30-Day Outcomes of Transcatheter Tricuspid Annuloplasty With the K-Clip System

Background Surgery for isolated functional tricuspid regurgitation (TR) poses a high risk. Several transcatheter approaches are being evaluated for the treatment of such patients. The K-Clip system is a percutaneous approach designed for functional TR; however, its utility remains unknown. Objectives This study aimed to report the 30-day echocardiographic and clinical outcomes with the K-Clip system for severe TR, including changes in TR severity and NYHA functional class. Methods Transcatheter tricuspid valve annuloplasty was performed in 39 patients with intermediate or high surgical risk who underwent the K-Clip system. The right internal jugular vein procedure was performed with annuloplasty guided by fluoroscopy and echocardiography. The primary outcomes were clinical success and all-cause mortality at the 30-day follow-up. Results The K-Clip was successfully implanted in all cases, with 1 to 3 devices deployed. At the 30-day follow-up, none of the patients had died. TR severity was reduced by at least one grade in all patients. There were no severe procedural or 30-day adverse events, except for 1 new pacemaker implantation. The proportion of NYHA class III-IV patients decreased from 79.5% to 5.1%, and the ascites disappeared. The 6-minute walk distance increased by 78 m (P < 0.05), and the Kansas City Cardiomyopathy Questionnaire score improved by 11 points (P < 0.05). Conclusions The K-Clip device is practical, safe, and effective for patients with severe TR. A 30-day reduction in TR and enhanced cardiac function and quality of life were associated with transcatheter tricuspid annuloplasty using the K-Clip device, according to short-term follow-up studies. (Confirmatory Clinical Study of Treating Tricuspid Regurgitation With K-Clip TM Transcatheter Annuloplasty System [TriStar]; NCT05173233)

M oderate-to-severe tricuspid regurgitation (TR), the most prevalent disease on the right side of the heart, has become a growing public health crisis.TR occurs in approximately 4% of elderly patients and is more common in women 1 ; most of them are unable to receive appropriate care.Although primary (organic) TR is uncommon, secondary (functional) TR (FTR) is dominant, accounting for 80% to 90% of TR. 2 The tricuspid valve (TV) is unaffected by organic disorders; however, FTR may occur in the context of left heart valve disease, pulmonary hypertension, atrial fibrillation, or other diseases. 3Although mitral valve surgery can somewhat improve FTR to a certain extent, untreated severe TR causes long-term heart failure and other consequences, affecting the quality of life and increasing mortality. 4though medication therapy alone is inadequate, the clinical therapies for TR include conservative drug treatments and surgery.Surgical correction of the FTR, particularly tricuspid valvuloplasty similar to left heart surgery, can significantly enhance the long-and short-term prognoses of patients. 5Nevertheless, investigations have discovered that the high recurrence rate and mortality after tricuspid valvuloplasty are severe and intractable issue. 6Solitary TV surgery is a risky contemporary valve procedure, with a mortality rate of 8.8% to 9.7%. 5erefore, there is a need for less-invasive treatments.Valve repair and replacement are the major components of TV transcatheter therapy and are currently in the early stages of clinical verification.
Less trauma, minimal procedural risk, few complications, quick recovery, and high patient acceptability are benefits of interventional therapy for TR.Patients with severe TR who cannot undergo surgery are good candidates.
The transcatheter TV repair techniques can be divided into edge-to-edge leaflet repair, annuloplasty, and regurgitation orifice filling. 7The main pathology in the majority of patients with TR is annular dilatation, and minimally invasive catheterbased devices are designed to shrink the size of tricuspid annular dimensions.In the context of the surging development of transcatheter TV intervention strategies, the results of the epoch-making randomized controlled trial TRILUMINATE Pivotal brought confidence to TV interventional therapies. 8e existing devices still have a number of common issues, including difficult operation procedures, steep learning curves, and a lack of large-scale clinical testing to confirm their efficacy.Transcatheter TV repair devices should be simple to use and widely available.Therefore, the K-Clip system was developed.The K-Clip transcatheter tricuspid annuloplasty system (Huihe Medical Technology) is a percutaneous approach designed for FTR through anchors on the annulus tissue utilizing a corkscrew, which lowers the dimensions of the tricuspid annulus by folding and clamping the tricuspid annulus tissue with a rigid clamping device.The K-Clip has potential benefits for TR caused by tricuspid annulus dilatation, especially in patients with large valve leaflet gaps (coaptation gaps >10 mm).Pan et al 9      PREPROCEDURAL IMAGING TTE.Echocardiography remains the most important imaging modality for evaluating the etiology and severity of TR.We conducted a TTE evaluation for each patient, targeting TV-related data collection following the American Society of Echocardiography guidelines. 11,12Various parameters, such as the degree of TR, right atrial superior to inferior and left to right diameters, pulmonary systolic blood pressure, TR vena contracta width (VCW) (Figure 1A), proximal isovelocity surface area estimated Doppler volume technique effective regurgitant orifice area (EROA) (Figure 1B), vena contracta area (Figure 1C), regurgitant volume (Figure 1B), septolateral diameter of the TV annulus (Figure 1D), anteroposterior diameter of the TV annulus, and the diameter of the RV (basal segment), were computed from echocardiography (EPIQ 7C, Philips Healthcare).The fractional area alterations of the RV (fractional area change [FAC]), inferior vena cava (IVC) width, IVC variability, hepatic vein systolic flow reversal, tricuspid annular plane systolic excursion (TAPSE), degree of mitral valve regurgitation, and ejection fraction were analyzed in the echocardiography core laboratory.All echocardiograms were evaluated at an independent core laboratory in Shanghai, China.We reported the grade of TR using a 6-grade scheme of 1 (trace or mild), 2 (moderate), 3 (significant/moderate-severe), 4 (severe), 5 (massive), or 6 (torrential), based on the recently updated echocardiographic assessment of interventional therapy for TR by Hahn et al. 13 PREPROCEDURAL IMAGING TEE.TEE and focused TV imaging employing 3-dimensional (3D) modalities were performed for each patient prior to surgery.
During diastole, 3D imaging of the TV was performed to determine the maximum circumference (Figure 1E) and area of the tricuspid annulus (Figure 1E).During systole, the gap shape (Figure 1F), regurgitation location, and regurgitation volume of the TV orifice were observed.
Data were stored for every 10% of cardiac cycles.
Computed tomographic assessment of the tricuspid annulus and right coronary artery (RCA) information was sustained by a semiautomated software-based approach. 14The recorded images were employed to compute the TV orifice area (Figure 2A), tricuspid annulus circumference (Figure 2A), TR orifice shape (Figure 2B), septolateral diameter of the TV annulus (Figure 2C), landing zone for the K-Clip, annulus to RCA distance such as posteroseptal commissure (Figure 2D), midpoint of the posterior valve annulus (Figure 2D), and anteroposterior commissure (Figure 2D), and evaluate whether a right-dominant circulation was present (3 mensio valves, Pie Medical Imaging).
PROCEDURE.Following single-lumen endotracheal tube intubation, patients were kept in the supine position while undergoing RCA angiography and

