The Volcano System is used for the qualitative and quantitative evaluation of vascular morphology in the 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.

ChromaFlo is indicated for qualitative blood flow information from peripheral and coronary vasculature; flow information can be an adjunct to other methods of estimating blood flow and blood perfusion.

VH IVUS is intended to be used in conjunction with imaging catheters during diagnostic ultrasound imaging of the peripheral and coronary vasculature. The Volcano VH IVUS System is intended to semi-automatically visualize boundary features and perform spectral analysis of RF ultrasound signals of vascular features that the user may wish to examine more closely during routine diagnostic ultrasound imaging examinations.

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.

Rotational 45MHz feature is intended for the qualitative evaluation of vascular morphology in the coronary arteries and vasculature as an adjunct to conventional angiographic procedures to provide an image of the vessel lumen and the wall structures. The Pullback feature of the imaging core within the protective sheath for a maximum of 15 cm.

The FFR v2.5 Modality of the s5/s5i/CORE and CORE Mobile Precision Guided Therapy System is indicated in all blood vessels, including coronary and peripheral arteries, to measure intravascular blood pressure angiography and/or interventional procedures.

The iFR Modality is intended to be used in conjunction with currently marketed Volcano pressure wires. In the coronary anatomy, the iFR modality has a diagnostic cut-point of 0.89 which represents an ischemic threshold and can reliably guide revascularization decisions during diagnostic catheterization procedure. When used as for a pullback assessment, the iFR modality is intended as a visual aid in decision making the relative location and severity of the stenoses such as, multiple lesions or diffuse disease.

Device Description

The Volcano s5 TM/s5i/CORETM Mobile Precision Guided Therapy System is a mobile imaging and pressure management system as previously described in K133323. The subject device incorporates the Volcano iFR® Modality cleared in K133323.

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

This FDA 510(k) submission describes the Volcano s5/s5i/CORE/CORE Mobile Precision Guided Therapy System and focuses on a change in the Indications for Use for its iFR Modality. The submission aims to adopt a new, single diagnostic cut-point for iFR guided revascularization based on recent clinical evidence, replacing a previous 'hybrid' approach.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria here re-frame the iFR Modality's diagnostic cut-point. The previous approach was likely a range (e.g., 0.75-0.80), and the new acceptance criteria is a single, dichotomous cut-point of 0.89. The device performance is evaluated against this new cut-point in terms of its clinical outcomes compared to FFR guidance.

Acceptance Criteria (for iFR Modality)	Reported Device Performance (as demonstrated by clinical studies)
iFR Modality has a diagnostic cut-point of 0.89.	ADVISE II study demonstrated that an iFR cut-point of 0.89 matches best with an FFR ischemic cut-point of 0.80 with a specificity of 87.8% and sensitivity of 73.0% (C statistic: 0.90).
iFR Modality can reliably guide revascularization decisions.	DEFINE-FLAIR Study: iFR-guided revascularization (6.8%) was non-inferior to FFR-guided revascularization (7.0%) for the composite primary endpoint (all-cause mortality, non-fatal MI, or unplanned revascularization within 12 months). D = -0.2%; 95% CI, -2.3 to 1.8; P<0.001 (for non-inferiority). iFR-SWEDEHEART Study: iFR-guided revascularization (6.7%) was non-inferior to FFR-guided revascularization (6.1%) for the composite primary endpoint. D = 0.7; 95% CI, -1.5-2.8, P=0.007 (for non-inferiority).
iFR Modality provides a visual aid for pullback assessments.	The document states this is the intended use, but no specific performance metric related to the efficacy of the visual aid itself is provided, rather the clinical equivalency of the iFR value is confirmed.
Significant reduction in adverse effects compared to FFR.	DEFINE-FLAIR: 3.1% iFR group vs. 30.8% FFR group reported adverse procedural signs/symptoms (P<0.001). iFR-SWEDEHEART: 3.0% iFR group vs. 68.3% FFR group reported chest discomfort (P<0.001).

