Case Report
JLA
J Lipid Atheroscler 2012;1(2):95-100
Recurrent Stent Thrombosis and Pulmonary Thromboembolism Associated with Hyperhomocysteinemia Min Chul Kim, Myung Ho Jeong, Soo Young Jang, Hong Sang Choi, Kyung Hoon Cho, Seung Hwan Hwang, Min Goo Lee, Keun Ho Park, Doo Sun Sim, Young Joon Hong, Ju Han Kim, Youngkeun Ahn, Jung Chaee Kang The Heart Center of Chonnam National University Hospital, Gwangju, Korea
Stent thrombosis is a fatal complication that can cause sudden cardiac death in patients implanted coronary stent. Also, pulmonary thromboembolism is associated with increased mortality. Usually, these vascular thromboembolic diseases did not occured simultaneously. If this circumstance develops, possible mechanisms and causes should be described. Here, we report a case of patient underwent percutaneous coronary intervention under diagnosis of ST-segment elevation myocardial infarction with recurrent stent thrombosis and pulmonary thromboembolism associated with hyperhomocysteinemia despite optimal medical therapy. Key Words: Hyperhomocysteinemia, Coronary thrombosis, Pulmonary embolism
INTRODUCTION
ST and PTE despite optimal medical therapy. Patient experienced all types of ST and concomitant PTE during
Coronary stenting is an effective management in patient
follow up period. However, precipitating factors of these
with acute myocardial infarction (AMI) with coronary
events were not detected except for hyperhomocys-
stenosis or obstruction. However, stent thrombosis (ST)
teinemia. We discussed the possible causes of recurrent
that can be developed after stenting is a fatal complication
ST with PTE and further therapeutic plans in these patients.
with higher mortality rates despite relative lower incidence.1 Also, pulmonary thromboembolism (PTE) is 2
CASE REPORT
associated with increased mortality rates. These two vascular thromboembolic diseases usually did not occured
A 75-year-old male developed sudden chest pain 3
simultaneously and have different pathophysiology,
hours ago. Pain lasted during 1 hour and he suddenly
etiology, risk factors and management.
collapsed. He was rushed unconscious to a neighborhood
Here, we report a case of patient underwent percu-
hospital by emergency medical services. And then he
taneous coronary intervention (PCI) under diagnosis of
transferred to our hospital for further evaluation. He was
ST-segment elevation myocardial infarction with recurrent
a current smoker at 70 Pack-Years and no other
Received: July 16, 2012 Corresponding Author: Myung Ho Jeong, Principal Investigator of Korea Acute Myocardial Infarction Registry, Accepted: September 15, 2012 Director of the Heart Research Center Designated by Korea Ministry of Health and Welfare, Chonnam National University Hospital, 671 Jaebongro, Dong-gu, Gwangju 501-757, Korea Tel: +82-62-220-6243, Fax: +82-62-228-7174, E-mail:
[email protected]
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Fig. 1. Primary PCI; CAG showed TTO in proximal RCA (A: white arrow) and successful PCI with coronary stenting (B: Coroflex-Blue 4.0x19 mm, B. Braun Systems).
Fig. 2. Filling defects in segmental pulmonary arteries in left lower lobe (A and B: white arrow).
atherosclerotic risk factors were presented. His initial
2-D echocardiography showed mild LV systolic dysfunction
rhythm was junctional bradycardia with 45 beats per
and hypokinesia in RCA territory. During admission, he
minutes of heart rate and blood pressure was 70/40
complained chest discomfort and chest X-ray showed
mmHg. Also, 12-lead electrocardiogram showed ST-
haziness in right lung. Therefore, chest computed
segment elevation in II, III, and aVF and V4R, V5R, V6R,
tomography (CT) was checked. CT revealed filling defects
V7, V8, and V9 leads on right posterior electrocardiogram.
in segmental pulmonary arteries in left lower lobe (Fig.
