Discussion
Device infections represent a relevant clinical problem with a significant proportion of patients affected, accounting for 10% (2020: 1,653) of the 18,000 revision procedures annually performed in Germany (20,21) and 1-2% of interventions worldwide (1). In this regard, international and national expert panels unanimously recommend immediate and complete removal of infected systems (11-15). Unfortunately, however, there is a lack of generally accepted strategies for the timing of subsequent reimplantation (1). For example, the EHRA ”consensus document” (18) also states that there are currently no randomized trials on the appropriate timing of reimplantation. Therefore, the timing and indication of reimplantation should be determined on an individual basis and the indication be re-evaluated before reimplantation. Moreover, reimplantation should be performed no earlier than 72 hours after retrieval and blood culture-based exclusion of persistent infection. In contrast, Baddour et al. recommends reimplantation for proven valvular vegetations not earlier than 14 days after retrieval and confirmation of negative blood cultures (11). However, if patients require continued pacing, placement of a contralateral percutaneous ”sacrificial electrode” or the implantation of an epicardial electrode should be performed at very high risk of reinfection. Nevertheless, in clinical practice, these recommendations are of limited use because a substantial proportion of infected patients require continued pacing therapy or uninterrupted CRT for heart failure support. Moreover, infections after percutaneous generator perforations may occur only locally in the pocket, as was the case in 74% of patients in our SI study group. These patients are usually pre-treated with antibiotics and may show only moderate laboratory signs of inflammation or physical discomfort immediately before the surgical procedures, if any.
In our hospital, the respective treatment strategies were therefore decided in close cooperation of the interdisciplinary device team and the interdisciplinary endocarditis board. Decisions were based on the individual clinical assessment of symptoms, underlying arrhythmias and existing device dependencies, comorbidities, and especially the extent and location of the infection foci. The retrospective analysis of the decisions made revealed group-specific differences that tended to support our decision for one of the three treatment pathways described. For example, we found no pacing-dependent patients in the SR group but the highest number of implanted ICDs (56.2%). This group also had the preoperatively highest NYHA (2.6) and second-highest ASA class (3.3), indicating the clinical relevance of the current severe infection event. Likewise, the EL group had significant comorbidities in a very severe infectious event (NYHA class: 2.5; ASA class: 3.4; hypertensive patients: 82.1%; coronary artery disease: 62.1%; prior PCIs: 39.3%; prior cardiac surgery: 42.9%). Notably, however, it showed the highest pacing dependence (75%) und the lowest LV-EF (39.4%). Furthermore, we found that the highest number of blood cultures (92.9%) was taken here and the highest percentage of microbes (78.6%) was detected. Also, the laboratory results showed the most significant inflammatory parameters (leukocytes 11.2 Ts/µl, CRP 6.3 dl/ml, PCT 3.2 ng/dl) and the most frequent intracardiac vegetations (60.7%). These observations suggested that this was the most severely diseased group in our collective, followed by the SR group. And in our consideration, this also justified ex ante our aggressive and invasive treatment strategies. In contrast, the SI cohort appeared less severely ill, had the lowest NYHA (2.4) and ASA class (3.0) and showed the lowest comorbidities (creatinine: 1.3 mg/dl, diabetes mellitus: 23.3%, prior coronary artery disease: 45.2%, PCIs: 21.9%, cardiac surgery: 24.7%). In addition, the lead dwelling time was significantly shorter (HSM: 3.7 years, ICD: 2.5 years) and in 74% of cases, complaints were limited to the generator pocket. These facts presumably conditioned the blood cultures taken so infrequently and the few positive bacterial detections (24.7%). Thus, we concluded that this was the least severely diseased study group with the best prognosis.
In our study, the infected material was removed in all groups with a class 1/B indication according to the current expert recommendations (12-15). On average, 2.3 to 2.6 leads per patient were completely removed in 93.2% to 96.4%. Interestingly, existing lead vegetations could be removed with the extraction instruments in 94.1% to 100%, which may have had a positive effect on prognosis and treatment duration in our patient population.
Overall, there was only one periprocedural complication (EL group), representing 0.5% of the total cohort. However, a total of 6 deaths (3.2%) occurred during hospitalization. Thus, there were fewer complications and deaths than would have been expected on the basis of the GALLERY registry (total complication: 4.3%; MAE: 2.1%; in-hospital mortality: 3.6%) or the ELECTRa study (total complication: 2.4%-4.1%; MAE: 1.7%) (22,23). However, our study showed a slightly higher in-hospital mortality compared with the ELECTRa registry (ELECTRa: 1.2%-2.5%) (23). We attributed this mainly to significantly higher mortality in the EL group and low case numbers (SR: n=2 / 2.2%; EL: n=3 / 10.7%; SI: n=1 / 1.4%).
