Etiology of Valvular Heart Disease in the 21 st Century
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1 Etiology of Valvular Heart Disease in the 21 st Century Genetic and Molecular Mechanisms Harisios Boudoulas, MD, Dr, Dr Hon. Professor, Academician (ant. mem.) The Ohio State University, USA Biomedical Research Foundation Academy of Athens, Greece
2 VALVE DISEASE Editor Harisios Boudoulas, MD, Dr., Dr. Hon. Mult. Bashore, TM Michler, RA Angouras, CD Boudoulas, K Raman, SV Barbetseas, J Carabello, B Shaver, JA Vavouranakis, M Daniels, CJ Sparks, EA Davies, MJ Wooley, CF Lewis, RP An Overview of Valvular Disease: Incidence and Etiology The Pathology of Aortic Valve Disease The Pathology of Mitral Valve Disease Valvular Heart Disease: Ventricular-Atrial-Aortic Inter-relationships Hemodynamics in Valvular Heart Disease Aortic Valvular Disease Mitral Valve Disease Tricuspid Valve Disease Prosthetic Valves Endocarditis Surgical Perspectives
3 Valvular Heart Disease: Definition Any structural or functional abnormality of a cardiac valve.
4 Mitral Stenosis
5 Valvular Heart Disease: Factors Contributing to Changing Etiology Prostetic Valves Transplantations Hemodialysis
6 Valvular Heart Disease: Prevalence Underestimated in surgical material Patients with cardiomyopathy (ischemic, dilated), chronic renal failure, adults with congenital heart disease, may not be included in the analysis. Nkomo VT, et al. Lancet. 2006; 368: 1005.
7 Valvular Heart Disease: Most Common Causes Today Floppy mitral valve/mitral valve prolapse Biscupid aortic valve Aortic sclerosis/stenosis in the elderly Mitral annular calcification Post interventional therapy Infective endocarditis Associated with other diseases/syndromes Cardiomyopathy (ischemic, dilated, hypertrophic) Chronic renal failure Congenital heart disease in adults (AI in VSD) Heritable connective tissue disorders (Marfan, polycystic kidney disease, aortic ectasia, other) Atrial fibrillation
8 Floppy Mitral Valve Floppy mitral valve (diffused or regional) is the central issue in the mitral valve prolapse, mitral valvular regurgitation story.
9 Floppy Mitral Valve Courtesy of Jos Roelandt, Thoraxcenter, Rotterdam
10 RV Ao LA RV LA LV AL PL PM LV Courtesy Subha Raman, MD, The Ohio State University
11 Floppy Mitral Valve (FMV) Genetics Four generations pedigree of a family with floppy mitral valve/mitral valve prolapse/mitral regurgitation Gene map loci: 16p12.1 p p q31.3 q32.1 xq28
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13 Bicuspid Aortic Valve: Genetics Mutations in different genes with dissimilar patterns of inheritance Gene map loci: 9q q, 59, 13q 10q (ACTA 2 gene) Often is associated with aortopathy
14 Zebrafish
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17 Endocarditis in the 21 st Century
18 Valvular Heart Disease: Associated with other Diseases/ Syndromes Chronic renal failure Congenital heart disease in adults (AI in VSD) Atrial fibrillation Mitral Regurgitation in Cardiomyopathy Papillary muscle dysfunction Changes in LV geometry Annular dilation?
19 Aortic Ectasia Heritable Connective Tissue Disorders (Marfan, Ehler-Danlos, polycystic kidney disease, other)
20 Valvular Heart Disease: Less Common Causes of Special Interest Rheumatic (rare in industrialized, but very common in developing countries) Antiphospholipid syndrome Ankylosing spondylitis (HLA B27) Ergotamine (serotonin), pergoline, cabergoline, other Radiation Fibroelastoma Trauma
21 Etiology of Multiple Valvular Involvement Mitral regurgitation plus tricuspid regurgitation Cardiomyopathy Heritable connective tissue disorders Mitral regurgitation plus aortic regurgitation Heritable connective tissue disorders Mitral stenosis plus aortic stenosis or regurgitation Rheumatic Mitral stenosis plus tricuspid stenosis or regurgitation Rheumatic
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23 Valvular Heart Disease: Molecular Mechanisms
24 Mitral Annular Calcification MAC MAC Burtany et al. Can J Cardiol January 25, 2009 Pomerance A. J Clin Pathol 1970; 23: 354
25 Aortic Sclerosis The role of stethoscope Freeman & Otto. Circulation 2005; 111: 3316
26 Inflammation in Aortic Stenosis Toutoulas K et al. The Aorta: Structure, Function, Dysfunction and Disease. Boudoulas H, Stefanadis C, eds 2009.
27 Computed Tomography (CT) and PET Images in Aortic Stenosis (AS) Marincheva-Savcheva G et al. JACC 2011; 57: 2507 Dweck MR, et al. Circulation 2012; 125: 76-86
28 Relationship Between Cardiovascular Calcification and Bone Mineral Loss Systemic Inflammatory State Local inflammation IL-6 TNF- Artery/valve Bone Circulating phosphate Circulating calcium PTH Mineral Mineral
29 Vascular Pattern in the Basal Region of a Porcine Aortic Valve Cusp Intraleaflet haemorrhage Akahori et al, Eur.Heart J 2011; 32:888
30 Identification of Neoangiogenesis Markers in Calcific Rheumatic Valves Rajamannan NM, et al. Circ 2005; 111:
31 Identification of Neoangiogenesis Markers in Human Degenerative Mitral Valves Rajamannan NM, et al. Circ 2005; 111:
32 Toll-Like Receptors (TLR) 2 and 4 in the Aortic and Pulmonic Valve Yang X, et al. JACC 2009; 53; 491
33 The Role of Pressure and Lipids in Valvular Heart Disease Rajamanan NM. J Cellular Biochem 2011 Rajamanan NM. Circulation 2011; 124: 1783
34 Atherosclerosis and Valvular Heart Disease Similarities Valve Plaque Angiogenesis - rupture Inflammation Toll like receptors Endothelial dysfunction Cardiovascular risk factors (pressure effect) Calcification Time
35 Etiology of Valvular Heart Disease (VHD) in the 21 st Century Concluding Remarks Metamorphosis in etiology of VHD has occurred over the last years Catheter hemodynamics, echocardiography and timing for surgery have dominated in the area of VHD over the last half a century, while genetics/molecular mechanisms related to etiology and the metamorphosis of etiology have received much less attention. VHD is a common cause of morbidity and mortality today; even mild VHD (aortic sclerosis, mitral annular calcification) constitutes a strong prognostic indicator for future cardiovascular events.
36 Etiology of Valvular Heart Disease in the 21 st Centery Concluding Remarks Heritable valve disease (floppy mitral valve, bicuspid aortic valve, aortic ectasia) and calcific aortic stenosis in the elderly are the most common abnormalities requiring surgery today. Family members of patients with heritable valve abnormalities should be studied. Pathogenetic mechanisms related to certain VHD are similar to those of atherosclerosis. Etiology should be taken into consideration for diagnosis and management. Understanding of the basic molecular mechanisms which contribute to the development of VHD will lead to new diagnostic and therapeutic modalities.
37 Valvular Heart Disease: Therapeutic Considerations Atherosclerosis Osteoporosis Aortic Stenosis Hypertension
38 Etiology of Valvular Heart Disease: An Evolution of Thoughts Over the Last Century Prostetic Valves Transplantations Hemodialysis Time
39 René Magritte. La Clairvoyance, 1936
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