The iFR® Modality of the s5/s5i/CORE/CORE Mobile Precision Guided Therapy System is indicated in all blood vessels, including coronary and peripheral arteries, to measure intravascular blood pressure during diagnostic angiography and/or interventional procedures. The iFR® Modality is intended to be used in conjunction with currently marketed Volcano pressure wires.

Device Description

The Volcano iFR® Modality is new software that calculates blood pressures in the coronary and peripheral vasculature through isolation of the cardiac wave cycle where intracoronary resistance is naturally constant and minimized and where intracoronary flow is maximized. This results in the ability to measure pressure without the administration of a hyperemic agent.

Pressure measurement is captured through the use of currently marketed pressure wires compatible with the currently marketed s5/s5i/CORE/CORE Mobile imaging and pressure measurement system.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Volcano iFR® Modality, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

The provided document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity, specificity, or accuracy thresholds. Instead, it presents the "Study Results" as the performance metrics achieved by the device. The conclusion states that "The results of the performance data demonstrate equivalence to the predicate device."

However, we can infer that the reported performance metrics (sensitivity, specificity, PPV, NPV, and diagnostic accuracy) act as the de facto "acceptance criteria" that the device met to demonstrate equivalence.

Parameter	Acceptance Criteria (Inferred from Study Results)	Reported Device Performance
Sensitivity	Sufficiently high for clinical utility	90.7% (225/248) [86.4%, 94.0%]
Specificity	Sufficiently high for clinical utility	96.2% (425/442) [93.9%, 97.7%]
Positive Predictive Value	Sufficiently high for clinical utility	93.0% (225/242) [89.0%, 95.9%]
Negative Predictive Value	Sufficiently high for clinical utility	94.9% (425/448) [92.4%, 96.7%]
Diagnostic Accuracy	Sufficiently high for clinical utility	94.2% (650/690) [92.2%, 95.8%]
Percentage of Lesions free from Hyperemic Agent	Sufficiently high for clinical utility	69.1% (477/690) [65.5%, 72.6%]
Percentage of Patients free from Hyperemic Agent	Sufficiently high for clinical utility	65.1% (389/598) [61.1%, 68.9%]

Interpretation: The "acceptance criteria" are implied by the demonstration of a "statistically high correlation" with FFR and the favorable percentages of patients/lesions where hyperemic agents could be avoided.

Study Information

Here's the detailed breakdown of the ADVISE II study, which provided the clinical data for the iFR® Modality:

Sample Size used for the test set and the data provenance:
- Sample Size: 690 lesions. 598 patients.
- Data Provenance: Prospective, observational, non-randomized, double-blind, global, multi-center registry. This indicates data from various countries/sites. Specific countries are not detailed in the summary.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document states that the iFR values were calculated at the "core lab using the HARVEST software (investigators were blinded to the iFR results)." The ground truth (FFR) was obtained using "standard guidelines for the FFR procedure."
- Number of Experts: Not explicitly stated how many individuals or experts were involved in the "core lab" analysis or in performing the FFR procedures.
- Qualifications of Experts: Not explicitly stated, but performing FFR and interpreting its results typically involves interventional cardiologists or highly trained catheterization lab personnel. The "core lab" would likely have experienced personnel for data processing and analysis.
Adjudication method for the test set:
- Not explicitly described as a formal adjudication process between multiple readers. The ground truth (FFR) was established from direct physiological measurement. The "Hybrid approach" used FFR to categorize a subset of iFR values, which is a predefined algorithm rather than an inter-expert adjudication. The "counts provided in the cells of the below 2x3 matrix were provided by the study core laboratory," suggesting a single source for applying the FFR criteria.
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:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study focusing on human reader improvement with/without AI assistance was not explicitly mentioned or conducted as described. This study directly compared the iFR modality (software-calculated pressure measurement) against FFR (a standard physiological measurement) as a diagnostic tool. It wasn't about humans interpreting images with or without AI.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance metrics (sensitivity, specificity, etc.) presented are for the iFR Hybrid method in comparison to FFR. The iFR calculation itself is an "algorithm only" process where the software calculates the iFR from pressure wire data. While physicians perform the initial data acquisition, the iFR value itself is generated by the device's software without human interpretation or adjustment of the core iFR calculation. The "Hybrid approach" then uses these iFR values to selectively determine if FFR is needed, which is also an algorithmic decision-making process.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The ground truth was established using Fractional Flow Reserve (FFR) measurements, which is a universally accepted physiological measurement of coronary stenosis severity performed using a pressure wire and a hyperemic agent (adenosine). FFR values ≤ 0.80 were considered indicative of ischemia, and FFR values > 0.80 were considered not ischemic. This is a physiological reference standard, often considered a gold standard in cardiology.
The sample size for the training set:
- The document describes the ADVISE II study as providing clinical data to support the iFR modification. It does not explicitly mention a separate "training set" for the iFR algorithm within the context of this 510(k) summary. The iFR modality is described as "new software that calculates blood pressures." It's possible the core iFR algorithm was developed and trained prior to this study, or it might be based on physiological principles rather than machine learning training on a dataset. The ADVISE II study appears to be a validation study for the overall performance of the iFR modality, not a study used for "training" the algorithm.
How the ground truth for the training set was established:
- As no training set is explicitly described in this submission for the iFR algorithm itself, the method for establishing its ground truth is not provided. The ADVISE II study focused on validating the iFR Modality against FFR.

