Single Leaflet Research Articles

Transcatheter Edge-To-Edge Valve Repair for Tricuspid Regurgitation


 The transcatheter edge-to-edge valve repair (TEER) device (TriClip) might be more effective in reducing tricuspid regurgitation severity and improving quality of life compared to medical therapy alone.
 The TEER device (TriClip) may have little impact on all-cause mortality, hospitalization due to heart failure, and 6-minute walk tests compared to medical therapy alone.
 The TEER device (TriClip) demonstrated a numerically higher rate of adverse events than a medical therapy control group in a clinical trial.
 Patients treated with the TEER device (TriClip) had fewer major adverse events (ranging from 2.5% to 7.1%) than the 10% performance goal in the included clinical trial; common major adverse events included major bleeding, single leaflet device attachment, and nonelective cardiovascular surgery. No device embolization or thrombosis were reported.
 We did not identify any studies that met our inclusion criteria to evaluate the effectiveness of the TEER device (TriClip) compared to open heart surgery.

Transcatheter edge-to-edge repair for mitral regurgitation using PASCAL or MitraClip.

There is a paucity of data regarding the comparative efficacy and safety of Mitral valve transcatheter edge-to-edge repair (MTEER) using the PASCAL or MitraClip systems for patients with mitral regurgitation (MR). An electronic search was conducted for MEDLINE, COCHRANE, and EMBASE, through February 2023, for studies comparing the clinical outcomes of MTEER using PASCAL versus MitraClip systems among patients with severe MR. The primary study outcome was residual MR ≤ 2 at discharge. Data were pooled using a random-effects model. The final analysis included six studies with a total of 1581 patients, with a weighted follow-up period of 3.5 months. Two studies only included patients with degenerative MR, while the remaining studies included both degenerative and functional MR. There was no significant difference in procedure duration between MTEER with the PASCAL or MitraClip systems. There was no difference in residual MR ≤ 2 at discharge (94.7% vs. 91.9%; odds ratio [OR]: 1.44; 95% confidence interval [CI]: 0.92-2.27) or residual MR ≤ 2 at the mid-term follow-up (94.6% vs. 91.0%, p = 0.05) among the PASCAL versus MitraClip systems. There was no difference between both groups in residual MR ≤ 1 at discharge (73.1% vs. 63.8%, p = 0.12), while there was greater incidence of residual MR ≤ 1 at midterm follow-up with the PASCAL system (71.3% vs. 56.2%, p < 0.001). There was no difference between the PASCAL and MitraClip MTEER systems in technical success (97.0% vs. 97.9%, p = 0.15), procedural success (89.1% vs. 87.1%, p = 0.78), single leaflet detachment (1.8% vs. 1.4%, p = 0.55), or all-cause mortality (3.6% vs. 4.6%, p = 0.71). In this meta-analysis, we demonstrated comparable efficacy and safety between the PASCAL and MitraClip MTEER systems at short- and mid-term assessments. Randomized trials are warranted to evaluate the comparative long-term outcomes between both MTEER systems.

MitraClip single-leaflet detachment and consequent migration in atrial functional mitral regurgitation.

An 84-year-old woman with symptomatic severe functional mitral regurgitation (MR) due to long standing atrial fibrillation underwent percutaneous edge-to-edge repair using the MitraClip system (Abbott Vascular, Santa Clara, CA, USA) (see Supplementary data online, Video S1). Following deployment of an XTR clip in the A2-P2 segment, a second MitraClip XT device was deployed laterally to prevent recurrence of MR caused by stretching of left atrium and mitral leaflets. However, single leaflet detachment of the anterior leaflet occurred immediately (Panel A, Supplementary data online, Video S2). Since only mild MR was observed after the procedure, additional clipping was not performed, and her symptoms were relieved. However, at 2 weeks after discharge, she presented with right inguinal pain and aggravated dyspnea. The lateral clip was not observed on chest x-ray (Panels B and C). Computed tomography revealed the migrated MitraClip at the right common iliac artery bifurcation (yellow arrows in Panel D). Transesophageal echocardiogram showed recurrence of severe MR with newly developed small chordae rupture (Panel E, Supplementary data online, Video S3). The embolized MitraClip was successfully retrieved using 10- and 15-mm Amplatz GooseNeck® snares (Ev3, Plymouth, MN, USA) through a 16-French Check-Flo® Introducer sheath (Cook Medical, Bloomington, IN, USA) (Panels F, G, and H, Supplementary data online, Video S4), and another NTW clip was deployed. Post-procedure transesophageal echocardiogram confirmed residual mild to moderate MR (Panel I, Supplementary data online, Video S5). Images from this case show the complications of MitraClip single leaflet detachment and distal migration, and how this problem was solved.

