Micra TPS Performance Analysis

Transcatheter pacing systems (TPS) combine the pacing functions of an IPG with the therapy delivery functions of an implantable lead into a single device implanted inside the heart. Therefore, TPS is subject to complications similar to pacing leads (e.g. cardiac perforation) and malfunctions or battery depletion events similar to an implanted pulse generator (IPG). Although both transvenous systems and Micra IPG experience similar system level major complications, Micra has been shown to reduce the likelihood of major complications at a system level in post-approval registry data.

The performance report information is determined from the analysis of Medtronic Cardiac Rhythm Management (CRM) United States registration, complaint and CareLink™ network data. A TPS model or model family will be included in this report when it has accumulated at least 10,000 implant months and will remain in the report as long as at least 500 devices remain active in the CareLink™ population.

Shortfalls of using returned products to Estimate Micra TPS Performance

Micra TPS devices 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 failure mechanisms, this data cannot be used by itself for determining the survival probability because only a small fraction of Micra devices are explanted and returned to Medtronic for analysis. Some devices are programmed off due to an adverse event, however, they are often not retrieved/ explanted. The devices that are retrieved and returned cannot be assumed to be statistically representative of the performance of the total population for a given model. For this same reason, devices that meet their expected longevity are also not expected to be returned to Medtronic CRM.

The CareLink™ Network

To account for the shortfalls of returned product analysis, a study of de-identified product data on the Medtronic CareLink™ network is used. The number of devices enrolled and transmitting actively enables a population large enough to give a representative volume of normal battery depletions and to provide insight into the complications that may occur after the device was successfully implanted. As the intent of the product performance report is to provide visibility to long-term device performance, the devices reviewed from the CareLink™ Network have been implanted for at least 30 days.

Categorization of Micra TPS Qualifying Complications or Malfunctions for Survival Analysis on CareLink™

For survival estimation, complication and premature battery depletion data from Medtronic’s Complaint Handling System is adjudicated and subsequently cross-referenced with an assessment of device performance from the Medtronic CareLink™ network to categorize if the device is 1) functioning normally, 2) has reached normal battery depletion, or 3) has experienced a qualifying malfunction or complication. This categorization is combined with the CareLink™ data for the total number of implants and implant durations to create survival estimates for the likelihood of experiencing a qualifying complication or malfunction, and normal battery depletion. Ultimately, the data is summarized in two survival curves, one with only qualifying complications or malfunctions and the other including normal battery depletion.

Definition of Qualifying Complication or Malfunction

A longevity analysis is completed for all de-identified devices followed on CareLink™ that have reached the Recommended Replacement Time (RRT), to identify devices that experienced possible early battery depletion. These are findings where the actual reported implant time is less than 80% of the expected longevity calculated using the available device diagnostic information.

Additionally, all reported Micra TPS complaints are adjudicated by subject matter experts and medical safety personnel for inclusion as a product performance event given available information. These product performance events are then cross-referenced with the CareLink™ population for inclusion in the survival analysis.

Product Performance events include, but are not limited to, these that occur 30 days after the implant procedure:

• Premature Battery Depletion
• Cardiac Perforation
• Dislodgement
• Failure to Capture
• Elevated Pacing Threshold

Normal Battery Depletion

A longevity analysis is completed for all devices followed on CareLink™ that are at or within 6 months of RRT to identify devices were taken out of service due to normal battery depletion. The population that is within six months of RRT is assessed against the expected longevity of the product. Normal Battery Depletion is defined as the condition when the device has reached its elective replacement indicator(s) with implant time exceeding 80% of the expected longevity calculated using the available device diagnostic information.

Medtronic CRM establishes expected longevity by statistically characterizing the power consumed by the device and the power available from the device battery. This characterization is applied to a number of parameter configurations. The statistical mean value minus three standard deviations is used as the expected longevity for determining if a battery depleted normally. The actual longevity achieved for any device while implanted will depend on the actual programmed parameters and patient factors and may differ significantly from these estimates.

Statistical and Data Analysis Methods

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

Active surveillance normally begins at the time of implant and continues until a product performance or censoring event occurs. Of the several different statistical methods available for survival analysis, PPR survival analysis is estimated using the Standard Actuarial Method, with suspensions assumed distributed evenly within the intervals (Cutler-Ederer Method), and incorporated data from these retrospectively enrolled devices. Thus, in some cases sample sizes may fluctuate from one time interval to the next interval.

The survival estimates is the probability that a device is free of a product performance event or normal battery depletion at a given time point. For example, if a survival probability is 95% after 5 years of service, then the device has a 5% chance of experiencing a related complication or battery depletion 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 effective sample size is less than 100 devices. The survival charts in the Product Performance Report show the effective sample size for each year interval where we have experience. When the effective sample size reaches 100, the next data point is added to the survival curve.

Because the de-identified information pulled from the CareLink™ network allows for assessment of all devices that were taken out of service there are no adjustments done for underreporting of malfunctions or battery depletion.

Definition of Analysis Dataset

To be included in the US survival analysis dataset, the product must have been successfully implanted and on the CareLink™ network for at least 30 days.

US Reports of Acute Observations

In the first weeks following implantation, physiologic responses and performance can vary until long-term stability is attained. Acute 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 performance stabilizes. It is for this reason that the CareLink™ analysis, which is intended to measure long-term performance, do not include complications that occur within the first 30 days after implant.

Acute performance information, defined as the first month after implant, but not including the day of the implant procedure, is included in our reporting. The source of this information is the Medtronic complaint handling system database that includes events reported to Medtronic. This information is summarized in tables titled "Acute Observations".

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 Observation categories. The categories are:

• Cardiac Perforation
• Dislodgement
• Failure to Capture
• Failure to Sense
• Elevated Pacing Threshold

Although multiple observations are possible for any given Micra, only one observation is reported per device. The observation reported is the observation highest on the list. For example, if an Event Report includes observations for both Cardiac Perforation and Elevated Pacing Thresholds, Cardiac Perforation is reported.

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

US Reports of the Day of Implant Observations

Due to the procedural differences with Micra products compared to transvenous leads and IPGs, information about the clinical experience on the day of implant is included in our reporting. The source of this information is the Medtronic complaint handling system database that includes events reported to Medtronic which may be related to either the Micra device or the delivery system. The information is summarized in tables titled "Day of Implant Observations."

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 Day of Implant Observation categories. The categories are:

• Cardiac Perforation
• Dislodgement
• Failure to Capture
• Failure to Sense
• Elevated Pacing Threshold

Although multiple observations are possible for any given Micra, only one observation is reported per device. The observation reported is the observation highest on the list. For example, if an Event Report includes observations for both Cardiac Perforation and Elevated Pacing Thresholds, Cardiac Perforation is reported.

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