105: INFECTIVE ENDOCARDITIS

EPIDEMIOLOGY Infective endocarditis = infection of the endocardial surface of the heart; heart valves are most commonly affected but can also occur on septal defects or on the mural endocardium Classification based on causative organism, anatomic site, and whether valve is native or prosthetic; acute/subacute classification less useful Mean age 60yo Decreasing importance of rheumatic heart disease Increasing importance of prosthetic heart valves Most have risk factor(s)... Rheumatic heart disease Prosthetic heart valve Intravenous drug abuse Pace maker AV fistulas, hemodialysis shunts Mital valve prolapse (with regurgitation) Other congenital heart disease patent ductus arteriosus ventricular septal defect coarctation of aorta hypertrophic obstructive cardiomyopathy bicuspid aortic valve tetrology of fallot Degenerative heart disease calcified mitral annulus astherosclerosis post-myocardial infarction Five steps of pathogenesis

PATHOGENESIS

(1) (2) (3) (4)

(5)

Endothelial injury: turbulent flow secondary to structural heart disease, damage from particulate matter from injection of drugs Nonbacterial thrombotic endocarditis: deposition of platelets and fibrin, may heal without becoming infected Bacteremia: transient (toothbrushing, flossing, dental procedures, GI/GU procedures) or sustained from another site of infection Adherence: bacteria adheres to platelet-fibrin matrix (NB: complement mediated bactericidal activity clears gram -ves easily but not gram +ves thus gram -ve endocarditis much less common than gram +ves) Endocardial lesions/vegetations develop/enlarge: leads to complications Complications Intracardiac mechanical obstruction of valves or rupture of papillary muscles and/or intraventricular septum -----> heart failure

myocardial abcess with invasion of AV node or conducting system may cause heart block or other conduction abnormalities Extracardiac septic emboli: pulmonary, cerebral, eye, kidney, spleen, intestine, vascular tree, joints, skin can lead to PE, blindness/endopthalmitis, renal failure, splenic/intestinal ishcemia, limb ischemia, mycotic aneurysms, septic arthritis, janeway lesions immune complexes: glomerulonephritis, arthritis, cutaneous vasculitis (oslers nodes) Locations Mitral Valve 50% Aortic Valve 25% Aortic/Mitral 15% Tricuspid 10% (Most common site with IVDA) Pulmonic 1% MICROBIOLOGY Native Valve Endocarditis Strep viridans 40% Staph aureus 25% Strep enterococci 10% Strep bovi 5% (GI cancer association) Staph epidermis 3% Fungi, HACEK,etc 15% Prosthetic Valve Endocarditis Early (< 2 months) Staph epidermidis (CNS) 30% Staph aureus 20% Strep species 10% Gram -ve bacilli 20% Fungi/other 20% Late (> 2 months) Strep viridans 40% Staph epidermidis 25% Staph aureus 10% Gram -ve bacilli 15% Fungi/other 12% IVDA Endocarditis Staph aureus 40% Pseudomonas 20% Candida 15% Enterococci 15% Culture Negative Endocarditis Previous antibiotics, nutritionally deficient strept species, or Fastidious organism (must continue culture for up to 3

weeks) H Hemophilus A Actinobacillus C Cardiobacterium E Eikenella K Kingella

COMMON CAUSES OF INFECTIVE ENDOCARDITIS Native Valve Endocarditis

. Strep viridans . Staph aureus Early Prosthetic Valve Endocardtis . Staph epidermidis . Staph aureus Late Prosthetic Valve Endocarditis . Strep viridans . Staph epidermidis IVDA Endocarditis 16712. Staph aureus 16713. Pseudomonas

CLINICAL MANIFESTATIONS History Fever (intermittent) 80% (90% in IVDAs) Malaise 80% Weakness 40% Dyspnea 40% Night sweats 25% Weight loss 25% Stroke symptoms 20% Arthralgia 15% Physical Examination Fever 90% Murmur 85% (as low as 35% in VDAs) Embolic events 40% Skin findings 30% Splenomegaly 30% Retinal changes 10% Clubbing 10% Periphal Stigmata of Infective Endocarditis Oslers nodes: painful erythematous nodules on finger tips from immune complex related vasculitis Janeways lesions: painless erythematous, flat, macular lesions on palms/soles that blanch with pressure related to emboli to skin