Xu et al
placement of a coronary guidewire implanted through the right femoral artery to help define the TA plane fluoroscopically.In all cases, the TV was approached using the right internal jugular vein technique after complete heparinization with a goalactivated clotting time of 250 to 300 second.The deflectable outer sheath (16-F) was placed with the tip in the middle RA (Figure 3C).The deflectable inner sheath (15-F), including the anchor and clip, was placed into the outer sheath and emerged to the superior vena cava.The fissure distribution of the TR was assessed using 3-day TEE guidance, and the angle of the delivery system was modified so that the corkscrew was perpendicular to the target annulus.
The corkscrew was drilled into the annulus with a beating heart using TTE guidance, and the firmness was verified using a pull test to grip the annulus (Figure 3A).Under the 3D guidance of TEE and digital subtraction angiography, the clip arms were unfolded, and the arm was rotated to make it flush with the annulus (Figure 3B) and then advanced in the direction of the annulus until the clip arms were close to the annulus tissue.Subsequently, the corkscrew with the annulus tissue was raised outward (Figure 3D), the clip arms were closed, and then the annulus and coaptation gaps were reduced.Right coronary angiography was performed to simultaneously evaluate the presence of coronary stenosis and clip stability (Figure 3E).If the assessment was satisfactory (TR reduction grade of $2), the clip was removed from the delivery sheath, and TEE assessment and angiography were performed again to assess vascular stenosis (Figure 3F).Otherwise, a new clip was implanted until satisfactory TEE results were obtained.Before release, the delivery system and clips can be retrieved and removed.All patients received oral anticoagulants (aspirin plus clopidogrel or warfarin alone) for 6 months after surgery.6), and the septolateral diameter of the TV ring decreased from 46.8 AE 9.3 mm to 32.0 AE 6.5 mm (P < 0.05).All 39 patients attained clinical success with the K-Clip repair system (both implantation and success rates were 100% [Table 2], and implantation success was defined as a reduction in TR of at least 1 grade).
Xu et al Annuloplasty With the K-Clip System

