LAUSR

Patients with Loeys‐Dietz Syndrome (LDS) are predisposed for pathologies of the cardiovascular system, in particular aortic aneurysm and aortic dissection. These patients require extremely careful management, and an attentive medical and surgical team. One often encounters the dilemma that patients with connective tissue disease present with one pathological aortic segment (often the ascending aorta), and after surgical therapy present only a few years later with an enlarged aorta just distal to the previously addressed aortic segment (i.e., the aortic arch). This raises the question: should LDS‐patients—who have a higher risk of aortic reoperation—undergo prophylactically a more extensive aortic repair? In the present issue of the Journal of Cardiac Surgery, Weininger et al. set out to find an answer to this difficult question. The authors present a study on 15 patients with LDS who underwent replacement of the aortic root or ascending aorta. Weininger et al. aimed to analyze the risk for long‐term complications of the aortic arch. Given that only two patients required aorta‐related reoperation during the follow up period, the authors concluded that prophylactic aortic arch repair may not be indicated during the initial operation. The Yale group presents a remarkable piece of work, yet I would like to discuss a few challenges inherent to studying LDS which we have to keep in mind when reading articles on this topic. A definitive answer to the above question is elusive given the barriers to producing studies robust enough to offer real certainty remain exceedingly high. One reason for this problem is the very low prevalence of LDS, which is estimated at approximately 1 per 1,000,000. This makes it very hard to compile enough patients and data to conduct sufficiently‐powered studies, and to allow for the formation of reliable conclusions. The Yale Aortic Institute enjoys an excellent reputation world‐wide and is well‐known for its databases including thousands of patients with an aortic pathology and even more diagnostic studies. Nonetheless, the present study contains only 15 patients with confirmed LDS illustrating the low prevalence of LDS. Of these 15 patients, only two required distal aortic repair during follow up, translating into a reoperation rate of 13.3%. This number is comparable to the 12% rate reported by the Johns Hopkins group, which have published extensively on the LDS. Of note, there are also other publications available reporting a higher rate of aortic reoperation (sample size = 10, arch interventions = 4). Divergent numbers generated by few studies with small sample sizes illustrates the difficulty of drawing clear conclusions. Furthermore, LDS does not represent a single genetic defect but involves a variety of different mutations associated with transforming growth factors. In turn, there are multiple mutations with a wide range of pathogenic significance. There are patients with a relatively benign course, but there are also documented cases of LDS patients with a more severe course requiring a large number of surgical procedures and reinterventions. This genetic playground makes it hard to talk about “the” LDS, and to compare patients. This is also one of the present study's limitations, as the 15 patients' mutations may be of different pathological significance and penetration. Another limitation of the present study concerns the follow up time. Despite the Yale Aortic Institute's enormous database, Weininger et al. can only report on a mean follow up time of 5 years. Surely, one has to keep in mind that LDS is a relatively young disease, which was described only recently in 2005. In turn, there is little data capturing long time periods. Still, the mean follow‐up time