Primary PCI was performed and diagnostic coronary
2A and 2B). Although RV dysfunction was presented, his
angiography showed thrombotic total occlusion in
vital sign and general condition was stable. We performed
proximal right coronary artery (RCA) (Fig. 1A) and lesion
only anticoagulation without thrombolysis. He was
was successfully revascularized with bare-metal stent
discharged with triple ant-platelet therapy on event-free
(Coroflex-Blue 4.0x19 mm, B. Braun Systems) (Fig. 1B).
state 7 days later.
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Min Chul Kim, et al: Stent Thrombosis and Pulmonary Thromboembolism with Hyperhomocyteinemia
Fig. 3. Stent thrombosis and de novo lesion in distal to stent (A and B: arrow heads). Successful PCI with direct stenting using bare-metal stent (C and D: arrow heads, Coroflex-Blue 3.5x19 mm, B. Braun Systems).
Fig. 4. Critical spasm over RCA and acute stent thrombosis (A: white arrow). Improved coronary flow after nitrate and abciximab infusion (B).
After 1 month, he revisited our emergency department
T-inversion in II, III, and aVF. Urgent coronary angiography
with typical angina. 12-lead electrocardiogram showed
(CAG) showed thrombosis and de novo lesion in distal
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Fig. 5. Follow up coronary angiogram after 6 months until first admission day (A: Right coronary artery, B: Left coronary artery). There were no in-stent restenosis, stent thrombosis, and de novo lesion.
Fig. 6. Stent thrombosis in proximal RCA stent (A). Successful primary PCI with intracoronary glycoprotein IIb/IIIa inhibitor. There are small amount of remnant thrombi in culprit lesion (B).
stent. We carried out direct stenting using bare-metal stent
After discharge with other event, he revisited our
(Coroflex-Blue 3.5x19 mm, B. Braun Systems) (Fig. 3A
hospital 5 months later. However, CAG at that time
to 3D). Despite of successful PCI, patient complained chest
showed no in-stent restenosis, thrombosis and de novo
pain immediately after PCI. 12-lead ECG during develop-
lesions (Fig. 5A and 5B). He was discharge and followed
ment of pain showed STE in II, III, and aVF with complete
up at outpatient department without angina. At 9 months
atrioventricular block. Emergent CAG showed critical
after last admission, he revisited our emergency depart-
spasm over RCA and stent thrombosis (Fig. 4A). After
ment with comatose mental status and hypotension.
nitrate and abciximab infusion, distal flow was improved
12-lead ECG showed ST-segment elevation in II, III, and
(Fig. 4B). He did not have trouble with medication
aVF with complete atrioventricular block. Emergent CAG
compliance and no chest pain was developed in other
revealed recurrent ST in proximal RCA (Fig. 6A) and we
day except for the secondary admission day.
performed successful PCI with ballooning and final CAG
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Min Chul Kim, et al: Stent Thrombosis and Pulmonary Thromboembolism with Hyperhomocyteinemia
Fig. 7. Duration of anti-platelet and oral anti-coagulation medication. His stent thrombosis events; acute, subacute, and very late stent thrombosis are presented in non painted box during clinical follow up period.
showed TIMI (Thrombolysis In Myocardial Infarction) III
DISCUSSION
antegrade flow with small amount of remnant thrombosis (Fig. 6B). During admission, no other cardiovascular events
In interventional cardiology era, especially with coronary
were developed and patient has been followed up at the
stenting, ST is a dreadful complication of PCI. It causes
outpatient department without any symptoms. In
AMI or sudden cardiac death in the most cases despite
laboratory tests, platelet resistance test showed no
its low incidence of 0.5% to 2.0% in bare metal stent
resistance to anti-platelet (aspirin 449 ARU / P2Y12 90
(BMS).3 BMS implantation, rapid re-endothelization
PRU and 35%). Also, both leg venous CT angiogram
occurs within a few weeks after procedure contrary to
showed no any filling defects and there were no
drug-eluting stent (DES). Although recent several studies
abnormality in laboratory findings for evaluation of
showed similar frequencies of ST episodes between DES
procoagulant state (antiphospholipid antibody, ANA,
and BMS, incidence of very late stent thrombosis (VLST)
ANCA, EPO, factor V and VIII assay, lupus anticoagulant,
is still higher in DES than BMS.4 There are little studies
protein C and S assay). But, hyperhomocysteinemia was
or case report considering BMS ST, but a few case reports
detected in other tests for detection of thrombotic
showed VLST in BMS or recurrent VLST in BMS.5 However,
tendency (19.43 u mol/L; reference range 4.72 to 14.05
development of ST concomitant with PTE is very rare.
