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Feasibility and diag- nostic value of cardiovascular magnetic resonance imaging after acute is- chemic stroke of undetermined origin. Stroke. 2017;48:1241 1247. doi: 530. Katsanos AH, Giannopoulos S, Frogoudaki A, Vrettou AR, Ikonomidis I, Paraskevaidis I, Zompola C, Vadikolias K, Boviatsis E, Parissis J, et al. The diagnostic yield of transesophageal echocardiography in patients with cryptogenic cerebral ischaemia: a meta-analysis. Eur J Neurol. 535. GaudronM,BonnaudI,RosA,PatatF,deToffolB,GiraudeauB,DebiaisS. Diagnostic and therapeutic value of echocardiography during the acute phase of ischemic stroke. J Stroke Cerebrovasc Dis. 2014;23:2105 2109. 532. Kim SJ, Choe YH, Park SJ, Kim GM, Chung CS, Lee KH, Bang OY. Routine cardiac evaluation in patients with ischaemic stroke and absence of known atrial fibrillation or coronary heart disease: transthoracic ech- ocardiography vs. multidetector cardiac computed tomography. Eur J 533. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial: TOAST: Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24:35 41. doi: 534. Galougahi KK, Stewart T, Choong CY, Storey CE, Yates M, Tofler GH. The utility of transoesophageal echocardiography to determine manage- ment in suspected embolic stroke. Intern Med J. 2010;40:813 818. doi: 535. Deleted in proof. 536. de Bruijn SF, Agema WR, Lammers GJ, van der Wall EE, Wolterbeek R, Holman ER, Bollen EL, Bax JJ. Transesophageal echocardiography is superior to transthoracic echocardiography in management of patients of any age with transient ischemic attack or stroke. Stroke. 2006;37:2531 537. Harloff A, Handke M, Reinhard M, Geibel A, Hetzel A. Therapeutic strategies after examination by transesophageal echocardiography in 503 patients with ischemic stroke. Stroke. 2006;37:859 864. doi: 538. Abreu TT, Mateus S, Correia J. Therapy implications of transtho- racic echocardiography in acute ischemic stroke patients. Stroke. 539.


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Update on Cardiovascular Implantable Electronic Device Infections and Their Management A Scientific Statement From the American Heart Association Endorsed by the Heart Rhythm Society Larry M. Baddour, MD, FAHA, Chair; Andrew E. Epstein, MD, FAHA, FHRS; Christopher C. Erickson, MD, FAHA; Bradley P. Knight, MD, FHRS; Matthew E. Levison, MD; Peter B. Lockhart, DDS; Frederick A. Masoudi, MD, MSPH; Eric J. Okum, MD; Walter R. Wilson, MD; Lee B. Beerman, MD; Ann F. Bolger, MD, FAHA; N.A. Mark Estes III, MD, FAHA, FHRS; Michael Gewitz, MD, FAHA; Jane W. Newburger, MD, MPH, FAHA; Eleanor B. Schron, PhD, RN, FAHA; Kathryn A. Taubert, PhD, FAHA; on behalf of the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Nursing; Council on Clinical Cardiology; and the Interdisciplinary Council on Quality of Care and Outcomes Research Abstract Despite improvements in cardiovascular implantable electronic device (CIED) design, application of timely infection control practices, and administration of antibiotic prophylaxis at the time of device placement, CIED infections continue to occur and can be life-threatening. This has prompted the study of all aspects of CIED infections. Recognizing the recent advances in our understanding of the epidemiology, risk factors, microbiology, management, and prevention of CIED infections, the American Heart Association commissioned this scientific statement to educate clinicians about CIED infections, provide explicit recommendations for the care of patients with suspected or established CIED infections, and highlight areas of needed research. (Circulation. 2010;121:458-477.)


