(256 days)
The Mi-CHORD System is indicated for the replacement of adult mitral chordae tendineae with the patient on cardiopulmonary bypass, with the heart either arrested or fibrillating, and the surgical field under direct visualization.
Direct visualization, in this context, requires that the surgeon is able to see the heart and target tissues in a bloodless field, with or without assistance from an operating telescope or videoscopy.
The Mi-CHORD™ System, shown in Figure 1, is a sterile, single use system, including the Mi-STITCH™ suturing device with its loaded LS-5™ expanded polytetrafluoro-ethylene (ePTFE) suture (Figure 2) and the Mi-KNOT™ device with its loaded Mi-KNOT™ titanium fastener (Figure 3).
The provided text describes a medical device (Mi-CHORD System) and its non-clinical and clinical performance data. However, it does not describe an AI/ML-based device, nor does it contain information about "acceptance criteria" in the context of an AI/ML study, or any "study that proves the device meets the acceptance criteria" in that context.
The document primarily focuses on:
- Device Description: The physical components and their functionality (Mi-STITCH and Mi-KNOT devices, ePTFE suture, titanium fastener).
- Nonclinical/Bench Studies: Biocompatibility, shelf life/sterility, and various engineering bench tests demonstrating mechanical performance, reliability, durability, and material properties. These are traditional engineering and material science tests for a physical medical device.
- Clinical Information: A single-center, single-cohort feasibility study conducted outside the United States (OUS) with 12 patients, focusing on operative times, echocardiographic outcomes, adverse events, and mortality in mitral valve repair.
- Regulatory Aspects: De Novo classification request, indications for use, risks to health, and special controls.
Since the prompt asks for information related to an AI/ML device's acceptance criteria and studies (e.g., sample size for test set, data provenance, expert ground truth, MRMC studies, standalone performance, training set details), the provided text does not contain the information requested in points 2-9 of your prompt. It describes the validation of a physical surgical device, not a classification algorithm or AI system.
Therefore, I cannot fulfill the request as presented, as the necessary information for an AI/ML device's acceptance criteria and proving study is absent from the provided text.
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DE NOVO CLASSIFICATION REQUEST FOR MI-CHORD SYSTEM
REGULATORY INFORMATION
FDA identifies this generic type of device as:
Artificial chordae tendineae surgical replacement system. An artificial chordae tendineae surgical replacement system is a standalone, prescription device consisting of nonabsorbable suture-based implant and suture placement device(s) that is used to replace mitral or tricuspid chordae tendineae in patients with atrioventricular valve insufficiency. The device includes clips or fasteners to secure the suture that are not embedded in the cardiac tissue. The system is used via surgical approach under direct visualization and not via transcatheter or percutaneous access.
NEW REGULATION NUMBER: 21 CFR 870.3490
CLASSIFICATION: Class II
PRODUCT CODE: SBK
BACKGROUND
DEVICE NAME: Mi-CHORD System
SUBMISSION NUMBER: DEN230069
DATE DE NOVO RECEIVED: September 29, 2023
SPONSOR INFORMATION: LSI Solutions, Inc. 7796 Victor-Mendon Rd. Victor, NY 14564
INDICATIONS FOR USE
The Mi-CHORD System is indicated for the replacement of adult mitral chordae tendineae with the patient on cardiopulmonary bypass, with the heart either arrested or fibrillating, and the surgical field under direct visualization.
Direct visualization, in this context, requires that the surgeon is able to see the heart and target tissues in a bloodless field, with or without assistance from an operating telescope or videoscopy.
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LIMITATIONS
The sale, distribution, and use of the Mi-CHORD System are restricted to prescription use in accordance with 21 CFR 801.109.
PLEASE REFER TO THE LABELING FOR A COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
DEVICE DESCRIPTION
The Mi-CHORD™ System, shown in Figure 1, is a sterile, single use system, including the Mi-STITCH™ suturing device with its loaded LS-5™ expanded polytetrafluoro-ethylene (ePTFE) suture (Figure 2) and the Mi-KNOT™ device with its loaded Mi-KNOT™ titanium fastener (Figure 3).
Image /page/1/Picture/5 description: The image shows the Mi-CHORD™ SYSTEM, which includes the Mi-STITCH DEVICE and the Mi-KNOT DEVICE. The Mi-STITCH DEVICE has a white handle with a purple trigger and a long, thin metal shaft with a purple tip. The Mi-KNOT DEVICE also has a white handle with a purple trigger, but its metal shaft has a loop at the end.
