Comparison of prognoses of patients with type A aortic dissection treated with surgery in acute, subacute and chronic phases

Introduction

Aortic dissection is an emergent macrovascular disease that poses a serious threat to human life and health. According to the location of the tear and the involvement of the aorta, the classic Stanford classification divides aortic dissection into Stanford type A dissection and Stanford type B dissection (1). Stanford type A aortic dissection is particularly dangerous, with the mortality rate of untreated patients increasing by 1% every 24 hours. The mortality rate at 48 hours can reach as high as 50%, with surgery being the only effective treatment for type A aortic dissection (2). Type A aortic dissection can be further divided into acute, subacute, and chronic stages based on the duration of the disease. Onset within 14 days is classified as acute type A aortic dissection (ATAAD), whereas a duration of more than 3 months is considered chronic type A aortic dissection (CTAAD). The subacute type A aortic dissection (STAAD) is defined as occurring between 14 days and 3 months according to the guidelines (3-5). Based on this classification, the current guidelines recommend emergency surgical treatment for patients with ATAAD, whereas surgical indication for patients with subacute and chronic ascending aortic dissection are based on aortic diameter or aortic valve insufficiency (AI) (6).

Previous studies have demonstrated that the postoperative prognosis of patients with CTAAD is superior to that of patients with ATAAD (7-9). However, the prognoses of patients undergoing surgery for STAAD and CTAAD remain unclear. This study aimed to compare the prognostic outcomes of surgery in patients with ATAAD, STAAD, and CTAAD to provide new strategies for the treatment of type A aortic dissection. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1655/rc).

Methods

Study population

We retrospectively screened the clinical data of patients who underwent surgical treatment for type A aortic dissection at the Department of Cardiac Surgery, Beijing Anzhen Hospital affiliated to Capital Medical University, between January 2015 and June 2017. The exclusion criteria were as follows: (I) age under 18 years; (II) pregnant women; (III) patients with missing data. Ultimately, 834 patients met the inclusion criteria and were enrolled in this study.

Ethics

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Human Research and Development Committee of Beijing Anzhen Hospital (Approval No. KS2024114), and individual consent for this retrospective analysis was waived.

Data collection and outcomes

We collected patients’ clinical data through the hospital’s electronic medical record system, including demographic information, comorbidities, imaging examinations, intraoperative details, and postoperative outcomes. We established a Case Report Form using EXCEL (Microsoft, SAN, CA, USA) to systematically gather the aforementioned data. Two investigators were responsible for data entry and cross-verification to ensure accuracy, and patients with incomplete data were excluded from the study.

The primary outcome was in-hospital all-cause mortality, defined as death occurring during hospitalization or within 30 days postoperatively. Secondary outcomes included: duration of mechanical ventilation, length of stay in the intensive care unit (ICU), postoperative hospital stay, and major adverse complications (including dialysis, stroke, hemiplegia/paraplegia, severe infections, and mechanical circulatory support).

Surgical technique

All procedures were conducted under general anesthesia utilizing cardiopulmonary bypass (CPB). To minimize cerebral oxygen demand, a cooling cap was applied, and continuous electroencephalographic monitoring was maintained throughout the operation. The selection of arterial cannulation sites—such as the axillary artery [169] and femoral artery [665]—was determined by intraoperative assessments. The surgical strategy was tailored according to the severity of the aortic dissection and the specific pathological features of the aortic root to achieve the best possible outcomes. For addressing aortic root pathology, techniques such as composite valve graft replacement (Bentall procedure), valve-preserving root replacement (David procedure), or combined aortic valve and ascending aorta replacement (Wheat procedure) were employed. Depending on the extent of the dissection, either total or partial aortic arch replacement was performed. If the dissection extended into the descending aorta, a distal elephant trunk graft was considered. Additionally, concurrent procedures such as coronary artery bypass grafting (CABG) or valve repair/replacement were performed based on intraoperative findings related to coronary artery and valve conditions (10-16).

Statistical analysis

Continuous data were presented as the means ± standard deviations (SDs) or medians (interquartile ranges), and categorical variables were presented as percentages (%). Tests of normality and homogeneity of variance were conducted prior to analyzing group differences. If the data were normally distributed and exhibited uniform variance, differences between the groups were analyzed using a t-test. Otherwise, the Mann-Whitney test was used to analyze differences between the two groups. Categorical variables were compared with the Chi-squared test or Fisher’s exact test.