Roth spots: retinal hemorrhages with pale center surrounded by halo Flame shaped retinal hemorrhages Splinter hemorrhages Laboratory Evaluation Anemia of chronic disease depending on duration Leukocytosis variable ESR elevation sensitive but nonspecific RF positive in 50% if illness > 6 weeks Blood cultures X 3 essential (+ve in 90%) Urine rbc.s/protein re complement related GN +/- renal emboli Diagnostic Evaluation ECG: look for first degree heart block with abcess invasion of AV node Mainly a clinical diagnosis and high index of suspicion most important Transthoracic echo 50 - 80% sensitive and 95% specific Transesophageal echo 90 - 95% sensitive and 95% specific Criteria for diagnosis do exist

MANAGEMENT OF INFECTIVE ENDOCARDITIS May need aggressive approach if in septic shock Indications for surgery Significant congestive heart failure Failure of medical treatment Multiple serious embolic complications Prosthetic endocarditis (most) Large vegetation Local suppurative complications (valve abcess, heart block) Anticoagulation Does anticoagulation risks outweigh benefit of reduced embolic events? Let specialists decide Empiric Antibiotics

KEY POINTS WITH INFECTIVE ENDOCARDITIS 1. Fever and new murmur = IE until proven otherwise

2. 3. 4. 5. 6. 7. 8.

IVDA + fever/no murmur = IE until proven otherwise IVDA + murmur = IE until proven otherwise IVDA + tricuspid regurg = IE until proven otherwise Blood cultures before antibiotics unless patient crashing IV antibiotics early, large doses, long treatment Complications may be presenting feature Absence of Roth spots, Oslers nodes, splinters, Janeway lesions, splenomegaly, clubbing does NOT rule out endocarditis Native Valve, no IVDA, subacute course PenG 4 X 10^6U iv q6hr or Vancomycin 15 mg/kg iv q6hr plus Gentamycin 1 mg/kg iv q 12hr Prostehtic Valve, IVDA, acute course Nafcillin 2gm iv q4hr + Gentamycin 1 mg/kg iv q12hr + Ampicillin 2 gm iv q4hr or Vancomycin + Gentamycin

VALVULAR HEART DISEASE

AORTIC STENOSIS Etiology Congenital: supravalvular, valvular (bicuspid valve), subvalvular Acquired: rheumatic fever, degenerative (calcific), syphilis Overall: bicuspid calcific 60% (60yo), degenerative calcific 20% (>60yo), rheumatic 20% Pathophysiology Pressure overload is cardinal feature resulting in LV outflow obstruction leads to severe LVH, LV dilates and eventually LVP and LAP rise LVH compensates well :. asymptomatic until late stages LVH increases O2 demand :. relative myocardial ischemia with angina History Angina (5yr survival): can have normal coronaries, angina due to hypertrophy Syncope (3yr survival): very high LVP , mechanoreceptor reflex bradycardia :. syncope = Vasojaris reflex Heart failure (2yr survival) Exersional dyspnea Risk for sudden death Classic triad = SOBOE + angina + exersional syncope\ Physical

Systolic ejection murmur; low frequency, loudest at aortic area, +/- thrill, radiates to carotids and LSB. Maneuvers: heard best w/ Pt sitting and leaning forward, increase w/ hand grip rules out aortic stenosis Gallavarden murmur: blowing murmur at mitral area (similar to MR) due to transmition of the high frequency sound through heart muscle; only the high freq component of the murmur is heard @ apex; sign of severe aortic stenosis Early diastolic murmur: occurs when regurgitation is associated w/ stenosis Pulsus parvus (low intensity) et tardus (slow upstroke) Apex forceful + sustained +diffuse, but usu not cardiomegaly Heart sounds: normal S1, soft or absent S2 (valve too stiff that it barely opens), S4 (early, due to LVH), S3 late with CHF. Paradoxical splitting of S2 with severe obstruction (delayed LV ejection thus S2 is split in expiration) ECG/CXR ECG: LVH + strain; AF is rare but may occur, LBBB may occur CXR: Dilated ascending aorta = post stenotic dilatation, heart size is frequently normal, LVH may not be apparrent, calcification on lateral view Management Asymptomatic: endocarditis prophylaxis, avoid strenuous exercise Indications for valve replacement: mainly onset of symptoms (angina, syncope, CHF is surgical emergency) or high gradients > 50mmHg Balloon valvotomy vs replacement Careful with afterload reduction Prognosis Most common fatal valve lesion Early mortality/sudden death with ventricular arrymias MCC of sudden death Complications: SBE, complete heart block 5yr survival w/ angina; 3yr survival w/ syncope, 2yr survival w/ CHF