Figure 1: Mi-CHORD™ System
The Mi-CHORD™ System includes one Mi-STITCH™ Device, shown in Figure 2, which is loaded with one LS-5" ePTFE suture. The lavender device tip (1) of this device angulates and rotates to enable accurate positioning of its integrated tissue jaw (2) for receiving tissue targeted for suture placement. Two curved needles (4) (shown partially advanced) emerge simultaneously from their protective compartments (not shown) to traverse the tissue jaw by
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rotating about a circular engraved needle axle indicator (5). An embossed jaw width indicator (3) is provided to depict the jaw location and width when the tissue jaw may be embedded in tissue. Two needle caps (7) for subsequently engaging each corresponding needle tip are attached to the ends of a single strand of LS-5" ePTFE suture (8). Each needle cap with its attached suture are held in specialized needle cap compartments (6), with alternating functions of suture pick-up or re-arming. An angulation indicator (9) depicting the direction and angulation of the device tip is embossed on the device tip located at the device tip hinge section where it intersects with the device shaft (10). The embossed arrow and word "IN" depict the direction the device tip moves when the white angulation knob (11) is turned clockwise; counterclockwise turning angles the tip in the direction opposite of the embossed arrow. The three embossed radial lines indicate the range of device tip angulation, which is approximately 30° in both directions. A lavender rotational knob (12) enables device tip rotation through six distinct positions. The rotational knob includes an indicator fin (13) with an integrated eyelet that stabilizes the suture tube (14) with its indwelling LS-5™ ePTFE suture. Note the suture loop near the suture's midsection emerging from the suture tube above the white handle (17). A yellow lever stop (16) is located behind the lavender lever to restrict inadvertent squeezing during device handling prior to use. Simultaneous needle advancement across the tissue jaw is achieved by a single complete squeeze of the lavender lever (15). Release of the lavender lever retracts both needles with their engaged needle caps and pulls the suture ends back through the targeted tissue in the tissue jaw. With the next squeeze of the lever, in addition to advancing the needles, needle caps and suture ends back into their corresponding needle cap compartments, an internal mechanism also automatically alternates the device to its rearming function. The release of the lavender lever rotates the needles back to their protective compartments on the opposite side of the tissue jaw, while holding the needle caps and their suture ends in their needle cap compartments ready for pick-up in the subsequent tissue bite. The next lavender lever squeeze begins the alternating cycle again by advancing the bare needles towards the rearmed needle caps and suture ends, plus automatically alternating to the rearming function.
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Image /page/3/Figure/0 description: This image is a diagram of a surgical device labeled with numbers 1-17. The diagram shows the device from multiple angles to highlight different features. The device has a long, thin shaft with a handle at one end and a tip at the other. The diagram labels parts such as the device tip, tissue jaw, jaw width indicator, curved needles, needle axle indicator, needle cap compartments, needle caps, LS-5 ePTFE suture, angulation indicator, device shaft, angulation knob, rotational knob, indicator fin, suture tube, lavender lever, lever stop, and white handle.
Figure 2: Mi-STITCH™ Device
The Mi-CHORD™ System also includes one Mi-KNOT™ Device, shown in Figure 3, which is loaded with a single Mi-KNOT™ fastener (1). Made from medical grade titanium, the Mi-KNOT™ fastener is a hollow sleeve with a rounded diamond-shaped base. A lavender target (2), (shown removed above) holds the loop shape of a wire snare (3). The wire snare passes through the Mi-KNOT™ fastener and is attached to a snare puller (4) knob. A suture slot (5) (not shown) in the device shaft (6), lies under the opening in the snare puller. The ends of LS-5" ePTFE suture are passed through the wire snare and subsequently threaded into the titanium fastener. The snare puller is pulled up or retracted along the device shaft until it snaps onto the puller retainer (7) feature of the lavender knob (8), which also has an integrated indicator fin (9). The suture slot and the indicator fin are located on the same side of the device shaft. The subsequently crimped fastener and remnant trimmed suture tails bend slightly in the direction away from or opposite from the suture slot and indicator fin. By rotating the lavender knob and the device's white handle (10) the surgeon can ergonomically orient the direction of the suture tails. A vellow lever stop (11) is located behind the lavender lever (12) to restrict inadvertent squeezing of the lavender lever during device handling before crimping. The lever stop is removed by pinching its sides together and pulling it out of the handle. By squeezing the lavender lever, the Mi-KNOT™ Device crimps the Mi-KNOT™ fastener to fasten together segments of suture and trim away excess suture.
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Image /page/4/Figure/0 description: This image shows a medical device with several labeled parts. The device has a white handle (10) and a lavender lever (12) near the bottom. A device shaft (6) extends from the handle, leading to a Mi-Knot fastener (1) and a lavender target (2) at the opposite end. Other labeled components include a wire snare (3), a snare puller (4), and a puller retainer (7).
Figure 3: Mi-KNOT™ Device
SUMMARY OF NONCLINICAL/BENCH STUDIES
Nonclinical studies conducted for the Mi-CHORD™ System are summarized below.
