determining the risks of mri at 1.5 tesla in patients …wcm/@sop/... · russo, rj. rationale and...

Robert J. Russo, MD, PhDfor the MagnaSafe InvestigatorsThe Scripps Research Institute

Determining the Risks of MRI at 1.5 Tesla in Patients with

Pacemakers and ICDs: The MagnaSafe Registry

Final Results

Disclosures

• Funding has been provided in the form of an unrestricted educational grant or research grant to support the MagnaSafe Registry from:

• Biotronik, Inc.• Boston Scientific/Guidant• St. Jude Medical• Hewitt Medical Research Foundation• Multiple philanthropic sources

• Off-Label Product Use:• MRI for patients with implanted cardiac

devices

• Given the volume of pacemaker (235,000) and ICD (133,000) implants each year in the US*, there are ~ 2.0 M existing/legacy devices in the US, and 6.0 M worldwide.

• Estimated 50-70%** of patients will require an MRI after placement of a cardiac device.

• MRI has become the imaging modality of choice for many disease states without an alternative (ACR Criteria‡).

• Clinical concerns: Lead in a static/pulsed magnetic field may result in transmission of current with local thermal injury, and a decline in pacing electrical properties due to short-term (edema) and long-term (fibrosis) changes.

Background

*Mond, HG, PACE 2011; 34 :1013; * *Multiple industry sources, ‡ACR Appropriateness Criteria, May 2014: acr.org/quality-safety

• REPLACE Trial: Low event rate (4-15 % MACE) with generator replacement ± lead addition1

• H owever, there is a paucity of trial and registry data regarding the risks of lead extraction (0.4-2.0% 2,3,4)

• MagnaSafe Thesis: (1) The heart has great capacity to dissipate heat energy due to a large circulating blood volume and myocardial perfusion (2) Risk of generator/lead removal greatly exceeds risk of MRI.

• Thus, there is great need to determine the risk of MRI for patients with conventional devices who undergo appropriate screening and monitoring

MRI Safety Concerns

1Poole, JE, et al, Circulation 2010; 122:1553 ; 2Hauser, JE, et al, Europace 2010; 12:395 (Manufacturers and User Defined Experience); 3Jones, SO, et al, HRS 2008;5:520; 4Wazni, O, et al (LExICon), JACC 2010;55:579

• The MagnaSafe Registry is a multicenter study • Purpose: To determine the risk of clinically-

indicated Magnetic Resonance Imaging (MRI) at 1.5T for patients with permanent pacemakers and Implanted Cardioverter-Defibrillators (ICD)

• Results:• Allow an informed conversation with patients

who require a clinically-indicated MRI• Used to update AHA/ACC recommendations for

MRI with non-conditional cardiac devicesRusso, RJ. Rationale and design of the MagnaSafe Registry, Am Heart J. 2013; 165:266-72.

ClinicalTrials.gov Identifier: NCT00907361

MagnaSafe InvestigatorsInvestigator(s) Institution CityR Russo Green Hospital La Jolla, CAS Uretsky, S Wolff Advanced Cardio Imaging New York, NY E Martin Oklahoma Heart Inst Tulsa, OKS Mattson Northern Indiana Res Alliance Fort Wayne, INS Higgins, G Tominaga Scripps Memorial Hosp La Jolla, CAC Machado Providence Heart Inst Southfield, MIT Florin Aventura Hospital Aventura, FLC Bloomgarden Aurora St. Luke’s Milwaukee, WIU Birgersdotter-Green UC San Diego La Jolla, CAG Ponce Spectrum Clinical Research Moreno Valley, CAR Schaerf Providence St. Joseph Burbank, CAR Lampert Yale University New Haven, CTD Shah Methodist Hospital/ DeBakey Houston, TXA Arshad The Valley Hospital Ridgewood, NJA Tonkin, J Anderson Intermountain Medical Center Salt Lake City, UTA Rivard, D Wolfe Univ. of Mississippi Med Cen Jackson, MSR Biederman Allegheny General Hospital Pittsburgh, PAJ Rubenstein Medical College of Wisconsin Milwaukee, WIG Tomassoni Baptist Health Lexington Lexington, KYN Boyle UCLA Los Angeles, CAJ Frabizzio, P Aquilina Abington Memorial Hospital Abington, PA

