Mechanisms of Lead Failure by Recall Status and Manufacturer: Results From the Pacemaker and Implantable Defibrillator Leads Survival Study (“PAIDLESS”)

Abstract: Objectives. The aim of this study was to determine the differences in lead failure mechanisms across the major United States implantable defibrillator lead manufacturers (Boston Scientific, Medtronic, and St. Jude Medical), between all non-recalled and recalled leads, and between two recalled lead families (Medtronic Sprint Fidelis and the St. Jude Medical Riata and Riata ST). Methods. This was a single-center, non-randomized, retrospective study analyzing 3802 patients with 4078 leads who underwent implantable defibrillator lead implantation between February 1, 1996 and December 31, 2011. Lead failure mechanisms were defined as lead fracture, insulation defect, and other. Results. A total of 153 leads (3.8%) failed during the trial period. Failed Medtronic and St. Jude Medical leads presented predominantly as lead fractures (75.8% and 52.8%, respectively). Failed Boston Scientific leads displayed greater variability, although many also failed by fracture (44.4%). The majority of failed non-recalled and recalled leads presented as fractures (50.7% and 82.9%, respectively). The recalled Medtronic Sprint Fidelis and St. Jude Medical Riata/Riata ST leads primarily presented as fractures (89.3% and 65.0%, respectively). Patients whose lead failed via an insulation defect or other mechanism appeared to have a faster time to mortality following lead failure than patients whose lead failed via fracture (P<.01 and P=.02, respectively). Conclusions. Lead fracture is the most common form of lead failure regardless of the failure points previously identified in these leads. Patients who experienced a lead failure as a result of an insulation defect or other mechanism appeared to die faster than patients whose lead failed via fracture.  

Key words: defibrillator lead, product recall, mortality

The Pacemaker and Implantable Defibrillator Leads Survival Study (“PAIDLESS”) was a single-center, retrospective study examining defibrillator lead failure among the major United States manufacturers.¹ In October 2007, the Medtronic Sprint Fidelis leads were recalled by the United States Food and Drug Administration.² In December 2011, the St. Jude Medical Riata and Riata ST leads were also recalled.³ PAIDLESS demonstrated a strong correlation between recalled lead status and patient mortality and lead failure.¹ In addition, PAIDLESS substudies have demonstrated the effects of gender and age on lead failure, the adverse impact of having two recalled leads in any given patient, and the differences in outcomes between high-volume and low-volume operators.^4-6 However, the mechanisms of lead failure have not previously been reported in PAIDLESS, especially as they relate to recalled and non-recalled leads. Consequently, the purpose of this substudy was to test the hypotheses that lead failure mechanisms differ across the three major United States manufacturers, between recalled and non-recalled leads, and between the two recalled lead families (Medtronic Sprint Fidelis and St. Jude Medical Riata/Riata ST).

Methods

PAIDLESS was a retrospective study that was approved by the Winthrop-University Hospital (now NYU Winthrop Hospital) Institutional Review Board in 2013. PAIDLESS analyzed a total of 3802 patients with 4078 defibrillator leads implanted between February 1, 1996 and December 31, 2011 at Winthrop-University Hospital.¹ This specific investigation analyzed the mechanisms of lead failure among manufacturers, non-recalled and recalled lead groups, and the different lead families within each category. Lead failure mechanisms were defined according to the Medtronic System Longevity study, which included lead fracture, insulation breach, lead dislodgment, failure to capture or sense, sudden increase in pacing thresholds, cardiac perforation, extramyocardial stimulation, abnormal impedance levels, and oversensing.^1,7 Information gathered for the PAIDLESS database was obtained from several sources, including Winthrop-University Hospital electronic records and manufacturer-provided lead analysis databases. Patient mortality information was obtained from the Social Security Death Index.⁸ The PAIDLESS database was de-identified in accordance with the Health Insurance Portability and Accountability Act (HIPAA).⁹ The investigators were blinded to patient and operator identifiers during lead failure analysis. Lead evaluations were performed via a combination of fluoroscopic, electrical, and explant analyses. 

A failed lead was classified as a fracture based on an impedance >2000 ohms, noise (with or without inappropriate shocks), and/or operator visual identification of lead fracture. The mechanism of failure was regarded as an insulation defect based on an impedance <400 ohms and/or visual signs of a breach in the insulation of the lead. All remaining lead failure mechanisms were grouped by the investigators into the category “other.”  

For the mortality subanalysis, patients with lead failures were stratified into the fracture, insulation defect, or other failure mechanism categories based on the patients’ most recent lead failure mechanism that was identified before either patient mortality or the end of the trial period. The index date was the implantation date of the replacement lead following lead failure.

