The presence of Microvolt T-wave Alternans as measured by the Analytic Spectral Method of the Heartwave™ Alternans Processing System in patients with known, suspected or at risk of ventricular tachyarrhythmia predicts increased risk of a cardiac event (ventricular tachyarrhythmia or sudden death).

The Heartwave™ Alternans Processing System should be used only as an adjunct to clinical history and the results of other non-invasive and/or invasive tests. The interpretive results of the Alternans Processing System should be reviewed by a qualified physician.

The predictive value of T-wave Alternans for cardiac events has not been established in patients with active, untreated ischemia.

*Microvolt T-wave Alternans is defined as T-wave alternans which (a) is measured from high-resolution multi-segment sensors, (b) is present in leads X, Y, Z, VM or two adjacent precordial leads, (c) is at the level of 1.9 microvolts after signal optimization and subtraction of the background noise level, (d) is at least three standard deviations greater than the background noise level, (e) has an onset heart rate at or below 110 beats per minute, and (f) is sustained for all heart rates above the onset heart rate.

Device Description

The Heartwave™ Alternans Processing System is intended for the measurement and recording of T-Wave alternans. The modification which is the subject of this pre-market submission is the modification of a parameter in Alternans Report Classifier software which was cleared for marketing on November 17, 2002 (K03564). Classification software provides the clinician with an indication of positive, negative, or indeterminate result for the Alternans Trend Reports. The results remain subject to the final review of a qualified medical practitioner. The Microvolt T-wave Alternans has been shown to be useful in predicting ventricular tachyarrhythmias and sudden cardiac death.

The Heartwave™ Alternans Processing System provides T-wave alternans diagnostic capabilities to standard stress labs. The Analytic Spectral Method of Alternans Processing used in the Heartwave is intended for the measurement of Microvolt T-wave alternans at rest and during treadmill, ergometer and pharmacologic stress testing. The Alternans Report Classifier provides input to the physician on interpreting the Alternans trend reports.

The alternans test using the Analytic Spectral Method of Alternans Processing is performed with seven standard stress test electrodes and seven proprietary multi-segment Micro-V Alternans™ Sensors. The electrodes and sensors are attached through a leadwire set to the belt-worn patient module, which provides digitized data to the Alternans Processor.

AI/ML Overview

This 510(k) submission describes a modification to the Heartwave™ Alternans Processing System, specifically to its Alternans Report Classifier software. The document asserts substantial equivalence to a previously cleared device (K013564) rather than presenting a de novo study with explicit acceptance criteria and performance data for the modified classifier.

Therefore, the requested information regarding acceptance criteria and a study proving device performance as traditionally understood for a new device submission is not explicitly detailed in this document. The submission focuses on hardware and software description, intended use, and equivalence to a predicate device.

However, based on the provided text, we can infer some aspects related to "acceptance criteria" through the definition of Microvolt T-wave Alternans (MTWA) and the general claims of safety and effectiveness.

Here's an attempt to answer the questions based on the provided text, highlighting where information is absent or inferred:

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

The document does not provide a formal table of acceptance criteria and device performance as would be expected for a primary clinical trial or analytical validation of a new device. Instead, the "acceptance criteria" are embedded within the definition of Microvolt T-wave Alternans (MTWA), which the device is designed to measure. The "reported device performance" is a claim of substantial equivalence and safety/effectiveness based on the predicate device.

Acceptance Criteria (Inferred from MTWA Definition)	Reported Device Performance (Claimed)
MTWA measured from high-resolution multi-segment sensors	Device uses proprietary multi-segment Micro-V Alternans™ Sensors.
MTWA present in leads X, Y, Z, VM or two adjacent precordial leads	Device uses seven standard stress test electrodes and seven proprietary sensors, implying capability to acquire signals from these leads.
MTWA at least 1.9 microvolts after signal optimization and subtraction of background noise	The device is designed for "Microvolt T-wave Alternans," and the Analytic Spectral Method is intended for its measurement. The classifier provides an indication of positive/negative/indeterminate results based on this measurement.
MTWA at least three standard deviations greater than background noise level	The device is designed for "Microvolt T-wave Alternans," and the Analytic Spectral Method is intended for its measurement. The classifier provides an indication of positive/negative/indeterminate results based on this measurement.
MTWA has an onset heart rate at or below 110 beats per minute	The device is intended for measurement during ECG stress testing (including treadmill, ergometer, pharmacologic) where heart rate changes. The system implicitly measures and considers heart rate.
MTWA sustained for all heart rates above the onset heart rate	The device is intended for measurement during ECG stress testing where heart rate changes. The system implicitly tracks alternans over heart rate ranges.
Overall functionality: Provides an indication of positive, negative, or indeterminate result for Alternans Trend Reports.	The Alternans Report Classifier software provides input to the physician on interpreting the Alternans trend reports.
Overall safety and effectiveness: Safe and effective for its intended use when used by qualified personnel.	"The Heartwave™ Alternans Processing System with Alternans Report Classifier is safe and effective, as indicated, for its intended use." (Conclusion statement)