BIOCOMPATIBILITY/MATERIALS
| Components &Classification | The Mi-CHORD TM System is composed of four components.The Mi-STITCHTM Device and Mi-KNOTTM Device areexternal communicating devices with limited patient contact(≤24 hours). The LS-5TM ePTFE Suture and Mi-KNOTTMtitanium fastener are implanted devices in permanent contactwith circulating blood (> 30 days). Materials of theimplanted components are listed in Table 1. |
|---|---|
| -------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
| Table 1: Mi-CHORD™ Implant Component Materials | |||
|---|---|---|---|
| -- | ------------------------------------------------ | -- | -- |
| Name of Component | Material of Finished Component | Contact Duration |
|---|---|---|
| LS-5TM ePTFE Suture | expanded polytetrafluoro-ethylene(ePTFE) | Permanent patientcontact |
| Mi-KNOTTTM Fastener | Titanium (ASTM F67 Grade 1 or 2) | Permanent patientcontact |
| BiocompatibilityAssessment | A biological evaluation plan and assessment (BEP) wascompleted for the Mi-CHORD™ System according to theFDA Guidance for Industry, Use of International StandardISO 10993-1, "Biological evaluation of medical devices – |
|---|---|
| -------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
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| Part 1: Evaluation and testing within a risk managementprocess," September 4, 2020, and ISO 10993-1:2018,Biological evaluation of medical devices - Part 1:Evaluation and testing within a risk management process.Biocompatibility evaluation consisted of new testing andleveraging from prior 510(k) clearances (K100593,K163639, and K202551) for individual components whichshare similar materials and design features as the Mi-CHORD™ System components. |
|---|
| The evaluated endpoints summarized below demonstrate thatthe Mi-CHORD™ System is biocompatible. |
| Mi-STITCH TM Device;Mi-KNOTTM Device(Limited patient contact) | LS-5TM ePTFE Suture;Mi-KNOTTM Fastener(Permanent Implant) |
|---|---|
| • Cytotoxicity: MEM Elution Test, L929 Cell Line | • Cytotoxicity: MEM Elution Test, L929 Cell Line or MHLW Colony Formation Test on Extracts |
| • Sensitization: Guinea Pig Maximization Test | • Sensitization: Guinea Pig Maximization Test |
| • Irritation: Intracutaneous (Intradermal) Reactivity Test | • Irritation: Intracutaneous (Intradermal) Reactivity Test |
| • Material Mediated Pyrogenicity: Rabbit Pyrogen Test | • Material Mediated Pyrogenicity: Rabbit Pyrogen Test |
| • Acute Systemic Toxicity: Mouse Injection Test | • Acute Systemic Toxicity: USP Systemic Toxicity Study in Mice – Extract or Mouse Injection Test |
| • Subacute/Subchronic Toxicity | |
| • Chronic Toxicity | |
| • Implantation: Modified USP Muscle Implantation in Rabbits – 7 Day or 12 Week or 90 Day Subchronic Muscle Implantation (in rabbit) | |
| • Hemocompatibility: Partial Thromboplastin Time (PTT) | |
| • Hemocompatibility: Complement Activation C3a and SC5b-9 Assay | |
| • Hemocompatibility: Platelet and Leukocyte Counts | |
| • Hemocompatibility: ASTM Hemolysis – Direct Contact and Extract Method (GLP) |
Table 2: Biocompatibility Endpoints Evaluated
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| CHARTER DE PARTER PROFICE POST CONSULTION CONTROLLER• Carcinogenicity | |
|---|---|
SHELF LIFE/STERILITY
| Sterility | Sterility testing conducted in accordance with the FDAGuidance for Industry, Submission and Review of SterilityInformation in Premarket Notification (510(k)) Submissionsfor Devices Labeled as Sterile, January 21, 2016,demonstrates the Mi-CHORDTM System is provided sterile.The Mi-CHORD System was adopted into an existing,validated ethylene oxide (EtO) sterilization cycle (AAMITIR28:2009). The sterilization cycle was assured by usingthe validated over kill (or the half-cycle) sterilization methodqualified in accordance with ISO 11135:2014. Based on thevalidation results, a sterility assurance level (SAL) of at least10-6 was achieved. The EO and ECH residuals of the Mi-CHORD™ System components were shown to meet thelimits specified by ISO 10993-7:2008 following one routinefull cycle sterilization. |
|---|---|
| Packaging | The packaging configuration for the Mi-CHORD™ Systemsuccessfully met the packaging distribution testingqualifications, following 2X sterilization, simulateddistribution consistent with ASTM D4169-16, and climaticconditioning cycles per ASTM F2825-18. The results of thetesting demonstrate that the packaging design met thepredetermined requirements, specifications, and acceptancecriteria for packaging validation under typical distributionand climatic conditions, via the following testing:• Sterile barrier integrity via bubble leak testing inaccordance with ASTM F2096;• Seal integrity via dye testing, visual inspection inaccordance with ASTM F1929, ASTM F3039, andASTM F1886;• Seal integrity via peel strength test in accordancewith ASTM F1886 and ASTM F88/F88M;• Unit box integrity, labeling condition, product insertlegibility, and device security via visual inspection. |
| Shelf Life | The shelf-life of the Mi-CHORD™ System has beenestablished at 2 years based on real-time aging up to 2 years.Following 2X sterilization and real-time aging, the devicepackaging validation testing was repeated (except devicesecurement) and functional tests listed below under"Performance Testing - Bench" which were deemed to bepotentially affected by device aging were repeated. All testspassed. |
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PERFORMANCE TESTING - BENCH
The Mi-CHORD ™ System was subjected to a series of bench tests to assess its functional performance. These tests were performed on final sterilized product, as well as subjected to simulated distribution consistent with ASTM D4169-16 and climatic conditioning cycles per ASTM F2825-18 when required. The engineering bench testing summarized in Table 3 below demonstrate acceptable performance of the device for its intended use.
