3/23/2017

Disclosures Native Valve 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 • 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 • 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 disease • hemodialysis • degenerative fibrocalcific 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 • • 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 papillary muscle) • cusp prolapse 47, F Recent ERCP 68, F Cirrhosis

H&E, 1X

C. albicans S. aureus H&E, 4X Gram, 100X H&E, 2X GMS, 40X

Complications Complications

• Cardiac • Cardiac • septic /vasculitis • (embolic) 52, M BAV 70, F

H&E, 20X

S. aureus H&E, 10X H&E, 2X

Complications Complications

• Cardiac • Systemic • • emboli 52, M BAV

S. aureus H&E, 10X H&E

14 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

Differential diagnoses Differential diagnoses

• Non‐bacterial thrombotic endocarditis (NBTE) • Non‐bacterial thrombotic endocarditis (NBTE) • sterile valve thrombi 69, M Degen • risk factors AV • structurally abnormal valves

• hypercoagulable states AV • endothelial damage

MV

Differential diagnoses Differential diagnoses

• Non‐bacterial thrombotic endocarditis (NBTE) • Fenestrations • age‐related degenerative change (semilunar valves) • no functional significance

H&E, 4X Elastic, 4XMV

15 3/23/2017

Differential diagnoses Differential diagnoses

• Fenestrations • Valvular dysplasia • congenitally abnormal valves

*

Differential diagnoses Differential diagnoses

• Valvular dysplasia • Valvular dysplasia

23, M Unicuspid Hyperbilirubinemia AV

Differential diagnoses Differential diagnoses

• Valvular dysplasia • Traumatic perforation • iatrogenic • other

16 3/23/2017

Differential diagnoses Differential diagnoses

• Traumatic perforation • Traumatic perforation

Conjoined cusp 52, M BAV ? NBTE

*

*

Differential diagnoses Differential diagnoses

• Traumatic perforation • Traumatic perforation

Conjoined cusp ? NBTE 52, M BAV

* ? *

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

17 3/23/2017

Selected References

1. Cahill TJ, et al. Challenges in Infective Endocarditis. J Am Coll Cardiol 2017; 69 (3): Native Valve Endocarditis 325‐344 and its Complications 2. Correa de Sa DD, et al. Epidemiological Trends in Infective Endocarditis: A Population‐Based Study in Olmsted County, Minnesota. Mayo Clin Proc 2010; 85 (5): 422‐426 SCVP and Binford‐Dammin Society of 3. Murdoch DR, et al. Clinical Presentation, Etiology, and Outcome of Infective Infectious Disease Pathologists st Endocarditis in the 21 Century. Arch Intern Med 2009; 169 (5): 463‐473 Shared Companion Meeting 4. Fedeli U, et al. Increasing Incidence and Mortality of Infective Endocarditis: A USCAP 2017 Annual Meeting Population‐Based Study Through a Record‐Linkage System. BMC Infect Dis 2011; 11: 48 5. Castonguay MC, et al. Surgical Pathology of Native Valve Endocarditis in 310 Mathieu C. Castonguay, MD, FRCP(C) Specimens from 287 Patients (1985‐2004). Cardiovasc Pathol 2013; 22: 19‐27 March 5, 2017

18