As newer technologies have emerged and the experience has grown, percutaneous lead extraction has become the preferred method for removal of CIED hardware. However, these procedures involve significant risks, including cardiac tam- ponade, hemothorax, pulmonary embolism, lead migration, and death, even in experienced hands. Thus, the performance of these procedures should be limited to centers with the appropriate facilities and training, which includes the pres- ence and imminent availability of cardiothoracic surgery on site to provide backup in the event of complications. In high-volume centers, percutaneous lead removal can be accomplished relatively safely with a high rate of success.73 A primary surgical approach to lead removal in patients with CIED infection should be limited to patients who have significant retained hardware after attempts at percutaneous removal. Another scenario in which a preference for surgical lead removal has been advocated74 is in patients with lead vegetations 2 cm in diameter, because of concerns about the risk of pulmonary embolism with percutaneous lead extrac- tion. Experience suggests, however, that percutaneous re- moval in patients with large vegetations can be done without precipitating a clinically apparent pulmonary embolism.38,72 Until additional data are available, decisions regarding per- cutaneous versus surgical removal of leads with vegetations larger than 2 cm in diameter should be individualized and based on a patient s clinical parameters and the extractor s evaluation. Antimicrobial therapy is adjunctive in patients with CIED infection, and complete device removal should not be de- layed, regardless of timing of initiation of antimicrobial therapy. Selection of the appropriate antimicrobial agent should be based on identification and in vitro susceptibility testing results. Because the bulk of infections are due to staphylococcal species, and some of them will be oxacillin resistant, vancomycin should be administered initially as empirical antibiotic coverage until microbiological results are known.


Because the bulk of infections are due to staphylococcal species, and some of them will be oxacillin resistant, vancomycin should be administered initially as empirical antibiotic coverage until microbiological results are known. Patients with infections due to oxacillin-susceptible staphylococcal strains can be given cefazolin or nafcillin alone with discontinuation of vancomycin. Vancomycin should be continued in patients who are not candidates for -lactam antibiotic therapy and those with infections due to oxacillin-re- sistant staphylococci. Pathogen identification and in vitro sus- ceptibility testing can be used to direct treatment in the minority of patients with nonstaphylococcal CIED infections. There are no clinical trial data to define the optimal duration of antimicrobial therapy for CIED infections, regard- less of the extent of infection, or to determine when conver- sion to an oral agent is appropriate once complete device removal has been achieved. Factors that influence medical decision making include the extent of device infection, the causative organism, the presence and duration of bloodstream infection, and associated complications such as valvular involvement, septic thrombophlebitis, or osteomyelitis (Fig- ure 2A). Blood cultures should be obtained from all patients after device removal. When CIED infection is limited to the pocket site, 7 to 10 days of therapy after device removal is reasonable if the presentation is device erosion without inflammatory changes; otherwise, 10 to 14 days of antimi- crobial treatment is recommended. Therapy can be switched to an oral regimen once susceptibility results are known if there is an oral agent available that is active against the pathogen and the infected CIED has been removed. At least 2 weeks of parenteral therapy is recommended after extraction of an infected device for patients with bloodstream infection.


At least 2 weeks of parenteral therapy is recommended after extraction of an infected device for patients with bloodstream infection. Patients with sustained ( 24 hours) positive blood cultures despite CIED removal and appropriate antimicrobial therapy should receive parenteral therapy for at least 4 weeks, even if TEE is negative for valvular vegetations. It is intuitive that adequate debridement and control of infection at all sites, both at the generator site and metastatic, if present, be achieved before new device placement. The con- tralateral side is preferred for new device placement, if required. There are several aspects of CIED removal for which data are needed so that management recommendations can be provided. These include whether the infected pocket site should be closed before new device placement, whether generator-capsule debridement is appropriate, and how to manage patients who have undergone device removal but have a remaining lead remnant. Patients with bloodstream infection and no localizing evi- dence of either generator-site infection or lead or endocardial involvement represent a difficult management group. Although bloodstream infection can be a manifestation of CIED infection, it can occur without CIED infection. There are several clinical parameters26,75 that may better characterize patients who have CIED infection and S aureus bacteremia but no localizing evidence of infection. These include the following: (1) Relapsing bacteremia after a course of appropriate antibiotic therapy; (2) if there is no other identified source for bacteremia; (3) if bacte- remia persists more than 24 hours; (4) if the CIED is an ICD; (5) presence of a prosthetic cardiac valve; and (6) bacteremia within 3 months of device placement. On the basis of findings from 1 investigation,27 CIED infection is unlikely in patients with Gram-negative bactere- mia and no other evidence of device infection; thus, CIED removal is not recommended in this setting.


On the basis of findings from 1 investigation,27 CIED infection is unlikely in patients with Gram-negative bactere- mia and no other evidence of device infection; thus, CIED removal is not recommended in this setting. In contrast, patients who have Gram-negative bacteremia that has re- lapsed despite administration of appropriate antibiotic ther- apy and with no other defined focus of infection should undergo CIED removal. CIED removal should also be per- formed in patients with sustained or persistent Gram-negative bacteremia despite administration of appropriate antibiotic therapy and no other defined source of infection. The likelihood of CIED infection in patients with bactere- mia or fungemia due to organisms other than S aureus or Gram-negative bacilli that more commonly cause blood- stream infection (coagulase-negative staphylococci, strepto- cocci, enterococci, and Candida species) and no other evi- Figure 2. A, Approach to management of adults with CIED infection. AHA indicates American Heart Association. Modified from Sohail et al38 with permission. *A history, physical examination, chest radiograph, electrocardiogram, and device interrogation are standard baseline procedures before CIED removal. Duration of antibiotics should be counted from the day of device explantation. Treatment can be extended to 4 or more weeks if there are metastatic septic complications (ie, osteomyelitis, organ or deep abscess, etc) or sus- tained bloodstream infection despite CIED removal. B, Approach to implantation of a new device in patients after removal of an infected CIED. Modified from Sohail et al38 with permission. Baddour et al Cardiovascular Device Infections 465 dence of CIED infection has received limited attention. Results of 2 relatively small case series33,76 suggest that the risk of CIED infection in these patients is low; however, more data are clearly needed in this clinical setting to permit recommendations on whether device removal is warranted.


Results of 2 relatively small case series33,76 suggest that the risk of CIED infection in these patients is low; however, more data are clearly needed in this clinical setting to permit recommendations on whether device removal is warranted. Recommendations for Antimicrobial Management of CIED Infection Class I 1. Choice of antimicrobial therapy should be based on the identification and in vitro susceptibility results of the infecting pathogen. (Level of Evidence: B) 2. Duration of antimicrobial therapy should be 10 to 14 days after CIED removal for pocket-site infection. (Level of Evidence: C) 3. Duration of antimicrobial therapy should be at least 14 days after CIED removal for bloodstream infection. (Level of Evidence: C) 4. Duration of antimicrobial therapy should be at least 4 to 6 weeks for complicated infection (ie, endocarditis, septic thrombophlebitis, or osteomyelitis or if blood- stream infection persists despite device removal and appropriate initial antimicrobial therapy. (Level of Evidence: C) Recommendations for Removal of Infected CIED Class I 1. Complete device and lead removal is recommended for all patients with definite CIED infection, as evidenced by valvular and/or lead endocarditis or sepsis. (Level of Evidence: A) 2. Complete device and lead removal is recommended for all patients with CIED pocket infection as evidenced by abscess formation, device erosion, skin adherence, or chronic draining sinus without clinically evident in- volvement of the transvenous portion of the lead sys- tem. (Level of Evidence: B) 3. Complete device and lead removal is recommended for all patients with valvular endocarditis without definite involvement of the lead(s) and/or device. (Level of Evidence: B) 4. Complete device and lead removal is recommended for patients with occult staphylococcal bacteremia. (Level of Evidence: B) Class IIa 1.


