C-series C60 DR C20 SR C60A3 C20A3. Pacemaker Manual. Caution: Federal Law (USA) restricts this device to sale by or on the order of a physician.

C-series C60 DR C20 SR C60A3 C20A3 Pacemaker Manual Caution: Federal Law (USA) restricts this device to sale by or on the order of a physician.

Contents 1 Device description............................................................. 3 2 Indications and usage.......................................................... 3 3 Contraindications.............................................................. 4 4 Warnings and precautions....................................................... 4 5 Adverse events................................................................ 9 6 Clinical studies............................................................... 12 7 Patient selection and treatment.................................................. 16 8 Patient counseling information................................................... 17 9 Implant procedures........................................................... 17 10 Measuring methods........................................................... 19 11 Technical information.......................................................... 20 1 Device description There are two Vitatron C-series pacemakers, the dual chamber Vitatron C60 DR, and the single chamber Vitatron C20 SR. 1.1 Features Beat-to-Beat mode switching Ventricular Rate Stabilization Atrial synchronization pacing Therapy Advisor Extensive diagnostics Selected Episodes with stored EGM EGM with annotated markers 1.2 Programmer The Vitatron CareLink programmer is used to program Vitatron pacemakers. Other programmers are not compatible. The Vitatron CareLink can be used for the following: to program the full range of parameters and therapies to monitor the pacemaker battery status to perform follow-up measurements and diagnostics The software needed to program the Vitatron C-series pacemakers is Vitatron C-series software. 1.3 About this manual This manual is intended primarily as an implant manual. Regular patient follow-ups should be scheduled after implant. The Reference Manual describes follow-up procedures and programming instructions and gives more extensive descriptions on how the pacemaker operates. 2 Indications and usage 2.1 Usage Vitatron C-series pacemakers are intended for use in patients for whom permanent cardiac pacing is indicated for the treatment of disorders in impulse formation or conduction. 3

2.2 Indications Dual chamber pacing is indicated if AV synchrony needs to be restored to optimize cardiac output (for example, in patients with symptomatic second or third degree AV block). Dual chamber rate responsive pacing modes are of specific benefit to patients with chronotropic incompetence of the sinus node. Rate responsive modes can help patients who have a requirement for an increase in pacing rate, in response to physical activity. Single chamber ventricular pacing can help patients with permanent atrial tachyarrhythmias, including atrial fibrillation and flutter. Single chamber atrial pacing can help patients with symptomatic bradyarrhythmias and normal AV conduction. 3 Contraindications Pacemakers are contraindicated in the following situations: dual chamber permanent supraventricular tachyarrhythmias, including atrial fibrillation and flutter expected aggravation of clinical symptoms (for example, angina pectoris) or congestive heart failure caused by fast heart rates inadequate intracavitary atrial complexes single chamber AAI(R) AV conduction disturbances inadequate intracavitary atrial complexes single chamber VVI(R) known pacemaker syndrome a need for AV synchrony expected aggravation of clinical symptoms (for example angina pectoris) or congestive heart failure caused by fast heart rates 4 Warnings and precautions 4.1 Pacemaker dependent patients 4.1.1 Using unipolar leads Do not use unipolar leads when the pacemaker is programmed to bipolar pacing as this will result in an open circuit and the inability to obtain capture. 4.1.2 Diagnostic modes Never program the diagnostic OOO mode in pacemaker dependent patients. For such patients, use the temporary ODO mode for brief output interruptions. 4.1.3 Ventricular safety pacing Pacemaker dependent patients must have the Ventricular Safety Pacing (VSP) programmed on. Note: This only applies to the Vitatron dual chamber pacemakers. 4.1.4 Area restrictions Patients should consult a physician before entering an area where there are signs placed prohibiting patients with an implanted pacemaker. 4

4.1.5 Effects of extreme conditions The pacemaker may be affected by abnormal impacts, such as those that can occur in contact sports, and high ambient pressures, such as those that can occur when scuba diving. Note: The maximum absolute pressure that the pacemaker can withstand is 300 kpa (44 psi). 4.2 Medical therapy Positioning a magnet or the programming head over the pacemaker switches the pacemaker to asynchronous operation and makes it receptive to programming. Do not use electrocautery, diathermy or any other source of electromagnetic interference near a patient once a magnet, or programming head is in position over the pacemaker. This is because inadvertent programming can result. 4.3 Handling and disposal 4.3.1 Storage The ambient temperature limits for pacemaker storage and handling are 5 C (41 F) to 40 C (104 F). Store the pacemaker package in a dry place away from direct sunlight. The operating temperature range is 22 C (72 F 4.3.2 Handling ) to 45 C (113 F). Normal handling is unlikely to damage the pacemaker, but do not implant the pacemaker under the following circumstances: The pacemaker has been dropped on a hard surface from a height of 30 cm (12 in) or more. This could damage the pacemaker components. The storage package has been pierced or altered. This could render the pacemaker non-sterile. The Use by date has expired. This could adversely affect the pacemaker longevity and sterility. 4.3.3 Use by date Check the Use by date shown on the pacemaker package before opening the sterile pack. The pacemaker loses approximately 10% of the available battery capacity for every 12-month storage period. 4.3.4 Opening the sterile pack Before shipment the pacemaker was sterilized as shown on the package. The sterile pack cover carries an illustration of the opening instructions. Before opening the sterile pack, check for any signs of damage that might invalidate the sterility of the contents. If there is any uncertainty about the sterility, do not implant the pacemaker. Non-sterile pacemakers should be returned to Vitatron. 4.3.5 Explant and disposal Remove the pacemaker before burial or cremation. In some countries, removal of battery-operated implantable devices is mandatory because of environmental concerns; please check local regulations. In addition, the cremation process could cause the battery to explode. Dispose of depleted batteries and worn-out devices according to local regulations. Notes: Vitatron implantable devices are for single use only. Do not resterilize and reimplant explanted devices. Please return explanted devices to Vitatron for analysis and disposal. 5

