Download advisa mri 3008 23 11 2010

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NATIONAL COMMISSION FOR THE EVALUATION OF MEDICAL DEVICES AND
HEALTH TECHNOLOGY
COMMISSION OPINION
November 23, 2010
CONCLUSIONS
Name :
ADVISA DR MRI, rate-controlled dual-chamber implantable cardiac pacemaker (DDDR).
Models and
references selected:
Model A3DR01
Maker :
MEDTRONIC INC.
Applicant:
MEDTRONIC France S.A.S.
Data for all conventional pacemakers
In 2008, the Commission reviewed the conditions for the treatment of conventional pacemakers due to new
data in the literature, the evolution of technologies and the heterogeneity of practices observed.
Thus, a HAS report dating from February 2009 provided a review of the literature carried out over the period
2002 to 2008 which made it possible to find 350 references to clinical studies and 79 technological
evaluation reports, meta-analyses, reviews and recommendations.
Analysis of these data finds little evidence to recommend the use of dual-chamber stimulators. Dualchamber stimulation ensures atrioventricular synchronization if necessary, but its superiority on survival
has not been demonstrated. In addition, it is associated with more perioperative complications (probe
displacements, compartment infections) and an increased risk of hospitalization for heart failure in the
event of sinus dysfunction.
Data specific to the ADVISA DR MRI device equipped with the SureScan system
No data specific to the ADVISA DR MRI device was provided on file.
Data
available:
Nevertheless, the clinical report as well as the publication of a study specific to the SureScan system were
provided. This is an international, prospective, controlled, randomized, open-label, multicenter clinical study.
All patients were implanted with a pacemaker (ENRHYTHM DR MRI, earlier version of the ADVISA DR
MRI pacemaker) equipped with the SureScan system and CapSureFix MRI probes. Patients randomized
to the MRI arm performed an MRI between 9 and 12 weeks (14 sequences with restriction of positioning of
the radiofrequency antennas above the C1 vertebra and below the T12 vertebra) while patients in the
control arm did not perform an MRI. no MRI.
MRI was performed under the following conditions: a magnetic field of 1.5 Tesla, a gradient slope per axis
restricted to 200/T/m/s and a specific absorption rate 2 W/kg.
The primary objective of the study was to confirm the safety and effectiveness in an MRI environment of
the pacemaker equipped with a SureScan system.
Forty-two centers included 484 patients. The number of patients actually implanted was 464 (258 in the
MRI arm and 206 in the control arm).
The safety criterion was evaluated based on the rate of patients without MRI-related complications in the
month following the examination by setting a priori the acceptability threshold value for non-inferiority at 0.9.
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Thus, the per-protocol analysis showed a rate of patients without MRI-related complications
in the month following the examination of 100% (p<0.001).
Materiovigilance data
The ADVISA DR MRI device has been marketed worldwide since March 2010. Since its
marketing, no complications have been reported. Nine events were reported between July
26 and September 8, 2010.
Sufficient:
ÿ The ADVISA DR MRI stimulator corresponds in all respects to the minimum technical
specifications required for registration on the LPP.
Expected Service
ÿ In view of the data provided, the ADVISA DR MRI stimulator has therapeutic benefit in
the treatment of atrioventricular blocks and sinus node dysfunction.
(SA) :
ÿ The impact of the SureScan function on the healthcare system cannot be assessed in
the absence of sufficient data. Overall, the available data do not make it possible to
specify the public health benefit expected from the SureScan function present on
ADVISA DR MRI model A3DR01 stimulators.
Primary implantation of a dual-chamber rate-controlled pacemaker in the following
indications :
ÿ Sinus dysfunctions except those that can be treated by an SSIR stimulator. (The
pacemaker must be programmed to preserve ventricular activation if possible);
ÿ BAV in sinus rhythm, unless atrioventricular synchronization is not necessary or
if the estimated ventricular pacing percentage is low (some paroxysmal BAVs).
To ensure complete system MRI compatibility, the ADVISA DR MRI Model A3DR01
Pacemaker must be implanted with compatible CapSureFix MRI Model 5086 leads and
used with the CareLink Model 2090 Programmer.
Indications :
The Commission recommends that MRIs performed with the ADVISA DR MRI stimulator
associated with CapSureFix MRI probes be performed in a center with a cardiological
team on the same geographic site and only under the following conditions: • restriction
of the positioning of radiofrequency
antennas to areas
cervical and pelvic, exclusion of the cardiopulmonary zone
• clinical MRI systems with cylindrical magnetic tunnel with a static magnetic field of 1.5 T
(tesla), MRIs of 3 Tesla constitute an absolute contraindication,
• maximum gradient slope per axis ÿ 200 T/m/s, • whole
body average specific absorption rate (SAR) reported by MRI equipment ÿ 2.0 W/kg ;
Head SAR reported by equipment < 3.2 W/kg.
Finally, the SureScan MRI mode must be programmed by a cardiologist or rhythmologist
before the MRI examination and then unprogrammed at the end of the examination.
The time interval between programming and unprogramming should be as short as
possible.
Contraindications to performing an MRI with the ADVISA stimulator
DR MRI equipped with the SureScan system:
ÿ Patients with previously implanted medical devices, leads, adapters or lead
extensions, whether active or abandoned;
ÿ Patients with broken probes or whose electrical connection is
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intermittent ;
ÿ Patients who have had a SureScan pacing system for less than
6 weeks ;
ÿ Patients with a SureScan stimulation system at other sites
whether the right or left pectoral region;
ÿ Patients without a complete SureScan pacing system (SureScan device and SureScan atrial and
ventricular leads);
ÿ Patients whose stimulation training threshold values are
greater than 2.0 V at a pulse duration of 0.4 ms;
ÿ Patients whose lead impedance value is less than 200 ÿ or greater than 1500 ÿ; ÿ Patients whose
device will be programmed
in asynchronous pacing mode when SureScan MRI mode is programmed to On and experiencing
diaphragmatic pacing at a pacing output of 5.0 V and a pulse duration of 1.0 ms; ÿ Patients
positioned in lateral decubitus position in the MRI tunnel.
