Status
Conditions
Treatments
About
SUMMARY OF THE CLINICAL PROTOCOL Background: The risks of Magnetic Resonance Imaging (MRI) at 1.5-tesla for patients with a non-MRI-conditional (NMRC) pacemaker have been documented, guidelines for clinical practice have been published by the Heart Rhythm Society, and the Medicare National Coverage Determination (NCD) has been modified to provide coverage for these patients (CAG-00399R4). However, for patients with an abandoned, epicardial, or fractured cardiac lead or subcutaneous array, with a "mixed-vendor" or same-vendor "mixed-component" CIED, or those undergoing MRI at 3.0-tesla with a device not labelled as MRI-conditional (MRC) for use at 3-tesla, the risks of MRI have not been determined.
Hypothesis: For patients with an MRC or NMRC pacemaker or defibrillator and specific indications or circumstances not presently addressed, the risks of MRI do not increase.
Purpose: The MagnaSafe-2 Registry is designed to determine the risks of MRI in patients with limited MRI access not previously addressed in peer-reviewed literature and to improve access for approximately 70% of whom are predicted to have a future clinical need for MRI.
Study Design: A prospective registry of patients undergoing clinically indicated MRI. The protocol is being developed in collaboration with the FDA's Center for Devices and Radiological Health, and an Investigational Device Exemption is being requested for event reporting and monitoring. Also, "Coverage with Evidence Development (CED)" has been requested from CMS.
Enrollment: Eligible patients are 18 years or older and have a MRC or NMRC pacemaker system from any manufacturer, (after 2001), with leads from any manufacturer (without date restriction), and if the ordering physician has determined that MRI is clinically indicated, the imaging method of choice, and NOT performed for the purpose of research. Exclusions are a leadless pacemaker, a device battery at "elective replacement indicator," or renal insufficiency (GFR <45 cc/min). All participants will be required to provide informed consent for the collection of data.
Methods: Patients will be enrolled in the registry at up to 30 clinical centers with: (1) an NMRC pacing system scheduled for MRI at a magnet field strength of 3-tesla, (2) an NMRC system due to a "mixed-vendor" or a same vendor "mixed-component" platform at 1.5-tesla or 3-tesla, or (3) an MRC or NMRC pacing system and an abandoned, epicardial, or fractured lead at 1.5-tesla.
Primary Endpoints: A new cardiac arrhythmia noted during the MRI scan, or a Troponin-T elevation (>upper limit of normal) at 18-24 hours post-MRI scan compared to baseline (obtained within 30 days before the MRI scan), Troponin-T levels pre-MRI. Secondary Endpoints: Death, generator or lead failure requiring immediate replacement, loss of pacing capture (pacing-dependent patients), partial or full generator-electrical reset, pacing lead threshold increase of ≥1.0 V, a P-wave amplitude decrease of ≥50%, an R-wave amplitude decrease of ≥50%, and a pacing lead impedance change of ≥50 ohms from baseline.
Sample Size: Using an event rate limit of ≤1%, 500 cases will be needed in each group to yield a 95% confidence interval of 0 to 1.0% if no events are observed. When a total of 500 cases have been enrolled in one group, enrollment in the other groups may be continued at the discretion of the investigators. The estimated study duration is 5 years, including enrollment and data analysis.
Clinical Implications and Impact: The anticipated results will support an amendment to the current HRS Expert Consensus Statement (2017) and Medicare NCD (April 2018) for the patient groups in the study.
Full description
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.
1.4.2 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 device reimplantation. In addition, no lead malfunctions or clinically significant changes in pacing thresholds were noted.
2 INNOVATION 2.1 Study design
The proposed study, the MagnaSafe-2 Registry, is a prospective, multicenter registry designed to determine the risks of MRI in three groups of patients presently without access to clinically indicated MRI and not previously addressed in clinical investigations or peer-reviewed literature. The three groups of patients presently without adequate access to MRI are those with (1) a patient with CIED system scheduled for MRI at a magnet field strength of 3-tesla and labelled NMRC at that field strength, (2) a patient with an NMRC system due to a "mixed-vendor" or a same vendor "mixed-component" system scheduled for imaging at 1.5-tesla or 3-tesla, and (3) a patient with an MRC or NMRC pacing system and an abandoned lead, epicardial lead, fractured lead or subcutaneous array scheduled for clinically indicated MRI at a field strength of 1.5-tesla.