4.4 Lead evaluation and lead connection 4.4.1 Lead compatibility Vitatron C-series pacemakers are available with IS-1 connectors. Verify connector compatibility before using any lead with this pacemaker. Using an incompatible lead can damage the connector or result in a leaking or intermittent connection. 4.4.2 Pacing and sensing safety margins Consider lead maturation when choosing pacing amplitudes, pacing pulse widths, and sensing levels. 4.4.3 Torque wrench Do not use a torque wrench without a torque limiter as the wrench could have a torque capability greater than the lead connector s design limit. 4.5 Programming and pacemaker operation 4.5.1 Rate increases caused by twiddler s syndrome Twiddler s syndrome is caused by patients manipulating, or twiddling their pacemaker. This can cause temporary increases in the pacing rate if a rate response mode is active. 4.5.2 Continuous myopotentials Continuous myopotentials cause reversion to asynchronous operation. Myopotential sensing is more likely when either the programmed atrial sensitivity is between 0.25 and 1.0 mv, or when the programmed ventricular sensitivity is 1.0 or 1.5 mv. 4.5.3 Rate adaptive pacing Take care when using rate adaptive pacing in patients who are unable to tolerate increased pacing rates. 4.5.4 Ventricular Rate Stabilization When Ventricular Rate Stabilization (VRS) is on, it is important to prevent far-field R-wave sensing (FFRW) as far as possible. An FFRW sense may lead to inappropriate atrial tachyarrhythmia detection, which may result in the activation of VRS after consecutive FFRW senses. 4.5.5 Single chamber atrial modes Do not use single chamber atrial modes in patients with impaired AV nodal conduction as it is not possible to ensure ventricular capture. 4.5.6 Shipping values Before using the pacing amplitude and sensitivity shipping values, verify that they provide adequate safety margins for the patient. In addition, check that both pacemaker and lead have the same polarity. 4.5.7 VDD(R) mode and Flywheel Vitatron advises switching the Flywheel mode off when programming the pacemaker to the VDD(R) mode as the Flywheel mode can prevent a rapid return to atrial tracking. 4.5.8 Crosstalk A to V Crosstalk occurs in dual chamber systems when the ventricular lead senses atrial pacing pulses. Crosstalk results in self-inhibition and is more likely to occur at high sensor-driven rates, high atrial amplitudes, and longer atrial pulse durations. To prevent self-inhibition caused by crosstalk, program VSP on. 6

4.5.9 Ageing and Replace PM indicators After the pacemaker sets the Ageing indicator, Vitatron recommends increasing the frequency of follow-ups. At standard settings, the advised period is three months. Arrange to replace the pacemaker as soon as possible after the pacemaker sets the Replace PM indicator. 4.5.10 Pacemaker partial restore VVI pacing and a magnet rate of 90 min 1 indicate that the pacemaker has partially restored. Note that if the pacemaker is a single chamber model configured to atrial pacing, then the default setting following a partial restore is AAI pacing. Refer to the Reference Manual for more information. 4.5.11 Slow retrograde conduction In dual chamber pacemakers, slow retrograde conduction, especially with a conduction time greater than 400 ms, may induce pacemaker-mediated tachycardia (PMT). 4.5.12 PMT intervention Even with the automatic PMT features in Vitatron C-series dual chamber pacemakers, PMTs may still require clinical intervention, such as pacemaker reprogramming, magnet application, drug therapy or lead evaluation. 4.5.13 Pacemaker syndrome Do not use single chamber ventricular pacing (VVI) for patients with known or suspected pacemaker syndrome. 4.6 Environmental and medical therapy hazards Pacemakers use spontaneous cardiac signals to inhibit or trigger pacemaker output. There are some signals existing in the environment, and during some forms of medical treatment, that have similar characteristics. Certain types of electromagnetic interference (EMI) can damage the pacemaker and could interfere with its operation, possibly leaving the patient without pacing therapy. In some circumstances, these signals can interfere with the pacemaker function. Contact Vitatron if there is concern about any particular patient. 4.6.1 Hospital and medical therapy hazards The influence of medical equipment on pacemaker performance varies considerably according to the type of unit and the energy levels employed. It is advisable in all cases to monitor the pacemaker function during the procedure and to check the pacemaker after the procedure. The following medical devices are likely to be a source of interference. Defibrillation (external) Do not defibrillate with the paddles placed on the skin above the pacemaker. Place the paddles at least 15 cm (6 in) away from the pacemaker and afterwards check that it is functioning properly. Defibrillation currents may cause changes in myocardial tissue with a subsequent loss of capture (increased stimulation threshold) and possibly, a loss of sensing (decreased amplitude of the intracardiac signal). Such changes are usually only temporary. Following defibrillation, perform a normal patient follow-up. Diathermy People with metal implants such as pacemakers, implantable cardioverter defibrillators (ICDs), and accompanying leads should not receive diathermy treatment. The interaction between the implant and the diathermy can cause tissue damage, fibrillation, or damage to device components, which could result in serious injury, loss of therapy, and the need to reprogram or replace the device. Electrosurgical cautery If possible, do not use an electrocautery unit when replacing a pacemaker. Currents generated from such units can cause a permanent loss of output. Spontaneous changes in the programmable parameter values may be observed following cauterization. Electrosurgical cautery could induce ventricular arrhythmias or fibrillation, and may cause asynchronous or inhibited pacemaker operation. If use of electrocautery is necessary, keep both the current path and ground plate as far from the pacemaker and leads as possible. 7

