Transcatheter Repair for Patients with Tricuspid Regurgitation.

BACKGROUND: Severe tricuspid regurgitation is a debilitating condition that is associated with substantial morbidity and often with poor quality of life. Decreasing tricuspid regurgitation may reduce symptoms and improve clinical outcomes in patients with this disease. METHODS: We conducted a prospective randomized trial of percutaneous tricuspid transcatheter edge-to-edge repair (TEER) for severe tricuspid regurgitation. Patients with symptomatic severe tricuspid regurgitation were enrolled at 65 centers in the United States, Canada, and Europe and were randomly assigned in a 1:1 ratio to receive either TEER or medical therapy (control). The primary end point was a hierarchical composite that included death from any cause or tricuspid-valve surgery; hospitalization for heart failure; and an improvement in quality of life as measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ), with an improvement defined as an increase of at least 15 points in the KCCQ score (range, 0 to 100, with higher scores indicating better quality of life) at the 1-year follow-up. The severity of tricuspid regurgitation and safety were also assessed. RESULTS: A total of 350 patients were enrolled; 175 were assigned to each group. The mean age of the patients was 78 years, and 54.9% were women. The results for the primary end point favored the TEER group (win ratio, 1.48; 95% confidence interval, 1.06 to 2.13; P = 0.02). The incidence of death or tricuspid-valve surgery and the rate of hospitalization for heart failure did not appear to differ between the groups. The KCCQ quality-of-life score changed by a mean (±SD) of 12.3±1.8 points in the TEER group, as compared with 0.6±1.8 points in the control group (P<0.001). At 30 days, 87.0% of the patients in the TEER group and 4.8% of those in the control group had tricuspid regurgitation of no greater than moderate severity (P<0.001). TEER was found to be safe; 98.3% of the patients who underwent the procedure were free from major adverse events at 30 days. CONCLUSIONS: Tricuspid TEER was safe for patients with severe tricuspid regurgitation, reduced the severity of tricuspid regurgitation, and was associated with an improvement in quality of life. (Funded by Abbott; TRILUMINATE Pivotal ClinicalTrials.gov number, NCT03904147.).

Five-Year Follow-up after Transcatheter Repair of Secondary Mitral Regurgitation.

BACKGROUND: Data from a 5-year follow-up of outcomes after transcatheter edge-to-edge repair of severe mitral regurgitation, as compared with outcomes after maximal doses of guideline-directed medical therapy alone, in patients with heart failure are now available. METHODS: We randomly assigned patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy to undergo transcatheter edge-to-edge repair plus receive medical therapy (device group) or to receive medical therapy alone (control group) at 78 sites in the United States and Canada. The primary effectiveness end point was all hospitalizations for heart failure through 2 years of follow-up. The annualized rate of all hospitalizations for heart failure, all-cause mortality, the risk of death or hospitalization for heart failure, and safety, among other outcomes, were assessed through 5 years. RESULTS: Of the 614 patients enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of hospitalization for heart failure through 5 years was 33.1% per year in the device group and 57.2% per year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.41 to 0.68). All-cause mortality through 5 years was 57.3% in the device group and 67.2% in the control group (hazard ratio, 0.72; 95% CI, 0.58 to 0.89). Death or hospitalization for heart failure within 5 years occurred in 73.6% of the patients in the device group and in 91.5% of those in the control group (hazard ratio, 0.53; 95% CI, 0.44 to 0.64). Device-specific safety events within 5 years occurred in 4 of 293 treated patients (1.4%), with all the events occurring within 30 days after the procedure. CONCLUSIONS: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite guideline-directed medical therapy, transcatheter edge-to-edge repair of the mitral valve was safe and led to a lower rate of hospitalization for heart failure and lower all-cause mortality through 5 years of follow-up than medical therapy alone. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079.).

Leaflet modification before transcatheter aortic valve implantation in patients at risk for coronary obstruction: the ShortCut study.