21 enrolling clinical sites

Inclusion Criteria*• Pacemaker or ICD generator implanted after 2001• Device (and leads) from any manufacturer• Scheduled for non-thoracic MRI• Strong clinical indication for MRI (as per ordering MD)

Exclusion Criteria**• Presence of abandoned leads• Active implanted device (other than PPM/ICD)• MRI-Conditional devices• Has an ICD and is pacemaker dependent• Cardiac device in abdominal position • Battery voltage at ERI

*Russo, RJ. Rationale and design of the MagnaSafe Registry, AHJ 2013; 165:266; * *MagnaSafe specific enrollment criteria (in addition to standard MRI requirements)

MagnaSafe Registry Protocol

Pt with cardiac device and MRI clinically indicated

Subjects enrolled

Parameters recorded Device reprogrammed

MRI

Parameter change?

Follow-up interrogation within 7 days

Yes

Parameters recordedBaseline settings restored

No

Follow-up interrogation 3-6 months when

clinically indicated

Follow-up interrogation at 3 mos

Follow-up interrogation at 6 mos

• Study entry requires a physician order stating that the MRI exam is:

• Clinically-indicated

• Assumed; imaging modality of choice for the disease state or anatomic region

• Without acceptable alternative imaging modality

• Monitored: ECG, SaO2


Pre-Scan

Post-Scan

Disable a nti -tachycar dia

therapy

and

Disable pacing and

sensing func tions

(OV O/ ODO)

Patient wi th a Pacemaker

Disable pacing and

sensing func tions

(OV O/ODO)

Patient wi th a n ICD

No

Reprogram to as ynchr o-nous paci ng

mode (VOO/DOO)

and

Disable magnet

response

Yes Yes

MRI

Pacemaker depe nde nt?

Pacemaker depe nde nt?

MRI MRI No MRI

No

Patient wi th a Cardiac Dev ice

• Study is supervised by cardiologist (PM/ICD) and may be observedby an MD/PA/NP

• Not pacemaker dependent:Asymptomatic, intrinsic (sinus) rate of > 40/min; programmed off (ODO)

• Pacemaker dependent: Programmed asynchronous (DOO)

• Magnet response: Off


• Death during the MRI scan

• Generator failure requiring immediate replacement

• Lead failure requiring immediate replacement

• New onset atrial or ventricular arrhythmia during the scan

• Loss of pacemaker capture during the scan*

• Electrical reset

Primary Clinical Outcomes

Russo, RJ. The MagnaSafe Registry, AHJ 2013; 165:266; *For pacemaker-dependent pacemaker patients; pacemaker dependent ICD patients are excluded

Battery VoltageDecrease in Battery Voltage ≥0.04V

Lead Impedance Change in pacing lead impedance ≥ 50 Ω

Change in high-voltage lead impedance ≥ 3 Ω

Lead Threshold Increase in pacing threshold ≥ 0.50 V @ 0.4 ms

Any increase at a wider pulse width

P and R Wave AmplitudeDecrease in P wave measurement ≥ 50%

Decrease in R wave measurement ≥ 25% (50%)

Secondary Clinical Outcomes

• Values were selected by the investigators (Jennifer Cohen, MD)• Reflect literature review and community “Standards-of-Care”• Validated by an internal advisory board (DSMB Chair Guy Curtis)

Clinically-Relevant Parameter Changes

• FDA post-market approval reports: average replacement rate/year (1999-2004) due to malfunction 0.46% pacemakers; 2.1% ICDs*

• Pacemakers: To achieve an upper bound of the 95% CI of 0.5 %, a total of 1000 cases are required if the observed failure rate is 0% (if 1 observed; 95% upper CI is 1.9%)

• ICDs: To achieve an upper bound of the 95% CI of 1.0 %, a total of 500 cases are required if the observed ICD failure rate is 0% (if 0.6% or 3 are observed, the 95% upper bound is 2%)

Sample Size (1500 MRI Studies)

*Maisel, WH, et al, JAMA 2006;295:1901

Investigational Device Exemption (IDE)

