The clinical presentation of endocarditis is often nonspecific and variable, with potential to affect nearly every organ system in an indolent or fulminant course. The vast majority of endocarditis is infective; diagnosis relies on a set of explicit criteria, which include findings from blood culture, echocardiography, and close clinical observation. Unrecognized infective endocarditis has frequent complications and high mortality.

In developed countries, the incidence of infective endocarditis ranges from 2 to 11.6 cases per 100,000 patient-years^{1,2,3,4,5,6,7} and is higher in urban versus rural settings, likely reflecting the impact of injection drug use. The disease is uncommon among children, where it is associated with structural congenital heart disease, rheumatic heart disease, or nosocomial, catheter-related bacteremia. The disorder affects men more commonly than women, and the hospital mortality rate is up to 18%, varying according to the microorganism involved and presence of complications.^1,2

Most cases occur either in those with a predisposing identifiable cardiac structural abnormality (congenital or acquired), prosthetic valve, or a recognized risk factor for disease (including injection drug use, intravascular devices, poor dental hygiene, chronic hemodialysis, or infection with the human immunodeficiency virus). The mitral valve is the most commonly affected site, followed in decreasing frequency by the aortic, tricuspid, and pulmonic valves.

For native valve–related infective endocarditis in the developed world, mitral valve prolapse is a common predisposing cardiac lesion. Other underlying structural defects include congenital defects (most commonly bicuspid aortic valve), degenerative cardiac lesions (particularly calcific aortic stenosis), and rheumatic heart disease. In developing countries, rheumatic heart disease creating valvulopathy remains the leading underlying risk factor. For native valve–related lesions, left-sided disease predominates, and mortality ranges from 16% to 27%. Short-term mortality increases in those with left-sided native valve endocarditis when accompanied by other severe comorbid illnesses, abnormal mental status, congestive heart failure, or a bacterial etiology other than Streptococcus viridans and Staphylococcus aureus, and when treated with medical therapy absent valve surgery.⁸

The estimated risk in injection drug users is 2% to 5% per year, with a mean age of diagnosis being 30 years old. When endocarditis occurs in injection drug users, it has a predilection for the tricuspid valve. Other features include increased susceptibility to recurrence (approximately 40%) and increased mortality in those with concurrent human immunodeficiency virus and evidence of immunosuppression (defined as a CD4+ T-cell count of <200/mm³). Large vegetation size and fungal organism are predictive of poor outcome in injection drug use–associated right-sided endocarditis.⁹

Indwelling vascular devices create greater risks that microorganisms will attach to valves during bacteremia. Healthcare-associated endocarditis occurs when (1) a diagnosis is made >72 hours after admission in patients with no evidence of endocarditis on admission or in whom the disorder develops within 6 months after hospital discharge; or (2) cardiovascular manipulations have occurred in the ambulatory setting within 6 months before endocarditis develops, including central venous catheter use, arteriovenous fistula for hemodialysis, invasive intravascular techniques, or intracardiac devices (e.g., prosthetic valves, pacemaker, left ventricular assist device).^10,11

Prosthetic valve endocarditis occurs in 1% to 4% of recipients during the first year following valve replacement and in approximately 1% per year thereafter. There is no difference in risk between mechanical versus bioprosthetic valves. Cases with onset within 60 days after surgery are called early prosthetic valve endocarditis and are usually acquired in the hospital. Cases starting beyond 60 days after surgery are called late prosthetic valve endocarditis and are usually community acquired. Hospital mortality rates are highest for those with early (30% to 80%) versus late (20% to 40%) prosthetic valve endocarditis, attributable to the greater virulence of the causative organisms involved.

The normal endothelium is resistant to infection and thrombus formation unless it is injured by high-pressure gradients and turbulent flow states. Such abnormal hemodynamic states occur commonly in those with preexisting valvular or congenital cardiac defects. In injection drug use, endothelial damage likely occurs by a different mechanism, such as from repetitive bombardment with particulate matter (i.e., talc) present in injected material or from ischemia brought on by vasospasm from the injected drug. Cocaine use is particularly associated with increased rates of endocarditis. The resultant endothelial damage promotes deposition of platelets and fibrin and the formation of sterile vegetations (nonbacterial thrombotic endocarditis).

Nonbacterial thrombotic endocarditis can also arise as a result of hypercoagulable states, such as in patients with malignancy (marantic endocarditis) or systemic lupus erythematosus (Libman-Sacks endocarditis), and in areas surrounding foreign bodies like vascular catheters or prosthetic valves. In the setting of preexistent nonbacterial thrombotic endocarditis, transient bacteremia may result in colonization of vegetations and conversion to infective endocarditis.