BACKGROUND AND AIMS: This trial sought to assess the safety and efficacy of ShortCut, the first dedicated leaflet modification device, prior to transcatheter aortic valve implantation (TAVI) in patients at risk for coronary artery obstruction. METHODS: This pivotal prospective study enrolled patients with failed bioprosthetic aortic valves scheduled to undergo TAVI and were at risk for coronary artery obstruction. The primary safety endpoint was procedure-related mortality or stroke at discharge or 7 days, and the primary efficacy endpoint was per-patient leaflet splitting success. Independent angiographic, echocardiographic, and computed tomography core laboratories assessed all images. Safety events were adjudicated by a clinical events committee and data safety monitoring board. RESULTS: Sixty eligible patients were treated (77.0 ± 9.6 years, 70% female, 96.7% failed surgical bioprosthetic valves, 63.3% single splitting and 36.7% dual splitting) at 22 clinical sites. Successful leaflet splitting was achieved in all (100%; 95% confidence interval [CI] 94-100.0%, p<0.001) patients. Procedure time, including imaging confirmation of leaflet splitting, was 30.6 ± 17.9 min. Freedom from the primary safety endpoint was achieved in 59 (98.3%; 95% CI [91.1-100%]) patients, with no mortality and one (1.7%) disabling stroke. At 30 days, freedom from coronary obstruction was 95% (95% CI 86.1-99.0%). Within 90 days, freedom from mortality was 95% (95% CI 86.1-99.0%]), without any cardiovascular deaths. CONCLUSIONS: Modification of failed bioprosthetic aortic valve leaflets using ShortCut was safe, achieved successful leaflet splitting in all patients, and was associated with favorable clinical outcomes in patients at risk for coronary obstruction undergoing TAVI.

Rationale and design of a randomized study comparing the Watchman FLX device to DOACs in patients with atrial fibrillation.

BACKGROUND: Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a nonpharmacologic alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacologic strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy. STUDY DESIGN: A total of 3,000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months postimplant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary end points will be evaluated at 3 years: (1) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for noninferiority, and (2) nonprocedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant nonmajor bleeding) tested for superiority in the device arm against DOACs. The third primary noninferiority end point is the composite of ischemic stroke and systemic embolism at 5 years. Secondary end points include 3- and 5-year rates of (1) ISTH-defined major bleeding and (2) the composite of cardiovascular death, all stroke, systemic embolism, and nonprocedural ISTH bleeding. CONCLUSIONS: This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF. CLINICAL TRIAL REGISTRATION: NCT04394546.

Three-year outcomes for transcatheter repair in patients with mitral regurgitation from the CLASP study.

BACKGROUND: Mitral valve transcatheter edge-to-edge repair (M-TEER) is an effective option for treatment of mitral regurgitation (MR). We previously reported favorable 2-year outcomes for the PASCAL transcatheter valve repair system. OBJECTIVES: We report 3-year outcomes from the multinational, prospective, single-arm CLASP study with analysis by functional MR (FMR) and degenerative MR (DMR). METHODS: Patients with core-lab determined MR ≥ 3+ were deemed candidates for M-TEER by the local heart team. Major adverse events were assessed by an independent clinical events committee to 1 year and by sites thereafter. Echocardiographic outcomes were evaluated by the core laboratory to 3 years. RESULTS: The study enrolled 124 patients, 69% FMR; 31% DMR (60% NYHA class III-IVa, 100% MR ≥ 3+). The 3-year Kaplan-Meier estimate for survival was 75% (66% FMR; 92% DMR) and freedom from heart failure hospitalization (HFH) was 73% (64% FMR; 91% DMR), with 85% reduction in annualized HFH rate (81% FMR; 96% DMR) (p < 0.001). MR ≤ 2+ was achieved and maintained in 93% of patients (93% FMR; 94% DMR) and MR ≤ 1+ in 70% of patients (71% FMR; 67% DMR) (p < 0.001). The mean left ventricular end-diastolic volume (181 mL at baseline) decreased progressively by 28 mL [p < 0.001]. NYHA class I/II was achieved in 89% of patients (p < 0.001). CONCLUSIONS: The 3-year results from the CLASP study demonstrated favorable and durable outcomes with the PASCAL transcatheter valve repair system in patients with clinically significant MR. These results add to the growing body of evidence establishing the PASCAL system as a valuable therapy for patients with significant symptomatic MR.

Impact of baseline renal dysfunction on cardiac outcomes and end-stage renal disease in heart failure patients with mitral regurgitation: the COAPT trial.

