(163 days)
ShortCut is indicated for use as a splitting device of bioprosthetic aortic valve leaflets to facilitate valve-in-valve procedures for patients at risk of coronary obstruction.
The ShortCut is a transfemoral catheter designed to split the bioprosthetic aortic valve leaflets prior to transfemoral aortic valve replacement (TAVR), to reduce the risk of coronary ostium obstruction and coronary access compromise and enable a valve-in-valve procedure for patients at risk of coronary obstruction. Splitting of a leaflet creates a triangular opening in the leaflet that allows blood flow into the adjacent coronary artery.
The ShortCut is a sterile, single use, 16 Fr device which is inserted through the femoral artery over a guidewire into the left ventricle using standard catheter placement techniques. The ShortCut is comprised of the following parts:
- a. Distal Unit (DU) Distal end of the catheter which contacts the valve leaflets and splits them (Figure 1). It is comprised of the Splitting Element (SE) and the Positioning Arm (PA). The Splitting Element penetrates the leaflet from the ventricular side at the bottom of the leaflet and performs the cut. The Positioning Arm is positioned on the aortic aspect of the leaflet and acts as a protective stabilizer for the activated SE. The DU is delivered in a sheathed 16 Fr configuration that is opened upon reaching the target site.
- b. Delivery System (DS) The catheter shafts connect the Handle to the DU and delivers the required movements from the Handle to the DU. The DS is compatible with a 16 Fr introducer sheath and is delivered over a 0.035" Guide Wire (GW). The outer shaft of the DS (Sheathing Tube) is used to sheathe the DU during introduction and removal from the body. The inner shafts of the DS. together with its pig-tailed tip, enable flexing and positioning of the DU at the valve.
- c. Handle The user interface, designed to control the DS and the DU and to enable correct positioning of the DU on the valve (Figure 2).
The provided document describes the acceptance criteria and the study that proves the ShortCut device meets these criteria. The device is a percutaneous catheter system intended to split bioprosthetic aortic valve leaflets prior to transcatheter aortic valve replacement (TAVR) to reduce the risk of coronary obstruction in valve-in-valve (ViV) procedures.
Here's an organized summary of the requested information:
1. A table of acceptance criteria and the reported device performance:
The acceptance criteria are implicitly derived from the success rates of the primary effectiveness and safety endpoints, as well as the composite technical success endpoint.
| Acceptance Criteria (Performance Goal/Target) | Reported Device Performance (Mean ± SD, n (%), or other metric) |
|---|---|
| Primary Effectiveness Endpoint: Per-subject leaflet splitting success (performance goal of 75% of subjects with evidence of a successful split) | 100.0% (60/60) of subjects with evidence of a split (p < 0.001 vs. 75%) |
| Primary Safety Endpoint: No more than a target rate (implicitly low, comparable to ViV TAVR) of stroke or death by discharge or 7 days post-procedure | Mortality: 0.0% (0/60) by discharge or 7 days post-procedure Stroke: 1.7% (1/60) by discharge or 7 days post-procedure |
| Technical Success: High percentage of successful access, delivery, retrieval, and freedom from major complications (implicitly near 100%) | Overall Technical Success: 98.3% (59/60) |
| Bench Testing (Qualitative/Quantitative): All specified bench tests must demonstrate acceptable performance for intended use. | All specified bench tests (e.g., Tubing Strength, Positioning Stability, Splitting Stability, Corrosion, Pushability, Simulated Use, etc.) "passed" or "demonstrate acceptable performance." |
| Animal Study: Acute safety and functionality (leaflet split verification, usability, no adverse events like thrombus). | All target leaflets successfully split. Usability scored 3 or 4. No thrombus observed on devices. No visible emboli or signs of ischemia. |
2. Sample size used for the test set and the data provenance:
- Test Set (Clinical Study):
- Sample Size: 60 enrolled subjects initiated the index procedure with ShortCut.
- Data Provenance: Prospective, international, multi-center study.
- Countries of Origin: 13 sites in the US, 8 in EU (Europe), and 2 in Israel.
- Nature of Data: Prospective clinical trial data.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The document doesn't explicitly state the exact number or detailed qualifications of experts used to establish the ground truth for the clinical test set in terms of "expert consensus." However, it mentions several points related to external review and assessment:
- Primary Effectiveness Endpoint: Assessed intraprocedurally by echocardiography or angiography. This would typically be interpreted by the interventional cardiologists performing the procedure or specialized imaging physicians (e.g., echocardiographers).
- Primary Safety and Secondary Endpoints (Adverse Events): Adjudicated by a Clinical Events Committee (CEC). The qualifications of the CEC members are not specified, but such committees are typically composed of independent medical professionals with relevant expertise (e.g., cardiologists, neurologists) who review reported events.
4. Adjudication method for the test set:
- Adjudication Method: A Clinical Events Committee (CEC) adjudicated adverse events (SAEs and AEs), including primary safety endpoints (mortality and stroke) and secondary safety endpoints.
- The document mentions that 23 AEs determined by the site as non-serious and not related were not adjudicated by the CEC, indicating a protocol-defined scope for CEC review.
5. 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, an MRMC comparative effectiveness study was not done. This device is a mechanical catheter for a surgical procedure, not an AI/imaging diagnostic tool that assists human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here. The study focuses on the device's direct performance in a procedural setting.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- No, a standalone (algorithm-only) performance study was not done. As mentioned, this is a mechanical device, not an algorithm. Its performance is intrinsically linked to its use by qualified physicians ("human-in-the-loop").
7. The type of ground truth used:
The ground truth for the clinical study was based on:
- Intraprocedural Assessments:
- "Evidence of a split": Visualized by intraprocedural Transesophageal Echocardiography (TEE) immediately post-ShortCut procedure and prior to TAVR, OR increase in aortic regurgitation from pre to post leaflet split, assessed by intraprocedural TEE or angiography. This relies on direct observation and established clinical imaging markers.
- Clinical Outcomes/Events:
- Safety Endpoints: Adjudicated clinical events (mortality, stroke, coronary obstruction, etc.) based on patient follow-up and CEC review.
- Procedural Metrics: Direct observations and measurements during the procedure (e.g., successful access, delivery, retrieval, device integrity).
8. The sample size for the training set:
- The document refers to "bench studies" and "animal studies" as nonclinical performance testing.
- Animal Training/Validation: One acute GLP animal study was conducted with 5 pigs to evaluate acute safety and functionality. This serves as a critical pre-clinical validation step but is not a "training set" in the machine learning sense.
- There is no mention of a "training set" in the context of machine learning, as this is a medical device, not an AI algorithm. The rigorous bench and animal testing, along with the compassionate use cases, serve as pre-clinical and early human experience data that inform the device's design and refine its use before the pivotal clinical trial.
9. How the ground truth for the training set was established:
- Given that this is not an AI/ML device, the concept of a "training set" with established ground truth in that specific sense is not applicable.
- For the bench studies, ground truth was established through engineering specifications, validated test methods (e.g., ISO, ASTM standards), and predefined acceptance criteria for physical and functional performance.
- For the animal study, ground truth was established through:
- Visual inspection for thrombus formation.
- Gross pathology and histopathology examination of explanted organs to assess tissue damage, leaflet split, and potential emboli.
- Direct observation of leaflet splitting and device usability during the procedure. These observations were then compared against the expected device function.
