XPECT StudyPhysician Presentation

XPECT Study1 Purpose

• Quantify the performance of the first implantable leadless cardiac monitor (ICM) with dedicated AF detection capabilities

1 Hindricks G, Pokushalov E, Urban L, Taborsky M, Kuck K. Performance of a new leadless implantable cardiac monitor in detecting and quantifying atrial fibrillation: results of the XPECT trial. Circulation. Arrhythmia and Electrophysiology. Published online February 16, 2010.

Background

Occurrence of Asymptomatic AF and Reliability of Symptoms

1 Strickberger SA, et al. Heart Rhythm. 2005;2:125-131.

Methods:

• “Almost 95% of documented AT episodes were asymptomatic, and symptoms attributed to atrial fibrillation were associated with AT only approximately 15% of the time.”

• “No significant differences in the specific symptoms that correlated with or without a documented atrial tachyarrhythmia were observed.”

• Multicenter trial following 48 patients for 12 months to correlate pacemaker-detected atrial tachyarrhythmia (AT) events with symptoms

Results/Conclusions:

Strickberger1

Unpredictable and Late Recurrences of AF

2 Martinek M, et al. J Cardiovasc Electrophysiol. 2007;18:818-823.

0

24

AT

B (hours/day)

0

24

0

24

0

240

24

0

24

0

24

0

240

24

0

24

0

24

1

2

3

4

5

6

7

8

9

10

11

ID

MONTHS FROM ABLATION

PRE POST

0

24

-36 -24 -12 0 12 24 36 48 60 720

24

13

14

0

2412

Atrial tachyarrhythmia burden plot (ATB, hours per day) in all 14 patients over time. Zero line indicates first ablation procedure; additional late-term ablations are marked by arrows.

Methods:

• “Continuous monitoring is able to detect significantly more AF episodes than routine follow-up. AF may reoccur very late after long-lasting (>1 year) episode-free intervals.”

• Fourteen patients with an implanted pacemaker device were selected for radiofrequency ablation, with a mean follow-up of 41.4 months

Results/Conclusions:

Martinek2

Intermittent and Symptom-Based Monitoring

3 Ziegler P, et al. Heart Rhythm. 2006;3:1445-1452.

Methods:

• “Intermittent and symptom-based monitoring is highly inaccurate for identifying patients with any or long-duration AT/AF and for assessing AT/AF burden.”

• Data from 574 AT500 IPG patients were analyzed retrospectively over 1 year

• Intermittent monitoring was simulated by analyzing data from randomly selected days within a prescribed monitoring window

Results/Conclusions:

Example: Quarterly Holter recordings detect AF in 54% of the patients

with AF, and is correct 29% of the time in ruling out AF in patients.

Ziegler3

Relationship between Atrial Arrhythmia Burden and Stroke Risk

4 Glotzer T, et al. Circ Arrhythm Electrophysiol. 2009;2:474-480.

Methods:

• AT/AF burden ≥ 5.5 hours on any of 30 prior days appeared to double TE risk

• Prospective, observational study analyzing 2,486 patients with ≥ 1 stroke risk receiving pacemakers or defibrillators that monitor atrial tachycardia (AT)/AF burden

• Annualized TE rates were determined according to AT/AF burden subsets: zero, low (< 5.5 hours [median duration of subsets with nonzero burden]), and high (≥ 5.5 hours)

Results/Conclusions:

Glotzer4 AT/AF Burden Subset Annualized TE Rate(95% Confidence

Interval)

Zero AT/AF burden 1.1 [0.8, 1.6] %

Low AT/AF burden (< 5.5 hours) 1.1 [0.4, 2.8] %

High AT/AF burden (≥ 5.5 hours) 2.4 [1.2, 4.5] %

Implications of Varying Levels of AF on Stroke Risk

5 Botto G, et al. J Cardiovasc Electrophysiol. 2009;20:241-248.

Methods:

• “In patients with recurrent AF episodes, risk stratification for thromboembolic events can be improved by combining CHADS2 score with AF presence/duration.”

• Analysis of 568 patients with an IPG and a history of AF

• Three AF groups were considered: patients with < 5-minutes AF on 1 day (AF-free); patients with > 5-minutes AF on 1 day but < 24 hours (AF-5 minutes); patients with AF episodes > 24 hours (AF-24 hours)

Results/Conclusions:

Risk of Thromboembolic EventsBotto5

• Assessment of rhythm

• “To assess freedom from AF, continuous ECG recording is the gold standard.”

