BIOTRONIK SE and KG LUMAXT50 UserMan

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Lumax
Family of Implantable Cardioverter
Defibrillators and Cardiac
Resynchronization Therapy
Defibrillators
VR ICD VR-T ICD VR-T DX ICD DR ICD DR-T ICD HF CRT-D HF-T CRT-D
Technical Manual
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X-ray Identification Lumax Family
Implantable Cardioverter Defibrillator and Cardiac Resynchronization Therapy Defibrillators Inside the housing:
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Belos Technical Manual iii
Model X-Ray Identification Year of Manufacture
Lumax 300 HR nn
Lumax 340 HR nn
Lumax 500 SH nn
Lumax 540 SH nn
Lumax 600 RH nn
Lumax 640 RH nn
Lumax 700 RH nn
Lumax 740 RH nn
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CAUTION
Federal (U.S.A.) law restricts this device to sale by, or on the order of, a physician.
2011 BIOTRONIK, Inc., all rights reserved.
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Lumax Technical Manual i
Contents
1. General ..............................................................................1
1.1 System Description .......................................................1
1.2 Indications and Usage...................................................4
1.3 Contraindications...........................................................5
1.4 Warnings and Precautions ............................................5
1.4.1 Sterilization, Storage, and Handling ......................8
1.4.2 Device Implantation and Programming .................8
1.4.3 Lead Evaluation and Connection ........................10
1.4.4 Follow-up Testing ................................................12
1.4.5 Pulse Generator Explant and Disposal ...............12
1.4.6 Hospital and Medical Hazards.............................12
1.4.7 Home and Occupational Hazards .......................14
1.4.8 Cellular Phones ...................................................14
1.4.9 Electronic Article Surveillance (EAS) ..................15
1.4.10 Home Appliances ................................................15
1.4.11 Home Monitoring® ..............................................15
1.5 Potential/Observed Effects of the Device on Health ...17
1.5.1 Potential Adverse Events ....................................17
1.5.2 Observed Adverse Events...................................18
1.6 Clinical Studies............................................................27
1.6.1 Kronos LV-T Study ..............................................28
1.6.2 Tupos LV/ATx Study............................................30
1.6.3 Lumax HF-T V-V Clinical Study...........................48
1.6.4 TRUST Clinical Study..........................................55
1.6.5 Deikos A+ ............................................................63
1.7 Patient Selection and Treatment.................................67
1.7.1 Individualization of Treatment .............................67
1.7.2 Specific Patient Populations................................68
1.8 Patient Counseling Information ...................................68
1.9 Evaluating Prospective CRT-D/ICD Patients ..............69
2. Device Features ..............................................................70
2.1 SafeSync Telemetry ....................................................70
2.2 Cardiac Resynchronization Therapy (CRT) ................73
2.3 Sensing (Automatic Sensitivity Control) ......................76
2.3.1 Right Ventricular Sensitivity Settings...................77
2.3.2 Minimum Right Ventricular Threshold .................79
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2.3.3 Atrial Sensitivity Settings .....................................79
2.3.4 Minimum Atrial Threshold....................................80
2.3.5 Left Ventricular Sensitivity Settings .....................80
2.3.6 Minimum Left Ventricular Threshold....................81
2.3.7 Far Field Protection .............................................81
2.3.8 Additional Sensing Parameters ...........................81
2.4 Automatic Threshold Measurement (ATM) .................83
2.4.1 Signal Quality Check ...........................................84
2.4.2 Threshold Measurement .....................................84
2.4.3 Loss of Capture Detection...................................84
2.4.4 ATM in Lumax HF-T Models ...............................84
2.4.5 RV & LV Capture Control ....................................85
2.5 Ventricular Tachyarrhythmia Detection........................85
2.5.1 VF Classifications ................................................86
2.5.2 VT Interval Counters............................................86
2.5.3 VT Classification..................................................86
2.5.4 SMART Detection™ ............................................87
2.5.5 Onset ...................................................................88
2.5.6 Stability ................................................................88
2.5.7 Sustained VT Timer.............................................88
2.5.8 VT Monitoring Zone .............................................89
2.5.9 Atrial Monitoring Zone .........................................89
2.6 Tachyarrhythmia Redetection......................................90
2.6.1 VT Redetection....................................................90
2.6.2 SMART Redetection............................................90
2.6.3 Forced Termination .............................................90
2.6.4 VF Redetection....................................................91
2.7 Tachyarrhythmia Termination ......................................91
2.8 Tachyarrhythmia Therapy ............................................91
2.8.1 Therapy Options ..................................................91
2.8.2 Anti-Tachycardia Pacing (ATP) ...........................91
2.8.3 Shock Therapy ....................................................95
2.8.4 Progressive Course of Therapy.........................101
2.9 Bradycardia Therapy .................................................102
2.9.1 Bradycardia Pacing Modes ...............................102
2.9.2 Basic Rate .........................................................103
2.9.3 Night Rate..........................................................103
2.9.4 Rate Hysteresis .................................................104
2.9.5 Dynamic AV Delay.............................................107
2.9.6 IOPT ..................................................................110
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2.9.7 Upper Tracking Rate .........................................110
2.9.8 Mode Switching .................................................111
2.9.9 PMT Management .............................................113
2.9.10 VES Discrimination after Atrial Sensed Events .115
2.9.11 Rate-Adaptive Pacing........................................116
2.9.12 Pulse Amplitude.................................................118
2.9.13 Pulse Width .......................................................118
2.9.14 Post Ventricular Atrial Refractory Period...........118
2.9.15 PVARP after VES ..............................................118
2.9.16 Auto PVARP ......................................................119
2.9.17 Noise Response ................................................119
2.9.18 Post Shock Pacing ............................................119
2.10 EP Test Functions......................................................120
2.10.1 P and R-wave Amplitude Measurements ..........120
2.10.2 Pacing Impedance Measurements....................121
2.10.3 Shock Impedance Measurements.....................121
2.10.4 Testing for Retrograde Conduction ...................122
2.10.5 Pacing Threshold...............................................122
2.10.6 Arrhythmia Induction Features ..........................123
2.10.7 Manual Shock ....................................................124
2.10.8 Test Shock.........................................................124
2.10.9 Manual ATP .......................................................125
2.10.10 Emergency Shock .............................................125
2.11 Special Features........................................................125
2.11.1 ICD Therapy Status ...........................................125
2.11.2 Thoracic Impedance ..........................................126
2.11.3 Home Monitoring®.............................................126
2.11.4 Real-time IEGM Transmission ..........................138
2.11.5 Capacitor Reforming .........................................139
2.11.6 Patient and Implant Data ...................................140
2.11.7 System Status ...................................................140
2.11.8 HF Monitor Statistics .........................................141
2.11.9 Holter Memory ...................................................142
2.11.10 Timing Statistics ................................................144
2.11.11 Atrial Arrhythmias ..............................................145
2.11.12 Ventricular Arrhythmias .....................................145
2.11.13 Sensor ...............................................................146
2.11.14 Sensing..............................................................146
2.11.15 Impedances.......................................................146
2.11.16 Automatic Threshold..........................................146
2.11.17 Asynchronous Pacing Modes............................146
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2.11.18 Far-Field IEGM for Threshold Testing (Leadless
ECG)..................................................................147
2.11.19 Advanced AT/AF Diagnostics (Lumax 700/740 only)
...........................................................................147
2.11.20 Atrial NIPS (Lumax 700/740 & 600/640 only) ...148
3. Sterilization and Storage .............................................149
4. Implant Procedure ........................................................151
4.1 Implant Preparation ...................................................151
4.2 Lead System Evaluation............................................156
4.3 Opening the Sterile Container...................................156
4.4 Pocket Preparation....................................................157
4.5 Lead to Device Connection .......................................158
4.6 Blind Plug Connection...............................................161
4.7 Program the ICD/CRT-D ...........................................162
4.8 Implant the ICD/CRT-D .............................................163
5. Follow-up Procedures..................................................167
5.1 General Considerations ............................................167
5.2 Longevity ...................................................................168
5.2.1 Lumax 300/340 Devices....................................169
5.2.2 Lumax 500/540 Devices....................................171
5.2.3 Lumax 600/640 & 700/740 Devices ..................174
5.3 Explantation...............................................................176
6. Technical Specifications..............................................179
Appendix A ..........................................................................198
Appendix B – Known Anomalies.......................................200
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Figure 1. Lumax 300/340 ICDs and CRT-D
VR(-T) DR(-T)/VR-T DX HF(-T)
Figure 2. Lumax 500/540, 600/640 & 700/740 ICDs and CRT-D
Table 1. Lumax Specifications
Battery Voltage 3.2 Volts Maximum Shock Energy
300/500/600/700 Models 30 Joules programmed
340/540/640/740 Models 40 Joules programmed Defibrillation Lead Ports Two DF1 (3.2 mm) Pacing Lead Ports
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VR(-T) Models One IS-1 (3.2 mm)
DR(-T)/VR-T DX Models Two IS-1 (3.2 mm)
HF(-T) Models Three IS-1 (3.2 mm) Materials
Housing Titanium
Header Epoxy Resin
Sealing Plug Silicone
Detailed technical specifications are provided in Section
6.
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Lumax Technical Manual 1

1. General

1.1 System Description

The Lumax family of Implantable Cardioverter Defibrillators (ICDs) and Cardiac Resynchronization Therapy Defibrillators (CRT-Ds) detect and treat ventricular tachyarrhythmias and provide rate adaptive bradycardia pacing support. The HF and HF-T versions of Lumax provide Cardiac Resynchronization Therapy (CRT) through biventricular pacing. Both CRT-Ds and ICDs detect and treat ventricular tachyarrhythmias and provide rate adaptive bradycardia pacing support. They are designed to collect diagnostic data to aid the physician’s assessment of a patient’s condition and the performance of the implanted device.
The Lumax family of devices provides therapy for ventricular tachyarrhythmias with a sophisticated range of programmable anti-tachycardia pacing (ATP), and/or defibrillation therapy features. The shock polarity and energy may be programmed to tailor the therapy to appropriately treat each patient's tachyarrhythmias. The ICDs/CRT-Ds provide shock therapies with programmable energies from 5 to 40 joules.
The Lumax family of ICDs/CRT-Ds includes the following members:
Lumax HF - provides three chamber rate-adaptive
bradycardia pacing support including biventricular pacing via a left ventricular pacing lead. The CRT-D uses right atrial and ventricular sensing/pacing leads to provide enhanced atrial and ventricular tachyarrhythmia discrimination through BIOTRONIK’s SMART Detection™ algorithm.
Lumax HF-T - In addition, to the functionality found with
HF model, Lumax HF-T also has BIOTRONIK’s Home Monitoring system. The Home Monitoring System enables automatic exchange of information about a patient’s cardiac status from the implant to the physician remotely.
Lumax DR - provides dual chamber rate adaptive
bradycardia pacing support. The ICD uses atrial and ventricular sensing/pacing leads to provide enhanced atrial and ventricular tachyarrhythmia discrimination through BIOTRONIK’s SMART Detection
TM
algorithm.
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Lumax DR-T - In addition, to the functionality found with
the DR model, it also has BIOTRONIK’s Home Monitoring® system. The Home Monitoring System enables automatic exchange of information about a patient’s cardiac status from the implant to the physician remotely.
Lumax VR - provides single chamber rate adaptive
bradycardia pacing support as well as tachyarrhythmia detection and therapy.
Lumax VR-T - In addition, to the functionality found with
standard VR model, it also has BIOTRONIK’s Home Monitoring system. The Home Monitoring System enables automatic exchange of information about a patient’s cardiac status from the implant to the physician remotely.
Lumax VR-T DX – provides ventricular rate adaptive
bradycardia pacing support that can include atrial tracking with a single pass ICD lead and also has BIOTRONIK’s Home Monitoring system.
The 300/500/600/700 and 340/540/640/740 designation for each of the above-described models denote the maximum programmable shock energy of 30 joules and 40 joules, respectively.
The Lumax 500/540, 600/640 and 700/740 models feature a third programmable shock path for delivery of defibrillation/cardioversion shocks. The shock path is programmable between the different shock coils (SVC/RV) and/or the device housing. Section
2.8.3.6 provides further details on
the available shock configurations. The Lumax 600/640 and 700/740 models also feature an additional left ventricular (LV) pacing polarity for HF-T devices from LV-tip to housing (unipolar).
Additionally, the Lumax 500/540 models feature Automatic Threshold Measurement (ATM) of ventricular pacing thresholds. This feature is separately programmable for the right (RV) and left (LV) ventricle. Section 2.4 provides further details.
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The Lumax 700/740 and 600/640 models feature ATM with automatic adjustment of pacing amplitudes (RV & LV Capture Control). This feature functions the same as ATM for threshold search and is also separately programmable for the right (RV) and left (LV) ventricle. In addition, it automatically adjusts the permanent pacing amplitude with a programmed safety margin. Section 2.4.5 provides a detailed description of this feature.
The Lumax 600/640 and 700/740 also provides wandless telemetry
to ease implantation and follow-up procedures. In addition, these devices include Thoracic Impedance monitoring and Atrial NIPS that can be used for an EP study to induce an arrhythmia or to burst pace a patient out of a stable tachyarrhythmia.
Lumax 700/740 and 600/640 will present with automatic Far-Field IEGM to provide a means to generate the surface ECG-like signal without the need for attaching the surface electrodes to the patients.
The Lumax HF (-T) models have three IS-1 pacing/sensing header ports and two DF-1 defibrillation/cardioversion ports. The Lumax DR (-T) models have two IS-1 pacing/sensing header ports. The Lumax VR (-T) models have one IS-1 pacing/sensing header ports. IS-1 refers to the international standard whereby leads and generators from different manufacturers are assured a basic fit [Reference ISO 5841-3:1992]. DF-1 refers to the international standard for defibrillation lead connectors [Reference ISO 11318:1993].
External devices that interact with and test the implantable devices are also part of the ICD/CRT-D System. These external devices include the Programming and Tachyarrhythmia Monitoring System and the Implant Module System Analyzer or Pacing System Analyzer for acute lead testing. The ICS 3000 or Renamic programmer are used to interrogate and program the ICD/CRT-Ds.
The Lumax 600/640 and 700/740 models also feature SafeSync Telemetry (RF-Telemetry) via the Renamic programmer or the ICS 3000 programmer in combination with the SafeSync Module (an external communication module).
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BIOTRONIK conducted the TRUST study to evaluate the safety and effectiveness of Home Monitoring, which is available in most models of this device. Refer to Section 1.6.4 for details regarding the study design and BIOTRONIK was able to show the following with regards to Home Monitoring:
BIOTRONIK Home Monitoring information may be used as a
replacement for device interrogation during in-office follow-up visits.
A strategy of care using BIOTRONIK Home Monitoring with
office visits when needed has been shown to extend the time between routine, scheduled in-office follow-ups of BIOTRONIK implantable devices in many patients. Home Monitoring data is helpful in determining the need for additional in-office follow-up.
BIOTRONIK Home Monitoring-patients—who are followed
remotely with office visits when needed—have been shown to have similar numbers of strokes, invasive procedures and deaths as patients followed with conventional in-office follow-ups.
BIOTRONIK Home Monitoring provides early detection of
arrhythmias.
BIOTRONIK Home Monitoring provides early detection of
silent, asymptomatic arrhythmias.
Automatic early detection of arrhythmias and device system
anomalies by BIOTRONIK Home Monitoring allows for earlier intervention than conventional in-office follow-ups.
BIOTRONIK Home Monitoring allows for improved access to
patient device data compared to conventional in-office follow-ups since device interrogation is automatically scheduled at regular intervals.
results. With the TRUST study,

1.2 Indications and Usage

The Lumax CRT-Ds are indicated for use in patients with all of the following conditions:
Indicated for ICD therapy  Receiving optimized and stable Congestive Heart Failure
(CHF) drug therapy
Symptomatic CHF (NYHA Class III/IV and LVEF 35%);
and
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Intraventricular conduction delay (QRS duration 130 ms)
The Lumax Implantable Cardioverter Defibrillators (ICDs) and Cardiac Resynchronization Therapy Defibrillators (CRT-Ds) are intended to provide ventricular anti-tachycardia pacing and ventricular defibrillation, for automated treatment of life­threatening ventricular arrhythmias.