In addition, program the pacemaker to an asynchronous mode (DOO/VOO/AOO). High radiation source Large doses of therapeutic and diagnostic radiation can adversely influence pacemaker function. Therefore shield the pacemaker during exposure, and carefully monitor pacemaker function after exposure to large radiation doses. Continue to monitor the pacemaker function for several weeks, since changes induced by radiation may not be immediately apparent. Lithotripsy Lithotripsy can permanently damage the pacemaker if the pacemaker is at the focal point of the lithotripsy beam. If lithotripsy is required, follow these procedures: Program the pacemaker to single chamber, non-rate responsive mode VVI/AAI or VOO/AOO before treatment. Keep the focal point of the lithotripsy beam at least 5 cm (2 in) away from the pacemaker. Magnetic Resonance Imaging Systems (MRIS) Magnetic resonance imaging of pacemaker patients has resulted in significant adverse effects. The use of MRI in pacemaker patients is therefore contraindicated. If MRI is required, closely monitor pacemaker patients subjected to MRI and verify programmed parameters after the MRI. Limited studies of the effects of MRI on pacemakers have shown the following traits. Magnetic and radio frequency (RF) fields produced by MRI may adversely affect the operation of the pacemaker and may inhibit the pacing output. Magnetic fields may activate magnet mode operation and cause asynchronous pacing. Reported 1 effects of MRI on pacing include increased ventricular pacing beyond the rate limit. Radiofrequency ablation The radiofrequency ablation procedure in a pacemaker patient may cause any of the following events: The pacemaker will pace asynchronously above or below the programmed rate. The pacemaker will revert to asynchronous operation. The pacemaker will reset. The pacemaker will prematurely trigger Replace PM indicators. Reduce the risks with the following procedures: Program the pacemaker to a non-rate responsive, asynchronous pacing mode prior to RF ablation. Avoid direct contact between the ablation catheter and the implanted lead or pacemaker (the advised minimum distance is 1.3 cm (0.5 in) between catheter and lead tip). Position the ground plate so that the current pathway does not pass through or near the pacing system (place the ground plate under the patient s buttocks or legs). Manage the risks with the following precautions: Have a Vitatron programmer available for emergency programming. Have defibrillation equipment available. Computed tomographic x-ray (CT scan) If the patient undergoes a CT scan procedure and the device is not directly in the CT scan x-ray beam, the device is not affected. If the device is directly in the CT scan x-ray beam, oversensing may occur for the duration of the time in the beam. If the duration of the time in the beam is longer than 4 s, take appropriate measures for the patient, such as enabling an asynchronous mode for pacemaker-dependent patients or enabling a non-pacing mode for non-pacemaker-dependent patients. These measures prevent false inhibition and false tracking. After completing the CT scan, restore the desired parameters. Transcutaneous Electrical Nerve Stimulators (TENS) The effects of TENS used in close proximity to the pacing system are dependent on the type of pulse train employed. The most probable effect is a temporary switch, by the pacemaker, to its interference mode (fixed rate pacing at the programmed rate). Temporary inhibition of the pacemaker is, however, also possible. Vitatron recommends closely monitoring the pacemaker function during nerve stimulation. Note: Because of the possible effects on pacemaker function, pacemaker patients should not be allowed to use TENS at home without adequate medical supervision. 1 Holmes, Hayes, Gray et al. The effects of magnetic resonance imaging on implantable pulse generators. Pace. 1986; 9 (3) 360-370. 8

4.7 Home and occupational environment High voltage power transmission lines can generate enough EMI to interfere with pacemaker operation if approached too closely. Communication equipment such as microwave transmitters, linear power amplifiers, or high-power amateur transmitters can generate enough EMI to interfere with pacemaker operation if approached too closely. Commercial electrical equipment such as arc welders, induction furnaces, or resistance welders can generate enough EMI to interfere with pacemaker operation if approached too closely. Home appliances that are in good working order and properly grounded do not usually produce enough EMI to interfere with pacemaker operation. There are reports of pacemaker disturbances caused by electric hand tools or electric razors used directly over the pacemaker implant site. Electronic Article Surveillance (EAS) Some types of EAS equipment, such as those found at store entrances and exits, can temporarily inhibit the pacemaker or cause the pacemaker to partially restore. Vitatron pacemaker wearers should walk through theft prevention systems, preferably through the middle, and not linger close to the theft prevention system. If a pacemaker wearer feels weak or dizzy, move away from the system. Cellular phones Vitatron C-series pacemakers have been tested through the frequency ranges (2 MHz to 3 GHz), used by common cellular phone transmission technologies. Based on this testing, the pacemakers should not be affected by the normal operation of cellular phones using such technologies. Normal operation includes keeping the cellular phone 15 cm (6 in) from the pacemaker. Note: If Vitatron pacemaker wearers experience dizziness or palpitations while using a cellular phone, they should move the phone antenna further away from the pacemaker. Similar symptoms may occur in close proximity to radio or radar transmitters. Moving away from the source will restore normal pacemaker function. 5 Adverse events Adverse events were compiled from the clinical studies of the Diamond II and the Clarity DDDR pacemakers. The Diamond II and Clarity DDDR pacemakers are the full-featured devices that preceded the C-series devices. The C-series devices are an update to the Diamond II and Clarity DDDR pacemaker platform and therefore are functionally equivalent. However, given the change in activity sensor, a strap-on study was conducted to verify the continued appropriateness of the rate response. Since there was no interaction with the device from a biological perspective, adverse events from the strap-on study are not provided here. Because of the similarity between Vitatron C-series devices and Diamond II and Clarity DDDR devices, the observed adverse effects reported during the Diamond II and Clarity clinical studies also apply to Vitatron C-series devices. In addition, a separate clinical study was performed to evaluate the safe and effective operation of the Ventricular Rate Stabilization feature. This feature is included in the C-series devices. Safety data from this study is also provided. 5.1 Diamond II The Vitatron Diamond II DDDR model 820 devices were evaluated in a multicenter prospective study (34 investigational centers, 20 centers in the US, and 14 centers outside the US) of the features and rate response of the device. There were 258 devices implanted in 258 patients worldwide. Mean duration of implant was 15.9 months with a range of 0.03 to 40.1 months. There were a total of eighteen deaths in the study; all were reviewed and judged to be non-device related. Three were attributed to carcinoma, two to sudden death, two to congestive heart failure, two to respiratory distress, two to arteriosclerotic cardiovascular disease, one to asbestosis, one to cardiopulmonary arrest, one to cardiac insufficiency, one to coronary disease, one to myocardial infarction, and two to unknown reasons. 9

