(211 days)
Not Found
Yes
The document explicitly states that the "physiologic data analysis performed using machine learning".
No.
The device is described as providing additive information and calculating risk, specifically stating it "is not intended to independently direct therapy." This indicates it is for risk assessment and monitoring, not for delivering a therapeutic effect.
Yes
The device explicitly states its intended use is to "calculate the risk of HF for a patient in the next 30 days" and provides "information regarding the patient's health status" and "alerts based on the SignalHF HF evaluation," which are all diagnostic functions.
Yes
The device description explicitly states "SignalHF is a software as medical device (SaMD)". It processes data from pre-existing hardware (CIEDs and EHRs) but does not include or modify any hardware itself.
Based on the provided information, the SignalHF System is not an In Vitro Diagnostic (IVD).
Here's why:
- IVDs analyze samples taken from the human body. The SignalHF System analyzes physiological data generated within the patient's body by an implanted device (CIED) and combines it with personal health records. It does not involve the analysis of biological samples like blood, urine, or tissue.
- The intended use is for physiological monitoring and risk assessment. The system calculates a risk score based on physiological parameters and patient history to predict the likelihood of a future heart failure event. This is distinct from the diagnostic process of identifying a disease or condition through the analysis of biological samples.
- The device description focuses on data analysis from implanted devices and patient records. The core function is processing data from the CIED and personal health records using an algorithm.
While the SignalHF System provides information used in the management of a medical condition (Heart Failure), its mechanism of action and the type of data it analyzes do not align with the definition of an In Vitro Diagnostic device.
No
The letter does not explicitly state that the FDA has reviewed and approved or cleared a PCCP for this specific device. The 'Control Plan Authorized (PCCP) and relevant text' section is marked 'Not Found'.
Intended Use / Indications for Use
The SignalHF System is intended for use by qualified healthcare professionals (HCP) managing patients over 18 years old who are receiving physiological monitoring for Heart Failure surveillance and implanted with a compatible Cardiac Implantable Electronic Devices (CIED) (i.e., compatible pacemakers, ICDs, and CRTs).
The SignalHF System provides additive information to use in conjunction with standard clinical evaluation.
The SignalHF HF Score is intended to calculate the risk of HF for a patient in the next 30 days.
This System is intended for adjunctive use with other physiological vital signs and patient symptoms and is not intended to independently direct therapy.
Product codes
QNL
Device Description
SignalHF is a software as medical device (SaMD) that uses a proprietary and validated algorithm, the SignalHF HF Score, to calculate the risk of a future worsening condition related to Heart Failure (HF). The algorithm computes this HF score using data obtained from (i) a diverse set of physiologic measures generated in the patient's remotely accessible pre-existing cardiac implant (activity, atrial burden, heart rate variability, heart rate, heart rate at rest, thoracic impedance (for fluid retention), and premature ventricular contractions per hour), and (ii) his/her available Personal Health Records (demographics). SignalHF provides information regarding the patient's health status (like a patient's stable HF condition) and also provides alerts based on the SignalHF HF evaluation. Based on an alert and a recovery threshold on the SignalHF score established during the learning phase of the algorithm and fixed for all patients, our monitoring system is expected to raise an alert 30 days (on median) before a predicted HF hospitalization event (see Figure 1).
SignalHF does not provide a real-time alert. Rather, it is designed to detect chronic worsening of HF status. SignalHF is designed to provide a score linked to the probability of a future decompensated heart failure event specific to each patient. Using this adjunctive information, healthcare professionals can make adjustments for the patient based on their clinical judgement and expertise.
The score and score-based alerts provided through SignalHF can be displayed on any compatible HF monitoring platform, including the Implicity platform. The healthcare professional (HCP) can utilize the SignalHF HF score as adjunct information when monitoring CIED patients with remote monitoring capabilities.
