HeartFlow Analysis

K213857 · HeartFlow, Inc. · PJA · Oct 14, 2022 · Cardiovascular

Device Facts

• Record ID: K213857
• Device Name: HeartFlow Analysis
• Applicant: HeartFlow, Inc.
• Product Code: PJA · Cardiovascular
• Decision Date: Oct 14, 2022
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 870.1415
• Device Class: Class 2
• Attributes: AI/ML, Software as a Medical Device

Intended Use

The HeartFlow Analysis is an AI-based medical device software for the clinical quantitative and qualitative analysis of previously acquired Computed Tomography DICOM data for patients with suspected coronary artery disease. It provides anatomic data, plaque identification and characterization, as well as the calculations of FFRCT, a coronary physiological simulation, 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 risk assessment and functional evaluation of coronary artery disease. The HeartFlow Analysis is provided to support qualified clinicians to aid in the evaluation and risk assessment of coronary artery disease. 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 Story

HeartFlow Analysis processes previously acquired coronary CT DICOM images; generates 3D computer models of coronary arteries; utilizes AI/ML algorithms to extract anatomic data, identify/characterize plaque, and simulate hemodynamic parameters (pressure, velocity, blood flow) to calculate FFRCT. Used by qualified clinicians (cardiologists/radiologists) in clinical settings to aid in coronary artery disease risk stratification and treatment planning. Output includes graphic/textual visualizations of anatomy, plaque, and functional metrics. Clinicians integrate these outputs with patient history and professional judgment to inform clinical decision-making. Benefits include non-invasive functional assessment of coronary lesions.

Clinical Evidence

Bench testing only. Validation included stress testing and repeatability testing. Medical device design validation utilized previously acquired diagnostic images from HeartFlow-sponsored clinical trials. No new clinical trials were conducted for this specific submission; safety and effectiveness were supported by results from current and previously referenced testing (K161772).

Technological Characteristics

Software-based medical device; DICOM compatible; non-invasive. Utilizes deep learning (AI/ML) algorithms for image analysis and hemodynamic simulation. Connectivity via internet for result access. Algorithms are frozen and validated prior to release. No physical hardware components; operates on commercial computer platforms.

Indications for Use

Indicated for patients with suspected coronary artery disease to support risk assessment and functional evaluation via quantitative and qualitative analysis of coronary CT images.

Regulatory Classification

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.

Special Controls

*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.

In combination with the general controls of the FD&C Act. the Coronary Physiologic Simulation Software Device is subject to the following special controls:

Predicate Devices

• HeartFlow FFRCT v3 (K203329)
• Autoplaque add-on ORS Visual (K122429)

Reference Devices

• ORS Visual software (K100335)
• K161772
• K182035
• K190925

Submission Summary (Full Text)

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October 14, 2022

HeartFlow, Inc. Windi Hary Chief Regulatory and Quality Officer 1400 Seaport Boulevard. Building B Redwood City, California 94063

Re: K213857

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, LLZ Dated: October 11, 2022 Received: October 13, 2022

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 ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

for

LCDR Stephen Browning Assistant Director Division of Cardiac Electrophysiology, Diagnostics, and Monitoring Devices Office of Cardiovascular Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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### Indications for Use

510(k) Number (if known) K213857

Device Name HeartFlow Analysis

#### Indications for Use (Describe)

The HeartFlow Analysis is an AI-based medical device software for the clinical quantitative and qualitative analysis of previously acquired Computed Tomography DICOM data for patients with suspected coronary artery disease. It provides anatomic data, plaque identification and characterization, as well as the calculations of FFRCT, a coronary physiological simulation, 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 risk assessment and functional evaluation of coronary artery disease.