1.3 Contraindications

The Lumax devices are contraindicated for use in patients with the following conditions:
Patients whose ventricular tachyarrhythmias may have
transient or reversible causes such as:
Acute myocardial infarction Digitalis intoxication Drowning Electrocution Electrolyte imbalance Hypoxia Sepsis Patients with incessant ventricular fibrillation (VF) and
ventricular tachycardia (VT)
Patients whose only disorder is brady arrhythmias or
atrial arrhythmias

1.4 Warnings and Precautions

MRI (Magnetic Resonance Imaging) - Do not expose a patient
to MRI device scanning. Strong magnetic fields may damage the device and cause injury to the patient.
Electrical Isolation - To prevent inadvertent arrhythmia induction, electrically isolate the patient during the implant procedure from potentially hazardous leakage currents.
Left Ventricular Lead Systems – BIOTRONIK CRT-Ds may be implanted with any legally marketed, compatible LV lead. Compatibility is defined as:
IS-1 pacing connector Active or passive fixation technology Insertion and withdrawal forces as specified by
ISO 5841-3 (IS-1)
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The following LV leads were evaluated in the OPTION CRT/ATx study with BIOTRONIK’s CRT-Ds:
Guidant-EASYTRAK® IS-1 Lead Guidant-EASYTRAK LV-1 Lead Guidant-EASYTRAK 2 Lead Guidant-EASYTRAK 3 Lead Medtronic-Attain® OTW Lead St. Jude-Aescula St. Jude-QuickSite® Lead Biomec-Myopore
TM
Lead
TM
Epicardial Lead
Medtronic-Epicardial 5071 Lead Medtronic-CapSure® EPI Lead BIOTRONIK-ELC 54-UP Lead
The following LV leads were bench tested for compatibility with BIOTRONIK’s CRT-Ds:
Guidant EASYTRAK 4512 (unipolar) Lead Guidant EASYTRAK 4513 (bipolar) Lead Guidant EASYTRAK 3 4525 (bipolar) Lead Medtronic Attain OTW 4193 (unipolar) Lead Medtronic Attain OTW 4194 (bipolar) Lead Medtronic Attain LV 2187 (unipolar) Lead St. Jude Medical QuickSite 1056K (unipolar) Lead ELA SITUS® OTW (unipolar) Lead BIOTRONIK Corox OTW 75-UP Steroid #346542
(unipolar) Lead
BIOTRONIK Corox+ LV-H 75-BP #341885 (bipolar) Lead
ICD Lead Systems – BIOTRONIK ICDs/CRT-Ds maybe implanted with any legally marketed, compatible ICD lead. Compatibility is defined as:
IS-1 pacing and sensing connector(s) DF-1 shock coil connector(s) Integrated or dedicated bipolar pacing and sensing
configuration
Active or passive fixation technology Single or dual defibrillation shock coil (s) High energy shock accommodation of at least 30 joules
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Insertion and withdrawal forces as specified by
ISO 5841-3 (IS-1) and ISO 11318:1993 (E) DF-1
The following leads were evaluated in a retrospective study with BIOTRONIK’s ICDs/CRT-Ds:
Medtronic Sprint Medtronic Sprint Lead 6943 Medtronic Sprint Quattro Medtronic Transvene St. Jude (Ventritex) TVL
TM
Lead 6932
TM
TM
RV Lead 6936
TM
Lead 6944
- ADX Lead 1559
St. Jude SPL® SP02 Lead Guidant ENDOTAK® DSP Lead Guidant ENDOTAK Endurance EZ Lead, ENDOTAK
Reliance Lead
Guidant (Intermedics) Lead 497-24.
The following leads were bench tested for compatibility with BIOTRONIK’s ICDs/CRT-Ds:
Guidant ENDOTAK Endurance Lead “CPI 0125” Guidant ENDOTAK Reliance Lead 0148 Medtronic Sprint Lead 6932 Medtronic Sprint Lead 6942 Medtronic Sprint Lead 6943 Medtronic Sprint Lead6945 Medtronic Sprint Quattro Lead 6944 St. Jude Riata® Lead 1571/65 St. Jude SPL SPO1 Lead.
Resuscitation Availability - Do not perform induction testing unless an alternate source of patient defibrillation such as an external defibrillator is readily available. In order to implant the ICD/CRT-D system, it is necessary to induce and convert the patient’s ventricular tachyarrhythmias.
Unwanted Shocks – Always program ICD Therapy to OFF prior to handling the device to prevent the delivery of serious shocks to the patient or the person handling the device during the implant procedure.
Rate-Adaptive Pacing – Use rate-adaptive pacing with care in patients unable to tolerate increased pacing rates.
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1.4.1 Sterilization, Storage, and Handling

Device Packaging - Do not use the device if the device’s
packaging is wet, punctured, opened or damaged because the integrity of the sterile packaging may be compromised. Return the device to BIOTRONIK.
Re-sterilization - Do not re-sterilize and re-implant explanted devices.
Storage (temperature) - Store the device between 5° to 45°C (41° - 113° F) because temperatures outside this range could damage the device.
Storage (magnets) - To avoid damage to the device, store the device in a clean area, away from magnets, kits containing magnets, and sources of electromagnetic interference (EMI).
Temperature Stabilization - Allow the device to reach room temperature before programming or implanting the device because temperature extremes may affect initial device function.
Use Before Date - Do not implant the device after the USE BEFORE DATE because the device may have reduced longevity.

1.4.2 Device Implantation and Programming

Blind Plug - A blind plug must be inserted and firmly connected
into any unused header port to prevent chronic fluid influx and possible shunting of high energy therapy.
Capacitor Reformation - Infrequent charging of the high voltage capacitors may extend the charge times of the ICD/CRT-D. The capacitors are reformed automatically at least every 90 days. For further information, please refer to Section Reforming.
Connector Compatibility – ICD/CRT-D and lead system compatibility should be confirmed prior to the implant procedure. Consult your BIOTRONIK representative regarding lead/pulse generator compatibility prior to the implantation of an ICD/CRT-D system. For further information, please refer to Appendix A
2.11.5, Capacitor
.
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ERI (Elective Replacement Indicator) - Upon reaching ERI, the battery has sufficient energy remaining to continue monitoring for at least three months and to deliver a minimum of six maximum energy shocks. After this period (EOS), all tachyarrhythmia detection and therapy is disabled. Bradycardia functions are still active at programmed values until the battery voltage drops below
1.75 volts.
Magnets - Positioning of a magnet or the programming wand over the ICD/CRT-D will suspend tachycardia detection and treatment. The minimum magnet strength required to suspend tachycardia treatment is 1.8 mT. When the magnet strength decreases to less than 1 mT, the reed contact is reopened.
Programmed Parameters – Program the device parameters to appropriate values based on the patient’s specific arrhythmias and condition.
Programmers - Use only BIOTRONIK ICS 3000 or Renamic programmers to communicate with the device.
Sealing System - Failure to properly insert the torque wrench into the perforation at an angle perpendicular to the connector receptacle may result in damage to the sealing system and its self-sealing properties.
Defibrillation Threshold - Be aware that changes in the patient’s condition, drug regimen, and other factors may change the defibrillation threshold (DFT) which may result in non-conversion of the arrhythmia post-operatively. Successful conversion of ventricular fibrillation or ventricular tachycardia during arrhythmia conversion testing is no assurance that conversion will occur post-operatively.
Manual Shocks – User-commanded shocks may be withheld if the ICD/CRT-D is already busy processing a manual command or the Battery Status is low.
Charge Time - When preparing a high energy shock the charge circuit stops charging the capacitors after 20 seconds, and delivers the stored energy as shock therapy. After the device reaches ERI the stored energy may be less than the maximum programmable energy for each shock.
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Programming Wand Separation Distance – The wand (with magnet) must not be placed closer than 2 cm to the device (implanted or out of the box). Programming wand (with magnet) distance closer than 2 cm may damage the device.
Shipment Mode – The shipment mode is a factory set mode that controls the charge current of automatic capacitor reformations. This mode controls the charge current to avoid temporary low battery readings. The shipment mode is automatically deactivated as soon as electrophysiological tests (e.g., Impedance measurement) have been performed. To ensure delivery of programmed shock energy, make sure shipment mode is disabled prior to completion of implant procedure.
Shock Therapy Confirmation – Programming CONFIRMATION to OFF may increase the incidence of the ICD/CRT-D delivering inappropriate shocks.
Shock Impedance - If the shock impedance is less than twenty­five ohms (25 ), reposition the lead system to allow a greater distance between the electrodes. Never implant the device with a lead system that has measured shock impedance of less than twenty-five ohms (25 ). Damage to the device may result.
Negative AV Hysteresis – This feature insures ventricular pacing, a technique which has been used in patients with hypertrophic obstructive cardiomyopathy (HOCM) with normal AV conduction in order to replace intrinsic ventricular activation. No clinical study was conducted to evaluate this feature, and there is conflicting evidence regarding the potential benefit of ventricular pacing therapy for HOCM patients. In addition, there is evidence with other patient groups to suggest that inhibiting the intrinsic ventricular activation sequence by right ventricular pacing may impair hemodynamic function and/or survival.

1.4.3 Lead Evaluation and Connection

Capping Leads - If a lead is abandoned rather than removed, it
must be capped to ensure that it is not a pathway for currents to or from the heart.
Gripping Leads - Do not grip the lead with surgical instruments or use excessive force or surgical instruments to insert a stylet into a lead.
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Kinking Leads - Do not kink leads. This may cause additional stress on the leads that can result in damage to the lead.
Liquid Immersion - Do not immerse leads in mineral oil, silicone oil, or any other liquid.
Short Circuit - Ensure that none of the lead electrodes are in contact (a short circuit) during delivery of shock therapy as this may cause current to bypass the heart or cause damage to the ICD/CRT-D system.
Far-Field Sensing of signals from the atrium in the ventricular channel or ventricular signals in the atrial channel should be avoided by appropriate lead placement, programming of pacing/sensing parameters, and maximum sensitivity settings. If it is necessary to modify the Far Field Blanking parameter, the parameter should be lengthened only long enough to eliminate far-field sensing as evidenced on the IEGMs. Extending the parameter unnecessarily may cause under sensing of actual atrial or ventricular events.
Suturing Leads - Do not suture directly over the lead body as this may cause structural damage. Use the appropriate suture sleeve to immobilize the lead and protect it against damage from ligatures.
Tricuspid Valve Bioprosthesis - Use ventricular transvenous leads with caution in patients with a tricuspid valvular bioprosthesis.
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 over tighten the setscrew(s). Use only the BIOTRONIK supplied torque wrench.
Sealing System – Be sure to properly insert the torque wrench into the perforation perpendicular to the connector receptacle. Failure to do so may result in damage to the plug and its self­sealing properties.
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1.4.4 Follow-up Testing

Defibrillation Threshold - Be aware that changes in the patient’s
condition, drug regimen, and other factors may change the defibrillation threshold (DFT), which may result in non-conversion of the arrhythmia post-operatively. Successful conversion of ventricular fibrillation or ventricular tachycardia during arrhythmia conversion testing is no assurance that conversion will occur post-operatively.
Resuscitation Availability - Ensure that an external defibrillator and medical personnel skilled in cardiopulmonary resuscitation (CPR) are present during post-implant device testing should the patient require external rescue.
Safe Program – Within the EP Test screen, pressing the “Safe Program” key on the programmer head immediately sends the safe program to the ICD/CRT-D.

1.4.5 Pulse Generator Explant and Disposal

Device Incineration – Never incinerate the ICD/CRT-D due to
the potential for explosion. The ICD/CRT-D must be explanted prior to cremation.
Explanted Devices – Return all explanted devices to BIOTRONIK.
Unwanted Shocks – Always program ICD Therapy to OFF prior to handling the device to prevent the delivery of serious shocks to the patient or the person handling the device during the procedure.

1.4.6 Hospital and Medical Hazards

Electromagnetic interference (EMI) signals present in hospital and medical environments may affect the function of any ICD/CRT-D or pacemaker. The ICD/CRT-D is designed to selectively filter out EMI noise. However, due to the variety of EMI signals, absolute protection from EMI is not possible with this or any other ICD/CRT-D.
The ICD/CRT-D system should have detection and therapy disabled (OFF) prior to performing any of the following medical procedures. In addition, the ICD/CRT-D should be checked after the procedures to assure proper programming:
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Diathermy - Diathermy therapy is not recommended for ICD/CRT-D patients due to possible heating effects of the pulse generator and at the implant site. If diathermy therapy must be used, it should not be applied in the immediate vicinity of the pulse generator or lead system.
Electrocautery - Electrosurgical cautery could induce ventricular arrhythmias and/or fibrillation, or may cause device malfunction or damage. If use of electrocautery is necessary, the current path and ground plate should be kept as far away from the pulse generator and leads as possible (at least 6 inches (15 cm)).
External Defibrillation - The device is protected against energy normally encountered from external defibrillation. However, any implanted device may be damaged by external defibrillation procedures. In addition, external defibrillation may also result in permanent myocardial damage at the electrode-tissue interface as well as temporary or permanent elevated pacing thresholds. When possible, observe the following precautions:
Position the adhesive electrodes or defibrillation paddles
of the external defibrillator anterior-posterior or along a line perpendicular to the axis formed by the implanted device and the heart.
Set the energy to a level not higher than is required to
achieve defibrillation.
Place the paddles as far as possible away from the
implanted device and lead system.
After delivery of an external defibrillation shock,
interrogate the ICD/CRT-D to confirm device status and proper function.
Lithotripsy - Lithotripsy may damage the ICD/CRT-D. If lithotripsy must be used, avoid focusing near the ICD/CRT-D implant site.
MRI (Magnetic Resonance Imaging) - Do not expose a patient to MRI device scanning. Strong magnetic fields may damage the device and cause injury to the patient.
Radiation - High radiation sources such as cobalt 60 or gamma radiation should not be directed at the pulse generator. If a patient requires radiation therapy in the vicinity of the pulse generator, place lead shielding over the device to prevent radiation damage and confirm its function after treatment.
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14 Lumax Technical Manual
Radio Frequency Ablation - Prior to performing an ablation procedure, deactivate the ICD/CRT-D during the procedure. Avoid applying ablation energy near the implanted lead system whenever possible.

1.4.7 Home and Occupational Hazards

Patients should be directed to avoid devices that generate strong electromagnetic interference (EMI) or magnetic fields. EMI could cause device malfunction or damage resulting in non-detection or delivery of unneeded therapy. Moving away from the source or turning it off will usually allow the ICD/CRT-D to return to its normal mode of operation.
The following equipment (and similar devices) may affect normal ICD/CRT-D operation: electric arc or resistance welders, electric melting furnaces, radio/television and radar transmitters, power-generating facilities, high-voltage transmission lines, and electrical ignition systems (of gasoline-powered devices) if protective hoods, shrouds, etc., are removed.

