Mintek LV-T, LV User Manual

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Stratos

Family of Cardiac Resynchronization

Therapy Pacemakers

Technical Manual

Stratos CRT-Ps

Implantable Cardiac Resynchronization Therapy Pacemakers

Stratos

X-Ray identification

Radiopaque Identification

A radiopaque identification code is visible on standard x-ray, and identifies the pulse generator:

Stratos LV/LV-T

CAUTION

Lead / CRT-P Compatibility – Because of the numerous

available 3.2-mm configurations (e.g., the IS-1 and VS-1 standards), lead/ CRT-P compatibility should be confirmed with the CRT-P and/or lead manufacturer prior to the implantation of the system.

IS-1, wherever stated in this manual, refers to the international standard, whereby leads and generators from different manufacturers are assured a basic fit. [Reference ISO 5841-3:1992(E)].

Stratos LV/LV-T Technical Manual i

Contents

1. General ..............................................................................1

1.1 Device Description ........................................................1

1.2 Indications .....................................................................2

1.3 Contraindications ..........................................................3

1.4 Note to Physician ..........................................................3

1.5 Warnings and Precautions ............................................3

1.5.1 Interactions with Other Medical Therapy...............4

1.5.2 Storage and Sterilization .......................................6

1.5.3 Lead Connection and Evaluation ..........................7

1.5.4 Programming and Operation.................................8

1.5.5 Home Monitoring ................................................. 11

1.5.6 Electromagnetic Interference (EMI) ....................13

1.5.7 Home and Occupational Environments...............13

1.5.8 Cellular Phones ................................................... 14

1.5.9 Hospital and Medical Environments....................15

1.5.10 Device Explant and Disposal............................... 15

1.6 Potential Effects of the Device on Health.................... 16

1.7 Clinical Studies............................................................17

1.7.1 Stratos LV Clinical Study – AVAIL CLS/CRT ......17

1.7.2 Stratos LV Clinical Study – OVID study ..............39

1.7.3 AVAIL and OVID Combined Primary

Endpoint-Complication-free Rate (Safety) ..........47

1.7.4 Tupos LV/ATx Clinical IDE Study -

OPTION CRT/ATx...............................................49

1.7.5 Conclusions Drawn from Studies ........................ 61

2. Programmable Parameters............................................63

2.1 Pacing Modes..............................................................63

2.1.1 Rate-adaptive Modes ..........................................63

2.1.2 DDD.....................................................................63

2.1.3 DDI ......................................................................67

2.1.4 DVI....................................................................... 67

2.1.5 VDD ..................................................................... 67

2.1.6 AAI and VVI .........................................................68

2.1.7 AAI, VVI ............................................................... 68

2.1.8 AOO, VOO...........................................................68

2.1.9 DOO ....................................................................68

2.1.10 VDI.......................................................................68

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2.1.11 OFF (ODO) ..........................................................69

2.2 Biventricular Synchronization of the Stratos CRT-Ps..69

2.3 Timing Functions .........................................................70

2.3.1 Basic Rate ...........................................................70

2.3.2 Rate Hysteresis ...................................................71

2.3.3 Scan Hysteresis...................................................72

2.3.4 Repetitive Hysteresis...........................................74

2.3.5 Night Mode ..........................................................75

2.3.6 Refractory Periods...............................................76

2.3.7 Atrial PMT Protection...........................................77

2.3.8 Ventricular Refractory Period ..............................78

2.3.9 AV Delay..............................................................78

2.3.10 VES Discrimination after Atrial Sensed Events ...80

2.3.11 Sense Compensation ..........................................80

2.3.12 Ventricular Blanking Period .................................81

2.3.13 Safety AV Delay ..................................................81

2.4 Pacing and Sensing Functions....................................82

2.4.1 Pulse Amplitude and Pulse Width .......................82

2.4.2 Sensitivity ............................................................83

2.4.3 Lead Polarity........................................................83

2.5 Automatic Lead Check ................................................84

2.6 Antitachycardia Functions: ..........................................86

2.6.1 Upper Rate and UTR Response .........................86

2.7 Wenckebach 2:1..........................................................86

2.8 Mode Switching ...........................................................88

2.9 PMT Management....................................................... 89

2.9.1 Protection ............................................................89

2.9.2 PMT Detection.....................................................90

2.10 Adjustment of the PMT Protection Window.................91

2.11 Atrial Upper Rate.........................................................92

2.12 Preventive Overdrive Pacing (Overdrive Mode) .........92

2.13 AES Detection and Pacing..........................................94

2.13.1 AES Detection .....................................................94

2.13.2 Post AES Stimulation ..........................................95

2.14 Parameters for Rate-Adaptive Pacing ........................95

2.14.1 Rate-Adaptation...................................................95

2.14.2 Sensor Gain.........................................................96

2.14.3 Automatic Sensor Gain .......................................96

2.14.4 Sensor Threshold ................................................97

2.14.5 Rate Increase ......................................................97

Stratos LV/LV-T Technical Manual iii

2.14.6 Maximum Activity Rate ........................................ 98

2.14.7 Rate Decay ..........................................................98

2.15 Sensor Stimulation ......................................................98

2.16 Rate Fading................................................................. 99

2.17 Home Monitoring (Stratos LV-T)................................100

2.17.1 Transmission of Information ..............................102

2.17.2 Patient Device ...................................................103

2.17.3 Transmitting Data ..............................................103

2.17.4 Types of Report Transmissions ........................105

2.17.5 Description of Transmitted Data........................107

2.18 Statistics ....................................................................109

2.18.1 Timing ................................................................109

2.18.2 Arrhythmia .........................................................109

2.18.3 Sensor ...............................................................109

2.18.4 Sensing..............................................................109

2.18.5 Pacing................................................................109

2.18.6 General Statistical Information ..........................110

2.19 Interrogating and/or Starting Statistics ......................110

2.20 Timing Statistics ........................................................ 111

2.20.1 Event Counter.................................................... 111

2.20.2 Event Episodes.................................................. 111

2.20.3 Rate Trend.........................................................112

2.20.4 Atrial and Ventricular Rate Histogram ...............112

2.21 Arrhythmia Statistics.................................................. 113

2.21.1 Tachy Episode Trend ........................................113

2.21.2 AF Classification................................................113

2.21.3 AES Statistics ....................................................114

2.21.4 VES Statistics ....................................................115

2.22 Sensor Statistics........................................................ 116

2.22.1 Sensor Rate Histogram .....................................116

2.22.2 Activity Report ...................................................117

2.22.3 Sensor Optimization ..........................................117

2.23 Sensing Statistics ...................................................... 117

2.24 Pacing Statistics ........................................................ 118

3. Follow-up Procedures.................................................. 119

3.1 General Considerations ............................................119

4. Real-Time IEGM ............................................................121

4.1 IEGM Recordings......................................................121

iv Stratos LV/LV-T Technical Manual

5. Battery, Pulse and Lead Data ......................................123

5.1 Threshold Test - Testing the Pacing Function ...........123

5.2 P/R Measurement - Testing the Sensing Function....124

5.3 Testing for Retrograde Conduction ...........................125

5.4 Non-Invasive Programmed Stimulation (NIPS).........125

5.4.1 Description.........................................................125

5.4.2 Burst Stimulation ...............................................126

5.4.3 Programmed Stimulation...................................126

5.4.4 Back up Pacing..................................................126

5.4.5 NIPS Safety Features........................................127

6. Other Functions/Features............................................129

6.1 Temporary Programming...........................................129

6.2 Patient Data Memory.................................................130

6.3 Safe Program Settings ..............................................130

6.4 Magnet Effect ............................................................131

6.5 Position Indicator.......................................................131

6.6 Pacing When Exposed to Interference .....................132

7. Product Storage and Handling....................................135

7.1 Sterilization and Storage ...........................................135

7.2 Opening the Sterile Container...................................136

7.3 Pulse Generator Orientation .....................................138

8. Lead Connection ..........................................................139

8.1 Lead Configuration....................................................139

8.2 Lead Connection .......................................................140

9. Elective Replacement Indication (ERI).......................145

10. Explantation ..................................................................149

11. Technical Data...............................................................151

11.1 Available Pacing Modes............................................151

11.2 Pulse- and Control Parameters................................. 151

11.3 Diagnostic Memory Functions...................................156

11.4 Home Monitoring (Stratos LV-T)................................156

11.5 Additional Functions..................................................157

11.6 Programmers.............................................................158

11.7 Default Programs ......................................................159

11.8 Materials in Contact with Human Tissue...................159

11.9 Electrical Data/Battery...............................................159

11.10 Mechanical Data ..................................................160

Stratos LV/LV-T Technical Manual v

12. Order Information.........................................................161

Appendix A ..........................................................................163

vi Stratos LV/LV-T Technical Manual Stratos LV/LV-T Technical Manual 1

1. General

1.1 Device Description

The Stratos LV and Stratos LV-T CRT-Ps are rate adaptive pacemakers designed to provide Cardiac Resynchronization Therapy (CRT). The Stratos CRT-Ps provide all standard bradycardia pacemaker therapy with the additional capabilities of biventricular pacing for CRT. Biventricular pacing in the Stratos CRT-Ps can be programmed to initially pace in either the right or left ventricular chambers with separately programmable outputs for both left and right channels. Sensing of cardiac signals only occurs in the right ventricular chamber.

The Stratos CRT-Ps can also provide single and dual chamber pacing in a variety of rate-adaptive and non-rate adaptive pacing modes. Pacing capability is supported by an extensive diagnostic set. For motion-based rate-adaptation, the Stratos CRT-Ps are equipped with an internal accelerometer. This sensor produces an electric signal during physical activity of the patient. If a rate-adaptive (R) mode is programmed, then the accelerometer sensor signal controls the stimulation rate.

The Stratos LV-T additionally also employs BIOTRONIK’s Home Monitoring™ technology, which is an automatic, wireless, remote monitoring system for management of patients with implantable devices. With Home Monitoring, physicians can review data about the patient’s cardiac status and CRT-P’s functionality between regular follow-up visits, allowing the physician to optimize the therapy process. Stratos CRT-Ps are also designed to collect diagnostic data to aid the physician’s assessment of a patient’s condition and the performance of the implanted device.

The bipolar IS-1 connections are used for pacing and sensing (right atrial and ventricle) and the additional IS-1 connection is used for pacing in the left ventricle in either a bipolar or unipolar configuration depending on the left ventricular lead. The pulse amplitude and pulse width of each of the three channels is separately programmable.

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Stratos CRT-Ps are designed to meet all indications for Cardiac Resynchronization Therapy in CHF patients as well as those for bradycardia therapy as exhibited in a wide variety of patients. The Stratos family is comprised of two CRT-Ps that are designed to handle a multitude of situations.

Stratos LV

Stratos LV-T

Throughout this manual, specific feature and function descriptions may only be applicable to the Stratos LV-T and those features will be referenced as such. Otherwise, reference to Stratos CRT-Ps refers to both devices.

Triple chamber, rate-adaptive, unipolar/bipolar pacing CRT-P

Triple chamber, rate-adaptive, unipolar/bipolar pacing CRT-P with Home Monitoring

1.2 Indications

The Stratos LV and Stratos LV-T Cardiac Resynchronization Therapy Pacemakers (CRT-Ps) are indicated for patients who have moderate to severe heart failure (NYHA Class III/IV), including left ventricular dysfunction (EF ≤ 35%) and QRS ≥ 120 ms and remain symptomatic despite stable, optimal heart failure drug therapy.

Stratos LV/LV-T Technical Manual 3

1.3 Contraindications

Use of Stratos LV and Stratos LV-T CRT-Ps are contraindicated for the following patients:

• Unipolar pacing is contraindicated for patients with an

implanted cardioverter-defibrillator (ICD) because it may cause unwanted delivery or inhibition of ICD therapy.

• Single chamber atrial pacing is contraindicated for

patients with impaired AV nodal conduction.

• Dual chamber and single chamber atrial pacing is

contraindicated for patients with chronic refractory atrial tachyarrhythmias.

1.4 Note to Physician

As with any implantable pulse generator, there are certain infrequent risks associated with Stratos CRT-Ps. Section 1.6 lists the adverse events that have been observed or may potentially occur with these Cardiac Resynchronization Therapy Pacemakers. The warnings and precautions listed in Section 1.5 should be taken under serious consideration in order to aid in avoiding device failures and harm to the patient.

Regular monitoring of the patient and their implanted device should be conducted to identify performance concerns and ensure appropriate therapy is being administered to the patient. Please communicate any performance concerns to BIOTRONIK and to FDA.

All explanted devices should be returned to the manufacturer for testing to help understand device reliability and performance. Refer to Section 10 for recommended procedures for handling explanted devices.

1.5 Warnings and Precautions

Certain therapeutic and diagnostic procedures may cause undetected damage to a Cardiac Resynchronization Therapy Pacemakers, resulting in malfunction or failure at a later time. Please note the following warnings and precautions:

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Magnetic Resonance Imaging (MRI) – Avoid use of magnetic resonance imaging as it has been shown to cause movement of the CRT-Ps within the subcutaneous pocket and may cause pain and injury to the patient and damage to the CRT-P. If the procedure must be used, constant monitoring is recommended, including monitoring the peripheral pulse.

Rate Adaptive Pacing – Use rate adaptive pacing with care in patients unable to tolerate increased pacing rates.

NIPS – Life threatening ventricular arrhythmias can be induced by stimulation in the ventricle. Ensure that an external cardiac defibrillator is accessible during tachycardia testing. Only physicians trained and experienced in tachycardia induction and reversion protocols should use non-invasive programmed stimulation (NIPS).

High Output Settings – High output settings combined with extremely low lead impedance may reduce the life expectancy of the Stratos CRT-Ps. Programming of pulse amplitudes, higher than 4.8 V, in combination with long pulse widths and/or high pacing rates may lead to premature activation of the replacement indicator.

1.5.1 Interactions with Other Medical Therapy

Before applying one of the following procedures, a detailed analysis of the advantages and risks should be made. Cardiac activity during one of these procedures should be confirmed by continuous monitoring of peripheral pulse or blood pressure. Following the procedures, CRT-P function and stimulation threshold must be checked.

Therapeutic Diathermy Equipment – Use of therapeutic diathermy equipment is to be avoided for pacemaker patients due to possible heating effects of the CRT-P and at the implant site. If diathermy therapy must be used, it should not be applied in the immediate vicinity of the CRT-P or leads. The patient's peripheral pulse should be monitored continuously during the treatment.

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Transcutaneous Electrical Nerve Stimulation (TENS) –

Transcutaneous electrical nerve stimulation may interfere with CRT-P function. If necessary, the following measures may reduce the possibility of interference:

• Place the TENS electrodes as close to each other as

possible.

• Place the TENS electrodes as far from the CRT-P/lead

system as possible.

• Monitor cardiac activity during TENS use.

Defibrillation – The following precautions are recommended to minimize the inherent risk of CRT-P operation being adversely affected by defibrillation:

• The paddles should be placed anterior-posterior or along

a line perpendicular to the axis formed by the CRT-P and the implanted lead.

• The energy setting should not be higher than required to

achieve defibrillation.

• The distance between the paddles and the CRT-P/leads

should not be less than 10 cm (4 inches).

Radiation – The CRT-P’s internal electronics may be damaged by exposure to radiation during radiotherapy. To minimize this risk when using such therapy, the CRT-P should be protected with local radiation shielding.

Lithotripsy – Lithotripsy treatment should be avoided for CRT-P patients since electrical and/or mechanical interference with the CRT-P is possible. If this procedure must be used, the greatest possible distance from the point of electrical and mechanical strain should be chosen in order to minimize a potential interference with the CRT-P.

