A Combination of Drug-Eluting Stents and Bioresorbable Vascular Scaffolds in the Treatment of Multivessel Coronary Artery Disease

Optimal management of multivessel coronary artery disease can be complex. We report a 67-year-old male patient who was admitted to the Padua University Hospital, Padua, Italy, in 2014 with a non-ST-elevation myocardial infarction. Coronary angiography showed diffuse multiple sub-occlusive lesions of the proximal and distal left coronary vessels involving a long segment of the vessel. On intravascular ultrasonography (IVUS), the left main artery was moderately diseased with critically stenotic and calcified branch ostia. A successful percutaneous coronary intervention using the T-stenting and small protrusion technique with two drug-eluting stents (DES) was performed on the left main artery and its main branches. Two bioresorbable vascular scaffolds were also deployed in overlap at the mid to distal segments of the left anterior descending artery and overlapping a previous DES at the proximal segment. The full expansion and apposition of the struts and scaffolds to the vessel wall without residual stenosis was confirmed by IVUS.

Due to the anatomical complexity of the distal coronary arteries, the patient was referred for a multiple lesion PCI.A decision was made to combine rigid cage stents for the proximal wide lumen segments and bioresorbable vascular scaffolds for the diffuse infarction without significant clinical sequelae as confirmed by echocardiographic follow-up which showed normal dimensions with preserved systolic left ventricular function (left ventricular end-diastolic volume index: 65 mL/m 2 ; ejection fraction: 58%) without wall motion abnormalities.At this time, the patient was asymptomatic without residual ischaemia.This was confirmed by a negative exercise stress test at 150 W. The patient was a smoker and had several other cardiovascular risk factors, including hypertension, dyslipidaemia and type 2 diabetes mellitus.
At presentation, the patient was immediately administered 250 mg of intravenous aspirin and 180 mg of oral ticagrelor.As he had a high Global Registry of Acute Coronary Events risk score (145), an emergency coronary angiogram was carried out using the right radial artery.This revealed non-significant stenosis of the dominant right coronary artery and  eluting stent (Xience Prime ® ) at the level of the left main trunk-proximal segment of the LAD artery.This was followed by another 3.5 x 12.0 mm everolimus-eluting stent (Xience Prime ® ) at the left main trunk-proximal segment of the LCx artery.Kissing balloon postdilation was then performed in the bifurcation of the left main, LAD and LCx coronary arteries.Finally, after the mid-distal LAD artery lesions were prepared using an incremental semi-compliant balloon, excluding the recurrent apical segment, two bioresorbable vascular scaffolds (Absorb Bioresorbable Vascular Scaffold, Abbott Vascular) of 3.0 x 28 mm and 2.5 x 28 mm, respectively, were positioned proximally to the distal segments, with minimal overlap (marker-to-marker implantation) at the mid-to mid-distal segment of the LAD artery and overlapping the metallic cage stent at the proximal segment of the LAD artery.
Following the intervention, a coronary angiogram showed that all vessel side branches were maintained without evidence of any complications.Full expansion and complete apposition of the metallic struts to the vessel wall at the proximal segments was confirmed via IVUS [Figure 3].Similarly, the uniform and full expansion of the bioresorbable scaffolds apposed to the intimo-medial membrane at the mid-distal LAD artery was observed without residual stenosis via angiography and IVUS [Figure 4].The patient remained asymptomatic without further cardiac events and was discharged one week after admission on a 12-month course of dual antiplatelet therapy.At a six month clinical follow-up, the patient was symptom-free.

