Scheduled Programming is an optional feature allowing the physician to program a titration schedule in one office
visit. The titration changes will be applied per the physician’s defined intervals while the patient is in the comfort of
his or her own home. Clinicians can either follow a recommended protocol or create their own when using this feature.
To use this feature, the generator must
already be programmed in Guided Mode:
1. To enable Guided Mode, from the Summary
Screen (Fig. 1), tap on the EDIT PARAMETERS
button, or tap on PARAMETERS in the
Navigation Bar at the bottom of the screen.
2. On the Parameters Screen (Fig. 2), tap on
SWITCH TO GUIDED MODE button at top
of screen
3. On the Switch to Guided Mode Screen
(Fig. 3), select either STANDARD or
CUSTOM PROTOCOL and tap NEXT.
Tap APPLY CHANGES to enable Guided Mode
To continue and turn on Scheduled
Programming follow these steps:
4. In Guided Mode View (Fig. 4), tap the
SCHEDULED-APPLY button
5. On the Scheduled-Apply Screen (Fig. 5), tap
on ENABLE NOW at the center of the screen
6. On the next screen (Fig. 6), select the time
interval between step increases, then tap
GENERATE SCHEDULE at the center of
the screen.
7. Once a schedule has been generated
(Fig. 7)* you can follow the onscreen prompts
to make adjustments to the schedule and tap
APPLY CHANGES to program your changes,
which will then be confirmed on a Apply
Changes Screen (Fig. 8).
Fig. 1 Summary Screen Fig. 2 Parameter Screen
Fig. 4 Guided Mode View Fig. 5 Scheduled-apply Screen
Fig. 7 Schedule
Adjustments Screen
Fig. 8 Apply Changes Screen (Confirmation)
Fig. 3 Switch to Guided
Mode Screen
Fig. 6 Time Interval Screen
NOTE:
At the end of each office
visit, the generator must be
interrogated by tapping the
INTERROGATE button followed
by tapping the END SESSION
button to ensure creation and
accuracy of the
SESSION REPORTS.
Scheduled Programming
(Sentiva™ M1000 and Sentiva DUO™ M1000-D only)
Please refer to the VNS Therapy™ System Epilepsy Physician’s Manual (OUS), LivaNova USA, Inc. that could be
found at www.vnstherapy.co.uk/physician-manuals for complete information on the implantation procedure.
For full prescribing and important safety information, please visit www.vnstherapy.co.uk/safety-information
or ask your VNS Therapy representative.
Clinical Technical Services
US, Latin America, Canada, Asia Pacific, Japan
+1-281-228-7330,
+1-866-882-8804
Europe, Middle East, Africa
+32-2-790-27-73
* Limited to 0.125mA increases every 7 days.
visit. The titration changes will be applied per the physician’s defined intervals while the patient is in the comfort of
his or her own home. Clinicians can either follow a recommended protocol or create their own when using this feature.
To use this feature, the generator must
already be programmed in Guided Mode:
1. To enable Guided Mode, from the Summary
Screen (Fig. 1), tap on the EDIT PARAMETERS
button, or tap on PARAMETERS in the
Navigation Bar at the bottom of the screen.
2. On the Parameters Screen (Fig. 2), tap on
SWITCH TO GUIDED MODE button at top
of screen
3. On the Switch to Guided Mode Screen
(Fig. 3), select either STANDARD or
CUSTOM PROTOCOL and tap NEXT.
Tap APPLY CHANGES to enable Guided Mode
To continue and turn on Scheduled
Programming follow these steps:
4. In Guided Mode View (Fig. 4), tap the
SCHEDULED-APPLY button
5. On the Scheduled-Apply Screen (Fig. 5), tap
on ENABLE NOW at the center of the screen
6. On the next screen (Fig. 6), select the time
interval between step increases, then tap
GENERATE SCHEDULE at the center of
the screen.
7. Once a schedule has been generated
(Fig. 7)* you can follow the onscreen prompts
to make adjustments to the schedule and tap
APPLY CHANGES to program your changes,
which will then be confirmed on a Apply
Changes Screen (Fig. 8).
Fig. 1 Summary Screen Fig. 2 Parameter Screen
Fig. 4 Guided Mode View Fig. 5 Scheduled-apply Screen
Fig. 7 Schedule
Adjustments Screen
Fig. 8 Apply Changes Screen (Confirmation)
Fig. 3 Switch to Guided
Mode Screen
Fig. 6 Time Interval Screen
NOTE:
At the end of each office
visit, the generator must be
interrogated by tapping the
INTERROGATE button followed
by tapping the END SESSION
button to ensure creation and
accuracy of the
SESSION REPORTS.
Scheduled Programming
(Sentiva™ M1000 and Sentiva DUO™ M1000-D only)
Please refer to the VNS Therapy™ System Epilepsy Physician’s Manual (OUS), LivaNova USA, Inc. that could be
found at www.vnstherapy.co.uk/physician-manuals for complete information on the implantation procedure.
For full prescribing and important safety information, please visit www.vnstherapy.co.uk/safety-information
or ask your VNS Therapy representative.
Clinical Technical Services
US, Latin America, Canada, Asia Pacific, Japan
+1-281-228-7330,
+1-866-882-8804
Europe, Middle East, Africa
+32-2-790-27-73
* Limited to 0.125mA increases every 7 days.
EC Representative
LIVANOVA USA, INC.
100 Cyberonics Boulevard
Houston, Texas 77058, USA
Tel: +1 (281) 228-7200 /
+1 (800) 332-1375
Fax: +1 (281) 218-9332
www.livanova.com
Manufacturer
LIVANOVA BELGIUM NV
Ikaroslaan 83
B-1930 Zaventem,
BELGIUM
Tel: +3227209593
Fax: +3227206053
www.VNSTherapy.co.uk
1 The information contained in this Brief Summary for Physicians represents partial excerpts of
important prescribing information taken from the physician’s manuals. (Copies of VNS Therapy
physician’s and patient’s manuals are posted at www.livanova.com)The information is not
intended to serve as a substitute for a complete and thorough understanding of the material
presented in all of the physician’s manuals for the VNS Therapy System and its component
parts nor does this information represent full disclosure of all pertinent information
concerning the use of this product, potential safety complications, or efficacy outcomes.
Not available in all regions.
All trademarks and trade names are the property of LivaNova or the property of LivaNova’s consolidated subsidiaries and are protected under applicable
intellectual property laws. Solely for convenience, LivaNova’s trademarks and trade names may appear without the ® or TM symbols, but such references
are not intended to indicate in any way that LivaNova will not assert, to the fullest extent under applicable law, LivaNova’s rights to these trademarks and
trade names. Prior permission from Livanova is required for the use or reproduction of such intellectual property rights. EPI-2300205
1. INTENDED USE / INDICATIONS
Epilepsy (Non-US)—The VNS Therapy System is indicated for use as an adjunctive therapy in reducing
the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures (with or
without secondary generalization) or generalized seizures that are refractory to seizure medications.
AspireSR™, SenTiva™ and SenTiva DUO™ feature an Automatic Stimulation Mode which is intended for
patients who experience seizures that are associated with cardiac rhythm increases known as
ictal tachycardia.
2. CONTRAINDICATIONS
Vagotomy—The VNS Therapy System cannot be used in patients after a bilateral or left
cervical vagotomy.
Diathermy—Do not use short-wave diathermy, microwave diathermy, or therapeutic ultrasound
diathermy on patients implanted with a VNS Therapy System. Diagnostic ultrasound is not included in
this contraindication.
3. WARNINGS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
physician’s manuals. This document is not intended to serve as a substitute for the complete
physician’s manuals.
The safety and efficacy of the VNS Therapy System have not been established for uses outside the
“Intended Use/Indications” chapter of the physician’s manuals.
The safety and effectiveness of the VNS Therapy System in patients with predisposed dysfunction
of cardiac conduction systems (re-entry pathway) have not been established. Post-implant
electrocardiograms and Holter monitoring are recommended if clinically indicated.
Postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias.
It is important to follow recommended implantation procedures and intraoperative product testing
described in the Implantation Procedure chapter of the physician’s manual. During the intraoperative
System Diagnostics (Lead Test), infrequent incidents of bradycardia and/or asystole have occurred.
If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is
encountered during a System Diagnostics (Lead Test) or during initiation of stimulation, physicians
should be prepared to follow guidelines consistent with Advanced Cardiac Life Support (ACLS).
Difficulty swallowing (dysphagia) may occur with active stimulation, and aspiration may result from the
increased swallowing difficulties. Patients with pre-existing swallowing difficulties are at greater risk
for aspiration.
Dyspnea (shortness of breath) may occur with active VNS Therapy. Any patient with underlying
pulmonary disease or insufficiency such as chronic obstructive pulmonary disease or asthma may be at
increased risk for dyspnea.
Patients with obstructive sleep apnea (OSA) may have an increase in apneic events during stimulation.
Lowering stimulus frequency or prolonging “OFF” time may prevent exacerbation of OSA. Vagus nerve
stimulation may also cause new onset sleep apnea in patients who have not previously been diagnosed
with this disorder.
Device malfunction could cause painful stimulation or direct current stimulation. Either event could
cause nerve damage. Patients should be instructed to use the magnet to stop stimulation if they
suspect a malfunction, and then to contact their physician immediately for further evaluation.
Patients with the VNS Therapy System or any part of the VNS Therapy System implanted should have
MRI procedures performed only as described in the MRI with the VNS Therapy System instructions
for use. In some cases, surgery will be required to remove the VNS Therapy System if a scan using a
transmit RF body coil is needed.
Excessive stimulation at an excess duty cycle (i.e., one that occurs when “ON” time is greater than “OFF”
time) and high frequency stimulation (i.e., stimulation at ≥50Hz) has resulted in degenerative nerve
damage in laboratory animals.
Patients who manipulate the generator and lead through the skin (Twiddler’s Syndrome) may damage
or disconnect the lead from the generator and/or possibly cause damage to the vagus nerve.
The Wand, Programmer, and patient magnet are MR unsafe devices. These devices are projectile hazards
and must not be brought into the MR scanner room.
Generators with AutoStim only — The AutoStim Mode feature should not be used in patients with
clinically meaningful arrhythmias or who are using treatments that interfere with normal intrinsic
heart rate responses (e.g., pacemaker dependency, implantable defibrillator, beta adrenergic blocker
medications). Patients also should not have a history of chronotropic incompetence [commonly seen in
patients with sustained bradycardia (heart rate < 50 bpm)].
4. WARNINGS — EPILEPSY
The VNS Therapy System should only be prescribed and monitored by physicians who have specific
training and expertise in the management of seizures and the use of this device. It should only be
implanted by physicians who are trained in surgery of the carotid sheath and have received specific
training in the implantation of this device.
The VNS Therapy System is not curative. Physicians should warn patients that the VNS Therapy System
is not a cure for epilepsy and that since seizures may occur unexpectedly, patients should consult with
a physician before engaging in unsupervised activities, such as driving, swimming, and bathing, and in
strenuous sports that could harm them or others.
Sudden unexpected death in epilepsy (SUDEP): Through August 1996, 10 sudden and unexpected deaths
(definite, probable, and possible) were recorded among the 1,000 patients implanted and treated
with the VNS Therapy device. During this period, these patients had accumulated 2,017 patient-years
of exposure. Some of these deaths could represent seizure-related deaths in which the seizure was
not observed, at night, for example. This number represents an incidence of 5.0 definite, probable,
and possible SUDEP deaths per 1,000 patient-years. Although this rate exceeds that expected in a
healthy (nonepileptic) population matched for age and sex, it is within the range of estimates for
epilepsy patients not receiving vagus nerve stimulation, ranging from 1.3 SUDEP deaths for the general
population of patients with epilepsy, to 3.5 (for definite and probable) for a recently studied antiepileptic
drug (AED) clinical trial population similar to the VNS Therapy System clinical cohort, to 9.3 for patients
with medically intractable epilepsy who were epilepsy surgery candidates.
5. PRECAUTIONS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
VNS Therapy physician’s manuals.
Prescribing physicians should be experienced in the diagnosis and treatment of depression or epilepsy
and should be familiar with the programming and use of the VNS Therapy System.
Physicians who implant the VNS Therapy System should be experienced performing surgery in the
carotid sheath and should be trained in the surgical technique relating to implantation of the
VNS Therapy System.
The safety and effectiveness of the VNS Therapy System have not been established for use during
pregnancy. VNS should be used during pregnancy only if clearly needed.
The VNS Therapy System is indicated for use only in stimulating the left vagus nerve in the neck area
inside the carotid sheath. The VNS Therapy System is indicated for use only in stimulating the left vagus
nerve below where the superior and inferior cervical cardiac branches separate from the vagus nerve.
It is important to follow infection control procedures. Infections related to any implanted device are
difficult to treat and may require that the device be explanted. The patient should be given antibiotics
preoperatively. The surgeon should ensure that all instruments are sterile prior to the procedure.
Children (<12 years of age) may have a greater risk for infection when compared to adolescent and adult
patients (≥ 12 years). Careful monitoring for site infection as well as the avoidance of manipulation of the
surgical site post implant in children should be stressed.
The VNS Therapy System may affect the operation of other implanted devices, such as cardiac
pacemakers and implanted defibrillators. Possible effects include sensing problems and inappropriate
device responses. If the patient requires concurrent implantable pacemaker, defibrillatory therapy
or other types of stimulators, careful programming of each system may be necessary to optimize the
patient’s benefit from each device.
Reversal of lead polarity has been associated with an increased chance of bradycardia in animal studies.
It is important that the electrodes are attached to the left vagus nerve in the correct orientation. It is
also important to make sure that leads with dual connector pins are correctly inserted (white marker
band to + connection) into the generator’s lead receptacles.
The patient can use a neck brace for the first week to help ensure proper lead stabilization.
Do not program the VNS Therapy System to an “ON” or periodic stimulation treatment for at least 14
days after the initial or replacement implantation.
For Models 100, 101, 102 and 102R do not use frequencies of 5 Hz or below for long-term stimulation.
Resetting the pulse generator turns the device OFF (output current = 0 mA). For Model 100, 101, 102 and
102R resetting the pulse generator will result in device history loss.
Patients who smoke may have an increased risk of laryngeal irritation.
Generators with AutoStim only — For devices that sense changes in heart rate, false positive detection
may cause unintended stimulation. Examples of instances where heart rate may increase include
exercise, physical activity, and normal autonomic changes in heart rate, both awake and asleep, etc.
Generators with AutoStim only — For the AutoStim feature, the physical location of the device critically
affects this its ability to properly sense heart beats. Therefore, care must be taken to follow the implant
location selection process outlined in the Implantation Procedure. Note that this implant location
selection procedure may be performed preoperatively as part of the patient’s surgical work-up.
M1000/1000-D only — Since the Scheduled Programming feature allows the generator to apply therapy
increases at scheduled intervals, it may not be appropriate for use in patients who are nonverbal or
are unable to use the patient magnet to stop undesired stimulation. Similarly, exercise caution for
use of this feature in patients with a history of obstructive sleep apnea, shortness of breath, coughing,
swallowing difficulties, or aspiration.
6. ENVIRONMENTAL AND MEDICAL THERAPY HAZARDS
Patients should exercise reasonable caution in avoiding devices that generate a strong electric or
magnetic field. If a generator ceases operation while in the presence of electromagnetic interference
(EMI), moving away from the source may allow it to return to its normal mode of operation.
VNS Therapy System operation should always be checked by performing device diagnostics after any of
the procedures mentioned in the physician’s manuals.
For clear imaging, patients may need to be specially positioned for mammography procedures, because
of the location of the generator in the chest.
Therapeutic radiation may damage the generator’s circuitry. Sources of such radiation include
therapeutic radiation, cobalt machines, and linear accelerators. The radiation effect is cumulative, with
the total dosage determining the extent of damage. The effects of exposure to such radiation can range
from a temporary disturbance to permanent damage, and may not be detectable immediately.
External defibrillation may damage the generator.
Use of electrosurgery [electrocautery or radio frequency (RF) ablation devices] may damage
the generator.
Magnetic resonance imaging (MRI) should not be performed using a transmit RF body coil for certain
VNS Therapy device configurations or under certain specific conditions. In some cases, heating of the
lead caused by the transmit RF body coil during MRI may result in serious injury. Static, gradient, and
radio frequency (RF) electromagnetic fields associated with MRI may change the generator settings
(i.e., reset parameters) or activate the VNS device if the Magnet Mode output remains “ON”. Note that
certain magnetic resonance (MR) system head coils operate in receive-only mode and require use of
the transmit RF body coil. Other MR systems use a transmit/receive RF head coil. Local or surface coils
may also be receive-only RF coils that require the transmit RF body coil for MRI. The use of a receive
RF coil does not alter hazards of the transmit RF body coil. Exposure of the VNS Therapy System to any
transmit RF coil must be avoided. Do not perform MRI scans using any transmit RF coil in the defined
exclusion zones. See the MRI with the VNS Therapy System instructions for use for details or further
instructions for special cases such as lead breaks or partially explanted VNS Therapy systems.
Extracorporeal shockwave lithotripsy may damage the generator. If therapeutic ultrasound therapy is
required, avoid positioning the area of the body where the generator is implanted in the water bath
or in any other position that would expose it to ultrasound therapy. If that positioning cannot be
avoided, program the generator output to 0 mA for the treatment, and then after therapy, reprogram the
generator to the original parameters.
If the patient receives medical treatment for which electric current is passed through the body (such as
from a TENS unit), either the generator should be set to 0 mA or function of the generator should be
monitored during initial stages of treatment.
Routine therapeutic ultrasound could damage the generator and may be inadvertently concentrated by
the device, causing harm to the patient.
For complete information related to home occupational environments, cellular phones, other
environmental hazards, other devices, and ECG monitors, refer to the physician’s manuals.
7. ADVERSE EVENTS — EPILEPSY
Adverse events reported during clinical studies as statistically significant are listed below in alphabetical
order: ataxia (loss of the ability to coordinate muscular movement); dyspepsia (indigestion); dyspnea
(difficulty breathing, shortness of breath); hypoesthesia (impaired sense of touch); increased coughing;
infection; insomnia (inability to sleep); laryngismus (throat, larynx spasms); nausea; pain; paresthesia
(prickling of the skin); pharyngitis (inflammation of the pharynx, throat); voice alteration (hoarseness);
vomiting. Adverse events reported in clinical investigation of the AutoStim feature were comparable.
26-0009-0100/6 (OUS) — 1
Brief Summary1 of Safety Information for the VNS Therapy™ System
[Epilepsy Indication] (February 2021)
LIVANOVA USA, INC.
100 Cyberonics Boulevard
Houston, Texas 77058, USA
Tel: +1 (281) 228-7200 /
+1 (800) 332-1375
Fax: +1 (281) 218-9332
www.livanova.com
Manufacturer
LIVANOVA BELGIUM NV
Ikaroslaan 83
B-1930 Zaventem,
BELGIUM
Tel: +3227209593
Fax: +3227206053
www.VNSTherapy.co.uk
1 The information contained in this Brief Summary for Physicians represents partial excerpts of
important prescribing information taken from the physician’s manuals. (Copies of VNS Therapy
physician’s and patient’s manuals are posted at www.livanova.com)The information is not
intended to serve as a substitute for a complete and thorough understanding of the material
presented in all of the physician’s manuals for the VNS Therapy System and its component
parts nor does this information represent full disclosure of all pertinent information
concerning the use of this product, potential safety complications, or efficacy outcomes.