Electrocautery – Electrocautery should never be performed within 15 cm (6 inches) of an implanted CRT-P or leads because of the danger of introducing fibrillatory currents into the heart and/or damaging the CRT-P. Pacing should be asynchronous and above the patient’s intrinsic rate to prevent inhibition by interference signals generated by the cautery. When possible, a bipolar electrocautery system should be used.

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For transurethral resection of the prostate, it is recommended that the cautery ground plate be placed under the buttocks or around the thigh, but not in the thoracic area where the current pathway could pass through or near the CRT-P system.

1.5.2 Storage and Sterilization

Storage (temperature) – Recommended storage temperature

range is 5° to 55°C (41°-131°F). Exposure to temperatures outside this range may result in CRT-P malfunction (see Section 7.1).

Low Temperatures – Exposure to low temperatures (below 0°C) may cause a false elective replacement indication to be present. If this occurs, warm the device to room temperature and reset the ERI with magnet application (see Section 7.1).

Handling – Do not drop. If an unpackaged CRT-P is dropped onto a hard surface, return it to BIOTRONIK (see Section 7.1).

FOR SINGLE USE ONLY - Do not re-sterilize the CRT-P or accessories packaged with the CRT-P, they are intended for one-time use.

Device Packaging – Do not use the device if the packaging is wet, punctured, opened or damaged because the integrity of the sterile packaging may be compromised. Return the device to BIOTRONIK.

Storage (magnets) – Store the device in a clean area, away from magnets, kits containing magnets, and sources of electromagnetic interference (EMI) to avoid damage to the device.

Temperature Stabilization – Allow the device to reach room temperature before programming or implanting the device. Temperature extremes may affect the initial device function.

Use Before Date – Do not implant the device after the USE BEFORE DATE because the device may have reduced longevity.

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1.5.3 Lead Connection and Evaluation

Lead Check –

Feature Description

: Lead Check is a feature that, when activated, automatically measures the lead impedance with every pace. Based on these measurements, the lead configuration will be set to either unipolar or bipolar. Refer to Section 2.5 for more details regarding this feature.

Caution

: Lead check will not lead to disabling of cardiac resynchronization therapy. It limits the use of the resynchronization features.

1. Lead check is possible only when the right ventricle is paced first.

2. Lead check works only when the pacing voltages are programmed between 2.4 and 4.8 V. The lead check feature can be programmed OFF in patients that require cardiac resynchronization therapy.

Care should be taken when programming Stratos CRT-Ps with Lead Check ON as the device may switch from bipolar to unipolar pacing and sensing without warning. This situation may be inappropriate when using a Stratos CRT-P for patients with an Implantable Cardioverter Defibrillator (ICD). The following associated message appears when programming this feature:

“Lead check may result in a switch to unipolar pacing and sensing, which may be inappropriate for patients with an ICD.”

Additionally, Lead Check should be programmed OFF before lead connection as the feature will automatically reprogram the device to unipolar in the absence of a lead.

Lead / CRT-P Compatibility – Because of the numerous available 3.2-mm configurations (e.g., the IS-1 and VS-1 standards), lead/ CRT-P compatibility should be confirmed with the CRT-P and/or lead manufacturer prior to the implantation of the system.

8 Stratos LV/LV-T Technical Manual

IS-1, wherever stated in this manual, refers to the international standard, whereby leads and generators from different manufacturers are assured a basic fit. [Reference ISO 58413:1992(E)].

Lead Configuration – The polarity of the implanted lead dictates what lead configuration can be programmed for the CRT-P. Pacing will not occur with a unipolar lead if the lead configuration of the respective channel is programmed to bipolar (see Section 8).

Setscrew Adjustment – Back-off the setscrew(s) prior to insertion of lead connector(s) as failure to do so may result in damage to the lead(s), and/or difficulty connecting lead(s).

Cross Threading Setscrew(s) – To prevent cross threading the setscrew(s), do not back the setscrew(s) completely out of the threaded hole. Leave the torque wrench in the slot of the setscrew(s) while the lead is inserted.

Tightening Setscrew(s) – Do not overtighten the setscrew(s). Use only the BIOTRONIK supplied torque wrench.

Sealing System – Be sure to properly insert the torque wrench into the perforation at an angle perpendicular to the

connector receptacle. Failure to do so may result in damage to the plug and its self-sealing properties.

1.5.4 Programming and Operation

IEGM – Due to the compression processes that the signals

undergo, the IEGM recordings are not suitable for making some specific cardiac diagnoses, such as ischemia; although, these tracings may be useful in diagnosing arrhythmias, device behavior or programming issues.

Post AES - Before activating post-AES, check whether the selected program can cause Pacemaker Mediated Tachycardia (PMT) and whether post-AES pacing results.

Overdrive Pacing Mode - When programming the overdrive pacing mode, check whether the selected program can cause PMT, and whether atrial over drive pacing would result. Corresponding to the measured retrograde conduction time, the PMT protection interval must be programmed to a correct value.

Stratos LV/LV-T Technical Manual 9

AV Hysteresis – If the AV hysteresis is enabled along with the algorithm for recognizing and terminating PMTs (PMT management), the AV delay for recognizing and terminating a PMT has a higher priority than the AV hysteresis.

Sensing – The Stratos CRT-Ps do not sense in the left ventricle.

AV Conduction – In patients with intact AV conduction, the

intrinsic atrial tachycardia is conducted to the ventricle 1:1. With the resynchronization mode activated, spontaneous rate of the right ventricle mode is synchronized for a rate up to 200 ppm in the left ventricle. For this reason, biventricular pacing mode should be turned OFF in such cases.

Unipolar/Bipolar – If the pacing or sensing function is to be programmed to bipolar in the atrial channel, it must be verified that bipolar leads have been implanted in that chamber. If the atrial lead is unipolar, unipolar sensing and pacing functions must be programmed in that chamber. Failure to program the appropriate lead configuration could result in patient experiencing entrance and/or exit block.

In addition, if the atrial lead polarity setting within the Patient Data Memory has been set to bipolar, the polarity of the corresponding implanted lead must be confirmed to be bipolar.

Safe Program – Activating the “Safe Program” is a way of quickly programming the device to multiple settings in the event of an emergency. These settings include unipolar pacing with pacing output OFF in the left ventricular channel. Refer to Section 6.3 for further details.

Programmers – Use only BIOTRONIK’s ICS 3000 programmer equipped with appropriate software to program Stratos CRT-Ps. Do not use programmers from other manufacturers.

Pulse Amplitude – Programming of pulse amplitudes, higher than 4.8 V, in combination with long pulse widths and/or high pacing rates can lead to premature activation of the replacement indicator. If a pulse amplitude of 7.2 V or higher is programmed and high pacing rates are reached, output amplitudes may differ from programmed values.

10 Stratos LV/LV-T Technical Manual

Pacing thresholds – When decreasing programmed output (pulse amplitude and/or pulse width), the pacing threshold must first be accurately assessed to provide a 2:1 safety margin.

EMI – Computerized systems are subject to (Electromagnetic Interference (EMI) or “noise”. In the presence of such interference, telemetry communication may be interrupted and prevent programming of the Stratos CRT-P.

Programming Modifications – Extreme programming changes should only be made after careful clinical assessment. Clinical judgment should be used when programming permanent pacing rates below 40 ppm or above 100 ppm.

Short Pacing Intervals – Use of short pacing intervals (high pacing rates) with long atrial and/or ventricular refractory periods may result in intermittent asynchronous pacing and, therefore, may be contraindicated in some patients.

OFF Mode – The OFF mode can be transmitted as a temporary program only to permit evaluation of the patient’s spontaneous rhythm. (see Section 2.1.11)

Myopotential Sensing – The filter characteristics of BIOTRONIK implantable devices have been optimized to sense electrical potentials generated by cardiac activity and to reduce the possibility of sensing skeletal myopotentials. However, the risk of CRT-P’s operation being affected by myopotentials cannot be eliminated, particularly in unipolar systems. Myopotentials may resemble cardiac activity, resulting in inhibition of pacing, triggering and/or emission of asynchronous pacing pulses, depending on the pacing mode and the interference pattern. Certain follow-up procedures, such as monitoring CRT-P performance while the patient is doing exercises involving the use of pectoral muscles, as well as Holter monitoring, have been recommended to check for interference caused by myopotentials. If sensing of myopotentials is encountered, corrective actions may include selection of a different pacing mode or sensitivity setting.

Muscle or Nerve Stimulation – Inappropriate muscle or nerve stimulation may occur with unipolar pacing when using a noncoated Stratos CRT-P.

Stratos LV/LV-T Technical Manual 11

Atrial Sensitivity – In dual chamber systems, the atrial sensitivity of 0.1 mV should only be programmed in conjunction with a bipolar lead configuration.

Programmed to Triggered Modes – When programmed to triggered modes, pacing rates up to the programmed upper limit may occur in the presence of either muscle or external interference.

Triggered Modes – While the triggered modes (DDT, DVT, DDTR/A, DDTR/V, DDI/T, VDT, VVT, and AAT) can be programmed permanently, these modes are intended for use as temporary programming for diagnostic purposes. In triggered pacing modes, pacing pulses are emitted in response to sensed signals, and therefore the pacing pulse can be used as an indicator, or marker of sensed events for evaluating the sensing function of the pulse generator using surface ECG. However, real-time telemetry of marker channels and/or intracardiac electrogram via the programmer and programming wand is recommended over the use of a triggered pacing mode in the clinical setting. A triggered pacing mode may be preferred in situations where positioning the programming head over the pulse generator would be impossible or impractical (i.e., during exercise testing or extended Holter monitoring).

Another possible application of triggered modes is to ensure pacing as a short term solution during a period of inhibition of pacing by extracardiac interference, mechanical noise signals, or other sensing abnormalities. Because triggered modes emit pacing pulses in response to sensed events, this may result in unnecessary pacing during the absolute refractory period of the myocardium, inappropriate pacing in response to oversensing of cardiac or extracardiac signals. The risks associated with triggered pacing include excessive pacing, arrhythmias due to the R-on-T phenomenon, and early battery depletion. Therefore, it is important that the triggered modes are not used for long term therapy, and that the CRT-P is always returned to a nontriggered permanent program.

1.5.5 Home Monitoring

Patient’s Ability - Use of the Home Monitoring system requires

the patient and/or caregiver to follow the system instructions and cooperate fully when transmitting data.

12 Stratos LV/LV-T Technical Manual

If the patient cannot understand or follow the instructions because of physical or mental challenges, another adult who can follow the instructions will be necessary for proper transmission.

Electromagnetic Interference (EMI) – Precautions for EMI interference with the Stratos CRT-Ps are provided in Section 1.5.6. Sources of EMI including cellular telephones, electronic article surveillance systems, and others are discussed therein.

Use in Cellular Phone Restricted Areas - The mobile patient device (transmitter/receiver) should not be utilized in areas where cellular phones are restricted or prohibited (i.e., commercial aircraft).

Event Triggered Report - A timely receipt of the event report cannot be guaranteed. The receipt is also dependent on whether the patient was physically situated in the required coverage range of the patient device at the time the event information was sent.

Patient-Activated Report - The magnet effect must be programmed “synchronous” if the [Patient Report] function is activated.

Not for Conclusive Diagnosis - Because not all information available in the implant is being transmitted, the data transmitted by Home Monitoring should be evaluated in conjunction with other clinical indicators (i.e., in-office follow-up, patient symptoms, etc.) in order to make a proper diagnosis.

Frequency of Office Follow-Ups When Using Home Monitoring - The use of Home Monitoring does not replace

regular follow-up examinations. When using Home Monitoring, the time period between follow-up visits may not be extended.

Stratos LV/LV-T Technical Manual 13

1.5.6 Electromagnetic Interference (EMI)

The operation of any implanted device may be affected by certain environmental sources generating signals that resemble cardiac activity. This may result in inhibition of pacing and/or triggering or in asynchronous pacing depending on the pacing mode and the interference pattern. In some cases (i.e., diagnostic or therapeutic medical procedures), the interference sources may couple sufficient energy into a pacing system to damage the device and/or cardiac tissue adjacent to the leads.

BIOTRONIK CRT-Ps have been designed to significantly reduce susceptibility to electromagnetic interference (EMI). However, due to the variety and complexity of sources creating interference, there is no absolute protection against EMI. Generally, it is assumed that EMI produces only minor effects, if any, in CRT-P patients. If the patient may be exposed to one of the following environmental conditions, then the patient should be given the appropriate warnings.

1.5.7 Home and Occupational Environments

The following equipment (and similar devices) may affect normal CRT-P operation: electric arc welders, electric melting furnaces, radio/television and radar transmitters, power-generating facilities, high-voltage transmission lines, electrical ignition systems (also of gasoline-powered devices) if protective hoods, shrouds, etc., are removed, electrical tools, anti-theft devices at retail stores and electrical appliances, if not in proper condition or not correctly grounded and encased.

Patients should exercise reasonable caution in avoidance of devices which generate a strong electric or magnetic field. If EMI inhibits pacing or causes a reversion to asynchronous pacing or pacing at magnet rate, moving away from the source or turning it off should allow the CRT-P to return to its normal mode of operation. Some potential EMI sources include:

High Voltage Power Transmission Lines – High voltage power transmission lines may generate enough EMI to interfere with CRT-P operation if approached too closely.

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Home Appliances – Home appliances normally do not affect CRT-P operation if the appliances are in proper condition and correctly grounded and encased. There are reports of CRT-P disturbances caused by electrical tools and by electric razors that have touched the skin directly over the CRT-P.

Communication Equipment – Communication equipment such as microwave transmitters, linear power amplifiers, or highpower amateur transmitters may generate enough EMI to interfere with CRT-P operation if approached too closely.

Commercial Electrical Equipment – Commercial electrical equipment such as arc welders, induction furnaces, or resistance welders may generate enough EMI to interfere with CRT-P operation if approached too closely.

Electrical Appliances – Electric hand-tools and electric razors (used over the skin directly above the CRT-P) have been reported to cause pacemaker disturbances. Home appliances that are in good working order and properly grounded do not usually produce enough EMI to interfere with implanted device operation.

Electronic Article Surveillance (EAS) – Equipment such as retail theft prevention systems may interact with the CRT-Ps. Patients should be advised to walk directly through and not to remain near an EAS system longer than necessary.

Radio-Frequency Identification (RFID) – RFID tags may interact with the CRT-Ps. Patients should be advised to avoid leaving a device containing such a tag within close proximity to the CRT-P (i.e., inside a shirt pocket).

1.5.8 Cellular Phones

Recent studies have indicated there may be a potential interaction between cellular phones and pacemaker operation. Potential effects may be due to either the radio frequency signal or the magnet within the phone and could include inhibition or asynchronous pacing when the phone is within close proximity (within 6 inches [15 cm]) to the CRT-P.

Stratos LV/LV-T Technical Manual 15

Based on testing to date, effects resulting from an interaction between cellular phones and the implanted pacemakers have been temporary. Simply moving the phone away from the implanted device will return it to its previous state of operation. Because of the great variety of cellular phones and the wide variance in patient physiology, an absolute recommendation to cover all patients cannot be made.

Patients having an implanted CRT-P who operate a cellular phone should:

• Maintain a minimum separation of 6 inches (15 cm) between a hand-held personal cellular phone and the implanted device. Portable and mobile cellular phones generally transmit at higher power levels compared to hand held models. For phones transmitting above 3 watts, maintain a minimum separation of 12 inches (30 cm) between the antenna and the implanted device.

• Patients should hold the phone to the ear opposite the side of the implanted device. Patients should not carry the phone in a breast pocket or on a belt over or within 6 inches (15 cm) of the implanted device as some phones emit signals when they are turned ON but not in use (i.e., in the listen or standby mode). Store the phone in a location opposite the side of implant.

