DEEPVESSEL FFR is a coronary physiological simulation software for the clinical quantitative analysis of previously acquired Computed Tomography DICOM data for clinically stable symptomatic patients with coronary artery disease. It provides DVFFR (a CT-derived FFR measurement) computed from static coronary CTA images using deep learning neural networks that encode imaging, structural, and functional characteristics of coronary arteries through learning.

DEEPVESSEL FFR analysis is intended to support the functional evaluation of coronary artery disease.

The results of the analysis are provided to support qualified clinicians to aid in the evaluation and assessment of coronary arteries. DEEPVESSEL FFR results are intended to be used by qualified clinicians in conunction with the patient's clinical history, symptoms, and other diagnostic tests, as well as the clinician's professional judgment.

Device Description

DEEPVESSEL FFR is a coronary physiological simulation software for the clinical quantitative and qualitative analysis of previously acquired Computed Tomography DICOM data for clinically stable symptomatic patients with coronary artery disease. It estimates FFR values from static coronary CTA images with extracted coronary tree structures using deep learning neural networks. DEEPVESSEL FFR analysis is intended to support the functional evaluation of CAD.

The software processes these images semi-automatically, and it generates a 3D model of the coronay artery tree and computes DVFFR (CT-derived FFR) values. Qualified image analysts interact with the software by providing manual edits to the 3D coronary artery tree segmentations when needed, and oversees outputs along the processing steps. DVFFR analysis results are sent electronically to the physicians via a third-party service portal application.

DVFFR software is independent of imaging equipment, imaging protocols and equipment vendors; the clinical validation study report includes the specific imaging scanner types and imaging acquisition parameters used in the clinical validation of the product.

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the DEEPVESSEL FFR device, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Metric (Per-vessel)	Acceptance Crit. (Target Rate)	Reported Performance (Estimate)	Lower Bound 95% CI	Met/Not Met
Sensitivity	75%	86.9%	80.6%	Met
Specificity	70%	86.7%	82.0%	Met

Additional Reported Performance (Per-vessel):

Accuracy: 86.8% (95% CI: 83.0%-90.4%)
PPV: 79.4% (95% CI: 71.8%-86.2%)
NPV: 91.9% (95% CI: 87.7%–95.6%)

Patient-level Diagnostic Performance:

Sensitivity: 87.4% (95% CI: 79.4%-93.1%)
Specificity: 83.7% (95% CI: 76.5%-89.4%)
Accuracy: 85.2% (95% CI: 80.2%-89.4%)
PPV: 79.6% (95% CI: 71.0%-86.6%)
NPV: 90.1% (95% CI: 83.6%-94.6%)

2. Sample Size Used for the Test Set and Data Provenance

Sample Size: 244 patients with 311 target vessels.
Data Provenance: Multi-national (US and EU), multi-center clinical validation study, conducted at 8 clinical sites (4 from EU and 4 from US). The study was prospective in its design to evaluate the device against an invasive reference standard, suggesting the data used for validation was gathered for this specific purpose.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

The document does not explicitly state the number of experts or their specific qualifications for establishing the ground truth. However, the ground truth was "invasive FFR measurement." Invasive FFR procedures are typically performed and interpreted by interventional cardiologists.

4. Adjudication Method for the Test Set

The document does not explicitly state an adjudication method (e.g., 2+1, 3+1). The ground truth was established by "invasive FFR measurement," which is a direct physiological measurement, lessening the need for expert adjudication of the ground truth itself, though interpretation of the invasive FFR values might have involved standard clinical protocols.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study that demonstrates how much human readers improve with AI vs. without AI assistance was not reported in this summary. The clinical study focused on the standalone performance of the DEEPVESSEL FFR device compared to invasive FFR. The device is described as supporting qualified clinicians and being used in conjunction with their judgment and other tests, but no study on human reader improvement with assistance was included.

