Long-Term Risk for Aortic Complications After Aortic Valve Replacement in Patients With Bicuspid Aortic Valve Versus Marfan Syndrome

Itagaki, Shinobu; Chikwe, Joanna; Chiang, Yu-Ting; Egorova, Natalia; Adams, David H.

doi:10.1016/j.jacc.2015.03.575

Cited by 83 publications

(67 citation statements)

References 28 publications

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“…Among patients with MFS, AoD has been reported to occur in approximately 0.17% per year (7). A more recent study reported an increased risk among patients with MFS versus patients with BAV who underwent aortic valve replacement (14). However, this study excluded patients with TAA, leaving a substantial knowledge gap with respect to AoD risk after aortic grafting, as well as uncertainty with regard to diagnostic categorizations and follow-up events due to the fact that analysis was performed via a retrospective review of an administrative database.…”

Section: Discussionmentioning

confidence: 99%

Aortic Dissection in Patients With Genetically Mediated Aneurysms

Weinsaft

Devereux

Preiss

et al. 2016

Journal of the American College of Cardiology

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BACKGROUND Aortic dissection (AoD) is a serious complication of thoracic aortic aneurysm (TAA). Relative risk for AoD in relation to TAA etiology, incidence, and pattern after prophylactic TAA surgery are poorly understood. OBJECTIVES This study sought to determine the incidence, pattern, and relative risk for AoD among patients with genetically associated TAA. METHODS The population included adult GenTAC participants without AoD at baseline. Standardized core laboratory tests classified TAA etiology and measured aortic size. Follow-up was performed for AoD. RESULTS Bicuspid aortic valve (BAV) (39%) and Marfan syndrome (MFS) (22%) were the leading diagnoses in the studied GenTAC participants (n = 1,991). AoD occurred in 1.6% over 3.6 ± 2.0 years; 61% of AoD occurred in patients with MFS. Cumulative AoD incidence was 6-fold higher among patients with MFS (4.5%) versus others (0.7%; p < 0.001). MFS event rates were similarly elevated versus those in patients with BAV (0.3%; p < 0.001). AoD originated in the distal arch or descending aorta in 71%; 52% of affected patients, including 68% with MFS, had previously undergone aortic grafting. In patients with proximal aortic surgery, distal aortic size (descending thoracic, abdominal aorta) was larger among patients with AoD versus those without AoD (both p < 0.05), whereas the ascending aorta size was similar. Conversely, in patients without previous surgery, aortic root size was greater in patients with subsequent AoD (p < 0.05), whereas distal aortic segments were of similar size. MFS (odds ratio: 7.42; 95% confidence interval: 3.43 to 16.82; p < 0.001) and maximal aortic size (1.86 per cm; 95% confidence interval: 1.26 to 2.67; p = 0.001) were independently associated with AoD. Only 4 of 31 (13%) patients with AoD had pre-dissection images that fulfilled size criteria for prophylactic TAA surgery at a subsequent AoD site. CONCLUSIONS Among patients with genetically associated TAA, MFS augments risk for AoD even after TAA grafting. Although increased aortic size is a risk factor for subsequent AoD, events typically occur below established thresholds for prophylactic TAA repair.

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Section: Discussionmentioning

confidence: 99%

Aortic Dissection in Patients With Genetically Mediated Aneurysms

Weinsaft

Devereux

Preiss

et al. 2016

Journal of the American College of Cardiology

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“…Itagaki and co-workers examined the natural history of aortopathy after aortic valve replacement (AVR) in a retrospective comparison of over 13,000 patients(31). The study very clearly showed that the risk of aortic complications in long-term follow-up for BAV patients was much closer to control patients than those with Marfan syndrome.…”

Section: Clinical Guidelines and The Evolving Approaches To Bicuspid mentioning

confidence: 99%

Year in review

Fedak

Barker

Verma

2016

Current Opinion in Cardiology

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Purpose of Review To review and outline the key research contribution to BAV aortopathy over the past 18 months. Recent Findings Investigators have further defined the current gaps in knowledge and the scope of the clinical problem of BAV aortopathy. Support for aggressive resection strategies is waning as evidence mounts to suggest that BAV is not similar to genetic connective tissue disorders with respect to aortic risks. The role of cusp fusion patterns and valve-mediated hemodynamics on disease progression is a major area of discovery Molecular and cellular mechanisms remain elusive and contradictory. Summary BAV aortopathy is a major public health problem that remains poorly understood. New insights on valve-mediated hemodynamics using novel imaging modalities may lead to more individualized resection strategies and improved clinical guidelines.

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“…The assessment of hemodynamic flow in BAV patients shows distinct differences of the flow patterns compared to TAV patients (Keane et al, 2000). However, even after aortic valve replacement to correct the hemodynamics, some BAV patients still develop an ascending aortic aneurysm (Itagaki et al, 2015). Studies using aortic tissue from BAV patients have shown potential evidence of aortopathy of the aortic wall, including immature smooth muscle cells (SMCs) (Grewal et al, 2014b, Nkomo et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves

et al. 2016

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Individuals with bicuspid aortic valves (BAV) are at a higher risk of developing thoracic aortic aneurysms (TAA) than patients with trileaflet aortic valves (TAV). The aneurysms associated with BAV most commonly involve the ascending aorta and spare the descending aorta. Smooth muscle cells (SMCs) in the ascending and descending aorta arise from neural crest (NC) and paraxial mesoderm (PM), respectively. We hypothesized defective differentiation of the neural crest stem cells (NCSCs)-derived SMCs but not paraxial mesoderm cells (PMCs)-derived SMCs contributes to the aortopathy associated with BAV. When induced pluripotent stem cells (iPSCs) from BAV/TAA patients were differentiated into NCSC-derived SMCs, these cells demonstrated significantly decreased expression of marker of SMC differentiation (MYH11) and impaired contraction compared to normal control. In contrast, the PMC-derived SMCs were similar to control cells in these aspects. The NCSC-SMCs from the BAV/TAA also showed decreased TGF-β signaling based on phosphorylation of SMAD2, and increased mTOR signaling. Inhibition of mTOR pathway using rapamycin rescued the aberrant differentiation. Our data demonstrates that decreased differentiation and contraction of patient's NCSC-derived SMCs may contribute to that aortopathy associated with BAV.

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Long-Term Risk for Aortic Complications After Aortic Valve Replacement in Patients With Bicuspid Aortic Valve Versus Marfan Syndrome

Cited by 83 publications

References 28 publications

Aortic Dissection in Patients With Genetically Mediated Aneurysms

Aortic Dissection in Patients With Genetically Mediated Aneurysms

Year in review

Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves

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