Study population
The AASCN contains the database of patients who suffered from acute aortic syndrome at ten heart centers (Beijing Anzhen hospitcal; Beijing Chaoyang Hospital; Guangdong General Hospital; China Medical University First Hospital; Shandong Provincial Hospital; People’s Hospital of Xinjiang Uygur Autonomous Region; First Affiliated Hospital of Harbin Medical University; Zhengzhou University First Affiliated Hospital; Ruijin Hospital and Sir Run Run Shaw Hospital) in China from April 2018, to December, 2019. The follow-up period was 10 years. Hospital related data were collected by a third party within 1 week after discharge. The long-term follow-up was mainly by telephone. The database is constantly updated. This study is mainly led by Anzhen Hospital, Beijing, China, and was approved by the hospital’s Ethics Committee in April 2018 (No. 2018004). The need for informed consent was waived.
Study cohort
We used ACI with ATAAD as an exposure factor to assemble a retrospective cohort study from the AASCN and eliminated patients without ATAAD, with MI or lack of follow-up. Missing data: there were 42 patients without record of ACI type, 39 patients without record of coronary artery treatment, 15 patients without indicators of myocardial ischemia before operation, 9 patients without record of operation type, 25 patients without the record of preoperative blood pressure, 4 patients without the record of cardiopulmonary bypass time, 8 patients without the record of circulatory arrest time. Ultimately, 931 ATAAD patients without MI were enrolled in our study. We observed patients from admission to 30-days postoperatively or death earlier than 30-days postoperatively. Diagnosis of ACI was mainly based on preoperative aortic computed tomography angiography (CTA) (after onset) with coincident of at least one cardiac surgeon and one radiologist or some suspicious ACI (according to CTA) were diagnosed based on direct vision of the cardiac surgeon intraoperatively (Tear of coronary artery ostium under direct vision) [ 4, 6].According to the CTA and Neri’s classification of ACI [10], we classified them into 3 types: type A (aortic dissection with a false lumen that involves the coronary ostium without coronary actual body); type B (aortic dissection false lumen that extends into the actual body of the coronary with successful administration of antegrade cardioplegia) and type C (crack of coronary artery). We divided these patients into ACI group and non-ACI group.
Definitions and end-point
We defined MI as elevated sensitive troponin I value with at least 1 value above the 99th percentile upper reference limit and combine one of the following: electrocardiogram indicates ST segment depression or elevation and abnormal wall motion indicated by echocardiography [11]. The type of ACI refers to Neri’s classification [10]. The primary end-point was all-cause death within 30 days after surgery. The secondary end-point were new-onset acute renal failure, low cardiac output syndrome, and malignant arrhythmia within 30 days after operation. Low cardiac output syndrome was defined as a cardiac index of < 2.2 L/min/m2 in the absence of hypovolemia [central venous pressure ≥ 8 mmHg and/or pulmonary capillary wedge pressure ≥ 12 mmHg and/or diastolic pulmonary artery pressure ≥ 12 mmHg] [12]. Acute kidney was defined according to KDIGO guidelines [13]. Malignant arrhythmia was defined as ventricular arrhythmias that cause hemodynamic changes [14].
Surgical techniques
All surgeries were performed by experienced cardiac surgeons (>30 aortic dissection surgery per year and postoperative mortality less than 10%). All ATAAD patients without surgical contraindications received surgery at the first time [15, 16]. All centers followed the same principles of major vascular surgery committee of cardiovascular surgery branch of Chinese Medical Association [16]. Cardiopulmonary bypass was performed in all patients in our study. Deep-hypothermia circulatory arrest and selective cerebral perfusion were performed if the aortic dissection involves the brachiocephalic vessels.
Distal and proximal aortic repair
All patients received surgery according to the previously described standardized procedure [15, 16]. For the proximal aortic repair, the ascending aortic replacement was performed in patients with ascending aortic dissection (AAD) without any other problem (aortic valve or aortic sinus problem). Bentall (a valve combined aortic root replacement) was performed in AAD patients with aortic valve and aortic sinus problem. David IV was performed in AAD patients with valve problem without aortic sinus problem.
Distal repair included the aortic arch repair, total arch replacement and hemiarch replacement. Aortic arch repair was performed in patients with uninvolved brachiocephalic vessels. Total arch replacement was performed in patients with total brachiocephalic vessels involved. Hemiarch replacement was performed in patients with part of brachiocephalic vessels involved.
Coronary ostium repair (COR) and coronary artery bypass grafting (CABG)
COR or CABG were performed according to Neri’s classification [10]. We consider that it is very important to explore the involvement of coronary artery ostium carefully for these patients without myocardial ischemia. Generally, the final type of ACI can be determined during the operation. For type A (Neri’s classification) patients, coronary ostium repair (COR) is the first choice. However, if the effect of COR is not good in some patients with type A (presented with coronary ostial stenosis after COR), we recommend switch to coronary artery bypass grafting (CABG). For type B patients, because the stenosis of coronary is not clear (whether CTA or intraoperative exploration may not fully determine the severity of coronary stenosis), we recommend CABG should be considered more actively to ensure coronary blood supply. For type C, the first choice is CABG, but there is no type C patients in our cohort. In addition, due to our study is a multicenter retrospective cohort analysis from database, there may be differences in the specific methods of COR and CABG from each center. According to the experience of our center (Beijing Anzhen Hospital), the specific method of COR are as follows: Start suturing from the junction of the left and right coronary sinus to the junction of the right or left coronary sinus and the noncoronary sinus by 6–0 prolene (Artificial shim are required for both the first needle and the last needle, suture along the upper edge of the affected coronary artery). When CABG was needed, considering the longer time of internal mammary artery acquisition, the great saphenous vein graft (SVG) was the first choice in all these patients. SVG was harvested and anastomosed to the distal of the involvement coronary in a standard manner with 8–0 prolene. Closing the affected coronary ostium with 5–0 prolene and then cardioplegia was applied through the proximal SVG. Proximal SVG was anastomosed to the brachiocephalic vessels after cardiac resuscitation.
Statistical analysis
We used PASS 15 to calculate the sample size (two-sided, power:0.90 Alpha:0.05, Hazard ratio is 0.5, duration time is 1 day to 30 day), the numeric results for the log-rank test in terms of sample size were 48 in non-ACI group and 49 in ACI group. Missing data were deleted (n = 146, 11.7%). Continuous variables conforming to normal distribution with homoscedasticity were analyzed via independent-sample t test and expressed as a mean with a standard deviation (SD). Continuous variables that do not conform to normal distribution were analyzed via Wilcoxon rank sum test and expressed as an interquartile range (IQR). Categorical variables were presented as frequencies with percentages and analyzed by chi-square or Fisher’s exact test, as appropriate. Kaplan-Meier plot was used to estimate survival rate and log-rank test was applied to intergroup comparisons. Risk factors for 30-day mortality were identified using cox regression. The variables in univariable factor analysis with P<0.1 or risk factors previously reported were included in Cox regression model [17,18,19,20]. Stratified analysis was used to identify differences of 30-day mortality among subgroups. In stratified analysis, continuous variables were categorized equally into three groups according to the number of people. Category boundaries were determined according to the separation value after equal division. Hazard Ratio (HR) was used to represents the difference of log-rank test between the two groups. We set the confidence interval to 95% (95%CI) in survival analysis. A two-tailed P < 0.05 indicated statistical significance. We used R software version 3.4.3 (Ihaka and Gentleman, 1996) for all of the above analysis.