Snapshot A 25-year-old woman presents to the emergency room for a fever. She has a history of intravenous drug use and had previously been treated for osteomyelitis. On physical exam, she is febrile, and heart auscultation reveals a new systolic murmur at the lower left sternal border. An echocardiogram reveals tricuspid valve vegetations. Summary Endocarditis is an acute cardiac condition characterized by inflammation of the heart valve, typically secondary to bacterial infection. It is typically the result of bacteremia, often due to surgery, dental procedures, or as a complication of congenital heart disease. Patients present with systemic symptoms such as fatigue, fever/chills, new onset cardiac symptoms (murmur, heart failure), and if severe enough, end-organ damage. Classic skin manifestations such as Osler nodes, Janeway lesions, and splinter hemorrhages are also characteristic of the condition. Diagnosis is made via the Duke criteria, which involves meeting 2 major criteria, 1 major and 3 minor criteria, or 5 minor criteria. Major criteria include two positive blood cultures and echocardiography evidence. Minor criteria include fever, embolic signs, one positive blood culture, and other immunologic phenomena such as skin manifestations or kidney damage. Treatment is antibiotics or surgical valve replacement depending on the severity and chronicity of the disease. Epidemiology Incidence common > 1/100,000 Demographics typically affects adults > 60 years old men are more commonly affected than females Location mitral valve > tricuspid valve tricuspid valve disease is associated with intravenous (IV) drug use Staphylococcus aureus, Pseudomonas, and Candida Risk factors rheumatic heart disease IV drug use immunosuppression prosthetic heart valve congenital heart disease ETIOLOGY Pathophysiology mechanism of injury endothelial damage on the surface of the cardiac valve can cause a thrombus to form factors include turbulent blood flow that can damage endothelium or deposition of fibrin-platelet aggregate on damaged endothelium bacteria can then adhere to thrombus vegetations are caused by further depositions of fibrin and platelets acute endocarditis Streptococcus pneumoniae Streptococcus pyogenes Staphylococcus aureus IV drug users large vegetations seen on the valves Neisseria gonorrhea subacute bacterial endocarditis characterized by slower onset and less severe symptoms Streptococcus galloyticus in the setting of colon cancer must perform colonoscopy Enterococcus in the setting of gastrointestinal/genitourinary procedures Streptococcus viridans often a complication of dental procedures can also occur with upper respiratory infections makes dextrans, which binds to fibrin-platelet aggregates on the heart valves Staphylococcus epidermidis often in the setting of prosthetic valves can cause bacteremia when central lines left in place for prolonged times Candida albicans IV drug users non-infectious endocarditis Libman-Sacks endocarditis from systemic lupus erythematosus mitral or aortic valve involvement non-bacterial thrombotic (marantic) endocarditis from inflammatory states very poor prognosis thrombi made of platelets with fibrin without organisms or neutrophils Associated conditions systemic infection can lead to cardiogenic shock and eventual heart failure septic emboli can dislodge and lead to end organ damage or stroke Anatomy Both native and prosthetic valves serve as the site for infection valves most frequently involved: mitral valve > aortic valve > tricuspid valve > pulmonic valve in IV drug users the tricuspid valve is most commonly affected since it is reached first from the venous return Presentation Symptoms persistent fevers (the most common symptom) shortness of breath systemic symptoms weakness fever malaise Physical exam auscultation findings new murmur tricuspid valve in IV drug users a systolic murmur along the left lower sternal border in tricuspid regurgitation mitral valve regurgitation holosystolic murmur heard best at the heart apex with radiation to the left axilla inspection from emboli Roth spots retinal hemorrhages on funduscopy Janeway lesions erythematous and nontender macules on palms or soles nail bed splinter hemorrhages from immune complex deposition Osler nodes tender nodules on fingers or toes Imaging Echocardiography indication for all patients views transthoracic echocardiography (TTE) is recommended for initial inspection transesophageal echocardiography (TEE) is indicated when TTE is positive or if initial TTE is negative but there is a high suspicion findings vegetations