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DE NOVO CLASSIFICATION REQUEST FOR SHORTCUT
REGULATORY INFORMATION
FDA identifies this generic type of device as:
Percutaneous catheter for cutting or splitting heart valve leaflets concomitant to transcatheter valve procedures. This device is a single use percutaneous catheter system that has a cutting element on the distal end. The cutting element makes physical contact with target tissue to cut or split heart valve leaflets in a manner that may reduce obstructive flow complications with transcatheter valve procedures. The device is indicated for use immediately prior to a transcatheter valve procedure.
NEW REGULATION NUMBER: 21 CFR 870.1254
CLASSIFICATION: Class II
PRODUCT CODE: SCZ
BACKGROUND
DEVICE NAME: ShortCut
SUBMISSION NUMBER: DEN240017
DATE DE NOVO RECEIVED: May 1, 2024
SPONSOR INFORMATION: Pi-Cardia Ltd. 5 David Fikes St. Rehovot 7632805 Israel
INDICATIONS FOR USE
ShortCut is indicated for use as a splitting device of bioprosthetic aortic valve leaflets to facilitate valve-in-valve procedures for patients at risk of coronary obstruction.
LIMITATIONS
The sale, distribution, and use of the ShortCut Device are restricted to prescription use in accordance with 21 CFR 801.109.
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The ShortCut should only be used by physicians and/or surgeons trained and qualified in interventional cardiology procedures and that have carefully read and fully understand the IFU and have completed all training required by Pi-Cardia.
At the time of granting of this De Novo, the safety and effectiveness of ShortCut have been demonstrated only for splitting bioprosthetic aortic valve leaflets in patients undergoing a concomitant valve-in-valve procedure, and who are determined to be at high risk of coronary ostia obstruction.
PLEASE REFER TO THE LABELING FOR A COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
DEVICE DESCRIPTION
The ShortCut is a transfemoral catheter designed to split the bioprosthetic aortic valve leaflets prior to transfemoral aortic valve replacement (TAVR), to reduce the risk of coronary ostium obstruction and coronary access compromise and enable a valve-in-valve procedure for patients at risk of coronary obstruction. Splitting of a leaflet creates a triangular opening in the leaflet that allows blood flow into the adjacent coronary artery.
The ShortCut is a sterile, single use, 16 Fr device which is inserted through the femoral artery over a guidewire into the left ventricle using standard catheter placement techniques. The ShortCut is comprised of the following parts:
- a. Distal Unit (DU) Distal end of the catheter which contacts the valve leaflets and splits them (Figure 1). It is comprised of the Splitting Element (SE) and the Positioning Arm (PA). The Splitting Element penetrates the leaflet from the ventricular side at the bottom of the leaflet and performs the cut. The Positioning Arm is positioned on the aortic aspect of the leaflet and acts as a protective stabilizer for the activated SE. The DU is delivered in a sheathed 16 Fr configuration that is opened upon reaching the target site.
- b. Delivery System (DS) The catheter shafts connect the Handle to the DU and delivers the required movements from the Handle to the DU. The DS is compatible with a 16 Fr introducer sheath and is delivered over a 0.035" Guide Wire (GW). The outer shaft of the DS (Sheathing Tube) is used to sheathe the DU during introduction and removal from the body. The inner shafts of the DS. together with its pig-tailed tip, enable flexing and positioning of the DU at the valve.
- c. Handle The user interface, designed to control the DS and the DU and to enable correct positioning of the DU on the valve (Figure 2).
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Image /page/2/Figure/0 description: The image shows a medical device with labels and measurements. The device is labeled as having a distal unit, a delivery system (16/14 Fr.), and a handle. The distal unit is 1150mm away from the start of the handle, and the handle is 600mm long. The handle has a diameter of 35mm.
Figure 1: The ShortCut Device
SUMMARY OF NONCLINICAL/BENCH STUDIES
Nonclinical studies conducted for the ShortCut device are summarized below.
| Classification | The ShortCut is considered an externally communicating devicethat is intended to come in direct contact with circulating bloodfor a limited duration (< 24 hours). A biocompatibilityassessment was performed per the requirements of ISO 10993-1:2018 Biological evaluation of medical devices - Part 1:Evaluation and testing within a risk management process andFDA Guidance for Industry Use of International Standard ISO10993-1, "Biological evaluation of medical devices- Part 1:Evaluation and testing within a risk management process"(September 2023). |
|---|---|
| BiocompatibilityAssessment | The biocompatibility of the ShortCut was evaluated with respectto cytotoxicity, sensitization, intracutaneous reactivity, acutesystemic toxicity, material mediated pyrogenicity andhaemocompatibility: hemolysis, thromboresistance andcomplement activation. This testing was partially leveragedfrom a similar device in the Pi-Cardia product family that sharessimilar materials and design features as the ShortCut. |
BIOCOMPATIBILITY/MATERIALS
SHELF LIFE/STERILITY
| Sterility | The ShortCut is provided as a single-use device, sterilized using ethylene oxide (EtO) gas. The device is intended for one procedure only (single-use, disposable). |
|---|---|
| Sterility testing conducted in accordance with ISO11135:2014/Amd1:2019, demonstrates ShortCut is providedsterile. The ShortCut was adopted into an existing, validated EtOsterilization cycle per AAMI TIR28:2016 Product Adoption andProcess Equivalence for Ethylene Oxide Sterilization. Thesterilization cycle was assured by using the validated overkillhalf-cycle sterilization method qualified in accordance with ISO11135:2014. Based on the validation results, a sterility assurancelevel (SAL) of at least b)(4 was achieved. The EO and ECHresiduals of the ShortCut was shown to meet the limits specifiedby ISO 10993-7:2008 following double EtO sterilization. | |
| Packaging | The packaging configuration for the Shortcut successfully metthe packaging distribution testing qualifications, following 2Xsterilization, simulated distribution consistent with ASTMD4169-16, and climatic conditioning cycles per ASTM F4332-14. The results of the testing demonstrate that the packagingdesign met the predetermined requirements, specifications, andacceptance criteria for packaging validation under typicaldistribution and climatic conditions, via the following testing:• ASTM 1886 / F1886M-16: Standard test method fordetermining integrity of seals for flexible packaging byvisual inspection• ASTM F88/F88M-15: Standard test method for sealstrength of flexible barrier materials• ASTM F2096-11(2019): Standard Test Method forDetecting Gross Leaks in Packaging by InternalPressurization (Bubble Test)• Visual inspection of packaging components condition,labeling legibility and durability, and product insertlegibility. |
| Shelf Life | The shelf-life of the ShortCut has been established at 1 yearbased on accelerated aging to simulate up to 1 year shelf-life.Following accelerated aging and 2X sterilization, simulateddistribution consistent with ASTM D4169-16, and climaticconditioning cycles per ASTM F4332-14, the device packagingvalidation testing was repeated and functional tests listed belowunder "PERFORMANCE TESTING-BENCH" which were deemed tobe potentially affected by device aging were repeated with agedtest samples. All tests passed. |
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ELECTROMAGNETIC COMPATIBILITY AND ELECTRICAL SAFETY
The ShortCut does not have active or powered electrical components.
MAGNETIC RESONANCE (MR) COMPATIBILITY
The ShortCut is intended as a temporary use device and has not been tested for MR compatibility.
PERFORMANCE TESTING - BENCH
The ShortCut was evaluated through a series of bench tests to verify that the design met the functional specifications. Certain verification tests were leveraged from testing performed on a similar device from the Pi-Cardia product family that shares similar design with ShortCut for the Delivery System and Handle components. The bench tests were performed on final sterilized product, as well as subjected to simulated distribution consistent with ASTM D4169-16, climatic conditioning cycles per ASTM F4332-14, and simulated use in a benchtop anatomical model per the clinical use instructions.
