Discussion
This observational single-centre prospective cohort study with 435 patients undergoing TLE showed a high long-term mortality, also after a complete resolution of CIED infection. With a very long-mortality rate of 34%, this first analysis on the cause of death-data after TLE, supported the notion that the survival continues to be burdened by multiple chronic diseases progression, beyond the clinical resolution of infection.
In the last two decades, numerous reports of single and multi-centres experiences outlined mainly positive short-term results, paving the way for guidelines definition (7). The largest “real-word” prospective registry confirmed both “acute” safety and efficacy of TLE, with a complete clinical success of 96.7% and all cause in-hospital deaths of 1.2% in high volume centres (2). Nonetheless, evidences on long-term mortality after TLE are still scarce, as described by recent studies focused on “CIED infection”-related predictors of long-term outcomes after TLE (8–15).
Our results showed how patients undergoing a successful TLE, especially for an infective cause, remain at high-risk of death at median follow-up of 54 months due to progression of underlying multiple chronic diseases. Conversely, the infective cause is the leading cause of death before discharge. However, it should be noted that, after the initial phase of short- and medium-term follow-up in which mortality may be due to septic relapses or complications such as valvular insufficiencies or heart failure, the mortality of the population could be similar to that of an equivalent group of patients.
Moreover, we observed a relatively short-time interval to death after discharge in elderly subjects, in patients with severe CKD and systolic LV dysfunction.
More in detail, our population is high-risk population with high rates of comorbidities and 92% of patients with evidence of infection as TLE indication: as formerly stated, infective indication itself represents a mortality risk enhancer as showed By Mehta et al. (11). Nonetheless, clear evidence regarding mortality rates for untreated patients supports the indication TLE in case of CIED-related infections (20).
With particular regard to long-term predictors, the postprocedural risk conveyed by age confirms previous findings (12) as also the risk conferred by chronic kidney disease strongly supported by the literature, mainly with regard to short-term follow-up (10,12,15,21).
Conversely, long-term data on systolic LV dysfunction after TLE remained unclear. According to Metha et al (11), our results showed LV systolic dysfunction as an independent long–term predictor of death at multivariate analysis in patients undergoing TLE with CIED infection as indication. Recently, Nishii et al demonstrated that the survival rate after TLE was not significantly different between patients with LVEF ≤ 35% and those with LVEF > 35% at 30 days and 1 year after TLE. Nevertheless, patients with systolic LV dysfunction were more likely to require additional hemodynamic support and temporary cardiac resynchronization therapy pacing  after TLE and brain natriuretic peptide levels as marker of heart failure represented a significant predictor for 1-year mortality (22).
With regard to lead related data, number of extracted leads or dwelling time were not significant predictors of mortality in our cohort, but the impact of leads on long term mortality was more noticeable in the non-infection group of patients undergoing TLE than in CIED infection group (11).
As important limitation of our study focused on tertiary care center dataset, referral bias could have affected the clinical data, thereby limiting the generalization of our results to other populations.
Our findings suggest the urgent need for a risk score including age at explant, CKD and reduced LVEF, in larger populations undergoing TLE to better define not only the risk/benefit analysis of lead extraction and related follow-up by the multidisciplinary team but also the cost-effectiveness of this entire clinical pathway (Figure 4). In particular, risk stratification allows a coherent segmentation that divides patients into groups with relative service needs is a relevant foundation for effective, equitable and sustainable care delivery consistent with a public health perspective. This main clinical implication is strongly reinforced by the analysis of the costs related to the TLE procedure which showed a significant economic impact for the national health service with particular regard for reimplanted patients. A “risk prediction model” should help optimizing clinical management since hospital admission, moving toward personalized, patient-centred medicine. Given the goal of improving outcomes, these assumptions also imply value-based care considerations in a global health perspective and economic sustainability.