DISCUSSION
To the best of our knowledge, this is the first study to report the 30-day results of a single-center, observational, first-in-human experience study testing transcatheter tricuspid annuloplasty with the K-Clip system for treating severe functional TR.The shortterm follow-up displayed promising outcomes, including the following (Central Illustration): 1) the K-Clip was a safe and reliable surgical procedure, 100% of the clips were successfully implanted, and the decrease in the grade of TR and reduction in the area of the valve ring were substantial and durable; 2) the quality of life and cardiac function improved; 3) the incidence of adverse events was low, with an MAE rate of 2.6%, which is lower than that of the CLASP TR EFS 15 results and close to the TRILUMINATE Pivotal 8 results; and 4) the RV remodeling was noted-30 days after surgery, the diameter of the RV substantially decreased.
All patients experienced a decrease in the TR of at least one grade when the K-Clip system was successfully implanted.At follow-up 30 days after surgery, this effect remained, with a decrease of $2 grades in 76.9% of patients.After annular reduction from 3D imaging, even though complete coaptation of the TV leaflets may not be accomplished or the degree of TR remained at grade 4, the relative reduction in EROA and TR was significant to lead to considerable clinical and hemodynamic improvement, linked to the enhancement in the stroke volume of the RV and increase in forward blood flow, which then caused increases in the preload of the left heart system and contractility.According to the CTA measurement data, the distance of the RCA from the tricuspid annulus changed in a wave-like pattern from its proximal end to its distal end.Thus, from the viewpoint of coronary safety, the potential landing zones from high to low safety variables are the posteroseptal commissure, anteroposterior commissure, and midpoint of the posterior valve annulus.
A strength of this study is that no deaths, massive pericardial effusion, or cases of conversion to thoracotomy were recorded at 30 days of follow-up.
The current results are somewhat equivalent to those of earlier clinical studies on transcatheter TV interventional therapy, [16][17][18][19][20] despite the short followup time, which gives us more confidence in our long-term efficacy outcomes.A 30-day short-term follow-up revealed significant clinical improvement in addition to minimal mortality and serious bleeding problems.The KCCQ score, 6MWD, and proportion of patients with NYHA functional class I/II significantly increased within 30 days, as did the symptoms of peripheral edema.Within 30 days, the readmission rate was only 2.6% (1 new pacemaker implanted).
Combining the unique structure of the K-Clip, we attribute the benefits to the following points.1) The thin tissue of the TV leaflet, complicated 3D anatomical structure, the large asymmetric annulus, and existence of imaging complications, 21 leading to difficulties and complications in repairing the leaflet.
The K-Clip system was targeted for the operation of the valve ring.The structure of the TV ring is firm, and the hinge area of the tricuspid annulus is relatively broad, simple to image on ultrasound, and easy to operate, has a high in safety factor and extensive clamping range and can be adjusted repeatedly.
Additionally, the same position could be clamped multiple times without causing considerable annular Currently, it is widely accepted that uncorrected severe TR enhances the risk of death and reduces the   Transcatheter tricuspid valve repair using the K-Clip system is technically feasible, safe, and effective.The major adverse event and mortality rates are low.The most commonly used landing zone for the K-Clip is posteroseptal commissure (56.4%), with high coronary safety.Shortterm follow-up shows that the K-Clip system is associated with a 30-day reduction in TR and improved cardiac function and quality of life.TR reduction is observed to be at least grade 1 in all patients.This effect persists at follow-up 30 days postoperatively, with a reduction of $2 grades in 76.9% of patients.TR ¼ tricuspid regurgitation.

