中文摘要

第一部分 同期冠状动脉旁路移植术对全主动脉弓置换联合支架象鼻技术治疗的A型主动脉夹层患者预后的影响

目的：外科手术是A型主动脉夹层 (Type A aortic dissection, TAAD) 的标准治疗方式。冠状动脉旁路移植术（Coronary artery bypass grafting, CABG）常与主动脉手术联合施行，以处理TAAD患者合并的冠状动脉病变，然而同期行CABG对TAAD患者预后的影响尚不明确。本研究旨在评估同期CABG对接受全主动脉弓置换联合支架象鼻技术治疗的TAAD患者预后的影响。

方法：选取自2019年6月至2024年1月于我院接受全主动脉弓置换联合支架象鼻技术治疗的TAAD患者。根据CABG实施情况将患者分为三组：计划性CABG组（针对冠状动脉开口受累或冠状动脉粥样硬化性心脏病施行CABG）、非计划CABG组（术中意外施行CABG）以及非CABG组。通过多因素Logistic回归和多因素Cox回归模型明确影响预后的相关因素，应用Kaplan-Meier生存曲线联合对数秩和检验评估各组患者的预后差异。

结果：研究共纳入1,002例患者，其中42例患者（4.19%）接受非计划CABG；总体手术死亡率为2.40%（24/1,002）。非计划CABG组患者的手术死亡率（23.81%）显著高于计划性CABG组（0.92%）及非CABG组（1.62%）（P<0.001）。多因素Logistic回归分析表明，非计划CABG是手术死亡的独立危险因素（比值比[Odds ratio, OR]=18.96，95%置信区间[Confidence interval, CI]：7.32-49.08，P<0.001）。中位随访时间为24.80个月（四分位数间距：11.73-39.10），总体失访率为5.89%。Kaplan-Meier生存曲线显示，非计划CABG组2年累积生存率（70.08%）显著低于计划性CABG组（97.36%）及非CABG组（90.89%）（Log-rank P<0.001）；多因素Cox回归分析进一步证实，与非CABG组相比，非计划CABG显著增加术后全因死亡风险（风险比[Hazard ratio, HR]=13.69，95% CI：6.53-28.70，P<0.001），而计划性CABG组与非CABG组的全因死亡风险无统计学差异。此外，在同期接受CABG的TAAD患者中，术后2年桥血管闭塞累积发生率为24.54%。

结论：在接受全主动脉弓置换联合支架象鼻技术治疗的TAAD患者中，非计划CABG是手术死亡的独立危险因素并且与术后全因死亡风险增加显著相关。需深入探讨非计划CABG的风险因素并制定针对性预防策略。

第二部分 Stanford A型主动脉夹层外科治疗患者非计划冠状动脉旁路移植术的危险因素分析

目的：在Stanford A型主动脉夹层（Type A aortic dissection, TAAD）外科治疗期间，非计划冠状动脉旁路移植术（Coronary artery bypass grafting, CABG）频发且具有致命风险，但其危险因素仍需深入探讨。冠状动脉开口受累的复杂形态学特征可能对非计划CABG的发生具有重要影响。本研究旨在评估不同程度的冠状动脉受累与非计划CABG发生风险之间的相关性。

方法：本研究为双向性队列研究，连续纳入2019年6月至2024年1月在我院就诊并接受外科手术治疗的TAAD患者。根据冠状动脉开口受累情况分为受累组（冠状动脉开口非显著受累：Neri A型—夹层内膜累及冠状动脉开口边缘；冠状动脉开口显著受累：Neri B型和Neri C型）与非受累组。非计划CABG定义为TAAD外科治疗期间意外实施的CABG。通过多因素Logistic回归分析明确非计划CABG的危险因素。

结果：在1,168例患者中，660例患者合并冠状动脉开口受累，508例无冠状动脉受累。共53例（4.54%）患者需施行非计划CABG。冠状动脉受累组的非计划CABG事件发生率显著高于非受累组（7.42% vs. 0.79%，P<0.001）。多因素Logistic回归分析显示，右冠状动脉显著受累与非计划CABG的发生显著相关（比值比[Odds ratio, OR]=20.32，95%置信区间[Confidence interval, CI]：7.26-56.88，P<0.001）。值得注意的是，44.61%的TAAD手术患者存在右冠状动脉非显著受累，且同样具有较高的非计划CABG发生风险（OR=6.15，95% CI：2.32-16.28，P<0.001）。