Statistical analysis. Continuous variables were presented as mean ± standard deviation and the categorical data as frequency (percentage). Lead failure mechanisms were compared across different manufacturers, recalled lead status, and recalled lead families using Fisher’s exact test. P-values were adjusted for multiple pair-wise comparisons using Bonferroni method (alpha=.017).

Time to death was compared among different strata of lead failure mechanisms. Survival estimates and cumulative event rates were compared by the Kaplan-Meier method using the time to event approach. The log rank test with Sidak adjustment method was used to compare the Kaplan-Meier survival curves and subsequent multiple comparison. A multivariable Cox regression hazard model was developed for time to death using a priori covariates in addition to lead failure mechanisms.

All calculations were performed using SAS 9.4 for Windows (SAS/STAT 13.1; SAS Institute) and results were considered statistically significant when the P-value was <.05 except for Bonferroni adjustment, for which we considered significance when P-value was <.017.

Results

Baseline characteristics of patients who experienced lead failure are summarized in Table 1. Of the 3802 patients analyzed in PAIDLESS, a total of 147 patients (3.9%) experienced lead failure during the trial period. Six of these patients experienced two lead failures during the trial period. 

A comparison of lead failures across the three manufacturers and their respective lead families is shown in Table 2. There were 153 lead failures: 102 fractures (66.6%), 18 insulation defects (11.8%), and 33 other failure mechanisms (21.6%). Of the 153 leads that failed, 76 (49.7%) were recalled leads; 56 were Medtronic Sprint Fidelis leads (73.7% of recalled leads) and 20 were St. Jude Medical Riata/Riata ST leads (26.3% of recalled leads). 

The mechanisms of lead failure with respect to each lead manufacturer, recall status, and recalled lead family are highlighted in Table 3. There were significant differences in lead failure mechanisms observed among the three major United States manufacturers (P=.01). The most common mechanism across all three manufacturers was lead fracture (Boston Scientific, 44.4%; Medtronic, 75.8%; and St. Jude Medical, 52.8%). Bonferroni-corrected (alpha=.017) pair-wise comparisons revealed no significant differences in lead failure mechanisms between Medtronic and St. Jude Medical (P=.03) or between Boston Scientific and St. Jude Medical (P=.44). A significant difference in lead failure mechanisms, however, was observed between Medtronic and Boston Scientific (P=.014). Overall differences in failure mechanisms between non-recalled and recalled leads were also observed to be significant (P<.001). The majority of failed non-recalled and recalled leads presented as fractures (50.7% and 82.9%, respectively); however, the percentages of insulation defects between failed non-recalled and recalled leads were fairly similar (13.0% vs 10.5%, respectively). Differences in lead failure mechanisms between the recalled Medtronic Sprint Fidelis and the St. Jude Medical Riata/Riata ST leads were also found to be statistically significant (P=.04). The majority of failed Sprint Fidelis and Riata/Riata ST leads presented as fractures (89.3% and 65.0%, respectively); meanwhile, 20.0% of failed Riata/Riata ST leads presented as insulation defects as compared to 7.1% of failed Sprint Fidelis leads. 

A mortality subanalysis was performed for the 147 patients included in this study. Sixteen patients whose follow-up data following lead failure were missing were excluded from the subanalysis. Of the 131 patients included in the mortality analysis, a total of 28 patients (21.4%) died after experiencing lead failure (etiology of death unknown). Figure 1 shows the Kaplan-Meier curves comparing patients’ survival times following the replacement of their failed lead based on the mechanism of lead failure (P<.01). The mean patient survival times following lead failure for lead fractures, insulation defects, and other failure mechanisms were 6.2 years (SE=0.32), 3.0 years (SE=0.44), and 3.4 years (SE=0.37), respectively. Pair-wise comparisons revealed that both insulation defects and other failure mechanisms appear to be associated with a faster time to patient mortality than lead fracture (P<.01 and P=.02, respectively). However, there was no significant difference when comparing patient mortality between the insulation defect and other failure mechanism groups (P=.98). Unadjusted Cox proportional hazard regression model revealed mechanisms of lead failure as the significant predictor of mortality (type III P-value=.01; hazard ratios [95% confidence intervals] are 3.6 [1.3-10] and 2.9 [1.3-6.8] for insulation defect and other failure mechanisms, respectively, compared to fracture). A multivariable Cox regression model was developed using an a priori list of predictors previously identified in the original PAIDLESS publication.¹ Adjusted for age, percutaneous coronary interventions, rhythms, insulation coating, and number of coils, the mechanism of lead failure was still a significant predictor of time to death (P=.02). 

Discussion

Comparisons of lead failure mechanisms among the different lead manufacturers have rarely been reported in the literature. In this study, lead fracture was the predominant mechanism of failure regardless of manufacturer. Qualitatively, a higher percentage of lead fractures was identified among Medtronic leads as compared to Boston Scientific and St. Jude Medical leads. The only statistically significant difference in lead failure mechanisms was observed between Medtronic and Boston Scientific. 

