Shedding light on type B aortic dissection in Marfan syndrome: implications for patient counselling and research priorities

In their study [1], Yildiz et al. shed light on the outcomes of type B aortic dissection (TBAD) in patients with Marfan syndrome (MFS) treated at a prominent interdisciplinary centre. The authors' investigation focused on a cohort of 188 patients, of whom 36 individuals (19%) developed TBAD. Notably, the reported aortic diameters at the time of dissection (39 mm) and the last measurement prior to the event (32.1 mm) were both well below the conventional surgical thresholds. A substantial majority (two-thirds) of patients who experienced TBAD required subsequent aortic interventions. These findings not only provide valuable insights for patient counselling but also underscore the urgent need for further research in predicting this critical complication. This report is a significant contribution to our understanding of TBAD in the context of MFS. MFS, a rare syndromic Heritable Thoracic Aortic disease caused by pathogenic variants in the Fibrillin1 (FBN1) gene, is strongly associated with the risk of aortic dissection, emphasizing the importance of identifying patients at risk and managing this potentially life-threatening condition [2]. Whereas risk estimation for type A aortic dissection in patients with MFS is more or less established, mainly related to aortic root diameter and the presence of additional factors, including arterial hypertension, aortic root growth rate (>3 mm/year), a family history of aortic dissection at low diameters and pregnancy, evidence to estimate the risk for TBAD is scarce. A disturbing but not unexpected finding of this study is the observed occurrence of TBAD in patients with aortic diameters well below the conventional surgical thresholds. According to guidelines, prophylactic (surgical) intervention has been recommended when the aortic diameter reaches 50 mm to prevent dissection [3]. However, the study findings suggest that relying solely on diameter measurements may not capture the full spectrum of risks in patients with MFS, as suggested by previous reports [4, 5]. Consequently, the authors' work raises crucial questions regarding our current understanding of TBAD risk assessment and the appropriate timing of surgical intervention. An important and known concern of TBAD in patients with MFS is the influence of prior aortic root replacement (ARR) surgery [6]. A high percentage (56%) of patients with TBAD in this report already had prior ARR surgery and 22% of all patients with MFS undergoing ARR surgery had a TBAD, but the percentage of patients in the entire cohort of 188 patients is not reported. To invoke a causal relationship between ARR surgery and subsequent TBAD might, however, not be appropriate because patients with prior ARR surgery might simply exhibit a more severe phenotype. Further investigation of this association is definitely warranted. A factor of increasing importance in risk assessment in the setting of Heritable Thoracic Aortic Disease is the underlying genetic profile. There is increasing evidence for gene- and even variant-specific differences in aortic outcome, and it is to be expected that in the current era of precision medicine, the importance to the genetic cause of pathology in an individual patient will increase, especially as the availability and performance of genetic testing have improved significantly [7, 8]. The genetic data in this paper did not specify whether the presence of an FBN1 variant and the type of variant influenced the incidence or clinical course of TBAD. The importance of this type of genetic information was recently supported by a recent meta-analysis of drug trials with beta blockers and angiotensin receptor blockers in which the presence of an FBN1 variant was one of the few factors that could be shown to influence a beneficial effect of medication [9]. The study nicely highlights the significant burden of subsequent interventions in patients who experienced TBAD. With two-thirds of individuals requiring additional medical procedures following the initial dissection event, the long-term management and care for these patients is a major concern. This finding necessitates a more comprehensive approach to managing TBAD in patients with MFS, including strategies to minimize the need for repeat interventions and optimize long-term outcomes. The implications of this study extend beyond the clinic. The data presented by Yildiz et al. underscore the importance of effective patient counselling in MFS. These findings should be incorporated into discussions with individuals and families affected by the condition, providing them with more accurate and nuanced information about the potential risks they face. Very important in this process is that we should be careful not to generalize the data from 1 particular study to the entire patient community. This reported cohort may differ from others, in several ways. First, there is a high percentage of patients who presented initially with aortic dissection (21%). Looking at other cohorts of patients, these figures vary widely which is in all likelihood influenced by the setting of the centre and the inherent referral pattern [4, 6, 10]. Centres in which Clinical Genetic services handle coordination and where patients of all ages, and also often less severely affected family members are screened, will see a different type of patient than a centre directed from a cardiosurgical setting (as the profile of these authors indicates) where usually more severe phenotypes are seen. In this context, it would be very interesting to have insight into the profile of patients at initial presentation: referral because of skeletal features, lens luxation, family history or aortic pathology. The study's results emphasize the need for continued research efforts to enhance our ability to predict TBAD in MFS. The conventional reliance on aortic diameter measurements alone may be insufficient to identify high-risk individuals, as demonstrated in this study. By investigating additional risk factors, such as aortic biomechanics, genetic markers or novel imaging techniques, predictive models could be refined and personalized risk stratification tools be developed. This, in turn, could aid clinicians in tailoring individualized management plans, including optimal timing of surgical intervention, to prevent catastrophic TBAD events in MFS patients. Conflict of interest: Grant for Medical Research by the Baillet Latour Funds awarded to Julie De Backer. Julie De Backer and Isabelle Van Herzele are funded as senior clinical researchers by the Research Foundation Flanders. The other author reports no conflict of interest.