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

The "test set" for this submission are the patient cohorts from the three clinical studies cited:

ADVISE II: The document does not explicitly state the total sample size for ADVISE II but mentions a C-statistic and confidence interval, indicating a substantial number of patients. It is a "[P]rospective Assessment," implying prospective data. As it's an "International, Multicenter Study," the data provenance is likely multi-country.
DEFINE-FLAIR: Enrolled 2492 patients with coronary artery disease. Data provenance is prospective and multi-country/international (implied by nature of trials with such large patient cohorts).
iFR-SWEDEHEART: Enrolled 2017 patients with coronary artery disease. Data provenance is prospective and primarily from Sweden (all 30 coronary intervention centers in Sweden plus one site in Iceland).

All data presented are from prospective, randomized controlled clinical trials or prospective diagnostic accuracy studies.

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

The document does not specify the number or qualifications of experts directly involved in establishing the "ground truth" for the test sets within these studies. Instead, the ground truth is established by:

FFR (Fractional Flow Reserve): This is the comparative "gold standard" for assessing lesion severity and guiding revascularization. FFR values themselves are physiological measurements, not interpretations by experts in the same way as imaging reads.
Clinical Outcomes: The primary endpoint of the DEFINE-FLAIR and iFR-SWEDEHEART studies was a composite of "all-cause mortality, non-fatal myocardial infarction or unplanned revascularization." These are objective clinical events, not subject to expert interpretation for ground truth.

Therefore, the "ground truth" is based on established physiological measurements (FFR) and objective clinical endpoints, rather than expert consensus on image interpretation.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for the test set in the context of expert review. Since the ground truth for the comparative studies (DEFINE-FLAIR, iFR-SWEDEHEART) was FFR measurements and objective clinical outcomes, traditional adjudication by a panel of readers is not applicable in the same way it would be for an AI-based imaging diagnostic. For the ADVISE II study, which focused on the diagnostic accuracy of iFR against FFR, the "ground truth" for comparison was the FFR value, not expert consensus. Clinical events in the RCTs would typically be centrally adjudicated by a clinical events committee (CEC), but details of such adjudication are not provided in this 510(k) summary.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and Effect Size of Human Reader Improvement with AI vs. without AI assistance

No, a traditional MRMC comparative effectiveness study was not performed as described for an AI device. This submission is for a change in the indications for use of a measurement modality (iFR) used by a human operator, not an AI interpreting images or assisting human readers. The "comparison" is between guiding revascularization with iFR vs. FFR, not human performance with or without AI.

The "effect size" is demonstrated by the non-inferiority of iFR-guided revascularization to FFR-guided revascularization for clinical outcomes, and the significant reduction in adverse effects due to iFR not requiring adenosine.

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

The iFR Modality is essentially a "standalone algorithm" in terms of its calculation of the iFR value itself. However, it's always "human-in-the-loop" in its clinical application – the iFR value is provided to a physician who then uses it to make treatment decisions. The studies presented (DEFINE-FLAIR, iFR-SWEDEHEART) are comparisons of clinical decision-making strategies (iFR-guided vs. FFR-guided), which inherently involve human decision-makers using the device.

7. The Type of Ground Truth Used

The primary ground truth used for proving the device's efficacy in guiding revascularization was:

Clinical Outcomes Data: This is the most significant ground truth (all-cause mortality, non-fatal MI, unplanned revascularization).
FFR (Fractional Flow Reserve): Used as the comparative gold standard for assessing lesion hemodynamics and as the basis for clinical decision-making in the control arms of the studies. The ADVISE II study specifically evaluated iFR's diagnostic accuracy against FFR.

8. The Sample Size for the Training Set

This submission does not discuss a "training set" in the context of machine learning. The device is a physiological measurement system, and the change being applied is based on new clinical evidence supporting a revised interpretation/cut-point for an existing measurement. The clinical studies (ADVISE II, DEFINE-FLAIR, iFR-SWEDEHEART) serve as the evidence base for this updated interpretation, rather than a training set for an AI model.