Recognizing the recent advances in our understanding of the epidemiology, risk factors, microbiology, management, and prevention of CIED infections, the American Heart Association commissioned this scientific statement to educate clinicians about CIED infections, provide explicit recommendations for the care of patients with suspected or established CIED infections, and highlight areas of needed research. (Circulation. 2010;121:458-477.) Key Words: AHA Scientific Statements infection device, cardiovascular implantable electronic device pacemaker implantable cardioverter-defibrillator endocarditis In 2003, the American Heart Association published a scientific statement that reviewed a variety of nonvalvular cardiovascular device infections.1 The document included an encyclopedic view of device infections involving cardiac, arterial, and venous structures. The primary focus of the statement was to formally recognize this group of cardiovas- cular infections and to highlight their clinical importance. The document also included a limited number of recommenda- tions regarding the prevention and management of nonvalvu- lar device infections. Perhaps the most noteworthy recom- mendation in the statement emphasized that antibiotic prophylaxis for routine dental, gastrointestinal, and genitouri- nary procedures was not indicated in patients with these devices. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on August 7, 2009. A copy of the statement is available at http://www.americanheart.org/presenter.jhtml?identifier 3003999 by selecting either the topic list link or the chronological list link (No. KJ-0732). To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com.


KJ-0732). To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com. The American Heart Association requests that this document be cited as follows: Baddour LM, Epstein AE, Erickson CC, Knight BP, Levison ME, Lockhart PB, Masoudi FA, Okum EJ, Wilson WR, Beerman LB, Bolger AF, Estes NAM 3rd, Gewitz M, Newburger JW, Schron EB, Taubert KA; on behalf of the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Nursing; Council on Clinical Cardiology; and the Interdisciplinary Council on Quality of Care and Outcomes Research. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation. 2010;121:458 477. Expert peer review of AHA Scientific Statements is conducted at the AHA National Center. For more on AHA statements and guidelines development, visit http://www.americanheart.org/presenter.jhtml?identifier 3023366. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.americanheart.org/presenter.jhtml? identifier 4431. A link to the Permission Request Form appears on the right side of the page. 2010 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.109.192665 AHA Scientific Statement The 6 years after the publication of the 2003 document1 have witnessed exceptional advances in our understanding of several clinical aspects of cardiovascular device infections. In particular, CIED infections have received the bulk of the attention, with sentinel observations regarding the epidemi- ology, associated risk factors, and management and preven- tion of permanent pacemaker (PPM) and implantable cardioverter-defibrillator (ICD) infections.


In particular, CIED infections have received the bulk of the attention, with sentinel observations regarding the epidemi- ology, associated risk factors, and management and preven- tion of permanent pacemaker (PPM) and implantable cardioverter-defibrillator (ICD) infections. Findings from several key clinical investigations that were published after 2003 prompted the Rheumatic Fever, Endocarditis, and Ka- wasaki Disease Committee of the Council on Cardiovascular Disease in the Young of the American Heart Association to provide an updated document limited to CIED infections. Because of the rarity of infection of implantable loop rec- orders and cardiovascular monitors, these devices are not considered in the present document. Classification System The writing group was charged with the task of developing evidence-based recommendations for care and designating a classification and a level of evidence for each recommendation. The American College of Cardiology/American Heart Associa- tion classification system was used as shown in Table 1. Background CIEDs have become increasingly important in cardiac disease management over the past 5 decades in the United States and have dramatically improved both patient quality and quantity of life. PPMs have been implanted since the 1960s. Advances in PPM technology have provided a strong foundation for the accelerated development of ICD and cardiac resynchroniza- tion systems.2 Over the years, CIEDs have become smaller in size despite a marked expansion of device functionality. Table 1. Applying Classification of Recommendations and Level of Evidence *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials.


Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. In 2003, the ACCF/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guideline recommendations have been written in full sentences that express a complete thought, such that a recommendation, even if separated and presented apart from the rest of the document (including headings above sets of recommendations), would still convey the full intent of the recommendation. It is hoped that this will increase readers comprehension of the guidelines and will allow queries at the individual recommendation level. Baddour et al Cardiovascular Device Infections 459 Guidelines from the American College of Cardiology/Amer- ican Heart Association/Heart Rhythm Society are available and are updated serially; the guidelines provide specific recommendations for CIED implantation.3 In an analysis4 of CIED implantation in the United States between 1997 and 2004, implantation rates for PPMs and ICDs increased by 19% and 60%, respectively. Approxi- mately 70% of device recipients were 65 years of age or older, and more than 75% of them had 1 or more coexisting illnesses. These data are consistent with findings from recent population-based surveys in Olmsted County, Minnesota,5,6 where patients undergoing PPM implantation between 1975 and 2004 had increasing numbers of coexisting illnesses. Simultaneously, dual-chamber pacing has become used much more frequently than single-chamber pacing.4 Similarly, the frequency of ICD implantation increased in the elderly (70 to 79 years of age) and very elderly (80 years of age or older).5 The 2001 World Survey7 found that in developed countries, between 20% and 35% of CIED recipients were more than 80 years old.


Simultaneously, dual-chamber pacing has become used much more frequently than single-chamber pacing.4 Similarly, the frequency of ICD implantation increased in the elderly (70 to 79 years of age) and very elderly (80 years of age or older).5 The 2001 World Survey7 found that in developed countries, between 20% and 35% of CIED recipients were more than 80 years old. The National Hospital Discharge Survey8 found a 49% increase in the number of new CIED implantations, including both PPMs and ICDs, in the United States between 1999 and 2003. In 2003, although the absolute number of PPM implan- tations was higher than for ICDs (180 284 versus 57 436), more of the increase in CIED device implantation was driven by ICD implantations (160% and 31% increases in ICD and PPM implantations, respectively).8 In summary, the increased rates of CIED implantation coupled with increased implan- tation in older patients with more comorbid conditions have set the stage for higher rates of CIED infection. Incidence and Epidemiology PPM endocarditis has been recognized since the early 1970s.9,10 In earlier years, the rates of PPM infection ranged widely between 0.13%11 and 19.9%.12 Although most infec- tions have been limited to the pocket, frank PPM endocarditis accounts for approximately 10% of PPM infections.13 The first ICD was implanted in 1980.14 Subsequent de- creases in the size of ICDs permitted implantation without thoracotomy, although initially, abdominal implantation with tunneling was required. Subsequently, the entire device could be implanted prepectorally. The infection rate with these less extensive operations was lower ( 7%).15 In a study of all ICD primary implantations, replacements, and revisions at a single center, there were 21 ICD-related infections (1.2%) among 1700 procedures, affecting 1.8% of 1170 patients.


The infection rate with these less extensive operations was lower ( 7%).15 In a study of all ICD primary implantations, replacements, and revisions at a single center, there were 21 ICD-related infections (1.2%) among 1700 procedures, affecting 1.8% of 1170 patients. Among 959 patients with long-term follow-up, the infection rate was 3.2% with abdominal and 0.5% with pectoral Despite the greater ease of device implantation with pectoral rather than other routes and increasing experience with implantation, the rate of CIED infection has been increasing. Cabell et al16 reported that among Medicare beneficiaries, the rate of cardiac device infections (PPMs, ICDs, valves, and ventricular assist devices) increased from a 124% increase during the study period. The rate of frank endocarditis was relatively unchanged (0.26 and 0.39 cases/ 1000 beneficiaries, respectively). These findings were mirrored when CIED implantations were analyzed in Olmsted County, Minnesota, from 1975 to 2004.17 A total of 1524 patients were included with a total person-time follow-up of 7578 years with device implanta- tion. The incidence of CIED infection was 1.9/1000 device- years (95% confidence interval [CI] 1.1 to 3.1), with an incidence of pocket infection alone of 1.37/1000 device-years (95% CI 0.62 to 0.75) and an incidence of pocket infection with bloodstream infection or device-related endocarditis of cumulative probability of CIED infection was higher among patients with ICDs than among those with PPMs. The National Hospital Discharge Survey8 similarly showed that between 1996 and 2003, the number of hospitalizations for CIED infections increased 3.1-fold (2.8-fold for PPMs and 6.0-fold for ICDs). The numbers of CIED infection related hospitalizations increased out of proportion to rates of new device implantation. Moreover, CIED infection increased the risk of in-hospital death by more than 2-fold. Risk Factors Several studies have identified characteristics associated with CIED infections.


