Cardiovascular Surgical Pathology Case 1
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1 Cardiovascular Pathology Specialty Conference USCAP, Boston, MA March 11, 2009 Cardiovascular Surgical Pathology Case 1 (No Disclosures; No Conflicts of Interest) William D. Edwards, M.D. Dept of Lab Medicine & Pathology Mayo Clinic, Rochester, MN
2 Case 1 Clinical History (73,M) Referral to Mayo Clinic Worsening chest pain and SOB Past medical history Exertional chest discomfort (2 yr) History of present illness Exertional chest pain (2 wk) More frequent than previously More intense than previously Now radiates to left shoulder Nocturnal chest pain (2 wk)
3 Case 1 Clinical History (73,M) Coronary angiography 100% occlusion of prox RCA 99% stenosis of prox LAD 80% stenosis of LAD-D1 80% stenosis of LCX-OM1 Echocardiography Severe aortic stenosis (0.6 cm 2 ) Moderate mitral regurgitation LV EF 34% (normal, 50-70%) Moderate LV and LA dilatation
4 Case 1 Clinical History (73,M) Clinical diagnoses Severe coronary artery disease Unstable angina pectoris Severe aortic stenosis Moderate systolic dysfunction Surgical procedures Coronary artery bypass surgery Aortic valve replacement, with 23-mm Carpentier-Edwards bovine pericardial bioprosthesis
5 Case 1 Aortic Valve Ao Aspect LV Aspect
6 Case 1 Aortic Valve Fibrocalcific Cusps (Gross & Micro)
7 Case 1 Aortic Valve Microscopy None! Case 1 Aortic Valve
8 Case 1 Diagnosis Heart, aortic valve, excision: Degenerative fibrocalcific aortic valve disease, associated with clinically severe aortic stenosis and no aortic regurgitation
9 Lecture Outline Mechanisms Causes Degenerative Bicuspid Rheumatic Myectomy Trends Summary
10 Mechanisms What processes interfere with valve opening? Calcification Any region Fibrosis Cusps Normal AV Fusion Commissures
11 Lecture Outline Mechanisms Causes Degenerative Bicuspid Rheumatic Myectomy Trends Summary
12 Causes and Demographics Causes % Age* M:F Degenerative :1 Bicuspid :1 Rheumatic :1 Other 5 <70 1:1 * Age at time of surgery (in years)
13 Lecture Outline Mechanisms Causes Degenerative Bicuspid Rheumatic Myectomy Trends Summary
14 Degenerative Type Calcium in Valve Pockets (Autopsy)
15 Degenerative Type 3 Cusps (Surgical) Calcium (X-Ray)
16 Degenerative Type Mild Commissural Fusion (Surgical)
17 Degenerative Type Unequal Sized Cusps (Surgical)
18 Degenerative Type Fenestrations and Strands (Surgical)
19 Degenerative Type Age-related abnormalities In U.S. population >65 yr old * Aortic valve sclerosis: 25% Aortic valve stenosis: 5% Pathogenesis of aortic stenosis Not by random wear-and-tear Interplay of numerous factors * Assessed by echocardiography
20 Degenerative Type Atherosclerotic risk factors Hyperlipidemia (esp apolipoprotein B, 2, & E), with Ox-LDL in valve; hypertension, age, & diabetes Inflammation and proliferation T cells, macrophages, monocytes, plasma cells, B cells, mast cells CAM s, TGF-β, TNF-α, MMP, BMP Myofibroblasts (GF, angio II, NO) Neoangiogenesis (VEG-F, PDGF)
21 Degenerative Type Calcification and ossification Cellular osteoblast-like phenotype Alkaline phosphatase, osteopontin, osteocalcin, osteonectin, bone sialoprotein, & tenascin-c Microfocal gross mass (CaPO 4 ) Genetic and metabolic factors Osteoporosis and aortic stenosis Vitamin D receptor polymorphism Apolipoprotein E4 allele
22 Degenerative Type Diagram (Circulation 2005;111:3316)
23 Degenerative Type Inflammation Calcium Calcium and Inflammation (H&E)
