The device is intended to capture, and report symptomatic and asymptomatic cardiac events and continuous electrocardiogram information for long-term monitoring. After wear, ECG data from compatible monitoring devices is processed and analyzed by the ZEUS System. A final report is generated on the beat-to-beat information from the entire ECG recording. For the Zio AT service, the ZEUS System supports the capture and analysis of automatically-detected arrhythmia events, as well as the analysis of uploaded patient-triggered events.

The ZEUS System is indicated for use on patients 18 years or older who may be asymptomatic or who may suffer from transient symptoms such as palpitations, shortness of breath, dizziness, light-headedness, pre-syncope, fatigue, or anxiety and patients who are asymptomatic. The reports are provided for review by the intended user to render a diagnosis based on clinical judgment and experience. It is not intended for use on critical care patients.

Device Description

The Zio® Service consists of single-patient-use monitoring devices and the Zio ECG Utilization Software (ZEUS) System, the subject device of this submission, for analysis and reporting of cardiac information derived from ECG data. The ZEUS System is a software system consisting of a collection of software modules designed to store and analyze data from compatible cardiac monitoring devices to curate a report of preliminary findings intended for use by clinicians as an aid in arrhythmia diagnosis and management.

The subject ZEUS System utilizes an artificial intelligence (AI) Al-based AutoTrigger Engine (ATE) software application for processing requests originating from the Gateway Service as part of the Zio AT system enabling asymptomatic ECG triggers, and Al-based ECG Analysis Software (ECGDL) to generate the initial ECG-based cardiac information.

The output of ECG Analysis Software of the ZEUS System is used by Certified Cardiographic Technicians (CCTs) prior to publishing the cardiac information in the patient report and is not utilized directly by the prescribing clinician or patient. The reported cardiac information includes beats, ectopic runs, ECG segments, rhythms, and heart rate measurements. Recorded ECG is processed by an automated ECG analysis platform; results are quality reviewed by CCTs, findings and associated ECG are captured in a report provided to clinicians via a secure website. For the Zio® AT Patch/Gateway, the ZEUS System provides capabilities to automatically detect clinically actionable arrhythmia during the monitoring period, as well as receive baseline, scheduled, symptomatic, and asymptomatic transmissions.

The subject of this 510(k) are proposed software modifications to the ZEUS System to allow AF/AFL burden estimate reporting in the daily reports. In addition, software modifications were made to the ECGDL software of the ZEUS System to target modest performance improvements.

AI/ML Overview

The ZEUS System, subject of K222389, is substantially equivalent to its predicate device (K202527), based on non-clinical performance data. Here's a summary of the available information:

1. A table of acceptance criteria and the reported device performance

The provided document refers to non-clinical verification and performance testing that established the device meets its design requirements. However, it does not explicitly list specific acceptance criteria thresholds (e.g., sensitivity, specificity, accuracy targets) for arrhythmia detection or AF burden estimation, nor does it provide a table of reported device performance against such specific criteria.

Instead, it states: "The nonclinical verification and performance test results established that the device meets its design requirements and intended use, that the design differences with the cleared device do not raise new questions of safety and efficacy." And, "The verification and validation testing demonstrate that the device meets all predetermined specifications."

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The document does not provide details on the sample size used for the test set in terms of the number of ECG recordings or patients, nor does it specify the data provenance (country of origin, retrospective/prospective). It only mentions "nonclinical verification and performance test results."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

The document states that the output of the ECG Analysis Software is "quality reviewed by CCTs" (Certified Cardiographic Technicians) before publishing the report. However, it does not specify:

The number of CCTs or other experts involved in establishing ground truth for the test set used in the non-clinical performance evaluation.
The specific qualifications or experience levels of these CCTs or any other experts who might have been involved in a ground truth process for testing.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for the test set. It mentions CCTs perform a "quality review," but the procedure for resolving discrepancies or establishing a "ground truth" for formal testing purposes is not detailed.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No MRMC comparative effectiveness study is mentioned in the provided text. The document explicitly states: "No clinical testing was performed in support of this premarket notification." The system's output is intended for review by clinicians, but the document does not describe any studies on the impact of the AI on human reader performance.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, a standalone performance of the algorithm is implied for the "ECGDL software of the ZEUS System to target modest performance improvements" and the "Al-based AutoTrigger Engine (ATE) software application." The non-clinical performance testing would evaluate the algorithm's output prior to human review, to ensure it meets design specifications. However, specific standalone performance metrics (e.g., sensitivity, specificity for various arrhythmias) are not provided in this document.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The document indicates that "the output of ECG Analysis Software of the ZEUS System is used by Certified Cardiographic Technicians (CCTs) prior to publishing the cardiac information in the patient report." This strongly suggests that for the operational process, the ground truth is essentially expert consensus/review by CCTs. For the non-clinical performance testing, it is implied that a similar expert review or a reference standard based on expert interpretation of ECG data would be used to establish ground truth, but this is not explicitly detailed.

8. The sample size for the training set

The document does not provide any information regarding the sample size used for the training set of the AI-based AutoTrigger Engine (ATE) and ECGDL software.

9. How the ground truth for the training set was established

The document does not specify how the ground truth for the training set was established. It describes the general function of the system and its review process by CCTs, but details concerning training data annotation are absent.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. FOOD & DRUG ADMINISTRATION" stacked on top of each other.

February 15, 2023

iRhythm Technologies, Inc. Vishal Kanani Senior Regulatory Affairs Program Lead 699 8th Street San Francisco, California 94103

Re: K222389

Trade/Device Name: ZEUS System Regulation Number: 21 CFR 870.1425 Regulation Name: Programmable Diagnostic Computer Regulatory Class: Class II Product Code: DQK, DXH, DSI Dated: January 13, 2023 Received: January 17, 2023

Dear Vishal Kanani:

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 (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 located 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.

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.

{1}------------------------------------------------

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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatoryinformation/postmarketing-safety-reporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 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,

Shruti N. Mistry -S

for

Jennifer Shih Kozen 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

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K22389

Device Name ZEUS System

Indications for Use (Describe)

	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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

510(k) Notification K222389

l. General Information

Applicant:

iRhythm Technologies, Inc. 699 8th Street, Suite 600 San Francisco, CA 94103 USA Phone: 415-632-5700 Fax: 415-632-5701

Contact Person:

Vishal Kanani Manager, Regulatory Affairs Phone: 213-400-0963 Email: vishal.kanani@irhythmtech.com

Date Prepared: July 29, 2022

II. Device Information

Trade Name: ZEUS System

Generic/Common Name:

Programmable diagnostic computer

Classification Names:

. Programmable diagnostic computer [21CFR§870.1425]
Arrhythmia detector and alarm (including ST-segment measurement and alarm) [21CFR§870.1025]
Telephone electrographic transmitter and receiver [21CFR§870.2920]

Regulatory Class:

Class II (Special controls)

Product Codes:

DQK, Computer, Diagnostic, Programmable
DSI, Detector and Alarm, Arrhythmia ●
DXH, Transmitters and Receivers, Electrocardiographic, Telephone

lll. Predicate Devices

The following predicate devices have been selected:

Primary Predicate: iRhythm Technologies, Inc. Zio® ECG Utilization Service (ZEUS) System [K202527]

{4}------------------------------------------------

IV. Indications for Use

The Indications for Use statement for the subject ZEUS System is as follows:

The device is intended to capture, analyze and report symptomatic and asymptomatic cardiac events and continuous electrocardiogram information for long-term monitoring. After wear, ECG data from compatible monitoring devices is processed and analyzed by the ZEUS System. A final report is generated on the beat information from the entire ECG recording. For the Zio AT service, the ZEUS System supports the capture and analysis of automatically-detected arrhythmia events, as well as the analysis of uploaded patient-triggered events.