Not available in all regions.
All trademarks and trade names are the property of LivaNova or the property of LivaNova’s consolidated subsidiaries and are protected under applicable
intellectual property laws. Solely for convenience, LivaNova’s trademarks and trade names may appear without the ® or TM symbols, but such references
are not intended to indicate in any way that LivaNova will not assert, to the fullest extent under applicable law, LivaNova’s rights to these trademarks and
trade names. Prior permission from Livanova is required for the use or reproduction of such intellectual property rights. EPI-2300205
1. INTENDED USE / INDICATIONS
Epilepsy (Non-US)—The VNS Therapy System is indicated for use as an adjunctive therapy in reducing
the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures (with or
without secondary generalization) or generalized seizures that are refractory to seizure medications.
AspireSR™, SenTiva™ and SenTiva DUO™ feature an Automatic Stimulation Mode which is intended for
patients who experience seizures that are associated with cardiac rhythm increases known as
ictal tachycardia.
2. CONTRAINDICATIONS
Vagotomy—The VNS Therapy System cannot be used in patients after a bilateral or left
cervical vagotomy.
Diathermy—Do not use short-wave diathermy, microwave diathermy, or therapeutic ultrasound
diathermy on patients implanted with a VNS Therapy System. Diagnostic ultrasound is not included in
this contraindication.
3. WARNINGS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
physician’s manuals. This document is not intended to serve as a substitute for the complete
physician’s manuals.
The safety and efficacy of the VNS Therapy System have not been established for uses outside the
“Intended Use/Indications” chapter of the physician’s manuals.
The safety and effectiveness of the VNS Therapy System in patients with predisposed dysfunction
of cardiac conduction systems (re-entry pathway) have not been established. Post-implant
electrocardiograms and Holter monitoring are recommended if clinically indicated.
Postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias.
It is important to follow recommended implantation procedures and intraoperative product testing
described in the Implantation Procedure chapter of the physician’s manual. During the intraoperative
System Diagnostics (Lead Test), infrequent incidents of bradycardia and/or asystole have occurred.
If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is
encountered during a System Diagnostics (Lead Test) or during initiation of stimulation, physicians
should be prepared to follow guidelines consistent with Advanced Cardiac Life Support (ACLS).
Difficulty swallowing (dysphagia) may occur with active stimulation, and aspiration may result from the
increased swallowing difficulties. Patients with pre-existing swallowing difficulties are at greater risk
for aspiration.
Dyspnea (shortness of breath) may occur with active VNS Therapy. Any patient with underlying
pulmonary disease or insufficiency such as chronic obstructive pulmonary disease or asthma may be at
increased risk for dyspnea.
Patients with obstructive sleep apnea (OSA) may have an increase in apneic events during stimulation.
Lowering stimulus frequency or prolonging “OFF” time may prevent exacerbation of OSA. Vagus nerve
stimulation may also cause new onset sleep apnea in patients who have not previously been diagnosed
with this disorder.
Device malfunction could cause painful stimulation or direct current stimulation. Either event could
cause nerve damage. Patients should be instructed to use the magnet to stop stimulation if they
suspect a malfunction, and then to contact their physician immediately for further evaluation.
Patients with the VNS Therapy System or any part of the VNS Therapy System implanted should have
MRI procedures performed only as described in the MRI with the VNS Therapy System instructions
for use. In some cases, surgery will be required to remove the VNS Therapy System if a scan using a
transmit RF body coil is needed.
Excessive stimulation at an excess duty cycle (i.e., one that occurs when “ON” time is greater than “OFF”
time) and high frequency stimulation (i.e., stimulation at ≥50Hz) has resulted in degenerative nerve
damage in laboratory animals.
Patients who manipulate the generator and lead through the skin (Twiddler’s Syndrome) may damage
or disconnect the lead from the generator and/or possibly cause damage to the vagus nerve.
The Wand, Programmer, and patient magnet are MR unsafe devices. These devices are projectile hazards
and must not be brought into the MR scanner room.
Generators with AutoStim only — The AutoStim Mode feature should not be used in patients with
clinically meaningful arrhythmias or who are using treatments that interfere with normal intrinsic
heart rate responses (e.g., pacemaker dependency, implantable defibrillator, beta adrenergic blocker
medications). Patients also should not have a history of chronotropic incompetence [commonly seen in
patients with sustained bradycardia (heart rate < 50 bpm)].
4. WARNINGS — EPILEPSY
The VNS Therapy System should only be prescribed and monitored by physicians who have specific
training and expertise in the management of seizures and the use of this device. It should only be
implanted by physicians who are trained in surgery of the carotid sheath and have received specific
training in the implantation of this device.
The VNS Therapy System is not curative. Physicians should warn patients that the VNS Therapy System
is not a cure for epilepsy and that since seizures may occur unexpectedly, patients should consult with
a physician before engaging in unsupervised activities, such as driving, swimming, and bathing, and in
strenuous sports that could harm them or others.
Sudden unexpected death in epilepsy (SUDEP): Through August 1996, 10 sudden and unexpected deaths
(definite, probable, and possible) were recorded among the 1,000 patients implanted and treated
with the VNS Therapy device. During this period, these patients had accumulated 2,017 patient-years
of exposure. Some of these deaths could represent seizure-related deaths in which the seizure was
not observed, at night, for example. This number represents an incidence of 5.0 definite, probable,
and possible SUDEP deaths per 1,000 patient-years. Although this rate exceeds that expected in a
healthy (nonepileptic) population matched for age and sex, it is within the range of estimates for
epilepsy patients not receiving vagus nerve stimulation, ranging from 1.3 SUDEP deaths for the general
population of patients with epilepsy, to 3.5 (for definite and probable) for a recently studied antiepileptic
drug (AED) clinical trial population similar to the VNS Therapy System clinical cohort, to 9.3 for patients
with medically intractable epilepsy who were epilepsy surgery candidates.
5. PRECAUTIONS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
VNS Therapy physician’s manuals.
Prescribing physicians should be experienced in the diagnosis and treatment of depression or epilepsy
and should be familiar with the programming and use of the VNS Therapy System.
Physicians who implant the VNS Therapy System should be experienced performing surgery in the
carotid sheath and should be trained in the surgical technique relating to implantation of the
VNS Therapy System.
The safety and effectiveness of the VNS Therapy System have not been established for use during
pregnancy. VNS should be used during pregnancy only if clearly needed.
The VNS Therapy System is indicated for use only in stimulating the left vagus nerve in the neck area
inside the carotid sheath. The VNS Therapy System is indicated for use only in stimulating the left vagus
nerve below where the superior and inferior cervical cardiac branches separate from the vagus nerve.
It is important to follow infection control procedures. Infections related to any implanted device are
difficult to treat and may require that the device be explanted. The patient should be given antibiotics
preoperatively. The surgeon should ensure that all instruments are sterile prior to the procedure.
Children (<12 years of age) may have a greater risk for infection when compared to adolescent and adult
patients (≥ 12 years). Careful monitoring for site infection as well as the avoidance of manipulation of the
surgical site post implant in children should be stressed.
The VNS Therapy System may affect the operation of other implanted devices, such as cardiac
pacemakers and implanted defibrillators. Possible effects include sensing problems and inappropriate
device responses. If the patient requires concurrent implantable pacemaker, defibrillatory therapy
or other types of stimulators, careful programming of each system may be necessary to optimize the
patient’s benefit from each device.
Reversal of lead polarity has been associated with an increased chance of bradycardia in animal studies.
It is important that the electrodes are attached to the left vagus nerve in the correct orientation. It is
also important to make sure that leads with dual connector pins are correctly inserted (white marker
band to + connection) into the generator’s lead receptacles.
The patient can use a neck brace for the first week to help ensure proper lead stabilization.
Do not program the VNS Therapy System to an “ON” or periodic stimulation treatment for at least 14
days after the initial or replacement implantation.
For Models 100, 101, 102 and 102R do not use frequencies of 5 Hz or below for long-term stimulation.
Resetting the pulse generator turns the device OFF (output current = 0 mA). For Model 100, 101, 102 and
102R resetting the pulse generator will result in device history loss.
Patients who smoke may have an increased risk of laryngeal irritation.
Generators with AutoStim only — For devices that sense changes in heart rate, false positive detection
may cause unintended stimulation. Examples of instances where heart rate may increase include
exercise, physical activity, and normal autonomic changes in heart rate, both awake and asleep, etc.
Generators with AutoStim only — For the AutoStim feature, the physical location of the device critically
affects this its ability to properly sense heart beats. Therefore, care must be taken to follow the implant
location selection process outlined in the Implantation Procedure. Note that this implant location
selection procedure may be performed preoperatively as part of the patient’s surgical work-up.
M1000/1000-D only — Since the Scheduled Programming feature allows the generator to apply therapy
increases at scheduled intervals, it may not be appropriate for use in patients who are nonverbal or
are unable to use the patient magnet to stop undesired stimulation. Similarly, exercise caution for
use of this feature in patients with a history of obstructive sleep apnea, shortness of breath, coughing,
swallowing difficulties, or aspiration.
6. ENVIRONMENTAL AND MEDICAL THERAPY HAZARDS
Patients should exercise reasonable caution in avoiding devices that generate a strong electric or
magnetic field. If a generator ceases operation while in the presence of electromagnetic interference
(EMI), moving away from the source may allow it to return to its normal mode of operation.
VNS Therapy System operation should always be checked by performing device diagnostics after any of
the procedures mentioned in the physician’s manuals.
For clear imaging, patients may need to be specially positioned for mammography procedures, because
of the location of the generator in the chest.
Therapeutic radiation may damage the generator’s circuitry. Sources of such radiation include
therapeutic radiation, cobalt machines, and linear accelerators. The radiation effect is cumulative, with
the total dosage determining the extent of damage. The effects of exposure to such radiation can range
from a temporary disturbance to permanent damage, and may not be detectable immediately.
External defibrillation may damage the generator.
Use of electrosurgery [electrocautery or radio frequency (RF) ablation devices] may damage
the generator.
Magnetic resonance imaging (MRI) should not be performed using a transmit RF body coil for certain
VNS Therapy device configurations or under certain specific conditions. In some cases, heating of the
lead caused by the transmit RF body coil during MRI may result in serious injury. Static, gradient, and
radio frequency (RF) electromagnetic fields associated with MRI may change the generator settings
(i.e., reset parameters) or activate the VNS device if the Magnet Mode output remains “ON”. Note that
certain magnetic resonance (MR) system head coils operate in receive-only mode and require use of
the transmit RF body coil. Other MR systems use a transmit/receive RF head coil. Local or surface coils
may also be receive-only RF coils that require the transmit RF body coil for MRI. The use of a receive
RF coil does not alter hazards of the transmit RF body coil. Exposure of the VNS Therapy System to any
transmit RF coil must be avoided. Do not perform MRI scans using any transmit RF coil in the defined
exclusion zones. See the MRI with the VNS Therapy System instructions for use for details or further
instructions for special cases such as lead breaks or partially explanted VNS Therapy systems.
Extracorporeal shockwave lithotripsy may damage the generator. If therapeutic ultrasound therapy is
required, avoid positioning the area of the body where the generator is implanted in the water bath
or in any other position that would expose it to ultrasound therapy. If that positioning cannot be
avoided, program the generator output to 0 mA for the treatment, and then after therapy, reprogram the
generator to the original parameters.
If the patient receives medical treatment for which electric current is passed through the body (such as
from a TENS unit), either the generator should be set to 0 mA or function of the generator should be
monitored during initial stages of treatment.
Routine therapeutic ultrasound could damage the generator and may be inadvertently concentrated by
the device, causing harm to the patient.
For complete information related to home occupational environments, cellular phones, other
environmental hazards, other devices, and ECG monitors, refer to the physician’s manuals.
7. ADVERSE EVENTS — EPILEPSY
Adverse events reported during clinical studies as statistically significant are listed below in alphabetical
order: ataxia (loss of the ability to coordinate muscular movement); dyspepsia (indigestion); dyspnea
(difficulty breathing, shortness of breath); hypoesthesia (impaired sense of touch); increased coughing;
infection; insomnia (inability to sleep); laryngismus (throat, larynx spasms); nausea; pain; paresthesia
(prickling of the skin); pharyngitis (inflammation of the pharynx, throat); voice alteration (hoarseness);
vomiting. Adverse events reported in clinical investigation of the AutoStim feature were comparable.
26-0009-0100/6 (OUS) — 1
Brief Summary1 of Safety Information for the VNS Therapy™ System
[Epilepsy Indication] (February 2021)
Scheduled Programming is an optional feature allowing the physician to program a titration schedule in one office
visit. The titration changes will be applied per the physician’s defined intervals while the patient is in the comfort of
his or her own home. Clinicians can either follow a recommended protocol or create their own when using this feature.
To use this feature, the generator must
already be programmed in Guided Mode:
1. To enable Guided Mode, from the Summary
Screen (Fig. 1), tap on the EDIT PARAMETERS
button, or tap on PARAMETERS in the
Navigation Bar at the bottom of the screen.
2. On the Parameters Screen (Fig. 2), tap on
SWITCH TO GUIDED MODE button at top
of screen
3. On the Switch to Guided Mode Screen
(Fig. 3), select either STANDARD or
CUSTOM PROTOCOL and tap NEXT.
Tap APPLY CHANGES to enable Guided Mode
To continue and turn on Scheduled
Programming follow these steps:
4. In Guided Mode View (Fig. 4), tap the
SCHEDULED-APPLY button
5. On the Scheduled-Apply Screen (Fig. 5), tap
on ENABLE NOW at the center of the screen
6. On the next screen (Fig. 6), select the time
interval between step increases, then tap
GENERATE SCHEDULE at the center of
the screen.
7. Once a schedule has been generated
(Fig. 7)* you can follow the onscreen prompts
to make adjustments to the schedule and tap
APPLY CHANGES to program your changes,
which will then be confirmed on a Apply
Changes Screen (Fig. 8).
Fig. 1 Summary Screen Fig. 2 Parameter Screen
Fig. 4 Guided Mode View Fig. 5 Scheduled-apply Screen
Fig. 7 Schedule
Adjustments Screen
Fig. 8 Apply Changes Screen (Confirmation)
Fig. 3 Switch to Guided
Mode Screen
Fig. 6 Time Interval Screen
NOTE:
At the end of each office
visit, the generator must be
interrogated by tapping the
INTERROGATE button followed
by tapping the END SESSION
button to ensure creation and
accuracy of the
SESSION REPORTS.
Scheduled Programming
(Sentiva™ M1000 and Sentiva DUO™ M1000-D only)
Please refer to the VNS Therapy™ System Epilepsy Physician’s Manual (OUS), LivaNova USA, Inc. that could be
found at www.vnstherapy.co.uk/physician-manuals for complete information on the implantation procedure.
For full prescribing and important safety information, please visit www.vnstherapy.co.uk/safety-information
or ask your VNS Therapy representative.
Clinical Technical Services
US, Latin America, Canada, Asia Pacific, Japan
+1-281-228-7330,
+1-866-882-8804
Europe, Middle East, Africa
+32-2-790-27-73
* Limited to 0.125mA increases every 7 days.
visit. The titration changes will be applied per the physician’s defined intervals while the patient is in the comfort of
his or her own home. Clinicians can either follow a recommended protocol or create their own when using this feature.
To use this feature, the generator must
already be programmed in Guided Mode:
1. To enable Guided Mode, from the Summary
Screen (Fig. 1), tap on the EDIT PARAMETERS
button, or tap on PARAMETERS in the
Navigation Bar at the bottom of the screen.
2. On the Parameters Screen (Fig. 2), tap on
SWITCH TO GUIDED MODE button at top
of screen
3. On the Switch to Guided Mode Screen
(Fig. 3), select either STANDARD or
CUSTOM PROTOCOL and tap NEXT.
Tap APPLY CHANGES to enable Guided Mode
To continue and turn on Scheduled
Programming follow these steps:
4. In Guided Mode View (Fig. 4), tap the
SCHEDULED-APPLY button
5. On the Scheduled-Apply Screen (Fig. 5), tap
on ENABLE NOW at the center of the screen
6. On the next screen (Fig. 6), select the time
interval between step increases, then tap
GENERATE SCHEDULE at the center of
the screen.
7. Once a schedule has been generated
(Fig. 7)* you can follow the onscreen prompts
to make adjustments to the schedule and tap
APPLY CHANGES to program your changes,
which will then be confirmed on a Apply
Changes Screen (Fig. 8).
Fig. 1 Summary Screen Fig. 2 Parameter Screen
Fig. 4 Guided Mode View Fig. 5 Scheduled-apply Screen
Fig. 7 Schedule
Adjustments Screen
Fig. 8 Apply Changes Screen (Confirmation)
Fig. 3 Switch to Guided
Mode Screen
Fig. 6 Time Interval Screen
NOTE:
At the end of each office
visit, the generator must be
interrogated by tapping the
INTERROGATE button followed
by tapping the END SESSION
button to ensure creation and
accuracy of the
SESSION REPORTS.
Scheduled Programming
(Sentiva™ M1000 and Sentiva DUO™ M1000-D only)
Please refer to the VNS Therapy™ System Epilepsy Physician’s Manual (OUS), LivaNova USA, Inc. that could be
found at www.vnstherapy.co.uk/physician-manuals for complete information on the implantation procedure.
For full prescribing and important safety information, please visit www.vnstherapy.co.uk/safety-information
or ask your VNS Therapy representative.
Clinical Technical Services
US, Latin America, Canada, Asia Pacific, Japan
+1-281-228-7330,
+1-866-882-8804
Europe, Middle East, Africa
+32-2-790-27-73
* Limited to 0.125mA increases every 7 days.
EC Representative
LIVANOVA USA, INC.
100 Cyberonics Boulevard
Houston, Texas 77058, USA
Tel: +1 (281) 228-7200 /
+1 (800) 332-1375
Fax: +1 (281) 218-9332
www.livanova.com
Manufacturer
LIVANOVA BELGIUM NV
Ikaroslaan 83
B-1930 Zaventem,
BELGIUM
Tel: +3227209593
Fax: +3227206053
www.VNSTherapy.co.uk
1 The information contained in this Brief Summary for Physicians represents partial excerpts of
important prescribing information taken from the physician’s manuals. (Copies of VNS Therapy
physician’s and patient’s manuals are posted at www.livanova.com)The information is not
intended to serve as a substitute for a complete and thorough understanding of the material
presented in all of the physician’s manuals for the VNS Therapy System and its component
parts nor does this information represent full disclosure of all pertinent information
concerning the use of this product, potential safety complications, or efficacy outcomes.
Not available in all regions.
