The most common heart valve affected by infective endocarditis (IE) is the aortic valve. Fortunately, significant progress has been made in our understanding and management of aortic valve IE. Clinical manifestations include fever, heart murmur, splenomegaly, embolic events, and bacteremia or fungemia. Early diagnosis is extremely important because progression invariably leads to devastating complications, including acute heart failure, cerebral embolism, and death, if the infection is not treated with antibiotics, surgery, or both. Increasingly, IE has become a “surgical disease,” particularly for aortic valve IE, and during the last decade, more than half of all patients have been operated on during the active phase of the disease (early surgery).¹

Among patients with aortic valve IE, congenitally bicuspid aortic valve is the most common predisposing lesion.² Other congenital abnormalities of the aortic valve predisposing to infection are degenerative calcific aortic stenosis, aortic regurgitation due to any cause, and rheumatic aortic valve disease. Occasionally, highly virulent microorganisms infect normal aortic valves. Patients with prosthetic heart valves run a constant higher risk of developing IE.

It is difficult to determine the incidence and prevalence of native aortic valve IE in the general population because the disease is continuously changing.^3,4 The annual incidence is estimated to range from 1.7 to 7.0 episodes per 100,000 person-years in North America,^5-7 and patients with prosthetic aortic valves are reported to have an incidence of 0.2 to 1.4 episodes per 100 patient-years.^8-10 Approximately 1.4% of patients undergoing aortic valve replacement develop prosthetic valve IE during the first postoperative year.¹¹

The incidence of nosocomial IE is increasing because more patients are undergoing invasive procedures. IE in hemodialysis patients is fortunately relatively infrequent, but when it happens, it is associated with high mortality.¹² Dental procedures, extractions in particular, have been shown to produce bacteremia. However, daily dental flossing can also produce bacteremia in periodontally healthy individuals at a rate comparable with that caused by dental procedures for which antibiotic prophylaxis is usually given to patients with valve disease to prevent endocarditis, suggesting that prophylaxis may be futile.¹³ Endoscopic procedures may also produce bacteremia. Intravenous drug users using nonsterile syringes and needles most often infect their structurally normal tricuspid valves (see “Prophylaxis of Infective Endocarditis” later in this chapter).

The key to understanding IE is appreciating the pathology progression.^6,14,15 Circulating organisms adhere and attach to areas with endocardial (valve) injury; such damaged areas often have deposition of platelets, fibrin, or clots, facilitating attachment and growth of the organisms. In 1928, Grant and colleagues¹⁶ theorized that platelet-fibrin thrombi on the heart valve serve as a nidus for bacteria to adhere, and in 1963, Angrist and Oka¹⁷ introduced the term nonbacterial thrombotic endocarditis to describe such sterile vegetations, providing experimental evidence supporting their role in the pathogenesis of endocarditis.¹⁸ As the organism multiplies, it produces matrix material, and this, together with leukocytes and thrombotic material, accumulates in the area and forms verrucous vegetations. Formation of vegetations means formation of a biofilm, allowing the organisms protection from the host’s defenses and antibiotics.

The infecting organisms produce and release virulence factors and enzymes that promote organism reproduction and survival and kill and disintegrate host tissue, primarily valve cusps and leaflets. The enzymes produced are organism specific with regard to their tissue specificity and efficiency. When tissue disintegration involves the valve annulus, the infection invades extravascular areas (invasive disease). Invasive disease develops in stages: cellulitis, abscess, abscess cavities, and finally, pseudoaneurysm formation. Invasive disease around the aortic root is generally deeper and more extensive than for any other valve because it is constantly highly pressurized. Internal fistulas, perforations, and heart block constitute specific consequences of invasion.¹⁴ IE of the aortic valve not only causes destruction of the aortic cusps, paravalvular abscesses, and cardiac fistulas, but is also a source of systemic embolization of vegetation material.¹⁹ Strokes and cerebral infarctions caused by embolism of vegetation material are common. An ischemic infarct may convert into a hemorrhagic infarct. However, when an infarct is hemorrhagic, there is a higher probability of a mycotic aneurysm.²⁰ Rupture of a mycotic aneurysm may cause devastating cerebral bleeding. Mycotic aneurysms, infarcts, and abscesses in other organs, such as the spleen, liver, kidneys, and limbs, are also common.¹⁸ Aortic valve IE with a large vegetation that prolapses into the left ventricle and comes into contact with the anterior mitral valve leaflet causes secondary involvement of this valve (kissing lesions).^14,21 Such kissing lesions are common and manifest themselves as anterior valve leaflet pseudoaneurysms or perforations (windsock lesions).¹⁴

Infection of a bioprosthetic valve, porcine or pericardial, may involve the cusps, the sewing ring, or both (Fig. 31-1). Infection of aortic valve allografts and pulmonary autografts resembles that of the native aortic valves: It may begin on the aortic cusps and destroy them, causing aortic regurgitation, or it may start at old suture lines and extend into surrounding structures (Fig. 31-2). Infection of a mechanical heart valve is usually located along the sewing ring (Fig. 31-3). Endocarditis after replacement with a prosthesis frequently causes dehiscence of the prosthesis from the annulus, with consequent development of ventricular-aortic separation.

Heart block with aortic valve IE is caused by destruction of the atrioventricular node and the bundle of His. This happens when the infection invades the right atrium and the triangle of Koch (Fig. 31-2).

