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CASE REPORTISSN 1738-3331, http://dx.doi.org/10.7704/kjhugr.2015.15.4.258

The Korean Journal of Helicobacter and Upper Gastrointestinal Research, 2015;15(4):258-263

A Case of Myocardial Infarction Occurred after Endoscopic Submucosal Dissection under Bridging Therapy with Low Molecular Weight HeparinDong Pil Kim, Seung Woo Lee, Su Sin Jin, Seung Hwa Choi, Kang Yeon Won, Jin Tak Yun, Seok-Hwan Kim, Jun Kyu ParkDivision of Gastroenterology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea

Myocardial infarction (MI) is a complication that can occur after endoscopic submucosal dissection (ESD). However, very few re-ports are available about this complication. A 71-year-old male, who had two drug eluting stents inserted due to ischemic heart dis-ease, was referred to the Division of Gastroenterology for ESD of a lesion suspicious of early gastric cancer. ESD was performed after dual antiplatelet agents were discontinued and bridging therapy with low molecular weight heparin (LMWH) was initiated. However, MI occurred immediately after the ESD procedure. A coronary angiogram did not show any significant stent thrombosis or restenosis. The patient recovered spontaneously. Here, we report a case of MI that occurred after ESD under bridging therapy with LMWH. (Korean J Helicobacter Up Gastrointest Res 2015;15:258-263)

Key Words: Stomach neoplasms; Myocardial infarction; Heparin

Received: July 31, 2015 Accepted: October 15, 2015

Corresponding author: Seung Woo LeeDivision of Gastroenterology, Department of Internal Medicine, The Catholic University of Korea, Daejeon St. Mary’s Hospital, 64 Daeheung-ro, Jung-gu, Daejeon 34943, KoreaTel: +82-42-220-9501, Fax: +82-42-252-6807, E-mail: leeseungwoo@hanmail.net

INTRODUCTION

Endoscopic submucosal dissection (ESD) is a minimally

invasive treatment modality for early gastric cancer. More

ESD procedures are being performed as detection of early

gastric cancer has increased. Gastroenterologists are con-

fronted with complications, such as bleeding, perforation,

stenosis, and rarely myocardial infarction (MI). In addition,

the number of patients with cardiovascular disease has

been increasing, making management of antiplatelet agents

and anticoagulants during ESD particularly difficult in pa-

tients with high risk for thromboembolism. Many insti-

tutions have reported management strategies for patients

with coronary stents who are undergoing dual antiplatelet

therapy and require a high bleeding risk procedure.1,2

However, no guidelines have been established. The

American Society for Gastrointestinal Endoscopy (ASGE)

recommends that patients with a high thromboembolic

risk, taking dual antiplatelet therapy, and who need a

high bleeding risk procedure such as ESD should consider

continuing aspirin during the procedure. Some institutions

including the Japanese Circulation Society (JCS) agree

with aspirin use, but they remark that heparin bridging

can be considered if dual antiplatelet therapy is discon-

tinued.3-6 Bridging therapy with heparin has been used as

perioperative anticoagulation after discontinuation of oral

anticoagulants and has been used in clinical practice after

discontinuing antiplatelet therapy.4 Here, we report a case

of MI that occurred after ESD using bridging therapy with

low molecular weight heparin (LMWH).

CASE REPORT

A 71-year-old male visited the Division of Gastroenter-

ology for treatment of gastric adenoma. He had a history

of ischemic heart disease, diabetes mellitus, hypertension,

and Parkinson’s disease. He underwent a percutaneous

coronary intervention and had two drug eluting stents

coated with paclitaxel and cilostazol inserted about 3

months ago. After implantation of the coronary stents, he

began taking aspirin and clopidogrel as dual antiplatelet

therapy, and was kept under observation in the cardiol-

ogy outpatient department. A screening endoscopy re-

Dong Pil Kim, et al: Myocardial Infarction as a Complication of Endoscopic Submucosal Dissection

259

Fig. 1. Initial gastroscopy. (A) Appro-ximate 1.8×1.2 cm, type IIa+IIc earlygastric cancer was observed on the posterior side of the angle. (B) Appro-ximate 2.0×2.0 cm, type IIa adenoma was observed on the posterior side of the lower body.

Fig. 2. Baseline electrocardiogram shows poor R progression and changesin Q waves on leads II, III, aVF, and changes in ST segment on leads V1∼V4 due to previous myocardial infarc-tion.

vealed a 1.8×1.2 cm lesion suspicious of early gastric

cancer on the posterior side of the gastric angle and a

2.0×2.0 cm lesion suspicious of gastric adenoma on the

posterior side of the lower body. A biopsy confirmed high

grade dysplasia (HGD) and low grade dysplasia (LGD) of

the two lesions, respectively (Fig. 1).

