Suspected pacemaker or defibrillator transvenous lead infection

Prospective assessment of a TEE-guided therapeutic strategy

Eric Dumonta, Christophe Camusb, Frédéric Victora, Christian de Placea, Dominique Pavina, Christine Alonsoa, Philippe Maboa and J.Claude Dauberta,*

a Département de Cardiologie & Maladies Vasculaires, Centre Cardio-Pneumologique, Hôpital Pontchaillou-CHU 35033, Rennes Cedex, France
b Service de Réanimation Médicale et Maladies Infectieuses, Hôpital Pontchaillou-CHU 35033, Rennes Cedex, France

* Correspondence to: Prof. J. Claude Daubert, Département de Cardiologie & Maladies Vasculaires, Centre Cardio-Pneumologique, Hôpital Pontchaillou-CHU 35033, Rennes Cedex, France. Tel: +33 2 99 28 25 25; Fax: +33 2 99 28 25 10
E-mail address: jean-claude.daubert{at}chu-rennes.fr

Received 16 December 2002; revised 7 July 2003; accepted 23 July 2003

Abstract

Aims The aim of this prospective study was to assess the clinical value of a management strategy principally based on the results of multiplane transoesophageal echocardiography (TEE) in patients with suspected lead infection.

Methods and results Seventy-seven consecutive patients were included. Based on Duke's modified criteria, PTLI was considered as definite in 54 patients (70%) and possible in 23 patients (30%). Nineteen patients with a diagnosis of possible infection, as defined by bacteraemia without abnormal TEE images and without evidence of pacemaker pocket infection, were treated by antibiotics alone. In all other cases, the pacing material was totally removed. During a mean follow-up time of 3.1±2.5 years, 21 patients (27%) died, mostly from cardiovascular causes. Only one patient died from infection and there was only one case of delayed infection recurrence in an other localization. No significant differences in outcome were observed between explanted and non-explanted patients.

Conclusions The results observed confirm that early and total explantation of pacing material has to be done in patients with bacteraemia and abnormal images at TEE. But conversely conservation of the pacing system can be proposed to patients with bacteraemia but without abnormal images at TEE provided prolonged antibiotic treatment is given.

Key Words: Pacemaker lead infection • Transoesophageal echocardiography • Bacteraemia

1. Introduction

Infection of a chronically implanted intracardiac lead (cardiac pacemaker or defibrillator) is a rare occurrence but is associated with poor prognosis when diagnosis and treatment initiation are belated. Its incidence has been variably assessed in literature, ranging from 0.13 to 19.9%.1,2In fact, the incidence has probably been overestimated in most previous reports because of often atypical clinical pattern and related diagnostic problems. Diagnosis is based by priority on blood cultures which are usually positive, and on multiplane transoesophageal echocardiography (TEE), which for some years has proven to be a significant diagnostic progress. But the absence of strict diagnostic criteria remains a major problem.

The few literature reports3–5available call for prolonged antibiotic therapy over several weeks and early explantation of the equipment in its entirety when lead infection has been established. Is such an approach justified? Should explantation be systematic, even when diagnosis is uncertain? To clarify this question we prospectively assessed a management strategy essentially based on TEE data from 1992 to 2000.

2. Methods

The diagnosis of lead infection was initially suspected from clinical findings,6then a classification as ‘definite’ or ‘possible’ infection was mostly based on TEE results.

The therapeutic strategy consisted of total explantation of the material in case of neostructures seen on TEE and/or in case of pacemaker pocket infection regardless of the TEE results. In case of bacteraemia without neostructures being seen on the TEE and without suspicion of pacemaker pocket infection, a conservative attitude was recommended (no material explantation), associated with prolonged antibiotic therapy.

2.1. Inclusion criteria
This cohort study involved all patients with suspected pacemaker or defibrillator lead infection admitted between 1 January 1992 and 1 June 2000 to the cardiology department, the infectious disease department and the intensive care units of a regional university and teaching hospital. The patients selected presented with at least two of the following criteria: clinical signs of pocket infection (local abscess, pain, loss of normal mobility under the skin, infection of the subcutaneous part of the lead, extrusion of the material), clinical (fever, chills, septic shock) and/or biological infection syndrome (hyperleukocytosis >12 000/mm3, CRP >10mg/l) potentially related to the pacing system, documented bacteraemia or fungaemia, and the presence of abnormal neostructure(s) seen on TEE.