1.4.8 Cellular Phones

Testing has indicated there may be a potential interaction between cellular phones and BIOTRONIK ICD/CRT-D systems. Potential effects may be due to either the cellular phone signal or the magnet within the telephone and may include inhibition of therapy when the telephone is within 6 inches (15 centimeters) of the ICD/CRT-D, when the ICD/CRT-D is programmed to standard sensitivity.
Patients having an implanted BIOTRONIK ICD/CRT-D who operate a cellular telephone should:
Maintain a minimum separation of 6 inches
(15 centimeters) between a hand-held personal cellular telephone and the implanted device.
Set the telephone to the lowest available power setting, if
possible.
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Lumax Technical Manual 15
Patients should hold the phone to the ear opposite the
side of the implanted device. Patients should not carry the telephone in a breast pocket or on a belt over or within 6 inches (15 centimeters) of the implanted device as some telephones emit signals when they are turned ON, but not in use (i.e., in the listen or stand-by mode). Store the telephone in a location opposite the side of
Based on results to date, adverse effects resulting from interactions between cellular telephones and implanted ICDs/CRT-Ds have been transitory. The potential adverse effects could include inhibition or delivery of additional therapies. If electromagnetic interference (EMI) emitting from a telephone does adversely affect an implanted ICD/CRT-D, moving the telephone away from the immediate vicinity of the ICD/CRT-D should restore normal operation. A recommendation to address every specific interaction of EMI with implanted ICDs/CRT-Ds is not possible due to the disparate nature of EMI.
implant.

1.4.9 Electronic Article Surveillance (EAS)

Equipment such as retail theft prevention systems may interact with pulse generators. Patients should be advised to walk directly through and not to remain near an EAS system longer than necessary.

1.4.10 Home Appliances

Home appliances normally do not affect ICD/CRT-D operation if the appliances are in proper working condition and correctly grounded and shielded. There have been reports of the interaction of electric tools or other external devices (e.g. electric drills, older models of microwave ovens, electric razors, etc.) with ICDs/CRT-Ds when they are placed in close proximity to the device.

1.4.11 Home Monitoring®

BIOTRONIK’s Home Monitoring system is designed to notify clinicians in less than 24 hours of changes to the patient’s condition or status of the implanted device. Updated data may not be available if:
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16 Lumax Technical Manual
The patient’s CardioMessenger is off or damaged and is
not able to connect to the Home Monitoring system through an active telephone link
The CardioMessenger cannot establish a connection to
the implanted device
The telephone and/or Internet connection do not operate
properly
The Home Monitoring Service Center is off-line (upgrades
are typically completed in less than 24 hours)
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.
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.
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).
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Lumax Technical Manual 17
1.5 Potential/Observed Effects of the
Device on Health

1.5.1 Potential Adverse Events

The following are possible adverse events that may occur relative to the implant procedure and chronic implant of the CRT-D:
Air embolism Allergic reactions to
contrast media
Arrhythmias Bleeding Body rejection
phenomena
Cardiac tamponade Chronic nerve damage Damage to heart valves Device migration Elevated pacing
thresholds
Extrusion Fluid accumulation Hematoma 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 Thromboembolism Under sensing of intrinsic
signals
Venous occlusion Venous or cardiac
perforation
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In addition, patients implanted with the ICD/CRT-D system may have the following risks. These are the same risks related with implantation of any ICD/CRT-D system:
Acceleration of
arrhythmias (speeding up heart rhythm caused by the CRT-D)
Dependency Depression Fear of premature
battery depletion (fear that battery will stop working before predicted time)
Fear of shocking while
awake
Fear that shocking
ability may be lost
There may be other risks associated with this device that are currently unforeseeable.
Anxiety about the CRT-D
resulting from frequent shocks
Imagined shock (phantom
shock)
Inappropriate detection of
ventricular arrhythmias
Inappropriate shocks Potential death due to
inability to defibrillate or pace
Shunting current or
insulating myocardium during defibrillation with external or internal paddles

1.5.2 Observed Adverse Events

Reported Adverse Events are classified as either observations or complications. Complications are defined as clinical events that require additional invasive intervention to resolve. Observations are defined as clinical events that do not require additional invasive intervention to resolve.
1.5.2.1 Kronos LV-T Study
NOTE:
The Kronos LV-T CRT-D is an earlier generation of BIOTRONIK devices. The Lumax CRT-Ds are based upon the Kronos LV-T and other BIOTRONIK CRT-Ds and ICDs (i.e., Tupos LV/ATx CRT-D, Lexos and Lumos families of ICDs).
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Lumax Technical Manual 19
s
The HOME-CARE Observational study, conducted outside the US on the Kronos LV-T cardiac resynchronization defibrillator (CRT-D) in patients with congestive heart failure (CHF) involved 45 devices implanted with a cumulative implant duration of 202 months (mean implant duration of 4.5 months).
Of the 31 adverse events reported, there have been 26 observations in 23 patients and 5 complications in 3 patients with a cumulative implant duration of 202 months (16.8 patient­years). 6.7% of the enrolled patients have experienced a complication with two patients experiencing 2 separate complications. The rate of complications per patient-year was
0.30. 51% of the enrolled study patients had a reported observation with 3 patients having more than 1 observation. The rate of observations per patient-year is 1.54. Complications and observations for the patient group are summarized in Table 2
Table 3
, respectively.
and
Table 2: Summary of Complications – Kronos LV-T
Category
Number
of
Patients
% of
Patient
Number
Per
patient-
year
Left Ventricular Lead Related
Dislodgement 1 2.2% 1 No Capture 1 2.2% 1
Total 2 4.4% 2
0.06
0.06
0.12
ICD Lead Related
Dislodgement 1 2.2% 1 Elevated Pacing
Threshold
1 2.2% 1
Total 2 4.4% 2
0.06
0.06
0.12
Unrelated to CRT-D or Leads
Hemathorax 1 2.2% 1
Total 1 2.2% 1
Overall
Complication Totals
Number of Patients = 45, Number of Patient-Years = 16.8
3 6.7% 5
0.06
0.06
0.30
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20 Lumax Technical Manual
Table 3: Summary of Observations – Kronos LV-T
Category
Unsuccessful LV lead implant
Elevated LV pacing threshold
Phrenic nerve stimulation
Elevated DFT measurement
T-wave oversensing
Worsening CHF Elevated RV pacing
threshold Hepatitis
Arrhythmias Cardiac
Decompensation
Number
of
Patients
%of
Patients
Number
8 17.8% 8 0.48
5 11.1% 5 0.30
3 6.7% 3 0.18
2 4.4% 2 0.12
2 4.4% 2 0.12 2 4.4% 2 0.12
1 2.2% 1 0.06
1 2.2% 1 0.06 1 2.2% 1 0.06
1 2.2% 1 0.06
per
patient-
year
All Observations 23 51.1% 26 1.54
Number of Patients = 45, Number of Patient-Years = 16
Two patient deaths were reported during the HOME-CARE Observational Study. One death resulted from worsening heart failure and the second death resulted from cardiogenic shock due to ischemic cardiomyopathy. None of the deaths were related to the implanted CRT-D system. There were no device explants during the HOME-CARE Observational Study.
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Lumax Technical Manual 21
1.5.2.2 Tupos LV/ATx Study
NOTE:
The clinical study information included in this section and in
Section
which is an earlier version of the Lumax CRT-D/ICD families. The clinical study data presented here is applicable because the Lumax family are downsized versions of the Tupos LV/ATx CRT-D and Tachos ICD families. The Lumax family is slightly different as compared to the Tupos LV/ATx (and Tachos family) in the following areas:
Reduced size from 50/48 cc to 40/35 cc Addition of Home Monitoring® functionality Addition of triggered pacing for biventricular pacing
True three chamber pacing and sensing capabilities
The OPTION CRT/ATx study was a prospective, randomized, multi-center study 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. All patients enrolled into the clinical study were randomly assigned to either the study group or the control group at a 2 to 1 ratio. Patients in the study group were implanted with the Tupos LV/ATx. Patients in the control group were implanted with a legally marketed ICD that provides CRT.
1.6.2 was performed with the Tupos LV/ATx CRT-D,
modes
(CRT-Ds)
Of the 278 adverse events reported in the Tupos LV/ATx study group, there have been 210 observations in 104 patients and 68 complications in 50 patients with a cumulative implant duration of
1240.4 months (101.9 patient-years). 37.6% of the enrolled study patients have experienced a complication. The rate of complications per patient-year is 0.67. 78.2% of the enrolled study patients have a reported observation. The rate of observations per patient-year is 2.06.
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Complications and observations for the Tupos LV/ATx study group are summarized in Table 4
and Table 5. The total number of patients may not equal the sum of the number of patients listed in each category, as an individual patient may have experienced more than one complication or observation.
Table 4: Summary of Complications – Tupos LV/ATx
Category
Number
of
Patients
Hematoma 4 3.01% 4 0.04 Pneumothorax 2 1.50% 2 0.02
Total 6 4.51% 6 0.06
Dislodgement 3 2.26% 3 0.03
Total 3 2.26% 3 0.03
High threshold/No capture
2 1.50% 2 0.02
Diaphragmatic/Interc ostal stimulation
1 0.75% 1 0.01
(RV)
Total 3 2.26% 3 0.03
High threshold/Intermitten t biventricular
11 8.27% 12 0.12
capture/No capture Unable to implant lead via coronary
11 8.27% 11 0.11
sinus Dislodgement 4 3.01% 4 0.04 Diaphragmatic/Interc
ostal stimulation
1 0.75% 2 0.02
Total 27 20.3% 29 0.28
% of
Patients
Number of
Complications
Procedure Related
Atrial Lead Related
ICD Lead Related
LV Lead Related
Complications
per patient-year
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Lumax Technical Manual 23
Table 4: Summary of Complications – Tupos LV/ATx
Category
Number
of
Patients
Infection 3 2.26% 7 0.07 Device migration 4 3.01% 4 0.04 Elective replacement
indicator reached Inductions and conversions Unable to interrogate device
4 3.01% 4 0.04
1 0.75% 1 0.01
1 0.75% 1 0.01
Total 12 9.02% 17 0.17
Total Procedure and Device Related
43 32.33% 58 0.57
Other Medical Related
Non-CHF Cardiac Symptoms Ventricular arrhythmias
4 3.01% 4 0.04
2 1.50% 3 0.03
Other medical 2 1.50% 2 0.02 Atrial arrhythmia 1 0.75% 1 0.01
Total 9 6.77% 10 0.10
Total – All Patients and Categories
50 37.59% 68 0.67
% of
Patients
Complications
Device Related
Number of
Complications
per patient-year
Number of Patients = 133, Number of Patient-Years = 101.9
* 1 Unanticipated Adverse Device Effect (UADE) occurred with a Tupos LV/ATx CRT-D during the OPTION clinical study. The device was explanted after it was unable to be interrogated with the programmer software and no pacing output was evident. The analysis showed an inappropriately depleted battery and no anomalies with the IC module. The battery depletion strongly suggests that the high voltage circuit was activated over a prolonged period due to a single-bit execution path failure. The current programmer software with Automatic Battery Management (ABM) would have prevented the battery from becoming completely depleted. There were no other instances of this failure mechanism in Tupos LV/ATx devices.
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For the Tupos LV/ATx study group, there were 210 observations in 104 patients with cumulative implant duration of 1240.4 months (101.9 patient years). 78.2% of the enrolled study patients have a reported observation. The rate of observations per patient-year was 2.06. Table 5
summarizes by category each type of
observation for the study group.
Table 5: Summary of Observations – Tupos LV/ATx
Number
Category
Hematoma 10 7.52% 10 0.10
Cardiac arrest 2 1.50% 2 0.02 Unable to implant
system
Total 13 9.77% 13 0.13
Dislodgement 1 0.75% 1 0.01
High threshold 1 0.75% 1 0.01
Total 2 1.50% 2 0.02
High threshold/No capture
Total 1 0.75% 1 0.01
High threshold/ Intermittent biventricular capture/ No capture Diaphragmatic/ Intercostal stimulation
Total 30 22.56% 32 0.31
of
Patients
Procedure Related
1 0.75% 1 0.01
Atrial Lead Related
ICD Lead Related
1 0.75% 1 0.01
LV Lead Related
24 18.05% 24 0.24
8 6.02% 8 0.08
% of
Patients
Number
per patient-
year
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Lumax Technical Manual 25
Table 5: Summary of Observations – Tupos LV/ATx
Number
Category
Infection 1 0.75% 1 0.01 Inductions and
conversions Inappropriate sensing 20 15.04% 20 0.20 Symptomatic with
biventricular pacing
Total 25 18.80% 29 0.28
Total Procedure, Lead and Device Related
Non-CHF Cardiac Symptoms Ventricular arrhythmias
Other medical 26 19.55% 32 0.31
Atrial arrhythmia 14 10.53% 14 0.14
Dizziness 4 3.01% 4 0.04
Medication 5 3.76% 5 0.05
Worsening CHF 46 34.59% 46 0.45
Total 82 61.65% 133 1.31
Total – All Patients and Categories
Number of Patients = 133 Number of Patient-Years = 101.9
of
Patients
Device Related
6 4.51% 6 0.06
2 1.50% 2 0.02
61 45.86% 77 0.76
Other Medical Related
21 15.79% 21 0.21
11 8.27% 11 0.11
104 78.20% 210 2.06
% of
Patients
Number
per patient-
year
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There have been 4 patient deaths reported for the control group (out of 67 total control patients) and 10 patient deaths have been reported for the study group (out of 133 total study patients). None of the deaths were related to the implanted CRT-D system. One patient in the control group died prior to receiving a biventricular device implant. There is no significant difference between the number of deaths in the study group versus the control group (p = 0.777, Fisher's Exact Test, 2 sided). Table 6 provides a summary of reported patient deaths and Table 7 provides survival percentages by follow-up interval during the first 12 months of study participation.
Table 6: Summary of Patient Deaths
Category of
Death
Study
(N = 133)
Control
(N = 67)
Number of Patients Number of Patients
Sudden Cardiac 1 1
Non-Sudden
5 2
Cardiac
Non-Cardiac 4 1
All Causes
10 4
Figure 3 shows the associated Kaplan-Meier survival curves for
the study and control group. The significance level for the difference between the two study groups based on a Log Rank test was p = 0.795.
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Lumax Technical Manual 27
Cumulative Survival
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Log Rank = 0.795
Control
Study
211815129630
Survival Time (months)
Figure 3: Kaplan-Meier Survival Curves
Table 7 Survival Table
Study Group
(n = 133)
Control Group
(n = 66)
Number % Number % Enrollment 133 100.00% 67 100.00% 3-month 131 98.50% 63 94.03% 6-month 127 95.49% 63 94.03% 12-month 123 92.48% 63 94.03%

1.6 Clinical Studies

The Kronos LV-T Clinical study (HOME-CARE, Section 1.6.1) supports the safety of the Lumax CRT-D/ICD device family. Additionally, because the Tupos LV/ATx and the Lumax CRT-D devices have identical CRT and ventricular ICD therapy, the effectiveness results from the OPTION CRT/ATx IDE Clinical study (Tupos LV/ATx, Section the Lumax family.
1.6.2) support the effectiveness of
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1.6.1 Kronos LV-T Study
The purpose of the HOME-CARE Observational Study is to demonstrate the safety of the CE-marked Kronos LV-T cardiac resynchronization defibrillator (CRT-D) in patients with congestive heart failure (CHF).
1.6.1.1 Methods
The multi-center, non-randomized observational study was designed to evaluate the safety of the Kronos LV-T through an analysis of the complication-free rate through three months.
HOME-CARE Observational Study Primary Endpoint was to
The evaluate complications (adverse events that require additional invasive intervention to resolve) related to the implanted CRT system which includes the Kronos LV-T, the right atrial lead, the right ventricular ICD lead, and the left ventricular lead
Inclusion Criteria
To support the objectives of this investigation, patients were required to meet the following inclusion criteria prior to enrollment:
Indication for Cardiac Resynchronization Therapy Sufficient GSM-network coverage in the patient’s area Age greater than or equal to 18 years
Exclusion Criteria
To support the objectives of this investigation, the exclusion criteria at the time of patient enrollment included the following:
Permanent atrial fibrillation Myocardial infarction or unstable angina pectoris within
the last 3 prior to enrollment
Planned cardio-surgical intervention within 3 months after
enrollment (e.g. PTCA, CABG, HTX)
Acute myocarditis Life expectancy less than 6 months Pregnant or breast-feeding woman Drug or Alcohol abuse The patient is mentally or physically unable to take part in
the observational study
No signed declaration of consent for the patient
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Lumax Technical Manual 29
At the enrollment screening, the physician evaluated the patient to verify that all inclusion/exclusion criteria were met in accordance to the protocol and the patient signed the informed consent. After successful enrollment, all patients were implanted with the Kronos LV-T CRT-D. Evaluations at the One- and Three­month follow-ups included resting ECG, NYHA classification, medications, and activation of Home Monitoring.
1.6.1.2 Summary of Clinical Results
The study involved 45 patients (37
males, 82.2%, and 8 females,
17.8%), with a mean age of 64 years (range: 36-79), a left ventricular ejection fraction of 26 % (range: 15-43), NYHA Class III (NHYA Class 1 (2.3%), Class II (11.4%), Class III (79.5%), Class IV (6.8%)) and QRS duration of 154 ms (range: 84-208).
The mean implant duration was 4.5 months with a cumulative implant duration of 202 months. The patient follow-up compliance rate was 95.9% out of 221 required follow-ups.
Primary Endpoint
The safety of the Kronos LV-T was evaluated based on complications (adverse events that require additional invasive intervention to resolve) related to the implanted CRT system which includes the Kronos LV-T, the right atrial lead, the right ventricular ICD lead, and the left ventricular lead. 5 complications were seen in 3 patients with cumulative implant duration of 202 months (16.8 patient-years). 6.7% of the patients had a reported complication. The rate of complications per patient-year is 0.30.
The freedom from Kronos LV-T system-related complications is
93.3% with a two sided lower 95% confidence bound of 83.8%. The null hypothesis is rejected, and it is concluded that the complication-free rate is equivalent to 85% within 10%.
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1.6.2 Tupos LV/ATx Study