The HCP's decision is not based solely on the device data which serves as adjunct information, but rather on the full clinical and medical picture and record of the patient.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
- physiologic data analysis performed using machine learning
- The algorithm computes this HF score using data obtained from (i) a diverse set of physiologic measures generated in the patient's remotely accessible pre-existing cardiac implant (activity, atrial burden, heart rate variability, heart rate, heart rate at rest, thoracic impedance (for fluid retention), and premature ventricular contractions per hour), and (ii) his/her available Personal Health Records (demographics). SignalHF provides information regarding the patient's health status (like a patient's stable HF condition) and also provides alerts based on the SignalHF HF evaluation. Based on an alert and a recovery threshold on the SignalHF score established during the learning phase of the algorithm and fixed for all patients, our monitoring system is expected to raise an alert 30 days (on median) before a predicted HF hospitalization event (see Figure 1).
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
patients over 18 years old
Intended User / Care Setting
qualified healthcare professionals (HCP) managing patients ... who are receiving physiological monitoring for Heart Failure surveillance and implanted with a compatible Cardiac Implantable Electronic Devices (CIED) (i.e., compatible pacemakers, ICDs, and CRTs).
Description of the training set, sample size, data source, and annotation protocol
The FORESEE-HF Study is a non-interventional clinical retrospective study designed to evaluate a SignalHF score resulting from the combination of multiple sensor measurements collected from multi-brands CIEDs and the data stored in the French national health database "SNDS" in order to detect signs of worsening HF. The follow-up period is defined as 2017-2021.
Inclusion criteria for patients:
- Implanted with a ICD / CRT-D / PM / CRT-P, manufactured by Medtronic, Boston Scientific and Biotronik, compatible with thoracic impedance recording
- With at least one remote monitoring data transmission during the follow-up period of 2018-2021
Exclusion criteria for patients:
- Patients with unspecified device type in the retrospective database
- Patients with multiple devices between 2010 and 2021
Training cohort sample size: 7556 patients.
Source: SNDS (the SYSTÈME NATIONAL DES DONNÉES DE SANTÉ) databases as well as Implicity proprietary databases.
Description of the test set, sample size, data source, and annotation protocol
The FORESEE-HF Study is a non-interventional clinical retrospective study designed to evaluate a SignalHF score resulting from the combination of multiple sensor measurements collected from multi-brands CIEDs and the data stored in the French national health database "SNDS" in order to detect signs of worsening HF. The follow-up period is defined as 2017-2021.
Inclusion criteria for patients:
- Implanted with a ICD / CRT-D / PM / CRT-P, manufactured by Medtronic, Boston Scientific and Biotronik, compatible with thoracic impedance recording
- With at least one remote monitoring data transmission during the follow-up period of 2018-2021
Exclusion criteria for patients:
- Patients with unspecified device type in the retrospective database
- Patients with multiple devices between 2010 and 2021
Validation cohort sample size: 3678 patients.
Clinical cohort sample size: 6,740 patients.
Source: SNDS (the SYSTÈME NATIONAL DES DONNÉES DE SANTÉ) databases as well as Implicity proprietary databases.
Summary of Performance Studies
Study Type: Non-clinical Performance and Algorithm Performance Testing / Non-interventional clinical retrospective study (FORESEE-HF Study).
Sample Size:
Algorithm performance testing used SNDS (the SYSTÈME NATIONAL DES DONNÉES DE SANTÉ) databases as well as Implicity proprietary databases.
FORESEE-HF Study population size: 17,974 patients (PM 7,360, ICD 5,642, CRT-D 4,116 and CRT-P 856; age 70.0 ± 13.3, male 70.20%).
Train cohort: 7556.
Validation cohort: 3678.
Clinical cohort: 6,740.
Key Results:
The three co-primary endpoints were reached in the FORESEE-HF study.
