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Surgical Treatment of Pacemaker and Defibrillator Lead Endocarditis
Surgical Treatment of Pacemaker and Defibrillator Lead Endocarditis* The Impact of Electrode Lead Extraction on Outcome Ana del Rı´o, MD; Ignasi Anguera, MD; Jose´ M. Miro´, MD, PhD; Lluis Mont, MD, PhD; Vance G. Fowler, Jr., MD, MHS; Manel Azqueta, MD; Carlos A. Mestres, MD; and the Hospital Clı´nic Endocarditis Study Group†
Background: Cardiac device (CD) endocarditis is an infrequent but potentially lethal infectious complication of permanent pacemakers or implantable cardioverter-defibrillators (ICDs), and mortality rates of 30 to 35% have been reported. Medical treatment has been suggested for the treatment of CD endocarditis, but there is increasing evidence that surgical treatment is to be preferred as the best approach to achieve eradication of the infection and reduce mortality. Objective: To evaluate the following: (1) the clinical and echocardiographic characteristics of patients with pacemaker or ICD endocarditis, (2) the outcome of this population depending on the mode of treatment (medical vs surgical treatment), and (3) the clinical, microbiological, echocardiographic, and therapeutic variables associated with patient outcome. Design: Prospective cohort study. Setting: Tertiary referral center in Barcelona, Spain. Patients: All consecutive patients with infectious endocarditis (IE) admitted to the study institution between 1990 and 2001 were prospectively evaluated by a multidisciplinary treatment team, and a definite diagnosis of CD endocarditis was established when cases met pathologic or clinical criteria according to the Duke criteria. Results: A total of 31 patients, 25 men and 6 women aged 61 ⴞ 15 years (mean ⴞ SD), with pacemaker or ICD endocarditis were identified among 669 consecutive patients (4.6%) with IE. During the study period, a total of 3,768 pacemakers and 460 ICDs were implanted in the study institution. In 22 cases of pacemaker endocarditis, the pacemaker was implanted in our institution, and 9 cases were referred from other institutions (incidences of endocarditis on pacemaker and ICD implanted in our institution of 0.58% and 0.65%, respectively). Medical treatment without removal of the pacing system was initially performed on seven patients; all of them (100%) had relapses of endocarditis, and one patient died. The remaining 24 patients underwent surgical removal of the pacing system; 1 patient had one relapse, 3 patients died after surgical treatment, and the others were successfully cured with no relapses after a mean follow-up of 38 ⴞ 9 months. Clinical, echocardiographic, microbiological, and therapeutic variables were evaluated in association with prognosis. The only prognostic factor for failure of treatment or mortality was the absence of surgical treatment (p < 0.0001). Conclusions: Electrode lead endocarditis occurred in < 1% of pacemaker and ICD implants. Conservative treatment without explantation of all hardware failed in all patients, and surgical treatment during antibiotic therapy was effective in eradication of infection but was associated with a 12.5% mortality. The only patient characteristic associated with treatment failure or death was the absence of surgical removal of all infected hardware. Complete extraction of the pacemaker or ICD should be considered as standard therapy for most patients with CD endocarditis. (CHEST 2003; 124:1451–1459) Key words: defibrillator; electrode lead; infective endocarditis; pacemaker; treatment Abbreviations: CD ⫽ cardiac device; CI ⫽ confidence intereval; CPB ⫽ cardiopulmonary bypass; ICD ⫽ implantable cardioverter-defibrillator; IE ⫽ infective endocarditis; TEE ⫽ transesophageal echocardiography; TTE ⫽ transthoracic echocardiography
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CHEST / 124 / 4 / OCTOBER, 2003
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use of cardiac devices (CDs) has T hegrownclinical considerably over the past 2 decades. A
Materials and Methods
1,2
growing list of indications for permanent pacemakers and implantable cardioverter-defibrillators (ICDs) and the increase in the geriatric population mean that more patients undergo pacemaker and ICD surgery; therefore, there is a larger population at risk of infection. CD infective endocarditis (IE) is an infrequent but potentially lethal infectious complication of pacemaker and ICD therapy. Infection of the pacemaker pouch and wire may occur in 1 to 7% of implanted pacing systems,3,4 and mortality rates in CD endocarditis have been reported to be 30 to 35%.5 Risk factors for CD endocarditis include chronic conditions such as diabetes mellitus, malignancies, immunosuppressive therapy, and local factors related to the pacing system such as erosion of the pacemaker pouch, and the number of previously inserted leads, etc.3 Despite advances in diagnostic approaches, treatment of CD endocarditis is still controversial. Medical treatment has been reported to be successful in some cases,6 –12 but there is increasing evidence that the entire pacing system should be removed to achieve complete infection eradication.13–17 However, most studies have been retrospective and have included few patients, and there are no controlled studies comparing medical vs surgical treatment; therefore, we designed a prospective study to identify all consecutive cases of pacemaker and ICD endocarditis over a decade. The purpose of this study is to describe the following: (1) the clinical and echocardiographic characteristics of pacemaker and ICD endocarditis, (2) the outcome of this population depending on the mode of treatment (conservative therapy vs surgical explantation of all hardware during antimicrobial therapy), and (3) the clinical, microbiological, echocardiographic, and therapeutic variables associated with patient outcome. *From the Hospital Clı´nic (Drs. del Rio, Miro´, Mont, Azqueta, and Mestres), Institut d’Investigacions Biome`diques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; Hospital de Sabadell (Dr. Anguera), Barcelona, Spain; and Duke University Medical Center (Dr. Fowler), Durham, NC. †A list of participants is given in the Appendix. This work has been supported in part by the Red Espan˜ola de Investigacı´on en Patologı´a Infecciosa (V-2003-REDC14A-0). Dr. Miro´ was a recipient of a research grant from the Institut d’Investigacions Biome`diques August Pi i Sunyer, Barcelona, Spain. Manuscript received October 18, 2002; revision accepted February 18, 2003. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]). Correspondence to: Jose´ M. Miro´ , MD, PhD, Division of Infectious Diseases, Hospital Clı´nic Universitari, Villarroel, 170, 08036, Barcelona, Spain; e-mail: [email protected] 1452
Study Patients All patients admitted to our tertiary referral center with IE between 1990 and 2001 were prospectively evaluated by a multidisciplinary treatment team. The multidisciplinary team for diagnosis and treatment of IE involves staff members from infectious disease, anatomic pathology, microbiology, and cardiovascular departments (see Appendix). Regular meetings of this treatment team served to include all patients who received a diagnosis at the study institution, and served to be certain that no cases were missed. Data were collected prospectively into an institutional protocol using a designed questionnaire for clinical, microbiological, echocardiographic, therapeutic, and follow-up variables; all data were stored in a database. The study institution is a tertiary referral center for complicated endocarditis, including antiarrhythmic device endocarditis, with a catchment area of 750,000 inhabitants. The study was approved by the ethics committee. Diagnostic Criteria of Endocarditis Pacemaker or ICD endocarditis were defined according to criteria suggested by Duke investigators,18 and only definite cases were included in the study. Because pacemakers and transvenous ICDs are structurally similar, patients with infection involving either of these devices were included in the present report. A definite diagnosis of CD endocarditis was established when cases met pathologic or clinical criteria according to the Duke criteria.18 Early onset endocarditis was defined as infection occurring ⬍ 12 months after implantation, and late-onset endocarditis was defined as infection ⬎ 12 months from implantation. An infected anatomic site was considered to be the source of bacteremia if consistent focal manifestations preceded the diagnosis of bacteremia and the microorganisms were recovered from adequate site specimens. Echocardiographic Definitions Results of two-dimensional transthoracic echocardiography (TTE) [Toshiba SSH-65A; Toshiba Corporation; Tokyo, Japan; and Sonos 1000, 2500, and 5500; Hewlett-Packard; Boston, MA] were routinely evaluated in each patient. Since 1992, transesophageal echocardiography (TEE) using monoplane or multiplane transducers was performed in all cases of suspected antiarrhythmic device endocarditis. Vegetations were defined as circumscribed masses or clumps of echoes that arose from leaflet tips or electrode leads, either as an irregular area of highly reflective leaflet thickening or as more discrete, pedunculated masses in the setting of electrode lead infection confirmed by imaging in more than one echocardiographic plane. Vegetations were measured at the point of maximal thickness in two orthogonal dimensions.19 To identify valvular involvement, clinical, echocardiographic, operative, and autopsy data were used. Microorganisms and Antibiotic Therapy Microorganisms were identified using standard criteria. Antibiotic susceptibility testing was performed by broth microdilution method and interpreted using standard methods.20 All patients received antimicrobial therapy according to the etiologic microorganism and its antimicrobial susceptibility test and the recommended antimicrobial therapy for IE.21,22 Decisions regarding medical and surgical therapy were made by the treating physicians independent of the current descriptive investigation. AntiClinical Investigations
biotics were administered IV for 4 to 6 weeks in all episodes. Treatment of methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci infection included cloxacillin (during 4 to 6 weeks) plus gentamicin (during 5 to 7 days); treatment of methicillin-resistant S aureus and coagulase-negative staphylococci infection included vancomycin plus gentamicin and rifampin. Surgical Treatment Surgical treatment was not randomized, and the decision to remove the pacing system was based on the judgement of the multidisciplinary treatment team. The indication for surgery during the active phase was considered in all cases with definite diagnosis, following standard recommendations.23,24 Percutaneous extraction of the electrodes was achieved by manual traction; when the operator felt a highly fixed electrode in the endocardium, special locking stylets were used. Factors that favored surgical treatment with cardiopulmonary bypass (CPB) were increased vegetation size and the time interval from implantation to diagnosis of definitive endocarditis. Electrode lead extraction under CPB was considered in cases of long-term leads (⬎ 12 months from implantation) or in cases of more than two leads. In cases of large vegetations with possibly higher embolic risk, patients were submitted to surgical removal of the entire pacing or defibrillating system with open-heart surgery and CPB. Temporary transvenous pacemakers were inserted after the operation for pacemaker-dependent patients, and new definitive pacemakers were again implanted approximately 2 weeks after surgery in both dependent and nondependent pacemaker patients. Statistical Analysis To preserve the independence of observations, only the initial episodes of CD endocarditis were included in the study. Data were processed with the BMDP statistical package (BMDP Statistical Software; Los Angeles CA). Clinical manifestations, echocardiographic findings, antimicrobic susceptibility, and mode of treatment for patients with and without adverse outcomes were compared with Student t test for continuous variables and the Fisher exact test for categorical variables. Failure of treatment (clinical relapse of CD endocarditis) and mortality were defined as adverse outcomes. The relation of covariates with failure of treatment or mortality was assessed by univariate analysis, and odd ratios (ORs) were then determined with a simple logistic regression model. ORs and 95% confidence intervals (CIs) were calculated with Stata Statistical Software, Release 6 (Stata Corporation; College Station, TX). Differences were considered significant only when two-sided p values were ⬍ 0.05. The McNemar test was used to compare TTE and TEE in the detection of cardiac vegetations.