Complete device and lead removal is recommended for patients with occult staphylococcal bacteremia. (Level of Evidence: B) Class IIa 1. Complete device and lead removal is reasonable in patients with persistent occult Gram-negative bactere- mia despite appropriate antibiotic therapy. (Level of Evidence: B) Class III 1. CIED removal is not indicated for a superficial or incisional infection without involvement of the device and/or leads. (Level of Evidence: C) 2. CIED removal is not indicated for relapsing blood- stream infection due to a source other than a CIED and for which long-term suppressive antimicrobials are required. (Level of Evidence: C) New Device Implantation It is imperative that there be an assessment of the need for new device placement in each patient with an infected CIED. One third to one half of patients in some series will not require new CIED placement.38 There are several factors, including reversal of the pathological processes that precipi- tated the need for CIED implantation, changing clinical circumstances, and lack of appropriate clinical indication initially, that obviate the need for new CIED placement and thus result in avoidance of new device infection. Removal of infected hardware should not be attempted until a careful assessment of a new implantation strategy has been performed, particularly in patients with pacemakers for complete heart block and resynchronization therapy devices. When implantation of a new device is necessary, it should be performed on the contralateral side if possible to avoid relapsing device infection. If this is not possible, a trans- venous lead can be tunneled to a device placed subcutane- ously in the abdomen. Implantation is usually postponed to allow for resolution of infection, but patients who are PPM dependent represent a challenge, because they cannot be discharged home with a temporary pacemaker.


Implantation is usually postponed to allow for resolution of infection, but patients who are PPM dependent represent a challenge, because they cannot be discharged home with a temporary pacemaker. Because of complications with passive-fixation leads that have been used in the past for temporary pacing in CIED infection cases, active-fixation leads attached to pacing gen- erators or defibrillators are now being used as a bridge until PPM implantation is deemed appropriate. Use of active- fixation leads connected to external devices in stimulation- dependent patients with infection permits earlier mobilization of the patient and has been associated with a reduced risk of pacing-related adverse events, including lead dislocation, resuscitation due to severe bradycardia, and local infection.77 The optimal timing of device replacement is unknown. Some have advocated proceeding 24 hours after remo- val.23,38,71,78 Sohail et al38 demonstrated a difference in timing of replacement based on (1) blood culture results (median time of 13 days for bacteremic patients versus 7 days for nonbacteremic patients) and (2) type of pathogen identified (median 7 days for CoNS versus 12 days for S aureus). There have been no prospective trial data that examined timing of new device replacement and risk of relapsing infection; however, several investigators recommend waiting for blood cultures to be negative before a new device is placed23,38,71 (Figure 2B). Only 1 medical center has described simultaneous contralat- eral (side-to-side) replacement of an infected CIED.79 A 1-stage exchange was performed in 68 consecutive patients over almost a 14-year period by 1 cardiologist, and two thirds of patients had dual-chamber devices. Clinical presentations included device erosion (41%), cellulitis or abscess (35%), and endocarditis (24%).


Clinical presentations included device erosion (41%), cellulitis or abscess (35%), and endocarditis (24%). Fifty-nine patients (87%) were followed up for more than 1 year, and 9 patients were lost to follow-up after 1 to 10 months after 1-stage contralateral device exchange, with no new identi- fied CIED infections. Additional experience with 1-stage con- tralateral device exchange is needed, however, before it can be recommended for routine use. There are reports of successful implantations of previously implanted devices from either deceased patients or from the same patient with a prior PPM infection.78,80 Mansour and coworkers78 described 17 patients with a previously infected PPM who underwent successful implantation (at a new site and after resterilization) without relapsing infection. The practice of reusing CIEDs after sterilization is not advocated, however. Recommendations for New CIED Implantation After Removal of an Infected CIED Class I 1. Each patient should be evaluated carefully to determine whether there is a continued need for a new CIED. (Level of Evidence: C) 2. The replacement device implantation should not be ipsilateral to the extraction site. Preferred alternative locations include the contralateral side, the iliac vein, and epicardial implantation. (Level of Evidence: C) Class IIa 1. When positive before extraction, blood cultures should be drawn after device removal and should be negative for at least 72 hours before new device placement is performed. (Level of Evidence: C) 2. New transvenous lead placement should be delayed for at least 14 days after CIED system removal when there is evidence of valvular infection.


New transvenous lead placement should be delayed for at least 14 days after CIED system removal when there is evidence of valvular infection. (Level of Evidence: C) Long-Term Suppressive Antimicrobial Therapy Long-term antimicrobial suppressive therapy is used in selected patients with CIED infections who, for a variety of reasons, are not candidates for device removal either by percutaneous or surgical methods.81 Often, these patients have a limited life expectancy or refuse device removal. Long-term suppressive therapy can be attempted in these cases if they meet several criteria, which include a stable cardiovascular status, clinical improvement with initial antimicrobial therapy, and clearance of bloodstream infection. Because there are no comparative trials, the optimal choice of antimicrobial therapy and its dosing are undefined. Moreover, treatment options are frequently limited, because many CIED infections are caused by multidrug-resistant pathogens that are acquired in the healthcare or nosocomial environment. Thus, prolonged suppression of infection can be difficult to achieve with oral antimicrobial therapy. Little is known about CIED infection relapse rates despite use of long-term suppressive therapy. Other factors that are relevant to the use of long-term suppressive therapy include the likelihood for selection of resistant organisms, both for the identified pathogen being suppressed and for normal colonizing strains; safety profile; patient compliance; and financial expense. Recommendations for Use of Long-Term Suppressive Antimicrobial Therapy Class IIb 1. Long-term suppressive therapy should be considered for patients who have CIED infection and who are not candidates for complete device removal. (Level of Evidence: C) Class III 1. Long-term suppressive therapy should not be adminis- tered to patients who are candidates for infected CIED removal. (Level of Evidence: C) Complications of Device Infection Complications of CIED infection can be either contiguous to the device or anatomically remote.