NOTE:
The clinical study information included in this section was performed with the Tupos LV/ATx CRT-D, which is an earlier version of the Lumax CRT-D/ICD families. The clinical study data presented here is applicable because the Lumax family are downsized versions of the Tupos LV/ATx CRT-D and Tachos ICD families. The Lumax family is slightly different as compared to the Tupos LV/ATx (and Tachos family) in the following areas:
Reduced size from 50/48 cc to 40/35 cc Addition of Home Monitoring functionality Addition of triggered pacing for biventricular pacing
modes
True three chamber pacing and sensing capabilities
1.6.2.1 Study Overview
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.
(CRT-Ds)
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Lumax Technical Manual 31
1.6.2.2 Methods
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 effectiveness of atrial therapy to automatically convert atrial tachyarrhythmias, 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.
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/CRT-D, optimal and
stable CHF drug regimen including ACE-inhibitors and beta-blockers 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
Ability to tolerate the surgical procedure required for
implantation
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Ability to complete all required testing including the six-
minute 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
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
1.6.2.3 Summary of Clinical 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.
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Lumax Technical Manual 33
Patient Accountability
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 4
.
Enrolled and Randomized
Patients
Study 133 Control 67
Implant Attempted
Study 130 Control 65
Successful implant
Study 129 Control 64
Patients completed 6-Month
Follow-up
Study 100 Control 49
No implant Attempted
Withdrawal of Consent
Study 2 Control 1
Not Meeting Inclusion Criteria
Study 1 Control 1
Unsuccessful implant
Withdrawal of IC before 2nd Attempt
Study 1 Control 0
Expired before Second Attempt
Study 0 Control 1
6-Month Follow-up Data
Patient Death before 6-Month
Study 7 Control 3
Withdrawal before 6-Month
Study 1 Control 2
Not Reached 6-Month FU
or Data Pending
Study 21 Control 10
Figure 4: Patient Accountability
Overall Results
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 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.
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The cumulative implant duration was 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.
For the study group, there have been 278 adverse events
(210 observations in 104 patients and 68 complications in 50 patients). There has been one unanticipated adverse device effect reported.
For the control group, there have been 105 adverse
events (81 observations in 44 patients and 24 complications in 19 patients). There have been no unanticipated adverse device effects reported.
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.
1.6.2.4 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 8
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.
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Lumax Technical Manual 35
Table 8: Composite of Six Minute Walk Test and QOL
(Effectiveness)
Category
Distance Walked at
Baseline
Distance Walked at
Six-Months
Distance Walked
QOL Score at
Baseline
QOL Score at Six-
Months
in QOL Score**
Study
Group
(N = 74)
Mean SE
310.51 ±
10.89
340.77 ±
12.32
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%
Control
Group
(N = 38)
Mean SE
288.76 ±
15.37
301.84 ±
17.02
13.08 ±
13.05
8.71% ±
5.26%
11.58 ± 3.45
-13.42% ±
34.54%
P-value*
0.249
0.067
0.322
0.326
0.376
0.281
Composite Rate***
*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 (non­inferiority). ** 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.
18.18% ±
7.07%
-2.36% ±
17.73%
0.030
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1.6.2.5 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 is (-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).
1.6.2.6 Primary Endpoint 2: Complication-Free Rate
(Safety
)
The purpose of Primary Endpoint 2 was to evaluate complications (adverse events that require additional invasive intervention to resolve) related to the implanted CRT system which includes the Tupos LV/ATx, the right atrial lead, the right ventricular ICD lead, the left ventricular lead, and the implant procedure. The target complication-free rate at Six-Months is 85%.
Table 9 provides the categorized complication rates at 6-months
for the study and the control group as well as a comparison between the study and the control group.
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Table 9: Complications at 6-Month – Study and Control
Study versus Control
Comparison
Delta 95% CI P-value
3.02% [-3.64%,
0.76% [-5.74%,
6.12% [-5.50%,
%
3.78 %
6.94% [-6.46%,
9.21% [-4.96%,
Category
Procedure Related Atrial Lead Related ICD Lead Related LV Lead Related
Device Related
Other Medical Related
Total Procedure, Lead and Device Related
Total
Study
N = 133
6 (4.51%) 1
3 (2.26%) 1
3 (2.26%) 0 (0%) 2.26% [-3.03%,
26
(19.55%) 9 (13.43%)
7 (5.26%) 5
9 (6.77%) 2
39
(29.32%)
46
(34.59%)
Control
N = 67
(1.49%)
(1.49%)
(7.46%) -2.20
(2.99%)
15
(22.39%)
17
(25.37%)
8.45%]
5.37%]
6.53%]
16.45%]
[-11.42%,
4.77%]
[-3.82%,
10.13%]
19.17%]
21.99%]
0.428
1.000
0.552
0.329
0.541
0.341
0.317
0.201
1.6.2.7 Primary Safety Enpoint Analysis and Conclusions
The observed procedure, lead and device related complication­free rate at 6 months was 70.68%. The 95% confidence interval for the complication-free rate was [62.16%, 78.25%]. The lower, one-sided 95% confidence bound for the complication-free rate was 63.50%. Therefore the procedure, lead and device related complication-free rate at 6 months did not meet the pre-specified acceptance criterion for this endpoint.
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1.6.2.8 Post-hoc Safety Analysis
BIOTRONIK did not meet the pre-specified objective performance criteria of 85% within 10% for the safety endpoint. Therefore, a post-hoc safety analysis was conducted. It was noted that
79.80% (39 out of 49 events) of the complications were right atrial lead, right ventricular ICD lead, left ventricular lead and procedure related. The atrial, ICD and LV leads used during this study are legally marketed devices.
This post-hoc analysis evaluated the LV lead complications that were “related” or “possibly related” to the Tupos LV/ATx CRT-D, but excludes the complications that were “not related” to the Tupos LV/ATx device (see Table 9). There were 11 patients who had an attempt to implant the LV lead, but the physician was unsuccessful in either obtaining coronary sinus (CS) access or unable to find a stable position for the LV lead. Additionally, there were 4 patients with a documented LV lead dislodgement that has no direct relationship to the implanted Tupos LV/ATx.
Table 10: Complications at 6-Months (Excluding LV Lead
Related) - Study versus Control
Difference
Study vs.
Control
8.36%
11.39%
Category
Procedure Related Atrial Lead Related ICD Lead Related LV Lead Related Device Related Other Medical Related
Total Procedure, Lead and Device
Related
Total
Study
N=133
Control
N=67
6 (4.51%) 2 (2.99%) 1.53% 3 (2.26%) 1 (1.49%) 0.76% 3 (2.26%) 0 (0%) 2.26%
11 (8.27%) 1 (1.49%) 6.78%
7 (5.26%) 5 (7.46%) -2.20% 9 (6.77%) 2 (2.99%) 3.78%
27
(20.30%) 8 (11.94%)
35
(26.32%)
10
(14.93%)
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The pulse generator related complication rate is higher in the control group as compared to the study group. The complication rates for procedure related, atrial lead related, ICD lead related, LV lead related and other medical related are higher in the study group as compared to the control group.
1.6.2.9 Post hoc Safety Analysis Conclusion
There are no clinically
substantial differences in the total complication rate or in the rates for the different complication rate categories between the study and the control group.
Table 11
compares this post-hoc Safety Endpoint analysis to
previous CRT-D clinical studies:
Table 11 Safety Endpoint Comparisons
CRT-D Study
BIOTRONIK OPTION (Original Analysis)
BIOTRONIK OPTION (Post-hoc Analysis)
Estimated
freedom from
Complications
Lower 95%
CI
@ 6mos.
70.68% 63.5% 75%
78.95% 72.29% 75%
95%
lower
bound
criteria
Medtronic Insync ICD 81.1% 77.6% 67% Guidant Contak CD N/A N/A 70% St. Jude Medical Epic
HF
93.4% 90.6% 70%
This analysis confirms that the safety profile of the Tupos LV/ATx is within a similar range determined during trials of other legally marketed CRT-D devices.
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1.6.2.10 Secondary Endpoint Results
1. The purpose of Secondary Endpoint 1 is to evaluate the
overall ability of the Tupos LV/ATx to appropriately convert spontaneous AT (atrial tachycardia) and AF (atrial fibrillation). The results from the OPTION study were compared to the results from BIOTRONIK’s TACT study (P000009/S4, dated 09-09-2002) that demonstrated the effectiveness of these atrial therapy features in the Tachos DR - Atrial Tx ICD.
Table 12
summarizes success rates for each individual atrial tachyarrhythmia therapy type and overall success rate from the OPTION study compared to the TACT study. The number of episodes and patients receiving any therapy is less than the total episodes of each therapy type, as episodes may have included more than one type of therapy.
Table 12 Overall Atrial Conversion Rate
OPTION Study
Patients Success Episodes
Conversion
rate
ATP 3 3 5 60.0%
HF Burst 17 45 111 40.5%
Shock 12 30 34 88.2%
All
Therapies
25 78 129 60.5%
TACT Study
ATP 29 62 142 43.6 %
HF Burst 49 156 408 38.2 %
Shock 42 84 108 77.8 %
All
Therapies
66 302 542 55.7 %
The overall conversion rate and the conversion rates for each therapy are comparable to the conversion rates observed in the TACT study, demonstrating that the Tupos LV/ATx device has similar atrial conversion capabilities as the legally marketed Tachos DR – Atrial Tx ICD.
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2. The purpose of Secondary Endpoint 2 is to evaluate VT (ventricular tachycardia) and VF (ventricular fibrillation) detection times of the Tupos LV/ATx. This is a measure of the ability of the ventricular detection algorithm to detect VT and VF in an appropriate timeframe. This endpoint was evaluated based on the review of electrograms following induced VT/VF episodes. A comparison of data from the TACT study that utilized the legally marketed Tachos DR – Atrial Tx ICD (P000009/S4, dated 09-09-2002) to data collected during the OPTION study for the Tupos LV/ATx was performed.
Table 13
summarizes and compares the results from these
two clinical studies.
Table 13: Summary of Detection Times
Detection
Time
Individual Readings
Tachos DR -
Atrial Tx ICD
Mean (SE)/N
2.27 (0.06)/52 2.26 (0.06)/71 0.01
Tupos
LV/ATx Mean
(SE)/N
Difference
By Patient 2.27 (0.07)/26 2.24 (0.06)/35 0.03
The analysis demonstrates that the average detection times of the Tupos LV/ATx are comparable to the detection times observed with the legally marketed Tachos DR - Atrial Tx ICD. Both devices utilize identical ventricular detection algorithms and only sense with the right ventricular lead. This clinical data demonstrates that the ventricular detection times are similar in both devices.
3. The purpose of Secondary Endpoint 3 is to evaluate the percentage of ventricular pacing (thus, CRT) as demonstrated by the device diagnostics at required follow­ups. This data was based on diagnostic data stored by the Tupos LV/ATx.
Table 14
summarizes the percentage of ventricular pacing between follow-ups as shown by device diagnostics for patients in the study group.
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Table 14: Percentage of Ventricular Pacing –
3-Month and 6-Month Follow-ups
Percentage of
Ventricular
Pacing
3-Months
Patients
(percentage)
6-Months Patients
(percentage)
<80% 9 (7.4%) 4 (4.0%)
81 – 85 % 4 (3.3%) 2 (2.0%)
86 – 90 % 13 (10.7%) 9 (9.1%)
91 – 95 % 19 (15.7%) 20 (20.2%)
96 – 100 % 76 (62.8%) 64 (64.7%)
Totals 121 (100%) 99 (100%)
The majority of the follow-ups (84.9%) show a percentage of ventricular pacing of 91% or more at Six-Months.
4. The purpose of secondary endpoint 4 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.
Table 15
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.
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Table 15: Six Minute Walk Distance
Distance
(meters)
Baseline
N
Mean SE
Range
Median
Study Control
127
283.14 9.27 23 to 511
269.43 13.77 29 to 507
302.00
61
244.00
Six-Month
N
Mean SE
Range
Median
* Student's t-test, 2-sided
93
329.73 10.82 78 to 596
335.00
44
310.70 15.49 91 to 489
313.00
There are no clinically relevant differences in the six minute walk test results between the study and the control group.
5. The purpose of Secondary Endpoint 5 is to evaluate the improvement in the patient’s NYHA classification. Table 16 summarizes the average improvement in NYHA from Baseline to Six-Months for 140 patients that were able to complete both NYHA classification evaluations.
Table 16: Improvement in NYHA Classification at Six-
Months from Baseline
NYHA Change During OPTION Study
Change in NYHA
Class
Improved 2 classes
Study Patients
(N=97)
(percentage)
Control Patients
(N=43)
(percentage)
10 (10.3%) 2 (4.7%)
Improved 1 class
Total improved
No change
Worsened 1 class
47 (48.5%) 20 (46.5%)
57 (58.8%) 23 (51.2%)
39 (40.2%) 20 (46.5%)
1 (1.0%) 1 (2.3%)
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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.
6. The purpose of Secondary Endpoint 6 is to evaluate the rate of hospitalization, for CHF and for all other causes. The occurrence rate and reasons for hospitalization of the study group were compared to the control group. To be consistent with other large-scale clinical trials, clinical sites were instructed to report hospitalizations for CHF using the following definitions: 1) hospitalization for heart failure management, 2) outpatient visit in which IV inotropes or vasoactive infusion are administered continuously for at least 4 hours, or 3) emergency room (ER) visit of at least 12 hours duration in which intravenous heart failure medications including diuretics are administered.
Table 17
summarizes hospitalization, ER visits and outpatient
visits for enrolled patients.
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Table 17: Hospitalization, ER Visits and Outpatient Visits
Medical Visits
Hospital
Admissions
Patients
Hospitalizations
Patients
Hospitalizations
Emergency
Room Visits
Patients
Visits
Patients
Visits
Outpatient Visits
Patients
Visits
Patients
Visits
Study
(N=128)
CHF Related:
20 (15.6%)
All causes:
68 (53.1%)
CHF Related:
1 (0.8%)
All causes:
13 (10.1%)
CHF Related:
1 (0.8%)
All causes:
5 (3.9%)
28
76
1