The microbiology of aortic IE depends on whether the valve is native or prosthetic, and whether the infection is hospital or community acquired. Staphylococcus aureus and Streptococcus viridans are the most common organisms responsible for native aortic valve endocarditis.^6,22 S. aureus is extremely virulent. S. viridans and various other streptococci are not as virulent and cause an infection that often follows a more protracted course. Coagulase-negative staphylococci are also less virulent, but have emerged as an important cause of native valve IE in both the community and health care settings.^6,23

IE caused by Gram-negative bacteria is less common, but these organisms are often resistant to many antibiotics and more difficult to treat and therefore more likely to cause complications. Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella (the HACEK group) are Gram-negative bacilli grouped together because of their characteristic fastidiousness requiring a prolonged incubation period before growth, although bacteriologic diagnostic methods have improved. Fungal IE is rare but extremely serious and very difficult to eradicate and cure. Candida albicans and Aspergillus fumigatus are the usual agents. Fungal IE is associated with large, sometimes huge, vegetations (Fig. 31-4).

The microbiology of prosthetic aortic valve IE is somewhat different from that of the native valve.^24,25 Prosthetic valve IE is classified as early when it occurs within the first year after surgery and late when it occurs after 1 year.⁶ Early prosthetic valve IE is likely caused by contamination of the valve by perioperative bacteremia or contamination of the operative field at the time of implantation.^6,11,26,27 This may be particularly true when the infection is caused by coagulase-negative staphylococci and the HACEK group of bacteria. Staphylococcus epidermidis, S. aureus, and Enterococcus faecalis are more common microorganisms responsible for early prosthetic valve IE.^11,27 The sources of late prosthetic valve IE are more difficult to determine. Although streptococci and staphylococci are commonly encountered in these patients, a myriad of microorganisms can cause late prosthetic valve IE.²⁷ Nosocomial infections are often caused by S. aureus or other staphylococci.⁶

In a small proportion of cases of aortic valve IE, no microorganism can be cultured from either the blood or surgical specimens.⁶ This is called “culture-negative endocarditis,” but in these cases it is important to rule out fastidious microorganisms, and every effort should be made to identify them. Valve sequencing (universal bacterial, mycobacterial, or fungal polymerase chain reaction [PCR]) is successful in identifying the causative organism in most cases.²⁸

It is helpful to classify IE as acute and subacute, because there are major differences between these two clinical presentations. Originally, before the availability of antibiotics, these concepts of acute, subacute, and chronic IE also described how long it would take patients to die. Subacute and chronic IE are caused by less virulent microorganisms, such as S. viridans, and the clinical course is protracted; antibiotics alone cure most cases if treatment is started before important destruction of the cusps or invasion have occurred. On the other hand, acute IE is frequently caused by a virulent and aggressive organism such as S. aureus. The clinical course is acute, and destruction and invasion occur fast, with antibiotics alone often failing to cure the infection.

The onset of subacute IE is usually subtle, with low-grade fever and malaise. Patients think they have the “flu,” are often treated with oral antibiotics, and symptoms improve. However, in most cases the symptoms recur a few days after the antibiotics are stopped. In the majority of cases, no extracardiac source of bacteremia is identified. An aortic valve murmur is present in nearly all patients because they have preexisting aortic valve disease. Splenomegaly is common. Clubbing of the fingers and toes may develop in long-standing cases. Skin and mucous membrane signs occur late in this form of IE. Petechiae appear on any part of the body. Small areas of hemorrhage may be seen in the ocular fundi. Hemorrhages in the nail beds usually have a linear distribution near the distal end, hence the name splinter hemorrhages. Osler nodes are acute, tender, barely palpable nodular lesions in the pulp of the fingers and toes, and bacteria have been cultured from these lesions. Embolization of large vegetation fragments may cause dramatic clinical events such as stroke, acute myocardial infarction, or splenic or hepatic infarcts. Any other organ may also be a target for an embolic event. Destruction of the aortic cusps causes aortic regurgitation and heart failure. The hematologic picture is not distinctive in subacute endocarditis. The leukocyte count is moderately elevated. Anemia without reticulocytosis develops after a few weeks in patients who are untreated. Blood cultures frequently identify the offending microorganism.

Acute IE is defined by a fulminant clinical course. A noncardiac source of bacteremia may often be identified. This form of IE can present with all the symptoms and signs described under subacute IE, but they are more severe and progress rapidly, and patients are often sicker and show signs of sepsis. Early metastatic infections are common. Two physical signs are seen only in acute IE: Janeway lesions (painless red-blue hemorrhagic lesions a few millimeters in diameter found on the palms of the hands and soles of the feet) and Roth spots (an oval pale area surrounded by hemorrhage near the optic disc). In patients with no preexisting aortic valve disease, the presentation is acute. Early extra-aortic infection and cardiac decompensation caused by severe aortic regurgitation is common. Invasion with paravalvular abscesses is also more common, and with invasion behind the central fibrous body, toward the floor of the right atrium and triangle of Koch (Fig. 31-2), the electrocardiogram may show an increased PR interval that within hours or days progresses to complete heart block. The blood picture is one of acute sepsis. Blood cultures often isolate the infecting agent.

Prosthetic valve IE may present as acute or subacute endocarditis.