ADVISA DR MRI box replacements are only possible if the implanted leads are CapSureFix MRI
model 5086 compatible leads.
Elements
conditioning the
AT :
- Technical
specifications :
Those of the generic line of DDDR stimulators comply with current European connection standards (updated
in the HAS report of February 2009).
- Terms of prescription
To ensure complete system MRI compatibility, the ADVISA DR MRI Model A3DR01 Pacemaker must be
implanted with compatible CapSureFix MRI Model 5086 leads and used with the CareLink Model 2090
Programmer.
and use:
Improvement of
AT :
ASA IV compared to non-MRI compatible dual chamber pacemakers.
Type of registration: Brand name
Registration duration: 3 years
The CNEDiMTS makes the renewal of registration of the ADVISA DR MRI stimulator subject to the
completion of a study specific to ADVISA DR MRI equipped with the SureScan system implemented on a
cohort of patients representative of the population treated under real conditions of use.
This study will aim to evaluate in the medium and long term (more than two years) the safety of the ADVISA
DR MRI stimulator equipped with the SureScan system in first-time implanted patients, in particular by
evaluating the rate of movement of the probes and the rate of reinterventions but also by assessing the rate
of patients who actually had an MRI examination.
Renewal
conditions:
For patients who have had an MRI examination, the study should provide information on the rates of clinical
events such as discomfort, syncope, palpitations in patients dependent on the stimulator, pain, heat or burns
in relation to the box. Data related to device control such as memory functions for arrhythmia detection,
stimulation thresholds, detection, or lead impedances must also be entered.
The industrialist is responsible for the study, he must ensure the establishment of a scientific committee, the
development of the protocol for the requested study, the implementation and monitoring of the study .
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This study must be implemented no later than one year after publication of this CNEDiMTS opinion.
An annual communication of the progress of this study must be made to the CNEDiMTS.
The evaluation of the results may lead to a recommendation by the Commission to maintain or eliminate
coverage for the stimulator concerned.
Materiovigilance data will also be requested for registration renewal.
Target population: 44,100 to 47,300 pacemakers per year
Final opinion
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ARGUMENTARY
Nature of request
Request for registration on the list of products and services (LPP) mentioned in article L 165-1 of the
Social Security Code
Conditioning :
Unitary and sterile
The packaging includes:
- One (1) implantable device
- One (1) torque wrench
Applications
The manufacturer's registration request concerns the indications as defined for dual-chamber frequencycontrolled pacemakers in the HAS report of February 2009: ÿ Sinus dysfunction with the exception of
those that
can be treated by an SSIR pacemaker. (The pacemaker must be programmed to preserve
ventricular activation if possible);
ÿ BAV in sinus rhythm, unless atrioventricular synchronization is not necessary or if the
estimated ventricular pacing percentage is low (some paroxysmal BAVs).
Reimbursement history
This is a first request for registration of the ADVISA DR MRI device.
Characteristics of the product or service
CE marking
Active implantable medical device (AMD), notification by TÜV Product service GMBH (0123), Germany.
Description and functions provided
The ADVISA DR MRI stimulator is a multiprogrammable DDDR1 type stimulator
A model is available: A3DR01
.
Model A3DR01
Volume
Weight
HxLxP
12.7 cm3
Probe connector
22 g
45 mm x 51 mm x 8 mm
IS-1 B1
Longevity*
7.9 years
1
The operation of a pacemaker is described globally by an international code.
The first letter corresponds to the stimulation site, the second to the detection site:
S: single chamber - A: atrial - V: ventricular - D: both chambers - ÿ: none
The third letter corresponds to the detection response:
I: inhibited - T: triggered - D: both simultaneously - ÿ: none
The letter R in the fourth position designates the possibility of programming a frequency control
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*Longevity is estimated under the following conditions: 2.5 V – 0.5
ms – 70 min-1 – 100% DDDR stimulation – 500 ÿ ± 1% (until
replacement indicated).
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The Advisa DR MRI stimulator and its CapSureFix MRI active fixation leads have undergone design
changes to ensure compatibility with MRI:
ÿ Installation of filters at the input of the circuit (probe/pacemaker connection) to minimize the energy
induced or diffused by the probe and transmitted into the pacemaker;
ÿ Protection of internal power circuits to prevent the fields generated by the MRI from disrupting the
operation of the cardiac pacemaker and causing a switch to reversion mode (emergency circuit);
ÿ Replacement of the flexible reed switch (mechanical) with a Hall effect sensor (electronic) to prevent
random switching to magnetized mode under the effect of MRI magnetization (asynchronous
stimulation, potentially pro-arrhythmic ) ;
ÿ Reduction of ferromagnetic components in order to reduce sensitivity to fields
magnetic;
ÿ Modification of the geometry of the probe body to prevent interactions with the fields
radio frequency and thus reduce the heating of the tip of the probe;
Associated act or service
The stimulators are implanted under local anesthesia in the pectoral region approached by a simple
incision; they are connected to one or two endocavitary probes whose ends are placed at the level of
the cardiac cavities.
To ensure complete system MRI compatibility, the ADVISA DR MRI Model A3DR01 Pacemaker
must be implanted with compatible CapSureFix MRI Model 5086 leads and used with the
CareLink Model 2090 Programmer.
