PATHOLOGY

Two conditions must be present for the development of nearly all cases of NVE: endocardial injury causing a disruption of the valvular endocardial surface, and subsequent infiltration of the injured site by blood-borne microorganisms, typically bacteria.⁵ Endocardial trauma results from degenerative calcific changes, rheumatic disease, mitral valve prolapse, regurgitant jet flow, congenital abnormalities (e.g., bicuspid aortic valve), or iatrogenic etiologies (e.g., cardiac catheterization). Endocardial injury results in the deposition of platelet-fibrin products, which then serve as a nidus for the attachment of microorganisms. Organisms that cause NVE enter the bloodstream through compromise of the skin, mucosal surfaces, or other sites of focal infection. Common causes of bacteremia or fungemia that predispose to NVE include intravenous drug use, indwelling catheters, debilitated condition, medical procedures, and even simple events such as tooth brushing and mastication.⁵^–⁷

In all cases of native valve endocarditis, complications and symptoms of the infection may be divided into two categories: (1) systemic manifestations of the disease result from sepsis and embolic phenomena, such as stroke, kidney failure, or fever; or (2) there are sequelae that are the direct result of infection and the location of that infection in the heart.

In native aortic valve endocarditis, infection may spread into the aortic anulus, destroy the aortic valve itself, or result in paravalvular abscess formation. Conduction system pathology may result, including heart block, depending on the extent of the infection. Other complications include cardiac fistulas, coronary and systemic embolization of vegetations, stroke, cerebral infarction, and mycotic aneurysms. Large aortic valve vegetations can prolapse into the left ventricular cavity, come into contact with the anterior leaflet of the mitral valve, and cause double-valve endocarditis. Typically, aortic insufficiency results from aortic valve endocarditis. Untreated cases can lead to destruction of the fibrous trigones and the tissue between the anterior mitral leaflet and the aorta. Heart failure may occur because of the volume overload resulting from aortic insufficiency. Fistulas between the aorta and the right atrium are also possible.

In native mitral valve endocarditis, the most common site of vegetations is the mitral valve leaflet near the annulus on the atrial side. Vegetations may be located anywhere on the leaflets or the chordae, however, and may occur on the ventricular side as well. Vegetations and debris may destroy part of the ventricular tissue. Complications include invasion into the atrioventricular (AV) groove, and abscess formation, with severe cases leading to separation at the AV junction and complete destruction of the fibrous skeleton surrounding the valve.

Native tricuspid valve endocarditis usually affects the free margins of the leaflets, and there is relatively infrequent involvement of the annular tissue. Complications of tricuspid NVE include cardiac and pulmonary sequelae as a consequence of valve destruction and embolism. Tricuspid regurgitation with chamber dilation and right-heart failure can result, and local extension can cause abscess and fistula formation. Septic pulmonary emboli lead to pulmonary infarction, pulmonary abscess, empyema, and, in rare cases, mycotic aneurysms of the pulmonary arteries.

MICROBIOLOGY

Endocarditis is caused principally by staphylococci and streptococci. The most common agents are Staphylococcus aureus (32%), viridans group streptococci (18%), enterococci (11%), coagulase-negative staphylococci (11%), and Streptococcus bovis (7%).^8,⁹ Gram-negative bacteria can also cause NVE and are classified into either the HACEK group (fastidious gram-negative bacilli including Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae) or non-HACEK group, with each accounting for approximately 2% of all cases. These organisms require a prolonged incubation period before growth and are often resistant to many antibiotics. Fungal NVE, usually caused by Candida albicans or Aspergillus fumigatus, is rare but can lead to devastating complications.^10,¹¹

The microbiology of NVE differs somewhat depending on individual risk factors and demographics. For example, viridans group streptococci are more prevalent in community-acquired endocarditis, whereas the more virulent S. aureus is more common in nosocomial cases.¹^–³ ⁸ NVE of the right heart is predominantly a disease of injection drug users, and in this population native tricuspid valve endocarditis caused by S. aureus is the predominant form of the disease.⁴

Approximately 2% to 7% of NVE cases are deemed culture-negative endocarditis, meaning that no microorganisms can be cultured from the blood or tissue samples.¹²^–¹⁵ This occurs more frequently in developing countries, where fastidious or rare organisms are more likely to cause human infection. The most common reasons for culture-negative endocarditis in developed countries are administration of antimicrobial agents before cultures are taken, inadequate microbiological techniques, and infection with highly fastidious bacteria or nonbacterial pathogens (e.g., fungi). In all cases of culture-negative NVE, it is important to ascertain that there is no underlying undiscovered infection and to initiate aggressive empiric treatment despite the negative culture data.

