System Overview Caution: Federal law restricts this device to sale by or on the order of a physician.
ABOUT THIS DOCUMENT This document is a portion of the Instructions for Use (IFU) for the Barostim NEO™ & NEO2™ Systems. The full IFU consists of: System Overview 900133-001 Surgical Procedures 900133-002 Programming 900133-003 Patient Instructions 900133-005 IFU documents are available at www.cvrx.
Table of Contents About this document ............................................................................... 1 1 System Description ................................................................................. 3 Implantable Pulse Generator (IPG) .............................................................. 5 Carotid Sinus Lead (CSL) kit ...................................................................... 5 Programmer System (PGM) .............................................................
1 System Description 3
The Barostim NEO™ & NEO2™ Systems include the following components: Description Implantable Pulse Generator Implantable Pulse Generator Carotid Sinus Lead Carotid Sinus Lead Programmer System Programmer System Carotid Sinus Lead Repair Kit Model Number 2102 2104 1036 1037 9010 9020 5010 The Barostim NEO & NEO2 Systems are minimally-invasive using CVRx® patented Barostim™ technology.
IMPLANTABLE PULSE GENERATOR (IPG) MODEL 2102 OR 2104 The Implantable Pulse Generator (IPG) contains a battery and circuitry in a hermetic enclosure. It provides control and delivery of Barostim through the Carotid Sinus Lead to the baroreceptors. The carotid sinus lead is attached to the pulse generator through the connector module. Model 2102 has two lead connections; Model 2104 has one lead connection.
OPTIONAL ACCESSORIES FOR USE WITH THE SYSTEM CSL Repair Kit Model 5010 The CVRx CSL Repair Kit contains tools and material to repair damage to the conductor coils of a healed in therapy lead.
2 Symbols and Definitions 7
Caution, Consult Accompanying Documents Consult Instructions for Use Do Not Reuse Do Not Resterilize Temperature Limitation Date of Manufacture Manufacturer Use By Date Peel Here Sterilized using Ethylene Oxide Equipment includes RF transmitter Batch Code (Lot Number) Product Model Number Serial Number Part Number Catalogue Number Package Contents Product Protected by One or More US Patents as listed (International patents & additional patents pending) Keep Dry This Way Up Fragile, Handle with Care Do Not U
3 Indications and Contra-indications 9
INDICATIONS: The Barostim NEO™ & NEO2™ Systems are indicated for the improvement of symptoms of heart failure—quality of life, six-minute hall walk and functional status—for patients who remain symptomatic despite treatment with guideline-directed medical therapy, are NYHA Class III or Class II (who had a recent history of Class III), have a left ventricular ejection fraction ≤ 35%, a NT-proBNP < 1600 pg/ml and excluding patients indicated for Cardiac Resynchronization Therapy (CRT) according to AHA/ACC/ESC
4 Warnings and Precautions 11
GENERAL The safety and effectiveness of Barostim has been demonstrated in clinical trials. General Warnings • Only trained physicians may use this system. • Prescribing physicians should be experienced in the diagnosis and treatment of hypertension and heart failure and should be familiar with the use of this system. • Monitor blood pressure and heart rate during Carotid Sinus Lead placement and when adjusting stimulation parameters intra-operatively.
General Precautions • The system should be implanted and programmed carefully to avoid stimulation of tissues near the electrode or in the area of the IPG pocket. Such extraneous stimulation could involve the following: o The regional nerves, causing laryngeal irritation, difficulty swallowing, or dyspnea. o The cervical musculature, causing intermittent contraction. o Skeletal muscles, causing intermittent contraction around the IPG pocket.
IPG IPG Warnings • The IPG is a single-use-only device. Do not re-sterilize or reuse. Reuse of this product may result in malfunction or adverse events such as infection or death. • Do not implant product if the expiration “Use By” date has been reached. • Do not implant the IPG if the storage package has been damaged, compromising the product sterility. • Persons allergic to silicone, titanium, or polyurethane may have an allergic reaction to the IPG.
• External defibrillation may cause damage to the IPG. During a defibrillation procedure, space electrodes as far as practical from the IPG. Verify proper IPG function after defibrillation procedures. In addition, if it is practical, it is suggested that the IPG be turned off during defibrillation. • Sterile package seal integrity can be damaged by moisture. Do not expose to liquids. • If any of these 3 situations is observed, a CVRx representative should be contacted immediately.