AORTIC REGURGITATION Etiology Acute: aortic dissection (dissecting aneurysm), endocarditis (most common of acute), perforation of sinus of valsalva Chronic: rheumatic fever, bicuspid valve, post endocarditis, aortic dilatation (HTN, coarctation, rheumatoid or syphilitic aortitis, AS, aneurysm, connective tissue diseases like marfans Pathophysiology LV volume overload :. increased SV and LV dilation;

ascending aorta dilation Increased LVEDV, increased LAV, early MV closure (dec S1) History Angina, arrythmia (palpitations), CHF symptoms Physical Early diastolic murmur: high frequently, blowing quality, loudest at left sternal border with Pt sitting forward, radiates to apex if loud, maneuvers: Pt sitting forward and must hold breath in exhalation Mid diastolic murmur = Austin Flint murmur: regurgitant murmur flows against septal mitral leaflet and causes, pseudo-mitral stenosis; heard at mitral area, differentiated by the absence of a loud S1 in AR which is usu heard in mitral stenosis Systolic ejection murmur: increased flow Pulse: bounding pulse (inc volume), collapsing pulse (water-hammer), wide pulse pressure (>60mmHg), corrigans sign (visible carotid pulse), demussets sign (head bobbing with wide pulse pressure), Quinckes sign (pulsatile blushing of nail bed) Duroziezs murmur - to and fro murmur over femoral a. w/ light compresn Hills sign - SBP difference of >15 b/w brachial and femoral aa. Pistol shot sounds over femoral aa. Apex: displaced to the left + diffuse + forceful (LV enlargement) + sustained Heart sounds: soft S1 - due to preclosure of MV by the regurgitant flow, soft S2, S3 in severe AR, S4 uncommon, ejection click ECG/CXR ECG: LVH + strain, LBBB, LA enlargement, P mitrale in lead II CXR: LV dilatation (always) :. cardiomegaly always present, increased LA, LV failure, ascending aorta dilated Management Sould correct b/f permanent LV damage; must repair when symptoms start Medical management asymptomatic with EF > 50% and LVESD < 55mm afterload reduction improves LV function and reduces regurgitant jet; nifedipine or ACE-Is; can delay surgery 2-3yrs Surgical management asymptomatic; surgery if EF < 55% or LVESD > 55mm replace if symptomatic Acute aortic regurgitation endocarditis is most common cause; aortic