2.2 Enrollment Inclusion Criteria:
Patients will be included in the registry if they fulfill all the following criteria:
Age of 18 years or older
Able to provide informed consent for entry in the research registry
Have a CIED from any manufacturer implanted after 2001
Have cardiac leads from any manufacturer without an implant date limitation
Documentation that the patient's ordering physician has determined that an MRI at 1.5-tesla or 3.0-tesla of any anatomic region is clinically indicated without an acceptable alternative imaging technology
The patient is scheduled for that imaging procedure
MRI will be performed for clinical purposes, and not for the purpose of entry into this research protocol
In addition, groups within the protocol require that an enrolled patient will have:
2.3 Enrollment Exclusion Criteria:
Patients will not be included in the registry if they fulfill any of the following criteria:
2.3.1 Conditions which do not require exclusion from the present protocol
Prior coronary stent placement (without minimum time from stent implant exclusion)
Prior non-coronary or peripheral vascular stent placement (including aortic stent grafts)
Vascular shunts
IVC filters for thromboembolic prophylaxis
Mechanical or bio-prosthetic heart valves, regardless of placement procedure
Prior coronary artery bypass grafting surgery (including associated sternal wires)
A retained temporary epicardial pacing wire after cardiac surgery
Prior joint replacement surgery
Left atrial appendage occlusion device placement
Atrial or ventricular septal defect closure device placement
Any other non-CIED MRC device 2.4 Group 1 - A patient with a CIED system not labelled for use at 3.0-tesla (NMRC) scheduled for MRI at a magnet field strength of 3.0-tesla
2.5 Group 2 - Patients with an NMRC system due to a "mixed-vendor" or a same vendor "mixed-component" system scheduled for MRI at a scanner field strength 1.5-tesla or 3-tesla
2.6 Group 3 - Patients with an MRC or NMRC CIED and an abandoned cardiac lead, epicardial lead, fractured lead, or subcutaneous array scheduled for MRI at a magnet field strength of 1.5-tesla
3 APPROACH 3.1 Study overview: The MagnaSafe-2 Registry involves an MRI performed for clinical purposes at the discretion of the ordering physician and will follow a similar study design as the previously performed and reported MagnaSafe Registry. MRI for patients with an implanted cardiac device will only be performed when, in the opinion of the ordering physician, MRI is the imaging modality of choice without an acceptable alternative, and the decision to have the scan will not be part of this research protocol. Completion of the MagnaSafe-2 Registry inclusion/exclusion form by the ordering physician or qualified medical professional responsible for study enrollment will document that MRI has been requested as the clinically indicated diagnostic imaging modality of choice for a specific disease or anatomic region without acceptable alternative imaging technology. A patient with a CIED who is scheduled for a clinically indicated MRI will be invited to enroll in this research study if they fall into three clinical groups. Enrollment will be open to all eligible patients until the target enrollment of 500 patients has been reached in the "abandoned lead" group. After reaching target enrollment in Group 3 (epicardial leads, abandoned leads, subcutaneous array), enrollment will be limited to Group 2 (mixed vendor/component) and Group 1 (3.0-tesla imaging) if that group has not yet reached a maximum enrollment of 500 patients. In the MagnaSafe-2 Registry, up to 30 clinical sites will enroll patients. MRI-compatible equipment will be required to monitor vital signs (pulse oximeter and single-lead cardiac rhythm monitor) while performing MRI scans on patients with an implanted pacemaker. Recommendations from the HRS in 2017 will be incorporated into the performance of MRI where appropriate, and the coverage criteria of the 2018 CMS decision memo will be observed. This protocol is being developed in cooperation with the FDA Center for Devices and Radiological Health, and an IDE will be requested for event reporting/monitoring. Also, a change in the CMS/NCD has been requested for CED payment.
3.1 MRI protocol
3.3 Primary Endpoints A rise in Troponin-T at 18-24 hours post-MRI compared to baseline Troponin-T (obtained within 30 days before the MRI scan) in the absence of renal insufficiency (a GFR of <45ml/min), death, or generator or lead failure requiring immediate device replacement.
