This was a single-center, retrospective observational study conducted at the Department of Cardiology, Xiangtan Central Hospital. A total of 256 consecutive patients who underwent IVUS-guided successful PCI for CTO lesions in the LAD artery between January 2016 and August 2022 were included. For patients without documented clinical evidence of occlusion duration, the chronicity of the lesion was assessed based on angiographic features indicative of long-standing occlusion (9). To ensure adequate assessment of MB, only patients with >40 mm analyzable IVUS image length distal to the LAD ostium were included (10). Inclusion criteria: successful PCI for de novo LAD CTO lesions; use of IVUS during the procedure; analyzable IVUS pullbacks with adequate segment length for MB detection. Patients were excluded if they had in-stent restenosis-related CTO, a history of heart transplantation, or significant comorbidities that could confound the analysis or affect outcomes. These included severe hepatic or renal dysfunction, hyperthyroidism, active malignancy with extensive metastatic spread, and bleeding disorders (Figure 1). All patients presented with symptoms consistent with myocardial ischemia, predominantly effort-induced angina pectoris or angina-equivalent symptoms such as dyspnea on exertion. Objective evidence of ischemia was evaluated prior to PCI decision-making based on a combination of clinical presentation, resting or stress electrocardiography, and echocardiographic assessment of regional wall motion abnormalities when clinically indicated. In addition, coronary angiography demonstrated LAD chronic total occlusion with impaired distal perfusion, supporting the diagnosis of significant myocardial ischemia. Demographic characteristics, clinical comorbidities, laboratory parameters, angiographic and IVUS imaging data, procedural details, and long-term clinical outcomes were retrospectively collected from the hospital's electronic medical records and imaging archives. The study complied with the ethical principles outlined in the Declaration of Helsinki (2013 revision) and was approved by the Ethics Committee of Xiangtan Central Hospital (Approval No. X201853). Written informed consent was obtained from all participants. For certain cases where written consent was not feasible, verbal consent was documented in accordance with institutional policy.

All CTO procedures were conducted by experienced interventionalists, with procedural strategies determined individually at the operator's discretion. Upon successful guidewire crossing, balloon predilation was initially performed under angiographic guidance. IVUS imaging was then utilized to verify the intraluminal position of the guidewire distally, evaluate the lesion architecture, and delineate optimal stent landing zones. Lesion preparation was undertaken when indicated. Stents were deployed in reference vessel segments demonstrating a plaque burden of less than 50%, as assessed by IVUS. In cases where an MB was located distal to the lesion, stent placement into the MB segment was generally avoided. Exceptions were made in the presence of significant dissection involving the MB or when critical disease existed just proximal to the MB, necessitating extension of the stent into the bridged segment. Technical success was defined by restoration of antegrade TIMI grade 3 flow and achieving residual diameter stenosis <30% in the treated segment. Total procedure time was recorded from the initiation of vascular access to the withdrawal of the final catheter. In this study cohort, all lesions were treated with second-generation DES implantation, and neither bioresorbable scaffolds nor drug-coated balloon strategies were utilized.

All patients received dual antiplatelet therapy (DAPT) consisting of aspirin (100 mg/day) and clopidogrel (75 mg/day). For patients who had not been on chronic DAPT for at least 7 days prior to the procedure, a loading dose was administered 24 h before the intervention, consisting of aspirin (300 mg) and either clopidogrel (300 mg) or ticagrelor (180 mg), in accordance with current guideline recommendations. Post-procedurally, patients continued DAPT with aspirin (100 mg/ day) and clopidogrel (75 mg/day) for 12 months. Additional pharmacotherapy—including statins, beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and nitrates—was prescribed as clinically indicated.

Coronary angiographic evaluation was conducted by an experienced interpreter (H.H.) who was blinded to all clinical and IVUS data. Quantitative analysis was performed using the QAngioXA software (Medis Medical Imaging Systems, Leiden, the Netherlands). The length of the CTO lesion was determined based on contrast opacification of the distal vessel using either antegrade or retrograde approaches, including simultaneous bilateral injections when appropriate. Lesion complexity was assessed utilizing the J-CTO score, as defined by the Multicenter CTO Registry of Japan (11). The extent of collateral circulation was graded according to the Rentrop classification system (12).

