Definition

Infective endocarditis (IE) is a subacute infectious disease of the heart and its surrounding vessels that carries a very high risk of morbidity and mortality. Unfortunately, a clear‐cut diagnosis of IE is rare in patients with congenital heart disease (CHD) and is reserved for those who fulfill the classic Oslerian manifestations: bacteremia or fungemia, evidence of active vasculitis, and/or peripheral emboli (Figure 41.1) and immunologic vascular phenomena. In most cases the clinical presentation is quite variable and therefore the diagnosis is related to an evidence‐based scoring system that includes clinical, microbiological, and echocardiographic findings (Tables 41.1 and 41.2). The Duke criteria [1] and their modification in 2000 [2] have been validated not only in adults but also in children [3,4]. It should be kept in mind that the Duke criteria were developed primarily to facilitate epidemiologic and clinical research efforts so that data could be compared between different centers and countries. In present clinical practice these criteria serve as a guide for diagnosing IE but can never replace final clinical judgment.

Incidence

The incidence of IE in infancy and childhood is unknown as no data exist from a population‐based cohort. CHD now constitutes the predominant underlying condition for IE in children over the age of 2 years in developed countries [5]. Some of the cases in this age group are due to the complexity of neonatal and pediatric intensive care and may be related to indwelling catheters and instrumentation in this population (Video 41.1).

In pediatric hospitals, IE accounts for about 1 in 1280 pediatric admissions per year [6]. In patients with CHD, ventricular septal defect, patent ductus arteriosus, aortic valve abnormalities (e.g., bicuspid aortic valve), and tetralogy of Fallot are the most common underlying conditions in which IE occurs. IE may afflict such patients before surgical intervention, but an increasing proportion of patients has had previous corrective or palliative surgery [7–10].

Corrective surgery without residual defects essentially eliminates the increased risk of IE within 6 months of surgery for ventricular and atrial septal defects and/or patent ductus arteriosus. The highest annual risk for IE has been found in children with repaired or palliated cyanotic CHD [10]. Palliative shunt procedures (Video 41.2) or complex intracardiac repairs increase the risk for postoperative IE [8]. The risk is highest among patients who have had prosthetic aortic valve replacement (Figure 41.2, Video 41.3) or operations performed because of reduced pulmonary blood flow. In those patients with prosthetic valves or conduits, the risk for IE is high even in the immediate postoperative period (first 2 weeks after surgery) whereas for all other patients with residual defects the risk increases with time after surgery [11].

Children with congenital or acquired immunodeficiencies but without identifiable risk factors for IE (such as central venous catheters) do not appear to be at increased risk for IE compared with the general population [5]. Intravenous (IV) drug use is infrequent in childhood, but the incidence is rising in adolescence and adulthood. The incidence of IE in IV drug users is unknown [12] but 1.5–3.3 cases per 1000 person‐years [13,14] is a conservative estimate. IE is more frequent in HIV‐seropositive IV drug users than in HIV‐seronegative patients [15]. It may be difficult to diagnose IE correctly in febrile IV drug users because 35% do not present with a heart murmur on admission [16]. The predilective site of infection in this group is typically the tricuspid valve even in those with structurally normal hearts (Figure 41.3, Video 41.4).

In the adult population, the incidence of IE is approximately five episodes/100,000 person‐years if IV drug users are excluded [17]. Apart from pre‐existing structural heart disease, which accounts for three‐quarters of all cases of IE, pacemaker and defibrillator implantations also account for a significant number of episodes of IE (Figure 41.4, Video 41.5) [18]. In a large multicenter study of 2760 patients with proven IE, 6.4% (177) occurred in patients with cardiac devices [19]. IE in patients who have septal defect occluder devices is rare but has been reported [20]. New interventional techniques such as percutaneous pulmonary valve implantation also involve a risk of IE [21]. A new patient group with a risk for IE is growing with the rising numbers of percutaneous implantations of valves (Melody® and Sapien) in the right ventricular outflow tract in repaired tetralogy of Fallot. An annualized risk of 1.9% for IE was found in a single‐center study [22].

A particularly vulnerable group at risk for IE is the adult population with CHD. IE accounts for 4% of hospital admissions of adults with CHD in specialized centers [23]. In those with repaired CHD, IE is most commonly seen in those with repaired tetralogy of Fallot and atrioventricular canal defects (Figure 41.5) [24]. In unoperated or palliated CHD, the most common sites of IE are ventricular septal defect, left ventricular outflow tract, and mitral valve. An isolated atrial septal defect (unrepaired or later than 6 months after operation/catheter intervention) has not been associated with an increased risk for IE in any age group.

