Medtronic CRM Product Performance Report

Method for Estimating Lead Performance

Medtronic CRDM has tracked lead survival for over 20 years with its multicenter, global chronic lead studies.

Leads Performance Analysis
Implanted leads operate in the challenging biochemical environment of the human body and the body’s response to foreign objects. Implanted leads are also subject to mechanical stresses associated with heart motion, body motion, and patient anatomy.


In this environment, pacemaker and defibrillation leads cannot be expected to last forever. While IPGs and ICDs have a battery that will deplete after a predictable length of time, a lead’s longevity cannot be predicted, nor are there simple indicators that a lead is approaching the end of its service life. Therefore, regular monitoring while implanted, and evaluation of lead integrity upon IPG or ICD replacement, is necessary to determine if a lead may be approaching the end of its service life.

Returned Product Analysis Shortfalls
All leads and lead segments returned to Medtronic are analyzed to determine whether or not they meet performance limits established by Medtronic. Although returned product analyses are valuable for gaining insight into lead failure mechanisms, this data cannot be used by itself for determining the survival probability of leads because only a small fraction of leads are explanted and returned for analysis. Additionally, those leads that are returned cannot be assumed to be statistically representative of the performance of the total population for a given lead model. Partial or total lead extraction can result in significant damage to a lead, making a definitive analysis of a suspected failure and its cause impossible. Thus, lead survival probabilities are more appropriately determined through a clinical surveillance study. Although returned product analysis results are presented in this report, Medtronic tracks lead survival through its System Longevity Study.

System Longevity Study (SLS)
The SLS is a prospective, multicenter, global study designed to monitor the performance of market-released cardiac therapy products. Medtronic has been monitoring the performance of its cardiac therapy products for 26 years and has evaluated the performance of more than 75,000 leads, with data reported from 14 countries on four continents.

Patients are eligible for enrollment in the study if:

1  They are within 6 months post-implant of a Medtronic market-released lead connected to a market-released CRT, ICD, or IPG device, and the lead is used for a pacing, sensing, or defibrillation application, or

2  They participated in a qualifying study of a market-released Medtronic cardiac therapy product; complete implant and follow-up data are available; and the data is appropriately and legally released for use in the study.

Lead Complications
The SLS complication criteria are defined below. These criteria do not, however, enable a lead integrity or “hardware” failure to be conclusively differentiated from other clinical events such as an undetected lead dislodgement, exit block, or concurrent pulse generator failure manifested as a sensing or capture problem.

A lead-related complication is considered to have occurred if at least one of the following clinical observations is reported and at least one of the following clinical actions is made 30 days or more after the implant.

Clinical Observations

The Standard Actuarial Method is used to determine estimates of lead survival.

Clinical Actions

Note: Successful lead repositioning is not a qualifying action.

Methods
The performance of leads is expressed in terms of lead survival estimates, where “survival” refers to the function of the lead, not the survival of the patient. These survival estimates are intended to illustrate the probability that a lead will survive for a given number of years without a lead-related complication.

The survival estimates are determined from the analysis of the data collected through the SLS. These data are presented graphically and numerically.

The SLS protocol requires regular follow-up reporting on all leads actively followed in the study. Each study center must inform Medtronic whenever a lead complication has occurred or when a patient is no longer participating in the study. Under the study protocol, each lead is assumed to be normally active unless a lead-related complication is confirmed, the lead is abandoned or explanted, or the patient is no longer available for follow-up. The data analyses assume that the patient is still part of the study and there are no lead complications at the time of the report cutoff date unless specifically reported by the center.

Medtronic evaluates center compliance with study protocol through, at a minimum, annual clinical monitoring at each study site. Additionally, study center personnel must be trained in the study procedures prior to participating, and they must adhere to the policies and procedures of their local ethics boards.

Implant times are calculated from the implant date to the earlier of the complication date, out-of-service date (for example, patient leaves the study or the lead is no longer being used), or the cutoff date of the report. If a lead experiences more than one complication, the first is used to calculate survival time; although all complications associated with a lead are reported in PPR tables.

Of the several different statistical methods available for survival analysis, the Standard Actuarial Method, with suspensions assumed distributed across the intervals (Cutler-Ederer Method), is used to determine estimates of lead survival. This method is commonly used by medical researchers and clinicians.