Propensity score matching (PSM) was utilized to balance baseline characteristic differences between groups. We first compare the clinical outcomes of patients in the acute phase with those in the non-acute phase (analysis 1), and then compare whether there are differences in outcomes between subacute and chronic phase surgeries in non-acute phase patients (analysis 2). Propensity scores were calculated using a multivariate logistic regression model, which represented the probability of each individual receiving treatment. The selection of variables in the model was primarily based on their presumed association with different phases. The matching algorithm employed was nearest-neighbor matching without replacement, with a 1:1 matching ratio and a caliper value of 0.05. The logistic regression model included the following variables: age, sex, body mass index, hypertension, diabetes mellitus, coronary artery disease, respiratory disease, and smoking history. Multivariate Cox Proportional Hazards Model (Cox) regression analysis was performed to identify independent factors associated with in-hospital mortality. First, univariate analysis was conducted on all variables listed in Table 1, and variables with a P value <0.05, along with some established risk factors (such as age and sex), were included in the multivariate regression analysis. A backward stepwise regression method was used to screen for the final independent risk factors. All statistical analyses and graphical representations were performed using Statistical Product and Service Solutions 27.0 (SPSS, Armonk, USA) and GraphPad Prism v.8 (GraphPad Software, San Diego, USA). A two-tailed test was applied, and a P value <0.05 was considered statistically significant.

Results

Baseline characteristics

A total of 834 patients were included in this study, from which 618 were ATAAD patients and 216 were non-ATAAD patients (145 STAAD patients and 71 CTAAD patients). The baseline characteristics and preoperative data of the patients are shown in Table 1. The average age of all patients was 48.2±11.5, with 610 males (73.1%) and 224 females (26.9%). Hypertension was the most common comorbidity. The age, sex, and medical history of the three groups of patients were comparable. In analysis 1, compared with ATAAD patients, non-ATAAD group had a greater proportion of patients with a history of valve surgery history (2.8% vs. 0.6%, P=0.02) and a greater proportion of patients with Marfan syndrome (2.8% vs. 1%, P=0.055). They also had lower systolic blood pressure [125.0 (115.0–132.0) vs. 127.0 (117.0–137.0), P=0.02] and higher low-density lipoprotein (LDL) (2.7±0.8 vs. 2.4±0.9, P=0.02). In analysis 2, the baseline differences in the CTAAD group were similar to those observed in the STAAD group.

To reduce bias from different baseline characteristics, the PSM method was used in this study. A total of 215 ATAAD patients vs. 215 non-ATAAD patients and 71 STAAD patients vs. 71 CTAAD patients were identified through PSM. The basic characteristics and preoperative data of these patients were comparable and listed in Table S1.

We further analyzed the differences in the initial symptoms of aortic dissection among the three groups. As shown in Table 2, compared with those in the non-ATAAD group, the first symptoms in the ATAAD group were primarily severe, and they included sudden pain (76.2% vs. 58.6%, P<0.001), limb numbness (6.8% vs. 1.9%, P=0.005), nausea (11.5% vs. 4.2%, P=0.002), and vomiting (10.8% vs. 3.7%, P=0.002). The proportion of severe symptoms in the STAAD and the CTAAD groups was low, and the proportion of symptoms of sudden pain, chest tightness, and chest and back pain was high. In addition, the proportion of severe symptoms in the CTAAD group was similar to that in the STAAD group. These milder symptoms may have contributed to the delayed timing of surgery in both the STAAD group and the CTAAD group. The comparison results of the PSM cohort, shown in Table S2, align with those of the overall cohort.

Comparison of surgical details

The surgical data are shown in Table 3. In analysis 1, compared with non-ATAAD patients, ATAAD patients underwent more aortic arch surgeries, including partial aortic arch replacement (5.4% vs. 0.5%, P<0.001) and Sun’s operation (73.5% vs. 56.0%, P<0.001), suggesting a greater proportion of aortic dissection involving the aortic arch. The proportion of patients who underwent surgery with mitral valve replacement (MVR) in the non-ATAAD group was greater than that in the ATAAD group (4.2% vs. 1.5%, P=0.02). In terms of operation time, the CPB time, aortic clamping time, and overall operation time in the non-ATAAD (STAAD and CTAAD) groups were shorter than those in the ATAAD group. In analysis 2, there were no significant differences in the surgical data of patients in the STAAD and CTAAD groups, indicating no significant differences in the surgical operations in the subacute or chronic phase. The comparison results of the PSM cohort are shown in Table S3, and they are consistent with those of the overall cohort comparison.