The engineering bench testing summarized in Table 1 below demonstrate acceptable performance of the device for its intended use.
| Test | Description / Acceptance Criteria |
|---|---|
| Tubing Strength | Longitudinal (tensile and/or compression) strength of theCatheter tubes:• Internal tube,• Frame tube - tensile and compressive,• Deflection tube - tensile, and• External tube - tensile and compressive |
| PositioningStability -Compression BondTest | Measure the axial forces the Positioning Arm mechanism canwithstand under worst-case conditions |
| Splitting StabilityBond Test | Evaluate the maximum axial forces the distal unit can withstandunder worst-case conditions |
| Handle BondStrength | Evaluate the bond strength of the joints and/or fixed connectionsof the handle mechanism:• Internal tube to Internal tube washer• Frame tube to Frame tube washer• External tube to External Tube Slider• Deflection tube to Deflection Tube washer |
| Tip Bond Strength | Evaluate the bond strength of the joints and/or fixed connectionsof the tip:• Soft Tip to insert |
| Tip connected to internal tube | |
| DU to Frame Tubebond | Evaluate the bond strength of the joint |
| Torsional Strength | Torsional strength of Catheter components under worst casetorsional conditions |
| Corrosion* | Evaluation of the corrosion resistance of the Catheter metal parts |
| Pushability Force | Measure the force required to track the Catheter over a guide-wire through a simulated tortuous path across the aortic arch andvalve (Pushing and Withdrawal forces) |
| Sheathing /Unsheathing forces | Measure the sheathing / unsheathing forces in worst-caseanatomical model (Sheathing and Unsheathing) |
| Axial Splitting | Measure the splitting axial force repeatability using the tensile |
| Force Repeatability | machine and a worst-case polymeric material (no statisticaldifference in splitting force after 4 cuts) |
| Flushing Test | Verify the ability to flush the air existing between the shafts andin the internal tube lumen |
| HydrophilicCoating integrity | Visual assessment of unintended delamination or degradation ofthe coating after simulated use ((b)(4) coverage of thehydrophilic coating, before and after simulated use is required) |
| ParticulateEvaluation | Evaluation of particulate generation from the ShortCut devicewhere the External tube and Deflection tube are coated with ahydrophilic coating, during simulated use:Pre-specified maximum allowed particles in each particlebin size quantified per deviceCoating integrity evaluation post particulate evaluationtest:o (b)(4) coverage of the hydrophilic coating, beforeand after simulated use is required |
| Simulated Use | Verify the ability of the catheter to successfully perform thesplitting procedure including all procedural steps according tothe IFU while maintaining the integrity of the catheter in aworst-case anatomical model and an engineered valve; includingcompatibility with introducer sheath, guidewire and connectors:1) Correct penetration point and successful leaflet split.2) Interface compatibility with off-the-shelf accessories(guidewire, sheath, embolic protection device, pigtailcatheter)3) Successful performance of all procedural steps accordingto the clinical Instructions for Use4) Intact catheter markings after test5) Catheter integrity after test |
| DimensionalVerification | Evaluation of the critical dimension of the system:1) Catheter weight2) Catheter working length3) Catheter Handle's length |
| 5) External Tube travel distance from DU unsheathed stateto DU sheathed state6) External shaft OD (Crossing profile) | |
| DeflectionVerification Test | Measure the angle and radius when the device is fully deflected(Deflection curve angle (b)(4)) |
| Leak Test | Measure the liquid leak rate through the ShortCut catheter andbetween the catheter and the introducer sheath in a simulated usescenario (b)(4) |
| Sheathing withBlockageVerification* | Evaluate the ability of the catheter to collapse the SplittingElement (SE) and sheath the device when blockage (tissue) isplaced under the SE mechanism |
| Abort SplittingVerification* | Evaluate the ability to terminate the splitting procedure (collapsethe SE) prior to completing the split |
| Usability Data | Summative usability evaluation and design validation of theShortCut device were conducted during animal and clinicalstudies. |
| Animal studies: Usability assessment scores for all categorieswere passing with scores of either 3 ('good and acceptable') or 4('very good and acceptable') for all procedures. | |
| Clinical studies: 24 physician users at 13 sites evaluated theShortCut device for usability in 60 subjects. The resultsdemonstrated acceptable performance in terms of its userinterface and clear instructions. Users reported high levels ofsatisfaction with its functionality and ease of operation. |
Table 1: Benchtop Performance Testing Summary
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*These characterization tests were performed on unaged devices only.
PERFORMANCE TESTING - ANIMAL
One in vivo animal study was performed according to Good Laboratory Practices (GLP) to support the acute safety and functionality of the ShortCut.
| Purpose | A GLP study was conducted to evaluate the acute safety (perthrombogenicity and hemodynamic stability evaluations) andfunctionality (per leaflet split verification and usabilityevaluation) of the ShortCut device. |
|---|---|
| Design | • A total of five (5) pigs were used in the acute study.• In each animal, a ShortCut procedure was performed to splitboth the left and right coronary leaflets of the aortic valve.• The study included assessment of device usability, visualinspection for thrombus formation, and gross pathology andhistopathology examination.• The study was performed at a GLP accredited laboratory. |
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| Results | For usability assessment, all categories were scored at either 3 ('good and acceptable', 1 animal) or 4 ('very good and acceptable', 4 animals) for all procedures. Visual examination of the intervened leaflets showed that all target leaflets were successfully split. In general, no hemodynamic abnormalities were observed during the procedures. Increased heart rate was observed in one animal. The following organs were evaluated: heart, aorta, lungs, kidneys, liver, brain and spleen: There were no visible emboli or signs of ischemia. Slight abrasions of the inner aortic walls were observed. Thrombus was not observed on the devices after removal from the animals. |
|---|---|
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SUMMARY OF CLINICAL INFORMATION
The clinical data that supported the ShortCut De Novo request included a primary pivotal study titled, "A Prospective, Multi-center, Non-Randomized, Single-Arm, Open-Label Pivotal Study to Demonstrate the Safety and Effectiveness of the ShortCut Device (The ShortCut Study)" and outside of the United States (OUS), first-in-human compassionate use cases. Details of the clinical experiences and selected results are provided below.
Pivotal Study - The ShortCut Study
Objective
To assess the safety and effectiveness of the ShortCut for splitting bioprosthetic aortic valve leaflets, and to demonstrate coronary artery ostia patency following leaflet split, in subjects who are at risk for TAVR-induced coronary artery ostium obstruction following a valve-invalve (ViV) procedure.
Study Design
Prospective, international, multi-center study sponsored by Pi-Cardia Ltd. The single-arm study analyzed sixty (60) subjects who were planned to undergo a percutaneous ViV procedure for an approved ViV indication, and who were determined at risk for TAVRinduced coronary artery ostium obstruction. The study included 23 sites worldwide: 13 in the US, 8 in EU and 2 in Israel.
Eligibility Criteria Summary
The study population consisted of male and female patients, at least 18 years of age.
Key inclusion criteria included the following:
- Plan for a percutaneous ViV procedure for an approved ViV indication due to a failed . bioprosthetic valve.
- . Subject is at risk for TAVR-induced coronary artery ostium obstruction.
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Key exclusion criteria included the following:
- Excessive aortic valve leaflet calcium morphology. .
- . Leaflet planned to be intervened is torn pre-ShortCut access.