1.5.9 Hospital and Medical Environments

Refer to Section 1.5.1 for information regarding CRT-P interaction with the following medical procedures / environments:

• Electrosurgical Cautery

• Lithotripsy

• External Defibrillation

• High Radiation Sources

1.5.10 Device Explant and Disposal

Device Incineration - Never incinerate a CRT-P. Be sure the

CRT-P is explanted before a patient who has died is cremated. (see Section 10)

Explanted Devices – Return all explanted devices to BIOTRONIK.

16 Stratos LV/LV-T Technical Manual

1.6 Potential Effects of the Device on Health

The following possible adverse events may occur with this type of CRT-P based on implant experience including:

Potential Adverse Events

• Air embolism

• Allergic reactions to

contrast media

• Arrhythmias

• Bleeding

• Body rejection

phenomena

• Cardiac tamponade

• Chronic nerve damage

• Damage to heart valves

• Elevated pacing

thresholds

• Extrusion

• Fluid accumulation

• Infection

• Keloid formation

• Lead dislodgment

• Lead fracture / insulation

damage

• Lead-related thrombosis

• Local tissue reaction / fibrotic tissue formation

• Muscle or nerve stimulation

• Myocardial damage

• Myopotential sensing

• Pacemaker mediated

tachycardia

• Pneumothorax

• Pocket erosion

• Hematoma

• Device migration

• Thromboembolism

• Undersensing of

intrinsic signals

• Venous occlusion

• Venous or cardiac

perforation

Stratos LV/LV-T Technical Manual 17

1.7 Clinical Studies

The subsequent sections summarize the following three clinical studies that were used to support the safety and effectiveness of the Stratos LV/LV-T CRT-Ps.

• The AVAIL CLS/CRT clinical study

• The OVID clinical study (OUS)

• The OPTION CRT/ATx clinical study

Two of the studies, AVAIL CLS/CRT and OVID, collected significant safety data supporting use of the Stratos LV/LV-T CRT-P system. The third study, OPTION CRT/ATx, supports the effectiveness of cardiac resynchronization therapy (CRT). The OPTION CRT/ATx study was conducted on a device that delivers CRT but, in addition, also offers defibrillation therapy (CRT-D).

1.7.1 Stratos LV Clinical Study – AVAIL CLS/CRT

Study Design

The AVAIL CLS/CRT was a multi-center, prospective, randomized, blinded clinical study designed to support approval for cardiac resynchronization therapy for a Heart Failure (HF) patient population not requiring back up defibrillation and that are indicated for an ablate and pace procedures. All patients enrolled into the clinical study were randomly assigned to one of three groups using a 2:2:1 ratio for randomization.

18 Stratos LV/LV-T Technical Manual

• Patients assigned to Group 1 received biventricular pacing with CLS-based rate adaptive pacing using BIOTRONIK’s Protos DR/CLS, which is a dual-chamber pulse generator with CLS-based rate adaptive pacing. During this study, the Protos DR/CLS devices were implanted with two ventricular leads: the right ventricular lead was connected to the ventricular port, and the left ventricular lead was connected to the atrial port. Protos DR/CLS was included in this study to evaluate biventricular pacing with a different type of rate adaptive sensor technology.

• Patients assigned to Group 2 received biventricular pacing with accelerometer-based rate adaptive pacing using the Stratos LV.

• Patients assigned to Group 3 (control group) received right ventricular pacing with accelerometer-based rate adaptive pacing using the Stratos LV. Therefore, 60% of the patients received a Stratos LV device.

Primarily, the study evaluated and compared the functional benefits of CRT between the three randomized groups using a composite endpoint consisting of a six-minute walk test (meters walked) and quality of life measurement (assessed using the Minnesota Living with Heart Failure Questionnaire). Relevant measurements were completed twice for each patient: once at the Baseline evaluation (prior to implant and ablation) and again at a six-month follow-up evaluation. The data collected during this clinical study was used to demonstrate superiority of CRT to RV only pacing. This study also evaluated the safety of both the Protos DR/CLS and Stratos LV devices through an analysis of the complication-free rate through six months. Secondarily, the study also evaluated the superiority of CRT with CLS rate adaptation compared to CRT with accelerometer rate adaptation.

Stratos LV/LV-T Technical Manual 19

Clinical Inclusion Criteria

To support the objectives of this investigation, patients were required to meet the following inclusion criteria prior to enrollment:

• Meet the indications for therapy

• Persistent (documented for more than 7 days),

symptomatic AF with poorly controlled rapid ventricular rates or permanent, (documented for more than 30 days with failed cardioversion, or longstanding AF of 6 months or more) symptomatic AF with poorly controlled rapid ventricular rates.

• Eligible for AV nodal ablation and permanent pacemaker implantation

• NYHA Class II or III heart failure

• Age ≥ 18 years

• Understand the nature of the procedure

• Ability to tolerate the surgical procedure required for

implantation

• Give informed consent

• Able to complete all testing required by the clinical

protocol

• Available for follow-up visits on a regular basis at the investigational site

20 Stratos LV/LV-T Technical Manual

Clinical Exclusion Criteria

To support the objectives of this investigation, the exclusion criteria at the time of patient enrollment included the following:

• Meet one or more of the contraindications

• Have a life expectancy of less than six months

• Expected to receive heart transplantation within six

months

• Enrolled in another cardiovascular or pharmacological clinical investigation

• Patients with an ICD, or being considered for an ICD

• Patients with previously implanted biventricular pacing

systems

• Patients with previously implanted single or dual chamber pacing system with > 50% documented ventricular pacing

• Patients with previous AV node ablation

• Six-minute walk test distance greater than 450 meters

• Any condition preventing the patient from being able to

perform required testing

• Presence of another life-threatening, underlying illness separate from their cardiac disorder

• Conditions that prohibit placement of any of the lead systems

Follow-Up Schedule

At the enrollment screening, the physician evaluated the patient to verify that all inclusion/exclusion criteria have been met in accordance to the protocol and the patient has signed the informed consent. After successful enrollment, all patients were implanted with either a Stratos LV CRT-P or Protos DR/CLS device. Evaluations at the Four Week, Three and Six Month follow-ups included NYHA classification, medications, and percentage of ventricular pacing.

Clinical Endpoints

Stratos LV/LV-T Technical Manual 21

Primary Endpoint: Complication-free Rate (Safety) The safety of the Stratos LV was evaluated based on complications (adverse events that require additional invasive intervention to resolve) related to the implanted CRT system which includes the Stratos LV, the right ventricular, the left ventricular lead, lead ventricular lead adapters (if used) and the implant procedure. The target complication-free rate at six months is 85%.

Primary Endpoint: Six Minute Walk Test & QOL (Effectiveness) The purpose of Primary Endpoint 1 was to evaluate the effectiveness of the CRT (Groups 1 and 2) compared to RV only (Group 3) pacing as measured by the average composite rate of improvement in six minute walk test and QOL.

Accountability of PMA Cohorts

After randomization and enrollment, 23 patients (8 in Group 1, 8 in Group 2 and 7 in Group 3) did not receive an implant. The reasons for patients not receiving an implant are outlined in

Figure 1

. Two additional patients in Group 1 had an unsuccessful first implant attempt (unable to implant the LV lead), but follow up data was not received.

22 Stratos LV/LV-T Technical Manual

Enrolled and Randomized Patients

Group 1 43 Group 2 50 Group 3 25

Implant Attempted

Group 1 39 Group 2 44 Group 3 21

Successful implant

Group 1 33 Group 2 42 Group 3 18

Completed 6-Month Follow-up

Group 1 23 Group 2 30 Group 3 15

No im pla nt Atte mpte d

Withdrawal of Consent

Not Meeting Inclusion Criteria

Unsuccessful implant

Withdrawal of IC before 2nd Attempt

Follow-up to failed implant data pending

Ablation/Abla tion Data Pending

6-Month Fol low-up Da ta

Patient Death before 6-Month

Withdrew before 6-Month FU

Not Reached 6-Month FU or Data Pending

6-month FU Not Completed

Figure 1: Patient Accountability

Demographics and Baseline Parameters

Group 1 2 Group 2 4 Group 3 3

Group 1 2 Group 2 2 Group 3 1

Group 1 4 Group 2 2 Group 3 3

Group 1 2 Group 2 0 Group 3 0

Group 1 3 Group 2 0 Group 3 0

Group 1 0 Group 2 2 Group 3 0

Group 1 1 Group 2 1 Group 3 0

Group 1 6 Group 2 8 Group 3 3

Group 1 0 Group 2 1 Group 3 0

Table 1

provides a summary of the patient demographics at enrollment. There were no statistical differences in enrollment demographics between the 3 groups.

Stratos LV/LV-T Technical Manual 23

Table 1: Patient Demographics at Enrollment

Characteristic Group1 Group 2 Group 3

Age @ Enrollment (Yrs)

Mean ± SE Range

Gender Male Female

Six-Minute Walk Distance (meters)

Mean ± SE Range

New York Heart Association Class

Class II Class III

Underlying Heart Disease

Dilated

Cardiomyopathy

Hypertrophic

Cardiomyopathy

Valvular Heart

Disease

Coronary Artery

Disease Hypertension No underlying

structural heart

disease

N=42

73.7 ± 1.3 56 to 90

N=42 18 (42.9%) 24 (57.1%)

N=42

262.7 ±

15.1

78 to 420

N=42 23 (54.8%) 19 (45.2%)

N=42

8 (19.0%)

4 (9.5%)

12 (28.6%)

19 (45.2%)

37 (88.1%)

3 (7.1%)

N=50

72.3 ± 1.2 51 to 86

N=50 19 (38.0%) 31 (62.0%)

N=50

283.6 ±

13.8

37 to 438

N=50 18 (36.0%) 32 (64.0%)

N=49 11 (22.4%)

1 (2.0%)

12 (24.5%)

28 (57.7%)

37 (75.5%)

2 (4.1%)

N=25

71.5 ± 1.6 52 to 85

N=25 13 (52.0%) 12 (48.0%)

N=25

267.8 ±

22.9

23 to 420

N=25 10 (40.0%) 15 (60.0%)

N=25

1 (4.0%)

2 (8.0%)

5 (20.0%)

6 (24.0%)

19 (76.0%)

7 (28.0%)

P-value

0.534*

0.553**

0.395*

0.189**

0.125**

0.216**

0.792**

0.031**

0.348**

0.007**

24 Stratos LV/LV-T Technical Manual

Table 1: Patient Demographics at Enrollment

Characteristic Group1 Group 2 Group 3

Other Medical History

Diabetes Chronic Lung

Disease Thyroid Disease Chronic Kidney

Disease Prior Ischemic

Stroke or TIA Prior Embolic

Events

(non-

cerebrovascular)

*One-way ANOVA, ** Chi-Square test (2-sided)

N=29

13 (44.8%)

7 (24.1%)

12 (41.4%)

4 (13.8%)

7 (24.1%)

1 (2.3%)

N=36

9 (25.0%)

16 (44.4%)

12 (33.3%)

5 (13.9%)

10 (27.8%)

3 (6.0%)

N=17 4 (23.5%) 7 (41.2%)

5 (29.4%)

1 (5.9%)

6 (35.3%)

2 (8.0%)

P-value

0.287**

0.211**

0.791**

0.836**

0.726**

0.653**

Table 2 provides a summary of the AF medical history. Table 3

provides a summary of cardiac medications patients were taking at the time of enrollment. Please note some categories may equal more than 100% as several categories allow more than one response. In some cases, complete demographic data was not provided for all patients. There were no statistical differences in AF medical history and cardiac medication at enrollment between the 3 groups.

Stratos LV/LV-T Technical Manual 25

Table 2: Atrial Fibrillation Demographics at Enrollment

Characteristic Group 1 Group 2 Group 3 P-value*

Classification of Atrial Fibrillation

Persistent AF Permanent AF

Classification of Symptoms Related to AF

Palpitations Chest Pain Dyspnea or shortness

of breath Fatigue Lightheadedness or

syncope Other

Previous AF Ablation

No Yes

Past Medications for Rate or Rhythm Control

Amiodarone Digoxin Diltiazem Disopyramide Dofetilide Flecanide Ibutilide Procainamide Propafenone Sotolol Verapamil Metoprolol Propranolol Other Beta-Blockers Other Medications

N=42 10 (23.8%) 32 (76.2%)

N=42 32 (76.2%)

6 (14.3%)

36 (85.7%)

34 (81.0%) 17 (40.5%)

9 (21.4%)

N=42 37 (88.1%)

5 (11.9%)

N=41 12 (29.3%) 17 (41.5%) 17 (41.5%)

0 (0.0%) 4 (9.8%)

5 (12.2%)

0 (0.0%) 0 (0.0%)

2 (4.9%) 9 (22.0%) 5 (12.2%)

19 (46.3%)

0 (0.0%) 7 (17.1%) 5 (12.2%)

N=50 17 (34%) 33 (66%)

N=49

34 (69.4%)

7 (14.3%)

40 (81.6%)

45 (91.8%) 13 (26.5%)

11 (22.4%)

N=50

47 (94.0%)

3 (6.0%)

N=48

10 (20.8%) 22 (45.8%) 23 (47.9%)

3 (6.3%) 3 (6.3%)

5 (10.4%)

0 (0.0%) 2 (4.2%) 4 (8.3%)

10 (20.8%)

8 (16.7%)

28 (58.3%)

0 (0.0%)

15 (31.3%)

5 (10.4%)

N=24

6 (25%)

18 (75%)

N=25

14 (56.0%)

3 (12.0%)

19 (76.0%)

18 (72.0%)

9 (36.0%)

10 (40.0%)

N=25

21 (84.0%)

4 (16.0%)

N=24 10 (41.7%) 13 (54.2%) 12 (50.0%)

0 (0.0%) 2 (8.3%) 1 (4.2%) 1 (4.2%) 0 (0.0%) 0 (0.0%) 2 (8.3%)

3 (12.5%)

10(41.7%)

1 (4.2%)

4 (16.7%)

1 (4.2%)

0.537

0.236

1.000

0.568

0.149

0.329

0.205

0.354

0.192

0.683

0.804

0.228

0.895

0.656

0.215

0.506

0.423

0.389

0.829

0.382

0.215

0.248

0.656

26 Stratos LV/LV-T Technical Manual

Table 2: Atrial Fibrillation Demographics at Enrollment

Characteristic Group 1 Group 2 Group 3 P-value*

Rate Control Medication, Reasons for Discontinuation

Ineffective Not tolerated Other

Rhythm Control Medication, Reasons for Discontinuation

Ineffective Not tolerated Other

Cardioversion History

Successful prior

electrical cardioversion

Transthoracic Transvenous

Unsuccessful prior

electrical cardioversion

Transthoracic Transvenous

No electrical

cardioversion attempted

Successful prior

pharmacological cardioversion

Unsuccessful prior

pharmacological cardioversion

No pharmacological

cardioversion attempted

*Chi-Square test (2-sided)

N=17

10 (58.8%)

8 (47.1%)

1 (5.9%)

N=22

17 (77.3%)

6 (27.3%)

1 (4.5%)

N=42

13 (31.0%)

13 (100.0%)

0 (0.0%)

15 (35.7%)

15 (100.0%)

0 (0.0%)

17 (40.5%)

5 (11.9%)

8 (19.0%)

23 (54.8%)

N=20

13 (65.0%)

7 (35.0%) 2 (10.0%)

N=25

20 (80.0%)

7 (28.0%)

1 (4.0%)

N=49

16 (32.7%)

15 (93.8%)

1 (6.3%)

14 (28.6%)

14 (93.3%)

2 (13.3%)

20 (40.8%)

3 (6.1%)

11 (22.4%)

29 (59.2%)

N=12 9 (75.0%) 3 (25.0%)

0 (0.0%)

N=13 8 (61.5%) 6 (46.2%) 2 (15.4%)

N=25

10 (40.0%)

10 (100.0%)

0 (0.0%)

7 (28.0%)

7 (100.0%)

0 (0.0%)

9 (36.0%)

3 (12.0%)

7 (28.0%)

15 (60.0%)

0.558

0.760

0.800

0.759

0.530

0.430

0.760

0.808

0.680

0.741

0.936

0.547

0.678

0.915

Stratos LV/LV-T Technical Manual 27

Table 3: Current Cardiac Medications at Enrollment

Drug Category

Anti-Arrhythmics 12 (28.6%) 10 (20.4%) 4 (16.0%)

Rate Control Medications 32 (76.2%) 43 (87.8%) 20(80.0%)

Anti-thrombic Agents 17 (40.5%) 19(38.8%) 11 (44.0%)

Anti-Coagulants 36 (85.7%) 40 (81.6%) 22 (88.0%)

ACE Inhibitors 16 (38.1%) 16 (32.7%) 8 (32.0%) Angiotensin-Receptor

Blockers Diuretics 30 (71.4%) 34 (69.4%) 13 (52.0%)

Inotropes 1 (2.4%) 2 (4.1%) 0 (0.0%)

Nitrates 3 (7.1%) 6 (12.2%) 2 (8.0%)

Beta-Blockers for CHF 6 (14.3%) 9 (18.4%) 4 (16.0%)

Other 23 (54.8%) 26 (53.1%) 14 (56.0%)

*Chi-Square test (2-sided)

Group 1

N=42

10 (23.8%) 7 (14.3%) 4 (16.0%) 0.491

Group 2

N=50

Group 3

N=25

P-

value*

0.480

0.462

0.863

0.686

0.848

0.255

0.803

0.714

0.947

0.941

Safety and Effectiveness Results

A total of 118 patients were enrolled in the AVAIL CLS/CRT clinical study at 20 sites:

There were 43 Group 1, 50 Group 2, and 25 Group 3 patients in this prospective, multi-center, randomized clinical study. For Group 1, there were 33 successful implants (76.7%) of the Protos DR/CLS system. For Groups 2 and 3, there were 44 and 21 successful implants (88.0% and 84.0%) respectively of the Stratos LV CRT-P system.

