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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 7  |  Issue : 3  |  Page : 110-117

Coronary artery aneurysms following drug eluting stents implantation: A retrospective analysis from series of cases at tertiary care cardiac centre over three years


1 Department of Cardiology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Cardiothoracic and Vascular Surgery, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Web Publication30-Sep-2019

Correspondence Address:
Sudarshan Kumar Vijay
Department of Cardiology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Gomti Nagar, Lucknow - 226 010, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_38_19

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  Abstract 


Background: Inflammation and healing after vascular injury during the procedure and other factors may be theoretically associated with a risk of coronary artery aneurysm (CAA) formation after drug eluting stent (DES) implantation. Very few studies have provided the epidemiological features and proposed causative factors of CAAs after DES implantation.
Aims and Objectives: We aim to retrospectively study the incidence, morphological features and proposed causative factors of coronary artery aneurysms noted after drug eluting stent implantation at a tertiary care cardiac centre over period of three years (2015-2018).
Methods: All cases of coronary artery aneurysms occurring after drug eluting stent implantation over a period of three years (2015-2018) were studied retrospectively. Incidence, morphological and clinical features of aneurysms were retrospectively analysed from case records and angiographic analysis from computerized database at our tertiary care cardiac centre.
Results: Over period of three years (2015-2018) seven cases (Incidence-0.52%) of coronary artery aneurysms were noted after DES implantation with 1340 coronary angioplasty and stenting procedures done during this period for any indication. Association of diabetes and and high pressure post dilation was seen in five (71.4%) cases. A male sex and Left anterior descending artery predilection was noted and all incriminated stents were durable polymer stents. Dissection during predilatation of the lesion was seen in two (28.5%) patients.
Conclusions: Coronary artery aneurysms associated with DES implantation are rare in the current era of biodegradable polymer stents. Various procedure and stent related factors are involved in its causation.

Keywords: Coronary artery aneurysms, drug eluting stents, stent polymer


How to cite this article:
Vijay SK, Srivastava DK, Tiwari BC, Misra M. Coronary artery aneurysms following drug eluting stents implantation: A retrospective analysis from series of cases at tertiary care cardiac centre over three years. Heart India 2019;7:110-7

How to cite this URL:
Vijay SK, Srivastava DK, Tiwari BC, Misra M. Coronary artery aneurysms following drug eluting stents implantation: A retrospective analysis from series of cases at tertiary care cardiac centre over three years. Heart India [serial online] 2019 [cited 2019 Nov 19];7:110-7. Available from: http://www.heartindia.net/text.asp?2019/7/3/110/268171




  Introduction Top


Coronary artery aneurysms (CAA) after percutaneous coronary interventions are uncommon occurrence as evidenced by dearth of literature regarding its true incidence and clinical course. Reported incidence of these aneurysms varies from 0.3% to 4% with roughly similar figures after DES and BMS implantation, published in various DES versus BMS randomized trials and few case series. Clinical spectrum and time frame of presentation of these aneurysms remains widely variable as some coronary aneurysms after stent implantation may be detected during routine follow up angiography incidentally or as a part of diagnostic work up of lesions elsewhere in the coronary tree and others may become clinically manifested with angina or fatal complications. Residual dissection after procedure and arterial wall injury (rupture or resection of the vessel media) resulted from oversized balloons or stents, high-pressure balloon inflations, atherectomy, and laser angioplasty have all been incriminated in coronary artery aneurysms formation after percutaneous coronary intervention.[1],[2],[3],[4]

DES have been shown to dramatically inhibit neointimal growth with local elution of drugs, thereby suppressing restenosis,[5],[6] but at the same time potentially causing coronary aneurysms due to other mechanisms, such as delayed re-endothelialisation, inflammatory changes of the medial wall, and polymer induced hypersensitivity reactions.[7],[8],[9],[10] Exaggerated positive remodeling after stent implantation may also play a role in aneurysm formation. Incomplete endothelialisation had been observed over DES by angioscopy and optical coherence tomography and also in autopsy studies.[11],[12],[13] Whether the presence of incomplete endothelization is a precursor of aneurysm formation or just a sign of vessel injury is unknown, but this phenomenon has not been reported after BMS implantation. An additional phenomenon that has been observed after DES implantation is late acquired incomplete stent apposition, which is observed in 8% to 10% of patients.[14],[15] Although incomplete stent apposition and incomplete endothelialisation may be precursor of aneurysm formation, the exact nature of the relationship between these two findings needs to be elucidated. Bacterial arteritis associated with catheter related or local site infection may also contribute to formation of mycotic pseudoaneurysms. In summary, combination of various factors like local injury induced by stent implantation and various biological reactions after DES implantation might together contribute to coronary aneurysm formation after DES implantation.

