The impact of age in acute type A aortic dissection: a retrospective study

Background Acute type A aortic dissection (aTAAD) is a lethal disease and age is an important risk factor for outcomes. This retrospective study was to analyze the impact of age stratification in aTAAD, and to provide clues for surgeons when they make choices of therapy strategies. Methods From January 2011 to December 2019, 1092 aTAAD patients from Nanjing Drum Tower Hospital received surgical therapy. Patients were divided into 7 groups according to every ten-year interval (20–80 s). The differences between the groups were analyzed in terms of the baseline preoperative conditions, surgical methods and postoperative outcomes of patients of different age groups. During a median follow-up term of 17 months, the survival rates were compared among 7 groups through Kaplan–Meier analysis. Results The median age was 52.0 years old in whole cohort. The multiple comorbidities were more common in old age groups (60 s, 70 s, 80 s), while the 20 s group patients had the highest proportion of Marfan syndrome (28.1%). Preoperative hypotension was highest in 80 s (16.7%, P = 0.038). Young age groups (20–60 s) had a higher rate of root replacement and total arch replacement, which led to a longer duration of operation and hypothermic circulation arrest. The overall mortality was 14.1%, the tendency of mortality was increased with age except 20 s group (33.3% in 80 s, P = 0.016). The postoperative morbidity of gastrointestinal bleeding and bowel ischemia were 16.7% and 11.1% in 80 s group. Conclusions Age is a major impact factor for aTAAD surgery. Old patients presented more comorbidities before surgery, the mortality and complications rate were significantly higher even with less invasive and conservative surgical therapy. But the favorable long-term survival indicated that the simple or less extensive arch repair is the preferred surgery for patients over 70 years old. Supplementary Information The online version contains supplementary material available at 10.1186/s13019-022-01785-y.

extensive one-stage surgery, total arch replacement and frozen elephant trunk, has become the preferred surgical strategy in China to avoid reintervention [6,7]. There are also reports on one-stage total aortic arch replacement in other counties.
However, as the number of patients with aTAAD increases in age groups in China, especially in the groups of 60-80 years of age, the long-term survival of this extensive surgery is largely unknown. Should age be factored in the consideration before such an extensive surgery be planed? The age-stratified clinical characteristics, treatment strategies, and outcomes in Chinese patients are not yet known. The aim of this retrospective study is to investigate the clinical characteristics, treatment strategy and surgical outcomes of aTAAD in different age stratification groups in our center.

Patients
Between January 2011 and December 2019, a total of 1174 patients with aTAAD were admitted to Nanjing Drum Tower Hospital (NDTH). 1092 patients who underwent open surgical repair were divided into seven groups according to every ten-year interval (20-80 s) and 82 patients who did not undergo surgical therapy were excluded. Diagnosis of aTAAD was confirmed by computed tomographic angiography (CTA) scanning within two weeks after the onset of symptoms.
All clinical data were collected prospectively by admission and during the in-hospital stay. We retrieved the data retrospectively by review of hospital records. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The current study was approved by the institutional review board of Nanjing Drum Tower Hospital (2020-185-01).

Treatment
Patients diagnosed with aTAAD were transferred to cardiac surgery intensive care unit and optimal medical therapy was initiated. Those with the signs of severe low blood pressure and tamponade will be taken in the operating room direct from emergency. Open surgery was recommended for all patients, but for patients with advanced age, dissection associated organ malperfusion or family refusal, medical therapy was the treatment of choice. The patients received open surgery underwent general anesthesia via a standard median sternotomy after signing the informed consents. Cardiopulmonary bypass (CPB) was initiated with femoral artery or axillary artery arterial cannulation and right atrium or superior/ inferior venous cannulation. Deep or mild hypothermic circulatory arrest (HCA) was used in all patients. Selective antegrade or retrograde cerebral perfusion was applied for brain protection during the period of HCA at operating surgeon's choice. The distal aortic arch surgical strategy included partial arch replacement, total arch replacement with or without frozen elephant trunk (Microport Corp.Ltd, Shanghai, China) and arch stent (Yuhengjia Sci Tech Corp.Ltd, Beijing, China) based on the pathological involvement of the aortic arch [7][8][9]. After finishing the distal repair, the re-warming stage begun as the proximal part of aorta or root was being reconstructed and the patients were weaned off CPB. Bentall procedure or root reinforcement reconstruction was applied based on the anatomic indications [10,11]. The patients were transferred to the floor after recovering in cardiac surgery ICU, and discharged from the hospital per institution protocol.

Statistical analysis
Statistical analysis was performed with SPSS 26.0 (IBM Corp. Released 2019. IBM SPSS Statistics for Macintosh, Version 26.0. Armonk, NY: IBM Corp.). Descriptive statistics were used to describe patient characteristics throughout the study. Means and standard deviations were presented for normally distributed continuous variables whereas median and the interquartile ranges were computed to describe non-normally distributed continuous data. Categorical data are presented as frequency distributions and simple percentages. Between group differences were analyzed using a Student's t-test, Kruskal-Wallis H test or Mann-Whitney U-test for continuous variables and a Chi-square or Fisher's exact test for categorical variables. The survival curve was draw using Kaplan-Meier method and compared using the log-rank test. The median follow-up time was calculated with reverse Kaplan-Meier method. Statistical significance was considered when P < 0.05.