-
For ICD/CRT-D devices:
- Sensitivity for detecting hospitalizations with HF as primary diagnosis: 59.8% [54.0%; 65.4%] (objective > 40%)
- Unexplained alert rate per patient-year: 0.654 [0.614; 0.692] (objective 15 days)
-
For pacemaker/CRT-P devices:
- Sensitivity for detecting hospitalizations with HF as primary diagnosis: 45.9% [38.1%; 53.8%] (objective > 30%)
- Unexplained alert rate per patient-year: 0.470 [0.441; 0.502] (objective 15 days)
Performance per manufacturer for ICD/CRT-D devices:
- Medtronic: Sensitivity 52.0%, UAR PPY 0.30, Lower quartile alerting time 39.3 days.
- Boston Scientific: Sensitivity 62.5%, UAR PPY 0.89, Lower quartile alerting time 28.0 days.
- Biotronik: Sensitivity 70.0%, UAR PPY 1.09, Lower quartile alerting time 39.0 days.
Performance per manufacturer for Pacemaker/CRT-P devices:
- Medtronic: Sensitivity 50.4%, UAR PPY 0.71, Lower quartile alerting time 64.5 days.
- Biotronik: Sensitivity 45.3%, UAR PPY 0.42, Lower quartile alerting time 37.0 days.
Summary: SignalHF performances are above target performances for all pre-defined patient groups except for Boston Scientific pacemaker/CRT-P devices, for which there was not enough data for training and evaluation. Medtronic Pacemaker 1 lead group did not meet endpoint requirements.
Key Metrics
- Sensitivity for detecting hospitalizations with HF as primary diagnosis
- Unexplained alert rate per patient-year (PPY)
- Lower quartile on alerting time (in days)
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 870.2210 Adjunctive predictive cardiovascular indicator.
(a)
Identification. The adjunctive predictive cardiovascular indicator is a prescription device that uses software algorithms to analyze cardiovascular vital signs and predict future cardiovascular status or events. This device is intended for adjunctive use with other physical vital sign parameters and patient information and is not intended to independently direct therapy.(b)
Classification. Class II (special controls). The special controls for this device are:(1) A software description and the results of verification and validation testing based on a comprehensive hazard analysis and risk assessment must be provided, including:
(i) A full characterization of the software technical parameters, including algorithms;
(ii) A description of the expected impact of all applicable sensor acquisition hardware characteristics and associated hardware specifications;
(iii) A description of sensor data quality control measures;
(iv) A description of all mitigations for user error or failure of any subsystem components (including signal detection, signal analysis, data display, and storage) on output accuracy;
(v) A description of the expected time to patient status or clinical event for all expected outputs, accounting for differences in patient condition and environment; and
(vi) The sensitivity, specificity, positive predictive value, and negative predictive value in both percentage and number form.
(2) A scientific justification for the validity of the predictive cardiovascular indicator algorithm(s) must be provided. This justification must include verification of the algorithm calculations and validation using an independent data set.
(3) A human factors and usability engineering assessment must be provided that evaluates the risk of misinterpretation of device output.
(4) A clinical data assessment must be provided. This assessment must fulfill the following:
(i) The assessment must include a summary of the clinical data used, including source, patient demographics, and any techniques used for annotating and separating the data.
(ii) The clinical data must be representative of the intended use population for the device. Any selection criteria or sample limitations must be fully described and justified.
(iii) The assessment must demonstrate output consistency using the expected range of data sources and data quality encountered in the intended use population and environment.
(iv) The assessment must evaluate how the device output correlates with the predicted event or status.