9. How the Ground Truth for the Training Set was Established

As there is no "training set" in the AI sense for this device, this question is not directly applicable. The "ground truth" supporting the revised iFR cut-point in this context comes from the results of large-scale, prospective, randomized controlled clinical trials (DEFINE-FLAIR, iFR-SWEDEHEART) demonstrating non-inferiority of iFR-guided care to FFR-guided care and the diagnostic accuracy study (ADVISE II) correlating iFR to FFR values.

Summary

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

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

April 11, 2018

Volcano Corporation Christopher McLellan Manager. Regulatory Affairs 9965 Federal Drive Colorado Springs, Colorado 80921

Re: K173860

Trade/Device Name: s5/s5i/CORE/CORE Mobile Precision Guided Therapy System Regulation Number: 21 CFR 892.1560 Regulation Name: Ultrasonic Pulsed Echo Imaging System Regulatory Class: Class II Product Code: IYO Dated: March 9, 2018 Received: March 12, 2018

Dear Christopher McLellan:

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 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820);

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

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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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, M & Thillel for

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

Enclosure

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

Indications for Use

510(k) Number (if known) K173860

Device Name

Volcano s5/s5i/CORE/CORE Mobile Precision Guided Therapy System

Indications for Use (Describe)

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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

Submitter l.

Volcano Corporation

3721 Valley Center Drive San Diego, CA 92130

Contact Person: Kimberly Simon

Telephone: (858) 720-4113 E-mail: kimberly.simon@philips.com

Date Prepared: December 19, 2017

II. Device

Name of Device:	Volcano s5 ™ /s5i/CORE/CORE™ Mobile Precision GuidedTherapy System
Common or Usual Name:	Ultrasonic pulsed echo imaging system.
Classification Name:	System, Imaging, Pulsed Echo, Ultrasonic (21 CFR 892.1560)
Regulatory Class:	II
Product Code:	IYO

III. Predicate Device

Volcano s5 ™/s5i/CORE/CORE™ Mobile Precision Guided Therapy System (K133323).

Secondary Predicate Device

FFR v2.5 (K170133)

Reference Submissions for the Volcano s5 ™/s5i/CORE/CORE™ Mobile Precision Guided Therapy System:

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

IV. Device Description

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.

V. Indications for Use

The Volcano s5™/s5i/CORE™ Mobile Precision Guided Therapy System is used for the qualitative and quantitative evaluation of vascular morphology in the 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.

Rotational 45MHz feature is intended for the qualitative and quantitative evaluation of vascular morphology in the coronary arteries and vasculature as an adjunct to conventional angiographic procedures to provide an image of the vessel lumen and the wall structures. The Pullback feature of the PIMr withdraws the imaging core within the protective sheath for a maximum of 15 cm.

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

catheterization procedure. When used for a pullback assessment, the iFR modality is intended as a visual aid in decision making by indicating the relative location and severity of the stenoses such as, multiple lesions or diffuse disease.

VI. Comparison with the Predicate Device

The predicate device is the currently marketed Volcano s5/s5i/CORE/CORE Mobile Precision Guided Therapy System iFR Modality (cleared under K133323 with the same trade name). This submission is for a change in the indications for use of the currently marketed device. The indications for use for the iFR Modality of the subject device has been revised to reflect the currently recognized, and clinically supported physiological, dichotomous 0.89 intravascular pressure index from a hybrid approach of 0.75 – 0.80 to provide information to help inform decisions on whether to perform or defer percutaneous coronary intervention (PCl). In the coronary anatomy, the iFR Modality has a diagnostic cut-point of 0.89 which represents an ischemic threshold and can reliably guide revascularization during diagnostic catheterization procedure. When used for a pullback assessment, the iFR modality is intended as a visual aid in decision making by indicating the relative location and severity of the stenoses such as, multiple lesions or diffuse disease.

