Feasibility Study of the Transcatheter Valve Repair System for Severe Tricuspid Regurgitation.

BACKGROUND: Tricuspid regurgitation (TR) is a prevalent disease with limited treatment options. OBJECTIVES: This is the first 30-day report of the U.S. single-arm, multicenter, prospective CLASP TR early feasibility study of the PASCAL transcatheter valve repair system in the treatment of TR. METHODS: Patients with symptomatic TR despite optimal medical therapy, reviewed by the local heart team and central screening committee, were eligible for the study. Data were collected at baseline, discharge, and the 30-day follow-up and were reviewed by an independent clinical events committee and echocardiographic core laboratory. Feasibility endpoints included safety (composite major adverse event [MAE] rate), echocardiographic, clinical, and functional endpoints. RESULTS: Of the 34 patients enrolled in the study, the mean age was 76 years, 53% were women, the mean Society of Thoracic Surgeons score was 7.3%, 88% had atrial fibrillation/flutter, 97% had severe or greater TR, and 79% had New York Heart Association (NYHA) functional class III/IV symptoms. Twenty-nine patients (85%) received implants; at 30 days, 85% of them achieved a TR severity reduction of at least 1 grade, with 52% with moderate or less TR (p < 0.001). The MAE rate was 5.9%, and none of the patients experienced cardiovascular mortality, stroke, myocardial infarction, renal complication, or reintervention. Eighty-nine percent of the patients improved to NYHA functional class I/II (p < 0.001), the mean 6-min walk distance improved by 71 m (p < 0.001), and the mean Kansas City Cardiomyopathy Questionnaire score improved by 15 points (p < 0.001). CONCLUSIONS: In this early experience, the repair system performed as intended, with substantial TR reduction, favorable safety results with a low MAE rate, no mortality or reintervention, and significant improvements in functional status, exercise capacity, and quality of life. (Edwards CLASP TR EFS [CLASP TR EFS]; NCT03745313).

Early Feasibility Study of Cardioband Tricuspid System for Functional Tricuspid Regurgitation: 30-Day Outcomes.

OBJECTIVES: The study reports for the first time the 30-day outcomes of the first U.S. study with the Cardioband tricuspid valve reconstruction system for the treatment of functional tricuspid regurgitation (TR). BACKGROUND: Increasing severity of TR is associated with progressively higher morbidity and mortality; however, treatment options for isolated significant disease are limited. METHODS: In this single-arm, multicenter, prospective Food and Drug Administration-approved early feasibility study (EFS), 30 patients with severe or greater symptomatic functional TR were enrolled who were deemed candidates for transcatheter tricuspid repair with the Cardioband tricuspid system by the local heart team and multidisciplinary screening committee. RESULTS: The mean patient age was 77 years, 80% were women, 97% had atrial fibrillation, 70% were in New York Heart Association functional class III to IV with mean left ventricular ejection fraction of 58%, and 27% had severe, 20% massive, and 53% torrential TR. Device success was 93% and all patients were alive at 30 days. Between baseline and 30 days, septolateral tricuspid annular diameter was reduced by 13% (p < 0.001), 85% of patients had ≥1 grade TR reduction and 44% had ≤moderate TR, 75% were in New York Heart Association functional class I to II (p < 0.001), and overall Kansas City Cardiomyopathy Questionnaire score improved by 16 points (p < 0.001). CONCLUSIONS: In patients with severe symptomatic functional TR, this is the first study in the United States with the Cardioband tricuspid system for direct transcatheter annular reduction. This early feasibility study demonstrates high procedural feasibility with no 30-day mortality. There is significant reduction of functional TR with clinically significant improvements in functional status and quality of life. (Edwards Cardioband Tricuspid Valve Reconstruction System Early Feasibility Study; NCT03382457).

Transcatheter Valve Repair for Patients With Mitral Regurgitation: 30-Day Results of the CLASP Study.