| Test | Test Purpose and Description |
|---|---|
| LS-5TM ePTFE Suture- Diameter andMaterial | The LS-5TM suture met specifications of (b)(4)diameter according to USP 42-NF37:2019 <861> Sutures –Diameter, suture is natural ePTFE, and material ismonofilament nonabsorbable ePTFE. |
| LS-5TM ePTFE Suture- Tensile KnotStrength | Testing demonstrated that the LS-5TM suture exceedsperformance requirements of non-absorbable surgical suturetensile knot strength as indicated in USP 42-NF37:2019<881> Sutures – Tensile Strength. |
| LS-5TM ePTFE Suture- Needle CapAttachment Strength | Testing demonstrated that the LS-5TM suture meetsperformance requirements of non-absorbable surgical suturefor suture/needle (needle cap) pull-off force as indicated inUSP 42-NF37:2019 <871> Sutures – Needle Attachment. |
| Mi-STITCHTMOrientation –Performance | Testing demonstrated that the Mi-STITCHTM device reliablyallows for suture placement at different shaft orientations viadevice shaft rotation, by ensuring that the device functionsequivalently at all the device's rotational detent positions. |
| Mi-STITCHTMReliability – ImplantDeployment | Testing demonstrated that the Mi-STITCHTM device reliablyplaces a stitch when the device lever is squeezed andreleased by ensuring 1) a squeeze of the Mi-STITCHTM leverwill actuate its dual curved needles simultaneously to drivethrough tissue, picking up a needle cap on each needle and 2)a release of the lever will pull the needles, needle caps, andsuture back through the tissue. |
| Mi-STITCHTMReliability – MultipleDeployment | Testing demonstrated that the Mi-STITCHTM device reliablypicks up and resets the same set of needle caps multipletimes by ensuring when the needle caps are on the needles,squeezing the lever again will cause the reset latch within theMi-STITCHTM device to remove the needle caps from theneedles and reset them into their corresponding needle capcompartments. |
| Mi-KNOTTMOrientation –Performance | Testing demonstrated that the Mi-KNOTTM device reliablyallows for titanium fastener orientation via device shaftrotation. |
| Mi-KNOTTMReliability – Prior toCrimping | Testing demonstrated that the Mi-KNOTTM device reliably retains the uncrimped titanium fastener prior to crimping, without the fastener dislodging from the tip. |
| Mi-KNOTTM Usability – Suture Loading | Testing demonstrated that LS-5TM ePFTE suture is reliably able to be loaded through the loaded titanium fastener in the distal end of a Mi-KNOTTM device. |
| Mi-KNOTTMReliability – FastenerCrimp | Testing demonstrated that a user of the Mi-KNOTTM device is reliably able to crimp a titanium fastener with one hand. |
| Mi-KNOTTMReliability – FastenerRelease | Testing demonstrated that the Mi-KNOTTM device reliably releases from a crimped fastener. |
| Mi-KNOTTMReliability – SutureCutting | Testing demonstrated that the Mi-KNOTTM device reliably trims the ePFTE suture tails and does not leave excess suture length. |
| LS-5TM ePTFE SutureDynamic Creep Test | Dynamic Creep Testing of the ePTFE suture was performed to assess the total elongation of LS-5TM ePTFE Suture under supra-physiologic loading. Acceptance criteria for this testing was: After a minimum of 1000 test hours, the 95th-percentile with 95% Confidence upper bound of LS-5TM Creep performance will be less than or equal to the 95th-percentile with 95% Confidence upper bound of comparator product performance indicated for chordae replacement. |
| Mi-KNOTTM Fastener – Holding Strength | Testing demonstrated that the crimped Mi-KNOTTM titanium fastener reliably secures two strands of LS-5TM ePTFE suture with a designated minimum pull apart force. |
| Mi-KNOTTM Fastener – Post-crimp Inspection | Testing demonstrated that the crimped Mi-KNOTTM titanium fasteners have no sharp edges, are free of burrs, and are less than a pre-determined size specification to prevent patient tissue or native chordae abrasion in situ . |
| Mi-STITCHTMVerification &Validation Testing | Testing demonstrated that the Mi-STITCHTM device met all design specifications, including dimensional specifications, interaction with pre-loaded LS-5TM ePTFE suture, and mechanical requirements for usability and function under anticipated use conditions. |
| Mi-KNOTTMVerification &Validation Testing | Testing demonstrated that the Mi-KNOTTM device met all design specifications, including dimensional specifications, interaction with pre-loaded Mi-KNOTTM Fasteners, compatibility with LS-5TM ePTFE suture, and mechanical requirements for usability and function under anticipated use conditions. |
| Fastener-SutureImplant – TissueSeparation Force | Testing demonstrated that the replacement chord formed from LS-5TM ePTFE suture (placed by a Mi-STITCHTM device) and a crimped Mi-KNOTTM titanium fastener (placed by a Mi-KNOTTM device) will not pull through anchoring tissue at forces less than a physiologically relevant minimum |
| mitral chordae force. | |
| Fastener-SutureInterface (FSI)Accelerated Life Test | Fatigue of the replacement chord was evaluated in anaccelerated life test. The testing validated the FSI portion ofthe replacement chord structure formed from LS-5TM ePTFEsuture secured by a Mi-KNOTTTM titanium fastener for use inthe replacement of mitral chordae tendineae under simulatingphysiological cyclic loading conditions. |