The Commission recommends that MRIs performed with the ADVISA DR MRI stimulator
associated with CapSureFix MRI probes be performed in a center with a cardiological team on
the same geographic site.
The SureScan MRI mode must be programmed by a cardiologist or rhythmologist before the
MRI exam and then unprogrammed after the exam. The time interval between programming
and unprogramming should be as short as possible.
Finally, replacements of ADVISA DR MRI model A3DR01 boxes are only possible if the
implanted probes are CapSureFix MRI model 5086 compatible probes.
The procedures associated with the implantation and control of a dual-chamber frequency-controlled
pacemaker are referenced in the Common Classification of Medical Procedures (CCAM): DELF005
and DEMP002.
Expected Service
1. Interest in the product or service
1.1 Data analysis: evaluation of the therapeutic effect / adverse effects
Data for all conventional pacemakers
In 2008, the Commission reviewed the conditions for the treatment of conventional pacemakers due
to new data in the literature, the evolution of technologies and the heterogeneity of practices observed.
Thus, a HAS report dating from February 2009 provided a review of the literature carried out over the
period 2002 to 2008 which made it possible to find 350 references to clinical studies and 79
technological evaluation reports, meta-analyses, reviews and recommendations.
The literature separates two main indications in which conventional stimulators are used:
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ÿ Sinus dysfunction; ÿ
Atrioventricular block (AVB).
On average, the installation of dual-chamber devices represents 70% of cases, and in 25% of cases
single-chamber stimulators, including less than 3% of AAI(R) stimulators, all indications combined.
The UKPACE study in BAV nevertheless highlighted a VVI(R) to DDD(R) crossover rate of only 3.1%
for an average follow-up of 3 years. Cases of intolerance to the ventricular mode are therefore quite
rare2 .
Dual-chamber stimulation ensures atrioventricular synchronization if necessary, but its superiority on
survival has not been demonstrated.
In addition, it is associated with more perioperative complications (probe displacements, compartment
infections) and an increased risk of hospitalization for heart failure in the event of sinus dysfunction.
This is why the Commission encourages practitioners to avoid the systematic use of dual-chamber
devices and encourages wider use of single-chamber devices, particularly in BAV (VVI(R)), but also
in sinus dysfunction (AAI (R)).
The data provided in this report therefore led the Commission to retain as indications for DDDR dualchamber frequency-controlled pacemakers:
ÿ Sinus dysfunctions with the exception of those that can be treated by an SSIR stimulator.
(The pacemaker must be programmed to preserve ventricular activation if possible); ÿ
The BAV in sinus rhythm,
unless atrioventricular synchronization is not necessary or if the estimated percentage of
ventricular stimulation is low (certain paroxysmal BAVs).
Data specific to the ADVISA DR MRI device equipped with the SureScan system
No studies regarding the ADVISA DR MRI stimulator are provided. Nevertheless, the clinical report
as well as the publication3 of a study specific to the SureScan system were provided.
This study is described in the Appendix.
This is an international, prospective, controlled, randomized, open-label, multicenter clinical study.
Forty-two centers participated in the study: 13 in the United States, 7 in Canada, 21 in Europe and 1
in Saudi Arabia.
The patient inclusion period ran from February 2007 to November 2008. To be included, patients had
to have an indication for implantation of a dual-chamber pacemaker (class I and II) according to ACC/
AHA recommendations. /NASPE.
All patients were implanted with a pacemaker (ENRHYTHM DR MRI, previous version of the ADVISA
DR MRI pacemaker) equipped with the SureScan system and CapSureFix MRI probes.
Patients randomized to the MRI arm underwent MRI between 9 and 12 weeks while patients in the
control arm did not undergo MRI.
Patients in the MRI group received 14 sequences with restricted positioning of the radiofrequency
antennas at the head and lumbar region (above the C1 vertebra and below the T12 vertebra) under
the following MRI conditions:
ÿ magnetic field 1.5 Tesla, ÿ
gradient slope per axis restricted to 200/T/m/s, ÿ
specific absorption rate 2 W/kg,
i.e. a total investigation time of 60 minutes (min) and an exposure duration of approximately 30 min.
2
Toff WD, Camm AJ, Skehan JD; United Kingdom Pacing and Cardiovascular Events Trial Investigators. Single chamber versus dual-chamber pacing for
highgrade atrioventricular block. N Engl J Med 2005;353 :145-155.
Wilkoff BL, Bello D, Taborsky M, Vymazal J, Kanal E, Heuer H et al. Magnetic Resonance Imaging in Patients with a Pacemaker System Designed for the
MR Environment. Heart Rhythm. 2010 Oct 5 < http://www.ncbi.nlm.nih.gov/pubmed/20933098> [consulté le 10.10.10].
3
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The primary objective of the study was to confirm the safety and effectiveness in an MRI environment of
the pacemaker equipped with a SureScan system.
In total, 42 centers included 484 patients. The number of patients actually implanted was 464 (258 in the
MRI arm and 206 in the control arm). The patients were seen again during a visit 2 months after implantation,
between 9 and 12 weeks, at 3 months (corresponding to 1 week post-MRI for the MRI group), at 4 months
(corresponding to 1 month post-MRI for the MRI group) then every 6 months until the end of the study.
Patients were followed for an average of 11.2 ± 5.2 months [0.1-21.5].
The safety criterion was evaluated based on the rate of patients without MRI-related complications in the
month following the examination by setting a priori the acceptability threshold value for non-inferiority at 0.9.
Thus, the per-protocol analysis showed a rate of patients without MRI-related complications in the month
following the examination of 100% (p<0.001).
