Aortic and vascular involvement in Loeys-Dietz Syndrome. Results from the REPAG registry (Spanish network of genetic aortic diseases)

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Abstract Background LDS is a rare disease due to genetic variants in the TGFB pathway. Limited information is available regarding the overall aortic and vascular outcome of these patients Purpose To evaluate aortic and vascular complications of patients with mutations in the TGFB pathway. Methods Retrospective longitudinal study including patients with (likely) pathogenic (LP/P) variants in the TGFbeta pathway from 10 tertiary centers. Clinical and imaging data were reviewed and data on aortic and vascular outcome included. Results A total of 163 patients were included (47.9% women, 38.6% index cases), mean age at first evaluation 32.3±20.4 years, 27.0% with age <16 years. 70 TGFBR1, 43 TGFBR2, 29 SMAD3, 9 TGFB2 and 12 TGFB3 (Table1) During a mean follow-up of 4.7±3.7 years, 54 (33.1%) patients had at least 1 aortic surgery (max 6). Mean age at first aortic surgery was 37.2±16.8 years (Range 1.2–72.9). First surgery was elective in 42 (77.8%), and included aortic root or ascending aorta in 40 (95.2%) and isolated descending aorta in 2 (4.8%). Emergent surgery included aortic root or ascending aorta in 11 (92.7%). Ascending aorta-root diameter previous to elective surgery was 48.9±4.9mm (range 41–65). 7 patients died during follow-up (2 intracranial bleeding, 1 SD, 2 aortic ruptures, 1post aortic surgery, 1 non-CV). Furthermore, 19 acute aortic syndromes (AAS) were reported (17 dissections, 2 haematomas) in 18 patients, 10 type A (52.6%). Mean age at first AAS was 42.3±11.1 years (min 19.7 years to 62.9 years) Median survival free of intervention, dissection or death was 57.1 years, being worst for men than women (44.7 yrs vs 69.1 years, p<0.001) (Figure 1), these gender-difference only remained significant in the TGFBR1 and SMAD3 groups (p=0.005 and p=0.008) Regarding aortic branch and intracranial aneurysms, a total of 383 imaging studies of aortic branches and 223 cranial imaging studies were performed during the clinical follow-up. 21 cranial aneurysms and 73 aortic branch aneurisms were reported. 14 (11.5%) patients suffered 19 aneurysms-related events (3 dissections, 3 ruptures, 13 interventions). Conclusions In patients with Loeys-Dietz Syndrome, there's a high prevalence of aortic surgeries and acute aortic events, with high numbers of peripheral and intracranial aneurysms. A worst prognosis in men than in women is observed in TGFBR1 and SMAD3 variants. Thus, specialized clinical and imaging follow-up is crucial in the management of these patients Funding Acknowledgement Type of funding sources: None.