背景：冠状动脉完全闭塞性病变（Chronic Total Occlusion，CTO）是冠心病患者中常见且预后不良的病变类型，其患病率达 16%-18%，与长期死亡风险显著升高密切相关，因而成为临床与研究焦点。然而，由于CTO病变复杂的病理生理特征，其在介入结局长期获益探索、技术操作个体化、抗栓方案优化及代谢风险评估等领域仍面临多重挑战。本研究基于多中心队列数据，从四个维度系统解析CTO诊疗关键问题：1）对比不同经皮冠状动脉介入（Percutaneous Coronary Intervention，PCI）结局（失败 / 部分开通 / 完全开通）与远期心血管事件风险的关系，明确CTO病变完全开通对患者预后的影响；2）通过 2010-2013 年与 2017-2018 年队列对比，明确CTO介入技术、成功率以及治疗效果的变化，并且揭示介入技术升级与手术成功率之间的关系；3）评估低分子肝素的使用与患者短期及长期预后之间的关系；4）结合葡萄糖-甘油三酯指数（Triglyceride-Glucose Index，TyG），探索胰岛素抵抗与CTO患者长期不良事件风险的关联。

方法：从 2017 年 1 月份至 2018 年 12 月份，该研究在阜外医院连续纳入 4,152 名至少确诊 1 处CTO病变的冠心病患者。术后每隔 6 个月进行一次随访，平均随访时间为 3.3 年，主要终点事件为心血管死亡和靶血管相关心肌梗死的复合事件。数据分析方面，在第一部分中，研究将纳入人群依据 PCI 结局分为开通失败组、开通部分成功组和开通完全成功组，运用多因素 Cox 比例风险回归模型评估 PCI 结局与主要终点事件风险之间的关系。在第二部分研究中，加入 2010-2013 年CTO人群，通过对比 2010-2013 年和 2017-2018 年两个队列的人群、病变基线特征、介入技术使用情况、手术成功率以及长期临床事件，明确CTO手术效果的变化趋势，同时使用 Logistics 回归分析所有介入协变量与成功介入概率的关系，明确介入技术使用与手术成功率的关系。第三部分，研究根据术后 24h 内是否使用低分子肝素，将人群分为低分子肝素组和非低分子肝素组，使用 Cox 模型对低分子肝素的使用与 30 天与 3 年的主要终点事件风险进行关联分析。在第四个部分中，该研究根据TyG三分位数水平将人群平均分为 3 组（T1，T2，T3），首先使用 Cox 模型对TyG指数水平与临床事件风险进行了关联分析。同时，采用限制立方样条（Restricted Cubic Spline，RCS）曲线进行分析，探究TyG指数与主要终点事件风险之间的潜在线性关系，并进一步进行了受试者工作特征（Receiver Operating Characteristic，ROC）曲线分析，计算曲线下面积（Area Under the Curve，AUC）以量化TyG指数对主要终点事件风险的预测能力。