The Road to Quantitative Lipid Biochemistry in Living Cells.

Traditional cell biological techniques are not readily suitable for studying lipid signaling events because genetic perturbations are much slower than the interconversion of lipids in complex metabolic networks. For this reason, novel chemical biological approaches have been developed. One approach is to chemically modify a lipid with a so-called "caging group" that renders it inactive, but this cage can be removed photochemically inside cells to release the bioactive molecule. These caged compounds offer unique advantages for studying the kinetics of cellular biochemistry and have been extensively used in the past. However, a limitation of conventional caged compounds is their ability to diffuse freely inside the cell, which does not permit localized activation below optical precision. This poses a challenge for studying lipid signaling as lipid function inside cells is tightly linked to their parent membrane. An ideal lipid probe should, therefore, be restricted to a single organelle membrane or preferentially to a single leaflet. We first demonstrated the plasma-membrane-specific photorelease of fatty acids by employing sulfonated caging groups. Using these caged fatty acid probes we demonstrated that lipid localization determines signaling outcome. Generalizing this approach, we designed a so-called "click cage" that can be coupled to lipids and offers the possibility to attach organelle targeting groups via click chemistry. Using this strategy, we have synthesized plasma membrane, lysosomal, mitochondria, and endoplasmic-reticulum-targeted lipids that can be used to dissect organelle-specific signaling events. To reduce the synthetic effort associated with generating caged compounds, we designed a coumarin triflate reagent that allows the direct functionalization of phosphate- or carboxylate-containing compounds. With this novel reagent, we synthesized a small library of photocaged G-protein-coupled receptor (GPCR) ligands to study the underlying lipid signaling dynamics. Most recently, we have focused on quantifying the kinetics of lipid signaling for different diacylglycerol (DAG) species using plasma-membrane-targeted caged DAGs. Using this approach, we quantitatively measured lipid-protein affinities and lipid transbilayer dynamics in living cells. After analyzing DAGs with different acyl chain length and saturation degree, we discovered that affinities can vary by up to an order of magnitude. This finding clearly shows that cells are able to distinguish between individual DAG species, thereby demonstrating that lipid diversity matters in cellular signal processing. Although the recent advances have yielded valuable tools to study lipid signaling, challenges remain on specifically targeting the different leaflets of organelle membranes. Furthermore, it is necessary to simplify the experimental approaches required for parametrizing and corroborating quantitative kinetic models of lipid signaling. In the future, we envision that the application of leaflet-specific caged lipids to model membrane systems will be of crucial importance for understanding lipid asymmetry.

Effect of leaflet laceration on transcatheter aortic valve replacement fluid mechanics and comparison with surgical aortic valve replacement

BackgroundLeaflet thrombosis after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) may be caused by blood flow stagnation in the native and neosinus regions. To date, aortic leaflet laceration has been used to mitigate coronary obstruction following TAVR; however, its influence on the fluid mechanics of the native and neosinus regions is poorly understood. This in vitro study compared the flow velocities and flow patterns in the setting of SAVR vs TAVR with and without aortic leaflet lacerations. MethodsTwo valves, (23-mm Perimount and 26-mm SAPIEN 3; Edwards Lifesciences) were studied in a validated mock flow loop under physiologic conditions. Neosinus and native sinus fluid mechanics were quantified using particle image velocimetry in the left and noncoronary cusp, with an increasing number of aortic leaflets lacerated or removed. ResultsAcross all conditions, SAVR had the highest average sinus and neosinus velocities, and this value was used as a reference to compare against the TAVR conditions. With an increasing number of leaflets lacerated or removed with TAVR, the average sinus and neosinus velocities increased from 25% to 70% of SAVR flow (100%). Diastolic velocities were substantially augmented by leaflet laceration. Also, the shorter frame of the SAVR led to higher flow velocities compared with the longer frame of the TAVR, even after complete leaflet removal. ConclusionsLeaflet laceration augmented TAVR native and neosinus flow fields, approaching that of SAVR. These findings may have potential clinical implications for the use of single or multiple leaflet lacerations to reduce leaflet thrombosis and thus potentially improve TAVR durability.