16
1
5
Control
(N=65)
CHF Related:
5 (7.7%)
9 All causes: 29 (44.6%)
46
CHF Related:
0 (0.0%)
0 All causes:
2 (3.1%)
2
CHF Related:
0 (0.0%)
0 All causes:
2 (3.1%)
2
A large percentage of All Cause hospitalizations can be attributed to pacing lead revisions, device infections, or other device-related interventions (e.g., pocket revision or device replacements for ERI or device recall). The CHF hospitalization rate for both the study and control groups is clinically acceptable considering the enrollment CHF status of the patients.
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7. The purpose of Secondary Endpoint 7 is to evaluate the observation rate. Observations are defined as clinical events that do not require additional invasive intervention to resolve. For the study group, there were 210 observations in 104 patients with cumulative implant duration of 1240.4 months (101.9 patient years). 78.2% of the enrolled study patients have a reported observation. The rate of observations per patient-year is 2.06. For the control group, there were 81 observations in 44 patients with cumulative implant duration of 596.5 months (49.0 patient years). 65.7% of the enrolled control patients had a reported observation. The rate of observations per patient-year was 1.65.
8. The purpose of Secondary Endpoint 8 is to evaluate peak VO2 as a measure of effectiveness of the Tupos LV/ATx system in providing CRT. The core lab was blinded to study randomization assignments during evaluation of the results of the cardiopulmonary exercise (CPX) testing in order to minimize the potential for bias. According to the protocol, to be included in the analysis, patients were required to attain a respiratory exchange ratio (RER) of 1.
Table 18
provides a summary of peak VO2 results for 42 patients with CPX testing completed at Baseline and the Six­Month follow-up and with an RER of 1.
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Table 18: Peak VO2 Testing Results – Patients with RER
1
Results Study Control
Peak VO2
(ml/kg/min)
N=32
Baseline:
Mean:
13.46 ± 0.57 Range:
6.9 to 21.1
Six-Month:
Mean:
13.39 ± 0.53 Range:
7.6 to 20.70
Difference:
Mean:
-0.06 ± 0.42 Range:
-7.9 to 4.9
N=10
Baseline:
Mean:
12.58 ± 0.75 Range:
8.0 to 14.8
Six-Month:
Mean:
12.89 ± 0.94 Range:
7.0 to 17.2
Difference:
Mean:
0.31 ± 0.67 Range:
-2.7 to 4.6
1.6.2.11 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.
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The gender distribution in this clinical investigation is consistent within the study groups and includes a representative proportion of female participants. There were no significant differences in any of the primary or secondary endpoints between the male and female population.
1.6.2.12 Conclusions
The IDE Clinical safety and effectiveness of the Tupos LV/ATx CRT-D device is equivalent to that of similar legally marketed CRT-D devices. Although the study missed its primary safety endpoint, additional post hoc analyses were conducted to reassure that the safety profile of the device is comparable to other legally marketed CRT-D devices.
study (OPTION LV/ATx) demonstrated that the
1.6.3 Lumax HF-T V-V Clinical Study
1.6.3.1 Study Overview
The Lumax HF-T V-V clinical study is a randomized, double­blinded, crossover, multi-center, prospective trial. The purpose of the study is to assess the safety and efficacy of adding programmable V-V delay biventricular pacing when used as part of echo optimization of V-V timing (OPT). The assessment consisted of comparing one-month periods of CRT with (OPT) and without (SIM) V-V programmability and optimization in the same patients to assess whether a statistically significant increase of worsened HF status occurred during V-V adjustment. The V-V delay feature is programmed to provide CRT through the selection of the first chamber paced and adjustment of the V-V delay. When V-V delay programmability is not available, CRT provides simultaneous biventricular pacing (V-V delay is 0 ms).
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1.6.3.2 Methods
The study primarily evaluates and compares the functional benefits of the Lumax HF-T with OPT versus the Lumax HF-T with SIM using an endpoint that includes both a 6-minute walk (6MW) test and quality of life (QOL) measurement assessed using the Minnesota Living with Heart Failure questionnaire (MLWHFQ). As such, relevant measurements are completed 3 times for each patient: once at the baseline evaluation (up to 14 days after enrollment), once at the 1-month follow-up (30 days after baseline) and once at the 2-month follow-up (30 days after the 1-month follow-up). Baseline data is collected with the Lumax HF-T programmed to SIM.
6MW testing was chosen as a meaningful measure of CRT therapy effect on HF status because 6MW has been shown to improve during chronic CRT therapy (Olsson LG, Swedberg K, Clark AL et al. Six minute corridor walk test as an outcome measure for the assessment of treatment in randomized, blinded intervention trials of chronic heart failure: a systematic review. Eur Heart J 2005; 26:778–793.) Example improvements of 6MW include increase in the range of 20 meters.
In this trial, the intent was to detect any loss of CRT benefit by assessing the incidence of HF “worsening”, defined as reduction of 35 meters distance on 6MW during CRT with V-V programmability and optimization compared to during CRT without V-V programmability and optimization.
QOL testing was chosen as a meaningful measure of CRT therapy effect on HF status because QOL has been shown to improve during chronic CRT therapy (Albouaini K, Egred M, Rao A, et al. Cardiac resynchronisation therapy: evidence based benefits and patient selection. Eur J Intern Med. 2008 May;19(3):165-72) Example magnitude improvements of QOL include change in the range of 10 points.
In this trial, the intent was to detect any loss of CRT benefit by assessing the incidence of HF “worsening”, defined as increase of 10 points in QOL score by MLWHFQ during CRT with V-V programmability and optimization compared to during CRT without V-V programmability and optimization.
Worsening in the trial was defined as either a worsening (as defined) in 6MW or in QOL score during CRT with V-V programmability and optimization.
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The primary endpoint hypothesis required that a high proportion of subjects remain “not worsened” when CRT with V-V programmability and optimization was delivered compared to when CRT without V-V programmability and optimization. A high proportion was defined according to an Objective Performance Criteria (OPC), derived from observations of how often stable subjects in the BIOTRONIK Tupos LV/ATX CRT-D trial (OPTION) experienced spontaneous worsening due to the underlying disease among other factors.
During the Lumax V-V clinical study, the V-V optimization was completed utilizing echocardiography specifically determining an optimal V-V delay using the velocity time integral (VTI) to non­invasively measure stroke volume. The assessment was performed by determining the V-V delay setting associated with the largest VTI value. The VTI of the aortic flow is measured in the apical 5 chamber view.
Prior to the V-V delay optimization procedure, each patient underwent an optimization of AV timing. Following the AV timing adjustment, this standardized procedure was followed for the optimization of V-V delay:
1. Program the Lumax HF-T “Initially Paced Chamber” parameter to either RV or LV based on preference.
2. Assess the VTI measurement at the following V-V delays (additional V-V settings may be utilized at the investigator’s discretion):
100 ms 80 ms 60 ms 40 ms 20 ms 0 ms
Note: Use the average VTI parameter over a 3 beat cycle and wait 10 to 15 seconds between changing V-V delay settings. Also, attempt to measure the VTI parameter within the same patient respiratory cycle.
3. Record the VTI measurement associated with each V-V delay setting
Repeat steps 1-3 for the remaining “Initially Paced Chamber” parameters
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Select permanent “Initially Paced Chamber” and “V-V delay after Vp” to reflect the maximum VTI measurement for final programming.
Inclusion Criteria
To support the objectives of this investigation, the inclusion criteria at the time of patient enrollment for this investigational study included the following requirements:
Meet the indications for therapy. Successfully implanted with a BIOTRONIK Lumax HF-T
CRT-D system and have received SIM for a minimum of 30 days prior to enrollment.
Treated with stable and optimal CHF medications. Age 18 years. Able to understand the nature of the study and give
informed consent.
Able to complete all testing required by the clinical
protocol, including the 6-minute walk test and QOL questionnaire.
Available for follow-up visits on a regular basis at the
investigational site.
Exclusion Criteria
To support the objectives of this investigation, the exclusion criteria at the time of patient enrollment included the following requirements:
Meet one or more of the contraindications. Have a life expectancy of less than 6 months. Expected to receive heart transplantation within 6
months.
Have had more than 1 CHF-related hospitalization within
past 30 days.
Currently receiving IV inotropic medications. Chronic atrial fibrillation. Enrolled in another cardiovascular or pharmacological
clinical investigation, except for FDA required post-market registries.
Any condition preventing the patient from being able to
perform required testing.
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Presence of another life-threatening, underlying illness
separate from their cardiac disorder.
1.6.3.3 Summary of Clinical Results
The
study involved 122 patients (96 males, 78.7%, and 26
females, 21.3%), with a mean age of 67.1 years (range: 35-87).
The cumulative enrollment duration is 621.3 months with mean enrollment duration of 5.1 months. The patient follow-up
compliance rate for all enrolled patients is 98.5% (394 of 400 required follow-ups).
1.6.3.3.1 Primary Endpoint 1: Effectiveness of the V-V Delay
Feature
The primary endpoint was intended
to detect whether V-V programmability and optimization contributed to significantly more patients with “worsened” HF. Worsened was defined as:
For 6MW, reduction of 35 meters distance on 6MW
during CRT with V-V programmability and optimization compared to during CRT without V-V programmability and optimization
For QOL score, increase of 10 points in QOL score by
MLWHFQ during CRT with V-V programmability and optimization compared to during CRT without V-V programmability and optimization
For each patient, i.e. as a responder’s analysis, the
occurrence of either worsened 6MW or QOL score during CRT with V-V programmability and optimization.
Table 19
presents the mean 6-minute walk test distances and QOL scores for Group 1 and Group 2 patients at the baseline, 1­month and 2-month follow-ups. Table 19
reports unpaired patient data for information purposes, with the primary endpoint analysis utilizing paired data from the 1-month and 2-month follow-ups.
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The analysis of the primary effectiveness endpoint is an intention­to-treat analysis based on the responder classification of changes in the MLWHFQ and 6-minute walk distance between periods of SIM and OPT, obtained at the 1-month and 2-month follow-ups.
Table 20
presents the percentage of all patients worsened and not worsened to evaluate the effectiveness of OPT vs. SIM utilizing the QOL and 6-minute walk responder classification. A total of 106 out of the 110 patients that completed the primary endpoint follow-up met the primary endpoint analysis based on paired QOL and 6-minute walk data at the 1-month and 2-month follow-up visits.
Table 19. QOL and 6-Minute Walk Test Results (Effectiveness)
Category Group 1 Group 2
QOL score at baseline
QOL score at 1-month follow-up
QOL score at 2-month follow-up
Distance walked at baseline (m)
Distance walked at 1­month follow-up (m)
Distance walked at 2­month follow-up (m)
N = 60
35.4 ± 23.0
N = 57
31.2 ± 24.0 OPT
N = 58
32.6 ± 25.5
SIM
N = 61
328.9 ± 152.8
N = 58
343.9 ± 161.8 OPT
N = 57
341.1 ± 152.6
SIM
N = 53
30.0 ± 21.6
N = 54
30.1 ± 22.5 SIM
N = 52
25.9 ± 19.8
OPT
N = 54
309.1 ± 139.7
N = 54
337.6 ± 160.7 SIM
N = 51
334.7 ± 148.9
OPT
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Table 20. QOL and 6-Minute Walk Responder Classification
(Effectiveness)
QOL
Group 1
(N = 56)
Group 2
(N = 52)
Total
(N = 108)
Worsened 9 (16.1%) 6 (11.5%) 15 (13.9%)
Not worsened 47 (83.9%) 46 (88.5%) 93 (86.1%)
6-Minute Walk (N = 56) (N = 51) (N = 107)
Worsened 14 (25.0%) 15 (29.4%) 29 (27.1%)
Not worsened 42 (75.0%) 36 (70.6%) 78 (72.9%)
Composite (N = 55) (N = 51) (N = 106)
Worsened 21 (38.2%) 18 (35.3%) 39 (36.8%)
Not worsened 34 (61.8%) 33 (64.7%) 67 (63.2%)
The estimate of the proportion of subjects who were classified as “Not Worsened” was 63.2% (67/106). The lower, exact, one-sided 95% confidence bound for this observed proportion is 54.8%. The difference between the performance goal of 63% and 54.8% is
8.2%. This is lower than the pre-specified clinically significant difference () of 12%.
1.6.3.3.2 Primary Endpoint 2: Safety of the V-V Delay Feature
The purpose of Primary Endpoint 2 is to evaluate adverse events that require additional invasive
intervention to resolve, specifically related to the V-V delay feature of the Lumax HF-T. These adverse events include any software issues related to V-V delay programming or any adverse event that occurs after V-V delay optimization and that can be directly attributed to the use of the V-V delay feature.
There have been 0 reported complications related to the V-V delay feature for the 122 patients enrolled into the study.
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The observed complication-free rate was 100.0%. The lower, exact, one-sided 95% confidence bound for this observed rate is
97.6%. This exceeds the pre-specified rate (90% - δ) required for demonstrating non-inferiority.
1.6.3.4 Conclusions
cumulative enrollment duration is 621.3 months with a mean
The duration of 5.1 months. Sixty-one (50.0%) of the patients have been enrolled for 91-180 days.
The proportion of subjects who are “Not Worsened” while their device was programmed to OPT was found to be not inferior to the performance goal of 63% within 12%. In addition, there have been 0 complications reported regarding the Lumax HF-T V-V delay feature.
The data received and analyzed demonstrates the general safety of the Lumax HF-T V-V timing feature, with 0 complications reported as caused by the feature. Also, the data received and analyzed demonstrates the effectiveness of the Lumax HF-T V-V timing feature, by providing evidence of non-inferiority to simultaneous biventricular pacing in a responder classification.

