I. Clinical diagnosis

The diagnosis of infective endocarditis (IE) is based on the Duke criteria, which consist of two major and five minor criteria.¹

In brief, the two major criteria are: (i) two positive blood cultures for a typical IE organism; (ii) echo finding of a vegetation or a new valvular regurgitation (worsening of a prior regurgitation or murmur is not enough).

The five minor criteria are: (i) fever; (ii) predisposing valvular condition or intravenous drug use; (iii) immunologic phenomenon, such as Osler nodes or glomerulopnephritis; (iv) vascular embolism, major (e.g., stroke, pulmonary embolism) or minor (e.g., Janeway lesions, conjunctival hemorrhage); (v) only one positive blood culture, or positive blood culture for an organism that is not a usual IE organism, or positive Coxiella titers. The diagnosis is made in the presence of two major criteria, or one major and three minor criteria, or all five minor criteria.

II. Echocardiography: timing and indications

When IE is suspected, TTE and TEE are often both required. TTE is the recommended initial imaging modality and may be sufficient in patients with a low clinical suspicion, good quality images, and negative valvular findings.²

TEE is recommended in patients with a high clinical suspicion of IE and normal TTE. In fact, the sensitivity of TTE for the diagnosis of TEE-confirmed endocarditis is ~55–60%, both for aortic and for mitral endocarditis.^3,4 TEE should also be performed in the majority of patients with positive TTE, in order to diagnose local abscess complications that will dictate urgent surgery. On both TTE and TEE, vegetations but also destructive valvular lesions and local infectious complications should be sought.

TEE may miss vegetations in 5–10% of patients, particularly in the following cases:^2,3 (1) very early stage; (2) very small vegetation <3 mm; (3) pre-existing, severe valvular lesion (myxomatous mitral valve, calcified AS, prosthetic valve). If the clinical suspicion remains high, TEE should be repeated 3–5 days after the initial examination (e.g., S. aureus bacteremia in a patient with prosthetic valve and negative initial TEE).^2,5 The diagnostic yield of a third examination is low.

Several abnormalities may mimic a vegetation:

1. Mitral valve abnormalities, such as myxomatous mitral leaflet thickening, prolapsed mitral cusp, or flail mitral chordae. In addition, a tumor may mimic a vegetation (e.g., papillary fibroelastoma which originates from the valve, or myxoma which originates from interatrial septum and extends towards the valve).
   
2. Aortic valve abnormalities, such as Lambl excrescence or prolapsed aortic cusp.

Also, a healed endocarditis may be hard to differentiate from active endocarditis. As compared to a recent vegetation, an old vegetation tends to be more echogenic or even calcified, but this cannot be reliably used to exclude acute IE.

For right-sided endocarditis, TTE and TEE may have a similar diagnostic yield.⁶ However, TEE is superior for the assessment of vegetations on pacemaker leads or indwelling catheters, and thus is required in those cases. It is also required when concomitant left-sided involvement or abscess complications need to be addressed.

A particular diagnostic case is Staphylococcus aureus bacteremia. Regardless of whether the source of bacteremia is known (osteomyelitis, cellulitis, central catheter infection, pneumonia), ~25% of all patients with S. aureus bacteremia and 23% of those with central catheter infection as the primary focus have evidence of endocarditis by TEE, without clinical or transthoracic echocardiographic findings.⁷ Contrary to a common misconception, IE most commonly involves the left-sided valves, in 65% of these patients. Thus, it seems warranted and cost-effective for all patients with S. aureus bacteremia to undergo TEE.^7,8 S. aureus is virulent and can even cause endocarditis of a normal native valve.

III. Organisms

The most common organisms responsible for IE are: streptococci (viridians streptococci and Streptococcus bovis: 40–60%), enterococci (5–15%), S. aureus (30–40%), HACEK organisms (5–10%), and coagulase-negative staphylococci (5%).² Streptococci and enterococci involve left-sided, abnormal valves and lead to subacute IE that progresses over weeks to months. S. aureus involves the right- or left-sided valves, and has a predilection to seed normal as well as abnormal valves; S. aureus IE is rapidly invasive and destructive and leads to acute IE that progresses over days to weeks. Coagulase-negative Staphylococcus infection of native valves may be seen in patients with a central line or intracardiac device and is often aggressive and complicated. Occasionally, Coxiella endocarditis may be seen in farmers.