OBJECTIVES: The authors report the procedural and 30-day results of the PASCAL Transcatheter Valve Repair System (Edwards Lifesciences, Irvine, California) in patients with mitral regurgitation (MR) enrolled in the multicenter, prospective, single-arm CLASP study. BACKGROUND: Severe MR may lead to symptoms, impaired quality of life, and reduced functional capacity when untreated. METHODS: Eligible patients had grade 3+ or 4+ MR despite optimal medical therapy and were deemed appropriate for the study by the local heart team. All outcomes were assessed through 30 days post-procedure. Major adverse events (MAEs) were adjudicated by an independent clinical events committee, and echocardiographic images were assessed by a core laboratory. The primary safety endpoint was the rate of MAEs at 30 days. RESULTS: Between June 2017 and September 2018, 62 patients with grade 3+ or 4+ MR were enrolled. The mean age was 76.5 years, and 51.6% of patients were in New York Heart Association functional class III or IV, with 56% functional, 36% degenerative, and 8% mixed MR etiology. At 30 days, the MAE rate was 6.5%, with an all-cause mortality rate of 1.6% and no occurrence of stroke; 98% had MR grade ≤2+, with 86% with MR grade ≤1+ (p < 0.0001); and 85% were in New York Heart Association functional class I or II (p < 0.0001). Six-minute walk distance improved by 36 m (p = 0.0018), and Kansas City Cardiomyopathy Questionnaire and EQ-5D scores improved by 17 (p < 0.0001) and 10 (p = 0.0004) points, respectively. CONCLUSIONS: The PASCAL repair system showed feasibility and acceptable safety in the treatment of patients with grade 3+ or 4+ MR. MR severity, irrespective of etiology, was significantly reduced and accompanied by clinically and statistically significant improvements in functional status, exercise capacity, and quality of life. (The CLASP Study Edwards PASCAL Transcatheter Mitral Valve Repair System Study; NCT03170349).

6-Month Outcomes of Tricuspid Valve Reconstruction for Patients With Severe Tricuspid Regurgitation.

BACKGROUND: Severe tricuspid regurgitation (TR) is associated with high morbidity and mortality rates with limited treatment options. OBJECTIVES: The authors report the 6-month safety and performance of a transcatheter tricuspid valve reconstruction system in the treatment of moderate to severe functional TR in 30 patients enrolled in the TRI-REPAIR (TrIcuspid Regurgitation RePAIr With CaRdioband Transcatheter System) study. METHODS: Between October 2016 and July 2017, 30 patients were enrolled in this single-arm, multicenter, prospective trial. Patients were diagnosed with moderate to severe, symptomatic TR in the absence of untreated left-heart disease and deemed inoperable because of unacceptable risk for open-heart surgery by the local heart team. Clinical, functional, and echocardiographic data were prospectively collected before and up to 6 months post-procedure. An independent core lab assessed all echocardiographic data, and an independent clinical event committee adjudicated the safety events. RESULTS: Mean patient age was 75 years, 73% were female, and 23% had ischemic heart disease. At baseline, 83% were in New York Heart Association (NYHA) functional class III to IV, and mean left ventricular ejection fraction was 58%. Technical success was 100%. Through 6 months, 3 patients died. Between 6 months and baseline, echocardiography showed average reductions of annular septolateral diameter of 9% (42 mm vs. 38 mm; p < 0.01), proximal isovelocity surface area effective regurgitant orifice area of 50% (0.8 cm2 vs. 0.4 cm2; p < 0.01), and mean vena contracta width of 28% (1.2 cm vs. 0.9 cm; p < 0.01). Clinical assessment showed that 76% of patients improved by at least 1 NYHA functional class with 88% in NYHA functional class I or II. Six-minute walk distance improved by 60 m (p < 0.01), and Kansas City Cardiomyopathy Questionnaire score improved by 24 points (p < 0.01). CONCLUSIONS: Six-month outcomes show that the system performs as intended and appears to be safe in patients with symptomatic and moderate to severe functional TR. Significant reduction of TR through decrease of annular dimensions, improvements in heart failure symptoms, quality of life, and exercise capacity were observed. Further studies are warranted to validate these initial promising results. (TrIcuspid Regurgitation RePAIr With CaRdioband Transcatheter System [TRI-REPAIR]; NCT02981953).