On the following pages, each graph includes a survival curve where events include qualifying lead-related complications. This survival estimate is a good representation of the probability a lead will survive a period of time without a lead-related complication. For example, if a survival probability is 95% after 5 years of service, then the lead has a 5% chance of experiencing a lead-related complication in the first 5 years following implant.

Since the survival estimate can become very imprecise with small effective sample sizes, Medtronic truncates the survival curve when the number of leads entering an interval is less than 50 leads. When the number of leads entering an interval reaches 50, the next data point is added to the survival curve.

Although the report provides tabular data in 1-year intervals, the curves are actually computed and plotted using 3-month intervals.

The data in the tables is rounded to the nearest tenth of one percent. Occasionally, a graph may show 100% survival, but have one or more complications. This occurs because even with the complications, the data rounds to 100%.

The survival curves are statistical estimates. As performance experience accumulates, the estimation improves. Confidence intervals are provided as a way to indicate the degree of certainty of the estimates. Greenwood’s formula is used to calculate corresponding 95% confidence intervals for the standard errors, and the complementary log-log method is used to produce the confidence bounds.

Medtronic urges all physicians to return explanted products and to notify Medtronic when a product is no longer in use, regardless of reason for explant or removal from use.

Sample Size and How the Population and Population Samples Are Defined
The population sample from which the survival estimates are derived is comprised of the patients successfully enrolled in the SLS as of the report cutoff date. The number of enrolled implants is listed for each model.

This sample based on SLS enrollments is considered to be representative of the worldwide population, including data from 14 countries on four continents, and therefore the survival estimates shown in this report should be representative of the performance worldwide of these models.

In general, a model or model family will be included in this report when more than 100 leads have been enrolled and no fewer than 50 leads followed for at least 6 months. Models will remain in the report as long as Medtronic estimates at least 500 leads remain active in the United States, based on estimated US implants.

Returned Product Analysis Results
Every lead or lead portion returned to Medtronic receives an analysis. Although the returned product analysis data is not used to generate the survival estimates, the data provides valuable insight into the causes of lead malfunction.

For reporting returned product analysis results, Medtronic CRDM considers a lead as having malfunctioned whenever the analysis shows that any parameter was outside the performance limits established by Medtronic while implanted and in service. To be considered a malfunction for returned product analysis reporting, the lead must have been returned to Medtronic and analyzed.

Lead malfunctions are divided into three categories: Implant Damage, Electrical, and Other. Typical examples of implant damage are stylet perforation, cut or torn insulation, bent or distorted conductors, over-retracted helixes, and conductor fracture due to over-torquing. An electrical malfunction is defined as a hardware malfunction resulting in a break in the insulation or a break in the conductor that could affect the electrical performance of the lead. A break in the insulation is defined as a breach allowing entry of body fluids or inappropriate current flow between the conductors, or between the conductor and the body. Examples include cuts, tears, depressions, environmental stress cracking (ESC), and metal ion oxidation (MIO). A break in the conductor of a lead is defined as the loss of continuity in the metallic components that could interrupt the current flow or voltage. Examples include fractured conductors and defective crimps.

Leads damaged after explant or damaged due to failure to heed warnings or contraindications in the labeling are not considered device malfunctions.

A lead subject to a safety advisory is not considered to have malfunctioned unless it has been returned to Medtronic CRDM and found, through analysis, to actually have performed outside the performance limits established by Medtronic.

For leads designed for either ventricular or atrial use, the numbers listed in the Returned Product Analysis tables include both.

The numbers of malfunctions listed in the Returned Product Analysis tables are the actual numbers confirmed in the returned product analysis from the United States. The numbers of complications listed in the complications tables are the actual numbers observed in the SLS centers around the world.

Estimated Number of Implanted and Active Leads in the United States
In addition to providing the number of leads enrolled in the SLS, this report also provides the number of leads registered as implanted and the number remaining active based on the status recorded in the Medtronic Device Registration System.

Some lead models do not have a survival curve presented in this report. These lead models do not have a survival curve because they have insufficient sample size in the System Longevity Study. Returned Product Analysis results for these models are included here for reference and comparison.