CSL CSL Warnings • The Carotid Sinus Lead is a single-use-only device. Do not re-sterilize or reuse. Reuse of this product may result in malfunction or adverse events such as infection or death. • Do not implant product if expiration “Use By” date has been reached. • Do not implant the Carotid Sinus Lead if the storage package has been damaged, compromising the product sterility.
PROGRAMMER Programmer Warnings • Do not locate any programmer system components inside the sterile operating field. Programmer Precautions • The components of the Programmer System should not be sterilized. • The following are requirements to comply with IEC 60601-1 and IEC 60601-1-1: o The computer/tablet and power supply should be located outside the patient environment when the computer is operated on mains power.
Precautions • Store between -4 F (-20 C) and 122 F (50 C). • Do not use if the storage package has been damaged, compromising the product sterility. • Sterile package seal integrity can be damaged by moisture. Do not expose to liquids.
5 Adverse Events 19
It is anticipated that subjects will be exposed to operative and post-operative risks similar to related surgical procedures involving the neck and/or a pacemaker implant.
• General injury to user or patient – may be due to surgical procedure, device use, or interaction with other devices • Need for reoperation – operation to explant/replace IPG or CSLs due to tissue damage, infection, and/or device failure • Secondary operative procedure – An increase in the complexity and risk of secondary operative procedures of the neck due to scar tissue and the presence of prosthetic material implanted for this device • Death 21
6 Clinical Summary 22
CLINICAL SUMMARY The Baroreflex Activation Therapy for Heart Failure (BeAT-HF) trial was a prospective, randomized (1:1), two-arm controlled trial to establish a reasonable assurance of safety and effectiveness of the Barostim NEO Systems for the reduction of the symptoms of heart failure in patients. The trial generated data from subjects who met the following key criteria: • • • • Currently NYHA Class II or III heart failure.
evaluation of the MANCE free rate includes all subjects in the BAT + MM arm in the Intended Use Population that have an attempted implant. Within the Intended Use Population supporting the Expedited Phase, there are two cohorts of data. Data that was previously analyzed in the original PMA dated December 14, 2018, called the Initial Cohort data, and data that had not been previously unblinded and analyzed and also is included here, called the Second Cohort data that was collected through April 22, 2019.
BAT + Medical Management Medical Management N Mean ± SD or N (%) Range N Mean ± SD or N (%) Range P-value 130 6 (4.6%) N/A 134 16 (11.9%) N/A 0.044 Female 130 24 (18.5%) N/A 134 29 (21.6%) N/A 0.542 Age at Screening (years) 130 62 ± 11 27 - 92 134 63 ± 10 35 - 83 0.614 BMI (kg/m2) 130 31 ± 5 17 - 40 134 31 ± 5 20 - 43 0.699 SBP (mmHg) 130 120 ± 17 80 - 183 134 121 ± 16 90 - 179 0.385 DBP (mmHg) 130 73 ± 10 48 - 107 134 73 ± 10 50 - 101 0.
BAT + Medical Management Variable N Medical Management Mean ± SD Rang or N (%) e N Mean ± SD Rang or N (%) e P-value Tachycardia 130 43 (33.1%) N/A 134 46 (34.3%) N/A 0.897 Atrial Fibrillation 130 38 (29.2%) N/A 134 57 (42.5%) N/A 0.029 Stroke or TIA 130 24 (18.5%) N/A 134 30 (22.4%) N/A 0.449 Chronic Kidney Disease 130 31 (23.8%) N/A 134 33 (24.6%) N/A 0.887 Type I 130 0 (0.0%) N/A 134 2 (1.5%) N/A 0.498 Type II 130 58 (44.6%) N/A 134 68 (50.7%) N/A 0.
BAT + Medical Management Medical Management N Mean ± SD or N (%) Range Pacemaker (non-ICD) 130 2 (1.5%) CRT 130 Other cardiac device (e.g., CardioMEMS) 130 Treatment N Mean ± SD or N (%) Range P-value N/A 134 1 (0.7%) N/A 0.618 3 (2.3%) N/A 134 4 (3.0%) N/A 1.000 6 (4.6%) N/A 134 4 (3.0%) N/A 0.536 Safety Results The system or procedure related Major Adverse Neurological and Cardiovascular Events (MANCE) endpoint includes all events that occur within 6-months post implant.