All trademarks and trade names are the property of LivaNova or the property of LivaNova’s consolidated subsidiaries and are protected under applicable
intellectual property laws. Solely for convenience, LivaNova’s trademarks and trade names may appear without the ® or TM symbols, but such references
are not intended to indicate in any way that LivaNova will not assert, to the fullest extent under applicable law, LivaNova’s rights to these trademarks and
trade names. Prior permission from Livanova is required for the use or reproduction of such intellectual property rights. EPI-2300205
1. INTENDED USE / INDICATIONS
Epilepsy (Non-US)—The VNS Therapy System is indicated for use as an adjunctive therapy in reducing
the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures (with or
without secondary generalization) or generalized seizures that are refractory to seizure medications.
AspireSR™, SenTiva™ and SenTiva DUO™ feature an Automatic Stimulation Mode which is intended for
patients who experience seizures that are associated with cardiac rhythm increases known as
ictal tachycardia.
2. CONTRAINDICATIONS
Vagotomy—The VNS Therapy System cannot be used in patients after a bilateral or left
cervical vagotomy.
Diathermy—Do not use short-wave diathermy, microwave diathermy, or therapeutic ultrasound
diathermy on patients implanted with a VNS Therapy System. Diagnostic ultrasound is not included in
this contraindication.
3. WARNINGS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
physician’s manuals. This document is not intended to serve as a substitute for the complete
physician’s manuals.
The safety and efficacy of the VNS Therapy System have not been established for uses outside the
“Intended Use/Indications” chapter of the physician’s manuals.
The safety and effectiveness of the VNS Therapy System in patients with predisposed dysfunction
of cardiac conduction systems (re-entry pathway) have not been established. Post-implant
electrocardiograms and Holter monitoring are recommended if clinically indicated.
Postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias.
It is important to follow recommended implantation procedures and intraoperative product testing
described in the Implantation Procedure chapter of the physician’s manual. During the intraoperative
System Diagnostics (Lead Test), infrequent incidents of bradycardia and/or asystole have occurred.
If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is
encountered during a System Diagnostics (Lead Test) or during initiation of stimulation, physicians
should be prepared to follow guidelines consistent with Advanced Cardiac Life Support (ACLS).
Difficulty swallowing (dysphagia) may occur with active stimulation, and aspiration may result from the
increased swallowing difficulties. Patients with pre-existing swallowing difficulties are at greater risk
for aspiration.
Dyspnea (shortness of breath) may occur with active VNS Therapy. Any patient with underlying
pulmonary disease or insufficiency such as chronic obstructive pulmonary disease or asthma may be at
increased risk for dyspnea.
Patients with obstructive sleep apnea (OSA) may have an increase in apneic events during stimulation.
Lowering stimulus frequency or prolonging “OFF” time may prevent exacerbation of OSA. Vagus nerve
stimulation may also cause new onset sleep apnea in patients who have not previously been diagnosed
with this disorder.
Device malfunction could cause painful stimulation or direct current stimulation. Either event could
cause nerve damage. Patients should be instructed to use the magnet to stop stimulation if they
suspect a malfunction, and then to contact their physician immediately for further evaluation.
Patients with the VNS Therapy System or any part of the VNS Therapy System implanted should have
MRI procedures performed only as described in the MRI with the VNS Therapy System instructions
for use. In some cases, surgery will be required to remove the VNS Therapy System if a scan using a
transmit RF body coil is needed.
Excessive stimulation at an excess duty cycle (i.e., one that occurs when “ON” time is greater than “OFF”
time) and high frequency stimulation (i.e., stimulation at ≥50Hz) has resulted in degenerative nerve
damage in laboratory animals.
Patients who manipulate the generator and lead through the skin (Twiddler’s Syndrome) may damage
or disconnect the lead from the generator and/or possibly cause damage to the vagus nerve.
The Wand, Programmer, and patient magnet are MR unsafe devices. These devices are projectile hazards
and must not be brought into the MR scanner room.
Generators with AutoStim only — The AutoStim Mode feature should not be used in patients with
clinically meaningful arrhythmias or who are using treatments that interfere with normal intrinsic
heart rate responses (e.g., pacemaker dependency, implantable defibrillator, beta adrenergic blocker
medications). Patients also should not have a history of chronotropic incompetence [commonly seen in
patients with sustained bradycardia (heart rate < 50 bpm)].
4. WARNINGS — EPILEPSY
The VNS Therapy System should only be prescribed and monitored by physicians who have specific
training and expertise in the management of seizures and the use of this device. It should only be
implanted by physicians who are trained in surgery of the carotid sheath and have received specific
training in the implantation of this device.
The VNS Therapy System is not curative. Physicians should warn patients that the VNS Therapy System
is not a cure for epilepsy and that since seizures may occur unexpectedly, patients should consult with
a physician before engaging in unsupervised activities, such as driving, swimming, and bathing, and in
strenuous sports that could harm them or others.
Sudden unexpected death in epilepsy (SUDEP): Through August 1996, 10 sudden and unexpected deaths
(definite, probable, and possible) were recorded among the 1,000 patients implanted and treated
with the VNS Therapy device. During this period, these patients had accumulated 2,017 patient-years
of exposure. Some of these deaths could represent seizure-related deaths in which the seizure was
not observed, at night, for example. This number represents an incidence of 5.0 definite, probable,
and possible SUDEP deaths per 1,000 patient-years. Although this rate exceeds that expected in a
healthy (nonepileptic) population matched for age and sex, it is within the range of estimates for
epilepsy patients not receiving vagus nerve stimulation, ranging from 1.3 SUDEP deaths for the general
population of patients with epilepsy, to 3.5 (for definite and probable) for a recently studied antiepileptic
drug (AED) clinical trial population similar to the VNS Therapy System clinical cohort, to 9.3 for patients
with medically intractable epilepsy who were epilepsy surgery candidates.
5. PRECAUTIONS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
VNS Therapy physician’s manuals.
Prescribing physicians should be experienced in the diagnosis and treatment of depression or epilepsy
and should be familiar with the programming and use of the VNS Therapy System.
Physicians who implant the VNS Therapy System should be experienced performing surgery in the
carotid sheath and should be trained in the surgical technique relating to implantation of the
VNS Therapy System.
The safety and effectiveness of the VNS Therapy System have not been established for use during
pregnancy. VNS should be used during pregnancy only if clearly needed.
The VNS Therapy System is indicated for use only in stimulating the left vagus nerve in the neck area
inside the carotid sheath. The VNS Therapy System is indicated for use only in stimulating the left vagus
nerve below where the superior and inferior cervical cardiac branches separate from the vagus nerve.
It is important to follow infection control procedures. Infections related to any implanted device are
difficult to treat and may require that the device be explanted. The patient should be given antibiotics
preoperatively. The surgeon should ensure that all instruments are sterile prior to the procedure.
Children (<12 years of age) may have a greater risk for infection when compared to adolescent and adult
patients (≥ 12 years). Careful monitoring for site infection as well as the avoidance of manipulation of the
surgical site post implant in children should be stressed.
The VNS Therapy System may affect the operation of other implanted devices, such as cardiac
pacemakers and implanted defibrillators. Possible effects include sensing problems and inappropriate
device responses. If the patient requires concurrent implantable pacemaker, defibrillatory therapy
or other types of stimulators, careful programming of each system may be necessary to optimize the
patient’s benefit from each device.
Reversal of lead polarity has been associated with an increased chance of bradycardia in animal studies.
It is important that the electrodes are attached to the left vagus nerve in the correct orientation. It is
also important to make sure that leads with dual connector pins are correctly inserted (white marker
band to + connection) into the generator’s lead receptacles.
The patient can use a neck brace for the first week to help ensure proper lead stabilization.
Do not program the VNS Therapy System to an “ON” or periodic stimulation treatment for at least 14
days after the initial or replacement implantation.
For Models 100, 101, 102 and 102R do not use frequencies of 5 Hz or below for long-term stimulation.
Resetting the pulse generator turns the device OFF (output current = 0 mA). For Model 100, 101, 102 and
102R resetting the pulse generator will result in device history loss.
Patients who smoke may have an increased risk of laryngeal irritation.
Generators with AutoStim only — For devices that sense changes in heart rate, false positive detection
may cause unintended stimulation. Examples of instances where heart rate may increase include
exercise, physical activity, and normal autonomic changes in heart rate, both awake and asleep, etc.
Generators with AutoStim only — For the AutoStim feature, the physical location of the device critically
affects this its ability to properly sense heart beats. Therefore, care must be taken to follow the implant
location selection process outlined in the Implantation Procedure. Note that this implant location
selection procedure may be performed preoperatively as part of the patient’s surgical work-up.
M1000/1000-D only — Since the Scheduled Programming feature allows the generator to apply therapy
increases at scheduled intervals, it may not be appropriate for use in patients who are nonverbal or
are unable to use the patient magnet to stop undesired stimulation. Similarly, exercise caution for
use of this feature in patients with a history of obstructive sleep apnea, shortness of breath, coughing,
swallowing difficulties, or aspiration.
6. ENVIRONMENTAL AND MEDICAL THERAPY HAZARDS
Patients should exercise reasonable caution in avoiding devices that generate a strong electric or
magnetic field. If a generator ceases operation while in the presence of electromagnetic interference
(EMI), moving away from the source may allow it to return to its normal mode of operation.
VNS Therapy System operation should always be checked by performing device diagnostics after any of
the procedures mentioned in the physician’s manuals.
For clear imaging, patients may need to be specially positioned for mammography procedures, because
of the location of the generator in the chest.
Therapeutic radiation may damage the generator’s circuitry. Sources of such radiation include
therapeutic radiation, cobalt machines, and linear accelerators. The radiation effect is cumulative, with
the total dosage determining the extent of damage. The effects of exposure to such radiation can range
from a temporary disturbance to permanent damage, and may not be detectable immediately.
External defibrillation may damage the generator.
Use of electrosurgery [electrocautery or radio frequency (RF) ablation devices] may damage
the generator.
Magnetic resonance imaging (MRI) should not be performed using a transmit RF body coil for certain
VNS Therapy device configurations or under certain specific conditions. In some cases, heating of the
lead caused by the transmit RF body coil during MRI may result in serious injury. Static, gradient, and
radio frequency (RF) electromagnetic fields associated with MRI may change the generator settings
(i.e., reset parameters) or activate the VNS device if the Magnet Mode output remains “ON”. Note that
certain magnetic resonance (MR) system head coils operate in receive-only mode and require use of
the transmit RF body coil. Other MR systems use a transmit/receive RF head coil. Local or surface coils
may also be receive-only RF coils that require the transmit RF body coil for MRI. The use of a receive
RF coil does not alter hazards of the transmit RF body coil. Exposure of the VNS Therapy System to any
transmit RF coil must be avoided. Do not perform MRI scans using any transmit RF coil in the defined
exclusion zones. See the MRI with the VNS Therapy System instructions for use for details or further
instructions for special cases such as lead breaks or partially explanted VNS Therapy systems.
Extracorporeal shockwave lithotripsy may damage the generator. If therapeutic ultrasound therapy is
required, avoid positioning the area of the body where the generator is implanted in the water bath
or in any other position that would expose it to ultrasound therapy. If that positioning cannot be
avoided, program the generator output to 0 mA for the treatment, and then after therapy, reprogram the
generator to the original parameters.
If the patient receives medical treatment for which electric current is passed through the body (such as
from a TENS unit), either the generator should be set to 0 mA or function of the generator should be
monitored during initial stages of treatment.
Routine therapeutic ultrasound could damage the generator and may be inadvertently concentrated by
the device, causing harm to the patient.
For complete information related to home occupational environments, cellular phones, other
environmental hazards, other devices, and ECG monitors, refer to the physician’s manuals.
7. ADVERSE EVENTS — EPILEPSY
Adverse events reported during clinical studies as statistically significant are listed below in alphabetical
order: ataxia (loss of the ability to coordinate muscular movement); dyspepsia (indigestion); dyspnea
(difficulty breathing, shortness of breath); hypoesthesia (impaired sense of touch); increased coughing;
infection; insomnia (inability to sleep); laryngismus (throat, larynx spasms); nausea; pain; paresthesia
(prickling of the skin); pharyngitis (inflammation of the pharynx, throat); voice alteration (hoarseness);
vomiting. Adverse events reported in clinical investigation of the AutoStim feature were comparable.
26-0009-0100/6 (OUS) — 1
Brief Summary1 of Safety Information for the VNS Therapy™ System
[Epilepsy Indication] (February 2021)
LIVANOVA USA, INC.
100 Cyberonics Boulevard
Houston, Texas 77058, USA
Tel: +1 (281) 228-7200 /
+1 (800) 332-1375
Fax: +1 (281) 218-9332
www.livanova.com
Manufacturer
LIVANOVA BELGIUM NV
Ikaroslaan 83
B-1930 Zaventem,
BELGIUM
Tel: +3227209593
Fax: +3227206053
www.VNSTherapy.co.uk
1 The information contained in this Brief Summary for Physicians represents partial excerpts of
important prescribing information taken from the physician’s manuals. (Copies of VNS Therapy
physician’s and patient’s manuals are posted at www.livanova.com)The information is not
intended to serve as a substitute for a complete and thorough understanding of the material
presented in all of the physician’s manuals for the VNS Therapy System and its component
parts nor does this information represent full disclosure of all pertinent information
concerning the use of this product, potential safety complications, or efficacy outcomes.
Not available in all regions.
All trademarks and trade names are the property of LivaNova or the property of LivaNova’s consolidated subsidiaries and are protected under applicable
intellectual property laws. Solely for convenience, LivaNova’s trademarks and trade names may appear without the ® or TM symbols, but such references
are not intended to indicate in any way that LivaNova will not assert, to the fullest extent under applicable law, LivaNova’s rights to these trademarks and
trade names. Prior permission from Livanova is required for the use or reproduction of such intellectual property rights. EPI-2300205
1. INTENDED USE / INDICATIONS
Epilepsy (Non-US)—The VNS Therapy System is indicated for use as an adjunctive therapy in reducing
the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures (with or
without secondary generalization) or generalized seizures that are refractory to seizure medications.
AspireSR™, SenTiva™ and SenTiva DUO™ feature an Automatic Stimulation Mode which is intended for
patients who experience seizures that are associated with cardiac rhythm increases known as
ictal tachycardia.
2. CONTRAINDICATIONS
Vagotomy—The VNS Therapy System cannot be used in patients after a bilateral or left
cervical vagotomy.
Diathermy—Do not use short-wave diathermy, microwave diathermy, or therapeutic ultrasound
diathermy on patients implanted with a VNS Therapy System. Diagnostic ultrasound is not included in
this contraindication.
3. WARNINGS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
physician’s manuals. This document is not intended to serve as a substitute for the complete
physician’s manuals.
The safety and efficacy of the VNS Therapy System have not been established for uses outside the
“Intended Use/Indications” chapter of the physician’s manuals.
The safety and effectiveness of the VNS Therapy System in patients with predisposed dysfunction
of cardiac conduction systems (re-entry pathway) have not been established. Post-implant
electrocardiograms and Holter monitoring are recommended if clinically indicated.
Postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias.
It is important to follow recommended implantation procedures and intraoperative product testing
described in the Implantation Procedure chapter of the physician’s manual. During the intraoperative
System Diagnostics (Lead Test), infrequent incidents of bradycardia and/or asystole have occurred.
If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is
encountered during a System Diagnostics (Lead Test) or during initiation of stimulation, physicians
should be prepared to follow guidelines consistent with Advanced Cardiac Life Support (ACLS).
Difficulty swallowing (dysphagia) may occur with active stimulation, and aspiration may result from the
increased swallowing difficulties. Patients with pre-existing swallowing difficulties are at greater risk
for aspiration.
Dyspnea (shortness of breath) may occur with active VNS Therapy. Any patient with underlying
pulmonary disease or insufficiency such as chronic obstructive pulmonary disease or asthma may be at
increased risk for dyspnea.
Patients with obstructive sleep apnea (OSA) may have an increase in apneic events during stimulation.
Lowering stimulus frequency or prolonging “OFF” time may prevent exacerbation of OSA. Vagus nerve
stimulation may also cause new onset sleep apnea in patients who have not previously been diagnosed
with this disorder.
Device malfunction could cause painful stimulation or direct current stimulation. Either event could
cause nerve damage. Patients should be instructed to use the magnet to stop stimulation if they
suspect a malfunction, and then to contact their physician immediately for further evaluation.
Patients with the VNS Therapy System or any part of the VNS Therapy System implanted should have
MRI procedures performed only as described in the MRI with the VNS Therapy System instructions
for use. In some cases, surgery will be required to remove the VNS Therapy System if a scan using a
transmit RF body coil is needed.
Excessive stimulation at an excess duty cycle (i.e., one that occurs when “ON” time is greater than “OFF”
time) and high frequency stimulation (i.e., stimulation at ≥50Hz) has resulted in degenerative nerve
damage in laboratory animals.
Patients who manipulate the generator and lead through the skin (Twiddler’s Syndrome) may damage
or disconnect the lead from the generator and/or possibly cause damage to the vagus nerve.
The Wand, Programmer, and patient magnet are MR unsafe devices. These devices are projectile hazards
and must not be brought into the MR scanner room.
Generators with AutoStim only — The AutoStim Mode feature should not be used in patients with
clinically meaningful arrhythmias or who are using treatments that interfere with normal intrinsic
heart rate responses (e.g., pacemaker dependency, implantable defibrillator, beta adrenergic blocker
medications). Patients also should not have a history of chronotropic incompetence [commonly seen in
patients with sustained bradycardia (heart rate < 50 bpm)].
4. WARNINGS — EPILEPSY
The VNS Therapy System should only be prescribed and monitored by physicians who have specific
training and expertise in the management of seizures and the use of this device. It should only be
implanted by physicians who are trained in surgery of the carotid sheath and have received specific
training in the implantation of this device.
The VNS Therapy System is not curative. Physicians should warn patients that the VNS Therapy System
is not a cure for epilepsy and that since seizures may occur unexpectedly, patients should consult with
a physician before engaging in unsupervised activities, such as driving, swimming, and bathing, and in
strenuous sports that could harm them or others.
Sudden unexpected death in epilepsy (SUDEP): Through August 1996, 10 sudden and unexpected deaths
(definite, probable, and possible) were recorded among the 1,000 patients implanted and treated
with the VNS Therapy device. During this period, these patients had accumulated 2,017 patient-years
of exposure. Some of these deaths could represent seizure-related deaths in which the seizure was
not observed, at night, for example. This number represents an incidence of 5.0 definite, probable,
and possible SUDEP deaths per 1,000 patient-years. Although this rate exceeds that expected in a
healthy (nonepileptic) population matched for age and sex, it is within the range of estimates for
epilepsy patients not receiving vagus nerve stimulation, ranging from 1.3 SUDEP deaths for the general
population of patients with epilepsy, to 3.5 (for definite and probable) for a recently studied antiepileptic
drug (AED) clinical trial population similar to the VNS Therapy System clinical cohort, to 9.3 for patients
with medically intractable epilepsy who were epilepsy surgery candidates.
5. PRECAUTIONS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
VNS Therapy physician’s manuals.
Prescribing physicians should be experienced in the diagnosis and treatment of depression or epilepsy
and should be familiar with the programming and use of the VNS Therapy System.