Discussion
Consideration of the coronary anatomy, disease complexity, the presence of left ventricular dysfunction and SYNTAX risk score, along with any atherosclerotic lesions which involved the long middistal segments of the left anterior descending (LAD) artery.Due to severe calcifications on the mid-distal LCx artery, percutaneous transluminal coronary angioplasty was performed.Instead of a bioresorbable vascular scaffold, a single 2.5 x 23.0 mm everolimuseluting stent (Xience Prime ® , Abbott Vascular, Santa Clara, California, USA) was implanted at the middistal LCx artery in order to avoid suboptimal scaffold expansion/apposition.After preparation of the lesions with semi-compliant balloons, a successful two-stent approach using the T-stenting and small protrusion technique was performed at the left main trunk and its main branches using a 3.5 x 33.0 mm everolimus-  comorbidities, interventional risks, long-term outcomes, local expertise and the patient's personal preferences, are imperative when making decisions regarding treatment for patients with multivessel CAD. 1,3For patients with SYNTAX scores over 22, CABG surgery is associated with better long-term outcomes than PCI, barring the presence of excessive preoperative risk factors. 35][6] One recent trial involving patients with diabetes mellitus and advanced multivessel CAD found that CABG treatment was beneficial in that it significantly reduced rates of death, myocardial infarction and repeated revascularisation at a five-year follow-up, although a higher rate of strokes was observed. 6Based on this trial, CABG surgery is recommended as the preferred treatment for patients with multivessel CAD, as it has the most favourable long-term outcomes in patients with a high SYNTAX score but without high surgical risk. 4,6lternatively, patients who are at high risk for surgery, or who have low-severity CAD, should undergo PCI treatment. 5The patient in the current case presented with a high-risk SYNTAX score and angiographic evidence of multivessel CAD; treatment with PCI was chosen as CABG surgery was deemed unsuitable due to the anatomical complexity of the distal coronary arteries.As distal coronary stenoses may affect adenosine-mediated vasodilation leading to a falsenegative result, the fractional flow reserve technique was not used to evaluate the PCI target.
The present case illustrates the importance of tomographic techniques-such as IVUS imagingover coronary angiography in the diagnosis and management of complex multivessel CAD.In the current case, IVUS showed moderate left main trunk disease and critically calcified ostial lesions of the LAD and LCx arteries.However, in comparison with conventional intravascular imaging modalities such as IVUS, optical coherence tomography has a higher resolution (range: 10-15 μm), allowing for the more accurate detection and quantification of scaffold malapposition, underexpansion, tissue prolapse or stent edge dissection.Recently, research has shown that optical coherence tomography can be used to identify adverse cardiac features requiring immediate intervention in a large proportion of patients, resulting in improved clinical outcomes. 7Unfortunately, this alternative imaging technology was not available at the Padua University Hospital at the time of the intervention.
][10] Permanent metallic platform stents also indefinitely impair the physiological vasomotor functioning of the vessel; hence the coronary geometry and systo-diastolic movement of coronary arteries treated with metallic stents remain similar up to a year after implantation. 9,10Bioresorbable vascular scaffolds have the potential to overcome these limitations as they provide a temporary scaffolding which disappears after 2-3 years, liberating the treated vessel, and can help to restore the vessel's original shape, preserving laminar blood flow, reducing the plaque-to-media ratio and restoring the vasomotion, pulsatility, cyclical strain, adaptive shear stress and mechanotransduction of the vessel. 8,9,11Following PCI, the absence of any residual foreign material and restoration of functional endothelial coverage can also reduce the risk of stent thrombosis, myocardial infarction, sudden death and the need for long-term dual antiplatelet therapy; in addition, PCI does not exclude the possibility of future graft anastomosis in case the need for future bypass surgery arises. 8,9However, there are as yet no data with regards to the feasibility of performing CABG surgery at coronary sites which have previously undergone implantation of a bioresorbable vascular scaffold.
After implantation, the bioresorbable vascular scaffold maintains sufficient radial strength to prevent vessel recoil and releases the drug to inhibit the proliferation of neointima.However, the scaffold's mass and radial strength gradually decrease over time and it vanishes completely after 2-3 years, leaving the vessel covered with a healthy endothelium and with normal vasomotor function. 8Bioresorbable vascular scaffolds should be predominantly used in young patients for whom multiple long stents are required, particularly those with long lesions or diffuse disease; patients with lesions located in the mid-distal portion of the coronary arteries will also benefit because the use of bioresorbable vascular scaffolds does not preclude potential bypass grafting in the future. 8For severely calcified vessels, preparation of the lesion with optimal pre-dilatation or the use of additional devices and procedures such as cutting and scoring balloons or rotational atherectomy is crucial for the successful implantation of the scaffold.Even severely calcified vessels will benefit from the disappearance of the scaffold, as this reduces the risk of late stent thrombosis and can lead to late lumen gain. 8o guidelines currently exist on the simultaneous use of drug-eluting stents and bioresorbable vascular scaffolds to manage diffuse critical atherosclerotic multivessel CAD.concurrent use of these devices might be safe and effective, with no mortality or incidents of myocardial infarction or stent thrombosis observed at a 12 month follow-up and very few cases of clinically-driven target lesion revascularisation. 12The rationale for using both devices in the current case was to treat the diffuse disease percutaneously while avoiding the use of long metallic stented segments.Due to the diffuse disease at the mid-distal LAD artery, the patient's anatomy was not deemed suitable for CABG surgery.On the other hand, the presence of lesions at the left main trunk and proximal LAD artery supports coronary revascularisation over medical treatment, especially for acute coronary syndromes such as non-ST-elevation myocardial infarctions. 2,13As a result, PCI was performed; however, as multiple lesions and segments required treatment, coronary bioresorbable vascular scaffolds were used to avoid mid-to-longterm drug-eluting stent-related adverse events (e.g.stent thrombosis and restenosis). 8,9In addition, implanting a long metallic drug-eluting stent at the distal coronary bed could potentially affect coronary flow or the outcome of future CABG surgeries. 9,10evertheless, metallic stents were also implanted at proximal sites due to the limitations of bioresorbable vascular scaffolds for large vessels, bifurcations (i.e. the left main trunk lesion in the current patient) and severely calcified lesions. 9,11

