**4. Pathogenesis of infective endocarditis with underlying cardiac disease**

The major predisposing categories of underlying cardiac pathology are DVD, CHD and RHD. Platelet-fibrin aggregates form on damaged or inflamed endothelium, resulting in nonbacterial thrombotic endocarditis (NBTE), a precursor of IE [8]. Microorganisms are able to attach to this nidus via adhesion molecules and stimulate a host inflammatory response [8].

Regurgitant valves are at higher risk of IE than stenotic valves [9]. In a large clinical-pathological study on native valve endocarditis (NVIE), 84% of valves were regurgitant [10]. Another found the majority of cases of IE presenting to surgery were for regurgitant valves compared to a control-group of non-IE cases undergoing surgery (9% of regurgitant bicuspid aortic valves (BAV), 1.2% of calcified BAVs, 1.6% of calcified trileaflet aortic valves (AV) and 7% of mitral valve prolapse (MVP)) [11]. Aortic regurgitation (AR) is a predisposing lesion in 17–36% of cases of IE, whilst mitral regurgitation (MR) accounts for 10–18% [12].

The pathogenesis of IE in structural cardiac abnormalities is characterised by the hydrodynamic theory [13]. A high velocity turbulent jet exerts a shearing effect on endothelium, at the site of a restrictive orifice (e.g. ventricular septal defect (VSD) or MR jet) and/or a distal point of contact (jet lesion). The narrowest diameter of flow is the vena contracta (VC), just distal to the restricted anatomical orifice. This is where the pressure is minimal and retrograde flow may occur, permitting platelets and bacteria to deposit [13]. The typical location of vegetation is on the upstream side of the valve, that is, the atrial aspect of the MV, tricuspid valve (TV) and ventricular aspect AV, pulmonary valve (PV) [9].

Structurally normal native right-sided valves in the absence of significant pulmonary hypertension, are exposed to lower pressure flows and are far less commonly involved with IE.In children, without CHD, native right-sided IE involving normal valves is rare but may occur in association with trauma to the valve from central lines or catheters [14, 15]. Other factors are important in risk of acquiring IE and include an interplay between microorganism virulence, altered host defence mechanisms, predisposing systemic illness, and environmental and social factors [16].