- Iliofemoral vessel characteristics that preclude safe insertion of the introducer sheath. .
- Anatomy that does not allow safe placement of a cerebral embolic protection device. .
- . Intervention ≤ 1 month prior to index procedure.
- . Planned provisional stents.
- . Coronary disease that should be treated, or treatment of coronary disease ≤ 1 month prior to index procedure.
- . Carotid or vertebral artery disease that should be treated, or treatment of carotid stenosis < 1 month prior to index procedure.
- . CVA or TIA ≤ 6 months prior to index procedure.
- . Inoperable for emergency open-heart surgery.
- . Identified thrombotic material on the valve by either CT or Echocardiography.
Primary Effectiveness Endpoints
Overall leaflet splitting success using the ShortCut for each subject, assessed intraprocedurally by echocardiography or angiography.
Per-subject leaflet splitting success was determined based on the splitting success of the first intervened leaflet, as follows:
-
Visualization of leaflet split, assessed by intraprocedural TEE immediately post-. ShortCut procedure and prior to TAVR.
OR -
Increase in aortic regurgitation from pre to post leaflet split, assessed by . intraprocedural TEE or angiography.
Primary Safety Endpoints
Each of the following ShortCut device- and/or ShortCut procedure-related serious adverse events were assessed at discharge or at 7 days post-procedure, whichever occurred first:
- · Mortality
- Stroke (fatal, disabling and non-disabling) .
Additional Endpoints
The Secondary Effectiveness endpoints are:
- Per intervened leaflet splitting success assessed intra-procedurally for each intervened . leaflet according to the criteria described above for per-subject leaflet splitting success
- The following endpoints assessed through 30 days post-index procedure: .
- · Freedom from coronary artery ostia obstruction related to the intervened leaflet:
- o Freedom from coronary artery intervention related to the intervened leaflet.
The following Secondary Safety endpoints were assessed through 30 days post index procedure (according to VARC-3):
- . All-cause mortality
- · All-cause stroke (fatal, disabling and non-disabling)
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- . Coronary obstruction
- Myocardial infarction with new evidence of coronary artery obstruction requiring . intervention
- Major vascular complications .
- Cardiac tamponade .
- Acute kidney injury .
- Access-related type 3-4 bleeding .
The following Technical Success endpoints were composites of the following assessed at exit from procedure room following the ShortCut™ procedure:
- Successful access, delivery, and retrieval of the ShortCut™ device .
- Freedom from ShortCut device and/or ShortCut procedure-related mortality .
- Freedom from ShortCut device and/or ShortCut procedure-related: .
- o Surgery or intervention
- Major vascular or access-related complications o
- · Cardiac structural complication
Statistical Methods
The data is summarized listing the mean. standard deviation, minimum, maximum and number of subjects for continuous data, or listing count (frequency) and percentage for categorical data.
The study was designed to provide 80% power to achieve significance for the primary effectiveness endpoint with a performance goal of 75% of subjects with evidence of a successful split.
The study was not statistically powered to achieve significance for the primary safety endpoint; however, a sample size of at least 60 subjects allows capturing at least 1 rare event, such as stroke or all-cause mortality, with an event rate of 2.8% or greater at high probability (>80%). Stroke or mortality rates in small ViV TAVR studies are reported at rates of 1.4% and 3.5%. respectively. Therefore, the study size is sufficient to observe stroke or mortality events for subjects receiving the ShortCut procedure within a 2-fold margin (i.e., 2.8%) of rates expected in ViV TAVR studies.
Accountability
A total of 137 subjects were screened for the study worldwide (US, Europe, and Israel). 66 of the 137 subjects were screening failures. 6 subjects dropped out of the study before treatment, and 5 subjects enrolled from OUS sites were considered not poolable by the conditions of the US protocol. Therefore, sixty (60) enrolled subjects were eligible for inclusion in the IDE Shortcut Pivotal study.
- . There were multiple reasons for the 66 screening failures, including but not limited to: subject not as risk for TAVR-induced coronary artery obstruction, subject not planning to undergo percutaneous ViV procedure for an approved indication, excessive aortic valve leaflet calcium morphology, and/or unsuitable anatomy or condition for the device or procedure.
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- · The 5 OUS subjects that did not meet the US eligibility criteria per the approved IDE clinical protocol were considered non-poolable for the following reasons:
- · Planned provisional stent (2);
- Coronary disease that should be treated or treatment of coronary disease =< 1 O month prior to index procedure (1);
- Subject is not planned to undergo a percutaneous ViV procedure for an o approved ViV indication (1);
- Surgery or interventional procedure ≤ 1 month prior to the index procedure o (1).
Reasons for the 6 subjects that dropped out of the study and did not undergo the procedure include are listed in Table 2 below.
Of the 60 subjects that initiated the overall transcatheter aortic valve procedure, 100% (60/60) underwent the index procedure with ShortCut. The 30-day visit compliance for the subjects was 95.0% (57/60), with 2 of the 3 missed visits due to death.
The disposition of study subjects up to 90-day follow-up is presented in Table 2.
| Table 2: Study Cohort Disposition & Compliance | |||
|---|---|---|---|
| Disposition / ComplianceVariable | US SubjectsN (%) | OUS SubjectsN (%) | All Subjects,N (%) |
| Consented Subjects | 68 | 69 | 137 |
| Passed Screening | 35 | 36 | 71 |
| IDE Study Eligible / Enrolled | 35 | 31 | 66 |
| Enrolled and Not Treated(Dropouts) 1 | 4 (11.4) | 2 (6.5) | 6 (9.1) |
| Subject Withdrew Consent 2 | 2 (50.0) | 0 | 2 (33.3) |
| Investigator excluded/withdrew subject 2 | 0 | 1 (50.0) | 1 (16.7) |
| Death 2 | 1 (25.0) | 1 (50.0) | 2 (33.3) |
| Other 2 | 1 (25.0) | 0 | 1 (16.7) |
| Started Overall Procedure | 31 | 29 | 60 |
| Started Index Procedure 3 | 31 (100.0) | 29 (100.0) | 60 (100.0) |
| At Least One Leaflet Split wasAttempted 3 | 31 (100.0) | 29 (100.0) | 60 (100.0) |
| Completed the Study Accordingto Protocol 3 | 28 (90.3) | 27 (93.1) | 55 (91.7) |
| 30-Day Visit Completed 3,† | 29 (93.5) | 28 (96.6) | 57 (95.0) |
| 90-Day Visit Completed 3,‡ | 28 (90.3) | 27 (93.1) | 55 (91.7) |
Table 2: Study Cohort Disposition & Compliance
1 Percentages are based on the 'IDE Study Eligible / Enrolled' total per column.
2 Percentages are based on the 'Enrolled and Not Treated' totals per column.
3 Percentages are based on the 'Started Overall Procedure' totals per column.
- Two (2) subjects died 19 and 24 days post-procedure; One (1) subject did not perform the 30-days follow-up visit (but did return for 90-day visit).
- One (1) additional subject died 57 days post-procedure; One (1) subject is lost to follow-up; One (1) subject did not perform the 90-day follow-up visit.