Conclusion
Lesions in the left main coronary artery are rarely isolated and the coronary anatomy is not always suitable for a CABG surgical approach, regardless of risk scores.As with the current case, a combination of drug-eluting stents and bioresorbable vascular scaffolds can be a feasible treatment option for complex diffuse multivessel CAD with left main trunk involvement.The use of non-metallic bioresorbable vascular scaffolds in long diffuse lesions of the middistal vessels, in combination with metallic struts in the proximal segment, may mitigate the adverse effects of metallic stents.This technique ensures adequate and temporary scaffolding while also promoting adequate healing of the vessel wall and allowing for the possibility of future graft anastomosis should the patient subsequently need CABG surgery.

Figure
Figure 1A-C: Coronary angiography of a 67-year-old male patient from the (A) cranial right anterior oblique (RAO), (B) caudal RAO and (C) caudal left anterior oblique views showing multiple diffuse critical lesions of the proximal and distal segments of the left coronary arteries involving the left main trunk with a hazy proximal left circumflex artery (LCx) lesion.Despite evaluation from several planes, the stenosis of the proximal LCx artery remained unclear.

Figure
Figure 2A-C: Intravascular ultrasonography (IVUS) of a 67-year-old male patient showing (A) moderate left main trunk disease, (B) multiple significant stenoses of the left anterior descending artery and (C) stenosis of the proximal left circumflex artery with eccentric superficial and deep dense calcific plaque (arrow).MLA = minimal lumen area.

Figure
Figure 4A-C: A: Post-interventional coronary angiography of a 67-year-old male patient following the implantation of two bioresorbable vascular scaffolds at the mid-distal portion of the left anterior descending artery and in overlap with a drug-eluting stent at the proximal portion.B and C: Cross-sectional intravascular ultrasonography images corresponding to sections of the coronary angiogram (yellow lines) showing the uniform and full expansion of the struts and scaffolds apposed to the intimo-medial membrane.All three concentric stents and scaffold layers were noted at overlap sites as discrete echo-bright structures.DES = drug-eluting stent; BVS = bioresorbable vascular scaffold.

Figure
Figure 3A-C: Post-interventional cross-sectional intravascular ultrasonography of a 67-year-old male patient following the implantation of two bioresorbable vascular scaffolds and two drug-eluting stents.The stents were well-apposed and expanded with no signs of dissection at the (A) left main trunk, (B) proximal portion of the left anterior descending artery and (C) proximal portion of the left circumflex artery.
Gil et al. recently reported that the