中文摘要

第一部分 室间隔穿孔短期保守治疗的预后分析及死亡风险评估

背景：当前指南建议对急性心肌梗死（Acute Myocardial Infarction, AMI）后室间隔穿孔（Ventricular Septal Rupture，VSR）患者先行保守治疗，以稳定病情并延迟外科修复时机。不过，目前关于这一过渡阶段的临床资料仍然有限。因此，本研究基于心血管病区域转诊中心的真实世界数据，系统评估AMI后30天内仅接受保守治疗的VSR患者的临床特征和治疗与生存情况，并进一步探讨早期死亡的危险因素，构建短期死亡风险预测模型，为分层管理和干预决策提供依据。

方法：连续纳入2000年1月至2022年12月于本中心就诊的VSR患者，排除曾行心脏手术、AMI后30天内已行外科修复术及30天生存状态信息缺失者，最终共纳入322例。回顾性检索电子病历系统，收集人口统计学、既往病史、超声心动图、冠状动脉造影、实验室指标及治疗方式等信息。主要结局为AMI后30天内全因死亡。采用Cox比例风险模型评估危险因素并构建预测模型，通过Harrell’s C指数、校准曲线及Bootstrap重采样进行模型性能评估和内部验证。

结果：患者中位年龄为67（60-72）岁，女性占46.9%，高血压（60.6%）、糖尿病（32.0%）及脑卒中（19.3%）等合并症比例较高。93.5%患者为首次AMI发作，26.7%接受了早期再灌注治疗。VSR主要位于心尖部（59.6%），穿孔直径中位值为12.0（9.0-15.0）毫米，78.6%的患者心肌梗死累及前壁。在完成冠状动脉造影的193例患者中，多支血管病变（72.0%）和动脉完全闭塞（51.3%）较为常见。30天观察期内，106例（32.9%）患者死亡，中位生存时间为8天。

与生存组相比，死亡组患者年龄更高（71.0岁 vs. 64.0岁，P < 0.001），女性比例（56.6% vs. 42.1%，P = 0.014）、入院时心原性休克发生率（57.5% vs. 31.0%，P < 0.001）和心率（104次/分 vs. 88次/分，P < 0.001）均显著更高，而AMI后12小时内行经皮冠状动脉介入治疗（Percutaneous Coronary Intervention，PCI）的比例较低（5.7% vs. 19.0%，P = 0.001）。多因素Cox回归分析显示：年龄 ≥ 71岁（71-75岁 vs. ≤ 60岁，HR：3.51，95% CI：1.88-6.57，P < 0.001；≥ 76岁 vs. ≤ 60岁，HR：5.67，95% CI：3.16-10.17，P < 0.001）、女性（HR：1.61，95% CI：1.08-2.40，P = 0.020）、入院时心原性休克（HR：2.01，95% CI：1.35-2.98，P < 0.001）及心率升高（HR：1.05，95% CI：1.03-1.06，P < 0.001）与30天内全因死亡显著相关；而AMI后12小时内行PCI（HR：0.32，95% CI：0.14-0.73，P = 0.007）以及更高的左心室射血分数（HR：0.98，95% CI：0.96-0.99，P = 0.030）为保护因素。基于上述变量构建的风险预测模型在原始数据集中具有良好区分度（校正后Harrell’s C指数为0.841）及校准度。将患者按预测风险三分位数分为低、中、高风险组后，其30天生存率分别为97.2%（95% CI，94.2-100）、75.7%（95% CI，68.0-84.3）和28.0%（95% CI，20.7-38.0），组间差异显著（P < 0.001）。

结论：VSR患者在接受初期保守治疗期间的死亡风险依然较高。高龄、女性、未行PCI、入院时心原性休克、心率升高及左心室射血分数降低是30天内死亡的独立危险因素。基于多变量构建的预测模型可有效识别高风险患者，为早期临床分层管理和个体化干预提供依据。

第二部分 室间隔穿孔修复手术时机与预后

背景：本研究旨在探讨急性心肌梗死（Acute Myocardial Infarction，AMI）后室间隔穿孔（Ventricular Septal Rupture，VSR）患者在不同时机行外科修复术的临床预后，并评估相关危险因素对围术期及远期结局的影响。