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Demographics
The mean subject age was 77.0+9.6 years and 70.0% of participants were female. The most common comorbidities included hypertension (85.0%), significant renal impairment (73.3%), and coronary artery disease (43.3%). Subjects presented with isolated bioprosthetic valve stenosis (58.3%), isolated aortic regurgitation (11.7%), or mixed bioprosthetic valve failure (30.0%). The majority of subjects (96.7%) had a failed surgically implanted bioprosthetic valve (SAVR), while two subjects (3.3%) had a failed transcatheter bioprosthetic valve replacement (TAVR). Information on the subject demographics and baseline characteristics is provided in Table 3 below.
| Demographic Parameter /Baseline Characteristic | n = 60 | |
|---|---|---|
| n (%) or mean ± SD | ||
| Age, yr | 77.0 ± 9.6 | |
| Male | 18 (30.0) | |
| Female | 42 (70.0) | |
| Race / Ethnicity | ||
| Asian | 1 (1.7) | |
| Black of African American | 1 (1.7) | |
| Hispanic/Latino | 1 (1.7) | |
| White | 42 (70.0) | |
| Unknown* | 15 (25.0) | |
| STS score, % | 4.5 ± 2.4 | |
| EuroSCORE II | 8.5 ±5.7 | |
| Surgical risk (assessed by the heart team) | ||
| Intermediate / low | 0 (0.0) | |
| High | 54 (90.0) | |
| Extreme | 6 (10.0) | |
| NYHA Class | ||
| I-II | 20 (33.3) | |
| III-IV | 40 (66.7) | |
| Left ventricular ejection fraction, % | 54.2 ± 10.4 | |
| AV peak gradient, mmHg | 65.3 ± 21.3 | |
| AV mean gradient, mmHg | 38.1 ± 13.2 | |
| AVA, cm² | 1.0 ± 0.5 | |
| Failed Valve Type | ||
| SAVR | 58 (96.7) | |
| TAVR | 2 (3.3) | |
| Failed Valve Disease | ||
| Isolated aortic stenosis (AS) | 35 (58.3) | |
| Isolated aortic regurgitation (AR) | 7 (11.7) | |
| Mixed (AS and AR) | 18 (30.0) | |
| Failed bioprosthetic valve label size | ||
| 19 mm | 8 (13.3) | |
| 21 mm | 26 (43.3) | |
| ≥ 23 mm | 26 (43.3) |
Table 3: Study Cohort Demographics & Baseline Characteristics
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- Unknown = Not applicable, Not asked, Asked but unknown, Not done, or Missing BMI, body mass index: AVA, aortic valve area: LVEF, left ventricular ejection fraction: NYHA. New York Heart Association: STS, Society of Thoracic Surgeons; AV, aortic valve; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement.
All subjects (100%) were determined to be at risk for coronary obstruction. Key anatomical risk factors included mean VTC distance of 3.3±1.2 mm. mean VTS distance of 2.2±1.4 mm, and coronary height<10mm for 91.7% of the subjects. Additional factors indicating risk for coronary obstruction in the study cohort are depicted in Table 4.
| Risk Factors of Coronary Artery OstiaObstruction | n = 60n (%) or mean ± SD |
|---|---|
| Anatomical Risk Factors (per CT core lab analysis) | |
| Coronary height, mm | $6.9 \pm 2.7$ |
| Coronary ostia eccentricity, deg | $10.6 \pm 8.0$ |
| Coronary height < 10 mm | 55 (91.7) |
| Sinus of Valsalva width, mm | $27.9 \pm 3.3$ |
| Sinus of Valsalva height, mm | $16.2 \pm 3.2$ |
| VTC distance, mm | $3.3 \pm 1.2$ |
| VTS distance, mm | $2.2 \pm 1.4$ |
| Bioprosthetic Valve Factors (per site evaluation) | |
| Supra-annular position | 16 (26.7) |
| Internal stent frame | 23 (38.3) |
| No stent frame | 4 (6.7) |
| Long, thick, or bulky bioprostheticleaflets | 11 (18.3) |
| Stents posts that extend beyondSinotubular Junction | 17 (28.3) |
| Intended over-expansion / fracture ofbioprosthetic valve frame during TAVR | 17 (28.3) |
| None of the above | 11 (18.3) |
| Transcatheter Valve factor (per site evaluation) | |
| Extended sealing cuff | 19 (31.7) |
| High implantation | 20 (33.3) |
| None of the above | 32 (53.3) |
Table 4: Study Cohort Risk Factors of Coronary Artery Ostia Obstruction
VTC, virtual transcatheter heart valve-to-coronary-artery; VTS, virtual transcatheter heart valve to sinotubular junction.
Results
Procedural Outcomes
All procedures were performed under general anesthesia utilizing TEE and all used an embolic protection device. A single leaflet split was performed in 63.3% of subjects and two leaflets split in 36.7% of subjects. ShortCut procedure time was 31±18 min (single split 26.9
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± 19.7 min, dual split 37.0±14.7 min). In all subjects, valves were implanted successfully following the ShortCut procedure. One subject required emergency open-heart surgery for replacement valve implant due to index procedure-related adverse event (guidewire perforation of left ventricle). Selected procedural outcomes are provided in Table 5 below.
| Procedure Detail | n = 60n (%) or mean ± SD |
|---|---|
| Transfemoral access for TAVR | 60 (100.0) |
| Embolic protection device placed | 60 (100.0) |
| Intervened Leaflet | |
| Left | 30 (50.0) |
| Right | 8 (13.3) |
| Left and Right | 22 (36.7) |
| Overall procedure time (skin-to-skin), min* | 119.7 ± 51.3 |
| ShortCut procedure time, min** | 30.6 ± 17.9 |
| One leaflet split, min | 26.9 ± 19.7 |
| Two leaflet split, min | 37.0 ± 14.7 |
| ShortCut procedure contrast media volume, ml | 23.3 ± 43.9 |
| ShortCut procedure fluoroscopy time, min | 16.8 ± 10.1 |
| ViV TAVR procedure time, min*** | 7.9 ± 7.1 |
Table 5: Summary of Procedural Outcomes
*Total procedure time - time from access site incision to access site closure.
** ShortCut procedure time between ShortCut catheter insertion to its full retrieval including imaging time for split documentation.
***n=59; Data does not exist for 1 subject who had surgical implant procedure rather than TAVR.
Fifty-three subjects (53/60) were treated using only the first ShortCut device attempted. In six cases (6), the first device was removed prior to cutting a leaflet and a second device was used to make either a single split (3) or dual split (3). For one subject (1), the first device successful performed the first leaflet split and a second device was used to make the second leaflet cut. Overall, fifty-nine subjects (59/60) had all leaflet intervention(s) performed by a single (either first or second introduced) ShortCut device, as shown in Table 6 below.
| ShortCut Procedure Outcome | First ShortCutDevice(n=60), n (%) | SecondShortCutDevice (n=7), n(%) | Overall |
|---|---|---|---|
| ShortCut Successfully Reached the LeftVentricle 1 | 59 (98.3) | 7 (100.0) | |
| ShortCut Successfully Positioned onLeaflet(s) 1 | 56 (93.3) | 7 (100.0) | |
| Number of subjects for whom splittingperformed 1 | 54 (90.0) | 7 (100.0) | 60 (100.0) |
| LCC Split Only 2 | 27 (50.0) | 3 (42.9) | 30 (50.0) |
Table 6: Procedural Outcomes Per Device and Intervened Leaflet
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| RCC Split Only 2 | 8 (14.8) | 0 (0.0) | 8 (13.3) |
|---|---|---|---|
| RCC and LCC 2 | 19 (35.2) | 4 (57.1) | 22 (36.7) |
| Withdrawn Successfully 1 | 58 (96.7) | 7 (100.0) |
1 Percentages are based on the number of devices per column.
2 Percentages are based on the 'Number of subjects for whom splitting performed' totals per column.
Primary Effectiveness Endpoints
The primary effectiveness endpoint of per-subject leaflet splitting success was achieved in all subjects (100%) by one of the two pre-defined methods using intra-procedural
echocardiography or angiography, and was statistically significantly higher (p<.001) then the study performance goal of 75%, as shown in Table 7 below.
| Primary EffectivenessEndpoint | Subjects withSuccessful First Split(n=60),n (%) | 95%ConfidenceInterval | P-Value |
|---|---|---|---|
| Evidence of a split | 60 (100.0) | (94.0, 100.0) | <0.001 |
| Split visualization | 54 (90.0) | (79.5, 96.2) | |
| Increase in transvalvular AR | 55 (91.7) | (81.6, 97.2) |
Table 7: Per-Subiect Splitting Success
Confidence intervals were calculated using Clopper-Pearson method.