The Volcano FFR and iFR Modality Operator's Manual is being revised to include a dichotomous cutpoint for Instantaneous Wave-free Ratio (iFR) guidance in coronary revascularization decision-making to replace the hybrid approach described in the Volcano FFR and iFR Modality Operator's Manual of the currently marketed device. There are no changes to the device materials or intended use.

The Volcano s5/s5i/CORE Mobile Intravascular Imaging and Pressure System and the predicate device share the same intended use. These devices are software measure blood pressure in the coronary and peripheral vasculature.

The Volcano s5™/s5i/CORE™ Mobile Precision Guided Therapy System and the predicate device share the same general operating principal. Both devices use the same pressure wires and are both compatible with only the Volcano imaging and pressure systems.

Volcano s5™/s5i/CORE/CORE™ Mobile Precision Guided Therapy System and the predicate device share the same technological features.

The only difference between the Volcano s5/s5i/CORE/CORE Mobile Intravascular Imaging and Pressure System with iFR "Modality and the predicate device is the indications for use. The indications for use for the iFR Modality of the subject device has been changed to measure intravascular blood pressure using the iFR Modality diagnostic cut-point of 0.89 which represents an ischemic threshold and can reliably guide revascularization decisions during diagnostic catheterization procedure. When used for a pullback assessment, the iFR modality is intended as a visual aid in decision making by indicating the relative location and severity of the stenoses such as, multiple lesions or diffuse disease.

The similarities between the subject Volcano s5/s5i/CORE/CORE Mobile Intravascular Imaging and Pressure System and the predicate device are illustrated in the table below.