Implanted Subjects (N=125) Number of Events Number of Subjects Event Rate Hypertensive Crisis 0 0 0.0% Severe Complication of HF Treatment 0 0 0.0% Systemic and Pulmonary Thromboembolism 0 0 0.0% Infection Requiring Explant 2 2 1.6% Cranial Nerve Damage 0 0 0.0% Non-Elective Major Restorative Procedures 0 0 0.0% Total 4 4 3.
Table 7: Six Month System or Procedure Related Complications in BAT + Medical Management - Intended Use 29
Implanted Subjects (N=125) Event Number of Number of Events Subjects Event Rate Heart Failure, Acute Decompensated Heart Failure 1 1 0.8% Muscle and Bone 1 1 0.8% Nerve Damage/Stimulation, Cranial Nerve Stimulation 1 1 0.8% Other Nerve, Hoarseness 1 1 0.8% Respiratory, Other Respiratory, Acute hypercarbic respiratory failure 1 1 0.8% Respiratory, Pneumonia 1 1 0.8% Stroke (CVA), Ischemic 1 1 0.
Implanted Subjects (N=125) Event Number of Number of Events Subjects Event Rate Surgical or Anesthetic Complications, Infection at Implant Site (No Explant) 1 1 0.8% Surgical or Anesthetic Complications, Infection at Implant Site Requiring Explanation 1 1 0.8% Surgical or Anesthetic Complications, Other Surgical Complication, prolonged intubation 1 1 0.8% Thromboembolism, Systemic 1 1 0.8% 12 9 7.
Serious Adverse Event BAT (N=125) Control (N=134) Number Event Rate of Events per patient (# year of subjects) follow-up Number of Events (# subjects) Event Rate per patient year of follow-up Relative Reduction in Event Rate (95% CI) p-value Cardiac 8 (6) Arrhythmias/Cardiac Arrest 0.054 18 (12) 0.109 0.50 (-0.14, 0.78) 0.100 Hypotension/Syncope 2 (2) 0.014 6 (4) 0.036 0.63 (-0.85, 0.92) 0.226 MI/Angina 5 (4) 0.034 10 (10) 0.060 0.44 (-0.63, 0.81) 0.288 Total 15 (11) 0.
BAT + Medical Management Mean±SD (95% CI) Medical Management N Difference* Mean±SD (95% CI) Δ Means (95% CI) pvalue Cohort N Second 49 48.1 ± 58.7 (31.2, 64.9) 40 0.1 ± 79.2 (-25.3, 25.4) 49.8 (21.8, 77.9) <0.001 Combined 118 48.6 ± 66.3 (36.5, 60.7) 120 -7.9 ± 88.4 (-23.9, 8.1) 60.1 (40.3, 79.9) <0.001 *The difference is evaluated based on an ANCOVA model adjusting for the baseline value.
Table 11: Change in Log10 NT-proBNP at 6 Months – Intended Use Second, Initial and Combined Cohorts BAT + Medical Management Medical Management Mean±SD (95% CI)** N Difference* Mean±SD (95% CI)** Δ Means (95% CI)** pvalue Cohort N Initial 67 -16.7% ± 0.3 (-30.2%, -0.5%) 82 1.9% ± 0.3 (-12.4%, 18.5%) -17.9% (-34.3%, 2.7%) 0.08 Second 53 -26.4% ± 0.4 (-43.7%, -3.9%) 41 6.4% ± 0.3 (-15.9%, 34.5%) -36.5% (-55.2%, -10.1%) 0.01 Combined 120 -21.1% ± 0.4 (-32.3%, -8.2%) 123 3.3% ± 0.
Adding New Class of Heart Failure Drugs Table 13 shows the data reported in Appendix Table 12, Subjects Adding New Class of Heart Failure Drugs by Six Months in Cohort D Control (n=125). in the JACC 2020 article supplementary material. During the 6-month follow-up there was a significant difference in medical management between the 2 arms, with a higher number of medications added in the control group (Supplemental Table 12, Zile et al).
Discussion and Conclusion In the Intended Use Population, safety was demonstrated in the BeAT-HF trial in the 125 implanted subjects with a system- or procedure-related MANCE-free rate of 96.8%. There were four MANCE events related to the system and/or the procedure of which all recovered, three with no residual effect. There were no deaths in the BAT + MM associated with either system or the procedure. There were no unanticipated adverse events.