A total of four devices were explanted. Two were explanted due to infection of the pacing system. One was explanted for further analysis after an apparent ventricular exit block. Analysis revealed an improperly tightened setscrew to be the most likely cause of this event. One patient required the implant of an ICD, which necessitated pacemaker explantation. In four cases, there was difficulty inserting the ventricular lead. This was subsequently resolved by adapting the connector design within the tolerances of the IS-1 standard. 5.2 Clarity DDDR The study was conducted in two phases, Phase A (eleven European investigational centers) and Phase B (eight European investigational centers). Patients enrolled in both study phases were monitored for adverse events. In Phase A, previously implanted Vitatron Diamond II pacemakers in 63 patients were downloaded with software which modified certain features of the devices to be equivalent to the Clarity DDDR device. In Phase B, 49 patients were implanted with Clarity DDDR devices. Mean device months documented for both studies was 6.1 months (Phase A: 1.05, Phase B: 10.3) with a range of 0 to 14.3 months (Phase A: 0 1.63, Phase B: 3.0 14.3). There was one death in Phase B due to multi-organ failure that was reviewed and judged non-device related. No unanticipated adverse events during either study phase were reported. One device in Phase B was explanted due to the patient having a heart transplant. 5.3 Ventricular Rate Stabilization The Ventricular Rate Stabilization (VRS) feature was evaluated in a separate, multicenter, prospective study (22 investigational centers outside the US). The feature was downloaded into commercially available Clarity DDDR and SSIR pacemakers. The study began on June 24, 2000. As of March 15, 2002 there were 103 patients enrolled. Mean device months of experience with VRS enabled was 2.0 months. There were no deaths and no device explants. 5.4 Observed adverse events 5.4.1 Diamond II Table 1 reports the pacing-related adverse events on a per patient and a per device-year basis in the descending order of frequency. Of the 297 events reported, 88 were pacing-related events. Table 1. Adverse events reported in three or more patients Total number of Number (%) of patients with events Total Total events per deviceyear Event events US (n=146) OUS (n=112) (n=258) (n=342) Any adverse event 297 95 (65.8%) 43 (38.4%) 139 (53.9%) 0.87 Any pacing-related 88 48 (32.9%) 23 (20.5%) 71 (27.5%) 0.26 event Atrial lead dislodgment 13 4 (2.7%) 8 (7.1%) 12 (4.7%) 0.04 Palpitations/rapid 10 10 (6.8%) 10 (3.9%) 0.03 pulse Implant site 8 7 (4.8%) 7 (2.7%) 0.02 discolored/swelling painful/ecchymosis Ventricular lead 7 3 (2.1%) 4 (3.6%) 7 (2.7%) 0.02 dislodgment Atrial undersensing 6 5 (3.4%) 1 (0.9%) 6 (2.3%) 0.018 Inappropriate 4 4 (3.6%) 4 (1.6%) 0.012 ventricular lead connection Infection of pocket/system 3 1 (0.7%) 2 (1.86%) 3 (1.2%) 0.009 10

Table 1. Adverse events reported in three or more patients (continued) Total number of Number (%) of patients with events Total Total events per deviceyear Event events US (n=146) OUS (n=112) (n=258) (n=342) Diaphragmatic 3 3 (2.1%) 3 (1.2%) 0.009 extracardiac stimulation Atrial exit block 3 2 (1.4%) 1 (0.9%) 3 (1.2%) 0.009 Table 2 reports the pacing-related complications (adverse events that required invasive measures to correct) on a per patient and a per device-year basis in the descending order of frequency. Of the 297 adverse events reported, 71 were complications, and 35 of these were pacing-related complications. Table 2. Complications a Number (%) of patients with complications Total Event number of comps. US (n=146) OUS (n=112) Total (n=258) Any adverse event 71 33 (22.6%) 24 (21.4%) 57 (22.1%) 0.21 Any pacing-related 35 12 (8.2%) 20 (17.9%) 32 (12.4%) 0.10 event Atrial lead dislodgment 12 3 (2.1%) 8 (7.1%) 11 (4.3%) 0.04 Palpitations/rapid 0 pulse 0 Implant site discolored/swelling painful/ecchymosis Total comps. per device-year (n=342) Ventricular lead 7 3 (2.1%) 4 (3.6%) 7 (2.7%) 0.02 dislodgment Atrial undersensing 0 Inappropriate 3 3 (2.7%) 3 (1.2%) 0.009 ventricular lead connection Infection of 2 2 (1.8%) 2 (0.8%) 0.006 pocket/system Diaphragmatic 0 extracardiac stimulation Atrial exit block 2 1 (0.7%) 1 (0.9%) 2 (0.8%) 0.006 a Complications (comps.) included those adverse events that required invasive measures to correct (for example, surgical intervention), and were related to the presence of the pacing system or procedure. The following other pacing-related adverse events were reported, but occurred in fewer than three patients: lack of atrial capture, fatigue/exercise intolerance, thrombosis, angina pectoris, inappropriate atrial lead connection, ventricular exit block (loose setscrew), intermittent loss of ventricular capture, elevated atrial threshold, ventricular lead perforation, pneumothorax, twiddler s syndrome, left subclavian vein approach abandoned, inappropriate programming, far-field R-wave sensing, pain in right shoulder, nocturnal palpitations/slow pulse, atrial fibrillation, apparent battery end of life, increased ventricular thresholds, atrial lead repositioned, superior vena cava syndrome, failure to mode switch, pacemaker reset, chest discomfort, lack of ventricular capture, tiredness/dizziness. The following adverse events were deemed not pacing related and occurred in at least two patients (209 events were reported): atrial flutter/fibrillation, chest pain/angina, dizziness, fatigue, dyspnea, cardiomyopathy, congestive heart failure, sleep problems, unstable angina, syncope, palpitations, diverticulosis, intravascular electrode lengths too short due to rapid growth, high blood pressure, urinary tract infection, colon carcinoma, upper respiratory infection, lymphoma, cold, atrial tachycardia, headache, paroxysmal atrial fibrillation, CABG surgery, shoulder stiffness/soreness/pain, acute myocardial infarction, presyncope, nausea, fast heart rate. 11