28 Stratos LV/LV-T Technical Manual

• The study was designed to enroll 265 patients. However, the study was terminated early due to slow patient enrollment. There were no safety issues involved in the termination decision. Due to the lack of patient data, the AVAIL CLS/CRT study alone was insufficient to support CRT pacing effectiveness or an ablate and pace indication.

• The cumulative enrollment duration was 416.7 months with a mean duration of 9.7 months for Group 1, 522.4 months with a mean duration of 10.4 months for Group 2, and 261.1 months with a mean duration of

10.4 months for Group 3. 73 (61.9%) of the study patients had enrollment durations greater than 6 months.

• There were 158 adverse events (115 observations in 68 patients and 43 complications in 34 patients). There were no unanticipated adverse device effects reported.

• The overall protocol violation non-compliance rate is

0.4% in Group 1, 0.5% in Group 2, and 0.4% in Group 3. The overall follow-up compliance rate is 99.8% in all groups.

• There were 3 patient deaths reported, two in Group 2 and one in Group 3. The clinical investigators and clinical events committee determined that none of these deaths were related to the study devices.

• Both the CRT pacing and the RV pacing only groups showed improvements in the primary composite endpoint of quality of life and six-minute walk distance between the baseline evaluation and the six-month follow-up. In addition, there was a trend towards improvement between the combined CRT pacing groups compared to the RV pacing only group at six months.

Stratos LV/LV-T Technical Manual 29

Primary Endpoint—Complication-free Rate (Safety)

The safety of the Stratos LV was evaluated based on complications (adverse events that require additional invasive intervention to resolve) related to the implanted CRT system which includes the Stratos LV, the right ventricular, the left ventricular lead, lead ventricular lead adapters (if used) and the implant procedure. The target complication-free rate at six months is 85%.

13 complications in these categories were seen in 11 patients with cumulative enrollment duration of 783.5 months (64.4 patient-years). 14.7% of the patients had a reported complication in these categories. The rate of complications per patient-year is 0.20. Details of the Stratos LV complications in the AVAIL CLS/CRT study are listed in Table 4

30 Stratos LV/LV-T Technical Manual

Table 4: AVAIL CLS/CRT Complication-Free Rate at

6 months – Stratos LV

Category

Number

Patients

% of

Patients

Number of

Complications

per patient-

year

Device-Related

Pocket Infection/Pain

1.3%

2 0.03

Total 1 1.3% 2 0.03

LV Lead Related

High Threshold No Capture

Diaphragmatic Stimulation

Dislodgement 2

1.3%

2.7%

1 0.02

2 0.03

Total 4 5.3% 4 0.06

RV Lead Related

High Threshold / No Capture

4 5.3% 4 0.06

Total 4 5.3% 4 0.06

Procedure

Pneumothorax 1 User error 1

1.3%

1 0.02 1 0.02

Hematoma 1 1.3% 1 0.02

Total 3 4.0% 3 0.05

Total Lead

and

Procedure

11 14.7% 13 0.20

Stratos LV/LV-T Technical Manual 31

Table 4: AVAIL CLS/CRT Complication-Free Rate at

6 months – Stratos LV

Category

Number

Patients

% of

Patients

Number of

Complications

per patient-

year

Other Medical

Worsening CHF Repeat Ablation

2 2.7% 2 0.03

3 4.0% 3 0.05

Non-CHF cardiac

3 4.0% 3 0.05

symptoms Other Medical

3 4.0% 3 0.05

Total 10 13.3% 11 0.17

Total—All

Patients and

19 25.3% 24 0.37

Category

Number

Patients

% of

Patients

Number of

Complications

per patient-

year

Device-Related

Pocket Infection or

2.7%

3 0.05

Pain

Total

2.7%

3 0.05

LV Lead-Related

High Threshold /

1 1.3% 1 0.02

No Capture Diaphragmatic

Stimulation

1 1.3% 1 0.02

Dislodgement 2 2.7% 2 0.03

Total

4 5.3% 4 0.06

RV Lead Related

High Threshold /

4 5.3% 4 0.06

No Capture

Total

4 5.3% 4 0.06

Procedure

Pneumothorax 1 1.3% 1 0.02 User error 1 1.3% 1 Hematoma 1 1.3% 1

Total

3 4.0% 3 0.05

0.02

Total Lead and Procedure

11 14.7% 14 0.22

Other Medical

Worsening CHF

2 2.7% 2 0.03

Non-CHF cardiac

5 6.7% 5 0.08

symptoms

34 Stratos LV/LV-T Technical Manual

Table 5: Summary of Complications – Stratos LV

Category

Repeated ablation

Number

Patients

% of

Patients

Number of

Complications

3 4.0% 3 0.05

Complications

per patient-

year

Lead addition 1 1.3% 1 0.02 Other medical 3 4.0% 3 0.05

Total

12 16.0% 14 0.22

Total—All Patients and

20 26.7% 28 0.43

Category

High Threshold / No Capture

Diaphragmatic Stimulation

Total

Number

Patients

% of

Patients

LV Lead-Related

Number of

Complications

1.3%

17.3%

1 0.02

13 0.20

14 18.7% 14 0.22

Observations

per patient-

year

Device Related

Pocket Infection or pain

Total

5 6.7% 5 0.08

Procedure

Pneumothorax 1 1.3% 1 0.02 Atrial edema 1 1.3% 1 0.02 User error 1 1.3% 1 0.02

Total

3 4.0% 3 0.05

Total Lead, Device and Procedure

19 25.3% 22 0.34

Stratos LV/LV-T Technical Manual 35

Table 6: Summary of Observations – Stratos LV

Category

Number

Patients

% of

Patients

Number of

Complications

Observations

per patient-

year

Other Medical

Dizziness 3 4.0% 3 0.05 Other Medical 24 32.0% 34 0.53 Worsening CHF 8 10.7% 8 0.12 Ventricular

arrhythmias Shortness of

Breath

2 2.7% 2 0.03

5 6.7% 5 0.08

Stroke / TIA 1 1.3% 1 0.02 Non-CHF

cardiac

1 1.3% 1 0.02

symptoms

Total

35 46.7% 54 0.84

Total—All Patients and

45 60.0% 76 1.18

Category

Distance Walked

at Baseline

Distance Walked

at Six-Months

∆ Distance

Walked (meters)

∆ Distance

Walked (%)

QOL Score at

Baseline

QOL Score at

Six-Months

CRT (Group 1 & 2)

(N = 53)

Mean ± SE

262.8 ± 13.7 288.5 ± 22.4 0.369

312.8 ± 14.6 345.8 ± 30.0 0.303

50.0 ± 12.2 57.2 ± 26.7 0.790

39.0% ± 13.1%

58.5 ± 2.9 49.3 ± 5.5 0.137

30.1 ± 3.2 27.7 ± 6.5 0.731

p value

t-test,

0.610

0.537

0.525

∆ in QOL Score

(%)

28.4 ± 3.4 21.6 ± 7.7 0.367

47.4% ± 5.1%

Composite Rate 43.2% ± 7.7%

40.4% ±

11.1%

33.0% ±

12.3%

p value is provided for informational purposes to show trends only; clinical

significance is not indicated by p values for analyses that were not prespecified.

38 Stratos LV/LV-T Technical Manual

Primary Effectiveness Endpoint Analysis and Conclusions

The primary effectiveness endpoint evaluated CRT effectiveness (Groups 1 and 2) compared to RV only effectiveness (Group 3), as measured by the composite rate of the six minute walk test and QOL improvement from Baseline to the Six-Month follow-up (Table 8

). For this analysis, both six minute walk test and QOL were equally weighted at 50%. Due to the small number of patients with data available for the analysis of the primary endpoint, the results lack power to demonstrate that biventricular pacing with either the Protos DR/CLS or Stratos LV device is statistically different from RV only pacing with the Stratos LV device in patients undergoing an “ablate and pace” procedure.

Multi-site Poolability and Gender Analysis

The AVAIL CLS/CRT clinical report included data from multiple centers with centralized coordination, data processing, and reporting at BIOTRONIK. All of the clinical centers followed the requirements of an identical clinical protocol, and all of the clinical centers used the same methods to collect and report the clinical data, including New York Heart Association evaluation, six-minute walk test, Minnesota Living with Heart Failure questionnaire, and echocardiographic measurements. In order to justify pooling of the data from multiple centers, several analyses were completed. All of the centers were divided into two groups (Small and Large sites) based on implant volume. Comparisons were then made between the patient populations based on the results of the safety and effectiveness endpoints. Additionally, analyses were performed on the data collected in the AVAIL clinical investigation in order to compare results between males and females. The first type of analysis compared enrollment by patient gender in each of the study groups. The second type of analysis compared effectiveness and safety outcomes in each gender.

The results of these analyses demonstrated poolability of the data between sites. There were no significant differences in the primary safety or effectiveness endpoints between high and low volume implant centers.

Stratos LV/LV-T Technical Manual 39

The gender distribution in this clinical investigation was consistent within the study groups and included a representative proportion of enrolled female participants (57.2% versus 42.7% male). There were no significant differences in the primary safety or effectiveness endpoints between the male and female population.

1.7.2 Stratos LV Clinical Study – OVID study

The OVID clinical study collected significant safety data supporting the Stratos LV/LV-T CRT-P system.

Study Design

BIOTRONIK conducted the Corox Over-the-Wire Lead Evaluation (OVID) prospective registry outside the United States (OUS) of the Corox OTW Steroid LV lead in a multi-center trial with legally marketed CRT-D and CRT-P pulse generators that provide biventricular pacing therapy. Data from this registry is presented in the following sections to support the safety of the Stratos LV CRT-P.

The multi-center investigation was designed to validate the safety of the Corox OTW Steroid LV lead through a comparison of successfully implanted LV leads against a pre-defined success rate threshold, when no anatomical restrictions prevent access to the coronary sinus. The evaluation of safety is based on the analysis of the incidence of adverse events, defined as any complications or observations judged by the investigator to be in probable relationship with Corox OTW Steroid LV lead system. Additionally, the effectiveness of the leads was evaluated using lead parameter data, including sensing amplitudes, pacing thresholds, and impedance values.

In the OVID study, enrolled patients could be implanted with any legally marketed CRT-P or CRT-D device. There were 121 patients enrolled in the OVID clinical study, and 89 patients were implanted with a Stratos LV device.

40 Stratos LV/LV-T Technical Manual

Clinical Inclusion Criteria

To support the objectives of this investigation, patients were required to meet the following inclusion criteria prior to enrollment:

• Meet the indications for bi-ventricular pacing

• Age ≥ 18 years

• Receiving optimal drug therapy for Congestive Heart

Failure treatment

• Give informed consent

Clinical Exclusion Criteria

To support the objectives of this investigation, the exclusion criteria at the time of patient enrollment included the following requirements:

• Myocardial infarction or unstable angina pectoris

• Acute myocarditis

• Life expectancy ≤ 6 months

• Planned cardiac surgical procedures or interventional

measures within the next 6 months

• Pregnancy

Follow-Up Schedule

All patients were implanted with the Corox OTW/Steroid LV lead system and a CRT-P or CRT-D pulse generator capable of providing bi-ventricular pacing for the treatment of CHF. The specific study procedures were performed at:

• Pre-operative Visit

• Implantation

• Pre-discharge follow-up

• One-month follow-up

• Three-month follow-up

• Six-month follow-up

• Twelve-month follow-up

Stratos LV/LV-T Technical Manual 41

Clinical Endpoints

The safety of the Stratos LV was evaluated based on complications (adverse events that require additional invasive intervention to resolve) related to the implanted CRT system which includes the Stratos LV device, the atrial lead, the right ventricular lead the left ventricular lead and the implant procedure. The target complication-free rate at six months was 85%.

Accountability of PMA Cohorts

During the OVID study, 84 patients were implanted with the Stratos LV CRT-P and Corox OTW/Steroid LV lead system. Additionally, 5 other patients were implanted with a Stratos LV CRT-P device following an unsuccessful Corox OTW/Steroid LV lead implant attempt. Of these 5 patients, three were not implanted with any LV pacing lead, one was implanted with a non-study LV pacing lead and one was implanted with a BIOTRONIK Elox P 60 BP placed in the RV outflow tract for bi-focal ventricular pacing. These 5 patients were excluded from the OVID study at 1 month post-implant, because the primary endpoint of the OVID study was the evaluation of the safety and effectiveness of the Corox OTW/Steroid lead.

Demographics and Baseline Parameters

Table 9

provides a summary of the patient demographics and medical history for the 89 enrolled patients implanted with a Stratos LV. The typical patient implanted with a Stratos LV CRT-P was a 68 year old male with NYHA Class III heart failure, Left Bundle Branch Block (LBBB), a mean QRS duration of 160 ms, and non-ischemic cardiomyopathy.

42 Stratos LV/LV-T Technical Manual

Table 9: Patient Demographics

Characteristic Results

Age at Implant (Years) n=88

Mean ± SD 68 ± 10 Range 34 to 84

Gender n=89

Male 66 (74%) Female 23 (26%)

QRS-width (ms) n=70

Mean ± SD 160 ± 23 Range 110 to 210

Etiology of Heart Failure n=87

Ischemic 32 (37%) Non-Ischemic 55 (63%)

New York Heart Association (NYHA) Classification

n=87

Class III 73 (84%) Class IV 14 (16%)

Atrial Tachyarrhythmias N=87

None 48 (55%) Atrial flutter 5 (5.7%) Paroxysmal atrial fibrillation 19 (22%)

Persistent atrial fibrillation

(11.5%)

Other 5 (5.7%)

Ventricular Tachyarrhythmias N=87

None 80 (92%) Ventricular fibrillation Sustained or non-sustained VT 5 (5.7%) Other VT 2 (2.3%)

Existing/chronic leads prior to Corox OTW/Steroid

n=88

None 73 (83%) Yes, due to previous pacemaker therapy 15 (17%)

non-sustained VT (n=4); no further information available (n=1); 2) VES (n=2)

Stratos LV/LV-T Technical Manual 43

Safety and Effectiveness Results

• The cumulative implant duration was 760 months with a mean duration of 9.2 months. Sixty-five (77%) of the patients had implant durations greater than 6 months.