Risk Factors Several studies have identified characteristics associated with CIED infections. In a single-center case-control study,18 case subjects were more likely to have diabetes mellitus and heart failure and to have undergone generator replacement; renal dysfunction (glomerular filtration rate 60 mL min 1 ) had the strongest (odds ratio [OR] 4.8) association with CIED infection. Renal dysfunction was also associated with risk of CIED infection in a more recent nested case-control investigation.19 In addition, Lekkerkerker et al19 identified oral anticoagulant use as an associated risk factor for infec- tion. In another single-center case-control study, 29 patients with PPM infection were included, and long-term corticoste- roid use (OR 13.9) and the presence of more than 2 pacing leads (OR 5.41) were identified as independent correlates of In addition to patient factors, procedural characteristics may also play an important role in the development of CIED infection. In a prospective cohort of 6319 patients receiving CIED implantation in 44 medical centers, Klug et al21 identified 42 patients who developed CIED infection during 1 year of follow-up. The factors associated with an increased risk of infection included fever within 24 hours before implantation (OR 5.83), use of preprocedural temporary pacing (OR 2.46), and early reintervention (OR 15.04). Implantation of a new system (OR 0.46 compared with partial or complete system replacement) and use of peripro- cedural antimicrobial prophylaxis (OR 0.40) were both asso- ciated with a lower risk of infection.


Implantation of a new system (OR 0.46 compared with partial or complete system replacement) and use of peripro- cedural antimicrobial prophylaxis (OR 0.40) were both asso- ciated with a lower risk of infection. The latter finding corroborated other evidence supporting perioperative antimi- crobial prophylaxis for CIED infection prevention.20,22 Other small studies suggest that pectoral transvenous device place- ment is associated with significantly lower rates of CIED infection than for those implanted abdominally15 or by thoracotomy.23,24 Thus, the pervasive use of a pectoral ap- proach is not only less invasive but also appears to confer an ancillary benefit of lower infection risk. Physician experience in CIED implantation may also play a role in the rate of subsequent CIED infection. In a study of Medicare administrative data, Al-Khatib et al25 found a significantly higher risk of ICD infection within 90 days of device implantation in patients whose device was placed by physicians in the lowest quartile of implantation volume (OR 2.47 compared with physicians in the highest-volume quar- tile). Rates of mechanical complications at 90 days were also higher for lower-volume physicians. Finally, among patients with bloodstream infection, the organism involved is strongly associated with the likelihood of serving as a manifestation of CIED infection, even in patients with no other evidence of CIED infection. In a cohort of 33 patients with implanted devices and subsequent Staph- ylococcus aureus bacteremia,26 nearly one half (45.4%) had confirmed CIED infection, and only a minority had local signs or symptoms that suggested generator-pocket infection.


In a cohort of 33 patients with implanted devices and subsequent Staph- ylococcus aureus bacteremia,26 nearly one half (45.4%) had confirmed CIED infection, and only a minority had local signs or symptoms that suggested generator-pocket infection. Similarly, in a cohort study from Olmsted County, Minne- sota, 55% of 22 patients with cardiac devices and subsequent S aureus bacteremia had definite or possible CIED infec- tion.17 In contrast, the risk of device infection with bacteremia with Gram-negative bacilli was substantially lower.27 Johansen et al28 followed up 36 076 patients in the Danish Pacemaker Register. The incidence of explantation due to infection was significantly higher after replacement proce- dures than after first implantation (2.06% versus 0.75%, P 0.01). Device revision was associated with CIED infec- tion in another investigation described recently.19 Although the incidence of infection decreased in the past 3 years of the study, the shorter follow-up of patients was thought to be a possible explanation. Whether multiple device revisions in- crease the risk of CIED infection exponentially is undefined. The importance of reinterventions and device replacement is highlighted in the current era of increased safety alerts and device advisories. Gould and Krahn29 reported that in Can- ada, the risk of major complications of ICD replacement in response to recalls that required reoperation was 5.8% (31 of 533 patients), which included 2 deaths after extraction for pocket infection. Kapa et al30 reported a 1.4% complication risk at Mayo Clinic.