DES associated polymer has been implicated in provoking intense eosinophilic infiltration in the adjacent arterial wall. CAAs have been shown to occur with systemic administration of anti-inflammatory agents (glucocorticoids and colchicine) after BMS implantation,[16] thus DES implantation may be associated with a greater risk of aneurysm formation. However, the exact incidence, clinical course, and management of coronary artery aneurysms after DES implantation remain largely unknown.

Coronary angiography is the gold standard modality for the diagnosis of coronary aneurysms, which are defined as a luminal dilation 50% larger than that of the adjacent reference segment.[17],[18] However, coronary angiography is limited by the fact that it provides only luminal information and cannot visualize other structures and vessel wall. Differentiation between true aneurysms and pseudoaneurysms, as well as identification of the aneurysm entry site (sometimes caused by stent edge dissection or stent edge injury at acute bends during vessel motion), are important for better management of CAAs after percutaneous coronary intervention.


  Materials and Methods Top


This retrospective study was conducted at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow a tertiary care cardiac centre of north India. Over a period of 3 (2015-2018)-years all patients undergoing coronary angioplasty and stenting with drug eluting stents were retrospectively studied with case records and for procedural characteristics using computerized data base. During this period all patients were given guideline directed dual antiplatelet therapy and statin therapy. All patients during this period who presented with coronary artery aneurysms following stent implantation underwent diagnosis (Defined by arterial dilatation at stent implantation site more than 50% of adjacent normal segment) closely related to DES or its underlying edges on repeat coronary angiography for symptoms were studied retrospectively and their clinical profile, angiographic characteristics and procedural characteristics during index procedure were analyzed. We calculated the incidence of these cases at a tertiary care cardiac centre and the percent distribution of associated factors incriminated in the etiology of these aneurysms were analyzed. Mean time duration of presentation with standard deviation was also calculated.

Cases

Case No-1

A 50-year old male diabetic, hypertensive, non smoker was admitted for elective percutaneous coronary intervention to left anterior descending artery (LAD). The patient had a prior history of inferior wall myocardial infarction. Recently he was having worsening of angina despite full medical therapy. His 2D echocardiography showed no wall motion abnormality with normal left ventricular ejection fraction. His coronary angiography revealed right coronary artery mild disease and a mid LAD 95% lesion. After an informed consent decision for revascularization of LAD with a drug eluting stent was taken. A floppy wire was passed and the lesion predilated with a 2.5 x 15 mm sprinter (Medtronic inc. USA) balloon at 10 atmosphere. There was no flow limiting dissection after predilatation. A 3.5 x 26 mm Endeavour stent (Medtronic inc.) was deployed at 10 atm pressure with good TIMI-3 flow and stent was post dilated at 22 atm. The patient received standard anticoagulant and antiplatelet medication and was discharged on 2nd day with optimal medical therapy. Two months later the patient had an episode of high grade fever with chills and the pyrexia persisted despite treatment by a local practioner and no cause could be ascertained. Patient also started experiencing left precordial dull aching pain. In this background a repeat angiography was planned. His glycemic control and renal status was normal throughout. This repeat angiography showed an aneurysmal dilatation of approximately 20 mm in the proximal LAD where the stent had been deployed along with lesion proximal to the stent. Angiographic characteristics revealed aneurysm to be pseudoaneurysm with narrow neck [Figure 1]a and [Figure 1]b. Patient underwent and emergent coronary artery bypass grafting (CABG) with resection of the aneurysmal sac [Figure 1]c. During surgery a giant aneurysm of the proximal LAD was noted. It was proximally ligated and a Left internal mammary graft (LIMA) to LAD was used to bypass the lesion. Patient is now well on follow up.
Figure 1: Large coronary aneurysm in LAD artery with associated instent restenosis (a and b), perioperative appearance of aneurysm (c)

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Case No-2

A 69 year old male with diabetes with a prior history of chronic stable angina and percutaneous coronary intervention with drug eluting stent implantation to mid LAD Endolimus 3 × 24 (Shahjanand Inc., India) at 12 atm with post dilatation at 24 atm. One year later presented to us with 3 hour history of severe chest pain and sweating. Electrocardiogram of the patient showed ST segement elevation in V1-V5 precordial leads with reciprocal ST changes in leads II, III and AVF. Echocardiography showed hypokinesia in the LAD territory with left ventricular ejection fraction of 50%. Patient was thrombolysed with streptokinase after diagnosis of acute anterior wall myocardial infarction was made. Subsequently, because of ongoing pain patient underwent coronary angiography which revealed large thrombus containing aneurysm arising from the proximal stent edge [Figure 2]a and [Figure 2]b. Patient successfully underwent CABG with LIMA graft implanted to LAD and resection of the aneurysm.
Figure 2: Thrombus containing fusiform aneurysm at the site of LAD stent (a and b)