Physicians who implant the VNS Therapy System should be experienced performing surgery in the
carotid sheath and should be trained in the surgical technique relating to implantation of the
VNS Therapy System.
The safety and effectiveness of the VNS Therapy System have not been established for use during
pregnancy. VNS should be used during pregnancy only if clearly needed.
The VNS Therapy System is indicated for use only in stimulating the left vagus nerve in the neck area
inside the carotid sheath. The VNS Therapy System is indicated for use only in stimulating the left vagus
nerve below where the superior and inferior cervical cardiac branches separate from the vagus nerve.
It is important to follow infection control procedures. Infections related to any implanted device are
difficult to treat and may require that the device be explanted. The patient should be given antibiotics
preoperatively. The surgeon should ensure that all instruments are sterile prior to the procedure.
Children (<12 years of age) may have a greater risk for infection when compared to adolescent and adult
patients (≥ 12 years). Careful monitoring for site infection as well as the avoidance of manipulation of the
surgical site post implant in children should be stressed.
The VNS Therapy System may affect the operation of other implanted devices, such as cardiac
pacemakers and implanted defibrillators. Possible effects include sensing problems and inappropriate
device responses. If the patient requires concurrent implantable pacemaker, defibrillatory therapy
or other types of stimulators, careful programming of each system may be necessary to optimize the
patient’s benefit from each device.
Reversal of lead polarity has been associated with an increased chance of bradycardia in animal studies.
It is important that the electrodes are attached to the left vagus nerve in the correct orientation. It is
also important to make sure that leads with dual connector pins are correctly inserted (white marker
band to + connection) into the generator’s lead receptacles.
The patient can use a neck brace for the first week to help ensure proper lead stabilization.
Do not program the VNS Therapy System to an “ON” or periodic stimulation treatment for at least 14
days after the initial or replacement implantation.
For Models 100, 101, 102 and 102R do not use frequencies of 5 Hz or below for long-term stimulation.
Resetting the pulse generator turns the device OFF (output current = 0 mA). For Model 100, 101, 102 and
102R resetting the pulse generator will result in device history loss.
Patients who smoke may have an increased risk of laryngeal irritation.
Generators with AutoStim only — For devices that sense changes in heart rate, false positive detection
may cause unintended stimulation. Examples of instances where heart rate may increase include
exercise, physical activity, and normal autonomic changes in heart rate, both awake and asleep, etc.
Generators with AutoStim only — For the AutoStim feature, the physical location of the device critically
affects this its ability to properly sense heart beats. Therefore, care must be taken to follow the implant
location selection process outlined in the Implantation Procedure. Note that this implant location
selection procedure may be performed preoperatively as part of the patient’s surgical work-up.
M1000/1000-D only — Since the Scheduled Programming feature allows the generator to apply therapy
increases at scheduled intervals, it may not be appropriate for use in patients who are nonverbal or
are unable to use the patient magnet to stop undesired stimulation. Similarly, exercise caution for
use of this feature in patients with a history of obstructive sleep apnea, shortness of breath, coughing,
swallowing difficulties, or aspiration.
6. ENVIRONMENTAL AND MEDICAL THERAPY HAZARDS
Patients should exercise reasonable caution in avoiding devices that generate a strong electric or
magnetic field. If a generator ceases operation while in the presence of electromagnetic interference
(EMI), moving away from the source may allow it to return to its normal mode of operation.
VNS Therapy System operation should always be checked by performing device diagnostics after any of
the procedures mentioned in the physician’s manuals.
For clear imaging, patients may need to be specially positioned for mammography procedures, because
of the location of the generator in the chest.
Therapeutic radiation may damage the generator’s circuitry. Sources of such radiation include
therapeutic radiation, cobalt machines, and linear accelerators. The radiation effect is cumulative, with
the total dosage determining the extent of damage. The effects of exposure to such radiation can range
from a temporary disturbance to permanent damage, and may not be detectable immediately.
External defibrillation may damage the generator.
Use of electrosurgery [electrocautery or radio frequency (RF) ablation devices] may damage
the generator.
Magnetic resonance imaging (MRI) should not be performed using a transmit RF body coil for certain
VNS Therapy device configurations or under certain specific conditions. In some cases, heating of the
lead caused by the transmit RF body coil during MRI may result in serious injury. Static, gradient, and
radio frequency (RF) electromagnetic fields associated with MRI may change the generator settings
(i.e., reset parameters) or activate the VNS device if the Magnet Mode output remains “ON”. Note that
certain magnetic resonance (MR) system head coils operate in receive-only mode and require use of
the transmit RF body coil. Other MR systems use a transmit/receive RF head coil. Local or surface coils
may also be receive-only RF coils that require the transmit RF body coil for MRI. The use of a receive
RF coil does not alter hazards of the transmit RF body coil. Exposure of the VNS Therapy System to any
transmit RF coil must be avoided. Do not perform MRI scans using any transmit RF coil in the defined
exclusion zones. See the MRI with the VNS Therapy System instructions for use for details or further
instructions for special cases such as lead breaks or partially explanted VNS Therapy systems.
Extracorporeal shockwave lithotripsy may damage the generator. If therapeutic ultrasound therapy is
required, avoid positioning the area of the body where the generator is implanted in the water bath
or in any other position that would expose it to ultrasound therapy. If that positioning cannot be
avoided, program the generator output to 0 mA for the treatment, and then after therapy, reprogram the
generator to the original parameters.
If the patient receives medical treatment for which electric current is passed through the body (such as
from a TENS unit), either the generator should be set to 0 mA or function of the generator should be
monitored during initial stages of treatment.
Routine therapeutic ultrasound could damage the generator and may be inadvertently concentrated by
the device, causing harm to the patient.
For complete information related to home occupational environments, cellular phones, other
environmental hazards, other devices, and ECG monitors, refer to the physician’s manuals.
7. ADVERSE EVENTS — EPILEPSY
Adverse events reported during clinical studies as statistically significant are listed below in alphabetical
order: ataxia (loss of the ability to coordinate muscular movement); dyspepsia (indigestion); dyspnea
(difficulty breathing, shortness of breath); hypoesthesia (impaired sense of touch); increased coughing;
infection; insomnia (inability to sleep); laryngismus (throat, larynx spasms); nausea; pain; paresthesia
(prickling of the skin); pharyngitis (inflammation of the pharynx, throat); voice alteration (hoarseness);
vomiting. Adverse events reported in clinical investigation of the AutoStim feature were comparable.
26-0009-0100/6 (OUS) — 1
Brief Summary1 of Safety Information for the VNS Therapy™ System
[Epilepsy Indication] (February 2021)
1. Main screen before interrogation.
Press Settings (bottom right)
2. Guided Mode Options
3. Choose Therapy Protocols
- here protocols can be imported from
other programmers or created manually
4. Create Protocol
5. Choose either Start from Scratch
or Use Other Protocols listed as a base
6. Click Add Step (up to 7 steps)
7. Select Persistent Parameters
8. Create Protocol name and save
Custom protocols can now be used under Guided Mode
Options after interrogating M1000 and M1000-D.
Creating Custom Therapy Protocols
(Sentiva™ M1000 and Sentiva DUO™ M1000-D only)
• Custom Therapy Protocol allows clinicians to create their own customized protocol
• Custom Therapy Protocols can be saved to the programmer so that the programming settings
and titration scheduled are easily applied and standardised
• Can be exported and imported using a USB drive and transferred to other programmers
Step 1 Step 2
Step 4 Step 6
Please refer to the VNS Therapy™ System Epilepsy Physician’s Manual (OUS), LivaNova USA, Inc. that could be
found at www.vnstherapy.co.uk/physician-manuals for complete information on programming and diagnostics.
For full prescribing and important safety information, please visit www.vnstherapy.co.uk/safety-information
or ask your VNS Therapy representative.
Clinical Technical Services
US, Latin America, Canada, Asia Pacific, Japan
+1-281-228-7330,
+1-866-882-8804
Europe, Middle East, Africa
+32-2-790-27-73
Press Settings (bottom right)
2. Guided Mode Options
3. Choose Therapy Protocols
- here protocols can be imported from
other programmers or created manually
4. Create Protocol
5. Choose either Start from Scratch
or Use Other Protocols listed as a base
6. Click Add Step (up to 7 steps)
7. Select Persistent Parameters
8. Create Protocol name and save
Custom protocols can now be used under Guided Mode
Options after interrogating M1000 and M1000-D.
Creating Custom Therapy Protocols
(Sentiva™ M1000 and Sentiva DUO™ M1000-D only)
• Custom Therapy Protocol allows clinicians to create their own customized protocol
• Custom Therapy Protocols can be saved to the programmer so that the programming settings
and titration scheduled are easily applied and standardised
• Can be exported and imported using a USB drive and transferred to other programmers
Step 1 Step 2
Step 4 Step 6
Please refer to the VNS Therapy™ System Epilepsy Physician’s Manual (OUS), LivaNova USA, Inc. that could be
found at www.vnstherapy.co.uk/physician-manuals for complete information on programming and diagnostics.
For full prescribing and important safety information, please visit www.vnstherapy.co.uk/safety-information
or ask your VNS Therapy representative.
Clinical Technical Services
US, Latin America, Canada, Asia Pacific, Japan
+1-281-228-7330,
+1-866-882-8804
Europe, Middle East, Africa
+32-2-790-27-73
All trademarks and trade names are the property of LivaNova or the property of LivaNova’s consolidated subsidiaries and are protected under applicable
intellectual property laws. Solely for convenience, LivaNova’s trademarks and trade names may appear without the ® or TM symbols, but such references
are not intended to indicate in any way that LivaNova will not assert, to the fullest extent under applicable law, LivaNova’s rights to these trademarks and
trade names. Prior permission from Livanova is required for the use or reproduction of such intellectual property rights. IM-7601541-EPI
LIVANOVA USA, INC.
100 Cyberonics Boulevard
Houston, Texas 77058, USA
Tel: +1 (281) 228-7200 /
+1 (800) 332-1375
Fax: +1 (281) 218-9332
www.livanova.com
LIVANOVA BELGIUM NV
Ikaroslaan 83
B-1930 Zaventem,
BELGIUM
Tel: +3227209593
Fax: +3227206053
www.vnstherapy.co.uk
1 The information contained in this Brief Summary for Physicians represents partial excerpts of
important prescribing information taken from the physician’s manuals. (Copies of VNS Therapy
physician’s and patient’s manuals are posted at www.livanova.com)The information is not
intended to serve as a substitute for a complete and thorough understanding of the material
presented in all of the physician’s manuals for the VNS Therapy System and its component
parts nor does this information represent full disclosure of all pertinent information
concerning the use of this product, potential safety complications, or efficacy outcomes.
1. INTENDED USE / INDICATIONS
Epilepsy (Non-US)—The VNS Therapy System is indicated for use as an adjunctive therapy in reducing
the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures (with or
without secondary generalization) or generalized seizures that are refractory to seizure medications.
AspireSR™, SenTiva™ and SenTiva DUO™ feature an Automatic Stimulation Mode which is intended for
patients who experience seizures that are associated with cardiac rhythm increases known as
ictal tachycardia.
2. CONTRAINDICATIONS
Vagotomy—The VNS Therapy System cannot be used in patients after a bilateral or left
cervical vagotomy.
Diathermy—Do not use short-wave diathermy, microwave diathermy, or therapeutic ultrasound
diathermy on patients implanted with a VNS Therapy System. Diagnostic ultrasound is not included in
this contraindication.
3. WARNINGS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
physician’s manuals. This document is not intended to serve as a substitute for the complete
physician’s manuals.
The safety and efficacy of the VNS Therapy System have not been established for uses outside the
“Intended Use/Indications” chapter of the physician’s manuals.
The safety and effectiveness of the VNS Therapy System in patients with predisposed dysfunction
of cardiac conduction systems (re-entry pathway) have not been established. Post-implant
electrocardiograms and Holter monitoring are recommended if clinically indicated.
Postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias.
It is important to follow recommended implantation procedures and intraoperative product testing
described in the Implantation Procedure chapter of the physician’s manual. During the intraoperative
System Diagnostics (Lead Test), infrequent incidents of bradycardia and/or asystole have occurred.
If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is
encountered during a System Diagnostics (Lead Test) or during initiation of stimulation, physicians
should be prepared to follow guidelines consistent with Advanced Cardiac Life Support (ACLS).
Difficulty swallowing (dysphagia) may occur with active stimulation, and aspiration may result from the
increased swallowing difficulties. Patients with pre-existing swallowing difficulties are at greater risk
for aspiration.
Dyspnea (shortness of breath) may occur with active VNS Therapy. Any patient with underlying
pulmonary disease or insufficiency such as chronic obstructive pulmonary disease or asthma may be at
increased risk for dyspnea.
Patients with obstructive sleep apnea (OSA) may have an increase in apneic events during stimulation.
Lowering stimulus frequency or prolonging “OFF” time may prevent exacerbation of OSA. Vagus nerve
stimulation may also cause new onset sleep apnea in patients who have not previously been diagnosed
with this disorder.
Device malfunction could cause painful stimulation or direct current stimulation. Either event could
cause nerve damage. Patients should be instructed to use the magnet to stop stimulation if they
suspect a malfunction, and then to contact their physician immediately for further evaluation.
Patients with the VNS Therapy System or any part of the VNS Therapy System implanted should have
MRI procedures performed only as described in the MRI with the VNS Therapy System instructions
for use. In some cases, surgery will be required to remove the VNS Therapy System if a scan using a
transmit RF body coil is needed.
Excessive stimulation at an excess duty cycle (i.e., one that occurs when “ON” time is greater than “OFF”
time) and high frequency stimulation (i.e., stimulation at ≥50Hz) has resulted in degenerative nerve
damage in laboratory animals.
Patients who manipulate the generator and lead through the skin (Twiddler’s Syndrome) may damage
or disconnect the lead from the generator and/or possibly cause damage to the vagus nerve.
The Wand, Programmer, and patient magnet are MR unsafe devices. These devices are projectile hazards
and must not be brought into the MR scanner room.
Generators with AutoStim only — The AutoStim Mode feature should not be used in patients with
clinically meaningful arrhythmias or who are using treatments that interfere with normal intrinsic
heart rate responses (e.g., pacemaker dependency, implantable defibrillator, beta adrenergic blocker
medications). Patients also should not have a history of chronotropic incompetence [commonly seen in
patients with sustained bradycardia (heart rate < 50 bpm)].
4. WARNINGS — EPILEPSY
The VNS Therapy System should only be prescribed and monitored by physicians who have specific
training and expertise in the management of seizures and the use of this device. It should only be
implanted by physicians who are trained in surgery of the carotid sheath and have received specific
training in the implantation of this device.
The VNS Therapy System is not curative. Physicians should warn patients that the VNS Therapy System
is not a cure for epilepsy and that since seizures may occur unexpectedly, patients should consult with
a physician before engaging in unsupervised activities, such as driving, swimming, and bathing, and in
strenuous sports that could harm them or others.
Sudden unexpected death in epilepsy (SUDEP): Through August 1996, 10 sudden and unexpected deaths
(definite, probable, and possible) were recorded among the 1,000 patients implanted and treated
with the VNS Therapy device. During this period, these patients had accumulated 2,017 patient-years
of exposure. Some of these deaths could represent seizure-related deaths in which the seizure was
not observed, at night, for example. This number represents an incidence of 5.0 definite, probable,
and possible SUDEP deaths per 1,000 patient-years. Although this rate exceeds that expected in a
healthy (nonepileptic) population matched for age and sex, it is within the range of estimates for
epilepsy patients not receiving vagus nerve stimulation, ranging from 1.3 SUDEP deaths for the general
population of patients with epilepsy, to 3.5 (for definite and probable) for a recently studied antiepileptic
drug (AED) clinical trial population similar to the VNS Therapy System clinical cohort, to 9.3 for patients
with medically intractable epilepsy who were epilepsy surgery candidates.
5. PRECAUTIONS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
VNS Therapy physician’s manuals.
Prescribing physicians should be experienced in the diagnosis and treatment of depression or epilepsy
and should be familiar with the programming and use of the VNS Therapy System.
Physicians who implant the VNS Therapy System should be experienced performing surgery in the
carotid sheath and should be trained in the surgical technique relating to implantation of the
VNS Therapy System.
The safety and effectiveness of the VNS Therapy System have not been established for use during
pregnancy. VNS should be used during pregnancy only if clearly needed.
The VNS Therapy System is indicated for use only in stimulating the left vagus nerve in the neck area
inside the carotid sheath. The VNS Therapy System is indicated for use only in stimulating the left vagus
nerve below where the superior and inferior cervical cardiac branches separate from the vagus nerve.
It is important to follow infection control procedures. Infections related to any implanted device are
difficult to treat and may require that the device be explanted. The patient should be given antibiotics
preoperatively. The surgeon should ensure that all instruments are sterile prior to the procedure.
Children (<12 years of age) may have a greater risk for infection when compared to adolescent and adult
patients (≥ 12 years). Careful monitoring for site infection as well as the avoidance of manipulation of the
surgical site post implant in children should be stressed.
The VNS Therapy System may affect the operation of other implanted devices, such as cardiac
pacemakers and implanted defibrillators. Possible effects include sensing problems and inappropriate
device responses. If the patient requires concurrent implantable pacemaker, defibrillatory therapy
or other types of stimulators, careful programming of each system may be necessary to optimize the
patient’s benefit from each device.
Reversal of lead polarity has been associated with an increased chance of bradycardia in animal studies.
It is important that the electrodes are attached to the left vagus nerve in the correct orientation. It is
also important to make sure that leads with dual connector pins are correctly inserted (white marker
band to + connection) into the generator’s lead receptacles.
The patient can use a neck brace for the first week to help ensure proper lead stabilization.
Do not program the VNS Therapy System to an “ON” or periodic stimulation treatment for at least 14
days after the initial or replacement implantation.
For Models 100, 101, 102 and 102R do not use frequencies of 5 Hz or below for long-term stimulation.
Resetting the pulse generator turns the device OFF (output current = 0 mA). For Model 100, 101, 102 and
102R resetting the pulse generator will result in device history loss.
Patients who smoke may have an increased risk of laryngeal irritation.
Generators with AutoStim only — For devices that sense changes in heart rate, false positive detection
may cause unintended stimulation. Examples of instances where heart rate may increase include
exercise, physical activity, and normal autonomic changes in heart rate, both awake and asleep, etc.
Generators with AutoStim only — For the AutoStim feature, the physical location of the device critically
affects this its ability to properly sense heart beats. Therefore, care must be taken to follow the implant
location selection process outlined in the Implantation Procedure. Note that this implant location
selection procedure may be performed preoperatively as part of the patient’s surgical work-up.
M1000/1000-D only — Since the Scheduled Programming feature allows the generator to apply therapy
increases at scheduled intervals, it may not be appropriate for use in patients who are nonverbal or
are unable to use the patient magnet to stop undesired stimulation. Similarly, exercise caution for
use of this feature in patients with a history of obstructive sleep apnea, shortness of breath, coughing,
swallowing difficulties, or aspiration.