1.6.4 TRUST Clinical Study

1.6.4.1 Study Overview
The TRUST study is a multi-center, prospective and randomized trial. The purpose of the study was to demonstrate that the use of the BIOTRONIK Home Monitoring system (HM) can safely reduce the number of regularly scheduled office follow up visits, compared to the conventional method of ICD follow-up. The assessment consists of comparing the number of in-office follow­ups for patients with HM (HM group) versus patients without HM (Control group). With the use of HM, the number of in-office follow up visits per year could be reduced from an expected five scheduled office follow up visits (3, 6, 9, 12 and 15 months) to two visits (3 and 15 months). Additionally, the time from onset to evaluation of arrhythmias in both groups was compared. It was expected that evaluation of cardiac events in the HM arm would occur earlier than those in the Control group.
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1.6.4.2 Methods
All enrolled patients received a BIOTRONIK ICD with Home Monitoring/IEGM-Online technology and were randomized to either Group 1 (Home Monitoring (HM)) or Group 2 (No Home Monitoring (Control)) using a randomization ratio of 2:1.
Group 1 (HM)
Device evaluations for scheduled follow-ups, patient-initiated inquiries and event triggered notifications were performed with HM/IEGM Online. Patients were scheduled for office device interrogations only at the 3 month and 15 month follow-up points (following the HM online check). At 6, 9 and 12 months, a HM check was performed first. Investigators may then elect to perform an office device interrogation if they determine that it is necessary after reviewing the HM data.
Group 2 (Control)
Patients were evaluated using conventional, calendar-based office visits at 3, 6, 9, 12 and 15 months post-implant. Interim visits were made according to physician discretion (e.g. following any ICD discharges or symptoms). Home Monitoring was programmed OFF for the duration of the study.
HM Event Triggered Device Evaluations
Investigators with patients in Group 1 (HM) may receive HM notifications in response to pre-programmed events such as VT1 detected and SVT detected. Upon the receipt of a HM Event Notification, investigators reviewed the notification and the associated information on the HM/IEGM-Online website and recorded the type of event and what type of action, if any, was taken as a result of this notification.
Patient-Initiated Device Evaluations
Investigators may be contacted by the patient for device/arrhythmia-related care (e.g. perceived device discharge, symptoms). For patients in Group 1 (HM), investigators triaged the complaint using the Home Monitoring website. Investigators recorded if the information from Home Monitoring was sufficient. For patients in Group 2 (Control), the complaint was assessed per standard of care or normal clinic procedures.
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Primary Endpoints
The purpose of primary endpoint 1 (HM efficacy) was to compare the number of in-office ICD follow-ups for patients in Group 1 (HM) to the conventional, calendar-based method of ICD follow­up as in Group 2 (Control).
The purpose of the primary endpoint 2 (safety) was to compare the Safety Event Rate (SER), which includes death, incidence of strokes and events requiring surgical interventions (e.g. device explants or lead revision) between the two groups.
Secondary Endpoints
The purpose of secondary endpoint 1 was to compare AF, VT and VF events between Group 1 and Group 2 in terms of the number, categories, and detection time relative to onset.
Inclusion Criteria
To support the objectives of this investigation, the inclusion criteria at the time of patient enrollment for this investigational study included the following requirements:
Implanted within the last 45 days or being considered for
implant with a BIOTRONIK ICD with Home Monitoring/IEGM-Online technology
Able to utilize the HM system throughout the study Ability to give informed consent Geographically stable and able to return for regular
follow-ups for fifteen (15) months
At least 18 years old
Exclusion Criteria
To support the objectives of this investigation, the exclusion criteria at the time of patient enrollment included the following requirements:
Patients who do not fulfill all inclusion criteria Patients who are pacemaker dependent Currently enrolled in any other cardiac clinical
investigation.
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Clinical Events Committee
The Clinical Events Committee (CEC) is an advisory review board comprised of three physicians that are not participating in the TRUST Study who reviewed and adjudicated all deaths, strokes, surgical interventions, and cardiac adverse events that occur during the study. The CEC also reviewed all divergent classifications of actionable vs. non-actionable office follow up visits between the physician and BIOTRONIK, and reviewed a random sampling of 1% of office follow up visits in which there is no disputed classification.
1.6.4.3 Summary of Clinical Results
The study involved
1443 patients (1038 males, 71.9%), with a
mean age of 63.5 years (range: 20-95). The cumulative
enrollment duration is 18,367 months with mean enrollment duration of 12.7 months. The patient follow-up compliance rate for
all enrolled patients is 87.5% in Group 1 and 78.8% in Group 2.
1.6.4.3.1 Primary Endpoint 1: Home Monitoring
Effectiv
eness
The purpose of primary endpoint 1 (HM efficacy) was to compare the number of in-office ICD follow-ups for patients in Group 1 (HM) to the conventional, calendar-based method of ICD follow-up as in Group 2 (Control).
Detailed primary endpoint 1 results are presented in Table 21
Table 21: Primary Endpoint Group 1 vs. Group 2
Group 1
(HM)
Group 2
(Control)
No. of
Pts**
898
414
Scheduled Unscheduled Total
n = 991
1.3 ± 1.0 per pt yr
13.1% actionable
n = 1110
3.0 ± 1.1 per pt yr
10.7% actionable
Office Follow-up Visits
n = 401
0.6 ± 1.7 per pt yr
29.7% actionable
n = 117
0.4 ± 1.4 per pt yr
29.1% actionable
p value < 0.001 0.032
* Up to and including 12 month follow-up data ** Number of patients that have contributed at least 1 follow-up
.
1.9 ± 1.9 per pt yr
3.4 ± 1.7 per pt yr
< 0.001
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Analysis
The comparison of the number of 3, 6, 9, and 12 month and unscheduled office follow-up visits in Group 1 versus Group 2 showed that there was an average number of 1.9 office follow-up visits on a per year basis in Group 1 (HM) and an average number of 3.4 office follow-up visits on a per year basis in Group 2 (Control). Therefore, the null hypothesis (HØ) can be rejected, indicating that the average number of office visits per year is statistical significantly less in the HM group than in the Control group (p < 0.001). The primary effectiveness endpoint was met.
1.6.4.3.2 Primary Endpoint 2: Safety Event Rate
The purpose of the primary endpoint 2 was to
compare the Safety Event Rate (SER), which includes death, incidence of strokes and events requiring surgical interventions (e.g. device explants or lead revision) between the two groups.
Table 22
patients for 12 months post-enrollment. Figure 5
summarizes the Safety Event Rate for the study
shows these
data in a Kaplan-Meier analysis.
Table 22: Safety Event Rate Comparison
Safety Event Rate* Group 1 Group 2 p value**
Type of Event
Death Stroke Surgical
36/608 (5.9%)
2/574 (0.3%)
57/605 (9.4%)
18/245 (7.3%)
22/239 (9.2%)
3/227(1.3%)
0.440
0.141
1.000
intervention
Any Event
95/643 (14.8%) 42/256 (16.4%) 0.539
* Only includes events occurring within 12 months of enrollment ** 2-sided Fisher Exact test
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Figure 5: Safety Event Rate Kaplan Meier
Analysis
The safety event rate for a 12-month duration was 14.8% for Group 1 (HM) and 16.4% for Group 2 (Control), with a non­inferiority p-value of 0.005. Therefore, the safety event rate for HM Group was non-inferior to the safety event rate for the Control Group within 5%. The upper, one-sided 95% confidence bound for the difference was 2.7%.
A rejection of the null hypothesis indicates that the safety event rate for Group 1 (HM) is equivalent (non-inferior) to that of Group 2 (Control).
1.6.4.3.3 Secondary Endpoint 1: Early Detection of Cardiac
ents (AF, VT & VF)
Ev
The purpose of secondary endpoint 1 was to compare AF, VT and VF events between Group 1 and Group 2 in terms of the number, categories, and detection time relative to onset.
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Table 23 compares the time from onset to evaluation of the first
AF, VT and VF events for each patient that have occurred in each group, as well as the first of any type of event for each patient in each group. Figure 6
illustrates the time from onset to evaluation
of arrhythmic events in a box plot graph.
Table 23: Time from First Event Onset to Evaluation
Time from Event Onset
to Evaluation of First
Event/Patient
Group 1
N=972
Group 2
N=471
p value
AF
Median Mean ± SD (days) Min Max # of patients with events
5.0
25.2 +/- 34.2 0
171
73 (7.5%)
39.5
46.8 +/- 33.7 1
114
28 (5.9%)
p < 0.001 p = 0.005
VT1 & VT2
Median Mean ± SD (days) Min Max # of patients with events
2.0
12.9 +/- 33.8 0
256
149 (15.3%)
32.0
46.6 +/- 46.9 0
245
53 (11.2%)
p < 0.001 p < 0.001
VF
Median Mean ± SD (days) Min Max # of patients with events
1.0
10.5 +/- 22.2 0
145
236 (24.3%)
35.5
45.0 +/- 47.0 0
287
92 (19.5%)
p < 0.001 p < 0.001
SVT
Median Mean ± SD (days) Min Max # of patients with events
2.0
16.6 ± 27.4 0
108
94 (9.7%)
39.0
42.1 ± 35.6 0
157
35 (7.4%)
p < 0.001 p < 0.001
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Figure 6: Median Time from Onset to Evaluation of
Arrhythmic Events
Analysis
The mean time from onset to evaluation of first AF, VT, and VF events in Group 2 is greater than the mean time from onset to evaluation of first AF, VT, or VF events in Group 1. A rejection of the null hypothesis for AF, VT and VF event types indicates that the mean time from onset to evaluation of the first AF, VT and VF events in Group 1 is significantly less than the mean time from onset to evaluation of the first AF, VT and VF events in Group 2. P-values are =0.005, <0.001 and <0.001 respectively.
1.6.4.4 Conclusions
Use of HM in Group 1 resulted in an average of 1.9 office
visits per patient year in the 12 months post-implant, versus an average of 3.4 office visits per patient year in Group 2, a 44% reduction in office visits. The average number of office visits is significantly less in the HM group than in the Control group (p < 0.001).
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The safety event rate for a 12 month duration for Group 1
(HM) was non-inferior to the safety event rate for Group 2 (Control) within 5% (p = 0.005). The upper, one-sided 95% confidence bound for the difference was 2.7%.
The mean time from onset to evaluation of AF, VT and VF
events indicates that those events for Group 1 patients are evaluated in significantly less time when compared to Group 2 patients (AF p = 0.005, VT p < 0.001, VF p < 0.001).

1.6.5 Deikos A+

NOTE:
The clinical study information included in this section was performed with the Deikos A+ ICD and the Kainox VDD ICD lead. Due to the similarities in detection and therapy a clinical study of the Lumax 540 VR-T DX with the Kainox A+ was not performed. The Deikos A+ was formed on the Tachos DR platform, whereas the Lumax 540 VR-T DX was formed on the Lumax DR-T platform. Both ICDs are designed to be used with a VDD lead. In this study, the Kainox VDD lead (single shock RV shock coil and dual atrial floating dipoles) was implanted. In order to enhance the intrinsic signal from the floating dipoles, both ICDs contain an atrial sensing amplifier. The signal is amplified 4 times in the Deikos A+ and 5 times in the Lumax 540 VR-T DX. Both the Kainox VDD and the Kainox A+ ICD leads have identical floating electrodes in the atrium and identical pacing electrode tip, ring and shock electrodes designed for placement in the right ventricle. The minor differences are in the ventricular shock coil (Kainox A+ coil has a slightly larger surface area, and the surface is not coated with fractal iridium).
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1.6.5.1 U.S. Clinical Study
1.6.5.1.1 Patients Studied
The Single-Lead ICD system clinical study involved 9 patients (7
and 2 female) with a mean age of 58.8 years (range: 25 to
males 83 years). 66.7% presented with ventricular fibrillation/polymorphic ventricular tachycardia as their primary tachycardia. The Single-Lead ICD system was selected for the diagnostic value of the atrial EGMs in 88.9% of the patients.
1.6.5.1.2 Methods
feasibility clinical investigation was designed to evaluate the
The quality of atrial signals obtained using the Single-Lead ICD. The study was also designed to evaluate the safety and effectiveness of the Single-Lead ICD system to detect and treat monomorphic ventricular tachycardia (MVT), polymorphic ventricular tachycardia (PVT), ventricular fibrillation (VF), and bradycardia. The specific predefined objectives of the investigation included UADE-free survival rate, appropriate bradycardia sensing and pacing, detection and treatment of ventricular tachyarrhythmias and appropriate atrial sensing during activities of daily living.
1.6.5.1.3 Results
The mean implant
duration was 6.1 ± 9.4 months with a cumulative implant duration of 54.5 months. There were 5 patients followed for over six months and 2 patients followed for over three months. The patient follow-up compliance rate was 100%, 43 out of 43 required follow-ups.
Table 24
provides a summary of the results of the study group.
Table 24: Clinical Study Results
Description Results
UADE-free Survival Rate 100% (9/9)
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Description Results
Complication Rate 11.1% (1/9)
Appropriate Atrial Sensing Rate1 97.6% (41/42)
Appropriate Atrial Sensing during 24-hour Holter Test
Appropriate Atrial Sensing during Exercise Treadmill Test
Detection and Conversion of Ventricular Tachyarrhythmias
2
100% (9/9)
100% (6/6)
100% (68/68)
1.6.5.2 European Clinical Study
1.6.5.2.1 Patients Studied
The European Deikos A+/Kainox VDD lead clinical study involved 82 patients (66 males and 16 female) with a mean age of 61.8 years (range: 29 to 84 years).
42.7% presented with monomorphic ventricular tachycardia as their primary tachycardia.
1
The investigator determined the appropriateness of atrial sensing. The rate is determined by the number of appropriate atrial sensing evaluations divided by the total number of evaluations.
2
Conversion data were collected in the clinical study for both induced and spontaneous ventricular tachyarrhythmia episodes. Therefore, both types of tachyarrhythmia episodes were included in the analysis.
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1.6.5.2.2 Study Objectives
This clinical investigation was designed to collect information on the performance and function of the Deikos A+/Kainox VDD ICD system. The specific predefined objectives of the investigation included the rate of inappropriate, i.e. unnecessary deliveries of antitachycardia therapy due to supraventricular tachycardia (SVT), the tachyarrhythmia conversion efficacy of the system with activated SMART Detection™ algorithm, the rate of appropriate atrial sensing and the morbidity rate.
1.6.5.2.3 Results
The mean implant
duration was 8.9 ± 4.4 months with a cumulative implant duration of 732 months. No unanticipated adverse events were reported during the study. There were two deaths reported, which were unrelated to the implanted device. A summary of the results obtained during the evaluation is provided in Table 25
.
Table 25: OUS Clinical Study Results
Description Results
UADE-free Survival Rate 100% (82/82)
Complication Rate 19.5% (16/82)
Inappropriate Therapies with SMART Detection™ algorithm ON Rate
Inappropriate Therapies with SMART Detection™ algorithm OFF Rate
94.8% (234/250)
84.7% (133/157)
Appropriate Atrial Sensing Rate1 92.7% (165/211)
Detection and Conversion of Ventricular Tachyarrhythmias
2
100% (211/211)
1
The investigator determined the appropriateness of atrial sensing. The rate is determined by the number of appropriate atrial sensing evaluations divided by the total number of evaluations.
2
Conversion data were collected in the clinical study for both induced and spontaneous ventricular tachyarrhythmia episodes. Therefore, both types of tachyarrhythmia episodes were included in the analysis.
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1.7 Patient Selection and Treatment

1.7.1 Individualization of Treatment

Determine whether the expected device benefits
outweigh the possibility of early device replacement for patients whose ventricular tachyarrhythmias require frequent shocks.
Determine if the device and programmable options are
appropriate for patients with drug-resistant supraventricular tachyarrhythmias (SVTs), because drug­resistant SVTs can initiate unwanted device therapy.
Direct any questions regarding individualization of patient
therapy to your BIOTRONIK representative or BIOTRONIK technical services at 1-800-547-0394.
The prospective patient’s size and activity level should be evaluated to determine whether a pectoral or abdominal implant is suitable. It is strongly recommended that candidates for an ICD/CRT-D have a complete cardiac evaluation including EP testing prior to device implant to gather electrophysiologic information, including the rates and classifications of all the patient’s cardiac rhythms. When gathering this information, delineate all clinically significant ventricular and atrial arrhythmias, whether they occur spontaneously or during EP testing.
If the patient’s condition permits, use exercise stress testing to do the following:
Determine the maximum rate of the patient’s normal
rhythm.
Identify any supraventricular tachyarrhythmias. Identify exercise-induced tachyarrhythmias.
The maximum exercise rate or the presence of supraventricular tachyarrhythmias may influence selection of programmable parameters. Holter monitoring or other extended ECG monitoring also may be helpful.
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If the patient is being treated with antiarrhythmic or cardiac drugs, the patient should be on a maintenance drug dose rather than a loading dose at the time of pulse generator implantation. If changes to drug therapy are made, repeated arrhythmia inductions are recommended to verify pulse generator detection and conversion. The pulse generator also may need to be reprogrammed.
Changes in a patient’s antiarrhythmic drug or any other medication that affect the patient’s normal cardiac rate or conduction can affect the rate of tachyarrhythmias and/or efficacy of therapy.
If another cardiac surgical procedure is performed prior to implanting the pulse generator, it may be preferable to implant the lead system at that time. This may prevent the need for an additional thoracic operation.

1.7.2 Specific Patient Populations

Pregnancy - If there is a need to image the device, care should
be taken to minimize radiation exposure to the fetus and the mother.
Nursing Mothers - Although appropriate biocompatibility testing has been conducted for this implant device, there has been no quantitative assessment of the presence of leachables in breast milk.
Geriatric Patients - Most (about 71%) of the patients receiving a CRT-D or ICD in the clinical studies detailed in this manual were over the age of 60 years (see Clinical Studies).
Handicapped and Disabled Patients - Special care is needed in using this device for patients using an electrical wheel chair or other electrical (external or implanted) devices.