Results Demographic Characteristics A total of 31 of 669 consecutive patients (4.6%) with IE (6 women and 25 men, aged 61 ⫾ 15 years [mean ⫾ SD]) with bacteriologically proven CD endocarditis were identified over a decade (Table 1). Infections of permanent cardiac pacemakers were observed in 28 patients (12 single chamber and 16 dual chamber); in 3 patients, infection was on a single-lead ICD. During the study period, a total of www.chestjournal.org
3,768 pacemakers and 460 ICDs were implanted in our institution. In 22 cases of pacemaker endocarditis, the pacemaker was implanted in our institution and 9 cases were referred from other institutions (incidences of endocarditis on pacemakers and ICDs implanted in our institution were 0.58% and 0.65%, respectively). Cultures of the removed wire yielded the causative pathogen in all but one case. All patients had two or more positive blood culture results. Eleven patients (35%; 2 women and 9 men, aged 62 ⫾ 18 years) had early onset infection (mean, 5 months; range, 1 to 10 months) after implantation; 20 patients (65%) had late-onset infection (4 women and 16 men, aged 60 ⫾ 16 years). Late-onset IE developed after a mean 65 months from primary implantation, and 35% had undergone previous surgical manipulation in the pacing system, principally replacement of an exhausted battery generator (17% ⬍ 3 months before endocarditis, 50% between 3 months and 9 months, and 33% ⬎ 1 year before endocarditis). All electrode leads had been transvenously implanted, and 17 patients (55%) had two or more electrodes. The mean number of electrodes was 1.7 per patient. Pocket erythema with pain, skin erosion, cutaneous ulcer, or purulent draining sinus from the pocket generator could be determined as a source of infection in seven patients (23%). Echocardiographic Results TTE recordings were reviewed in all patients, and TEE became available for the last 23 patients (74%). Definitive echocardiographic vegetations were detected in 20 patients (87%) with variable sensitivities for TTE and TEE (Table 2). The mean maximal vegetation size was higher with TTE than with TEE (p ⫽ 0.02). Tricuspid valve vegetations were observed in six patients (26%). No vegetations were detected in left-sided valves in any patient. Vegetations ⬎ 15 mm were observed in 11 patients (35%), and vegetations ⬎ 20 mm were observed in 6 patients (15%). Microbiological Data The most frequently detected causative microorganisms were staphylococci. Coagulase-negative staphylococci were detected in 15 cases (48%) [Staphylococcus epidermidis in 35%, Staphylococcus lugdunensis in 9%, and Staphylococcus hominis in 3%]. S aureus was isolated in nine cases (29%). Other organisms growing on blood or tissue (electrode) cultures and the results of antibiotic susceptibility tests performed in patients with endocarditis caused by staphylococci are shown in Table 3. CHEST / 124 / 4 / OCTOBER, 2003
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Table 1—Clinical Characteristics of Patients* Characteristics
Overall (n ⫽ 31)
Early-Onset Infection (n ⫽ 11)
Late-Onset Infection (n ⫽ 20)
Mean age, yr (range) ⬍ 55 yr 56–69 yr ⬎ 70 yr Male gender Antiarrhythmic device Permanent pacemaker ICD Comorbidities Diabetes mellitus Liver cirrhosis Chronic renal failure Indication for implantation Atrioventricular block Sinus node disease Ventricular tachycardia Other† Source of infection Skin ulcer on the generator pocket Unknown Duration of symptoms, d Mean (range) ⬎ 90, % Clinical presentation Fever Pulmonary septic emboli Tricuspid regurgitant murmur Right-heart failure
61 (31–90) 9 (29) 9 (29) 13 (42) 25 (80)
62 (31–82) 3 (27) 4 (36) 4 (36) 9 (82)
60 (38–90) 6 (30) 5 (25) 9 (45) 16 (80)
28 (90) 3 (10) 14 (45) 8 (26) 3 (10) 3 (10)
10 (91) 1 (9) 4 (36) 3 (27) 1 (9) 1 (9)
18 (90) 2 (10) 10 (50) 5 (25) 2 (10) 2 (10)
18 (58) 6 (20) 3 (10) 4 (13)
7 (64) 2 (18) 1 (9) 2 (18)
11 (55) 4 (20) 2 (10) 2 (10)
7 (23) 24 (77)
1 (9) 10 (91)
6 (30) 14 (70)
64 (2–180) 25
58 (2–145) 20
73 (15–180) 38
31 (100) 9 (29) 6 (20) 2 (7)
11 (100) 2 (18) 2 (18) 1 (9)
20 (100) 7 (35) 4 (20) 1 (5)
*Data are presented as No. (%) unless otherwise indicated. †Hypertrophic obstructive cardiomyopathy (n ⫽ 2), syncope of unknown origin (n ⫽ 1), supraventricular tachycardia (n ⫽ 1).
Antibiotics prior to the diagnosis of CD endocarditis were administered in six patients (19%) before hospital admission. Outcome All patients were treated with IV antibiotics following approved international recommendations and guided by antibiotic susceptibility tests. Table 4 shows the outcome after medical and surgical treatment. Medical treatment without removal of the pacing system was initially performed on seven patients; all of them (100%) had relapses of endocarditis, and one patient died after the third relapse.
