Coronary Aneurysm Formation after Titanium

Nitric Oxide-Coated Stent Implantation

Wei-Wen Lin,1 Jui-Peng Tsai,1,2 Chih-Hsuan Yen,1,2 Jen-Yuan Kuo1 and Chung-Lieh Hung1,2

Coronary artery aneurysm (CAA) formation is a rare complication after percutaneous coronary intervention (PCI)

with stent implantation. Why CAA occurs in these unusual instances is not well understood. Though cases with

drug-eluting stent (DES) induced CAA have been reported before, none was reported to be associated with a

titanium nitric oxide-coated bioactive stent. Herein, we describe the first case where CAA developed after titanium

nitric oxide-coated bioactive stent implantation. Several mechanisms may account for stent-related CAA formation,

including mechanical trauma, vessel remodeling, acute myocardial infarction, long or multiple DES stent

implantation, DES malapposition and hypersensitivity reaction to polymers.

A 53-year-old man presented initially with recent MI and ongoing chest pains. Coronary angiography revealed a

90% occlusion of the middle left anterior descending coronary artery (LAD). PCI was performed on the patient, and

a titanium nitric oxide-coated bioactive stent was implanted. Due to a positive thallium scan 28 months later, a

follow-up coronary angiography scan revealed a true CAA, which was then further confirmed by intravascular

ultrasound. Thereafter, the patient remained asymptomatic at subsequent follow-ups, and continued medical

treatment without further intervention. Herein, we discuss the possible etiologies, mechanisms and further treatments

of CAA formation after titanium nitric oxide-coated bioactive stent implantation.

Key Words: Coronary artery aneurysm � Intravascular ultrasound � Titanium nitric oxide-coated stent

CASE REPORT

In June 2007, a 53-year-old man visited our cardio-

vascular outpatient clinic with intermittent chest tight-

ness which had persisted for 10 days. The patient was an

ex-smoker, and taking medication for hypertension. An

initial thallium scan revealed reversible myocardial

ischemia at the left ventricle (LV) anterior wall. Labora-

tory data showed mildly elevated cardiac enzymes (tro-

ponin I: 1.42 ng/mL), and recent myocardial infarct was

diagnosed. Coronary angiography revealed a high de-

gree of stenosis with irregular surface at the middle por-

tion of the left anterior descending coronary artery

(LAD), with nearly 90 percent stenosis (Figure 1, panel

A). A Sprinter balloon (2.25*20 mm semi-compliant bal-

loon, Medtronic, U.S.A) was initially utilized to pre-

dilate the lesion (pressure: 10 atm), with subsequent

successful Titan 2 stent implantation (3.0*28 mm, tita-

nium nitric oxide-coated bioactive stent, Hexacath,

France). A final coronary angiography showed no re-

sidual stenosis (Figure 1, panel B). After discharge, the

patient remained asymptomatic, and was prescribed dual

anti-platelet agents at regular follow-ups with our outpa-

tient clinic. However, the patient suffered angina symp-

toms almost two years later, and a follow-up thallium

scan showed a small region myocardial ischemia at the

LV anterior wall. Further diagnostic coronary angio-

graphy incidentally revealed an aneurysm formation (at

267 Acta Cardiol Sin 2011;27:267�70

Coronary Aneurysm Formation after Bioactive Stent ImplantationCase Report Acta Cardiol Sin 2011;27:267�70

Received: December 24, 2010 Accepted: March 3, 20111Division of Cardiology, Department of Internal Medicine, Mackay

Memorial Hospital; 2Department of Medicine, Mackay Medical

College, and Mackay Medicine, Nursing and Management College,

Taipei, Taiwan.

Address correspondence and reprint requests to: Dr. Chung-Lieh

Hung, Division of Cardiology, Department of Internal Medicine,

Mackay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Rd.,

Zhongshan Dist., Taipei City 10449, Taiwan. Tel: 886-2-2543-3535

ext. 2456; E-mail: jotaro3791@gmail.com

middle-LAD) within the previous stent implantation seg-

ment (Figure 1, panels C&D). Intravascular ultrasound

confirmed that the aneurysm was in-stent true, with the

size estimated to be 7.0 mm in diameter (Figure 2). In-

stead of using a surgical approach, we implemented a

regimen of close observation and conservative medical

treatment, prescribing atrovastatin 40 mg once daily, as-

pirin 100 mg once daily, clopidogrel 75 mg once daily,

ramipril 5 mg once daily and carvedilol 3.125 mg twice

daily. Eight months later, the patient remained asymp-

tomatic under conservative medication treatment.

DISCUSSION

The most common etiology of coronary artery an-

eurysm (CAA) could be atherosclerosis, which presents

itself in 50-80% of all CAA cases.1 It may also occur

secondary to mechanical trauma, such as blunt trauma or

iatrogenic injury related to coronary intervention. The

incidence of CAA after DES implantation is low, occur-

ring in 0.2% to 2.3% of the reported cases. This may

partly be explained by the coated anti-proliferative drugs

on the stents which inhibit neointimal growth and pro-

liferation.2 From our literature review, CAA after bio-

active stent implantation has never been reported before.