The effectiveness criteria were evaluated by taking into account two components: ÿ on
the one hand the variation of the atrial and ventricular stimulation thresholds ÿ 0.5V before and after
MRI then compared with the control group
ÿ on the other hand, variations in detected amplitude ÿ 50% while maintaining an amplitude ÿ 5 mV at the
ventricular level and ÿ 1.5 mV at the atrial level before and after the MRI then by comparison with the
control group.
The clinical equivalence margins were defined a priori at 10%.
The analyzes showed that the patient rates were not different in the two arms for these two criteria, cf.
Tables 1 and 2 below.
Table 1: Variation of atrial and ventricular stimulation thresholds
% of success
N
Measure
MRI group
165/165
100%
164/164
100%
190/190
100%
183/184
165
Atrial
Control group 164
MRI group
190
Ventricle
Control group 184
P
Test
impossible
<0,001
99,5%
Table 2: Amplitude detected
Measure
% of success
N
MRI group
131
94,7%
129/139
Atrial
Control group 139
MRI group
P
124/131
<0,001
92,8%
130/134
134
97,0%
129/136
Ventricle
Control group 136
<0,001
94,9%
Eleven deaths were reported in the study. None were considered in connection with the implantation of the
pacemaker, its lead or the MRI.
Materiovigilance data
The ADVISA DR MRI device has been marketed worldwide since March 2010. Since its marketing, no
complications have been reported.
Nine events were reported between July 26 and September 8, 2010: ÿ Seven
events concerned a software problem (battery longevity displayed low).
These events did not cause any complications for the patients.
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ÿ Two events related to the placement of a probe which required in one case a
repositioning of the probe, in the other case reconnection of the probe.
1.2 Place in the therapeutic strategy
The HAS4 report and analysis of the literature show that there is no therapeutic alternative to cardiac
stimulation in atrioventricular blocks and in sinus node dysfunction.
While taking into account recent recommendations5,6,7,8, HAS retains as indications for
these stimulators:
ÿ sinus dysfunctions, which most often involve a dual-chamber stimulator (DDDR), sometimes a single
chamber (AAIR or, more rarely, VVIR). ÿ atrioventricular blocks (AVB),
which involve a single ventricular chamber pacemaker (VVIR) or, if synchronization at the atria is necessary,
a dual chamber pacemaker (DDDR or, more rarely, VDD/R).
To date, in patients with an implantable pacemaker, when a diagnosis by imaging is necessary, a
conventional CT scan should be preferred9,8,10,11 .
When performing Magnetic Resonance Imaging (MRI), risks are incurred for the patient such as
asynchronous stimulation, inhibition of stimulation, very rapid ventricular stimulation, burns due to heating
at the ends of the probe on the myocardium and at the box level, a complete breakdown of the stimulator
or even a movement of the box in its compartment.
Although MRI is a common examination in 2010, for people with a pacemaker it is replaced by CT which
has no proven adverse effects but which has the disadvantage of significant irradiation.
MRI has the main advantage of being non-irradiating while providing high-resolution images. In addition,
the radiation protection of patients has been part of the legal obligations since Ordinance 2001-270 of
March 28, 2001 which transposed Directive 97/43 Euratom into French law.
It is for this purpose that the “Guide to the proper use of medical imaging examinations” was developed in
2005. This document, intended to guide the choice of the prescribing doctor towards the examination most
suited to the pathology explored, underlines the necessity of respecting the principle of justification.
This regulation aims in particular to eliminate obsolete equipment and unacceptable practices. Its aim is
also to encourage radiologists to favor non-irradiating examinations such as MRI.
4
High Authority of Health (HAS) – Conventional cardiac pacemakers: respective place of single and double chamber pacemakers. <http://www.has-sante.fr/
portail/upload/docs/application/pdf/2009FEBRUARY
2009.
02/rapport_stimulateurs_cardiaques_conventionnels.pdf> [consulted on 16.11.10]
5
National Institute for Health and Clinical Excellence (NICE). 2005. http://www.nice.org.uk
6
Healey JS, Toff WD, Lamas GA, Andersen HR, Thorpe KE, Ellenbogen KA et al. Cardiovascular outcomes with atrial-based pacing
compared with ventricular pacing: meta-analysis of randomized trials, using individual patient data. Circulation 2006;114:11-17
7
Vardas PE, Auricchio A, Blanc JJ, Daubert JC, Drexler H, Ector H et al. Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task
Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in collaboration with the European Heart
Rhythm Association. European Heart Journal 2007;28(18):2256-95.
8
Levine GN, Gomes AS, Arai AE, Bluemke DA, Flamm SD, Kanal E et al . Safety of magnetic resonance imaging in patients with cardiovascular devices: an
American Heart Association scientific statement from the Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology,
and the Council on Cardiovascular Radiology and Intervention: endorsed by the American College of Cardiology Foundation, the North American Society for
Cardiac Imaging, and the Society for Cardiovascular Magnetic Resonance. Circulation. 2007;116:2878-2891.
9
Afssaps – Interactions between active implantable medical devices and medical devices. February 2005. <
http://www.afssaps.fr/var/afssaps_site/storage/original/application/0792db7b6f52d8721e07dd2a07fcf7ed.pdf> [accessed 16.11.10].
10
Channel E, Barkovich AJ, Bell C, Borgstede JP, Bradley WG Jr, Froelich JW et al. ACR guidance document for safe MR practices:2007.
AJR. American Journal of Roentgenol. 2007 Jun;188:1447-1474.
11
FDA Alert – July 2008. <http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/UCM061994 >
[accessed 16.11.10]
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There is no alternative to the implantation of a pacemaker in the selected indications.