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Case No-3

A 66 year old diabetic and hypertensive male who had the history of chronic stable angina in past and underwent percutaneous coronary intervention and cypher select stent implantation in proximal LAD and proximal LCX 3 year back, presented to us with history of effort angina for 1 year and sudden onset chest pain at rest of 8 hours duration. Electrocardiogram of the patient showed T inversion in leads II, III and AVF. Troponin-T levels were raised. patient subsequently underwent coronary angiography which revealed proximal to mid right coronary artery (RCA) 80% diffuse disease with small aneurysm arising from the proximal edge of the LAD stent and patent LCX stent. Patient underwent successful drug eluting stent XIENCE-V 3.5 x28 (Abbott Vasc., USA) implantation in mid RCA and because of small size of LAD stent aneurysm it was not intervened [Figure 3]a and [Figure 3]b. Patient is doing well after 6 months of follow up.
Figure 3: Aneurysm in proximal LAD stent (a) with new lesion in RCA (b)

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Case No-4

A 54 year old male hypertensive with history of exertional angina for 3 years with positive exercise stress test underwent coronary angiography which revealed mid LAD 80% lesion and proximal D1 70% lesion with mild plaquing in posterior descending artery. PTCA with stenting to LAD lesion was decided. Lesion was crossed with Allstar wire and predilated with 2 x12 sprinter balloon (Medtronic inc., USA) at 12 atm. There was mild dissection after predilatation. Paclitaxel eluting stent Taxus element (Boston Scientific, USA) 3 x 28 was deployed in mid LAD at 14 atm pressure. Perioperative course of the patient was uneventful and he was discharged in a stable condition on optimal medical treatment. 15 days later the patient presented in the emergency room with severe chest pain of 6 hour duration. patient was stable hemodynamically. ECG of the patient was suggestive of acute anterior wall myocardial infarction. Echocardiography revealed hypokinesia of the distal interventricular septum and the apex with LVEF of 48%. Patient was thrombolysed with streptokinase and subsequently coronary angiography revealed patent LAD stent with large thrombus containing aneurysm surrounding proximal stent edge [Figure 4]. After stabilization patient was shifted for CABG with LIMA graft to LAD. Patient has stable course postoperatively.
Figure 4: Giant aneurysm in proximal LAD stent with instent restenosis

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Case No-5

A 60-year old male with history of smoking and diabetes presented with anterior wall MI in the cardiology and subsequently underwent PCI of the left anterior descending artery with 2.75 x 30 mm resolute integrity (Medtronic Inc., USA) stent was deployed at 14 atm pressure without post dilation subsequent TIMI-3 flow was achieved [Figure 5]a and [Figure 5]b. Two months later he again presented with chest pain with positive troponin test. His check angiogram revealed giant aneurysm from the proximal edge of the LAD stent with significant in stent restenosis [Figure 5]c and [Figure 5]d. Patient was referred to cardiac surgery unit where he underwent aneurysm resection and LIMA to LAD was placed. Patient is doing well after 6 months of follow up.
Figure 5: Proximal LAD lesion with stent deployment (a and b), Large aneurysm was noted in LAD stent 3 months later(c and d)

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Case-6

A 45-year old male presented with complaints of acute onset chest pain for 3 days and diagnosed to have NSTEMI. His coronary angiogram revealed severe disease in the Mid LAD and he underwent PCI of LAD with Promus Element (Boston scientific, USA) coronary stent 3 x 32 mm at 12 atm with post dilatation at 20 atm using NC balloon and discharged uneventfully [Figure 6]a. One year later he again presented with acute coronary syndrome and his check coronary angiogram showed large coronary aneurysm at the proximal stent edge without instent restenosis [Figure 6]b. He was referred to cardiac surgery and he underwent aneurysm resection and CABG.
Figure 6: Result after stent deployment (a), and large aneurysm not in proximal stent (b) in LAD artery

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Case-7

A 57-year old male with diabetes presented to cardiology OPD with effort angina her angiogram revealed tight disease in the distal RCA for which she underwent DES implantation with 3.5 x 28 mm Xience-V (Abbott vascular, USA) stent in the RCA at 14 atm with post dilatation with NC balloon at 22 atm. During the procedure he had grade-I perforation at the lesion site which was managed conservatively She was discharged asymptomatically but 4 month later he had recurrence of angina with check angiogram revealing small coronary pseudoaneurysm at distal edge of the RCA stent with no evidence of instent restenosis. Because of the small size of the aneurysm patient was managed conservatively with medical therapy for angina.