(5) Labeling must include:
(i) A description of what the device measures and outputs to the user;
(ii) Warnings identifying sensor acquisition factors that may impact measurement results;
(iii) Guidance for interpretation of the measurements, including a statement that the output is adjunctive to other physical vital sign parameters and patient information;
(iv) A specific time or a range of times before the predicted patient status or clinical event occurs, accounting for differences in patient condition and environment;
(v) Key assumptions made during calculation of the output;
(vi) The type(s) of sensor data used, including specification of compatible sensors for data acquisition;
(vii) The expected performance of the device for all intended use populations and environments; and
(viii) Relevant characteristics of the patients studied in the clinical validation (including age, gender, race or ethnicity, and patient condition) and a summary of validation results.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
October 25, 2023
Implicity Inc. Caroline Florequin - Head of Quality and Reguatory Affairs 185 Alewife Brook Parkway: Suite 210 Cambridge, Massachusetts 02138
Re: K230842
Trade/Device Name: SignalHF Regulation Number: 21 CFR 870.2210 Regulation Name: Adjunctive Predictive Cardiovascular Indicator Regulatory Class: Class II Product Code: QNL Dated: September 25, 2023 Received: September 25, 2023
Dear Caroline Florequin:
We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
1
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Stephen C. Browning -S
LCDR Stephen Browning Assistant Director Division of Cardiac Electrophysiology, Diagnostics and Monitoring Devices Office of Cardiovascular Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
2
Indications for Use
510(k) Number (if known) K230842
Device Name SignalHF
Indications for Use (Describe)
The SignalHF System is intended for use by qualified healthcare professionals (HCP) managing patients over 18 years old who are receiving physiological monitoring for Heart Failure surveillance and implanted with a compatible Cardiac Implantable Electronic Devices (CIED) (i.e., compatible pacemakers, ICDs, and CRTs).
The SignalHF System provides additive information to use in conjunction with standard clinical evaluation.
The SignalHF HF Score is intended to calculate the risk of HF for a patient in the next 30 days.
This System is intended for adjunctive use with other physiological vital signs and patient symptoms and is not intended to independently direct therapy.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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3
510(k) Summary
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of 21 CFR 807.92
Submitter 1
| Applicant | IMPLICITY INC
185 ALEWIFE BROOK PARKWAY - SUITE 210
CAMBRIDGE, MA 02138
USA
Phone: +33 6 76 731 731 |
|----------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person | Caroline Florequin
Head of QARA
IMPLICITY INC
185 ALEWIFE BROOK PARKWAY -
SUITE 210 CAMBRIDGE, MA 02138
USA
caroline.florequin@implicity.com
Phone: +33 6 66 21 35 91 |
| Assisted by | Mark Johnson
Regulatory consultant to Implicity Inc
MJ Medtech Consulting Services LLC
4587 Canvasback rd
Blaine, Washington
98230
+1 (503) 575-5886 |
| Date prepared:
510(k) number: | October, 25th 2023
K230842 |
| 2 Device Information | |
| Trade Name | SignalHF |
| Common Name | IM008 |
| Classification | 21CFR- 870.2210 - Adjunctive predictive cardiovascula |
indicator, Class II – Medium
4
Product Code QNL
3 Predicate Device
The predicate and reference device for SignalHF are:
Acumen™ Hypotension Prediction Index (HPI), Edwards Lifesciences, LLC K203224 Predicate Device
| | Subject Device | Predicate Device | Comparison
to
Predicate Device |
|-----------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Name | SignalHF | Acumen™ Hypotension
Prediction Index (HPI) | |
| Manufacturer | IMPLICITY INC | Edwards Lifesciences, LLC | |
| 510(k) # | | K203224 | |
| Regulation
Number | 21 CFR 870.2210 | 21 CFR 870.2210 | Same |
| Class | II | II | Same |
| Device Class /
Name | Medium term adjunctive
predictive cardiovascular
indicator. | Adjunctive predictive
cardiovascular indicator. | Same |
| Product Code | QNL | QAQ | Similar, Product
codes are not the
same, but similar.
Both devices are
SaMD. Incoming
data is similar but
not the same.