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

This information is not provided in the document. As this is a 510(k) submission for a modification based on substantial equivalence, a new large-scale clinical test set for the modified classifier's performance is not detailed. The submission relies on the established performance of the predicate device and the analytical validation of the software change.

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)

This information is not provided in the document. No specific test set with expert-established ground truth is described for the modified classifier. The general statement mentions that the "interpretive results... should be reviewed by a qualified physician," but this pertains to clinical usage, not ground truth establishment for a study.

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

This information is not provided in the document.

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

There is no indication that an MRMC comparative effectiveness study was done for this specific modification. The "Alternans Report Classifier" provides an "indication" to the clinician, but no study is presented to quantify how this "assistance" improves human reader performance or its effect size.

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

A standalone performance study for the modified classifier is not explicitly detailed. The document focuses on the system as an adjunct to clinical history and other tests, with final review by a physician. The classifier itself generates "positive, negative, or indeterminate results," implying an algorithmic output, but a standalone performance study with metrics like sensitivity, specificity, or accuracy against an independent ground truth is not presented.

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

The document does not specify the type of ground truth used for validating the modified classifier. For the underlying science of MTWA, the "Indications for Use" state that its presence predicts increased risk of a cardiac event (ventricular tachyarrhythmia or sudden death), suggesting a correlation with clinical outcomes data for the broader concept of MTWA detection. However, for the specific classifier's validation, this is not detailed.

8. The sample size for the training set

This information is not provided in the document.

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

This information is not provided in the document.

Summary

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510(k) Summary

June 30, 2002

Submitter: Cambridge Heart, Inc 1 Oak Park Drive Bedford. Ma 01730 (781) 271-1200 (781) 275-8431 (Fax)

Contact: David Chazanovitz

510(k) Numbers and Product Codes of equivalent devices.

Cambridge Heartwave™ Alternans Processing System 510K Number; #K013564 Product Code: 74 DPS CFR Section: 870.2340

Indications for Use and Intended Population

The Heartwave™ Alternans Processing System is intended for the measurement of Microvolt T-Wave Alternans* at rest and during ECG stress testing.

The predictive value of T-wave Alternans for cardiac events has not been established in patients with active, untreated ischemia.

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Device Description

Standard Hardware Components

Alternans Processor:	Configured for English language and U.S. leaddesignations
Power Supply:	Modular medical-grade, in-line power supply withuniversal power input for Alternans Processor
PM-3 w/ Hi-Res™ Leads:	With U.S. lead designations
Printer, w/ data cable:	Inkjet Printer w/data cable & power cord
Line Cords:	IEC 320 line cord with NEMA 5-15P hospital gradeplug for Alternans Processor; printer line cordsupplied with printer.
Documentation:	Domestic Operator's Manual, Physicians Guide, anTWA Training Program
Shipping Containers:	Mobile pole, Processor unit and Display are shippedin a single container.

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Standard Hardware Accessories

Patient Cable:	Set of 14 separately detachable lead wires whichmeet the requirements of 21CFR 898.12 and complywith IEC-601-1; 56.3c part 1.1, General Requirementsfor Safety
	Individual patient leads are either not detachable, oruser detachable with female socket connections suchthat no conductive surface is exposed whenunconnected.
User Manuals:	Operators manual supplied standard with everysystem. Training manual supplied in conjunction withtraining course.
Patient Electrodes:	Patient electrodes designed and approved specificallyfor use during exercise stress testing should be usedat all times with the Heartwave™ AlternansProcessing System.
	Measurement of alternating beat to beat T-waveamplitude (alternans) requires the use of theCambridge Heart Micro-V Alternans Sensor (Ref:#K002230) in conjunction with other patientelectrodes designed and approved specifically for useduring exercise stress testing.

