3/23/2017 Disclosures Native Valve Endocarditis and its Complications Relevant financial relationships • None SCVP and Binford‐Dammin Society of Infectious Disease Pathologists Off‐label usage Shared Companion Meeting • None USCAP 2017 Annual Meeting Mathieu C. Castonguay, MD, FRCP(C) March 5, 2017 Outline Outline • Basics of infective endocarditis • Basics of infective endocarditis • Epidemiology • Epidemiology • Clinical features • Clinical features • Pathologic features • Pathologic features • Complications • Complications • Differential diagnoses • Differential diagnoses Basics Basics • Definition • Historical overview (“We cannot escape history”) ‐‐ A. Lincoln, 1862 • bacterial or fungal infection of the endocardium • first description (1646, Lazare Rivière) • usually valvular • native (NVE) or prosthetic (PVE) valves “… round carbuncles … resembled a cluster of hazelnuts and filled the opening of the aorta …” 1 3/23/2017 Basics Basics • Historical overview • Historical overview • “valvular vegetation” (1806, Jean‐Nicolas Corvisart) • “valvular vegetation” (1806, Jean‐Nicolas Corvisart) “… perfect resemblance to venereal nodules and cauliflowers … that their nature may be syphilitic” Basics Basics • Historical overview • Historical overview • “endocarditis” (1835, Jean‐Baptiste Bouillaud) • emboli (1852, William Senhouse Kirkes) Coined the word “endocardium” Basics Basics • Historical overview • Historical overview • emboli (1852, William Senhouse Kirkes) • parasitic disease (1869, Emanuel Winge) “filaments … entangled with Endocarditis as a disease with micro‐organisms … short round multi‐systemic manifestations beads or tiny sticks …” 2 3/23/2017 Basics Basics • Historical overview • Historical overview • acute and chronic forms (1885, William Osler) • effective treatments (1940’s onward) Basics Basics • Pathogenesis • Pathogenesis • bacteremia • bacteremia • mucosal or cutaneous entry points • adhesion • adhesins • pre‐existing microthombi (microtrauma) Basics Outline • Pathogenesis • Basics of infective endocarditis • bacteremia • Epidemiology • adhesion • Clinical features • colonization • Pathologic features • proliferation • Complications • thrombosis • Differential diagnoses • inflammation • biofilm 3 3/23/2017 Outline Epidemiology • Basics of infective endocarditis • General (developed world) • Epidemiology • annual incidence 3‐10/100,000 • Clinical features • M : F > 2 : 1 • Pathologic features • 15‐20% in‐hospital mortality • Complications • ~ 40% one‐year mortality • Differential diagnoses • > 25% healthcare‐acquired • > $120,000/patient (US) Epidemiology Epidemiology • Predisposing conditions • Predisposing conditions • structural abnormalities • structural abnormalities • rheumatic disease • intracardiac devices • congenital heart disease • coexisting conditions • unrepaired cyanotic • diabetes mellitus • congenitally BAV • HIV infection • myxomatous mitral valve disease • hemodialysis • degenerative fibrocalcific aortic valve disease • IVDU Epidemiology Epidemiology • Predisposing conditions • Predisposing conditions • structural abnormalities • 50% none identified • intracardiac devices • coexisting conditions • recent invasive procedure • previous endocarditis 4 3/23/2017 Epidemiology Epidemiology • Sites of involvement (clinical) • Sites of involvement (surgical pathology) left‐sided IE (75‐80%) right‐sided IE (10‐15%) left‐sided IE right‐sided IE (90‐95%) (5%) bilateral (1%) Modified from Arch Intern Med 2009; 169: 463‐473 Modified from Cardiovasc Pathol 2013; 22: 19‐27 Epidemiology Epidemiology • Microbiology • Microbiology • Staphylococcus • Staphylococcus • S. aureus • S. aureus • 30% of cases (stable) • coagulase‐negative staphylococci • aggressive disease • 10% (increasing) • healthcare‐related infections • antibiotic resistance • IVDU • aggressive disease • healthcare‐related infections, IVDU Epidemiology Epidemiology • Microbiology • Microbiology • Staphylococcus • Staphylococcus • Streptococcus • Streptococcus • oral (viridans) streptococci • oral (viridans) streptococci • 20% (decreasing) • other streptococci • invasive dental procedures • 10% • group D (S. gallolyticus) colorectal ca 5 3/23/2017 Epidemiology Epidemiology • Microbiology • Microbiology • Staphylococcus • Staphylococcus • Streptococcus • Streptococcus • Enterococcus • Enterococcus • 10% • HACEK organisms • GU/GI • zoonoses 5‐10% • fungal • others Epidemiology Epidemiology • Microbiology • Microbiology • polymicrobial • polymicrobial • 1‐2% • culture negative • 10‐20% • recent antibiotic use • fastidious organism • may decrease with better identification methods Epidemiology • Changes Houston, TX, 1943 Mayo Clin Proc 2010; 85 (5): 422‐426 6 3/23/2017 Epidemiology Epidemiology • Changes • Changes Mayo Clin Proc 2010; 