Each patient's demographic and clinical characteristics were analysed from their hospitalization records. The indication for device implantation and the number of leads implanted were documented.

Other characteristics were reported: the suspected infection entry site, the period between the last intervention on the pacing system and the onset of infection, so as to distinguish between early (<2 months) and late (>2 months) infections.

Microbiological data included the number of positive blood cultures, the result of lead culture whenever explantation had been performed, and in some patients, culture of a specimen collected from the pacemaker pocket. Blood cultures were carried out before any antibiotic therapy except in patients who had already been given antibiotic treatment before admission and in whom a microorganism had already been identified.

2.2. Echocardiographic study
Each patient underwent transthoracic (TTE) (2.5Mhz lead) and transoesophageal (TEE) (SONOS 2500–5000, Agilent-Philips, USA) echocardiography with multiplane transducers (5MHz). Echographic views from several angles were systematically performed with multiplane TEE to best visualize the course of the lead(s) inside the right cardiac cavities, from the upper vena cava lumen to the right ventricular apex. The leads were scrutinized all along their course as well as valve leaflets, tricuspid and pulmonary in particular. The relationship between the leads and the valvular leaflets were described. Valvular endocarditis was defined by the existence of valvular mutilation or vegetation or both or by the discovery of a peri-annular abscess. The neostructures noted on the pacemaker leads were located, numbered and measured. Vegetations appeared on echocardiography as a local thickening of the lead or adherent mass, either sessile or pedicular, of variable size, rarely obstructive. Their relationship with the tricuspid valve was analysed. The strands were defined as 1 to 2mm wide and several centimetres long fine, mobile, dense structures attached to the leads.7

2.3. Patient classification
Patients were classified as presenting with ‘definite’ or ‘possible’ lead infection according to Duke's modified criteria.3,6Lead infection was qualified as ‘definite’: when typical microorganisms were demonstrated from lead culture or vegetation histological examination showing active endocarditis, or when a combination of two major ‘clinical’ criteria (positive blood cultures with typical infective endocarditis microorganisms, abnormal neostructures seen by TEE) or a combination of one major and three minor criteria (see section "inclusion criteria") were met.

The infection was qualified as ‘possible’ if the diagnosis was neither definite nor ruled out.

2.4. Therapeutic management
2.4.1. Material extraction
Our team's attitude towards material extraction has not changed since 1992 and throughout the study period. Total explantation was performed whenever TEE revealed neostructures on the lead(s), the tricuspid valve or both and/or in the presence of pocket infection, regardless of the TEE results. Material extraction was performed either percutaneously as a first intent, using specific instruments developed by C. Byrd8(Cook Pacemaker Corporation), or surgically with or without extracorporeal circulation (ECC). That therapeutic option was proposed following the failure of percutaneous explantation or as a first intent in case of very large size and highly mobile vegetations seen on TEE, or when simultaneous valve surgery was indicated.

2.4.2. Antibiotic treatment
The strategy did not include specific guidelines for antimicrobial therapy. General principles for the treatment of endocarditis were applied and advice from an infectious diseases specialist was required in all cases.

2.5. Follow-up
After the baseline infectious episode, patients’ clinical follow-up consisted in periodically sending questionnaires to the patients’ physicians (general practitioner and cardiologist). Questions focused on the existence of an infectious relapse, its clinical form, the date and cause of death if patients were no longer alive, and such were the main assessment criteria.

2.6. Statistical analysis
Data were statistically processed with EXCEL (7.0 version) and SPSS (9.0 version) software. Comparison of categorical variables was made with either the Chi-square test or Fisher's exact test when there were fewer than five subjects in the theoretical sample. Quantitative variables were expressed as means±standard deviation.

Comparisons were made with Student's t-test or Mann–Whitney's test when variables were not normally distributed. Survival curves were determined by Kaplan–Meier's method and compared using the log rank test. The significance threshold was set as P<0.05.

3. Results

3.1. Patients
Eleven patients fulfilled only one selection criteria and were not included in the study. Nine had only local signs at the site of the generator and two had isolated neostructures on a lead. None of them met the criteria for infection related to a transvenous electrode.

Finally seventy-seven patients were included in the study (Fig. 1). Seventy-four patients had a pacemaker and three had a defibrillator. Thirteen patients were fitted with one lead, 48 with two, 12 with three and four patients had four leads. The first implantation was done in our hospital in 40 patients, indicating a global 1% incidence of suspected lead infection during the study period. The other 37 patients were referred from other hospitals for management of their suspectedlead-infection.



