**8.1 Clinical presentation**

 The most common type of CIED infection (~60%) is a generator pocket infection with symptoms of localized inflammation including erythema, pain, swelling, warmth, erosion, and purulent drainage or skin dehiscence [45]. In less than half of these cases, there are also systemic signs of infection or positive blood cultures [25, 45]. Often, these signs are easily identified, motivating the patient to seek medical attention. But sometimes, the symptoms are more subtle, presenting soon after implantation and thereby hard to differentiate from pure postoperative inflammation, skin reactions to dressings, disinfection agents, and sutures or a restricted and superficial infection [7, 11].

 A second major manifestation is that of infection affecting either cardiac valves, device leads, or a combination of these two (CIED-IE or CIED-LI). This accounts for 10–23% of all CIED infections [25, 46]. Many of these patients have typical signs of systemic infection, presenting with fever, rigors, malaise, fatigue, or anorexia. Most, but not all, show positive blood cultures [11, 45]. Parallel symptoms of device pocket infection make the diagnosis easier, but this is not always the case. Instead, the presence of a CIED is often disregarded by the first doctor seeing the patient [24]. Major diagnostic tools recommended by guidelines are cardiac imaging, repeated blood cultures and use of the modified Duke criteria (**Table 4**) [7, 12].

In the case of cardiac vegetations, the tricuspid valve is the most common site, but vegetations may also appear on both the pulmonic and left-sided valves. *S. aureus* is the most common pathogen. In this patient group, it is common with symptoms or radiographic findings indicating septic embolism to the lungs (~40%) as well as other organs (18%), and occasionally distant abscess formation [46–48]. Possible embolic phenomena are important to keep in mind, as secondary foci of infection, such as vertebral osteomyelitis or discitis, can be the main symptom presented by the patient [7, 47]. Other possible sites of metastatic abscesses are brain, liver, kidney, and spleen. In some cases, it will be hard to distinguish if a distal site of infection is the result of


#### **Table 4.**

*The Duke criteria, adapted from Li et al. [12].* 

hematogenous seeding from a cardiac device or if the opposite is true [25]. Less than 10% present with septic shock, usually caused by virulent pathogens such as *S. aureus*  or *Pseudomonas aeruginosa* [7, 44]. Less virulent pathogens are generally associated with a more subacute or chronic presentation. In rare cases, this can be coupled with immune-complex mediated conditions such as nephritis or vasculitis [44].

In contrast to the diversity of symptoms mentioned above, occult bacteremia (or in rare cases fungemia) without localized symptoms at the generator pocket represents a diagnostic challenge primarily by the absence of findings [11, 25]. Studies indicate that laboratory abnormalities are present in less than half of the cases of CIED infection, hence normal laboratory results should not rule out CIED infection [9, 25]. Distant foci of infection could result in hematogenous seeding of the device but should not always be interpreted as evidence of actual CIED infection. To avoid misdiagnosis and unnecessary and riskful extractions, an algorithm for managing bacteremia among CIED patients has been presented by DeSimone and Sohail [49].

Except for these three main presentations, there are occasional cases of device erosion through the skin with neither positive blood cultures nor any other local inflammatory changes. Usually, erosion is a slow process of fat necrosis and migration from deeper layers of the skin and seldom presents shortly after implantation. The exact cause often remains unclear but can be low grade device infection, other local infections or mechanical factors alone [11]. Whenever a generator or lead has eroded through the skin, the whole device system should be regarded as infected [7].
