摘要

主动脉弓部病变的外科治疗一直是困扰世界各国心血管外科医师的一项难题。主动脉弓部解剖结构复杂，病理类型多样，治疗尤为困难。主动脉弓部病变的外科治疗经过了几十年的艰难发展，诊治效果得显著提升，但是，无论在围术期安全性还是在远期预后方面尚存不足。

基于国人主动脉弓部病变的临床及解剖特点，“广泛主动脉弓部修复手术”逐步成为我国主流的主动脉弓部病变外科治疗的策略体系，手术方式主要包括全主动脉弓置换并支架象鼻术和杂交全主动脉弓修复术。尽管广泛主动脉弓部修复术具有诸多优势，但是，患者在术中、术后及长期随访中仍面临着许多风险和挑战，这值得引起高度重视。主动脉外科医师应不断创新手术方法，改进治疗策略以提升主动脉弓部病变外科治疗的围术期安全性及远期预后。

全主动脉弓置换并支架象鼻术中不可避免地需要停循环以完成主动脉弓部重建，停循环时间通常为20~25分钟，长时间的停循环不可避免地造成脏器功能受损，严重者可引起围术期严重并发症甚至死亡，严重威胁着围术期安全性。为了缩短术中停循环时间，阜外医院在全主动脉弓置换并支架象鼻术中创新使用主动脉球囊封堵技术，将停循环时间缩短至3~5分钟，并安全地将停循环期间体温提升至28℃左右。本论文第一部分详细描述了主动脉球囊封堵技术的应用细节并分析了其对肾脏的保护效果。

主动脉弓部手术后神经系统并发症一直是困扰主动脉外科医师的一大难题，通过不断探索，目前，脑保护策略与方法日趋成熟，但仍存在术前神经系统评估手段单一、匮乏，术中脑灌注缺乏实时监测，术后不重视神经系统评估等不足。为克服这些不足，阜外医院新探索建立了主动脉弓部手术围术期中枢神经系统评估、监护及保护策略一体化流程，包括术前多维度神经影像学及功能学评估指导的患者危险分层并初步指导术中脑保护策略，术中神经系统强化监护指导的脑灌注策略以及术后神经系统评估指导的并发症的早期识别与救治。本论文第二部分详细描述了该一体化流程的技术细节及其早期临床应用的初步结果。

随着外科、麻醉、体外循环及术后监护技术的进步，主动脉弓部手术的围术期安全性已得到显著提升，改善远期预后逐步成为研究的焦点。本论文第一篇章的第一、二部分详细探讨了广泛主动脉弓部修复手术中提升围术期临床结局的两项方法改进，接下来的第二篇章将着眼于提升广泛主动脉弓部修复手术远期预后的方法改进。

支架锚定在0区的杂交主动脉弓修复术已成为传统全主动脉弓置换手术的一种常用替代方案。但是，支架引起的相关并发症，尤其是支架近端并发症是一个不容忽视的问题。支架锚定在0区的杂交主动脉弓修复术分为两种亚型，二者的主要区别在于是否进行0区升主动脉置换以提供支架近端锚定区。0区升主动脉如果既无扩张也无病变并可以提供稳定的近端锚定区，是否需要预防性置换尚缺乏一致观点。本论文第三部分详细探索了0区升主动脉预防性置换是否可以在不损害围术期安全性的前提下改善支架锚定在0区的杂交主动脉弓修复术的远期预后。

Stanford A型主动脉夹层是国人主动脉弓部病变最为常见的病理类型，尽管我国普遍采用“广泛主动脉弓部修复手术”的策略体系，仍不可避免胸降主动脉残余部分主动脉夹层不能同期修复，其能否良好重塑成为影响远期预后的关键。随着人口老龄化进程的加速，Stanford A型主动脉夹层患者发病年龄增加，接受长期抗血小板治疗的患者增多，术后长期抗血小板治疗是否影响残余夹层假腔血栓化及重塑从而影响远期预后尚缺乏研究证实。本论文第四部分详细探索了抗血小板治疗对广泛主动脉弓部修复术后的Stanford A型主动脉夹层患者远期胸降主动脉重塑及远期预后的影响。

