Management of Marfan syndrome Innovations in imaging and treatment

Marfan syndrome is a heritable connective tissue disorder caused by pathogenic variants in the FBN1 gene, leading to an increased risk of thoracic aortic aneurysm and dissection. Current management relies on surveillance of aortic diameters and growth, pharmacological therapy, and prophylactic surgery when the aortic diameter has reached a certain threshold. However, evidence on the efficacy of pharmacological therapy to prevent aortic dissection is currently lacking, and aortic diameter alone inadequately predicts the risk of aortic dissection.
This thesis addresses these limitations through clinical and imaging studies. A multinational cohort study revealed variation in treatment strategies, with no independent protective effect of betablockers or angiotensin II receptor blockers on type B dissection, while prior root surgery emerged as a consistent risk factor. Resveratrol, a dietary supplement with promising preclinical effects, showed a non-significant trend toward reduced aortic growth and no measurable short-term impact on aortic hemodynamics, indicating the need for larger trials.
4D flow MRI and 4D bSSFP MRI sequences were developed and applied to assess aortic hemodynamics and biomechanics. Reduced 3D distensibility and displacement were observed in patients, reflecting increased arterial stiffness and associations with age and aortic size. Combined analyses of motion and flow demonstrated regional abnormalities, particularly after root surgery, with altered wall shear stress and displacement patterns in areas prone to dissection.
Overall, this work highlights the potential of advanced imaging to improve the understanding of aortic vulnerability and supports future efforts toward personalized risk assessment and treatment in Marfan syndrome.