④Useofclopidogrel

☞정답:③Hypertensionisdefined>systolicbloodpressure160mmHg

4. 심방세동 환자의 고주파 전극도자 절제술 과정 중 적절한 INR은 얼마인가?

① 1.5-2.0

②2.0-2.5

③2.5-3.0

④3.0-3.5

☞정답:②절제술과정중INR(internationalnormalizedratio)은2.0-2.5정도를추천한다.

Vol.16 No.1 |통권52호 |자율 학습 문제 [모범 답안]

1. 좌심방이 폐색술의 적응증으로 적당하지 않은 것은 무엇인가?

① 항응고제사용후에반복적인출혈이있는경우

②항응고제과민증이있는경우

③항응고제사용후에도뇌줄중이발생한경우

④항응고제사용후추가적인항혈전제사용이필요한경우

☞정답:④추가적인항혈전제사용자체가적응증이되지는않는다.

2. 좌심방이 폐색술 시 전달용 와이어를 풀기 전에 확인해야 할 사항으로 적당하지 않은 것은 무엇인가?

① 장치주변에서혈류의흐름이유의하게남아있는지

②장치가30%이상눌려있는지

③전달용와이어로장치를흔들어보아안정성이있는지

④좌심방이의모든엽을덮었는지

☞정답:②장치가10-20%이상눌려있는지확인할필요가있다.

3. 좌심방이 결찰을 위한 LARIAT® device에 대한 설명으로 적당하지 않은 것은 무엇인가?

① 심외막에서좌심방이를봉합,결찰하는방식이다.

②심외막접근법(epicardialapproach)은통상적인방법으로시행하되,

가급적전방(anteriorapproach)을향하도록한다.

③출혈성부작용은다른기기에비해크지않다.

④1/3의환자에서는좌심방이의전기적활성이없어짐이보고되었다.

☞정답:③한연구에의하면10%의환자에서주요출혈성부작용이보고되었다.

4. 흉강경하 부정맥 수술 시 시행되는 시술이 아닌 것은 무엇인가?

① Pulmonaryveinisolation

②Carvotricuspidisthmusablation

③Ganglionatedplexiablation

④DivisionofligamentofMarshall

☞정답:②흉강경하부정맥수술은아래와같은술식으로구성되어있다.

・Pulmonaryveinisolation(폐정맥주위차단):심방세동의주된원인차단

・Ganglionatedplexiablation(신경절차단):재발의원인이되는부분제거

・Resectionofleftatrialauricle(좌심방이제거):혈전이가장흔한장소제거

・Posteriorandsuperiorlineablation(추가차단술):장기성적향상도모

・DivisionofligamentofMarshall(마샬밴드절제):심방세동재발의드문원인이됨