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Burn-out rheumatic mitral valve disease: Morphology and predictability of repair Charles A. Yankah, MD, PhD. Deutsches Herzzentrum Berlin / Charité Medical.

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Presentation on theme: "Burn-out rheumatic mitral valve disease: Morphology and predictability of repair Charles A. Yankah, MD, PhD. Deutsches Herzzentrum Berlin / Charité Medical."— Presentation transcript:

1 Burn-out rheumatic mitral valve disease: Morphology and predictability of repair Charles A. Yankah, MD, PhD. Deutsches Herzzentrum Berlin / Charité Medical University Berlin DHZB Charité

2 Throat infection by Group A Streptococci Rheumatic fever and heart disease in Africa Prevalence: 24/1000, Age: 5-22 years

3 Cases per 100,000 population USA Time (years) 1920 Ayoub EM. Postgrad Med 1992;93: Denmark Decline in Rheumatic Fever in Developed Countries

4 Prevalence of CVD among children in Liberia Screened population: 5197 children Prevalence0.34% Distribution of cardiovascular diseases Congenital 58% Rheumatic 16.7% Others25.3% Yankah et al. Tropical Cardiology, 1981 Pure MS: 48.7%, Pure MR: 7.7%, Mixed: 42.3% Rettig, Ghana, 2007

5 Prevalence of rheumatic heart disease Clinical vs echocardiographic diagnosis CambodiaMozambique n=3677n=2170 Age12 years11 years Boys52%48% Clinical 2.2/ /1000 Echo 21.5/ /1000 Marijon et al. N Engl J Med 2007

6 Patients in the ambulance of CHUB / Butare Ruanda Uwe Schultz, Der Kardiologe, 2009, Vol. 3, No. 5

7 Causes of heart insufficiency Butare Heart Failure Study Valvulopathy 38% Others ( e.g. EMF,Pericarditis) 6% Cor pulmonale 17% Hypertensive heart failure 11% Dilatative Cardiomyopathy 28%

8 Death due to rheumatic heart disease in relation to all cardiovascular deaths

9 Rheumatic heart valve disease ► 36% of surgical load– Nigeria ► 52.8% – Abidjan Pure MR Mixed lesion Burden of rheumatic heart disease in West Africa Bertrand et al.; Abidjan, Ivory Coast, 1979,

10 Contemporary Use of Mitral Valve Repair 49%Repair 51%Replacement Society of Thoracic Surgeons Database, 2003 n= %Replacement 46.5%Repair Euro Heart Survey Iung et al, Eur Heart J 2003;24:1231 n=115 Frequency of MV repair?

11 Mitral valve rheumatic valvulitis and degeneration Acute valvulitis Subacute valvulitis Binotto et al. Images Paediatr Cardiol 2002;11:12-25 Fibroelastic deficiency Pliable valve with mild fibrosis Severe calcification Post rheumatic valvulitis

12 Native and allograft aortic valve degeneration Normal native aortic valve Fibrotic degenerative native AI Severe calcific degenerative native AS Calcific degenerative allograft AS

13 Schematic representation of the pathogenesis of rheumatic heart disease (carditis, valvulitis) Binotto et al. Images Paediatr Cardiol 2002;11:12-25 A molecular mimicry between streptococcus M protein and human proteins (myosin, tropo- myosin, vimentin) as triggering factor for leading to autoimmunity in RF and RHD

14 Pathogenesis of rheumatic heart disease: Molecular mimicry between strept. M protein and human proteins (myosin, tropo-myosin, vimentin) as triggering factor for leading to autoimmunity in RF and RHD

15 Myocardial Aschoff body – large, elongated, large nuclei/multinucleate cells Binotto et al. Images Paediatr Cardiol 2002;11:12-25 Histology of a Normal Heart and Rheumatic Carditis Normal heart histology

16 Cytokines produced by infiltrating mononuclear cells from heart tissue fragments of RHD patients. IFN- gamma, TNF- alpha, IL-4, and IL-10 (Peroxidase (DAB) and alkaline phosphatase (Fast Red) immunohistochemistry ). Aschoff bodies are indicated by short arrows and mononuclear infiltrating cells by long arrows. neutrophilic infiltrations by long arrows. H&E stain. Original magnifications: x160 (A–D); x20 (E, F). Guilherme et al. Am J Pathol 2004;165: Rheumatic Fever and Rheumatic Heart Valve Disease: Autoimune Humoral and Cellular Responses A B CD E F

17 Histologic and immunohisto- chemical findings of control valves. (A) Valvular leaflets obtained from the control group showed well-preserved leaflet architecture without fibrosis or inflammatory cell infiltration (H&E, ×40). (B) Immunohistochemical staining for TGF- 1 demonstrated positivity in the subendothelial stroma of valvular leaflets (TGF- 1, ×40). B A

18 (A)Rheumatic mitral valves showed severe fibrosis and distorted architecture (H&E, ×40). (B)A high-power view demonstrated small thin-walled vessels and perivascular lymphocytic infiltration (H&E, ×200). Kim et al. J Korean Med Sci 2008;23:41-8 Histology and immunohistochemistry of rheumatic mitral valves. A B

19 (C) High TGF- 1 expression was seen in the endothelial cells and smooth muscle cells of the vessels, in the perivascular interstitial cells, and stroma of the valves (×200). (D) Myofibroblasts that were positive for SMA immunostaining were present in the subendothelial densely fibrotic area (×40). Kim et al. J Korean Med Sci 2008;23:41-8 TGF- 1 expression in rheumatic mitral valve C D

20 Pathways of molecular mechanism of rheumatic heart and valve diseases Endo-myocarditis, Myocarditis, Valvulitis Angiotensin II ▼ Tenascin-C regulation of cell behaviour ▼ EMT stimulation by Endothelin ▼ Myofibroblast proliferation Myocardial fibrosis Endomyocardial fibrosis (EMF) Chondromulin (downregulation) ▼ VEGF-A expression ▼ Vascularisation ▼ VIC ►Myofibroblast proliferation Fibrosis Calcification TGF: Transforming Growth Factor; VEGF: Vascular Endothelial Growth Factor; VIC: Vascular Interstitial cells; EMT: Endothelial- to-Mesenchymal Transition; Ref.: Kim et al. J Korean Med sci 2008, 23: 41-8; Hakuno et al J Mol Med 2006, 12: TGF-Beta1 expression

21 Pathways of Molecular Mechanism of Rheumatic Valve Disease Native valves Immune reaction Inflammatory process by: Streptococcal toxin endocarditis Bacterial endocarditis Allogra fts (Homografts) EMT stimulation by endothelin Vascularisation VIC (mesenchymal profibrotic cells)  Myofibroblast proliferation Valvular fibrosis Calcification EMT: Endothelial to mesenchymal transition, TGF: Transforming growth factor, VIC: Vascular interstitial cells EMT: Endothelial to mesenchymal transition, TGF: Transforming growth factor, VIC: Vascular interstitial cells VEGF –A expression Remodeling of valve matrix Angiotensin II


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