Intravenous drug users are prone to S. aureus IE (~70%), which in this case more commonly involves the tricuspid valve (~60%) rather than the left-sided valves (~40%), many of which are previously normal valves. This is in contradistinction to patients with focal S. aureus infections, such as osteomyelitis or catheter infections, who tend to be older with intrinsic left valvular disease, in whom S. aureus more frequently seeds the abnormal, left-sided valves. IV drug users with abnormal left-sided valves may have streptococcal and enteroccoccal infection of these left-sided valves. Pseudomonas aeruginosa and fungi may also be seen in intravenous drug users.

Prosthetic valves may be infected early postoperatively (<60 days to 1 year) or late (>1 year). Early infections are usually surgical infections, predominantly caused by Staphylococcus coagulase-negative (~35%) and positive (~20%); enterococci and Gram-negative bacilli are second in frequency. Late infections are caused by the same organisms as native valve endocarditis: streptococci (viridians, S. bovis) are the most common, followed by staphylococci and enteroccoci. Coagulase-negative staphylococci may still be seen, especially with central line or device placement.

IV. Morphology

Vegetations are typically located on the upstream side of the valve, in the path of a regurgitant jet, but may be located anywhere on the components of the valvular or subvalvular apparatus, as well as the mural endocardium of the cardiac chambers (LA, LV) or ascending aorta. Large vegetations are almost always associated with significant valvular regurgitation or, less often, valvular stenosis. Regurgitation results from the bulk of the vegetation impeding valvular closure, from valvular perforation/tear, or from rupture of an infected chorda. In fact, a large mass without valvular regurgitation argues against vegetation (in this case, other cardiac masses should be considered). Smaller vegetations, on the other hand, may not be associated with any significant regurgitation in up to 25% of cases.³

V. Anatomical complications

Periannular extension is common, occurring in 10–40% of all native valve endocarditis, more commonly aortic endocarditis than mitral or tricuspid endocarditis. Periannular infection is even more common with prosthetic valve endocarditis, occurring in 56–100% of cases, and leading to prosthetic dehiscence and paraprosthetic regurgitation.² Perivalvular abscesses are common with prosthetic valves because the annulus, rather than the leaflet, is usually the primary site of infection.²

Aortic valve vegetation can extend to the aortic annulus and lead to aortic abscess. The infection tends to spread through the weakest annular structure, the membranous interatrial septum, which contains the AV node.⁹ This explains why AV block is common with perivalvular abscess. This abscess may communicate with the aortic lumen and lead to pseudo-aneurysm formation. An abscess or pseudoaneurysm may rupture and communicate with the pericardium surrounding the base of the aorta (full-blown rupture or microperforation), leading to a hemorrhagic pericardial effusion. It may communicate with a cardiac chamber such as LV, leading to paravalvular AI; LA, leading to severe pulmonary edema; or RA or RV, leading to a massive left-to-right shunt and severe left ± right failure (Figures 28.1, 28.2). The annular abscess may lead to dehiscence of a prosthetic valve with perivalvular regurgitation. Therefore, worsening HF, persistent infection, new murmur, pericardial effusion, or new AV block in a patient with IE is a hint to abscess formation and warrants repeating TEE. AV block (including a new first-degree AV block or bundle branch block) has a high positive predictive value for abscess formation (88%) but low sensitivity (45%).^2,9

A narrow fibrous space, called the mitral–aortic intervalvular fibrosa (or interannular fibrosa), separates the aortic root and mitral annulus. Aortic root abscess or mitral annular abscess may extend into this space and lead to pseudoaneurysm of this space, with subsequent seeding of the mitral valve from the aortic valve (or vice versa) and extension throughout the cardiac cytoskeleton (Figure 28.1).

Aortic root abscess manifests initially as aortic root wall thickening. If only slight thickening is visualized, TEE may need to be repeated a few days later, at which time a clear aortic free space, with or without fistulization on color Doppler, confirms the diagnosis.

VI. Indications for valvular surgery and special situations