These findings raise the question of whether there are other, less invasive treatment options with good prognosis for stimulation-dependent patients. One possibility is the insertion of a temporary transvenous ”sacrificial electrode” or, alternatively, the implantation of a leadless pacemaker (LP). Unfortunately, we could not include these options in our analysis because of the small number of cases. Nevertheless, it remains to report that the concept of the percutaneous ”sacrificial pacemaker electrode” was initially criticized because of the risk of infection and dislocation (12, 18). However, publications reporting good results with this bridging method are now accumulating. Frausing et al. recently published the results of a nationwide Danish analysis on the incidence of infections after over 40,000 CIED implantations in which a temporary percutaneous pacing electrode was inserted for bridging. In the follow-up period of one year, there was no increased rate of all-cause CIED infections (24). Zhou et al. investigated the patient population of pacemaker-dependent CIED infections in the Temporary Pacing using Active Fixation Leads (TPAFL) study (25). In this study, a contralateral temporary stimulating electrode was implanted in 334 patients during removal of an infected CIED system. Afterwards, they received a new permanent system a median of 10 days later. There they observed a total of five adverse events (1.5%) and one infection (0.3%) in the entire cohort. Pecha et al. previously described comparable results in a smaller study in which there were even no reinfections or complications (26). Regarding the implantation of leadless devices, most current publications refer to an approximately 30-day delayed LP implantation after the extraction of an infected CIED system - i.e., non-pacemaker-dependent patients - and report low reinfection rates (27,28). In contrast, simultaneous implantation of an LP during an existing infection has been described only rarely and in small studies or individual case reports. For example, Chang et al. reported on 17 patients who received an LP for continued ventricular pacing during extraction of an infected device. Among these, no re-infection occurred after 143 days (29). Equally hopeful results were provided by case reports such as Wu et al. (30) or Jacobs et al. (31), who also found no reinfections after simultaneous implantation of an LP during extraction procedures. Nevertheless, with these methods it should be kept in mind that the introduction of new materials into the intravascular compartment may promote endocarditic processes by contact infection.
Furthermore, a comparison of our findings with those of the prospective Multicenter Electrophysiologic Device Infection Cohort (MEDIC) study by Boyle et al. (32) in 434 patients seems to be of interest. Of these, 381 underwent extraction treatment and 220 of them (57.7%) received new device systems after a median of 13 days. In comparison, significantly more patients (76.3%) received a new system in our overall collective. Only in the SR subgroup was the figure slightly lower (49.4%). However, Boyle’s study did not focus on the outcome of different treatment strategies but rather on a possible correlation between the timing of device reimplantation after extraction and the frequency of re-infection. Six months after initial extraction procedure, an overall re-infection rate of 11.3% and an overall mortality of 26.4% were observed, which our numbers could not confirm even after one year of follow-up. Comparing similar groups in both studies, his cohort had 23 patients who, like our SI group (n=73), received a new permanent CIED system during the extraction procedure. Six months later, 69.6% of his patients remained free from re-infection. Additionally, there was one re-infection (4.3%) and four patients (17.4%) died. In our study, however, we observed no re-infection after one year and three deaths (4.1%). Comparing our one-year follow-up of the SR group (n=89, reimplantation 26 days after extraction) and our EL group (n=28, reimplantation 62 days after extraction) with Boyle’s ”reimplantation group” (n=42, reimplantation 21 days after extraction), we would have expected a mortality rate of 14.3%, 2.4% of re-infections, and uncomplicated healing in 83.3%. In contrast, we found no re-infections in our study cohort. In addition, our SR group performed significantly better with 100% uncomplicated wound healing and a mortality rate of 3.4% (n=3). However, our EL group had a high mortality rate of 21.4% (n=6) after one year, which we attributed to the proven severe illness and the more invasive treatment with the epicardial lead and secondary system upgrade. Overall, Boyle’s group concluded that the risk of re-infection after complete removal of an infected system is very low regardless of the timing of reimplantation. We can confirm this statement with our retrospective data analysis. In addition, our long-term follow-up with a good detection rate (51.7% to 67.9%) showed that irritation-free wound conditions were found in 94.7% to 100% and properly functioning CIEDs in 95.1% to 100%.
Last but not least, the observations made in our study showed a significant decrease in inflammatory parameters (Figure 1) and improvement in NYHA classes and LV-EF (Figure 2) after one year in all groups, which we attribute to the healing of the infection. However, it was also shown that there was a transient decrease in LV EF in the EL group due to the higher operative trauma of a lateral thoracotomy on the one hand and in the SR group due to the lack of adequate pacing on the other hand. However, these increased again even above baseline levels after implantation of a final system and resolution of the infection. These courses suggest that the clinical decisions made regarding method selection were appropriate.
However, significant delays in patient transfer from 14 to 19.5 days after diagnosis were also evident in our study. This delay could be due to difficulties in diagnosis, blood culture analysis, or organizational issues that cannot always be resolved quickly. On the other hand, the suspicion remains that a repeated attempt at purely conservative treatment was made, which is contrary to international recommendations (12,32). Abandoning this approach could significantly improve outcomes. Upon arrival at the extraction center, the process accelerates, but still there was a delay of 1 to 3 days. This was mostly due to poor quality imaging or missing test results. To avoid these delays, we recommend that referring hospitals provide timely, up-to-date, high-quality test results — because removing infected devices within three days of diagnosis can significantly reduce in-hospital mortality rates (33,34).