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

| 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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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.<br>331 E. Evelyn Ave<br>Mountain View, CA 94041 |
|--------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Primary Contact Person: | Windi Hary, RAC<br>Chief Regulatory and Quality Officer<br>HeartFlow, Inc.<br>331 E. Evelyn Ave,<br>Mountain View, CA 94041<br>T [phone]<br>F [phone]<br>[e-mail] |
| Additional Contact Person: | James R. Davis<br>Director, Regulatory Affairs<br>HeartFlow, Inc.<br>T [phone]<br>F [phone]<br>[e-mail] |
| Date Prepared: | April 20, 2022 |

# 2 Device Identification

| Product Name | HeartFlow<br>Analysis | Common Name | FFRct |
|---------------------------------------------------------------------------------|-----------------------|----------------|-------------------------------------------------------------|
| Product Feature Description | Product Code | Classification | Classification Name |
| FFRct | PJA-Primary | 870.1415 | Coronary vascular physiologic<br>simulation software device |
| PreRead (Anatomy extracted<br>from FFRct 3D model) and<br>system plaque volumes | LLZ-Secondary | 892.2050 | Medical image management<br>and processing system |

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| Plaque characterization<br>presented with FFRct model<br>(automated AI/ML detection) | LLZ-Secondary | 892.2050 | Medical image management<br>and processing system |
|--------------------------------------------------------------------------------------|---------------|----------|-------------------------------------------------------------|
| Planner | PJA-Secondary | 870.1415 | Coronary vascular physiologic<br>simulation software device |

### 3 Predicates

HeartFlow FFR -- v3 (K203329) is the identified primary predicate and Autoplaque add-on ORS Visual (K122429) is an additional predicate for this submission.

### 4 Device Description

The HeartFlow Analysis is an Al-based medical device 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 in the risk stratification and evaluation of coronary artery disease.

The software displays coronary and functional information using graphics and text, including computed and derived quantities of percent stenosis, plaque volumes, 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.

## 5 Indications for Use

The HeartFlow Analysis is an Al-based medical device software for the clinical quantitative and qualitative analysis of previously acquired Tomography DICOM data for patients with suspected coronary artery disease. It provides anatomic data, plaque identification and characterization, as well as the calculations of FFRCT, a coronary physiological simulation, 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 risk assessment and functional evaluation of coronary artery disease.

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

# 6 Technological Characteristics of Device

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

The core technology remains unchanged from the primary predicate and continues to be trained using deep learning (Al and machine learning) since 2015, to incorporate learnings from the volumes of CT data and studies. All algorithms are then frozen and validated prior to product release. There are no differences between the subject device and the predicates with respect to intended use.