In view of the data provided, the Commission found therapeutic benefit in the ADVISA DR MRI
stimulator in the treatment of sinus dysfunctions with the exception of those that can be
treated by an SSIR stimulator and atrioventricular blocks in sinus rhythm, unless a
Atrioventricular synchronization is not necessary or if the estimated ventricular pacing
percentage is low (some paroxysmal AVBs).
To ensure complete system MRI compatibility, the ADVISA DR MRI Model A3DR01 Pacemaker
must be implanted with compatible CapSureFix MRI Model 5086 leads and used with the
CareLink Model 2090 Programmer.
In the current state of the data, the Commission recommends that MRIs performed with the
ADVISA DR MRI stimulator associated with CapSureFix MRI probes be performed in a center
with a cardiological team on the same geographic site and only under the following conditions:
• restriction of the positioning of
radiofrequency antennas to the cervical and
pelvic, exclusion of the cardiopulmonary zone
• clinical MRI systems with cylindrical magnetic tunnel with a static magnetic field of 1.5 T
(tesla), MRIs of 3 Tesla constitute an absolute contraindication,
• slope of gradients per axis maximum ÿ 200 T/m/s, •
average specific absorption rate (SAR) of the whole body reported by the equipment
MRI ÿ 2.0 W/kg; Head SAR reported by equipment < 3.2 W/kg.
Finally, the SureScan MRI mode must be programmed by a cardiologist or rhythmologist
before the MRI examination and then unprogrammed at the end of the examination. The time
interval between programming and unprogramming should be as short as possible.
2. Expected public health benefit
2.1 Severity of the pathology
Sinus dysfunction can lead to atrial fibrillation, with associated thromboembolic complications and/or
progress to heart failure.
Sinus dysfunction causes a marked deterioration in quality of life.
In atrioventricular blocks, symptoms are common. They are related to bradycardia or ventricular
arrhythmia (dizziness, syncope, absences).
Certain atrioventricular blocks can be life-threatening.
2.2 Epidemiology of the pathology
According to data from the 2006 French file from the French College of Cardiac Stimulation, sinus
diseases and atrioventricular blocks represent respectively 30 and 40% of indications for first-time
French implantations of cardiac pacemakers.
Implantations are most often carried out in men (around 59%). The median age of patients is 79
years12 .
Analysis of the PMSI 2008 database showed that nearly 3% of patients had, at the time of implantation,
an associated pathology requiring monitoring using MRI.
12
French cardiac stimulation college. French file statistics. The 2006 national file of patients with
pacemaker 2006. <http://pacingrp.online.fr/> [accessed 9-1-2009].
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(grade A or B recommendations according to the Good Use Guide for medical imaging examinations
2005).
The proportion of patients likely to require an MRI over the lifespan of the stimulator remains difficult
to estimate.
2.3 Impact
The study presented has several limitations which do not make it possible to correctly estimate the
impact of the SureScan function on the healthcare system.
In addition, it should be noted that the reprogramming of the stimulator in the event of an MRI actually
being performed is not automatic. It is therefore necessary to program the SureScan function by a
cardiologist or rhythmologist before the MRI examination and then to deprogram it at the end of the
examination, the time interval between programming and deprogramming having to be as short as
possible. possible. This can lead to significant time and organizational constraints.
The impact of the SureScan function on the healthcare system cannot therefore be assessed
in the absence of sufficient data.
Overall, the available data do not make it possible to specify the public health benefit expected
from the SureScan function present on ADVISA DR MRI model A3DR01 stimulators.
Elements conditioning the Expected Service
Minimum technical specifications
Those of the generic line of DDDR stimulators compliant with current European connection standards
(updated in the HAS report of February 2009).
Terms of use and prescription Those of
the generic line of DDDR stimulators compliant with current European connection standards (updated
in the HAS report of February 2009).
To ensure complete system MRI compatibility, the ADVISA DR MRI Model A3DR01 Pacemaker must
be implanted with compatible CapSureFix MRI Model 5086 leads and used with the CareLink Model
2090 Programmer.
In the current state of the data, the Commission recommends that MRIs performed with the ADVISA
DR MRI stimulator associated with CapSureFix MRI probes be performed in a center with a
cardiological team on the same geographic site and only under the following conditions: •
restriction of the positioning
of radiofrequency antennas to the cervical and
pelvic, exclusion of the cardiopulmonary zone
• clinical MRI systems with cylindrical magnetic tunnel with a static magnetic field of 1.5 T (tesla),
MRIs of 3 Tesla constitute an absolute contraindication,
• maximum gradient slope per axis ÿ 200 T/m/s, • whole
body average specific absorption rate (SAR) reported by MRI equipment ÿ
2.0 W/kg ; Head SAR reported by equipment < 3.2 W/kg.
Finally, the SureScan MRI mode must be programmed by a cardiologist or rhythmologist before the
MRI examination and then unprogrammed at the end of the examination. The time interval between
programming and unprogramming should be as short as possible.
In conclusion, CNEDiMTS considers that the expected service of the ADVISA DR MRI dualchamber stimulator model A3DR01 is sufficient for inclusion on the list of Products and
Services provided for in Article L. 165-1 of the Social Security Code.
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Improvement of the Expected Service
The ADVISA DR MRI stimulator offers in addition to minimum technical specifications, several
therapeutic and diagnostic functions, most of which are offered on other stimulators already available
with varying degrees of development and automation which do not allow them to be distinguished.
The Commission highlights the limits of the study set up to validate the SureScan system.
However, it notes that the provision of this function allowing a patient with a pacemaker to perform an
MRI should improve the conditions of care for implanted patients.
The CNEDiMTS has therefore decided in favor of an Improvement in the Expected Level IV
Service of ADVISA DR MRI compared to non-MRI compatible dual-chamber pacemakers.