本论文的四部分的研究内容摘要如下：

第一部分

主动脉球囊封堵技术在全主动脉弓置换并支架象鼻手术中的肾脏保护效果分析

目的：低温停循环下实施全主动脉弓置换并支架象鼻手术已成为治疗国人广泛主动脉弓部病变的常规手术策略。低温停循环造成的术后脏器功能障碍一直是困扰外科医生的难题。主动脉球囊封堵技术可以显著缩短术中停循环时间至5分钟以内，从而可能对腹腔脏器，尤其是对肾脏带来潜在的保护效果。因此，本研究旨在探索全主动脉弓置换并支架象鼻手术中应用主动脉球囊封堵技术对肾脏的保护效果，并分析术后急性肾损伤（acute kidney injury，AKI）和持续肾替代治疗（continuous renal replacement therapy，CRRT）的独立危险因素。

方法：回顾性分析2017年8月至2018年9月在阜外医院接受全主动脉弓置换并支架象鼻手术的247例患者的临床资料，根据术中是否应用主动脉球囊封堵技术将患者分为两组，其中主动脉球囊封堵技术组100例患者，传统中低温停循环技术组147例患者。主要终点事件定义为术后AKI，且由Kidney Disease Improving Global Outcomes（KDIGO）标准对其进行分级诊断。采用多因素logistic回归分析的方法确定术后AKI和CRRT的独立危险因素。

结果：主动脉球囊封堵技术的应用显著缩短了术中停循环时间（4 [四分卫间距（interquartile range，IQR）：3~6] vs 18 [IQR：16~20] 分钟，P＜0.001），同时也安全地提高了停循环期间的最低鼻咽温（28.1 [IQR：27.4~28.5] vs 24.7 [IQR：24.1~25.1] ℃，P＜0.001）。主动脉球囊封堵技术组术后48 h内峰值血清肌酐值低于传统中低温停循环技术组（124 [IQR：97~173] vs 146 [IQR：108~221] μmol/L，P=0.008）。根据KDIGO诊断标准，AKI的分级诊断在两组之间存在统计学差异（P=0.04）。主动脉球囊封堵技术组中无AKI（0级）的患者多于传统中低温停循环技术组（33% vs 23.1%），而高级别AKI（2级和3级）的患者比例低于传统中低温停循环技术组（21% vs 32%）。主动脉球囊封堵技术组患者术中输注红细胞患者比例较低（8.0% vs 26.5%，P＜0.001）。两组患者术后CRRT使用率（8.0% vs 8.2%，P=0.96），围术期死亡率（3.0% vs 4.8%，P=0.72）均未见显著差异。多因素logistic回归分析提示主动脉球囊封堵技术是术后AKI的保护因素（比值比 [odds ratio，OR]：0.52，95%置信区间 [confidence interval，CI]：0.28~0.96；P=0.03），但是，单因素logistic回归分析提示主动脉球囊封堵技术不是术后CRRT的保护因素（OR：0.97，95% CI：0.38~2.47；P=0.95）。

结论：主动脉球囊封堵技术可以显著缩短全主动脉弓置换并支架象鼻手术中的停循环时间，并安全地提高了停循环期间的最低体温。该技术降低了术后AKI的发生率，但不能降低术后CRRT的使用率，也没能降低围术期死亡率或主要不良事件发生率。总之，主动脉球囊封堵技术可以根据术者习惯安全地应用于全主动脉弓置换并支架象鼻手术中。

第二部分

主动脉弓部手术围术期中枢神经系统评估、监护及保护策略一体化流程的建立

目的：主动脉弓部手术中不可避免地需要短暂中断脑血流，这可能导致术后神经系统并发症。虽然，主动脉弓部手术中的脑保护策略已日趋完善，但仍存在着术前评估不足，术中缺乏监测，过于依赖术者经验等问题。因此本研究拟建立一套便于推广的主动脉弓部手术围术期中枢神经系统评估、监护及保护策略一体化流程。

方法：通过组建主动脉弓部病变外科治疗的多学科诊疗团队，融合术前多维度神经影像学及功能学评估对患者进行危险分层并初步指导术中脑保护策略、术中强化神经监护指导脑灌注的实施、术后联合应用多种手段早期识别神经系统并发症并展开早期救治，以建立主动脉弓部手术围术期中枢神经系统评估、监护及保护策略一体化流程。在主动脉弓部病变外科治疗中应用该一体化流程实施围术期脑保护。