Performance Standards

The Cambridge Heartwave™ Alternans Processing System meets the following Performance Standards:

. ANSI/AAMI EC11-1991
. EN60601-1: 1988, "Medical Electrical Equipment, Part 1: General Requirements for Safety" including Amendments A1 and A2
◆ EN60601-1-1: 1993, "Medical Electrical Equipment, Part 1: General Requirements for Safety - Section 1.1 Collateral standard: Safety requirements for medical electrical systems"
EN60601-1-2: 1993, "Medical Electrical Equipment, Part 2: Collateral . Standard: Electromagnetic Compatibility - Requirements and Tests"
UL2601-1, "Medical Electrical Equipment, Part 1: General Requirements for
Safety" 2nd Edition, including Amendments A1 and A2 �
CAN/CSA C22.2 No. 601.1-M90, "Medical Electrical Equipment, Part 1: . General Requirements for Safety" including C22.2 No. 601.1S1-94 (IEC 601-1, Amendment 1:1991)

HeartWave Alternans Processing System Special 510(k) Pre-market Submission Section 4 Summary of Safety and Effectiveness page 3

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K022152
page 4 of 4

Similarities and Differences to Predicates

The Heartwave™ Alternans Processing System (new) is the same device as in K013564 with the exception of the modification described in this pre-market submission. The Heartwave Alternans Processing System uses the same Analytic Spectral Method as the predicate Heartwave™ for measuring T-Wave Alternans.

Conclusion

There are more similarities than differences between the predicate device and the Cambridge Heart Heartwave™ Alternans Processing System. Both devices use the Analytic Spectral Method. When used by qualified personnel in accordance with the directions for use, the Heartwave™ Alternans Processing System with Alternans Report Classifier is safe and effective, as indicated, for its intended use.

HeartWave Alternans Processing System Special 510(k) Pre-market Submission Section 4 Summary of Safety and Effectiveness page 4

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image contains the text "Public Health Service". The text is written in a simple, sans-serif font. The words are arranged on a single line, with "Public" and "Health" being the most prominent words.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

JUL 16 2002

'JUL 1 6 2002

Cambridge Heart, Inc. c/o Mr. John D. Greenbaum Consultant Generic Devices Consulting 20310 SW 48th Street Ft. Lauderdale, FL 33332

Re: K022152

Trade Name: Heartwave™ Alternans Processing System Regulation Number: 21 CFR 870.2340 and 870.1425 Regulation Name: Electrocardiograph and Programmable Diagnostic Computer Regulatory Class: Class II (two) Product Code: DPS and DQK Dated: June 30, 2002 Received: July 2, 2002

Dear Mr. Greenbaum:

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. 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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.

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Page 2 - Mr. John D. Greenbaum´

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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 21 CFR Part 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4646. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html

Sincerely yours.

NQa G. Tule

Donna-Bea Tillman, Ph.D. Acting Director Division of Cardiovascular Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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000009

Page 1 of 1

510(k) Number(if known):_____________________________________________________________________________________________________________________________________________________

Device Name: Heartwave™ Alternans Processing System

Indications For Use:

The Heartwave™ Alternans Processing System is intended for the measurement of Microvolt T-Wave Alternans* at rest and during ECG stress testing.

The predictive value of T-wave Alternans for cardiac events has not been established in patients with active, untreated ischemia.

*Microvolt T-wave Alternans is defined as T-wave alternans which (a) is measured from high-resolution multi-segment sensors, (b) is present in leads X. Y. Z. VM or two adiacent precordial leads. (c) is at the level of 1.9 microvolts after signal optimization and subtraction of the background noise level, (d) is at least three standard deviations greater than the background noise level, (e) has an onset heart rate at or below 110 beats per minute, and (f) is sustained for all heart rates above the onset heart rate.

PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Prescription Use_X(Per 21 CRF 801.109)	OR / Over The-Counter Use_
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(Division Sign-Off)

Division of Cardiovascular

and Respiratory Devices

(Optional Format 1-2-96)

510(k) Number	K022152
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Concurrence of CDRH, Office of Device Evaluation (ODE)

Regulation Number and Section

§ 870.2340 Electrocardiograph.

(a)
Identification. An electrocardiograph is a device used to process the electrical signal transmitted through two or more electrocardiograph electrodes and to produce a visual display of the electrical signal produced by the heart.(b)
Classification. Class II (performance standards).