• The implant success rate for the Stratos LV CRT-P was 100% (89 out of 89). The implant success of the Stratos LV CRT-P in combination with the Corox OTW/Steroid LV lead was 94.4% (84 out of 89).

• The mean LV pacing threshold at implant was 0.9 and at 6-months was 0.9 volts.

• The mean R-wave at implant was 15.7 mV.

• The mean LV lead impedance at implant was 729 ohms

and at 6-months was 603 ohms.

• There were 29 adverse events (18 observations in 17 patients and 11 complications in 10 patients). There were no unanticipated adverse device effects reported.

• There were 10 patient deaths reported in the OVID study. The clinical investigators have determined that no deaths were related to the Stratos LV CRT-P system.

• The overall follow-up compliance rate for the OVID study is 93%.

Primary Endpoint—Complication-free Rate (Safety)

The safety of the Stratos LV was evaluated based on complications (adverse events that require additional invasive intervention to resolve) related to the implanted CRT system which includes the Stratos LV device, the atrial lead, the right ventricular lead, the left ventricular lead and the implant procedure. The target complication-free rate at six months was 85%.

Ten (10) complications in these categories were seen in 10 patients with cumulative implant duration of 760 months (63.3 patient-years). 11.2% of the patients had a reported complication in these categories. The rate of complications per patient-year was 0.16. Details of the Stratos LV complications in the OVID study are listed in Table 10

44 Stratos LV/LV-T Technical Manual

The freedom from Stratos LV system-related and procedurerelated complications was 88.76% with a one sided lower 95% confidence bound of 81.69%. Therefore, the null hypothesis was rejected, and it was concluded that the complication-free rate at 6 months is equivalent to 85% within 10% (p = 0.0014).

Observed Adverse Events

Of the 29 adverse events reported, there were 18 observations and 11 complications in a total of 89 patients. Table 10

Table 11

provide a summary by category of each type of

and

adverse event (complications and observations).

Table 10: Summary of Complications at 6 months

Category

Loss of capture

Phrenic nerve stimulation

Total

Number

Patients

Corox OTW/Steroid Lead-Related

% of

Patients

Number of

Complications

2 2.2% 2 0.03

1 1.1% 1 0.02

3 3.3% 3 0.05

Complications

per patient-

year

Atrial Lead Related

Loss of capture

Total

1 1.1% 1 0.02

RV Lead Related

Loss of capture

3 3.3% 3 0.05

Elevated Pacing

2 2.2% 2 0.03

thresholds

Total

5 5.6% 5 0.08

Stratos LV/LV-T Technical Manual 45

Table 10: Summary of Complications at 6 months

Category

Number

Patients

% of

Patients

Number of

Complications

per patient-

year

Device Related

Pocket infection

Total Total System

1 1.1% 1 0.02

10 11.2% 10 0.16

Other Medical

Arrhythmias 1 1.1% 1 0.02

Total

1 1.1% 1 0.02

Overall Complication

10 11.2% 11 0.17

Totals

Number of Patients = 89; Number of Patient-Years = 63.3

Table 11: Summary of Observations at 6 months

Observations

per patient-

year

Category

Number of

Patients

% of

Patients

Number of

Observations

Corox OTW/Steroid Lead-Related

Implant failure 5 5.6% 5 0.08 Phrenic nerve

stimulation

Total

4 4.5% 4 0.06

9 10.1% 9 0.14

Atrial Lead Related

Loss of capture

Total

1 1.1% 1 0.02

RV Lead Related

Elevated Pacing

2 2.2% 2 0.03

thresholds

Total

2 2.2% 2 0.03

46 Stratos LV/LV-T Technical Manual

Table 11: Summary of Observations at 6 months

Observations

per patient-

year

Category

Number of

Patients

% of

Patients

Number of

Observations

Device Related

Pocket infection/ Pericardial

1 1.1% 1 0.02

Effusion

Total Total System

1 1.1% 1 0.02

12 13.5% 13 0.21

Medical

Arrhythmias 2 2.2% 2 0.03 Shortness of

breath,

1 1.1% 1 0.02

palpitations

Total

3 3.3% 3 0.05

Miscellaneous

Malfunction of hemostatic

1 1.1% 1 0.02

valve Improper

Lead

1 1.1% 1 0.02

preparation

Total

2 2.2% 2 0.04

Overall Observation

17 19.1% 18 0.28

Totals

Number of Patients = 89; Number of Patient-Years = 63.3

There were a total of 10 patient deaths reported in the OVID study for patients with the Stratos LV device. The clinical investigators determined that no deaths were related to the Stratos LV device system.

Stratos LV/LV-T Technical Manual 47

1.7.3 AVAIL and OVID Combined Primary Endpoint-Complication-free Rate (Safety)

The results from for the AVAIL CLS/CRT and OVID studies were pooled to evaluate the safety of the Stratos LV device. The safety of the Stratos LV was evaluated based on complications (adverse events that require additional invasive intervention to resolve) related to the implanted CRT system which includes the Stratos LV, the atrial lead, the right ventricular lead, the left ventricular lead and the implant procedure. The target complication-free rate at six months was 85%.

Twenty-three (23) complications in these categories were seen in 21 patients with cumulative implant duration of 127.7 years.

12.8% of the patients had a reported complication in these

categories. The rate of complications per patient-year was 0.18. Details of the Stratos LV complications in the AVAIL CLS/CRT and OVID studies are listed in Table 12

Table 12: OVID and AVAIL Complication-Free

Rate - Stratos LV

Category

Number

Patients

% of

Patients

LV Lead-Related

High Threshold / No

1.8%

Capture Diaphragmatic

Stimulation

Dislodgement 1

1.2%

Total 7 4.3% 7 0.06

RV Lead Related

High Threshold / No

9 5.5% 9 0.07

Capture

Total 9 5.5% 9 0.07

Atrial Lead Related

No Capture

1 0.6% 1 0.01

Total 1 0.6% 1 0.01

Number of

Complications

per patient-

year

3 0.02

2 0.02

2 0.01

48 Stratos LV/LV-T Technical Manual

Table 12: OVID and AVAIL Complication-Free

Rate - Stratos LV

Category

Number

Patients

% of

Patients

Number of

Complications

per patient-

year

Device Related

Pocket Infection

2 1.2% 3 0.02

Total 2 1.2% 3 0.02

Procedure

Pneumothorax 1 0.6% 1 0.01 User error 1 0.6% 1 Hematoma 1 0.6% 1

0.01

Total 3 1.8% 3 0.02

Total Lead, Device and

Procedure

21 12.8% 23 0.18

Other Medical

Arrhythmias Repeated

ablation Worsening CHF Other Medical

1 0.6% 1 0.01

3 1.8% 3 0.02

2 1.2% 2 0.02

3 1.8% 3 0.02 Non-CHF cardiac

3 1.8% 3 0.02 symptoms

Total 11 6.7% 12 0.09

Total—All

Patients and

29 17.7% 35 0.27

Categtories

Number of Patients = 164 Number of Patient-Years = 127.7

Stratos LV/LV-T Technical Manual 49

The freedom from Stratos LV system-related and procedurerelated complications was 87.2% with a one sided lower 95% confidence bound of 82.09%. Therefore, the null hypothesis was rejected, and it was concluded that the complication-free rate at 6 months is equivalent to 85% within 10% and the primary safety endpoint was met (p = 0.0002)

1.7.4 Tupos LV/ATx Clinical IDE Study OPTION CRT/ATx

The CRT functionality of the Stratos CRT-P devices is based on the FDA approved Tupos LV/ATx. Therefore, the data from the OPTION CRT/ATx study supports the effectiveness of CRT. The OPTION CRT/ATx study was conducted on the Tupos LV/ATx, a device that delivers CRT but, in addition, also offers defibrillation therapy (CRT-D).

Study Design

The purpose of the prospective, randomized, multi-center OPTION CRT/ATx study was to demonstrate the safety and effectiveness of the investigational Tupos LV/ATx Cardiac Resynchronization Therapy Defibrillator (CRT-D) in patients with congestive heart failure (CHF) and atrial tachyarrhythmias. Patients in the study group were implanted with a BIOTRONIK Tupos LV/ATx. Patients in the control group were implanted with any legally marketed CRT-D. Patients in both the study and control groups were implanted with a legally marketed left ventricular lead.

p value is provided for informational purposes to show trends only; clinical

significance is not indicated by p values for analyses that were not prespecified.

50 Stratos LV/LV-T Technical Manual

Primarily, the study evaluates and compares the functional benefits of CRT between the two randomized groups using a composite endpoint consisting of a six-minute walk test (meters walked) and quality of life measurement (assessed using the Minnesota Living with Heart Failure Questionnaire). Relevant measurements were completed twice for each patient: once at the Baseline evaluation (two-week post implant follow-up) and again at a six-month follow-up evaluation. The data collected during this clinical study was used to demonstrate equivalent treatment of CHF in both the study and control groups. This study also evaluated other outcomes including: the percentage of time CRT is delivered, and other measures of CHF status, including NYHA classification, peak oxygen consumption during metabolic exercise testing, and the rate of hospitalization for CHF.

Clinical Inclusion Criteria

To support the objectives of this investigation, patients were required to meet the following inclusion criteria prior to enrollment:

• Stable, symptomatic CHF status

• NYHA Class III or IV congestive heart failure

• Left ventricular ejection fraction ≤ 35% (measured within

six-months prior to enrollment)

• Intraventricular conduction delay (QRS duration greater than or equal to 130 ms)

• For patients with an existing ICD, optimal and stable CHF drug regimen including ACE-inhibitors and betablockers unless contraindicated (stable is defined as changes in dosages less than 50% during the last 30 days)

• Indicated for ICD therapy

• History or significant risk of atrial tachyarrhythmias

• Willing to receive possibly uncomfortable atrial shock

therapy for the treatment of atrial tachyarrhythmias

• Able to understand the nature of the study and give informed consent

Stratos LV/LV-T Technical Manual 51

• Ability to tolerate the surgical procedure required for implantation

• Ability to complete all required testing including the sixminute walk test and cardiopulmonary exercise testing

• Available for follow-up visits on a regular basis at the investigational site

• Age greater than or equal to 18 years

Clinical Exclusion Criteria

To support the objectives of this investigation, the exclusion criteria at the time of patient enrollment included the following:

• Previously implanted CRT device

• ACC/AHA/NASPE indication for bradycardia pacing

(sinus node dysfunction)

• Six-minute walk test distance greater than 450 meters

• Chronic atrial tachyarrhythmias refractory to

cardioversion shock therapy

• Receiving intermittent, unstable intravenous inotropic drug therapy (patients on stable doses of positive inotropic outpatient therapy for at least one-month are permitted)

• Enrolled in another cardiovascular or pharmacological clinical investigation

• Expected to receive a heart transplant within 6 months

• Life expectancy less than 6 months

• Presence of another life-threatening, underlying illness

separate from their cardiac disorder

• Acute myocardial infarction, unstable angina or cardiac revascularization within the last 30 days prior to enrollment

• Conditions that prohibit placement of any of the lead systems

52 Stratos LV/LV-T Technical Manual

Follow-Up Schedule

After successful enrollment, all patients were randomly assigned to either the study group or the control group. The specific procedures of this study were:

• Pre-enrollment screening

• Randomization

• System implantation

• Pre-discharge follow-up

• Baseline evaluation / CRT activation

• One-Month follow-up

• Three-Month follow-up

• Six-Month follow-up

• Subsequent routine follow-ups (every three months)

Clinical Endpoints

Primary Endpoint 1: Six Minute Walk Test & QOL (Effectiveness) The purpose of Primary Endpoint 1 is to evaluate the effectiveness of the Tupos LV/ATx system in providing CRT as measured by the average composite rate of improvement in six minute walk test and QOL.

Secondary Endpoint Results

1. The purpose of this secondary endpoint is to evaluate improvement in functional capacity as measured by the six minute walk test. The six minute walk test is a well-accepted measure of functional capacity and exercise tolerance. Also, this test more closely mimics the patient’s day-to-day activities than maximal exercise testing.

2. The purpose of this secondary endpoint is to evaluate the improvement in the patient’s NYHA classification.

Accountability of PMA Cohorts

After randomization and enrollment, 7 patients (4 in the study group and 3 in the control group) did not receive an implant. The reasons for patients not receiving an implant are outlined in

Figure 2

Stratos LV/LV-T Technical Manual 53

Enrolled and Randomized

Patients

Study 133 Control 67

No implant Attempted

Withdrawal of Consent

Study 2 Control 1

Not Meeting Inclusion Criteria

Study 1 Control 1

Implant Attempted

Study 130 Control 65

Unsuccessful implant

Withdrawal of IC before 2nd Attempt

Expired before Second Attempt

Successful implant

Study 129 Control 64

6-Month Follow-up Data

Patient Death before 6-Month

Withdrawal before 6-Month

Not Reached 6-Month FU

Patients completed 6-Month

Follow-up

Study 100 Control 49

Figure 2: Patient Accountability

Demographics and Baseline Parameters

Study 1 Control 0

Study 0 Control 1

Study 7 Control 3

Study 1 Control 2

or Data Pending

Study 21 Control 10

Table 13

provides a summary of the pre-enrollment

demographics of enrolled patients.

54 Stratos LV/LV-T Technical Manual

Table 13: Patient Demographics at Pre-Enrollment

Characteristic

Age at Enrollment (Years)

Mean ± SE Range

Gender

Male Female

Underlying Heart Disease

Ischemic Cardiomyopathy Nonischemic Cardiomyopathy

Type of Bundle Branch Block

Left Bundle Branch Block Right Bundle Branch Block Other

New York Heart Association Class

Class III Class IV

Intrinsic QRS Duration (ms)

Mean ± SE Range

Left Ventricular Ejection Fraction (%)

Mean ± SE Range

Six Minute Walk Distance (meters)

Mean ± SE Range

Quality of Life Questionnaire Score

Mean ± SE Range

*Student's t-test (2-sided) for means, **Fisher's Exact Test (2-sided) for 2 possible answers, ***Chi-Square test (2-sided) for more than 2 possible answers

Study

N=133

69.5 ± 0.9 43 to 88

93 (69.9%) 40 (30.1%)

100 (75.2%)

34 (25.6%)

91 (68.4%) 26 (19.5%) 19 (14.3%)

121 (91.0%)

12 (9.0%)

161.9 ± 2.0 130 to 252

22.1 ± 0.6 5 to 35

254.8 ± 8.9 20 to 451

54.3 ± 2.1 0 to 105

Control

N=67

69.1 ± 1.2 38 to 84

51 (76.1%) 16 (23.9%)

54 (80.6%) 15 (22.4%)

49 (73.1%) 10 (14.9%) 11 (16.4%)

60 (89.6%)

7 (10.4%)

156.1 ± 2.3 130 to 200

23.3 ± 0.8 10 to 35

250.5 ±

11.9

27 to 447

52.5 ± 3.1 0 to 102

P-

value

0.781*

0.407**

0.294***

0.877***

0.800**

0.073*

0.255*

0.775*

0.638*

Stratos LV/LV-T Technical Manual 55

Table 14 provides a summary of cardiac medications patients

were taking at the time of enrollment. Some categories may be more than 100% as several categories allow more than one response.