Transient bacteremia can occur from trauma to the skin or mucosal surfaces of the oropharynx or GI or GU tracts (all of which are normally laden with endogenous flora). Even in the absence of trauma, spontaneous bacteremia can occur in patients with periodontal disease or other localized infections. In cases of bacteremia, the bacterial load usually does not exceed 10 organisms per milliliter of blood, and the bloodstream is usually sterilized in <30 minutes. In the presence of nonbacterial thrombotic endocarditis, this time interval is sufficient for bacteria to adhere to the vegetation and transform it into an infected lesion.

The coexistence of bacteremia and nonbacterial thrombotic endocarditis does not uniformly result in infective endocarditis. To cause infective endocarditis, the infecting organism must be able to adhere to the nonbacterial thrombus on the endothelium. Different organisms vary in this ability. Furthermore, although nonbacterial thrombotic endocarditis is often present in those who develop infective endocarditis, it not an absolute prerequisite, and highly invasive organisms (e.g., S. aureus) can directly invade the endocardium. Adherent organisms stimulate further deposition of platelets and fibrin, leading to sequestration of organisms into a “protected site” that phagocytic cells cannot easily penetrate. As the disease progresses, the vegetation continuously fragments, shedding surface organisms into the circulation and causing sustained bacteremia.

MICROBIOLOGY

A wide range of bacteria and fungi, as well as Rickettsia and Chlamydophila species, can cause infective endocarditis. Bacteria are the predominant cause overall, with a small number of species responsible for the majority of cases. Causative microorganisms vary based on the specific conditions (i.e., native vs prosthetic valve) and risk factors (injection drug use or intracardiac devices; Table 155-1). Overall, recent reports from the United States and European countries indicate that Staphylococcus is the single most common cause, followed by streptococci and enterococci.^1,3,12,13,14

The increase in the number of cases caused by staphylococci is likely linked to the observed increase in healthcare-associated endocarditis and also more frequent intravenous drug use. Staphylococcal endocarditis can cause rapid destruction of valves, multiple distal abscesses, myocardial abscesses, conduction defects, and pericarditis. Staphylococcal endocarditis has an increased risk of in-hospital death.¹ In contrast, streptococcal endocarditis tends to be indolent. Patients with enterococcal endocarditis generally have underlying valvular disease and risk factors such as diabetes mellitus or manipulation of the GU or lower GI tract.

Blood cultures are the best initial method for detection but are negative in about 5% of patients; in one third to one half of patients, cultures are negative because of prior antibiotic administration. For those cases associated with negative blood cultures and without prior antibiotic administration, infection is due to fastidious organisms, such as the HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella), Bartonella species, or Coxiella burnetii.

Skin flora and contaminated injection devices are the most frequent sources of microorganisms in injection drug use–associated endocarditis. S. aureus accounts for >50% of cases, followed in decreasing frequency by streptococcal species (including enterococci) and coagulase-negative staphylococci. The well-established predilection for S. aureus to infect normal heart valves, particularly tricuspid valves, is seen in injection addicts, although streptococci and enterococci often infect abnormal mitral or aortic valves in these patients.

Microorganisms involved in prosthetic valve endocarditis often reflect contamination during the perioperative period, with Staphylococcus epidermidis being a commonly isolated organism. Aspergillus and Candida albicans account for the majority of cases of mycotic prosthetic valve endocarditis and often have large vegetations and emboli.

The clinical manifestations of endocarditis are on a continuum, from acute in onset to insidious and indolent.¹² Common presenting symptoms include fever, chills, weakness, and dyspnea. The most common complications are congestive heart failure (44%), CNS disorder (30%), and peripheral embolization (22%).¹⁴

FEVER

Early bacteremia produces nonspecific signs and symptoms (Table 155-2), usually beginning within 2 weeks of infection. Symptoms include fever, chills, nausea, vomiting, fatigue, and malaise.¹⁵ Fever (>38°C [100.4°F]) is present in almost all patients (>90% overall and >98% in those with injection drug use–associated infective endocarditis).^5,11,12,13 Fever may be absent in the elderly, those with a history of antibiotic or antipyretic use, and those with congestive heart failure, renal failure, or immunosuppression. Clinical symptoms of sepsis may be present.

CARDIAC MANIFESTATIONS

Congestive heart failure occurs in up to 70% of patients from distortion or perforation of valvular leaflets, rupture of the chordae tendineae or papillary muscles, or perforation of cardiac chambers. Heart murmurs are common, heard in 50% to 85% of patients, although less so in cases of right-sided endocarditis (<50%). Valvular abscesses and pericarditis can result from local extension. Other cardiac complications include heart blocks and dysrhythmias that result from extension of infection through the interventricular septum to the conduction system.

NEUROLOGIC MANIFESTATIONS

About 20% to 40% of patients develop neurologic symptoms, notably cerebral ischemic events (often in multiple areas), CNS abscess, intracranial hemorrhage, mycotic aneurysm, meningitis, or seizures.¹⁶ Embolic stroke involving the middle cerebral artery is the most common CNS complication.¹⁵

ARTERIAL EMBOLIZATION