二叶式主动脉瓣疾病——发病机理和治疗的新感悟英文PPT课件

1、Bicuspid Aortic Valve Disease New Insights in Pathogenesis 106(8):900-4 Etiology and Development of Congenital BAV 1. Abnormal aortic cusp formation. 2. Adjacent cusps fail to separate, resulting in a single aberrant cusp. 3. Phenotypic continuum (unicuspid, bicuspid, tricuspid) Fedak P, Verma S, Ci

2、rculation 2002; 106(8):900-4 Fedak, David, Borger, Verma, Expert Rev Cardiovasc Ther 2005 Bicuspid Aortic Valve (BAV) Morphology Sabet et al, Mayo Clin Proc, 1994;74:14-26 Leaflet Position Anterior-PosteriorLeft-Right Etiology and Mechanisms Abnormal blood flow through aortic valve during valvulogen

3、esis results in a failure of cusp seperation Embryonic theory (abnormalities in conotruncal seperation) Cono-truncus divided by the spiral conotruncal septum Right 126(3): 797-806 - 50% of young asymptomatic patients - Independent of valve function - Associated degeneration of aortic media - Etiolog

4、y and mechanisms unknown Aortic Dilatation and BAV Aortic Dilatation and BAV Poor Correlation Between Degree of AS and Aortic Dilation Magrad et al. JTCVS 2001 Media Intima Adventitia Human Aorta Elastic Lamellae of Media Elastin 96: 3891 Fibrillin-1 Deficient Mouse: Progressive Aortic Dilation Verm

5、a S, Circ Res 2001; 88(1): 37 Fibrillin-1 Deficient Mouse: Matrix Disruption in Aortic Media Normal MouseFbn-1 Deficient Mouse Disrupted Matrix Aortic Aneurysm Normal Matrix No Aortic Dilation Fibrillin-1 Deficient Mouse: Fibrillin-1 Deficient Tissues Release MMPs Fibrillin-1 Deficiency Increased Ma

6、trix Metalloproteinases (MMP) Matrix Disruption Aortic Dilation Matrix Disruption in BAV Patients AORTIC MEDIA Tricuspid AV (TAV)Bicuspid AV (BAV) Objective Hypothesis In BAV patients, fibrillin-1 deficiency and increased MMP matrix degradation result in aortic dilation Methods Aorta Fibrillin-1 Con

7、tent Immunohistochemistry Fluorescence Microscopy Quantitative Image Analysis Elastin 126(3): 797-806 Increased MMP-2 Activity Active BAV AortaTAV Aorta Latent * 0 1000 2000 3000 MMP-2 Mean Activity TAV BAV Increased MMP-2 Activity Novel Mechanism of Aortic Dilation FBN-1 Gene Mutation (?) Decreased

8、 FBN-1 Production FBN-1 Deficiency SMC Detachment from Elastin Laminae MMP-2 Release Matrix Degradation Apoptosis Medial Degeneration Aortic Dilatation A Novel Mechanism for Aortic Dilatation Secondary Events Anatomic Patterns of Aortic Dilation Custom Tailoring Required Patterns of Aortic Dilation

9、in Bicuspid Aortic Valves A: aortoventricular jxn B: Sinuses of Valsalva C: Sinotubular jxn D: Tubular ascending aorta E: Proximal innominate F: Distal innominate G: Proximal left subclavian H: Distal left subclavian I: Proximal descending J: Descending at diaphragm Patterns of Aortic Dilation in Bi

10、cuspid Aortic Valves Root (Sinuses) Dilation (Valved Conduit or Repair) Ascending Aorta (Supracoronary Graft) Ascending+Transverse Arch (RAA and Hemiarch) Aortopathy in Bicuspid Valve Borger, Fedak, Verma et al. JTCVS 2005 Current recommendations for replacement of the ascending aorta (RAA): 5.5 cm

11、in diameter 5.0 cm in Marfans patients Kouchoukos NT, Dougenis D. N Engl J Med 1997;336:1876-88 Optimal diameter for RAA in pts undergoing aortic valve surgery is unknown Hinge Point (6cm) may be different in BAV 30 times higher risk of post- operative dissection post AVR if AA 5.0cm Lower threshold