• The MagnaSafe Registryprotocol was written after consultation with the Center for Devices and Radiological Health of the FDA

• Asked to apply for an IDEfor the performance of the study (collection of device parameter data; not MRI)

• IDE obtained in April 2009

• The study is not designed to change product labeling (Pacemaker/ICD-IDE)

Medicare Coverage (CMS)

• CMS National Coverage Determination (NCD) stated that MRI with pacemakers was not covered

• Formal request for change to NCD in June 2010; completed period of public comment in August 2010; and a decision memo posted March 2011

• NCD now allows coverage of MRIs in patients with pacemakers or ICDs: “ …if they are performed in a research study, such as MagnaSafe, that meets CED (coverage with evidence development) criteria.”

• The full text of the Decision Memo can be found on the Medicare web site, Analysis (NCA) for Magnetic Resonance Imaging (MRI) (CAG-00399R2)

Baseline Clinical CharacteristicsFinal Results 1500 Cases

Device PM ICD

Number of cases 1000 500

Leads 1928 995**

Mean age, years (SD) 73 (14) 65 (13)

Men (%) 58 61

Mean time since generator implant in years (SD)

3.2 (2.4)* 2.7 (2.2)*

Pacemaker-dependent (%) 28 0

Mean scan length min (SD) 45 (21) 42 (20)

*MRI within 30 days of implant PM 9, ICD 3; 90 days PM 33, ICD 13; * * 34 cases with an LV lead

Anatomic Location of MRI Scan

Brain 35%

Abdomen/Pelvis 5% Other 10%

Joint 10%

Spine 40%

“ Other” category: Carotid MRA, ear, neck, foot, orbit, peripheral MRA; No significant difference when pacemakers are compared to ICDs

Final Results 1500 Cases

(T-spine excluded)

Clinical event PM ICD

Death during the MRI scan 0/1000 0/500

Generator failure requiring immediate replacement 0/1000 1/500‡

Lead failure requiring immediate replacement 0/1924 0/995

Lossof capture during the scan 0/280 n/a

Induced arrhythmia* 5/1000 1/500

Electrical reset 6/1000 0/500

MagnaSafe: Primary Clinical OutcomesFinal Results 1500 Cases

*Five patients with a history of paroxysmal atrial fibrillation on anticoagulation therapy experienced asymptomatic episodes of atrial fibrillation; One patient had no history of

arrhythmia (49 hours); ‡An ICD, inappropriately programmed (tachycardia-therapy active)


Device Failure Requiring Replacement: ICD

• Tachycardia-therapy was inappropriately left in the active mode during the MRI (with bradycardia-therapy disabled)

• Post-MRI the ICD could not be interrogated/reprogrammed

• Immediate generator replacement was required

• Vendor evaluation found the ICD to be fully functional

• With tachycardia therapy active during the exam, the device interpreted the MRI pulses as ventricular fibrillationand repetitive attempts were made to charge the capacitor

• No ICD shocks were delivered during the MRI

MagnaSafe: Atrial Fibrillation

Case Device Paced? Scan History Meds Resolution

1-0541 Bi-V ICD No3 Abd Yes Amio Warfarin Prior to discharge

1-146 Pacemaker4 Yes Brain Yes Sotalol Warfarin ≤ 2 days

1-166 Pacemaker No3 Neck Yes Warfarin ≤ 2 days

1-3901 Pacemaker4 Yes C-spine Yes Warfarin Prior to discharge2

1-401 Pacemaker No Brain Yes5 Warfarin Prior to discharge2

3-076 Pacemaker4 Yes L-spine No No Resolved < 48 hours


1Atrial flutter; 2Required overdrive pacing for conversion; 3(DOO/VOO at minimum values) could not inactivate pacing functions; 4Pacer dependent; paced DOO/VOO; 5High AF burden

MagnaSafe: Partial Electrical Reset

*Paced DOO/VOO during the MRI; * *Paced DOO/VOO mode, set at minimum values


Case Device Scan Paced? Reset Parameters reset

3-066 Pacemaker L-Spine Paced* Partial Patient info; Implant date

6-046 Pacemaker Brain Not paced** Partial Back-up mode

6-070 Pacemaker Brain Not paced** Partial

Multiple pacing parameters;Bipolar to Unipolar

9-030 Pacemaker Brain Not paced Partial Rate parameters

9-043 Pacemaker L-Spine Not paced Partial Patient data and programming parameters