Medical treatment was used in these seven patients due to a variety of reasons (patient preference in two cases, associated comorbid conditions in two cases, absence of vegetations on echocardiography in two cases, and infection due to S lugdunensis in one patient). Percutaneous lead extraction involving complete extraction of all hardware was performed after a mean of 1.6 relapses, and was effective in eradication of the infection in the six patients with failed medical treatment. In patients with failed medical treatment, the mean interval from initial diagnosis of CD endocarditis to surgical treatment was 5.1 ⫾ 2.9 months. The remaining 24 patients
Table 2—Comparison of TTE and TEE Results in Patients Who Underwent Both Studies Variables
TTE (n ⫽ 23)
TEE (n ⫽ 23)
OR (95% CI)
p Value
Vegetation location, No. (%) Tricuspid valve Wire Overall Vegetation size, mm* Tricuspid regurgitation, No. (%)
4 (17) 5 (21) 9 (39) 22 ⫾ 8 (7–40) 7 (30)
6 (26) 18 (78) 20 (87) 15 ⫾ 7 (4–29) 14 (60)
1.7 (0.32–10) 12.9 (2.7–71.4) 10.4 (2.0–66.6) Not applicable 3.5 (0.9–14.5)
0.3 0.0003 0.001 0.02 0.07
*Data presented as mean ⫾ SD (range). 1454
Clinical Investigations
Table 3—Microbiology* Etiologic Agents
No. (%)
Staphylococci Coagulase-negative staphylococci S epidermidis S lugdunensis S hominis S aureus Viridans group streptococci Pseudomonas aeruginosa Serratia spp. Oligella urethralis Polymicrobial§
24 (78) 15 (48)† 11 (35) 3 (9) 1 (3) 9 (29)‡ 2 (6) 1 (3) 1 (3) 1 (3) 2 (6)
*Data are presented as No. (%). †Methicillin resistant (n ⫽ 3, 20%). ‡Methicillin resistant (n ⫽ 4, 45%). §Viridans group streptococci plus Acinetobacter calcoaceticus and S epidermidis plus S hominis.
underwent surgical removal of the entire device (in 5 patients [21%] with median sternotomy and CPB, and in 19 patients [79%] with percutaneous external counter traction). The mean interval from diagnosis of CD endocarditis to surgical treatment was 13.8 ⫾ 6.3 days. Three patients (12.5%) died after surgical treatment, one patient had a relapse, and the others were successfully cured with complete eradication of the infection and absence of relapses after a mean follow-up of 38 ⫾ 9 months. One patient treated with percutaneous lead extraction and two patients treated with CPB died after the procedure (due to GI hemorrhage in one patient, laceration of the superior vena cava in one patient, and massive thrombosis of the superior vena cava in another patient, respectively). Overall mortality was 13%. Mortality in patients surgically treated with percutaneous lead extraction or CPB was 5% and 40%, respectively. No demographic, clinical, microbiological, or echocardiographic characteristics significantly distinguished patients with successful outcome from those with failure of treatment or death. Table 5 shows the
factors influencing mortality in the univariate analysis. The only patient characteristic associated with treatment failure or death was the absence of surgical removal of all infected hardware. Although staphylococcal infection was not statistically associated with increased mortality (Table 5), all patients that died had staphylococcal endocarditis (one patient with S aureus, one patient with S lugdunensis, and two patients with S epidermidis). Discussion Infections of implantable antiarrhythmic devices may range from 0.2 to 12% and are considered as serious complications of pacing therapy because of the inherent difficulties in the management of CD endocarditis and the adverse outcome. The incidence of pacemaker- and ICD-related infections has been reported as between 0.5% and 12% in the past; in more recent publications, the incidence is ⬍ 5%.3,25,26 The present investigation found an incidence of endocarditis on pacemakers and ICDs of 0.58% and 0.65%, respectively, which is in the range of reported values.3,4 The Role of Echocardiography TTE may identify lead vegetations, but it has not been established as a major diagnostic criteria for CD endocarditis due to its low sensitivity.15 TEE allows the exploration of the entire pacing system from the superior vena cava to the right ventricle. Our study did not differ from previous publications in which detection of lead vegetations increased from sensitivities of TTE in the range of 22 to 30% to sensitivities of approximately 95% with the use of TEE14,15,17,27; however, TEE appears to be of limited additive value in the detection of tricuspid valve vegetations. We observed no statistical differences between TTE and TEE in the detection of tricuspid valve vegetations (Table 2). Our results confirm previous observations that TEE does not improve the diagnostic accuracy of TTE in the detection of vegetations associated with right-sided endocarditis.28
Table 4 —Failure of Treatment or Mortality (Adverse Outcomes) According to Therapeutic Management* Treatment
Treated Patients
Cures/Relapses
Deaths
Overall Adverse Outcomes
Medical treatment† Surgical treatment in patients with failed medical treatment Surgical treatment as initial therapy Percutaneous lead extraction CPB Global mortality
7 6
0/7 6/0
1 (14) 0 (0)
7 (100) 0 (0)
24 19 5 31
20/1 17/1 3/0
3 (13) 1 (5) 2 (40) 4 (13)
4 (17) 2 (10) 2 (40)
*Data are presented as No. or No. (%). †Three patients had one relapse, two patients had two relapses, two patients had three relapses (one patient died without surgery). www.chestjournal.org
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Table 5—Prognostic Factors of Adverse Outcomes in Endocarditis Associated With Pacemaker or ICDs (Univariate Analysis) Variables
Patients, No. (n ⫽ 31)
Age ⬍ 65 yr Yes No Gender Male Female Single chamber Yes No Underlying disease Yes No Known source of infection Yes No Presence of ⱖ 2 electrodes Yes No Late-onset endocarditis Yes No Previous manipulation in late-onset endocarditis Yes No Tricuspid valve vegetation Yes No Echocardiogram positive Yes No Diagnosis after 1995 Yes No Vegetation ⬎ 10 mm Yes No Pulmonary embolism Yes No Staphylococcal infection Yes No S aureus infection Yes No S epidermidis infection Yes No Death due to staphylococcal infection Yes No Medical treatment alone Yes No
OR (95% CI)
p Value
15 16
6 (40) 5 (31)
1.47 (0.264–8.312) 1
0.611
24 7
9 (38) 2 (29)
1.5 (0.188–18.665) 1
0.664
15 16
3 (20) 8 (50)
0.25 (0.034–1.528) 1
0.081
14 16
4 (29) 7 (44)
0.514 (0.082–2.942) 1
0.389
7 24
3 (43) 8 (33)
1.5 (0.173–11.284) 1
0.643
17 14
8 (47) 3 (21)
4.19 (0.657–31.632) 1
0.076
20 11
7 (35) 4 (36)
0.942 (0.162–6.015) 1
0.939
7 13
2 (29) 5 (38)
0.64 (0.045–6.327) 1
0.658
8 23
2 (25) 9 (39)
0.518 (0.043–3.894) 1
0.472
20 11
8 (40) 3 (27)
1.78 (0.290–13.376) 1
0.478
23 8
7 (30) 4 (50)
0.437 (0.062–3.165) 1
0.319
11 20
4 (36) 7 (35)
1.061 (0.166–6.172) 1
0.939
9 22
4 (44) 7 (32)
2.82 (0.431–17.351) 1
0.177
24 7
10 (42) 1 (14)
4.28 (0.396–216.47) 1
0.182
9 22
3 (33) 8 (36)
0.875 (0.111–5.653) 1
0.872
11 20
4 (36) 7 (35)
1.061 (0.166–6.172) 1
0.939
24 7
4 (17) 0 (0)
Not applicable
0.33
7 24
7 (100) 4 (17)
Not applicable
⬍ 0.0001
Microbiology Positive blood culture results have been found in 80 to 100% of pacemaker-related endocarditis.9,14,27,29 In our study, cultures of the removed wire yielded the causative pathogen in all but one case, and all patients had two or more positive blood 1456
Failure of Treatment or Mortality, No. (%)
culture results. The most frequently detected causative microorganisms were staphylococci (coagulasenegative staphylococci in 48% of cases, and S aureus in 29% of cases). Previous reports5,6,9,14,15,17,30 –32 documented similar microbiologic findings. Early onset infection is associated with infection by S Clinical Investigations
aureus, and the most common portal of entry is the subcutaneous site of implantation of the pacemaker. By contrast, late infections are caused predominantly by coagulase-negative staphylococci, and infection tends to have a more indolent course related to the low virulence of this organism. Staphylococci seem to be particularly capable of adhering to and forming microcolonies on the polyethylene or silicone rubber sheaths covering the electrodes. Infection caused by Gram-negative microorganisms, fungae, anaerobic bacteria, and multiple microorganisms have seldom been reported.6,14,30,31,33 Data33,34 suggest the hypothesis that CD endocarditis is mainly caused by local contamination during the implantation procedure. Hematogenous colonization of the pacemaker conducting system during the course of a bacteremia from a distant focus has rarely been demonstrated since the pacing system is rapidly covered by neoendothelium and fibrous tissue, which prevents the foreign surface from being coated by microorganisms. Hematogeneous seeding of the device from distant sites of infection has been reported, but with the exception of S aureus bacteremia appears to be rare.3,9 In our study, all patients were bacteremic with fever and positive blood culture results. Among the 65% of patients with lateonset endocarditis, no previous manipulation of the pacing system had been performed, and hematogeneous seeding of the device was presumed to be the mode of colonization of the system. In one study34 of 21 patients with S aureus bacteremia occurring a year or more after device placement, 29% acquired a subsequent device infection. By contrast, 35% of the patients from this study had early onset infection, and 35% of patients with late-onset infection had a previous surgical manipulation of the pacing system (replacement of an exhausted battery generator). This fact has clinical implications for the reduction of the incidence of CD endocarditis and reinforces the value of antibiotic prophylaxis during all types of surgical manipulation of the pacing system (including replacement of generators). In a recent metaanalysis by Da Costa et al,35 systemic antibiotic prophylaxis at the time of insertion of permanent pacemakers or replacements showed a consistent protective effect reducing the incidence of pocket infections and pacemaker endocarditis. Treatment of CD Endocarditis Management of CD-related infection is based on a combined approach using both antimicrobial agents with surgical eradication. The results of this investigation demonstrate that patients with CD endocarditis should undergo extraction of the device and leads, followed by a course of IV antibiotics and www.chestjournal.org