Atomic insights into amyloid-induced membrane damage.

Amphipathic peptides can cause biological membranes to leak either by dissolving their lipid content via a detergent-like mechanism or by forming pores on the membrane surface. These modes of membrane damage have been related to the toxicity of amyloid peptides and to the activity of antimicrobial peptides. Here, we will discuss all-atom simulations in which membrane-bound amphipathic peptides self-assemble into beta-sheets that subsequently either form stable pores inside the bilayer or drag lipids out of the membrane surface. An analysis of these simulations shows that the acyl tail of lipids interact strongly with non-polar side chains of peptides deposited on the membrane. These strong interactions enable lipids to be dragged out of the bilayer by oligomeric structures accounting for detergent-like damage. They also disturb the orientation of lipid tails in the vicinity of peptides. These distortions are minimized around pore structures. We also show that membrane-bound beta-sheets become twisted with one of their extremities partially penetrating the lipid bilayer. This allows peptides on opposite leaflets to interact and form a long transmembrane beta-sheet, which initiates poration. In simulations, where peptides are deposited on a single leaflet, the twist in beta-sheets allows them to penetrate the membrane and form pores. In addition, our simulations show that fibril-like structures produce little damage to lipid membranes, as non-polar side chains in these structures are unavailable to interact with the acyl tail of lipids.

Periprocedural, short-term, and long-term outcomes following transcatheter tricuspid valve repair: a systemic review and meta-analysis.

There has been an increasing use of transcatheter tricuspid valve repair (TTVR) recently. However, the periprocedural, short-term, and long-term outcomes of TTVR remain unclear. To determine the clinical outcomes in patients with significant tricuspid regurgitation undergoing TTVR. Systematic review and meta-analysis. The systematic review and meta-analysis is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and EMBASE were searched for clinical trials and observational studies until March 2022. Studies reporting the incidence of clinical outcomes after TTVR were included. The clinical outcomes included periprocedural, short-term (in-hospital or within 30 days), and long-term (>6-month follow-up) outcomes. The primary outcome was all-cause mortality whereas the secondary outcomes included technical success, procedural success, cardiovascular mortality, rehospitalization for heart failure (HHF), major bleeding, and single leaflet device attachment. The incidence of these outcomes across studies was pooled by a random-effects model. A total of 21 studies with 896 patients were included. A total of 729 (81.4%) patients underwent isolated TTVR while only 167 (18.6%) patients underwent combined mitral and tricuspid valve repair. Over 80% of the patients used coaptation devices while approximately 20% used annuloplasty devices. The median follow-up duration was 365 days. Technical and procedural success was high at 93.9% and 82.1%, respectively. The pooled perioperative, short-term, and long-term all-cause mortality for patients undergoing TTVR was 1.0%, 3.3%, and 14.1%, respectively. The long-term cardiovascular mortality rate was 5.3% while the HHF rate was 21.5%. Major bleeding and single leaflet device attachment were two major complications, accounting for 14.3% and 6.4%, respectively, during long-term follow-up. TTVR is associated with high procedural success and low procedural and short-term mortality. However, all-cause mortality, cardiovascular mortality, and HHF rates remain high during long-term follow-up. PROSPERO (CRD42022310020).

Two Cases of Surgical Correction of Recurrent Mitral Regurgitation due to Failed Catheter- Delivered Mitral Clip (MitraClip).

From April 2018 to February 2021, 150 patients underwent MitraClip implantation for severe functional mitral regurgitation (MR) at our hospital. Two of our patients, an 85-year-old man and an 84-year-old woman, developed a single leaflet device attachment in the acute phase after the implantation and had severe residual MR requiring surgical correction. The recurrent MR was first pointed out on day 5 and day 4, and the duration between MitraClip implantation and surgery was 13 and 55 days, respectively. Due to strong adhesions with the clips and severe valve damage after MitraClip implantation, both cases underwent mitral valve replacement with a good postoperative course. In patients with a high-risk baseline profile, surgical mitral valve replacement after failed MitraClip implantation should be considered at an optimal timing, and a detailed echocardiographic follow-up is required.

ECHO ROUND: THREE DIMENSIONAL TRIMMING, THE FREE ANGLE ALTERNATIVE FOR MITRAL AND AORTIC VALVE VITIUM ASSESSMENT.