24 Degenerative Type Chronic Inflammation (H&E, High Power)
25 Degenerative Type T Cells (CD3) B Cells (CD20) Mac s (CD68) Mast Cells (SAB) Inflammation (Special Stains)
26 Lecture Outline Mechanisms Causes Degenerative Bicuspid Rheumatic Myectomy Trends Summary
27 Congenitally Bicuspid Valve Raphe (RAY-fee) Two Cusps (Autopsy)
28 Congenitally Bicuspid Valve Raphe 2 Cusps (Surgical) Calcium (X-Ray)
29 Congenitally Bicuspid Valve Location of Raphe (n = 567; 7 Studies) P P P R L R L R L Right-Left 460 (81%) Right-Post 90 (16%) Left-Post 17 (3%) Diagram (Mayo Clin Proc 1999;74:14-26)
30 Congenitally Bicuspid Valve Relative Size of Cusps (n = 524) 180º 0º 150º 30º Equal 27 (5%) Unequal 484 (92%) Thirds 13 (2%) Diagram (Mayo Clin Proc 1999;74:14-26)
31 Congenitally Bicuspid Valve Equal (5%) Unequal (90%) Thirds (5%) Relative Cusp Size (Surgicals)
32 Congenitally Bicuspid Valve Raphe Commissural Fusion (Surgical)
33 Congenitally Bicuspid Valve Raphe Commissural Fusion (Surgical)
34 Congenitally Bicuspid Valve Atypical BAV Seen With Regurgitation > Stenosis Raphe Raphe Fenestrated Raphe (Surgical)
35 Congenitally Bicuspid Valve Occurrence Incidence (%): 1-2 Sex (M:F ratio): 2-3:1 Fate (by age 75) % Stenosis 85 Regurgitation 10 Infection 3 Dissection 2 Normal 0
36 Congenitally Bicuspid Valve Etiology Inheritance: autosomal dominant trait, with incomplete penetrance Mutation: Notch-1 gene encoding for membrane receptor important for normal cardiac development Association: defective microfibrils in aortic valve & ascending aorta Result: weak mechanical support (fibrocalcific valve, dilated aorta)
37 Congenitally Unicommissural Valve Opened and Closed (Autopsy)
38 Congenitally Unicommissural Valve R R Fibrosis (Surgical)
39 Congenitally Unicommissural Valve R R Calcification (Surgical)
40 Congenitally Unicommissural Valve 1 Cusp (Surgical) Calcium (X-Ray)
41 Lecture Outline Mechanisms Causes Degenerative Bicuspid Rheumatic Myectomy Trends Summary
42 Rheumatic Type Fibrocalcific (Autopsy) Candlewax
43 Rheumatic Type Fibrosis (Surgical) Calcium (X-Ray)
44 Rheumatic Type C C C Three Fused Commissures (Surgical)
45 Rheumatic Type Two Fused Commissures (Surgical)
46 What Type Is It? Rheumatic, Bicuspid, or Degenerative? One Fused Commissure (Surgical)
47 What Type Is It? Rheumatic Type What if no history of rheumatic fever? Postinflammatory (probably rheumatic) One Fused Commissure (Surgical)
48 Lecture Outline Mechanisms Causes Degenerative Bicuspid Rheumatic Myectomy Trends Summary
49 Subaortic Septal Myectomy Ao RV LA LV Long-Axis View Angled Septum in Elderly (Autopsy)
50 Subaortic Septal Myectomy Gross Usually <10 g Multiple pieces Microscopy Hypertrophy & focal fibrosis H&E stain only Amyloid stain if >65 years old (CR or SAB) Surgical Tissue
51 Lecture Outline Mechanisms Causes Degenerative Bicuspid Rheumatic Myectomy Trends Summary
52 70 60 Aortic Stenosis Past Trends 1159 Surgically Excised Valves Cases (%) Degenerative Bicuspid Year Rheumatic
53 Past and Future Trends Changes ( ) & Projections ( ) 65 and over 85 and over U.S. Census Bureau (1993)
54 Future Trends Prevalence of various causes Degenerative: steady increase Bicuspid valve: stable rate (1-2%) Rheumatic: steady decrease Natural history of symptomatic AS High risk for sudden death ( CPR) 5-yr survival: 50% (worse than CA) Effective therapy for aortic stenosis Aortic valve replacement (surgery) Major impact on health care costs
55 Lecture Outline Mechanisms Causes Degenerative Bicuspid Rheumatic Myectomy Trends Summary