Apical pressure created during irrigation with the GentleWave™ system compared to conventional syringe irrigation.

OBJECTIVES: The purpose of this study is to compare pressures at the apical foramen created by conventional syringe irrigation and the GentleWave™ System, which releases high-velocity degassed irrigants to the pulp chamber and uses broad-spectrum sound energy for cleaning. MATERIALS AND METHODS: The apical pressure generated during irrigation was measured for palatal and distobuccal root canals of four extracted maxillary molars after no instrumentation, minimal instrumentation to a size #15/.04, instrumentation to a size #40/.04 taper, and after perforating the apical foramen to size #40. The root canals opened into an air-tight custom fixture coupled to a piezoresistive pressure transducer. Apical pressures were measured for the GentleWave™ System and syringe-needle irrigation at different irrigant flow rates, with the needle tip at 1 and 3 mm from the apical foramen using 30-gauge (G) open-ended or side-vented safety tip needles. RESULTS: The GentleWave™ System generated negative apical pressures (P < 0.001 compared with syringe irrigation); the mean pressures were between -13.07 and -17.19 mmHg. The 30 G needles could not reach the 1 and 3 mm from the working length in uninstrumented and 1 mm in minimally instrumented canals. The mean positive pressures between 6.46 and 110.34 mmHg were measured with needle irrigation depending on the flow rate, needle insertion depth, and size of the root canal. CONCLUSIONS: The GentleWave™ System creates negative pressure at the apical foramen during root canal cleaning irrespective of the size of canal instrumentation. Positive apical pressures were measured for syringe irrigation. CLINICAL RELEVANCE: Negative pressure during irrigation contributes to improved safety as compared to high-positive pressure.

Effectiveness of the GentleWave System in Removing Separated Instruments.

INTRODUCTION: A separated instrument in a root canal system has the potential of severely affecting the outcome of endodontic therapy. This study evaluated the effectiveness of the minimally invasive GentleWave System (Sonendo Inc, Laguna Hills, CA) in removing separated stainless steel endodontic files from the apical and midroot regions of molar root canals. METHODS: Thirty-six extracted human molars were accessed, and the glide path was confirmed to the apex. ISO #10, #15, and #20 K-file fragments of 2.5-mm length were separated at the apical (n = 18) or midroot (n = 18) region of the molars by engaging a weakened file with downward pressure. During analysis, the teeth were divided into 2 curved groups based on the curvature of the root (<30° and >30°). The success rate of instrument removal and the treatment time were noted. Statistical comparison was done with the Fisher exact test and independent 2-sample t test (P < .05). RESULTS: The overall success rate of instrument removal when the separated files were engaged in the apical region was 61%, and for the midroot region, it was 83%. Less curved canals (<30°) showed a 91% success rate (n = 24), whereas canals with an angle of curvature greater than 30° showed a 42% success rate (n = 12). The median treatment time for instrument retrieval was 10 minutes 44 seconds. CONCLUSIONS: The results revealed that the GentleWave System is effective in retrieving separated instruments while conserving the dentinal structure.

Evaluation of Root Canal Debridement of Human Molars Using the GentleWave System.