Three-dimensional (3D) Technology provides real time dynamic assessment and allows for multiplanar reconstruction (MPR) for the different cardiac structures. However, it is much more demanding regarding the Echo device specification, and operator experience in both loop acquisition, enhancement and of course interpretation. Trimming function is one of the post-acquisition software tools, which can be used in step-by-step assessment of the Mitral valve (MV) and aortic valve (AV) vitrium. It didn't overcome the required experience required for the interpretation of 3D images. But when systematically done, it makes it more objective and allows for assessment of the coaptation line along the valve leaflets, even in cases where it is impossible to assess in 2D as between non-coronary and left coronary AV cusps. The loops in this poster were acquired with the Philips Affinity 70 and the X7-2T transoesophageal matrix array transducer. The basic requirement of the 3D loop acquisition is guided by the published recommendation as it is and when possible multibeat acquisition is used.1. In MV Our examination started in Midesophageal Intercommisural View with 3D Zoom function. We rotated the acquired loop to obtain the surgical view of the MV with the Aorta at 12 O'clock (Figure 1, Step 1). At this point we rotated the aorta to be positioned at 9 O'clock. (Figure 1 Step 2). Then, using the track ball, we rotated the 3D picture 90 degrees in the vertical axis to be facing the lateral annulus of the MV (Figure 1, Step 3) . Starting from this view, using the face Trimming function (figure 1 Step 4) we have adjusted the trimming level going deeper all through the MV from lateral to medial, examining the coaptation line all through all parts of the leaflets. What also helped to delineate the leaflets was to add more gain (in controversy to what is normally done to improve the 3D Image). For orientation, we recommend rotating the 3D loop back to surgical view to localize the trimming level. Color Flow Examination normally requires a multibeat acquisition to get a reasonable frame rate. We also trimmed from lateral to medial till we could see the Regurgitation Jet. (Figure 3) For AV we started with the Midesophageral AV short axis view and using loop was acquired using the 3D zoom function (Figure 4). Using the same technique we have adjusted the trimming line to go through the coaptation line needed to be examined between Non coronary cusp (NCC) – Right coronary cusp (RCC), RCC- Left coronary cusp (LCC) and NCC-LCC . (figure 5) .In each level we used the track ball to rotate the 3D image to get an inface view where we could see the coaptation. We could also measure coaptation height, coaptation length and identify single leaflet pathology. <b>Conclusion:</b> In contrast to 2D images the Trimming function allows a free angle generation of 2D images for angles difficult or sometimes impossible to be obtained with normal 2D cutting or even biplane.

Atomic Insights into Amyloid-Induced Membrane Damage.

Amphipathic peptides can cause biological membranes to leak either by dissolving their lipid content via a detergent-like mechanism or by forming pores on the membrane surface. These modes of membrane damage have been related to the toxicity of amyloid peptides and to the activity of antimicrobial peptides. Here, we perform the first all-atom simulations in which membrane-bound amphipathic peptides self-assemble into β-sheets that subsequently either form stable pores inside the bilayer or drag lipids out of the membrane surface. An analysis of these simulations shows that the acyl tail of lipids interact strongly with non-polar side chains of peptides deposited on the membrane. These strong interactions enable lipids to be dragged out of the bilayer by oligomeric structures accounting for detergent-like damage. They also disturb the orientation of lipid tails in the vicinity of peptides. These distortions are minimized around pore structures. We also show that membrane-bound β-sheets become twisted with one of their extremities partially penetrating the lipid bilayer. This allows peptides on opposite leaflets to interact and form a long transmembrane β-sheet, which initiates poration. In simulations, where peptides are deposited on a single leaflet, the twist in β-sheets allows them to penetrate the membrane and form pores. In addition, our simulations show that fibril-like structures produce little damage to lipid membranes, as non-polar side chains in these structures are unavailable to interact with the acyl tail of lipids.

Complications of the Percutaneous Mitral Valve Edge-To-Edge Repair: Role of Transesophageal Echocardiography

The use of transcatheter edge-to-edge repair for the treatment of mitral regurgitation has markedly increased in the last few years. The rate of adverse events related to the procedure is low; however, some of the complications that may occur are potentially dangerous. Due to the growing popularity of the technique, which is no longer limited to high-volume centers, knowledge of the complications related to the procedure is fundamental. Transesophageal echocardiography has a key role in the guidance of the intervention while allowing for the avoidance of most of these adverse events, as well as enabling us to diagnose them early. In this article, we review the main complications that might present during a transcatheter mitral edge-to-edge repair procedure (tamponade, thromboembolic events, single leaflet device attachment, device embolization, vascular injury…) while highlighting key aspects of transesophageal echocardiographic monitoring in the prevention and prompt diagnosis of these complications.