6. ENVIRONMENTAL AND MEDICAL THERAPY HAZARDS
Patients should exercise reasonable caution in avoiding devices that generate a strong electric or
magnetic field. If a generator ceases operation while in the presence of electromagnetic interference
(EMI), moving away from the source may allow it to return to its normal mode of operation.
VNS Therapy System operation should always be checked by performing device diagnostics after any of
the procedures mentioned in the physician’s manuals.
For clear imaging, patients may need to be specially positioned for mammography procedures, because
of the location of the generator in the chest.
Therapeutic radiation may damage the generator’s circuitry. Sources of such radiation include
therapeutic radiation, cobalt machines, and linear accelerators. The radiation effect is cumulative, with
the total dosage determining the extent of damage. The effects of exposure to such radiation can range
from a temporary disturbance to permanent damage, and may not be detectable immediately.
External defibrillation may damage the generator.
Use of electrosurgery [electrocautery or radio frequency (RF) ablation devices] may damage
the generator.
Magnetic resonance imaging (MRI) should not be performed using a transmit RF body coil for certain
VNS Therapy device configurations or under certain specific conditions. In some cases, heating of the
lead caused by the transmit RF body coil during MRI may result in serious injury. Static, gradient, and
radio frequency (RF) electromagnetic fields associated with MRI may change the generator settings
(i.e., reset parameters) or activate the VNS device if the Magnet Mode output remains “ON”. Note that
certain magnetic resonance (MR) system head coils operate in receive-only mode and require use of
the transmit RF body coil. Other MR systems use a transmit/receive RF head coil. Local or surface coils
may also be receive-only RF coils that require the transmit RF body coil for MRI. The use of a receive
RF coil does not alter hazards of the transmit RF body coil. Exposure of the VNS Therapy System to any
transmit RF coil must be avoided. Do not perform MRI scans using any transmit RF coil in the defined
exclusion zones. See the MRI with the VNS Therapy System instructions for use for details or further
instructions for special cases such as lead breaks or partially explanted VNS Therapy systems.
Extracorporeal shockwave lithotripsy may damage the generator. If therapeutic ultrasound therapy is
required, avoid positioning the area of the body where the generator is implanted in the water bath
or in any other position that would expose it to ultrasound therapy. If that positioning cannot be
avoided, program the generator output to 0 mA for the treatment, and then after therapy, reprogram the
generator to the original parameters.
If the patient receives medical treatment for which electric current is passed through the body (such as
from a TENS unit), either the generator should be set to 0 mA or function of the generator should be
monitored during initial stages of treatment.
Routine therapeutic ultrasound could damage the generator and may be inadvertently concentrated by
the device, causing harm to the patient.
For complete information related to home occupational environments, cellular phones, other
environmental hazards, other devices, and ECG monitors, refer to the physician’s manuals.
7. ADVERSE EVENTS — EPILEPSY
Adverse events reported during clinical studies as statistically significant are listed below in alphabetical
order: ataxia (loss of the ability to coordinate muscular movement); dyspepsia (indigestion); dyspnea
(difficulty breathing, shortness of breath); hypoesthesia (impaired sense of touch); increased coughing;
infection; insomnia (inability to sleep); laryngismus (throat, larynx spasms); nausea; pain; paresthesia
(prickling of the skin); pharyngitis (inflammation of the pharynx, throat); voice alteration (hoarseness);
vomiting. Adverse events reported in clinical investigation of the AutoStim feature were comparable.
26-0009-0100/6 (OUS) — 1
Brief Summary1 of Safety Information for the VNS Therapy™ System
[Epilepsy Indication] (February 2021)
intellectual property laws. Solely for convenience, LivaNova’s trademarks and trade names may appear without the ® or TM symbols, but such references
are not intended to indicate in any way that LivaNova will not assert, to the fullest extent under applicable law, LivaNova’s rights to these trademarks and
trade names. Prior permission from Livanova is required for the use or reproduction of such intellectual property rights. IM-7601541-EPI
LIVANOVA USA, INC.
100 Cyberonics Boulevard
Houston, Texas 77058, USA
Tel: +1 (281) 228-7200 /
+1 (800) 332-1375
Fax: +1 (281) 218-9332
www.livanova.com
LIVANOVA BELGIUM NV
Ikaroslaan 83
B-1930 Zaventem,
BELGIUM
Tel: +3227209593
Fax: +3227206053
www.vnstherapy.co.uk
1 The information contained in this Brief Summary for Physicians represents partial excerpts of
important prescribing information taken from the physician’s manuals. (Copies of VNS Therapy
physician’s and patient’s manuals are posted at www.livanova.com)The information is not
intended to serve as a substitute for a complete and thorough understanding of the material
presented in all of the physician’s manuals for the VNS Therapy System and its component
parts nor does this information represent full disclosure of all pertinent information
concerning the use of this product, potential safety complications, or efficacy outcomes.
1. INTENDED USE / INDICATIONS
Epilepsy (Non-US)—The VNS Therapy System is indicated for use as an adjunctive therapy in reducing
the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures (with or
without secondary generalization) or generalized seizures that are refractory to seizure medications.
AspireSR™, SenTiva™ and SenTiva DUO™ feature an Automatic Stimulation Mode which is intended for
patients who experience seizures that are associated with cardiac rhythm increases known as
ictal tachycardia.
2. CONTRAINDICATIONS
Vagotomy—The VNS Therapy System cannot be used in patients after a bilateral or left
cervical vagotomy.
Diathermy—Do not use short-wave diathermy, microwave diathermy, or therapeutic ultrasound
diathermy on patients implanted with a VNS Therapy System. Diagnostic ultrasound is not included in
this contraindication.
3. WARNINGS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
physician’s manuals. This document is not intended to serve as a substitute for the complete
physician’s manuals.
The safety and efficacy of the VNS Therapy System have not been established for uses outside the
“Intended Use/Indications” chapter of the physician’s manuals.
The safety and effectiveness of the VNS Therapy System in patients with predisposed dysfunction
of cardiac conduction systems (re-entry pathway) have not been established. Post-implant
electrocardiograms and Holter monitoring are recommended if clinically indicated.
Postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias.
It is important to follow recommended implantation procedures and intraoperative product testing
described in the Implantation Procedure chapter of the physician’s manual. During the intraoperative
System Diagnostics (Lead Test), infrequent incidents of bradycardia and/or asystole have occurred.
If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is
encountered during a System Diagnostics (Lead Test) or during initiation of stimulation, physicians
should be prepared to follow guidelines consistent with Advanced Cardiac Life Support (ACLS).
Difficulty swallowing (dysphagia) may occur with active stimulation, and aspiration may result from the
increased swallowing difficulties. Patients with pre-existing swallowing difficulties are at greater risk
for aspiration.
Dyspnea (shortness of breath) may occur with active VNS Therapy. Any patient with underlying
pulmonary disease or insufficiency such as chronic obstructive pulmonary disease or asthma may be at
increased risk for dyspnea.
Patients with obstructive sleep apnea (OSA) may have an increase in apneic events during stimulation.
Lowering stimulus frequency or prolonging “OFF” time may prevent exacerbation of OSA. Vagus nerve
stimulation may also cause new onset sleep apnea in patients who have not previously been diagnosed
with this disorder.
Device malfunction could cause painful stimulation or direct current stimulation. Either event could
cause nerve damage. Patients should be instructed to use the magnet to stop stimulation if they
suspect a malfunction, and then to contact their physician immediately for further evaluation.
Patients with the VNS Therapy System or any part of the VNS Therapy System implanted should have
MRI procedures performed only as described in the MRI with the VNS Therapy System instructions
for use. In some cases, surgery will be required to remove the VNS Therapy System if a scan using a
transmit RF body coil is needed.
Excessive stimulation at an excess duty cycle (i.e., one that occurs when “ON” time is greater than “OFF”
time) and high frequency stimulation (i.e., stimulation at ≥50Hz) has resulted in degenerative nerve
damage in laboratory animals.
Patients who manipulate the generator and lead through the skin (Twiddler’s Syndrome) may damage
or disconnect the lead from the generator and/or possibly cause damage to the vagus nerve.
The Wand, Programmer, and patient magnet are MR unsafe devices. These devices are projectile hazards
and must not be brought into the MR scanner room.
Generators with AutoStim only — The AutoStim Mode feature should not be used in patients with
clinically meaningful arrhythmias or who are using treatments that interfere with normal intrinsic
heart rate responses (e.g., pacemaker dependency, implantable defibrillator, beta adrenergic blocker
medications). Patients also should not have a history of chronotropic incompetence [commonly seen in
patients with sustained bradycardia (heart rate < 50 bpm)].
4. WARNINGS — EPILEPSY
The VNS Therapy System should only be prescribed and monitored by physicians who have specific
training and expertise in the management of seizures and the use of this device. It should only be
implanted by physicians who are trained in surgery of the carotid sheath and have received specific
training in the implantation of this device.
The VNS Therapy System is not curative. Physicians should warn patients that the VNS Therapy System
is not a cure for epilepsy and that since seizures may occur unexpectedly, patients should consult with
a physician before engaging in unsupervised activities, such as driving, swimming, and bathing, and in
strenuous sports that could harm them or others.
Sudden unexpected death in epilepsy (SUDEP): Through August 1996, 10 sudden and unexpected deaths
(definite, probable, and possible) were recorded among the 1,000 patients implanted and treated
with the VNS Therapy device. During this period, these patients had accumulated 2,017 patient-years
of exposure. Some of these deaths could represent seizure-related deaths in which the seizure was
not observed, at night, for example. This number represents an incidence of 5.0 definite, probable,
and possible SUDEP deaths per 1,000 patient-years. Although this rate exceeds that expected in a
healthy (nonepileptic) population matched for age and sex, it is within the range of estimates for
epilepsy patients not receiving vagus nerve stimulation, ranging from 1.3 SUDEP deaths for the general
population of patients with epilepsy, to 3.5 (for definite and probable) for a recently studied antiepileptic
drug (AED) clinical trial population similar to the VNS Therapy System clinical cohort, to 9.3 for patients
with medically intractable epilepsy who were epilepsy surgery candidates.
5. PRECAUTIONS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
VNS Therapy physician’s manuals.
Prescribing physicians should be experienced in the diagnosis and treatment of depression or epilepsy
and should be familiar with the programming and use of the VNS Therapy System.
Physicians who implant the VNS Therapy System should be experienced performing surgery in the
carotid sheath and should be trained in the surgical technique relating to implantation of the
VNS Therapy System.
The safety and effectiveness of the VNS Therapy System have not been established for use during
pregnancy. VNS should be used during pregnancy only if clearly needed.
The VNS Therapy System is indicated for use only in stimulating the left vagus nerve in the neck area
inside the carotid sheath. The VNS Therapy System is indicated for use only in stimulating the left vagus
nerve below where the superior and inferior cervical cardiac branches separate from the vagus nerve.
It is important to follow infection control procedures. Infections related to any implanted device are
difficult to treat and may require that the device be explanted. The patient should be given antibiotics
preoperatively. The surgeon should ensure that all instruments are sterile prior to the procedure.
Children (<12 years of age) may have a greater risk for infection when compared to adolescent and adult
patients (≥ 12 years). Careful monitoring for site infection as well as the avoidance of manipulation of the
surgical site post implant in children should be stressed.
The VNS Therapy System may affect the operation of other implanted devices, such as cardiac
pacemakers and implanted defibrillators. Possible effects include sensing problems and inappropriate
device responses. If the patient requires concurrent implantable pacemaker, defibrillatory therapy
or other types of stimulators, careful programming of each system may be necessary to optimize the
patient’s benefit from each device.
Reversal of lead polarity has been associated with an increased chance of bradycardia in animal studies.
It is important that the electrodes are attached to the left vagus nerve in the correct orientation. It is
also important to make sure that leads with dual connector pins are correctly inserted (white marker
band to + connection) into the generator’s lead receptacles.
The patient can use a neck brace for the first week to help ensure proper lead stabilization.
Do not program the VNS Therapy System to an “ON” or periodic stimulation treatment for at least 14
days after the initial or replacement implantation.
For Models 100, 101, 102 and 102R do not use frequencies of 5 Hz or below for long-term stimulation.
Resetting the pulse generator turns the device OFF (output current = 0 mA). For Model 100, 101, 102 and
102R resetting the pulse generator will result in device history loss.
Patients who smoke may have an increased risk of laryngeal irritation.
Generators with AutoStim only — For devices that sense changes in heart rate, false positive detection
may cause unintended stimulation. Examples of instances where heart rate may increase include
exercise, physical activity, and normal autonomic changes in heart rate, both awake and asleep, etc.
Generators with AutoStim only — For the AutoStim feature, the physical location of the device critically
affects this its ability to properly sense heart beats. Therefore, care must be taken to follow the implant
location selection process outlined in the Implantation Procedure. Note that this implant location
selection procedure may be performed preoperatively as part of the patient’s surgical work-up.
M1000/1000-D only — Since the Scheduled Programming feature allows the generator to apply therapy
increases at scheduled intervals, it may not be appropriate for use in patients who are nonverbal or
are unable to use the patient magnet to stop undesired stimulation. Similarly, exercise caution for
use of this feature in patients with a history of obstructive sleep apnea, shortness of breath, coughing,
swallowing difficulties, or aspiration.
6. ENVIRONMENTAL AND MEDICAL THERAPY HAZARDS
Patients should exercise reasonable caution in avoiding devices that generate a strong electric or
magnetic field. If a generator ceases operation while in the presence of electromagnetic interference
(EMI), moving away from the source may allow it to return to its normal mode of operation.
VNS Therapy System operation should always be checked by performing device diagnostics after any of
the procedures mentioned in the physician’s manuals.
For clear imaging, patients may need to be specially positioned for mammography procedures, because
of the location of the generator in the chest.
Therapeutic radiation may damage the generator’s circuitry. Sources of such radiation include
therapeutic radiation, cobalt machines, and linear accelerators. The radiation effect is cumulative, with
the total dosage determining the extent of damage. The effects of exposure to such radiation can range
from a temporary disturbance to permanent damage, and may not be detectable immediately.
External defibrillation may damage the generator.
Use of electrosurgery [electrocautery or radio frequency (RF) ablation devices] may damage
the generator.
Magnetic resonance imaging (MRI) should not be performed using a transmit RF body coil for certain
VNS Therapy device configurations or under certain specific conditions. In some cases, heating of the
lead caused by the transmit RF body coil during MRI may result in serious injury. Static, gradient, and
radio frequency (RF) electromagnetic fields associated with MRI may change the generator settings
(i.e., reset parameters) or activate the VNS device if the Magnet Mode output remains “ON”. Note that
certain magnetic resonance (MR) system head coils operate in receive-only mode and require use of
the transmit RF body coil. Other MR systems use a transmit/receive RF head coil. Local or surface coils
may also be receive-only RF coils that require the transmit RF body coil for MRI. The use of a receive
RF coil does not alter hazards of the transmit RF body coil. Exposure of the VNS Therapy System to any
transmit RF coil must be avoided. Do not perform MRI scans using any transmit RF coil in the defined
exclusion zones. See the MRI with the VNS Therapy System instructions for use for details or further
instructions for special cases such as lead breaks or partially explanted VNS Therapy systems.
Extracorporeal shockwave lithotripsy may damage the generator. If therapeutic ultrasound therapy is
required, avoid positioning the area of the body where the generator is implanted in the water bath
or in any other position that would expose it to ultrasound therapy. If that positioning cannot be
avoided, program the generator output to 0 mA for the treatment, and then after therapy, reprogram the
generator to the original parameters.
If the patient receives medical treatment for which electric current is passed through the body (such as
from a TENS unit), either the generator should be set to 0 mA or function of the generator should be
monitored during initial stages of treatment.
Routine therapeutic ultrasound could damage the generator and may be inadvertently concentrated by
the device, causing harm to the patient.
For complete information related to home occupational environments, cellular phones, other
environmental hazards, other devices, and ECG monitors, refer to the physician’s manuals.
7. ADVERSE EVENTS — EPILEPSY
Adverse events reported during clinical studies as statistically significant are listed below in alphabetical
order: ataxia (loss of the ability to coordinate muscular movement); dyspepsia (indigestion); dyspnea
(difficulty breathing, shortness of breath); hypoesthesia (impaired sense of touch); increased coughing;
infection; insomnia (inability to sleep); laryngismus (throat, larynx spasms); nausea; pain; paresthesia
(prickling of the skin); pharyngitis (inflammation of the pharynx, throat); voice alteration (hoarseness);
vomiting. Adverse events reported in clinical investigation of the AutoStim feature were comparable.
26-0009-0100/6 (OUS) — 1
Brief Summary1 of Safety Information for the VNS Therapy™ System
[Epilepsy Indication] (February 2021)
Steps to follow:
1. Confirm correct date and time
2. Interrogate the Generator
3. Go to parameters screen
4. Enable Day – Night
5. Respond YES to « Do you want to create a Day-
Night program? »
6. Select Nighttime Start and End Times
7. Make parameter adjustments
8. Select Detection Tab and then
Set Autostim Threshold
9. Apply changes
10. Review changes and confirm
11. Interrogate
12. End session
Day-Night Programming
(Sentiva™ M1000 and Sentiva DUO™ M1000-D only)
• Day-Night programming allow physicians
to customize two independent sets of
parameters that alternate based on time
of day within a 24-hour period
• Is only available in Manual Mode and not in
Guided Mode
• Time zone changes and Daylight savings time
changes must be programmed manually as
the programmer does not automatically adjust
for these changes. After programming on this
feature, the patient will experience 15 minutes
of the alternate parameter set
Step 1
Step 3 Step 4
Step 5 Step 6
Step 8
Please refer to the VNS Therapy™ System Epilepsy Physician’s Manual (OUS), LivaNova USA, Inc. that could be
found at www.vnstherapy.co.uk/physician-manuals for complete information on programming and diagnostics.
For full prescribing and important safety information, please visit www.vnstherapy.co.uk/safety-information
or ask your VNS Therapy representative.
Clinical Technical Services
US, Latin America, Canada, Asia Pacific, Japan
+1-281-228-7330,
+1-866-882-8804
Europe, Middle East, Africa
+32-2-790-27-73
1. Confirm correct date and time
2. Interrogate the Generator
3. Go to parameters screen
4. Enable Day – Night
5. Respond YES to « Do you want to create a Day-
Night program? »
6. Select Nighttime Start and End Times
7. Make parameter adjustments
8. Select Detection Tab and then
Set Autostim Threshold
9. Apply changes
10. Review changes and confirm
11. Interrogate
12. End session
Day-Night Programming
(Sentiva™ M1000 and Sentiva DUO™ M1000-D only)
• Day-Night programming allow physicians
to customize two independent sets of
parameters that alternate based on time
of day within a 24-hour period
• Is only available in Manual Mode and not in
Guided Mode
• Time zone changes and Daylight savings time
changes must be programmed manually as
the programmer does not automatically adjust
for these changes. After programming on this
feature, the patient will experience 15 minutes
of the alternate parameter set
Step 1
Step 3 Step 4
Step 5 Step 6
Step 8
Please refer to the VNS Therapy™ System Epilepsy Physician’s Manual (OUS), LivaNova USA, Inc. that could be
found at www.vnstherapy.co.uk/physician-manuals for complete information on programming and diagnostics.