Renewal conditions and registration duration
Renewal conditions: The
CNEDiMTS makes the renewal of registration of the ADVISA DR MRI stimulator subject to the
completion of a study specific to ADVISA DR MRI equipped with the SureScan system implemented
on a cohort of patients representative of the population treated in real-world conditions. 'use.
This study will aim to evaluate in the medium and long term (more than two years) the safety of the
ADVISA DR MRI stimulator equipped with the SureScan system in first-time implanted patients, in
particular by evaluating the rate of movement of the probes and the rate of reinterventions but also by
assessing the rate of patients who actually had an MRI.
For patients who have had an MRI examination, the study should provide information on the rates of
clinical events such as discomfort, syncope, palpitations in patients dependent on the stimulator, pain,
heat or burns in relation to the box.
Data related to device control such as memory functions for arrhythmia detection, stimulation
thresholds, detection, or lead impedances must also be entered.
The industrialist is responsible for the study, he must ensure the establishment of a scientific
committee, the development of the protocol for the requested study, the implementation and monitoring
of the study .
This study must be implemented no later than one year after publication of this CNEDiMTS opinion.
An annual communication of the progress of this study must be made to the CNEDiMTS.
The evaluation of the results may lead to a recommendation by the Commission to maintain or
eliminate coverage for the stimulator concerned.
Materiovigilance data will also be requested for registration renewal.
Proposed registration duration:
3 years
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Target population
The latest published data from the French file of the College of Cardiac Stimulation12 show that the
indications for conventional pacemakers are distributed as follows: 40% BAV and 30% sinus
dysfunction, approximately 10% bilateral bundle branch blocks and 10% to 15% FA. Marginal
indications such as hypertrophic cardiomyopathy, ablation of the Hissian pathway, vaso-vagal syncope
or “malignant” carotid sinus syndrome correspond to less than 2% of implantation indications and are
therefore negligible for the calculation of the target population.
Taking into account the indications contained in the HAS report of February 2009, the target population
for dual-chamber DDDR type stimulators is estimated at between 70 to 75% of implantations, i.e.
44,100 to 47,300 stimulators per year in total (including approximately 28 000 for sinus dysfunction).
The proportion of patients likely to require an MRI over the lifespan of the pacemaker is difficult to
estimate. Experts agree that it is impossible to predict in the future of a stimulated patient whether an
indication for MRI will be proposed.
In total, the target population of ADVISA DR MRI is of the order of 44,100 to 47,300 pacemakers per
year.
An increase of 2% per year in the target population is expected.
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ANNEX – Clinical data
Wilkoff BL, Bello D, Taborsky M, Vymazal J, Kanal E, Heuer H et al. Magnetic Resonance Imaging in Patients with a Pacemaker System Designed
for the MR Environment. Heart Rhythm. 2010 Oct 5.
REFERENCES
Sutton R, Kanal E, Wilkoff BL, Bello D, Luechinger R, Jenniskens I et al. Safety of magnetic resonance imaging of patients with a new Medtronic
EnRhythm MRI SureScan pacing system: clinical study design. Trials. 2008 Dec 2;9:68
Clinical report of the “EnRhythm MRI SureScan Pacing System” study
Type of study
Date and duration of
the study
International, prospective, controlled, randomized, open-label, multicenter study.
Inclusion period: February 2007 to November 2008
ÿ Evaluate the rate of patients without MRI-related complications in the month following the examination.
Main
objectives of the
study
ÿ Compare the variation in atrial and ventricular stimulation thresholds before MRI and after a period of 4 months
between the MRI group and the control group.
ÿ Evaluate the amplitude variations detected before the MRI and after a period of 4 months between the MRI group and the
control group.
METHOD
Main inclusion criteria:
ÿ Patients with an indication for implantation of a dual-chamber pacemaker (Class I and II) according to the
ACC/AHA/NASPE recommendations;
ÿ Implantation at pectoral level; ÿ Patients
capable of performing an MRI examination without sedation.
Selection
criteria
Main exclusion criteria:
ÿ History of tricuspid valve pathologies/carriers of a mechanical tricuspid valve;
ÿ Patients who have previously had a pacemaker, defibrillator, or other implantation
active implantable medical devices; ÿ Patients who
are candidates for implantation of a defibrillator; ÿ Patients requiring an
MRI examination other than those provided for in the protocol.
Forty-two (42) centers distributed: ÿ in the
Setting and location of
the study
United States (13), ÿ in Canada
(7), ÿ in Europe (21), ÿ
in Saudi Arabia (1).
Products studied
ÿ The EnRhythm MRI model EMDR01 pacemaker; ÿ The SW005 model
programming software; ÿ The CapSureFix MRI model 8056
probe; ÿ The CareLinkR model 2090 programmer.
Products studied
and specificity
IRM
MRI specificity
Patients in the MRI group received 14 sequences with restricted positioning of the radiofrequency antennas at the head and lumbar region (above
the C1 vertebra and below the T12 vertebra) under the following MRI conditions: ÿ magnetic field 1.5 Tesla, ÿ slope of the gradients per axis
restricted to 200/T/m/s, ÿ specific absorption rate 2 W/kg, i.e. a
total investigation time of 60 minutes (min)
and a duration exposure of approximately 30 min.
Security criterion
ÿ Rate of patients without MRI-related complications in the month following the examination.
Effectiveness criteria
ÿ Variation in atrial and ventricular stimulation thresholds at 0.5 ms between the pre-MRI period and 1 month post-MRI
then comparison with the control group.
Main
endpoints
ÿ Amplitude variations detected between the pre-MRI period and 1 month post-MRI then comparison with the group
control.