(Level of Evidence: C) Complications of Device Infection Complications of CIED infection can be either contiguous to the device or anatomically remote. Contiguous complications include chest wall abscess, septic thrombophlebitis, and right-sided heart endocarditis. More remote complications include skeletal complications, both local (clavicular osteo- myelitis and sternoclavicular arthritis) and remote (metastatic osteomyelitis, discitis, and septic arthritis); cardiopulmonary complications (septic pulmonary emboli, mycotic pulmonary artery aneurysm, and left-sided endocarditis with its potential complications); metastatic complications, including soft tis- sue and organ or muscle abscess formation; and sepsis, with its potential complications. Outcomes CIED infection is a serious complication associated with substantial morbidity, mortality, and cost.8,28,56,82 Reported mortality rates for these infections range widely and tend to be higher in patients with confirmed device-related endocarditis and in those treated without device removal (Table 2).23,24,28,56,83 87 Because of a lack of adequate comparison groups, substantial heterogeneity among stud- ies, and marked differences in populations who do and do not receive device removal, precise estimates of the benefits of device removal are not available. A risk factor analysis88 was conducted that examined clinical and echocardiographic variables that identified pa- tients with CIED infections who were at increased risk of mortality. All-cause mortality at 6 months among 210 pa- tients with CIED infections was 18%. Variables associated with increased mortality risk among this cohort included systemic embolization, moderate to severe tricuspid regurgi- tation, abnormal right ventricular function, and abnormal renal function. Size and mobility of lead vegetations were not independently associated with mortality. Prevention Prophylaxis at CIED Implantation Prevention of CIED infection can be addressed before, during, and after device implantation. Before device implan- tation, it is important to ensure that patients do not have clinical signs of infection. A parenterally administered anti- biotic is recommended 1 hour before the procedure.


A parenterally administered anti- biotic is recommended 1 hour before the procedure. Data from a meta-analysis,22 2 case-control studies that examined purported risk factors of CIED infection,20,21 and a large, prospective, randomized, double-blinded, placebo-controlled trial strongly support the administration of antibiotic prophy- laxis for CIED implantation.89 Most experts continue to advocate a first-generation cephalosporin, such as cefazolin, for use as prophylaxis. Although not generally recommended, some advocate the use of vancomycin instead of cefazolin, particularly in centers where oxacillin resistance among staphylococci is high. If vancomycin is used, then it should be administered 90 to 120 minutes before the procedure. Van- comycin also represents an alternative to a first-generation cephalosporin in patients who are allergic to cephalosporins. In patients who are allergic to both cephalosporins and vancomycin, daptomycin and linezolid represent prophylaxis Baddour et al Cardiovascular Device Infections 467 options. Antibiotic prophylaxis is also recommended if sub- sequent invasive manipulation of the CIED is required. Preoperative antiseptic preparation of the skin of the surgical site should be done. Intraprocedurally, compulsive attention to sterile technique is mandatory. If a patient has limited subcutaneous tissue and/or poor nutrition and is at increased risk for erosion, a retropectoral pocket should be considered. In a survey of pediatric patients, 9 (13.8%) of 65 with subcutaneously placed device-pocket transvenous sys- tems developed infection compared with none of the 82 who underwent retropectorally placed systems.90 Hematoma within the pocket that complicates CIED place- ment or invasive manipulation has been identified as a risk factor associated with device placement.19 Therefore, prevention of hematoma during the procedure is desirable, and several inter- ventions have been used, although there are no data to support their use.


In a survey of pediatric patients, 9 (13.8%) of 65 with subcutaneously placed device-pocket transvenous sys- tems developed infection compared with none of the 82 who underwent retropectorally placed systems.90 Hematoma within the pocket that complicates CIED place- ment or invasive manipulation has been identified as a risk factor associated with device placement.19 Therefore, prevention of hematoma during the procedure is desirable, and several inter- ventions have been used, although there are no data to support their use. This can be achieved by meticulous cautery of bleeding sites and consideration of packing the pocket with antibiotic-soaked sponges to provide tamponade while leads are being placed. The application of topical thrombin may be helpful, particularly in anticoagulated patients. Irrigation of the pocket is useful to remove debris and may reveal persistent bleeding that could lead to a pocket hematoma. In addition, irrigation with an antimicrobial-containing solution for pocket cleansing has been used. Use of monofilament suture for closure of the subcuticular layer may avoid superficial postoperative cellulitis. A pressure dressing applied for 12 to 24 hours after skin closure and dressing may further decrease the risk of hematoma formation. In the immediate postoperative period, recent data indicate that low-molecular-weight heparin predisposes to hematoma formation and should be avoided.91 A hematoma should be evacuated only when there is increased tension on the skin. Needle aspiration should otherwise be avoided because of the risk of introducing skin flora into the pocket and subsequent development of infection. Routine ambulatory care follow-up after CIED place- ment to detect early infectious complications has been performed in many centers. Recent data from 1 investiga- tion92 failed to demonstrate the utility of early follow-up and advocated that instead, patients should be instructed to call their implanting physician for development of fever or incision findings of inflammation.


Recent data from 1 investiga- tion92 failed to demonstrate the utility of early follow-up and advocated that instead, patients should be instructed to call their implanting physician for development of fever or incision findings of inflammation. The writing group believes that both early follow-up in a clinic setting and Table 2. Published Case Series That Report Outcomes of CIED Infection Reference Year n Population Treatment Follow-Up, y Outcomes Arber et al13 1994 44 Pacemaker endocarditis categorized as definite (n 25), probable ? ? ? Klug et al34 1997 57 Pacemaker lead endocarditis Plan for initial device removal and parenteral antibiotic therapy removal 2 after removal); 26.9% mortality at end of follow-up O Nunain et al84 1997 21 ICD infection Total system removal in 15; partial system removal in 2; no explantation in 4.


Klug et al34 1997 57 Pacemaker lead endocarditis Plan for initial device removal and parenteral antibiotic therapy removal 2 after removal); 26.9% mortality at end of follow-up O Nunain et al84 1997 21 ICD infection Total system removal in 15; partial system removal in 2; no explantation in 4. All received parenteral antibiotics 1.75 No clinical recurrence of infection; 1 sudden death (1) IV antibiotics without device system removal with 2 weeks of parenteral antimicrobials (n 19); (3) complete removal with 6 weeks of parenteral antimicrobials 0.75 to 5 y 100% Failure and 17% mortality in those treated conservatively; no deaths or recurrent infections in the groups treated with device removal Cacoub et al42 1998 33 Definite pacemaker endocarditis Lead removal and prolonged subsequent antibiotic therapy Chua et al37 2000 123 Patients with either pacemaker (n 87) or ICD (n 36) infections Extraction in 95% with antibiotic therapy (median 28 days) 2001 51 Patients with device-related infections not candidates for surgery (from survey of providers) Long-term suppressive antibiotics (3 mo to 10 y) Not specified 3 Developed relapsing infection del Rio et al40 2003 31 Pacemaker or ICD endocarditis Initial conservative therapy (n 7); surgical removal (n 24) 3.17 Initial conservative therapy: 100% relapse, 1 death; initial surgical therapy: 1 relapse, 3 deaths Rundstrom et al86 episodes in 38 patients) Pacemaker removal in 28 episodes, conservative therapy in Not specified 64% Infection-free in group with pacemaker removal; 19% infection-free in conservative-therapy group Sohail et al37 2007 189 Patients with CDI Initial surgical removal in 183 (96%); removal after failure of medical therapy in 3 (2%); all received parenteral antimicrobial therapy, most for at least 2 wk 0.48 3.7% In-hospital mortality; of those followed up after discharge, 5% relapse or persistent pocket infection; 95% infection-free at end of follow-up Sohail et al87 2008 44 Pacemaker or ICD endocarditis (from 2007 series with CDI) Surgical removal in 43 (98%) with parenteral antimicrobial therapy thorough patient education should be conducted for early identification of CIED-related infectious complications.