P-value was calculated using Exact Binomial test versus the performance goal of 0.75.
Primary Safety Endpoints
The study primary safety endpoint of stroke or death by discharge or 7 days post-index procedure was analyzed per CEC adjudication and is provided in Table 8. There were no deaths (0.0%) within 7 days post-procedure or by discharge. There was one stroke (1.7%) occurring at 4 days post-procedure that was determined not related to the ShortCut device and possibly related to ShortCut procedure.
| Table 8: Mortality & Stroke Through Discharge or 7-Day Follow-up | |||
|---|---|---|---|
| -- | ------------------------------------------------------------------ | -- | -- |
| Primary Safety Endpoint | Subjects withSuccessful First Split(n=60),n (%) |
|---|---|
| Mortality | 0 (0.0) |
| Stroke | 1 (1.7) |
| Fatal Stroke | 0 (0.0) |
| Disabling* | 1 (1.7) |
| Non-disabling** | 0 (0.0) |
- Disabling Stroke (mRS ≥2 and increase of at least 1 from baseline).
** Non disabling Stroke (mRS <2 or without increase from baseline).
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Additional Endpoints:
The Secondary Effectiveness endpoints of per-intervened leaflet splitting success and freedom from coronary artery ostia obstruction or interventions are summarized in Tables 9 and 10 below:
When considering all splitting attempts, successful leaflet split was demonstrated in 80 out of the 82 (97.6%) intervened leaflets. For the two cases in which successful leaflet split was not determined, one case indicated unsuccessful split per the pre-established conditions and the other case was inconclusive due to inadequate imaging.
| Per-Leaflet Splitting EffectivenessEndpoint | Intervened Leaflet withSuccessful Split (n=82), n (%) |
|---|---|
| Evidence of a split | 80 (97.6) |
| Split visualization | 73 (91.3) |
| Increase in transvalvular AR | 68 (85.0) |
| Table 9: Per-Leaflet Splitting Success | |
|---|---|
| ---------------------------------------- | -- |
There were 3 cases of coronary artery ostia obstruction (5%) within 30 days of the procedure, as well as 1 additional case of coronary artery intervention without evidence of coronary ostia obstruction.
Table 10: Coronary Artery Ostia Obstruction or Intervention within 30 Days Post-procedure
| Secondary Effectiveness Endpoints | Total Subjects (n=60),n (%) |
|---|---|
| Freedom from Coronary Artery Ostia Obstruction related tothe intervened leaflet | 57 (95.0) |
| Freedom from Coronary Artery Intervention related to theintervened leaflet | 56 (93.3) |
The Secondary Safety endpoints were assessed through 30 days post-index procedure according to VARC-3 and per CEC adjudication, as presented in Table 11 below:
| Secondary Safety Endpoints | Total Subjects (n=60),n (%) |
|---|---|
| All-cause mortality | 2 (3.3) |
| Cardiovascular mortality | 0 (0.0) |
| Non-cardiovascular mortality | 2 (3.3) |
| All-cause stroke | 1 (1.7) |
| Coronary obstruction | 3 (5.0) |
| Myocardial infarction with new evidence of coronaryartery obstruction requiring intervention | 2 (3.3) |
| Major vascular complications | 0 (0.0) |
Table 11. Safety Endnoints Through 30 Days Post-procedure
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| Secondary Safety Endpoints | Total Subjects (n=60),n (%) |
|---|---|
| Cardiac tamponade | 1 (1.7) |
| Acute kidney injury (AKI) | 2 (3.3) |
| Access-related type 3-4 bleeding | 0 (0.0) |
The Technical Success endpoints evaluated at exit from procedure room following the ShortCut procedure on a per-subject basis are summarized in Table 12 below. One subject had cardiac tamponade caused by the guidewire position who underwent open-heart valve replacement, accounting for both reported technical failure reasons.
| Technical Success Endpoints | Total Subjects(n=60), n (%) |
|---|---|
| Overall Technical Success | 59 (98.3) |
| Successful access, delivery, or retrieval of the ShortCut™ device | 60 (100.0) |
| Freedom from ShortCut device and/or procedure related mortality | 60 (100.0) |
| Freedom from ShortCut device and/or procedure related: | 59 (98.3) |
| - surgery or intervention | 59 (98.3) |
| - major vascular or access-related complications | 60 (100.0) |
| - cardiac structural complication | 59 (98.3) |
Table 12: Technical Success Endpoints following ShortCut Procedure
Adverse Events
The total number of events adjudicated by the CEC for treated subjects from the point of index procedure through the study was 91 events. Following CEC adjudication, the reviewed events were classified as 40 serious adverse events (SAE) and 51 adverse events (AE), as shown in Table 13 below.
| Table 13: Summary of Adverse Events and Serious Adverse Events Through 90- | |
|---|---|
| Day Study Duration |
| Type of Event | Adjudicated eventsn (%) | Events with relatednessto the ShortCut device orprocedure, n (%) |
|---|---|---|
| Total # as adjudicated * | 91 | 25 |
| SAE1 | 40 (44.0) | 9 (36.0) |
| AE1 | 51 (56.0)** | 16 (64.0) |
1 Percentages are based on the total number of events per column.
- Additional 23 AEs, determined by site as non-serious and not related to the ShortCut device or the overall ViV, were not adjudicated by the CEC, per protocol.
** 3 out of the 51 AEs were adjudicated as 'no event'.
Three total deaths occurred in the study cohort: two deaths prior to 30 days (see Table 11) and one additional death within 90 days. The deaths were determined to be noncardiovascular causes and were not related to ShortCut device or procedure, as shown in Table 14 below.
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| Adverse Event | Not Related toShortCut* | Related toShortCut* | Total Subjects(n=60),n (%) |
|---|---|---|---|
| All-cause mortality | 3 (5.0) | 0 (0.0) | 3 (5.0) |
| Cardiovascular mortality | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Non-cardiovascular mortality | 3 (5.0) | 0 (0.0) | 3 (5.0) |
| All-cause stroke | 0 (0.0) | 1 (1.7) | 1 (1.7) |
| Myocardial infarction with newevidence of coronary arteryobstruction requiring intervention | 2 (3.3) | 0 (0.0) | 2 (3.3) |
Table 14: Critical Adverse Events Through 90-Dav Study Duration by Relation to ShortCut Device or Procedure
- Assesses "Not Related" or "Related" that includes Possibly / Definitely Related AEs to either ShortCut Device or Procedure, per CEC adjudication.
Conclusions
Key findings of the ShortCut Study include:
- . The primary effectiveness endpoint of per-subject leaflet splitting success using the ShortCut device was achieved for the first intervened leaflet in 100% subjects, which was significantly higher (p < 0.001) than the study performance goal of 75%.