Product Code QAQ
specifically identifies
hypotension as the
target area. |
| Product
Code
Device
Definition | Medium-Term Adjunctive
Predictive Cardiovascular
Indicator
The adjunctive predictive
cardiovascular indicator is a
prescription device that uses
software algorithms to
analyze cardiovascular vital | Adjunctive Predictive
Cardiovascular Indicator
The adjunctive predictive
cardiovascular indicator is
a prescription device that
uses software algorithms
to analyze cardiovascular
vital signs and predict | Same |
| | signs and predict future
cardiovascular status or
events within a defined
medium-term period. This
device is intended for
adjunctive use with other
physical vital sign parameters
and patient information and is
not intended to
independently direct therapy. | future cardiovascular
status or events. This
device is intended for
adjunctive use with other
physical vital sign
parameters and patient
information and is not
intended to independently direct
therapy. | |
| Software
Level of
Concern | Moderate | Moderate | Same |
5
Device Description 4
SignalHF is a software as medical device (SaMD) that uses a proprietary and validated algorithm, the SignalHF HF Score, to calculate the risk of a future worsening condition related to Heart Failure (HF). The algorithm computes this HF score using data obtained from (i) a diverse set of physiologic measures generated in the patient's remotely accessible pre-existing cardiac implant (activity, atrial burden, heart rate variability, heart rate, heart rate at rest, thoracic impedance (for fluid retention), and premature ventricular contractions per hour), and (ii) his/her available Personal Health Records (demographics). SignalHF provides information regarding the patient's health status (like a patient's stable HF condition) and also provides alerts based on the SignalHF HF evaluation. Based on an alert and a recovery threshold on the SignalHF score established during the learning phase of the algorithm and fixed for all patients, our monitoring system is expected to raise an alert 30 days (on median) before a predicted HF hospitalization event (see Figure 1).
Image /page/5/Figure/5 description: The image shows a graph titled "HF Watch Risk score of hospitalization for Heart Failure within the next 30 Days". The graph plots the HF score over time, with the x-axis representing dates from June to December and the y-axis representing the HF score from 0 to 100. The HF score is shown as a blue line, and there are also dashed lines representing the alert threshold at 50 and the recovery threshold at 30. The text indicates that the HFWatch score has crossed the alert threshold and is still above the recovery threshold since November 3, 2022, indicating a high risk of hospitalization within the next 30 days.
Figure 1. An example of a graph displaying the SignalHF score over time, crossing the alert threshold.
SignalHF does not provide a real-time alert. Rather, it is designed to detect chronic worsening of HF status. SignalHF is designed to provide a score linked to the probability of a future decompensated heart failure event specific to each patient. Using this adjunctive information, healthcare professionals can make adjustments for the patient based on their clinical judgement and expertise.
The score and score-based alerts provided through SignalHF can be displayed on any compatible HF monitoring platform, including the Implicity platform. The healthcare professional (HCP) can utilize the
6
SignalHF HF score as adjunct information when monitoring CIED patients with remote monitoring capabilities.
The HCP's decision is not based solely on the device data which serves as adjunct information, but rather on the full clinical and medical picture and record of the patient.
Indication for Use 5
Indication for use :
The SignalHF System is intended for use by qualified healthcare professionals (HCP) managing patients over 18 years old who are receiving physiological monitoring for Heart Failure surveillance and implanted with a compatible Cardiac Implantable Electronic Devices (CIED) (i.e., compatible pacemakers, ICDs, and CRTs). The SignalHF System provides additive information to use in conjunction with standard clinical evaluation. The SignalHF HF Score is intended to calculate the risk of HF for a patient in the next 30 days.
This System is intended for adjunctive use with other physiological vital signs and patient symptoms and information and is not intended to independently direct therapy.