Table 14: Cardiac Medications at Pre-Enrollment

Drug

Category

Specific CHF Medications

ACE inhibitors

Angiotensin receptor blockers

Beta blockers Cardiac glycosides (Digoxin) Diuretic Inotropes

Anti-arrhythmics Nitrates

*Student's t-test (2-sided) for means, **Fisher's Exact Test (2-sided) for 2 possible answers, ***Chi-Square test (2-sided) for more than 2 possible answers

Study

(N=133)

89 (66.9%) 21 (15.8%)

111 (83.5%)

60 (45.1%)

114 (85.7%)

1 (0.8%)

34 (25.6%)

36 (27.1%)

Control

(N=67) P-value

45 (67.2%) 16 (23.9%) 55 (82.1%) 35 (52.2%) 57 (85.1%)

3 (4.5%)

19 (28.4%)

14 (20.9%)

1.000**

0.180**

0.843**

0.370**

1.000**

0.110**

0.735**

0.390**

Safety and Effectiveness Results

A total of 200 patients were enrolled in the OPTION CRT/ATx clinical study at 25 sites:

There were 133 study patients and 67 active control patients in this prospective, multi-center, randomized clinical study. For the study group, there were 129 successful implants (91.4%) of the Tupos LV/ATx CRT-D system. For the active control group, there were 64 successful implants (92.2%) of the legally marketed CRT-D systems.

56 Stratos LV/LV-T Technical Manual

• There were 192 endocardial and 19 epicardial leads implanted in 193 patients. Investigators were allowed to choose among any legally marketed LV lead according to their familiarity with the lead and patient anatomy. The Tupos LV/ATx CRT-D was implanted with 7 endocardial and 4 epicardial lead models from 6 different manufacturers. There were no adverse events reported attributable to lead-generator incompatibility.

• The cumulative implant duration is 1240.4 months with a mean duration of 9.6 months for the study group. The cumulative implant duration is 596.5 months with a mean duration of 9.3 months for the control group.

• The overall protocol compliance rate is 79.2% in the study group and 85.9% in the control group. The overall follow-up compliance rate is 99.4% in the study group and 98.3% in the control group.

• There have been 10 patient deaths reported in the study group and 4 patient deaths reported in the control group. The clinical investigators have determined that no deaths were related to the study device.

Primary Endpoint 1: Six Minute Walk Test & QOL (Effectiveness)

The purpose of Primary Endpoint 1 is to evaluate the effectiveness of the Tupos LV/ATx system in providing CRT as measured by the average composite rate of improvement in six minute walk test and QOL.

Table 15

presents the average composite rate of improvement in six minute walk test distance and QOL score, the average 6minute walk test distance and the average QOL score at Baseline and at the Six-Month follow-up, as well as the average difference in 6-minute walk test distance and QOL score between Baseline and the Six-Month follow-up for the Study and Control Groups for those patients with six minute walk test data and complete QOL data at both Baseline and the Six-Month follow-up.

Stratos LV/LV-T Technical Manual 57

Table 15: Composite of Six Minute Walk Test and QOL

(Effectiveness)

Category

Study Group

(N = 74)

Mean ± SE

Control Group

(N = 38)

Mean ± SE

Distance

Walked at

310.51 ± 10.89 288.76 ± 15.37 0.249

Baseline Distance

Walked at

340.77 ± 12.32 301.84 ± 17.02 0.067

Six-Months

∆ Distance

Walked

QOL Score at

Baseline

QOL Score at

Six-Months

∆ in QOL

Score†

Composite

Rate

‡

30.26 ± 10.40

17.27% ± 5.59%

44.39 ± 2.78 45.53 ± 4.13 0.817

28.68 ± 2.66 33.95 ± 4.35 0.279

15.72± 2.83

19.08% ± 12.21%

18.18% ± 7.07% -2.36% ± 17.73% 0.030

13.08 ± 13.05

8.71% ± 5.26%

11.58 ± 3.45

-13.42% ±

34.54%

P-value

0.322

0.326

0.376

0.281

The calculated p-values are associated with a Student's t-test (2-sided) of the equality of means in the two groups, except for the p-value of the composite rate, which is associated with a test of equivalence (non-inferiority).

†

∆ in QOL Score is calculated as the average of the individual differences

between Baseline and Six-Months for each patient. Negative values for mean ∆ QOL in percent are possible when positive mean values for absolute changes in QOL are recorded. In some cases, small, negative changes in absolute QOL scores resulted in relatively large percentage changes.

‡

The Composite Rate (=(∆ Distance Walked (%) + ∆ QOL Score (%)) / 2) is

calculated for each patient and then averaged to obtain the Composite Rates. For all calculations, a positive number represents improvement from Baseline to Six-Months.

58 Stratos LV/LV-T Technical Manual

Primary Effectiveness Endpoint Analysis and Conclusions

A composite rate of six minute walk test and QOL improvement from Baseline to the Six-Month follow-up is evaluated as a measure of CRT effectiveness. For this analysis both six minute walk test and QOL are equally weighted at 50%.

The mean difference in the composite rate between study and control group was 20.53% with an associated one-sided, 95% confidence bound of (-6.10%). The p-value for non-inferiority within 10% is 0.030. The analysis of the composite rate in six minute walk test distance and QOL score demonstrates that the study group is non-inferior to the control group and that the primary effectiveness endpoint was met (p=0.030).

Secondary Endpoint Results

Table 16

summarizes the six minute walk test distance at Baseline and the Six-Month follow-up for patients in the study group and the control group.

Table 16: Six Minute Walk Distance

Distance

(meters)

Baseline

Mean ± SE

Range

Median

Six-Month

Mean ± SE

Range

Median

* Student's t-test, 2-sided

Study Control

127

283.14 ± 9.27

269.43 ± 13.77

23 to 511

302.00

329.73 ± 10.82

310.70 ± 15.49

78 to 596

335.00

29 to 507

244.00

91 to 489

313.00

Stratos LV/LV-T Technical Manual 59

There are no clinically relevant differences in the six minute walk test results between the study and the control group.

2. The purpose of this secondary endpoint is to evaluate the improvement in the patient’s NYHA classification. Table 17 summarizes the average improvement in NYHA from Baseline to Six-Months for 140 patients that were able to complete both NYHA classification evaluations.

Table 17: Improvement in NYHA Classification at

Six-Months from Baseline

Change in

NYHA class

Number of

Improved 2

classes

Improved 1

class Total

improved

No change 39

Worsened 1

class

Study

(N=97)

Patients

% of Total

Patients

Number of

10.3% 2 4.7%

48.5% 20 46.5%

58.8% 23 51.2%

40.2% 20 46.5%

1.0% 1 2.3%

Control

Patients

(N=43)

% of

Total

Patients

The study and the control group have similar NYHA classes and similar rates of improvement in NYHA class from Baseline to the Six-Month follow-up.

60 Stratos LV/LV-T Technical Manual

Multi-site Poolability and Gender Analysis

The OPTION CRT/ATx clinical report includes data from multiple centers with centralized coordination, data processing, and reporting at BIOTRONIK. All of the clinical centers followed the requirements of an identical clinical protocol, and all of the clinical centers used the same methods to collect and report the clinical data. In order to justify pooling of the data from multiple centers, several analyses were completed. All of the centers were divided into two groups based on implant volume. Comparisons were then made between the patient populations based on the results of each of the endpoints. Additionally, analyses were performed on the data collected in the OPTION CRT/ATx clinical investigation in order to compare results between males and females. The first type of analysis compared enrollment by patient gender in each of the study and control groups. The second type of analysis compared effectiveness outcomes in each gender.

The results of these analyses demonstrate poolability of the data between sites. There were no significant differences in the second primary endpoint or any of the secondary endpoints between high and low volume implant centers.

The gender distribution in this clinical investigation is consistent within the study groups and includes a representative proportion of enrolled female participants (28.0% versus 72.0% male). There were no significant differences in any of the primary or secondary endpoints between the male and female population.

Stratos LV/LV-T Technical Manual 61

1.7.5 Conclusions Drawn from Studies

The clinical study results support the safety and effectiveness of the Stratos LV CRT-P device.

• The OPTION CRT/ATx clinical study completed and

reviewed under P050023 provided a reasonable assurance that bi-ventricular pacing is effective in NYHA class III/IV heart failure patients with a prolonged QRS and a left ventricular ejection fraction <35%. The addition of ICD back-up therapy does not affect the biventricular pacing performance of the device.

• The AVAIL CLS/CRT and Corox (OVID) clinical studies

demonstrated the safety of the Stratos LV CRT-P in NYHA class III/IV heart failure patients with a prolonged QRS and a left ventricular ejection fraction <35%.(OVID).

62 Stratos LV/LV-T Technical Manual

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2. Programmable Parameters

For a complete list of programmable parameters and the available settings for the Stratos CRT-Ps, see Section 11.

2.1 Pacing Modes

For a complete list of pacing modes available in each Stratos CRT-P configuration, see Section 11.1.

2.1.1 Rate-adaptive Modes

The rate-adaptive modes are designated with an “R” in the fourth position of the NBG pacemaker code on the programmer screen. The rate-adaptive modes function identically to the corresponding non-rate-adaptive modes, except that the basic rate increases when physical activity is detected by the motion sensor.

In demand modes (i.e., DDDR, DDIR, DVIR, VDDR, VVIR, AAIR), it is possible that the atrial and/or ventricular refractory period can comprise a major portion of the basic interval at high sensor-modulated rates. This may limit the detection of spontaneous events or even exclude their recognition altogether.

WARNING

Rate Adaptive Pacing – Use rate-adaptive pacing with care

in patients unable to tolerate increased pacing rates.

2.1.2 DDD

The timing of the Stratos CRT-Ps is based on atrial events.

In the case of an atrial sensed or paced event, the AV delay starts the same time as the basic interval. If a ventricular sensed event does not occur within the AV delay, ventricular pacing is initiated at the end of the AV delay. If ventricular sensing occurs within the AV delay, ventricular pacing is inhibited.

If atrial sensing occurs outside the atrial refractory period, atrial pacing is inhibited and the basic interval is restarted.

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In the case of ventricular sensed events outside of the AV delay and the VES discrimination interval after a ventricular extrasystole (VES or PVC), the basic interval starts without simultaneously starting an AV delay. To protect the atrium from retrograde conduction, an extended PMT protection window is started at the same time as the basic interval. If an atrial sensed event does not occur within the basic interval (but outside the refractory period), atrial pacing occurs after the basic interval has elapsed, and the basic interval and AV delay are restarted. Upon an atrial paced event, the AV safety interval starts with a long basic interval. If a ventricular sensed event occurs within the AV delay, ventricular pacing is inhibited.

Table 18

summarizes the intervals initiated by sensing or pacing. The table distinguishes between two kinds of ventricular sensed and ventricular paced events: VP at the end of the AV delay; VP at the end of the safety AV delay, referred to as ventricular safety pace (V

); VS within the AV delay; and VS

outside of the AV delay, referred to as “ventricular extrasystole” (VES).

Table 18: Timing Intervals

Event Timing

Interval

Ap As As

Vp Vsp VS VES

(PMT)

Basic interval

(DDD) Basic interval

†

(DDI) Atrial refractory

‡

period Upper basic rate Ventricular

Refractory Period

X X

X X X

X X

X X X X

This timing interval is also applicable to the following modes: DDD(R), VDD(R),

AAI(R), DDT, VDT, AAT, DOO(R) and AOO(R)

†

In DDI(R), DVI(R), VVI(R), DVT(R), DDI/T(R) and V00(R) lower rate timing starts with Vp, and/or Vs, and/or Vs event outside of the AV delay and the VES discrimination window (VES).

‡

In DDI(R), DDI/T, VDD(R), and VDT, the atrial refractory period will also be reset upon time-out of the VA-interval whether or not an atrial pulse is emitted.

Table 18: Timing Intervals

Interval

AV delay X X Safety AV delay X Interference

interval (A) Interference

interval (V) Blanking time

(A) after Ap Blanking time

(V) after RVp Atrial upper rate

(AUR) Far-field

Protection (A) PMT Protection

(A) PMT protection

extension (A)

Ap As As

Trigger Pacing

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Event Timing

Vp Vsp VS VES

(PMT)

X X

X X X X

X X

The triggered pacing modes are identical to the respective demand modes except that the sensing of an atrial/ventricular event outside of the refractory period does not result in inhibition of pacing, but instead a pacing pulse is delivered in the respective chamber.

The corresponding pacing modes are:

Demand

DDD VDD DDI DVI AAI VVI

Pacing

Triggered

DDT VDT DDI/T DVT AAT VVT

pacing

However, the following differences exist. There is no AV safety interval in DDT, DDI/T and DVT pacing modes. The safety interval is unnecessary as “cross talk” (ventricular sensing of atrial pulses) can not occur during these modes.

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In the DDI/T and DVT pacing modes, the basic interval is not restarted if ventricular sensing occurs within the AV delay.

CAUTION

Programmed to Triggered Modes – When programmed to

triggered modes, pacing rates up to the programmed upper limit may occur in the presence of either muscle or external interference.

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2.1.3 DDI

In contrast to DDD mode, the basic interval in the DDI mode is not restarted by sensed P-waves, but by ventricular sensed or paced events. The VA delay is started together with the basic interval. If atrial or ventricular sensing does not occur during the VA delay, the atrial pacing occurs at the end of the VA delay.

Atrial pacing starts the AV delay. If atrial sensing occurs outside of the atrial refractory period (ARP), a PMT safety interval or the FFP (far-field protection) window, atrial pacing is inhibited. However, the AV delay does not start with a sense event, but at the end of the VA interval. Therefore, P-waves in the DDI mode do not trigger ventricular events.

NOTE:

For additional information on far-field protection window, see Section 2.3 “Timing Functions”.

An atrial sensed event that occurs during the PMT protection window starts the atrial upper basic rate to avoid pacing during the vulnerable phase of the atrium. If the interval of the atrial upper rate is longer than the basic interval, the AV delay is shortened by that same amount after atrial pacing, but only until the end of the safety interval.

2.1.4 DVI

The DVI mode is derived from the DDI mode. In contrast to the latter, atrial sensing does occur. Therefore, atrial pacing is delivered at the end of the AV delay. Ventricular sensing within the AV delay inhibits atrial and ventricular pacing. Ventricular sensing within the AV delay inhibits ventricular pacing.

2.1.5 VDD

The VDD mode corresponds to the DDD mode with the exception that it does not provide atrial pacing. In the absence of a sense event, the basic interval starts with either an atrial sense event, a ventricular extrasystole or after expiration of the preceding basic interval.

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2.1.6 AAI and VVI

The pacing modes AAI and VVI provide atrial and ventricular demand pacing. The lower rate timer is started by a sense or pace event. A sense event outside of the refractory period inhibits pacing and resets the lower rate timer; in the absence of a sense event, a pulse generator pulse will be emitted at the end of the lower rate interval.

2.1.7 AAI, VVI

The AAI and VVI single-chamber pacing modes are used in atrial and demand pacing. In each case, pacing and sensing only occur in the atrium (AAI) or the ventricle (VVI).

The basic interval is started by a sense or pace event. If the sense event occurs before the basic interval has expired, pacing is inhibited. Otherwise, pacing occurs at the end of the basic interval.

2.1.8 AOO, VOO

In these modes, atrial, ventricular and AV sequential pulses, respectively, are emitted asynchronously. These modes primarily serve diagnostic purposes during follow-up. When programming to the VOO or VOO mode, the risks associated with asynchronous ventricular pacing should be considered.

2.1.9 DOO

Asynchronous, AV sequential pacing pulses are emitted in this pacing mode. When programming DOO mode, the risks of asynchronous ventricular pacing should be considered.