device reimplantation at another site during a delayed surgical procedure if indication for pacing or defibrillation persists. Our study found a statistically significant difference in successful outcomes with surgical treatment as opposed to medical treatment. Patients treated medically had a mean of 1.6 relapses per patient until they underwent surgical treatment. Patients treated with surgery were more likely to have absence of recurrences or mortality than medically treated patients (p ⬍ 0.0001). No other demographic, clinical, echocardiographic, or microbiological variables were associated with adverse outcome (Table 5). The most widely recommended approach for generator-pocket infection is removal of the entire pacing system, which achieves the highest rates of cure,31,32 but electrode infections generally require removal of the system. Following implantation of cardiac antiarrhythmic devices, the generator pocket and intravascular lead become encased in dense layers of endotheliazed fibrous tissue, so that infection is complicated by lack of penetration of antimicrobial agents into the avascular matrix, necessitating removal of some or all of the components to eradicate infection. Attempts at a conservative approach, including combined bactericidal antibiotics and local debridement techniques, not only failed to cure CD-related infections, but were also responsible for higher mortality rates.5,6,9,15,16,30,31,34,36 Some authors11,12,16 have advocated a conservative approach consisting of antibiotic therapy with hardware in place or partial device removal. Partial device removal is likely to be sufficient only when infection is limited to the removed component, and it is aimed to avoid invasive surgical procedures in debilitated individuals; however, most large studies6,9,15–17 suggest that complete removal of all parts of an infected device is necessary to achieve a definitive cure in CD endocarditis. Klug et al17 suggested that vegetations ⬎ 10 mm may be removed by percutaneous lead traction without a significant increase in subsequent pulmonary embolic complications; they also suggested that the indication for percutaneous removal should be expanded to include larger vegetation sizes. In our study, percutaneous removal was performed in vegetations up to 23 mm in length without any associated complications, although these have been reported in the literature.17 Removal of the material involves technical difficulties. Removal of the leads or electrodes may not be possible by percutaneous traction, and damage of the myocardium or tearing of the tricuspid valve may result as electrodes become imbedded over time. Extraction of the leads remains difficult and may require an invasive surgical approach, including sternotomy with or without extracorporeal circulation.36 CHEST / 124 / 4 / OCTOBER, 2003
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Timing from pacemaker implantation to diagnosis of endocarditis is another variable that may favor surgical removal of the electrode system with CPB. Within several months of implantation (usually ⬍ 12 months), extraction may be accomplished by simple manual traction; after 12 months from implantation, the use of locking stylets has been proposed be the method of choice.37 Chronic electrode tips are attached to the right ventricular endocardium and are embedded in a dense fibrotic plaque, making electrode removal by direct traction dangerous. In our study, percutaneous traction was carried out in patients with an implantation to diagnosis of endocarditis interval up to 106 months. There were neither deaths nor failures of eradication of the infection among the 12 patients with late-onset endocarditis treated with percutaneous removal of the electrode (mean implantation to diagnosis, 65.5 ⫾ 41 months; range, 21 to 106 months). Five patients in this study underwent surgical removal of the electrode with CPB, with a mean of 99 ⫾ 96 months from implantation to diagnosis of endocarditis (range, 1 to 240 months). Mortality in this subgroup was 40% (two of five patients). The number of implanted electrodes (recent implants or long-term electrodes) is a further fact that may favor surgical treatment with CPB. In this study, two patients with three and four electrodes, respectively, were treated with surgical excision of the pacing system under CPB, with one of two deaths (50%). Direct counter traction was performed in all but three patients with two or fewer electrodes in patients surgically treated. Mortality in this group was only 1 of 22 patients (4.5%). Study Limitations The first limitation of this study is the size of the population studied, its nonrandomized nature, and the low number of patients. Secondly, therapeutic management was based on the judgement of the physicians involved, including the multidisciplinary team for the diagnosis and treatment of endocarditis and varied according to individual patient characteristics. Therefore, comparison of different surgical options is difficult. Conclusions Electrode lead endocarditis occurred in ⬍ 1% of pacemaker and ICD implants. Conservative treatment without explantation of all hardware failed in all patients, and surgical treatment during antibiotic therapy was effective in eradication of infection but was associated with 12.5% mortality. The only patient characteristic associated with treatment failure 1458
or death was the absence of surgical removal of all infected hardware. Complete extraction of the pacemaker or ICD should be considered as standard therapy for most patients with CD endocarditis.
Appendix Members of the Hospital Clinic Endocarditis Study Group of the Hospital Clinic, Institut d’Investigacions Biome`diques August Pi i Sunyer, University of Barcelona, Barcelona, Spain include the following: Miro´ JM, del Rı´o A, de Benito N, Claramonte X, Baraldes MA, Jimenez-Alzate MP, Dı´az ME, Soriano A, Moreno A, Gatell JM (Division of Infectious Diseases); Marco F, Garcı´a de la Marı´a C, Armero Y, Almela M, Jime´ nez de Anta MT (Department of Microbiology); Pare´ JC, Azqueta M, Mestres CA, Sitges M, Mont LL, Ninot S, Cartan˜ a´ R, Pomar JL (Cardiovascular Institute); De Lazzari E (Epidemiology and Biostatistics Unit); and Ramı´rez J, Ribalta T, Pe´ rez N (Department of Anatomical Pathology); and Anguera I, Guma´ JR (Hospital de Sabadell). ACKNOWLEDGMENT: We thank Marı´a Antonia Rodrı´guez Jove´ for technical assistance, and Fundacio´ n Privada Ma´ ximo Soriano Jime´ nez for the grant supporting the Hospital Clı´nic Endocarditis database.
References 1 Lamas GA, Oray EJ, Stambler BS, et al. Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. N Engl J Med 1998; 338:1097–1104 2 Mirowski M, Ried PR, Mower M, et al. Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med 1980; 303:322–324 3 Bluhm G. Pacemaker infections: a clinical study with special reference to prophylactic use of some isoxazolyl penicillins. Acta Med Scand 1985; 699;1– 62 4 Morgan G, Ginks W, Siddons QH, et al. Septicemia in patients with endocardial pacemaker. Am J Cardiol 1979; 44:221–224 5 Kugener H, Rey JL, Tribouilloy C, et al. Infectious endocarditis on permanent endocavitary pacemakers: value of echocardiography and review of the literature. Ann Cardiol Angeiol (Paris) 1993; 42:331–338 6 Arber N, Pras E, Copperman Y, et al. Pacemaker endocarditis: report on 44 cases and review of the literature. Medicine (Baltimore) 1994; 73;299 –305 7 Tylman T, Seaworth B. Pacemaker-associated sepsis: successful medical management. South Med J 1985; 78:1140 –1141 8 Zeller NH, Lusk PH, Palmer DL. Nonsurgical cure of endocarditis associated with a pacemaker. Arch Intern Med 1975; 135:580 –581 9 Camus C, Leport C, Raffi F, et al. Sustained bacteremia in 26 patients with a permanent endocardial pacemaker: assessment of wire removal. Clin Infect Dis 1993; 17:46 –55 10 Kearney RA, Eisen HJ, Wolf JE. Nonvalvular infections of the cardiovascular system. Ann Intern Med 1994; 121:219 – 230 11 Lee JH, Geha AS, Ratehalli NM, et al. Salvage of infected ICDs: management without removal. Pacing Clin Electrophysiol 1996; 19:437– 442 Clinical Investigations
12 Turkisher V, Priel I, San M. Successful management of an infected implantable cardioverter defibrillator with oral antibiotics and without removal of the device. Pacing Clin Electrophysiol 1997; 20:2268 –2270 13 Myers MR, Parsonnet V, Bernstein AD. Extraction of implanted transvenous pacing leads: a review of a persistent clinical problem. Am Heart J 1990; 121:881– 888 14 Victor F, De Place C, Camus C, et al. Pacemaker lead infection: echocardiographic features, management and outcome. Heart 1999; 81:82– 87 15 Cacoub P, Leprince P, Nataf P, et al. Pacemaker infective endocarditis. Am J Cardiol 1998; 82:480 – 484 16 Molina JE. Undertreatment and overtreatment of patients with infected antiarrhythmic implantable devices. Ann Thorac Surg 1997; 63:504 –509 17 Klug D, Lacroix D, Savoye C, et al. Systemic infection related to endocarditis on pacemaker leads: clinical presentation and management. Circulation 1997; 95:2098 –2107 18 Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings; Duke Endocarditis Service. Am J Med 1994; 96:200 –209 19 SanFilippo AJ, Picard MH, Newell JB, et al. Echocardiographic assessment of patients with infective endocarditis. J Am Coll Cardiol 1991; 18:1191–1199 20 National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing: eleventh informational supplement. Wayne, PA: National Committee for Clinical Laboratory Standards, 2001. NCCLS document M100 –S11 21 Wilson WR, Karchmer AW, Dajani AS, et al. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci and HACEK microorganisms. JAMA 1995; 274:1706 –1713 22 Wilson WR. Antibiotic treatment of infective endocarditis due to viridans streptococci, enterococci, and other streptococci. Clin Microbiol Infect 1998; 4:S17–S26 23 Pettersson G, Carbon C. Recommendations for the surgical treatment of endocarditis. Clin Microbiol Infect 1998; 4:S34 – S46 24 Bayer AS, Bolger AF, Taubert KA, et al. Diagnosis and management of infective endocarditis and its complications. Circulation 1998; 98:2936 –2948
