Eric J. Charles and Kenan W. Yount
This chapter is a revision and update of that included in previous editions of the TSRA Review written by Kelly M. Wanamaker (2nd edition) and Zain Khapley (1st edition).
Infective endocarditis (IE) is an infection of the endocardium, a native or prosthetic heart valve, or an indwelling cardiac device. It is associated with significant morbidity and mortality regardless of intervention and management. The epidemiology and microbiology of infective endocarditis have changed recently as a result of the opioid epidemic, injection drug use, an increased utilization of implantable cardiac devices, and an increased incidence of hemodialysis, chronic liver disease, diabetes, and compromised immunity. Infective endocarditis can be categorized according to disease presentation (acute versus subacute), valve involvement (native versus prosthetic), acquisition environment (community versus hospital-associated), and responsible microorganism. Additionally, culture-negative endocarditis and noninfectious causes of endocarditis are rare but important cases.
Epidemiology
Approximately 10,000 to 15,000 new cases of IE are diagnosed in the United States each year with an incidence of hospitalization at 12.7 per 100,000. The incidence of IE in other countries is similar to that in the United States. As our population survival rate increases, there has been a coinciding increase of age in those with endocarditis, at a mean age of 60.8 in 2009. More than 50% of patients are older than 50 years. IE is 3 times as common in males as in females. It has no racial predilection.
Approximately three-fourths of patients with IE have a pre-existing structural cardiac abnormality at the time that endocarditis develops. The incidence of nosocomial endocarditis is increasing because more patients are undergoing invasive procedures. Prosthetic valve endocarditis (PVE) develops in 1-4% of valve recipients during the first year following valve replacement. The frequency of valve involvement includes: mitral valve (~40%), aortic valve (~36%), then multi-valve involvement. The pulmonary valve is rarely involved.
Pathophysiology
The initiating event in vegetation formation is injury to the valvular endothelium or endocardium, which then exposes subendothelial collagen and matrix components, thus attracting platelets and fibrin to form a sterile vegetation. The sterile platelet-fibrin nidus becomes secondarily infected by microorganisms circulating in the blood, either from a distant source of focal infection, or as a result of transient bacteremia from a mucosal or skin source. The cardinal anatomic changes of the valve include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords. Some organisms with a high virulence such as Staphylococcus aureus are capable of infecting normal, non-injured heart valves.
A bicuspid aortic valve is the most common predisposing disease for endocarditis of the aortic valve, followed by ventricular septal defects, acquired aortic stenosis, and rheumatic heart disease. The risk of PVE after surgical aortic valve replacement during the first postoperative year is approximately 1%, while data suggests an estimate of 0.6 to 3.4% after transcatheter aortic valve replacement. Infection associated with aortic valve prostheses is mainly associated with local or root abscess and fistula formation as well as valvular dehiscence.
Mitral valve IE, if left untreated, is universally fatal. Rheumatic heart disease was the most common risk factor in the 1980s but now is rare in the developed world. Mitral valve prolapse is now the most common predisposing condition found in young adults. Predisposing factors more frequently encountered today include IV drug abuse (IVDA), immunosuppression, intracardiac devices, hemodialysis catheters, and nosocomial infections. The usual site at which valvular destruction occurs is at the base of the atrial aspect of the mitral valve leaflets. Annular or subannular invasion can cause separation at the AV junction. Invasion into the AV groove fat can lead to abscess formation. An infected aortic valve can seed the anterior mitral leaflet (“drop lesion”) resulting in double-valve endocarditis; the mechanism may be a large vegetation directly infecting the mitral leaflet or a jet lesion that becomes infected.
In 75% of cases of IE associated with IVDA, there are no underlying valvar abnormalities, and 50% of these infections involve the tricuspid valve. Risk factors for PVE include CHF, persistent bacteremia, renal failure, and the early postoperative period (<60 days) after prosthetic valve implantation. Despite optimal care, the overall 1-year mortality rate is approximately 30%.
Microbiology
Staphylococcus aureus is the most prominent organism causing IE worldwide.
70% of native valve endocarditis is caused by Streptococci, including S viridans, S. gallolyticus (part of the S. bovis group) and Enterococci. Staphylococcus species cause 25% of cases and are generally more aggressive.
PVE is most commonly caused by coagulase-negative Staphylococci. Corynebacterium, non-Enterococcal Streptococci, fungi (e.g., Candida albicans, Candida stellatoidea, Aspergillus species), Legionella, and the HACEK organisms (i.e., Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) cause the remaining cases. HACEK organisms tend to cause subacute forms of the disease and can be difficult to isolate.
Staphylococcus aureus is the most common organism in patients with IVDA IE.
Approximately 0.5% of implanted pacemakers develop IE. 75% are produced by Staphylococci, both coagulase-negative and coagulase-positive.