3-219 Pacemaker L-Spine Not paced Partial Patient data, device and lead numbers

Parameter Change Event Pacemaker(n= 1000)

ICD(n= 500)

Battery voltage decrease ≥ 0.04 V 0.4% 7%

Pacing lead threshold increase ≥ 0.5 V* 1% (2%‡) 1% (3%‡)

P-w ave am plitude decrease ≥50% 1% 0.3%

R-wave amplitude decrease ≥ 25% 4% 2%

R-w ave am plitude decrease ≥50% 0% 0.2%

Pacing lead im pedance change ≥50 Ω 3% 4%

H igh-voltage impedance change ≥ 3 Ω N/A 17%

*Measured at a pulse width of 0.4 ms; ‡Any pacing threshold increase at a wider pulse width


MagnaSafe: Secondary Clinical Outcomes

Parameter Change Event (Post MRI – Pre MRI)

Pacemaker(n= 1000)

ICD(n= 500)

Battery voltage (V) 0.00 ± 0.01 -0.01 ± 0.02‡

Pacing lead threshold (V) 0.00 ± 0.15 -0.01 ± 0.15**

P-wave amplitude (V) -0.04 ± 0.60 0.00 ± 0.62

R-wave amplitude (V) -0.10± 1.24* -0.14 ± 1.27**

Pacing lead impedance (Ω) -8.6 ± 22.0‡ -5.6 ± 22.8‡

High-voltage impedance (Ω) N/A 0.0 ± 2.5



A single-sample t-test determining a departure or difference from zero or no change when post-scan and pre-scan measurements are compared: *P= < 0.05, * *P= 0.01, ‡P= < 0.001

Secondary Clinical Outcomes: ImpedanceImpedance Change for ICDs+ Pacemakers (n= 2737 leads)

Atrial Leads (n= 1247)

RV Leads (n= 1490)

10

20

30

40

0

Perc

ent o

f Lea

ds

1% 1%

4% 1%

Impedance ∆ (Post – Pre) in Ω20 40-20 0 60-40

Decrease 54% Increase 19%

No change 27%

10

20

30

40

0-60

-50 Ω + 50 Ω

Decrease 56% Increase 22%

No change 22%

Secondary Clinical Outcomes: ImpedanceCompared ∆ Impedance with ∆ P/R Wave and Threshold

No Correlation with ∆ Im pedance

Pacemakers (r ) ICDs (r )

Obs 95% CI Obs 95% CI

∆ Measured P wave .02 -.05 to .09 -.03 -.14 to .07

∆ Atrial pacing threshold‡ .02 .05 to .09 -.04 -.14 to .07

∆ Measured R wave .08* .02 to .15 .14** .05 to .22

∆ Ventricular pacing threshold‡ -.06 -.12 to .002 -.15† -.24 to -.07

*P= .01, R2= 0.006; * *P= .002, R2= .02, †P< .001; R2= .02; Obs= Observed‡Any pacing threshold increase at any pulse width; n= 1000+ 500

Atria

l Lea

dRV

Lea

d

Secondary Outcomes: Multiple MRI Scans1

1First or previous MRI scan in MagnaSafe; 2Measured at 0.4 ms; No group difference.

Parameter Change Event Multiple1 Single

Battery voltage decrease ≥ 0.04 V 1% 3%

Pacing lead threshold increase ≥ 0.5 V2 1% 1%

P-w ave am plitude decrease ≥ 50% 1% 1%

R-wave amplitude decrease ≥ 25% 5% 3%

R-w ave am plitude decrease ≥ 50% 0% 0.2%

Pacing lead impedance change ≥ 50 Ω 4% 3%

H igh-voltage impedance change ≥ 3 Ω 16% 15%

Multiple Scans in 321 Cases (21%)


Long-Term Effect of MRI Examination

• Patients who did not exceed predefined device parameter values were asked to undergo routine, clinically-indicated re-interrogation within 3-6 months.