All received parenteral antibiotics 1.75 No clinical recurrence of infection; 1 sudden death (1) IV antibiotics without device system removal with 2 weeks of parenteral antimicrobials (n 19); (3) complete removal with 6 weeks of parenteral antimicrobials 0.75 to 5 y 100% Failure and 17% mortality in those treated conservatively; no deaths or recurrent infections in the groups treated with device removal Cacoub et al42 1998 33 Definite pacemaker endocarditis Lead removal and prolonged subsequent antibiotic therapy Chua et al37 2000 123 Patients with either pacemaker (n 87) or ICD (n 36) infections Extraction in 95% with antibiotic therapy (median 28 days) 2001 51 Patients with device-related infections not candidates for surgery (from survey of providers) Long-term suppressive antibiotics (3 mo to 10 y) Not specified 3 Developed relapsing infection del Rio et al40 2003 31 Pacemaker or ICD endocarditis Initial conservative therapy (n 7); surgical removal (n 24) 3.17 Initial conservative therapy: 100% relapse, 1 death; initial surgical therapy: 1 relapse, 3 deaths Rundstrom et al86 episodes in 38 patients) Pacemaker removal in 28 episodes, conservative therapy in Not specified 64% Infection-free in group with pacemaker removal; 19% infection-free in conservative-therapy group Sohail et al37 2007 189 Patients with CDI Initial surgical removal in 183 (96%); removal after failure of medical therapy in 3 (2%); all received parenteral antimicrobial therapy, most for at least 2 wk 0.48 3.7% In-hospital mortality; of those followed up after discharge, 5% relapse or persistent pocket infection; 95% infection-free at end of follow-up Sohail et al87 2008 44 Pacemaker or ICD endocarditis (from 2007 series with CDI) Surgical removal in 43 (98%) with parenteral antimicrobial therapy thorough patient education should be conducted for early identification of CIED-related infectious complications. Currently, there are no data to support the administration of postoperative antibiotic therapy, and it is not recom- mended because of the risk of drug adverse events, selection of drug-resistant organisms, and cost.


Currently, there are no data to support the administration of postoperative antibiotic therapy, and it is not recom- mended because of the risk of drug adverse events, selection of drug-resistant organisms, and cost. Recommendations for Antimicrobial Prophylaxis at the Time of CIED Placement Class I 1. Prophylaxis with an antibiotic that has in vitro activity against staphylococci should be administered. If cefazolin is selected for use, then it should be administered intrave- nously within 1 hour before incision; if vancomycin is given, then it should be administered intravenously within 2 hours before incision. (Level of Evidence: A) Antibiotic Prophylaxis for Invasive Procedures Bacterial pathogens commonly gain entrance to the circulation, whether from routine daily activities such as toothbrushing or from invasive procedures.93 There is a general and longstanding focus on secondary antibiotic prophylaxis to prevent hematog- enous infections from invasive procedures in patients with a wide variety of medical devices and conditions. However, controversy surrounds this practice because there are few data to show efficacy, and the risk from prophylaxis likely outweighs any benefit. For example, there is concern about the develop- ment of antibiotic-resistant bacterial pathogens, the possibility of a fatal allergic reaction, and the costs associated with this practice, which include malpractice litigation and, additional medical and dental office visits.


For example, there is concern about the develop- ment of antibiotic-resistant bacterial pathogens, the possibility of a fatal allergic reaction, and the costs associated with this practice, which include malpractice litigation and, additional medical and dental office visits. Since the original American Heart Association recommen- dations were made more than 50 years ago, there has been a proliferation of purported indications for the use of prophy- lactic antibiotics for patients thought to be at risk for distant site infection from invasive procedures.94 97 There is little, if any, scientific justification for administration of antibiotic prophylaxis for invasive procedures, although there is a wide range of opinions.96 A review of the literature from 1950 to 2007 for publications on cardiac electrophysiological device infections reveals more than 140 articles, none of which report hematologic infection from dental, gastrointestinal, genitourinary, dermatologic, or other procedures. The predominance of staphylococci as pathogens in CIED infections rather than oral flora98 suggests that antibiotic prophylaxis for dental procedures is of little or no value.1,89,99,100 In the rare event of a device infection due to an oral pathogen, it is most likely to have arisen from a bacteremia from a common daily event such as toothbrushing or chewing food.98 Therefore, there is currently no scientific basis for the use of prophylactic antibiotics before routine invasive dental, gastrointestinal, or genitourinary procedures to prevent CIED infection. Recommendations for Antimicrobial Prophylaxis for Invasive Procedures in Patients With CIEDs Class III 1. Antimicrobial prophylaxis is not recommended for dental or other invasive procedures not directly related to device manipulation to prevent CIED infection.


Antimicrobial prophylaxis is not recommended for dental or other invasive procedures not directly related to device manipulation to prevent CIED infection. (Level of Evidence: C) Emerging Technology Advances in molecular, gene, and cell therapies make the development of a biological pacemaker, a tissue that could be implanted in the heart, a future possibility.101 As pointed out in a recent report,102 our total dependence on a biological pacemaker will have to await the demonstration of the safety and long-term efficacy of the biological tissue. Advancement in the development of gene and cell-transfer therapies to restore myocardial function in a failing heart and to inhibit ventricular arrhythmias103,104 could potentially im- pact the need for ICDs in the future. Technical advances could also impact the risk of infection in cases in which a device, rather than a biological therapy, is required. These include development of a totally subcutaneous ICD and a leadless pacing system. Pediatric Concerns Pediatric and young adult patients with congenital heart disease represent a population with unique medical and surgical issues. These include smaller body size, vascular anomalies, congenital heart defects with and without surgical correction or palliation, and arrhythmias due to congenital disease or surgical repair. The decision to place a CIED in 1 of these patients requires long-term planning with the expec- tation of prolonged survival that will include numerous generator changes and lead replacement due to lead fracture or stress related to somatic growth. In addition, adults with some forms of congenital heart disease that do not allow traditional transvenous access to cardiac chambers will re- quire modified pacemaker/ICD systems. With that in mind, a variety of approaches to implantation of these systems are required.


With that in mind, a variety of approaches to implantation of these systems are required. Epicardial implants are frequently preferred or necessary because of a patient s size and growth potential, the presence of intracardiac shunts that allow the possibility of right-to-left shunting, and anatomic or surgical barriers to a transvenous approach. Biventricular pacing often requires epi- cardial placement of a left ventricular lead because of the small size of the coronary sinus. ICD implants are particularly chal- lenging in a patient who weighs less than 15 kg and usually require novel and nonstandard approaches with nonthoracotomy ICD coil arrays, epicardial patches, or shock leads placed in or adjacent to the pericardial space (Figures 3A and 3B). Another technique that is occasionally used to obtain the advantage of an endocardial lead while preserving the integrity of small veins is to perform a thoracotomy with placement of a lead through an atrial wall via a purse-string suture, with the lead connector extended to an abdominal device. Klug et al105 demonstrated that young patients with or without congenital defects have a greater prevalence of PPM lead infections than older ( 40 years of age) individuals. They speculated that several factors could be operative in causing an increased infection rate among younger patients, including a higher rate of reinterventions at the generator site, placement of a relatively larger device based on a higher ratio between the volume of the generator and body size, and the likelihood of local trauma to the generator site in younger, Baddour et al Cardiovascular Device Infections 469 more active individuals.