Clinical Presentation and Diagnosis
Acute IE presents with fever (90%) and heart murmur (75%). Subacute IE on the other hand, has an insidious presentation that is often difficult diagnose, and is associated with nonspecific findings of fatigue, malaise, dyspnea, and weight loss.
Other potential diagnostic findings of IE include petechiae, subungual (splinter) hemorrhages, Osler nodes (tender subcutaneous nodules found on the distal pads of the digits), Janeway lesions (nontender maculae on the palms and soles), and Roth spots (retinal hemorrhages with small, clear centers).
Blood cultures are vital to making the diagnosis of IE (3 sets drawn over 30 minutes with separate venipunctures). Other useful diagnostics include EKG, CXR, V/Q scanning (right-sided endocarditis), and echocardiography.
TEE is recommended in patients with prosthetic valves, those rated at least “possible infective endocarditis” by clinical criteria, or complicated infective endocarditis (paravalvular abscess).
Culture negative endocarditis accounts for 2-7% of cases of endocarditis and is attributable to infection with fungi or fastidious bacteria, prior administration of antibiotics, or improper blood culture techniques. Noninfectious causes of valvular or intracardiac vegetations include antiphospholipid syndrome, acute rheumatic fever, atrial myxoma, nonbacterial thrombotic endocarditis (NBTE, also known as marantic or Libman-Sacks endocarditis), vasculitis, cholesterol emboli syndrome, and mural thrombi.
Definitive diagnosis of IE is generally made by using the Modified Duke criteria (see below). The criteria incorporate echocardiographic findings in the diagnostic strategy. Major diagnostic weight is given to only 3 typical findings: mobile, echodense masses attached to valvular leaflets or mural endocardium; periannular abscesses; or new dehiscence of a valvular prosthesis. A definitive clinical diagnosis can be made based on the following: 2 major criteria; 1 major criterion and 3 minor criteria; or 5 minor criteria.
Major criteria
- Microbiologic evidence of IE
- Typical microorganisms consistent with infective endocarditis from two separate blood cultures:
- Viridans Streptococci, Streptococcus gallolyticus, HACEK group, Staphylococcus aureus; or
- Community-acquired enterococci, in the absence of a primary focus
- Persistently positive blood cultures with other organisms:
- At least two positive cultures of blood samples drawn >12 hours apart; or
- All 3 or majority of 4 separate cultures of blood (with first and last sample drawn at least 1 hour apart); or
- Single positive culture for Coxiella burnetii or antiphase I IgG antibody titer >1:800
- Typical microorganisms consistent with infective endocarditis from two separate blood cultures:
- Evidence of endocardial involvement
- Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; or
- Abscess; or
- New partial dehiscence of prosthetic valve; or
Minor Criteria
- Predisposition to IE (predisposing heart condition or IVDA)
- Fever >38°C
- Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions
- Immunologic phenomena: glomerulonephritis, Osler’s nodes, Roth spots, and rheumatoid factor
- Microbiological evidence: positive blood culture that does not meet a major criterion as noted above or serological evidence of active infection with organism consistent with IE
Management
The major goals of therapy for IE are to eradicate the infectious agent from the thrombus and to address the complications of valvar infection.
Antibiotics remain the mainstay of treatment for IE. Empiric antibiotic therapy is chosen based on the most likely infecting organisms. Penicillin G (or ceftriaxone for allergic patients) plus gentamicin are used for synergistic coverage of Streptococci in patients with native valve IE. Nafcillin (or cefazolin) without gentamicin are first line for MSSA. Vancomycin or daptomycin are used for MRSA. Prosthetic valve IE caused by MRSA or coagulase-negative Staphylococci is treated with vancomycin and gentamicin. Rifampin is added because it can penetrate the biofilm of most of the pathogens that infect prosthetic devices. Linezolid or daptomycin are used for patients with intolerance to vancomycin or resistant organisms. HACEK microorganisms are treated with ceftriaxone or ampicillin combined with gentamicin. The only proven cure for fungal IE is with surgical excision of the infected valve combined with amphotericin B.
Indications for Surgery
Patients with IE should be managed by a multispecialty Heart Valve Team including an infectious disease specialist, as well as a neurologist for those who have had neurologic events. In patients with suspected IE, initial TTE is recommended to evaluate for the presence of a vegetation and its possible effects on valvular function (Class I). Subsequent TEE is indicated when TTE is nondiagnostic, or when complications are suspected, or when intracardiac device leads are present (Class I). TEE is reasonable in patients with S. aureus bacteremia without a known source, as well as patients with prosthetic valves and persistent fever without bacteremia (Class IIa). The newer imaging modality of 18F-fluorodeoxyglucose positron emission tomography/CT is now considered a valuable adjunct for patients classified by Modified Duke Criteria as having “possible IE” (Class IIa), particularly when prosthetic valves are not optimally visualized on standard TTE or TEE imaging.