For full prescribing and important safety information, please visit www.vnstherapy.co.uk/safety-information
or ask your VNS Therapy representative.
Clinical Technical Services
US, Latin America, Canada, Asia Pacific, Japan
+1-281-228-7330,
+1-866-882-8804
Europe, Middle East, Africa
+32-2-790-27-73
All trademarks and trade names are the property of LivaNova or the property of LivaNova’s consolidated subsidiaries and are protected under applicable
intellectual property laws. Solely for convenience, LivaNova’s trademarks and trade names may appear without the ® or TM symbols, but such references
are not intended to indicate in any way that LivaNova will not assert, to the fullest extent under applicable law, LivaNova’s rights to these trademarks and
trade names. Prior permission from Livanova is required for the use or reproduction of such intellectual property rights. IM-7601540-EPI
LIVANOVA USA, INC.
100 Cyberonics Boulevard
Houston, Texas 77058, USA
Tel: +1 (281) 228-7200 /
+1 (800) 332-1375
Fax: +1 (281) 218-9332
www.livanova.com
LIVANOVA BELGIUM NV
Ikaroslaan 83
B-1930 Zaventem,
BELGIUM
Tel: +3227209593
Fax: +3227206053
www.vnstherapy.co.uk
1 The information contained in this Brief Summary for Physicians represents partial excerpts of
important prescribing information taken from the physician’s manuals. (Copies of VNS Therapy
physician’s and patient’s manuals are posted at www.livanova.com)The information is not
intended to serve as a substitute for a complete and thorough understanding of the material
presented in all of the physician’s manuals for the VNS Therapy System and its component
parts nor does this information represent full disclosure of all pertinent information
concerning the use of this product, potential safety complications, or efficacy outcomes.
1. INTENDED USE / INDICATIONS
Epilepsy (Non-US)—The VNS Therapy System is indicated for use as an adjunctive therapy in reducing
the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures (with or
without secondary generalization) or generalized seizures that are refractory to seizure medications.
AspireSR™, SenTiva™ and SenTiva DUO™ feature an Automatic Stimulation Mode which is intended for
patients who experience seizures that are associated with cardiac rhythm increases known as
ictal tachycardia.
2. CONTRAINDICATIONS
Vagotomy—The VNS Therapy System cannot be used in patients after a bilateral or left
cervical vagotomy.
Diathermy—Do not use short-wave diathermy, microwave diathermy, or therapeutic ultrasound
diathermy on patients implanted with a VNS Therapy System. Diagnostic ultrasound is not included in
this contraindication.
3. WARNINGS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
physician’s manuals. This document is not intended to serve as a substitute for the complete
physician’s manuals.
The safety and efficacy of the VNS Therapy System have not been established for uses outside the
“Intended Use/Indications” chapter of the physician’s manuals.
The safety and effectiveness of the VNS Therapy System in patients with predisposed dysfunction
of cardiac conduction systems (re-entry pathway) have not been established. Post-implant
electrocardiograms and Holter monitoring are recommended if clinically indicated.
Postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias.
It is important to follow recommended implantation procedures and intraoperative product testing
described in the Implantation Procedure chapter of the physician’s manual. During the intraoperative
System Diagnostics (Lead Test), infrequent incidents of bradycardia and/or asystole have occurred.
If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is
encountered during a System Diagnostics (Lead Test) or during initiation of stimulation, physicians
should be prepared to follow guidelines consistent with Advanced Cardiac Life Support (ACLS).
Difficulty swallowing (dysphagia) may occur with active stimulation, and aspiration may result from the
increased swallowing difficulties. Patients with pre-existing swallowing difficulties are at greater risk
for aspiration.
Dyspnea (shortness of breath) may occur with active VNS Therapy. Any patient with underlying
pulmonary disease or insufficiency such as chronic obstructive pulmonary disease or asthma may be at
increased risk for dyspnea.
Patients with obstructive sleep apnea (OSA) may have an increase in apneic events during stimulation.
Lowering stimulus frequency or prolonging “OFF” time may prevent exacerbation of OSA. Vagus nerve
stimulation may also cause new onset sleep apnea in patients who have not previously been diagnosed
with this disorder.
Device malfunction could cause painful stimulation or direct current stimulation. Either event could
cause nerve damage. Patients should be instructed to use the magnet to stop stimulation if they
suspect a malfunction, and then to contact their physician immediately for further evaluation.
Patients with the VNS Therapy System or any part of the VNS Therapy System implanted should have
MRI procedures performed only as described in the MRI with the VNS Therapy System instructions
for use. In some cases, surgery will be required to remove the VNS Therapy System if a scan using a
transmit RF body coil is needed.
Excessive stimulation at an excess duty cycle (i.e., one that occurs when “ON” time is greater than “OFF”
time) and high frequency stimulation (i.e., stimulation at ≥50Hz) has resulted in degenerative nerve
damage in laboratory animals.
Patients who manipulate the generator and lead through the skin (Twiddler’s Syndrome) may damage
or disconnect the lead from the generator and/or possibly cause damage to the vagus nerve.
The Wand, Programmer, and patient magnet are MR unsafe devices. These devices are projectile hazards
and must not be brought into the MR scanner room.
Generators with AutoStim only — The AutoStim Mode feature should not be used in patients with
clinically meaningful arrhythmias or who are using treatments that interfere with normal intrinsic
heart rate responses (e.g., pacemaker dependency, implantable defibrillator, beta adrenergic blocker
medications). Patients also should not have a history of chronotropic incompetence [commonly seen in
patients with sustained bradycardia (heart rate < 50 bpm)].
4. WARNINGS — EPILEPSY
The VNS Therapy System should only be prescribed and monitored by physicians who have specific
training and expertise in the management of seizures and the use of this device. It should only be
implanted by physicians who are trained in surgery of the carotid sheath and have received specific
training in the implantation of this device.
The VNS Therapy System is not curative. Physicians should warn patients that the VNS Therapy System
is not a cure for epilepsy and that since seizures may occur unexpectedly, patients should consult with
a physician before engaging in unsupervised activities, such as driving, swimming, and bathing, and in
strenuous sports that could harm them or others.
Sudden unexpected death in epilepsy (SUDEP): Through August 1996, 10 sudden and unexpected deaths
(definite, probable, and possible) were recorded among the 1,000 patients implanted and treated
with the VNS Therapy device. During this period, these patients had accumulated 2,017 patient-years
of exposure. Some of these deaths could represent seizure-related deaths in which the seizure was
not observed, at night, for example. This number represents an incidence of 5.0 definite, probable,
and possible SUDEP deaths per 1,000 patient-years. Although this rate exceeds that expected in a
healthy (nonepileptic) population matched for age and sex, it is within the range of estimates for
epilepsy patients not receiving vagus nerve stimulation, ranging from 1.3 SUDEP deaths for the general
population of patients with epilepsy, to 3.5 (for definite and probable) for a recently studied antiepileptic
drug (AED) clinical trial population similar to the VNS Therapy System clinical cohort, to 9.3 for patients
with medically intractable epilepsy who were epilepsy surgery candidates.
5. PRECAUTIONS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
VNS Therapy physician’s manuals.
Prescribing physicians should be experienced in the diagnosis and treatment of depression or epilepsy
and should be familiar with the programming and use of the VNS Therapy System.
Physicians who implant the VNS Therapy System should be experienced performing surgery in the
carotid sheath and should be trained in the surgical technique relating to implantation of the
VNS Therapy System.
The safety and effectiveness of the VNS Therapy System have not been established for use during
pregnancy. VNS should be used during pregnancy only if clearly needed.
The VNS Therapy System is indicated for use only in stimulating the left vagus nerve in the neck area
inside the carotid sheath. The VNS Therapy System is indicated for use only in stimulating the left vagus
nerve below where the superior and inferior cervical cardiac branches separate from the vagus nerve.
It is important to follow infection control procedures. Infections related to any implanted device are
difficult to treat and may require that the device be explanted. The patient should be given antibiotics
preoperatively. The surgeon should ensure that all instruments are sterile prior to the procedure.
Children (<12 years of age) may have a greater risk for infection when compared to adolescent and adult
patients (≥ 12 years). Careful monitoring for site infection as well as the avoidance of manipulation of the
surgical site post implant in children should be stressed.
The VNS Therapy System may affect the operation of other implanted devices, such as cardiac
pacemakers and implanted defibrillators. Possible effects include sensing problems and inappropriate
device responses. If the patient requires concurrent implantable pacemaker, defibrillatory therapy
or other types of stimulators, careful programming of each system may be necessary to optimize the
patient’s benefit from each device.
Reversal of lead polarity has been associated with an increased chance of bradycardia in animal studies.
It is important that the electrodes are attached to the left vagus nerve in the correct orientation. It is
also important to make sure that leads with dual connector pins are correctly inserted (white marker
band to + connection) into the generator’s lead receptacles.
The patient can use a neck brace for the first week to help ensure proper lead stabilization.
Do not program the VNS Therapy System to an “ON” or periodic stimulation treatment for at least 14
days after the initial or replacement implantation.
For Models 100, 101, 102 and 102R do not use frequencies of 5 Hz or below for long-term stimulation.
Resetting the pulse generator turns the device OFF (output current = 0 mA). For Model 100, 101, 102 and
102R resetting the pulse generator will result in device history loss.
Patients who smoke may have an increased risk of laryngeal irritation.
Generators with AutoStim only — For devices that sense changes in heart rate, false positive detection
may cause unintended stimulation. Examples of instances where heart rate may increase include
exercise, physical activity, and normal autonomic changes in heart rate, both awake and asleep, etc.
Generators with AutoStim only — For the AutoStim feature, the physical location of the device critically
affects this its ability to properly sense heart beats. Therefore, care must be taken to follow the implant
location selection process outlined in the Implantation Procedure. Note that this implant location
selection procedure may be performed preoperatively as part of the patient’s surgical work-up.
M1000/1000-D only — Since the Scheduled Programming feature allows the generator to apply therapy
increases at scheduled intervals, it may not be appropriate for use in patients who are nonverbal or
are unable to use the patient magnet to stop undesired stimulation. Similarly, exercise caution for
use of this feature in patients with a history of obstructive sleep apnea, shortness of breath, coughing,
swallowing difficulties, or aspiration.
6. ENVIRONMENTAL AND MEDICAL THERAPY HAZARDS
Patients should exercise reasonable caution in avoiding devices that generate a strong electric or
magnetic field. If a generator ceases operation while in the presence of electromagnetic interference
(EMI), moving away from the source may allow it to return to its normal mode of operation.
VNS Therapy System operation should always be checked by performing device diagnostics after any of
the procedures mentioned in the physician’s manuals.
For clear imaging, patients may need to be specially positioned for mammography procedures, because
of the location of the generator in the chest.
Therapeutic radiation may damage the generator’s circuitry. Sources of such radiation include
therapeutic radiation, cobalt machines, and linear accelerators. The radiation effect is cumulative, with
the total dosage determining the extent of damage. The effects of exposure to such radiation can range
from a temporary disturbance to permanent damage, and may not be detectable immediately.
External defibrillation may damage the generator.
Use of electrosurgery [electrocautery or radio frequency (RF) ablation devices] may damage
the generator.
Magnetic resonance imaging (MRI) should not be performed using a transmit RF body coil for certain
VNS Therapy device configurations or under certain specific conditions. In some cases, heating of the
lead caused by the transmit RF body coil during MRI may result in serious injury. Static, gradient, and
radio frequency (RF) electromagnetic fields associated with MRI may change the generator settings
(i.e., reset parameters) or activate the VNS device if the Magnet Mode output remains “ON”. Note that
certain magnetic resonance (MR) system head coils operate in receive-only mode and require use of
the transmit RF body coil. Other MR systems use a transmit/receive RF head coil. Local or surface coils
may also be receive-only RF coils that require the transmit RF body coil for MRI. The use of a receive
RF coil does not alter hazards of the transmit RF body coil. Exposure of the VNS Therapy System to any
transmit RF coil must be avoided. Do not perform MRI scans using any transmit RF coil in the defined
exclusion zones. See the MRI with the VNS Therapy System instructions for use for details or further
instructions for special cases such as lead breaks or partially explanted VNS Therapy systems.
Extracorporeal shockwave lithotripsy may damage the generator. If therapeutic ultrasound therapy is
required, avoid positioning the area of the body where the generator is implanted in the water bath
or in any other position that would expose it to ultrasound therapy. If that positioning cannot be
avoided, program the generator output to 0 mA for the treatment, and then after therapy, reprogram the
generator to the original parameters.
If the patient receives medical treatment for which electric current is passed through the body (such as
from a TENS unit), either the generator should be set to 0 mA or function of the generator should be
monitored during initial stages of treatment.
Routine therapeutic ultrasound could damage the generator and may be inadvertently concentrated by
the device, causing harm to the patient.
For complete information related to home occupational environments, cellular phones, other
environmental hazards, other devices, and ECG monitors, refer to the physician’s manuals.
7. ADVERSE EVENTS — EPILEPSY
Adverse events reported during clinical studies as statistically significant are listed below in alphabetical
order: ataxia (loss of the ability to coordinate muscular movement); dyspepsia (indigestion); dyspnea
(difficulty breathing, shortness of breath); hypoesthesia (impaired sense of touch); increased coughing;
infection; insomnia (inability to sleep); laryngismus (throat, larynx spasms); nausea; pain; paresthesia
(prickling of the skin); pharyngitis (inflammation of the pharynx, throat); voice alteration (hoarseness);
vomiting. Adverse events reported in clinical investigation of the AutoStim feature were comparable.
26-0009-0100/6 (OUS) — 1
Brief Summary1 of Safety Information for the VNS Therapy™ System
[Epilepsy Indication] (February 2021)
intellectual property laws. Solely for convenience, LivaNova’s trademarks and trade names may appear without the ® or TM symbols, but such references
are not intended to indicate in any way that LivaNova will not assert, to the fullest extent under applicable law, LivaNova’s rights to these trademarks and
trade names. Prior permission from Livanova is required for the use or reproduction of such intellectual property rights. IM-7601540-EPI
LIVANOVA USA, INC.
100 Cyberonics Boulevard
Houston, Texas 77058, USA
Tel: +1 (281) 228-7200 /
+1 (800) 332-1375
Fax: +1 (281) 218-9332
www.livanova.com
LIVANOVA BELGIUM NV
Ikaroslaan 83
B-1930 Zaventem,
BELGIUM
Tel: +3227209593
Fax: +3227206053
www.vnstherapy.co.uk
1 The information contained in this Brief Summary for Physicians represents partial excerpts of
important prescribing information taken from the physician’s manuals. (Copies of VNS Therapy
physician’s and patient’s manuals are posted at www.livanova.com)The information is not
intended to serve as a substitute for a complete and thorough understanding of the material
presented in all of the physician’s manuals for the VNS Therapy System and its component
parts nor does this information represent full disclosure of all pertinent information
concerning the use of this product, potential safety complications, or efficacy outcomes.
1. INTENDED USE / INDICATIONS
Epilepsy (Non-US)—The VNS Therapy System is indicated for use as an adjunctive therapy in reducing
the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures (with or
without secondary generalization) or generalized seizures that are refractory to seizure medications.
AspireSR™, SenTiva™ and SenTiva DUO™ feature an Automatic Stimulation Mode which is intended for
patients who experience seizures that are associated with cardiac rhythm increases known as
ictal tachycardia.
2. CONTRAINDICATIONS
Vagotomy—The VNS Therapy System cannot be used in patients after a bilateral or left
cervical vagotomy.
Diathermy—Do not use short-wave diathermy, microwave diathermy, or therapeutic ultrasound
diathermy on patients implanted with a VNS Therapy System. Diagnostic ultrasound is not included in
this contraindication.
3. WARNINGS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
physician’s manuals. This document is not intended to serve as a substitute for the complete
physician’s manuals.
The safety and efficacy of the VNS Therapy System have not been established for uses outside the
“Intended Use/Indications” chapter of the physician’s manuals.
The safety and effectiveness of the VNS Therapy System in patients with predisposed dysfunction
of cardiac conduction systems (re-entry pathway) have not been established. Post-implant
electrocardiograms and Holter monitoring are recommended if clinically indicated.
Postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias.
It is important to follow recommended implantation procedures and intraoperative product testing
described in the Implantation Procedure chapter of the physician’s manual. During the intraoperative
System Diagnostics (Lead Test), infrequent incidents of bradycardia and/or asystole have occurred.
If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is
encountered during a System Diagnostics (Lead Test) or during initiation of stimulation, physicians
should be prepared to follow guidelines consistent with Advanced Cardiac Life Support (ACLS).
Difficulty swallowing (dysphagia) may occur with active stimulation, and aspiration may result from the
increased swallowing difficulties. Patients with pre-existing swallowing difficulties are at greater risk
for aspiration.
Dyspnea (shortness of breath) may occur with active VNS Therapy. Any patient with underlying
pulmonary disease or insufficiency such as chronic obstructive pulmonary disease or asthma may be at
increased risk for dyspnea.
Patients with obstructive sleep apnea (OSA) may have an increase in apneic events during stimulation.
Lowering stimulus frequency or prolonging “OFF” time may prevent exacerbation of OSA. Vagus nerve
stimulation may also cause new onset sleep apnea in patients who have not previously been diagnosed
with this disorder.
Device malfunction could cause painful stimulation or direct current stimulation. Either event could
cause nerve damage. Patients should be instructed to use the magnet to stop stimulation if they
suspect a malfunction, and then to contact their physician immediately for further evaluation.
Patients with the VNS Therapy System or any part of the VNS Therapy System implanted should have
MRI procedures performed only as described in the MRI with the VNS Therapy System instructions
for use. In some cases, surgery will be required to remove the VNS Therapy System if a scan using a
transmit RF body coil is needed.
Excessive stimulation at an excess duty cycle (i.e., one that occurs when “ON” time is greater than “OFF”
time) and high frequency stimulation (i.e., stimulation at ≥50Hz) has resulted in degenerative nerve
damage in laboratory animals.
Patients who manipulate the generator and lead through the skin (Twiddler’s Syndrome) may damage
or disconnect the lead from the generator and/or possibly cause damage to the vagus nerve.
The Wand, Programmer, and patient magnet are MR unsafe devices. These devices are projectile hazards
and must not be brought into the MR scanner room.
Generators with AutoStim only — The AutoStim Mode feature should not be used in patients with
clinically meaningful arrhythmias or who are using treatments that interfere with normal intrinsic
heart rate responses (e.g., pacemaker dependency, implantable defibrillator, beta adrenergic blocker
medications). Patients also should not have a history of chronotropic incompetence [commonly seen in
patients with sustained bradycardia (heart rate < 50 bpm)].
4. WARNINGS — EPILEPSY
The VNS Therapy System should only be prescribed and monitored by physicians who have specific
training and expertise in the management of seizures and the use of this device. It should only be
implanted by physicians who are trained in surgery of the carotid sheath and have received specific
training in the implantation of this device.