EP-296 Introduction of an Information Leaflet for Patients Presenting with Hand Injuries

Abstract Aim Patient Information Leaflets (PILs) are an effective way to educate patients, involve them in their care, and improve communication between patient and clinician. Our department did not have a PIL covering all hand injuries in single leaflet, therefore we decided to make one. Method We created a PIL to give to all patients with hand injuries that were seen in the Emergency Department by Plastic Surgery. The PIL explains what will happen if they need surgical intervention, or if the injury can be managed conservatively. In our hospital, Plastic Surgery covers hand injuries on Fridays, Saturdays, and Sundays and then patients are either planned for dedicated trauma lists during the week or for follow up in the Hand Trauma Review Clinic. Results The leaflet detailed the follow up patients could expect, as well as red flag symptoms to look out for, and who to contact should any problems arise. The PIL enabled us to emphasise the importance of adherence to advice given by healthcare professionals, particularly on any dressings and splints provided to the patients. Conclusion While the leaflet is generic in nature to cover all injuries, specific advice is given in addition to the leaflet to ensure that patients have the best possible care. In the future, we would like to make the leaflet electronic in order to reduce waste and risk of infection. Ideally, patients could scan a QR code taking them directly to the relevant part of the leaflet.

Reoperation after Coronary Artery Bypass Grafting; On-Pump Beating Heart Minimally Invasive Mitral Valve Replacement for Single Leaflet Device Attachment after MitraClip Placement

Reoperation after Coronary Artery Bypass Grafting; On-Pump Beating Heart Minimally Invasive Mitral Valve Replacement for Single Leaflet Device Attachment after MitraClip Placement

The interaction and orientation of Peptide KL[formula omitted] in model membranes

We report on the orientation and location of synthetic pulmonary surfactant peptide KL4, (KLLLL)4K, in model lipid membranes. The partitioning depths of selectively deuterated leucine residues within KL4 were determined in DPPC:POPG (4:1) and POPC:POPG (4:1) bilayers by oriented neutron diffraction. These measurements were combined with an NMR-generated model of the peptide structure to determine the orientation and partitioning of the peptide at the lipid–water interface. The results demonstrate KL4 adopting an orientation that interacts with a single membrane leaflet. These observations are consistent with past 2H NMR and EPR studies (Antharam et al., 2009; Turner et al., 2014).

MitraClip Treatment of Moderate-to-Severe and Severe Mitral Regurgitation in High Surgical Risk Patients - Real-World 1-Year Outcomes From Japan.

The MitraClip NT System was approved for marketing in Japan on October 31, 2017, and a prospective, multi-center, single-arm Post-Marketing use Surveillance (PMS) study was launched in 2018. This is the first report of the Japan PMS study with 1-year subject outcomes.Methods and Results:A total of 500 patients were registered between April 2018 and January 2019. Patients with symptomatic chronic moderate-to-severe (3+) or severe mitral regurgitation (MR; 4+), MR with a Society of Thoracic Surgery (STS) replacement score of ≥8%, or presence of 1 pre-defined risk factor were enrolled. Primary outcome measures included acute procedural success (APS), and rate of Single Leaflet Device Attachment (SLDA) at 30 days. The overall cohort was elderly (77.9±9.48 years) with functional MR etiology in 71.6% of the subjects. The majority of subjects were New York Heart Association (NYHA) class III/IV (68.9%), with mean STS replacement score of 11.95±9.66%. The APS rate was 91.13% and the 30-day SLDA rate was 1.21%. Durable MR reduction was achieved with 88.1% of subjects at MR ≤2+ at 1 year. Significant improvement in the functional capacity was observed, with 93% of subjects at NYHA class I/II at 1 year. In the Japan PMS experience, the MitraClip procedure resulted in improvements in MR severity, with significantly improved functional outcomes. These results demonstrate safety and efficacy of MitraClip therapy in the eligible Japanese population.

Developmental Analysis of Compound Leaf Development in Arachis hypogaea.