12、 for RAA in BAV patients (because of congenital aortopathy)? To determine incidence of long-term ascending aorta complications (aneurysm, dissection or sudden death) and survival in BAV pts with mild aortic dilatation (40 50 mm) versus no dilatation To determine the threshold diameter for RAA in BAV

13、 patients undergoing aortic valve surgery Diameter of ascending aorta determined by direct measurement, TEE, or intaoperative description: less than 4.0 cm 4.0 4.4 cm 4.5 4.9 cm Patients with aortic diameters 5.0 cm underwent RAA and were excluded BAV Dysfunction Prevalence (%) JTCVS 2005 Valve Pros

14、thesis Prevalence (%) JTCVS 2005 Causes of Reoperation SVD 28 Aortic aneurysm 7 (+11) Endocarditis 3 Pannus formation 2 Aortic dissection 1 Mitral regurg 1 LVOT obstruction 1 Heart transplant 1 Total reoperations = 44 (22%) 11 of these pts also had ascending aortic aneurysms 012345678910 11 12 13 14

15、 15 0 10 20 30 40 50 60 70 80 90 100 Years Postoperatively Free from Composite Outcome (%) 114 64 22 98 58 17 69 44 8 13 10 3 At 15 yrs 4.5 mm43 15% p0.001 JTCVS 2005 Freedom from Aortic Complications 012345678910 11 12 13 14 15 0 10 20 30 40 50 60 70 80 90 100 Years Postoperatively Survival (%) 114

16、 64 22 98 58 17 69 44 8 13 10 3 At 15 yrs 4.5 mm41 14% p=0.004 JTCVS 2005 Long-Term Survival BAV disease is associated with a moderate risk of ascending aortic complications after AVR In BAV patients at the time of AVR, replace the ascending aorta if 4.5 cm in diameter to reduce aortic complications

17、 and improve long-term survival An approach to ascribe moderate dilation to “post-stenotic dilation” may be misleading Isolated AS/AI and AD 4.5 AVR + RAA (supracoronary) Reduction aortoplasty Bentall Valve Repair No valvular involvement and AD 4.5-5 Rate of growth Toronto General Hospital Composi t

18、e Graft Separate Graft N=8 9 N=5 0 Mechanical (55%) Stented- Tissue (16%) Stentless- Tissue (29%) Mechanical (36%) Stented- Tissue (60%) Stentless- Tissue (4%) Aortic diameter increased in 9% by 4-8 mm over the follow up BAV is a common congenital cardiac malformation that occurs during valve develo

19、pment, perhaps due to aberrant gene expression. Disrupted ECM, endothelial injury and changes in cell-death pathways have been implicated in BAV associated aortopathy. BAV implies disease of entire aortic root, and ascending aorta, and predisposes to valve dysfunction, endocarditis, dilation/dissect

20、ion. Several distinct patterns of aortic dilation are prevalent, and require custom tailoring At surgery, attention to early replacement of aorta (4.5) should be given At SMH we have a special interest in following patients with BAV, with or without valvular lesions, to evaluate natural history and

21、timing of surgery Targeting MMP in Aneurysm Remodeling and Rupture Verma S, NEJM 2006 Ongoing Areas of Interest Can statins alter the natural history of BAV disease? Verma S, Errett L et al. Am J Physiol 2005 Does eNOS deficiency and BAV share similar gene loci? Are patients with BAV predisposed to

22、systemic endothelial dysfunction? Verma S, Anderson TJ. CCC 2006 BAV v TAV gene profiling (collaboration with Dr. Robert Roberts) Prospective evaluation of ascending aortic strategy in BAV with AS Etiology and Development of Congenital BAV 1. Abnormal aortic cusp formation. 2. Adjacent cusps fail to

23、 separate, resulting in a single aberrant cusp. 3. Phenotypic continuum (unicuspid, bicuspid, tricuspid) Fedak P, Verma S, Circulation 2002; 106(8):900-4 Fedak, David, Borger, Verma, Expert Rev Cardiovasc Ther 2005 Anomalies Associated With BAV Disease Aortic dilation and aneurysm formation Aortic dissection Aortic coarctation and interruption Coronary anomalies (dominant Cx) VSD, bicuspid PV (rare)