Kapa et al30 reported a 1.4% complication risk at Mayo Clinic. In summary, several factors associated with a greater risk of CIED infection have been described in this section, including the following: (1) Immunosuppression (renal dys- function and corticosteroid use); (2) oral anticoagulation use; (3) patient coexisting illnesses; (4) periprocedural factors, including the failure to administer perioperative antimicrobial prophylaxis; (5) device revision/replacement; (6) the amount of indwelling hardware; (7) operator experience; and (8) the microbiology of bloodstream infection in patients with in- dwelling CIEDs. Future study of CIED infection pathogene- sis should better define how associated factors contribute to infection risk and whether intervention can decrease the risk. Risk factor analyses reported to date have noteworthy limitations, generally have included relatively small numbers of patients with CIED infections, and, with few exceptions, reflect the experience of single centers. Thus, although the existing literature provides some insight into CIED infection risk factors, larger, more representative studies would be useful in identifying and addressing the most important factors that are responsible for the development of CIED infection. Financial Burden Precise data regarding the actual healthcare burden of CIED infections are not available and are sorely needed. Consider- ing the acquisition costs of CIED,31 it is not surprising that the economic consequences, including healthcare resource utili- zation, of CIED infections are substantial. The financial impact is due to multiple factors, including but not limited to the costs of device removal, a new device (which would be required in the majority of patients), cardiac and other medical evaluations, diagnostic procedures, surgical interven- tions for infected device removal, new device placement and certain infectious complications, medical therapy of infec- tion, and critical care stays that are often prolonged.


The financial impact is due to multiple factors, including but not limited to the costs of device removal, a new device (which would be required in the majority of patients), cardiac and other medical evaluations, diagnostic procedures, surgical interven- tions for infected device removal, new device placement and certain infectious complications, medical therapy of infec- tion, and critical care stays that are often prolonged. Even when a CIED is ultimately proven not to be infected, the cost of an evaluation for device infection among those with S aureus bacteremia is sizable.32 Microbiology Staphylococcal species cause the bulk of CIED infec- tions17,33 40 and account for 60% to 80% of cases in most reported series (Figure 1). A variety of coagulase-negative Staphylococcus (CoNS) species have been described to cause CIED infections.41 CoNS is well recognized as a common cause of microbiological specimen contamination, and thus, repeated isolation of the same species of CoNS with an identical antibiotic susceptibility pattern is desired to support its role as an etiologic agent in CIED infections. Polymicro- bial infection sometimes involves more than 1 species of CoNS.36,40,42 The prevalence of oxacillin resistance among staphylococcal strains has varied among studies, but it is prevalent and should influence initial empirical therapy de- cisions in CIED infections. Corynebacterium species, Propi- onibacterium acnes, Gram-negative bacilli37,38 including Pseudomonas aeruginosa,43 and Candida species account for a minority of CIED infections. Fungi other than Candida44 and nontuberculosis mycobacteria45,46 are rarely identified as pathogens in CIED infection. The microorganisms that cause CIED infections may be acquired either endogenously from the skin of patients or Figure 1. Microbiology of PPM/ICD infections (n 189). From Sohail et al,38 with permission. Baddour et al Cardiovascular Device Infections 461 exogenously from the hospital inanimate environment or from the hands of hospital workers.