| Fastener-SutureInterface (FSI)Durability | Durability of the FSI was evaluated with a 600 million cycletest where LS-5TM ePFTE suture test specimens secured withcrimped Mi-KNOTTTM titanium fasteners were cycled underclinically worst-case loading conditions for the duration ofthe test. The FSI samples were evaluated for suture fray ordamage, Mi-KNOTTTM Fastener integrity via pull-apart forceafter 600 million cycles, and suture slippage or pull-through.All test specimens passed acceptance criteria. |
| Mi-KNOTTTM FastenerMRI Compatibility | Applicable testing demonstrates MRI compatibility of theMi-KNOTTTM titanium fastener. Test results show the Mi-KNOTTTM fastener, will not present an additional risk orhazard to a patient in a MR field of 3-Tesla or less and underthe MRI-related heating conditions. |
| Mi-KNOTTTM CorrosionResistance | Corrosion resistance of the implanted Mi-KNOTTTM titaniumfastener was assessed. Risk of corrosion was mitigated byleveraging testing and evidence from prior 510(k) clearances(K100593 and K202551) for titanium fasteners with identicalmaterials and similar design as the Mi-KNOTTTM Fastener. |
Table 3: Engineering Bench Testing Summary
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PERFORMANCE TESTING – USABILITY &/OR ANIMAL
| Simulated Use | Simulated use testing demonstrated the feasibility of using thedevice under worst-case clinical conditions. In testing,cardiothoracic surgeons were trained in the use of the systemand completed a summative test to validate all criticalprocedural tasks (adjusting and positioning Mi-STITCHTMdevice tip over leaflet tissue, adjusting and positioning Mi-STITCHTM device tip over papillary muscle tissue, orientingthe Mi-KNOTTM indicator fin and suture slot, Squeezing andholding the Mi-KNOTTM lever), as well as other non-criticalprocedural tasks. The usability testing models simulatedmitral valve anatomy and indicated surgical accessapproaches and was performed under direct visualization withor without assistance by videoscopic endoscope. Usabilitytesting demonstrated the feasibility of the Mi-CHORDTMSystem when operated by the intended users according to theIndication for Use under clinically-representative conditions. |
|---|---|
| --------------- | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
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SUMMARY OF CLINICAL INFORMATION
Overview
The Mi-CHORD™ System was supported by one outside the United States (OUS) singlecenter, single-cohort clinical trial to assess the feasibility of the Mi-CHORD™ System for mitral chordal replacement.
Objective:
To evaluate the Mi-CHORD™ System (Mi-STITCH™ and Mi-KNOTTM devices) for mitral valve repair in terms of operative times, echocardiographic outcomes, adverse events, and mortality in a single-center clinical safety and feasibility study. The study was initiated on August 3, 2021, and 1-year follow-up was completed on January 23, 2023.
Study Design:
Clinical. single-center safety and feasibility pilot trial. Prospective 12 patient cohort study. with 1-year postoperative follow-up.
Eligibility Criteria Summary:
All patients with severe primary mitral regurgitation with an indication for mitral valve repair according to the current guidelines with or without concomitant procedures were eligible for inclusion after a review of inclusion and exclusion criteria. A left ventricular function of more than 35%, a life expectancy of more than one year, a surgical risk of less than 8% (EuroScore II), a signed informed consent, and the willingness to perform the planned follow-up were the essential inclusion criteria. Patients with previous heart surgery, with a heavily calcified mitral valve annulus, with severe mitral valve stenosis, active endocarditis or myocarditis, as well as patients under 18 years of age, pregnant women, patients undergoing emergency surgery or patients who did not consent to the study had to be excluded from the study.
Primary Safety Endpoints:
The primary safety endpoint is 30-day mortality.
Primary Effectiveness Endpoint:
The primary efficacy endpoint is implantation time (defined as the period from start of valve assessment until the completion of the repair; i.e., initiation of left atrial closure).
Secondary Endpoints:
The secondary safety endpoints are:
- . Mortality at 6 and 12 months after surgery; and
- Number of serious adverse events (SAE) at 1, 6 and 12 months. .
The secondary efficacy endpoints are:
- Procedural times (surgical time, aortic cross-clamp time, cardiopulmonary . bypass time, valve repair time (from initial suturing to final knot securement);
- . Placement of ePTFE sutures: and
- Echocardiographic evaluation of mitral regurgitation at 6 months follow-up. .
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Statistical Methods:
Descriptive statistical methods were used. Continuous variables are presented as mean ± standard deviation; skewed data as median and interquartile range [25th & 75th percentile].
Demographics:
A summary of the preoperative characteristics of the 12 enrolled subjects is provided below. Severe mitral regurgitation without mitral stenosis was present in all patients - classified as a Carpentier Type II valve pathology with excessive leaflet motion. Seven patients (58%) presented with isolated P2 prolapse, while three patients (25%) presented with prolapse of the P2 and the P3 segment, one patient (8%) showed isolated P1 prolapse, and one patient. (8%) showed prolapse of the P1 and P2 segment. Ruptured chordae corresponding to the prolapsing segments were observed in 9 patients (75%).