7 Physician and Training Experience 37
TRAINING REQUIREMENTS CVRx requires training for physicians who wish to use this system.
8 Emergency Personnel Information 39
RADIOPAQUE IDENTIFIER The IPGs have a unique radiopaque identifier located in the connector portion of the device. This allows medical personnel to use X-ray to identify information about the implanted medical device. An example of an IPG radiopaque identifier is shown along with a description of the identifying characters. The radiopaque identifier indicates the following. • CVRx® as the company for which the IPG was manufactured. • The model of the IPG (example: A5 = Model 2102, A6 = Model 2104).
9 Warranty & Disclaimer of Warranty 41
IMPORTANT NOTICE – LIMITED WARRANTY This Limited Warranty is provided by CVRx, Inc. 9201 West Broadway Avenue, Suite 650, Minneapolis, MN 55445. This LIMITED WARRANTY assures the patient who receives Barostim NEO & NEO2 (referred to as the “Product”) that, should the Product not function to specification for any reason within one year after implant (“Warranty Period”), CVRx® will provide a replacement at no charge. All Warnings contained in the Product labeling are an integral part of this LIMITED WARRANTY.
10 Specifications 43
IMPLANTABLE PULSE GENERATOR Specification 2104 2102 Mass 55 grams 60 grams Height 68 mm 72 mm Width 50 mm 50 mm Thickness 14 mm 14 mm Volume < 36 CC < 40 CC Connectors No sensing Unipolar Stimulation 1.5 mm lead pin bore diameter 3.
Implantable Pulse Generator Parameters Parameter Description Therapy Schedule From/To Times for Therapy (N) or Therapy Off Pulse Amplitude for Therapy (N) Pulse Width for Therapy (N) Therapy Frequency for Therapy (N) Burst The amplitude of each applied pulse. Burst Duration Burst Interval Units Programmable Values HH:MM Up to 3 entries allowed Any time during the day In 15 minute steps milliamp 1.0 to 20.0 The width of each applied pulse.
LEAD (MODELS 1036 AND 1037) Specification Value (Nominal) Length Model 1036: 40 cm Model 1037: 50 cm Compatibility Compatible with CVRx® Barostim NEO & NEO2™ Connector Connector Type Compatible with CVRx® Barostim NEO IPG Pin Active: Diameter = 1.41 mm, Active Length = 5.18 mm Ring Inactive: Diameter = 2.67 mm, Active Length = 4.06 mm Connector (Pin to Ring) Length 14.
CAROTID SINUS LEAD REPAIR KIT Specification Value (Nominal) Length (as provided) 28 cm Compatibility Compatible with CVRx® Rheos, Barostim NEO & NEO2, and Barostim™ Legacy Systems Connector Connector Type Bipolar, compatible with, Neo, NEO2 and Legacy IPG Pin Diameter = 1.41 mm, Active Length = 5.18 mm Ring Diameter = 2.67 mm, Active Length = 4.06 mm Connector (Pin to Ring) Length 14.
PROGRAMMER SYSTEM Specification Value Operating temperature 9010: 50° F to 95° F (10° C to 35° C) 9020: 50° F to 95° F (10° C to 35° C) If equipment has been stored at temperature extremes, then the equipment should be placed at operating temperature for at least 1 hour prior to use. Atmospheric pressure 525 mmHg to 760 mmHg (700 hPa to 1010 hPa)(10.2 psia to 14.7psia) Vibration 0.5G, 10 to 500 Hz, 0.
Programmer System Components Component Specification Value Programmer Interface Power Supply Input From computer/tablet Programmer System IEC60601-1-2 System Clause Additional equipment connected to medical electrical equipment must comply with the respective IEC or ISO standards (e.g., IEC 62368-1 for information technology equipment). Furthermore, all configurations shall comply with the requirements for medical electrical systems (see clause 16 of the 3rd Ed. Of IEC 60601-1).
Programmer Miscellaneous Information Description Information Type of protection against electric shock The Programmer Interface is not mains powered equipment. Degree of protection against electric shock The Programmer Interface meets IEC 60601-1 touch current requirements. Degree of protection against the ingress of water Ordinary Methods of sterilization or disinfecting Cannot be sterilized. Information regarding electromagnetic or other interference and advice regarding avoidance as necessary.