结果：该研究在2017-2018年队列随访期间总共记录了 143 例心血管死亡和靶血管心肌梗死复合事件方面，其中失败组发生 35 例（5.9%），部分开通组发生 23 例（6.4%），完全开通组发生 85 例（2.7%），相比于失败组，部分开通组主要终点事件发生风险显著升高（风险比 [Hazard Ratio，HR] 1.77，95% 置信区间 [Confidence Interval，CI]：1.02-3.1，P = 0.044），完全开通组则显著降低（HR 0.64，95% CI：0.41-0.98，P = 0.040）。第二部分研究中，对比 2010-2013 年和 2017-2018 年队列，发现 2017-2018 年队列CTO病变复杂程度显著增高，但完全成功率从58.7% 提升至 77.1%（提升了 18.4%），手术失败率从 26.3% 降至 14.3%。同时，在3年随访中，2017-2018 年队列心血管死亡和靶血管心肌梗死复合事件风险较 2010-2013 年队列显著降低（HR 0.44，95% CI 0.25-0.80，P = 0.006）。Logistics 多因素回归模型发现双侧血管造影、逆向导丝技术和血管内超声（Intravascular Ultrasound，IVUS）的应用与介入失败率下降显著相关（双侧血管造影比值比（Odds Ratio，OR）0.47，95% CI：0.38-0.58；逆向导丝技术 OR 0.37，95% CI：0.25-0.55；IVUS OR 0.45，95% CI：0.36-0.56；P 值均 < 0.001）。在第三个部分的研究中，低分子肝素组较非低分子肝素组在 30 天以及 3 年的主要终点风险均有所下降，但并无显著差异（30 天：HR 0.49，95% CI 0.05-4.91，P = 0.548；3 年：HR 0.56，95% CI 0.26-1.22，P = 0.144）。第四部分，研究发现高TyG指数升高与主要终点事件风险升高呈显著相关（T3 vs T1：HR 2.02，95% CI：1.29-3.18，P = 0.002）。RCS 分析明确了TyG水平与主要终点事件风险呈线性正相关（非线性 P 值 = 0.457），ROC 曲线进一步明确TyG指数评估心血管死亡和靶血管心肌梗死复合事件的 AUC 为 0.607（95% CI：0.560-0.655），TyG 指数的最佳截断值为 8.717。

结论：冠状动脉CTO患者PCI完全成功开通可使心血管死亡和靶血管心肌梗死复合事件发生风险显著降低，而部分开通则会使风险显著升高。相比于2010-2013年队列，2017-2018 年队列在 CTO 病变复杂度增加的情况下，完全成功率提高18.4%。相较于2010-2013年队列，2017-2018年队列中双侧血管造影、逆向导丝技术及 IVUS 应用使用率显著增加，且这三种技术的使用与介入失败率降低显著相关。术后常规使用低分子肝素虽可降低围术期血栓事件发生率，但30 天及 3 年主要终点风险的随访中均未达显著统计学差异。高TyG 指数与复合事件风险升高显著相关，且存在线性剂量反应关系，其预测效能 AUC 为 0.607。本研究为 CTO 介入治疗提供关键证据：1）完全血运重建是改善预后的核心目标；2）双侧造影联合逆向导丝及 IVUS 技术可显著提升复杂病变成功率；3）CTO患者术后常规低分子肝素抗凝的使用需要更加谨慎；TyG 指数可作为独立于传统指标的新型代谢风险标志物。

Background: Chronic total occlusion (CTO), a common and prognostically adverse type of coronary artery disease, affects 16%-18% of patients with coronary heart disease and is strongly associated with significantly elevated long-term mortality risk, thereby becoming a focal point in clinical research. However, due to the complex pathophysiological characteristics of CTO lesions, challenges persist in exploring long-term benefits of interventional outcomes, personalizing technical approaches, optimizing antithrombotic regimens, and assessing metabolic risks. Based on multicenter cohort data, this study systematically addresses key issues in CTO management through four dimensions: 1) Comparing the relationship between percutaneous coronary intervention (PCI) outcomes (failure/partial revascularization/complete revascularization) and long-term cardiovascular event risks to clarify CTO-PCI efficacy; 2) Revealing the impact of interventional technology advancements on procedural success rates and prognosis through comparisons between 2010-2013 and 2017-2018 cohorts; 3) Evaluating short- and long-term benefits of low-molecular-weight heparin (LMWH) in postoperative anticoagulation therapy to optimize strategies; 4) Exploring the association between insulin resistance (via triglyceride-glucose index, TyG) and long-term adverse events in CTO patients, providing evidence for dynamic risk management.