- . There was no mortality (0.0%) and one stroke (1.7%) within 7 days post-procedure or at discharge, which are comparable to death and stroke rates expected for patients undergoing ViV TAVR. The stroke event occurred 4 days post-procedure and determined to be possibly related to the ShortCut procedure.
- Coronary obstruction was reported in three subjects (5%); however, these events were . adjudicated as not related to the ShortCut device or procedure, and all were successfully managed via coronary intervention post-TAVR. An observed occurrence of 5% coronary obstruction is not unreasonable in the study patient population of high risk for coronary obstruction receiving ViV.
- . Technical success was achieved in 98.3% of the subjects.
The ShortCut Pivotal Study demonstrated that splitting failed bioprosthetic aortic valve leaflets using ShortCut is safe and effective in subjects at high risk for coronary artery obstruction undergoing ViV TAVR.
OUS Compassionate Use Cases
Scope
The eight (8) initial clinical cases performed with the ShortCut device during December 2020 - December 2021 and with follow-up data up to 18 months.
Study Design
All patients consented to the treatment under Compassionate Use provision. The institutional ethics committees and relevant regulatory agencies reviewed and approved each patient per the local regulations.
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Eight patients (n=8) were treated with the ShortCut by two physicians at 2 sites in Israel and in Germany. Patients were followed according to the hospitals' standard-of-care protocols.
Eligibility Criteria Summary
All patients were at risk of left coronary obstruction, and three patients were at additional risk for right coronary obstruction. Patients were required to be >18 years old and recommended for an approved ViV TAVR indication. Patients were not suitable in cases of severe or moderate thickened and calcified aortic valve leaflets at the intended laceration site, or anatomy that would not allow safe placement of an embolic protection device. In addition, patients who had a cerebral vascular accident or transient ischemic attack in the 12 months prior to procedure were not approved.
Demographics
Subject demographics, baseline characteristics, and risk factors for coronary artery obstruction are presented in the Table 15, below:
| n=8n or mean $\pm$ SD | |
|---|---|
| Age, yr | $77.0 \pm 9.6$ |
| Male | 2 |
| Female | 6 |
| STS score, % | $6.6 \pm 4.5$ |
| NYHA Class | |
| I-II | 0 |
| III-IV | 8 |
| Left ventricular ejection fraction, % | $56 \pm 9$ |
| Failed Valve Type | |
| SAVR | 6 |
| TAVR | 2 |
| Failed Valve Disease | |
| Isolated aortic stenosis (AS) | 4 |
| Isolated aortic regurgitation (AR) | 1 |
| Mixed (AS and AR) | 3 |
| Risk factors for coronary obstruction (8 patients, 11 leaflets) | |
| Coronary height, mm | $7.7 \pm 3.8$ |
| Sinus of Valsalva width, mm | $27.2 \pm 5.6$ |
| Sinus of Valsalva height, mm | $15.6 \pm 7.0$ |
| VTC distance, mm | $2.9 \pm 0.7$ |
| VTS distance, mm | $2.9 \pm 0.8$ |
Table 15: Compassionate Use Patient Demographics, Baseline Characteristics, and Risk Factors for Coronary Obstruction
Clinical Results
Procedural Outcomes
The procedural outcomes of the compassion use cases are shown below.
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| Procedure Detail | n=8n or mean ± SD |
|---|---|
| Intervened Leaflet | |
| Left | 5 |
| Right | 0 |
| Left and right | 3 |
| Total procedure time* (min) | 141.1 ± 46.9 |
| ShortCutTM procedure time* (min) | 18.0 ± 5.9 |
| ViV TAVR procedure time* (min) | 11.0 ± 10.5 |
| Procedure Outcome – post TAVR | |
| Coronary obstruction | 0 |
| AR ≥ moderate AR | 0 |
| Mean gradient (mmHg) | 9.5 ± 3.7 |
Table 16: Summary of Procedural Outcomes & Results
Safety Outcomes
No serious adverse events (SAE) related to the ShortCut device or ShortCut procedure were reported for the 8 compassionate cases. All patients were discharged from the hospital in good condition and without coronary obstruction, stroke, or major complications. With follow-up between 15 to 18 months post-procedure, there were no reports of stroke or coronary obstruction.
Conclusions
The results from the first human experience in 8 reported compassionate use cases demonstrated that the ShortCut device and procedure is feasible to safely split one or two aortic bioprosthetic valve leaflets.
Pediatric Extrapolation
In this De Novo request, existing clinical data were not leveraged to support the use of the device in a pediatric patient population.
LABELING
The ShortCut labeling consists of Instructions for Use and packaging labels. The labeling satisfies the requirements of 21 CFR 801.109.
The Instructions for Use includes:
- . Indications for Use;
- Description of the device; .
- Patient population the device has been demonstrated to be effective; .
- . Contraindications, warnings, & precautions;
- . Recommended training for safe use of the device;
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- . Instructions for the safe use of the device, including the maximum number of cutting actions and deployments for each device and target site;
- . Detailed summary of the clinical data collected in support of the device;
- Prescription statement; .
- Shelf life. .
Please see the Limitations section above for important warnings and precautions presented in the device labeling.
RISKS TO HEALTH
The table below identifies the risks to health that may be associated with heart valve leaflet splitting devices and the measures necessary to mitigate these risks.
| Risks to Health | Mitigation Measures |
|---|---|
| Infection | Sterilization validationShelf life testingLabeling |
| Adverse tissue reaction | Biocompatibility evaluation |
| Incomplete valve tissue splitting | Clinical performance testingIn vivo performance testingNon-clinical performance testingElectrical safety testingElectromagnetic compatibility testingShelf life testingLabeling |
| Tissue injury: non-targeted tissue, vascularinjury, dissection | Clinical performance testingIn vivo performance testingNon-clinical performance testingElectrical safety testingElectromagnetic compatibility testingLabeling |
| Embolic events: thromboembolic, e.g. ; stroke;bioprosthetic embolism; device embolism | Clinical performance testingIn vivo performance testingBiocompatibility evaluationNon-clinical performance testingShelf life testingLabeling |
| Blood flow obstruction | Clinical performance testingIn vivo performance testing |
| Interaction with cardiac conduction systemleading to postoperative arrythmias, includingatrial fibrillation and heart block | Clinical performance testingIn vivo performance testingLabeling |
Table 17: Identified Risks to Health and Mitigation Measures
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SPECIAL CONTROLS
In combination with the general controls of the FD&C Act, the percutaneous catheter for cutting or splitting heart valve leaflets concomitant to transcatheter valve procedures is subject to the following special controls:
- (1) Clinical performance testing of the device must demonstrate that the device performs as intended under anticipated conditions of use. Testing must evaluate:
- (i) The ability to safely deliver and remove the device;
- (ii) Performance in cutting or splitting of the target valve leaflets;
- Compatibility with concomitant transcatheter valve procedures; and (iii)
- All adverse events observed, including device malfunctions, tissue or vascular injury, (iv) hemodynamic abnormalities, embolic events, cerebrovascular adverse events, and unanticipated surgical interventions.
- (2) In vivo performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be assessed:
- (i) Delivery, use, and retrieval of the device:
- (ii) Cutting or splitting of target leaflet(s); and
- Gross pathology and histopathology assessing leaflet splitting, soft tissue damage, (iii) and downstream embolization.
