The MagnaSafe-2 Registry: Assessing the Risks of Magnetic Resonance Imaging in Three Patient Groups

1\. INTRODUCTION 1.1 Specific aims The specific aims of the MagnaSafe-2 registry are to document the risks of magnetic resonance imaging (MRI) at a scanner strength of 3-tesla for patients with a non-MRI-conditional (NMRC) pacing system, to document the risks of MRI at 1.5-tesla for patients with an abandoned lead, epicardial lead, fractured lead or subcutaneous array, and to document the risks of MRI at 1.5-tesla or 3-tesla for patients with a "mixed-vendor" or "mixed-component" Cardiovascular Implantable Electronic Devices (CIED) system. A "mixed-vendor" system is defined as a combination of leads and a generator, both labeled for use in the MRI environment but from different manufacturers, and as a result, considered NMRC. A "mixed-component" system is defined as leads and a generator from the same manufacturer but not labelled as MRC as a combined device.

The study is a prospective multicenter registry of patients undergoing clinically indicated MRI. We anticipate that the results of the MagnaSafe-2 registry will support a change in MRI access for the three patient groups that are not addressed in the current HRS Expert Consensus Statement on MRI in Patients with CIED (2017), and are not covered by the updated Centers for Medicare and Medicaid Services (CMS) National Coverage Determination (CAG-000399R-4; April 2018).

1.2 Background and Significance Overall, 3 million people in the United States have a cardiac pacemaker or an implanted defibrillator, with approximately 600,000 being implanted each year. While CIED placement has increased, MRI has also become the imaging modality of choice for the evaluation of an increasing number of diseases of the brain, spinal cord, heart, and musculoskeletal system. Previous investigators have estimated that after placement of a pacemaker or a defibrillator, a patient will have a 50-75% chance of requiring a clinically indicated MRI study.

MRI was once believed to pose a risk for patients with a CIED, including a pacemaker, an implantable cardioverter defibrillator (ICD), or a cardiac resynchronization device. Most safety concerns regarding MRI were focused upon the potential of radiofrequency (RF) induced thermal injury at the interface of a cardiac lead and the distal myocardial implantation site in the right atrium, right ventricle, or coronary sinus. As a result of these safety concerns, it was long recommended that patients with a CIED should not undergo MRI scanning, even when MR was determined to be the most appropriate imaging modality for a specific clinical problem or anatomic location. To provide optimal care to the increasing number of patients with a CIED, health care professionals must have the capability to perform an MRI with full knowledge of the possible risks of the examination and have appropriate access to imaging for CIED patients.

1.3 MRI in Patients with Cardiac Devices Over the past two decades, CIED generator-plus-lead systems have been developed by many manufacturers to limit the potential risks associated with MRI. Device-plus-lead systems with a low or acceptable theoretical risk to the patient when used under specific conditions are labeled MRC by the US Food and Drug Administration (FDA) Center for Devices and Radiological Health in response to a manufacturer's request, accompanied by corroborating safety data. In February 2011, the first MRC pacemaker and lead system (Medtronic Revo MRI SureScan with 5086 leads) was approved by the FDA for scanning at an MR field strength of 1.5-tesla. Since that time, more than 50 pacemakers and defibrillator systems have received MRC labelling by the FDA Center for Devices and Radiological Health for use in the MR environment, and guideline documents have been published by several cardiovascular and radiological professional societies worldwide to address care for CIED patients.

In 2017, two landmark studies addressing the risks of MRI for patients with NMRC pacemakers or defibrillators were published. In the MagnaSafe Registry, MRI was performed in 1000 cases in which patients had a pacemaker and in 500 cases in which patients had an ICD. This study did not identify any deaths, lead failures, losses of capture, or ventricular arrhythmias during an MRI. One ICD generator could not be interrogated after MRI and required immediate replacement; the device had not been appropriately programmed per protocol before the MRI. Six cases of self-terminating atrial fibrillation or flutter and six cases of partial electrical reset were noted, most with an established history of arrhythmia. Changes in lead impedance, pacing threshold, battery voltage, and P-wave and R-wave amplitude exceeded pre-specified thresholds in a small number of cases. Multiple MRI scans were not associated with an increase in adverse clinical events.

Nazarian and colleagues found that in 1509 patients with a CIED, no long-term clinically significant adverse events were reported after MRI. In nine MRI examinations (0.4%), the patient's device reset to a backup mode. The reset was transient in eight of the nine examinations. In one case, a pacemaker with less than 1 month left of battery life reset to ventricular inhibited pacing and could not be reprogrammed; the device was subsequently replaced. The most common notable change in device parameters (\>50% change from baseline) immediately after MRI was a decrease in P-wave amplitude, which occurred in 1% of the patients. At long-term follow-up (results available for 63% of the patients), the most common notable changes from baseline were decreases in P-wave amplitude (in 4% of the patients), increases in atrial capture threshold (4%), increases in right ventricular capture threshold (4%), and increases in left ventricular capture threshold (3%). The observed changes in lead settings were not clinically significant.

In 2017, an expert consensus statement was published by the Heart Rhythm Society (HRS). The objective of this document was to provide "practical recommendations in appropriate detail for health care providers of various backgrounds for the management of patients with a CIED so that they could undergo imaging and treatments in a manner that balanced benefit and risk." This HRS consensus statement addressed the use of MRI for patients with an implanted MRC or NMRC pacemaker or defibrillator.