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25 Lutwick LI, Vaghjimal A, Connolly MW. Postcardiac surgery infections. Crit Care Clin 1998; 14:221–250 26 Smith PN, Vidaillet HJ, Hayes JJ, et al. Infections with nonthoracotomy implantable cardioverter defibrillators: can these be prevented? Pacing Clin Electrophysiol 1998; 21: 42–55 27 Vilacosta I, Sarria C, San Roman JA, et al. Usefulness of transesophageal echocardiography for diagnosis of infected transvenous permanent pacemakers. Circulation 1994; 89: 2684 –2687 28 San Roman JA, Vilacosta I, Zamorano JL, et al. Transesophageal echocardiography in right-sided endocarditis. J Am Coll Cardiol 1993; 21:1226 –1230 29 Harcombe AA, Newell SA, Ludman PF, et al. Late complications following permanent pacemaker implantation or elective unit replacement. Heart 1998; 80:240 –244 30 Lewis AB, Hayes DL, Holmes DR, et al. Update on infections involving permanent pacemakers: characterization and management. J Thorac Cardiovasc Surg 1985; 89:758 –763 31 Choo MH, Holmers DR, Gersch BJ, et al. Permanent pacemaker infections: characterization and management. Am J Cardiol 1981; 48:559 –564 32 Chua J, Wilkoff B, Lee I, et al. Diagnosis and management of infections involving implantable electrophysiologic cardiac devices. Ann Intern Med 2000; 133:604 – 608 33 Da Costa A, Lelievre H, Kirkorian G, et al. Role of the axillary flora in pacemaker infections: a prospective study. Circulation 1998; 97:1791–1795 34 Chamis AL, Peterson GE, Cabell CH, et al. Staphylococcus aureus bacteremia in patients with permanent pacemakers or implantable cardioverter-defibrillators. Circulation 2001; 104: 1029 –1033 35 Da Costa A, Kirkorian G, Chucherat M, et al. Antibiotic prophylaxis for permanent pacemaker implantation: a metaanalysis. Circulation 1998; 97:1796 –1801 36 Vogt PR, Sagdic K, Lachat M, et al. Surgical management of infected permanent transvenous pacemaker systems: ten year experience. J Card Surg 1996; 11:180 –186 37 Wilkoff BL, Byrd CL, Love CJ, et al. Pacemaker lead extraction with the laser sheath: results of the pacing lead extraction with the excimer sheath (PLEXES) trial. J Am Coll Cardiol 1999; 33:1671–1676
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Background: Cardiac device (CD) endocarditis is an infrequent but potentially lethal infectious complication of permanent pacemakers or implantable cardioverter-defibrillators (ICDs), and mortality rates of 30 to 35% have been reported. Medical treatment has been suggested for the treatment of CD endocarditis, but there is increasing evidence that surgical treatment is to be preferred as the best approach to achieve eradication of the infection and reduce mortality. Objective: To evaluate the following: (1) the clinical and echocardiographic characteristics of patients with pacemaker or ICD endocarditis, (2) the outcome of this population depending on the mode of treatment (medical vs surgical treatment), and (3) the clinical, microbiological, echocardiographic, and therapeutic variables associated with patient outcome. Design: Prospective cohort study. Setting: Tertiary referral center in Barcelona, Spain. Patients: All consecutive patients with infectious endocarditis (IE) admitted to the study institution between 1990 and 2001 were prospectively evaluated by a multidisciplinary treatment team, and a definite diagnosis of CD endocarditis was established when cases met pathologic or clinical criteria according to the Duke criteria. Results: A total of 31 patients, 25 men and 6 women aged 61 ⴞ 15 years (mean ⴞ SD), with pacemaker or ICD endocarditis were identified among 669 consecutive patients (4.6%) with IE. During the study period, a total of 3,768 pacemakers and 460 ICDs were implanted in the study institution. In 22 cases of pacemaker endocarditis, the pacemaker was implanted in our institution, and 9 cases were referred from other institutions (incidences of endocarditis on pacemaker and ICD implanted in our institution of 0.58% and 0.65%, respectively). Medical treatment without removal of the pacing system was initially performed on seven patients; all of them (100%) had relapses of endocarditis, and one patient died. The remaining 24 patients underwent surgical removal of the pacing system; 1 patient had one relapse, 3 patients died after surgical treatment, and the others were successfully cured with no relapses after a mean follow-up of 38 ⴞ 9 months. Clinical, echocardiographic, microbiological, and therapeutic variables were evaluated in association with prognosis. The only prognostic factor for failure of treatment or mortality was the absence of surgical treatment (p < 0.0001). Conclusions: Electrode lead endocarditis occurred in < 1% of pacemaker and ICD implants. Conservative treatment without explantation of all hardware failed in all patients, and surgical treatment during antibiotic therapy was effective in eradication of infection but was associated with a 12.5% mortality. The only patient characteristic associated with treatment failure or death was the absence of surgical removal of all infected hardware. Complete extraction of the pacemaker or ICD should be considered as standard therapy for most patients with CD endocarditis. (CHEST 2003; 124:1451–1459) Key words: defibrillator; electrode lead; infective endocarditis; pacemaker; treatment Abbreviations: CD ⫽ cardiac device; CI ⫽ confidence intereval; CPB ⫽ cardiopulmonary bypass; ICD ⫽ implantable cardioverter-defibrillator; IE ⫽ infective endocarditis; TEE ⫽ transesophageal echocardiography; TTE ⫽ transthoracic echocardiography
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use of cardiac devices (CDs) has T hegrownclinical considerably over the past 2 decades. A
Materials and Methods
1,2
growing list of indications for permanent pacemakers and implantable cardioverter-defibrillators (ICDs) and the increase in the geriatric population mean that more patients undergo pacemaker and ICD surgery; therefore, there is a larger population at risk of infection. CD infective endocarditis (IE) is an infrequent but potentially lethal infectious complication of pacemaker and ICD therapy. Infection of the pacemaker pouch and wire may occur in 1 to 7% of implanted pacing systems,3,4 and mortality rates in CD endocarditis have been reported to be 30 to 35%.5 Risk factors for CD endocarditis include chronic conditions such as diabetes mellitus, malignancies, immunosuppressive therapy, and local factors related to the pacing system such as erosion of the pacemaker pouch, and the number of previously inserted leads, etc.3 Despite advances in diagnostic approaches, treatment of CD endocarditis is still controversial. Medical treatment has been reported to be successful in some cases,6 –12 but there is increasing evidence that the entire pacing system should be removed to achieve complete infection eradication.13–17 However, most studies have been retrospective and have included few patients, and there are no controlled studies comparing medical vs surgical treatment; therefore, we designed a prospective study to identify all consecutive cases of pacemaker and ICD endocarditis over a decade. The purpose of this study is to describe the following: (1) the clinical and echocardiographic characteristics of pacemaker and ICD endocarditis, (2) the outcome of this population depending on the mode of treatment (conservative therapy vs surgical explantation of all hardware during antimicrobial therapy), and (3) the clinical, microbiological, echocardiographic, and therapeutic variables associated with patient outcome. *From the Hospital Clı´nic (Drs. del Rio, Miro´, Mont, Azqueta, and Mestres), Institut d’Investigacions Biome`diques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; Hospital de Sabadell (Dr. Anguera), Barcelona, Spain; and Duke University Medical Center (Dr. Fowler), Durham, NC. †A list of participants is given in the Appendix. This work has been supported in part by the Red Espan˜ola de Investigacı´on en Patologı´a Infecciosa (V-2003-REDC14A-0). Dr. Miro´ was a recipient of a research grant from the Institut d’Investigacions Biome`diques August Pi i Sunyer, Barcelona, Spain. Manuscript received October 18, 2002; revision accepted February 18, 2003. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]). Correspondence to: Jose´ M. Miro´ , MD, PhD, Division of Infectious Diseases, Hospital Clı´nic Universitari, Villarroel, 170, 08036, Barcelona, Spain; e-mail: [email protected] 1452