- (3) Non-clinical performance testing data must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
- (i) Simulated use testing in a clinically relevant bench anatomic model to assess feasibility of device operation under worst-case clinical conditions, including device delivery, use, retrieval, and compatibility with accessory devices via transcatheter approach:
- (ii) Consistency and reliability of cutting action;
- Ability to advance and position the device to reach the target site: (iii)
- (iv) Mechanical integrity testing (e.g., bond/joint strength, torsional strength) of the device under anticipated loading conditions;
- Assessment of material-specific risks, such as corrosion if the device contains metal (v) components, or coating integrity and particulates if the device contains lubricious coatings: and
- Characterization and verification of critical dimensions. (vi)
- (4) Compatibility testing for devices that contain electrical components must include:
- Electrical safety and electromagnetic compatibility (EMC) testing: and (i)
- Software verification, validation, and hazard analysis for all devices that contain (ii) software.
- (5) All patient-contacting components of the device must be demonstrated to be biocompatible.
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- (6) Performance data must demonstrate the sterility of the device components intended to be provided sterile.
- (7) Performance data must support the shelf-life of the device by demonstrating continued sterility, package integrity, and device functionality over the labeled shelf life.
- (8) Labeling must include the following:
- The recommended training for safe use of the device; (i)
- Information on the patient population for which the device has been demonstrated to (ii) be effective;
- (iii) Identification of the maximum number of cutting actions and deployments for each device and for each target site; and
- (iv) A detailed summary of the clinical testing conducted; and
- (v) A shelf life.
BENEFIT-RISK DETERMINATION
The ShortCut device is indicated for use as a splitting device of bioprosthetic aortic valve leaflets to facilitate valve-in-valve procedures for patients at risk of coronary obstruction. In general, the risks of ShortCut are expected to be similar to those observed with transcatheter cardiac devices and procedures.
The probable risks of the device are based on nonclinical laboratory and/or animal studies, as well as data collected in a clinical study described above. There are known difficulties and risks associated with ShortCut that are inherent to transcatheter heart valve procedures, and which are outlined below:
- Aortic regurgitation .
- Cardiovascular injury including perforation or dissection of vessels, aorta, ventricles, . myocardium or valvular structures that may require intervention
- Conduction system disturbance or injury which may require a permanent pacemaker .
- . Cardiogenic shock
- Coronary ostium obstruction .
- . Embolization including air. calcific valve material or thrombus
- . Hematoma or hemorrhage requiring transfusion or intervention
- . Infection including septicemia and endocarditis, pneumonia
- . Myocardial infarction
- . Pain or bleeding at the access site
- . Pericardial tamponade
- Acute kidney injury .
- Stroke or transient ischemic attack .
- . Death
Clinical investigation of ShortCut for splitting bioprosthetic aortic valve leaflets to facilitate valve-in-valve procedures for patients at risk of coronary obstruction demonstrated 0% mortality
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through discharge or 7-day follow-up period. Three (3) deaths were reported occurring through the 90-day follow-up period which were determined non-cardiovascular related to the ShortCut device or procedure. There was one (1) disabling stroke reported, which was adjudicated as not related to the ShortCut device, possibly related to ShortCut procedure, and definitely related to the overall ViV procedure. Through the 90-dav follow-up, there were 114 adverse events reported in the study cohort (91 events adjudicated per protocol as 40 serious adverse events (SAE) and 51 adverse events (AE)). Overall, the adverse events reported in the clinical study are anticipated events for transcatheter cardiac procedures. As the ShortCut procedure is performed concomitant with TAVR, isolating events and risks specific to ShortCut is confounded; however, the frequency of adverse events reported in the clinical study, including death and stroke, are at rates that are expected and reasonable for a patient population undergoing ViV TAVR. Therefore, ShortCut does not add new or different clinical risks, nor does it exacerbate the risks inherent with transcatheter cardiac procedures.
The probable benefits of the device are also based on nonclinical laboratory and/or animal studies, as well as data collected in a clinical study described above. Probable benefits of the device are based on demonstration that ShortCut performs reliably and effectively in splitting the targeted aortic leaflet(s) on a failed bioprosthetic valve in preparation for ViV TAVR. Nonclinical and animal studies demonstrated the device met all design specifications and achieved repeatable leaflet cutting. In the clinical study, the primary effectiveness endpoint of per-subject leaflet splitting success was achieved in all subjects (100%) with only one technical failure (98.3% technical success). The clinical study was not statistically powered to demonstrate subsequent clinical benefit of leaflet splitting; however, it can be reasonably expected that successful leaflet splitting will provide the following benefits:
- · Provide ViV TAVR as a treatment option for patients at high risk of coronary obstruction who may otherwise be denied treatment or undergo risky surgical procedures:
- . Reduce occurrence of coronary obstruction compared to the expected rates in the high-risk target population.
All subjects enrolled and treated in the clinical study were determined to be at high risk of coronary artery ostia obstruction in the context of ViV TAVR and the clinical outcomes were favorable with use of ShortCut to facilitate ViV TAVR. Partial or complete coronary artery obstruction was noted in 3 subjects (5%) despite use of ShortCut. Of these subjects, no mortality or significant change in LV function occurred throughout study duration. Further, all three patients were successfully managed using standard percutaneous coronary intervention technique without surgical bailout. Overall, the reported 5% coronary obstruction and subject outcomes in the ShortCut Study compare favorably to reported rates of coronary artery ostia obstruction and related-mortality in patients at high-risk of coronary obstruction undergoing ViV TAVR without ShortCut assistance.
Additional factors to be considered in determining probable risks and benefits for the ShortCut include: limitations of the ShortCut Pivotal Study; that the ShortCut is intended to be used concomitant with TAVR procedure; and that the treatment principle of splitting aortic valve leaflets to facilitate a TAVR procedure has been validated in clinical practice. Limitations of the submitted clinical study are that the study was designed to analyze sixty (60) subjects with
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primary endpoints assessed no later than 7 days post-index procedure. The study cohort had low racial and ethnic diversity. The study was powered for an effectiveness endpoint of functional performance: vet, the study was not designed to statistically determine clinical effectiveness or powered to assess the primary safety endpoint. While identifying adverse events or risks specific to ShortCut is confounded by concomitant TAVR, it is not expected that use of ShortCut will increase the risks of the TAVR procedure. Moreover, the treatment principle of ShortCut is similar to that validated in the BASILICA (Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction during TAVR) procedure and study, which also splits aortic valve leaflets but using a different cutting modality. Therefore, clinical outcomes with BASILICA may be leveraged to address certain limitations of the ShortCut Study, as listed above.
Overall. the known or probable risks are considered not to be meaningfully different than risks associated with other transcatheter cardiac procedures. When considering the totality of evidence, there is a reasonable expectation that ShortCut will provide an effective treatment option for patients at risk of coronary obstruction when undergoing a valve-in-valve procedure.
Patient Perspectives
This submission did not include specific information on patient perspectives for this device.
Benefit/Risk Conclusion
In conclusion, given the available information, the probable benefits outweigh the probable risks of ShortCut for the following indication statement:
The ShortCut is indicated for use as a splitting device of bioprosthetic aortic valve leaflets to facilitate valve procedures for patients at risk of coronary obstruction.
The device provides benefits and the risks can be mitigated by the use of general controls and the identified special controls.
CONCLUSION
The De Novo request for ShortCut is granted and the device is classified as follows:
| Product Code: | SCZ |
|---|---|
| Device Type: | Percutaneous catheter for cutting or splitting heart valve leafletsconcomitant to transcatheter valve procedures |
| Regulation: | 21 CFR 870.1254 |
| Class: | II |
N/A