Appropriate antibiotic therapy should be initiated after obtaining blood cultures and then tailored to antibiotic sensitivity data. Stable patients with left-sided IE caused by streptococcus, E. faecalis, S. aureus, or coagulase negative staph without evidence of paravalvular infect ion on TEE, can change to oral antibiotic therapy after initial intravenous (IV) therapy. A follow-up TEE is recommended 1-3 days prior to completion of the antibiotic course (Class IIb).
Early surgical intervention (during initial hospitalization and before completion of full therapeutic course of antibiotics) is recommended for patients with the following characteristics: heart failure symptoms; left-sided IE caused by S. aureus, fungal organism, or other highly resistant organisms; persistent bacteremia or fevers >5 days; recurrent emboli and persistent vegetation; native left-sided valve IE with a mobile vegetation >10 mm in length. In patients with prosthetic valve IE and relapsing infection after completion of an antibiotic course, surgery is recommended (Class I).
In patients with IE with an indication for surgery who suffered a stroke without intracranial hemorrhage, surgery without delay may still be considered. However, if there has been extensive neurologic damage or intracranial hemorrhage, it is advised to wait ≥4 weeks (Class IIb).
There are 3 broad indications for surgery in endocarditis: heart failure, uncontrolled infection (e.g., abscess, paravalvular extension resulting in heart block, persistent bacteremia despite antibiotics, fungal infection, resistant bacteria), and prevention of cerebral embolization.
Indications for emergent surgery
- Severe acute AI (with early closure of mitral valve)
- Rupture into the pericardium or heart chamber
Indications for urgent surgery
- Progressive heart failure with severe valvular regurgitation
- Abscess (aortic root or perivalvular) or aneurysm defined by TEE
- Valve obstruction
- EKG changes indicating conduction disturbance/heart block
- Persistent sepsis after 72 hours of appropriate antibiotic treatment
- Unstable prosthetic valve
- Septal perforation
Indications for early surgery (within 48-72 hours)
Indications for elective surgery
- Continued symptomatic heart failure refractory to diuresis/medical therapy
- Recurrent septic embolic
- Fungal IE (except that caused by Histoplasma capsulatum)
- Recurrent septic emboli
Surgical treatment
Surgery is guided by some basic principles of good exposure, radical debridement of all infected tissue, optimal choice for reconstruction including repair or replacement of the valve, and postoperative antibiotics for 6 weeks. Controversy exists as to whether mechanical or biologic valves are more appropriate in endocarditis, weighing the competing demands of the young age of patents against uncertain long-term longevity and risk factors.
Mitral valve: Bicaval cannulation with exposure via left atriotomy through Waterston’s groove (sometimes transseptal needed if the patient has NOT had longstanding mitral regurgitation and thus does NOT have a large left atrium). All necrotic and vegetation tissue should be resected. Repair is sometimes feasible for isolated leaflet perforations but replacement is often needed if the chordae or annulus are involved.
Aortic valve: Exposure via transverse aortotomy. If limited to the aortic valve cusps, complete removal and replacement of the valve itself is sufficient. For annular dehiscence or root abscess, bovine patch repair of the annulus or sinus (if one-third annulus is involved) may be needed. If more of the annulus is involved, replacement of the entire aortic root with an aortic homograft or biologic Bentall composite graft is needed.
Double valve endocarditis: Endocarditis of the aorto-mitral curtain can be approached via a Commando procedure. Venous drainage is bicaval. The SVC is transected. Exposure via transverse aortotomy that is extended through the noncoronary sinus, annulus, anterior mitral leaflet and onto the dome of the left atrium. Both the aortic valve and mitral valves can be excised and replaced through this incision. Bovine pericardium can be used to anchor the aorto-mitral curtain and close the dome of the left atrium.
Tricuspid endocarditis: Replacement is avoided if possible by utilizing de Vega annuloplasty and leaflet patching if feasible. Sometimes annuloplasty ring or tissue valve replacement are needed. Some centers favor excision of the valve with delayed replacement at the expense of severe tricuspid regurgitation for some time.
Operative mortality varies widely from 3-20% and is highest for extension beyond the valve itself (e.g., annular abscess) and prosthetic valve endocarditis. The 10-year survival after surgery for IE is 50-60%. Recurrence rate is approximately 10% (range 5-12%).
Suggested Readings
- Pettersson GB, Coselli JS, Hussain ST, Griffin B, Blackstone EH, Gordon SM, et al. 2016 The American Association for Thoracic Surgery (AATS) consensus guidelines: surgical treatment of infective endocarditis: executive summary. J Thorac Cardiovasc Surg. 2017;153(6):1241-58.e29.
- Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F, et al. 2015 ESC guidelines for the management of infective endocarditis: the task force for the management of infective endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;36(44):3075-3128.
- Kang DH, Kim YJ, Kim SH, Sun BJ, Kim DH, Yun SC. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-73.
- Prendergast BD, Tornos P. Surgery for infective endocarditis: who and when? Circulation. 2010;121:1141-52.
