CMN is often observed in the resected aorta in patients with CTD and tends to be associated with the worst long-term prognoses; this also causes aortic dilatation and dissection in non-CTD patients as well as in CTD patients [1, 17, 18]. However, it is difficult to demonstrate pathologically remarkable differences in the fragmentation of elastic fibers and accumulation of extracellular matrix in the formation of the cystic structures between CTD and non-CTD patients, especially in elderly patients with systemic hypertension [4, 5]. In this study, we hypothesized that coexistence of genetically identified CTD would be associated with worse postoperative prognoses after surgeries for aortic dissection in patients with CMN. To elucidate it, we compared early and late outcomes, including occurrence of new aortic events after the initial surgeries for aortic dissection of CMN-positive patients, between the CTD and non-CTD groups.
CMN might be due to long-term hemodynamic forces (hypertension) and age [4, 5]. It was demonstrated that patients with CMN have increased risks of serious vascular complications [19, 20]. However, few studies have seemed to look at adverse effects of CMN on the surgical outcomes of aortic dissection, as far as we investigated. With regard to findings of histological examinations, Trotter and Olsen reported that the degrees of elastic fragmentation were variable in Marfan patients, and can also be found even in non-Marfan subjects [4]. Nakajima et al. pointed out a higher degree of elastic fiber loss or fragmentation in Marfan patients, compared with non-Marfan patients having CMN [21]. Similarly, in our study, the grade of loss or fragmentation of elastic fibers was higher in the CTD patients than that of the non-CTD patients. Clinically, in this study, the age of the onset of initial aortic dissection was also significantly younger in the CTD patients, and aortic re-dissection occurred only in the patients with high-grade CMN, that is, loss of elastic fibers. Such clinical phenomena may be affected directly by such fragility of the aortic walls due to higher degree of loss or fragmentation of elastic fibers in the aortic wall. Consequently, the presence of coexisting CTD should be suspected or examined genetically in relatively young patients with higher grades of loss or fragmentation of elastic fibers in the aortic wall.
With regard to occurrence of re-dissection in the long term after the initial aortic dissection, the incidence was higher in CTD patients, despite no significant statistical differences. Interestingly, in the CTD group, 2 patients had suffered from three-channel dissection before the initial surgery and another 3 patients developed it in the long term after surgery; this may show a more severe fragility of the degenerative aortic wall in CTD patients. In the histopathological examinations, the grades of loss or fragmentation of elastic fibers were higher in CTD patients than in those of the non-CTD group. Looking at the relationship between the histopathological findings and the re-dissection rate, there were no significant differences between patients with no or minimal loss of elastic fibers and those with loss of elastic fibers. However, interestingly, all of the CTD and non-CTD patients suffering from aortic re-dissection had high-grade CMN, that is, loss of elastic fibers in the histopathological examinations. Consequently, it is important to estimate the long-term outcome after initial surgery for aortic dissection according to the results of genetic examinations as well as the histopathological findings.
In contrast, regarding re-operations, in CTD patients, higher rates of redo surgery were reported than in non-CTD patients [22, 23]. In our study, redo surgeries were also required more frequently in CTD patients. In particular, the rate of descending aortic repairs was significantly higher, compared with non-CTD patients. In patients with CMN combined with CTD, higher onset rates of type B aortic dissection were demonstrated than the others [24]. Our study also demonstrated the higher rate of type B aortic dissection in CTD patients. Related to this issue, Schoenhoff et al. reported that 86% of Marfan patients with type B aortic dissection required redo surgery for residual aortic enlargement [25]. In our study, similar findings were revealed. In the CTD group, 80.0% of the patients required re-operations after the initial surgical repairs in the long term, 72.7% in type A and 84.2% in type B.
The rate of surgical interventions to the aortic root was also significantly higher in the CTD group. Progressive enlargement of the aortic root is one of the characteristics of CTD patients, which is related directly to the early onset of type A aortic dissection. In cases with aortic root enlargement of 40 to 50 mm in diameter, prophylactic root repairs such as aortic valve-sparing surgery or composite valve-graft root replacement are recommended in the guidelines to eliminate risks of ruptured type A aortic dissection [26]. Progressive aortic root enlargement also should be one of the reasons for redo surgery after various surgical repairs for type A or B aortic dissection, whether it is associated with aortic dissection or not. In our study, a total of 39.5% of all patients underwent aortic root repairs; this included 63.6% of CTD patients and 20.0% of non-CTD patients with type A aortic dissection, and 42.1% of CTD patients with type B aortic dissection. Moreover, simultaneous aortic root repair was a significant risk factor for re-operation in the univariate and multivariate analyses. Consequently, these circumstances resulted in the higher rates of redo surgeries in the CTD patients.
Obviously, there are some limitations to this study. First, this is a retrospective study dealing with a small number of enrolled patients. In particular, the number of the patients undergoing genetic examinations was too small to elucidate exactly the impact of CTD on the outcomes of surgeries for aortic dissection. Aortic dissection was also variable, such as acute or chronic, and type A or B. Apart from the histological aortic pathologies, there are other factors or requirements for redo surgeries after initial surgeries for aortic dissection, relating to types of aortic dissection, conditions of the false channels, surgical techniques, extent of repairs, and so on. The surgical procedures of the initial operations for aortic dissection were variable, which depended on a variety of conditions, including the stages of aortic dissection, such as acute and chronic, and the settings of the surgery, such as emergent/urgent and elective. Theoretically, the re-operation rates become significantly higher in cases with no tear resection and patent false channel [27, 28]. Actually, there may be some differences in the incidences of re-operation between limited ascending/hemiarch replacement and entire arch replacement. The rates should also be different after the total arch replacement between with or without elephant trunk procedures on the distal anastomosis site [29]. The conditions of aortic dissection, including the patency of the false channel, were also variable. More detailed studies dealing with a larger number of patients is required to elucidate precisely the impact of genetically identified CTD on the surgical outcomes of aortic dissection in patients with CMN.
Finally, most (90.0%) of the CTD patients showed high-grade CMN, that is, loss of elastic fibers. However, similar findings were also found in a half (53.8%) of non-CTD patients. The genetic examinations are still limited by the issue of availability. There might be other different CTDs with unknown genetic characteristics. Consequently, in case of high-grade CMN, it is necessary to recognize, even without genetically diagnosed CTD at present, potentially high-risk subjects who would develop re-dissection and require re-operations at relatively shorter intervals after surgery for aortic dissection.