Ethical Approval

The study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The study protocol is available upon request and was reviewed and approved by the ethics committees at all participating centers (Approval Numbers of the three centers: 2025-58-BO; 06-04-9-41,665; 1351-1/6) and the study was appropriately registered (DRKS00038956). All participants provided written informed consent prior to enrolment. Patient confidentiality and data protection were strictly maintained throughout the study. Any adverse events were monitored and reported according to study protocol.

Study Design

The COR-KNOT® MIS and COR-KNOT MINI® devices (LSI SOLUTIONS®) use titanium fasteners to secure 2–0 and 3–0 polypropylene and braided polyester sutures, automating knot tying and trimming, thereby reducing operative time. This multicenter, prospective single-arm, observational study aimed to assess the technical feasibility and short-term safety of heart valve repair or replacement using COR-KNOT® titanium fastener technology for suture fixation.

Study Population

A total of 120 patients undergoing heart valve repair or replacement surgery were prospectively enrolled from August 2025 to January 2026 after informed consent at three active study sites: the Department of Cardiac Surgery, University Hospital Bonn (n = 79), the Institute of cardiovascular diseases Vojvodina (n = 16), and the University of Sarajevo (n = 25). Enrolment was discontinued upon reaching the predefined sample size. No losses or exclusions occurred. The sample size of 120 patients was determined a priori according to regulatory requirements for market approval in certain countries. A formal power calculation was not performed, as the study was primarily designed to meet regulatory rather than hypothesis-testing objectives.

Inclusion Criteria

Patients willing and able to sign the informed consent

Patients above the age of 18 years

Patients with heart valve pathology and indication for valve surgery

This surgery is performed with 2–0 or 3–0 braided or polypropylene sutures

Life expectancy above 1 year based on operator assessment

This surgery will be a minimally invasive or conventional surgery

Surgery may be a combined or isolated procedure

Exclusion Criteria

Patients unable to read or understand the informed consent

Patients who did not sign the informed consent form and/ or refuse to participate

Infective endocarditis at time of surgery

Emergency surgery (surgery within the day of admission)

Treatment Duration and Modification

COR-KNOT titanium fastener technology is intended for use in heart valve surgery. Patients underwent treatment with the subject device technology within its intended use after giving informed consent, and they were enrolled in the study before undergoing surgery.

Mean skin-to-skin times, aortic cross-clamp (ACC) and cardio-pulmonary bypass (CPB) times have been shown to decrease with the use of this technology. After treatment day and follow-up period (30 days) patients undergo a telephone follow-up.

Study Intervention and Device

As shown in Fig. 1, Each COR-KNOT QUICK LOAD® unit provides one sterile COR-KNOT fastener (No. 1) held in a customized loading unit consisting of a purple target (No. 2), a wire snare (No. 3), and a blunt curved handle (No. 4). Made from medical grade titanium, a COR-KNOT fastener is a mushroom-shaped hollow sleeve, which is crimped by the COR-KNOT MINI device to fasten together segments of suture (No. 5). Each device is intended for single patient use. A COR-KNOT fastener is loaded into the distal tip of the 4-mm-diameter shaft (No. 6). A rotational knob (No. 7) with an indicator fin (No. 8), a white handle (No. 9) and purple lever (No. 10) are located at the proximal end of the device. By squeezing the purple lever, the COR-KNOT MINI device crimps the COR-KNOT fastener at the closure site and can trim away excess suture.

Fig. 1

Titanium fastener device with numbered components and magnified view of device tip (upper left). Used with permission from LSI Solutions (Victor, NY, USA)

Both the COR-KNOT MIS and COR-KNOT MINI Devices are surgical hand-operated instruments that can be manually actuated by squeezing the device lever to crimp a sterile titanium fastener onto 2–0 or 3–0 PP or braided polyester suture (already placed by the surgeon) to secure the suture. The device also automatically trims excess suture tails after crimping the titanium fastener. This titanium fastener technology eliminates the need to hand-tie knots in valve suture.

The intended use for the COR-KNOT MIS and COR-KNOT MINI Devices is the same. Suture ends are threaded through the wire snare, then pulled through the titanium fastener. The device is positioned at the surgical site while the suture is tensioned, and the lever is squeezed and held to crimp the titanium fastener and cut the loose suture ends. The lever is released, and the device is removed from the surgical site, the titanium fastener remains implanted in the patient (see Fig. 2).