Following successful guidewire advancement, all CTO lesions underwent balloon predilation prior to prestenting IVUS imaging. To reduce the risk of vasospasm, an intracoronary dose of 100–200 μg nitroglycerin was routinely administered before image acquisition. Two IVUS catheters were used during the study period: the 40 MHz Atlantis SR catheter (Boston Scientific, USA) from 2016 to 2019, and the OptiCross catheter (Boston Scientific, USA) from 2019 to 2022. Both devices were compatible with the iLab IVUS system and provided similar image quality and acquisition characteristics. The IVUS catheter was positioned distally beyond the lesion and withdrawn proximally toward the aorta under fluoroscopy at a consistent speed of 0.5 mm/s or 1.0 mm/s. Imaging sequences were digitally stored. Offline interpretation was performed using QIvus® software (Medis, Leiden, the Netherlands), a dedicated IVUS analysis platform. Quantitative and qualitative measurements were independently performed by two trained reviewers blinded to clinical data. In the event of disagreement, a third senior analyst adjudicated the final value. Identical analysis protocols and scoring criteria were employed for both catheter systems to maintain methodological uniformity.

All analyses were conducted according to contemporary recommendations for IVUS imaging acquisition, interpretation, and reporting, as outlined in expert consensus guidelines (13) on intravascular imaging and physiologic assessment. An MB was identified as a segment of epicardial coronary artery showing systolic compression surrounded by echolucent muscular tissue on IVUS (14) (Figure 2). Within this segment, the following parameters were evaluated: minimum lumen area (MLA), plaque burden at the MLA, maximum MB thickness, total MB length, and diastolic vessel restriction, calculated as (1—diastolic vessel area/interpolated reference vessel area) (14). True CTO length was determined by coregistering IVUS images with angiography via fiduciary landmarks. The IVUS-defined CTO segment was characterized by cross-sections lacking a smooth, concave lumen contour, distinguishing it from adjacent reference regions. CTO length was then calculated based on the pullback speed and duration. For manually withdrawn catheters, measurements were derived from the coregistered angiogram. Extraplaque tracking was defined as guidewire passage outside the plaque but within the adventitia, recognized by the absence of the classic three-layer vessel wall pattern (15). Stent expansion was defined as the ratio of minimum stent area (MSA) to the average lumen area of the proximal and distal reference segments. All IVUS measurements were obtained during phases of maximal vessel diameter, presumed to correspond with diastole. Anatomical assessments from both IVUS and angiographic data were independently reviewed by two experienced interventional cardiologists (X.W. and L.W.) blinded to patient presentation and laboratory data. Inter-observer and intra-observer agreement were excellent, with κ coefficients of 0.90 and 0.93, respectively.

Patients were followed up at 1, 6, and 12 months post-discharge and annually thereafter. Follow-up data were collected via outpatient visits, hospital records, telephone interviews, and verification through referring physicians or national mortality databases. The primary outcome was the occurrence of major adverse cardiovascular events (MACE), defined as a composite of cardiac death, target vessel myocardial infarction (MI), clinically driven target lesion revascularization (TLR), or in-stent thrombosis (IST), as per the Academic Research Consortium definitions (16). Clinically driven TLR was defined as revascularization performed in the presence of recurrent ischemic symptoms or objective evidence of myocardial ischemia, in combination with angiographic restenosis of ≥50% within the target lesion, in accordance with guideline recommendations.

All statistical analyses were conducted using IBM SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA). The Kolmogorov–Smirnov test was employed to assess the distributional normality of continuous variables. Variables following a normal distribution were presented as mean ± standard deviation (SD) and compared between groups using independent-samples t-tests. For variables not normally distributed, data were expressed as median and interquartile range [M (P25, P75)] and compared using the Mann–Whitney U test. Categorical variables were summarized as frequencies and percentages [n (%)] and analyzed using either Pearson's χ² test or Fisher's exact test, depending on cell counts. All statistical evaluations were two-sided, and a p-value < 0.05 was considered to indicate statistical significance. Variables identified as potential predictors of MACE in univariate analysis were subsequently entered into a multivariate Cox proportional hazards regression model using backward stepwise selection to determine independent predictors of adverse outcomes. The cumulative incidence of MACE was estimated using Kaplan–Meier survival curves, and differences between groups were assessed with the log-rank test. A two-tailed P value < 0.05 was defined as the threshold for statistical significance.