u mol/L). On genetic evaluation for hyperhomocys-
Among risk factors of BMS ST such as noncompliance
teinemia, the point mutation of methyltetrahydrofolate
with antiplatelet agents, procoagulant state, history of
reductase (MTHFR) gene was not identified. So, we
coronary brachytherapy, small stent size, underde-
prescribed folate in addition to triple antiplatet therapy.
ployment of the stent, diabetes mellitus, renal failure, old
Although he ceased warfarin ealier compared with
age, and smoking, hyperhomocysteinemia and current
recommended medication periods, other medication
smoking history can be applied to our patient.5 Because
compliance was good (Fig. 7).
patient stopped smoking during follow-up periods, hyperhomocysteinemia might be associated with throm-
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JOURNAL OF LIPID AND ATHEROSCLEROSIS events in hyperhomocysteinemic patients who suffered
botic tendency. There has been controversy that hyperhomocysteinemia
from recurrent vascular thromboembolic episodes without
should be corrected in patients with vascular thromem-
any correctable risk factors. Although there are no
bolic disorders. Although experimental and clinical studies
definitive evidences to support using folate, we think it
showed progression of atherosclerosis in hyperhomo-
is valuable in patient without other cardiovascular risk
cysteinemia and relationship of homocysteine with
factors. It needs large scale randomized control trial to
coronary artery disease, homocysteine-lowering therapy
prove this issue.
using folate, vitamin B6 and B12 could not reduce risk of venous thromembolism.6,7 Also, our patient had only
REFERENCES
moderate elevation of serum homocysteine level and did not have the point mutation of methyltetrahydrofolate
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of hyperhomocysteinemia was found in all patients with
4. Jensen LO, Maeng M, Kaltoft A, et al. Stent thrombosis,
no significant differences.8 However, Karalezli et al.
myocardial infarction, and death after drug-eluting and
reported that 46 patients with PTE showed increased level
bare-metal stent coronary interventions. J Am Coll
9
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Cardiol 2007;50:463-470. 5. Celik T, Iyisoy A, Celik M, Isik E. A case of very late stent thrombosis after bare metal coronary stent implantation: a neglected complication. Int J Cardiol 2009;134:111-113.
vation is needed to find association PTE and ST. He suffered
6. Lentz SR. Mechanisms of homocysteine-induced athero-
from recurrent angina and stent thrombosis (all types of
thrombosis. J Thromb Haemost 2005;3:1646-1654.
stent thrombosis except for late stent thrombosis) despite
7. Den Heijer M, Lewington S, Clarke R. Homocysteine,
ex-smoking, triple antiplatelet therapy and medications
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earlier due to non-compliance compared to recommend periods, there are no evidences that antiplatelet medication combined with oral anticoagulation could reduce
2005;3:292-299. 8. Grifoni E, Marcucci R, Giutu G, et al. The thrombophilic pattern of different clinical manifestations of venous thromboembolism: a survey of 443 cases of venous
the incidence of coronary stent thrombosis.10 Because
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there were no further correctable factors in this patient,
234.
we corrected hyperhomocysteinemia using folate. After then, he did not complain of any symptoms and follow-up CAG after 3-months since last ST episode showed no ST and in-stent restenosis (photo not shown). In conclusion, homocysteine-lowering therapy such as
9. Karalezli A, Parlak ES, Kanbay A, Senturk A, Hassanoglu HC. Homocysteine and serum-lipid levels in pulmonary embolism. Clin Appl Thromb Hemost 2011;17:E186-189. 10. Holmes DR Jr, Kereiakes DJ, Kleiman NS, Moliterno DJ, Patti G, Crines CL. Combining antiplatelet and anticoagulant therapies. J Am Coll Cardiol 2009;54:95-109.
folate might be considered to prevent vascular thrombotic
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