Methods: From January 2017 to December 2018, 4,152 coronary artery disease patients with at least one CTO lesion were consecutively enrolled at Fuwai Hospital. Follow-ups were conducted every 6 months post-procedure, with a mean follow-up duration of 3.3 years. The primary endpoint was a composite of cardiovascular death and target vessel-related myocardial infarction. In the first analysis, patients were categorized into PCI failure, partial success, and complete success groups based on procedural outcomes. Multivariable Cox proportional hazards models were used to assess the relationship between PCI outcomes and primary endpoint risks. The second analysis compared baseline characteristics, lesion complexity, interventional techniques, procedural success rates, and long-term clinical events between the 2010-2013 and 2017-2018 cohorts. Logistic regression analyzed associations between interventional variables and procedural success probability. In the third analysis, patients were divided into LMWH and non-LMWH groups based on postoperative anticoagulation use within 24 hours, with Cox models evaluating 30-day and 3-year endpoint risks. The fourth analysis stratified patients into TyG tertiles (T1, T2, T3), employing Cox models, restricted cubic spline (RCS) curves, and receiver operating characteristic (ROC) analyses to investigate TyG's predictive value for endpoint risks.

Results: During follow-up of the 2017-2018 cohort, 143 composite endpoint events (cardiovascular death and target vessel myocardial infarction) were recorded: 35 (5.9%) in the failure group, 23 (6.4%) in the partial success group, and 85 (2.7%) in the complete success group. Compared to the failure group, partial revascularization significantly increased risk (HR 1.77, 95% CI: 1.02-3.1, P=0.044), while complete revascularization reduced risk (HR 0.64, 95% CI: 0.41-0.98, P=0.040). In cohort comparisons, despite higher lesion complexity in 2017-2018, complete procedural success rates improved from 58.7% to 77.1% (+18.4%), with failure rates decreasing from 26.3% to 14.3%. The 2017-2018 cohort exhibited a 56% lower 3-year composite endpoint risk versus 2010-2013 (HR 0.44, 95% CI: 0.25-0.80, P=0.006). Bilateral angiography (OR 0.47, 95% CI: 0.38-0.58), retrograde wiring (OR 0.37, 95% CI: 0.25-0.55), and IVUS use (OR 0.45, 95% CI: 0.36-0.56) independently predicted reduced procedural failure (all P<0.001). LMWH showed non-significant reductions in 30-day (HR 0.49, 95% CI: 0.05-4.91, P=0.548) and 3-year risks (HR 0.56, 95% CI: 0.26-1.22, P=0.144). High TyG tertile (T3 vs. T1) doubled endpoint risk (HR 2.02, 95% CI: 1.29-3.18, P=0.002), with RCS confirming a linear dose-response relationship (nonlinear P=0.457). ROC analysis yielded an AUC of 0.607 (95% CI: 0.560-0.655) and an optimal TyG cutoff of 8.717.

Conclusion: Complete successful PCI for CTO significantly reduces the risk of composite cardiovascular death and target vessel myocardial infarction, whereas partial revascularization markedly increases this risk. Compared to the 2010-2013 cohort, the 2017-2018 cohort achieved an 18.4% improvement in complete procedural success rates despite higher CTO lesion complexity. The increased utilization of bilateral angiography, retrograde wiring techniques, and IVUS in the 2017-2018 cohort were identified as potential factors significantly associated with reduced procedural failure rates. Although routine postoperative LMWH anticoagulation may lower perioperative thrombotic events, no statistically significant differences were observed in 30-day or 3-year primary endpoint risks. Elevated TyG index was significantly correlated with increased composite event risk, demonstrating a linear dose-response relationship and a predictive AUC of 0.607. This study provides critical evidence for CTO intervention: 1) Complete revascularization remains the cornerstone for improving prognosis; 2) Combined bilateral angiography, retrograde wiring, and IVUS significantly enhance success rates in complex lesions; 3) Postoperative LMWH anticoagulation in CTO patients requires more cautious evaluation; 4) The TyG index serves as a novel metabolic risk biomarker independent of traditional indicators.