Leaves are the primary photosynthetic structures, while photosynthesis is the direct motivation of crop yield formation. As a legume plant, peanut (Arachis hypogaea) is one of the most economically essential crops as well as an important source of edible oil and protein. The leaves of A. hypogaea are in the tetrafoliate form, which is different from the trifoliate leaf pattern of Medicago truncatula, a model legume species. In A. hypogaea, an even-pinnate leaf with a pair of proximal and distal leaflets was developed; however, only a single terminal leaflet and a pair of lateral leaflets were formed in the odd-pinnate leaf in M. truncatula. In this study, the development of compound leaf in A. hypogaea was investigated. Transcriptomic profiles revealed that the common and unique differentially expressed genes were identified in a proximal leaflet and a distal leaflet, which provided a research route to understand the leaf development in A. hypogaea. Then, a naturally occurring mutant line with leaf developmental defects in A. hypogaea was obtained, which displayed a pentafoliate form with an extra terminal leaflet. The characterization of the mutant indicated that cytokinin and class I KNOTTED-LIKE HOMEOBOX were involved in the control of compound leaf pattern in A. hypogaea. These results expand our knowledge and provide insights into the molecular mechanism underlying the formation of different compound leaf patterns among species.

Management and Outcome of FailedPercutaneous Edge-to-Edge MitralValvePlasty: Insight From an International Registry.

This study evaluated the incidence, management, and outcome of patients who experienced MitraClip (Abbott Vascular) failure secondary to loss of leaflet insertion (LLI), single leaflet detachment (SLD), or embolization. Transcatheter edge-to-edge repair with MitraClip is an established therapy for the treatment of mitral regurgitation (MR), but no data exist regarding the prevalence and outcome according to the mode of clip failure. Between January 2009 and December 2020, we retrospectively screened 4,294 procedures of MitraClip performed in 19 centers. LLI was defined as damage to the leaflet where the MitraClip was attached, SLD as demonstration of complete separation between the device and a single leaflet tissue, and clip embolization as loss of contact between MitraClip and both leaflets. A total of 147 cases of MitraClip failure were detected (overall incidence=3.5%), and these were secondary to LLI or SLD in 47 (31.9%) and 99 (67.3%) cases, respectively, whereas in 1 (0.8%) case clip embolization was observed. MitraClip failure occurred in 67 (45.5%) patients with functional MR, in 64 (43.5%) patients with degenerative MR, and 16 (10.8%) with mixed etiology. Although the majority of MitraClip failures were detected before discharge (47 intraprocedural and 42 in the hospital), up to 39.5% of cases were diagnosed at follow-up. In total, 80 (54.4%) subjects underwent a redo procedure, either percutaneously with MitraClip (n=51, 34.7%) or surgically (n=36, 24.5%) including 4 cases of surgical conversion of the index procedure and 7 cases of bailout surgery after unsuccessful redo MitraClip. After a median follow-up of 163days (IQR: 22-720days), 50 (43.9%) subjects presented moderate to severe MR, and 43 (29.3%) patients died. An up-front redo MitraClip strategy was associated with a trend toward a reduced rate of death at follow-up vs surgical or conservative management (P=0.067), whereas postprocedural acute kidney injury, age, and moderate to severe tricuspid regurgitation were independent predictors of death. MitraClip failure secondary to LLI and SLD is not a rare phenomenon and may occur during and also beyond hospitalization. Redo MitraClip strategy demonstrates a trend toward a reduced risk of death compared with bailout surgery and conservative management. A third of those patients remained with more than moderate MR and had substantial mortality at the intermediate-term follow-up.

Incidence and standardised definitions of mitral valve leaflet adverse events after transcatheter mitral valve repair: the EXPAND study.

An independent panel of experts reviewed all investigator-reported cases of mitral valve leaflet adverse events (LAE) after MitraClip NTR/XTR in the EXPAND study. We aimed to report the findings of the expert panel and standardise definitions for LAE. Standard definitions for different types of LAE were formulated and events adjudicated after detailed review by the expert panel. Enrolling centres reported LAE in 35 cases, 11 leaflet injuries (9 tears, 2 perforations) and 24 single leaflet device attachment (SLDA). The panel confirmed LAE in 20 cases (2.0% incidence), 18 patients had SLDA and 4 had leaflet injury (2 cases had both SLDA and injury). Leaflet injury occurred during device implant and resulted in surgical valve replacement or death. SLDA-alone events were identified during implant (n=2), pre-discharge (n=7) or at 30 days of follow-up (n=7) and were resolved (≤2+ residual MR) with additional clips in 75% of cases. Mitral valve repair with MitraClip NTR/XTR is safe. The rate of LAE is lower than previously reported using older-generation devices. The proposed definitions and findings will help to differentiate leaflet injury from inadequate leaflet insertion and SLDA and provide guidance for consistent diagnosis of LAE post MitraClip implantation.