Baddour et al Cardiovascular Device Infections 461 exogenously from the hospital inanimate environment or from the hands of hospital workers. In support of endogenous acquisition, an association has been noted between the presence of preaxillary skin flora and the pathogens isolated from pacemaker infection.35 Although low concentrations of methicillin-resistant CoNS have been detected in individuals with no healthcare contact and no recent antibiotic expo- sure,47 a disproportionate frequency of CIED infections due to multidrug-resistant staphylococci26,40 suggests that a healthcare environment is the site of infection acquisition.48,49 Pathogenesis The pocket may become infected at the time of implantation, during subsequent surgical manipulation of the pocket, or if the generator or subcutaneous electrodes erode through the skin. In the latter case, erosion can also occur as a secondary event due to underlying infection. Pocket infection may track along the intravascular portion of the electrode to involve the intracardiac portion of the pacemaker or ICD. Alternatively, the pocket or intracardiac portion of the electrode may become infected as a result of hematogenous seeding during a bout of bacteremia or fungemia secondary to a distant infected focus. Hematogenous seeding of a CIED is unlikely to occur in cases of Gram-negative bacillary bacteremia, as discussed below. Bacteremia due to S aureus can result in device infection, but the prevalence of this occurrence and the differentiation of this mechanism of device infection from intraoperative contamination at the time of device placement or manipulation are difficult to determine. There are no data that examine the likelihood of hematogenous seeding of a device due to other Gram-positive cocci that are more common causes of bloodstream infection or due to fungi, in particular Candida species. Device-related infection is the result of the interaction between the device, the microbe, and the host.


Device-related infection is the result of the interaction between the device, the microbe, and the host. Initial attach- ment of bacteria to the device is mediated by physical- chemical properties, such as hydrophobicity, surface tension, and electrostatic charge, of the plastic surface of the device and the bacterial surface.50 Bacteria, particularly Gram- positive cocci, can also adhere to and be engulfed by endothelial cells that can cover an endothelialized lead over a period of time, which is thought to be an important mecha- nism of device infection by the hematogenous route. Device Factors Device-related factors, such as the type of plastic polymer, irregularity of its surface, and its shape, can affect bacterial adherence to the device.51 Plastic polymers that encase medical devices, as well as the pathogens that adhere to them, are hydrophobic. The greater the degree of hydrophobicity, the greater is the adherence.52 Polyvinyl chloride favors more adherence than Teflon (duPont, Wilmington, Del), polyeth- ylene more than polyurethane, silicone more than polytetra- fluoroethylene, and latex more than silicone; some metals (eg, stainless steel) favor adherence more than others (eg, titanium). An irregular surface of the device favors microbial adherence more than a smooth surface. Indirect device factors previously addressed in this document as risk factors associ- ated with CIED infection include subsequent invasive manip- ulation of an implanted CIED and a limited number of device implantations previously performed by the physician per- forming the procedure. Microbial Factors None of the major virulence factors or toxins of S aureus have been found in CoNS, and it seems clear that the development and persistence of CoNS infections, which are so often associated with foreign materials, are due to different mech- anisms, such as adherence.


Microbial Factors None of the major virulence factors or toxins of S aureus have been found in CoNS, and it seems clear that the development and persistence of CoNS infections, which are so often associated with foreign materials, are due to different mech- anisms, such as adherence. The initial nonspecific attachment by means of physicochemical forces is followed or accom- panied simultaneously by the specific interaction of bacterial surface adhesins with the uncoated device directly and with host proteins that coat the device. CoNS may adhere directly to plastic polymers on the surface of the device via fimbria- like surface protein structures53 or via a capsular polysaccha- ride (polysaccharide/adhesin). Antibodies to polysaccharide/ adhesin (either produced actively by immunization or infused passively as polyclonal or monoclonal antibodies) prevent experimental S epidermidis catheter infections54 and experi- mental endocarditis55 in animals. Bacteria may also adhere to host matrix proteins that coat the surface of an implanted device.56 Host extracellular matrix proteins include fibrinogen, fibronectin, and collagen that are deposited on newly implanted biomaterials.57,58 Staphylococci have a variety of surface adhesins, some known collectively by the acronym MSCRAMM (microbial surface components reacting with adherence matrix mole- cules), that allow the pathogen to establish a focus of Biofilm Formation Subsequent accumulation of bacteria on top of bacteria that adhere to a device surface requires the production of so-called polysaccharide intercellular adhesin, which is strongly asso- ciated with the staphylococcal cell surface and mediates cell-to-cell adhesion.50,59 The layers of bacteria on the surface of an implanted device are encased in this extracellular slime60 and constitute a biofilm. Biofilm is defined as a surface-associated community of 1 or more microbial species that are firmly attached to each other and the solid surface and are encased in an extracellular polymeric matrix that holds the biofilm together.