• “This gold standard is not available at present, and will be available only using advanced technology (implanted devices or special garments with ECG-recording capabilities and satellite- or GSM-based transmission) in the foreseeable future.”1

• 2009 EHRA position paper on indications for the use of loop recorders

• “…only continuous monitoring is able to elucidate the full amount of symptomatic and asymptomatic AF episodes.”2

Consensus Conference on Trials in AF

1 Kirchhof P, et al. Europace. 2007;9:1006-1023.2 Brignole, et al. Europace. 2009;11:671-687.

IndicationsThe Reveal® XT Insertable Cardiac Monitor is an implantable patient-activated and automatically activated monitoring system that records subcutaneous ECG and is indicated in the following cases:

• Patients with clinical syndromes or situations at increased risk of cardiac arrhythmias

• Patients who experience transient symptoms such as dizziness, palpitation, syncope, and chest pain, that may suggest a cardiac arrhythmia

Reveal® XTImplantable Cardiac Monitor (ICM)• 49.5 minutes of ECG storage, with additional episode logs

(22.5 minutes patient-activated and 27 minutes auto-activated ECG data)

• 3 years longevity

• MRI conditional (tested with 1.5 and 3 Tesla)

• Triggers: AT/AF detection; asystole, Brady, VT/FVT

• Cardiac Compass® summary report

• Histograms (ventricular rate during AF, AF duration)

• Remote patient management through the Medtronic CareLink® Network

Reveal® XT Clinician Manual

• Monitor the patient’s AT/AF burden and the occurrence of asymptomatic episodes of AT/AF, to assess whether medical treatment is necessary or should be adjusted

• Monitor the patient’s ventricular rhythm during atrial arrhythmia episodes, to assess whether a rate control therapy is having the desired effect or needs to be adapted

• Record incidents of symptomatic events to correlate symptoms with cardiac rhythm and aid diagnosis

• Continuously record other patient information that may help you to assess the patient’s condition, such as heart rate variability or patient activity

Information recorded in the Reveal® XT ICM may help you to

monitor and assess the patient’s condition in the following ways:

Source: Reveal ® XT Clinician Manual

AF detection via R-R variability pattern recognition

Atrial Fibrillation Normal Sinus Rhythm

2 minutes

Automatic detection

ICM Detection Algorithm

Source: Reveal ® XT Clinician Manual

• Purpose: – To quantify the AF detection performance of the Reveal® XT ICM

• Method:– Comparative analysis of automatically detected AF episodes

by Reveal® XT ICM and 46 hours of Holter recordings– All arrhythmias detected on the surface ECG were reviewed on a

beat-by-beat basis by a cardiologist (blinded to Reveal® XT ICM data)

• 24 enrolling study sites from Europe and Canada, 247 patients enrolled

• 206 patients included in analysis, 76 (36.9%) had AF during

the study

Study Overview

• Gender: 66.8% male, 33.2% female• Age: 57 ± 10 years (26 – 82 years)

• Hypertension: 55.3%• Diabetes: 7.7% • Prior CVA or TIA: 10.2%

• Any structural cardiovascular disease: 27.6%– CAD: 16.7%– Valvular disease: 6.5%– MI: 5.7%– HF: 2.8%– Nonischemic cardiomyopathy: 1.6%

Results: Patient Population

Correctly detected episodeFalse positive episodes

1:1 Comparison of Holter and ICM Data

Sensitivity 96.1%

Specificity 85.4%

PPV 79.3%

NPV 97.4%

Results (I)Patient detection metrics:247 patients enrolled

206 patients with analyzableHolter recordings

76 patients had AF on Holter 130 patients had no AF on Holter

71 patients had AF burden

> 1% on Holter

5 patients had AF burden

< 1% on Holter

71 patients had

AF classifiedby ICM

3 patients had no AF classified

by ICM

2 patients had

AF classifiedby ICM

111 patients had no AF classified

by ICM

19 patients had AF classified

by ICM

AF Burden (Pearson correlation)

Sensitivity 98.1%

Specificity 98.5%

PPV 91.9%

NPV 99.7%

Results (II)