Abstract 14158: Cardiac Leaflet Enhancement (CARLEN) Treats Functional Mitral Regurgitation While Preserving the Native Valve Dynamics

Introduction: Interventional repair of functional mitral regurgitation (FMR) is rapidly replacing traditional surgical correction as surgery is contraindicated in most FMR patients. Current treatments reduce FMR acutely but unfavorably alter mitral valve (MV) geometry resulting in MR recurrence over time and are restricted to use in specific anatomies. We developed a new focal leaflet augmentation approach ( Fig. 1A ) that augments a single leaflet to correct FMR without the disturbing MV dynamics. Hypothesis: We hypothesize that Cardiac leaflet enhancing (CARLEN) implant can effectively correct regurgitation in different geometries seen clinically in FMR patients. Methods: CARLEN was laser cut from a thin sheet of nitinol and shape set to form a 3D structure with two arms that grasp the leaflet and a balloon like section that enables leaflet enhancement ( Fig. 1B ). A trans-septal delivery system was developed and the feasibility of deployment was tested in a swine model ( Fig. 2 ). CARLEN functionality was tested and compared to Edge-to-Edge repair (EE) in an in-vitro left heart simulator with an isolated pig MV (n=6) in different valve geometries seen in FMR patients: a) Annular dilation (AD) alone (aFMR), b) AD+asymmetric tethering (iFMR), and c) AD+symmetric tethering (dFMR). Results: CARLEN consistently and significantly decreased FMR in all geometries (aFMR: 14.79±3.11% vs 6.79±1.90%; iFMR: 20.52±2% vs 6.64±2.16%; dFMR: 21.93±7.2% vs 7.12±2.83%, p&lt;0.05). However, significant reduction after EE was seen only in iFMR and dFMR ( Fig. 3 ). CARLEN did not perturb leaflet kinematics whereas leaflet mobility was significantly decreased after EE ( Fig. 4 ) in all geometries. Conclusion: Focal leaflet enhancement with CARLEN can effectively correct regurgitation in all clinically relevant valve geometries associated with FMR, potentially expanding the opportunity for transcatheter repair to a larger patient population.

Abstract 11144: Mitral Valve Leaflet Strains Are Unphysiologically Altered After Mitraclip to Repair Functional Mitral Regurgitation

Introduction: Transcatheter edge-to-edge repair (TEER) by approximating the leaflet edges with the MitraClip system ( Fig. A ) is rapidly gaining momentum as the primary therapy for repair of functional mitral regurgitation. Though effective acutely, the unphysiological mechanics that TEER imposes on the valve can be substantial and effect durability of the repair. In this study, we used stereo digital image correlation (sDIC) to quantify the leaflet strains that TEER imposes on the mitral valve in the repair of FMR. Hypothesis: TEER imposes an unphysiological diastolic and early systolic strain on the mitral valve leaflets, which may be associated with poor long-term outcomes. Methods: MVs with intact papillary muscles (PMs) were isolated from porcine hearts and mounted within an acrylic left ventricle chamber. A speckle pattern was imprinted on the valve leaflet surface and a sDIC system with two high-speed cameras imaging at 250 fps recorded synchronized image sequences upon pressurization of the chamber to 120 mm Hg in three different configurations: baseline/healthy, FMR/tethered valve configuration, and with TEER/MitraClip. Results: FMR configuration ( Fig. A2 ) did not alter the peak systolic leaflet strains but elevated the diastolic leaflet strains. The time to peak strain was delayed as well in the FMR configuration. TEER reduced the overall systolic strains on the leaflet from the disease state, but the diastolic strains were further elevated compared to FMR condition. Sub-regional analysis depicted that the leaflet edge section where the TEER was applied was under constantly high strain throughout the cardiac cycle, without an unloading phase. Conclusions: TEER imposes a supraphysiological strain field on the mitral valve leaflet when used to repair FMR. The impact of such strains is not yet known, but may be associated with leaflet remodeling and the 2% of the procedures in which single leaflet detachment has been reported.