1.8 Patient Counseling Information

The implanted devices are subject to random component failure. Such failure could cause inappropriate shocks, induction of arrhythmias or inability to sense arrhythmias, and could lead to the patient’s death.
Persons administering CPR may experience the presence of voltage on the patient’s body surface (tingling) when the patient’s CRT-D/ICD system delivers a shock.
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A patient manual is available for the patient, patient’s relatives, and other interested people. Discuss the information in the manual with concerned individuals both before and after pulse generator implantation so they are fully familiar with operation of the device. (For additional copies of the patient manual, contact BIOTRONIK at the address listed in this manual.)
1.9 Evaluating Prospective CRT-D/ICD
Patients
The prospective ICD/CRT-D implant candidate should undergo a cardiac evaluation to classify any and all tachyarrhythmias. In addition, other patient specific cardiac information will help in selecting the optimal device settings. This evaluation may include, but is not limited to:
an evaluation of the specific tachycardia rate(s) the confirmation and/or evaluation of any supraventricular
arrhythmias or bradyarrhythmias
the evaluation of various ATP and cardioversion
therapies
the presence of any post-shock arrhythmias, and an evaluation of the maximum sinus rate during exercise.
If a patient’s drug regimen is changed or adjusted while the CRT-D/ICD is implanted, additional EP testing may be required to determine if detection or therapy parameter settings are relevant and appropriate.
Empirical changes to the detection or therapy parameters should be assessed based on patient safety. Some changes may necessitate a re-assessment of sensing, pacing, or arrhythmia conversion treatment. Thorough technical knowledge of BIOTRONIK CRT-D/ICDs, additional CRT-D/ICD experience, and individual medical judgment will aid in determining the need for additional testing and follow-up.
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2. Device Features

The Lumax family feature set is presented under the following sub-headings: Tachyarrhythmia Detection, Tachyarrhythmia Redetection/Acceleration, Tachyarrhythmia Therapy, Tachyarrhythmia Termination, Bradycardia Therapy, EP Test Functions and Special Features. The features apply to all members of the Lumax family except where specifically referenced differently.
CAUTION
Programmed Parameters – Program the device
parameters to appropriate values based on the patient’s specific arrhythmias and condition.

2.1 SafeSync Telemetry

The Lumax 700/740 and 600/640 models offer ”wandless” communication between the device and the programmer by using radio frequency (RF) telemetry, in addition to the currently available telemetry used by applying the programming head (PGH) over the implanted device. This function is called SafeSync Telemetry.
SafeSync Telemetry can be used with the Renamic programmer or with the ICS 3000 programmer (using the SafeSync Module, an external communication module).
To Establish SafeSync Telemetry contact:
The programmer (or the SafeSync module) must be no more than 9 feet (3 m) from the device; ideally there should be no obstacles between the patient and the programmer.
Switch on RF telemetry on the programmer. Select:
Preferences→ConnectivityRF telemetry InterrogationON. Or, select: MoreLumax TelemetryRF, during the follow-up.
Apply the programming head for about 2 seconds until
successful initialization is displayed on the programmer:
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The SafeSync symbol is displayed in the navigator and the signal strength is displayed in green bars on the information line. The SafeSync telemetry status is shown in five increments: 1 bar = 20% up to 5 bars = 100%. A weak contact shows only one bar in green, whereas all five bars are shown in green when there is optimal contact. The bars are shown in gray if RF telemetry is lost. The display should have at least three green bars. Otherwise, it is recommended to reposition the programmer until an adequate signal strength is achieved.
Remove the programming head.
To restore the SafeSync Telemetry after an interruption
during follow-up or after a programmer restart: select SpecialContinue RF session on the start screen to restore the most recent active session. This SafeSync Telemetry session must not have been inactive for longer than five minutes, since the device's SafeSync Telemetry activity is automatically switched off after five minutes of inactivity.
Note: If the SafeSync Telemetry session has been inactive for more than 5 minutes, the programming head must be reapplied to reinitialize the SafeSync Telemetry.
To End SafeSync Telemetry contact:
To end the SafeSync Telemetry session:
End Follow-up session
To switch to telemetry via the programming head (PGH):
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Apply the programming head on the patient over the
device.
Select: MoreLumax TelemetryPGH.
Power Consumption Consideration:
SafeSync telemetry requires somewhat more power than telemetry via the programming head. Power consumption during implantation corresponds to approximately 10 days of service time and consumption during 20-minute follow-up corresponds to approximately 3 days. As a result:
Do not establish SafeSync Telemetry sessions
unnecessarily.
After 5 minutes without input, SafeSync Telemetry
switches to the economy mode. In order to re-establish telemetry from the economy mode, select “Close” in the pop-up window with the patient’s name:
Check the battery capacity of the device at regular
intervals.
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2.2 Cardiac Resynchronization Therapy
(CRT)
HF versions only
For Cardiac Resynchronization Therapy (CRT), a sensing/pacing lead is placed in the right atrium, while an ICD lead is placed in the right ventricle. The third lead is positioned to pace the left ventricle. When connected together, this system provides coordinated, simultaneous stimulation of the right and left ventricles. This resynchronization therapy is designed to coordinate the contraction of both ventricles, which allows the heart to contract more efficiently. As a result, patients with CHF and intraventricular conduction delay may have a greater ability to complete physical activities thus improving their quality of life.
As a result of the device design and header configuration, ventricular pacing pulses can be delivered between the right/left ventricular lead tip electrodes simultaneously (cathode) and at programmed intervals. In some configurations the ring of the right ventricular lead works as LV anode. Ventricular sensing primarily uses the poles of the right ventricular lead tip and ring. This design avoids sensing of ventricular activity twice during a single cardiac cycle (double counting) in patients with a wide QRS complex. However, for diagnostic purposes and LV pacing protection the Lumax HF devices can be programmed to sense in the left ventricle.
Atrial Channel
The Lumax ICDs/CRT-Ds pace and sense in bipolar configuration, between the atrial lead’s tip and ring electrodes. A bipolar atrial lead must be used to ensure reliable sensing of atrial activity.
Ventricular Channel
The Lumax HF devices can be programmed to pace in both the right and left ventricle (as well as RV only). The Lumax HF primarily senses in a bipolar configuration in the right ventricle. However, for diagnostic purposes and LV pacing protection the Lumax HF devices can be programmed to sense in the left ventricle.
Potential Ventricular lead configurations are provided in Table 26
.
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Table 26. Lead Configurations
Configuration Explanation
Sensing
RV Only
Sensing takes place between the tip and ring electrodes of the right ventricular lead.
Pacing
Pacing
LV Only
RV & LV Together (BiV)
RV Only
Sensing takes place between the tip and ring electrodes (bipolar) or the tip electrode of the left ventricular lead and the CRT-D housing (unipolar).
Pacing configuration is programmable between the tip and ring electrodes of the right and left ventricular leads. See Figure 7
Pacing takes place between the tip and ring electrodes of the right ventricular lead.
See Figure 7
Figure 7 Programmable Pacing Configurations
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For CRT to be effective, ventricular pacing must occur. Therefore, AV delays must be programmed short enough to override intrinsic ventricular contractions. Additional information to further optimize AV delays can be obtained with echocardiography.
CRT can be programmed ON or OFF via the programmer using the [Ventricular Pacing] parameter. Ventricular Pacing Configuration allows standard right ventricular [RV] (CRT = OFF) pacing or Cardiac Resynchronization Therapy [BiV] (CRT = ON).
The Lumax HF CRT-D can provide triggered biventricular pacing. This is a functional expansion of the basic ventricular modes (DDD(R); DDI(R); VDI(R); VDD(R); VVI(R)) used for biventricular pacing. The “RVs triggering” was designed to ensure CRT is delivered even when rapid intrinsic activation interferes with pacing, such as in the case of conducted atrial fibrillation. This function triggers LV pacing (Vp) after intrinsic sensing (RVs) in the right ventricle. Triggered pacing can be programmed to react to only normal RV sensed events or to right ventricular extrasystoles as well as normal RV sensed events. The maximum trigger rate is normally limited by the programmed UTR (+20bpm), but can also be programmed to function up to a separate and higher maximum trigger rate.
V-V Delay Programming
V-V delays should be programmed based on optimization of the echocardiographic parameter Aortic Valve Velocity Time Integral, evaluating the full range of available delays, as was performed in the clinical study demonstrating the safety and effectiveness of this feature. RV pre-excitation may cause a decline of LV function.
The V-V delay features for the Lumax HF-T devices include the ability to program the following parameters “first chamber paced,” which allows either the right or the left ventricle to be paced first, and “VV delay” for setting a delay between the left and right ventricular pacing pulses (programmable range: 0 ms … (5ms) … 100 ms).
Suggested optimization procedure:
During the V-V clinical study assessment was performed by determining the V-V delay setting associated with the largest VTI value. The VTI of the aortic flow is measured in the apical 5 chamber view.
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Prior to the V-V delay optimization procedure, each patient underwent an optimization of AV timing. Following the AV timing adjustment, this standardized procedure was followed for the optimization of V-V delay:
1. Program the Lumax HF-T “Initially Paced Chamber”
parameter to either RV or LV based on preference
2. Assess the VTI measurement at the following V-V delays
(additional V-V settings may be utilized at the physician’s discretion):
•100 ms • 80 ms • 60 ms • 40 ms • 20 ms • 0 ms
Note: Use the average VTI parameter over a 3 beat cycle and wait 10 to 15 seconds between changing V-V delay settings. Also, attempt to measure the VTI parameter within the same patient respiratory cycle.
3. Record the VTI measurement associated with each V-V
delay setting
Repeat steps 1-3 for the remaining “Initially Paced Chamber” parameters
Select permanent “Initially Paced Chamber” and “V-V delay after Vp” to reflect the maximum VTI measurement for final programming.

2.3 Sensing (Automatic Sensitivity Control)

The Lumax ICDs/CRT-Ds use Automatic Sensitivity Control (ASC) to adjust the input stage sensitivity threshold for each channel to appropriately detect the various cardiac signals. The characteristics of the sensing circuitry have been optimized to ensure appropriate sensing during all potential cardiac rhythms.
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Cardiac signals vary in amplitude; therefore detection thresholds cannot be static. With the Automatic Sensitivity Control (ASC) every paced/sensed event is measured, and the upper and lower thresholds are re-set accordingly (also known as beat-by-beat adaptation). The ASC begins by tracking the cardiac signals (R and P-waves) during the sensed refractory periods. The peak values measured during this time are used to set the sensing thresholds during the active detection periods.

2.3.1 Right Ventricular Sensitivity Settings

There are three programmable preset options for setting the sensitivity of the right ventricular input stage. The sensitivity selections are designed to adapt the parameters of the input stage to various signal conditions. The predefined parameter sets are described in Table 27
Table 27: Sensitivity Settings
Setting Definition for Use
Standard This setting is recommended for most
Enhanced T Wave Suppression
Enhanced VF Sensitivity
Typically, the upper threshold is reset with each sensed R-wave, but in order to ensure that pacing does not occur during an episode of VF, the ASC behaves differently with paced events. Each paced event is followed by a paced refractory period after which the ventricular threshold is set to the minimum programmed value.
.
patients, especially for those with measured R-wave amplitude of 3 mV.
This setting offers suppression of T-wave oversensing. This mode should not be used on patients with the following conditions:
Sinus rhythms with small signal
amplitudes, R-waves 4 mV
VF with highly fluctuating signal
amplitudes.
This setting enhances VF detection, in cases of highly fluctuating signal amplitudes. It is not to be used for patients that have sinus rhythms containing large amplitude T-waves.
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For example, the upper threshold is set at 50% of the measured R-wave for the Standard sensitivity setting following the 100 ms sensed refractory period. The upper threshold decays 0.125 mV every 250 ms through the T-wave discrimination period (hold of upper threshold: 360 ms). After the T-wave discrimination period, the threshold is decreased to the lower threshold. The lower threshold is set to 25% of the measured peak R-wave. The lower threshold then decreases 0.125 mV every 500 ms until the Minimum Threshold is reached or until the next sensed (or paced) event.
For Lumax 600/640 and 700/740 devices, the decrease is controlled on a percentage basis. Every 156 ms 87.5% of the threshold reference. Initially this is the maximum amplitude. Hold of upper threshold: 400 ms.
Figure 8 Automatic Sensitivity Control with Standard Setting
Figure 8
provides an illustration of Automatic Sensitivity Control with the sensitivity programmed to Standard. The tracked R – wave is measured to be 6.0 mV, following the sensed refractory period the upper threshold is set to 3.0 mV. After the T-wave discrimination period, the threshold is further reduced to 1.5 mV. Both the Upper and Lower Thresholds decay over time, but the Minimum Threshold is never violated. Nominally, the minimum threshold is set to 0.8 mV, but it can be adjusted by the user.
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The Enhanced VF Sensitivity setting is specifically designed to improve VF detection when the VF signal is very small. Two adjustments are made to ASC with this setting:
The T-wave discrimination period (hold of upper
threshold) is decreased to 100 ms [110 ms for Lumax 600/640 and 700/740 models], thus eliminating the Upper Threshold.
The decay rate of the Lower Threshold is increased to
0.125 mV every 250 ms. This is not applicable for the Lumax 600/640 and 700/740 models.
These adjustments ensure that the threshold reaches the lower values more quickly in order to assure that all VF signals are sensed appropriately.
The Enhanced T-Wave Suppression setting is specifically designed to avoid double counting of each QRS-T complexes during normal sinus rhythms. With sensitivity programmed to Enhanced T-Wave Suppression:
High pass filtering is increased to reduce low frequency
signal components such as T-waves and respiratory artifacts.
The Upper Threshold is increased to 75% of the
measured R-wave.
The Upper Threshold may not retrigger with each sensed
event, it is only triggered when the new sensed R-wave crosses the 50% point of the previous measured R-wave.

2.3.2 Minimum Right Ventricular Threshold

This parameter limits the minimum sensitivity of the ICD/CRT-D to a programmable value. Nominally, the minimum threshold is set to 0.8 mV, but it can be adjusted from 0.5 to 2.5 mV.

2.3.3 Atrial Sensitivity Settings

DR and HF versions only
The primary option for setting the sensitivity of the atrial input stage is “Standard”. When atrial sensing is active, the sensitivity is set to “Standard” for most patients, which is designed to adapt the parameters of the input stage to various signal conditions. The available settings are described in Table 28
.
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Table 28: Atrial Sensitivity Settings
Setting Definition for Use
Standard This setting is recommended for all
patients with a functioning atrial lead.
Inactive This setting deactivates the atrial channel
for sensing, EGM telemetry and Holter recording and is typically used when no atrial lead is implanted.
Typically, the upper threshold is reset with each sensed P-wave, but in order to ensure that pacing does not occur during an episode of AF/VF, the ASC behaves differently with paced events. Each paced event is followed by a paced refractory period after which the atrial threshold is set to the minimum programmed value.

2.3.4 Minimum Atrial Threshold

This parameter limits the minimum sensitivity of the ICD/CRT-D to a programmable value. Nominally, the minimum threshold is set to 0.4 mV, but it can be adjusted from 0.2 to 2.0 mV.

2.3.5 Left Ventricular Sensitivity Settings

HF versions only
The primary option for setting the sensitivity of the left ventricular input stage is “Standard”. When LV sensing is active, the sensitivity is set to “Standard” for most patients, which is designed to adapt the parameters of the input stage to various signal conditions. The available settings are described in Table 29
.
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Table 29: Left Ventricular Sensitivity Settings
Setting Definition for Use
Standard This setting is recommended for all
patients with a functioning left ventricular lead.
Inactive This setting deactivates the left ventricular
channel for sensing, EGM telemetry and Holter recording and is typically used when no LV lead is implanted.

2.3.6 Minimum Left Ventricular Threshold

This parameter limits the minimum sensitivity of the CRT-D to a programmable value. Nominally, the minimum threshold is set to
0.8 mV, but it can be adjusted from 0.5 to 5.0 mV.