Indication for use of predicate:
The Edwards Lifesciences Acumen Hypotension Prediction Index feature provides the clinician with physiological insight into a patient's likelihood of future hypotensive events (defined as mean arterial pressure 40%
- Unexplained alert rate per patient-year 30% ।
- -Unexplained alert rate per patient-year 15 days for ICD and CRT-D from all the manufacturers analyzed, except for Boston Scientific ICD/CRT-D devices, where it is > 15 days on average only. Concerning IPG and CRT-P devices, the sensitivity is 50.4 % for Medtronic devices and 45.3% for Biotronik and UAR PPY is always 15 days for Biotronik IPG/CRT-P devices, and on average due to low sample size for Medtronic IPG/CRT-Ps. Therefore, the three co-primary endpoints are reached.
Global Performance
The following presents the performance of SignalHF by device type as it relates to:
- Sensitivity for detecting hospitalizations with HF as primary diagnosis, and ●
- Unexplained alert rate per patient-year (PPY) ●
- Lower quartile on alerting time (in days)
All SignalHF performance metrics are available in the Clinical Evaluation Report (CER-IM008)
| Endpoints | ICD/CRT-D population objective | SignalHF performance for ICD/CRT-D devices |
|---|---|---|
| Sensitivity (%) | > 40% | 59.8% [54.0%; 65.4%] |
| Unexplained Alert Rate PPY | 15 days | 35.0 [27.0; 52.0] |
| Endpoints | Pacemaker/CRT-P
population
objective | SignalHF performance
for
pacemaker/CRT-P devices |
|----------------------------------------------|--------------------------------------------|--------------------------------------------------------|
| Sensitivity (%) | > 30% | 45.9% [38.1%; 53.8%] |
| Unexplained Alert Rate PPY | 15 days | 37 [24.5; 53.0] |
Performance per manufacturer
MEDTRONIC
10
| Endpoints | ICD/CRT-D population
objective | SignalHF performance for
Medtronic ICD/CRT-D |
|----------------------------------------------|-----------------------------------|-------------------------------------------------|
| Sensitivity (%) | > 40% | 52.0% [43.6%; 60.2%] |
| Unexplained Alert Rate
PPY | 15 days | 39.3 [21.0; 59.0] |
| Endpoints | Pacemaker/CRT-P
population objective | SignalHF performance for
Medtronic pacemaker/CRT-P |
|----------------------------------------------|-----------------------------------------|-------------------------------------------------------|
| Sensitivity (%) | > 30% | 50.4% [30.6%; 70.2%] |
| Unexplained Alert
Rate PPY | 15 days | 64.5 [8.0; 119.0] |
BOSTON SCIENTIFIC
| Endpoints | ICD/CRT-D population
objective | SignalHF performance for
Boston Scientific ICD/CRT-D |
|----------------------------------------------|-----------------------------------|---------------------------------------------------------|
| Sensitivity (%) | > 40% | 62.5% [46.9%; 75.8%] |
| Unexplained Alert Rate
PPY | 15 days | 28.0 [13.0; 55.5] |
BIOTRONIK
11
| Endpoints | ICD/CRT-D population
objective | SignalHF performance for
Biotronik ICD/CRT-D |
|----------------------------------------------|-----------------------------------|-------------------------------------------------|
| Sensitivity (%) | > 40% | 70.0% [60.6%; 77.9%] |
| Unexplained Alert Rate
PPY | 15 days | 39.0 [25.8 ; 60.0] |
| Endpoints | Pacemaker/CRT-P
population objective | SignalHF performance for
Biotronik pacemaker/CRT-P |
|----------------------------------------------|-----------------------------------------|-------------------------------------------------------|
| Sensitivity (%) | > 30% | 45.3% [36.9%; 53.9%] |
| Unexplained Alert Rate
PPY | 15 days | 37.0 [25.5; 53.0] |
SUMMARY
SignalHF performances are above target performances for all pre-defined patient groups except for Boston Scientific pacemaker/CRT-P devices, for which we did not have enough data for training and evaluation of a HF prediction algorithm.