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Fig. 1 Management strategy in patients with suspected pacemaker or defibrillator transvenous lead infection. Legends: PTLI: pacemaker transvenous lead infection; TEE: transoeophageal echocardiography. *One patient refused TEE. Her device was explanted and lead culture was positive. **Lead culture not done in two patients.

 
Fifty-four patients were finally classified as having definite lead infection and 23 possible lead infection. (Fig. 1). Lead infection was deemed as definite (n=54): i) if positive blood cultures were associated with positive TEE, irrespective of the result of lead culture (n=44), ii) if lead culture was positive for a significant pathogen in the patients who had positive TEE but negative blood cultures (n=7) or in those who had evidence of pocket infection associated with positive blood cultures but negative TEE (n=2) or when TEE was not done (n=1).

Lead infection was deemed as possible (n=23): I) if blood cultures were negative whereas TEE revealed abnormal neostructures (n=3)-ii) if blood cultures were positive, TEE was normal and no firm alternate diagnosis was established (n=20).

The patient population included 27 women (35.1%) and 50 men (64.9%), whose mean age at diagnosis was 68.8±15.5 years (range: 21–90 years). Four patients were diabetic. The main indication for permanent cardiac pacing was the existence of atrio-ventricular conduction disorders (n=43, 56%). The origin of the infection was most often unknown (66.2% of cases). Among the causes identified, the pacemaker pocket and the skin were the most frequent starting sites (15.6% and 7.8%, respectively), whereas other entry sites were less frequent: catheter (n=2), pneumonia (n=2), digestive tract (n=1), surgical sites (n=1) and dental infection (n=1). The mean time interval between the last intervention on the pacing system and the first signs of infection was 2.9±2.6 years. Thirteen patients (16.9%) presented with early infection (<2 months between the last intervention and the first signs of infection): median=6 days; range 1–60 days. Septic emboli were recognized in seven patients.

3.2. Bacteriological data
3.2.1. Blood cultures
They were positive in 67 patients. The number of positive cultures varied greatly between patients but so did the total number of samples. The median number of positive blood cultures per patient was 3 (range 0 to 10). There was no difference between definite and possible infections (P=0.42).

3.2.2. Lead culture
Of the 58 patients who were explanted, lead culture results were available for 56. Sixty-seven of the 106 leads available for culture were positive. The localization of culture-positive leads was atrial in seven patients, ventricular in 16, both atrial and ventricular in 17 and not defined in five. Nine patients had a single-chamber ventricular pacemaker, 33 had a dual chamber pacemaker, one patient had a biventricular pacing system and two had a defibrillator. Culture was negative in 11 patients (20%) and positive in 45 (80%). The proportion of positive lead cultures in case of association of TEE neostructures with positive blood cultures was 83%.

3.2.3. Pocket specimen culture
Culture of specimens collected from the pacemaker pocket was positive in 11 of the 12 patients who presented with such a pocket infection (same species and same antibiogram as in the lead culture) (Fig. 1). No pocket specimen was collected in one patient in whom infection was clinically evident.

3.2.4. Microorganism responsible
The microorganism responsible was isolated from blood cultures, or from the lead culture when blood cultures were negative. A single microorganism was found in 70 patients (Fig. 2), and two microorganisms, including a Staphylococcus, were found in four patients, exclusively from lead cultures (n=3) or blood cultures (n=1). No microorganism was found in three patients. A microorganism was isolated both in blood culture and in lead culture in 38 explanted patients; in all cases the species and antibiogram were the same. The proportion of infections due to a Staphylococcus species was similar in those classified as definite (78%) and in those classified as possible (65%, P=0.28). We observed a greater proportion of S. aureus infections in those occurring up to 2 months after the last operation on the pacing system than in those occurring later (69% vs23%, P=0.002).



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Fig. 2 Typical images of large vegetations attached to the ventricular pacing lead in its atrial part, visualized by both transthoracic (left panel/apical 4-chamber view) and transoesophageal (right panel) echocardiography. In this particular case, TEE principally served to analyse the precise relationships between vegetations and the tricuspid valve, and to show the absence of any tricuspid valve involvement. Legends: L=lead; T=tricupid valve; RA=right atrium; RV=right ventricle; LA=left atrium; AO=aorta.