{7}------------------------------------------------

Attribute/Feature	Volcano s5/s5i/CORE/CORE Mobile PrecisionGuided Therapy System iFR Modality – K133323(Predicate Device)	Volcano s5/s5i/CORE/COREMobile Precision GuidedTherapy System(Subject Device)
Indications for Use	The iFR Modality of the s5™/s5i/CORE/CORE™Mobile Series Precision Guided Therapy System isindicated in all blood vessels, including coronaryand peripheral arteries, to measure intravascularblood pressure during diagnostic angiographyand/or interventional procedures. The iFR Modalityis intended to be used in conjunction withcurrently marketed Volcano pressure wires.	The Volcanos5™/s5i/CORE/CORE™ MobilePrecision Guided TherapySystem is used for thequalitative and quantitativeevaluation of vascularmorphology in the coronaryarteries and vessels of theperipheral vasculature. It isalso indicated as an adjunct toconventional angiographicprocedures to provide animage of vessel lumen and wallstructures.ChromaFlo is indicated forqualitative blood flowinformation from peripheraland coronary vasculature; flowinformation can be an adjunctto other methods of estimatingblood flow and bloodperfusion.VH IVUS is intended to be usedin conjunction with imagingcatheters during diagnosticultrasound imaging of theperipheral and coronaryvasculature. The Volcano VHIVUS System is intended tosemi-automatically visualizeboundary features and performspectral analysis of RFultrasound signals of vascularfeatures that the user may wish
Attribute/Feature	Volcano s5/s5i/CORE/CORE Mobile PrecisionGuided Therapy System iFR Modality – K133323(Predicate Device)	Volcano s5/s5i/CORE/COREMobile Precision GuidedTherapy System(Subject Device)
		routine diagnostic ultrasoundimaging examinations.The pressure feature isintended for use in all bloodvessels, including coronary andperipheral arteries, to measureintravascular blood pressureduring diagnostic angiographyand/or interventionalprocedures.Rotational 45MHz feature isintended for the qualitativeand quantitative evaluation ofvascular morphology in thecoronary arteries andvasculature as an adjunct toconventional angiographicprocedures to provide animage of the vessel lumen andthe wall structures. ThePullback feature of the PIMrwithdraws the imaging corewithin the protective sheath fora maximum of 15 cm.The FFR v2.5 Modality of thes5/s5i/CORE and CORE MobilePrecision Guided TherapySystem is indicated in all bloodvessels, including coronary andperipheral arteries, to measureintravascular blood pressureduring diagnostic angiographyand/or interventionalprocedures.
Attribute/Feature	Volcano s5/s5i/CORE/CORE Mobile PrecisionGuided Therapy System iFR Modality – K133323(Predicate Device)	Volcano s5/s5i/CORE/COREMobile Precision GuidedTherapy System(Subject Device)
		The iFR Modality is intended tobe used in conjunction withcurrently marketed Volcanopressure wires. In the coronaryanatomy, the iFR modality hasa diagnostic cut-point of 0.89,which represents an ischemicthreshold and can reliablyguide revascularizationdecisions during diagnosticcatheterization procedure.When used for a pullbackassessment, the iFR modality isintended as a visual aid indecision making by indicatingthe relative location andseverity of the stenoses suchas, multiple lesions or diffusedisease.
Pressure Wires	SmartWire II, PrimeWire, PrimeWire Prestige,PrimeWire Prestige Plus, Verrata, Verrata PLUS	SAME
Patient Isolation	Contained in the Patient Interface Module (PIM):Electronic and Electrical Defibrillation proofIsolation through 8mm bare fiberglass PCAcreepage with optical isolators and speciallywound transformers with 5KV insulation.	SAME
EnvironmentalOperatingTemperature,Humidity andPressure Range	Operating Temperature: +10°C to +35°C Operating / Storage Humidity: 10% ≤ RH ≤ 95% Non-condensing Operating Pressure Range: 70-106kPa (526.3 – 797 mmHG) Storage Pressure Range: 50-106kPa (376 – 797 mmHg)	SAME
Display	Control room	SAME
Attribute/Feature	Volcano s5/s5i/CORE/CORE Mobile PrecisionGuided Therapy System iFR Modality – K133323(Predicate Device)	Volcano s5/s5i/CORE/COREMobile Precision GuidedTherapy System(Subject Device)
	19" Non-medical grade powered through anisolation transformerExam room
	Use an existing Monitor in "Monitor Bank" Add a 19: non-medical grade to the x-ray boom (requires isolated power) 15" or 17" DC Powered Medical Grade Monitor mounted on the patient exam table 19" Monitor mounted on an additional boom (requires isolated power)
User Controls	Control ConsoleCustom control panel that can be placed in control room or mounted bedside Touch Pad Custom touch pad that is mounted bedside Joy Stick Custom joystick that can be mounted bedside	SAME
Signal Processing	Base Band (identical custom PCI boards used)	SAME
FFR	Through identical custom PCI board	SAME
iFR®	Through identical custom PCI board (same custom PCI board as used for FFR)	SAME
Inputs	100-240 VAC 50/60Hz Power Catheter/PIM connection ECG. Aortic high-level (from hemodynamic system) Ethernet (for DICOM Worklist) USB (for control devices) PS2 (for control devices) Touchpad	SAME
Attribute/Feature	Volcano s5/s5i/CORE/CORE Mobile PrecisionGuided Therapy System iFR Modality – K133323(Predicate Device)	Volcano s5/s5i/CORE/COREMobile Precision GuidedTherapy System(Subject Device)
	- Joystick
Outputs	- Monitor display: 1280 x 1024 resolution- 19" Monitor- 19" Boom Monitor- 17" Bedside Monitor- Printer	SAME
Patient InterfaceModule (PIM)	Compatible with Digital IVUS, Rotational IVUS, FFRPimmette	SAME
Connection to PIMs	Via direct connection to CPU or Connection Box	SAME
Accessories andPeripherals	Bedside Touchpad Controller, Joystick Controller,Connection Box, Control Console	SAME
ImagingSpecifications	Imaging boards and software	SAME
FFR Software(includes iFRModality)	FFR Software Version v2.3	FFR Software Version v2.5(cleared in K170133)

{8}------------------------------------------------

{9}------------------------------------------------

{10}------------------------------------------------

{11}------------------------------------------------

VII. Performance Data

The subject device is the same as the currently marketed predicate device. There are no changes to the pressure measurement wires for collection of data using the iFR" Modality. Performance data establishing the electrical safety and electromagnetic compatibility (EMC) of the device was previously reviewed in K133641 and K140291.

