Epidemiology
The overall incidence of infective endocarditis in the general population ranges from 3 to 11 cases per 100,000 person-years. The most common underlying conditions are native valvular heart disease, previously implanted prosthetic valves and congenital heart disease. Endocarditis is more common in the elderly and males. The increasing use of indwelling intravenous catheters and leads for cardiac rhythm devices is associated with iatrogenic endocarditis.
Pathophysiology
There are five distinct steps in the sequence of events resulting in endocarditis. First, there is damage to the endocardial surface of the valve or other cardiac structure. Second, there is the accumulation of thrombus and platelets on the damaged surface, termed nonbacterial thrombotic endocarditis (NBTE). Third, the patient develops a transient blood stream infection, usually bacteremia. Fourth, there is deposition and adherence of infectious organisms on the focus of NBTE. Fifth, the organisms grow and multiply at the NBTE site.
Clinical Features
The clinical presentation of endocarditis depends upon the rapidity of onset, the virulence of the underlying organism, and the coexistence of underlying cardiac disease. Patients with acute endocarditis usually present early in the infection with substantial illness. Complications are common and are due to embolism and valvular destruction. Such complications include brain embolism, intracranial hemorrhage, heart failure, myocardial infarction, and peripheral embolism.
Diagnostics
Physical examination, blood cultures and echocardiography are the cornerstones for the diagnosis of endocarditis. Adherence to the major and minor criteria of the modified Duke classification guide diagnosis and subsequent management. Transthoracic echocardiography is usually sufficient to identify the vegetation, but transesophageal provides the optimal method for establishment of endocarditis according to the Duke major criteria.
Treatment
Prompt and accurate antimicrobial therapy should be initiated for the patient with endocarditis. In general, antibiotic therapy will be administered intravenously in high dosages for a prolonged period of time. The primary goals of operation for endocarditis are removal of all infected tissue and correction of the hemodynamic abnormality. Infection of a cardiac valve necessitates either repair or replacement.
Outcome
Mortality after operation for endocarditis ranges widely, with reports of hospital death between 4 and 30 percent. In general, operative mortality is affected by the urgency of the operation, concomitant preoperative heart failure, nonstreptococcal organisms, and prosthetic valve endocarditis. Neurologic deficits can be worsened if surgery is performed within the first few weeks after the initial event. Recurrent endocarditis is uncommon (2–5 percent) if all infected tissue has been removed and there is no active infection at the time of operation.
Infective endocarditis (IE) is defined as any condition in which an infective process has affected a structure of the heart. The valves are the most common location for endocarditis, but the process may also involve atrial or ventricular septal defects, patent ductus arteriosus, or any of a wide range of congenital heart defects, including the aorta and great vessels. Depending on the involved area, the infective process can lead to progressive valvular dysfunction, systemic embolization, congestive heart failure, fistula formation, conduction abnormalities, and other organ dysfunction.
The presentation of IE includes acute, subacute, and chronic forms. In addition, the process can involve either the native structures of the heart or previously placed prostheses, such as valves or shunts. Organisms that cause endocarditis include bacteria, viruses, and fungi. Demonstration of both the organism and the sequelae of infection on cardiovascular function is essential for proper treatment.
The knowledge of established treatment guidelines for IE as well as the long-term sequelae of medically managed endocarditis is important for correct surgical therapy. Osler described the classical findings of endocarditis in 1885, and later stressed the importance of blood cultures for diagnosis.1,2 Kay and colleagues were the first to describe successful surgical treatment of endocarditis in 1961, performing debridement of an infected tricuspid valve and simultaneous closure of a ventricular septal defect.3 Wallace and colleagues performed the first valve replacement for aortic valve endocarditis in 1965.4
There are five distinct steps in the sequence of events resulting in endocarditis. First, there is damage to the endocardial surface of the valve or other cardiac structure. Second, there is the accumulation of thrombus and platelets on the damaged surface, termed nonbacterial thrombotic endocarditis (NBTE). Third, the patient develops a transient blood stream infection, usually bacteremia. Fourth, there is deposition and adherence of infectious organisms on the focus of NBTE. Fifth, the organisms grow and multiply at the NBTE site.