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

Yes, a standalone performance study was done. The reported sensitivity, specificity, accuracy, PPV, and NPV values reflect the performance of the DEEPVESSEL FFR software (DVFFR) itself in detecting ischemic conditions compared to invasive FFR. While image analysts perform semi-automatic processing and manual edits to 3D coronary artery tree segmentations, the diagnostic performance metrics provided represent the device's output.

7. The Type of Ground Truth Used

The ground truth used was invasive FFR measurement. This is considered a direct physiological measurement and a gold standard for assessing the hemodynamic significance of coronary artery stenoses.

8. The Sample Size for the Training Set

The document does not specify the sample size for the training set. It mentions that the device uses "deep learning neural networks that encode imaging, structural, and functional characteristics of coronary arteries through learning," but provides no details on the data used for this learning phase.

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 only mentions the use of deep learning neural networks. Typically, for such devices, the training data's ground truth would also be established by invasive FFR measurements or a similar reference standard.

Summary

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April 1, 2022

KeyaMed NA Inc. % Kelliann Payne Partner Hogan Lovells US LLP 1735 Market Street, Floor 23 Philladelphia, Pennsylvania 19103

Re: K213657

Trade/Device Name: DEEPVESSEL FFR Regulation Number: 21 CFR 870.1415 Regulation Name: Coronary Vascular Physiologic Simulation Software Device Regulatory Class: Class II Product Code: PJA Dated: March 1, 2022 Received: March 1, 2022

Dear Kelliann Payne:

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. You must comply with all the Act's

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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-regulatory-information/postmarketing-safety-reportingcombination-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,

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

Enclosure

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510(k) Number (if known)

K213657

Device Name

DEEPVESSEL FFR

Indications for Use (Describe)

DEEPVESSEL FFR analysis is intended to support the functional evaluation of coronary artery disease.

Type of Use (Select one or both, as applicable)

7 Prescription Use (Part 21 CFR 801 Subpart D)

[ Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) SUMMARY Keya Medical's DEEPVESSEL FFR K213657

Submitter

KeyaMed NA Inc. 107 Spring Street Seattle, WA 98104, USA

Phone: 1 (206) 508-1036 Contact Person: Xiaoxiao Liu Date Prepared: March 25, 2022

Name of Device: DEEPVESSEL FFR

Classification Name: Coronary Vascular Physiologic Simulation Software

Regulatory Class: Class II

Product Code: PJA

Predicate Device: HEARTFLOW, INC.'s FFRcT V2.0 (K161772)

Device Description

Intended Use / Indications for Use

DEEPVESSEL FFR is a coronary physiological simulation software for the clinical quantitative and qualitative analysis of previously acquired Computed Tomography DICOM data for clinically stable

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symptomatic patients with coronary artery disease. It provides DVFFR (a CT-derived FFR measurement) computed from static coronary CTA images using deep learning neural networks that encode imaging, structural, and functional characteristics of coronary arteries through learning.

DEEPVESSEL FFR analysis is intended to support the functional evaluation of coronary artery disease. The results of the analysis are provided to support qualified clinicians to aid in the evaluation and assessment of coronary arteries. DEEPVESSEL FFR results are intended to be used by qualified clinicians in conjunction with the patient's clinical history, symptoms, and other diagnostic tests, as well as the clinician's professional judgment.

Summary of Technological Characteristics

DEEPVESSEL FFR is a software medical device that is designed to be used by qualified image analysts (trained and certified professionals) to analyze coronary CTA images of clinically stable symptomatic patients with CAD. It calculates CT-derived FFR values from static coronary CTA images using deep learning neural networks. DEEPVESSEL FFR analysis is intended to support the functional evaluation for clinical stable CAD patients.

The software generates the DVFFR analysis results in two main steps. The first step generates a 3D coronary artery tree model from the CTA image automatically using deep learning-based segmentation algorithms. Manual corrections of the segmentation results are allowed when necessary to confirm the accuracy of the 3D coronary artery tree segmentation. In the second step, the deep learning framework consists of a multi-layer perceptron network (MLP) and a bidirectional multi-layer recursive neural network (BRNN), which utilize the segmentation results and the CTA image, to estimate semi-continuous FFR values along the coronary artery centerlines. The output of the analysis is a PDF report with detailed DVFFR assessment and branch visualizations, along with a 3D DVFFR tree model where the DVFFR values are mapped on top of the surface model.