INTRODUCTION: Studies using conventional endodontic protocols show insufficient cleaning of root canal systems, often resulting in persistent infection and treatment failure. The GentleWave System (GWS; Sonendo, Inc, Laguna Hills, CA) has been shown to result in a higher tissue dissolution rate in a study using bovine muscle. The purpose of this study was to compare the debridement efficacy of the GWS with a traditional method for cleaning root canals. METHODS: Forty-five freshly extracted molars were randomly separated into 3 treatment groups (n = 15/group): group 1, no treatment; group 2, conventional rotary instrumentation and needle irrigation; and group 3, minimal instrumentation and the GWS treatment. Roots were prepared per standard histologic tissue processing after hematoxylin-eosin staining; sections were microscopically examined, and the percentage of soft tissue and debris remaining within the canals was morphometrically calculated. Images of the apical and middle regions of the roots were blindly analyzed. RESULTS: Significant differences (Welch's t test) were found between groups 2 and 3 in both apical (P = .0015) and middle (P = .0179) regions of the mesial roots of mandibular molars and mesiobuccal roots of maxillary molars. Groups 2 and 3 resulted in cleaning 67.8% and 97.2% of the mesiobuccal and mesiolingual root canals of mandibular molars and the mesiobuccal canals of maxillary molars, respectively, whereas the results were similar among groups 2 and 3 in the apical and middle regions of distal roots. Groups 2 and 3 revealed significantly less debris than group 1 (P < .005). CONCLUSIONS: The GWS showed a significantly greater cleaning capacity and reduction in residual debris within the mesiobuccal and mesiolingual canals of mandibular molars and the mesiobuccal canals of maxillary molars than those cleaned conventionally.

Comparative endothelial cell response on topographically patterned titanium and silicon substrates with micrometer to sub-micrometer feature sizes.

In this work, we evaluate the in vitro response of endothelial cells (EC) to variation in precisely-defined, micrometer to sub-micrometer scale topography on two different substrate materials, titanium (Ti) and silicon (Si). Both substrates possess identically-patterned surfaces composed of microfabricated, groove-based gratings with groove widths ranging from 0.5 to 50 µm, grating pitch twice the groove width, and groove depth of 1.3 µm. These specific materials are chosen due to their relevance for implantable microdevice applications, while grating-based patterns are chosen for the potential they afford for inducing elongated and aligned cellular morphologies reminiscent of the native endothelium. Using EA926 cells, a human EC variant, we show significant improvement in cellular adhesion, proliferation, morphology, and function with decreasing feature size on patterned Ti substrates. Moreover, we show similar trending on patterned Si substrates, albeit to a lesser extent than on comparably patterned Ti substrates. Collectively, these results suggest promise for sub-micrometer topographic patterning in general, and sub-micrometer patterning of Ti specifically, as a means for enhancing endothelialization and neovascularisation for novel implantable microdevice applications.

Microfluidic space-domain time-resolved emission spectroscopy of terbium(III) and europium(III) chelates with pyridine-2,6-dicarboxylate.

This article describes the utilization of laminar microflows for time-resolved emission measurements with steady-state excitation and detection. Passing a laminar flow through a short illuminated section of a microchannel provided a means for pulsed-like photoexcitation of the moieties carried by the fluid. Imaging the microchannel flows carrying thus photoexcited chelates of lanthanide ions allowed us to extract their excited-state lifetimes from the spatial distribution of the changes in the emission intensity. The lifetime values obtained using this space-domain approach agreed well with the lifetimes from time-domain measurements. This validated space-domain microfluidic approach reveals a means for miniaturization of time-resolved emission spectroscopy.

Flow-dependent mass transfer may trigger endothelial signaling cascades.

It is well known that fluid mechanical forces directly impact endothelial signaling pathways. But while this general observation is clear, less apparent are the underlying mechanisms that initiate these critical signaling processes. This is because fluid mechanical forces can offer a direct mechanical input to possible mechanotransducers as well as alter critical mass transport characteristics (i.e., concentration gradients) of a host of chemical stimuli present in the blood stream. However, it has recently been accepted that mechanotransduction (direct mechanical force input), and not mass transfer, is the fundamental mechanism for many hemodynamic force-modulated endothelial signaling pathways and their downstream gene products. This conclusion has been largely based, indirectly, on accepted criteria that correlate signaling behavior and shear rate and shear stress, relative to changes in viscosity. However, in this work, we investigate the negative control for these criteria. Here we computationally and experimentally subject mass-transfer limited systems, independent of mechanotransduction, to the purported criteria. The results showed that the negative control (mass-transfer limited system) produced the same trends that have been used to identify mechanotransduction-dominant systems. Thus, the widely used viscosity-related shear stress and shear rate criteria are insufficient in determining mechanotransduction-dominant systems. Thus, research should continue to consider the importance of mass transfer in triggering signaling cascades.