Demographics and Preoperative characteristics
Eighty-two of the 1174 aTAAD patients chose medical management that was chosen by 30.8% of patients in 80 years group due to rupture of the dissection (Fig. 1a,  b). The patients aged 40-60 years constituted the largest proportion of patients (71.2%) and the youngest 20 s (2.9%) and oldest 80 s (1.6%) groups accounted for minimum percentage of patients. There was higher proportion of female patients as age increases.
Further analysis showed that the 20 s group patients had the highest proportion of connective tissue diseases (Marfan's syndrome) (28.1%). History of hypertension was present in 63% patients ages between 40 and 70 years old and hypotension on admission was highest in 80 s group (16.7%, P = 0.038) ( Table 1). The average BMI was 25.6 with the highest 33.1 in 30 s group and lowest 19.5 in 80 s group. There is significantly increased history of stroke (9.6% vs 1.9%, OR 5.5, 95% CI 2.6-11.5), coronary artery disease (CAD) (5.9% vs 2.0%, OR 3.1, 95% CI 1.3-7.2) in patients over 70 years old.
Pain was the main presenting symptom, while chest pain presented as similar among groups. Preoperative malperfusion were present in 34% of patients with no significant difference among age groups.

Operative characteristics
The duration of surgery, CPB, X-clamp and HCA decreased with advanced age starting from age group of 50 years old. Cannulating both femoral and axillary artery were preferred arterial cannulation approach compared to single femoral or axillary artery. Bentall procedure accounted for a large part of root methods in young age group (43.8% in 20 s) and total arch replacement with FET had a higher rate in age group of 50 s (45.8%), 60 s (41.7%) than the 70 s (26.3%) and 80 s (16.7%) (P < 0.001) ( Table 2).
A decreasing trend of mortality rate in 70 s and 80 s group was shown with year ( Fig. 2b). Age was related to postoperative complications. The stroke rates (died and not died) were 8.5%, 5.1% and 5.6% in 60 s, 70 s and 80 s group respectively. Among patients succumbed in the 80-year group, there were significant high rate of GI bleeding and ischemia (16.7% and 11.1%, respectively) compared with other groups of 50 s, 60 s and 70 s (1.4%, 0%, 0.8%, respectively). The 70 s group had higher duration of ICU stay when compared with other groups (20 s group: P = 0.048, 30 s group: P = 0.047, 50 s group: P = 0.011); however, the duration of hospital stay showed no significant difference in all age groups. There was no significant difference in mechanical ventilation, reintubation, tracheotomy, neurological complications, renal complications and re-exploration. The 20 s group showed lowest postoperative neurological and gastrointestinal complications as they presented at admission (Table 3).  Figure 3b, c shows the ratio of patients readmission for recurrence of aortic dissection, the tendency of readmission for abdominal aortic dissection decreased with age.

Discussion
The average age of aTAAD patients was significantly younger in China, the results from Sino-RAD was 50.5 years [12] and 52 years in our center's previous reports [5]13. In this study, we found the median age of patients of aTAAD is 52. Furthermore, there was a significant increasing number of aTAAD patients in 70 s and 80 s group who underwent surgical repair. The underlining reasons maybe multi-factorial. One of the main reasons is the increasing awareness of aTAAD among the public and emergency room physicians particularly since the introduction of our aTAAD refereral program (6 h life circle); the second is attributed to the improvement of surgical successful rate of aTAAD surgery; and 3rd maybe related to the recent increase of national and regional healthcare coverage [14] and especially in the second half of the study period (2016-2019). For older patients with aTAAD, the optimal treatment strategy is in debate depending on the risk and benefit ratio and the upper age limit is unknown. A study by Trimarchi et al. using IRAD data showed that patients older than 70 years old received higher rates of medical therapy than those of surgical repair (28.6% vs 10.9%; P < 0.0001), and there was no difference in survival between the two treatment  Our present study also demonstrated that the proportion of patients who received surgical treatment over 70 years old remained relatively stable in last decade in our center. The higher 30 mortality in this group of patients suggested the negative impact of surgery on the postoperative recovery of patients with advanced age. In addition, the favorable long-term survival indicated that the simple or less extensive arch repair is the preferred surgery for patients over 70 years old. This finding is also corroborated by other studies [2]18.
Chest pain is the common clinical presentations of aTAAD for younger patients; however, the main etiology of aTAAD for patients in their 20 s is connective tissue disorders, such as Marfan syndrome while history of hypertension is more common in patients of aging 30, 40 and 50 s. Compared to the patients older than 70 years, the surgical strategies are totally different. More extensive surgical methods are applied for younger patients in order to avoid re-intervention because of aortic events [19][20][21][22][23]. Our study demonstrated that the recurrence rate of aTAAD was significantly lower in younger patients between 30 and 50 years old. The patients of 20 s group had the highest recurrent AD, consistant with the findings in Marfan's syndrome paitents reported by Isselbacher et al. from the IRAD data [24]. The ratio of readmission for aortic dissection is also decreased with age. Because older patients had more complications than younger patients. These complications not only affect the time and strategies of surgery, but also affect the outcomes of the patients. And they had to have readmission to deal with the complications after surgery. On the contrary, the 20 s group had readmission most likely to deal with the recurrent aortic dissection. Therefore, extensive surgery strategy with higher surgical risk could not lower late recurrence and re-intervention.
The mode of the age was in the 40 s group, these patients were at the middle age of their life. It was necessary to pay more attention to their long term follow up and the quality of life. In the next years, we would focus on their changes and show what would happen to these post-operative aortic dissection patients. For the increasing number of hypertension patients in China, it was meaningful to know whether the 40 s group patients could totally recovery from the emergency surgery and go back to the society.

Limitations
First, the retrospective study has its design limitation. Data were collected retrospectively so there are defects like incomplete, missing or inaccurate to report the event. The long-term survival rate would be underestimate as the follow-up interval is large and the follow-up time of some patients is shorter than one year. Second, the data obtained are of a single center and therefore could not represent the whole population. Third, as the number of patients in 20 s and 80 s group being limited, there is a need for further studies.