Two Cases of Management of Coronary Artery Perforation During Percutaneous Coronary Intervention Using Injection of Combined Histoacryl (n-Butyl-2-Cyanoacrylate) and Lipiodol (Ethiodized Oil)

Background

Coronary artery perforation is one of the most severe complications of percutaneous coronary intervention (PCI). Between 1993 and 2001, a reported series of >10 000 PCIs included 6836 cases that required stenting, with coronary artery perforation in 0.84% of cases [1]. The incidence of coronary artery perforation is higher (4–9%) in chronic total occlusion (CTO) PCI owing to the higher complexity of these lesions and the techniques used to recanalize them [2]. According to the British Cardiovascular Intervention Society database, the risk of perforation was significantly higher in CTO PCI [3].

According to the Ellis classification, type I coronary artery perforation is defined as an extraluminal crater without extravasation; type II is myocardial or pericardial blushing without contrast extravasation; type IIIa is defined as clear perforation (>1 mm) with evidence of extravasation; and type IIIb is defined as perforations into the left ventricle, coronary sinus, or another anatomic circulatory chamber [4]. Mild coronary artery perforation (type I and type II) is considered to have a better outcome and can be conservatively managed, with most patients undergoing prolonged balloon inflation alone. For more severe cases (type III), the in-hospital mortality rate is very high (15.2%), and these patients require urgent treatment [5]. Treatment includes covered stents, coils, micro-spheres, or other methods, such as autologous blood clots, thrombin, and fat injection.

The first-line treatment is covered stents, especially in proximal larger perforations; however, this treatment requires expertise and time. Microspheres, including Histoacryl (n-Butyl-2-Cyanoacrylate; B. Braun Medical Ltd, Melsungen, Germany) and Lipiodol (ethiodized oil) mixtures typically can be used for distal sites of coronary artery perforation; the mixtures are delivered through microcatheters and cause precise sealing of perforations [6]. The advantages are an uncomplicated technique, low cost, and wide availability in many hospitals. This report is of 2 cases of coronary artery perforation during PCI managed successfully using injection of combined Histoacryl (n-Butyl-2-Cyanoacrylate) and Lipiodol (ethiodized oil).

Case Reports

CASE 1:

A 51-year-old man with a past medical history of hypertension, dyslipidemia, and multivessel coronary artery disease presented to our hospital. One month earlier, he was diagnosed with ST-elevated myocardial infarction (STEMI). Diagnostic coronary angiography showed severe stenosis of the right coronary artery (RCA) and CTO of the mid-left anterior descending artery and mid-left circumflex artery (Figure 1). Revascularization was done with 1 stent placed in the mid-RCA, and the patient was discharged with an optimal dose of statin, duo-antiplatelet therapy, and beta-blocker. After the event, he continued to experience angina symptoms, associated with shortness of breath, which interfered with his daily activity and quality of life, leading him back to the hospital. An electrocardiogram show fixed T-wave inversion in DII, DIII, and aVF, similar to 1 month before. Laboratory tests were done, and the basic metabolic panel results were in the reference range. The troponin T level was 13 pg/mL. An echocardiogram showed left ventricular dilation with hypokinesia of the posterior wall and interventricular septum. The ejection fraction was 41%. Moderate anterior ischemia was detected in the myocardial perfusion single-photon emission computerized tomography (SPECT) scan. The patient was evaluated by the Heart Team and was found to have the indication for CTO revascularization to improve symptoms and to reduce the risk of death or MI [7]. After discussing interventional and surgical revascularization with the patient, we decided to do PCI to the CTO of the left anterior descending artery (LAD), owing to the patient’s preference.

The procedure was done via radial access with a 6F guiding catheter (Launcher, Medtronic); run-through guidewire with balloon support was passed through the lesion. Because there was no collateral from the other vessels, we could not check the distal vessel of the LAD. We used a small balloon 1.5×15 NC Emerge (Boston Scientific) to dilate, and then increased it to 2.5×15, with pressure to 20 atmospheres of pressure. After a few balloon inflations, the contrast injection showed a type 3 perforation (Figure 2, Video 1). The balloon was deployed immediately to stop bleeding, and after 30 min, the patient was stable, although he still had a sign of bleeding. We decided to put a microcatheter (Corsair, Asahi) to inject 3 mL of Histoacryl-Lipiodol mixture, with a ratio 1: 3, into the distal LAD (Figure 3). Immediately, the bleeding stopped (Figure 4, Video 2). During the procedure, the patient remained asymptomatic, and his vital signs were within normal limits. A serial echocardiogram showed no significant pericardial effusion. The patient was discharged after 5 days.

CASE 2:

A 72-year-old man with underlying hypertension presented to our hospital with chest pain and was diagnosed with unstable angina. A coronary angiogram showed severe stenosis of the LAD, CTO of the left circumflex artery (LCx) (Figure 5), and minor atherosclerosis in the RCA. After revascularization of the LAD with 1 stent, he was discharged with an optimal dose of anti-platelet therapy, statin, and beta-blocker. The following month, he continued to have significant angina with daily activities that reduced his quality of life, even with good medication adherence. He was admitted for further investigation. His electrocardiogram was normal except for left axis deviation. Laboratory test results showed basic metabolic panel results in the reference range and a troponin T level of 41 pg/mL (reference range, 14 pg/mL). The echocardiogram showed apical and lateral hypokinesia, with an ejection fraction of 45%. Dobutamine stress echocardiography revealed lateral ischemia. According to the 2021 American College of Cardiology/American Heart Association guidelines, in patients being considered for coronary revascularization for whom the optimal treatment strategy is unclear, a multidisciplinary Heart Team approach is recommended [7]. This patient consulted with the Heart Team, the surgical option was excluded owing to the patient’s preference, and we decided to do percutaneous revascularization of the CTO of the LCx.