Etiology and pathogenesis

The pathogenesis of IE is characterized by the triad of endothelial damage, platelet adhesion, and microbial adherence to the vegetation or intact valvar tissue [25]. An intact endothelium within the heart is generally a poor stimulator of blood coagulation and therefore not predestined for bacterial attachment [5]. However, in children with CHD, abnormal high‐velocity jet streams of blood (as seen in such lesions as ventricular septal defect, patent ductus arteriosus, aortic or pulmonary valve stenosis, or regurgitant atrioventricular valves) lead to damage of the endothelium due to shear stress forces and activation of the prothrombotic cascade in the circulating blood. Subsequently, a sterile platelet–fibrin deposition on the endothelial lesion provides a milieu for bacterial colonization. In addition to CHD, the administration of indwelling intravenous catheters into the right side of a structurally normal heart may traumatize the endocardium or valvar endothelium by exposing the subendothelial collagen [26]. This is one of the major mechanisms resulting in IE of the newborn.

Once the inciting lesion has been formed, bacteremia must be present to colonize the vegetation. Even in the presence of an endothelial lesion and a sterile thrombus formation, not every bacteremia event leads to IE. Bacteria must be able to survive in the bloodstream in sufficient numbers and adhere to the platelet–fibrin–fibronectin complex on the lesion. Organisms such as Staphylococcus aureus, Streptococcus viridans, Streptococcus pneumoniae, HACEK organisms, and group A, C, and G streptococci as well as Candida albicans are known to have specific surface receptors for fibronectin that promote the adhesion of bacteria to the thrombus formation [27]. After adhesion, the microorganisms are trapped within the vegetation and thus protected from phagocytic cells and other host defense mechanisms [5]. Within the growing vegetation, proliferation is possible up to a maximum bacterial density of 10⁷ to 10¹⁰ colony‐forming units per gram of tissue [28,29].

Morphology and classification

The morphology of IE vegetations is dependent on the location of the endothelial lesion and typically follows the “pathologic” bloodstream. When IE occurs in association with a ventricular septal defect, the vegetation is typically visualized on the right ventricular aspect of the septum and/or the site where the high‐velocity jet strikes the right ventricular free wall (Figure 41.6). In the case of patent ductus arteriosus, the vegetation may float through the pulmonary opening of the ductus into the main pulmonary artery (Figure 41.7, Video 41.6). With regurgitant atrioventricular valves, the lesion is usually located on the atrial side (Figures 41.8 and 41.9, Videos 41.7 and 41.8). Vegetations on valves may cause perforation (Figure 41.10, Video 41.9), or chordal rupture, but can also extend to the outside of the valve into surrounding structures (Figure 41.11). When semilunar valves are affected, the primary vegetation is typically on the ventricular surface of the valve (Figure 41.12) but may also extend more proximally through the valve into the supravalvar region in systole. When the aortic valve is affected, perforation through the annulus into the myocardium or into either atrium is possible. Newly acquired atrioventricular block (Figure 41.13) together with clinical suspicion of IE may be a strong indicator for the presence of a para‐aortic ring abscess (Figure 41.14, Video 41.10) [30].

In a series of 153 patients [31], the major underlying cardiac lesion associated with IE in childhood was the unoperated ventricular septal defect (30%) followed by mitral regurgitation (15%) and bicuspid aortic valve (9%) (Figure 41.15). In patients who undergo palliative surgery, infected aortopulmonary shunts (80%) predominate. In those who have corrective surgery, the most common sites for development of IE include right ventricle‐to‐pulmonary artery valved conduits (27%) (Figure 41.16), prosthetic valves (22%), and ventricular septal defect patch (22%) (Table 41.3) [31,32]. Endocarditis on prosthetic valves usually initiates on the valvar cuff (Figure 41.2, Video 41.3) and often extends outside the annulus, causing dehiscence (Figure 41.17) and myocardial involvement [25]. Mechanical prosthetic valves appear to have higher risk for IE in the early period after surgery whereas the risk with bioprosthetic valves appears to be higher later on [33,34]. Bovine jugular vein grafts appear to be at higher risk for IE [35], whereas implantable rings appear to have the lowest risk [36].

Pathophysiology

The pathophysiologic consequences of IE are primarily defined by the underlying CHD and the complications that arise from the insult, such as valvar obstruction, regurgitation and/or perforation, ventricular dysfunction, embolic phenomena, and conduction disturbances. Age at presentation and location of IE (right‐sided versus left‐sided) also play a pivotal role. In newborns, symptoms are generally related to septicemia rather than cardiac failure [37,38]. In children with systemic–pulmonary artery shunts, increasing cyanosis may be the primary symptom together with pulmonary findings related to septic pulmonary embolization [39].

In adult patients with left‐sided IE, congestive heart failure is one of the complications with the greatest impact on prognosis [40–42]. Moderate to severe heart failure is identified as one of the independent risk factors for 6‐month mortality along with abnormal mental status, bacterial etiology other than viridans streptococci, and medical therapy without valve surgery [40]. The severity of symptoms is often not influenced by appropriate antibiotic therapy. Compensation of heart failure is dependent on the valve affected, with acute aortic regurgitation being tolerated the least and acute tricuspid regurgitation being tolerated the best. Congestive heart failure will develop acutely when there is perforation of a native or bioprosthetic valve leaflet, acute valve dehiscence (Figure 41.18, Video 41.11), rupture of an infected mitral chord, obstruction to outflow from a bulky vegetation, or sudden intracardiac shunt from a fistulous tract [12].

Imaging