56 Summary Handling surgical specimens Diagnostic versus research purposes Routine diagnostic evaluation Gross examination (no microscopy) Raphe vs commissural fusion Raphe: shallow, single ridge, obtuse Fusion: high, two cusps, acute angle Calcium: difficult distinction if marked
57 Summary Comparison of Surgical Specimens
58 Cardiovascular Pathology Specialty Conference USCAP, Boston, MA March 11, 2009 Case 1 Surgical Pathology of Aortic Valve Stenosis William D. Edwards, M.D. Dept of Lab Medicine & Pathology Mayo Clinic, Rochester, MN
59 References Textbooks Schoen FJ, Edwards WD. Valvular heart disease: general principles and stenosis. In Cardiovascular Pathology, 3/e. MD Silver, AI Gotlieb, FJ Schoen (ed). Churchill Livingstone, New York, 2001: R Virmani, A Burke, A Farb, JB Atkinson. Pathology of cardiac valves. In Cardiovascular Pathology, 2/e. WB Saunders Co, Philadelphia, 2001:
60 Surgical Pathology Aortic Stenosis References Butany J, Collins MJ, El Demellawy D, et al. Morphological and clinical findings in 247 surgically excised native aortic valves. Can J Cardiol 2005;21: Chuangsuwanich T, Warnnissorn M, Leksrisakul P, et al. Pathology and etiology of 110 consecutively removed aortic valves. J Med Assoc Thai 2004;87:
61 Surgical Pathology Aortic Stenosis References Dare AJ, Veinot JP, Edwards WD, Tazelaar HD, Schaff HV. New observations on the etiology of aortic valve disease: a surgical pathologic study of 236 cases from Hum Pathol 1993;24: Turri M, Thiene G, Bortolotti U, et al. Surgical pathology of aortic valve disease: a study based on 602 specimens. Eur J Cardiothorac Surg 1990;4:
62 Surgical Pathology Aortic Stenosis References Peterson MD, Roach RM, Edwards JE. Types of aortic stenosis in surgically removed valves. Arch Pathol Lab Med 1985;109: Subramanian R, Olson LJ, Edwards WD. Surgical pathology of pure aortic stenosis: A study of 374 cases. Mayo Clin Proc 1984;59:
63 Bicuspid Aortic Valve Aortic Stenosis References Sievers HH, Schmidtke C. A classification system for the bicuspid aortic valve from 304 surgical specimens. J Thorac Cardiovasc Surg 2007;133: Sabet HY, Edwards WD, Tazelaar HD, Daly RC. Congenitally bicuspid aortic valves: a surgical pathology study of 542 cases (1991 through 1996) and a literature review of 2,715 additional cases. Mayo Clin Proc 1999;74:14-26.
64 References Temporal Changes in Etiology Edwards WD. The changing spectrum of valvular heart disease pathology. In: Harrison s Advances in Cardiology. E Braunwald (ed). McGraw-Hill, New York, 2003: Passik CS, Ackermann DM, Pluth JR, Edwards WD. Temporal changes in the causes of aortic stenosis: a surgical pathologic study of 646 cases. Mayo Clin Proc 1987;62:
65 Histopathology Aortic Stenosis References Somers P, Knaapen M, Mistiaen W. Histopathology of calcific aortic valve stenosis. Acta Cardiol 2006;61: Matthias Bechtel JF, Noack F, Sayk F, et al. Histopathological grading of ascending aortic aneurysm: comparison of patients with bicuspid versus tricuspid aortic valve. J Heart Valve Dis 2003;12:54-59.
66 References Subaortic Septal Myectomy Allen RD, Edwards WD, Tazelaar HD, Danielson GK. Surgical pathology of subaortic septal myectomy not associated with hypertrophic cardiomyopathy: a study of 98 cases ( ). Cardiovasc Pathol 2003;12:
Case 1 Clinical History (73,M) Cardiovascular Surgical Pathology Case 1. Case 1 Clinical History (73,M) Case 1 Clinical History (73,M)
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