 
3.3. Echocardiographic data
Transthoracic echocardiography documented neostructures in the right atrium in only 15 patients (19.5%) and no abnormal images in the other 62 patients.

Transoesophageal echocardiography was considered as normal in 22 patients (29%). Fifty-four patients (71%) presented with abnormal images of neostructures on the lead (s) and/or the tricuspid valve, suspected of being infectious. Forty-seven patients (87% of TEE showing abnormal images) exhibited neostructures on the leads only. Three patients (5%) exhibited neostructures on the lead(s) associated with one or several tricuspid vegetations. One of them presented with major tricuspid regurgitation. At the first examination one patient presented with a ventricular on-lead vegetation which preceded the discovery of pulmonary endocarditis with extensive valve mutilation and major pulmonary regurgitation. Three patients (5%) exhibited isolated vegetations on the tricuspid valve without any abnormal lead images.

A typical vegetation aspect was found in 49/54 patients (91%) (Fig. 3). A so-called ‘atypical’ aspect was found in three patients (6%) in the form of a microfilament structure (Fig. 4). Microfilament and vegetations were associated in one patient. In another case, a sheathing aspect surrounding the intra-atrial part of the leads was associated with vegetations.



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Fig. 3 Transoesophageal echocardiography images of long and thinly pediculated vegetation with large ovalar distal extremity, attached to the atrial pacing lead and visualized in the upper part of the righ atrium. Legends: L=lead; RA=right atrium.

 


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Fig. 4 Transoesophageal echocardiography image of ‘strand’ or microfilament (length=20mm; diameter=3mm) attached to the ventricular pacing lead in its atrial course, with normal tricuspid valve. Legends: L=lead; RA=right atrium; RV=right ventricule.

 
Thirty patients (55%) exhibited a single abnormal image and 24 (4%) exhibited multiple abnormal images. Maximal length was under 5mm in four patients (8%), between 5 and 10mm in ten (18%), between 10 and 20mm in 28 patients (52%) and equal to or greater than 20mm in 12 patients (22%). In the 51 patients with on-lead neostructures, abnormal images were visible at different sites: the superior vena cava/right atrium junction in two patients (4%), the coronary sinus ostium in one patient (2%), the atrial portion of the leads in 31 patients (60%), the atrioventricular position in eight patients (16%) and the right ventricular portion of the lead in seven (14%). Several localizations were noted in two patients, in the form of an atrial microfilament and ventricular vegetation in one and atrial and ventricular vegetations in the other.

Of the five patients with ‘atypical’ images, two of the three who displayed an aspect of isolated microfilaments had positive blood and lead cultures that identified a Staphylococcus species. No germ was found in the third one.

3.4. Therapeutic management
3.4.1. Device extraction
Pacemaker leads were explanted according to the proposed strategy in 58 cases (75%): 39 percutaneousexplantations as a first intent (67% of explantations) and 19 (33%) surgical explantations following either total or partial failure of percutaneous extraction (n=13), or because of the large size of the vegetations, possibly associated to high mobility on TEE, indicating a risk of pulmonary embolism (n=4), or due to the concomitance of valvular surgery (n=2). Those patients did not experience any noticeable peri- or post-operativecomplication.

3.4.2. Antibiotic treatment
Antibiotics were administered in all patients but one. Treatment was initiated before material explantation in 82% of cases. Otherwise, it was initiated on the same day as explantation. It was adapted to the susceptibility of the responsible microorganism. There were 53 cases of methicillin-susceptible Staphylococcus infection (87% of all Staphylococcus infections). Treatment included penicillin M in 38 cases (72%), penicillin G in five cases (9%) and the other ten cases were treated with various other anti-staphylococcal drugs. There were eight cases of methicillin-resistant Staphylococcus infection (13% of all Staphylococcus infections): treatment included a glycopeptide in all cases. Thirteen patients (17%) were given monotherapy (ß-lactams, glycopeptides) whereas 63 (83%) were given a combination of various antibiotics. The mean overall duration of the treatment course was 44.7±28.1 days (range: 0–180). The mean duration of post-explantation treatment was 29.1±20 days (range: 0–132). In 8 patients who were explanted and early reimplanted, post-explantation antibiotic treatment duration was short (14 days, mean duration 8.2±5.4 days). These patients had favourable clinical and biological outcome.