Study Patients All patients admitted to our tertiary referral center with IE between 1990 and 2001 were prospectively evaluated by a multidisciplinary treatment team. The multidisciplinary team for diagnosis and treatment of IE involves staff members from infectious disease, anatomic pathology, microbiology, and cardiovascular departments (see Appendix). Regular meetings of this treatment team served to include all patients who received a diagnosis at the study institution, and served to be certain that no cases were missed. Data were collected prospectively into an institutional protocol using a designed questionnaire for clinical, microbiological, echocardiographic, therapeutic, and follow-up variables; all data were stored in a database. The study institution is a tertiary referral center for complicated endocarditis, including antiarrhythmic device endocarditis, with a catchment area of 750,000 inhabitants. The study was approved by the ethics committee. Diagnostic Criteria of Endocarditis Pacemaker or ICD endocarditis were defined according to criteria suggested by Duke investigators,18 and only definite cases were included in the study. Because pacemakers and transvenous ICDs are structurally similar, patients with infection involving either of these devices were included in the present report. A definite diagnosis of CD endocarditis was established when cases met pathologic or clinical criteria according to the Duke criteria.18 Early onset endocarditis was defined as infection occurring ⬍ 12 months after implantation, and late-onset endocarditis was defined as infection ⬎ 12 months from implantation. An infected anatomic site was considered to be the source of bacteremia if consistent focal manifestations preceded the diagnosis of bacteremia and the microorganisms were recovered from adequate site specimens. Echocardiographic Definitions Results of two-dimensional transthoracic echocardiography (TTE) [Toshiba SSH-65A; Toshiba Corporation; Tokyo, Japan; and Sonos 1000, 2500, and 5500; Hewlett-Packard; Boston, MA] were routinely evaluated in each patient. Since 1992, transesophageal echocardiography (TEE) using monoplane or multiplane transducers was performed in all cases of suspected antiarrhythmic device endocarditis. Vegetations were defined as circumscribed masses or clumps of echoes that arose from leaflet tips or electrode leads, either as an irregular area of highly reflective leaflet thickening or as more discrete, pedunculated masses in the setting of electrode lead infection confirmed by imaging in more than one echocardiographic plane. Vegetations were measured at the point of maximal thickness in two orthogonal dimensions.19 To identify valvular involvement, clinical, echocardiographic, operative, and autopsy data were used. Microorganisms and Antibiotic Therapy Microorganisms were identified using standard criteria. Antibiotic susceptibility testing was performed by broth microdilution method and interpreted using standard methods.20 All patients received antimicrobial therapy according to the etiologic microorganism and its antimicrobial susceptibility test and the recommended antimicrobial therapy for IE.21,22 Decisions regarding medical and surgical therapy were made by the treating physicians independent of the current descriptive investigation. AntiClinical Investigations
biotics were administered IV for 4 to 6 weeks in all episodes. Treatment of methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci infection included cloxacillin (during 4 to 6 weeks) plus gentamicin (during 5 to 7 days); treatment of methicillin-resistant S aureus and coagulase-negative staphylococci infection included vancomycin plus gentamicin and rifampin. Surgical Treatment Surgical treatment was not randomized, and the decision to remove the pacing system was based on the judgement of the multidisciplinary treatment team. The indication for surgery during the active phase was considered in all cases with definite diagnosis, following standard recommendations.23,24 Percutaneous extraction of the electrodes was achieved by manual traction; when the operator felt a highly fixed electrode in the endocardium, special locking stylets were used. Factors that favored surgical treatment with cardiopulmonary bypass (CPB) were increased vegetation size and the time interval from implantation to diagnosis of definitive endocarditis. Electrode lead extraction under CPB was considered in cases of long-term leads (⬎ 12 months from implantation) or in cases of more than two leads. In cases of large vegetations with possibly higher embolic risk, patients were submitted to surgical removal of the entire pacing or defibrillating system with open-heart surgery and CPB. Temporary transvenous pacemakers were inserted after the operation for pacemaker-dependent patients, and new definitive pacemakers were again implanted approximately 2 weeks after surgery in both dependent and nondependent pacemaker patients. Statistical Analysis To preserve the independence of observations, only the initial episodes of CD endocarditis were included in the study. Data were processed with the BMDP statistical package (BMDP Statistical Software; Los Angeles CA). Clinical manifestations, echocardiographic findings, antimicrobic susceptibility, and mode of treatment for patients with and without adverse outcomes were compared with Student t test for continuous variables and the Fisher exact test for categorical variables. Failure of treatment (clinical relapse of CD endocarditis) and mortality were defined as adverse outcomes. The relation of covariates with failure of treatment or mortality was assessed by univariate analysis, and odd ratios (ORs) were then determined with a simple logistic regression model. ORs and 95% confidence intervals (CIs) were calculated with Stata Statistical Software, Release 6 (Stata Corporation; College Station, TX). Differences were considered significant only when two-sided p values were ⬍ 0.05. The McNemar test was used to compare TTE and TEE in the detection of cardiac vegetations.
Results Demographic Characteristics A total of 31 of 669 consecutive patients (4.6%) with IE (6 women and 25 men, aged 61 ⫾ 15 years [mean ⫾ SD]) with bacteriologically proven CD endocarditis were identified over a decade (Table 1). Infections of permanent cardiac pacemakers were observed in 28 patients (12 single chamber and 16 dual chamber); in 3 patients, infection was on a single-lead ICD. During the study period, a total of www.chestjournal.org
3,768 pacemakers and 460 ICDs were implanted in our institution. In 22 cases of pacemaker endocarditis, the pacemaker was implanted in our institution and 9 cases were referred from other institutions (incidences of endocarditis on pacemakers and ICDs implanted in our institution were 0.58% and 0.65%, respectively). Cultures of the removed wire yielded the causative pathogen in all but one case. All patients had two or more positive blood culture results. Eleven patients (35%; 2 women and 9 men, aged 62 ⫾ 18 years) had early onset infection (mean, 5 months; range, 1 to 10 months) after implantation; 20 patients (65%) had late-onset infection (4 women and 16 men, aged 60 ⫾ 16 years). Late-onset IE developed after a mean 65 months from primary implantation, and 35% had undergone previous surgical manipulation in the pacing system, principally replacement of an exhausted battery generator (17% ⬍ 3 months before endocarditis, 50% between 3 months and 9 months, and 33% ⬎ 1 year before endocarditis). All electrode leads had been transvenously implanted, and 17 patients (55%) had two or more electrodes. The mean number of electrodes was 1.7 per patient. Pocket erythema with pain, skin erosion, cutaneous ulcer, or purulent draining sinus from the pocket generator could be determined as a source of infection in seven patients (23%). Echocardiographic Results TTE recordings were reviewed in all patients, and TEE became available for the last 23 patients (74%). Definitive echocardiographic vegetations were detected in 20 patients (87%) with variable sensitivities for TTE and TEE (Table 2). The mean maximal vegetation size was higher with TTE than with TEE (p ⫽ 0.02). Tricuspid valve vegetations were observed in six patients (26%). No vegetations were detected in left-sided valves in any patient. Vegetations ⬎ 15 mm were observed in 11 patients (35%), and vegetations ⬎ 20 mm were observed in 6 patients (15%). Microbiological Data The most frequently detected causative microorganisms were staphylococci. Coagulase-negative staphylococci were detected in 15 cases (48%) [Staphylococcus epidermidis in 35%, Staphylococcus lugdunensis in 9%, and Staphylococcus hominis in 3%]. S aureus was isolated in nine cases (29%). Other organisms growing on blood or tissue (electrode) cultures and the results of antibiotic susceptibility tests performed in patients with endocarditis caused by staphylococci are shown in Table 3. CHEST / 124 / 4 / OCTOBER, 2003
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Table 1—Clinical Characteristics of Patients* Characteristics
Overall (n ⫽ 31)
Early-Onset Infection (n ⫽ 11)
Late-Onset Infection (n ⫽ 20)
Mean age, yr (range) ⬍ 55 yr 56–69 yr ⬎ 70 yr Male gender Antiarrhythmic device Permanent pacemaker ICD Comorbidities Diabetes mellitus Liver cirrhosis Chronic renal failure Indication for implantation Atrioventricular block Sinus node disease Ventricular tachycardia Other† Source of infection Skin ulcer on the generator pocket Unknown Duration of symptoms, d Mean (range) ⬎ 90, % Clinical presentation Fever Pulmonary septic emboli Tricuspid regurgitant murmur Right-heart failure
61 (31–90) 9 (29) 9 (29) 13 (42) 25 (80)
62 (31–82) 3 (27) 4 (36) 4 (36) 9 (82)
60 (38–90) 6 (30) 5 (25) 9 (45) 16 (80)
28 (90) 3 (10) 14 (45) 8 (26) 3 (10) 3 (10)
10 (91) 1 (9) 4 (36) 3 (27) 1 (9) 1 (9)
18 (90) 2 (10) 10 (50) 5 (25) 2 (10) 2 (10)
18 (58) 6 (20) 3 (10) 4 (13)
7 (64) 2 (18) 1 (9) 2 (18)
11 (55) 4 (20) 2 (10) 2 (10)
7 (23) 24 (77)
1 (9) 10 (91)
6 (30) 14 (70)
64 (2–180) 25
58 (2–145) 20
73 (15–180) 38
31 (100) 9 (29) 6 (20) 2 (7)
11 (100) 2 (18) 2 (18) 1 (9)
20 (100) 7 (35) 4 (20) 1 (5)
*Data are presented as No. (%) unless otherwise indicated. †Hypertrophic obstructive cardiomyopathy (n ⫽ 2), syncope of unknown origin (n ⫽ 1), supraventricular tachycardia (n ⫽ 1).
