Stent therapy remains the first-line treatment for patients with severe coronary heart disease. Despite improvements in stent design, pharmacotherapy, and the polymers used in modern drug-eluting stents (DESs), approximately 5–10% of patients will experience in-stent restenosis (ISR) during angiographic follow-up [1, 2]. ISR continues to pose a therapeutic challenge and can be classified as focal, diffuse (with or without involvement of the stent edge), and chronic total occlusion (CTO) based on the results of angiography [3]. Due to the diffuse neointimal proliferation or neoatherosclerosis that may occur in the stents, the most severe ISR CTOs are more challenging to treat, and the outcomes of conventional treatments such as plain old balloon angioplasty (POBA), drug-coated balloon (DCB) angioplasty, and new stent implantations are usually unsatisfactory [4‐6].

One treatment option is excimer laser coronary atherectomy (ELCA), which uses a xenon chloride laser generator to generate a 308 nm laser that can reduce plaque volume. ELCA has acceptable indications, including in the treatment of ISR lesions [7]. However, the outcomes of patients with ISR CTOs who have undergone ELCA treatment have not been previously described. Therefore, the aim of this study was to evaluate the therapeutic efficacy and safety of ELCA therapy in this population.

The aim of the present study was to evaluate the immediate effects and 9-month outcomes of ELCA treatment in patients with ISR CTO. The main findings were as follows: (1) ELCA achieved good immediate angiographic results, as measured by QCA, without increasing the number of peri-procedural complications, including coronary perforation, coronary slow flow/no re-flow problems, and PCI-related MI. (2) ELCA did not alter the incidence of 9-month MACEs.

PCI with DESs is the current standard of care for the treatment of native coronary artery stenoses. However, the optimum percutaneous treatment strategy for patients presenting with ISR is still debated. Current studies have shown that for ISR, the use of DCBs can reduce the incidence of binary restenosis compared with that of POBA treatment [14]. DCBs offer the advantage of not requiring the implantation of an additional metallic layer when treating ISR, and they are recommended by the European Society of Cardiology and Chinese guidelines as the first-line treatment option [15, 16]. Because DCB technology has not yet received U.S. Food and Drug Administration approval for use in the coronary vasculature, repeated stent implantation and POBA are the regular choices in the USA [17].

Regardless of whether DCBs or DESs are used, it is impossible to truly remove the hyperplastic tissue or neoatherosclerosis present in the stent area. Unlike de novo lesions, this atherosclerotic plaque can expand and become redistributed. Due to the limitations of the original metallic stent structure, it is difficult to achieve sufficient expansion of ISR lesions through POBA. This inability to open up the coronary lumen reduces the therapeutic effects of the treatment. Therefore, it is common for a patient to experience binary restenosis within a short time following a procedure. When POBA is performed alone, the incidence of TLR at six months post-procedure is as high as 63.1% [18]. Lee et al. compared ISR CTOs and de novo CTOs that were mostly treated with DESs (> 90%); although the procedure success rate for treating ISR CTOs was higher because the previous stents could be used as a roadmap, the prognosis was worse, and the incidence of TLR was significantly higher (14% vs 4.3%, respectively; p < 0.001) [19]. Therefore, in this type of situation, techniques such as ELCA for removing the hyperplastic tissue could be a promising therapeutic option.

ELCA mainly exerts photothermal, photochemical, and photomechanical effects that result in the removal of hyperplastic tissue. Both in vitro and in vivo experiments have revealed that ELCA treatment can break the chemical bonds of cellular molecules by forming microbubbles in the cells. This can completely remove the proliferated cells by reducing them into microparticles, resulting in a therapeutic effect through plaque volume reduction [7, 20]. Another possible mechanism that could explain the benefits of performing ELCA for ISR is that ISR develops as a result of stent under-expansion, as the stent is constrained by external layers of calcium. ELCA can ablate the tissue around the stent and improve its ability to expand. At baseline, all of the patients in this study were experiencing CTO; therefore, the percentage diameter stenosis may be the best indicator of the effects of PCI. In this study, the patients treated by ELCA achieved a lower percentage diameter stenosis, which reflected a “debulking effect” of the treatment. Furthermore, the patients in the ELCA group had a larger reference lumen diameter than that of the non-ELCA group, which indicated that those with greater hyperplastic tissue burden can achieve a larger MLD (2.36 ± 0.29 mm vs. 1.78 ± 0.64 mm, respectively; p < 0.001).

The incidence rates of 9-month MACEs were similar in both groups, and most events were TLRs. The TLR rate was lower in the ELCA group than in the non-ELCA group (9.5% vs. 13.2%, respectively), although the groups did not significantly differ. Early clinical studies have shown that for diffuse in-stent restenosis, ELCA combined with POBA can achieve satisfactory therapeutic effects similar to the outcome of rotational atherectomy combined with POBA, although the TLR rate at one year post-procedure remained as high as 26% [21]. Herein, ELCA combined with DCB treatment for ISR CTOs resulted in a lower 9-month incidence rate of TLRs. However, due to an insufficient sample size, it was not possible to fully confirm the advantages of DEBs over POBA.

ELCA treatment can theoretically increase the total operation time; however, there were no significant differences in the fluoroscopic times or doses of contrast agents administered between the two groups. These two indicators were used instead of the overall operation time because these factors better reflect the extent of each patient’s injury and the complexity of the procedures. Some possible reasons for this were considered. For example, ELCA treatment itself does not require much time, generally speaking; once the wire passes the CTO lesion, the entire procedure can be completed in approximately 15 min, and ELCA treatment can reduce the amount of hyperplastic tissue in the area, which could reduce the subsequent balloon pre-dilation time.

In the present study, two patients (9.5%) in the ELCA group developed coronary perforation without clinical sequelae; however, coronary perforation is one of the recognized serious complications of PCI. Danek et al. [22], in a study based on data from the PROGRESS-CTO registry, the rate of coronary perforation was much higher when ELCA was used than when it was not (7% vs. 2%, respectively; p < 0.009). Protty et al. [23] also reported that ELCA was associated with a higher coronary perforation rate (odds ratio: 2.18, 95% confidence interval: 1.44–3.30) based on data from the British Cardiovascular Intervention Society database. For ISR CTO procedures, the wires may not remain in the true lumen as they are advanced in some segments; therefore, ELCA requires experienced operators, and operators must be cautious to avoid this kind of serious complication. Careful observation is recommended when a perforation does occur, as complications may develop over the course of several hours post-procedure. Laser light combined with simultaneous contrast injection can generate a powerful acoustic-mechanical effect, forming microbubbles that will increase the disruptive forces that result in an improved outcome, especially in cases of under-expanded stents [24, 25]. However, this is not our recommendation, as it could result in a higher perforation rate and more serious types of perforations.

The results of this study demonstrated that ELCA may be an effective treatment for ISR CTOs. It can significantly improve the immediate angiographic effects without increasing the occurrence of peri-procedural complications or the incidence rates of 9-month MACEs.