Biofilm is defined as a surface-associated community of 1 or more microbial species that are firmly attached to each other and the solid surface and are encased in an extracellular polymeric matrix that holds the biofilm together. Microbes in a biofilm are more resistant to antibiotics and host defenses, perhaps as a result of the dense extracellular matrix that protects the microbes secluded in the interior of the community. When a bacterial cell switches modes from free-floating (planktonic) organisms to biofilm, it undergoes a phenotypic shift in behavior in which large groups of genes are regulated.50 Microbial Persistence Phenotypic variation is also thought to be operative in supporting the persistence of infection due to staphylococci in a biofilm that coats the surface of a CIED. Small colony variants are phenotypes that have caused CIED infec- tions61 63 and harbor several characteristics that are thought to enhance the survival of staphylococci either in a biofilm or in endothelial cells that cover the device, including resistance to certain antibiotics.64 66 Host Factors Host factors associated with increased risk of CIED infection were outlined in a previous section of this document. These include renal failure, corticosteroid use, congestive heart failure, hematoma formation, diabetes mellitus, and antico- agulation use. Diagnosis CIED infection can present as different syndromes. In the majority of cases, local inflammatory changes of the generator-pocket site are present, or cutaneous erosion with percutaneous exposure of the generator and/or leads is seen. These local changes, often accompanied by pain or discom- fort, usually prompt patients to seek medical attention. Fever and other signs of systemic toxicity are frequently absent. Some patients present with vague symptoms that include malaise, fatigue, anorexia, or decreased functional capacity.


Some patients present with vague symptoms that include malaise, fatigue, anorexia, or decreased functional capacity. Less commonly, the diagnosis of CIED infection is suspected in patients with fever of undefined origin who harbor no local inflammatory changes at the generator-pocket site. At least 2 sets of blood cultures should be obtained before the initiation of antimicrobial therapy in all patients with suspected CIED infection; some patients with bloodstream infection may not manifest systemic toxicity or peripheral leukocytosis. Posi- tive blood cultures, particularly due to staphylococcal spe- cies, provide a strong clue that the clinical syndrome is due to CIED infection. Patients should be educated about the need to be evaluated for CIED infection by cardiologists or special- ists in infectious diseases if they develop fever or blood- stream infection for which there is no initial explanation. Transesophageal echocardiography (TEE) may be useful in demonstrating CIED-related endocarditis in adults. Because of its poor sensitivity, transthoracic echocardiography is frequently not helpful in ruling out a diagnosis of lead-related endocarditis, particularly in adults. Moreover, patients can develop both right-sided (lead-related) and left-sided endo- carditis; the sensitivity of TEE for left-sided involvement and for perivalvular extension of infection is superior to that of transthoracic echocardiography. Additionally, visualization of the lead in the proximal superior vena cava from TEE views may identify tissue along that region that is difficult to visualize by other methods. TEE examination is critical among patients with S aureus bacteremia, because the rate of endocarditis is significant.67 Several prognostic features may be better defined on transthoracic echocardiography than on TEE, such as pericardial effusion, ventricular dysfunction and dyssynchrony, and pulmonary vascular pressure estimations.