The endocardial surface may become damaged from one of several methods. Congenitally malformed valves or anomalous flow pathways, such as a ventricular septal defect or patent ductus arteriosus, result in turbulent flow. The development of stenosis or insufficiency across a native valve is another important contributing factor. Prosthetic devices, such as biologic or mechanical valves and synthetic grafts, are a common site for infection. Chronic indwelling catheters and pacemaker leads traumatize the chambers and valves, damaging the endocardial surface.
The subendocardium becomes exposed to the circulation after the endocardium has been damaged. The subendocardium is thrombogenic, and platelets and thrombi become adherent in an attempt to heal the breach in the endocardium. This accumulation forms into a mass, or vegetation, that either remains adherent or embolizes to varying degrees.
The vegetation is a susceptible area for colonization by infectious organisms. Typically, there is a transient bacteremia resulting in bacterial deposition on the NBTE vegetation. Such transient bacteremia is common after oral cavity manipulation, upper or lower gastrointestinal (GI) endoscopy, urinary tract instrumentation, and childbirth. Percutaneous interventions and untreated skin infections are also sources of bacteremia. More invasive procedures produce a higher degree of bacteremia, and a longer duration and degree of bacteremia will allow more bacteria to adhere to the vegetation.
The vegetation becomes infected when bacteria or other organisms adhere to the NBTE. The ability of various organisms to adhere to the NBTE is variable. Gram-positive bacteria such as Staphylococcus and Streptococcus, for example, have a greater ability to adhere and form endocarditis than gram-negative bacilli.
The platelets in the NBTE also have a role in bacterial adherence. Certain strains of bacteria that more commonly cause endocarditis have been shown to bind to and activate platelets.5 This may occur through the release of thrombin-induced platelet-microbicidal proteins (tPMPs) by activated platelets. Bacteria can directly activate platelets or result in thrombin formation, which is a platelet agonist.6
After deposition and adherence to the NBTE, the bacteria grow and multiply, enlarging the vegetation. Recurrent or persistent bacteremia can reseed the vegetation, also contributing to progressive growth. Gross examination of the vegetation demonstrates a mass of bacteria, platelets, and fibrin (Fig. 38-1).
The overall incidence of IE in the general population ranges from 3 to 11 cases per 100,000 person-years.7–9 About 75 percent of established cases occur in patients with an underlying structural defect of the heart.10 Most commonly, these individuals have native valvular heart disease. Other common underlying conditions include previously implanted prosthetic valves and congenital heart disease. Endocarditis is more common in the elderly and males.11
Congenital heart disease represents a significant risk factor for the development of endocarditis. It has been estimated that the incidence of endocarditis in patients with any congenital heart defect is as high as 10 to 50 times the incidence of the general population. The most common congenital heart lesions associated with endocarditis are ventricular septal defect, transposition of the great arteries, tetralogy of Fallot, patent ductus arteriosus, and coarctation of the aorta. Those lesions with a cyanotic component are considered to be higher risk.
Mitral valve prolapse and bicuspid aortic valve are forms of congenital heart disease that most commonly present in older patients. The presence of a murmur is thought to be important to the development of endocarditis in these individuals, as the absence of a murmur is not associated with an increased prevalence in mitral valve prolapse.12,13 Degenerative valve disease is also an important risk factor. The increasing use of indwelling intravenous catheters and leads for cardiac rhythm devices is associated with iatrogenic endocarditis.
The clinical presentation of endocarditis depends upon the rapidity of onset, the virulence of the underlying organism, and the coexistence of underlying cardiac disease. More aggressive organisms in the setting of preexisting valvular disease will result in an accelerated course, with rapid diagnosis and early surgical intervention. Less virulent organisms may cause less destruction of cardiac structures, resulting in an elusive clinical course and prolonged illness.
Patients with acute endocarditis usually present early in the infection with substantial illness. Findings include high fevers, chills, rigors, and malaise, with progression to sepsis and circulatory collapse if untreated. Complications are common (see following) due to the aggressive nature of the infection, particularly embolic phenomena. Valvular disease may be extensive with resultant congestive heart failure in otherwise healthy individuals.
The initial presentation in the subacute setting commonly occurs between 2 and 4 weeks after infection. The symptoms are milder and more subtle, with lower fevers and generalized malaise. Other symptoms include weight loss, myalgias, and fatigue, which can mimic malignancy or other chronic illness. If there has not been significant cardiac destruction, most symptoms will resolve on appropriate antibiotic therapy.