Inspired by the new HRS guidelines, the data from two large clinical registries, and the findings from several smaller studies, a formal request was made to CMS to revise the existing NCD regarding MRI for Medicare/CMS beneficiaries with a NMRC cardiac pacemaker or defibrillator, and to remove the "Coverage with Evidence Development" (CED) requirement. In response, the CMS Coverage and Analysis Group proposed that any MRI examination for patients with an implanted cardiac device that did not have FDA labeling specific for use in an MRI environment (or NMRC) would be covered only if the MRI field strength was less than or equal to 1.5-tesla, if it has been 6 weeks or more since device and lead implantation or any lead revision, if the patient was not pacing dependent, and if no fractured, epicardial, or abandoned leads were present.

After the submission of a subsequent rebuttal letter by an expert group in response to the proposed NCD changes, the CMS Coverage and Analysis group released a subsequent and final decision memorandum in April 2018. In that memorandum (CAG-00399R4), the covered MRI field strength for NMRC systems was changed to 1.5-tesla only, and the exclusion for both a minimum time from device and lead implantation to the time of MR scanning was dropped, as well as the exclusion for pacing-dependent patients. However, the exclusion for fractured, epicardial, and abandoned leads remained. In the NCD memorandum, the CMS group stated that there was insufficient data to comment on the safety of MRI with abandoned leads and that they would "continue to monitor peer-reviewed medical literature for further evidence development and can reconsider this exclusion when sufficient evidence emerges which allows for the reassessment of the benefits and harms." 1.4 Preliminary data

1.4.1 Imaging at 3.0-tesla: Recent studies have suggested that MRI at a field strength of 3.0-tesla may be performed with minimal or no risk if patients are appropriately screened before the scan, monitored during the scan, and if the device is reprogrammed pre-scan and post-scan according to established imaging protocols. Previously, five studies have reported the results of MRI at a field strength of 3-tesla in patients with a CIED not labelled for use at that field strength. A total of 362 MRI scans at a field strength of 3.0-tesla have been performed in 328 patients, with most scans focused upon imaging of the brain and spine. No study has reported a serious adverse event related to exposure to MRI at 3.0-tesla.

1. Naehle et al. performed 51 MRI scans of the brain at a field strength of 3-tesla in 44 patients and did not find an increase in post-scan troponin levels measured to identify myocardial thermal injury due to lead tip heating. In addition, no serious adverse cardiac events were reported. This study identified no clinically significant device setting changes, no new arrhythmias, or other adverse clinical events. The authors concluded that MRI access should not be withheld from patients with an NMRC CIED and with a clinical need for a 3.0-tesla MRI scanning. 2. Gimbel studied 14 patients who underwent 16 MRI scans at a field strength of 3.0-tesla. There were no restrictions for pacing-dependence or the anatomic region scanned. A programming strategy using a no-pacing mode in patients who were not pacing dependent, and asynchronous pacing at the highest output was used in pacing-dependent patients. Device interrogation was performed before the MRI, immediately after the MRI, and at 1-3 months after the MRI. For non-pacing-dependent patients, attempts were made to turn all device features off. In pacemaker-dependent patients, the device was programmed to asynchronous mode at the highest output for the duration of the scan to render the device resistant to exposure to MRI. The specific absorption rate (SAR) was limited to 2W/kg. In this study, no arrhythmias were noted, and no significant changes were noted in the device settings, pacing thresholds, sensing, or lead impedance.

1.4.2 MRI for patients with abandoned, fractured, and epicardial leads A recent review by Meier et al. summarized safety data for patients with a CIED and with an abandoned or epicardial lead who underwent clinically indicated MRI. The authors identified 21 publications reporting data from 656 patients with 854 abandoned and/or epicardial leads who underwent 929 MRI scans of various regions of the body and found no major adverse cardiac events. Two studies in this review measured troponin levels and did not identify a significant change in post-MRI-scan troponin levels. Studies on patients with fractured leads have also been conducted by Greenhill et al., who reported the results of 126 MRI scans at a field strength of 1.5-tesla in 80 patients, with 67 patients having abandoned leads and 13 having lead fragments. In this study, no adverse clinical events were reported.

Higgins et al performed a single-center retrospective study to examine the outcomes of patients who had a pacemaker or a defibrillator generator removed before MRI, thus rendering the pacing leads abandoned. Pacing threshold settings after generator reimplantation were later assessed, as well as clinical patient outcomes. A total of 19 patients underwent MRI after pacemaker generator removal with retained pacing leads. There was a mean of 1.63 abandoned leads at the time of imaging, and none of the leads were MRC. Most of the scans performed were of the central nervous system, including the brain and spine. There were no adverse events within 7 days of the MRI scan in any of the patients with an abandoned lead after dev

• Arrythmia [Time frame: Periprocedural]
• Changes to pacemaker [Time frame: Periprocedural]
• Heart function [Time frame: Periprocedural]
• Heart function [Time frame: Periprocedural]
• Changes to pacemaker [Time frame: Periprocedural]
• Changes to pacemaker [Time frame: Periprocedural]