方法：本研究为回顾性队列研究，连续纳入2003年1月至2022年12月于本中心接受外科修复术的VSR患者。根据AMI发作至手术间隔时间，将患者分为早期手术组（< 28天）和延期手术组（≥ 28天）。主要终点为全因死亡；次要终点为主要不良心脑血管事件（Major Adverse Cardiovascular and Cerebrovascular Events，MACCE），包括心肌梗死、脑卒中、再次血运重建及因心力衰竭再入院。采用Kaplan-Meier法比较终点事件发生率，Logistic回归分析早期全因死亡的危险因素，Cox比例风险回归模型评估远期预后的影响因素。

结果：最终纳入152例VSR患者，其中早期手术组27例（17.8%），延期手术组125例（82.2%）。早期手术组患者平均年龄更大（67.6 ± 7.0岁 vs. 61.7 ± 8.4岁，P < 0.001），女性占比更高（59.3% vs. 33.6%，P = 0.023），术前心原性休克（74.1% vs. 44.0%，P = 0.005）、急性肾损伤（51.9% vs. 26.4%，P = 0.018）及主动脉内球囊反搏应用比例（85.2% vs. 32.0%，P < 0.001）显著更高。此外，该组主动脉阻断时间（85.0分钟 vs. 74.5分钟，P = 0.023）和体外循环时间（130.0分钟 vs. 114.5分钟，P = 0.009）显著延长，术后死亡率更高（18.5% vs. 3.2%，P = 0.009）。多因素Logistic回归显示，早期手术是早期死亡的独立危险因素（OR：5.12，95% CI：1.01-26.09，P = 0.049）。对术后存活患者平均随访75.3个月，早期与延期手术组的10年累积生存率（77.3% vs. 83.1%，P = 0.583）和免于MACCE生存率（49.0% vs. 57.9%，P = 0.401）差异均无统计学意义。多因素Cox回归分析显示，完全血运重建（HR：0.40，95% CI：0.17-0.95，P = 0.037）与体外循环时间（HR：1.01，95% CI：1.01-1.02，P = 0.008）是远期全因死亡的独立预测因素。

结论：VSR早期修复手术的死亡率显著高于延期手术，但该差异可能部分源于患者术前状态的异质性。对于循环稳定的患者，进行延期修复及完全血运重建可改善远期预后。

第三部分 室间隔穿孔修复术中不同血运重建策略的疗效对比研究

背景：外科修复是当前治疗室间隔穿孔（Ventricular Septal Rupture，VSR）的主要方式。然而，针对这一由心肌缺血引发的并发症，血运重建策略仍存在争议。本研究从梗死相关动脉（Infarct-Related Artery，IRA）血运重建、完全血运重建及桥血管类型选择三方面，探讨不同血运重建方式的疗效差异。

方法：本研究为回顾性队列研究，连续纳入2004年1月至2022年12月于本中心接受外科修复术的VSR患者，根据临床特征和血运重建策略进行三部分分析：（1）总体队列中IRA血运重建组与无IRA血运重建组的比较；（2）多支血管病变患者中完全血运重建组与不完全血运重建组的比较；（3）同期行冠状动脉旁路移植术（Coronary Artery Bypass Grafting，CABG）患者中动脉桥组与静脉桥组的比较。主要终点为全因死亡，次要终点为主要不良心脑血管事件（Major Adverse Cardiovascular and Cerebrovascular Events，MACCE），包括心肌梗死、脑卒中、再次血运重建及因心力衰竭再入院。

结果：共纳入132例VSR患者，心肌梗死至手术间隔时间中位数为48天。28例患者未行IRA血运重建，主要原因为靶血管走行于室壁瘤内、弥漫性病变或严重钙化。Kaplan-Meier分析显示，IRA血运重建组与无重建组的10年生存率（81.4% vs. 84.0%，P = 0.547）及免于MACCE生存率（55.2% vs. 58.3%，P = 0.396）无显著差异。多因素Cox分析表明，IRA血运重建与全因死亡（HR：0.62，95% CI：0.22-1.79，P = 0.376）或MACCE（HR：1.30，95% CI：0.52-3.27，P = 0.575）无显著关联。经皮冠状动脉介入治疗或CABG完成IRA血运重建亦未导致显著预后差异（P = 0.515）。