• Patients who did exceed one or more predefined device interrogation parameter changes were asked to return for a protocol mandated re-interrogation at: • 7 days, 3 months, and 6 months• Pacemakers 12%; ICDs 29% (High voltage lead Ω)

• Terminal follow up interrogation (3-6 months): All cases 83%, Pacemakers 85%, ICDs 79%

Device Reprogramming During Follow-up

Parameter Change Event PM (%) ICD (%)

Acute/Chronic Acute/Chronic

Battery voltage decrease ≥ 0.04 V 0.4 0 7 4

Pacing lead threshold increase ≥ 0.5 V 2 1 3 2

P-wave amplitude decrease ≥ 50% 1 0.3 0.3 0

R-wave amplitude decrease ≥ 50% 0 0.4 0.2 0

Pacing lead impedance change ≥ 50 Ω 3 2 4 3

H igh-voltage impedance change ≥ 3 Ω n/a 17 12

*Acute: Parameter change rate post-MRI; Chronic: Did not normalize at last follow-up (% cohort total);


MagnaSafe: Acute/Chronic Changes*

Conclusions• In total, 1500 cases have been successfully

enrolled in The MagnaSafe Registry (1.5 Tesla)• One patient experienced a device failure (ICD)

requiring immediate replacement after the MRI as a result of inappropriate device programming

• Six episodes of atrial fibrillation/flutter were detected; No ventricular arrhythmias occurred

• Parameters changes were small, not clinically significant, and did not require reprogramming

• Patients with multiple scans not at increased risk

Conclusions• The MagnaSafe Registry demonstrates that:

• Clinically-indicated non-thoracic MRI at 1.5T • Can be performed with non-conditional

devices at no significant clinical risk • When patients are appropriately screened

and the device is appropriately programmed

• Results of the MagnaSafe Registry may change AHA/ACC recommendations, CMS coverage,and improve access to clinically-indicated MRIfor patients with standard pacemakers and ICDs.

Clinical event PM (%) ICD (%)Obs. 95% CI Obs. 95% CI

Death during the MRI scan 0 0.4 0 0.8Generator failure requiring immediate replacement 0 0.4 0.2‡ 1.3

Lead failure requiring immediate replacement 0 0.2 0 0.4

Lossof capture during MRI 0 0.4 0 0.8

Induced arrhythmia* 0.5 (0.1) 1.2 (0.7) 0.2 1.3

Electrical reset 0.6 1.4 0 0.8


*Five patients with a history of paroxysmal atrial fibrillation on anticoagulation therapy experienced asymptomatic episodes of atrial fibrillation; One patient had no history of

arrhythmia (49 hours); ‡An ICD, inappropriately programmed (tachycardia-therapy active)

Parameter Change Event (Post MRI – Pre MRI)

Pacemaker(n= 1000)

ICD(n= 500)

Battery voltage (V) 0.00 ± 0.01 -0.01 ± 0.02‡

Pacing lead threshold (V) 0.00 ± 0.15 -0.01 ± 0.15**

P-wave amplitude (%) 2.6 ± 31.3* 3.8 ± 32.6*

R-wave amplitude (%) -0.2 ± 13.6 -0.5 ± 13.7

Pacing lead impedance (Ω) -8.6 ± 22.0‡ -5.6 ± 22.8‡

H igh-voltage impedance (Ω) N/A 0.0 ± 2.5



A single-sample t-test determining a departure or difference from zero or no change when post-scan and pre-scan measurements are compared: *P= < 0.05, * *P= 0.01, ‡P= < 0.001

Lead Replacement During Follow-up

Device Scan Lead Event Reported Findings

1 ICD L-spine, Hips

LV Impedance intermittent conduction

Increasing impedance began 4 months post MRI

2 ICD Brain RV RV lead noise Known lead advisory; non-compliant with activity

3 Pacemaker Knee LV Threshold increase

Lead displacement noted on pre-MRI CXR

4 Pacemaker C-spine RV Right sided shaking/jerking

Lead fracture at generator insertion

5 Pacemaker Brain,Liver

RA Threshold after pocket revision

Lead dislodgement; lead tie-down vs MRI (x2)

6 Pacemaker Brain RV RV lead noise reversions

Exposed proximal lead due to external device abrasion

Final Results of 2923 leads scanned (0.21%)

Estimated spontaneous lead mechanical failure rate 2-5%/5 years; Borek and Wilkoff, 2008 (Expected: 58-146 leads)

Final Results 1500 cases

Patient Reported Symptoms: Heating

During and after the MRI study patients are asked to report symptoms of generator-site discomfort (0.4%)

1No parameter change events were noted. 2The patient complained of generator-site “ burning and stinging” which occurred 10 minutes into the exam; symptoms resolved over 5 minutes after removal from the scanner.