Fig. 2

Intended use for titanium fastener device. Used with permission from LSI solutions (Victor, NY, USA)

Primary and Secondary Endpoints

The primary endpoint was ‘device success’ at the conclusion of the procedure, meaning successful deployment of each titanium fastener with proper clip formation, secure suture fixation, and trimming of excess suture material, without device malfunction or the need to convert to manual knot tying. This endpoint was intended as a measure of technical performance and not clinical efficacy. The second primary endpoint is prosthesis implantation time, defined as time from first suture placement to end of prosthesis seating with last titanium fastener used. The prespecified hypothesis of this study is that heart valve repair or replacement using automated titanium fastener deployment can be performed technically feasible with a high rate of device success, as evidenced by absence of device related short-term safety events. Secondary objectives include assessment of patient well-being and serious adverse events, which were site-reported only (reoperation for bleeding, paravalvular leak, valve dysfunction, embolic events, pacemaker etc.), at 30-days follow-up.

Adverse Event Adjudication

Adverse events (AEs) were prospectively collected and systematically adjudicated with respect to their relationship to the titanium fastener system. Causality assessment was performed using a predefined classification adapted from established pharmacovigilance frameworks, categorizing events as definite, probable, possible, unlikely, or not device-related. Events were considered device-related if a direct or indirect causal link to the device was established (definite or probable), based on temporal association, a plausible mechanistic explanation (e.g., incomplete fastener deployment, clip dislodgement, or device malfunction), and the absence of a more likely alternative cause. Events were classified as non-device-related if they were deemed unlikely or unrelated to the device, including complications attributable to patient-specific factors, underlying pathology, or standard surgical risks independent of the fastening system. Events categorized as possible were analyzed separately. All AEs were reviewed by two experienced cardiac surgeons. In cases of disagreement, consensus was reached through discussion, and, if necessary, adjudication by a third reviewer. Source data included operative reports, intra-operative findings, and post-operative imaging. Events were further stratified according to timing (intra-operative, early post-operative ≤ 30 days, and late post-operative > 30 days) to support causality assessment.

Sample Size and Data Collection

A total sample of 120 patients was predefined; this number was determined pragmatically based on regulatory considerations rather than derived from a formal statistical power calculation. A formal power calculation was not performed, as the study was primarily designed to meet regulatory objectives. The selected patients were enrolled from August 2025 to January 2026. None of the eligible patients who were planned for enrolment refused. Multi-center data were collected and managed using REDCap (Research Electronic Data Capture, Vanderbilt University, Nashville, TN, USA) electronic data capture tools with the server hosted at the University Hospital Bonn, Germany. A full-time data manager was responsible for the creation of electronic records in REDCap, program support, and data entry oversight. All entered data were independently verified by a third investigator.

Statistical Analysis

Descriptive statistical methods were used to characterize the study population at baseline and during follow-up. Continuous variables are reported as mean ± standard deviation (SD) for approximately normally distributed data, or as median with interquartile range (IQR) where appropriate. The distribution of continuous variables was assessed where relevant, by tests of normality.

Categorical variables are presented as absolute frequencies and percentages. Comparisons between groups, if applicable, were performed using Student’s t test or the Mann–Whitney U test for continuous variables, depending on data distribution, and the chi-square test or Fisher’s exact test for categorical variables, as appropriate.

All statistical tests were two-sided, and a p value < 0.05 was considered statistically significant. Given the exploratory nature of the study, no formal adjustment for multiple testing was applied.

Missing data were not imputed. As all patients completed at least 30-days follow-up, the dataset for the primary analysis was considered complete for the main outcome measures.

Adverse events were systematically collected and classified as device-related or non-device-related according to predefined criteria.

All statistical analyses were performed using MedCalc Statistical Software (MedCalc Software, Ostend, Belgium). The software was used for descriptive statistics and all inferential analyses. Results adjusted for center were not presented.

Use of Artificial Intelligence

An artificial intelligence-assisted language editing tool was used to improve the linguistic quality of the manuscript without altering the scientific content; the authors retain full responsibility for all statements and conclusions.