5.4.2 Clarity DDDR A total of 53 adverse events were reported during the study (Phase A: 5 events, Phase B: 48 events) of which 20 were pacing related. Of the 53 adverse events, nine were classified as complications (adverse events that required invasive measures to correct) of which four were pacing related. Table 3 reports the pacing-related adverse events, including complications, on a per patient and a per device-year basis in descending order of frequency. Table 3. Adverse events reported in two or more patients Number (%) of patients with events Total events per deviceyear Number (%) of patients with comps. Total comps. per deviceyear Event Total number of events (n=112) (n=47.6) Total number of comps. (n=112) (n=47.6) All adverse 53 32 (28.6%) 1.11 9 6 (5.4%) 0.19 events Pacing-related 20 16 (14.3%) 0.42 4 3 (2.7%) 0.08 adverse events Programmer 3 3 (2.7%) 0.06 0 lock-up Pocket pain/ 3 3 (2.7%) 0.06 0 pocket infection Chest pain/ 3 3 (2.7%) 0.06 0 angina Ventricular lead 3 2 (1.8%) 0.06 3 2 (1.8%) 0.06 dislodgment Pneumothorax 2 2 (1.8%) 0.04 1 1 (0.9%) 0.02 The following other pacing-related adverse events were reported, but occurred in fewer than two patients: palpitations, insufficient labeling, shoulder pain, inappropriate programming, increase in lead impedance, intermittent loss of ventricular capture. The following adverse events were deemed not pacing related and occurred in at least two patients (33 events were reported): chest pain/angina, atrial fibrillation, atrial flutter, influenza, and antrumgastritis. 5.4.3 Ventricular Rate Stabilization In the clinical study of the VRS feature, a total of 61 adverse events were reported in 44 patients. One event was device-related, where device-related is defined as related to the pacemaker while VRS is enabled. The one device-related event was pocket stimulation. Of the 61 adverse events, 17 were classified as complications, none of which were device-related. 5.5 Potential adverse events Adverse events associated with pacemaker systems, including those reported in Table 1, Table 2, and Table 3 are: cardiac perforation, cardiac tamponade, death, erosion through the skin, hematoma/seroma, infection, improper operation caused by theft-prevention systems, myopotential sensing, nerve stimulation, muscle stimulation, pacemaker syndrome, rejection phenomena (local tissue reaction, fibrotic tissue formation, pacemaker migration), threshold elevation, and transvenous lead-related thrombosis. 6 Clinical studies The Vitatron C-series platform is an update to the Diamond and Clarity DDDR pacemaker platform. Clinical studies have been conducted on Diamond II and Clarity DDDR pacemakers. The rate response in C-series pacemakers uses a single sensor accelerometer, which replaces the dual sensor piezo-electric activity sensor and QT sensor of the previous devices. The functionality of the activity rate response remains the same. 12

Clinical data from the Diamond II study supports the safety and effectiveness of the features of the Vitatron C-series pacemakers. More recent studies for the Clarity DDDR were only for specific features not available in the C-series. However, given the change in activity sensor, a strap-on study was conducted with the C-series to verify the continued appropriateness of the rate response. In addition, a separate study was conducted to demonstrate the safe and effective operation of Ventricular Rate Stabilization. 6.1 Diamond II 6.1.1 Methods The Diamond II DDDR model 820 pacemaker study was a prospective evaluation of the major device features as well as the dual sensor and single QT sensor rate response of the device. The primary objective was to evaluate dual sensor rate response, a feature not present in Vitatron C-series pacemakers and therefore not presented here. However, a number of secondary objectives were evaluated which are relevant to Vitatron C-series pacemakers. 6.1.2 Objectives During the Diamond II study a number of secondary objectives were evaluated, covering the performance of the following programmable features: auto polarity check, night rate drop, adaptive mode switching and atrial synchronization pacing, rate adaptive AV delay, AV delay hysteresis and AV delay scanning, PVC synchronous atrial stimulation, atrial hysteresis, Flywheel, PMT termination and atrial blanking. 6.1.3 Description of patients In the Diamond II study, a total of 258 patients were enrolled and implanted: median age was 72 years (range: 0.6 to 91 years); 96 patients were female, 162 were male. Patients met the indications for dual chamber pacing: sick sinus syndrome in 161, atrial fibrillation/flutter in 42, and normal AV conduction in 85 patients (patients could have more than one indication). Mean duration of implant was 15.9 months with a range of 0.03 to 40.1 months and a total experience of 4102 patient months. 6.1.4 Study results The results of the evaluation of secondary objectives of the Diamond II study were all satisfactory and support the safety claims of the C-series of pacemakers. 6.2 Vitatron C-series 6.2.1 Methods Given the change in activity sensor, a strap-on study was conducted with the Vitatron C-series to verify the continued appropriateness of the rate response, which was tested using a prospective study at four investigational centers in Europe. The accelerometer was tested in a Vitatron prototype pacemaker strapped to the chest of patients with implanted Vitatron pacemakers in a dual sensor rate response setting. Patients acted as their own control and were asked to perform a graded treadmill exercise test according to the Chronotropic Assessment Exercise Protocol (CAEP). Patients were selected from the general dual chamber pacing population and were required to have had a Vitatron rate-responsive pacemaker implanted for at least one month. They were also required to be able and willing to perform a graded treadmill exercise test. Patients were excluded if they had unstable angina, a history of ventricular tachycardia, a recent myocardial infarction, recent surgery, AF prior to exercise, or if they were restricted by local law because of their age. 6.2.2 Objectives The C-series rate response study had two objectives: 1. Demonstrate that the sensor-indicated rate derived from the input of the accelerometer during a graded exercise test (CAEP) is proportional to the workload. 13