结果：主动脉弓部手术围术期中枢神经系统评估、监护及保护策略一体化流程已成功建立。对拟接受主动脉弓部手术的患者，术前全面评估有助于早期识别高危患者，术中强化监护有助于精准指导术中脑灌注策略，术后多种诊治手段有助于早期识别神经系统并发症并展开救治。阜外医院已经在6例主动脉弓部病变患者中应用该一体化流程，通过术前评估识别3例高危患者，术中采用经颅多普勒+近红外光谱脑氧饱和度监测的强化监护方案指导的脑灌注策略，另3例患者为低危患者，术中采用常规神经监护+常规脑灌注策略。6例患者术后均顺利康复，无神经系统并发症发生。选取3例典型患者进行病例汇报分析。

结论：主动脉弓部手术围术期中枢神经系统评估、监护及保护策略一体化流程已在阜外医院顺利建立，初步应用的临床效果良好，需进一步开展前瞻性临床试验以明确本一体化流程的安全性及有效性。

第三部分

支架锚定在0区的杂交主动脉弓修复术中实施0区升主动脉预防性置换对远期预后及围术期安全性的影响

目的：锚定在0区升主动脉的主动脉支架远期并发症发生率较高，严重影响远期预后。本研究拟探讨在0区升主动脉既无扩张也无病变的情况下， 0区升主动脉预防性置换对支架锚定在0区的杂交主动脉弓修复术（zone hybrid arch repair, zone 0 HAR）的远期预后及围术期安全性的影响。

方法：回顾性分析2009年1月至2020年12月因主动脉弓部病变（但患者0区升主动脉既无扩张也无病变）在阜外医院接受zone 0 HAR的115例患者的资料，根据是否置换0区升主动脉将患者分为两组，0区升主动脉未置换组46例患者，0区升主动脉置换组69例患者。使用逆概率加权处理（inverse probability of treatment weighting，IPTW）的方法平衡两组患者基线资料的差异，然后比较两组患者的近、远期临床结果。主要终点事件定义为生存率和不良主动脉事件。次要终点事件定义为围术期复合不良事件和其他围术期并发症。根据患者年龄、诊断、0区升主动脉最大直径和欧洲心脏手术风险评分系统危险分层将患者分为不同亚组并进行亚组分析。

结果：0区升主动脉置换组经IPTW调整后的1年、5年及10年生存率分别为92.9%、89.8%和73.4%，与0区升主动脉未置换组87.3%、83.7%和67.4%的1年、5年及10年生存率相似（P=0.61）。以死亡为竞争风险，0区升主动脉置换组经IPTW调整后的1年、5年和10年不良主动脉事件累计发生率分别为5.1%、14.2%和25.3%，与0区升主动脉未置换组的10.9%、23.3%和41.2%的1年、5年和10年不良主动脉事件累计发生率未见明显统计学差异（亚分布风险比 [subdistribution hazard ratio，sHR]：0.56，95%置信区间 [confidence interval，CI]：0.23~1.39；P=0.23）。如仅考虑支架近端并发症，0区升主动脉置换组1年（1.0% vs 7.9%）、5年（3.2% vs 17.6%）和10年（5.8% vs 35.5%）支架近端并发症累计发生率显著低于0区升主动脉未置换组（sHR：0.11，95% CI：0.01~0.91；P=0.04）。亚组分析结果提示，0区升主动脉预防性置换对年龄≤60岁（sHR：0.15， 95% CI：0.03~0.75，P=0.02）和B型主动脉夹层（sHR：0.24，95% CI：0.07~0.82，P=0.02）患者具有降低主动脉不良事件发生率的优势。此外，0区升主动脉预防性置换并没有增加围术期复合不良事件发生率（9.3% vs 21.4%，P=0.08）和围术期死亡率（6.8% vs 6.0%，P=0.87）。

结论：即使0区升主动脉既无扩张也没有病变，在zone 0 HAR中，预防性置换0区升主动脉可以在不损害围术期安全性的前提下显著降低支架近端并发症发生率，从而潜在改善远期预后。另外，0区升主动脉预防性置换在降低年轻（年龄≤60岁）患者和B型主动脉夹层患者的不良主动脉事件发生率方面具有显著优势。因此，采用zone 0 HAR治疗主动脉弓部病变时，应考虑预防性置换0区升主动脉，为支架近端锚定提供更加稳定的锚定区，以改善远期临床结局。