  Analysis and Results Top


Out of 1340 coronary angioplasty and stenting procedures done over 3-year period we recorded seven patients who developed coronary artery aneurysms associated with DES implantation. Baseline clinical characteristics and other morphological features of aneurysms are presented in [Table 1].
Table 1: Clinical presentation, morphological features and management strategy of all cases of coronary artery aneurysms associated with DES implantation

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Mean time of presentation of these aneurysms was 301.42 ± 377.66 days. The overall incidence of coronary aneurysm associated with DES was found to be 0.52% at our centre with annual incidence rate of 0.17%. A predilection for coronary artery aneurysms in male sex was recorded as all patients who had aneurysms were male. All of the cases presented with symptoms thus incidence of asymptomatic coronary artery aneurysm after DES is usually not known. Five patients (71.4%) had co existing diabetes and 3 patients had poor glycemic control and thus it supports the notion that diabetics shows varied response to vessel wall healing after index procedure. Most of the aneurysms were seen in the LAD artery with proximal edge of the stent involved most commonly except in one patient (14.2%) which had stenting of distal RCA with contained perforation which later on developed into pseudoaneurysm. Most of the aneurysms were managed surgically with aneurysm resection with arterial bypass grafting to affected vessel.

All (100%) the incriminated stents were durable polymer stents. All aneurysms were recorded in first and second generation of drug eluting stents. Dissection during predilatation of the lesion was seen in two (28.5%) patients who developed coronary aneurysm later during follow up. Aggressive high pressure post dilatation was seen in 5 (71.4%) of the seven patients who underwent PCI at the initial setting which could support the hypothesis that injury to vessel wall at the time of index PCI can be responsible for subsequent aneurysm formation at the stent implantation site. Pseudoaneurysm was seen in two cases (28.5%) as identified with angiographic appearance and clinical presentation. Six patients (85.7%) of coronary aneurysm had associated significant in stent restenosis in the implanted stent, which supports the hypothesis that exaggerated response of the vessel wall to injury can be incriminated in the aneurysm formation. Percent wise distribution of various causative factors is shown in [Figure 7].
Figure 7: Percent wise distribution of proposed causative factors in coronary aneurysm formation

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  Discussion Top


The occurrence of coronary artery aneurysms after DES implantation is a rarely reported phenomenon.[19] The latest DES and BMS trials have angiographic follow-up data in a large subset of patients at 6 to 9 months after the initial procedure.[20],[21],[22] In these trials, the definition of coronary artery aneurysms was vessel distension of 20% or more in diameter compared with the adjacent reference vessel at follow-up, a stricter definition compared with the definition used in the BMS era (vessel distension of ≥50%). In our study a stringent definition of arterial dilatation of >50% showed incidence of CAAs to be 0.52%, slightly lower as compared to some previous DES Vs BMS trials.[1],[2],[3],[4] However, data in these trials were derived from early angiographic follow-up of patients enrolled in these trials and, at this point, it remains unclear whether late aneurysm formation occurs more frequently. Current generation of DES with lower strut thickness and improved polymer technology have low incidences of stent associated hypersensitivity or other reactions. Furthermore, it is currently unknown whether DES or BMS predispose to different types of aneurysm formation (such as pseudo vs. true aneurysms, and saccular vs. nonsaccular).

First-generation DES based on biostable polymeric drug carriers, such as poly (ethylene-co-vinyl acetate) (PEVA), poly (n-butyl methacrylate) (PBMA), and poly (styrene-b-isobutylene-b-styrene) block polymers (SIBS), were associated with incidences of death or myocardial infarction after implantation. Most of the current generation of stents have biodegradable polymer coating that contains poly-L lactic glyolide (PLGA) or poly L lactic acid (PLLA). In our study all stents which were associated with aneurysm formation were durable polymer stents. From our study no information regarding polymer hypersensitivity or vessel inflammation could be ascertained, as pathological, imaging or biochemical or cellular markers of allergy were not tested.