84例多支病变患者中，31例接受不完全血运重建（11例未干预IRA，19例仅干预部分非IRA病变，1例未行血运重建）。完全血运重建组与不完全组相比，10年生存率无显著差异（87.8% vs. 62.2%，P = 0.152），但MACCE发生率显著降低（25.5% vs. 70.6%，P = 0.010）。多因素Cox分析进一步支持此结果（HR：0.26，95% CI：0.10-0.67，P = 0.005）。此外，不完全血运重建组中，干预非IRA病变患者的远期MACCE发生率较仅干预IRA者呈下降趋势（HR：0.256，95% CI：0.06-1.19，P = 0.083）。

92例同期CABG患者中，60例使用动脉桥，32例仅使用静脉桥。动脉桥组吻合口数量更多（2.38 ± 0.99个 vs. 1.88 ± 0.98个，P = 0.011），但主动脉阻断时间、体外循环时间及早期死亡率（3.3% vs. 3.1%，P > 0.999）无组间差异。生存分析显示，两组远期生存率（82.8% vs. 80.0%，P = 0.940）及免于MACCE生存率（49.6% vs. 58.6%，P = 0.491）无显著差异。Cox回归分析表明，桥血管类型与全因死亡（HR：0.78，95% CI：0.26-2.29，P = 0.644）或MACCE（HR：0.74，95% CI：0.21-2.65，P = 0.640）无显著关联。然而，在多支血管病变患者中，动脉桥用于非IRA血运重建可能降低MACCE风险（HR：0.41，95% CI：0.01-1.55，P = 0.079）。

结论：对于接受延期外科修复的VSR患者，IRA血运重建及CABG中应用动脉桥虽未显著改善预后，但围术期安全性良好；而完全血运重建可显著降低多支血管病变患者的远期MACCE风险。未来仍需进一步探索基于病变特征和血流动力学状态的个体化血运重建策略对预后的影响。

ABSTRACT

Part Ⅰ. Short-Term Prognosis and Risk Prediction in Patients with Ventricular Septal Rupture Undergoing Initial Conservative Treatment

Background: Current guidelines recommend initial conservative management for patients with post-acute myocardial infarction (AMI) ventricular septal rupture (VSR) to stabilize their condition before surgical repair. However, clinical data regarding this transitional phase remain limited. This study aimed to systematically evaluate the clinical characteristics, treatment patterns, and 30-day mortality of patients with post-AMI VSR who received only conservative management. Additionally, we sought to identify early mortality risk factors and develop a short-term mortality risk prediction model to facilitate stratified management and evidence-based intervention.

Methods: A retrospective cohort study was conducted, including consecutive patients diagnosed with VSR at our center between January 2000 and December 2022. Exclusion criteria were a history of prior cardiac surgery, surgical repair within 30 days of AMI, or missing 30-day survival data. A total of 322 patients were included in the final analysis. Data on demographics, medical history, echocardiography, coronary angiography, laboratory findings, and treatment strategies were retrieved from electronic medical records. The primary outcome was all-cause mortality within 30 days of AMI. Risk factors were identified using Cox proportional hazards regression, and a predictive model was developed and validated using Harrell’s C-index, calibration curves, and bootstrap resampling.

Results: The median age of the cohort was 67 years (IQR: 60–72), with females accounting for 46.9%. Hypertension (60.6%), diabetes mellitus (32.0%), and prior stroke (19.3%) were common comorbidities. A majority (93.5%) experienced their first AMI, and 26.7% underwent early reperfusion therapy. The VSR was predominantly apical (59.6%), with a median defect diameter of 12.0 (IQR: 9.0–15.0) mm, and 78.6% of cases involved an anterior wall infarction. Among 193 patients who underwent coronary angiography, multivessel disease (72.0%) and total occlusion of a culprit artery (51.3%) were common findings. During the 30-day observation period, 106 patients (32.9%) died, with a median survival of 8 days.

Compared with survivors, non-survivors were older (71.0 years vs. 64.0 years, P < 0.001), had higher proportions of females (56.6% vs. 42.1%, P = 0.014), cardiogenic shock at admission (57.5% vs. 31.0%, P < 0.001), and heart rate (104 beats/min vs. 88 beats/min, P < 0.001), but lower rates of percutaneous coronary intervention (PCI) within 12 hours post-AMI (5.7% vs. 19.0%, P = 0.001).