Summary

{0}------------------------------------------------

K133323

510(K) SUMMARY

SPONSOR:	Volcano Corporation3721 Valley Center DriveSan Diego, CA 92130
CONTACT:	Neeta SharmaDirector, Regulatory AffairsVolcano Corporation3721 Valley Center DriveSan Diego, CA 92130Tel: (858) 720-4187Fax: (858) 720-0335
DATE PREPARED:	March 12, 2014
DEVICE:	Volcano iFR® Modality
TRADE NAME:	Volcano iFR® Modality
COMMON NAME:	Ultrasonic Pulsed Echo Imaging System
CLASSIFICATION:	21 CFR Part 892.1560IYO: System, Imaging, Pulsed Echo, UltrasonicClass II Device
PREDICATE DEVICE:	Volcano s5/s5i/CORE/CORE Mobile Precision GuidedTherapy System (K123898)
DEVICE DESCRIPTION:	The Volcano iFR® Modality is new software that calculatesblood pressures in the coronary and peripheral vasculaturethrough isolation of the cardiac wave cycle whereintracoronary resistance is naturally constant andminimized and where intracoronary flow is maximized.This results in the ability to measure pressure without theadministration of a hyperemic agent.Pressure measurement is captured through the use ofcurrently marketed pressure wires compatible with thecurrently marketed s5/s5i/CORE/CORE Mobile imagingand pressure measurement system.
INTENDED USE:	The Volcano s5™/s5i/CORE/CORE™ Mobile PrecisionGuided Therapy System is used for the qualitative andquantitative evaluation of vascular morphology in the

{1}------------------------------------------------

coronary arteries and vessels of the peripheral vasculature. It is also indicated as an adjunct to conventional angiographic procedures to provide an image of vessel lumen and wall structures.

The pressure feature is intended for use in all blood vessels. including coronary and peripheral arteries, to measure intravascular blood pressure during diagnostic angiography and/or interventional procedures

COMPARISON OF CHARACTERISTICS:

PERFORMANCE DATA:

Performance testing completed for a determination of substantial equivalence included the following:

The proposed device the same as the currently marketed

changes to the pressure measurement wires for collection of

device with the exception of software. There are no

. Software Validation
data using the iFR® Modality.
Repeatability and Reproducibility of measurements
. Clinical Data

One primary clinical study was used to provide clinical data in support of the iFR® modification. ADVISE II (Adenosine Vasodilator Independent Stenosis Evaluation) was a prospective, observational, non-randomized, double blind, global, multi-center registry sponsored by Volcano Corporation investigating the diagnostic utility of iFR in assessing coronary stenosis relevance (NCT01740895). The purpose of this registry was to assess the clinical value of iFR to characterize, without concomitant administration of hyperemic agents and outside a specified range of iFR values, coronary stenosis severity as determined with fractional flow reserve (FFR).

In ADVISE II, data were obtained in patients with coronary stenoses between 40-90% by visual assessment on angiography. These lesions were interrogated by FFR assessment with a Volcano Corporation pressure wire. A per lesion analysis was recorded with both baseline and hyperemic measurements. The baseline recording was used to calculate iFR at the core lab using the HARVEST software (investigators were blinded to the iFR results). This iFR value was compared with the FFR value measured in the same recording during maximal hyperemia. The FFR assessment was obtained using standard guidelines for the FFR procedure with the patient's heart being functionally stressed by a hyperemic agent called adenosine at 140 mcg/kg/min.

Study Results

Of the 690 lesions assessed in the ADVISE II analysis the patient characteristics were: mean age was 63.6 + 10.8, 68.8% were Male, 77.9% with Hypertension, 34.6% had Diabetes, 21.6% were

{2}------------------------------------------------

Smokers and 33.9% had a prior MI. The clinical presentations of the patients varied with the majority (50.3%) presenting with stable angina and 25.4% presenting with unstable angina. 18.4% of patients had presented with myocardial ischemia in a non-invasive stress test, 3.3% presenting with a STEMI that was more than 48 hours, 5.5% presenting with an NSTEMI more than 48 hours and 7.7% deemed "Other."

The counts provided in the cells of the below 2x3 matrix were provided by the study core laboratory. The Hybrid approach specifies that, for iFR values between and including 0.86 and 0.93, FFR is performed to determine lesion category. Hence, the 114 lesions in the top cell of the center column are categorized as "negative" because FFR is >0.80; conversely, the 99 lesions in the bottom cell of the center column are categorized as "positive" because FFR is ≤ 0.80.