DIAGNOSIS

Clinical Presentation

The onset of NVE usually begins with fever and malaise. Common physical examination findings include a new heart murmur or a change to an existing one, petechiae, splenomegaly, clubbing of the digits, splinter hemorrhages, Osler nodes, Janeway lesions, and Roth spots. The latter two are found almost exclusively in acute endocarditis when overwhelming signs of sepsis are displayed early in the clinical course. The virulence of the offending organism affects the severity of the symptoms seen, with less virulent organisms such as viridans group streptococci causing a subacute, protracted clinical course that can often be cured with antibiotics alone.

Laboratory findings include moderate leukocytosis, anemia without reticulocytosis, and hematuria. Blood cultures must be drawn from separate sites and, in cases of bacterial NVE, will usually lead to identification of the infective organisms. Cultures should be drawn before antibiotics are started.

Imaging Studies

Doppler echocardiography is the single most useful diagnostic modality for documenting endocarditis.¹⁶^–¹⁹ Transesophageal echocardiography is the preferred study, with a sensitivity and a specificity of 95% and 90%, respectively.²⁰ Transthoracic echocardiography is less sensitive for endocarditis, but it can be used when transesophageal studies are not feasible. Echocardiography can be used to identify vegetations, paravalvular leaks, abscesses, and fistulae. When there is concern about metastatic or embolic disease, patients with NVE should undergo further imaging with computed tomography (CT) scans of the abdomen or head, or both, as appropriate. Embolic involvement of the brain can also be investigated with magnetic resonance imaging (MRI).²¹

Duke Criteria

The diagnosis of endocarditis is based on a combination of clinical findings rather than a single test result. Several classification systems for the diagnosis of endocarditis have been published, but the most commonly used is the Duke system.²² First described by Duke University researchers in 1994, this system uses both clinical and pathologic criteria to confirm or reject the diagnosis of infective endocarditis. There are two groups of criteria: major (e.g., positive blood cultures, positive echocardiographic findings) and minor (e.g., fever, predisposing conditions, vascular phenomena, immunologic phenomena, equivocal microbiological findings). On the basis of the number of criteria met, cases are classified into one of three diagnostic categories: low clinical likelihood of endocarditis, possible endocarditis, or definite endocarditis. Definite endocarditis is diagnosed by documentation of two major criteria, of one major and three minor criteria, or of five minor criteria. Cases are considered possible endocarditis when either one major and one minor criterion or three minor criteria are identified. Most authorities accept a recently modified version of the Duke criteria, as shown in Box 80-1.²³

Box 80–1 Modified Duke Criteria for Infective Endocarditis

HACEK, group including Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae. From Li JS, Sexton DJ, Mick N, et al. Clin Infect Dis 2000;30:633.

Major Criteria

MANAGEMENT

Aggressive antibiotic therapy is the first and most important intervention in all cases of NVE. Antibiotics should be started as soon as possible after obtaining blood cultures. Combinations of broad-spectrum agents should be administered empirically and then adjusted once culture data become available. Surveillance blood cultures and frequent echocardiograms, at least in the first 2 weeks after initiating treatment, can help to determine therapy and follow its efficacy. Surgical intervention is indicated in patients who develop worsening symptoms and continued sepsis despite antibiotics. Early surgical treatment is often required in cases involving virulent organisms such as S. aureus and gram-negative bacteria, as these infections progress rapidly despite antimicrobial therapy. Fungal infection is an absolute indication for surgery.

For the cardiac surgeon, the first management decision is to determine the optimal timing for operation. Should surgery be undertaken now or after appropriate antibiotic treatment? Most indications for surgical intervention are not absolute, and therefore the decision to operate must be based on each individual patient’s clinical status and assessment of the risks and benefits. In general, the more serious and persistent the symptoms and complications of any particular endocarditis case, the sooner surgery should be undertaken. Once the decision to operate has been made, expeditious intervention should occur. If an indication for surgery is identified, it should not be delayed simply to complete antibiotic therapy, as this has been associated with increased mortality.²⁴^–²⁶

With either mitral or aortic endocarditis, one common indication for immediate surgery is congestive heart failure. Early surgery in such cases is always warranted, as medical therapy alone is usually ineffective and associated with a poor prognosis. Risk factors for early mortality from NVE include New York Heart Association (NYHA) functional class IV heart failure, cardiogenic shock, advanced age, preoperative acute renal failure, paravalvular extension, and staphylococcal infection.²⁴^–²⁶ In 2006, the American College of Cardiology and the American Heart Association (ACC/AHA) issued guidelines on the management of valvular heart disease including recommendations on surgical treatment of NVE, shown in Box 80-2.²⁷ In addition to heart failure, the generally accepted indications for surgery are ongoing sepsis, fungal infection, S. aureus infection, myocardial abscess, and recurrent systemic embolism. For aortic valve endocarditis, conduction abnormalities are a relative indication for surgery as well.

Box 80–2 2006 ACC/AHA Guidelines for the Management of Valvular Heart Disease

ACC/AHA, American College of Cardiology/American Heart Association. From Bonow RO, Carabello BA, Chatterjee K, et al. J Am Coll Cardiol 2006;48:e1.