2.1.10 VDI

The VDI mode corresponds to the VVI mode, with the additional function of providing atrial sensing. However, the timing is the same as the VVI mode. The purpose of the VDI mode is to permit the use of the marker function with the IEGM for the atrial channel, for example, to measure the retrograde conduction time.

The VA conduction time between a ventricular pace or sense event (with marker) and the atrial sense event can be measured directly on the display or printout from the programmer or on an ECG strip chart recorder (IEGM/marker output function).

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2.1.11 OFF (ODO)

In this mode, pacing and sensing functions are off. The OFF mode is used to determine and evaluate the morphology of an intrinsic rhythm. With external pulse control, the OFF mode is used for electrophysiological studies. The OFF mode can be programmed temporarily.

CAUTION

OFF Mode – The OFF mode can be transmitted as a

temporary program only to permit evaluation of the patient’s spontaneous rhythm. (see Section 2.1.11).

2.2 Biventricular Synchronization of the Stratos CRT-Ps

For the Stratos CRT-Ps, there are 2 possible settings for the BiV Sync parameter: OFF and BiV RV RV-T.

OFF - If the BiV sync parameter is set to OFF, the CRT-P ignores the left-ventricular channel and functions like a conventional dual-chamber pacemaker. Consequently, pacing is not delivered into the left ventricle.

BiV RV RV-T - When set to "BiV RV RV-T" the device provides biventricular pacing with sensing in the right ventricle and triggering of a right ventricular sensing event in the left ventricle.

The biventricular synch settings can be activated together with the DDD(R), DDI(R), VDD(R), and VVI(R) pacing modes.

CAUTION

Sensing – The Stratos CRT-Ps do not sense in the left

ventricle.

AV Conduction – In patients with intact AV conduction, the intrinsic atrial tachycardia is conducted to the ventricle 1:1. With the resynchronization mode activated, spontaneous rate of the right ventricle mode is synchronized for a rate up to 200 ppm in the left ventricle. For this reason, biventricular pacing mode should be turned OFF in such cases.

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During biventricular pacing in the Stratos CRT-Ps, the right ventricle is paced first. Starting from the initially paced chamber (RV), the intraventricular conduction time (VV delay) is permanently set to 5 ms after a right ventricular sensed or paced event.

NOTE:

While ventricular pacing and sensing events are synchronized, synchronization does not occur during ventricular extrasystoles.

The following table presents in detail the effects of the standard pacing modes with the biventricular modes:

Table 19. Biventricular Pacing Modes

RVs inhibits RVp X X X X X X X X X RVs triggers LVp X X X X X X X X X

Biventricular Pacing Modes

(BiV RV RV/T)

DDD

VDD

DDI

VDI

VVI

DDD

VDD

DDI

VDI

2.3 Timing Functions

The availability of parameters and parameter values is determined by the software used for programming / interrogating the CRT-Ps.

2.3.1 Basic Rate

The basic rate is the pacing rate in the absence of an intrinsic rhythm and is programmable up to 180 ppm. The interval for the basic rate is the time between two pacing pulses and is thus called the basic interval.

The basic rate is programmable:

32… (1)…60… (1)…88… (2)…122… (3)…140… (5)…180 ppm.

In atrial-controlled modes, the basic interval is started by an atrial event. In atrial-controlled, dual-chamber modes, the basic interval is also started by a ventricular extrasystole.

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In the ventricular-controlled modes, the basic interval is started by a ventricular event.

CAUTION

Programming Modifications – Extreme programming

changes should only be made after careful clinical assessment. Clinical judgment should be used when programming permanent pacing rates below 40 ppm or above 100 ppm.

2.3.2 Rate Hysteresis

Rate Hysteresis can be programmed in DDD(R), DDT(R), DDT(R)/A, DDI(R), VDD(R), VDT(R), VDI(R), VVI(R), VVT(R), AAI(R) and AAT(R) modes. Hysteresis can be programmed OFF or to values as low as -50 bpm. The Hysteresis rate is based on the lower rate and the value of the programmable parameter. Hysteresis is initiated by a sensed event. The resulting Hysteresis rate is always less than the lower rate. A conflict symbol (>>) will appear and transmission will be prohibited for Hysteresis rates which are less than 30 bpm. The ability to decrease the effective lower rate through Hysteresis is intended to preserve intrinsic rhythm. The Stratos CRT-Ps operate by waiting for a sensed event throughout the effective lower rate interval (Hysteresis interval). If no sensed event occurs, a pacing pulse is emitted following the Hysteresis interval.

In DDD(R), DDT(R)/A, DDT(R), VDD(R), VDT(R), AAT(R) and AAI(R) pacing modes, the hysteresis interval starts with an atrial sense event. In DDI(R), VVI(R), VVT(R) and VDI(R) pacing modes, the hysteresis interval starts with a ventricular sense event. In DDD(R), DDT(R)/A, DDT(R), VDD(R) and VDT(R) pacing modes, the hysteresis interval also starts with ventricular extrasystoles.

NOTE:

If rate adaptation is active, the Hysteresis rate is based on the current sensor-indicated rate and the value of the programmable parameter.

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The rate hysteresis is deactivated in the standard setting, but can be programmed from -5… (-5) … -90.

If Hysteresis is used in the DDI mode, the AV delay must be programmed shorter than the spontaneous AV conduction time. Otherwise, stimulation in the absence of spontaneous activity occurs at the hysteresis rate instead of the lower rate.

Hysteresis is suspended during the Night Mode activated time. Programming conflicts arise when the total decrease in rate is below 30 ppm. Care should be exercised to avoid programming a Night Mode rate and hysteresis that is below what is appropriate and may be tolerated by the individual patient.

2.3.3 Scan Hysteresis

Scan hysteresis is expanded programmability of the Hysteresis feature. Scan hysteresis searches for an underlying intrinsic cardiac rhythm, which exists slightly below the programmed lower rate (or sensor-indicated rate) of the CRT-P. Following 180 consecutive paced events, the stimulation rate is temporarily decreased to the hysteresis rate for a programmed number of beats. If a cardiac rhythm is not detected within the programmed number of beats at the hysteresis rate, the stimulation rate returns back to the original lower rate (or sensor-indicated rate). Several programmable beat intervals are available to allow a greater probability of detecting a spontaneous rhythm.

If an intrinsic cardiac rhythm is detected within the programmed number of beats between the hysteresis rate and the lower rate, the intrinsic rhythm is allowed and the CRT-P inhibits pacing.

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Figure 3. Scan Hysteresis

Scan hysteresis has been incorporated to promote intrinsic cardiac rhythm and may reduce device energy consumption.

The number of scan interval is programmable, OFF, 1…(1)…15 cycles.

NOTES:

Scan Hysteresis is not active during the programmed Night Mode. Scan Hysteresis is only available when Hysteresis is selected on. Magnet application (closing of reed switch) suspends 180 consecutive event counter independent of the magnet effect.

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2.3.4 Repetitive Hysteresis

Repetitive hysteresis is expanded programmability of the Hysteresis feature. Repetitive hysteresis searches for an underlying intrinsic cardiac rhythm, which may exist slightly below the programmed lower rate (or sensor-indicated rate) of the patient. Following 180 consecutive sensed events, this feature allows the intrinsic rhythm to drop to or below the hysteresis rate. During the time when the intrinsic rate is at or below the hysteresis rate, pacing occurs at the hysteresis rate for the programmed number of beats (up to 10). Should the number of programmed beats be exceeded, the stimulation rate returns to the lower rate (or sensor-indicated rate).

If an intrinsic cardiac rhythm is detected within the programmed number of beats between the hysteresis rate and the lower rate, the intrinsic rhythm is allowed and inhibits pacing by the CRT-P.

Figure 4. Repetitive Hysteresis

Repetitive hysteresis has been incorporated to promote spontaneous cardiac rhythm and may reduce device energy consumption.

NOTES:

Repetitive Hysteresis is not active during the programmed Night Mode.

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Repetitive Hysteresis is only available when Hysteresis is selected on. Magnet application (closing of reed switch) suspends 180 consecutive event counter independent of synchronous or asynchronous magnet effect. There is one Standard Hysteresis interval which occurs before the programmable number of Repetitive Hysteresis occurs. The repetitive rate hysteresis is deactivated in the standard setting, but can be programmed to 1… (1) …15 cycles.

2.3.5 Night Mode

Programmable Night Time Begin and End in 10 minute steps. The Night Mode feature allows a temporary reduction of the base rate during normal sleeping hours. If selected, the base rate is gradually and temporarily reduced to the programmed night pacing rate. At the end of night mode, the base rate gradually returns to the original values.

The Night Mode feature has been incorporated to allow the patients spontaneous night rhythm and may reduce pulse generator energy consumption.

NOTES:

Over time, the Stratos CRT-Ps internal time-of-day clock may exhibit a discrepancy with the actual time (less than 1 hour per year). This may cause a corresponding discrepancy between the programmed sleep and wake times and the actual times that the system changes the rate. The programmer automatically updates the CRT-P timeof-day clock each time the device is programmed. The actual time when the respective increase or decrease in rate occurs may begin up to 4 minutes after the programmed time because of internal device timing. The rate (ppm/s) at which Night Mode decreases and increases is a function of the Sensor Gain decrease and increase parameters.

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2.3.6 Refractory Periods

Sensed events that occur during the refractory period have no effect on pacemaker timing. These atrial or ventricular sensed events are classified as “unused” for normal CRT-P timing.

In the Stratos CRT-Ps, the total atrial refractory period has been subdivided into an atrial refractory period (ARP), atrial far-field protection (FFP) and a PMT protection window (PMT). In terms of priority FFP is first, ARP second and PMT third.

When mode switching is turned ON, the atrial events in the atrial refractory period and the PMT protection window are used as the criteria in order to sense atrial tachyarrhythmias and to ensure high atrial rates are not transmitted to the ventricle.

The behavior of BIOTRONIK CRT-Ps reacts differently depending on the timing interval in which the atrial event occurs. The behavior is summarized in Table 20.

Table 20. Response to Atrial Sense Events in Different

Timing Intervals in Stratos CRT-Ps

Timing Interval Response

As occurs during the far-field protection (FFP)

As occurs during the Atrial Refractory Period (ARP)

As occurs in the PMT protection window

No consequence. As is ignored (unused). Neither the AV delay nor the ARP is started. There is no influence on mode switching.

The event influences mode switching.

The AUI (atrial upper interval) starts. The AV delay is not restarted. Post-AES pacing is started if the atrial sense is classified as an AES.

2.3.6.1 Atrial Refractory Period

In all modes in which atrial depolarization can be sensed, the Stratos CRT-Ps will start an atrial refractory period upon each atrial depolarization (programmable: AUTO, 225…(25)…775). In standard “Auto” setting, the atrial refractory period (ARP) is automatically preset to a minimum value of 225 ms and is automatically extended if the AV delay is longer.

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In the case an atrial sense event falls within the PMT protection window, the Stratos CRT-Ps start a minimal ARP.

2.3.6.2 Atrial Far-Field Protection

In all dual chamber modes with atrial sensing, the Stratos CRT-Ps start an atrial FFP window upon each ventricular event to prevent sensing of far-field potentials in the ventricle. The atrial far-field protection window is separately programmable for ventricular sensed events at 30…(10)…100…(1)…200 ms and for ventricular paced events at 30…(10)…100 and 100…(10)…220 ms. If an atrial event occurs during the FFP window, the atrial event is classified as an invalid FFP event and has no influence on the timing of the CRT-P.

With ventricular events (right ventricular sensed or paced, left ventricular paced, VES), the Stratos CRT-Ps start an FFP interval.

2.3.7 Atrial PMT Protection

In all atrial-controlled dual-chamber modes, Stratos CRT-Ps start the PMT protection interval after each ventricular stimulus. This prevents retrograde conduction and triggering of pacemaker-mediated tachycardias (PMTs). Right ventricular extrasystoles begin an extended PMT interval.

In all dual-chamber modes controlled by the ventricle, the Stratos CRT-Ps start the PMT protection interval after each initial (right or left) ventricular event.

The PMT protection interval after a Vp is freely programmable, while the PMT interval after VES is automatically set to 225 ms greater than the PMT interval after Vp (Nominal value: 250 ms/ AUTO (175…(5)…600 ms).

If an atrial event occurs within the atrial PMT protection interval, the atrial event is classified such that the AV delay is not restarted.

In the Stratos CRT-Ps, the PMT protection interval is started with a right or left ventricular paced event.

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2.3.8 Ventricular Refractory Period

In all modes in which a ventricular depolarization can be sensed, the Stratos CRT-Ps begin a ventricular refractory period after each ventricular event, using a standard value of 250 ms (programmable as 150…(35)…500 ms).

2.3.9 AV Delay

2.3.9.1 Dynamic AV Delay

Programmable values

Lower AV limit:

Nominal value: 60 ppm, (30…(10)…180 ppm)

Upper AV limit:

Nominal value: 130 ppm, (30…(10)…180 ppm)

AV Interval Length for Low Rate:

Standard value: 150 ms (programmable 15… (5) …300 ms)

The AV delay defines the interval between an atrial paced or sensed event and the ventricular pacing pulse. The AV delay can be dynamically programmed in DDD(R), DDT(R)A and VDD(R) modes. In all other mode the AV delay is a fixed value. If the CRT-P is programmed to a dual chamber sensing mode, an intrinsic ventricular event falling within the AV delay will inhibit the ventricular pacing pulse. If not contraindicated, a longer AV delay can be selected to increase the probability of ventricular output pulse inhibition. Short AV delays are available for testing purposes or if ventricular pre-excitation is desired (i.e., hemodynamic considerations). When the dynamic AV delays are programmed, the dynamics are calculated from the difference between two atrial sense events (As or Ap).

Dynamic AV Delay provides independent selection of AV Delays from five rate ranges at pre-set AV Delay values. In addition, the AV Delay after atrial pace events can be differentiated from the AV interval after atrial sense events for dual chamber pacing modes.

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The Dynamic AV Delay is intended to mimic the physiologic, catecholamine-induced shortening of the AV Delay with increasing rate. It also serves for automatic prevention/termination of “circus movement” pacemaker mediated tachycardia and for prevention of reentrant supraventricular tachycardia (see PMT Management section).

2.3.9.2 AV Hysteresis

AV Hysteresis allows a user-programmable change in AV delay that is designed to encourage normal conduction of intrinsic signals from the atrium into the ventricles. An AV hysteresis interval can be programmed OFF or a value range of 10…(10)…1000. With AV hysteresis enabled, the AV delay is extended by a defined time value after sensing a ventricular event. The long AV interval is used as long as intrinsic ventricular activity is detected. The programmed short AV delay interval resumes after a ventricular paced event.

CAUTION

AV Hysteresis – If the AV hysteresis is enabled along with

the algorithm for recognizing and terminating PMTs (PMT management), the AV delay for recognizing and terminating a PMT has a higher priority than the AV hysteresis.

2.3.9.3 AV Repetitive Hysteresis

With AV Repetitive Hysteresis, the AV delay is extended by a defined hysteresis value after sensing an intrinsic ventricular event. When a ventricular stimulated event occurs, a long AV delay is used for the programmed number of cycles. (OFF; 1…(1)…10 cycles). If an intrinsic rhythm occurs during one of the repetitive cycles, the long duration AV delay interval remains in effect. If an intrinsic rhythm does not occur during the repetitive cycles, the original AV delay interval resumes.

80 Stratos LV/LV-T Technical Manual

2.3.9.4 AV Scan Hysteresis

With AV Scan Hysteresis enabled, after 180 consecutive pacing cycles, the AV delay is extended for the programmed number of pacing cycles (OFF; 1…(1)…10 cycles). If an intrinsic rhythm is detected within the extended AV delay and the longer AV delay remains in effect. If an intrinsic rhythm is not detected within the number of scan cycles, the original AV delay value resumes.