| Variables | Data (n=12) |
|---|---|
| Age (years) | 66±12 |
| Sex (male) | 6 (50%) |
| BMI (kg/m²) | 26.9±4.7 |
| EuroSCORE II (%) | 1.36% [0.71, 4.05] |
| Preoperative Creatinine (mg/dl) | 0.94±0.2 |
| NT-proBNP (pg/ml) | 1249 [221, 2172] |
| NYHA | |
| I | 3 (25%) |
| II | 5 (41.7%) |
| III | 4 (33.3%) |
| IV | 0 |
| Comorbidities | |
| Arterial Hypertonus | 7 (58.3%) |
| Diabetes | 1 (8.3%) |
| Smoking History | 6 (50%) |
| Peripheral Vascular Disease | 1 (8.3%) |
| AFIB History | 5 (41.7%) |
| LVEF (%) | 62±8 |
| Preoperative Tricuspid regurgitation >3 | 2 (16.7%) |
Table 4. Clinical Subiects Demographics
BMI= Body Mass Index, proBNP= b-type natriuretic peptide, NYHA= New York Heart Association, LVEF= Left Ventricular Ejection Fraction
Accountability:
The study was performed in compliance with the Helsinki Declaration after receiving a positive ethical vote from the local ethics committee of the Medical University of Vienna. Informed consent was obtained at least one-day before surgery in all patients. Data quality assurance was ensured by monitoring visits following GCP and the ISO 14155 standards.
All patients screened were enrolled into the study and completed follow up as planned. There was no subject discontinuation.
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Results
Procedural:
All patients underwent mitral valve repair (MVr) with the study device system by one of two board-certified cardiac surgeons. One (n=3; 25%) or two (n=9; 75%) permanent ePTFE sutures for chordal replacement were implanted with the study device system; no other chordal replacements were performed in study patients. There was no distinguishable difference in the mean time to place the first ePTFE suture between open and minimally invasive cases (04:31 ± 02:48 minutes versus 05:44 ± 03:25 minutes) using the Mi-CHORD System. During the procedures, 27.6% of the total sutures implanted by the Mi-CHORD System were removed and replaced using another Mi-CHORD System to achieve better placement. Additional procedural results are shown below in Table 5.
| Procedural Details | Values |
|---|---|
| Mini-Thoracotomy | 33.3% (n=4) |
| Concomitant Procedure | 58.3% (n=7) |
| Duration Surgery (min) | $247\pm67$ |
| CBP (min) | $128\pm48$ |
| ACC (min) | $92\pm38$ |
| Valve Repair (min) | $11\pm7$ |
| Number of Implanted Chords | 2 [1,2] |
Table 5: Mi-CHORD™ Procedure Results
A retrospective comparison to patients treated with conventional suture chordae replacement from the same single-center database was reported (n=39 comparator patients, from January 2009 to December 2021). For patients in the reference cohort, the average duration of surgery, cardiopulmonary bypass, and aortic cross-clamp times were 286+71, 175±61, and 117±39 minutes, compared to the times reported when using Mi-CHORD System (247±67, 128±48, and 92±38 minutes, respectively). Therefore, procedure times were nominally reduced with Mi-CHORD System compared to conventional methods; however, the times were not statistically analyzed.
There were no device failures. Final placement of ePTFE sutures was satisfactory in all patients. The median duration of stay at the intensive care unit was 1 day.
Safety:
There were no deaths at 30 days after the procedure (0% mortality). All subjects survived through 12-month follow-up. The mitral valve reoperation rate was 0%.
Effectiveness:
All patients (n=12) underwent echocardiography measurements preoperatively and at discharge, as well as 1-month, 6-month, and 12-month follow-up time points. Echocardiographic evaluation at discharge (n=12) revealed no residual MR in 11 patients (91.7%) and mild regurgitation in one patient (8.3%). At 6-month follow-up, eleven
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patients (91.7%) presented with no residual MR. and one patient (8.3%) presented with trace MR. At 1 year, no MR was present in 7 (58.3%) patients, with trace in 2 patients (16.7%), mild in 2 patients (16.7%), and moderate in 1 patient (8.3%). The patient with moderate MR underwent transesophageal echocardiography, which revealed a cleft reopening in the posterior mitral leaflet and the implanted ePTFE suture with titanium fastener still in position; therefore, this patient's later-onset moderate MR is unlikely to be device-related. When compared to the reference cohort of patients treated with conventional suture chordae replacement, 28.6% of evaluable comparator patients (n=20) had recurrent moderate or greater MR at 1 year versus 8.3% of patients in the Mi-CHORD System treatment group.
Additional echocardiographic results are summarized in Table 6 below.
| Table 6: Echocardiographic Results | |||||
|---|---|---|---|---|---|
| EchocardiographicMeasurements | Preoperative | Discharge | 1-monthFollow-up | 6-monthFollow-up | 12-monthFollow-up |
| LV ejection fraction (%) | $60\pm7$ | $54\pm7^c$ | $62\pm6$ | $61\pm7$ | $62\pm5$ |
| LA diameter (mm) | $48\pm3^a$ | $53\pm6^d$ | $50\pm5^g$ | $47\pm6$ | $48\pm5$ |
| LVEDD (mm) | $49\pm5^b$ | $46\pm6^e$ | $44\pm5^h$ | $45\pm4$ | $46\pm6$ |
| MV mean pressuregradient (mmHg) | - | $3.2\pm1.2^f$ | $3.2\pm1.3$ | $3.1\pm1.2$ | $2.9\pm1.4$ |
| MR | |||||
| 0 (None) | 0 | 11 (92%) | 8 (67%) | 11 (92%) | 7 (58%) |
| ≤ 1 (Trace) | 0 | 0 | 2 (17%) | 1 (8%) | 2 (8%) |
| ≤ 2 (Mild) | 0 | 1 (8%) | 2 (17%) | 0 | 2 (8%) |
| ≥ 3 (Moderate, Severe) | 12 (100%) | 0 | 0 | 0 | 1 (8.3%) |
| TR > 3 | 3 (25%) | 0 | 1 (8.3%) | 0 | 0 |
itional echocardiographic results are summarized in Table 6 below.