3.4.3. Reimplantation
Pacemaker reimplantation was performed in 37 patients (64%) wether by the epicardial or the transvenous approach. The mean latency phase was 67.8±14.8 days (range: 0–78.1 days). Pacing was epicardial in 14 cases (38% of reimplanted patients) and intracardiac in 23 cases (62%). Epicardial reimplantations were performed at the same time as surgical explantation in all cases.

3.5. Follow-up
At the time of analysis (1 June 2001), data were available for all patients. The mean follow-up duration was 3.1 years, median 2.4, range 0.1–9.8, IQR (interquartile range) 1.1–4.5, IQ (interquartile) 3.4. 21 patients died during follow-up (27%). The estimated survival rate at 1 year was 90.4% (Fig. 5). The mean follow-up duration of the surviving patients was 3.4 years, median 3.1, range 0.2–9.8, IQR 1.4–4.8, IQ 3.4. Only one patient died of septic shock secondary to persistent candidaemia despite a 2-month course of amphotericin B therapy, and 20 patients died from non-infectious cause, including 13 from cardiovascular causes (heart failure: 77% of cases). The age of the deceased patients was 76.3±9.7 years. Fifty-six patients were still alive at the end of follow-up; 55 patients never went into infectious relapse. A single patient presented with recurrence on a hip prosthesis due to the same microorganism (Staphylococcus aureus) 6 months after the lead infection episode, and despite total explantation of the pacing material. This patient secondarily died of a non-infectious cause. One of the non-reimplanted patients died suddenly as a probable result of paroxysmal atrio-ventricular block. Of the eight patients who received short-duration antibiotic treatment following explantation, three died of non-infectious cause without experiencing any relapse.



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Fig. 5 Actuarial survival curve (Kaplan–Meier) in the overall population (n=77).

 
Survival was not significantly different, whether patients had a single or a dual chamber pacemaker (log rank: P=0.67), and whether they had one, two or three or more implanted leads (log rank: P=0.26).

3.6. Comparative outcome of explanted and non-explanted patients
We compared the baseline characteristics and the long-term outcome of explanted and non-explanted patients (Fig. 6), although these two populations differed in numbers. Non explanted patients were significantly older (75.6±10.1 vs 66.6±16.4, P=0.026) but there was no significant difference regarding sex ratio, time of onset of pacemaker lead infection, the proportion of early infections, the proportion of infections without identified entry site, the number of positive blood cultures, the responsible microorganism or the overall duration of treatment (Fig. 5). Similarly, there was no statistically significant crude difference between survival curves (logrank P=0.40, Fig. 6). We did not compare the clinical, microbiological characteristics or the long-term outcome of patients who presented with possible or definite lead infection. Indeed, 93% of explanted patients presented with definite infection and all non-explanted patients presented with possible infection. Such a comparison was almost equivalent to that of explanted vs non-explanted patients.



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Fig. 6 Comparative actuarial survival curves (Kaplan–Meier) in explanted (n=58) and non-explanted (n=19) patients. After adjustment for age by the median value (72 years), survival distributions were not significantly different (log rank P=0.56).

 
4. Discussion

This 77-patient cohort study, based on a restrictive diagnostic definition of definite or possible lead infection, constitutes one of the largest series of pacemaker transvenous lead infections currently reported and provides valuable information for the management of this complication.

4.1. Clinical expression
Two major forms of pacemaker lead infection can be identified from the results of this study. The most frequent one (84.4%) corresponds to pacing lead colonization, either proven or suspected, in the presence of late-occurring bacteraemia following implantation, from an identified (18.2%) or more often unknown (66.2%) infection site. The other form occurs secondarily to pacemaker pocket infection (15.6%). That is consistent with Chamis's paper9involving 33 subjects who exhibited Staphylococcus aureus bacteraemia. Of the 15 patients where pacemaker infection was confirmed, nine (60%) presented with hematogenic diffusion from an infection site that was either remote from the pacemaker pocket, or unidentified.

Both studies on that point contradict what had classically been accepted in literature. To many authors, the entry site most often identified as the origin of infection was the pacemaker pocket.3,4,8Lead colonization following bacteraemia was not often recognized, estimated as 14% only in Kugener's and Bryan's11,12series. The presence of a fibrous sheath insulating the lead from the blood flow and thus hampering hematogenic contamination, has been evoked as an explanation.