Additionally, lead failure mechanisms have not been systematically compared between recalled and non-recalled leads as a whole. A significant difference in lead failure mechanisms was observed between these two groups. Although slightly more than one-half of the non-recalled leads failed via fracture (50.7%), a greater percentage of recalled leads failed via that mechanism (82.9%). This difference is likely tempered by the fact that over three-quarters of the failed recalled leads were Sprint Fidelis leads, and 89.3% of those leads failed via fracture. 

The mechanisms of lead failure among recalled defibrillator leads (Medtronic’s Sprint Fidelis and St. Jude Medical’s Riata/Riata ST) have been studied extensively.^10,12-23 A significant difference in lead failure mechanisms was observed between the two recalled lead families, with a greater fracture rate in the failed Sprint Fidelis leads (89.3%) as compared to the failed Riata/Riata ST leads (65.0%). This is consistent with prior studies in which the conductor of the Sprint Fidelis was identified as its main failure point.^10-18 Failed Riata/Riata ST leads demonstrated a higher rate of insulation defects than failed Sprint Fidelis leads (20.0% vs 7.1%, respectively); however, the majority of Riata/Riata ST leads still failed via fracture. This is in contrast to the available literature, which in general emphasizes insulation defects as the main failure point of the Riata/Riata ST leads.^10,11,19-23   

Failure rates reported for Riata/Riata ST leads are dependent upon the specific lead failure definition and method of surveillance. Studies utilizing methods such as fluoroscopy or x-ray report higher insulation defect rates than those that use electrical abnormalities as an indication of lead failure.¹⁰ Two prospective studies used fluoroscopic and electrical analyses and reported externalized conductor rates of 30% and 57% in failed Riata/Riata ST leads.^21,22 In an electrical analysis of Riata and Riata ST failures conducted by Porterfield et al, only 5% of these leads failed due to insulation defects.²³ Our study noted that 20% of malfunctioning Riata/Riata ST leads failed due to an insulation breach. All of the Riata/Riata ST leads that failed via an insulation breach were identified as an electrical malfunction and not via fluoroscopic evidence of an externalized conductor; yet, the rate of insulation defects observed in Riata/Riata ST leads in this investigation was four times higher than Porterfield et al. 

No studies that examine the impact of lead failure mechanisms on mortality were found in the literature. Our study noted a significantly faster time to patient mortality in the insulation defect and other failure mechanism groups as compared to the lead fracture group. These results must be tempered by the limited power of the subanalysis as well as the unknown cause of death in these patients. The timing of PAIDLESS may also be a factor in this mortality analysis as physicians had more time to closely monitor Sprint Fidelis patients (who were more likely to experience lead fracture) than Riata/Riata ST patients (who were more prone to insulation defects). Further research is warranted to address the impact of lead failure mechanisms on time to patient mortality.

Study limitations. The PAIDLESS trial and follow-up were conducted between 1996 and 2011. St. Jude Medical’s Riata and Riata ST leads were only placed under advisory on November 28, 2011 and classified as recalled on December 21, 2011 (essentially at the completion of our trial surveillance), whereas the Medtronic Sprint Fidelis leads were recalled in October 2007, over 4 years before trial completion.^2,3 There was plenty of time for the physicians to notify and analyze those affected by the Medtronic Sprint Fidelis lead recall, but not those affected by the St. Jude Medical Riata/Riata ST lead recall. Consequently, very few Riata/Riata ST leads were examined during PAIDLESS using fluoroscopy and all of the failures were identified purely based on interrogations and/or reprogrammings. This surveillance timing difference may have had a significant impact on the identification and classification of failed Riata and Riata ST leads. Lastly, the etiology of patient mortality was not collected in PAIDLESS, and therefore, none of the deaths that occurred in PAIDLESS can be purely attributed to lead malfunction. 

Conclusions

This study demonstrated that the most frequent mechanism of lead failure across manufacturers and in both recalled and non-recalled leads is lead fracture. Differences in lead failure mechanisms exist among manufacturers, particularly between Medtronic and Boston Scientific. The failed Sprint Fidelis group had a higher percentage of lead fractures when compared to the failed Riata/Riata ST group (the latter having a greater percentage of insulation defects than the former). Differences in patient mortality were also noted among the three lead failure mechanism categories. Patients who experienced insulation defects or other lead failure mechanisms appear to have a significantly faster time to mortality following lead failure replacement than those with lead fracture. Recalled status notifications and their timing may have played a role in differences identified in this trial. Additional prospective, large, single-center trials are required to confirm the findings of this study.

References

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