AIMS: Baseline renal dysfunction (RD) adversely impacts outcomes among patients with heart failure (HF) and severe secondary mitral regurgitation (MR). Heart failure and MR, in turn, accelerate progression to end-stage renal disease (ESRD), worsening prognosis. We sought to determine the impact of RD in HF patients with severe MR and the impact of transcatheter mitral valve repair (TMVr) on new-onset ESRD and the need for renal replacement therapy (RRT). METHODS AND RESULTS: The COAPT trial randomized 614 patients with HF and severe MR to MitraClip plus guideline-directed medical therapy (GDMT) vs. GDMT alone. Patients were stratified into three RD subgroups based on baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m2): none (≥60), moderate (30-60), and severe (<30). End-stage renal disease was defined as eGFR <15 mL/min/1.73 m2 or RRT. The 2-year rates of all-cause death or HF hospitalization (HFH), new-onset ESRD, and RRT according to RD and treatment were assessed. Baseline RD was present in 77.0% of patients, including 23.8% severe RD, 6.0% ESRD, and 5.2% RRT. Worse RD was associated with greater 2-year risk of death or HFH (none 45.3%; moderate 53.9%; severe 69.2%; P < 0.0001). MitraClip vs. GDMT alone improved outcomes regardless of RD (Pinteraction = 0.62) and reduced new-onset ESRD [2.9 vs. 8.1%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.15-0.76, P = 0.008] and the need for new RRT (2.5 vs. 7.4%, HR 0.33, 95% CI 0.14-0.78, P = 0.011). CONCLUSION: Baseline RD was common in the HF patients with severe MR enrolled in COAPT and strongly predicted 2-year death and HFH. MitraClip treatment reduced new-onset ESRD and the need for RRT, contributing to the improved prognosis after TMVr.

Primary Outcome Evaluation of a Next-Generation Left Atrial Appendage Closure Device: Results From the PINNACLE FLX Trial.

BACKGROUND: Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation. Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with nonvalvular atrial fibrillation in whom oral anticoagulation is indicated, but who have an appropriate rationale to seek a nonpharmaceutical alternative. METHODS: This was a prospective, nonrandomized, multicenter US Food and Drug Administration study. The primary safety end point was the occurrence of one of the following events within 7 days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness end point was the incidence of effective LAA closure (peri-device flow ≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. RESULTS: A total of 400 patients were enrolled. The mean age was 73.8±8.6 years and the mean CHA2DS2-VASc score was 4.2±1.5. The incidence of the primary safety end point was 0.5% with a 1-sided 95% upper CI of 1.6%, meeting the performance goal of 4.2% (P<0.0001). The incidence of the primary effectiveness end point was 100%, with a 1-sided 95% lower CI of 99.1%, again meeting the performance goal of 97.0% (P<0.0001). Device-related thrombus was reported in 7 patients, no patients experienced pericardial effusion requiring open cardiac surgery, and there were no device embolizations. CONCLUSIONS: LAA closure with this next-generation LAA closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02702271.

Relationship Between Residual Mitral Regurgitation and Clinical and Quality-of-Life Outcomes After Transcatheter and Medical Treatments in Heart Failure: COAPT Trial.

BACKGROUND: In the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation), among 614 patients with heart failure with 3+ or 4+ secondary mitral regurgitation (MR), transcatheter mitral valve repair (TMVr) with the MitraClip reduced MR, heart failure hospitalizations, and mortality and improved quality of life compared with guideline-directed medical therapy (GDMT) alone. We aimed to examine the prognostic relationship between MR reduction and outcomes after TMVr and GDMT alone. METHODS: Outcomes in COAPT between 30 days and 2 years were examined on the basis of the severity of residual MR at 30 days. RESULTS: TMVr-treated patients had less severe residual MR at 30 days than GDMT-treated patients (0/1+, 2+, and 3+/4+: 72.9%, 19.9%, and 7.2% versus 8.2%, 26.1%, and 65.8%, respectively [P<0.0001]). The rate of composite death or heart failure hospitalizations between 30 days and 2 years was lower in patients with 30-day residual MR of 0/1+ and 2+ compared with patients with 30-day residual MR of 3+/4+ (37.7% versus 49.5% versus 72.2%, respectively [P<0.0001]). This relationship was consistent in the TMVr and GDMT arms (Pinteraction=0.92). The improvement in Kansas City Cardiomyopathy Questionnaire score from baseline to 30 days was maintained between 30 days and 2 years in patients with 30-day MR ≤2+ but deteriorated in those with 30-day MR 3+/4+ (-0.3±1.7 versus -9.4±4.6 [P=0.0008]) consistently in both groups (Pinteraction=0.95). CONCLUSIONS: In the COAPT trial, reduced MR at 30 days was associated with greater freedom from death or heart failure hospitalizations and improved quality of life through 2-year follow-up whether the MR reduction was achieved by TMVr or GDMT. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

Transcatheter Mitral-Valve Repair in Patients with Heart Failure.