4.2. Patient classification
Several diagnostic criteria have been proposed in literature, to classify patients with suspected pacemaker lead infection as accurately as possible. The earliest classification was Arber's,12which now appears obsolete because it did not integrate TEE data to ascertain diagnosis. We have shown in this study that when TEE and blood cultures were positive, lead cultures were positive in 83% of cases, hence the interest of echocardiographic investigation to confirm lead infection diagnosis.

More recently, Klug5and Chamis7proposed two new classifications. One of them, initially designed to evaluate infectious endocarditis, is an adaptation of Duke's criteria for pacemaker lead infections.4It may be logically criticized with regard to the clinical and microbiological characteristics of pacemaker lead infections. Klug's study does not clearly define an attitude in patients with a so-called possible lead infection according to Duke's modified classification, especially in subjects with bacteraemia and no echocardiographic abnormality. The main shortcoming of these classifications is that they do not accurately identify those patients in whom explantation is necessary. Chamis et al.7discussed a therapeutic approach, as part of their study on pacemaker patients with Staphylococcus aureus bacteraemia: because of the high prevalence of confirmed lead infection in that population (75% in case of early bacteraemia and 71.5% in case of late bacteraemia), total removal of all pacing material was recommended when no clear source of bacteraemia could be identified, even in the absence of local infection or echocardiographic abnormalities. These recommandations differ from our own approach where the pacing material would have been left in place even if the bacteraemia source was unknown, whichever microorganism was responsible.

One of the main difficulties involves subjects with bacteraemia without clinical or echographic signs of lead infection. Those subjects are the matter of heated debate in literature: to Chamis,7those patients would not have lead infection and would be classified as rejected whereas to Klug they would have been classified as possible lead infection.

4.3. Value of echocardiography
In this study, neostructures were seen on leads by TTE in 19.5% of patients, a proportion very close to that described in earlier studies, between 22 and 30%.10,13All authors there underlined the difficulties they had with locating the intra-atrial images in relation to the lead on the one hand, and to the tricuspid valve on the other.

We visualized on-lead neostructures in 51 of the 76 patients (67%) who underwent TEE. Our study elicited a lower sensitivity of TEE than in other literature series5,13although it must still be overrated because the echocardiographic criterion was required to ascertain lead infection diagnosis. Comparative performances of TTE and TEE have been assessed by different groups.5,10,13–15Vilacosta et al.13were the first to confirm the superiority of TEE used in a single-plane technology in 10 patients with suspected lead infection. More recently the generalization of multiplane technology has significantly improved exploration quality.16In our series, on-lead vegetations were localized in the atrial part in most cases. This was consistent with literature reports. There are two possible explanations: first, the greater number of leads in the atrium than in the ventricle, and secondly, low velocities that may promote infectious agent development.

As a rule, if voluminous vegetation images do not constitute a diagnostic difficulty, such is not the case with other aspects where discriminating between infectious lesions, thrombosis or fibrin deposits is not easy. In our study, three patients isolatedly exhibited atypical echographic images in the form of microfilaments. Their exact significance is still a matter of debate. Systematically performing TEE in a group of chronically implanted patients without any sign of infection elicited images of that type in high proportions, up to 29% in Victor's series.13Their specificity therefore was very poor. It is worth noting however that in our series, two of the three patients with isolated microfilament images had definite lead infection, as proven by positive lead cultures. Prospective studies are therefore necessary to assess the actual sensitivity and specificity of those images. In literature, Klug5did not describe any microfilament structure but reported a sheath-like aspect surrounding the leads, most often in combination with one or several vegetations. We believe that sheath aspect around leads constitutes an atypical image. On the other hand, it takes significant value only when associated with other images like vegetations. In Klug's classification, that aspect is considered as a minor clinical criteri