| | FFRCT v3 (primary<br>predicate) | Autoplaque (predicate) | FFRCT v3.plus |
|-----------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 510(k) | K203329 | K122429 | K213857 |
| | FFRCT v3 (primary<br>predicate) | Autoplaque (predicate) | FFRCT v3.plus |
| Manufacturer | HeartFlow, Inc. | Object Research Systems,<br>Inc. | HeartFlow, Inc. |
| Regulation<br>Number | 870.1415 | 892.2050 | 870.1415 |
| Regulation<br>Name | Coronary Physiologic<br>Simulation Software<br>Device | System, Image Processing,<br>Radiological | Coronary Physiologic<br>Simulation Software Device |
| Classification | Class II | Class II | Class II |
| Device Common<br>Name | HeartFlow FFRCT | Image Processing<br>System,<br>Radiology,Software<br>PACS | HeartFlow Analysis |
| Product Code | PJA | LLZ | PJA |
| Functions | -Extract anatomic data<br>from digital cardiac<br>images for the display<br>and visualization of the<br>anatomy of patient's<br>coronary arteries<br>-Compute FFRct | -Users of Autoplaque can<br>edit the lumen and<br>vessel walls of the<br>suggested<br>segmentation.<br>-Users are provided with<br>image viewing tools to<br>aid in their analysis.<br>-Plaque and stenosis<br>measurements are<br>output based on the<br>combination of fully<br>user-editable<br>segmentation and user-<br>placed demarcations of<br>coronary artery<br>characteristics. | -Extract anatomical and<br>plaque data from digital<br>cardiac images for the<br>display and visualization<br>of the anatomy of<br>patient's coronary<br>arteries<br>-Compute FFRct |
| Intended use | -Review of CT<br>angiographic images<br>to confirm the<br>coronary vessels<br>-Semi-automated tools<br>for extraction of<br>anatomic data<br>(including heart<br>structures) for<br>coronary physiologic<br>simulation to aid in<br>diagnosis of coronary<br>artery disease | -Provide a non-invasive<br>application to analyze<br>coronary anatomy and<br>pathology<br>-Post processing<br>application option for<br>the ORS visual platform<br>(K100335).<br>-A non-invasive<br>diagnostic reading<br>software add-on<br>intended for use by<br>cardiologists and<br>radiologists as an | -Review of CT<br>angiographic images to<br>confirm the coronary<br>vessels<br>-Semi-automated tools<br>for extraction of anatomic<br>data (including heart<br>structures) for coronary<br>physiologic simulation to<br>aid in diagnosis of<br>coronary artery disease<br>-Centerline detection |
| | FFRCT v3 (primary<br>predicate) | Autoplaque (predicate) | FFRCT v3.plus |
| | -Centerline detection<br>-Provides additional<br>data derived from<br>coronary CT anatomy<br>and pathology<br>-Provide simulated<br>hemodynamic<br>information | interactive tool for<br>viewing and analyzing<br>cardiac CT data for<br>determining the<br>presence and extent of<br>coronary plaques.<br>-ORS Visual software<br>(K100335) and the<br>Autoplaque add-on must<br>be installed on a suitable<br>commercial computer<br>platform. | -Provides additional data<br>derived from coronary CT<br>anatomy and pathology<br>-Provide simulated<br>hemodynamic<br>information |
| Data source<br>(input) | CT | CT | CT |
| Output/<br>Accessibility | Graphic and text<br>results of coronary<br>anatomy and<br>simulated data are<br>accessed via a device<br>with internet<br>connectivity | Graphic and text results<br>provided on a suitable<br>commercial computer<br>platform. It is the user's<br>responsibility to ensure the<br>monitor quality and ambient<br>light conditions are<br>consistent with the clinical<br>applications. | Graphic and text results of<br>coronary anatomy and<br>simulated data are accessed<br>via a device with internet<br>connectivity |
| Physical<br>characteristics | -Non-invasive software<br>package<br>-DICOM compatible | -Software installed and<br>used by the user<br>-Suitable commercial<br>computer platform | -Non-invasive software<br>package<br>-DICOM compatible |
| Safety | Clinician review and<br>assessment of analysis<br>prior to use as<br>supplemental<br>diagnostic aid | Clinician review, and assessment of analysis<br>prior to use as supplemental<br>diagnostic aid | Clinician review and<br>assessment of analysis prior<br>to use as supplemental<br>diagnostic aid |

### Table 5-1. Predicate Device Comparison

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Table 5-2. Predicate Device Feature Comparison

| Feature | FFRct v3<br>(primary<br>predicate) | Autoplaque<br>(predicate) | FFRct<br>v3.plus<br>(subject) |
|----------------------------------------------------------------------|------------------------------------|---------------------------|-------------------------------|
| Presentation of CT images for confirmation of<br>extracted model | x | | x |
| Automatic extraction of anatomic data from CT<br>images for analysis | x | x | x |
| Modeled stenosis and plaque* information | | x (user edit) | x |

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| Volume rendering based on centerlines | x | | x |
|---------------------------------------------------------------------------------------|---|---------------|---|
| Automatic/Semi-automatic lumen boundary<br>determination | x | x (user edit) | x |
| Annotate, tag, measure and record selected views | x | x (user edit) | x |
| View the coronary vessels | x | x (user edit) | x |
| Modify anatomic model to remove luminal<br>narrowing(s) | x | | x |
| Expose interim calculations used as input of FFRct<br>(e.g., mass and volume) | x | | x |
| Calculate functional parameters of the heart (e.g.,<br>Fractional Flow Reserve, %myo) | x | | x |
| Visualize plaque information* | | x (user edit) | x |
| Graphic and text results | x | x | x |

*Anatomical plaque calculation and visualization is supported by comparison to the Autoplaque predicate device

## 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 original predicate of K182035/K190925/K203329). The results concluded the device was acceptable for use.

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

### 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 devices identified in section 2 above.