Multivariate Cox regression analysis revealed that age ≥ 71 years (HR: 3.51 for 71–75 years vs. ≤ 60 years, 95% CI: 1.88–6.57, P < 0.001; HR: 5.67 for ≥ 76 years vs. ≤ 60 years, 95% CI: 3.16–10.17, P < 0.001), female sex (HR: 1.61, 95% CI: 1.08–2.40, P = 0.020), cardiogenic shock at admission (HR: 2.01, 95% CI: 1.35–2.98, P < 0.001), and elevated heart rate (HR: 1.05 per bpm increase, 95% CI: 1.03–1.06, P < 0.001) were independently associated with higher 30-day mortality. Conversely, PCI within 12 hours of AMI (HR: 0.32, 95% CI: 0.14–0.73, P = 0.007) and higher left ventricular ejection fraction (HR: 0.98 per % increase, 95% CI: 0.96–0.99, P = 0.030) were protective factors. The prediction model demonstrated excellent discrimination (adjusted Harrell’s C-index: 0.841) and calibration. Stratified by risk tertiles, 30-day survival rates were 97.2% (95% CI: 94.2-100), 75.7% (95% CI: 68.0-84.3), and 28.0% (95% CI: 20.7-38.0) for low-, intermediate-, and high-risk groups, respectively (P < 0.001).

Conclusion: Patients with VSR managed conservatively face substantial early mortality. Advanced age, female sex, absence of early PCI, cardiogenic shock, elevated heart rate, and reduced left ventricular ejection fraction are independent predictors of 30-day mortality. The developed multivariable prediction model effectively identifies high-risk patients, supporting risk-stratified management and personalized intervention.

Part Ⅱ. Impact of Surgical Timing on Clinical Outcomes in Ventricular Septal Rupture Repair

Background: This study aims to evaluate the clinical outcomes of patients undergoing surgical repair for ventricular septal rupture (VSR) following acute myocardial infarction (AMI) at different time intervals. Additionally, it assesses the impact of various risk factors on perioperative and long-term outcomes.

Methods: This retrospective cohort study included consecutive patients who underwent surgical repair for VSR at Fuwai Hospital between January 2003 and December 2022. Based on the time from AMI onset to surgery, patients were categorized into an early surgery group (< 28 days) and a delayed surgery group (≥ 28 days). The primary endpoint was all-cause mortality, while secondary endpoints included major adverse cardiovascular and cerebrovascular events (MACCE), comprising myocardial infarction, stroke, repeat revascularization, and heart failure-related rehospitalization. The Kaplan-Meier method was used to compare event rates, logistic regression was employed to identify risk factors for early all-cause mortality, and a Cox proportional hazards model was applied to assess predictors of long-term prognosis.

Results: A total of 152 VSR patients were included, with 27 (17.8%) in the early surgery group and 125 (82.2%) in the delayed surgery group. Patients in the early surgery group were older (67.6 ± 7.0 years vs. 61.7 ± 8.4 years, P < 0.001) and had a higher proportion of females (59.3% vs. 33.6%, P = 0.023). They also exhibited significantly higher rates of preoperative cardiogenic shock (74.1% vs. 44.0%, P = 0.005), acute kidney injury (51.9% vs. 26.4%, P = 0.018), and intra-aortic balloon pump use (85.2% vs. 32.0%, P < 0.001). Moreover, the early surgery group had longer aortic cross-clamp time (85.0 min vs. 74.5 min, P = 0.023) and cardiopulmonary bypass time (130.0 min vs. 114.5 min, P = 0.009), as well as a significantly higher postoperative mortality rate (18.5% vs. 3.2%, P = 0.009). Multivariate logistic regression analysis identified early surgery as an independent risk factor for early mortality (OR: 5.122, 95% CI: 1.006–26.087, P = 0.049).

Among postoperative survivors, the mean follow-up duration was 75.3 months. The 10-year cumulative survival rate (77.3% vs. 83.1%, P = 0.583) and MACCE-free survival rate (49.0% vs. 57.9%, P = 0.401) did not significantly differ between the early and delayed surgery groups. Multivariate Cox regression analysis identified complete revascularization (HR: 0.402, 95% CI: 0.171-0.947, P = 0.037) and cardiopulmonary bypass time (HR: 1.012, 95% CI: 1.003-1.021, P = 0.008) as independent predictors of long-term all-cause mortality.