Description Information Disposal of Product Please contact CVRx® representative to return product to CVRx. Product should not be disposed of in trash.
11 Regulatory Notices 52
REGULATORY LABELING REQUIREMENTS This system is equipped with an RF transmitter for wireless communications.
12 Electromagnetic Compatibility Declarations Model 9010 Programmer System 54
PROGRAMMER SYSTEM EMC PRECAUTIONS The Model 9010 Programmer System needs special precautions regarding Electromagnetic Compatibility (EMC) and needs to be installed and put into service according to the EMC information provided in this guide. Portable and mobile RF communications equipment can affect the Model 9010 Programmer System. The use of power cords or USB cables other than those supplied with the Model 9010 Programmer System may result in increased emissions or decreased immunity.
Table 14: Electromagnetic Emissions Guidance and manufacturer’s declaration – electromagnetic emissions The Model 9010 Programmer System is intended for use in the electromagnetic environment specified below. The customer or the user of the Model 9010 Programmer System should assure that it is used in such an environment.
Table 15: Electromagnetic Immunity Guidance and manufacturer’s declaration – electromagnetic immunity The Model 9010 Programmer System is intended for use in the electromagnetic environment specified below. The customer or the user of the Model 9010 Programmer System should assure that it is used in such an environment.
Guidance and manufacturer’s declaration – electromagnetic immunity The Model 9010 Programmer System is intended for use in the electromagnetic environment specified below. The customer or the user of the Model 9010 Programmer System should assure that it is used in such an environment.
Table 16: Separation Distance Recommended separation distance between portable and mobile RF communications equipment and the Model 9010 Programmer System The Model 9010 Programmer System is intended for use in the electromagnetic environment in which radiated RF disturbances are controlled.
13 Electromagnetic Compatibility Declarations Model 9020 Programmer System 60
PROGRAMMER SYSTEM EMC PRECAUTIONS The Programmer System requires special precautions regarding Electromagnetic Compatibility (EMC) and is to be installed and put into service according to the EMC information provided in this guide. Portable and mobile RF communications equipment can affect the Programmer System. The use of power cords or USB cables other than those supplied with the Programmer System may result in increased emissions or decreased immunity.
Table 17: Electromagnetic Emissions Guidance and manufacturer’s declaration – electromagnetic emissions The Programmer System is intended for use in the electromagnetic environment specified below. The customer or the user of the Programmer System should ensure that it is used in such an environment. Emissions Test Compliance Electromagnetic environment – guidance RF emissions CISPR 11 Group 1 The Programmer System must emit electromagnetic energy in order to perform its intended function.
Table 18: Electromagnetic Immunity Guidance and manufacturer’s declaration – electromagnetic immunity The Programmer System is intended for use in the electromagnetic environment specified below. The customer or the user of the Programmer System should ensure that it is used in such an environment.
Guidance and manufacturer’s declaration – electromagnetic immunity The Programmer System is intended for use in the electromagnetic environment specified below. The customer or the user of the Programmer System should ensure that it is used in such an environment.
Table 3: Immunity to Proximity Fields from RF Wireless Communications Equipment Test Frequency (MHz) 385 450 Band (MHz) Service Modulation TETRA 400 Pulse modulation 18Hz GMRS 460, FRS 460 FM ± 5 kHz deviation 1kHz sine 704-787 LTE Band 13, 17 Pulse modulation 217 Hz 800-960 GSM 800/900, TETRA 800, IDEN 820, CDMA 850, LTE Band 5 17001990 GSM 1800; CDMA 1900; GSM 1900; DECT; LTE Band 1, 3, 4, 25; UMTS 24002570 Bluetooth, WLAN, 802.
Table 4: Separation Distance Recommended separation distance between portable and mobile RF communications equipment and the Programmer System The Programmer System is intended for use in the electromagnetic environment in which radiated RF disturbances are controlled.
CVRx, BAROSTIM, NEO, BAROSTIM NEO, BAROSTIM NEO2, BAT and BAROSTIM THERAPY are all trademarks of CVRx, Inc. All other trademarks are property of their respective owners. For a list of applicable patents, see www.cvrx.com/patent-marking. CAUTION: Federal law restricts this device to sale by or on the order of a physician. ©2021 CVRx, Inc. All rights reserved.
900133-001 Rev. B V1.