TEE examination is critical among patients with S aureus bacteremia, because the rate of endocarditis is significant.67 Several prognostic features may be better defined on transthoracic echocardiography than on TEE, such as pericardial effusion, ventricular dysfunction and dyssynchrony, and pulmonary vascular pressure estimations. Concomitant or subsequent transthoracic echocardiography acquired at the time of diagnosis of CIED infection can serve as a baseline for additional studies that may be required during the course of the patient s illness or follow-up. A mass adherent to the lead that is seen on echocardiog- raphy is usually a thrombus or infected vegetation. Because it is impossible to distinguish between the 2 with echocardiog- raphy and recognizing that 5% of adherent masses were deemed thrombus in 1 retrospective survey,68 there will be some patients who are labeled as manifesting CIED-related endocarditis who may not have a lead infection. Masses that are detected in patients without positive blood cultures or other suggestive features for infection are likely to represent thrombus and by themselves do not require lead removal or antibiotic treatment. In addition, the failure to visualize a mass adherent to a lead with TEE does not exclude lead infection. Cultures of generator-pocket site tissue and lead tips at the time of device removal are useful in identifying the causative organism and to support a diagnosis of CIED infection. The sensitivity of pocket-site tissue culture is higher than that of swab culture of the pocket.69 Gram staining, in addition to both anaerobic and aerobic bacterial cultures, should be done. Both tissue and the lead tip should be cultured for fungi and mycobacteria if the initial Gram stain is negative; mycobac- teria and fungal stains also should be obtained on resected pocket tissue.


Both tissue and the lead tip should be cultured for fungi and mycobacteria if the initial Gram stain is negative; mycobac- teria and fungal stains also should be obtained on resected pocket tissue. Percutaneous aspiration of the device pocket should not be done, in general, because of the lack of adequate diagnostic yield and the theoretical risk of introduc- ing microorganisms into the pocket site and causing device infection. Because leads are extracted through an open generator pocket in most cases, lead contamination can occur if a pocket is infected. This likely explains the lack of systemic manifestations and negative blood cultures in many cases in which a positive lead-tip culture is demonstrated. Recommendations for Diagnosis of CIED Infection and Associated Complications Class I 1. All patients should have at least 2 sets of blood cultures drawn at the initial evaluation before prompt initiation of antimicrobial therapy for CIED infection. (Level of Evidence: C) 2. Generator-pocket tissue Gram s stain and culture and lead-tip culture should be obtained when the CIED is explanted. (Level of Evidence: C) 3. Patients with suspected CIED infection who either have positive blood cultures or who have negative blood cultures but have had recent antimicrobial therapy before blood cultures were obtained should undergo TEE for CIED infection or valvular endocarditis. (Level of Evidence: C) 4. All adults suspected of having CIED-related endocar- ditis should undergo TEE to evaluate the left-sided heart valves, even if transthoracic views have demonstrated lead-adherent masses. In pediatric patients with good views, transthoracic echocardiography may be suffi- cient. (Level of Evidence: B) Class IIa 1. Patients should seek evaluation for CIED infection by cardiologists or infectious disease specialists if they develop fever or bloodstream infection for which there is no initial explanation. (Level of Evidence: C) Class III 1.


Patients should seek evaluation for CIED infection by cardiologists or infectious disease specialists if they develop fever or bloodstream infection for which there is no initial explanation. (Level of Evidence: C) Class III 1. Percutaneous aspiration of the generator pocket should not be performed as part of the diagnostic evaluation of CIED infection. (Level of Evidence: C) Baddour et al Cardiovascular Device Infections 463 Management CIED removal is not required for superficial or incisional infection at the pocket site if there is no involvement of the device. Seven to 10 days of antibiotic therapy with an oral agent with activity against staphylococci is reasonable. Complete removal of all hardware, regardless of location (subcutaneous, transvenous, or epicardial), is the recom- mended treatment for patients with established CIED infec- tion.37,38,70 This includes cases in which a localized pocket infection occurs in the absence of signs of systemic infection. Complete removal of hardware is needed because infection relapse rates due to retained hardware are high.1,37,38,71,72 Erosion of any part of the CIED should imply contamination of the entire system, including the intravascular portion of leads, and complete device removal should be performed. Complete CIED removal should be performed when pa- tients undergo valve replacement or repair for infective endocarditis, because the CIED could serve as a nidus for relapsing infection and subsequent seeding of the surgically treated heart valve. An epicardial system should be consid- ered if a new CIED is required after valve surgery with initial CIED removal. The first issue to address in the treatment of CIED infections is the approach to hardware removal. As newer technologies have emerged and the experience has grown, percutaneous lead extraction has become the preferred method for removal of CIED hardware.