Medtronic CRM Product Performance Report

Method for Estimating Lead Performance

Medtronic CRDM has tracked lead survival for over 26 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, non-randomized 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 with a multicenter study for 26 years and has evaluated the performance of more than 75,000 leads, with data reported from 14 countries on four continents. All Medtronic market-released leads and all market-released IPG, ICD, and CRT devices are eligible to be included in this study.

The primary purpose of the SLS is to evaluate and publish the long-term reliability and performance of Medtronic market-released cardiac therapy products by analyzing product survival probabilities. Product-related adverse events, indicating the status of the product, are collected to measure survival probabilities. The data gathered in this study may also be used to support the design and development of investigational plans for new cardiac therapy products. The SLS is designed to continue indefinitely, encompassing new products as they become commercially available.

Eligible products for study enrollment include all Medtronic market-released cardiac therapy products. Medtronic may limit overall enrollment of any product when the number of enrollments provides an adequate number to effectively assess product survivability. Medtronic reserves the right to close enrollment of a product at a site level in order to ensure all participating sites have an equal opportunity to enroll.

To ensure a sufficiently large and representative source of data, participating clinical centers must meet specific selection criteria. In addition, centers are selected to be representative of the range of clinical environments in which Medtronic conducts business.

Investigators enroll qualified subjects with specific Medtronic market-released cardiac therapy products and follow these subjects from their implant date until they can no longer be followed (e.g., death and lost to follow-up). Using a Clinical Investigation Plan, each center monitors and reports on the performance of specific Medtronic market-released cardiac therapy products (e.g., product-related adverse events, replacements and abandonments) and subject status (e.g., subject death and subject withdrawal from the study). Subjects will be followed by their respective center in accordance with the center’s established practices for routine follow-up.

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.

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

The SLS protocol requires regular follow-up reporting on all leads actively followed in the study. The follow-up schedule for this study is based on utilizing routine, scheduled office/clinic visits and unscheduled office/clinic visits prompted by symptoms or complaints. Data collected at each follow-up includes routine clinical electrical data, any system modifications, and any lead or generator adverse events.

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, the patient is no longer available for follow-up, or more than 24 months have passed since last follow-up. The data analyses assume that the patient is still part of the study and no lead complications had occurred as of the report cutoff date unless specifically reported by the center.

Medtronic evaluates center compliance with study protocol through 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.

Lead Complications
All adverse events are critically evaluated by a Medtronic technical review committee and the investigator is asked to assess the relationship of the adverse event to the presence or performance of the implanted system, generator and/or lead(s).

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

Clinical Actions

Note: Successful lead repositioning is not a qualifying action.

Data Analysis 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.

Survival times are calculated from the implant date to the earlier of the complication date, out-of-service date (for example, subject leaves the study, the lead is no longer being used, or no data has been reported within a specified time interval), 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 for at least 20 years as long as Medtronic estimates at least 500 leads remain active in the United States, based on estimated US implants.

Medtronic, at its discretion, may stop providing updated performance information on lead models that received original US market-release approval 20 or more years ago. These models may be removed from this report at that time.

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.

NEW! With this issue of the CRDM Product Performance Report, Medtronic is expanding the number of lead analysis reporting categories from three to five. This change is being made to comply with the May 2009 AdvaMed Industry Guidance for Uniform Reporting of Clinical Performance of Cardiac Rhythm Management Pulse Generators and Leads.

The lead reporting categories are:

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.

NEW! US Reports of Acute Lead Observations (Occurring within First Month of Service)

In the first weeks following lead implantation, physiologic responses and lead performance can vary until long-term lead stability is attained. Acute (defined as the first month after implant) lead performance may be subject to a number of factors, including patient-specific anatomy, clinical conditions and/or varying implant conditions/techniques. After a period of time, the implant and the lead performance stabilizes. It is for this reason that the System Longevity Study results, which are intended to measure long-term performance, do not include complications that occur within the first 30 days after implant.

With this issue of the CRDM Product Performance Report, Medtronic is including information about the clinical experience in the first month of service. The source for this information is Medtronic’s complaint handling system database. The information is summarized in tables titled “US Reports of Acute Lead Observations.” To be included in this summary of observations, a lead must first be successfully implanted and registered in Medtronic’s Device and Registrant Tracking system.

Each Event Report received by Medtronic’s complaint handling system is assigned one or more Reason for Report codes based on the information received. The Reason for Report codes have been grouped into Acute Lead Observation categories. The categories used for this product performance report are drawn from the “FDA Guidance for Submission of Research and Marketing Applications for Permanent Pacemaker Leads and for Pacemaker Lead Adapter 510(k) Submissions.” The categories are:

  1. Cardiac Perforation
  2. Conductor Fracture
  3. Lead Dislodgement
  4. Failure to Capture
  5. Oversensing
  6. Failure to Sense
  7. Insulation Breach
  8. Impedance Abnormal
  9. Extracardiac Stimulation
  10. Unspecified

Although multiple observations are possible for any given lead, only one observation is reported per lead. The observation reported is the observation highest on the list. For example, if an Event Report includes observations for both Lead Dislodgement and Failure to Sense, Lead Dislodgement is reported.

The lead event reported to Medtronic may or may not have involved clinical action or product returned to Medtronic. The lead may have remained implanted and in service.

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 and Registration Tracking 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.