Comparison of clinical outcomes

The short-term prognosis data are shown in Table 4. Significant differences in short-term outcomes were observed between the groups. Compared with those in the ATAAD group, patients in the non-ATAAD group had fewer ICU hospitalization days [1.3 (0.9–3.0) vs. 2.3 (1.2–5.1), P<0.001] and shorter ventilator times [41.5 (26.0–84.0) vs. 64.0 (28.5–157.5), P=0.004], indicating that the patients in the STAAD and CTAAD groups recovered faster after surgery. However, patients in the STAAD and CTAAD groups had longer hospital stays [15.5 (12.0–21.0) vs. 12.0 (9.0–17.0), P<0.001], likely because the CTAAD patients had routine preoperative examinations, whereas ATAAD patients had incomplete preoperative examinations. However, there were no significant differences between the STAAD and CTAAD groups.

Regarding the incidence of postoperative complications, the non-ATAAD group had lower rates of postoperative complications. Specifically, the incidence of neurological complications (11.7% vs. 5.1%, P=0.006), postoperative continuous renal replacement therapy (CRRT) (15.2% vs. 6.0%, P<0.001), cardiovascular complications (8.1% vs. 2.8%, P=0.007), and postoperative reintubation (4.4% vs. 0.5%, P=0.004) were lower in the non-ATAAD group than in the ATAAD group. Among neurological complications, the incidence of cerebral infarction in the ATAAD group significantly higher (5.5% vs. 0.5%, P<0.001), and among the cardiovascular complications, the incidence of pericardial tamponade in the ATAAD group also significantly higher (2.4% vs. 0%, P=0.02). These findings suggest that the STAAD and CTAAD groups experienced fewer postoperative complications and had better prognoses. In terms of the difference between the STAAD and CTAAD groups, there were no significant differences in the incidence of these complications. The comparison results of the PSM cohort are shown in Table S4, and they are consistent with those of the overall cohort.

We further analyzed the differences in postoperative mortality among the three groups. In the overall cohort, the 30-day mortality rates were significantly different between the acute and nonacute groups. The 30-day mortality rate of patients in the non-ATAAD group was 3.3%, and in the ATAAD group was 14.0% (Figure 1A). Furthermore, in the PSM cohort, the 30-day mortality rate of patients in the non-ATAAD group was 3.3%, while the 30-day mortality rate of patients in the ATAAD group was 8.9% (Figure 1B). These results indicate that the postoperative prognosis of patients in the non-ATAAD group was significantly better than that of patients in the ATAAD group, with no significant differences in prognosis between patients in the STAAD group and those in the CTAAD group (Figure 2A,2B).

Figure 1 Kaplan-Meier survival curves for the ATAAD and non-ATAAD groups in the overall cohort (A) and in the PSM cohort (B). ATAAD, acute type A aortic dissection; PSM, propensity scoring match.

Figure 2 Kaplan-Meier survival curves for the STAAD and CTAAD groups in the overall cohort (A) and in the PSM cohort (B). CTAAD, chronic type A aortic dissection; PSM, propensity scoring match; STAAD, subacute type A aortic dissection.

Analysis of risk factors for 30-day mortality

We performed Cox regression analysis to explore whether the timing of aortic dissection surgery was an independent protective factor for 30-day postoperative mortality (Table 5). Multivariate Cox regression analysis revealed that the timing of surgery, age, blood pressure, and creatinine levels were independent risk factors for in-hospital mortality. Compared to surgery performed during the chronic phase, patients who underwent surgery in the acute phase had a higher mortality rate [hazard ratio (HR) =4.749, 95% confidence interval (CI): 1.495–15.089, P=0.008]; however, there was no significant difference in mortality for surgeries conducted during the subacute phase (HR =1.053, 95% CI: 0.234–4.734, P=0.95). Apart from this, higher systolic blood pressure was also found to be a protective factor for 30-day postoperative mortality (HR =0.973, 95% CI: 0.956–0.990, P=0.002). In addition, older age (HR =1.023, 95% CI: 1.004–1.044, P=0.02), and higher preoperative creatinine (HR =1.006, 95% CI: 1.004–1.008, P<0.001) were found to be independent risk factors for 30-day postoperative mortality. These findings suggest that patients who undergo chronic aortic dissection surgery have a better prognosis than those who undergo acute surgery.