Adverse Events:
Over the 12-month follow-up, there were 49 adverse events (AE) reported in 12 patients and 6 serious adverse events (SAE) reported in 6 patients. Postoperative atrial fibrillation or flutter was present in 9 (75%) patients, with two requiring electrical cardioversion. None of the AEs or SAEs were judged to be device-related by the principal investigator.
Conclusions
In the presented OUS single-center, single-cohort clinical trial to assess the feasibility of the Mi-CHORD™ System for mitral chordal replacement, 12 patients underwent mitral valve repair using the Mi-CHORDTM System.
Results demonstrated that the Mi-CHORD™ System can be used successfully through median sternotomy and minimally invasive access as a standalone procedure or with concomitant procedures. The number of suture-fastener implants may be selected by the surgeon per patient anatomy (1 or 2 replacement chordae were implanted) and procedure times are reasonable. Satisfactory repair was obtained in all patients without any devicerelated AEs or SAEs. All subjects survived through 1-year, with 100% of patients at 6 months and 92% of patients at 12 months showing mild or lower MR, suggesting durable mitral valve repair using the Mi-CHORDTM System.
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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 Mi-CHORD™ System labeling consists of Instructions for Use, Patient Implant Card, and packaging labels. The labeling satisfies the requirements of 21 CFR 801.109 for prescription devices.
The labeling addresses:
- . Patient population that the device is intended to treat;
- The recommended training for safe use of the device; .
- . Instruction describing how to perform the surgical chordae replacement procedure;
- . Requirement for surgical access and visualization of the tissues to be treated;
- Identification of the maximum number of deployments and actuations for each device(s): .
- . A shelf-life
The Instructions for Use also includes the Indications for Use; a description of the device; warnings, precautions, and contraindications for use of the Mi-CHORD™ System: MRI Safety information; and a prescription statement. PLEASE REFER TO THE LABELING FOR A COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
The Mi-CHORD™ System Patient Implant Card identifies the device, manufacture contact information, product number, UDI and device lot information, MRI Safety information, and space to enter the patient's name, the health institution name, and date of implant.
RISKS TO HEALTH
The table below identifies the risks to health that may be associated with an artificial chordae tendineae surgical replacement system and the measures necessary to mitigate these risks.
| Risks to Health | Mitigation Measures |
|---|---|
| Infection | Sterilization validationShelf life testingLabeling |
| Adverse tissue reaction | Biocompatibility evaluation |
| Failure to deploy suture and/or anchorcorrectly (i.e. partial deployment, tangle, ) | In vivo performance testingNon-clinical performance testingSimulated use testing |
Table 7: Identified Risks to Health and Mitigation Measures
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| Risks to Health | Mitigation Measures |
|---|---|
| un-crimped, unable to cut/leave excesssuture) | Shelf life testingLabeling |
| Abnormal leaflet motion and/orcoaptation, relapse of valvularregurgitation, loss of function | In vivo performance testingLabeling |
| Leaflet tearing; papillary muscle tearing | In vivo performance testingNon-clinical performance testingLabeling |
| Embolic events: thromboembolic; deviceemboli | In vivo performance testingBiocompatibility evaluationLabeling |
| Mechanical injury to coronary arteries orproximal tissues (e.g. native chordae) | In vivo performance testingNon-clinical performance testingSimulated use testingLabeling |
| Needle penetration through cardiacconduction system leading topostoperative arrythmias, including atrialfibrillation and heart block | In vivo performance testingSimulated use testingLabeling |
SPECIAL CONTROLS
In combination with the general controls of the FD&C Act, the artificial chordae tendineae surgical replacement system use is subject to the following special controls:
- (1) In vivo evaluation of the device must demonstrate that the device performs as intended under anticipated conditions of use. Testing must:
- Demonstrate that the device performs as intended for atrioventricular valve (i) repair:
- Demonstrate that the technology and techniques can be performed by the (ii) intended user population; and
- Evaluate all adverse events, including device malfunctions, tissue or vessel (iii) damage, unanticipated surgical interventions, and relapse of atrioventricular valve regurgitation.
- Simulated use testing must demonstrate the feasibility of device implantation and (2) translatability to clinical use under worst-case clinical conditions, considering indicated anatomies, surgical access, and visualization.
- Non-clinical performance testing data must demonstrate that the device performs as (3) intended under anticipated conditions of use. The following performance characteristics must be tested:
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- (i) Verification of diameters, tensile strengths, and bond or joint strengths of sterile suture components;
- (ii) Ability to orient the device appropriately to prevent damage to surrounding tissue structures:
- Consistency and reliability of implant deployment to achieve the desired (iii) treatment effect, including implant locations, leaflet tethering, and implant fixation:
- (iv) Mechanical integrity (e.g., tensile strength, fatigue or creep, bond failure) of the implant and placement devices to function under anticipated loading conditions;
- (v) Assessment of implant-tissue separation force;
- Durability of the implant; (vi)
- (vii) Compatibility of the implant in a magnetic resonance environment, if the implant contains magnetic or metallic materials; and
- (viii) Corrosion assessment, if the implant contains metal components.