No extension into the gastric wall, adherence to sur-

rounding tissue, or enlarged lymph nodes were detected

on abdominopelvic computed tomography. We planned to

delay the ESD 6∼12 months after the stents were im-

planted considering his thromoboembolic risk. However,

the patient wanted treatment immediately considering

cancer progression. First, we planned ESD for the HGD

lesion suspected to be early gastric cancer, and decided

to delay the ESD for the LGD lesion until 12 months after

the coronary stent implantation. We consulted with car-

diology about managing the antiplatelet agents during ESD.

Cardiology recommended that aspirin should be used

continuously during ESD, and that discontinuing the anti-

platelet agents and using heparin bridging was an appro-

priate alternative plan. Because we had more experience

with heparin bridging therapy after discontinuing anti-

coagulants, we decided to use heparin bridging therapy

after discontinuing dual antiplatelet therapy. We discon-

tinued aspirin and clopidogrel 7 days before the proce-

dure and administered 1 mg/kg LMWH until 12 hours be-

fore the procedure. The patient’s vital signs were stable

on the day of ESD. The baseline electrocardiogram (ECG)

showed no interval change and his cardiac enzyme levels

were normal (Fig. 2).

ESD was performed under moderate sedation with 2

mg midazolam and 25 mg meperidine. No additional sed-

atives were used. The submucosal injection fluid consisted

of a mixture of saline and 1:1,000 epinephrine and indi-

gocarmine. A dual knife (KD-650L; Olympus, Tokyo,

Japan) and an insulation-tipped knife (KD-611L; Olympus)

were used to make the mucosal incision and for the sub-

mucosal dissection, respectively. Endocut and an electro-

surgical unit (VIO 300D; ERBE Elektromedizin GmbH,

Tübingen, Germany) set on forced coagulation mode were

used for dissection and bleeding control. Total procedure

time was 49 minutes, and vital signs were stable during

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Fig. 3. Electrocardiogram (ECG) during chest pain complaint. ECG shows ＞2 mm ST segment elevation in leads V1∼V4 compared to an ECG before the procedure.

Fig. 4. Emergent coronary angiogram shows no stent thrombosis or reste-nosis and no definite visible throm-bus in the coronary artery (stent in-sertion lesion indicated by arrows).

the procedure. As the patient complained of chest pain

immediately after the procedure, ECG, CK-MB, and tro-

ponin T were checked. The ECG showed ＞2 mm ST

segment elevation in leads V1 - V4 compared to that be-

fore the procedure (Fig. 3).

CK-MB and troponin T levels had increased to 199.5

ng/mL (normal: 0.1∼1.5 ng/mL) and 3.33 ng/mL (normal:

0∼0.1 ng/mL), respectively. A portable echocardiogram

showed regional wall motion abnormalities on territories

supplied by the left anterior descending and right circum-

flex arteries but no apical ballooning suggesting stress-in-

duced cardiomyopathy and no significant changes com-

pared to the last examination. A coronary angiogram

showed no stent thrombosis or stent restenosis, and no

definite visible thrombus in the coronary arteries (Fig. 4).

The cardiologist remarked that MI thought to be caused

by coronary artery vasospasm near the stent implantation

site. The patient recovered spontaneously, and the ECG

and cardiac enzymes normalized. Second look endoscopy

revealed no bleeding on the dissection plane. Therefore,

dual antiplatelet therapy was started immediately. The

pathological result of the ESD specimen was well differ-

entiated adenocarcinoma confined to the lamina propria.

The resection margin was clear, and no lymphovascular

invasion was observed. We performed a follow-up endo-

scopic examination 3 months after ESD and a 3×3 cm,

adenoma on the posterior side of the lower body had in-

creased in size compared to that at the last examination.

A biopsy confirmed tubular adenoma with LGD. We plan-

ned to perform an endoscopic procedure 12 months after

the stents were inserted due to the previous MI. The sec-

ond ESD was performed with LMWH bridging using the

same method. The pathological result of the ESD speci-

men was well differentiated tubular adenocarcinoma con-

fined to the muscularis mucosa with curative resection.

No adverse events occurred during the second ESD.

We found a 3.5×3.0 cm, lateral spreading tumor on

the ascending colon during follow-up assessments. A bi-

Dong Pil Kim, et al: Myocardial Infarction as a Complication of Endoscopic Submucosal Dissection

261

opsy confirmed tubulovillous adenoma. ESD was per-

formed successfully with bridging therapy, and the patient

was followed-up regularly at the outpatient department.

DISCUSSION

National Cancer Screening Programs are implemented

in Korea and Japan because of the high incidence of gas-

tric cancer. As a result, early detection of gastric cancer

as well as endoscopic treatment have increased.7 The ma-

jor complications of gastric ESD include bleeding, perfo-

ration, stenosis, and aspiration pneumonia, but rarely MI.7

Only three cases of MI after ESD have been reported in

Korea.8,9

Although the mechanism of MI after ESD is unclear, it

is thought to be caused by three factors. First, the mixed

epinephrine solution could be absorbed into the sub-

mucosa, and could cause MI. It has reported that epi-

nephrine causes coronary artery vasospasm and poten-

tiates platelet aggregation by increasing adenosine diphos-

phate and arachidonate-induced thromboxane B2 produc-

tion. Second, a large volume of submucosal injection sol-

ution can induce hemodynamic stress. Third, the stressful

condition induced by ESD escalates sympathetic tone and

stimulates the hypothalamic-pituitary adrenocortical axis.