BACKGROUND: Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes. METHODS: At 78 sites in the United States and Canada, we enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Patients were randomly assigned to transcatheter mitral-valve repair plus medical therapy (device group) or medical therapy alone (control group). The primary effectiveness end point was all hospitalizations for heart failure within 24 months of follow-up. The primary safety end point was freedom from device-related complications at 12 months; the rate for this end point was compared with a prespecified objective performance goal of 88.0%. RESULTS: Of the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.40 to 0.70; P<0.001). The rate of freedom from device-related complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P<0.001 for comparison with the performance goal). Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001). CONCLUSIONS: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone. The rate of freedom from device-related complications exceeded a prespecified safety threshold. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079 .).

Impact of Percutaneous Edge-to-Edge Repair in Patients With Atrial Functional Mitral Regurgitation.

BACKGROUND: The aim of this study was to clarify the clinical outcomes of patients with atrial functional mitral regurgitation (FMR) who underwent the MitraClip procedure compared with those with conventional FMR and sinus rhythm (SR).Methods and Results:Of 303 patients with FMR who underwent the MitraClip procedure, 40 with "atrial-FMR" defined as FMR with permanent atrial fibrillation and normal left ventricular (LV) function/size and 115 with "sinus-FMR" defined as FMR with SR and LV dysfunction were reviewed. Transthoracic and 3D transesophageal echocardiography, and the cardiac complication rate (composite of all-cause death, heart failure admission, mitral valve (MV) surgery, and redo MitraClip procedure) during the 12-month follow-up were compared between the groups. After the MitraClip procedure, reductions in the mitral annular area and its anteroposterior dimension and in the leaflet closure area were observed in both groups. MV orifice area was smaller with greater transmitral pressure gradient (P<0.05) after the procedure in atrial-FMR patients than in those with sinus-FMR. The prevalence of residual MR was similar, but significant tricuspid regurgitation (TR) was more prevalent in the atrial-FMR group at follow-up. Cardiac complication rate was comparable between groups (20% vs. 25%, P=0.63). CONCLUSIONS: Reduction of MR occurred in atrial-FMR probably because of the increase in leaflet coaptation area. Significant TR was more common after the MitraClip procedure in patients with atrial-FMR than with sinus-FMR. However, mid-term outcomes were comparable between patients with atrial-FMR and sinus-FMR.

Left atrial appendage size in patients with atrial fibrillation in Japan and the United States.

Left atrial appendage (LAA) evaluation is important to select the optimal LAA closure device for patients with atrial fibrillation (AF). The LAA characteristics of Japanese patients remain uninvestigated. We compared the LAA size and morphology between 212 Japanese AF patients before catheter ablation and 119 AF patients undergoing LAA closure in the United States (US). We measured the LAA ostial dimension and depth by transesophageal echocardiography in all patients and determined the LAA morphology types of Japanese patients by multidetector cardiac computed tomography and those of US patients by LAA angiography. The maximum LAA ostial dimension was significantly larger in Japanese patients than in US patients (22.6 ± 4.1 mm vs. 21.5 ± 3.5 mm, P = 0.02). Also, Japanese patients had larger maximum dimension and depth corrected by body surface area than US patients in both paroxysmal and nonparoxysmal AF groups. The angle showing the maximum dimension was 0° or 135° in approximately 75% of patients in both groups. The common LAA morphology types were "cauliflower" and "chicken wing" in Japanese patients and "cactus" and "windsock" in US patients. In this study, Japanese patients had a larger LAA size than US patients. Because the maximum LAA dimension was obtained at the same angles, the LAA measurement method for US patients can be applicable to Japanese patients.

Left ventricular outflow tract area after percutaneous transseptal transcatheter mitral valve implantation: A three-dimensional transesophageal echocardiography study.