第四部分

抗血小板治疗对广泛主动脉弓部修复术后的Stanford A型主动脉夹层患者胸降主动脉重塑及远期预后的影响

目的：广泛主动脉弓部修复术已成为国人Stanford A型主动脉夹层（type A aortic dissection，TAAD）的常规手术策略。即便如此，仍不可避免地在胸降主动脉（descending thoracic aorta，DTA）残留部分夹层难以同期修复，这部分主动脉能否良好重塑是影响远期预后的关键，而残余夹层假腔血栓化又是影响主动脉重塑的关键。我国老龄化进程加速，TAAD患者发病年龄增高，更多的患者合并心脑血管疾病，这增加了抗血小板治疗在此人群中的应用。抗血小板治疗是否因其影响血栓形成的药理作用而影响假腔血栓化从而影响远期预后尚无一致结论。因此，本研究拟探讨抗血小板治疗对广泛主动脉弓部修复术后的TAAD患者DTA重塑及远期预后的影响。

方法：回顾性收集2010年1月至2019年12月于阜外医院就诊的2032例TAAD患者的病例资料，通过严格的筛选，最终纳入1147例符合条件的急性或亚急性TAAD患者进行分析，根据随访期间是否接受抗血小板治疗将所有患者分为抗血小板治疗组（n=393）和非抗血小板治疗组（n=754）。主要终点事件定义为总体生存率和远期DTA重塑情况，包括DTA残余夹层假腔完全血栓化率和DTA直径随时间的变化率。次要终点事件定义为DTA再干预或突发破裂及严重出血事件。

结果：抗血小板治疗组患者1年、5年及10年生存率分别为99.2%，94.3%和85.3%，与非抗血小板治疗组患者99.0%，95.6%和86.4%的1年、5及10年生存率相似（风险比 [hazard ratio，HR]：1.18，95%置信区间 [confidence interval，CI]：0.71~1.95，P=0.53）。无论在主动脉支架覆盖段（HR：1.07，95% CI：0.95~1.22，P=0.27）还是支架未覆盖段（HR：1.19，95% CI：0.96~1.48，P=0.12）DTA，两组患者假腔完全血栓化率均相似。术后肺动脉分叉水平的DTA直径逐年减小（非抗血小板治疗组：-0.25mm/年；抗血小板治疗组：-0.44mm/年），而膈肌水平（非抗血小板治疗组：1.48mm/年；抗血小板治疗组：1.19mm/年）和腹腔干动脉水平（非抗血小板治疗组：1.62mm/年；抗血小板治疗组：1.43mm/年）的DTA直径逐年增加。但是，抗血小板治疗不是肺动脉分叉水平（β±标准误 [standard error，SE]：-0.128±0.203，P=0.53）、膈肌水平（β±SE：0.143±0.152，P=0.35）及腹腔干水平（β±SE：0.049±0.136,P=0.72）DTA直径变化的独立危险因素。以死亡为竞争风险，抗血小板组1年，5年和10年DTA再干预或突发破裂的累计发生率分别为0.8%，4.0%和10.9%，与非抗血小板治疗组患者1.0%，4.6%和11.9%的1年、5及10年DTA再干预或突发破裂的累计发生率相似（亚分布风险比 [subdistribution hazard ratio，sHR]：0.85，95% CI：0.49~1.19；P=0.58），抗血小板治疗亦不增加远期严重出血事件风险（sHR：0.82，95% CI：0.56~2.67；P=0.62）。

结论：急性或亚急性TAAD患者接受广泛主动脉弓部修复术后，使用抗血小板治疗不影响DTA残余夹层假腔血栓化，不影响DTA直径变化，不增加DTA再干预或突发破裂的风险，不影响远期生存率，也不增加出血风险。因此，如果有抗血小板治疗的指征，抗血小板治疗可安全地应用于接受了广泛主动脉弓部修复术的急性或亚急性TAAD患者中。

Abstract

The surgical treatment of aortic arch disease has always been a challenge for cardiac surgeons around the world. The aortic arch disease is difficult to be treated due to its complex anatomy and diverse pathology. After decades of tough development, the surgical treatment of aortic arch disease has been significantly improved, but there are still deficiencies in both perioperative safety and long-term prognosis.

