1. Introduction
Chronic total occlusion (CTO) represents a challenging and complex subtype of coronary artery disease, characterized by Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow and estimated occlusion duration of greater than or equal to 3 months [
1]. The treatment of CTOs is a critical aspect of interventional cardiology, aimed at restoring coronary blood flow, relieving symptoms of ischemia, improving patient prognosis, and enhancing quality of life [
2]. CTO PCI is proven to reduce anginal symptoms compared to optimal medical therapy, but the reduction in major adverse cardiac events remains uncertain, according to data from large randomized studies [
3,
4].
CTOs have been extensively studied using percutaneous coronary intervention (PCI) with drug-coated balloons or drug-eluting stents (DESs) [
5,
6,
7,
8,
9]. The advancements in techniques and tools for CTO PCI, such as non-invasive and invasive imaging, have led to success rates of up to 80–90% [
10]. The introduction of bioresorbable scaffolds (BRSs) has brought a new dimension to the percutaneous treatment paradigm [
11]. BRSs offer several potential advantages over their metal and balloon counterparts, including the temporary provision of mechanical support to the vessel with the ability to dissolve and be absorbed after a certain period of time, thereby restoring the natural vasomotion and physiological responsiveness of the artery [
12].
BRSs are particularly appealing in the context of CTOs because they can reduce the burden of permanent material in the coronary arteries, which is often considerable given the length and complexity of these occlusions. Many studies have assessed the safety and outcomes of BRSs in CTOs, but the main limitation has been the relatively short follow-up time [
13,
14,
15]. Therefore, our study fills this gap by evaluating the long-term outcomes and safety of BRSs in CTO lesions.
4. Discussion
Our study shows that BRSs are a feasible and safe option for the treatment of CTOs. Most commonly, one DES and one BRS (Absorb or Magmaris) were implanted in the CTO artery, avoiding a full metal jacket. The primary endpoint of target vessel re-occlusion occurred in only 5.9% (n = 2) of patients due to one DES restenosis and one DES thrombosis, indicating effective long-term follow-up results. Of the 31 patients with angiographic follow-up, the target vessel was patent during follow-up in 96.8% (n = 30) of patients. The secondary endpoint of TLF was observed in 35.3% (n = 12) of patients, the same as TLR. TLF and TLR had a mean survival time to an event of 62.5 (95% CI, 53.9–71.2) months. A higher rate of TVR of 38.2% (n = 13) suggests that the disease may progress in other parts of the CTO artery that require revascularization. This could be due to the natural progression of coronary artery disease, and the survival time free from TVR was at a mean of 60.8 (95% CI, 51.8–69.7) months.
BRSs provide several advantages over traditional metallic stents, including the ability to offer temporary vascular support and then dissolve, allowing the artery to regain its natural structure and functionality [
16]. In recent years, the use of BRSs in practice has been questioned regarding their safety and efficacy. For example, the ABSORB III trial [
18] emphasized these concerns, as target vessel myocardial infarction was more frequent with BRSs compared with everolimus-eluting stents (EESs) (8.6% vs. 5.9%;
p = 0.03) and scaffold thrombosis (ScT) was significantly higher in BRS patients (2.3% vs. 0.7%;
p = 0.01). The Food and Drug Administration raised this safety concern and sales of Absorb BRS were discontinued [
19]. The pathophysiology of these adverse effects could be related to incomplete endothelialization or early dismantling of the scaffold which can promote thrombosis, and the structural integrity of the BRS can also be compromised over time as the material degrades, leading to potential scaffold disruption and late adverse events such as vessel restenosis or late thrombosis [
16].
Interestingly, procedural aspects were analyzed in detail in the ABSORB trials [
20], which showed that implantation in properly sized vessels (reference vessel diameter between 2.25 mm and 3.75 mm) independently predicted freedom from TLF through the first year (hazard ratio (HR): 0.67;
p = 0.01) and over three years (HR: 0.72;
p = 0.01). Also, aggressive pre-dilation was an independent predictor of reduced ScT rate between the first and third year (HR: 0.44;
p = 0.03). Optimal post-dilation was independently associated with a reduced rate of TLF between the first and third year (HR: 0.55;
p = 0.05) as well. These technical BRS implantation factors were strictly fulfilled in our study.
Later in the ABSORB IV trial, despite improved implantation technique, a slightly higher five-year TLF rate of 17.5% compared to 14.5% for cobalt chromium EESs was demonstrated, with a statistically significant difference (
p = 0.03). This increased risk was primarily observed during the first three years post implantation, coinciding with the scaffold’s bioresorption period. The study also noted a non-significant difference in device thrombosis rates within five years, occurring in 1.7% of BVS patients versus 1.1% of CoCr-EES patients (
p = 0.15) [
21].
