MFS is a common autosomal dominant genetic disorder caused by FBN1 mutations . The reported prevalence varies from 1 to 3 per 10,000 individuals, depending on the diagnostic criteria and ethnicity, while no sex predilection is apparent in MFS[7, 8]. Although this monogenic connective tissue disorder generally segregates as a dominant trait in families, novo mutations are responsible for nearly 25% of cases. Even though MFS affects various systems including skeletal, oclar and cardiovascular systems, the latest nosology emphasizes on the alterations in the cardiovascular system which is the most detrimental phenotype. Indeed, dissection or rupture of the dilated aortic root which is seen in nearly three quarters of patients with MFS is the predominant cause of mortality in these cases, with a peak incidence in the third and fourth decades of life[3, 6, 9].
Usually, MFS patients are asymptomatic while the dilated aorta remains stable. However, the dilation rate of the aorta is heterogeneous and cannot be predicted. Although the risk of type A dissection clearly increases with the increasing aortic root diameter, it can also occur even in patients with mild aortic dilation, just like an unstable deadly “bulging balloon”. Moreover, if the dilation involves the aortic annulus and aortic valve is anatomically changed, cardiac dysfunction secondary to valvular regurgitation would be the dominant clinical feature. In our patient, even though the aortic root aneurysm has dilated to such rare giant scale, it remained stable and the clinical symptoms were mainly due to cardiac dysfunction secondary to aortic regurgitation and an enlarged left ventricle.
Early screening and establishment of the diagnosis of aortic aneurysm in patients with a family history of MFS is critical since prophylactic intervention can reduce the risk of aortic dissection and rupture effectively, which requires effective screening methods. As most of the early stage patients are asymptomatic, the aortic aneurysm is usually found occasionally during a routine X-ray, which shows a widened mediastinum. Furthermore, echocardiographic assessment can provide us with detailed information regarding the morphological features of the left ventricle, aortic annulus, aortic sinuses and ascending aorta in multiple views and dynamic videos in evaluating aortic valve morphology and the mechanism of aortic insufficiency[10, 11]. Due to its convenience and safety, echocardiography has been widely used in young individuals who require repetitive imaging and long-term follow-up. However, echocardiographic evaluation alone cannot offer information on adjacent structures or the involvement of aortic branches. In this case, furthermore, we performed an enhanced thoracic CT scan to visualize the main aortic branches and measure the extent and size of the aneurysm accurately.
Once the diagnosis of aortic aneurysm has been confirmed in patients with MFS, intense physical activity such as weightlifting should be avoided due to the potential risk inducing rupture or dissection of the aortic aneurysm Meanwhile, regular follow-up is necessary. Concurrently, conservative management is aimed at decreasing the heart rate and lowering the blood pressure to reduce the hemodynamic stress on the proximal aorta. β-adrenergic receptor antagonists, including propranolol, atenolol and nebivolol[14–16] have become the most prescribed medications for MFS patients as they might decrease the aortic dilation rate. Losartan, one of the angiotensin II receptor 1 blockers (ARBs), is useful in inhibiting the dilation of the aorta as it was recently discovered that angiotensin II is involved in MFS pathophysiological process. However, more clinical trials are required to verify the ability of ARBs to interfere with the MFS pathology. Even though several novel therapeutic strategies are under investigation, the goal of precision medicine is laborious to achieve. Surgical intervention remains as the gold standard treatment strategy for aneurysm in MFS.
Surgical treatment should be considered in MFS patients who have aortic root dilatation with a maximal diameter ≥ 50 mm. If there are additional risk factors including family history of aortic dissection, severe aortic regurgitation, desire for pregnancy, systemic hypertension and/or aortic size increase > 3 mm/year, surgical intervention is recommended when maximal aortic diameter ≥ 45 mm. Bentall procedure (composite replacement of the aortic valve and dilated ascending aorta combined with coronary artery reimplantation) has become a low-risk and durable operation with 5- and 10-year survival rates of 84% and 75%, respectively. It should be noted that bioprosthetic valves have limited durability and mechanical valves poses the risk of bleeding due to anticoagulation therapy. Thus, aortic valve-sparing operations such as David’s procedure (reimplantation of the aortic valve) and Yacoub’s procedure (remodeling of the aortic root) in young patients with aortic aneurysm have represented promising treatment strategies in recent years. Even though Yacoub’s procedure has been reported to be inappropriate for patients with Marfan syndrome because of the significant aortic insufficiency and reoperation rate, David’s procedure shows excellent outcomes. In this case, the significant dilation of the aortic annulus caused structural damage to the aortic cusps and multiple fenestrations were detected around commissures. While David’s procedure with an external annuloplasty band can correct the dilated aortic annulus, this outcome may not last for long. Moreover, in our case, the patient is not a suitable candidate for the long surgery due to the extremely poor cardiac function. After comprehensive perioperative assessment, we finally decided to perform Bentall procedure for our patient. Based on our limited experience learned from this case, we suggested that the management options for MFS patients with aortic root aneurysm should depend on the valvular anatomical morphology and patients’ overall health status. For patients with anatomically normal valve combined with acceptable cardiac function, valve-sparing operation should be attempted as it reduces the risk of thromboembolism, hemorrhage and infective endocarditis, especially in young patients. Otherwise, traditional Bentall procedure should be performed, and lifelong anticoagulation therapy is mandatory in young patients.