dissection also surgical emergency b/c LV doesnt have time to compensate diagnosis: diastolic murmur + soft S1 stabilize with afterload reduction, diuretics, intra-aortic balloon pump until patient can get to OR MITRAL STENOSIS Etiology Congenital: very rare, found only in newborns Aquired: rheumatic (most common), mitral annular Ca++ Pseudostenosis: myxoma = benign tumor of heart which causes obstruction Pathophysiology Decreased LV filling, LV small but has normal systolic function, increased LAP, atrial fibrillation very common result of this Also leads to pulmn HTN, RVH, RV dilatation ---- RV failure, and TR History CHF symptoms History of stroke re Afib Bronchitis like symptoms re pulmonary venous HTN Physical Mid diastolic rumble w/ presystolic accentuation: low frequency, heard best at apex, little or no radiation, fouttata-rou, maneuvers: place bell exactly on the PMI, Pt in left lateral position, mild exercise to accentuate murmur; diastolic thrill, palpable S1; presystolic murmur absent if Pt in AF Pulses: weak, narrow, and irregular b/c of AF Heart sounds: loud S1 (differentiation from Austin Flint murmur; mitral shuts very hard), opening snap (OS) (sudden opening of mitral valve if calcified), normally split S2 with loud pulmonic cmpt b/c of pulmn HTN Cyanosis: stagnant hypoxia; malar flush, mucosa, finger tips cyanosed RV heave from pulmonary HTN RV failure: JVD, edema, ascites, hepatomegaly S2 - 02 interval prognosticator: decreased S2 - OS interval is a bad sign; this means that the mitral valve opens earlier b/c of increased LAP ECG/CXR ECG: p mitrale (lead II, V1), RVH, AF (very common) CXR: increased LA size, signs of Management Medical: anticoagulation with MS, rate control AF, manage CHF Surgical: balloon valuloplasty, valvotomy, valve replacement depends on severity, gradients,

complications, and onset Natural History Symptoms arise >20 yrs after rheumatic fever Severe incapacitation develops 10 yrs after onset of symptoms Major complication is AF and systemic embolism and CVA Other: hemoptysis (pulmn HTN), PE, SBE (rare), respiratory infections, pulmonary hemorrhage from ruptured bronchial venous connections

MITRAL REGURGITATION Etiology Acute: rupture of chordae tendinae, papillary muscle or perforation of valve; most common in setting of MI, endocarditis, or trauma Primary chronic: myxomatous degeneration, mitral valve prolapse (+/- myxomatous degeneration), rheumatic, endocarditis, ischemic heart disease, congenital Secondary chronic: LV dilatation, hypertrophic cardiomyopathy, mitral annular calcification Pathophysiology Diastolic volume overload :. increased LV size Preload - afterload mismatch Increased LAP :. pumn HTN and eventually right heart failure EF 70% (>normal) History CHF symptoms Afib/palpitations Physical Pansystolic murmur: outlasts S2, blowing quality, loudest at apex, radiates to left axilla, maneuvers: does NOT b/cm louder with inspiration (TR does) Pulses: fast, weak, and irregular due to AF Apex: displaced to the left + diffuse + forceful Heart sounds: soft S1/S2, S3 in severe MR (volume overload for LV), loud P2 due to pulmn HTN, ejection click due to mitral valve prolapse if present RV heave NB with acute MR: fulminant CHF in previously healthy patient, loud crescendo-decrescendo murmur, loudest at base, ends before S2 (note difference from chronic murmur) ECG/CXR ECG: increased LA size, LVH + strain, AF (less likely in acute MR) CXR: increased LV and LA size, signs of LV failure Management Acute MR: aggressive management of CHF with inotropes, IABP, mechanical ventilation, nitroprusside; needs urgent

PULMONIC STENOSIS

echo or cath to determine need for immediate surgery Chronic MR: medical management for mild symptoms or unsuitable for surgery (digoxin, preload reduction diuretics, nitrates; afterload reduction ACE-Is, hydralzine, amiodipine) Chronic MR: surgical management for severe symptoms or asymptomatic with low ejection fraction, LV end systolic dilation, new onset Afib Natureal History Pts > 75 do not do as well as young Pts following surgery Progress especially poor w/ valve replacement (vs repair) and when CAD is present LESS thromboembolism as compared to MS MORE endocarditis than MS b/c of high P jet Etiology Congenital: Noonans syndrome (triangular faces, low set ears, dysmorphic pulmn valve), associated with other congenital heart defects (ToF, VSD) Acquired (rare): rheumatic (also involves mitral), carcinoid sequence (tumor produces serotonin which causes fibrosis of pulmn and tricuspid valves) History Dyspnea Syncope Physical Systolic ejection murmur maximal at pulmonic post Prominent a waves Single S2 Ejection click ECG/CXR ECG: P pulmonale (prominent P waves in lead II), RVH CXR: post-stenotic dlalatation (pulmn aa. dilation) Management Gradient > 50 mmHg: balloon angioplasty or valvotomy