The corticotrophin-releasing hormone and cortisol re-

leased can facilitate MI and arrhythmia.8,9 We suggest that

MI in our case may have been caused by coronary vaso-

spasm induced by epinephrine and increased sympathetic

tone. However, we cannot completely exclude other rea-

sons, such as an earlier timing of ESD, premature dis-

continuation of antiplatelet agents, unclear efficacy of

heparin bridging therapy, or a hemodynamic effect of

sedatives.

Management of antiplatelet and antithrombotic agents

for endoscopic procedures has been reported in many

institutions. However, no guidelines have been esta-

blished. The ASGE and the European Society for Gastroin-

testinal Endoscopy recommend that patients at high

thromboembolic risk who are taking dual antiplatelet

therapy and need a high bleeding risk procedure such as

ESD, should consider continuing aspirin during the pro-

cedure.1,2 However, continuous aspirin use can increase

the risk for post-ESD bleeding (relative risk, 4.49) and de-

crease the en-bloc resection rate.10 Therefore, an alter-

native plan, such as bridging therapy, is used in clinical

practice. The JCS, the Cardiac Society of Australia/New

Zealand, the French Task Force, and the American College

of Chest Physicians agree to aspirin use. However, they

remarked that it can be considered a bridge with heparin

if dual antiplatelet therapy is discontinued.11 Bridging

therapy is traditional management for perioperative anti-

coagulation using unfractionated heparin or LMWH after

discontinuation of oral anticoagulants.12 Unlike aspirin,

heparin has a short half-life and there is an antidote to

reverse the antithrombotic effect. In this respect, heparin

bridging in a patient taking dual antiplatelet therapy is

empirically conducted in many institutions.13 However,

our patient suffered MI after ESD despite bridging therapy

with LMWH. Therefore, the efficacy of bridging therapy

should be further investigated.

Lee et al.14 reported a discrepancy of clinical practice

patterns to manage anticoagulation and antiplatelet ther-

apy between Eastern and Western endoscopists. Eastern

endoscopists are more concerned with the risk of bleed-

ing, whereas Western endoscopists are more concerned

about the risk of thromboembolism. This discrepancy is

based on racial differences in bleeding and thromboemb-

olism between Asians and Caucasians which is thought to

cause the low dispersal of Western guidelines.15,16 There-

fore, consistent guidelines are needed for managing anti-

coagulation and antiplatelet medications during endoscopic

procedures.

The American Heart Association and JCS Guidelines for

percutaneous coronary intervention recommend that elec-

tive surgery or high bleeding risk procedures should be

postponed 4∼6 weeks after implantation of a bare metal

stent and for 6∼12 months after implantation of a drug

eluting stent. According to these guidelines, ESD should

be postponed at least 6∼12 months after insertion of a

drug eluting stent.17-19 In our case, we considered the

thromboembolic risk and recommended postponing ESD

by 6∼12 months after implantation of coronary stents.

The natural course of early gastric cancer is unclear, but

rapid disease progression over 3∼9 months would be

rare. In contrast, Jeong et al.20 reported that one-fourth

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Korean J Helicobacter Up Gastrointest Res: Vol 15, No 4, December 2015

of untreated patients with early gastric cancer develop to

advanced gastric cancer within 5∼12 months. Thus, we

discussed the issue with the patient and decided to per-

form the ESD procedure within the recommended period

because the patient was afraid of disease progression dur-

ing observation. However, we should have considered

timing the ESD and discontinuation of antiplatelet agents

because the patient suffered a MI. A short-term follow-up

of at least 6 months might be necessary after inserting

coronary artery stents rather than performing a procedure

immediately. We delayed the second ESD procedure by

12 months after stent insertion. However, the pathological

result of the ESD specimen was tubular adenocarcinoma

confined to the muscularis mucosa. This lesion could

have advanced more with an additional delay.

In conclusion, MI is a rare, but fatal complication of

ESD. Thus, use of local epinephrine injections, antith-

rombotic agents, and sedatives should be considered

carefully in older patients with cardiovascular disease.

Bridging therapy with heparin is a good option to prevent

bleeding and thromboembolic events before an ESD pro-

cedure, but efficacy should be further investigated.

Elective high bleeding risk procedures, such as ESD,

should be delayed 6∼12 months after insertion of coro-

nary stents. The timing of the ESD procedure should be

determined cautiously considering both cancer pro-

gression and thromboembolic risk, particularly in patients

with cancer who had a coronary artery stent inserted.

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