Based on the clinical and anatomical characteristics of aortic arch disease in China, “extensive aortic arch repair”, mainly including total arch replacement (TAR) with frozen elephant trunk (FET) procedure and hybrid total arch repair, has gradually become the mainstream surgical strategy for aortic arch disease. Despite the advantages of extensive aortic arch repair, patients still face many risks and challenges intraoperatively, postoperatively and in the long-term follow-up, which deserves to raise great attentions. Aortic surgeons should continually create innovative surgical methods and strategies to improve the perioperative safety and long-term prognosis in the surgical treatment of aortic arch disease.

In the TAR with FET procedure, it is inevitable to use circulatory arrest for aortic arch reconstruction, and the circulatory arrest time is usually 20~25 minutes. Long-term circulatory arrest will cause organ impairment, and may cause serious complications or even death perioperatively in severe cases, which seriously threatens the perioperative safety. In Fuwai Hospital, aortic balloon occlusion technique was used in the TAR with FET procedure, which can reduce the circulatory arrest time to about 3~5 minutes, and safely raised the temperature to about 28℃ during circulatory arrest. In the Part Ⅰ, the application of aortic balloon occlusion technique was described in detail, and its renal protective effect was also analyzed in detail.

Neurological complications after aortic arch surgery have always been a challenge for aortic surgeons. Through continuous exploration, brain protection strategy has been mature gradually, but there are still deficiencies, such as insufficient preoperative neurological evaluation, lack of real-time monitoring for intraoperative cerebral perfusion, and neglect of postoperative neurological evaluation. In order to overcome these deficiencies, Fuwai Hospital established an integrated process for perioperative central nervous system evaluation, monitoring and protecting strategy in the aortic arch surgery, including risk stratification of patients and initial guidance of intraoperative brain protection strategies guided by preoperative multidimensional neuroimaging and functional evaluation, and brain perfusion strategy guided by intensive monitoring of the nervous system intraoperatively, and early recognition and treatment of postoperative neurological complications guided by comprehensive evaluation. In the part Ⅱ, the technical details of the integrated process and its preliminary outcomes of early clinical application were described.

With the advancement of surgery, anesthesia, cardiopulmonary bypass and postoperative care, the perioperative safety of aortic arch surgery has been significantly improved, and the long-term prognosis has gradually become the focus of research. Two methods for improving the perioperative outcome of extensive aortic arch repair surgery were discussed in the Parts Ⅰ and Ⅱ of Section Ⅰ. The next section will focus on the methods for improving the long-term prognosis of extensive aortic arch repair surgery.

Zone 0 hybrid arch repair (zone 0 HAR) has become a practical alternative for conventional TAR procedure. However, the complications caused by the stents, especially the proximal complications, cannot be ignored. There are two subtypes of zone 0 HAR, the main difference between which is whether the zone 0 ascending aorta is replaced to provide the proximal landing zone. When zone 0 ascending aorta is neither dilated nor pathologic to provide a stable proximal landing zone, there is no consensus about whether to replace zone 0 ascending aorta prophylactically. Whether prophylactical zone 0 ascending aorta replacement improve the long-term prognosis without compromising perioperative safety in zone 0 HAR was analyzed in the Part Ⅲ with detail.

Stanford type A aortic dissection (TAAD) is the most popular pathological type of aortic arch lesions in China. Despite of the extensive aortic arch repair strategy, it is inevitable that the descending thoracic aorta dissection cannot be repaired in the first operation. Whether it can be remodeling well is the key to the long-term prognosis. With the acceleration of the aging society, it is estimated that the age of TAAD patients is increasing which will increase the use of antiplatelet therapy. Whether antiplatelet therapy impacts the false lumen thrombosis and remodeling of the residual dissection and then impacts the long-term prognosis remains to be unknown. The impact of antiplatelet therapy on the descending thoracic aorta remodeling and long-term prognosis of TAAD after extensive aortic arch repair was analyzed in the Part Ⅳ with detail.

The four parts of this thesis are summarized as follows.