The VNS Therapy System is not curative. Physicians should warn patients that the VNS Therapy System
is not a cure for epilepsy and that since seizures may occur unexpectedly, patients should consult with
a physician before engaging in unsupervised activities, such as driving, swimming, and bathing, and in
strenuous sports that could harm them or others.
Sudden unexpected death in epilepsy (SUDEP): Through August 1996, 10 sudden and unexpected deaths
(definite, probable, and possible) were recorded among the 1,000 patients implanted and treated
with the VNS Therapy device. During this period, these patients had accumulated 2,017 patient-years
of exposure. Some of these deaths could represent seizure-related deaths in which the seizure was
not observed, at night, for example. This number represents an incidence of 5.0 definite, probable,
and possible SUDEP deaths per 1,000 patient-years. Although this rate exceeds that expected in a
healthy (nonepileptic) population matched for age and sex, it is within the range of estimates for
epilepsy patients not receiving vagus nerve stimulation, ranging from 1.3 SUDEP deaths for the general
population of patients with epilepsy, to 3.5 (for definite and probable) for a recently studied antiepileptic
drug (AED) clinical trial population similar to the VNS Therapy System clinical cohort, to 9.3 for patients
with medically intractable epilepsy who were epilepsy surgery candidates.
5. PRECAUTIONS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
VNS Therapy physician’s manuals.
Prescribing physicians should be experienced in the diagnosis and treatment of depression or epilepsy
and should be familiar with the programming and use of the VNS Therapy System.
Physicians who implant the VNS Therapy System should be experienced performing surgery in the
carotid sheath and should be trained in the surgical technique relating to implantation of the
VNS Therapy System.
The safety and effectiveness of the VNS Therapy System have not been established for use during
pregnancy. VNS should be used during pregnancy only if clearly needed.
The VNS Therapy System is indicated for use only in stimulating the left vagus nerve in the neck area
inside the carotid sheath. The VNS Therapy System is indicated for use only in stimulating the left vagus
nerve below where the superior and inferior cervical cardiac branches separate from the vagus nerve.
It is important to follow infection control procedures. Infections related to any implanted device are
difficult to treat and may require that the device be explanted. The patient should be given antibiotics
preoperatively. The surgeon should ensure that all instruments are sterile prior to the procedure.
Children (<12 years of age) may have a greater risk for infection when compared to adolescent and adult
patients (≥ 12 years). Careful monitoring for site infection as well as the avoidance of manipulation of the
surgical site post implant in children should be stressed.
The VNS Therapy System may affect the operation of other implanted devices, such as cardiac
pacemakers and implanted defibrillators. Possible effects include sensing problems and inappropriate
device responses. If the patient requires concurrent implantable pacemaker, defibrillatory therapy
or other types of stimulators, careful programming of each system may be necessary to optimize the
patient’s benefit from each device.
Reversal of lead polarity has been associated with an increased chance of bradycardia in animal studies.
It is important that the electrodes are attached to the left vagus nerve in the correct orientation. It is
also important to make sure that leads with dual connector pins are correctly inserted (white marker
band to + connection) into the generator’s lead receptacles.
The patient can use a neck brace for the first week to help ensure proper lead stabilization.
Do not program the VNS Therapy System to an “ON” or periodic stimulation treatment for at least 14
days after the initial or replacement implantation.
For Models 100, 101, 102 and 102R do not use frequencies of 5 Hz or below for long-term stimulation.
Resetting the pulse generator turns the device OFF (output current = 0 mA). For Model 100, 101, 102 and
102R resetting the pulse generator will result in device history loss.
Patients who smoke may have an increased risk of laryngeal irritation.
Generators with AutoStim only — For devices that sense changes in heart rate, false positive detection
may cause unintended stimulation. Examples of instances where heart rate may increase include
exercise, physical activity, and normal autonomic changes in heart rate, both awake and asleep, etc.
Generators with AutoStim only — For the AutoStim feature, the physical location of the device critically
affects this its ability to properly sense heart beats. Therefore, care must be taken to follow the implant
location selection process outlined in the Implantation Procedure. Note that this implant location
selection procedure may be performed preoperatively as part of the patient’s surgical work-up.
M1000/1000-D only — Since the Scheduled Programming feature allows the generator to apply therapy
increases at scheduled intervals, it may not be appropriate for use in patients who are nonverbal or
are unable to use the patient magnet to stop undesired stimulation. Similarly, exercise caution for
use of this feature in patients with a history of obstructive sleep apnea, shortness of breath, coughing,
swallowing difficulties, or aspiration.
6. ENVIRONMENTAL AND MEDICAL THERAPY HAZARDS
Patients should exercise reasonable caution in avoiding devices that generate a strong electric or
magnetic field. If a generator ceases operation while in the presence of electromagnetic interference
(EMI), moving away from the source may allow it to return to its normal mode of operation.
VNS Therapy System operation should always be checked by performing device diagnostics after any of
the procedures mentioned in the physician’s manuals.
For clear imaging, patients may need to be specially positioned for mammography procedures, because
of the location of the generator in the chest.
Therapeutic radiation may damage the generator’s circuitry. Sources of such radiation include
therapeutic radiation, cobalt machines, and linear accelerators. The radiation effect is cumulative, with
the total dosage determining the extent of damage. The effects of exposure to such radiation can range
from a temporary disturbance to permanent damage, and may not be detectable immediately.
External defibrillation may damage the generator.
Use of electrosurgery [electrocautery or radio frequency (RF) ablation devices] may damage
the generator.
Magnetic resonance imaging (MRI) should not be performed using a transmit RF body coil for certain
VNS Therapy device configurations or under certain specific conditions. In some cases, heating of the
lead caused by the transmit RF body coil during MRI may result in serious injury. Static, gradient, and
radio frequency (RF) electromagnetic fields associated with MRI may change the generator settings
(i.e., reset parameters) or activate the VNS device if the Magnet Mode output remains “ON”. Note that
certain magnetic resonance (MR) system head coils operate in receive-only mode and require use of
the transmit RF body coil. Other MR systems use a transmit/receive RF head coil. Local or surface coils
may also be receive-only RF coils that require the transmit RF body coil for MRI. The use of a receive
RF coil does not alter hazards of the transmit RF body coil. Exposure of the VNS Therapy System to any
transmit RF coil must be avoided. Do not perform MRI scans using any transmit RF coil in the defined
exclusion zones. See the MRI with the VNS Therapy System instructions for use for details or further
instructions for special cases such as lead breaks or partially explanted VNS Therapy systems.
Extracorporeal shockwave lithotripsy may damage the generator. If therapeutic ultrasound therapy is
required, avoid positioning the area of the body where the generator is implanted in the water bath
or in any other position that would expose it to ultrasound therapy. If that positioning cannot be
avoided, program the generator output to 0 mA for the treatment, and then after therapy, reprogram the
generator to the original parameters.
If the patient receives medical treatment for which electric current is passed through the body (such as
from a TENS unit), either the generator should be set to 0 mA or function of the generator should be
monitored during initial stages of treatment.
Routine therapeutic ultrasound could damage the generator and may be inadvertently concentrated by
the device, causing harm to the patient.
For complete information related to home occupational environments, cellular phones, other
environmental hazards, other devices, and ECG monitors, refer to the physician’s manuals.
7. ADVERSE EVENTS — EPILEPSY
Adverse events reported during clinical studies as statistically significant are listed below in alphabetical
order: ataxia (loss of the ability to coordinate muscular movement); dyspepsia (indigestion); dyspnea
(difficulty breathing, shortness of breath); hypoesthesia (impaired sense of touch); increased coughing;
infection; insomnia (inability to sleep); laryngismus (throat, larynx spasms); nausea; pain; paresthesia
(prickling of the skin); pharyngitis (inflammation of the pharynx, throat); voice alteration (hoarseness);
vomiting. Adverse events reported in clinical investigation of the AutoStim feature were comparable.
26-0009-0100/6 (OUS) — 1
Brief Summary1 of Safety Information for the VNS Therapy™ System
[Epilepsy Indication] (February 2021)
Guided Programming establishes a safe and easy pathway towards achieving targeted therapy levels through
one touch programming.
1 Interrogate the Generator
2. Go to Parameters Screen
3. Switch to Guided Mode
4. (Model 1000 and 1000-D only) Select Standard
Protocol or Custom Protocol* and Tap
Next (See Creating Protocols Technical
Information Sheet)
5. Review Changes and Select Apply Changes
To increase parameters: (Steps 6-7)
6. Increase Step
7. Review Step Increase and Apply Changes
To decrease parameters: (Steps 8-9)
8. Decrease Step
9. Review Step Decrease and Apply Changes
10. Interrogate
11. End Session
Step 3 Step 5
Step 6 and 8 Step 9
Step Normal Mode
Output Current (mA)
Autostim Mode
Output Current (mA)
Magnet Mode
Output Current (mA)
1 0.25 0.375 0.50
2 0.50 0.625 0.75
3 0.75 0.875 1.00
4 1.00 1.125 1.25
5 1.25 1.375 1.50
6 1.50 1.625 1.75
7 1.75 1.875 2.00
All other variables remain constant. Signal Frequency 20Hz, Pulse Width 250μsec, (Magnet 500μsec), Duty Cycle 10% (30sec On, 5 Min Off)
Autostim and Magnet Mode On Time 60sec
Standard Protocol Steps
Guided Programming
(All Generator types)
Please refer to the VNS Therapy™ System Epilepsy Physician’s Manual (OUS), LivaNova USA, Inc. that could be found at www.vnstherapy.co.uk/
physician-manuals for complete information on the implantation procedure. For full prescribing and important safety information, please visit
www.vnstherapy.co.uk/safety-information or ask your VNS Therapy representative.
Clinical Technical Services
US, Latin America, Canada, Asia Pacific, Japan
+1-281-228-7330,
+1-866-882-8804
Europe, Middle East, Africa
+32-2-790-27-73
one touch programming.
1 Interrogate the Generator
2. Go to Parameters Screen
3. Switch to Guided Mode
4. (Model 1000 and 1000-D only) Select Standard
Protocol or Custom Protocol* and Tap
Next (See Creating Protocols Technical
Information Sheet)
5. Review Changes and Select Apply Changes
To increase parameters: (Steps 6-7)
6. Increase Step
7. Review Step Increase and Apply Changes
To decrease parameters: (Steps 8-9)
8. Decrease Step
9. Review Step Decrease and Apply Changes
10. Interrogate
11. End Session
Step 3 Step 5
Step 6 and 8 Step 9
Step Normal Mode
Output Current (mA)
Autostim Mode
Output Current (mA)
Magnet Mode
Output Current (mA)
1 0.25 0.375 0.50
2 0.50 0.625 0.75
3 0.75 0.875 1.00
4 1.00 1.125 1.25
5 1.25 1.375 1.50
6 1.50 1.625 1.75
7 1.75 1.875 2.00
All other variables remain constant. Signal Frequency 20Hz, Pulse Width 250μsec, (Magnet 500μsec), Duty Cycle 10% (30sec On, 5 Min Off)
Autostim and Magnet Mode On Time 60sec
Standard Protocol Steps
Guided Programming
(All Generator types)
Please refer to the VNS Therapy™ System Epilepsy Physician’s Manual (OUS), LivaNova USA, Inc. that could be found at www.vnstherapy.co.uk/
physician-manuals for complete information on the implantation procedure. For full prescribing and important safety information, please visit
www.vnstherapy.co.uk/safety-information or ask your VNS Therapy representative.
Clinical Technical Services
US, Latin America, Canada, Asia Pacific, Japan
+1-281-228-7330,
+1-866-882-8804
Europe, Middle East, Africa
+32-2-790-27-73
EC Representative
LIVANOVA USA, INC.
100 Cyberonics Boulevard
Houston, Texas 77058, USA
Tel: +1 (281) 228-7200 /
+1 (800) 332-1375
Fax: +1 (281) 218-9332
www.livanova.com
Manufacturer
LIVANOVA BELGIUM NV
Ikaroslaan 83
B-1930 Zaventem,
BELGIUM
Tel: +3227209593
Fax: +3227206053
www.VNSTherapy.co.uk
1 The information contained in this Brief Summary for Physicians represents partial excerpts of
important prescribing information taken from the physician’s manuals. (Copies of VNS Therapy
physician’s and patient’s manuals are posted at www.livanova.com)The information is not
intended to serve as a substitute for a complete and thorough understanding of the material
presented in all of the physician’s manuals for the VNS Therapy System and its component
parts nor does this information represent full disclosure of all pertinent information
concerning the use of this product, potential safety complications, or efficacy outcomes.
Not available in all regions.
All trademarks and trade names are the property of LivaNova or the property of LivaNova’s consolidated subsidiaries and are protected under applicable
intellectual property laws. Solely for convenience, LivaNova’s trademarks and trade names may appear without the ® or TM symbols, but such references
are not intended to indicate in any way that LivaNova will not assert, to the fullest extent under applicable law, LivaNova’s rights to these trademarks and
trade names. Prior permission from Livanova is required for the use or reproduction of such intellectual property rights. EPI-2300206
1. INTENDED USE / INDICATIONS
Epilepsy (Non-US)—The VNS Therapy System is indicated for use as an adjunctive therapy in reducing
the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures (with or
without secondary generalization) or generalized seizures that are refractory to seizure medications.
AspireSR™, SenTiva™ and SenTiva DUO™ feature an Automatic Stimulation Mode which is intended for
patients who experience seizures that are associated with cardiac rhythm increases known as
ictal tachycardia.
2. CONTRAINDICATIONS
Vagotomy—The VNS Therapy System cannot be used in patients after a bilateral or left
cervical vagotomy.
Diathermy—Do not use short-wave diathermy, microwave diathermy, or therapeutic ultrasound
diathermy on patients implanted with a VNS Therapy System. Diagnostic ultrasound is not included in
this contraindication.
3. WARNINGS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
physician’s manuals. This document is not intended to serve as a substitute for the complete
physician’s manuals.
The safety and efficacy of the VNS Therapy System have not been established for uses outside the
“Intended Use/Indications” chapter of the physician’s manuals.
The safety and effectiveness of the VNS Therapy System in patients with predisposed dysfunction
of cardiac conduction systems (re-entry pathway) have not been established. Post-implant
electrocardiograms and Holter monitoring are recommended if clinically indicated.
Postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias.
It is important to follow recommended implantation procedures and intraoperative product testing
described in the Implantation Procedure chapter of the physician’s manual. During the intraoperative
System Diagnostics (Lead Test), infrequent incidents of bradycardia and/or asystole have occurred.
If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is
encountered during a System Diagnostics (Lead Test) or during initiation of stimulation, physicians
should be prepared to follow guidelines consistent with Advanced Cardiac Life Support (ACLS).
Difficulty swallowing (dysphagia) may occur with active stimulation, and aspiration may result from the
increased swallowing difficulties. Patients with pre-existing swallowing difficulties are at greater risk
for aspiration.
Dyspnea (shortness of breath) may occur with active VNS Therapy. Any patient with underlying
pulmonary disease or insufficiency such as chronic obstructive pulmonary disease or asthma may be at
increased risk for dyspnea.
Patients with obstructive sleep apnea (OSA) may have an increase in apneic events during stimulation.
Lowering stimulus frequency or prolonging “OFF” time may prevent exacerbation of OSA. Vagus nerve
stimulation may also cause new onset sleep apnea in patients who have not previously been diagnosed
with this disorder.
Device malfunction could cause painful stimulation or direct current stimulation. Either event could
cause nerve damage. Patients should be instructed to use the magnet to stop stimulation if they
suspect a malfunction, and then to contact their physician immediately for further evaluation.
Patients with the VNS Therapy System or any part of the VNS Therapy System implanted should have
MRI procedures performed only as described in the MRI with the VNS Therapy System instructions
for use. In some cases, surgery will be required to remove the VNS Therapy System if a scan using a
transmit RF body coil is needed.
Excessive stimulation at an excess duty cycle (i.e., one that occurs when “ON” time is greater than “OFF”
time) and high frequency stimulation (i.e., stimulation at ≥50Hz) has resulted in degenerative nerve
damage in laboratory animals.
Patients who manipulate the generator and lead through the skin (Twiddler’s Syndrome) may damage
or disconnect the lead from the generator and/or possibly cause damage to the vagus nerve.
The Wand, Programmer, and patient magnet are MR unsafe devices. These devices are projectile hazards
and must not be brought into the MR scanner room.
Generators with AutoStim only — The AutoStim Mode feature should not be used in patients with
clinically meaningful arrhythmias or who are using treatments that interfere with normal intrinsic
heart rate responses (e.g., pacemaker dependency, implantable defibrillator, beta adrenergic blocker
medications). Patients also should not have a history of chronotropic incompetence [commonly seen in
patients with sustained bradycardia (heart rate < 50 bpm)].
4. WARNINGS — EPILEPSY
The VNS Therapy System should only be prescribed and monitored by physicians who have specific
training and expertise in the management of seizures and the use of this device. It should only be
implanted by physicians who are trained in surgery of the carotid sheath and have received specific
training in the implantation of this device.
The VNS Therapy System is not curative. Physicians should warn patients that the VNS Therapy System
is not a cure for epilepsy and that since seizures may occur unexpectedly, patients should consult with
a physician before engaging in unsupervised activities, such as driving, swimming, and bathing, and in
strenuous sports that could harm them or others.
Sudden unexpected death in epilepsy (SUDEP): Through August 1996, 10 sudden and unexpected deaths
(definite, probable, and possible) were recorded among the 1,000 patients implanted and treated
with the VNS Therapy device. During this period, these patients had accumulated 2,017 patient-years
of exposure. Some of these deaths could represent seizure-related deaths in which the seizure was
not observed, at night, for example. This number represents an incidence of 5.0 definite, probable,
and possible SUDEP deaths per 1,000 patient-years. Although this rate exceeds that expected in a
healthy (nonepileptic) population matched for age and sex, it is within the range of estimates for
epilepsy patients not receiving vagus nerve stimulation, ranging from 1.3 SUDEP deaths for the general
population of patients with epilepsy, to 3.5 (for definite and probable) for a recently studied antiepileptic
drug (AED) clinical trial population similar to the VNS Therapy System clinical cohort, to 9.3 for patients
with medically intractable epilepsy who were epilepsy surgery candidates.
5. PRECAUTIONS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
VNS Therapy physician’s manuals.
Prescribing physicians should be experienced in the diagnosis and treatment of depression or epilepsy
and should be familiar with the programming and use of the VNS Therapy System.
Physicians who implant the VNS Therapy System should be experienced performing surgery in the
carotid sheath and should be trained in the surgical technique relating to implantation of the
VNS Therapy System.
The safety and effectiveness of the VNS Therapy System have not been established for use during
pregnancy. VNS should be used during pregnancy only if clearly needed.
The VNS Therapy System is indicated for use only in stimulating the left vagus nerve in the neck area
inside the carotid sheath. The VNS Therapy System is indicated for use only in stimulating the left vagus
nerve below where the superior and inferior cervical cardiac branches separate from the vagus nerve.
It is important to follow infection control procedures. Infections related to any implanted device are
difficult to treat and may require that the device be explanted. The patient should be given antibiotics
preoperatively. The surgeon should ensure that all instruments are sterile prior to the procedure.