They speculated that several factors could be operative in causing an increased infection rate among younger patients, including a higher rate of reinterventions at the generator site, placement of a relatively larger device based on a higher ratio between the volume of the generator and body size, and the likelihood of local trauma to the generator site in younger, Baddour et al Cardiovascular Device Infections 469 more active individuals. A number of studies86,106 114 of infected PPMs in the pediatric population have demonstrated that congenital heart disease is present in a large percentage (44% to 83%) of young patients, with overall infection rates that ranged between 1% and 8%. Patients with endocardial and epicardial leads composed 70% and 30%, respectively, of reported cases. With the exception of 1 study, there were no differences in rates of epicardial and transvenous pacemaker infections. In the largest review of pediatric pacemaker infections, Cohen et al90 analyzed 385 pacemaker procedures over a 20-year period and identified 30 infections (7.8%). Of these infections, 19 (4.9%) were superficial and were treated successfully with antibiotics only, whereas 9 (2.3%) were deep pocket infections that required removal of the generator and leads. By multivariable analysis, the only risk factors for infection were the presence of Down syndrome and reinter- vention for revision of the pacing system. Although the numbers were small, the authors suggested that a subpectoral placement of a device yielded a reduced infection risk compared with a prepectoral location. No study has compared rates of pacemaker and ICD infec- tions in a pediatric population, although several investigations have examined pediatric and congenital heart disease patients after ICD implantation. Silka et al115 described 125 pediatric patients with 4 ICD wound infections and 2 pocket erosions.


Silka et al115 described 125 pediatric patients with 4 ICD wound infections and 2 pocket erosions. A erosions in the first 30 days after device implantation and 13 (2.9%) chronic infections among 443 patients. One study116 compared ICD complications between adults and pediatric patients ( 21 years of age) at the same institution. The infection rate in the pediatric group was 18% (2 of 11) compared with epicardial and 1 transvenous system infection in the pediatric group. There was no specific information provided in the report to indicate how many of the systems in adults were epicardial.117 The authors speculated that pediatric patients may have had a higher infection rate due to returning to activity sooner and less than optimal wound care. The same principles of diagnosis and management of device infections in the general population apply to pediatric and congenital heart disease patients; however, there are some additional considerations. The excellent imaging provided by standard transthoracic echocardiography may supplant the need for a transesophageal study in some pediatric patients. Because of the high prevalence of nontransvenous systems and the unique configurations required to implant CIEDs in some pediatric patients and individuals with congenital heart disease, there must be a thorough evaluation of the need to remove all components of a device. This includes a review of a patient s ongoing need for the device; if the device therapy is no longer required, it should be removed. Epicardial and other nontrans- venous systems in use can necessitate extensive surgical proce- dures for complete device removal, including a full or limited sternotomy or thoracotomy. Therefore, the suspicion of device- component infection must be balanced against the risk of surgical removal.


Therefore, the suspicion of device- component infection must be balanced against the risk of surgical removal. An experienced team of physicians with expertise in cardiac electrophysiology, infectious diseases, pedi- atrics and congenital heart disease, and cardiothoracic surgery is pivotal in CIED infection management. Ethical Considerations Consideration for withdrawal of CIED support in terminally ill patients is common and will become more frequent as the age and accompanying comorbid conditions increase among recipi- ents of these devices. Although a thorough review of related ethical considerations is beyond the scope of the present state- ment, the topic is important to highlight, because the occurrence of a device infection has prompted some patients to refuse implantation of a new device after removal of an infected device. Many of the same ethical concerns that apply to deactivation of a noninfected implanted CIED apply to removal of an infected device without new CIED placement. The American College of Cardiology/American Heart Association/Heart Rhythm Society 2008 guidelines3 for device-based therapy of cardiac rhythm abnormalities outlines specific recommendations regarding terminal Figure 3. A and B, Nonthoracotomy ICD system placed in a 39-year-old man with inoperable pulmonary atresia with ventric- ular septal defect who had ventricular tachycardia with syncope. Note the retrosternal and intrapericardial coil arrays, the epicar- dial pace/sense leads, and the abdominal ICD. Table 3. Summary of Recommendations Recommendation Class and Level of Evidence A. Recommendations for diagnosis of CIED infection and associated complications 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. IC 2. Generator-pocket tissue Gram stain and culture and lead-tip culture should be obtained when the CIED is explanted. IC 3.


Generator-pocket tissue Gram stain and culture and lead-tip culture should be obtained when the CIED is explanted. IC 3. Patients with suspected CIED infection who either have positive blood cultures or have negative blood cultures but have had recent antimicrobial therapy before blood cultures were obtained should undergo TEE for CIED infection or valvular endocarditis. IC 4. All adults suspected of having CIED-related endocarditis 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, TTE may be sufficient. IB 5. 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. IIaC 6. Percutaneous aspiration of the generator pocket should not be performed as part of the diagnostic evaluation of CIED infection. IIIC B. Recommendations for antimicrobial management of CIED infection 1. Choice of antimicrobial therapy should be based on the identification and in vitro susceptibility results of the infecting pathogen. IB 2. Duration of antimicrobial therapy should be 10 to 14 days after CIED removal for pocket-site infection. 1C 3. Duration of antimicrobial therapy should be at least 14 days after CIED removal for bloodstream infection. 4. Duration of antimicrobial therapy should be at least 4 to 6 weeks for complicated infection (ie, endocarditis, septic thrombophlebitis, or osteomyelitis or if bloodstream infection persists despite device removal and appropriate initial antimicrobial therapy). C. Recommendations for removal of infected CIED 1. Complete device and lead removal is recommended for all patients with definite CIED infection, as evidenced by valvular and/or lead endocarditis or sepsis. IA 2.


Complete device and lead removal is recommended for all patients with definite CIED infection, as evidenced by valvular and/or lead endocarditis or sepsis. IA 2. Complete device and lead removal is recommended for all patients with CIEM pocket infection, as evidenced by abscess formation, device erosion, skin adherence, or chronic draining sinus without clinically evident involvement of the transvenous portion of the lead system. 3. Complete device and lead removal is recommended for all patients with valvular endocarditis without definite involvement of the lead(s) and/or device. 4. Complete device and lead removal is recommended for patients with occult staphylococcal bacteremia. 5. Complete device and lead removal is reasonable in patients with persistent occult Gram-negative bacteremia despite appropriate antibiotic therapy. IIaB 6. CIED removal is not indicated for a superficial or incisional infection without involvement of the device and/or leads. IIIC 7. CIED removal is not indicated for relapsing bloodstream infection due to a source other than a CIED and for which long-term suppressive antimicrobials are required. IIIC D. Recommendations for new CIED implantation after removal of an infected CIED 1. Each patient should be evaluated carefully to determine whether there is a continued need for a new CIED. IC 2. The replacement device implantation should not be ipsilateral to the extraction site. Preferred alternative locations include the contralateral side, the iliac vein, and epicardial implantation. 3. When positive before extraction, blood cultures should be drawn after device removal and should be negative for at least 72 hours before new device placement is performed. IIaC 4. New transvenous lead placement should be delayed for at least 14 days after CIED system removal when there is evidence of valvular infection. IIaC E. Recommendations for use of long-term suppressive antimicrobial therapy 1.