Part Ⅰ

Renal protective effect of the aortic balloon occlusion technique in the total aortic arch replacement with frozen elephant trunk procedure

Objective: Total arch replacement (TAR) with frozen elephant trunk (FET) procedure under hypothermia circulatory arrest (HCA) has become a routine surgical strategy for the treatment of extensive aortic arch lesions in China. The postoperative organ dysfunction caused by HCA continues to concern surgeons. The aortic balloon occlusion (ABO) technique can significantly shorten the HCA time to 3~5 minutes in TAR with FET procedure, which may have a potential protective effect on the abdominal organs, especially on the kidneys. Therefore, this study aimed to investigate the renal protective effect of the ABO technique in the TAR with FET procedure, and to analyze the independent risk factors for postoperative acute kidney injury (AKI) and continuous kidney replacement therapy (CRRT).

Methods: 247 patients who underwent TAR with FET procedure from August 2017 to September 2018 in Fuwai Hopital were retrospectively reviewed and stratified into two groups depending on whether the ABO technique was used, with 100 patients in the ABO group and 147 in the conventional HCA group. The primary endpoint was the postoperative AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariable logistic analysis was used to identify the predictors of postoperative AKI and CRRT.

Results: With the application of the ABO technique, the HCA time was significantly shortened (4 [interquartile range (IQR): 3~6] vs 18 [IQR: 16~20] mins, P＜0.001), meanwhile, the lowest nasopharyngeal temperature was also increased (28.1 [IQR: 27.4~28.5] vs 24.7 [IQR: 24.1~25.1] ℃, P＜0.001). The peak serum creatinine (Scr) values within 48 hours after the surgery was lower in the ABO group (124 [IQR: 97~173] vs 146 [IQR: 108~221] μmol/L, P=0.008). The distribution of AKI grade depending on the KDIGO criteria differed between the two groups (P=0.04). In the ABO group, more patients (33% vs 23.1%) were free from postoperative AKI (Grade 0), and less patients (21% vs 32%) were diagnosed with high-grade postoperative AKI (Grades 2 and 3). The rate of erythrocyte used intraoperatively was lower in the ABO group (8.0% vs 26.5%, P＜0.001). Both CRRT morbidity (8.0% vs 8.2%, P=0.96) and perioperative mortality (3.0% vs 4.8%, P=0.72) were similar between the two groups. The ABO technique was identified as protective factor for postoperative AKI by multivariable logistic regression analysis (odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.28~0.96; P=0.03), but was not protective factor for CRRT by univariable logistic regression analysis (OR: 0.97, 95% CI: 0.38~2.47; P=0.95).

Conclusion: The ABO technique significantly shortened the HCA time and elevated the intraoperative lowest body temperature safely. The ABO technique reduced the AKI morbidity but cannot reduce the postoperative CRRT morbidity, nor did it reduce the perioperative mortality or major adverse events morbidity. In summary, the ABO technique can be safely applied in the TAR with FET procedure depending on the surgeon’s preference.

Part Ⅱ

Establishment of an integrated process for perioperative central nervous system evaluation, monitoring and protecting strategy in the aortic arch surgery

Objective: A transitory interruption of bloodstream to the brain is inevitable intraoperatively due to the characteristic of the aortic arch anatomy, which may cause to postoperative neurological complications. Although the brain protection strategy in the aortic arch surgery has improved gradually, there are still some deficiencies, such as insufficient preoperative evaluation, lack of intraoperative monitoring, and over-dependence on the experience of the surgeon. Therefore, this study aimed to establish an integrated process of perioperative central nervous system evaluation, monitoring and protection strategy in the aortic arch surgery.

Methods: A multidisciplinary team was set for the surgical treatment of aortic arch disease. Preoperative multidimensional neuroimaging and functional evaluation were performed to stratify patients at risk and initially guided the intraoperative brain protection strategy. The enhanced intraoperative nervous system monitoring strategy guided the implementation of cerebral perfusion. A variety of ways were used to early identify neurological complications and carry out early treatment. Through the above methods, an integrated process of perioperative central nervous system evaluation, monitoring and protection strategy in the aortic arch surgery is established. This integrated process is applied for perioperative brain protection in the surgical treatment of the aortic arch disease.

