Type B aortic dissection (TBAD) is a life-threatening condition with high morbidity of approximately 3 in 100,000 people (1), and of whom more than 60% present have no signs of rupture or malperfusion [termed uncomplicated TBAD (uTBAD)] (2, 3). Thoracic endovascular aortic repair (TEVAR) has been now recommended as first lifesaving option for patients with TBAD in the setting of complications (4–6) according to recent guidelines (7–10). As it is traditionally recommended that uTBAD be managed through optimal medication (OMT) (9, 11), TEVAR is rarely used to treat uTBAD in actual clinical work, which leads to limited research on it in uTBAD. But OMT remains bad compliance (12) and also has a high incidence of late aorta-related complications. Considering that drug therapy accompanied by poor long-term prognosis, high aneurysm variability and low late survival rate (13, 14), more and more doctors have begun to accept the application of endovascular intervention in the treatment of acute uTBAD, so as to achieve survival benefits by preventing late complications (8, 15).

As increasing use of TEVAR in uTBAD, the complications, mortality and reintervention seems to be related to the timing of treatment (16, 17). The related Research confirmed that aortic remodeling after TEVAR is a continuous process, and chronic dissections have a more rigid intimal flap resulting in slower remodeling than in acute dissection (18–20). However, the complication rate is higher in the acute phase caused by the higher intima fragility in this phase (21). We sought to determine the optimal intravascular “treatment window” to achieve the goal of maximizing the survival benefit of early preventive TEVAR by ensuring better utilization of aortic remodeling and minimizing the incidence of complications (16). At present, relevant studies have not reached a consistent conclusion. A retrospective multicenter study analyzed the impact of timing on survival and postoperative complications following TEVAR for uTBAD suggest that the patients receiving treatment in subacute period is associated with improved 30-day and 1-year survival (21), which is the reverse of Gupta and colleagues' conclusion (22). Therefore, the aim of this systematic review and meta-analysis was to obtain the optimal timing.

With the release of the Long-term results from studies such as INSTEAD-XL (36), prospective multicentre ADSORB trial (37), consensus on treatment of uncomplicated type B aortic dissection, seems to be challenged. Default medical management with focus on blood pressure and surveillance is no longer the only treatment, and more aggressive early intervention is widely accepted (38, 39). Jubouri et al., in a recent review, summarized a number of studies and found that long-term aortic remodeling is affected by the timing of intervention and different areas of dissection (40). Tadros et al. in their review mentioned that there was no difference in the regression of false lumen between the subacute and acute groups in patients with uncomplicated type B aortic dissection who receivingTEVAR. However, patients treated in the subacute phase had fewer complications such as RTAD and aortic rupture (15). Several studies have compared aortic remodeling, clinical outcomes, and procedure-related complications in uTBAD patients treated with TEVAR in the acute and subacute phases, and found that there was no statistically significant difference among timing groups in early and late outcomes (31–35). However, there is a significantly higher trend in perioperative complication rate, reintervention rate and mortality rate in the acute phase which should be a concern. The latest guidelines offer some advice, but do not specify when it is the optimal “therapeutic window” to do TEVAR. So far, studies on the timing of TEVAR are varied. Apart from a study conducted by our group in 2022, no other relevant meta-analyses have been published (24). Due to the limited number of included studies, the results of the previous meta-analysis were not significant and the evidence level was low. As a result, with the further development of related research, it is necessary to update and summarize the literature in time. herein, We try to perform a systematic review and meta-analysis aimed to identify the optimal timing of treatment by analyzing and evaluating the available evidence. Our study showed that the early outcome of TEVAR in the subacute uTBAD group was better than that in the acute group, while there was no significant difference in the late outcome, suggesting that the subacute stage seems to have emerged as the optimal time window for TEVAR in uTBAD.

We combined the results about 30-day complications and mortality of each study and obtained OR values by the fixed effects model, suggesting that the perioperative complications (p < 0.0001) and mortality (p < 0.0001) rates in the acute group were both more than twice as high as those in the subacute group, with a high statistical significance in both cases. Compared with the conclusion that had no statistical significance among two groups, the meta-analysis made use of statistical advantages and obtained a more clear conclusion through the increase of sample size. The significant increasing risk of complications in the acute phase should be owed to the fact that dissecting membranes are usually thinner and more fragile than usual (41). Acute surgical intervention aggravated the damage to the delicate intima of the inflamed aorta (21). Further analysis of common perioperative complications of general concern in aortic dissection showed that stroke was more than twice as high as those in the acute phase than in the subacute phase (p < 0.0001). Stents covering left subclavian artery (LSA) during TEVAR were associated with increased incidence of stroke and perioperative mortality which was also confirmed by the STABLE trial (42, 43). Therefore, for patients undergoing acute surgery, doctors should pay more attention to the anchoring point of stent implantation during the operation and be highly alert to the occurrence of perioperative stroke.