Performance analysis per manufacturer, device model type and number of
leads
Medtronic ICD/CRT-D devices
12
| Endpoints | ICD/CRT-D
population
objective | One lead | Two leads | Three leads |
|-------------------------------------------------|--------------------------------------|-------------------------|-------------------------|-------------------------|
| Sensitivity (%) | > 40% | 43.5%
[29.6%; 58.5%] | 49.3%
[35.8%; 63.0%] | 62.7%
[48.0%; 75.4%] |
| Unexplained
alert rate PPY | 15 days | 59.0
[19.0; 163.0] | 31.0
[10.0; 55.0] | 57.0
[16.0; 96.0] |
Medtronic PM/CRT-P devices
| Endpoints | Pacemaker
/CRT-P
population
objective | One lead | Two leads | Three leads |
|-------------------------------------------------|------------------------------------------------|-----------------------------|-------------------------|------------------------|
| Sensitivity (%) | > 30% | 16.7%
[2.3%; 63.1%] | 64.6%
[34.5%; 86.3%] | Not available |
| Unexplained
alert rate PPY | 15 days | 10.0
(CI not computable) | 91.8
[20.0; 129.0] | 106.3
[98.0; 131.0] |
Boston Scientific ICD/CRT-D devices
13
| Endpoints | ICD/CRT-D
population
objective | One lead | Two leads | Three leads |
|-------------------------------------------------|--------------------------------------|-------------------------|-----------------------|-------------------------|
| Sensitivity (%) | > 40% | 71.2%
[40.3%; 90.0%] | Not available | 60.5%
[39.4%; 78.4%] |
| Unexplained
alert rate PPY | 15 days | 52.5
[15.0; 140.3] | 53.8
[29.0; 179.0] | 43.0
[11.3; 94.0] |
Biotronik ICD/CRT-D devices
| Endpoints | ICD/CRT-D
population
objective | One lead | Two leads | Three leads |
|-------------------------------------------------|--------------------------------------|-------------------------|-------------------------|-------------------------|
| Sensitivity (%) | > 40% | 73.1%
[55.4%; 85.6%] | 67.5%
[50.3%; 81.1%] | 63.1%
[48.4%; 75.8%] |
| Unexplained
alert rate PPY | 15 days | 41.0
[22.0; 64.8] | 62.75
[30.0; 157.0] | 54.0
[18.5; 88.0] |
Biotronik PM/CRT-P devices
14
| Endpoints | Pacemaker/
CRT-P
population
objective | One lead | Two leads | Three leads |
|----------------------------------------------------|------------------------------------------------|-------------------------|-------------------------|-------------------------|
| Sensitivity
(%) | > 30% | 29.4%
[11.2%; 58.0%] | 40.2%
[30.9%; 50.2%] | 48.0%
[26.3%; 70.4%] |
| Unexplained
alert rate PPY | 15 days | 108.0
[3.0; 395.0] | 64.0
[34.0; 105.5] | 10.0
[9.0; 34.5] |
SUMMARY
Defibrillators with 1, 2 or 3 leads from all manufacturers, as well as pacemakers with 2 and 3 leads from Medtronic and pacemakers with 1, 2 or 3 leads from Biotronik passed the required performances on every endpoint (sensitivity, unexplained alert rate, median alerting time). The results show in particular no specific group overperforming and causing performance overestimation.
Medtronic Pacemaker 1 lead is the only group not meeting endpoint requirements as defined in the CEP IM008. However, this population does not have any alternative to assess a potential risk of Heart Failure based on their device data. Implicity believes bringing IM008 to this population could avoid some hospitalization in a population that is for the moment not addressed by any other solution.
Warning: In patient populations unlikely to have acute decompensation of HF, the use of the algorithm may have less and possibly poor PPV and NPV.
8 Conclusion
The results of non-clinical testing demonstrate that SignalHF meets its intended use which is equivalent to that of the predicate device. Testing also ensured that SignalHF performed as intended and does not raise different questions of safety or effectiveness to the predicate device.