IIaC E. Recommendations for use of long-term suppressive antimicrobial therapy 1. Long-term suppressive therapy should be considered for patients who have CIED infection and who are not candidates for complete device removal. IIbC 2. Long-term suppressive therapy should not be administered to patients who are candidates for infected CIED removal. IIIC (Continued) Baddour et al Cardiovascular Device Infections 471 care of dying patients and device deactivation. In addition, there will be a thorough addressing of the ethics of CIED use in a pending statement on CIED extraction from the Heart Rhythm Society. Removal of Noninfected CIEDs Avoidance of Microbiological Studies Noninfectious device-related complications or device malfunc- tion may occur that requires CIED removal with new device placement. At the time of device removal, specimens from the generator pocket or the explanted device should not be routinely sent for microbiological studies unless there are intraoperative findings to suggest concurrent infection. As evidenced in a previous investigation,69 intraoperative culture specimens fre- quently yield bacteria, although there is no other evidence of infection. In these cases, it is presumed that contamination during device explantation and processing of specimens likely account for the majority of positive cultures. In these cases, no antimicrobial therapy has been administered, and the rate of subsequent device infection has been no greater than expected. Thus, cultures should not be obtained routinely, because if positive, they could be misinterpreted as being clinically signif- icant and lead to the inappropriate administration of antimicro- bials, or worse, removal of the newly implanted device. Recommendations to Avoid Microbiological Studies in Cases of CIED Removal for Noninfectious Reasons Class III 1. Routine microbiological studies should not be con- ducted on CIEDs that have been removed for noninfec- tious reasons.


Routine microbiological studies should not be con- ducted on CIEDs that have been removed for noninfec- tious reasons. (Level of Evidence: B) Areas in Need of Further Research Tremendous gains in our knowledge of CIED infections have occurred over the past 5 years. Because of the increasing rate of these infections among an increasing pool of device recipients, it is imperative that aggressive investigation of all aspects of device infection be conducted. The following topics represent areas that the writing group identified as critical for further study: 1. Determine the safety of 1-stage contralateral device replacement compared with delayed device replace- ment as a management scheme. 2. Define a scoring system that distinguishes patients with S aureus bacteremia and no other evidence of device infection who prove to have CIED infection from those who do not, so that unnecessary device removal can be avoided. 3. Develop CIEDs that are less prone to infection. 4. Develop adjunctive therapies that eliminate biofilm- laden microorganisms. 5. Determine whether there is a floor of vegetation size, among other characteristics, that reliably predicts the occurrence of clinically significant pulmonary embolism with percutaneous extraction of an infected lead. 6. Define more clearly the circumstances in which van- comycin should be used as primary prophylaxis for CIED implantation. 7. Identify risk factors and characterize outcomes of CIED infections in large populations that are represen- tative of those treated in clinical practice. 8. Develop a scoring system to assess the risk of serious complications associated with percutaneous removal that will identify a subset of patients for whom median sternotomy for CIED removal is recommended. 9. Assess implantation strategies in infants and children for CIED with respect to both leads and generators that will reduce both short- and long-term infection rates. 10.


Assess implantation strategies in infants and children for CIED with respect to both leads and generators that will reduce both short- and long-term infection rates. 10. Develop gene and cell therapies to obviate the need for CIED devices. 11. Define the current financial cost of CIED infection in the United States. 12. Determine whether generator capsule excision and pocket closure before new device placement are benefi- cial in reducing the likelihood of new CIED infection. 13. Determine the risk of CIED infection among patients with bloodstream infection due to coagulase-negative staphylococci, streptococci, enterococci, and Candida species and no other evidence of device infection. Summary of Recommendations This document has addressed critical aspects of CIED infec- tions. In particular, management strategies have been presented, and a summary of recommendations is outlined in Table 3. Acknowledgments The authors thank Drs John Bradley, Charles Love, Anne Rowley, and Jon Weinstock for their critical review of the manuscript. Table 3. Continued Recommendation Class and Level of Evidence F. Recommendations for antimicrobial prophylaxis at the time of CIED placement 1. Prophylaxis with an antibiotic that has in vitro activity against staphylococci should be administered. If cefazolin is selected for use, then it should be administered intravenously within 1 hour before incision; if vancomycin is given, then it should be administered intravenously within 2 hours before incision. IA G. Recommendations for antimicrobial prophylaxis for invasive procedures in patients with CIEDs 1. Antimicrobial prophylaxis is not recommended for dental or other invasive procedures not directly related to device manipulation to prevent CIED infection. IIIC H. Recommendations to avoid microbiological studies in cases of CIED removal for noninfectious reasons 1. Routine microbiological studies should not be conducted on CIEDs that have been removed for noninfectious reasons. IIIB TTE indicates transthoracic echocardiography.


Routine microbiological studies should not be conducted on CIEDs that have been removed for noninfectious reasons. IIIB TTE indicates transthoracic echocardiography. Disclosures Writing Group Disclosures Writing Group Member Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/Advisory Board Other Larry M. Baddour Mayo Clinic None None None None None Cardinal Health*; Talecris Biotherapeutics* None Lee B. Beerman University of Pittsburgh None None None Yes; no recent active cases* None None None Ann F. Bolger UCSF None None None None None None None Andrew E. Epstein University of Pennsylvania Biotronik*; Boston Scientific*; Medtronic*; St Jude Medical None Biotronik*; Boston Scientific*; Medtronic*; St Jude Medical Yes, in cases involving ICDs* None None None Christopher C. Erickson University of Nebraska St. Jude Medical None Received honorarium from Medtronic to give a lecture in 2007* None None None None N.A. Mark Estes III Tufts-New England Medical Center None None Boston Scientific*; Medtronic*; St. Jude Medical* None None None None Michael Gewitz New York Medical College None None None None None NDTI*; Jefferson University* None Bradley P. Knight University of Chicago Two of my electrophysiology fellows are supported by industry.


Mark Estes III Tufts-New England Medical Center None None Boston Scientific*; Medtronic*; St. Jude Medical* None None None None Michael Gewitz New York Medical College None None None None None NDTI*; Jefferson University* None Bradley P. Knight University of Chicago Two of my electrophysiology fellows are supported by industry. One grant from Boston Scientific and 1 from St. Jude None Medtronic, for speaking at fellow educational courses, often exceeds None None None None Matthew E. Levison Drexel University None None None None None None Editor, Infectious Disease Section, Merck Manual Peter B. Lockhart Carolinas Medical Center None None None None None None None Frederick A. Masoudi Denver Health Medical Center AHRQ ; NHLBI None None None None None American College of Cardiology (contract)* Jane W. Newburger Harvard None None None None None None None Eric J. Okum Rush University, Chicago None None Two speaking engagements for training staff of Sanofi-Aventis in the role of Lantus insulin use in cardiac surgery patients (total $1000)* None None None None Eleanor B. Schron Was with NIH but retired None None None None None InCirculation.net Advisory Board, an international educational Web site for dissemination of findings from studies in cardiovascular disease. I have provided advice concerning groups of nurses who may be interested in the Web site and identified nurse researchers with expertise in cardiovascular nursing. Payment zero to no more than $1000 in a particular year* None Kathryn A. Taubert American Heart Association None None None None None None None Walter R. Wilson Mayo Clinic None None None None None None None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit.


