CathWorks FFRangio™ is a software device for the clinical quantitative and qualitative analysis of previously acquired angiography DICOM data for patients with coronary artery disease. It provides FFRangio™, a mathematically derived quantity, computed from simulated blood flow information obtained from a 3D computer model, generated from coronary angiography images. FFRangio™ analysis is intended to support the functional evaluation of coronary artery disease. The results of this analysis are provided as a supportive aid for qualified clinicians in the evaluation and assessment of coronary arteries physiology. The results of CathWorks FFRangio™ 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 evaluation.

Device Description

The FFRangio™ system is a computer system installed on a mobile cart that is to be located inside the catheterization room or in an adjacent technical/viewing area. The cart holds the computer processing unit, user interface control station (LCD screen and keyboard/mouse), medical isolation transformer, and network isolator. Operation requires only connections to mains and a DICOM communication port. The system supports optional visual media output to the Cath Lab main displays, so the system GUI may be observed on both the system's LCD display and on the Cath Lab's main display (boom monitor).

FFRancio™ uses standard angiographic images (angiograms) that are retrieved from the X-ray Imaging System (C-arm) in DICOM format. The user selects the images and, following the system prompts, marks key features on the images including the target lesion, ostium location, main vessel, target vessel, and its side branches. The system then matches the corresponding vessels among the projections and generates a 3D computer model of the vessels. The 3D model is used for blood flow analysis and determination of the FFRangio.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the CathWorks FFRangio™ system, based on the provided text:

Acceptance Criteria and Device Performance

Criteria	Performance Goal / Criteria	Reported Device Performance (Lower 95% CI)
Sensitivity	70%	93.5% (87.8%)
Specificity	75%	91.2% (86.0%)
Correlation Coefficient (R)	0.65	0.80
Intercept	-0.20 - 0.20	0.04 (0.03 - 0.05)
Slope	0.80 - 1.20	0.93 (0.92 - 0.95)

Notes:

The reported performance for Sensitivity and Specificity includes the lower one-sided 95% confidence interval, which was used to determine if the device met the pre-specified target goals. Both were significantly above the targets.
The correlation coefficient, intercept, and slope were secondary endpoints, and their direct "performance goals" are stated along with the achieved values.

Study Information

The primary study referenced is the FAST-FFR Trial.

2. Sample Size and Data Provenance:

Test Set (Efficacy Analysis): 301 adult subjects and 319 coronary lesions.
Study Enrollment: 382 subjects (30 roll-in, 352 study subjects).
Data Provenance: Prospective, multicenter, international trial conducted at 10 sites in 5 countries: United States, Europe, and Israel.
- 124 subjects (32.5%) were enrolled at sites in the United States.

3. Number and Qualifications of Experts for Test Set Ground Truth:

The document does not explicitly state the number of experts or their specific qualifications (e.g., years of experience) for establishing the ground truth of the invasive FFR. However, it does state:

"All invasive FFR data were reviewed post-hoc by an independent FFR physiology core laboratory."

4. Adjudication Method for Test Set:

The document does not explicitly describe an adjudication method like 2+1 or 3+1 for the test set's ground truth by the independent FFR physiology core laboratory. It simply states that the data was "reviewed."

Furthermore, it states for the FFRangio™ data:

"all FFRangio™ data were reviewed post-hoc by a core laboratory at CathWorks."

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

No, a multi-reader multi-case (MRMC) comparative effectiveness study evaluating human readers with and without AI assistance was not explicitly mentioned or presented in the provided text. The study primarily focused on the standalone diagnostic accuracy of the FFRangio™ system compared to invasive FFR.

6. Standalone (Algorithm Only) Performance:

Yes, a standalone performance study was conducted. The FAST-FFR trial specifically evaluated the FFRangio™ system's accuracy as compared to invasive wire FFR, with on-site hospital users blinded to the invasive FFR and the FFRangio™ not being used for diagnostic or clinical decisions. This demonstrates the algorithm's performance independent of real-time human-in-the-loop influence on clinical decisions.

7. Type of Ground Truth Used:

Invasive Wire FFR: The ground truth for the test set was obtained from "invasive wire FFR" measured using a coronary pressure wire and hyperemic stimulus. This is considered the gold standard for FFR measurement.

8. Sample Size for the Training Set:

The document does not explicitly state the sample size for the training set used to develop the FFRangio™ algorithm. It mentions two clinical studies:
- A two-phase validation study using an "earlier version of the operator interface but the same image processing and computation algorithms as the final device." This study analyzed "203 coronary lesions" and demonstrated sensitivity, specificity, and diagnostic accuracy. While this study helped validate the algorithms, it's not explicitly labeled as the training set.
- The FAST-FFR trial (the pivotal study), which serves as the test set.

9. How the Ground Truth for the Training Set Was Established:

Similar to the training set size, the document does not explicitly detail how the ground truth for an independent training set was established.
- The "two-phase validation study" mentioned in point 8, which used an earlier version of the algorithm, compared FFRangio™ to "invasive FFR obtained from patients already scheduled for coronary assessment in the cath lab." This suggests invasive FFR was used as ground truth for that prior validation, which likely informed the development and refinement of the final algorithm's "image processing and computation algorithms." However, a specific training set and its ground truth acquisition are not explicitly isolated in the provided text.

Summary

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December 19, 2018

CathWorks Ltd. % Sheila Hemeon-Heyer President Heyer Regulatory Solutions LLC 125 Cherry Lane Amherst, Massachusetts 01002

Re: K182149

Trade/Device Name: FFRangio™ System Regulation Number: 21 CFR 870.1415 Regulation Name: Coronary Vascular Physiologic Simulation Software Regulatory Class: Class II Product Code: OEK Dated: December 17, 2018 Received: December 18, 2018

Dear Sheila Hemeon-Heyer:

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 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

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devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

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igitally signed by Shawn W. Forrest US o=ll S Government HHS. ou=FDA. ou=People 0 9 2342 19200300 100 1 1=130040334 Shawn W. Forrest -A Date: 2018.12.19 14:48:08 -05'00

Bram D. Zuckerman, M.D. Director Division of Cardiovascular Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K182149

Device Name

FFRangio™

Indications for Use (Describe)

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

☑ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted per the requirements of 21 CFR 807.92.

A.	Submitter:	Heyer Regulatory Solutions LLC
		P.O. Box 2151
		Amherst, MA 01004-2151
		Contact: Sheila Hemeon-Heyer
		Sheila@heyer-regulatory.com

B. Manufacturer Contact: CathWorks, Ltd. llanit Frank Hakim 3 Rappaport St. Kfar Saba 4465141, ISRAEL Tel: +972 9 7467387 ilanit@cath.works
C. Date Prepared: December 19, 2018

D. Device Name and Classification Information:

Trade Name:	FFRangio™ System
Classification Name:	Coronary Vascular Physiologic Simulation SoftwareDevice
Common Name:	Digital FFR System
Regulation:	21 CFR 870.1415
Product Code:	QEK
Review Panel:	Cardiovascular
Class:	II

K161772 for FFRcT, manufactured by HeartFlow, Inc. E. Predicate Device(s):

F. Summary Device Description:

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G. Indications for Use Statement:

CathWorks FFRangio™ is a software device for the clinical quantitative and qualitative analysis of previously acquired angiography DICOM data for patients with coronary artery disease. It provides FFRangio ™, a mathematically derived quantity, computed from simulated blood flow information obtained from a 3D computer model, generated from coronary angiography images. FFRangio™ analysis is intended to support the functional evaluation of coronary artery disease. The results of this analysis are provided as a supportive aid for qualified clinicians in the evaluation and assessment of coronary arteries physiology. The results of CathWorks FFRangio™ 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 evaluation.

H. Comparison with Predicate Device

The CathWorks FFRangio™ and the HeartFlow FFRct are both coronary physiologic simulation software devices that use data extracted from coronary imaging to provide a noninvasive assessment of fractional flow reserve (FFR). The primary difference between the two devices for the purposes of 510(k) substantial equivalence is that the FFRancio™ uses data extracted from angjographic images, while the FFRct uses data extracted from CT scans. The table below provides a technological comparison between the two devices. Discussion of the differences is provided following the table.

	CathWorks FFRangioTM	Predicate DeviceHeartFlow FFRCT2.0
Indicationsfor Use	CathWorks FFRangioTM is a softwaredevice for the clinical quantitative andqualitative analysis of previouslyacquired angiography DICOM datafor patients with coronary arterydisease. It provides FFRangioTM, amathematically derived quantity,computed from simulated blood flowinformation obtained from a 3Dcomputer model, generated from	HeartFlow FFRCT is a coronaryphysiologic simulation software for theclinical quantitative and qualitativeanalysis of previously acquiredComputed Tomography DICOM datafor clinically stable symptomaticpatients with coronary artery disease.It provides FFRCT, a mathematicallyderived quantity, computed fromsimulated pressure, velocity and blood

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	CathWorks FFRangio™	Predicate DeviceHeartFlow FFRCT2.0
	coronary angiography images.FFRangio™ analysis is intended tosupport the functional evaluation ofcoronary artery disease. The resultsof this analysis are provided as asupportive aid for qualified cliniciansin the evaluation and assessment ofcoronary arteries physiology. Theresults of CathWorks FFRangio™ areintended to be used by qualifiedclinicians in conjunction with thepatient's clinical history, symptoms,and other diagnostic tests, as well asthe clinician's professional evaluation.	flow information obtained from a 3Dcomputer model generated from staticcoronary CT images. FFRCT analysisis intended to support the functionalevaluation of coronary artery disease.The results of this analysis areprovided to support qualified cliniciansto aid in the evaluation andassessment of coronary arteries. Theresults of HeartFlow FFRCT areintended to be used by qualifiedclinicians in conjunction with thepatient's clinical history, symptoms,and other diagnostic tests, as well asthe clinician's professional judgment.
Systemoverview	Computer system with software thatconstructs and displays a 3Dcomputer model of the coronaryarteries to simulate blood flow	Computer system with software thatconstructs and displays a 3D computermodel of the coronary arteries tosimulate blood flow
Image source	Standard DICOM angiographicimages taken in Cath Lab	Previously obtained CT images
Softwarecontrolled	Yes	Yes
On-lineprocessing	Yes	No
Sensitivity*	93.5% (lower 95% CI, 87.8%)	84.2% (lower 95% CI, 75.8%)
Specificity*	91.2% (lower 95% CI, 86.0%)	84.9% (lower 95% CI, 80.4%)

*Sensitivity and specificity are the per vessel estimates as reported for the proposed and predicate device pivotal clinical studies.

Discussion of Differences

The key difference between the FFRancio™ and FFR-T devices is that FFRance™ analysis is based on standard angiograms taken in the cath lab, while FFRct uses previously obtained CT scans. This enables FFRangio™ to be used on-line in the cath lab to provide the FFR measure during the procedure. Clinical data collected in the FFRangio™ pivotal clinical study demonstrated high sensitivity and specificity. Subgroup analyses demonstrated that the FFRange ™ system is effective for both symptomatic and nonsymptomatic patients with coronary artery disease.

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l. Performance Data to Support Substantial Equivalence

The following pre-clinical testing was presented to demonstrate the appropriate functionality of the software, the basis of the computational methods, and verification of hardware functionality. Some testing (e.g., biocompatibility, shelf life, etc.) was not applicable for this software only device. Animal testing was not conducted as animal models do not permit evaluation of the technology in relevant anatomic or physiologic models reflecting diseased human coronary vessels.

Software: Software documentation consistent with FDA's quidance for the Content of Premarket Submissions for Software Contained in Medical Devices," May 11, 2005, for moderate level of concern software including a comprehensive risk analysis, software verification and validation, off-the-shelf software integrity, and cybersecurity considerations.

Electrical Safety Testing: The FFRangio™ computer system and cart were evaluated and found to be in compliance with the applicable requirements of IEC 60601-1:2005 (3ª Edition) +C1:2006 +C2:2007 +A1:2012, "Medical electrical equipment - Part 1: General requirements for basic safety and essential performance." All emissions and immunity tests were passed.

Electromagnetic Compatibility Testing: The FFRango ™ computer system was tested and found to be in compliance with the applicable requirements of IEC 60601-1-2:2014 (4th edition), "Medical electrical equipment - Part 1-2: General requirements for basic safety and essential performance - Collateral Standard: Electromagnetic disturbances -Requirements and tests."

Hardware Verification Testing: The FFRancio™ computer system and cart underwent type testing per an internal CathWorks protocol. All hardware requirements of the system were evaluated/tested and found to meet the pre-defined acceptance criteria.

Transportation Testing: The FFRangio™ computer system and cart are shipped in a padded, wooden box. Transportation testing was conducted in accordance with ASTM D4169-16. "Standard Practice for Performance Testing of Shipping Containers and Systems." All tests were passed.

Human Factors Evaluation: Usability testing of the FFRango™ system and its operator manual was conducted in accordance with ANSI/AAMI/IEC 62366-1:2015, "Application of usability engineering to medical devices" and the FDA guidance document ""Applying Human Factors and Usability Engineering to Medical Devices," February 3, 2016. Participants in the usability testing were 19 healthcare personnel including physicians, nurses, technicians, and imaging fellows. All critical tasks identified for the use of the FFRancio™ system were completed in the usability testing without any use errors. All of the questions in the knowledge-based assessment were answered correctly with the exception of one question that was answered partially correctly by one participant.

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Overall, the usability of the system was graded as a 4.5 out of 5 by the test participants. The conclusion of the testing was that the FFRangio™ system can be used safely and effectively by the intended user population. No residual use-related risks were identified.

Clinical Studies:

Two clinical studies were conducted using the FFRance™ system. The first was a twophase validation study using an earlier version of the operator interface but the same image processing and computation algorithms as the final device. The clinical validation study compared the FFRangio™ to invasive FFR obtained from patients already scheduled for coronary assessment in the cath lab. The patient's angiographic images were shipped to an off-line location, where they were processed using the FFRango™ system by two independent operators who were blinded to the invasive FFR and blinded to each other. Analysis of the results from 203 coronary lesions with data collected at four centers (one in the US, one in the EU, and two in Israel) demonstrated sensitivity, specificity, and diagnostic accuracy for FFRangio to be 88%, 95% and 93%, respectively. The average intraclass correlation coefficient for the two measurements of FFRangi ™ conducted by the two operators was 0.962 with a 95% confidence interval from 0.95 to 0.971 (P<0.001).

The second study. the FAST-FFR Trial, was the pivotal clinical study to support the substantial equivalence of the FFRangio™ system. FAST-FFR was a prospective, multicenter, international trial with the primary goal of determining the accuracy of FFRance ™ as compared to invasive wire FFR. Coronary angiography was performed in a routine fashion in patients with suspected coronary artery disease. When clinically indicated, invasive FFR was measured in vessels with coronary lesions of varying severity using a coronary pressure wire and hyperemic stimulus. On-site hospital users who were blinded to the invasive FFR used the FFRancio™ system following acquisition of the diagnostic angiograms to generate the patient's FFRancio ™. The FFRancia ™ was not used for diagnostic or clinical decisions. Co-primary endpoints were the sensitivity and specificity of the dichotomously scored FFRangio™ for predicting pressure wirederived FFR using a cutoff value of 0.80. Secondary endpoints included the accuracy of FFRangio™ and its correlation with invasive FFR.

The FAST-FFR study was conducted at 10 sites in 5 countries in the United States, Europe and Israel, from September 2017 to June 2018, with 382 subjects enrolled of which 30 were roll-in subjects and 352 were study subjects. 124 Subjects in total were enrolled at sites in the United States (32.5%).

Subjects had an overall mean age of 64.9 ± (9.9) years and 74.6% were men. 92.5% were white and the remaining from other races. A total of 31.4% had diabetes mellitus, 69.1 % had hypertension, and 76.2% had hyperlipidemia. 45.3% of subjects presented with stable angina, 31.4% with unstable angina, and 14.1% with silent ischemia. Overall 15.4% of the patient population had CCS classification 0 and were asymptomatic.

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In total, 301 adult subjects and 319 coronary lesions with both a qualifiable invasive FFR and FFRancio™ measurements were available for efficacy analysis. Of these, 54% were LAD lesions, 24% RCA, 19% LCX and 3% Ramus. 14% of lesions involved a bifurcation and 24% were calcified. Diagnostic angiograms were acquired from all four C-arm types (Phillips (27%), GE (20%), Siemens (43%) and Toshiba (10%)), and coronary pressure and flow wires used included Abbott-St. Jude (48%), Opsens (6%) or Volcano-Phillips (46%). All invasive FFR data were reviewed post-hoc by an independent FFR physiology core laboratory and all FFRangio" data were reviewed post-hoc by a core laboratory at CathWorks.

The co-primary endpoints were sensitivity and specificity of the dichotomously scored FFRango" measured index per vessel as compared with invasively-derived FFR; Index ≤0.80 was scored "positive" while Index >0.8 was negative. The pre-specified performance goals identified by the Sponsor and agreed upon by FDA for sensitivity and specificity were 70% and 75%, respectively. The primary endpoint for study success required that the lower bounds of the 95% confidence intervals for both sensitivity and specificity be above these performance goals.

The per vessel sensitivity of FFRangio"" was 93.5% with a lower one-sided 95% Cl of 87.8%. The per-vessel specificity of FFRangio™ was 91.2% with a lower one-sided 95% CI of 86.0%. Both of the lower one-sided confidence limits for sensitivity and specificity were significantly above the pre-specified target goals of 70% and 75%, respectively, and were considered acceptable. The results are shown in the table below.

	Statistic	95% CI limits	Performance goal /criteria
Sensitivity	93.5%	87.8% - 96.6%	70%
Specificity	91.2%	86.0% - 94.6%	75%
Correlation Coefficient (R)	0.80		0.65
Intercept	0.04	0.03 - 0.05	-0.20 - 0.20
Slope	0.93	0.92 - 0.95	0.80 - 1.20

As the FFRangio" analysis was not used in any clinical decision making and did not add any risk to the study subjects, and the trial did not include clinical follow-up, only procedure-related adverse events were captured. Only two adverse events were reported, neither of which was related to the device.

The FAST-FFR study confirmed that FFRangio™ produces accurate results, with very high sensitivity and specificity for the measurement of FFR.

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Special Controls (abbreviated fromregulation)	How Fulfilled
1) Adequate software verification andvalidation based on comprehensivehazard analysis, with identification ofappropriate mitigations, must beperformed.,	The FFRangio system software was designed,developed and tested in accordance with ISO62304:2006 Medical device software -- Softwarelife cycle processes and includedcomprehensive hazard analysis, identification ofappropriate risk mitigations, and softwaretesting at all stages of development to verify andvalidate the software algorithms, systemoperation, privacy/security issues, and theimpact of failures (e.g., inadequate imagequality, image data corruption, improperoperation steps).
2. Adequate non-clinical performancetesting must be provided to demonstratethe validity of computational modelingmethods for flow measurement.	A series of in vitro and animal studies wereconducted by CathWorks to validate thecomputational modelling methods for theFFRangio system.
3. Clinical data supporting the proposedintended use must be provided.	A multi-center clinical study was conducted tovalidate the sensitivity and specificity of theFFRangio in the intended use population. Seethe detailed summary of this study presented inSection I above.
(4) Adequate validation must beperformed and controls implemented tocharacterize and ensure consistency(repeatability and reproducibility) ofmeasurement output.	The clinical pivotal study was conducted at 10sites with multiple device users at each site. Acovariate analysis showed no site interaction onthe FFRangio results.A reproducibility and repeatability analysis wasperformed in a separate clinical validation study.
(5) Human factors evaluation andvalidation must be provided todemonstrate adequate performance of theuser interface to allow for users toaccurately measure intended parameters,particularly where parameter settings thathave impact on measurements requiresignificant user intervention.	A human factors study was conducted inaccordance with FDA's Guidance ApplyingHuman Factors and Usability Engineering toMedical Devices, 2016. The study evaluated thecritical tasks associated with use of the device.The study results demonstrated that theintended use population was able to safety andaccurately use the FFRangio system. Noadditional risk mitigations were identified fromthis study.
(6) Device labeling must be provided thatadequately describes the following:(i) The device's intended use,(ii) Appropriate warnings	The device instructions for use include all of theelements required by this special control,including:● Intended use statement the devicemechanism of action and intended patient
Special Controls (abbreviated fromregulation)	How Fulfilled
(iii) Key assumptions	population
(iv) The measurement performance of thedevice for all presented parameters(v) A detailed description of the clinicalstudy subjects and results(vi) A detailed description of the analysisprocedure using the device and any datafeatures that could affect accuracy ofresults.	• Appropriate warnings and precautions forsafe use of the device, including factors thatcould adversely affect the device output andcautions to use the device output in contextwith other clinical factors for patient care• Limitations describing patient populationsand lesion types for which the safety andeffectiveness of FFRangio has not beenevaluated
	• Instructions for use providing guidelines forthe compatible image acquisition systemsand the required criteria for the images toprocess the FFRangio.
	• Detailed steps for the system operation andanalysis procedures
	• A detailed summary of the FAST-FFRclinical study protocol

J. Compliance with Special Controls for 21 CFR 870.1415

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K. Conclusion

The information and testing presented in this 510(k) demonstrate that the CathWorks FFRancio™ is substantially equivalent to the HeartFlow FFRct. Performance data provided in this 510(k) demonstrate that the FFRangio™ system is safe and effective for the non-invasive assessment of FFR from standard angiographic images obtained in the coronary cath lab.

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.