Regarding the bioresorbable magnesium scaffold (Magmaris), the BIOSOLVE-IV study demonstrated BRSs to be both safe and effective in treating coronary artery disease, with a 12-month TLF rate of 4.3%, a device success rate of 97.3%, and a procedure success rate of 98.9%. The study found a low scaffold thrombosis rate of 0.5%, with most events linked to early cessation of antiplatelet therapy [
22]. The results align well with the BIOSOLVE-II and BIOSOLVE-III trials, which also showed favorable safety and performance outcomes with no definite or probable scaffold thrombosis [
23].
So far, the choice of scaffold, whether polymer based like Absorb or metal based like Magmaris, impacts clinical outcomes and procedural success. However, CTOs are more complicated coronary artery disease lesions that have not been studied as extensively as simple lesions. In our study, we found TLF to be related to an equal count of Magmaris and Absorb restenosis.
In studies assessing the efficacy and safety of DESs in de novo CTO lesions during 5-year follow-up, 6.3% TLR and 7.1% TVR were recorded [
24] with similar results in another study with a 4-year follow-up [
4]. Comparably, in the ABSORB-CTO study [
25] of 35 lesions, a rate of only 3% for TLF and TLR was recorded in the 3-year follow-up, but a rate of 11.4% was recorded for target vessel re-occlusion. Another study demonstrated that the Absorb BRS is non-inferior to EESs after 12 months of follow-up [
15]. We assessed TLF and TLR in 35.3% of cases, while only two re-occlusions were noted in our study. The higher TLF and TLR rates in our study may be due to more complex lesions and procedures compared to those in the ABSORB-CTO study. According to the J-CTO score in our study, most of the lesions were difficult (38.2%) or very difficult (41.1%) to examine, while in the ABSORB study, the CTOs were mostly intermediate (48.6%) or easy (25.6%) to examine. As a result, the retrograde approach was more often used in our study (32.4% vs. 14.3%) [
26]. Scheduled angiographic follow-up may increase the rate of revascularization due to oculostenotic reflex more than ischemia-driven indication for PCI [
27]. Another important factor is the lack of intravascular imaging in PCI guidance. Our earlier study involving the use of Absorb in treating left main distal bifurcation lesions demonstrated that the use of intravascular ultrasound for optimization was a protective factor against major adverse coronary events [
28]. Intravascular imaging also plays a crucial role in CTO treatment. IVUS offers deeper tissue penetration compared to optical coherence tomography (OCT). It also has the ability to operate without contrast and is effective in real-time imaging and stent optimization in the CTO treatment [
29]. In contrast, OCT is less suited for the broad requirements of CTO PCI, where flexibility and a comprehensive view of the vessel are paramount [
29]. CTO-IVUS and AIR-CTO studies showed that IVUS-guided CTO revascularization notably decreased major cardiovascular events during follow-up [
30,
31]. In our study, IVUS was employed during follow-up, showing a minimal lumen area of 5.35 ± 1.2 mm
2 and a mean lumen area of 8.83 ± 1.9 mm
2. QCA demonstrated that the residual diameter increase was around 10%. This showcases the durability of the BRS CTO approach.
4.1. Limitations
While we have described the long-term efficacy and safety of BRSs in CTO lesions, our study has some limitations. The study was conducted at a single center, which may limit the generalizability of the findings to other populations or settings. With only 34 patients, the sample size is relatively small, which could affect the statistical power and the ability to detect more minor effects or differences. It is important to note that enrollment occurred at a time when concerns about BRS safety had arisen, which led to the withdrawal of Absorb. We did not have a comparative group using drug-eluting stents only, which limits the ability to directly compare the effectiveness and safety of BRS to other established treatment options. IVUS was performed only during follow-up, which limits the assessment of differences from the index procedure. The different absorption rates of the scaffolds (Magmaris vs. Absorb) and their impact over time were not extensively analyzed, which could influence long-term outcomes like scaffold integrity and vessel reactivity.
4.2. Suggestions for Future Research
As one of the bioresorbable scaffolds used in this study has been taken off the market (Absorb; Abbott Vascular) and the other (Magmaris, Biotronik) has the third generation available, future studies are needed to explore the potential advantages of recently developed bioresorbable vascular scaffolds in the treatment of CTO. Larger randomized trials with DESs as a control group should be undertaken to evaluate the superiority of new BRSs over currently available DESs.