4.4. Therapeutic approach
Several studies have suggested rapid and total removal of the whole pacing material as soon as the diagnosis has been established. Choo's and Harjula's retrospectiveseries8,17focused on the infections related to the pacing system. Most patients presented with marked local signs of infection. Bacteremic infections were rare (20% of septicaemia cases in Choo's study, 11% in Harjula's). Isolated antibiotic treatment8and partial explantation of the material17ended up in failure. Only total and swift explantation of the pacing material resulted in total recovery. That was confirmed in Camus's study18of patients with pacemaker pocket infection. Studies involving a relatively large number of subjects with bacteraemia but without evidence of pocket infection1819were not able to determine whether it was necessary to remove the pacing material in its entirety. It is worth reminding that early studies did not include TEE performance and that the proportion of local pocket infection was clearly higher than that of bacteremic infections. In Chamis's series,7explantation was only performed in patients in whom infection was considered as confirmed by clinical and microbiological data. In patients with bacteraemia and no clinical abnormalities, the diagnosis was rejected and the intracardiac material was left in place. But the high mortality rate (47.6% at 12 weeks) in non-explanted patients led the authors to recommending systematic and total explantation of the material in case of Staphylococcus aureus bacteraemia with or without clear device involvement. Our results do not support this approach. In our experience, when pacing material is left in place in case of positive blood cultures and normal TEE and in the absence of infectious signs localized in the pocket, we observed no relapse or death for any infectious cause. No major difference was found, except age and the presence of vegetations by TEE, between explanted and non-explanted subjects. A non-significant trend to shorter survival was observed in non-explanted patients, but this could be related to more advanced age. These results demonstrate that it is probably unnecessary to remove the pacing leads in patients with bacteraemia who present neither vegetation images in the right heart nor any infection of the pacemaker pocket.

In contrast, if diagnosis is certain, the approach taken with explanted patients appears to be safe. Total material removal appears to have been beneficial as a single patient died of infection and another one had infectious relapse much later. Percutaneous explantation was a safe and effective technique, applicable even for large vegetations. Only 38% of patients with one or several vegetations whose maximum size exceeded 10mm required surgical explantation.

Contrary to the group of explanted patients who presented morphological arguments in favour of lead infection, either in its proximal part in case of pocket infection or in the distal part in case of detectable vegetations, the diagnosis of lead infection remains questionable in non-explanted patients. Nevertheless, the similarities noted between the two groups with regard to the time of onset, the absence of entry site in 2/3 of cases and the predominance of methicillin-sensitive Staphylococcus epidermidis or aureus, argue in favour of a ‘possible’ infection despite the absence of vegetations detected by TEE and the absence of pocket infection signs. A few cases of definite lead infection with normal TEE have been reported,5,10possibly related to ‘normalization’ in the event of septic embolic events. We also know that atypical images may be difficult to evidence with TEE. The relatively high frequency of that situation has to be underlined (25% of all suspected infections).

In most cases antibiotic treatment was started after blood cultures because positive. However empirical therapy should include antistaphylococcal drugs. There is currently no consensus on the overall duration of antibiotic treatment or its duration after explantation. If vegetations are strictly localized on the leads without affecting the valves, post-duration explantation treatment (<14 days) could be sufficient, because we did not record any relapse or death from infection in the eight patients who were managed as described. In non-explanted patients, a prolonged antimicrobial therapy18would be more suitable, although prospective assessment would be necessary. In contrast, in Chamis's study7antibiotic treatment duration in non-explanted patients was shorter than in explanted patients (15 days vs 35 days). That could partly explain the high mortality and the existence of recurrent bacteraemia in non-explanted patients (Table 1).


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Table 1 Responsible microorganism according to the diagnosis and time of onset of infection

 
4.5. Long-term outcome
In our study, 27% of patients died, mostly from non-infectious cause (95% of deaths) after a mean follow-up duration of 3.1±2.5 years. Comparing our study with those of Klug5and Cacoub10revealed identical overall mortality but our mean follow-up duration was much longer. The actual 12-month mortality rate in our study was 6% and 17% at 20 months. Only one patient died of septic shock whereas the above-cited studies reported three deaths associated with sepsis and two non-fatal septic shocks, respectively. The main mortality causes were cardiovascular, heart failure being number one (43%).

5. Conclusion

This cohort study involving 77 patients with definite or possible lead infection, is one of the largest series reported so far. At the end of follow-up, 56 patients were alive, 21 died. Only one female patient went into infectious relapse and one patient died of persistent infection. This would support the therapeutic approach we proposed. Subjects who present with neostructures at TEE and/or pacemaker pocket infection should be explanted as soon as possible. In subjects with a first documented episode of bacteraemia and no TEE neostructures, the pacing material could be left in place provided that adapted and prolonged antibiotic treatment is given. Recurrence of bacteraemia in TEE-negative patients was not observed in the present study. In that case, removal of the pacing material could be safer, especially if no septic localization has been identified.

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