This objective was evaluated using the Metabolic Chronotropic Response model described by Wilkoff as applied by Kay. 2 Patients who performed the treadmill test for at least six minutes with periods of pacing were included in the analysis. 2. Demonstrate that the sensor-indicated rate derived from the input of the accelerometer is comparable to the patient s heart rate (either paced or sensed). This objective was evaluated by defining the difference between the normalized slope of the sensor rate of the strap-on device versus normalized workload and the normalized heart rate versus normalized workload. 6.2.3 Description of patients The strap-on accelerometer study included 32 patients at four European centers. The mean age was 65.6 years (range: 31 to 77.7 years); 12 patients were female, 20 were male. Patients were from the investigator s general pacing population and were required to have a Vitatron rate-responsive pacemaker implanted for at least one month. 6.2.4 Study results The study results are shown in Table 4. Of the 32 patients enrolled in the study, 24 met the inclusion criteria for usage in the analyses. The functionality of the accelerometer was assessed in two ways: by demonstrating that the sensor-indicated rate derived from the input of the accelerometer during a graded exercise test (CAEP) was proportional to the workload by demonstrating that the sensor-indicated rate derived from the input of the accelerometer was comparable to the patient s heart rate (either paced or sensed) The accelerometer performed as expected with sensor rate increasing proportionally to activity (slope = 1.01). The rate determined by the accelerometer and the patient s heart rate were also very similar (difference in slope = 0.04). Table 4. Results of strap-on study Objective Analysis results 95% confidence level Objective 1: 1.01 (0.74, 1.28) Averaged regression slope of normalized heart rate versus normalized workload. Objective 2: Averaged difference in regression slopes of C-series device and the patient s heart rate. 0.04 (0.0, 0.1) 2 Kay, Neal G., Quantification of Chronotropic Response: Comparison for Methods of Rate-Modulating Permanent Pacemakers, JACC 20(7): 1533-41, Dec 1992. 14

0.0 0.2 0.4 0.6 0.8 1.0 Figure 1. Normalized sensor-indicated rate versus expected rate during CAEP Normalized Strap-on Sensor Rate Expected (Wilkoff) SIR Mean Normalized SIR 95% Confidence Bounds 0.0 0.2 0.4 0.6 0.8 1.0 Normalized Workload There were no patient deaths during the study. The study was terminated prematurely in five patients (one failed to meet the inclusion/exclusion criteria, two had unsuccessful Fast Learn procedures, one had problems with the treadmill during the first visit and programming problems at the second, and one patient s knee collapsed during the exercise test). Based on the results of the strap-on study and of previous studies, the Vitatron C-series implantable pulse generators were shown to function appropriately. 6.3 Ventricular Rate Stabilization (VRS) The RASTAF (Rate Stabilization in Atrial Fibrillation) II study was designed to demonstrate the safe and effective operation of VRS for single and dual chamber pacemaker applications. VRS was clinically evaluated in a multicenter, prospective, randomized and single-blind, crossover study. 6.3.1 Methods The performance of VRS was determined by comparing the ventricular irregularity observed during two 2-month crossover periods, one period with VRS disabled and one period with VRS enabled. The study was performed in patients who received Clarity DDDR and Clarity SSIR pacemakers with a standard unipolar or bipolar pacing lead. The investigational VRS software was temporarily downloaded into the Clarity DDDR and Clarity SSIR pacemakers. Patients with permanent atrial fibrillation (AF) received single chamber Clarity SSIR devices. The performance of the VRS feature in these patients was evaluated by means of the 24-hour ambulatory Holter recordings. Patients with paroxysmal AF were implanted with dual chamber Clarity DDDR devices. In these patients the performance of VRS was evaluated by means of the pacemaker diagnostic Selected Event Recording. Patients were randomized in the order in which VRS was enabled and disabled. 6.3.2 Objectives The primary objective of the RASTAF II study was to demonstrate the effectiveness of VRS in reducing ventricular irregularity. 15

The mean absolute difference (MAD) of successive VV intervals was determined from the 24-hour ambulatory Holter recordings and the pacemaker Selected Event Recording. The MAD was calculated for both patient groups, VVIR and DDDR, with and without VRS programmed on. 6.3.3 Description of patients In the RASTAF II study, the data from 101 patients was analyzed in 22 centers in Europe and Canada. The mean age was 68.9 years (with a standard deviation of 9.0 years). The mean age in the VVIR patient group was 69.5 years (with a standard deviation of 9.8 years). The mean age in the DDDR patient group was 68.4 years (with a standard deviation of 8.2 years). There were 52 males (28 in the VVIR and 24 in the DDDR patient group) and 49 females (24 in the VVIR and 25 in the DDDR patient group). The cumulative total number of device months of experience was 204.5 months with VRS enabled. 6.3.4 Study results The data from 10 VVIR patients who performed a 24-hour ambulatory Holter recording was included in the analysis for the primary objective. The Selected Event Recording data of 13 DDDR patients was also included in the analysis for the primary objective. A summary of the data is provided in Table 5. Table 5. Summary of Study Data Study Group VRS off VRS on P-value off vs on MAD (ms) VVIR (N=10) 134 ±44 95 ±28 0.0032 MAD (ms) DDDR (N=13) 116 ±49 64 ±43 0.0145 The study results showed that the primary objective was met, both in the VVIR and the DDDR patient group. VRS reduces the ventricular irregularity (expressed in MAD of successive VV intervals) in patients with conducted AF, in VVIR patients (p-value 0.0032) and in DDDR patients (p-value 0.0145). 7 Patient selection and treatment The following basic decision tree is an aid in selecting the best pacing mode for a particular patient. Figure 2. Basic decision tree (from den Dulk, K et al. Selection of the optimal pacing mode. The Netherlands Journal of Cardiology 1992; 5:214-225) Sinus Node Dysfunction Permanent Atrial Fibrillation/Flutter? AV Block Y N AV Block Y AV Block Y N Y Paroxysmal Atrial Fibrillation/Flutter? Paroxysmal Atrial Fibrillation/Flutter? Y N Y N Y DDDR + MS DDD(R) AAI(R) DDDR + MS DDD/VDD VVIR 16