85 (5): 422‐426 BMC Infect Dis 2011; 11: 48 Epidemiology Outline • Changes • Basics of infective endocarditis • Epidemiology • Clinical features • Pathologic features • Complications • Differential diagnoses BMC Infect Dis 2011; 11: 48 Outline Clinical Features • Basics of infective endocarditis • Presentation • Epidemiology • protean • Clinical features • constitutional features of infection • Pathologic features • fever, sweats • Complications • fatigue • Differential diagnoses • anorexia • weight loss • joint pain 7 3/23/2017 Clinical Features Clinical Features • Presentation • Presentation • protean • protean • constitutional features of infection • constitutional features of infection • cardiac findings • cardiac findings • new/changed murmur • vascular phenomena • heart failure • emboli • new conduction abnormality Clinical Features Clinical Features • Presentation • Diagnostic criteria • protean • modified Duke • constitutional features of infection Major criteria Minor criteria • cardiac findings Blood cultures Predisposing condition • vascular phenomena Endocardial involvement Fever • immunologic phenomena Echocardiographic Vascular phenomenon New regurgitation Immunologic phenomenon • glomerulonephritis Microbiological evidence • Osler nodes, Roth spots Clin Infect Dis 2000; 30: 633‐638 Clinical Features Clinical Features • Diagnostic criteria • Diagnostic criteria • modified Duke • modified Duke • definite IE (clinical criteria) • definite IE (pathologic criteria) • 3 major • micro‐organism by culture or histology • 1 major + 3 minor • pathologic lesion confirmed by histology • 5 minor Clin Infect Dis 2000; 30: 633‐638 Clin Infect Dis 2000; 30: 633‐638 8 3/23/2017 Outline Outline • Basics of infective endocarditis • Basics of infective endocarditis • Epidemiology • Epidemiology • Clinical features • Clinical features • Pathologic features • Pathologic features • Complications • Complications • Differential diagnoses • Differential diagnoses Pathologic Features • Local • vegetations Source: dreamicus.com/vegetation.html Pathologic Features Pathologic Features • Local • Local • vegetations • vegetations 71, M • a growth or excrescence of any sort BAV • specifically, a clot, composed largely of fused blood platelets, fibrin, and sometimes microorganisms, adherent to a diseased heart orifice or valve, and often initiated by infection of the structures involved Steadman’s Medical Dictionary, 27th Edition 9 3/23/2017 Pathologic Features Pathologic Features • Local • Local • vegetations • vegetations H&E, 1X Elastic, 1X Pathologic Features Pathologic Features • Local • Local • vegetations • vegetations 56, M Prev MV annuloplasty (IHD) H&E, 10X H&E, 10X Viridans streptococcus S. mitis H&E, 20X Gram, 100X Elastic, 2X Gram, 40X Pathologic Features Pathologic Features • Local • Local • vegetations • vegetations ‐‐ healing 51, M MV prolapse H&E, 1X 10 3/23/2017 Pathologic Features Pathologic Features • Local • Local • vegetations ‐‐ healing • vegetations 44, M Staphylococcus aureus H&E, 10X S. mitis H&E, 4X H&E, 20X Gram, 40X Pathologic Features Pathologic Features • Local • Local • vegetations • vegetation 69, M Urosepsis 31, M BAV Aerococcus urinae Gram, 40X Pathologic Features Pathologic Features • Local • Local • vegetation • vegetation 31, M BAV 31, MBAV Aggregatibacter aphrophilus (HACEK) Gram, 100X 11 3/23/2017 Pathologic Features Pathologic Features • Local • Local • vegetation • perforation 54, M BAV 82, M Degen • frequently submitted to microbiology first AV • cultures, molecular studies * • may not get infected material in surg path lab • integration of all available data is key * S. aureus S. mitis Pathologic Features Pathologic Features • Local • Local • perforation ‐‐ healed • perforation 27, M BAV Shone syndrome (69%) (46%) * H&E, 4X Modified from Cardiovasc Pathol 2013; 22: 19‐27 Pathologic Features Pathologic Features • Local • Local • valve aneurysm • valve aneurysm 43, F BAV (5%) (8%) viridans streptococcus Modified from Cardiovasc Pathol 2013; 22: 19‐27 12 3/23/2017 Pathologic Features Pathologic Features • Local • Local • effect on valve function • effect on valve function • regurgitation • stenosis • combined Modified from Cardiovasc Pathol 2013; 22: 19‐27 Outline Outline • Basics of infective endocarditis • Basics of infective endocarditis • Epidemiology • Epidemiology • Clinical features • Clinical features • Pathologic features • Pathologic features • Complications • Complications • Differential diagnoses • Differential diagnoses Complications Complications • Cardiac • Local • abscess (may progress to fistula) • abscess (25%) (13%) Courtesy of Dr. W. D. Edwards Modified from Cardiovasc Pathol 2013; 22: 19‐27 13 3/23/2017 Complications Complications • Cardiac • Cardiac • rupture (cord or