- (4) The patient-contacting components of the device must be demonstrated to be biocompatible.
- Performance data must validate the sterility of the patient-contacting components of the (5) device.
- (6) Performance data must support the shelf-life of the device by demonstrating continued sterility, package integrity, and device functionality over the labeled shelf life.
- (7) Labeling must include the following:
- The recommended training for safe use of the device; (i)
- A precaution to use clinical judgment in selecting patients eligible for (ii) atrioventricular valve surgery and suitable for the device;
- (iii) A precaution to maintain direct visualization of the tissues to be treated during use of the device:
- Identification of the maximum number of deployments and actuations for each (iv) device(s); and
- A shelf life. (v)
BENEFIT-RISK DETERMINATION
The Mi-CHORD™ System is indicated for the replacement of adult mitral chordae tendineae with the patient on cardiopulmonary bypass, with the heart either arrested or fibrillating, and the surgical field under direct visualization. In general, the risks and benefits of the Mi-CHORD™ System are expected to be similar to those observed with established techniques for surgical replacement of chordae tendineae using suture.
The probable risks of the device are based on nonclinical laboratory studies, as well as data collected in an OUS feasibility clinical study as described above. There are known difficulties and risks associated with mitral valve repair procedures using conventional surgical technology
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and techniques. Some selected risks are outlined below, which are inherent risks for the Mi-CHORD™ System due to similarity of technique:
- . Residual MR
- Systolic anterior motion of the mitral valve .
- Occlusion or injury of the left circumflex artery .
- . Postoperative arrythmias, including atrial fibrillation and heart block
- . Surgical site bleeding and infection
- . Acute renal insufficiency
- . Respiratory insufficiency
- . Thromboembolic events
- . Vascular injury
- . Mortality
Clinical investigation of the Mi-CHORD™ System to treat severe MR subjects with a 12-month follow-up demonstrated 0% mortality through the follow-up period. There were no device failures reported in the clinical study. The risk of improper suture placement was mitigated in that 27.6% of total implanted sutures were removed and replaced to achieve better placement without compromising patient outcomes. Over the 12-month follow-up, there were 49 adverse events (AE) reported in 12 patients and 6 serious adverse events (SAE) reported in 6 patients. No valve thrombosis, endocarditis, or pacemaker implantation occurred in the postoperative course. Postoperative atrial fibrillation or flutter was present in 9 (75%) patients, with two requiring electrical cardioversion, which is an anticipated risk of mitral valve surgery.
The probable benefits of the device are also based on nonclinical laboratory studies, as well as data collected in an OUS feasibility clinical study as described above. Probable benefits of the device include reduction of mitral regurgitation and reduced procedural time. Nonclinical bench testing demonstrated the device met all design specifications and feasibility of open access or minimally invasive approach with or without videoscopic assistance. The nonclinical results were confirmed in clinical study, in which the Mi-CHORD™ System was successfully used to treat severe MR patients through median sternotomy and minimally invasive access. Satisfactory repair was obtained in all patients without any device-related AEs or SAEs. There were no mitral valve reoperations through 1 year. All (100%) of patients at 6 months and 92% of patients at 12 months demonstrated mild or lower MR. suggesting durable mitral valve repair using the Mi-CHORD™ System.
Additional factors to be considered in determining the probable risks and benefits for the Mi-CHORD™ System include that treatment of the Mi-CHORD™ System is similar to current surgical. suture-based mitral valve chordae tendineae replacement. Nonclinical and clinical data gathered for the Mi-CHORDIM System informed the Instruction for Use to provide detailed instruction to surgeons to mitigate possible risks. However, limitations of the submitted clinical study are that the trial design was single-center and single-arm for 12 patients with up to 12month follow-up, which may limit the ability to identify and mitigate unknown risks. Furthermore, the small number of investigators in the study (2 surgeons) may not be representative of likely real-world users of the device. As a result, an additional probable risk is that surgeon experience with conventional techniques and their experience with the device may
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affect clinical results. It is also important to note that manual surgical techniques are not precluded by use of the Mi-CHORD™ System, should device failure occur or should manual suture placement be preferred with a particular case.
Overall, the known or probable risks are considered minimal or are not thought to be meaningfully different than risks associated with conventional surgical repair techniques. Therefore, the probable benefits outweigh the risks when taking into account these considerations.
Patient Perspectives
This submission did not include specific information on patient perspectives for this device.
Benefit/Risk Conclusion
In conclusion, given the available information above, for the following indication statement:
The Mi-CHORD System is indicated for the replacement of adult mitral chordae tendineae with the patient on cardiopulmonary bypass, with the heart either arrested or fibrillating, and the surgical field under direct visualization.
Direct visualization, in this context, requires that the surgeon is able to see the heart and target tissues in a bloodless field, with or without assistance from an operating telescope or videoscopy.
The probable benefits outweigh the probable risks for the Mi-CHORD™ System. 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 the Mi-CHORD™ System is granted and the device is classified as follows:
Product Code: SBK Device Type: Artificial chordae tendineae surgical replacement system Regulation Number: 21 CFR 870.3490 Class: II
N/A