DEEPVESSEL FFR and the predicate device have similar technological characteristics, utilizing computational models to generate CT-derived FFR value for interpretation.

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	Subject Device	Predicate Device
	DEEPVESSEL FFR 1.0	HeartFlow FFRCT V2.0
		(K161772)
Manufacturer	Keya Medical	HeartFlow, Inc.
Intended	DEEPVESSEL FFR is a coronary	HeartFlow FFRCT is a coronary
Use/Indications for	physiological simulation software for	physiologic simulation software for
use	the clinical quantitative and	the clinical quantitative and
	qualitative analysis of previously	qualitative analysis of previously
	acquired Computed Tomography	acquired Computed Tomography
	DICOM data for clinically stable	DICOM data for clinically stable
	symptomatic patients with coronary	symptomatic patients with coronary
	artery disease. It provides DVFFR (a	artery disease. It provides FFRCT,
	CT-derived FFR measurement)	a mathematically derived quantity,
	computed from static coronary CTA	computed from simulated
	images using deep learning neural	pressure, velocity and blood flow
	networks that encode imaging,	information obtained from a 3D
	structural, and functional	computer model generated from
	characteristics of coronary arteries	static coronary CT images. FFRCT
	through learning.	analysis is intended to support the
		functional evaluation of coronary
	DEEPVESSEL FFR analysis is	artery disease.
	intended to support the functional
	evaluation of coronary artery	The results of this analysis are
	disease.	provided to support qualified
	The results of the analysis are	clinicians to aid in the evaluation
	provided to support qualified	and assessment of coronary
	clinicians to aid in the evaluation and	arteries. The results of HeartFlow
	assessment of coronary arteries.	FFRCT are intended to be used by
	DEEPVESSEL FFR results are	qualified clinicians in conjunction
	intended to be used by qualified	with the patient's clinical history,
	clinicians in conjunction with the with	symptoms, and other diagnostic
	the patient's clinical history,	tests, as well as the clinician's
	symptoms, and other diagnostic	professional judgment.
	tests, as well as the clinician's
	professional judgment.
Intended End User	Clinicians	Clinicians
Clinical Condition	Coronary Artery Disease	Coronary Artery Disease
Input	Coronary CTA DICOM image data	Coronary CTA DICOM image data
Output	3D Model & Analysis Report	3D Model & Analysis Report

Table 1. Key Feature Comparison

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Performance Data

The following testing have been conducted to demonstrate the substantial equivalence:

Software: Software verification and validation activities were performed according to written procedures and FDA Guidance document Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices. Verification and validation testing confirmed that the predefined acceptance criteria have been fulfilled.

Human Factors Evaluations: Two human factors studies were conducted in accordance with FDA's Guidance Applying Human Factors and Usability Engineering to Medical Devices, 2016. The studies evaluated the critical tasks associated with use of the device for both physicians and analysts. The findings from the study demonstrated that all critical tasks were completed without use error or difficulty. These study results concluded that the DEEPVESSEL reports are safe and effective for the physician user group for the intended uses and use environment. Additionally, the analyst user group were able to safety and accurately use the DVFFR software and generate reports.

Reproducibility/Repeatability Evaluations: Reproducibility (R&R) testing was performed on a group of CT scans with diverse disease conditions and image qualities to evaluate the variation of repeated analyses of DEEPVESSEL FFR with different image analysts (reproducibility) at different days with a washout-period in between to avoid memory effects (repeatability). Testing results met the pre-specified variability metric threshold and thus demonstrated acceptable performance.

Clinical Studies: The software was also validated via a multi-national (US and EU), multicenter clinical validation study with intended patient population to ensure the clinical effectiveness. The primary endpoints of the study were per-vessel sensitivity and specificity of DVFFR to detect ischemic condition comparing with invasive FFR measurement. DVFFR analysis was conducted on a total of 244 patients with 311 target vessels from 8 clinical sites (4 from EU and 4 from US).

At the vessel level, the observed sensitivity of DVFFR was 86.9% with a two-sided lower bound 95% CI of 80.6%, and the observed specificity of DVFFR was 86.7% with a two-sided lower bound 95% Cl of 82.0%. Both 95% Cl lower bounds for sensitivity and specificity exceeded the performance target of 75% and 70%, respectively, as shown in Table 1.

	Estimate, %(two-sided 95% CI)	Lower Bound of thetwo-sided 95% CI	Target Rate	Met/Not Met
Sensitivity	86.9%(80.6%-92.7%)	80.6%	75%	Met
Specificity	86.7%(82.0%-91.1%)	82.0%	70%	Met
Positive: measured or estimated FFR values ≤ 0.80

Table 1. Per-vessel sensitivity and specificity of DVFFR

The observed diagnostic accuracy, PPV (positive predictive value) and NPV (negative predictive value) of DVFFR were 86.8% (95% Cl: 83.0%-90.4%), 79.4% (95% Cl: 71.8%-86.2%) and 91.9% (95% CI: 87.7%–95.6%), respectively. The results are summarized in Table 2.

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	Accuracy(two-sided 95% CI)	PPV(two-sided 95% CI)	NPV(two-sided 95% CI)
DVFFR	86.8%(83.0%-90.4%)	79.4%(71.8%-86.2%)	91.9%(87.7%-95.6%)

Table 2. Per-vessel diagnostic accuracy, PPV and NPV of DVFFR

At the patient level, the observed sensitivity, specificity, accuracy, PPV, and NPV were 87.4% (95% Cl: 79.4%-93.1%), 83.7% (95% Cl: 76.5%-89.4%), 85.2% (95% Cl: 80.2%-89.4%), 79.6% (95% Cl: 71.0%-86.6%), and 90.1% (95% Cl: 83.6%-94.6%), respectively, as shown in Table 3.

	Sensitivity(95% CI)	Specificity(95% CI)	Accuracy(95% CI)	PPV(95% CI)	NPV(95% CI)
DVFFR	87.4%(79.4%–93.1%)	83.7%(76.5%–89.4%)	85.2%(80.2%–89.4%)	79.6%(71.0%–86.6%)	90.1%(83.6%–94.6%)
At the patient level, if a patient had more than one ischemic lesion, ICA-FFR value for this patient would be determined as the minimum ICA-FFR measurement from all the coronary arteries. Similarly, patient-level DVFFR value is the minimum DVFFR measurement from all the vessels measured for the patient.

Table 3. Patient-level diagnostic performance of DVFFR

The study demonstrated that DEEPVESSEL FFR yielded good diagnostic performance and met the pre-specified criteria for study success.

Conclusions

DEEPVESSEL FFR, a coronary physiological simulation software, is substantially equivalent to the predicate device, HeartFlow FFRct V2.0 (K161772). DEEPVESSEL FFR and HeartFlow FFRct V2.0 (K161772) share the same intended use and very similar indications for use, technological characteristics, and principles of operation. The only differences between the subject and predicate devices are the algorithms used to calculate the CT-derived FFR values, and these differences do not raise new questions of safety or effectiveness.

Regulation Number and Section

§ 870.1415 Coronary vascular physiologic simulation software device.

(a)
Identification. A coronary vascular physiologic simulation software device is a prescription device that provides simulated functional assessment of blood flow in the coronary vascular system using data extracted from medical device imaging to solve algorithms and yield simulated metrics of physiologic information (e.g., blood flow, coronary flow reserve, fractional flow reserve, myocardial perfusion). A coronary vascular physiologic simulation software device is intended to generate results for use and review by a qualified clinician.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Adequate software verification and validation based on comprehensive hazard analysis, with identification of appropriate mitigations, must be performed, including:
(i) Full characterization of the technical parameters of the software, including:
(A) Any proprietary algorithm(s) used to model the vascular anatomy; and
(B) Adequate description of the expected impact of all applicable image acquisition hardware features and characteristics on performance and any associated minimum specifications;
(ii) Adequate consideration of privacy and security issues in the system design; and
(iii) Adequate mitigation of the impact of failure of any subsystem components (
e.g., signal detection and analysis, data storage, system communications and cybersecurity) with respect to incorrect patient reports and operator failures.(2) Adequate non-clinical performance testing must be provided to demonstrate the validity of computational modeling methods for flow measurement; and
(3) Clinical data supporting the proposed intended use must be provided, including the following:
(i) Output measure(s) must be compared to a clinically acceptable method and must adequately represent the simulated measure(s) the device provides in an accurate and reproducible manner;
(ii) Clinical utility of the device measurement accuracy must be demonstrated by comparison to that of other available diagnostic tests (
e.g., from literature analysis);(iii) Statistical performance of the device within clinical risk strata (
e.g., age, relevant comorbidities, disease stability) must be reported;(iv) The dataset must be adequately representative of the intended use population for the device (
e.g., patients, range of vessel sizes, imaging device models). Any selection criteria or limitations of the samples must be fully described and justified;(v) Statistical methods must consider the predefined endpoints:
(A) Estimates of probabilities of incorrect results must be provided for each endpoint,
(B) Where multiple samples from the same patient are used, statistical analysis must not assume statistical independence without adequate justification, and
(C) The report must provide appropriate confidence intervals for each performance metric;
(vi) Sensitivity and specificity must be characterized across the range of available measurements;
(vii) Agreement of the simulated measure(s) with clinically acceptable measure(s) must be assessed across the full range of measurements;
(viii) Comparison of the measurement performance must be provided across the range of intended image acquisition hardware; and
(ix) If the device uses a cutoff threshold or operates across a spectrum of disease, it must be established prior to validation, and it must be justified as to how it was determined and clinically validated;
(4) Adequate validation must be performed and controls implemented to characterize and ensure consistency (
i.e., repeatability and reproducibility) of measurement outputs:(i) Acceptable incoming image quality control measures and the resulting image rejection rate for the clinical data must be specified, and
(ii) Data must be provided within the clinical validation study or using equivalent datasets demonstrating the consistency (
i.e., repeatability and reproducibility) of the output that is representative of the range of data quality likely to be encountered in the intended use population and relevant use conditions in the intended use environment;(A) Testing must be performed using multiple operators meeting planned qualification criteria and using the procedure that will be implemented in the production use of the device, and
(B) The factors (
e.g., medical imaging dataset, operator) must be identified regarding which were held constant and which were varied during the evaluation, and a description must be provided for the computations and statistical analyses used to evaluate the data;(5) Human factors evaluation and validation must be provided to demonstrate adequate performance of the user interface to allow for users to accurately measure intended parameters, particularly where parameter settings that have impact on measurements require significant user intervention; and
(6) Device labeling must be provided that adequately describes the following:
(i) The device's intended use, including the type of imaging data used, what the device measures and outputs to the user, whether the measure is qualitative or quantitative, the clinical indications for which it is to be used, and the specific population for which the device use is intended;
(ii) Appropriate warnings specifying the intended patient population, identifying anatomy and image acquisition factors that may impact measurement results, and providing cautionary guidance for interpretation of the provided measurements;
(iii) Key assumptions made in the calculation and determination of simulated measurements;
(iv) The measurement performance of the device for all presented parameters, with appropriate confidence intervals, and the supporting evidence for this performance. Per-vessel clinical performance, including where applicable localized performance according to vessel and segment, must be included as well as a characterization of the measurement error across the expected range of measurement for key parameters based on the clinical data;
(v) A detailed description of the patients studied in the clinical validation (
e.g., age, gender, race or ethnicity, clinical stability, current treatment regimen) as well as procedural details of the clinical study (e.g., scanner representation, calcium scores, use of beta-blockers or nitrates); and(vi) Where significant human interface is necessary for accurate analysis, adequately detailed description of the analysis procedure using the device and any data features that could affect accuracy of results.