Children (<12 years of age) may have a greater risk for infection when compared to adolescent and adult
patients (≥ 12 years). Careful monitoring for site infection as well as the avoidance of manipulation of the
surgical site post implant in children should be stressed.
The VNS Therapy System may affect the operation of other implanted devices, such as cardiac
pacemakers and implanted defibrillators. Possible effects include sensing problems and inappropriate
device responses. If the patient requires concurrent implantable pacemaker, defibrillatory therapy
or other types of stimulators, careful programming of each system may be necessary to optimize the
patient’s benefit from each device.
Reversal of lead polarity has been associated with an increased chance of bradycardia in animal studies.
It is important that the electrodes are attached to the left vagus nerve in the correct orientation. It is
also important to make sure that leads with dual connector pins are correctly inserted (white marker
band to + connection) into the generator’s lead receptacles.
The patient can use a neck brace for the first week to help ensure proper lead stabilization.
Do not program the VNS Therapy System to an “ON” or periodic stimulation treatment for at least 14
days after the initial or replacement implantation.
For Models 100, 101, 102 and 102R do not use frequencies of 5 Hz or below for long-term stimulation.
Resetting the pulse generator turns the device OFF (output current = 0 mA). For Model 100, 101, 102 and
102R resetting the pulse generator will result in device history loss.
Patients who smoke may have an increased risk of laryngeal irritation.
Generators with AutoStim only — For devices that sense changes in heart rate, false positive detection
may cause unintended stimulation. Examples of instances where heart rate may increase include
exercise, physical activity, and normal autonomic changes in heart rate, both awake and asleep, etc.
Generators with AutoStim only — For the AutoStim feature, the physical location of the device critically
affects this its ability to properly sense heart beats. Therefore, care must be taken to follow the implant
location selection process outlined in the Implantation Procedure. Note that this implant location
selection procedure may be performed preoperatively as part of the patient’s surgical work-up.
M1000/1000-D only — Since the Scheduled Programming feature allows the generator to apply therapy
increases at scheduled intervals, it may not be appropriate for use in patients who are nonverbal or
are unable to use the patient magnet to stop undesired stimulation. Similarly, exercise caution for
use of this feature in patients with a history of obstructive sleep apnea, shortness of breath, coughing,
swallowing difficulties, or aspiration.
6. ENVIRONMENTAL AND MEDICAL THERAPY HAZARDS
Patients should exercise reasonable caution in avoiding devices that generate a strong electric or
magnetic field. If a generator ceases operation while in the presence of electromagnetic interference
(EMI), moving away from the source may allow it to return to its normal mode of operation.
VNS Therapy System operation should always be checked by performing device diagnostics after any of
the procedures mentioned in the physician’s manuals.
For clear imaging, patients may need to be specially positioned for mammography procedures, because
of the location of the generator in the chest.
Therapeutic radiation may damage the generator’s circuitry. Sources of such radiation include
therapeutic radiation, cobalt machines, and linear accelerators. The radiation effect is cumulative, with
the total dosage determining the extent of damage. The effects of exposure to such radiation can range
from a temporary disturbance to permanent damage, and may not be detectable immediately.
External defibrillation may damage the generator.
Use of electrosurgery [electrocautery or radio frequency (RF) ablation devices] may damage
the generator.
Magnetic resonance imaging (MRI) should not be performed using a transmit RF body coil for certain
VNS Therapy device configurations or under certain specific conditions. In some cases, heating of the
lead caused by the transmit RF body coil during MRI may result in serious injury. Static, gradient, and
radio frequency (RF) electromagnetic fields associated with MRI may change the generator settings
(i.e., reset parameters) or activate the VNS device if the Magnet Mode output remains “ON”. Note that
certain magnetic resonance (MR) system head coils operate in receive-only mode and require use of
the transmit RF body coil. Other MR systems use a transmit/receive RF head coil. Local or surface coils
may also be receive-only RF coils that require the transmit RF body coil for MRI. The use of a receive
RF coil does not alter hazards of the transmit RF body coil. Exposure of the VNS Therapy System to any
transmit RF coil must be avoided. Do not perform MRI scans using any transmit RF coil in the defined
exclusion zones. See the MRI with the VNS Therapy System instructions for use for details or further
instructions for special cases such as lead breaks or partially explanted VNS Therapy systems.
Extracorporeal shockwave lithotripsy may damage the generator. If therapeutic ultrasound therapy is
required, avoid positioning the area of the body where the generator is implanted in the water bath
or in any other position that would expose it to ultrasound therapy. If that positioning cannot be
avoided, program the generator output to 0 mA for the treatment, and then after therapy, reprogram the
generator to the original parameters.
If the patient receives medical treatment for which electric current is passed through the body (such as
from a TENS unit), either the generator should be set to 0 mA or function of the generator should be
monitored during initial stages of treatment.
Routine therapeutic ultrasound could damage the generator and may be inadvertently concentrated by
the device, causing harm to the patient.
For complete information related to home occupational environments, cellular phones, other
environmental hazards, other devices, and ECG monitors, refer to the physician’s manuals.
7. ADVERSE EVENTS — EPILEPSY
Adverse events reported during clinical studies as statistically significant are listed below in alphabetical
order: ataxia (loss of the ability to coordinate muscular movement); dyspepsia (indigestion); dyspnea
(difficulty breathing, shortness of breath); hypoesthesia (impaired sense of touch); increased coughing;
infection; insomnia (inability to sleep); laryngismus (throat, larynx spasms); nausea; pain; paresthesia
(prickling of the skin); pharyngitis (inflammation of the pharynx, throat); voice alteration (hoarseness);
vomiting. Adverse events reported in clinical investigation of the AutoStim feature were comparable.
26-0009-0100/6 (OUS) — 1
Brief Summary1 of Safety Information for the VNS Therapy™ System
[Epilepsy Indication] (February 2021)
LIVANOVA USA, INC.
100 Cyberonics Boulevard
Houston, Texas 77058, USA
Tel: +1 (281) 228-7200 /
+1 (800) 332-1375
Fax: +1 (281) 218-9332
www.livanova.com
Manufacturer
LIVANOVA BELGIUM NV
Ikaroslaan 83
B-1930 Zaventem,
BELGIUM
Tel: +3227209593
Fax: +3227206053
www.VNSTherapy.co.uk
1 The information contained in this Brief Summary for Physicians represents partial excerpts of
important prescribing information taken from the physician’s manuals. (Copies of VNS Therapy
physician’s and patient’s manuals are posted at www.livanova.com)The information is not
intended to serve as a substitute for a complete and thorough understanding of the material
presented in all of the physician’s manuals for the VNS Therapy System and its component
parts nor does this information represent full disclosure of all pertinent information
concerning the use of this product, potential safety complications, or efficacy outcomes.
Not available in all regions.
All trademarks and trade names are the property of LivaNova or the property of LivaNova’s consolidated subsidiaries and are protected under applicable
intellectual property laws. Solely for convenience, LivaNova’s trademarks and trade names may appear without the ® or TM symbols, but such references
are not intended to indicate in any way that LivaNova will not assert, to the fullest extent under applicable law, LivaNova’s rights to these trademarks and
trade names. Prior permission from Livanova is required for the use or reproduction of such intellectual property rights. EPI-2300206
1. INTENDED USE / INDICATIONS
Epilepsy (Non-US)—The VNS Therapy System is indicated for use as an adjunctive therapy in reducing
the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures (with or
without secondary generalization) or generalized seizures that are refractory to seizure medications.
AspireSR™, SenTiva™ and SenTiva DUO™ feature an Automatic Stimulation Mode which is intended for
patients who experience seizures that are associated with cardiac rhythm increases known as
ictal tachycardia.
2. CONTRAINDICATIONS
Vagotomy—The VNS Therapy System cannot be used in patients after a bilateral or left
cervical vagotomy.
Diathermy—Do not use short-wave diathermy, microwave diathermy, or therapeutic ultrasound
diathermy on patients implanted with a VNS Therapy System. Diagnostic ultrasound is not included in
this contraindication.
3. WARNINGS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
physician’s manuals. This document is not intended to serve as a substitute for the complete
physician’s manuals.
The safety and efficacy of the VNS Therapy System have not been established for uses outside the
“Intended Use/Indications” chapter of the physician’s manuals.
The safety and effectiveness of the VNS Therapy System in patients with predisposed dysfunction
of cardiac conduction systems (re-entry pathway) have not been established. Post-implant
electrocardiograms and Holter monitoring are recommended if clinically indicated.
Postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias.
It is important to follow recommended implantation procedures and intraoperative product testing
described in the Implantation Procedure chapter of the physician’s manual. During the intraoperative
System Diagnostics (Lead Test), infrequent incidents of bradycardia and/or asystole have occurred.
If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is
encountered during a System Diagnostics (Lead Test) or during initiation of stimulation, physicians
should be prepared to follow guidelines consistent with Advanced Cardiac Life Support (ACLS).
Difficulty swallowing (dysphagia) may occur with active stimulation, and aspiration may result from the
increased swallowing difficulties. Patients with pre-existing swallowing difficulties are at greater risk
for aspiration.
Dyspnea (shortness of breath) may occur with active VNS Therapy. Any patient with underlying
pulmonary disease or insufficiency such as chronic obstructive pulmonary disease or asthma may be at
increased risk for dyspnea.
Patients with obstructive sleep apnea (OSA) may have an increase in apneic events during stimulation.
Lowering stimulus frequency or prolonging “OFF” time may prevent exacerbation of OSA. Vagus nerve
stimulation may also cause new onset sleep apnea in patients who have not previously been diagnosed
with this disorder.
Device malfunction could cause painful stimulation or direct current stimulation. Either event could
cause nerve damage. Patients should be instructed to use the magnet to stop stimulation if they
suspect a malfunction, and then to contact their physician immediately for further evaluation.
Patients with the VNS Therapy System or any part of the VNS Therapy System implanted should have
MRI procedures performed only as described in the MRI with the VNS Therapy System instructions
for use. In some cases, surgery will be required to remove the VNS Therapy System if a scan using a
transmit RF body coil is needed.
Excessive stimulation at an excess duty cycle (i.e., one that occurs when “ON” time is greater than “OFF”
time) and high frequency stimulation (i.e., stimulation at ≥50Hz) has resulted in degenerative nerve
damage in laboratory animals.
Patients who manipulate the generator and lead through the skin (Twiddler’s Syndrome) may damage
or disconnect the lead from the generator and/or possibly cause damage to the vagus nerve.
The Wand, Programmer, and patient magnet are MR unsafe devices. These devices are projectile hazards
and must not be brought into the MR scanner room.
Generators with AutoStim only — The AutoStim Mode feature should not be used in patients with
clinically meaningful arrhythmias or who are using treatments that interfere with normal intrinsic
heart rate responses (e.g., pacemaker dependency, implantable defibrillator, beta adrenergic blocker
medications). Patients also should not have a history of chronotropic incompetence [commonly seen in
patients with sustained bradycardia (heart rate < 50 bpm)].
4. WARNINGS — EPILEPSY
The VNS Therapy System should only be prescribed and monitored by physicians who have specific
training and expertise in the management of seizures and the use of this device. It should only be
implanted by physicians who are trained in surgery of the carotid sheath and have received specific
training in the implantation of this device.
The VNS Therapy System is not curative. Physicians should warn patients that the VNS Therapy System
is not a cure for epilepsy and that since seizures may occur unexpectedly, patients should consult with
a physician before engaging in unsupervised activities, such as driving, swimming, and bathing, and in
strenuous sports that could harm them or others.
Sudden unexpected death in epilepsy (SUDEP): Through August 1996, 10 sudden and unexpected deaths
(definite, probable, and possible) were recorded among the 1,000 patients implanted and treated
with the VNS Therapy device. During this period, these patients had accumulated 2,017 patient-years
of exposure. Some of these deaths could represent seizure-related deaths in which the seizure was
not observed, at night, for example. This number represents an incidence of 5.0 definite, probable,
and possible SUDEP deaths per 1,000 patient-years. Although this rate exceeds that expected in a
healthy (nonepileptic) population matched for age and sex, it is within the range of estimates for
epilepsy patients not receiving vagus nerve stimulation, ranging from 1.3 SUDEP deaths for the general
population of patients with epilepsy, to 3.5 (for definite and probable) for a recently studied antiepileptic
drug (AED) clinical trial population similar to the VNS Therapy System clinical cohort, to 9.3 for patients
with medically intractable epilepsy who were epilepsy surgery candidates.
5. PRECAUTIONS — GENERAL
Physicians should inform patients about all potential risks and adverse events discussed in the
VNS Therapy physician’s manuals.
Prescribing physicians should be experienced in the diagnosis and treatment of depression or epilepsy
and should be familiar with the programming and use of the VNS Therapy System.
Physicians who implant the VNS Therapy System should be experienced performing surgery in the
carotid sheath and should be trained in the surgical technique relating to implantation of the
VNS Therapy System.
The safety and effectiveness of the VNS Therapy System have not been established for use during
pregnancy. VNS should be used during pregnancy only if clearly needed.
The VNS Therapy System is indicated for use only in stimulating the left vagus nerve in the neck area
inside the carotid sheath. The VNS Therapy System is indicated for use only in stimulating the left vagus
nerve below where the superior and inferior cervical cardiac branches separate from the vagus nerve.
It is important to follow infection control procedures. Infections related to any implanted device are
difficult to treat and may require that the device be explanted. The patient should be given antibiotics
preoperatively. The surgeon should ensure that all instruments are sterile prior to the procedure.
Children (<12 years of age) may have a greater risk for infection when compared to adolescent and adult
patients (≥ 12 years). Careful monitoring for site infection as well as the avoidance of manipulation of the
surgical site post implant in children should be stressed.
The VNS Therapy System may affect the operation of other implanted devices, such as cardiac
pacemakers and implanted defibrillators. Possible effects include sensing problems and inappropriate
device responses. If the patient requires concurrent implantable pacemaker, defibrillatory therapy
or other types of stimulators, careful programming of each system may be necessary to optimize the
patient’s benefit from each device.
Reversal of lead polarity has been associated with an increased chance of bradycardia in animal studies.
It is important that the electrodes are attached to the left vagus nerve in the correct orientation. It is
also important to make sure that leads with dual connector pins are correctly inserted (white marker
band to + connection) into the generator’s lead receptacles.
The patient can use a neck brace for the first week to help ensure proper lead stabilization.
Do not program the VNS Therapy System to an “ON” or periodic stimulation treatment for at least 14
days after the initial or replacement implantation.
For Models 100, 101, 102 and 102R do not use frequencies of 5 Hz or below for long-term stimulation.
Resetting the pulse generator turns the device OFF (output current = 0 mA). For Model 100, 101, 102 and
102R resetting the pulse generator will result in device history loss.
Patients who smoke may have an increased risk of laryngeal irritation.
Generators with AutoStim only — For devices that sense changes in heart rate, false positive detection
may cause unintended stimulation. Examples of instances where heart rate may increase include
exercise, physical activity, and normal autonomic changes in heart rate, both awake and asleep, etc.
Generators with AutoStim only — For the AutoStim feature, the physical location of the device critically
affects this its ability to properly sense heart beats. Therefore, care must be taken to follow the implant
location selection process outlined in the Implantation Procedure. Note that this implant location
selection procedure may be performed preoperatively as part of the patient’s surgical work-up.
M1000/1000-D only — Since the Scheduled Programming feature allows the generator to apply therapy
increases at scheduled intervals, it may not be appropriate for use in patients who are nonverbal or
are unable to use the patient magnet to stop undesired stimulation. Similarly, exercise caution for
use of this feature in patients with a history of obstructive sleep apnea, shortness of breath, coughing,
swallowing difficulties, or aspiration.
6. ENVIRONMENTAL AND MEDICAL THERAPY HAZARDS
Patients should exercise reasonable caution in avoiding devices that generate a strong electric or
magnetic field. If a generator ceases operation while in the presence of electromagnetic interference
(EMI), moving away from the source may allow it to return to its normal mode of operation.
VNS Therapy System operation should always be checked by performing device diagnostics after any of
the procedures mentioned in the physician’s manuals.
For clear imaging, patients may need to be specially positioned for mammography procedures, because
of the location of the generator in the chest.
Therapeutic radiation may damage the generator’s circuitry. Sources of such radiation include
therapeutic radiation, cobalt machines, and linear accelerators. The radiation effect is cumulative, with
the total dosage determining the extent of damage. The effects of exposure to such radiation can range
from a temporary disturbance to permanent damage, and may not be detectable immediately.
External defibrillation may damage the generator.
Use of electrosurgery [electrocautery or radio frequency (RF) ablation devices] may damage
the generator.
Magnetic resonance imaging (MRI) should not be performed using a transmit RF body coil for certain
VNS Therapy device configurations or under certain specific conditions. In some cases, heating of the
lead caused by the transmit RF body coil during MRI may result in serious injury. Static, gradient, and
radio frequency (RF) electromagnetic fields associated with MRI may change the generator settings
(i.e., reset parameters) or activate the VNS device if the Magnet Mode output remains “ON”. Note that
certain magnetic resonance (MR) system head coils operate in receive-only mode and require use of
the transmit RF body coil. Other MR systems use a transmit/receive RF head coil. Local or surface coils
may also be receive-only RF coils that require the transmit RF body coil for MRI. The use of a receive
RF coil does not alter hazards of the transmit RF body coil. Exposure of the VNS Therapy System to any
transmit RF coil must be avoided. Do not perform MRI scans using any transmit RF coil in the defined
exclusion zones. See the MRI with the VNS Therapy System instructions for use for details or further
instructions for special cases such as lead breaks or partially explanted VNS Therapy systems.
Extracorporeal shockwave lithotripsy may damage the generator. If therapeutic ultrasound therapy is
required, avoid positioning the area of the body where the generator is implanted in the water bath
or in any other position that would expose it to ultrasound therapy. If that positioning cannot be
avoided, program the generator output to 0 mA for the treatment, and then after therapy, reprogram the
generator to the original parameters.
If the patient receives medical treatment for which electric current is passed through the body (such as
from a TENS unit), either the generator should be set to 0 mA or function of the generator should be
monitored during initial stages of treatment.
Routine therapeutic ultrasound could damage the generator and may be inadvertently concentrated by
the device, causing harm to the patient.
For complete information related to home occupational environments, cellular phones, other
environmental hazards, other devices, and ECG monitors, refer to the physician’s manuals.
7. ADVERSE EVENTS — EPILEPSY
Adverse events reported during clinical studies as statistically significant are listed below in alphabetical
order: ataxia (loss of the ability to coordinate muscular movement); dyspepsia (indigestion); dyspnea
(difficulty breathing, shortness of breath); hypoesthesia (impaired sense of touch); increased coughing;
infection; insomnia (inability to sleep); laryngismus (throat, larynx spasms); nausea; pain; paresthesia
(prickling of the skin); pharyngitis (inflammation of the pharynx, throat); voice alteration (hoarseness);
vomiting. Adverse events reported in clinical investigation of the AutoStim feature were comparable.
26-0009-0100/6 (OUS) — 1
Brief Summary1 of Safety Information for the VNS Therapy™ System
[Epilepsy Indication] (February 2021)