While MB has traditionally been regarded as a benign anatomical variation, accumulating evidence suggests it plays a pivotal role in modifying local coronary hemodynamics. This alteration predisposes the segment proximal to the bridge to the development of atherosclerosis and CTO, rather than the tunneled or distal segments of the artery.

In our analysis, IVUS demonstrated that patients with MB-related LAD CTO lesions exhibited a lower prevalence of calcified plaques and a reduced extent of calcification within the occluded segment compared to those without MB. This observation underscores a key structural divergence between the two patient cohorts and may reflect the distinct hemodynamic conditions imposed by the presence of MB. The repetitive systolic compression characteristic of MB alters local vascular wall mechanics and generates unique shear stress distributions that are less favorable to chronic arterial remodeling and calcific plaque development.

Specifically, the bridged region and its upstream segment—particularly the pre-bridge area—are subjected to disturbed flow patterns and diminished shear stress, a combination that is more commonly associated with non-calcified or mixed plaque morphologies (18, 23). Unlike calcified lesions, non-calcified plaques—often termed soft or vulnerable plaques—are defined by a large lipid-rich core, a thin fibrous cap, and an abundance of inflammatory cell infiltration, characteristics that render them susceptible to rupture (24). Although coronary artery calcification is traditionally considered a surrogate marker of chronic plaque stability and burden, its relative paucity in MB-associated CTO lesions does not equate to clinical quiescence. On the contrary, the predominance of non-calcified, unstable plaque—particularly proximal to the MB where adverse hemodynamic influences are concentrated—may signal a higher risk profile. This insight urges caution in interpreting low calcific burden in such lesions; although it may suggest technical ease in lesion crossing or reduced stent length, the underlying plaque vulnerability increases the likelihood of peri-procedural complications during PCI. Therefore, meticulous imaging assessment and vigilant post-intervention surveillance are essential when managing these patients.

In our investigation, both the IVUS-assessed length of CTO lesions and the total stent length were significantly reduced in patients with MB compared to those without. This finding likely reflects the distinct anatomical and pathophysiological profile associated with MB, particularly its capacity to shield the tunneled segment from atherosclerotic involvement, thereby localizing disease predominantly to the proximal LAD.

Multiple mechanisms have been proposed to explain this relative resistance to plaque accumulation within MB segments. Firstly, the bridged arterial portion is anatomically segregated from surrounding perivascular adipose tissue, which is a recognized contributor to atherogenesis via pro-inflammatory paracrine signaling (25). Secondly, advanced imaging modalities such as optical coherence tomography (OCT) have revealed an absence of adventitial vasa vasorum in MB regions (26), potentially limiting the transvascular infiltration of inflammatory stimuli. Moreover, the cyclical systolic compression exerted on the tunneled artery may promote enhanced lymphatic drainage, thereby facilitating the removal of lipids and inflammatory cytokines from the vessel wall (27). Lastly, elevated or physiologically favorable wall shear stress within the MB region has been implicated in the upregulation of atheroprotective genes and maintenance of endothelial function (20).

While these factors may account for the shorter lesion length and reduced stent requirement, they also pose procedural complexities. Stenting into MB segments is generally avoided due to the risks of inadequate expansion under systolic compression and the potential for mechanical complications such as stent fracture or malapposition. As a result, the selection of appropriate landing zones becomes more constrained, particularly in MB-associated CTOs characterized by focal disease (8). Thus, although MB appears to offer a form of anatomical protection against extended atherosclerotic development, this benefit is offset by technical challenges in PCI planning.

The observed reduction in lesion and stent lengths in the MB cohort should not be viewed purely as a procedural advantage. Rather, it underscores a set of anatomical limitations that necessitate careful pre-procedural imaging, strategic lesion preparation, and individualized stenting approaches to minimize the risk of incomplete lesion coverage or geographic miss.

Our study demonstrates that the presence of MB in LAD CTO lesions is significantly associated with higher incidences of MACE (19.7% vs. 8.7%, P = 0.033) and TLR (18.0% vs. 6.7%, P = 0.016) at the 2-year mark. Moreover, MB was identified as an independent prognostic factor for MACE in multivariate analysis (HR = 2.173, P = 0.021). These results underscore the clinical importance of tailoring PCI strategies for this distinct anatomical and hemodynamic subgroup.