V. Device Description

VI. Comparison of Technological Characteristics with Predicate Devices (Substantial Equivalence) The subject ZEUS System has the same intended use as the predicate devices. The differences in the technological characteristics between the subject and predicate devices do not raise any issues of safety or efficacy as the fundamental scientific technology and intended use is unchanged. Thus, the ZEUS System is considered substantially equivalent to the predicate device.

{5}------------------------------------------------

A comparison table outlining the differences and similarities between the subject device and the predicate devices is provided in Table 1.

Feature	Subject Device:ZEUS System	Primary Predicate Device: ZEUSSystem(K202527)
Manufacturer	iRhythm Technologies, Inc.	Identical
Classification	Class II	Identical
Product Code	Classification Product Code: DQKSubsequent Product Codes: DSI, DXH	Identical
Review Panel	Cardiovascular	Identical
Prescription/OTC	Prescription	Identical
Rhythm DetectionAlgorithm	ECGDL	Identical
Beat Detection	ECGDL	Same
Interoperability	Zio XT Patch Zio AT Patch Zio Monitor	Identical
AF Burden Reporting	Final Report Daily Report (AF Burden Estimates)	Final Report

Table 1: Substantial Equivalence Summary Table

VII. Performance Data

Safety and performance of the subject ZEUS System has been evaluated and verified in accordance with design specifications and to support a determination of substantial equivalence to the predicate device.

The design verification and validation testing performed on the subject device demonstrates that the subject ZEUS System is in conformance with FDA-recognized consensus standards and FDA guidance documents as highlighted in Table 2.

FDA #	Body	Number/Version	Title
5-40	AAMI ANSI ISO	14971:2012(R)2010(Corrected 4 October 2017)	Medical Devices – Application of RiskManagement to Medical Devices
13-79	IEC	62304 Edition 1.12015-06CONSOLIDATEDVERSION	Medical Device Software - Software LifeCycle Processes
3-127	AAMI ANSI IEC	60601-2-47:2012	Medical Electrical Equipment -- Part 2-47:Particular Requirements For The BasicSafety And Essential Performance OfAmbulatory Electrocardiographic Systems
3-118	AAMI ANSI	EC57:2012	Testing and Reporting Performance Resultsof Cardiac Rhythm and ST SegmentMeasurement Algorithms

Table 2: FDA-Recognized Consensus Standards & Guidance Document Summary
-------------------------------------------------------------------------

{6}------------------------------------------------

N/A	U.S. FDA	October 2, 2014	Guidance for Industry and FDA Staff -Content of Premarket Submissions forManagement of Cybersecurity in MedicalDevices
N/A	U.S. FDA	May 5, 2005	Guidance for the Content of PremarketSubmissions for Software Contained inMedical Devices
N/A	U.S. FDA	September 6, 2017	Design Considerations and PremarketSubmission Recommendations forInteroperable
N/A	U.S. FDA	July 2014	The 510(k) Program: Evaluating SubstantialEquivalence in Premarket Notifications[510(k)]

The nonclinical verification and performance test results established that the device meets its design requirements and intended use, that the design differences with the cleared device do not raise new questions of safety and efficacy. During development, potential hazards were evaluated and controlled by risk management activities, including risk analysis, risk mitigation, verification and benefit-risk analysis. The verification and validation testing demonstrate that the device meets all predetermined specifications.

VIII. Clinical Testing in Support of Substantial Equivalence Determination

No clinical testing was performed in support of this premarket notification.

IX. Conclusion

The results confirm by evaluation and provision of objective evidence that the design outputs met the design input requirements. The results of the nonclinical testing performed demonstrate that the subject ZEUS System meets the requirements of established conformance standards and performance specifications necessary for its intended use and does not raise new questions of safety or effectiveness as compared to the predicate device. The subject ZEUS System is substantially equivalent to its predicate device.

Regulation Number and Section

§ 870.1425 Programmable diagnostic computer.

(a)
Identification. A programmable diagnostic computer is a device that can be programmed to compute various physiologic or blood flow parameters based on the output from one or more electrodes, transducers, or measuring devices; this device includes any associated commercially supplied programs.(b)
Classification. Class II (performance standards).