Payment zero to no more than $1000 in a particular year* None Kathryn A. Taubert American Heart Association None None None None None None None Walter R. Wilson Mayo Clinic None None None None None None None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be significant if (1) the person receives $10 000 or more during any 12-month period, or 5% or more of the person s gross income; or (2) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Significant. Baddour et al Cardiovascular Device Infections 473 References 1. Baddour LM, Bettmann MA, Bolger AF, Epstein AE, Ferrieri P, Gerber MA, Gewitz MH, Jacobs AK, Levison ME, Newburger JW, Pallasch TJ, Wilson WR, Baltimore RS, Falace DA, Shulman ST, Tani LY, Taubert KA. Nonvalvular cardiovascular device-related infections. Circulation. 2003;108:2015 2031. 2. Hayes DL, Furman S. Cardiac pacing: how it started, where we are, where we are going. Pacing Clin Electrophysiol. 2004;27:693 704. 3.


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Long-term infection rates associated with pectoral versus abdominal approach to cardioverter-defibrillator implants. Am J Cardiol. 2001;88:750 753. 16. Cabell CH, Heidenreich PA, Chu VH, Moore CM, Stryjewski ME, Corey GR, Fowler VG Jr. Increasing rates of cardiac device infections among Medicare beneficiaries: 1990 1999. Am Heart J. 2004;147: 582 586. 17. Uslan DZ, Sohail MR, St Sauver JL, Friedman PA, Hayes DL, Stoner SM, Wilson WR, Steckelberg JM, Baddour LM. Permanent pacemaker and implantable cardioverter-defibrillator infection: a population-based study. Arch Intern Med. 2007;167:669 675. 18. Bloom H, Heeke B, Leon A, Mera F, Delurgio D, Beshai J, Langberg J. Renal insufficiency and the risk of infection from pacemaker or defi- brillator surgery. Pacing Clin Electrophysiol. 2006;29:142 145. 19.


Bloom H, Heeke B, Leon A, Mera F, Delurgio D, Beshai J, Langberg J. Renal insufficiency and the risk of infection from pacemaker or defi- brillator surgery. Pacing Clin Electrophysiol. 2006;29:142 145. 19. Lekkerkerker JC, van Nieuwkoop C, Trines SA, van der Bom JG, Bernards A, van de Velde ET, Bootsma M, Zeppenfeld K, Jukema JW, Borleffs JW, Schalij MJ, van Erven L. Risk factors and time delay Reviewer Disclosures Reviewer Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/ Advisory Board Other Martin Burke University of Chicago AJ Medical Devices, Inc ; Cameron Health, Inc ; Boston Scientific ; Medtronic* None Boston Scientific*; Biotronik*; Spectranetics* None None Boston Scientific*; Cameron Health, Inc*; Medtronic* None Anne Dubin Stanford University None None None None None None None Loren Hiratzka Bethesda North Hospital None None None None None None None Richard L. Page University of Washington None None None None None None None Michael Silka University of Southern California None None None None None None None Bruce Wilkoff Cleveland Clinic None None Medtronic*; St Jude Medical*; Boston Scientific*; LifeWatch None None Medtronic*; St Jude Medical*; Boston Scientific*; LifeWatch None This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be significant if (1) the person receives $10 000 or more during any 12-month period, or 5% or more of the person s gross income; or (2) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity.


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National Institute for Health and Care Excellence Final Chronic heart failure in adults Diagnosis and management Full Guideline Final Developed by the National Guideline Centre, hosted by the Royal College of Physicians Chronic Heart Failure Contents NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Chronic Heart Failure Disclaimer The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and, where appropriate, their carer or guardian. Local commissioners and providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties. NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn. Copyright NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Chronic Heart Failure Contents NICE 2018. All rights reserved.


ISBN: 978-1-4731-3093-7 Chronic Heart Failure Contents NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Contents Guideline committee members 11 NGC technical team members 11 Co-optees 12 Peer reviewers 12 Acknowledgements 13 1 Guideline summary 14 1.1 Full list of recommendations 14 1.2 Diagnostic algorithm 23 1.4 Key research recommendations 24 2.1 Diagnosis and definition of chronic heart failure 26 2.3 Definition of a specialist 27 2.4 Definitions used in the guideline 28 2.5 Rationale for the update 29 3 Development of the guideline 30 3.1 What is a NICE guideline? 30 3.3 Who developed this guideline? 31 3.3.1 What this guideline covers 31 3.3.2 What this guideline does not cover 32 3.3.3 Relationships between the guideline and other NICE guidance 33 4.1 Developing the review questions and outcomes 34 4.2 Searching for evidence 41 4.2.1 Clinical literature search 41 4.2.2 Health economic literature search 42 4.3 Identifying and analysing evidence of effectiveness 42 4.3.1 Inclusion and exclusion criteria 43 4.3.2 Type of studies 44 4.3.3 Methods of combining clinical studies 44 4.3.4 Appraising the quality of evidence by outcomes 48 4.3.5 Publication bias 57 4.3.6 Assessing clinical importance 57 Chronic Heart Failure Contents NICE 2018. All rights reserved. Subject to Notice of rights.


31 3.3.1 What this guideline covers 31 3.3.2 What this guideline does not cover 32 3.3.3 Relationships between the guideline and other NICE guidance 33 4.1 Developing the review questions and outcomes 34 4.2 Searching for evidence 41 4.2.1 Clinical literature search 41 4.2.2 Health economic literature search 42 4.3 Identifying and analysing evidence of effectiveness 42 4.3.1 Inclusion and exclusion criteria 43 4.3.2 Type of studies 44 4.3.3 Methods of combining clinical studies 44 4.3.4 Appraising the quality of evidence by outcomes 48 4.3.5 Publication bias 57 4.3.6 Assessing clinical importance 57 Chronic Heart Failure Contents NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 4.3.7 Clinical evidence statements 57 4.3.8 Appendix D-Practical notes 57 4.4 Identifying and analysing evidence of cost effectiveness 58 4.4.2 Undertaking new health economic analysis 60 4.4.4 In the absence of health economic evidence 61 4.5.1 Research recommendations 62 4.5.3 Updating the guideline 62 5 Diagnosing heart failure 64 5.1 BNP and NT-proBNP in diagnosing heart failure 64 5.1.2 Review question: In people with suspected heart failure, what thresholds of pro-B-type natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) are most accurate in identifying heart failure (as indicated by the reference standard)? 64 5.1.3 Review question: In people with suspected heart failure, what is the clinical and cost effectiveness of N-terminus pro-B-type natriuretic peptide (NT- proBNP) compared to B-type natriuretic peptide (BNP), when each is followed by the appropriate patient pthway, in order to improve patient 5.2 BNP and NT-proBNP in diagnosing heart failure in people with atrial fibrillation 84 5.2.1 Review question: In people with suspected heart failure who also have atrial fibrillation, what thresholds of N-terminus pro-B-type natriuretic peptide (NT- proBNP) and B-type natriuretic peptide (BNP) are most accurate in identifying heart failure (as indicated by the reference standard)?