Image /page/2/Figure/3 description: The image is a matrix comparing negative and positive FFR and iFR values. For negative FFR (>0.80) and negative iFR (≥ 0.94), the value is 311. For negative FFR and the FFR Zone (iFR 0.86 to 0.93), the value is 114, and for negative FFR and positive iFR (≤ 0.85), the value is 17. For positive FFR (≤ 0.80) and negative iFR, the value is 23, for positive FFR and the FFR Zone, the value is 99, and for positive FFR and positive iFR, the value is 126.

Two hundred and forty eight (248) lesions were ischemic as determined by the reference method (FFR ≤ 0.80); of these 225 were properly categorized by the Hybrid method: there were 23 false negatives. Four hundred and forty two (442) lesions were not ischemic as determined by the reference method (FFR > 0.80); of these, 425 were properly categorized by the Hybrid method; there were 17 false positive lesions.

The overall accuracy of sensitivity, specificity, positive value, negative predictive value and diagnostic accuracy were:

Parameter	Estimate	95% CI
Sensitivity	90.7% (225/248)	[86.4%, 94.0%]
Specificity	96.2% (425/442)	[93.9%, 97.7%]
Positive Predictive Value	93.0% (225/242)	[89.0%, 95.9%]
Negative Predictive Value	94.9% (425/448)	[92.4%, 96.7%]
Diagnostic Accuracy	94.2% (650/690)	[92.2%, 95.8%]

Note: All iFR values falling within the FFR Zone were deferred to FFR for determination of treatment and were therefore accounted for as true positives or true negatives per FFR criteria.

{3}------------------------------------------------

These lesions (or patients) represent the group that is not spared from hyperemic agent when using the hybrid iFR/FFR approach.

The iFR Hybrid Approach Analysis performed on the independently-held ADVISE II dataset, was the first prospective, real world registry comparing iFR and demonstrated a statistically high correlation (sensitivity 90.7% for FFR less than or equal to 0.80. specificity 96.2% for FFR greater than 0.80). The hybrid method would have avoided the need to use a hyperemic agent in 65.1% of this patient population.

Parameter	Percentage Free FromHyperemic Agent	95% CI
Lesions free fromAdenosine	69.1% (477/690)	[65.5%, 72.6%]
Patients free fromAdenosine	65.1% (389/598)	[61.1%, 68.9%]

The ADVISE II study illustrated a 5.8%. i.e., (17+23)/690, classification discordance . between the iFR Hybrid Approach and FFR. Among 477 lesions that would be assessed without hyperemia by the iFR Hybrid Approach, 40 (17+23) were due to classification discordance.
Lesion is free from Adenosine if iFR ≤ 0.85 or iFR ≥ 0.94 o
Patient is free from Adenosine if all of his/her lesions are free from Adenosine �
Excludes patients for whom no iFR value is available ●

The results of the performance data demonstrate equivalence to the predicate device.

{4}------------------------------------------------

Public Health Service

Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized depiction of an eagle or bird with three wing-like shapes, symbolizing health and human services. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the bird symbol.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center . WO66-G609 Silver Spring, MD 20993-0002

March 14, 2014

Volcano Corporation Necta Sharma Regulatory Affairs Director 3721 Valley Centre Drive, Suite 500 San Diego, CA 92130

Re: K133323

Trade/Device Name: Volcano iFR Modality Regulation Number: 21 CFR 892.1560 Regulation Name: Ultrasonic Pulsed Echo Imaging System Regulatory Class: Class II Product Code: IYO Dated: February 7, 2014 Received: February 10, 2014

Dear Ms. Sharma.

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warrantics. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (sec above) into cither 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.

{5}------------------------------------------------

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 (2) CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act): 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Small Manufacturers, International and Consumer Assistance at its tollfree number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

FDA

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

Enclosure

{6}------------------------------------------------

Indications for Use Statement

510(k) Number (if known) K133323

Page I of I

Volcano iFR® Modality Device Name

Indications for Use

Prescription Use X (Per 21 CFR 801.109) OR

Over the Counter Use

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

Concurrence of CDRH, Office of Device Evaluation (ODE),

Date:
2014.03.14
07:40:01 -04'00'
for Bram Zuckerman

Page 1 of 1

Regulation Number and Section

§ 892.1560 Ultrasonic pulsed echo imaging system.

(a)
Identification. An ultrasonic pulsed echo imaging system is a device intended to project a pulsed sound beam into body tissue to determine the depth or location of the tissue interfaces and to measure the duration of an acoustic pulse from the transmitter to the tissue interface and back to the receiver. This generic type of device may include signal analysis and display equipment, patient and equipment supports, component parts, and accessories.(b)
Classification. Class II (special controls). A biopsy needle guide kit intended for use with an ultrasonic pulsed echo imaging system only is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 892.9.