PULMONARY REGURGICATION Etiology Acquired, Valvular: carcinoid, post surgery for congenital heart disease, rheumatic (rare), endocarditis (common in IVDAs) Valvular Ring Dilation: idiopathic, Marfans syndrome, primary pulmn HTN, secondary pulmonary HTN (A) lung diseases COPD, pulmn embolism (B) left heart disease mitral stenosis, MR/AR, multivalvular HD (C) L to R shunts VSD, PDA, ASD History CHF symptoms Physical

 TRICUSPID STENOSIS

Early diastolic murmur: heard best at L ICS2, sounds similar to AR Graham steel murmur: murmur of pulmn regurg due to pulm HTN ECG/CXR ECG: RVH CXR: RV enlargement; dilated pulmn aa. Management Replace in RV failure

Etiology Congenital Acquired: rheumatic (rare), right atrial myoma (RA tumor obstructs flow) Physical Giant a wave Slow y descent Mid diastolic rumble Opening snap FOUR features not found in MS giant a waves and impaired y decent kussmauls sign jugular/clavicular presystolic click increased diastolic rumble with inspiration

TRICUSPID REGURGITATION Etiology Congenital: Ebsteins anomaly (tricuspid valve starts lower down - septal leaflet - :. severe regurg Acquired/valvular: rheumatic, carcinoid, endocarditis (IVDAs), prolapse Acquired/ring dilatation: pulmn HTN RV dilation ring dilation tricuspid regurg, RV infarction, dilated cardiomyopathy Physical Pansystolic murmur: heard best at tricuspid area (xiphoid point), radiates to R of sternum, to L of sternum, but not to left axilla, manuevers: INCREASED INTENSITY WITH INSPIRATION differentiates it from MR Increased JVP (CVcomplex=CV MERGER) Rapid ydescent RV heave Pulsatile liver and hepatojugular reflex Winking earlobe: R ear lobe blinks in time w systole b/c retrograde blood flow Heart sounds: S3 at lower LSB in severe disease RV failure: ascites, jaundice, leg edema, hepatomegaly, JVD Management

Valve replacement/repair: Ebstein or rheumatic Valvotomy: IVDAs; take valve out and dont replace it until drug abuse stops b/c of high risk of endocarditis Secondary TR: anuloplasty = tighten the ring

VENTRICULAR SEPTAL DEFECT Pansystolic murmur: left ICS 3-5, wide radiation, A2 may be obscured by loud murmur PATENT DUCTUS ARTERIOSUS Continuous murmur at LSB pathognomonic for PDA Often with silent interval late in diastole Left ICS 2, radiates toward the left clavicle MITRAL VALVE PROLAPSE Introduction Very commmon, up to 10% MC in young females Usually asymptomatic; rarely can get chest pain, palpitations, etc Complications are rare Pathophysiology Etiology unknown Myxomatous proliferation of spongiosa layer within valve causes foacal interuption of fibrosa layer allowing stretching of valve during systole Posterior leaflet alone is most common and doesnt lead to regurgitation Anterior and posterior involvement less common and leads to regurgitation Associated with Marfans, Ehlers-Danlos, pectus excavatum, severe scoliosis History Chest pain: sharp, localized, variable duration, nonexertional (unknown etiology) Palpitations due to PVCs, PACs and rarely SVT, Vtach Fatigue, lightheadedness, dyspnea ? increased incidence of anxiety disorders versus confusion with anxiety and panic attacks ....... should be on ddx of panic attack Physical Classic midsystolic click follow by late systolic crescendo murmur loudest at apex and LLSB (20%) Anything that decreases venous return will cause click to move closer to S1 and may bring out additional clicks Variety of clicks, murmurs can be heard and they are often intermittent Diagnosis

 RHEUMATIC FEVER

History/Physical ECG: ST depression in inferior leads, prolonged QT, PACs, PVCs Echo Complications Infective endocarditis: significant risk only with regurgitation Arrythmias/sudden death (rare) ? association with migraines, TIAs, CVAs Management BetaBlocker for palpitations, chest pain, anxiety Reassurance Valve surgery for serious regurgitation