3-different types of aneurysms after DES or BMS implantation have been described in the available literature.[19] Although there is scarce data regarding the prognostic effect of differing aneurysm types, a system of aneurysm classification may be useful to guide therapies because some coronary aneurysms are fatal without prompt and appropriate treatment,[23],[24] and some coronary aneurysms do not lead to life-threatening events and need only careful observation without treatment.[25],[26] Type-I aneurysm is a type of aneurysm that shows rapid early growth with pseudoaneurysm formation detected within 4 weeks.[27],[28] This type is usually associated with clinical pericarditis. Given the rapid time course of aneurysm formation, it is likely that arterial injury during index procedure is the probable contributor to aneurysm formation in these cases rather than the chronic arterial response to the stent, polymer, and drug. The second kind of aneurysm described in the literature is that with a “subacute to chronic” presentation (type II) and is usually detected incidentally during angiography for recurrent symptoms or as part of protocol mandated follow-up (usually detected 6 months after the procedure).[29],[30],[31] These aneurysms appear to have wide variety of clinical presentations; some patients are asymptomatic, but some have complaints of angina or present with acute coronary syndrome. It is more plausible in this scenario that a chronic arterial response to a metal stent, polymer, and/or drug, may be the basis for aneurysm formation in this subtype.

The third subtype in the published literature is mycotic or infectious in etiology (type III.[32],[33],[34] Large mycotic aneurysms infected with Staphylococcus aureus after DES or BMS implantation have been reported. In these rare cases, patients typically present with systemic manifestations and fever as the result of bacteremia. In our study one patient had type-I aneurysm, 5-patients had type-II aneurysm and one patient developed infected type-III aneurysm.

LAD was the most common artery involved in our study. The reason for the preferential development of CAA in the LAD is the same as that for preferential development of atherosclerosis in the LAD. LAD segments are exposed to higher wall stress during systole and it is the result of the different contractile properties of the left vs right ventricle. Moreover, the LAD exhibits twice the torsion of other arteries generating helical flow patterns. Furthermore, the increasing branching pattern of the LAD contributes to the development of disturbed flow and thus even slightest injury to wall during pre or post dilatation can predispose to aneurysm formation which can be further aggravated by hypersensitivity to stent polymer and inflammation.[35]

Early CAAs development may be due to consequence of mechanical problems due to complicated procedures, large dissections, contained perforation or even rupture. Two patients had dissections and one patient had contained rupture leading to aneurysm formation in our study. Aggressive high pressure post dilations were identified in five of our patients.

One patient in our study had suspected infected mycotic aneurysm. It has been suggested that local DES infection may result from direct contamination of the device at the time of delivery or from subsequent bacteremia. Whether the local immunosuppressive effects of eluted drugs from stents tend to increase the incidence of these rare infectious aneurysms is unknown. In most cases Staphylococcus aureus infections have been shown. These patients typically present with fever and systemic manifestations.[36]

Imaging modalities such as optical coherence tomography (OCT) or intravascular ultrasound (IVUS) can sometimes better delineate coronary aneurysm topography or possible etiology such as stent mal apposition.[37]

A single study has reported similar 5-year mortality of patients with chronic native coronary aneurysms compared with patients without coronary aneurysms.[38] The treatment of coronary aneurysms is usually decided on a case based individualized approach using a combination of aneurysm size, expansion history, pathophysiology, and symptoms. In our study 5-patients underwent surgery except in two patients where aneurysms were followed conservatively on prolonged dual antiplatelet therapy. Covered stent grafts or coiling are interventional options as compared to surgical resection and CABG. Concerns relating to stent graft treatment of coronary aneurysms include closure of contiguous side branches arising next to the aneurysm site, stent thrombosis, and recurrent restenosis. The placement of coronary coils behind stents to thrombose the aneurysm sac can also be challenging and requires considerable expertise.

For pseudoaneurysms that are large at presentation (i.e., at least twice the reference vessel diameter) or large true aneurysms (type II), or aneurysms that show significant expansion over time, especially in the presence of symptoms, surgery is usually required. The threshold for treatment is lower for pseudoaneurysms than for true aneurysms, because of the presumed greater likelihood for rupture.

Immediate surgical therapy is recommended for any confirmed infected aneurysm (type III). In addition, it must be taken into account that meticulous handling techniques (i.e., washing of hands, using a mask, and minimal handling of catheters and guidewires) and sterilization of the operating room may minimize the risk of bacterial contamination that results in infected aneurysms.

The relative rarity of overall events makes it difficult to definitively rule out a treatment effect upon aneurysm formation and thus a certain conclusion regarding possible etiology can not be made in every patient who develop CAAs after coronary stent implantation and as this study is an observational study, need for large angiographic follow up data of stent trials may be necessary to better understand CAAs.


  Conclusions Top


Development of CAAs after coronary stent implantation is rare. Some CAAs have benign clinical course while other may lead to DES restenosis or thrombosis. Many factors may play a role in formation of aneurysm in varied patients. More studies are needed to identify patients at risk of adverse events from aneurysms and to detect most suitable intervention.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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