PICTURE Study P lace of Reveal I n the C are pathway and T reatment of patients with U nexplained R ecurrent Syncop E

SYNCOPE – Background Syncope is common in the general population 1 Syncope accounts for 3- 5% of Emergency Department (ED) visits and 1-3% of all hospital admissions 2,3 Cardiac syncope doubled the risk of death from any cause 4

Challenges in Diagnosing Unexplained Syncope Occurrence of syncope tends to be unpredictable, observers are unlikely to have the opportunity to record ECGs at the time of an event 5 Gold standard of diagnosis: when a correlation between the symptoms and a documented arrhythmia is recorded 6

What did PICTURE aim to do? The PICTURE registry aimed to collect information on the use of the Reveal ® ICM in the patient care pathway and to investigate the effectiveness of the Reveal ICM in the diagnosis of unexplained recurrent syncope and pre- syncope in everyday clinical practice PICTURE was a prospective, multi-center, observational post-marketing study conducted from November 2006 until October 2009 Data was gathered after the publication of the 2004 ESC guidelines and before the new 2009 version became available

To evaluate the time to diagnosis in relation to the timing of the Reveal ® ICM implant PICTURE: Primary Objective

PICTURE Study Plan 88 participating sites in 11 countries –(Austria, the Czech Republic, Denmark, Finland, France, Germany, Israel, The Netherlands, the Slovak Republic, Sweden and Switzerland). A total of 71 sites contributed to patient enrolment Germany Sweden Finland Denmark Netherlands Austria Slovak Rep. Israel France Czech Rep. Switzerland

Patients were eligible if they had recurrent unexplained syncope or pre-syncope Patients were followed up until the first recurrence of a syncopal event leading to a diagnosis or for at least 1 year Study Methods

650 patients enrolled ( ) –570 patients followed-up Average Follow-Up time: 10±6 months Study Methods

Patient Characteristics Age61±17 years Gender54% females Mean age at first syncope55±20 years Primary Indication Unexplained syncope91% Pre-syncope7% Classification missing2% Reveal ® ICM (DX/XT)55% Reveal ® Plus45%

Physicians Consulted and Diagnostic Tests Performed (before Reveal ® ICM implant) 5 Overall, patients had seen an average of 3 different specialists for management of their syncope Most patients (70%) had been hospitalized at least once for syncope, –one third (36%) of these patients had experienced significant trauma in association with a syncopal episode

Diagnostic Tests Performed Before Reveal ® ICM implant 5 Total recruitment570 (100%) Standard ECG556 (98%) Echocardiography490 (86%) Basic laboratory tests488 (86%) Ambulatory ECG monitoring382 (67%) In-hospital ECG monitoring311 (55%) Exercise testing297 (52%) Orthostatic blood pressure measurements 275 (48%) MRI / CT scan267 (47%) Neurological or psychiatric evaluation270 (47%) EEG222 (39%) Carotid sinus massage205 (36%) Tilt test201 (35%) Electrophysiology testing144 (25%) Coronary angiography133 (23%) External loop recording67 (12%) ATP test15 (3%) Other tests52 (9%) No tests performed1 (0%) The median number of tests performed per patient in the total study population was 13 (inter- quartile range ) ” No studies evaluated the use of brain imaging for syncope. CT or MRI in uncomplicated syncope should be avoided.” 6

Results 5 During follow-up, –218 patients (38%) had a recurrence of syncope within 12 months (shaded area) Reveal ® ICMs guided the diagnosis in 170 (78%) patients with recurrent syncope, 75% of these patients had cardiac causes. Blue Line: time to syncopal episode Red Line: time to syncopal episode where Reveal ® ICMs played a role in the diagnosis *Patients were followed for a maximum of 720 days *

Treatment of Patients with Episodes 5 Treatment decisions made in relation to syncope after diagnosis.

Treatment Statistics 5 Pacemaker implantations (86)51% Antiarrhythmic drug therapy7% ICD implantations6% Ablation therapy5% No specific treatment18%

Conclusions PICTURE is the largest observational study to date to evaluate the usage and diagnostic effectiveness of ICMs in the everyday clinical work-up of patients with unexplained syncope 5 Reveal ® ICMs contributed to establishing the mechanism of syncope in the vast majority of patients with a recurrence 5 The PICTURE study found a great diversity and number of physicians consulted, plus a large number of tests performed 5 The findings support the recommendation in the 2009 EXC/HRS Syncope Guidelines that the Reveal ® ICMs should be implanted early rather than late in the evaluation of unexplained syncope 6

References 1. Amer A, et al. Incidence and Mortality Rates of Syncope in the United States. The American Journal of Medicine (2009) 122, Day SC. Et al. Evaluation and outcome of emergency room patients with transient loss of consciousness. Am J Med. 1982;73: Silverstein MD et al. Patients with syncope admitted to medical intensive care units. JAMA. 1982;248: Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347(12): [Framingham Study Population] 5. Edvardsson N, Frykman V, van Mechelin R, et al. Use of an implantable loop recorder to increase the diagnostic yield in unexplained syncope: results from the PICTURE registry. Europace. February 2011; 13(2): Moya A. et al. Guidelines for the diagnosis and management of syncope (version 2009) The Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). European Heart Journal; 2009.

Indications 9529 Reveal ® XT and 9528 Reveal ® DX Insertable Cardiac Monitors The Reveal ® XT and Reveal ® DX Insertable Cardiac Monitors are implantable patient-activated and automatically- activated monitoring systems that record subcutaneous ECG and are 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 ® XT and 9538 Reveal ® Patient Assistants The Reveal ® XT and Reveal ® Patient Assistants are 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. (Model 9539 only) -To initiate recording of cardiac event data in the implanted device memory. Contraindications There are no known contraindications for the implant of the Reveal ® XT or Reveal ® DX Insertable Cardiac Monitors. However, the patient’s particular medical condition may dictate whether or not a subcutaneous, chronically implanted device can be tolerated. Warnings/Precautions 9529 Reveal ® XT and 9528 Reveal ® DX Insertable Cardiac Monitors Patients with the Reveal ® XT or Reveal ® DX 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 Reveal ® XT and 9538 Reveal ® Patient Assistants Operation of the Model 9539 or 9538 Patient Assistant near sources of electromagnetic interference, such as cellular phones, computer monitors, etc., may adversely affect the performance of this device. Potential Complications Potential 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 and/or consult Medtronic’s website at Caution: Federal law (USA) restricts this device to sale by or on the order of a physician. Brief Statement

World Headquarters Medtronic, Inc. 710 Medtronic parkway Minneapolis, MN USA Tel: (763) Fax: (763) Medtronic USA, Inc. Toll-free: 1 (800) (24-hour technical support for physicians and professionals) © Medtronic, Inc Minneapolis, MN All Rights Reserved 02/2011