Antibiotics prior to the diagnosis of CD endocarditis were administered in six patients (19%) before hospital admission. Outcome All patients were treated with IV antibiotics following approved international recommendations and guided by antibiotic susceptibility tests. Table 4 shows the outcome after medical and surgical treatment. Medical treatment without removal of the pacing system was initially performed on seven patients; all of them (100%) had relapses of endocarditis, and one patient died after the third relapse.
Medical treatment was used in these seven patients due to a variety of reasons (patient preference in two cases, associated comorbid conditions in two cases, absence of vegetations on echocardiography in two cases, and infection due to S lugdunensis in one patient). Percutaneous lead extraction involving complete extraction of all hardware was performed after a mean of 1.6 relapses, and was effective in eradication of the infection in the six patients with failed medical treatment. In patients with failed medical treatment, the mean interval from initial diagnosis of CD endocarditis to surgical treatment was 5.1 ⫾ 2.9 months. The remaining 24 patients
Table 2—Comparison of TTE and TEE Results in Patients Who Underwent Both Studies Variables
TTE (n ⫽ 23)
TEE (n ⫽ 23)
OR (95% CI)
p Value
Vegetation location, No. (%) Tricuspid valve Wire Overall Vegetation size, mm* Tricuspid regurgitation, No. (%)
4 (17) 5 (21) 9 (39) 22 ⫾ 8 (7–40) 7 (30)
6 (26) 18 (78) 20 (87) 15 ⫾ 7 (4–29) 14 (60)
1.7 (0.32–10) 12.9 (2.7–71.4) 10.4 (2.0–66.6) Not applicable 3.5 (0.9–14.5)
0.3 0.0003 0.001 0.02 0.07
*Data presented as mean ⫾ SD (range). 1454
Clinical Investigations
Table 3—Microbiology* Etiologic Agents
No. (%)
Staphylococci Coagulase-negative staphylococci S epidermidis S lugdunensis S hominis S aureus Viridans group streptococci Pseudomonas aeruginosa Serratia spp. Oligella urethralis Polymicrobial§
24 (78) 15 (48)† 11 (35) 3 (9) 1 (3) 9 (29)‡ 2 (6) 1 (3) 1 (3) 1 (3) 2 (6)
*Data are presented as No. (%). †Methicillin resistant (n ⫽ 3, 20%). ‡Methicillin resistant (n ⫽ 4, 45%). §Viridans group streptococci plus Acinetobacter calcoaceticus and S epidermidis plus S hominis.
underwent surgical removal of the entire device (in 5 patients [21%] with median sternotomy and CPB, and in 19 patients [79%] with percutaneous external counter traction). The mean interval from diagnosis of CD endocarditis to surgical treatment was 13.8 ⫾ 6.3 days. Three patients (12.5%) died after surgical treatment, one patient had a relapse, and the others were successfully cured with complete eradication of the infection and absence of relapses after a mean follow-up of 38 ⫾ 9 months. One patient treated with percutaneous lead extraction and two patients treated with CPB died after the procedure (due to GI hemorrhage in one patient, laceration of the superior vena cava in one patient, and massive thrombosis of the superior vena cava in another patient, respectively). Overall mortality was 13%. Mortality in patients surgically treated with percutaneous lead extraction or CPB was 5% and 40%, respectively. No demographic, clinical, microbiological, or echocardiographic characteristics significantly distinguished patients with successful outcome from those with failure of treatment or death. Table 5 shows the
factors influencing mortality in the univariate analysis. The only patient characteristic associated with treatment failure or death was the absence of surgical removal of all infected hardware. Although staphylococcal infection was not statistically associated with increased mortality (Table 5), all patients that died had staphylococcal endocarditis (one patient with S aureus, one patient with S lugdunensis, and two patients with S epidermidis). Discussion Infections of implantable antiarrhythmic devices may range from 0.2 to 12% and are considered as serious complications of pacing therapy because of the inherent difficulties in the management of CD endocarditis and the adverse outcome. The incidence of pacemaker- and ICD-related infections has been reported as between 0.5% and 12% in the past; in more recent publications, the incidence is ⬍ 5%.3,25,26 The present investigation found an incidence of endocarditis on pacemakers and ICDs of 0.58% and 0.65%, respectively, which is in the range of reported values.3,4 The Role of Echocardiography TTE may identify lead vegetations, but it has not been established as a major diagnostic criteria for CD endocarditis due to its low sensitivity.15 TEE allows the exploration of the entire pacing system from the superior vena cava to the right ventricle. Our study did not differ from previous publications in which detection of lead vegetations increased from sensitivities of TTE in the range of 22 to 30% to sensitivities of approximately 95% with the use of TEE14,15,17,27; however, TEE appears to be of limited additive value in the detection of tricuspid valve vegetations. We observed no statistical differences between TTE and TEE in the detection of tricuspid valve vegetations (Table 2). Our results confirm previous observations that TEE does not improve the diagnostic accuracy of TTE in the detection of vegetations associated with right-sided endocarditis.28
Table 4 —Failure of Treatment or Mortality (Adverse Outcomes) According to Therapeutic Management* Treatment
Treated Patients
Cures/Relapses
Deaths
Overall Adverse Outcomes
Medical treatment† Surgical treatment in patients with failed medical treatment Surgical treatment as initial therapy Percutaneous lead extraction CPB Global mortality
7 6
0/7 6/0
1 (14) 0 (0)
7 (100) 0 (0)
24 19 5 31
20/1 17/1 3/0
3 (13) 1 (5) 2 (40) 4 (13)
4 (17) 2 (10) 2 (40)
*Data are presented as No. or No. (%). †Three patients had one relapse, two patients had two relapses, two patients had three relapses (one patient died without surgery). www.chestjournal.org
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Table 5—Prognostic Factors of Adverse Outcomes in Endocarditis Associated With Pacemaker or ICDs (Univariate Analysis) Variables
Patients, No. (n ⫽ 31)
Age ⬍ 65 yr Yes No Gender Male Female Single chamber Yes No Underlying disease Yes No Known source of infection Yes No Presence of ⱖ 2 electrodes Yes No Late-onset endocarditis Yes No Previous manipulation in late-onset endocarditis Yes No Tricuspid valve vegetation Yes No Echocardiogram positive Yes No Diagnosis after 1995 Yes No Vegetation ⬎ 10 mm Yes No Pulmonary embolism Yes No Staphylococcal infection Yes No S aureus infection Yes No S epidermidis infection Yes No Death due to staphylococcal infection Yes No Medical treatment alone Yes No
OR (95% CI)
p Value
15 16
6 (40) 5 (31)
1.47 (0.264–8.312) 1
0.611
24 7
9 (38) 2 (29)
1.5 (0.188–18.665) 1
0.664
15 16
3 (20) 8 (50)
0.25 (0.034–1.528) 1
0.081
14 16
4 (29) 7 (44)
0.514 (0.082–2.942) 1
0.389
7 24
3 (43) 8 (33)
1.5 (0.173–11.284) 1
0.643
17 14
8 (47) 3 (21)
4.19 (0.657–31.632) 1
0.076
20 11
7 (35) 4 (36)
0.942 (0.162–6.015) 1
0.939
7 13
2 (29) 5 (38)
0.64 (0.045–6.327) 1
0.658
8 23
2 (25) 9 (39)
0.518 (0.043–3.894) 1
0.472
20 11
8 (40) 3 (27)
1.78 (0.290–13.376) 1
0.478
23 8
7 (30) 4 (50)
0.437 (0.062–3.165) 1
0.319
11 20
4 (36) 7 (35)
1.061 (0.166–6.172) 1
0.939
9 22
4 (44) 7 (32)
2.82 (0.431–17.351) 1
0.177
24 7
10 (42) 1 (14)
4.28 (0.396–216.47) 1
0.182
9 22
3 (33) 8 (36)
0.875 (0.111–5.653) 1
0.872
11 20
4 (36) 7 (35)
1.061 (0.166–6.172) 1
0.939
24 7
4 (17) 0 (0)
Not applicable
0.33
7 24
7 (100) 4 (17)
Not applicable
⬍ 0.0001
Microbiology Positive blood culture results have been found in 80 to 100% of pacemaker-related endocarditis.9,14,27,29 In our study, cultures of the removed wire yielded the causative pathogen in all but one case, and all patients had two or more positive blood 1456
Failure of Treatment or Mortality, No. (%)
culture results. The most frequently detected causative microorganisms were staphylococci (coagulasenegative staphylococci in 48% of cases, and S aureus in 29% of cases). Previous reports5,6,9,14,15,17,30 –32 documented similar microbiologic findings. Early onset infection is associated with infection by S Clinical Investigations