on valves appear as abnormal, echogenic masses with independent motion Studies Serum labs leukocytosis with left shift positive bacterial blood cultures ↑ C-reactive protein ↑ erythrocyte sedimentation rate Electrocardiogram indications patients with associated chest pain findings rule out acute coronary syndrome Differential Noninfective endocarditis findings found in noninfective endocarditis and not infective endocarditis negative peripheral blood cultures asymptomatic unless embolization occurs Osteomyelitis findings found in osteomyelitis and not infective endocarditis lack of systemic embolic symptoms diagnosis Duke Criteria Major (2 Criteria) Minor (5 Criteria) 1. Positive blood cultures from 2 separate blood cultures drawn > 12 hours apart, 3 out of 4 blood cultures that are positive, with first and last samples drawn 1 hour apart, single positive blood culture for Coxiella burnetti, or antiphase I IgG antibody titer > 1:800 1. Fever 2. Abnormal echocardiogram with vegetation or abscess or partial dehiscence of prosthetic valve 2. Presence of risk factors, including intravenous drug use, structural heart disease, prosthetic heart valve, dentla procedures, or history of endocarditis 3. Vascular phenomena, including Janeway lesions, emboli, mycotic aneurysm, and conjunctival hemorrhage 4. Immunologic phenomena, including glomerulonephritis, Osler nodes, and Roth spots 5. Positive blood cultures not meeting major criterion 6. Echocardiographic findings consistent with endocarditis but not meeting major criterion Making the diagnosis based on clinical presentation and Duke criteria pathologic criteria blood culture of the organism (best initial step) drawn at least 12 hours apart OR multiple positive cultures (at least 3 of 4) with the first and last drawn at least 1 hour apart histologic evidence of endocarditis from vegetation or intracardiac abscess clinical criteria: one of the following 2 major criteria 1 major and 3 minor criteria 5 minor criteria if blood cultures are negative but echocardiography shows endocarditis, consider one of the causes of culture-negative endocarditis (CNE) Coxiella burnetii Bartonella spp HACEK organisms Haemophilus Aggregatibacter Cardiobacterium Eikenella Kingella Treatment Management approach choice of antibiotics ultimately depend on causative agent and susceptibility as well as presence of prosthetic material in the heart all anitbiotics should given intravenously Nonoperative Medical penicillin or ceftriaxone indications empiric antibiotic therapy for patients with no prosthetic valve often for 4-6 weeks vancomycin indications antibiotic therapy for patients with Streptococcus viridans and no prosthetic valve often for 4-6 weeks vancomycin plus gentamicin and rifampin indications empiric antibiotic therapy for patients with prosthetic valve often for 4-6 weeks vancomycin plus cefepime/piperacillin-tazobactam for critically ill/unstable patients coverage for Pseudomonas aeruginosa as more common in IV drug users Operative surgical valve replacement approach typically done by cardiothoracic surgery under general anesthesia indications heart failure patients who are refractory to medical therapy abscess formation technique endoscopic approach complications bleeding infection pericardial effusion Complications Heart failure incidence up to 40-50% of patients treatment pharmacological agents angiotensin receptor neprilysin inhibitor (ARNI), angiotensin-converting enzyme (ACE) inhibitor, or angiotensin II receptor blockers (ARB) ß-blockers diuretics operative heart transplantation Perivalvular abscess incidence up to 30-40% of patients treatment antibiotic treatment for <1 cm abscess surgical removal if >1 cm Splenic abscesses incidence around 5% of patients treatment antibiotics splenectomy Cerebrovascular accident incidence estimated to be 35% of patients treatment thrombolytics thrombectomy Prognosis Overall poor prognosis 1-year mortality rate is around 30% poor prognostic factors include high risk for emboli large vegetations multiple vegetations visible vegetations prosthetic valve endocarditis female gender advanced age history of drug abuse Endocarditis prophylaxis may be required before dental procedures 2017 American Heart Association guidlines indicate antibiotic prophlaxis to prevent endocarditis only in patients with: history of prosthetic valve (or with valve components) history of unrepaired congential heart disease history of repaired congential heart disease with residual shunt post-cardiac transplant with valve regurgitation history of prior infectious endocarditis