结论：TAAD外科治疗中非计划CABG发生率为4.54%。右冠状动脉显著受累与非计划CABG强相关，而临床中更为常见的右冠状动脉非显著受累同样具有较高的非计划CABG发生风险，需引起临床重视。

第三部分 保护性冠状动脉旁路移植术在冠状动脉开口受累的Stanford A型主动脉夹层外科治疗中的应用研究

目的：Stanford A 型主动脉夹层（Type A aortic dissection, TAAD）导致的冠状动脉开口受累给手术治疗带来了巨大挑战。本研究回顾性研究了本中心两种治疗冠状动脉开口受累的手术方案，评估并比较两种方案对患者预后的影响。

方法：2019年1月至2023年12月，总共649例TAAD合并冠状动脉开口受累的患者被纳入本研究。其中538例患者仅接受冠状动脉开口重建（Coronary ostial reconstruction, COR），111例患者接受了保护性冠状动脉旁路移植术（Coronary artery bypass grafting, CABG）。保护性CABG是指在合并严重冠状动脉开口受累（包括Neri A伴开口外缘>50%受累、Neri B伴冠状动脉远端破口及Neri C型）的TAAD手术患者中，于冠状动脉开口重建或缝闭后施行的CABG。严重不良事件定义为术后院内死亡、脑卒中或使用机械循环辅助装置支持治疗。采用多因素Logistic回归模型分析与严重不良事件相关的危险因素。Kaplan-Meier曲线联合Log-rank检验进行生存分析。

结果：总体手术死亡率为3.85%（25/649），严重不良事件发生率为7.24%（47/649）。尽管保护性CABG组患者冠状动脉受累更为严重，且合并冠状动脉灌注不良比例显著高于COR组（33.64% vs. 14.37%，P<0.001），但该组患者的手术相关心肌损伤事件发生率显著降低（8.92% vs. 2.70%，P=0.043），严重不良事件发生率亦呈降低趋势（8.18% vs. 2.70%，P=0.068）。多因素Logistic 回归分析表明，保护性CABG可显著降低严重不良事件发生风险（比值比=0.24，95%置信区间：0.07-0.85，P=0.027）。中位随访时间为 25.9个月。排除术后院内死亡病例后，Kaplan-Meier 生存分析显示两种手术方案的累积生存率无显著差异（Log-rank P=0.43）。CABG患者术后第2年桥血管闭塞累积发生率为 20.45%。

结论：针对合并冠状动脉开口受累的TAAD患者，本中心的手术方案总体安全有效。对于冠状动脉严重受累的患者，保护性CABG在降低术后严重不良事件发生率的同时，未影响患者长期生存。研究结果显示对冠状动脉严重受累患者采取积极的保护性CABG治疗策略可能带来获益。

第四部分 冠状动脉旁路移植术对合并冠状动脉粥样硬化性心脏病的A型主动脉夹层患者外科治疗预后的影响

目的：A型主动脉夹层（Type A aortic dissection, TAAD）合并冠状动脉粥样硬化性心脏病（简称冠心病）显著增加外科治疗风险。TAAD合并的冠状动脉病变多通过冠状动脉计算机断层扫描血管成像（Computed tomography angiography, CTA）评估，极少进行冠状动脉造影检查，导致术前不能精确地评估冠状动脉狭窄情况。TAAD外科治疗期间，针对冠状动脉狭窄施行冠状动脉旁路移植术（Coronary artery bypass grafting, CABG）的临床决策带有一定的主观性。本研究旨在通过回顾性分析，明确合并冠心病的TAAD患者接受CABG干预对临床预后的影响。

方法：本研究基于一项已完成随访的双向队列研究数据，纳入2019年6月至2024年1月期间于我院接受全主动脉弓置换联合冷冻象鼻技术治疗且合并冠心病的270例TAAD患者。根据是否因冠心病行CABG干预，将患者分为CABG组（N=156）和非CABG组（N=114）。采用逆概率加权法（Inverse probability of treatment weighting, IPTW）校正组间基线差异。使用Kaplan-Meier生存曲线结合Log-rank检验评估两组生存差异，并评估桥血管通畅率随时间变化趋势。

