Editorial: Diagnosis and Treatment for Arteriosclerosis and Thrombosis

Yang Liu¹Yao Liu^2*Yihao Zheng³

• ¹Global Institute of Future Technology, Shanghai Jiao Tong University, Shanghai, China
• ²School of Mechanical Engineering, North University of China, Taiyuan, China
• ³Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, Worcester, United States

Arteriosclerosis and thrombosis remain leading contributors to morbidity with peripheral artery disease (PAD) affecting over 110 million individuals worldwide (1). Despite recent advances in endovascular approaches, challenges persist in managing complex lesions such as those classified as the Trans-Atlantic Inter-Society Consensus (TASC) II type C/D. Determining the optimal treatment strategy to achieve high long-term patency rate while minimizing short-term risks remains an area of active investigation and discussion (2). This editorial summarizes findings from three studies published within this Research Topic, highlighting innovations in vessel preparation, hybrid approaches to complex lesions, and spinal cord stimulation (SCS) for PAD with chronic limb-threatening ischemia (CLTI).Vessel preparation has almost become an essential step prior stenting to improve outcome in endovascular management of PAD, especially for long or calcified lesions. Vessel preparation is achieved by debulking the plaque using atherectomy or modifying the plaque using intravascular lithotripsy or balloons (undersized plain balloons, cutting balloons, scoring balloons). For vessel preparation using balloons, suboptimal/uneven expansion in calcified lesions exerting uneven forces is a persisting challenge and calls for development of new technologies. In a single-arm study of 43 patients, Zhang et al. evaluated the safety and efficacy of using nitinol-constrained chocolate balloons for vessel preparation followed by drug coated balloons (DCBs) in femoropopliteal artery lesions (3). The “pillow effect” of the chocolate balloon increases the balloon-vessel contact area, and distributed the radial load more evenly than plain balloons. This mechanism was validated by the low severe dissection rate (10.6%) and stent bailout rate (4.3%). This cohort achieved 78.7% 12-month freedom from clinically-driven target lesion revascularization rate, similar to that (78.8%) reported in the Chocolate Touch study (4). This study provided initial clinical data supporting the two-step strategy combining chocolate balloons and DCBs.For complex lesions classified as TASC II type C/D, endovascular approaches have suffered from technical failures due to difficulty in lesion crossing, need of multiple devices for long lesions, and heavy calcifications. Some patients with TASC II type C/D lesions are poor candidates for extensive open surgery due to comorbidities. The hybrid approach combines the durability of open surgery for critical segments and minimal invasiveness of endovascular approaches for others. However, quantifiable mechanistic explanations, especially on how the intraoperative changes in lesion complexity by open surgery, has seldomly been reported. In a cohort of 103 patients, Park et al. demonstrated that femoral endarterectomy (FE) resulted in reduction of TASC II type from C/D to A/B in 91% of the cases (5). The one-year and five-year primary patency rates were 89% and 77%, respectively, demonstrating great efficacy. This study reinforced femoral endarterectomy and iliac angioplasty (FEIA) as a viable option for managing multilevel lesions and first reported the “downgrading” effect of FE. In a recent retrospective study including 26 patients of aorto-iliac occlusive disease with TASC II type C/D lesions, the pure endovascular approaches also demonstrated great efficacy, with the one-year and five-year primary patency rates being 100% and 91%, respectively (6). These exceptionally high patency rates were likely contributed by the lack of femoral lesion involvement, and implied the efficacy of the hybrid approach depends on the specific pattern of PAD. While endovascular technologies have dramatically improved over the years, the hybrid approach retains a critical role in managing complex lesions.PAD can progress to its most severe form, CLTI. Patients with CLTI are often not eligible for open surgery due to comorbidities, and the efficacy of endovascular approaches is limited as the occlusion is usually diffused, multi-level, and heavily calcified, presenting significant technical challenges and leading to low intraprocedural success rates (7). These no-option patients lack effective therapeutic solutions and are faced with a one-year amputation rate as high as 30%-45% (8). To relief the pain, clinical evidence has supported the use of SCS but its effects on limb salvage has been under debate. In the pioneering ESES trial, SCS in addition to best medical care did not prevent amputation in patients with CLTI (9). In a small cohort of 13 diabetic patients with CLTI and unsuitable for vascular reconstruction, Cyrek et al. reported a 92.3% one-year limb salvage rate and an ulcers healing rate of 75% with SCS implantation (10). The pain score decreased from 7.8 to 3.5 and the quality-of-life scores increased by about 50%. The non-significant change in Ankle-Brachial Index during the one-year follow-up implied that SCS likely did not impact macrovascular flow, and the relieved pain and improved quality of life may be contributed by SCS’ microcirculatory and pain modulation effects. These results, although preliminary and with short follow-up period, provided real-world evidence that SCS may provide tangible benefits to no-option patients with CLTI. The study's primary limitation, as acknowledged by the authors, is its design: a retrospective analysis of a very small, single-center cohort without a control group.In summary, the highlighted studies addressed critical challenges in managing arteriosclerosis and thrombosis and emphasized the importance of tailored approaches for patients with complex PAD and CLTI.