64 5.1.3 Review question: In people with suspected heart failure, what is the clinical and cost effectiveness of N-terminus pro-B-type natriuretic peptide (NT- proBNP) compared to B-type natriuretic peptide (BNP), when each is followed by the appropriate patient pthway, in order to improve patient 5.2 BNP and NT-proBNP in diagnosing heart failure in people with atrial fibrillation 84 5.2.1 Review question: In people with suspected heart failure who also have atrial fibrillation, what thresholds of N-terminus pro-B-type natriuretic peptide (NT- proBNP) and B-type natriuretic peptide (BNP) are most accurate in identifying heart failure (as indicated by the reference standard)? 84 5.2.2 Review question: In people with suspected heart failure who also have atrial fibrillation, what is the clinical and cost effectiveness of N-terminus pro-B- type natriuretic peptide (NT-proBNP) compared to B-type natriuretic peptide (BNP), when each is followed by the appropriate patient pathway, in order to improve patient outcomes? 85 5.3 BNP and NT-proBNP in diagnosing heart failure in people with chronic kidney disease 86 Chronic Heart Failure Contents NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 5.3.1 Review question: In people with suspected heart failure who also have chronic kidney disease, what thresholds of N-terminus pro-B-type natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) are most accurate in identifying heart failure (as indicated by the reference standard)? 86 5.3.2 Review question: In people with suspected heart failure who also have chronic kidney disease, what is the clinical and cost effectiveness of N- terminus pro-B-type natriuretic peptide (NT-proBNP) compared to B-type natriuretic peptide (BNP), when each is followed by the appropriate patient pathway, in order to improve patient outcomes?


86 5.3.2 Review question: In people with suspected heart failure who also have chronic kidney disease, what is the clinical and cost effectiveness of N- terminus pro-B-type natriuretic peptide (NT-proBNP) compared to B-type natriuretic peptide (BNP), when each is followed by the appropriate patient pathway, in order to improve patient outcomes? 87 5.3.6 Recommendations and link to evidence 90 5.4 Recommendations for diagnosing heart failure 103 5.4.1 Symptoms, signs and investigations 103 5.4.2 Heart failure caused by valve disease 104 5.4.3 Reviewing existing diagnoses 104 5.5 Cardiac Magnetic Resonance Imaging (cMRI) 105 5.5.2 Review question: In people with heart failure what is the clinical and cost effectiveness of cardiac MRI followed by the appropriate patient pathway? 105 5.5.6 Recommendations and link to evidence 106 6 Treating Heart Failure 109 6.1.1 Salt and fluid restriction 109 6.1.2 Recommendations on lifestyle 120 6.2 Pharmacological treatment 121 6.2.2 Beta-blockers in people with heart failure and atrial fibrillation 122 6.2.3 Mineralocorticoid Receptor Antagonists in HFPEF 134 6.2.4 Mineralocorticoid Receptor Antagonists in HFREF 144 6.2.5 Iron supplementation for iron deficiency in heart failure 159 6.2.6 Pharmacological treatment for heart failure in people with heart failure and chronic kidney disease 180 6.2.7 All recommendations for the pharmacological treatment of heart failure 202 6.3 Invasive procedures 207 6.3.1 Coronary revascularisation 207 6.3.2 Recommendations for invasive procedures 222 Chronic Heart Failure Contents NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 7 Rehabilitation in chronic heart failure 223 7.1 Home-based versus centre-based rehabilitation 223 7.1.2 Review question: What is the clinical and cost effectiveness of home-based versus centre-based rehabilitation (that includes an exercise element) for people with heart failure (HF)?


ISBN: 978-1-4731-3093-7 7 Rehabilitation in chronic heart failure 223 7.1 Home-based versus centre-based rehabilitation 223 7.1.2 Review question: What is the clinical and cost effectiveness of home-based versus centre-based rehabilitation (that includes an exercise element) for people with heart failure (HF)? 223 7.1.6 Recommendations and link to evidence 233 8.1 Monitoring using repeated biomarker measurement or imaging for management of chronic heart failure 238 8.1.2 Review question: What is the clinical and cost effectiveness of biomarker- based monitoring, monitoring with cardiac MRI, and monitoring with repeated echocardiography in people with heart failure? 239 8.2 Monitoring using repeated biomarker measurement or imaging for management of chronic heart failure in people who also have chronic kidney disease 259 8.2.2 Review question: What is the clinical and cost effectiveness of biomarker- based monitoring, monitoring with cardiac MRI, and monitoring with repeated echocardiography in people with heart failure who also have CKD? 259 8.3 Monitoring using repeated biomarker measurement or imaging for management of chronic heart failure in people who also have atrial fibrillation 265 8.3.2 Review question: What is the clinical and cost effectiveness of biomarker- based monitoring, monitoring with cardiac MRI, and monitoring with repeated echocardiography in people with heart failure who also have atrial fibrillation? 266 8.3.6 Recommendations and link to evidence 267 8.4 Telemonitoring and self-monitoring 275 Chronic Heart Failure Contents NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 8.4.2 Review question: What is the clinical and cost effectiveness of telemonitoring and self-monitoring compared with usual care, in people with heart failure?


ISBN: 978-1-4731-3093-7 8.4.2 Review question: What is the clinical and cost effectiveness of telemonitoring and self-monitoring compared with usual care, in people with heart failure? 275 8.4.6 Recommendations and link to evidence 303 8.5 Recommendations for monitoring heart failure 308 8.5.1 Clinical review 308 8.5.2 Measuring NT-proBNP 308 9 Referral and approach to care 309 9.2 Team working in the management of heart failure 309 9.2.2 Review question: What competencies should be present in the multidisciplinary teams involved in the outpatient or community-based care of people with heart failure? 309 9.2.6 Recommendations and link to evidence 353 9.3 Transition between heart failure care settings 360 9.3.2 Review question: What are the experiences/preferences of staff and patients during transition between different heart failure care settings (including primary, secondary and community care)? 360 9.3.6 Recommendations and link to evidence 381 9.4 Information and support needs regarding diagnosis and prognosis 389 9.4.2 Review question: What are the information and support needs to be considered when communicating a diagnosis and consequent prognosis, to people with heart failure, their families and carers? 389 9.4.6 Recommendations and link to evidence 413 Chronic Heart Failure Contents NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 9.5.2 Transition between heart failure care settings 419 9.5.3 Information and support needs regarding diagnosis and prognosis 420 10 Advanced heart failure and palliative care 421 10.1 Diuretics in advanced heart failure 421 10.1.2 Review question: Which route of administration of diuretics (intravenous (IV), subcutaneous or oral) is most clinically and cost effective in people with advanced heart failure who are in the community, including patients receiving palliative care?