Reintervention is also an important prognostic indicator. Previous studies did not meta-analyze this index. Except the study that Daniel J et al. clearly pointed out that the 30-day reintervention and long-term reintervention in the acute phase were both more than twice as high as those of the sub-acute group, while the existing other studies showed no significant statistical difference in the re-intervention rate between the two groups. Through the summary of six articles, we reached a similar conclusion to Daniel J et al., namely, there was no significant difference in the re-intervention between the two groups within 30 days, but the long-term re-intervention rate in the group receiving endovascular therapy in the acute phase was 1.42 times as high as that in the subacute phase.

For studies of long-term prognosis, our conclusions seem to be somewhat different. All current studies seem to support the conclusion that the timing of TEVAR for uTBAD does not appear to be independently predictive of or 1-year mortality. By conducted the meta-analysis of published data on long-term survival outcomes, we found no significant difference in long-term mortality between the two group but with significant heterogeneity. This is consistent with the conclusions of published meta-analysis (24). Through data analysis, we suggest that this heterogeneity may be caused by differences in follow-up time. Therefore, we performed a subgroup analysis based on the length of follow-up. After deleting the highly sensitive literature, we found that the mortality rate in the 1-year survival study was much higher in the acute stage group than in the subacute stage group. For longer follow-up studies over 3 or 5 years, the relatively high mortality rate in the subacute phase appears to indicate that the long-term benefit of the acute phase group is superior to that of the subacute phase group. Studies have shown that surgical treatment in the acute phase is a better option because the acute phase of the dissection flap is the softest and provides the best opportunity for remodeling (44). This favorable remodeling also reduces the likelihood of long-term aneurysm degeneration and aortic related mortality (13). Further studies have shown that this relatively good plasticity can be maintained up to 3 months after the initial dissection, while the dissection flap rapidly thickens, straightens, and becomes less flexible within 3 months as aortic wall fibrosis progresses (16, 19, 20). This theory provides favorable support for our results. TEVAR may have the best effect on aortic remodeling in the acute phase after primary dissection, which is reflected in the relatively ideal long-term follow-up results in the acute phase group. However, there are concerns about acute group related with high risky in perioperative complications and increased 30-day and 1-year mortality. In contrast, patients treated in the subacute phase had fewer complications, such as RTAD and aortic rupture. To strike a balance between aortic vulnerability and aortic plasticity, we believe that the subacute phase seems to be a more appropriate window of time to maximize the benefits of early prophylactic TEVAR in patients with TBAD. It remains to be seen whether future technological changes and further risk-benefit assessment can perfectly balance the long-term benefits with the 30-day risk of complications and death.

It is important to note that, as proposed by Torrent et al. (32), the difference in outcomes between the acute and subacute phases may be due in part to the fact that patients in the acute phase represent an inherently higher anatomical or physiological risk population, and this difference cannot be completely eliminated by propensity analysis. With the addition of high-risk characteristics to the new SVS/STS guidelines (7, 26, 28), High-risk aortic dissection is starting to become a separate category. We asked the new questions are patients undergoing acute surgery more likely to have high-risk dissection characteristics? Does the presence of this high-risk dissection have a hidden effect on the conclusions of the existing studies? Potter et al.'s study highlights early intervention has risky for HRF and points out that patients with HRF appear to benefit from at least a short stabilization period prior to TEVAR. At present, there are no other relevant studies on high-risk interlayers. Whether the timing of surgery has a more significant effect on prognosis in patients with high-risk aortic dissection is unknown. The classification of uTBAD or cTBAD according to the characteristics of high-risk dissection marks the gradual maturity of individualized management and refined treatment in clinical practice. Further in-depth study will provide a clearer diagnosis and treatment idea for the management of high-risk patients without complex TBAD. Therefore, in the future, we should pay more attention to the correlation analysis of long-term efficacy and collect more information about the prognostic outcome of patients with high-risk characteristics. More detailed records of risk factors and long-term follow-up data should be used to assess the short-term risk and long-term benefit of different patients to reach the most appropriate individual treatment options.