AF Burden metrics:

AF Episode Detection Performance

Results (III)

• Continuous monitoring with Reveal® XT ICM reliably identifies patients with AF (sensitivity = 96.1%) and correctly confirms the absence of AF (negative predictive value = 97.4%) in patients without AF

• Reveal® XT ICM is the only insertable continuous monitoring device with a dedicated AF detection algorithm and a published clinical study that provides the information physicians need to make informed decisions

Conclusions

• To detect AF in patients who experience transient symptoms or are at high risk for the presence of AF (e.g., cryptogenic stroke)1

• To provide information that may assist in AF patient management strategies such as:1. Determine if an AF patient is in sinus rhythm following a rhythm control

intervention (e.g., antiarrhythmic drugs, cardioversion, ablation) to guide ongoing therapy2

2. Monitor the patient’s ventricular rhythm during AF episodes to assess if rate control therapy is effective or needs to be adapted3 (e.g., beta blockers, AV nodal ablation)

3. Document AF presence and duration to assist in anticoagulation management in intermediate stroke risk patients4 (e.g., CHADS 1 or 2 patients)

When May Continuous Long-Term Monitoring Be an Applicable Option?

1 Kimmel SE, et al. Arch Intern Med. 2007;167:229-235.2 Ziegler P, et al. Heart Rhythm. 2006; 3:1445-1452.3 Ziegler, et al. Poor ventricular rate control in the persistent versus paroxysmal atrial fibrillation population: continuous monitoring data from 141,231 patients in the CareLink® database. Poster submitted HRS, May 2009.4 Botto GL, et al. J Cardiovasc Electrophysiol. 2009;20:241-248.

Backup

Brief StatementIndications9529 Reveal® XT Insertable Cardiac MonitorThe Reveal ® XT Insertable Cardiac Monitor is an implantable patient-activated and automatically activated monitoring system that records subcutaneous ECG and is indicated in the following cases: patients with clinical syndromes or situations at increased risk of cardiac arrhythmias patients who experience transient symptoms such as dizziness, palpitation, syncope, and chest pain, that may suggest a cardiac arrhythmia

9539 Reveal® XT Patient AssistantThe Reveal ® XT Patient Assistant is intended for unsupervised patient use away from a hospital or clinic. The Patient Assistant activates one or more of the data management features in the Reveal Insertable Cardiac Monitor: To verify whether the implanted device has detected a suspected arrhythmia or device related event. To initiate recording of cardiac event data in the implanted device memory.

ContraindicationsThere are no known contraindications for the implant of the Reveal ® XT Insertable Cardiac Monitor. However, the patient’s particular medical condition may dictate whether or not a subcutaneous, chronically implanted device can be tolerated.

Warnings/Precautions9529 Reveal ® XT Insertable Cardiac Monitor

Patients with the Reveal ® XT Insertable Cardiac Monitor should avoid sources of diathermy, high sources of radiation, electrosurgical cautery, external defibrillation, lithotripsy, therapeutic ultrasound, and radiofrequency ablation to avoid electrical reset of the device, and/or inappropriate sensing. MRI scans should be performed only in a specified MR environment under specified conditions as described in the device manual.

9539 Reveal ® XT Patient Assistant

Operation of the Model 9539 Patient Assistant near sources of electromagnetic interference, such as cellular phones, computer monitors, etc., may adversely affect the performance of this device.

Potential ComplicationsPotential complications include, but are not limited to, device rejection phenomena (including local tissue reaction), device migration, infection, and erosion through the skin.

See the device manual for detailed information regarding the implant procedure, indications, contraindications, warnings, precautions, and potential complications/adverse events. For further information, please call Medtronic at 1 (800) 328-2518 and/or consult Medtronic’s website at www.medtronic.com.

Caution: Federal law (USA) restricts this device to sale by or on the order of a physician.

www.medtronic.com

World HeadquartersMedtronic, Inc.710 Medtronic parkwayMinneapolis, MN 55432-5604USATel: (763) 514-4000Fax: (763) 514-4879

Medtronic USA, Inc.Toll-free: 1 (800) 328-2518(24-hour technical support forphysicians and professionals)

UC201004626 EN© Medtronic, Inc. 2010Minneapolis, MNAll Rights Reserved01/2010