aureus, and the most common portal of entry is the subcutaneous site of implantation of the pacemaker. By contrast, late infections are caused predominantly by coagulase-negative staphylococci, and infection tends to have a more indolent course related to the low virulence of this organism. Staphylococci seem to be particularly capable of adhering to and forming microcolonies on the polyethylene or silicone rubber sheaths covering the electrodes. Infection caused by Gram-negative microorganisms, fungae, anaerobic bacteria, and multiple microorganisms have seldom been reported.6,14,30,31,33 Data33,34 suggest the hypothesis that CD endocarditis is mainly caused by local contamination during the implantation procedure. Hematogenous colonization of the pacemaker conducting system during the course of a bacteremia from a distant focus has rarely been demonstrated since the pacing system is rapidly covered by neoendothelium and fibrous tissue, which prevents the foreign surface from being coated by microorganisms. Hematogeneous seeding of the device from distant sites of infection has been reported, but with the exception of S aureus bacteremia appears to be rare.3,9 In our study, all patients were bacteremic with fever and positive blood culture results. Among the 65% of patients with lateonset endocarditis, no previous manipulation of the pacing system had been performed, and hematogeneous seeding of the device was presumed to be the mode of colonization of the system. In one study34 of 21 patients with S aureus bacteremia occurring a year or more after device placement, 29% acquired a subsequent device infection. By contrast, 35% of the patients from this study had early onset infection, and 35% of patients with late-onset infection had a previous surgical manipulation of the pacing system (replacement of an exhausted battery generator). This fact has clinical implications for the reduction of the incidence of CD endocarditis and reinforces the value of antibiotic prophylaxis during all types of surgical manipulation of the pacing system (including replacement of generators). In a recent metaanalysis by Da Costa et al,35 systemic antibiotic prophylaxis at the time of insertion of permanent pacemakers or replacements showed a consistent protective effect reducing the incidence of pocket infections and pacemaker endocarditis. Treatment of CD Endocarditis Management of CD-related infection is based on a combined approach using both antimicrobial agents with surgical eradication. The results of this investigation demonstrate that patients with CD endocarditis should undergo extraction of the device and leads, followed by a course of IV antibiotics and www.chestjournal.org
device reimplantation at another site during a delayed surgical procedure if indication for pacing or defibrillation persists. Our study found a statistically significant difference in successful outcomes with surgical treatment as opposed to medical treatment. Patients treated medically had a mean of 1.6 relapses per patient until they underwent surgical treatment. Patients treated with surgery were more likely to have absence of recurrences or mortality than medically treated patients (p ⬍ 0.0001). No other demographic, clinical, echocardiographic, or microbiological variables were associated with adverse outcome (Table 5). The most widely recommended approach for generator-pocket infection is removal of the entire pacing system, which achieves the highest rates of cure,31,32 but electrode infections generally require removal of the system. Following implantation of cardiac antiarrhythmic devices, the generator pocket and intravascular lead become encased in dense layers of endotheliazed fibrous tissue, so that infection is complicated by lack of penetration of antimicrobial agents into the avascular matrix, necessitating removal of some or all of the components to eradicate infection. Attempts at a conservative approach, including combined bactericidal antibiotics and local debridement techniques, not only failed to cure CD-related infections, but were also responsible for higher mortality rates.5,6,9,15,16,30,31,34,36 Some authors11,12,16 have advocated a conservative approach consisting of antibiotic therapy with hardware in place or partial device removal. Partial device removal is likely to be sufficient only when infection is limited to the removed component, and it is aimed to avoid invasive surgical procedures in debilitated individuals; however, most large studies6,9,15–17 suggest that complete removal of all parts of an infected device is necessary to achieve a definitive cure in CD endocarditis. Klug et al17 suggested that vegetations ⬎ 10 mm may be removed by percutaneous lead traction without a significant increase in subsequent pulmonary embolic complications; they also suggested that the indication for percutaneous removal should be expanded to include larger vegetation sizes. In our study, percutaneous removal was performed in vegetations up to 23 mm in length without any associated complications, although these have been reported in the literature.17 Removal of the material involves technical difficulties. Removal of the leads or electrodes may not be possible by percutaneous traction, and damage of the myocardium or tearing of the tricuspid valve may result as electrodes become imbedded over time. Extraction of the leads remains difficult and may require an invasive surgical approach, including sternotomy with or without extracorporeal circulation.36 CHEST / 124 / 4 / OCTOBER, 2003
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Timing from pacemaker implantation to diagnosis of endocarditis is another variable that may favor surgical removal of the electrode system with CPB. Within several months of implantation (usually ⬍ 12 months), extraction may be accomplished by simple manual traction; after 12 months from implantation, the use of locking stylets has been proposed be the method of choice.37 Chronic electrode tips are attached to the right ventricular endocardium and are embedded in a dense fibrotic plaque, making electrode removal by direct traction dangerous. In our study, percutaneous traction was carried out in patients with an implantation to diagnosis of endocarditis interval up to 106 months. There were neither deaths nor failures of eradication of the infection among the 12 patients with late-onset endocarditis treated with percutaneous removal of the electrode (mean implantation to diagnosis, 65.5 ⫾ 41 months; range, 21 to 106 months). Five patients in this study underwent surgical removal of the electrode with CPB, with a mean of 99 ⫾ 96 months from implantation to diagnosis of endocarditis (range, 1 to 240 months). Mortality in this subgroup was 40% (two of five patients). The number of implanted electrodes (recent implants or long-term electrodes) is a further fact that may favor surgical treatment with CPB. In this study, two patients with three and four electrodes, respectively, were treated with surgical excision of the pacing system under CPB, with one of two deaths (50%). Direct counter traction was performed in all but three patients with two or fewer electrodes in patients surgically treated. Mortality in this group was only 1 of 22 patients (4.5%). Study Limitations The first limitation of this study is the size of the population studied, its nonrandomized nature, and the low number of patients. Secondly, therapeutic management was based on the judgement of the physicians involved, including the multidisciplinary team for the diagnosis and treatment of endocarditis and varied according to individual patient characteristics. Therefore, comparison of different surgical options is difficult. Conclusions Electrode lead endocarditis occurred in ⬍ 1% of pacemaker and ICD implants. Conservative treatment without explantation of all hardware failed in all patients, and surgical treatment during antibiotic therapy was effective in eradication of infection but was associated with 12.5% mortality. The only patient characteristic associated with treatment failure 1458
or death was the absence of surgical removal of all infected hardware. Complete extraction of the pacemaker or ICD should be considered as standard therapy for most patients with CD endocarditis.
Appendix Members of the Hospital Clinic Endocarditis Study Group of the Hospital Clinic, Institut d’Investigacions Biome`diques August Pi i Sunyer, University of Barcelona, Barcelona, Spain include the following: Miro´ JM, del Rı´o A, de Benito N, Claramonte X, Baraldes MA, Jimenez-Alzate MP, Dı´az ME, Soriano A, Moreno A, Gatell JM (Division of Infectious Diseases); Marco F, Garcı´a de la Marı´a C, Armero Y, Almela M, Jime´ nez de Anta MT (Department of Microbiology); Pare´ JC, Azqueta M, Mestres CA, Sitges M, Mont LL, Ninot S, Cartan˜ a´ R, Pomar JL (Cardiovascular Institute); De Lazzari E (Epidemiology and Biostatistics Unit); and Ramı´rez J, Ribalta T, Pe´ rez N (Department of Anatomical Pathology); and Anguera I, Guma´ JR (Hospital de Sabadell). ACKNOWLEDGMENT: We thank Marı´a Antonia Rodrı´guez Jove´ for technical assistance, and Fundacio´ n Privada Ma´ ximo Soriano Jime´ nez for the grant supporting the Hospital Clı´nic Endocarditis database.
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