In our reported case, CAA was found 2 years post ti-

tanium nitric oxide-coated bioactive stent implantation.

Several possible mechanisms may be involved in the for-

Acta Cardiol Sin 2011;27:267�70 268

Wei-Wen Lin et al.

Figure 1. (A) Post myocardial infarction, coronary angiography

showed 90% stenosis (white arrow) at middle portion of left anterior de-

scending coronary artery. (B) Immediately after deployment of titanium

nitric oxide-coated bioactive stent (white arrow), there was no signifi-

cant residual stenosis with TIMI 3 flow observed. (C&D) angiography

illustrating coronary artery aneurysm formation at left anterior de-

scending coronary artery after titanium nitric oxide-coated bioactive

stent deployment about 28 months later (white arrows).

Figure 2. Intravascular ultrasound-guided imaging for coronary structural assessment and lumen size quantification relating to the CAA (B) and

the distal (C) and proximal (A) segments by pull-back loops recording. Continuous recording of the coronary structure and morphology was also

shown (From A to L in the lower panel: From distal to proximal segment). Outer large white arrows indicated border of aneurysm while the inner

white or yellow small arrows indicated stent struts. The size of aneurysm was estimated to be 7 mm in the maximum diameter.

A B

C D

mation of a CAA in this case. Previous study suggests

that DES-related CAA may be induced by mechanical

trauma from a coronary intervention, including over-

sized balloon angioplasty or high-pressure inflation lead-

ing to coronary artery dissection. There is no doubt that

a hypersensitive reaction to polymer of the stent could

be one of the mechanisms in this case. Aneurysmal dila-

tion has even been reported at the stented segment in a

case with severe hypersensitivity.3 In addition, weaken-

ing of the medial layer of the vascular wall, which may

be in part be due to chronic overstimulation of endothe-

lium-derived relaxation factor such as endogenous nitric

oxide, has also been postulated to be the cause of an-

eurysm formation.4 Nitric oxide released from the tita-

nium nitric oxide-coated bioactive stent may theoreti-

cally induce coronary artery ectasia and contribute to

CAA formation as well.5

Coronary angiography as a diagnostic tool of CAA

helps portray the silhouette of the lumen, but may fail to

distinguish true from false aneurysms. In this regard,

intravascular ultrasound (IVUS) is a useful tool which

directly images the vessel inside, allowing measurement,

distribution and the determination of exact vessel com-

position. Therefore, IVUS can now provide more accu-

rate measurement of tissue properties than traditional

gray-scale images by different methods of tissue charac-

terization,6 and it was performed in patients with possi-

ble CAA with coronary angiography in order to differen-

tiate the exact type aneurysm (true or false), and the size

of the aneurysms.7 Unlike true aneurysms, pseudoan-

eurysms may lack the normal 3 layers (intima, media,

and adventitia) because of the loss of vessel wall inte-

grity and damage to the adventitia or perivascular tissue.

In this case, intravascular ultrasound was used to depict

the ectasia of the middle portion of LAD which mea-

sured up to 7 mm, with a true aneurysm identified to be

the main pathology.

The appropriate treatment for patients with CAA re-

mains controversial. So far, there is no statistically sig-

nificant association between aneurysm size and long-

term survival rate; instead, the type of the aneurysm

found seems to be the major determinant. A true aneu-

rysm is associated with low morbidity and mortality,

while a pseudo aneurysm has the potential to progres-

sively enlarge, or eventually rupture.8 Possible treatment

options include percutaneous treatment, surgical inter-

vention, and conservative medical management with

continued dual antiplatelet agent therapy. Percutaneous

treatment is a newer option that involves the placement

of a covered stent (ex: a polytetrafluoroethylene-covered

stent) to obstruct blood flow into the aneurysmal sac.

The synthetic membrane of the stent-graft may effec-

tively seal the inlet of the aneurysm � a safer and less in-

vasive alternative in the treatment of coronary an-

eurysms.9 Surgical treatment may be a choice in patients

who have giant saccular-form aneurysms, where the po-

tential incidence of future adverse events is elevated and

concerning,11 such as rupture, thrombosis and fistula for-

mation. The surgical procedures for dealing with CAA

include total resection or plication of the aneurysm, liga-

tion, aneurismal thrombectomy, aneurysmorrhectomy

and isolation of blood flow to the aneurysm.10,11 Earlier

studies indicate that prolonged dual antiplatelet agent

therapy can be effective in DES-related CAA to reduce

stent thrombosis.12 Regarding whether and how often

CAA developed after implantation of a bioactive stent,

however, the published data is limited. In our reported

patient, a 7.0 mm true aneurysm was identified in the

middle portion of the left anterior descending coronary

artery. The patient was kept on medical treatment and

remained asymptomatic during subsequent follow-up.

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