结果：全组患者手术死亡率为2.22%（6/270）。经IPTW调整后，CABG组严重不良事件发生率（2.5% vs. 8.3%，P=0.048）及手术死亡率（0.5% vs. 4.6%，P=0.02）均显著低于非CABG组。生存分析显示，CABG组早期累积生存率高于非CABG组，但后期显著下降，两组总体生存率无统计学差异（Log-rank P=0.58）。排除术后院内死亡病例后，CABG组累积生存率显著低于非CABG组（Log-rank P=0.01）。值得注意的是，CABG患者桥血管闭塞累积发生率较高（2年25.96%，4年62.22%）。

结论: 对于合并冠心病的TAAD患者，术中同期行CABG可降低围术期死亡风险，但远期可能会因为桥血管通畅率低导致预后欠佳。

ABSTRACT

Part I: Impact of Concomitant Coronary Artery Bypass Grafting on the Outcomes of Total Arch Repair with Frozen Elephant Trunk for Type A Aortic Dissection

Objective: Coronary artery bypass grafting (CABG) is often performed alongside surgery for type A aortic dissection (TAAD). However, the association between concomitant CABG and the clinical outcomes of TAAD repair remains uncertain. This study aims to investigate the impact of concomitant coronary artery bypass grafting (CABG) on the clinical outcomes of total aortic arch replacement (TAR) with frozen elephant trunk (FET) in TAAD patients.

Methods: This study included 1,002 consecutive TAAD patients from June 2019 to January 2024. CABG was performed under three conditions: planned CABG for coronary ostial involvement, planned CABG for coronary artery disease, and unplanned CABG. Patients who underwent unplanned CABG (N=42) were compared with those who had planned CABG (N=218) and those who did not undergo CABG (N=742). Logistic regression, Kaplan-Meier, and Cox regression analyses were employed.

Results: Operative mortality rate was 2.40%; 42(4.19%) patients underwent unplanned CABG. The unplanned CABG group had the highest operative mortality (23.81%) among the three groups (P<0.001). Unplanned CABG was associated with increased operative mortality compared with non-CABG [odds ratio:18.96, 95%confidence interval (CI):7.32-49.08, P<0.001], whereas planned CABG was not significant. The median follow-up period was 24.80 (interquartile range:11.73-39.10) months. Kaplan-Meier analysis demonstrated poorer overall survival in the unplanned CABG group (log-rank p-value<0.001). Unplanned CABG significantly increased all-cause late mortality compared with non-CABG (hazard ratio:13.69, 95%CI:6.53-28.70, P<0.001), while planned CABG did not. The 2-year cumulative incidence of graft occlusion among CABG patients was 24.54%.

Conclusions: Unplanned CABG is significantly associated with increased operative and all-cause mortality in patients undergoing TAR and FET for TAAD. Further research is required to identify the causes of unplanned CABG.

Part II: Impact of Non-Significant Right Coronary Ostial Involvement on Unplanned coronary Artery Bypass Grafting in Type A Aortic Dissection Surgery

Objective: Unplanned coronary artery bypass grafting (CABG) constantly occurs during type A aortic dissection (TAAD) surgical repair and are potentially fatal, yet their risk factors require further investigation. The intricate morphology of coronary artery ostial involvement may have a substantial impact. This study aims to evaluate the association between varying degrees of coronary ostial involvement and the risk of unplanned CABG.

Methods: From June 2019 to January 2024, consecutive type A aortic dissection patients who underwent open surgery were included. Patients were divided into the coronary involvement group (non-significant involvement: Neri A-dissected intima involving the margin of the coronary ostium; significant involvement: Neri B and Neri C) and the non-involvement group. Bailout CABG referred to a CABG procedure performed unexpectedly during TAAD repair. Logistic regression analysis identified risk factors associated with bailout CABG.

Results: Of 1,168 patients, 660 patients had coronary involvement, while 508 did not. A total of 53(4.54%) patients required bailout CABG. Patients with coronary involvement had a higher incidence of bailout CABG (7.42% vs. 0.79%, P<0.001). Logistic regression analysis revealed that significant right coronary involvement was associated with bailout CABG (odds ratio: 20.32, 95% confidence interval: 7.26-56.88, P<0.001). Notably, non-significant right coronary involvement, accounting for 44.61% of patients, was also associated with coronary events compared to those without involvement (odds ratio:6.15, 95% confidence interval:2.32-16.28, P<0.001).

