Incidence, Management Patterns, and Outcomes of Cardiovascular Implantable Electronic Device-Related Infection – A Retrospective Registry-Based Analysis

Abstract

Introduction: 

Cardiovascular implantable electronic device (CIED) infection contributes to a significant clinical and financial burden. We sought to assess CIED postimplant infection rates and the effect of different treatment modalities on reinfection over a long-term follow-up.

Methods: 

We retrospectively analyzed CIED recipients presenting with complications during 2010–2019 at our center. Data related to the different management modalities used as per the discretion of treating physician, were collected and patients were followed up telephonically.

Results: 

A total of 3394 patients underwent CIED implantation of which 122 (3.5%) patients developing complications were included in the study. Mean age of the patients was 66.4 ± 12.5 years. Single-chamber ventricular pacing (VVI), dual-chamber (DDD) pacing, and biventricular pacing were seen in 68 (56.2%), 51 (41%), and 3 (2.8%) patients, respectively. CIED infection was seen in 61 patients (1.8%). Strategies used for CIED infection management included: new device implantation on contralateral side (n = 34; 55.7%), old device repositioning on same side (n = 14; 22.8%), antibiotic therapy alone (n = 5; 8.5%), resterilized device implantation on contralateral side (n = 3; 4.9%), epicardial lead placement (n = 3; 4.9%), and permanent device removal (n = 2; 3.3%). The CIED reinfection rates for the above strategies were 2.9%, 71.4%, 80%, 100%, 0% and 0%, respectively.

Conclusion: 

Multiple strategies are being used in real-world practice for the management of CIED infection. Previously advocated strategy of reimplanting resterilized CIED is associated with high recurrence rates. The best practice still remains to implant a new device on the contralateral side post extraction of infected hardware.

INTRODUCTION

Cardiovascular implantable electronic device (CIED) infections constitute a major burden for patients and healthcare providers. They are usually associated with significant morbidity, high treatment costs, prolonged hospital stay, frequent outpatient visits, and in a few cases, may even result in mortality.[¹²³] Few large prospective studies have characterized the clinical and microbiological profile of CIED-related infections that has led to the framing of clinical practice guidelines regarding their management. Extraction of infected device components in-toto is now a class I recommendation in all cases of pocket infection and endocarditis, regardless of whether there is definite evidence of device involvement.[⁴]

When considering the same device reimplantation, there is relatively scarce evidence underpinning management strategies. An ideal reimplant strategy should minimize the number of procedures and patient discomfort without raising the risk of reinfection. Based on high relapse rates among patients managed with antimicrobial therapy alone, experts have recommended combined treatment of CIED infections with antimicrobials and complete device removal. However, in real-world clinical practice, the strategy of complete device removal and implantation of new device on opposite side is often delayed and underemployed as opposed to prolonged antimicrobial therapy which was favored in earlier trials of CIED infection.[⁵] Evidence from some studies has even supported the reuse of a previously infected device after meticulous and protocol-directed resterilization and reburial of an infected device into deeper planes on the same or opposite side.[⁵⁶⁷] These practices and considerations are important in developing countries where financial constraints often lead to attempts at reusing the same device.

We, therefore, planned to study based out of our clinical practice pattern which was independently guided by different treating physicians within the department and an outcome analysis was done based on different treatment modalities used over a period of time.

METHODS

This is a single-center, non-randomized, retrospective, registry-based descriptive analysis. We retrospectively reviewed all patients presenting with complications related to CIED implantation at our tertiary care center between 2010 and 2019. The various management strategies executed for CIED-related infections along with documented patient outcome details were obtained from the hospital information system and telephonic follow-up.

Procedural protocol

On presentation, patients were admitted and evaluated on the basis of nature of their CIED related complications. In patients diagnosed with CIED infection, investigations including pus discharge swab cultures, blood cultures, complete blood count, and chest roentgenogram were carried out. Transthoracic echocardiogram and if required, a transesophageal echocardiogram (TOE) was also performed to detect pacemaker lead vegetations. Antibiotic therapy guided by local swab culture results with or without surgical drainage/debridement was instituted in all patients. Further management strategies namely new device implantation on contralateral side, old device repositioned into ipsilateral side, antibiotic therapy alone, old device reimplanted into contralateral side after resterilization, epicardial implantation of new device, and permanent device removal were as per treating physician discretion. The decision to administer medical therapy and/or followed by complete removal and reimplantation of a new device on opposite side was entirely based on treating physician. As a result, the timing of these procedures varied considerably. Lead extraction was carried out only in few of the CIED infection cases (n = 4) in which there was conclusive evidence of infection involving pacemaker leads by TOE or radiolabeled white blood cell positron emission tomography-computed tomography showing increased uptake on CIED leads or in cases of definite lead malfunction with CIED pocket infection