Conclusion: Early surgical repair of VSR is associated with significantly higher mortality compared to delayed surgery; however, this difference may be attributed to preoperative patient heterogeneity. For hemodynamically stable patients, delayed repair and complete revascularization may improve long-term outcomes.

Part Ⅲ. Comparative Effectiveness of Coronary Revascularization Strategies in Surgical Repair of Ventricular Septal Rupture

Background: Surgical repair remains the primary treatment for ventricular septal rupture (VSR) complicating acute myocardial infarction (AMI). However, the optimal revascularization strategy for this ischemia-driven complication remains controversial. This study aimed to evaluate the impact of different revascularization approaches on the prognosis of VSR patients, specifically focusing on infarct-related artery (IRA) revascularization, complete revascularization, and conduit selection in coronary artery bypass grafting (CABG).

Methods: This retrospective cohort study included consecutive patients who underwent surgical repair for VSR at our center from January 2004 to December 2022. Based on clinical characteristics and revascularization strategies, the study compared patients who underwent IRA revascularization with those who did not, evaluated complete versus incomplete revascularization in patients with multivessel disease, and analyzed outcomes in CABG patients receiving arterial versus venous grafts. The primary endpoint was all-cause mortality, while the secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including myocardial infarction, stroke, repeat revascularization, and heart failure-related readmission.

Results: A total of 132 VSR patients were included, with a median interval of 48 days from AMI to surgery. Among them, 28 patients did not undergo IRA revascularization, primarily due to aneurysmal involvement, diffuse disease, or severe calcification. Kaplan-Meier analysis showed no significant differences in 10-year survival (81.4% vs. 84.0%, P = 0.547) or MACCE-free survival (55.2% vs. 58.3%, P = 0.396) between the IRA revascularization and non-revascularization groups. Multivariate Cox regression analysis indicated no significant association between IRA revascularization and all-cause mortality (HR: 0.62, 95% CI: 0.22-1.79, P = 0.376) or MACCE (HR: 1.30, 95% CI: 0.52-3.27, P = 0.575). There was no significant prognostic difference between percutaneous intervention and CABG for IRA revascularization (P = 0.515).

Among the 84 patients with multivessel disease, 31 underwent incomplete revascularization (11 without IRA intervention, 19 with partial non-IRA intervention, and 1 without any revascularization). While no significant difference in 10-year survival was observed between the complete and incomplete revascularization groups (87.8% vs. 62.2%, P = 0.152), complete revascularization was associated with a significantly lower incidence of MACCE (25.5% vs. 70.6%, P = 0.010). Multivariate Cox analysis further confirmed this association (HR: 0.26, 95% CI: 0.10-0.67, P = 0.005). Additionally, among patients undergoing incomplete revascularization, those who received intervention for non-IRA lesions showed a trend toward a lower MACCE risk compared to those who only underwent IRA intervention (HR: 0.26, 95% CI: 0.06-1.19, P = 0.083).

Among the 92 patients who underwent CABG, 60 received arterial grafts, while 32 received only venous grafts. The arterial graft group had more anastomoses (2.38 ± 0.99 vs. 1.88 ± 0.98, P = 0.011), but no significant differences in aortic cross-clamp time, cardiopulmonary bypass time, or early mortality (3.3% vs. 3.1%, P > 0.999) were observed. Long-term survival (82.8% vs. 80.0%, P = 0.940) and MACCE-free survival (49.6% vs. 58.6%, P = 0.491) were also comparable between groups. Cox regression analysis showed no significant association between graft type and all-cause mortality (HR: 0.78, 95% CI: 0.26-2.29, P = 0.644) or MACCE (HR: 0.74, 95% CI: 0.21-2.65, P = 0.640). However, in patients with multivessel disease, the use of arterial grafts for non-IRA revascularization showed a potential trend toward a lower MACCE risk (HR: 0.41, 95% CI: 0.01-1.55, P = 0.079).

Conclusion: In patients undergoing delayed surgical repair for VSR, IRA revascularization and arterial graft use in CABG did not significantly improve prognosis but demonstrated good perioperative safety. However, complete revascularization significantly reduced the long-term MACCE risk in patients with multivessel disease. Future studies should further explore individualized revascularization strategies based on lesion characteristics and hemodynamic status to optimize outcomes in this population.