8 Patient counseling information Physicians should consider the following points in counseling the patient about this device: Providing the patient with a (temporary) pacemaker ID card. Tell them that a permanent ID card will be issued by the pacemaker manufacturer. The need to notify other health care providers of the presence and type of pacemaker. Examples of other health care providers are dentists, physical therapists, anesthesiologists, and surgeons. Informing the patient on the symptoms of pacemaker syndrome (single chamber mode), and of twiddler s syndrome and its consequences. 9 Implant procedures 9.1 Pacemaker package contents Pacemaker Torque wrench (hex) Individual technical specification sheet Device tracking registration form Removed product report Temporary ID-card Warranty card Patient manual 9.2 Implant Implant techniques vary according to the physician s preference, the patient s anatomy and the patient s physical condition. For a more extensive description of implant procedures and methods, please refer to the professional literature on the subject. Warning: The use of silicone grease or medical adhesive is strictly prohibited. Cautions: Only use the torque wrench supplied with this pacemaker. The torque wrench is designed to slip when overtorqued to prevent damage to the socket or the setscrews. Care should be taken when there is a need to loosen a setscrew because if unscrewed too far it may disengage from the connector block. Bending the wrench may break it. The torque wrench is designed for single use only. If the torque wrench is dropped onto the floor it should not be used. 9.2.1 Lead compatibility and polarity Vitatron C-series pacemakers are compatible with unipolar or bipolar IS-1 leads (acute or chronic). The programmed polarity is specified on the pacemaker package. When unipolar leads are connected to the pacemaker, the polarity must be programmed to unipolar. When the pacing polarity is reprogrammed from unipolar to bipolar the pacemaker checks if a bipolar lead is actually implanted by measuring the bipolar lead impedance. When the measured lead impedance is below 200 Ω or above 2 kω the programmer assumes that no bipolar lead is connected and displays a warning. Warning: Do not reprogram pacemakers co-implanted with an ICD device to unipolar pacing. 9.2.2 Lead connection Refer to the lead manual for information on how to implant the lead and test its performance. 17

Connect the leads in the following way: 1. If implanting a dual chamber pacemaker, correctly identify the atrial and ventricular leads and the corresponding pacemaker connector holes (see Figure 3). A single chamber pacemaker is shown in Figure 4. Figure 3. Dual chamber lead connection Figure 4. Single chamber lead connection 2. If implanting a dual chamber pacemaker, start by connecting the ventricular lead. 3. Make sure that the lead connector is clean. 4. Push the lead firmly into the pacemaker connector. The lead connector can be lubricated with saline solution or sterile water, if required. 5. If lead insertion is difficult, check to see if the setscrew is blocking the lead. If so, insert the torque wrench and loosen the setscrew with one or two counterclockwise revolutions, until the connector hole is unobstructed. 6. Make sure that the lead connector has been fully inserted and that the terminal pin is visible behind the connector block (see Figure 5). Figure 5. Lead insertion 1 Dual chamber connection 2 Single chamber connection 7. Carefully push the torque wrench through the self-sealing plug without damaging the plug (see Figure 6). 18

Figure 6. Tightening the setscrews 1 Dual chamber 2 Single chamber 8. Tighten the setscrews by turning the torque wrench clockwise until it begins to click. 9. Again check that the lead connector has been fully inserted and that the terminal pin completely fills the hole behind the connector block (see Figure 5). 10. Make sure that the lead is securely fastened by gently pulling it. 11. Now repeat steps 3 to 10 for the atrial lead. 9.2.3 Securing the pacemaker Use the suture hole to secure the pacemaker to the underlying tissue to minimize rotation and migration of the device after implant. Use normal surgical needles to penetrate the suture hole. Caution: When using the suture hole, take care not to damage the connector, or the self-sealing plugs, with the needle tip. 9.3 Post-implant configuration When the pacemaker detects the connection of an implanted lead, post-implant configuration starts automatically. Once configuration has ended, after about two hours, the pacemaker automatically programs the implant date. Setting the implant date activates the diagnostic features. 9.4 Pacemaker replacement When replacing an implanted pacemaker, you may require an adaptor to connect the new pacemaker to the implanted lead(s). For further information please contact your Vitatron representative. 10 Measuring methods Important parameters such as pulse duration, pulse amplitude and sensitivity are factory measured at the standard conditions of 37 C (98.6 F), 60 min 1, 3.75 V, 0.4 ms, 2.0 mv, VVI, 100% pacing, 500 Ω load. Pulse duration Pulse duration is measured at one third of peak voltage according to standard EN 45502-2-1 (2003) (see Figure 7). 19

Figure 7. Pulse duration and amplitude 10 µs 1 V peak 2 Pulse duration 3 Pulse amplitude Pulse amplitude The pulse amplitude is defined as the voltage deflection from the base line measured 10 µs into the pulse (see Figure 7). The amplitude according to standard EN 45502-2-1 (2003) is 0.90 x this value at a pulse duration of 0.4 ms and with a 500 Ω load. Sensitivity The atrial and ventricular sensitivity are defined as the voltage amplitude of a standard EN 45502-2-1 (2003) test signal that is just sufficient to be sensed by the pacemaker (see Figure 8). Figure 8. P-wave and R-wave test signal 15 ms 2 ms 1 Amplitude Notes: When measuring the pacing and sensing parameters with pacing systems analyzers it should be realized that considerable differences may be observed when the results are compared with the specifications presented in this manual, because the measuring methods employed by such systems may differ from those described here. Lead impedance measurement results may be disturbed by electrocardiogram monitoring equipment. 11 Technical information Table 6. Mode Vitatron C60 DR Vitatron C20 SR DDDR DDIR DDD a DDI DOO VDDR VDD VVIR VVI a VVT 20

Table 6. Mode (continued) Vitatron C60 DR Vitatron C20 SR VOO AAIR AAI AAT AOO OOO a Delivery setting. Table 7. Physical characteristics Model name Vitatron C60 DR Vitatron C20 SR Model number C60A3 C20A3 Dimensions 50.9 x 45.9 x 7.25 a mm 46.8 x 45.9 x 7.25 a mm Mass 28.6 (±0.5) g 27.3 (±0.5) g Volume 12.7 (±0.5) cm 3 11.9 (±0.5) cm 3 Surface area 33.1 cm 2 33.1 cm 2 X-ray identification b VF VF Connector IS-1 dual chamber IS-1 single chamber a Connector thickness may vary. b See Figure 9 for exact location. Figure 9. Location of x-ray identification 1 Dual chamber pacemaker 2 Single chamber pacemaker Table 8. Calculated lifetime (after 18 months shelf life) Model Mode 2.5 V 5.0 V 500 Ω 300 Ω 500 Ω 100% pacing 100% pacing 100% pacing 70 min 1, 0.5 ms 70 min 1, 0.5 ms 70 min 1, 0.5 ms Vitatron C60 DR DDDR 6.8 years 6.0 years 3.5 years Vitatron C20 SR VVIR 10.3 years 9.4 years 6.5 years Note: During periods in which the pacemaker senses high frequency atrial rhythms, especially AF, there will be an increase in power consumption. This will result in a reduction in battery lifetime. As an example, battery life could be reduced by 15% if the pacemaker were to sense an AF rhythm of 300 min 1 through 25% of the pacemaker lifetime. 21