Antimicrobial therapy

Antimicrobial therapy (comprising of Cefepime and Teicoplanin) was initiated empirically and later on modified according to the locally prevalent microbiological profile guided by the blood and pus drug susceptibility cultures. Superficial incisional infections received a 1-week course of antibiotic therapy. Isolated pocket infections without any systemic sepsis received a 2-week course of antibiotic therapy. CIED infections having evidence of systemic involvement in the absence of any vegetations on leads or valve structures received a 4-week course of intravenous antibiotics. In the absence of contraindications, patients with definite or possible CIED-related IE received a 6-week course of intravenous antibiotic therapy adapted to the sensitivity of the isolate. Antibiotic therapy was carefully monitored during hospitalization. Any extracted hardware was sent for microbial cultures, and all patients received antibiotic therapy in accordance with the susceptibility-guided, institutional infection control guidelines. After discharge, when indicated, the treatment was continued under medical surveillance.

Cardiovascular implantable electronic device resterilization and reimplantation technique

Prior to reimplanting CIEDs, indications for implant were carefully reassessed. After extraction and surgical debridement of all the infected CIED hardware, a culture from the infection site was taken and patients were kept on antibiotics for 5–7 days following which device (new or sterilized) was implanted after documenting the eradication of residual infection on serial blood and wound-site cultures. The patients who had pacemaker implantation on the same side had either re-suturing of the wound or re-exploration of the pacemaker pocket followed by the insertion of the pacemaker into deeper planes of subpectoral pocket. The inspection, cleaning, disinfection, packaging, and resterilization of CIED meant to be reimplanted were done in accordance with the American National Standards Institute, Association for the Advancement of Medical Instrumentation, and International Organization for standardization (ANSI/AAMI/ISO) 11135 standards.[⁸]

Definitions

Successful treatment/cure of CIED related infection was defined as completion of prescribed antibiotic course with or without surgical management in the absence of clinical evidence of an infection at discharge as reflected by erythema, warmth, purulence, erosion, tenderness, fever, or positive cultures from the local site. This also entailed fulfillment of pacing and/or defibrillation requirements of the patient by implanting new or old device according to the discretion of treating physician. Any readmission after initial cure, suggestive of CIED related infection will be considered a relapse irrespective of time interval between the two infectious episodes.

Treatment failure of CIED-related infection was defined by the presence of clinical evidence of an infection as reflected by erythema, warmth, purulent discharge, erosion, tenderness, fever, or positive cultures from the local site even after 4 weeks of antibiotic course, surgical debridement, and adoption of above-mentioned CIED infection management strategies resulting in inability to discharge the patient after index hospitalization.

CIED reinfection/relapse was defined as the reappearance of clinical evidence of CIED infection (fever, erythema, tenderness, warmth, and purulence over the implantation site), CIED erosion, with or without positive blood/pus cultures after initial successful cure of CIED infection at discharge from index hospitalization. Reinfection was defined by repeat infection with the same microbe after initial cure of index infection. Relapse was defined by repeat infection with a different microbe after initial cure of index infection.

Statistical analysis

Descriptive statistics were used in this study because of the nonrandomized application of various reimplantation strategies to the study participants. Analyses were performed using SPSS statistical software (IBM SPSS Statistics version 20.0, IBM SPSS, USA). Categorical variables were presented as percentages. Continuous variables are presented as mean ± standard deviation or median with interquartile range.

RESULTS

Of 3394 CIED implants, 2451 were de novo CIED implantations and 943 were pulse generator replacements being performed over a span of 10 years (2010-2019) at our institution [Figure 1].