Results: The integrated process of perioperative central nervous system evaluation, monitoring and protection strategy in the aortic arch surgery has been successfully established. For those patients who are candidates of aortic arch surgery, the comprehensive preoperative evaluation is helpful for early identification of high-risk patients, the enhanced intraoperative monitoring is helpful for accurate guidance of intraoperative cerebral perfusion strategy, and a variety of postoperative diagnosis and treatment methods are helpful for early identifying neurological complications and implementing treatment. In Fuwai Hospital, the integrated procedure has been implemented in six patients with aortic arch lesions. Three high-risk patients were identified through preoperative evaluation, and the strengthening cerebral perfusion strategy guided by the enhanced monitoring scheme of transcranial doppler with near-infrared reflectance spectroscopy cerebral oxygen saturation monitoring were used intraoperatively; the other three patients were identified as low-risk patients, and the conventional neurological monitoring and cerebral perfusion strategy were used intraoperatively. The six patients recovered uneventfully after operation without neurological complications. Three typical patients were selected for case report analysis.

Conclusion: The integrated process of perioperative central nervous system evaluation, monitoring and protection strategy in the aortic arch surgery has been successfully established in Fuwai Hospital, and the initial application achieved desirable clinical outcomes. Further prospective clinical trial is needed to confirm the safety and effectiveness of this integrated procedure.

Part Ⅲ

The impact of prophylactical zone 0 ascending aorta replacement on the long-term prognosis and perioperative safety of zone 0 hybrid arch repair

Objectives: It was reported that deploying the aortic stent to zone 0 ascending aorta was associated with higher late complications and impacted long-term prognosis. This study aimed to investigate the impact of prophylactical zone 0 ascending aorta replacement (AAR) on the long-term prognosis and perioperative safety of zone 0 hybrid arch repair (zone 0 HAR) when zone 0 ascending aorta is neither dilated nor pathologic.

Methods: 115 patients whose zone 0 ascending aorta was neither dilated nor pathologic and who underwent zone 0 HAR from January 2009 to December 2020 in Fuwai Hospital were retrospectively reviewed, and stratified into two groups depending on whether zone 0 ascending aorta was replaced, with 46 patients in the no-replacement group and 69 patients in the replacement group. Inverse probability of treatment weighting (IPTW) was used to balance the baseline difference, and outcomes were compared after IPTW adjustment. The primary endpoints were overall survival and adverse aortic events (AAEs). The secondary endpoints were perioperative composite adverse events and other perioperative complications. Subgroup analysis was performed by age, diagnosis, zone 0 ascending aorta maximum diameter and European System for Cardiac Operative Risk Evaluation risk stratification.

Results: The 1-year, 5-year and 10-year IPTW-adjusted overall survival rate was 92.9%, 89.8% and 73.4%, respectively, in the replacement group, which is similar to 87.3%, 83.7% and 67.4% in the no-replacement group (P=0.61). With death as a competing risk, the IPTW-adjusted cumulative incidence of AAEs at 1-year, 5-year and 10-year was 5.1%, 14.2% and 25.3% respectively, in the replacement group, which is similar to 10.9%, 23.3% and 41.2% in the no-replacement group (subdistribution hazard ratio [sHR]: 0.56, 95% confidence interval [CI]: 0.23~1.39; P=0.23). Considering proximal complications alone, the replacement group exhibited lower 1-year (1.0% vs 7.9%), 5-year (3.2% vs 17.6%) and 10-year (5.8% vs 35.5%) cumulative incidences of proximal complications (sHR: 0.11, 95% CI: 0.01~0.91; P=0.04) after IPTW adjustment. Subgroup analysis demonstrated that the benefits of prophylactical zone 0 AAR in reducing AAEs were observed in the age ≤ 60-year-old (sHR 0.15, 95% CI: 0.03~0.75; P=0.02) and type B aortic dissection (sHR: 0.24, 95% CI: 0.07~0.82, P=0.02) subgroups. Additionally, prophylactical zone 0 AAR did not increase perioperative composite adverse event morbidity (9.3% vs 21.4%，P=0.08) or mortality (6.8% vs 6.0%，P=0.87).