CONCLUSIONS
This study demonstrates that the K-Clip device is technically feasible, safe, and effective in patients with severe FTR.Short-term follow-up revealed that transcatheter tricuspid annuloplasty using the K-Clip system was associated with a 30-day reduction in TR and enhanced cardiac function and quality of life.In addition, further studies are required to determine the long-term outcomes.
introduced the working principle and efficacy of the K-Clip in animals.The device concept and details of the implantation process have been detailed previously.Herein, we reported 39 patients completed in our center from July to October 2022.All patients were at intermediate or high surgical risk (Tri-Score $4) 10 and concluded a short-term 30-day follow-up.METHODS DEVICE DESCRIPTION.A catheter-based treatment for TR, the K-Clip tricuspid annuloplasty system, consists of an anchor device, clip device, delivery system, and holder system. 9The K-Clip precisely reaches the desired location of the TV area through the internal jugular vein approach.The anchor and clip devices are similar in shape to a crocodile mouth, which bites the enlarged TV annulus tissue and shrinks the TV annulus.The circumference of the TV is reduced, thus bringing together the TV leaflets in areas of malcoaptation and enhancing sufficient valve closure.Four clip sizes are available with arm lengths of 12, 14, 16, and 18 mm.All patients provided signed informed consent.This study was registered at Clin-icalTrials.gov (NCT05173233).PATIENT SELECTION.Patients aged >60 years had an FTR severity grade $4 and NYHA functional class $II.The heart team identified patients at intermediate or high surgical risk with a Tri-Score $4 and left ventricular ejection fraction (LVEF) $40%.The etiology of FTR included TR due to right atrial disease and/or right ventricular (RV) dysfunction.The causes of the latter included RV cardiomyopathy, RV myocardial infarction, left valvular disease, and congenital heart disease.The exclusion criteria are listed in Supplemental PREOPERATIVE SCREENING ASSESSMENT.In addition to evaluating the patients' basic information prior to surgery, symptoms, past medical history, andA B B R E V I A T I O N S A N D A C R O N Y M valveheart-related surgery history were obtained to analyze the 6-minute walk distance (6MWD), Kansas City Cardiomyopathy Questionnaire (KCCQ), blood indicators such as blood routine, biochemistry, Btype natriuretic peptide, N-terminal pro-B-type natriuretic peptide, and cardiac function.Transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and coronary computed tomographic angiography (CTA) are among the imaging techniques.

FIGURE 1
FIGURE 1 Preprocedural TTE and TEE

FIGURE 2
FIGURE 2 Preprocedural CTA CLINICAL OUTCOMES.All-cause mortality, stroke, transient ischemic attacks, myocardial infarction, significant/life-threatening bleeding (defined as Bleeding Academic Research Consortium type $3a), acute kidney injury (defined as the need for unplanned dialysis or renal replacement therapy), renal insufficiency (estimated glomerular filtration rate <60 mL/min/1.73m 2 ), new pacemaker

Figures 4 and 7
Figures 4 and 7 show that significant clinical improvements were observed in the NYHA functional class after a 30-day follow-up (94.9% of patients had NYHA class I/II, and the proportion of class III-IV patients decreased from 79.5% to 5.1%).The 6MWD improved from 284.6 AE 111.6 m to 362.7 AE 116.5 m (P < 0.01), and the KCCQ score improved from 64.9 AE 15.1 to 75.9 AE 11.8 (P < 0.01).

FIGURE 4
FIGURE 4 The K-Clip Transcatheter Tricuspid Annuloplasty System

FIGURE 5 Annuloplasty
FIGURE 5 Reduction in TR From Baseline to 30 Days With the K-Clip System

FIGURE 7
FIGURE 7 The K-Clip System Improves the 6MWD and KCCQ Scores From Baseline to 30 Days

FIGURE 6 3 Annuloplasty
FIGURE 6 The K-Clip System Reduces the TV Area and Ring Circumference From Baseline to 30 Days

JAnnuloplasty
A C C : A D V A N C E S , V O L . 2 , N O .9 With the K-Clip Systemapplicability cannot be fully encompassed in all patients with TR.For instance, a lead pacemaker causing TR was excluded from the study because the inclusion and exclusion criteria were established during patient selection.It is noted that the pacemaker lead-induced TR accounted for 10% to 25%, which is an extremely high proportion, and the left heart function of the enrolled patients is relatively good, making the outcomes of this investigation feasible and likely not applicable to all types of patients with TR.Although the effect of the clip on the RCA does not seem to be shortterm issues, it is also an issue that we need to worry about.Additionally, concerning the grading technique of TR, we adopted the latest updated 6-grade scheme by Hahn et al,13 different from the 5-grade scheme used in previous TR studies.This offers some complications for the horizontal comparison of reflux grade decline among different studies.Finally, we anticipate the 1-year follow-up outcomes and multicenter research findings, hoping to provide new treatments to patients with TR.

Table 2
lists the key features of the procedure.The K-Clip was successfully implanted in all 39 patients with 1 to 3 devices installed, with a mean of 1.5 implants per patient (one implant in 56.4%, 2 implants in 38.5%, and 3 implants in 5.1% of patients).The treatment took a mean of 137.6 AE 55.6 minutes.The mean fluoroscopy time was 43.1 AE 15.3 minutes, the volume of contrast medium was 69.7 AE 28.2 mL, and there were no complications such as conversion to open heart surgery, procedure-