Figure 1: Flowchart showing patient screening, selection, and categorization according to management strategies

Baseline characteristics

3.6% (n = 122) patients reported either to pacemaker outpatient clinic or were hospitalized with CIED related complications. The mean age of the patients was 66.4 ± 12.5 years. Of all patients with CIED related complications, 77.8% (n = 95; 77.8%) were male. 56.2% (n = 68) CIED implantations were single-chamber pacemaker, 41.0% (n = 51) were dual-chamber pacemaker and 2.8% (n = 3) were cardiac resynchronization therapy (CRT). None of the automated implantable cardioverter-defibrillator (AICD) recipients had CIED-related complication. The incidence of a variety of CIED-related complications observed was as follows:

1. CIED infection (1.8% [n = 61])
2. Lead displacement (0.71% [n = 24])
3. Lead fracture (0.27% [n = 9])
4. Pneumothorax (0.71% [n = 24])
5. Twiddler syndrome, CIED procedure-related pericardial effusion, subclavian vein thrombosis, and pulmonary artery thrombosis in 0.03% (n = 1) patients each.

Outcomes related to different cardiovascular implantable electronic device infection management strategies

Sixty-one patients presented with CIED infections, of which 44 patients had de novo CIED implantation, 16 patients had pulse generator replacement and 1 patient underwent lead replacement. Annualized CIED infection rate was estimated to be 0.18% per year. The mean age of patients was 64.8 ± 14.2 years, with male preponderance (n = 50, 82%). Median time from device implantation to clinical CIED infection presentation was 510 days with an interquartile range of 60-1440 days [Table 1]. In 37 (60.5%) patients, the infected device was explanted while in 19 (31.1%) patients the original device was maintained. Infected CIED device was removed permanently in 2 patients while epicardial implantation of new device was one in 3 patients. Table 2 shows clinical characteristics of patients divided into various groups as per CIED management strategy opted by the treating physician. Table 3 shows the clinical outcomes as infection cure and relapse rates of various management strategies which were as follows:-

Table 1: Baseline clinical characteristics of patients having cardiovascular implantable electronic device infection

Table 2: Clinical characteristics of patients having cardiac implantable electronic device infection classified according to strategy based on endocardial reimplantation of device

Table 3: Cardiac implantable electronic device infection outcomes according to the adopted device management strategy

New device implantation on contralateral side

In 34 (55.7%) patients, a new device was implanted to the opposite side. Pulse generator was removed in all patients and complete removal of leads was done wherever possible, followed by a course of broad-spectrum, culture-guided antibiotics for 7-10 days followed by device implantation to the opposite side. Patients who had complete device-related hardware removal and new device insertion done on the opposite side had the best outcome with CIED infection relapse rate of 2.9% (n = 1).

Old device repositioning on the same side

Fourteen patients had device reinsertion into a deeper plane. Same side reimplantation after removal of infected hardware and medical management of CIED infection was based on operator's discretion especially in cases of mild superficial pocket infections coupled with financial constraints. Blood cultures were withdrawn and swabs were taken for culture from the discharge site following which the patients were initiated broad-spectrum (negative culture) or culture-directed antimicrobials. After the resolution of inflammation and infection, pacemaker insertion into deeper submuscular plane was done with the assistance of cardiothoracic surgeon. In 14 patients in whom the device insertion was done into a deeper plane, 10 patients relapsed within a median duration of 3.7 months. Of these 10 relapsed ones, in 1 patient the infected CIED was explanted, and the patient was discharged without pacemaker reimplant (indications for device reimplant deemed to be unnecessary by the operator), 2 patients had reburial of pacemaker on the same side for a second time (with 1 patient requiring readmission within a month of reburial for which the a new device had to be implanted onto the opposite side), 6 patients had opposite side new device implantation and 1 patient was treated successfully with medical management only.

Antibiotic therapy alone

Five patients were managed conservatively on medical therapy as device manipulation was seemed to be unnecessary by the primary operator. Out of 5 patients receiving medical management only, CIED infection was cured in 1 patient, 1 patient died due to sepsis, and 3 patients had CIED infection relapse which was managed with ipsilateral reburial of the same pacemaker into a deeper pocket in 2 patients (of which 1 patient had repeat relapse after one month which was managed with opposite side implantation) and opposite side implantation of a new pacemaker in 1 patient.

Resterilized device reimplantation on contralateral side

In only 3 (4.9%) patients, the same old device was reimplanted after sterilization. However, in all of them, CIED infection relapsed within 3 months of reimplantation.