Conclusions: Although zone 0 ascending aorta was neither dilated nor pathologic, prophylactical zone 0 AAR in zone 0 HAR significantly reduced the incidence of proximal complications and potentially improve long-term prognosis, without impairing perioperative safety. Additionally, this strategy was associated with benefits in reducing AAEs in younger (age ≤ 60-year-old) and type B aortic dissection patients. Thus, when zone 0 HAR was performed for treating aortic arch lesions, prophylactical zone 0 AAR should be considered for reconstructing a stable proximal landing zone in zone 0 HAR to improve long-term clinical outcomes.

Part Ⅳ

The impact of antiplatelet therapy on the descending thoracic aorta remodeling and long-term prognosis of Stanford type A aortic dissection after extensive aortic arch repair

Objectives: Extensive aortic arch repair has become a routine strategy for Stanford type A aortic dissection (TAAD) in China. Even so, residual dissection in the descending thoracic aorta (DTA) after extensive aortic arch repair is still inevitable. DTA remodeling is the key factor to impact the long-term prognosis, and false lumen thrombosis of residual dissection is also the key factor to impact the DTA remodeling. With the accelerated aging process in China, the on-set age of TAAD patients is increasing and more patients have cardiovascular and cerebrovascular diseases, which will increase the use of antiplatelet therapy in TAAD patients. There is no consensus on whether antiplatelet therapy affect the false lumen thrombosis and then impact the long-term prognosis due to its pharmacological action of anticoagulation. This study aimed to evaluate the impact of antiplatelet therapy on the DTA remodeling and long-term prognosis of TAAD after extensive aortic arch repair.

Methods: Data of 2032 TAAD patients treated at Fuwai Hospital from January 2010 to December 2019 were retrospectively collected. After exclusion criteria, 1147 eligible acute or subacute TAAD patients were included and stratified into antiplatelet (n=393) and non-antiplatelet (n=754) groups. The primary endpoints were defined as overall survival, and DTA remodeling, including long-term false lumen thrombosis rate and the DTA diameter change over time. The secondary endpoints were defined as DTA reintervention or sudden rupture and major bleeding events.

Results: The 1-year, 5-year and 10-year overall survival rates were 99.2%, 94.3% and 85.3%, respectively, in the antiplatelet group, which were similar to 99.0%, 95.6% and 86.4%, respectively, in the non-antiplatelet group (hazard ratio [HR]: 1.18, 95% confidence interval [CI]: 0.71~1.95, P=0.53). No matter in the stent covering segment (HR：1.07, 95% CI: 0.95~1.22, P=0.27) or stent uncovering segment (HR: 1.19, 95% CI: 0.96~1.48, P=0.12) of DTA, the long-term false lumen complete thrombosis rates were similar between the non-antiplatelet and antiplatelet group. Over time, the DTA diameter at the pulmonary artery bifurcation level decreased (non-antiplatelet group: -0.25mm/year; antiplatelet group: -0.44mm/year), and increased at the diaphragm (non-antiplatelet group: 1.48mm/year; antiplatelet group: 1.19mm/year) and celiac artery level (non-antiplatelet group: 1.62mm/year; antiplatelet group: 1.43mm/year). However, antiplatelet therapy was not an independent predictor of DTA diameter change over time at the pulmonary artery bifurcation (β±standard error [SE]: -0.128±0.203, P=0.53), diaphragm (β±SE: 0.143±0.152, P=0.35) or celiac artery (β±SE: 0.049±0.136, P=0.72) levels. With death as a competing risk, the cumulative incidences of DTA reintervention or sudden rupture at 1-year, 5-year and 10-year were 0.8%, 4.0% and 10.9%, respectively, in the antiplatelet group, which were similar to 1.0%, 4.6% and 11.9%, respectively, in the non-antiplatelet group (subdistribution hazard ratio [sHR]: 0.85, 95% CI: 0.49~1.19; P=0.58). Antiplatelet therapy also did not increase late hemorrhage risks (sHR: 0.82, 95% CI: 0.56~2.67; P=0.62).

Conclusions: After extensive aortic arch repair for acute or subacute TAAD, antiplatelet therapy did not impact false lumen thrombosis, DTA diameter change over time, the risk of the DTA reintervention or sudden rupture, and long-term survival, and also did not increase the risk of hemorrhage. Therefore, if indicated, antiplatelet therapy can be administered safely in those acute or subacute TAAD patients after extensive aortic arch repair.