Introduction 1920 - 50: leading cause of death in children Sporatic cases of Strep pharyngitis rarely cause rheumatic fever (RF) Most cases occur with epidemics of Strep pharyngitis Children 4yo - 8yo are at greatest risk Pathophysiology unknown: ? abnormal immunological response which leads to cross reactivity with heart valves, joints, skin, CNS Clinical Features Many will not remember preceeding pharyngitis RF occurs after latency of 1 - 5 weeks (average 2weeks) post pharyngitis Various combinations of migratory polyarthritis, fever, chorea, nodules, rash Jones Criteria Requires evidence of preceeding Streptococcal infection (+ve throat cultures or ASOT) and two major or one major + two minor criteria MAJOR CRITERIA Subcutaneous nodules Pancarditis Arthritis (polyarthritis) Chorea Erythema marginatum MINOR CRITERIA Arthralgias CRP elevation ESR elevation PR prolongation Fever Notalbles Polyarthritis: migratory, most common symptom, knees/ankles/elbows/wrists are most common locations; pain greater than physical findings, occurs early

Carditis: 40% with pancarditis, heart murumur, cardiomegaly, pericardial effusion, occasional CHF, mitral valve is most common, MR most common Chorea: Syndenhams chorea or St. Vituss dance; random, rapid, purposeless movements usually of upper extremity and face. Rare, never occurs with arthritis, may be only finding. Erythema marginatum: 10%, nonpuritic, painless, smoke-ring of erythema that commonly appears on trunk and proximal extremities Subcutaneous nodules: 10%, pea sized, nontender, extensor surfaces Fever: only in acute phase usually, rare > 2wks Laboratory Elevated ESR and CRP nonspecific Antistrep antibody (ASOT) +ve for 4-6 wks Throat cultures often negative by the time of rheumatic fever Urine with protein/casts in 50% ECG: PR prolongation Treatment Prevention by 10 days course of penicillin/erythromycin for streptococcus pharyngitis; full 10 days important to fully eradicate bug Acute tx: penicillin, NSAIDs, manage CHF if present, corticosteriods for carditis (not arthritis), penicillin V or erythromycin po bid X 5 year for prophylaxis

COMPLICATIONS OF PROSTHETIC VALVES

THROMBOSIS/EMBOLISM Most frequent and serious complication NO difference in rates between anticoagulated mechanical and biological valves Mechanical valves require permanent anticoagulation; still 3% risk/year of thromboembolism Persantine used if systemic embolic develop while anticoagulated HEMORRHAGE ENDOCARDITIS 1%/year riks Early < 2months: Staph epi, Staph aureus Hemorrhage from anticoagulation Minor hemorrhage 2%/year Major hemorrhage 1%/year Overall hemorrhage 3%/year Management: stop warfarin, vit K, FFP, look for source

Late > 2months: Strep viridans, Staph epi Prophylaxis important for dental, GI, GU, etc procedures Surgical intervention common

PROSTHESIS DYSFUNCTION Obstruction Tissue ingrowth: slow prossess, mitral most common, replace if causing CHF Thrombosis: usually due to inadequate anticoagulation; presents with acute CHF, hypotension, absent or muted metallic sound with NO/minimal murmur; manage CHF, heparin iv, +/- thrombolysis and valve replacement Strut Fracture of mechanical valve Fracture of strut and disk escape Presents with dramatic CHF, hypotension, absence of metallic sound and regurgitant murmur, may see dislodged valve on CXR Requires immediate OR Degeneration/Calcification of biological valve 40% fail in 10yrs Stenosis or regurgitation Hemolytic Anemia Most are subclinical and due to rbc aggregation and consumption on valve Aggravated by paravalvular regurgitation which should be suspected Diagnosis: anemia, increases unconjugated bilirubin +/jaundice, increased LDH, reticulocytosis, hemosiderin in urine Treatment: mild gets iron and folic acid supplementation; severe gets beta-blocker or replaced valve Prothesis Dehiscence Paravalvular regurgitation Minimal regurg is common Caused by friable tissues, broken sutures, or infections (most common cause) Severe cases result in CHF and severe hemolytic anemia May require replacement