Patient Device1 Study Symptom SAR Completed

01-39 PPM L-Spine Heating No Yes

01-226 ICD L-Spine Burning No No2

08-02 ICD Abdomen Pelvis

Shoulder ache

No Yes

18-01 ICD Brain Heating No Yes

Parameter Change Event PM (%) ICD (%)

Battery voltage decrease ≥ 0.04 V 0.4 0 7 4

Pacing lead threshold increase ≥ 0.5 V 2 1 3 2

P-wave amplitude decrease ≥ 50% 1 0.3 0.3 0

R-wave amplitude decrease ≥ 25% 4 2 1 0.1

R-wave amplitude decrease ≥ 50% 0 0.4 0.2 0

Pacing lead impedance change ≥ 50 Ω 3 2 4 3

H igh-voltage impedance change ≥ 3 Ω N/A 17 12

*Parameter change rate post-MRI/Did not normalize at last follow-up (% cohort total)

Final Results 1500 cases

MagnaSafe: Acute/Chronic Changes*

*P< 0.001 by Fisher’s exact test

Secondary Clinical Outcomes: ImpedanceImpedance Change for Pacemakers+ ICDs (n= 2743 Leads)

Additional lead specific events (pacing threshold and measured P/R wave voltage are not associated with a decrease in lead impedance when continuous data are analyzed

Pacemakers ICDs

≤50Ω-49 to 49Ω

≥50Ω ≤50Ω-49 to 49Ω

≥50Ω

Atrial 1/7*(14.3%)

19/878 (2.2%)

0/4 (0%)1/5

(20%)8/349 (2.3%)

1/4 (25.0%)

RV 6/39*(15.3%)

42/952 (4.4%)

0/9 (0%)5/21

(23.8%)20/471 (4.2%)

0/4 (0%)

Events at FU No event % w/FU eventPacing Lead Impedance (P< .001; ∆= 33%; 95% CI= 20 to 46%)

Day 0Event 31 29 52%***

No event 287 1276 18%

Pacing Lead Threshold (P< .001; ∆= 62%; 95% CI= 38 to 80%)

Day 0Event 14 7 67%***

No event 65 1261 5%

P-wave (P< .17; ∆= 16%; 95% CI= -5 to 55%)

Day 0Event 2 6 25%

No event 58 580 9%

R wave (25% cutoff) (P< .001; ∆= 36%; 95% CI= 18 to 55%)

Day 0Event 14 16 47%***

No event 71 592 11%

Battery voltage (P= .99; ∆= -6%; 95% CI= to -63 to 8%)

Day 0Event 0 3 0%

No event 38 646 6%

MagnaSafe: PM Acute/Chronic Changes*

Events at FU No event % w/FU eventPacing Lead Impedance (P< .001; ∆= 39%; 95% CI= 22 to 53%)

Day 0Event 26 16 62%***

No event 184 611 23%

Pacing Lead Threshold (P< .001; ∆= 42%; 95% CI= 24 to 60%)

Day 0Event 16 15 52%***

No event 65 607 10%

P-wave (P= .99; 95%; ∆= -4%; 95% CI= -7 to 91%)

Day 0Event 0 1 0%

No event 11 285 4%

R wave (25% cutoff) (P= .04; ∆= 28%; 95% CI= 0 to 64%)

Day 0Event 3 5 38%*

No event 40 362 10%

Battery voltage (P= .08; ∆= 19%; 95% CI= -3 to 39%)

Day 0Event 13 11 54%

No event 88 161 35%

MagnaSafe: ICD Acute/Chronic Changes*

determining the risks of mri at 1.5 tesla in patients …wcm/@sop/... · russo, rj. rationale and...

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