Discussion

In the 1950s, Hurst analyzed the outcomes of 425 patients with acute aortic dissection and reported mortality rates of 21% at 24 hours, 49% at 4 days, and 74% at 2 weeks (17). Two weeks after onset, the mortality rate decreased significantly compared with that in the acute phase. It has been reported that only 25% of the patients with type A aortic dissection survive and progress to the chronic stage without surgical intervention (17,18). Based on this observation, the 2024 European Association for Cardio Thoracic Surgery/The Society of Thoracic Surgeons (EACTS/STS) Guidelines for the diagnosis and treatment of aortic diseases divide aortic dissection into acute (14 days), subacute (14 days to 3 months) and chronic (>3 months) stages according to the time of symptom onset (5). ATAAD has been widely studied and published, and there are valid data from acknowledged centers and databases such as International Registry of Acute Aortic Dissection (IRAD) and German Registry for Acute Aortic Dissection Type A (GERAADA) (19,20). However, to date, data on subacute and CTAAD, especially STAAD, remain very limited. Moreover, unlike patients with acute aortic dissection, which requires emergency surgery, patients with subacute and chronic dissection are more stable, so they can receive elective surgery. To achieve better surgical outcomes, it is necessary to determine an appropriate intervention time to better guide treatment for subacute and chronic dissections.

The most common symptom of acute aortic dissection is severe, tearing-like pain in the chest and back. However, in our present study, we found that the first symptoms, such as chest pain, back pain, and organ ischemia, were not evident in patients with subacute or chronic aortic dissection. There are two possible explanations for this. First, according to the preoperative data, tear is mostly confined to the proximal part of the aorta in patients with nonacute aortic dissection, and the extent of the lesion is significantly less than that of acute patients. As a result, patients with chronic dissection are more likely to undergo aortic root and ascending aorta replacement. Therefore, patients with chronic aortic dissection have less severe tears, which are reflected in less pronounced physical symptoms. Second, patients with chronic aortic dissection are more likely to have undergone cardiac surgery. Patients who have undergone previous heart surgery are less likely to experience chest or back pain, possibly because prior surgery impairs the sympathetic nervous system function of the heart.

The postoperative outcomes of non-ATAAD patients were significantly better than those of acute patients, as evidenced by fewer postoperative complications and significantly lower short-term mortality. In addition, no significant differences were observed between subacute and chronic dissection patients. By screening for factors affecting the risk of postoperative mortality after surgery via multifactorial logistic modeling, we found that the acute and chronic status of aortic dissection is one of the most important indicators of short-term survival within one month of surgery. First, nonacute patients have a more stable hemodynamic state, as indicated by lower levels of inflammation, mild myocardial damage, and a more stable coagulation system. Another possible reason is that aortic tears in patients with nonacute dissection are confined to the arch, which allows the surgeon to fully repair a complete aortic lesion. Second, intraoperative data showed that the CPB time, aortic clamp time, and operative time, known risk factors for postoperative complications and mortality, are significantly shorter in patients with chronic dissection than in patients with acute dissection. Based on these findings, we propose that, for patients with ATAAD who are unable to undergo emergency surgery, conservative treatment should be the preferred option to help them pass through the acute phase and enter the subacute stage before surgery. However, there is no difference between the subacute and chronic stages of surgical intervention; thus, it may be appropriate for these patients to receive surgery as early as possible to avoid unexpected adverse aortic events. Current conservative treatments are limited to blood pressure reduction, sedation, and analgesia. However, the risk of death remains high (21). Therefore, there is an urgent need to explore new therapeutic strategies to promote aortic wall repair and reduce mortality during the transition period.

This study has the following limitations. First, it is a single-center retrospective study with a relatively small sample size, and it is subject to various biases, such as selection bias and information bias, which may limit the generalizability of the findings to some extent. Second, due to the retrospective nature of this study, it is susceptible to numerous confounding factors. Although PSM method was performed to enhance comparability between groups, there remain potential factors that may weaken the credibility of our conclusions. Thirdly, this study lacks long-term follow-up data on patients. Future research should extend the follow-up period to provide more robust evidence.

Conclusions

For type A aortic dissection, our research has confirmed that patients undergoing surgery during the acute phase indeed face higher risks, which is consistent with previous studies. However, the clinical outcomes for patients receiving surgery during the subacute phase are similar to those in the chronic phase. Based on our experience, even after patients have passed the acute phase of the dissection, they still face a significant risk of rupture. Therefore, in clinical practice, for non-acute phase patients, surgery should also be performed as soon as possible, rather than opting for a wait-and-see approach or choosing elective surgery.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1655/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1655/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1655/prf

Funding: This study was supported by the National Science Foundation of China (82241205, and 82300535), the National Key Research and Development Program of China (2017YFC1308000), the Beijing Lab for Cardiovascular Precision Medicine (PXM2017_014226_000037), the Beijing Advanced Innovation Center for Big Data-based Precision Medicine (PXM2021_014226_000026), and the China Postdoctoral Science Foundation (2022M722235).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1655/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Human Research and Development Committee of Beijing Anzhen Hospital (Approval No. KS2024114), and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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