Secondary criteria
ÿ Number of complications relating to the SureScan system;
ÿ Compliance with the instructions relating to the correct performance of an MRI examination in a patient wearing a system
SureScan ;
ÿ Number of ventricular arrhythmias and persistent asystoles during the MRI examination;
ÿ Number of adverse events relating to the implant, MRI or implantation;
ÿ Variation in lead impedance (monitoring 4 months after implantation);
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ÿ Maneuverability of the CapSureFix MRI probe compared to the 5076 probe currently on the market;
ÿ Variations in stimulation threshold and amplitude of the MRI and control groups compared to the 5076 probe at this
day marketed (monitored for 4 months).
Number of 470 implanted patients.
Sample
size
Randomization of subjects with a ratio 2:1 then 1:1 (additions to the protocol, in order to achieve the inclusion objectives defined by
the calculation of the sample).
Randomization
method
Randomization tables, in blocks, sent to each center in a sealed envelope.
Methods
ÿ The analysis of the main endpoints was carried out on the per-protocol population:
The analysis of the safety criterion was carried out using a one-sided binomial test (97.5% CI).
Analyzes of the effectiveness criteria were carried out using the one-sided Farrington-Manning test (97.5% CI).
for analyzing
results
ÿ The Student's t-test on paired data was used for the secondary endpoints.
ÿ Descriptive analyzes were also conducted (descriptive statistics and 95% CI).
RESULTS
42 centers.
484 patients included including 464 patients implanted successfully (IRM group, n=258 and control group, n=206).
Population per protocol, n=211 patients who performed an MRI examination according to the conditions required by the protocol.
Patient distribution diagram included:
Number of subjects
analyzed
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Duration of follow-up
Mean duration of follow-up: 11.2 ± 5.2 months [0.1-21.5]
Patient characteristics at inclusion:
MRI group
(n=258)
Control Group
(n=206)
69,3 ± 12,9
71,5
27,8-95,4
68,0 ± 12,6
71,0
19,2-87,3
Feminine
154 (59,7%)
104 (40,3%)
135 (65,5%)
71 (34,5%)
Classification NYHA (New York Heart Association)
Class I
Class II
Class III
Class IV
Does not meet the classification criteria
53 (20,5%)
57 (22,1%)
5 (1,9%)
1 (0,4%)
142 (55,0%)
42 (20,4%)
35 (17,0%)
14 (6,8%)
1 (0,5%)
114 (55,3%)
Primary indications for implantation
MRI group
(n=258)
Control Group
(n=206)
Tachyarythmie atriale
Atrioventricular block (AVB)
Carotid sinus hypersensitivity
Sinus node dysfunction
Syncope vasovagale
Carotid sinus syndrome
Other
19 (7,4%)
95 (36,8%)
5 (1,9%)
122 (47,3%)
4 (1,6%)
2 (0,8%)
11 (4,3%)
15 (7,3%)
84 (40,8%)
4 (1,9%)
90 (43,7%)
4 (1,9%)
6 (2,9%)
3 (1,5%)
Medical history (at least 1)
MRI group
(n=258)
Control Group
(n=206)
General cardiovascular history
History of cardiovascular surgery
History of atrial arrhythmia
History of ventricular arrhythmia
History of AV junction disorder
234 (90,7%)
94 (36,4%)
204 (79,1%)
55 (21,3%)
160 (62,0%)
84 (32,6%)
189 (91,7%)
71 (34,5%)
156 (75,7%)
31 (15,0%)
131 (63,6%)
54 (26,2%)
Demographic characteristics
Age at implantation
Mean ± standard deviation
Median
Interval
Sex
Male
Patient
characteristics
and group
comparability
Vascular history
No statistical comparison of the characteristics of the groups at inclusion.
Security criterion:
The rate of patients without MRI-related complications in the month following the examination is 100% (n=211).
Starting hypothesis
Results
inherent to the
primary
endpoints
The rate of patients without
complications in the MRI group
is > 90%
N
(MRI per protocol)
211
Rate of patients without complications
P
211/211
100%
<0,001
H0 : pÿ0,90
H1 : p>0.90
Please note: the study distinguishes between information reported as “complications” or as “observations”.
In the study, a complication is defined as an adverse event requiring invasive treatment or cessation of the main functions of the
device without taking into account other treatments. IV or IM drug treatment is considered invasive treatment.
An observation is defined as any adverse event not corresponding to a complication.
Thus, no complications were noted, however 4 observations were reported as potentially linked to MRI: 1 observation of palpitation
and 3 observations of paresthesia.
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Effectiveness criteria:
1. Variation in atrial and ventricular stimulation thresholds at 0.5 ms between the pre-MRI period and 1 month post-MRI
then comparison with the control group.
Starting hypothesis
Measure
The proportion of patients with a
Atrial
N
165
MRI group
variation ÿ 0.5 V is clinically
equivalent, equivalence margin
defined at 10%
Control group 164
Ventricle
190
MRI group
Control group 184
% of success
P
165/165
100%
164/164
100%
190/190
100%
183/184
Test
impossible
<0,001
99,5%
H0: % MRI group success - % control group success ÿÿ
H1: % MRI group success - % control group success <ÿ
2. Amplitude variations detected between the pre-MRI period and 1 month post-MRI then comparison with the group
control.