2.3.10 VES Discrimination after Atrial Sensed Events

Stratos CRT-Ps have a special timing interval (VES/As) – VES discrimination after atrial sense events to identify ventricular extrasystoles.

With each As, a VES discrimination interval is started in the ventricle. If a ventricular sensed event occurs within the discrimination interval, this event is interpreted as a Vs (ventricular sensed event), and no extended PMT protection interval is started.

In the factory setting, the VES discrimination after As is set to 350 ms (programmable: OFF, 250 …(5)… 450 ms). The VES/As terminates with each ventricular event.

If a ventricular event does not fall within the AV delay or the VES discrimination interval, it is classified as a VES. A ventricular event that is sensed within the VES discrimination interval, but outside the AVE delay, starts a VA delay after which an atrial paced is delivered.

2.3.11 Sense Compensation

For hemodynamic reasons, it is desirable to keep constant time between an atrial and a ventricular contraction such that physiological conditions are attained. To this end, the AV delay after atrial sensing can be shortened by sense compensation. For sense compensation, the values are programmable from OFF, -10…(-10)…-120 ms (standard valued -50 ms). The AV delay after an atrial sensing event is shorter by the programmed value after pacing. The AV delay after atrial pacing then corresponds to the programmed AV delay.

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2.3.12 Ventricular Blanking Period

The ventricular blanking time is the period after an atrial pacing pulse during which ventricular sensing is deactivated. It is intended to prevent ventricular sensing of the atrial pacing pulse (“crosstalk”).

The blanking time shall be as short as possible in order to provide ventricular sensing when a ventricular depolarization could occur.

Crosstalk may be encountered if a shorter blanking time, unipolar ventricular sensing, a higher ventricular sensitivity (lower value) and/or a high atrial pulse amplitude and pulse width are programmed.

Values between 30 ms and 70ms (30… (10) …70 ms) can be set for the ventricular blanking period. The value should be set as low as possible and yet high enough to ensure ventricular sensing.

However, it must be programmed to ensure atrial pacing is not sensed in the ventricle.

2.3.13 Safety AV Delay

The safety AV delay (set at 100 ms) applies to all dual chamber pacing modes

To prevent ventricular pulse inhibition in the presence of crosstalk, a ventricular pulse will be emitted at the end of the safety AV delay (Figure 5 pre-set safety AV delay, the presence of crosstalk should be considered and appropriate reprogramming performed (lengthen the ventricular blanking time, lower ventricular sensitivity, bipolar configuration, and/or lower atrial pulse energy).

). When pacing is AV sequential at the

82 Stratos LV/LV-T Technical Manual

Figure 5. Ventricular blanking time and safety AV

2.4 Pacing and Sensing Functions

2.4.1 Pulse Amplitude and Pulse Width

The pulse amplitude and pulse width can be independently programmed for all three channels of the Stratos CRT-Ps.

The programmed pulse amplitude determines the voltage applied to the heart during each pacing pulse. The pulse amplitude is independently programmable for the atrial and ventricular channels up to 7.2 volts. The pulse amplitude remains consistent throughout the service life of the CRT-Ps. The pacing safety margin is therefore not reduced by a decrease in the CRT-P's battery voltage.

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CAUTION

Pulse Amplitude – Programming of pulse amplitudes, higher

than 4.8 V, in combination with long pulse widths and/or high pacing rates can lead to premature activation of the replacement indicator. If a pulse amplitude of 7.2 V or higher is programmed and high pacing rates are reached, output amplitudes may differ from programmed values.

2.4.2 Sensitivity

The parameter “sensitivity” is used to set the pulse generator’s threshold for detecting intracardiac signals. The lower the programmed sensitivity values the higher the device’s sensitivity.

If intracardiac signals are of low amplitude, a change to a higher sensitivity (lower value) may be indicated. Conversely, if the sensing amplifier is responding to extraneous signals, such as artifacts or interference, a change to a lower sensitivity (higher value) may resolve the difficulty. In dual chamber sensing modes, the sensitivity values for the atrial and ventricular channels are independently programmable. With Unipolar programming, the highest possible sensitivity setting is 1.0 mV.

2.4.3 Lead Polarity

The programmed lead polarity determines whether the CRT-P senses or paces in a unipolar or bipolar configuration. Lead polarity can be programmed separately for sensing and pacing in all three chambers.

CAUTION

Atrial Sensitivity – In dual chamber systems, the atrial

sensitivity of 0.1 mV should only be programmed in conjunction with a bipolar lead configuration.

84 Stratos LV/LV-T Technical Manual

The Stratos CRT-Ps have a specially designed header that allows the CRT-Ps to simultaneously sense and pace in both the right and left ventricles. Biventricular pacing therapy requires programming of a bipolar pacing configuration in the ventricle. Refer to Section 8.1 for a summary of the sensing and pacing configurations in the ventricle.

If a bipolar lead is connected to the CRT-P, unipolar or bipolar configuration can be programmed for pacing and sensing. As compared to bipolar pacing, the unipolar pacing pulse has the advantage of being clearly identifiable on the ECG. Unipolar pacing occasionally results in muscle stimulation in the device pocket or diaphragm.

2.5 Automatic Lead Check

When Lead Check is activated, the lead impedance is automatically measured with every pace. If the impedance values are consecutively greater or less than the limits (<200 Ω and >3000 Ω) for repeated measurements, the system automatically switches from bipolar to a unipolar lead configuration. A bipolar lead failure is verified if the lead impedance measurement falls outside of the acceptable range for three consecutive readings. When a lead failure has been detected, a message is displayed on the programmer screen at the next follow-up visit in order to notify the physician of the change.

Lead Check also may be activated with unipolar leads. The pass-fail criterion remains the same as with bipolar leads. In the event that a lead failure occurs, the Lead Check feature is disabled and a message is displayed on the programmer screen at the next follow-up visit to notify the physician of the lead status.

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CAUTION

Lead Check – Lead check will not lead to disabling of cardiac

resynchronization therapy. It limits the use of the resynchronization features.

1. Lead check is possible only when the right ventricle is paced first.

2. Lead check works only when the pacing voltages are programmed between 2.4 and 4.8 V. The lead check feature can be programmed OFF in patients that require cardiac resynchronization therapy.

“Lead check may result in a switch to unipolar pacing and sensing, which may be inappropriate for patients with an ICD.”

Additionally, Lead Check should be programmed OFF before lead connection as the feature will automatically reprogram the device to unipolar in the absence of a lead.

Lead Check is temporarily suspended during magnet application and is inactive during ERI.

NOTE:

In the Stratos CRT-Ps, an automatic lead check cannot be programmed ON if left ventricular paces are programmed to occur before right ventricular paces.

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2.6 Antitachycardia Functions:

The antitachycardia functions include:

• Upper basic rate

• Tachycardia mode

• Tachycardia behavior

• Mode Switching

• PMT Management

• Preventive Overdrive Pacing

• Post-AES Pacing

2.6.1 Upper Rate and UTR Response

In atrial-controlled dual chamber modes, the upper tracking interval (UTI), along with the atrial refractory period or PMT protection window limits the ventricular pacing rate such that it will never exceed the programmed upper rate regardless of the patient's atrial rate.

In all triggered modes, the upper tracking interval limits the pacing rate that is triggered by sensing.

NOTE:

Select the upper rate based upon the patient’s tolerance for the rate. The upper rate limit determines the minimal interval between a sense or pace event and the subsequent atrial or ventricular pacing event. A shortening of the pacing interval to the upper rate interval may also be initiated at rest (e.g., by detection of muscle potentials). Therefore, for patients with increased vulnerability a lower programmed upper rate is recommended.

2.7 Wenckebach 2:1

Wenckebach behavior or 2:1 behavior is available depending on the programming of the atrial refractory period, the PMT protection window and the upper tracking interval in the modes DDD, DDT/A, VDD, DDT and VDT.

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Wenckebach Behavior

If the end of the AV delay falls within the upper threshold rate interval, ventricular pacing occurs at the end of the upper tracking interval.

2:1 Behavior

If the high-rate atrial event occurs in the ARP, the FFP or PMT protection window, an AV delay is not started.

In Wenckebach mode, the CRT-P switches to ventricular timing. This means that a VA delay is started after a ventricular event to avoid the atrial basic interval extend the duration of the Wenckebach mode. The VA delay is calculated from the basic (hysteresis) interval minus the AV delay (or the AV safety interval).

The timing of the Stratos CRT-Ps ensures that the ventricular paced event (Vp) following the VA delay allows atrial pacing at the end of the AV delay; thus, terminating the Wenckebach cycle.

The CRT-P counts the number of Wenckebach cycles. In more than four Wenckebach cycles are detected, a shortened VA delay is started after a right or left ventricular paced event to guarantee constancy of the ventricular rate. The short VA delay is in this instance calculated from the ventricular interval of the upper tacking interval minus the AV delay (or the AV safety interval). If the Wenckebach mode has been terminated, the counter of the CRT-P is reset.

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2.8 Mode Switching

Mode switching prevents the conduction of paroxysmal atrial tachycardias to the ventricle. Therefore, after sensing an atrial tachycardia while in activated mode switching, the CRT-P automatically switches to an atrial-controlled Rmode. Like the programmed atrial-controlled P-mode, the corresponding R-modes can be programmed:

Table 21. Mode Switching

Programmed P mode Programmed R mode in case of

sensed atrial tachycardias

DDD DDI DDD DDIR DDDR DDIR VDD VDI VDD VDIR VDDR VDIR DDTA DDI DDTA DDIR DDTAR DDIR

The Mode Switching algorithm causes the CRT-P to change pacing modes when a programmed number of atrial intervals (X) out of 8 consecutive atrial intervals (p-p) are faster than the programmed mode switch intervention rate (X out of 8). X is programmable from 3 to 8. The rate at which an atrial interval is determined to signify an atrial tachyarrhythmia is called the mode switch intervention rate. The mode switch intervention rate is programmable from 100…(10)…250 bpm.

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Reversion back to the programmed pacing mode occurs in a similarly programmable manner. If a programmable number of atrial intervals (Z) out of 8 consecutive atrial intervals (p-p) are slower than the programmed mode switch intervention rate (Z out of 8), the device will revert back to the permanently programmed parameters. Z is programmable from 3 to 8. The device will also revert back to the permanent program if 2 atrial-paced events occur or if no atrial paced or sensed events have occurred for at least 2 seconds. Each occurrence of mode switching resets the corresponding counter (X or Z) to a value of zero.

Mode Switch Events are recorded in memory and are available to the user through the following diagnostics:

• IEGM Recordings

• Tachy Episode Trends

• Mode Switch Trends

• Mode Switch Histogram

• Mode Switch Counter

Mode Switching is temporarily suspended during magnet application and are inactive during ERI.

2.9 PMT Management

A PMT is defined as a tachycardia caused by inadvertently tracking the retrograde P-waves. The PMT management feature includes PMT Protection/Termination and a programmable PMT detection and termination algorithm.

2.9.1 Protection

Pacemaker-mediated tachycardia (PMT) is normally triggered by ventricular depolarizations that are not synchronized with atrial depolarizations (e.g., VES). The tachycardia is maintained in a retrograde direction by intrinsic VA conduction of the stimulated ventricular depolarization and in an antegrade direction by ventricular pacing of the pacemaker that is triggered by P-waves. It is the objective of the atrial PMT protection interval to not use retrogradely conducted atrial sensed events for pacemaker timing, but only to statistically evaluate them for detection of atrial tachycardia incidents.

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To prevent occurrence of a PMT, Stratos CRT-Ps start an atrial PMT protection interval after each ventricular paced event (right or left). If an atrial even is sensed within this PMT protection interval, this will neither start an AV delay nor a basic interval.

The length of the PMT protection can be set to automatic (Auto). In this case, the PMT protection window can be automatically extended after the PMT is detected and terminated.

NOTE:

The initial values of the PMT protection interval in the automatic setting at 175 ms after a Vp, and 400 ms after VES.

2.9.2 PMT Detection

It is the objective of PMT detection to identify ongoing PMTs, to distinguish them from the sinus rhythm and to terminate them. The detection of a PMT starts by measuring the Vp-As intervals. If these lie below the programmable PMT VA criterion (programming depends on the retrograde conduction time of the patient), the measurement of the stability of the Vp-As interval is started.

The Stratos CRT-P’s PMT detection/termination algorithm consists of suspicion, confirmation and termination components and is described as follows.

Suspicion

A PMT is suspected when two criteria are met:

• 8 successive V pace-A sense (Vp-As) sequences have

• The mean deviation of these 8 Vp-As intervals is less

occurred with a length shorter than the VA criterion. This VA criterion is programmable between 250 and 500 ms.

than the Stability criterion parameter, defined with respect to upper and lower values is ±25 ms.

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Confirmation

When the suspicion criterion has been met, the Stratos CRT-Ps slightly modify the AV delay interval (+ or - 50 ms) for one cardiac cycle. If the Vp-As interval remains stable, a PMT is confirmed. Otherwise, a PMT is not confirmed and the algorithm restarts. Once the PMT algorithm has confirmed a PMT, the cycle is terminated.

The upper interval limit range must be shorter than the limit of the VA delay (350 ms, for example). The test method is based on the length of the pacing interval or the AV delay (refer to

Table 22

> UTI (upper tracking interval)

> UTI + 50 ms > 200 ms Reducing the AV

≤ UTI ≤ 200 ms Increasing the UTI

≤ UTI > 200 ms Increasing the UTI

> UTI and ≤ UTI + 50 ms

Table 22. PMT Test Method

Interval Length AV Delay Test Method

≤ 200 ms Increasing the AV

delay by 50 ms

by 50 ms

> 200 ms Length of UTI = TA

+ 50 ms

Termination

Stratos CRT-Ps extend TARP (Total Atrial Refractory Period) for one cycle to equal the V-V interval + 50 ms.

2.10 Adjustment of the PMT Protection Window

The PMT protection window can be automatically adjusted. This automatic adjustment functions in the following manner:

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When the PMT is detected and terminated, the PMT protection interval is extended by 50 ms. If no additional PMTs arise within two days, the length of the PMT protection interval is reduced by another 50 ms. If additional PMTs occur, the PMT protection interval is increased by another 50 ms. This occurs until no more PMTs are detected. In the absence of PMTs, the PMT protection interval is successively reduced. The initial values of the PMT protection interval in the automatic setting at 175 ms after Vp and 400 ms after VES.

2.11 Atrial Upper Rate

The atrial upper rate (AUR) prevents atrial pacing from occurring in the vulnerable phase after an atrial sensed event during the PMT protection interval, and ensures that the next atrial paced event occurs after the heart’s natural atrial refractory period.

To avoid this, an atrial upper rate of 200 ppm (atrial upper interval (AUI), 300 ms) is started after a PMT-As.

The next Ap can only be emitted after the expiration of the AUI. When there are high sensor rates, the atrial pacing is shifted. To guarantee stability of the ventricular rate, the AV delay is shortened to no less than the safety interval when the basic interval is lengthened.

NOTE:

Right atrial pacing does not occur when mode switching is activated, and when the atrial upper rate is activated in DDI mode at the end of the sensor or basic interval.

2.12 Preventive Overdrive Pacing (Overdrive Mode)

The atrial pacing rate increases after each atrial sensed event that is not classified as an atrial extrasystole, in an attempt to suppress atrial tachyarrhythmias. The overdrive algorithm triggers atrial overdrive pacing and guarantees that pacing occurs at a rate slightly above the intrinsic sinus rate. Atrial overdrive pacing thereby minimizes the number of atrial sensed events. The overdrive mode is available in modes DDD(R), DDT/A(R), AAI(R) and AAT(R).

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