The procedure was done via 7F sheath femoral access, and a good supporting 7F guiding catheter (Launcher, Medtronic) was used. A run-through guidewire in a microcatheter (Corsair, Asahi) was used to cross the lesion. However, the lesions were calcified. After a few wire manipulations, we observed an LCx small branch perforation with bleeding to the epicardial space (Figure 6, Video 3). Microcatheter corsair can stop bleeding but is unstable (Figure 7); therefore, we decided to inject 2 mL of Histoacryl-Lipiodol mixture (ratio 1: 3) through the micro-catheter into the false lumen, and after several seconds, the extravasation was stopped (Figure 8, Video 4). We stopped the procedure, and the patient was referred to the Cardiovascular Intensive Care Unit, with close monitoring. No sign of pericardial effusion was detected afterward, and his symptoms improved significantly. He was discharged after 2 days.

Discussion

Our cases suggest that a Histoacryl-Lipiodol mixture could be a good alternative method to manage coronary perforation during CTO PCI.

Our first patient was a middle-aged man with multivessel coronary artery disease who experienced significant angina symptom after RCA STEMI, even with optimal medication and good flow in the stent. Thus, revascularization was indicated to improve his symptoms. In addition, according to the 2021 American College of Cardiology/American Heart Association guidelines, in selected hemodynamically stable patients with STEMI and multivessel disease, after successful primary PCI, staged PCI of a significant noninfarct artery stenosis is recommended to reduce the risk of death or MI [7]. Our second case was an elderly man with a similar presentation. He had unstable angina with severe LAD stenosis and LCx CTO. The symptoms were significant even with successful LAD stenting and optimal medications. The indication for PCI was to reduce the patient’s symptoms. Unfortunately, the procedures were complicated by coronary perforation type IIIa with evidence of extravasation. However, pericardial effusion was minimal in both cases.

In a study including 6245 cases of coronary intervention, the incidence of vessel perforation was 0.8%, and most lesions were complex, including CTO. Among them, 46% of patients had significant pericardial effusion and 12% died [8].

The consideration of treatment of coronary artery perforation is based on many factors. The general approach includes stabilizing the patient with hemodynamic support and stopping antiplatelets and anticoagulants; platelet transfusion and protamine infusion can be considered. Urgent pericardiocentesis in cases of cardiac tamponade and prolonged balloon inflation to stop bleeding is necessary [6]. In more severe cases that require additional intervention, the treatment of choice includes a covered stent, coils, microspheres, and surgery [6]. Initially used to treat in-stent stenosis, covered stents are used to seal the perforation site and stop blood from leaking. These are commonly used for proximal larger perforations. Coil embolisms are considered the criterion standard for emergent sealing type III coronary perforation in distal parts. Ideally, coils should be prepared before inserting the microcatheter into the CTO lesion, but this is not always available. Also, it is time-consuming and significantly costly, with complicated perforation, and requires experienced interventionists. The other options, including auxiliary embolic agents such as subcutaneous fat tissue, clots, or thrombin, are widely available, although in our experience, they are time-consuming and inconvenient to prepare. Also, their effects are sometimes not predictable and are unreliable to stop the bleeding. The next option is micro-spheres, the particles used in many artery and venous embolisms. They are typically used for distal coronary artery perforation, similar to coils. Among microspheres, the Histoacryl and Lipiodol mixture has several advantages.

Histoacryl (n-Butyl-2-Cyanoacrylate) is a regulatory-approved tissue adhesive. It is considered the best choice for portal vein embolism [9]. Lipiodol (ethiodized oil) is a radio-opaque contrast agent that is used widely in radiological investigation. The mixture of Histoacryl and Lipiodol at a 1: 3 ratio provided an optimal embolization material with good flow properties, a polymerization time of approximately 7 s, and excellent contrast definition. This mixture can be handled quickly, with minimum risk involved, when used with a 40% glucose solution [10]. Previously, the mixture has been widely used in clinical settings such as skin closure, sclerotherapy for gastrointestinal bleeding, mesh fixation, portal vein embolism, and hepatic embolization in hepatocellular carcinoma [11]. Interventional radiologists have a rich experience using the mixture, and it has recently become available in many hospitals.

In our first case, we confidently embolized the distal LAD because SPECT imaging showed moderate ischemia and there were no collaterals from the other vessels. The second case was done following the first case, as we gained more experience dealing with perforation. In both cases, we worked together with interventional radiologists in the same cardiac catheterization laboratory, and they always stood by to help. We have been using coils and covered stents for several coronary artery perforation cases and, during the procedure, we were challenged with many difficulties. Intracoronary injection of the Histoacryl-Lipiodol mixture has proved the fastest, most inexpensive and effective method of management for our cases. Previously, n-Butyl-Cyanoacrylate was reported to be effective in managing coronary perforation in a CTO case that was similar to our cases; the authors also suggested that the glue plug could be “passed by a low tip load guide wire and undergo balloon angioplasty recreating a lumen” [12].

The adverse events expected after microsphere embolization include unintended vascular embolization, prolonged material polymerization time, and catheter retention. The unexpected embolization risk can be prevented with microcatheters and skill. The other adverse events are related to the interventionist’s inexperience. This highlights the essential role of the doctor’s experience in this high-risk procedure and leads us to use the Histoacryl-Lipiodol mixture. The effectiveness was observed in our cases: the perforation was sealed almost immediately, and the adverse effect was insignificant.

Conclusions

Coronary artery perforation is a life-threatening adverse event of PCI that requires immediate treatment. The operator’s experience, equipment availability, and cost should be considered while dealing with the problem. Histoacryl and Lipiodol injection was a rapid and effective management method in 2 rare cases of coronary artery perforation during PCI.