Table 9. Calculated lifetime (after 4 months shelf life) Model Mode 2.5 V, 500 Ω 100% pacing 50% pacing 100% inhibited 70 min 1 0.5 ms 60 min 1 0.4 ms 70 min 1 0.5 ms 60 min 1 0.4 ms 70 min 1 0.5 ms Vitatron C60 DR DDDR 7.5 years 8.6 years 8.7 years 9.7 years 10.3 years Vitatron C20 SR VVIR 11.1 years 12.1 years 12.4 years 13.3 years 14.0 years Table 10. Exposed materials Item Can Connector Material Titanium Polyether-Urethane (PUR) and silicone rubber Table 11. Magnet mode Parameter Magnet pacing mode Magnet rate, battery status Good Magnet rate, battery status Ageing Magnet rate, battery status Replace PM Rate Fixed rate pacing in programmed mode. 100 min 1 (600 ms) 95 min 1 (630 ms) 86 min 1 (700 ms) Warning: In magnet mode the pacemaker operates in an asynchronous pacing mode. If the intrinsic rate is higher than the magnet rate, this may induce ventricular tachycardia or ventricular fibrillation. Table 12. Pacing and sensing parameters Delivery settings per model Parameter name Range Vitatron C60 DR Vitatron C20 SR Lower rate 40 (5) 130 min 1 60 min 1 60 min 1 Maximum pacing rate 90 (5) 170 min 1 120 min 1 120 min 1 Maximum tracking rate 90 (5) 190 min 1 140 min 1 Pulse amplitude 0.5 (0.25) 4.0 (0.5) 8.0 V 3.75 V 3.75 V Pulse duration 0.1 (0.05) 1.0 ms 0.4 ms 0.4 ms Atrial sensitivity Uni:0.5 (0.1) 1.0 0.7 mv 0.7 mv 1.0 (0.5) 7.5 mv Bi:0.25,0.3 (0.1) 1.0 1.0 (0.5) 7.5 mv Ventricular sensitivity 1.0 (0.5) 10 mv 2.0 mv 2.0 mv Sensing/pacing polarity unipolar, bipolar bipolar bipolar Atrial blanking on VP 50 (25) 300 ms 150 ms Atrial blanking on VS 25 (25) 150 ms 50 ms Ventricular blanking on AP 20 (5) 50 ms 30 ms Ventricular Safety Pacing On, Off On Atrial refractory period a 250 (10) 500 ms 330 ms 330 ms Ventricular refractory period 250 (10) 500 ms 260 ms 330 ms Maximum Sensed AV delay 45 (5) 260 ms 120 ms Maximum Paced AV delay 80 (5) 300 ms 160 ms SAV/PAV offset 20 (5) 50 ms 40 ms Adaptive AV delay Off, Median b, Fast c Median a Only applies to atrial-only modes. b Median = 5 ms per atrial rate change of 10 min 1. c Fast = 10 ms per atrial rate change of 10 min 1. 22

Table 13. Tolerances (valid between 22 C (72 F ) and 45 C (113 F) throughout the pacemaker lifetime) Parameter Tolerance Lower rate [ min 1 ] Programmed value ±15 ms Maximum pacing rate [ min 1 ] Programmed value ±15 ms Maximum tracking rate [ min 1 ] Programmed value ±15 ms Pulse amplitude [ V] Programmed value 1.0 : +40%/ 10% Programmed value > 1.0 4.0 : +20%/ 10% Programmed value > 4.0 7.0 : +10%/ 10% Programmed value > 7.0 : +10%/ 20% Pulse duration [ ms] Programmed value -0.02/+0.04 Atrial sensitivity [ mv] Programmed value ±(10% +0.16) at 37 C (99 F) Ventricular sensitivity [ mv] Programmed value ±(20% +0.16) at 37 C (99 F) Blanking period [ ms] Programmed value ±15 Refractory period [ ms] Programmed value ±15 Sensed or paced AV delay [ ms] Programmed value ±15 SAV/PAV offset [ ms] Programmed value ±15 Lead impedance [ Ω] Measured value ±(20% +20) Battery voltage [ V] Measured value ±0.03 a Add ±10% over temperature range 22 C (72 F) to 45 C (113 F). Table 14. Electrical specifications Characteristic Value Output capacitor 3.4 µf Input impedance: atrium 100 kω Input impedance: ventricle 100 kω Current/Energy consumption DDDR DDD VVIR VVI Pacing a 24.2 µa 23.7 µa 15.4 µa 14.8 µa Inhibited 12.9 µa 12.3 µa 9.4 µa 8.9 µa a 100% pacing at 60 min 1, 3.75 V, 0.4 ms, 500 Ω. Table 15. Power source Characteristic Value Cell type Pi 223 lithium iodine Voltage 2.8 V (RRT a 2.6 V) Capacity 1.4 Ah (RRT a 0.1 Ah) Battery manufacturer MECC a RRT = Recommended Replacement Time. Table 16. Emergency settings Mode a VVI AAI Lower rate 60 min 1 60 min 1 Pulse duration 1.0 ms 1.0 ms Pulse amplitude 7.5 V 5.0 b V Sensitivity 2.0 mv 0.7 mv Refractory period 400 ms 400 ms Polarity (pacing and sensing) unipolar unipolar a Mode is VVI, except for single chamber pacemakers programmed to AXX mode. b Keeps value if greater than 5 V. 23