2.3.7 Far Field Protection

DR and HF versions only
This parameter blanks the atrial channel of the ICD/CRT-D to the period before and after each ventricular event. This blanking period is programmable separately based on whether the ventricular event is a paced or sensed event and is designed to prevent sensing of ventricular signals with the atrial leads.
CAUTION
Far-field sensing of signals from the atrium in the
ventricular channel or ventricular signals in the atrial channel should be avoided by appropriate lead placement, programming of pacing/sensing parameters, and maximum sensitivity settings. If it is necessary to modify the Far Field Blanking parameter, the parameter should be lengthened only long enough to eliminate far-field sensing as evidenced on the IEGMs. Extending the parameter unnecessarily may cause undersensing of actual atrial or ventricular events.

2.3.8 Additional Sensing Parameters

The parameters of the Additional Sensing Parameters menu are to provide additional flexibility for physicians to non-invasively correct over/undersensing situations. The ranges and nominal values are located in the Technical Specifications in Section
6.
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Upper Threshold (A, RV & LV) - This feature allows the user to change the upper sensing threshold level (UT in Figure 8
) from the nominal value of 50% of the sensed R-wave/P-wave amplitude to either 75% or 87.5% of the R-wave/P-wave value. This feature is used in the ventricle for example to eliminate oversensing of large T-waves. This is not applicable to the Lumax 600/640 and 700/740 models.
Hold of Upper Threshold (RV & LV) - This parameter determines when the sensing decrement begins after an event (small step-down on the 50% threshold before LT in the figure above). This parameter “holds” the threshold at a constant value (UT in Figure 8
) for the programmed time. Maximum Hold Time is programmable from 100 to 600 ms in Lumax 300/340 & 500/540 and 110 to 500 ms in the Lumax 600/640 & 700/740 models (T­Wave discrimination period). Additionally, the Lumax 600/640 & 700/740 models are separately programmable between the paced and sensed signals.
Lower Threshold (A, RV & LV)- This feature allows the user to change the lower sensing threshold (labeled LT in Figure 8
) from the default value of 25% of the sensed R-wave/P-wave amplitude to either 12.5 or 50% of the measured R-wave/P-wave value. This is not applicable to the Lumax 600/640 and 700/740 models. This feature is also used in the ventricles to alleviate T-wave oversensing and/or undersensing of small amplitude events (e.g., fine VF).
Blank after atrial pacing (RV) - This feature is used to eliminate sensing of artifacts after atrial paced events. Blank Post atrial Pace in the RV is programmable from 50 to 100 ms. For the left ventricle, this parameter is equal to the safety window time (100 ms).
VES Discrimination after As - This feature is used to correctly identify and classify ventricular extrasystoles (VES). With each atrial sensed event (also with Ars falling into PVARP) a special timing interval is started for the ventricle, if the subsequent ventricular event does not fall within the AV delay or the programmed VES discrimination interval, it is classified as a VES.
LV T-wave Protection - Used to eliminate unintended pacing in the vulnerable period of the left ventricle. This feature is only used when left ventricular sensing is active. HF versions only.
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2.4 Automatic Threshold Measurement
(ATM)
Lumax 500/540 Models only
The Lumax 500/540 models have an automatic threshold measurement (ATM) feature for determining ventricular pacing thresholds. This feature is separately programmable for the right (RV) and left (LV) ventricles.
ATM is initiated once each day, typically during the nighttime while the patient is normally sleeping. It can measure the right and the left ventricular pacing thresholds and stores this information for use in trends of daily threshold values. This information is available on the programmer during in-office follow­ups and via BIOTRONIK’s Home Monitoring system. The permanent pacing amplitude is not adjusted by the ATM feature.
The ATM features of Lumax 500/540 are based on the evaluation of the morphology of the ventricular evoked response (VER) to determine if the pacing pulse has captured the myocardium. In order to measure the pacing threshold, a sequence of two algorithmic steps is carried out:
Signal Quality Check (SQC)
Threshold Measurement
The signal quality check determines if the morphology of the evoked response of a captured beat is sufficiently different from the morphology of the evoked response of a non-captured pace. If the SQC is sufficient (i.e., if the algorithm can clearly distinguish between capture and non-capture), then the automatic threshold measurement is activated by initiating a series of pacing pulses. The amplitude of these pulses is continuously decreased until a loss of capture is detected. When loss of capture is detected a back-up pulse is delivered (right ventricle only) to avoid ventricular pauses caused by the threshold measurement.
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2.4.1 Signal Quality Check

During the Signal Quality Check, five single effective pacing pulses are delivered. These pulses are followed by five double pulses. The second pulse of each double pulse is delivered into the refractory phase of the ventricle (as a non-capturing pulse). The VER morphology of the single pulses and the second pulse of the double pulses are assessed. The signal quality check is successful if the single pulses are recognized as capturing pulses and the second pulses of the double pulses are classified as non­capturing pulses. The AV delay of the 2 x 5 pulses is shortened to 50 ms after pace and by 15 ms after sense, in order to avoid ventricular fusion beats which would otherwise disturb the SQC. If the SQC is successful, then the threshold measurement is started, if not, the SQC is repeated once again after 30 minutes.

2.4.2 Threshold Measurement

The threshold measurement begins by delivering pulses at the programmed pacing amplitude. The pulse amplitude is decreased in steps of 0.6 Volts (V) each until loss of capture is detected. During the loss of RV-capture sequence, a backup pulse is issued. The back-up is set to a value of the programmed pacing amplitude plus 0.6 V with a pulse width of 1.0 ms. There are no backup paces for left ventricular ATM (LV-ATM).
The pulse amplitude is then set to the last effective value (0.6 Volts above the initial non-capture level) and then subsequent pacing pulses are reduced in 0.1 V steps until loss of capture reoccurs. The last effective pacing amplitude is then recorded as the pacing threshold.

2.4.3 Loss of Capture Detection

In order to ensure against ATM loss of capture detection due to an isolated non-capture event (i.e. as a result of VES), loss of capture is only declared if two out of three consecutive cycles show loss of capture.

2.4.4 ATM in Lumax HF-T Models

If the device is programmed to biventricular pacing (BiV), the RV ATM functions in the RV mode as described above. The LV ATM, if active, is initiated after the RV ATM is complete. For the LV ATM, the left ventricle is stimulated first with a VV delay of 50 ms and then completed in a similar manner.
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Lumax 600/640 & 700/740 Models only

2.4.5 RV & LV Capture Control

RV & LV Capture Control uses the determined pacing threshold to adjust the permanent pulse amplitude. The new permanent pulse amplitude is composed of the determined pacing threshold plus a safety margin (1.0 or 1.2 V) and is automatically programmed in the ICD.

2.5 Ventricular Tachyarrhythmia Detection

The Lumax ICDs/CRT-Ds detect and measure the rate of sensed cardiac signals to discriminate ventricular tachyarrhythmias from supraventricular tachycardias, sinus rhythm or sinus bradycardia. This is accomplished through programmable rate detection parameters in the device. When a tachyarrhythmia is present, the ICD/CRT-D classifies the arrhythmia and delivers the appropriate therapy. If a tachyarrhythmia continues following the first therapy attempt, then the ICD/CRT-D will redetect the tachyarrhythmia and deliver subsequent therapies as necessary.
WARNING
Unwanted Shocks – Always program ICD therapy to OFF
prior to handling the device to prevent the delivery of serious shocks to the patient or the person handling the device during the implant procedure.
Classification of cardiac signals is accomplished primarily by measuring the cardiac cycle length (R-R, P-R and P-P). In addition, the ICD/CRT-D can also utilize abrupt changes in rate or irregularity of the cardiac signal to further differentiate ventricular tachyarrhythmias. Each detected ventricular tachyarrhythmia is classified into one of the following zones:
VT-1 Lower rate ventricular tachycardia VT-2 Higher rate ventricular tachycardia VF Ventricular fibrillation
Each rhythm class is programmable to a separate rate with the zone limit defining the lowest rate in each class. The upper rate limit of each class is equal to the zone limit of the next higher class, creating a continuous range of rate classes.
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2.5.1 VF Classifications

Detection of ventricular fibrillation (VF) utilizes programmable X out of Y criterion. For the Lumax 300/340 & 500/540 models, both X and Y are programmable. For the Lumax 600/640 and 700/740 models there are fixed combinations of X out of Y criterion. If X number of intervals within the sliding window (defined by Y) are shorter than the programmed VF rate interval (>bpm), VF is detected. After fibrillation is detected, the programmed therapy sequence for VF is initiated.
Nominal settings for classification of ventricular fibrillation (VF) are 8 of 12 intervals; meaning that within a sample window of 12 intervals, 8 intervals must meet or exceed the VF zone rate criteria.

2.5.2 VT Interval Counters

The VT Interval Counters are separately programmable for VT-1 and VT-2 rate classifications. The Counter: Detection is the number of intervals required to declare a tachyarrhythmia as VT. A tachyarrhythmia must meet the rate/interval criteria and the programmed Counter/Detection criteria, in addition to any other detection enhancements to be declared a tachycardia.

2.5.3 VT Classification

Both VT-1 and VT-2 classification zones utilize separately programmable detection parameters. Classification of VT-1 or VT-2 is based on the last interval average preceding declaration of tachyarrhythmia detection. If this average falls within the VT-1 zone, the programmed VT-1 therapy is delivered. If the average falls within the VT-2 limits, the programmed VT-2 therapy is delivered. If additional detection parameters are activated, each of these supplemental criteria must also be satisfied before a VT rhythm can be classified and treated.
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The ICDs/CRT-Ds may be programmed to use ventricular-only information, or both atrial and ventricular information for the discrimination of ventricular tachyarrhythmias. With SMART Detection™ turned ON, the Lumax ICDs/CRT-Ds use atrial and ventricular signals for discrimination of fast heart rhythms. With SMART Detection™ turned OFF, only the ventricular rate is used to discriminate between ventricular rhythm classes. If SMART Detection is enabled, this algorithm evaluates all cardiac signals within the VT range and increments the VT Sample Count for all intervals that are deemed VT. A full description of SMART Detection™ is provided in Section
In addition, when the Lumax senses the programmed number of consecutive intervals (termination count) within the sinus rate zone, all tachyarrhythmia detection criteria, including the VT sample counters are reset.
2.5.4.

2.5.4 SMART Detection™

DR and HF versions only
This discrimination algorithm enhances VT-1 and VT-2 detection by applying a series of tests to the sensed cardiac signal. SMART Detection™ is intended to discriminate VT from a variety of supraventricular arrhythmias that are conducted to the ventricle and that would otherwise satisfy VT-1 or VT-2 rate detection criteria.
First, the average ventricular rate is compared to the average atrial rate. In the event that the measured ventricular rate is faster than the atrial rate, the device immediately declares the rhythm a VT and delivers programmed ventricular therapy for the detected VT zone.
In the event that an atrial rate is faster compared to the ventricular rate one of three tests are performed:
Ventricular rhythm stability, (see Stability in Section ventricular signal is unstable, then the rhythm is declared a supraventricular tachyarrhythmia, (SVT) and ventricular therapy is typically withheld.
If the ventricular signal is stable, and the atrial rate is a multiple of the ventricle rate, then the rhythm is declared a supraventricular tachyarrhythmia (SVT) and ventricular therapy is typically withheld.
2.5.6 if the
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If the ventricular rhythm is stable and the atrial rate is not a multiple of the ventricular rate, then the rhythm is declared a VT and ventricular tachycardia therapy is delivered.
In the event that both the atrial and ventricular signals are detected at the same rate, a series of additional discrimination tests are applied.

2.5.5 Onset

Another detection enhancement that may be used independently (VT-1 or VT-2, when SMART Detection is active) or as an adjunct to the SMART Detection™ algorithm is the Onset parameter. This parameter measures abrupt changes in ventricular cycle length to discriminate between sinus tachycardias and ventricular and atrial tachyarrhythmias, which characteristically begin with an abrupt change in cardiac rate.
This feature allows therapy to be withheld if a sinus tachycardia rate crosses into one of the VT zones.

2.5.6 Stability

In VT-1 and VT-2 zones, the purpose of STABILITY is to assist in discriminating between stable ventricular tachyarrhythmias and supraventricular tachyarrhythmias that conduct irregularly to the ventricles. STABILITY evaluates sudden changes in the regularity of cardiac events (R-R and P-P intervals) on a beat by beat basis. The STABILITY criterion compares the current measured interval with the three preceding cardiac intervals. If a difference between the current interval and each of the three preceding intervals is less than the stability range, then the current intervals are stable.
The SMART Detection™ algorithm utilizes both atrial and ventricular STABILITY as integral parts of the discrimination algorithm. Therefore, when SMART Detection™ is enabled, the STABILITY parameter must also remain enabled and set to 12%.

2.5.7 Sustained VT Timer

The Sustained VT Timer can be programmed between 30 seconds and 30 minutes (or to OFF) for the Lumax 300/340 & 500/540 models and 1 min to 30 minutes (or to OFF) in the Lumax 600/640 and 700/740 models. When the timer expires, therapy is initiated regardless of the detection enhancements.
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The Sustained VT parameter is intended to force tachycardia therapy in cases where a cardiac rhythm meets the VT rate criteria but does not satisfy one or more detection enhancement criterion (Onset, SMART Detection, or Stability) for an extended duration. This “safety” timer is initiated within one of the VT zones. If the programmed Sustained VT time period expires without tachycardia detection, redetection is initiated without utilizing the detection enhancements.
A simple up/down counter is used to initiate the safety timer. The counter is incremented by one when an interval falls into a VT zone and decrements by one when an interval falls into the sinus zone. When the counter reaches a number equal to the programmed VT detection counter, the safety timer is started. The timer runs until the programmed time expires and therapy is delivered or until the timer is reset. The timer is reset with initial detection or VT termination.
The safety timer is not used in redetection. If initial detection was due to the safety timeout and SMART Redetection is programmed “ON”, then SMART Detection will not be used for redetection.

2.5.8 VT Monitoring Zone

The VT1 zone can be programmed to monitor for non-sustained arrhythmias not requiring therapy. The monitoring zone can be programmed with all the standard detection enhancements including SMART Detection ventricular tachycardia or atrial tachyarrhythmias. Any tachyarrhythmia meeting the Monitor Zone criteria will store an IEGM.
TM
to monitor for non-sustained

2.5.9 Atrial Monitoring Zone

This feature allows the device to store an IEGM for atrial tachyarrhythmias such as Atrial Fibrillation or Atrial Flutter. The zone is programmed by rate with a range of 100 bpm to 250 bpm. Any atrial tachyarrhythmia meeting the Atrial Arrhythmia Monitor Zone criteria will store an IEGM.
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2.6 Tachyarrhythmia Redetection

The Lumax ICDs/CRT-Ds offer independently programmable settings for determining if tachyarrhythmias remain after therapy has been delivered. The redetection routine allows the ICDs/CRT-Ds to determine whether further therapy is required when the initial therapy was unsuccessful in terminating the arrhythmia.
Tachyarrhythmia redetection criteria are based on cardiac cycle length and number of intervals. The number of intervals is distinct and independent of the initial detection criteria.

2.6.1 VT Redetection

The Counter: Redetection parameter may be programmed separately for each arrhythmia class, independent of the initial detection parameters:
Redetection of an ongoing tachyarrhythmia is declared when the Counter: Redetection is satisfied (based on individual cycles). If a sensed cardiac signal meets any VT rate criteria, following therapy, that signal is counted and compared to the programmed Counter: Redetection setting.
Redetection functions are based exclusively on the VT criterion.

2.6.2 SMART Redetection

DR and HF versions only
With SMART Redetection programmed ON, both atrial and ventricular signals are used for redetection after initial detection and therapy for a VT. SMART Detection™ will function identically as in initial VT detection. SMART Redetection is autotmatically programmed ON in the Lumax 600/640 and 700/740 models.

2.6.3 Forced Termination

DR and HF versions only
With SMART Redetection programmed ON, this programmed parameter sets a time after which the SMART Redetection will be terminated even if the SVT is still ongoing. This forces the device to terminate the episode and allow detection of a new VT or VF episode.
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