Conclusion: Bailout CABG occurred in 4.54% patients. Significant right coronary involvement is strongly associated with bailout CABG; non-significant right coronary involvement, which is relatively common in surgical patients, also poses a substantial risk for bailout CABG and warrants attention.

Part III: Protective Coronary Artery Bypass Grafting Improves Surgical Outcomes in Acute Type A Aortic Dissection with Coronary Ostial Involvement

Objective: Coronary ostial involvement caused by type A aortic dissection (TAAD) presents significant challenges in surgical management. We describe two surgical approaches to managing coronary involvement and assess their outcomes.

Methods: Between January 2019 and December 2023, 649 TAAD patients with coronary involvement were enrolled. Based on our institutional surgical protocol, 538 patients underwent isolated coronary ostial reconstruction (COR), whereas 111 received protective coronary artery bypass grafting (CABG) following coronary ostial reconstruction or closure in cases of severe coronary involvement. Protective CABG is defined as the adjunctive CABG performed after coronary ostial reconstruction or closure in TAAD patients with severe coronary ostial involvement (including Neri A lesions with >50% of the ostial margin involvement, Neri B with distal re-entry, and Neri C lesions). Serious adverse events were defined as operative mortality, mechanical support, or stroke. Logistic regression identified factors associated with serious adverse events. Kaplan-Meier curves with the log-rank tests were used for survival analysis.

Results: Operative mortality occurred in 25 patients (3.85%), and 47 patients (7.24%) experienced serious adverse events. Despite having more severe coronary involvement and coronary malperfusion, patients in the CABG group experienced lower procedural myocardial injury (8.92% vs. 2.70%, P=0.043) and a trend toward fewer serious adverse events (8.18% vs. 2.70%, P=0.068). Logistic regression further revealed that protective CABG was associated with a reduced risk of serious adverse events (odds ratio:0.24, 95% confidence interval:0.07-0.85, P=0.027). The median follow-up was 25.9 months. Kaplan-Meier analysis revealed no significant difference in midterm mortality between the two approaches (log-rank=0.43). The cumulative incidence of graft occlusion among CABG population was 20.45% two years postoperatively.

Conclusion: Our institutional surgical protocol is safe and effective. Protective CABG was associated with fewer serious adverse events without impacting midterm mortality, supporting its more aggressive use in patients with severe coronary involvement.

Part IV: Early and Midterm Outcomes of Concomitant Coronary Artery Bypass Grafting for Coronary Atherosclerotic Heart Disease in Surgical Repair of Type A Aortic Dissection

Objective: Type A aortic dissection (TAAD) is frequently complicated by coronary atherosclerotic heart disease (CHD), which significantly increases the risk of surgical treatment. Coronary lesions in TAAD patients are mostly evaluated by coronary computed tomography angiography (CTA), while coronary angiography is rarely performed, resulting in an imprecise assessment of coronary stenosis. Therefore, the decision to perform coronary artery bypass grafting (CABG) for coronary stenosis during TAAD surgery is somewhat subjective. This study aimed to evaluate the impact of CABG for CHD on short- and mid-term outcomes following TAAD surgical repair.

Methods: This is a post-hoc sub-study that retrospectively analyzes a bidirectional cohort of TAAD patients who underwent total arch replacement and frozen elephant trunk between June 2019 and January 2024, with follow-up data extending through July 2024. Among them, 270 patients with CHD were stratified into two groups based on whether CABG for CHD was performed: the CABG and non-CABG groups. Inverse probability of treatment weighting (IPTW) was utilized to adjust for imbalanced characteristics. Kaplan-Meier survival analysis was employed to assess all-cause and midterm mortality.

Results: The overall cohort experienced six operative deaths (2.22%). After IPTW adjustment, the CABG group exhibited a significantly lower incidence of serious adverse events (2.5%vs.8.3%, P=0.048) and operative mortality (0.5%vs.4.6%, P=0.02) compared to the non-CABG group. The Kaplan-Meier all-cause survival curve initially showed improvement but deteriorated significantly later, revealing no significant difference between the groups (Log-rank P=0.58). However, midterm mortality was significantly higher in the CABG group (Log-rank P=0.01). Notably, a high incidence of graft occlusion was observed during follow-up period (42.67% at three years and 62.22% at four years).

Conclusion: Concomitant CABG for CHD in TAAD patients lowers operative mortality but worsens midterm outcomes. The increased midterm mortality is mainly due to the high incidence of graft occlusion.