Starting hypothesis
Measure
N
The proportion of patients having Atrial
a decrease in detected amplitude
ÿ 50% while maintaining
an amplitude ÿ 1.5 mV at the atrial
131
MRI group
% of success
P
124/131
<0,001
94,7%
129/139
Control group 139
92,8%
level and ÿ 5 mV at the ventricular
Ventricle
level is clinically equivalent,
equivalence margin defined at 10%
134
MRI group
130/134
<0,001
97,0%
Control group 136
129/136
94,9%
H0: % MRI group success - % control group success ÿÿ
H1: % MRI group success - % control group success <ÿ
Secondary criteria:
Number of complications related to the SureScan system;
Results
inherent to
secondary
Starting hypothesis
N
Rate of patients without complications
P
The rate of patients without complications
linked to the system
SureScan between inclusion and 4-month
follow-up is > 80%
447
410/447
<0,001
91,7%
H0 : pÿ0,80
H1 : p>0.80
endpoints
Complications related to the systems are detailed below:
Number of
complications
Name of patients
N=467
Pacemaker Events Atrial Lead Events
0
0 (0,0%)
Ventricular Lead Events Programmer
Events Pacemaker Implantation Events Atrial Lead
3
5
3 (0,6%)
5 (1,1%)
Implantation Events Ventricular Lead
Implantation Events Related Events for implantation of the
2
0 (0,0%)
2 (0,4%)
9
9 (1,9%)
20
4
18 (3,9%)
4 (0,9%)
43
37 (7,9%)
atrial and ventricular lead
Total
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Number of patients with events related to poor compliance with instructions related to the MRI exam
No errors related to instructions.
No user-related errors.
Number of ventricular arrhythmias and persistent asystoles during the MRI examination; No
ventricular arrhythmia or persistent asystole attributed to MRI.
Number of adverse events relating to the implant, MRI or implantation (System + MRI): Event-free patient rate 80.3%.
Adverse events relating to the implant, MRI or implantation (system + MRI) are detailed below:
Observations Complications Number of patients
N=467
Pacemaker Events Atrial Lead Events
Ventricular Lead Events Programmer
Events Surgical Procedure Events Pacemaker
6
1
5
Implantation Events Atrial Lead Implantation
Events Implantation Events ventricular lead 1
Events related to implantation of the atrial and ventricular
lead 3 Events related to MRI
0
0
0
4
6 (1,3%)
4 (0,9%)
5 (1,1%)
0 (0,0%)
43 (9,2%)
4 (0,9%)
11 (2,4%)
19 (4,1%)
7 (1,5%)
4
0
4 (0,9%)
48
61
89 (19,1%)
3
18
0
2
9
29 2 2
20
Total
Change in mean lead impedance before and after MRI.
Mean difference in impedance variations ÿ
(IRM group)
Probe atrials -0.6 ± 61.8
Mean difference in impedance variations ÿ
(Control group)
7,3 ± 50,4
-5,7 ± 51,8
Ventricular leads -9.0 ± 48.5
No statistical comparison
Handling of the CapSureFix MRI probe compared to the 5076 probe marketed to date.
Sins
Starting hypothesis
The mean differences in Atriales maneuverability
score are statistically equivalent (ÿ=1.5
Ventricular
units on a scale of -3 to +3)
Average difference*
P
0,15
<0,001
0,18
<0,001
H0: average (5076) – average (5086) ÿÿ
H1: average (5076) – average (5086) <ÿ
Variations in stimulation threshold and amplitude of the MRI and control groups of the 5086 probe compared to the
5076 probe marketed to date (monitoring for 4 months).
Stimulation threshold
Starting hypothesis
Sins
Average difference*
P
The stimulation thresholds
are statistically equivalent
(ÿ=0.5 V)
Atrial
MRI group versus 5076 probe: 0.16
Control group versus Probe 5076: 0.16
p < 0,001
p < 0,001
Ventricular MRI group versus 5076 probe: 0.08
Control group versus Probe 5076: 0.15
p < 0,001
p < 0,001
H0: average (5086) – average (5076) ÿÿ
H1: average (5086) – average (5076) <ÿ
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Amplitude
Starting hypothesis
The statistically
equivalent
East
amplitude (ÿ=0.9 mV for the atrial
amplitude and ÿ= 2.5 mV for the
ventricular amplitude
Sins
Average difference*
P
Atrial
MRI group versus 5076 probe: 0.1
Control group versus Probe 5076: 0.1
p < 0,001
p < 0,001
0
Ventricular MRI Group versus 5076 Probe:
Control group versus Probe 5076: -0.2
p < 0,001
p < 0,001
H0: average (5076) – average (5086) ÿÿ
H1: average (5076) – average (5086) <ÿ
* mean differences obtained from the handling scores of the 5076 probe from a “Medtronik lead model 5076 study cohort”.
Lost to follow-up and study dropouts:
Reasons for leaving study
Number of days postimplantation
Total
Withdrawal of the patient from the study by decision of the investigator
0
14 1
Withdrawal of the patient from the study by decision of the investigator
55
1
Withdrawal of the patient from the study by decision of the investigator
Lost view
93
1
118
1
Inclusion period ended
0
1
Infection staphyloccocus aureus
401
1
On the day of implantation patient with high CRP, refusal of the operation by the surgeon
0
Patient withdrawal from the study based on their decision
0
1
Total
21
Adverse events were classified using the Medical Dictionary for Regulatory Activities (MedDRA).
adverse events
Name of patients
N=484
527
260 (53,7%)
Observations Complications Total
215
Total adverse events 312
Side
effects
Deaths, numbering 11 in the study : 9 in the MRI group (3 deaths before the MRI examination and 6 after the MRI examination). The deaths were
investigated by a committee; none were considered in relation to the implantation of the pacemaker, its lead or the MRI.
A complication is defined as an adverse event requiring invasive treatment or cessation of major device functions without regard to other treatments.
IV or IM drug treatment is considered invasive treatment.
An observation is defined as any adverse event not corresponding to a complication.
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