While earlier studies have reported favorable long-term survival in patients with isolated MB—approximately 98% over 11 years (28)—the outcomes are markedly less favorable when MB coexists with coronary artery disease (CAD), particularly in individuals undergoing PCI. Our findings align with growing evidence that stent implantation within MB segments may be associated with adverse outcomes, including increased neointimal hyperplasia, elevated rates of in-stent restenosis, and higher incidence of TLR (10, 29). Tsujita et al. observed a significant rise in TLR (from 3% to 24%) when stent deployment extended into MB regions (10). Additional studies using OCT and IVUS have revealed substantial neointimal tissue proliferation and even mechanical complications, such as stent fracture, within bridged segments (1).

These unfavorable outcomes are likely a result of the unique biomechanical environment inherent to MB. Stents positioned within MB segments are subjected to repetitive systolic compression, non-physiological shear stress patterns, and the so-called “sandwich effect”, in which the device is compressed between the coronary artery wall and the overlying myocardium (1, 30). This dynamic stress environment promotes the release of vasoactive substances, activates local inflammatory pathways, and may accelerate mechanical fatigue of the stent, thereby contributing to maladaptive remodeling and subsequent clinical complications.

From a technical perspective, the reduced CTO lesion length and the clinical preference to avoid stenting within MB segments result in limited options for stent landing zones. This constraint may elevate the risk of incomplete lesion coverage or geographic miss. Therefore, the presence of MB should be carefully evaluated during pre-procedural planning—ideally with high-resolution imaging modalities such as IVUS or CT—to facilitate accurate landing zone selection and optimal stent deployment strategy. Collectively, these findings suggest that conventional PCI algorithms may be insufficient for managing MB-associated LAD CTO lesions. Instead, a customized revascularization approach should be considered—one that aims to mitigate mechanical strain on the stent, avoid unnecessary implantation within bridged segments, and explore alternative therapies such as drug-coated balloon (DCB) angioplasty or ultrashort stent platforms. Additionally, rigorous post-PCI monitoring and extended follow-up are warranted to identify and manage potential TLR events or stent-related complications.

This study has several noteworthy limitations that should be acknowledged. First, it was conducted as a single-center, retrospective observational study, which inherently introduces potential selection bias and limits the generalizability of the findings to other centers, populations, and practice settings. Second, various procedural decisions—including selection of stents, lesion preparation techniques, and strategy choice (antegrade vs. retrograde)—were made at the discretion of individual operators. This operator-dependent variability may have introduced heterogeneity that influenced clinical outcomes. Third, the analysis was confined to CTO lesions of the LAD, limiting the extrapolation of the results to CTO lesions in other coronary vessels such as the RCA or LCX, where the presence of MB is uncommon but may still be clinically relevant. Fourth, referral bias may have influenced the composition of the study population, complicating efforts to determine the true prevalence of MB in either LAD CTO or non-CTO scenarios. Fifth, no routine angiographic or intravascular imaging follow-up was performed after the index procedure, limiting our ability to evaluate stent-related complications such as in-stent restenosis, stent fracture, or neoatherosclerosis, and to correlate imaging findings with clinical outcomes. Sixth, although multivariate analysis was feasible for MACE, the relatively small number of events related to both MACE and TLR constrained the statistical power of the Cox regression models, resulting in wide confidence intervals and necessitating cautious interpretation of these findings. Seventh, subgroup analyses comparing clinical outcomes between patients with stenting within MB segments vs. those without, and interaction analyses incorporating clinical modifiers such as CTO score or lesion calcification, could not be performed due to limited sample size and low event rates in these subgroups. Lastly, although critical anatomical variables such as plaque burden and stent length are known to impact long-term clinical outcomes, these were not consistently matched or adjusted in subgroup comparisons. Despite these limitations, our findings are consistent with prior literature suggesting that stent placement within MB segments may predispose patients to unfavorable outcomes, including neointimal proliferation and restenosis (29, 31). Future multicenter, prospective studies with larger sample sizes are warranted to validate and extend these findings to broader patient populations.