Many patients with subacute endocarditis will be diagnosed after a complication has arisen, such as an embolic neurologic event. Other complications of embolism include arterial insufficiency, abdominal pain (bowel or splenic infarction), visual changes (retinal artery occlusion), myocardial infarction (coronary artery occlusion), and hematuria (renal infarction). Multiple septic emboli to the lungs can present as recurrent pneumonia or chest pain from pulmonary infarction.
Two potentially lethal complications of subacute endocarditis are heart failure and intracranial hemorrhage. Although the infection may be successfully treated with antibiotics, the residual structural damage to the heart may progress to heart failure. Thus, a patient with “healed” endocarditis should not be considered cured unless the valvular and ventricular function is stable over a period of time. Mycotic aneurysms from septic emboli to the brain are usually asymptomatic, but can rupture and result in devastating intracranial hemorrhage.
As with acute and subacute endocarditis, prosthetic valve endocarditis is classified according to time frame from surgery. Early prosthetic valve endocarditis is defined as infection occurring within 60 days of operation, and is usually due to either intraoperative contamination or infection in the early postoperative period. Common organisms are skin colonizers and respiratory tract pathogens. The presentation is similar to acute endocarditis and is associated with complications after surgery. Late prosthetic valve endocarditis is defined as infection occurring after 60 days from operation and presents similar to subacute endocarditis. The offending organisms are the same as those with native subacute infections.
The majority of patients with endocarditis will have developed complications, either as the initial presentation or during the course of the disease. The most common complications include congestive heart failure, abscess formation, and embolism. Other less common complications include pseudoaneurysm, mycotic aneurysm, fistula, and conduction disturbances.
Congestive heart failure is the most common cause of death and typically is caused by valvular destruction and insufficiency. Less common causes of congestive heart failure from endocarditis are coronary artery embolization with subsequent myocardial infarction, acute papillary muscle rupture, and valvular stenosis from very large vegetations. Patients with aortic valve disease are particularly prone to develop congestive heart failure.
Extension of the endocarditis process into surrounding myocardium results in abscess formation. This most commonly occurs with aortic valve involvement, forming a root abscess (Fig. 38-2). Mitral valve involvement can result in interventricular or interatrial abscess. Suspicion of abscess should be raised in patients with conduction abnormalities, pericarditis, congestive heart failure, and prosthetic valves. Transesophageal echocardiography (TEE) has the highest sensitivity for the detection of perivalvular abscess.14 Echocardiographic criteria for abscess include aortic root thickness greater than 9 mm, perivalvular density greater than 14 mm in the septum, sinus of Valsalva aneurysm or fistula, and instability (“rocking”) of a prosthetic valve.15
Embolism of the vegetation has the potential for significant morbidity and mortality, and is more common in younger patients.16,17 Stroke occurs most commonly from native mitral valve endocarditis, as these lesions are usually larger than aortic valve vegetations.18 In patients with prosthetic valve endocarditis, there is no difference in stroke rate between aortic and mitral valve involvement.18 Predictors of stroke include left-sided endocarditis, mitral valve involvement, and size greater than 7 mm.18
Pseudoaneurysm occurs when the infective process liquefies and forms a cavity. Pulsatile pressure weakens the cavity and eventually blood enters the space, forming the pseudoaneurysm. The incidence of pseudoaneurysm ranges from 2 to 10 percent, and can occur in the setting of root abscess as well as along previous suture lines.19 Rupture of pseudoaneurysm from IE is likely and requires prompt surgical attention.
Persistent bacteremia or embolization of infected vegetative material from the active endocarditis can result in metastatic abscess. Mycotic aneurysm occurs when a distant abscess forms in an arterial branch. Intracranial mycotic aneurysms typically form in the middle cerebral artery and can produce intracranial hemorrhage. Metastasis of infected material to other organs can result in splenic abscess, septic arthritis, and septic pulmonary embolism.
Fistula formation occurs when an abscess or pseudoaneurysm ruptures into a surrounding structure. Rupture into a cardiac chamber forms an intracardiac shunt, whereas rupture into the pericardium will produce tamponade. Although fistulas are rare, mortality exceeds 50 percent.20
Conduction abnormalities are the result of infective destruction of conduction tissue. First-degree atrioventricular block is most commonly observed.21 Any new change in the electrocardiogram should raise the suspicion of abscess. Mortality can be increased in the presence of a conduction abnormality.21