DISCUSSION

Although this database was not designed to directly compare reimplantation strategies, this retrospective registry analysis exemplifies certain data sets that can be used to assess outcomes following different management strategies for CIED site infection. The present study features a variety of reimplantation strategies in a heterogeneous patient population presenting with CIED-related infection.

Those patients whose therapy did not include device removal had the worst outcomes in terms of device reinfection rates, rehospitalization rates, need for long-term antibiotic therapy (including intravenous antimicrobial drugs), duration of hospital stay, and financial costs. Only a few (n = 5) of them not undergoing infected CIED extraction remained free of infection at 6 months of follow-up in the absence of chronic antimicrobial suppression therapy. Even then there was a higher recurrence rate in this group of patients in contrast with the other studies.[⁵⁶⁷] There was a 68.4% recurrence or relapse rate in this group versus 2.9% among patients whose treatment included device removal and fresh device implantation to opposite side. The frequency of reinfection in patients who did not undergo device removal is more or less on the expected lines, to be seen in the light of recently updated CIED infection management guidelines[⁹] that recommend for removal of all device components, regardless of the extent of definite CIED infection except in cases of superficial incisional infection where only antibiotic treatment would suffice. Not only were reinfection rates low in patients who had their devices removed, but those rates remained low, regardless of the timing of reimplantation. It is important to note that out of 4 patients which had a CIED infection relapse after hardware removal and reimplantation, 3 patients had reimplantation of old hardware after sterilization. Alarmingly, high re-infection rate noted while implanting re-sterilized device on contralateral side may be superfluous as the number of cases in this category was rather small and it may just be a coincidence. Theoretically, relapse in cases of re-sterilized device on opposite side may be related to improper sterilization technique, residual index infection with systemic sepsis, and breech in procedural sterility. It is conceivable that these patients had have some residual infectious microorganisms or spores retained in the old hardware which could not be destroyed in the due sterilization process which in turn contributed to repeat infection. This is in contrast to a recent propensity-matched cohort, multinational study involving more than 4000 patients which showed no significant difference in device infection or device-related mortality among patients receiving resterilized reused CIED in underserved countries versus those implanted brand-new devices in high-income countries at 2-year follow-up (2.0% vs. 1.2%; P = 0.06).[¹⁰] However, the annualized device infectivity rates (0.2% per year) were similar to that observed in our study (0.18% per year).

Interestingly, only one out of 34 patients who had complete device removal and reimplant to opposite side relapsed. This particular patient, however, had multiple risk factors such as diabetes mellitus, old age, and chronic kidney disease which might have contributed to increased susceptibility to repeat infections. Prior to reimplant, all patients should be thoroughly evaluated to reassess their need for a CIED. Reasons for not reimplanting devices may include improved ejection fraction in case of CRT implant, recovery of sino-atrial node function, and improvement of symptomatic bradycardia. We do not have patient-level data regarding these considerations, but the reimplant rate in this study is similar to that reported in the previous studies.[¹¹] The potential role of emerging therapies in the form of a leadless pacemaker or subcutaneous AICD implantation in the management of CIED infection after infected device removal is yet to be realized and needs further evaluation.

Study limitations

Our study had a few limitations. This was a single-center, nonrandomized study where the choice of CIED infection management strategy was left at the discretion of the treating physician only. Furthermore, information regarding microbiological profile of infections and long-term survival of study patients was not available for interpretation. We could not obtain details regarding the clinical profile of repeat infections and the external validation of resterilization process of infected devices, so we are unable to discern whether they were persistent infection or new infection. In this study, we only identified and analyzed data for the patients who were admitted to us with CIED infection. However, a comparative analysis of infected and noninfected patient's characteristics could have helped in identifying possible factors responsible for increased risk of CIED infection.

CONCLUSION

Our study findings confirm that a broad range of reimplant strategies are prevalent in clinical practice for the management of patients with CIED infections, of which the safest and also the recommended one is reimplantation of a new endocardial device on the contralateral side or epicardial insertion after extraction of previously infected hardware. This, therefore, ensures that the risk of a repeat infection would be really very low, regardless of the timing of reimplantation.

Ethics approval and consent to participate

Written informed consent was obtained from all individual participants included in the study.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Acknowledgment

We would like to acknowledge the contribution of Mr. Mritunjay Mishra, Research Assistant in the department of cardiology, SGPGIMS, for data collection, telephonic follow-ups, and documentation of records.