3.4 Secondary Endpoints: A new onset atrial or ventricular cardiac arrhythmia noted during the MRI scan, loss of pacing capture (for pacing-dependent patients), partial or full generator-electrical reset, pacing lead threshold increase of ≥1.0 V, a P-wave amplitude decrease of ≥50%, an R-wave amplitude decrease of ≥50%, a pacing lead impedance change (positive or negative) of ≥50 ohms from baseline, and patient reported heating, vibration, or discomfort at the generator implant site.
3.5 Sample Size Using a device failure or event rate of ≤1% as a limit, 500 cases will be needed in each group to yield a 95% confidence interval of 0 to 1.0% if no events are observed. When a total of 500 cases has been enrolled in one of the three groups, enrollment in the other 2 groups may be continued at the discretion of the investigators and the Data Safety Monitoring Board (DSMB).
3.6 Patient preparation Current clinical guidelines recommend removing and disposing of transdermal drug delivery patches before the MRI scan. As per standard individual institutional standards, all patients undergoing MRI must remove all readily removable metallic personal belongings, as well as clothing items which may contain metallic fasteners, hooks, zippers, loose metallic components, or metallic threads. The importance of having patients change into safe facility-provided garments before MR imaging is emphasized.
3.7 Examinations A case will be defined as an instance in which a patient who provides informed consent enters the scanner and undergoes an MRI of one or more anatomical regions during a single study session. If the patient returns on a subsequent day for a repeat MRI, then a separate informed consent will be obtained, and the data will be entered as a separate and unique case. No limit will be placed on the total number of repeat MRI examinations for an enrolled patient, the number of anatomic areas studied during each examination, or the interval between repeat MRI examinations during study enrollment. However, a patient may only be enrolled in one group of the study and may not return as part of a second or different study group.
3.7.1 Device programming during the scan:
3.7.2 Pacemaker post-scan interrogation:
3.7.3 Decision not to analyze battery status post-MRI scanning: When pre-MRI and post-MRI battery voltage measurements were compared in the first MagnaSafe Registry, a small decrease was noted for both pacemakers and ICDs. The RF energy generated during MRI scanning creates a temporary decrease in battery voltage, which has typically been reported to resolve within 2 weeks.
In the MagnaSafe Registry (2017), post-MRI battery voltage decreases of 0.04 V or more returned to baseline at the time of the last follow-up interrogation, which was typically between 3-6 months after the MRI scan. Thus, in the present study (MagnaSafe-2), the battery voltage, lifetime, or status will be measured and recorded post-MRI scan, but a change in battery voltage, lifetime, or status will not be used as a primary or secondary study endpoint.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria:
Patients will be included in the registry if they fulfill all the following criteria:
Age of 18 years or older
Able to provide informed consent for entry in the research registry
Have a CIED from any manufacturer implanted after 2001
Have cardiac leads from any manufacturer without an implant date limitation
Documentation that the patient's ordering physician has determined that an MRI at 1.5-tesla or 3.0-tesla of any anatomic region is clinically indicated without an acceptable alternative imaging technology
The patient is scheduled for that imaging procedure
MRI will be performed for clinical purposes, and not for the purpose of entry into this research protocol
In addition, groups within the protocol require that an enrolled patient will have:
An NMRC CIED scheduled for MRI at 3.0-tesla with a CIED that is not MRC at that field strength.
A "mixed-vendor" or same vendor "mixed-component" system that is NMRC because the generator and lead combination are not labeled as MRC for use in the MR-environment.
A CIED and abandoned lead, a fractured cardiac lead, an epicardial lead, or a subcutaneous array.
Exclusion Criteria:
Patients will not be included in the registry if they fulfill any of the following criteria:
A generator battery at the elective replacement indicator (ERI)
Renal insufficiency (GFR <45 cc/min)
In addition, all standard clinical exclusion criteria for MRI in patients without a cardiac device will be observed.
Standard clinical exclusion criteria include pregnancy, severe claustrophobia (not responsive to pre-procedure medications), morbid obesity (abdominal diameter of greater than 60 cm), and the presence of ferro-magnetic metallic objects (such as intra-orbital or intra-ocular retained metal fragments, and intracranial vascular clips and coils)
-
Loading...
Central trial contact
Robert J Russo; Nicola Mair
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal