The HeartFlow Analysis is a coronary physiologic 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 provides the calculations of FFR-cf a mathematically derived quantity, computed from simulated pressure, velocity and blood flow information obtained from a 3D computer model generated from static coronary CT images. The HeartFlow Analysis is intended to support the functional evaluation of coronary artery disease.

The HeartFlow Analysis is provided to support qualified clinicians to aid in the evaluation and assessment of coronary arteries. The HeartFlow Analysis is 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.

Device Description

The HeartFlow Analysis is a coronary physiological simulation software developed for the clinical quantitative and qualitative analysis of CT DICOM data. It is a tool for the analysis of CT DICOM-compliant cardiac images and data, to assess the anatomy and function of the coronary arteries.

The software displays the anatomy combined with function using graphics and text, including computed and derived quantities of blood flow, pressure and velocity, to aid the clinician in the assessment and treatment planning of coronary artery disease.

The HeartFlow Analysis is performed on previously physician-acquired image data and is unrelated to acquisition equipment and clinical workstations.

AI/ML Overview

The provided document is a 510(k) summary for the HeartFlow Analysis (FFRct v3) device. It describes the device and claims substantial equivalence to a predicate device (HeartFlow FFRct v2.Planner, K190925). However, it does not contain the detailed acceptance criteria or the specific study results that directly prove the device meets said criteria for FFRct v3.

The document states: "Summaries of pre-clinical studies were reviewed as part of a prior predicate review (K161772, the predicate of K182035 that is the predicate of K190925). The results concluded the device was acceptable for use." This refers to studies for previous versions of the device, not specifically for "FFRCT v3" and its new solver.

The document claims: "Changes to flow and distribution calculations within the Gen3 solver do not raise new questions of safety and effectiveness." and "Results of all current and previously referenced testing conclude the device is acceptable for use." This implies that the new version is acceptable based on the previous version's validation studies and that the changes are not significant enough to warrant new clinical studies to prove effectiveness.

Therefore, many of the requested details, such as specific acceptance criteria for FFRct v3, reported device performance data, sample sizes, ground truth establishment for a new study, and multi-reader multi-case study results for this specific version, are not provided in this document.

Based only on the provided text, here's what can be extracted and what is missing or implied:

Table of acceptance criteria and the reported device performance:

Acceptance Criteria	Reported Device Performance (for FFRct v3)
Not explicitly stated for FFRct v3 in this document. The document refers to prior predicate review studies (K161772) that concluded the device was acceptable for use, implying prior acceptance metrics were met by older versions.	The document states: "Changes to flow and distribution calculations within the Gen3 solver do not raise new questions of safety and effectiveness." and "Results of all current and previously referenced testing conclude the device is acceptable for use." This implies that the performance of FFRct v3, with its Gen3 solver, is considered equivalent to and meets the same acceptable standards as its predicates, without providing new quantitative performance metrics for FFRct v3 itself.

Acceptance Criteria

Reported Device Performance (for FFRct v3)

Not explicitly stated for FFRct v3 in this document. The document refers to prior predicate review studies (K161772) that concluded the device was acceptable for use, implying prior acceptance metrics were met by older versions.

The document states: "Changes to flow and distribution calculations within the Gen3 solver do not raise new questions of safety and effectiveness." and "Results of all current and previously referenced testing conclude the device is acceptable for use." This implies that the performance of FFRct v3, with its Gen3 solver, is considered equivalent to and meets the same acceptable standards as its predicates, without providing new quantitative performance metrics for FFRct v3 itself.

Sample sizes used for the test set and the data provenance:
- Test set sample size: Not specified for FFRct v3. The document refers to "previously acquired diagnostic images received through HeartFlow sponsored clinical trials" for earlier versions of the device.
- Data provenance: Not specified for FFRct v3. For previous versions, it's implied the data came from "HeartFlow sponsored clinical trials," but country of origin or retrospective/prospective nature is not detailed for any specific version.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not specified for FFRct v3. This information might be detailed in the "pre-clinical studies" mentioned for the predicate devices (K161772), but those details are not included in this summary.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not specified for FFRct v3.
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:
- Not specified for FFRct v3. The document mentions the device is intended "to support qualified clinicians to aid in the evaluation and assessment," but no MRMC study details or effect sizes are provided.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- The core claim of the HeartFlow Analysis (FFRct) is to "compute FFRCT, a mathematically derived quantity." This inherently describes a standalone algorithmic function. However, the document also states, "Clinician review and assessment of analysis prior to use as supplemental diagnostic aid." This suggests the standalone performance is part of a human-in-the-loop clinical workflow, but results for standalone performance are not explicitly detailed.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Not specified for FFRct v3. For the underlying FFRCT technology, the ground truth for FFR (Fractional Flow Reserve) is typically invasive coronary angiography with pressure wire measurements. This is only implied from the known context of FFRct validity, but not explicitly stated in this document for the validation of FFRct v3.
The sample size for the training set:
- Not specified for FFRct v3, or any previous versions addressed in this summary. The document mentions "Medical device design included testing and evaluation using previously acquired diagnostic images," which would likely include training data, but no specifics are given.
How the ground truth for the training set was established:
- Not specified for FFRct v3, or any previous versions discussed in this summary.

In summary, the provided FDA 510(k) summary for HeartFlow Analysis (FFRct v3) primarily focuses on establishing substantial equivalence to a predicate device based on technological characteristics and intended use. It does not provide specific new study data, acceptance criteria, sample sizes, or ground truth details for the current FFRct v3 version, instead referring to earlier predicate device reviews where such studies were reportedly conducted. The implication is that the changes in FFRct v3 (specifically the Gen3 solver) are not significant enough to require new comprehensive clinical validation studies to prove safety and effectiveness beyond what was already established for its predecessors.

Summary

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January 8, 2021

HeartFlow, Inc. Windi Hary Senior Vice President, Clinical, Ouality and Regulatory Compliance 1400 Seaport Boulevard, Building B Redwood City, California 94063

Re: K203329

Trade/Device Name: HeartFlow Analysis Regulation Number: 21 CFR 870.1415 Regulation Name: Coronary Vascular Physiologic Simulation Software Device Regulatory Class: Class II Product Code: PJA Dated: November 10, 2020 Received: November 12, 2020

Dear Windi Hary:

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,

for LT 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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Indications for Use

510(k) Number (if known) K203329

Device Name HeartFlow Analysis

Indications for Use (Describe)

The HeartFlow Analysis is a coronary physiologic simulation software for the clinical quantitative and qualitative analysis of previously acquired Tomography DICOM data for clinically stable symptomatic patients with coronary artery disease. It provides the calculations of FFRCT, a mathematically derived quantity, computed from simulated pressure, velocity and blood flow information obtained from a 3D computer model generated from static coronary CT images. The HeartFlow Analysis is intended to support the functional evaluation of coronary artery disease.

Type of Use (Select one or both, as applicable)
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X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510k Summary

This 510(k) summary of safety and effectiveness information is submitted in accordance with the requirements of 21 CFR Part 807.87(h).

1 Submitter Information

Submitter / Manufacturer Name:	HeartFlow, Inc.1400 Seaport Boulevard, Building BRedwood City, CA 94063
Contact Person:	Windi Hary, RACSenior Vice President, Clinical, Quality & RegulatoryComplianceHeartFlow, Inc.1400 Seaport Boulevard, Bldg BRedwood City, CA 94063T +1 (650) 241-1250F +1 (650) 368-2564whary@heartflow.com
Date Prepared:	November 10, 2020

2 Device Identification

Device Name:	HeartFlow Analysis
Common Name:	FFRCT
Classification Name:	Coronary Physiologic Simulation Software Device
Product Code:	PJA
Product Class:	Class II (21 CFR 870.1415)

3 Predicates

HeartFlow FFRct v2.Planner (K190925) is the identified predicate for this submission.

Image /page/3/Picture/10 description: The image shows the HeartFlow logo. The logo consists of a stylized blue wave-like shape on the left, followed by the word "HeartFlow" in blue. There is a registered trademark symbol to the right of the word "HeartFlow".

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4 Device Description

The HeartFlow Analysis is performed on previously physician-acquired image data and is unrelated to acquisition equipment and clinical workstations.

5 Indications for Use

The HeartFlow Analysis 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 provides the calculations of FFR-cf a mathematically derived quantity, computed from simulated pressure, velocity and blood flow information obtained from a 3D computer model generated from static coronary CT images. The HeartFlow Analysis is intended to support the functional evaluation of coronary artery disease.

6 Technological Characteristics of Device

The HeartFlow Analysis is a software medical device that allows for the quantitative analysis of Coronary Computed Tomography Angiography (cCTA). The predicate and this product have the same technological characteristics.

The core technology remains unchanged. There are no differences between the subject device and the predicate(s) with respect to indications and intended use.

	FFRCT v2.Planner (predicate)	FFRCT v3
510(k)	K190925	TBD
Manufacturer	HeartFlow, Inc.	HeartFlow, Inc.
Regulation Number	870.1415	870.1415
Regulation Name	Coronary Physiologic SimulationSoftware Device	Coronary Physiologic SimulationSoftware Device
Classification	Class II	Class II
Device Common Name	HeartFlow FFRCT	HeartFlow FFRCT
	FFRCT v2.Planner (predicate)	FFRCT V3
Product Code	PJA	PJA
Functions	- Extract anatomic data from digitalcardiac images for the 3D display andvisualization of the anatomy of patient'scoronary arteries- Compute FFRCT	- Extract anatomic data from digitalcardiac images for the 3D display andvisualization of the anatomy of patient'scoronary arteries- Compute FFRCT
Intended use	- Review of CT angiographic images toconfirm the coronary vessels- Semi-automated tool for extraction ofanatomic data (including heartstructures) for coronary physiologicsimulation to aid in diagnosis ofcoronary artery disease,- Centerline detection- Provides additional data derived fromcoronary CT anatomy and pathology- Provide simulated hemodynamicinformation	- Review of CT angiographic images toconfirm the coronary vessels- Semi-automated tool for extraction ofanatomic data (including heartstructures) for coronary physiologicsimulation to aid in diagnosis ofcoronary artery disease,- Centerline detection- Provides additional data derived fromcoronary CT anatomy and pathology- Provide simulated hemodynamicinformation
Data source (input)	CT	CT
Output/ Accessibility	Graphic and text results of coronaryanatomy and simulated data areaccessed via a device with internetconnectivity	Graphic and text results of coronaryanatomy and simulated data areaccessed via a device with internetconnectivity
Physicalcharacteristics	- non-invasive software package- DICOM compatible	- non-invasive software package- DICOM compatible
Safety	Clinician review and assessment ofanalysis prior to use as supplementaldiagnostic aid	Clinician review and assessment ofanalysis prior to use as supplementaldiagnostic aid

Table 5-1. Predicate Device Comparison

Image /page/4/Picture/14 description: The image shows the HeartFlow logo. The logo consists of a stylized blue heart shape on the left and the word "HeartFlow" in blue on the right. The heart shape is made up of three curved lines that resemble waves. The word "HeartFlow" is written in a sans-serif font, and there is a registered trademark symbol next to the word "Flow".

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K203329

Table 5-2. Predicate Device Feature Comparison

Feature	FFRCT Planner(predicate)	FFRCT v3
Presentation of CT images for confirmation of extracted model	X	X

Image /page/5/Picture/6 description: The image shows the HeartFlow logo. The logo consists of a stylized heart shape made of three curved lines on the left, followed by the word "HeartFlow" in a sans-serif font. There is a registered trademark symbol next to the word "HeartFlow".

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Automatic extraction of anatomic data from CT images foranalysis	X	X
Volume rendering based on centerlines	X	X
Automatic / Semi-automatic lumen boundary determination	X	X
Annotate, tag, measure and record selected views	X	X
View the coronary vessels	X	X
Modify anatomic model to remove luminal narrowing(s)	X	X
Expose interim calculations used as input of FFRct (e.g., massand volume)	X	X
Calculate functional parameters of the heart (e.g., FractionalFlow Reserve, %myo)	X	X
Graphic and Text Results	X	X

Table 12-3. Predicate Device Solver Comparison

	Gen 2 Solver (predicate)	Gen3 Solver (FFRCT v3)
Total coronary baseline flow	X	X
Flow distribution between ostia	X	X
Flow distribution within ostium	X	X

Changes to flow and distribution calculations within the Gen3 solver do not raise new questions of safety and effectiveness.

7 Summary of Studies

The software was designed, developed, tested and validated according to written procedures. These procedures specify individuals within the organization responsible for developing and approving product specifications, coding, testing, validating and maintenance.

Validation studies included stress testing, and repeatability testing to ensure the safety and effectiveness of the device. Software and medical device design validation has been completed. Medical device design included testing and evaluation using previously acquired diagnostic images received through HeartFlow sponsored clinical trials.

Summaries of pre-clinical studies were reviewed as part of a prior predicate review (K161772, the predicate of K182035 that is the predicate of K190925). The results concluded the device was acceptable for use.

Results of all current and previously referenced testing conclude the device is acceptable for use.

Image /page/6/Picture/12 description: The image contains the HeartFlow logo. The logo consists of a stylized blue wave-like design on the left, followed by the text "HeartFlow" in a sans-serif font, also in blue. A registered trademark symbol is present to the right of the word "Flow".

FFRct v 3 510(k) Submission 2020

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8 Conclusion

The conclusions drawn from the testing demonstrate that the device is as safe, as effective, and performs as well as the legally marketed device identified in section 2 above.

Image /page/7/Picture/5 description: The image contains the logo for HeartFlow. The logo consists of a stylized blue wave-like symbol on the left, followed by the text "HeartFlow" in a sans-serif font, also in blue. A registered trademark symbol is present to the upper right of the word "Flow".

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.