VIII. Clinical Data

Clinical evidence suggests the adoption of a dichotomous cut-point for Instantaneous Wave-free Ratio (iFR) guidance in coronary revascularization decision-making rather than the use of a hybrid approach as was previously documented in the Volcano FFR and iFR Modality Operator's Manual.

The clinical data submitted to support the proposed modifications is documented in the ADVISE II, DEFINE-FLAIR and iFR SWEDEHEART studies. The ADVISE II study demonstrated that Traditional 510(k) for Volcano s5/s5i/CORE/CORE Mobile Precision Guided Therapy System

{12}------------------------------------------------

an iFR cut-point of 0.89 matches best with an FFR ischemic cut-point of 0.80 with a specificity of 87.8% and sensitivity of 73.0% (C statistic: 0.90 (95% confidence interval (CI): 0.88 to 0.92, p < 0.001]).1

The use of this dichotomous cut-point for iFR-guided revascularization was compared to FFR-guided revascularization in two large prospective randomized controlled trials. 3 DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularization) enrolled 2492 patients with coronary artery disease in a 1:1 ratio to undergo revascularization using either FFR or iFR-guidance. The second study, iFR-SWEDEHEART (Instantaneous Wave-free Ratio versus Fractional Flow Reserve in Patients with Stable Angina Pectoris or Acute Coronary Syndrome) was similar; it enrolled 2017 patients with coronary artery disease included in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). The registry contains data on patients from all 30 coronary intervention centers in Sweden plus a single site in Iceland.

Both studies had a primary end-point that was the composite rate of all-cause mortality, non-fatal myocardial infarction or unplanned revascularization within 12 months after the index procedure. The non-inferiority margin was 3.4 in DEFINE-FLAIR, and 3.2 in iFR-SWEDEHEART. Both studies met their respective primary endpoint by demonstrating non-inferiority at 12 months:

DEFINE-FLAIR:	6.8% (iFR) vs 7.0% (FFR); D = -0.2%; 95% CI, -2.3 to 1.8; P<0.001
iFR-SWEDEHEART:	6.7% (iFR) vs 6.1% (FFR); D = 0.7; 95% CI, -1.5-2.8, P=0.007

Both studies also demonstrated a significant reduction in adverse effects associated with the adenosine-mediated hyperemia required for FFR-guidance. 68.3% of patients in the FFR arm of iFR-SWEDEHEART reported chest discomfort, while only 3.0% of patients in the iFR arm reported any chest discomfort (P<0.001). Similarly, DEFINE-FLAIR patients in the FFR group reported adverse procedural signs or symptoms in 30.8% of cases compared to 3.1% in the iFR group (P<0.001).

The iFR guided procedures demonstrated a significant reduction in acute adverse signs or symptoms associated with the adenosine-mediated hyperemia required for FFR. The use of iFR in stable ischemic heart disease is now considered appropriate by the major American cardiology societies. A hybrid iFR-FFR strategy is thus outdated.

4 Escaned J, Echavarria-Pinto M, Garcia HM, et. al. Prospective Assessment of the Diagnostic Accuracy of Instantaneous Wave-Free Ratio to Assess Coronary Stenosis Results of ADVISE II International, Multicenter Study (ADenosine Vasodilator Independent Stenosis Evaluation II). JACC Cardiovasc Interv. 2015 May;8(6):824-33.

2 Davies JE, Sen S, Dehbi H-M, et. al. Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI. N Engl J Med. 2017 May 11;376(19):1824-1834.

3 Götberg M, Christiansen EH, Gudmundsdottir IJ, et al. Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI. N Engl J Med. 2017 May 11;376(19):1813-1823.

{13}------------------------------------------------

IX. Conclusions

Based upon the information submitted in this premarket notification 510(k), the Volcano s5™/s5i/CORE/CORE™ Mobile Precision Guided Therapy System is substantially equivalent to the currently marketed predicate devices.

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.