BACKGROUND: Left ventricular (LV) outflow tract (LVOT) obstruction increases mortality in patients undergoing transcatheter mitral valve implantation (TMVI) in degenerated bioprostheses, annuloplasty rings, and native mitral valves. We aimed to evaluate the LVOT area after TMVI using 3-dimensional (3D) transesophageal echocardiography (TEE) and to investigate the preprocedural cardiac geometry that affects the LVOT area after TMVI. METHODS: We retrospectively reviewed echocardiography data in 43 patients who had TMVI. A change in pressure gradient across LVOT from before to after TMVI (∆PG) and postprocedure 3D LVOT cross-sectional area at the level of the most distal portion of the mitral valve stent that was closest to the LV apex were assessed as evidence of LVOT narrowing. RESULTS: Transcatheter mitral valve implantation with the use of balloon-expandable valve system was performed for 24 bioprostheses, 7 annuloplasty rings, and 12 native valves. Compared to patients without increase in LVOT gradient (∆PG <10 mm Hg; n = 33), patients with increase in LVOT gradient (∆PG ≥10 mm Hg; n = 10) had smaller LV end-systolic volume (LVESV), greater LV ejection fraction (LVEF), and smaller aorto-mitral (AM) angle. The LVOT area at the valve stent distal edge showed strong association with ∆PG (r = -.68, P < .0001). Only a small AM angle was associated with a small LVOT area at the valve stent distal edge on multivariable analysis, independent of LVESV and LVEF. CONCLUSION: Small LV size, preserved LVEF, and small AM angle were associated with LVOT narrowing. 3D-derived AM angle might be independently associated with LVOT narrowing in patients undergoing transcatheter mitral valve-in-valve, valve-in-ring, and valve-in-native valve implantation, independent of LVESV and LVEF.

One-Year Outcomes After MitraClip for Functional Mitral Regurgitation.

BACKGROUND: Secondary mitral regurgitation (SMR) occurs in the absence of organic mitral valve disease and may develop as the left ventricle dilates or remodels or as a result of leaflet tethering with impaired coaptation, most commonly from apical and lateral distraction of the subvalvular apparatus, with late annular dilatation. The optimal therapy for SMR is unclear. This study sought to evaluate the 1-year adjudicated outcomes of all patients with SMR undergoing the MitraClip procedure in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) Investigational Device Exemption program, which is comprised of the randomized clinical trial, the prospective High-Risk Registry, and the REALISM Continued Access Registry (Multicenter Study of the MitraClip System). METHODS: Patients with 3+/4+ SMR enrolled in EVEREST II were stratified by non-high surgical risk (non-HR) and high surgical risk (HR) status (defined as Society of Thoracic Surgeons risk of mortality ≥12% or predefined risk factors). Clinical, echocardiographic, and functional outcomes at 1 year were evaluated. RESULTS: A total of 616 patients (482 HR, 134 non-HR; mean age, 73.3±10.5 years; Society of Thoracic Surgeons risk, 10.2±6.9%) with SMR underwent the MitraClip procedure. At baseline, 80.5% of patients were in New York Heart Association class III/IV. Major adverse events at 30 days included death (3.6%), stroke (2.3%), and renal failure (1.5%). At discharge, 88.8% had MR ≤2+. At 1 year, there were 139 deaths, and the Kaplan-Meier estimate of freedom from mortality was 76.8%. The majority of surviving patients (84.7%) remained with MR ≤2+ and New York Heart Association class I/II (83.0%). Kaplan-Meier survival at 1 year was 74.1% in HR patients and 86.4% in non-HR patients ( P=0.0175). At 1 year, both groups achieved comparable MR reduction (MR ≤2+, 84.0% versus 87.0%) and improvement in left ventricular end-diastolic volume (-8.0 mL versus -12.7 mL), whereas New York Heart Association class I/II was found in 80.1% versus 91.8% ( P=0.008) of HR and non-HR patients, respectively. In HR patients, the annualized rate of heart failure hospitalizations decreased from 0.68 to 0.46 in the 12 months before to 12 months after the procedure ( P<0.0001). CONCLUSIONS: Transcatheter mitral valve repair with the MitraClip in patients with secondary MR is associated with acceptable safety, reduction of MR severity, symptom improvement, and positive ventricular remodeling. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov . Unique identifiers: NCT00209274, NCT01940120, and NCT01931956.

Long-term transesophageal echocardiography after patent foramen ovale closure by BioSTAR and Amplatzer patent foramen ovale occluders.

OBJECTIVES: To compare transesophageal echocardiography (TOE) findings after patent foramen ovale (PFO) closure by BioSTAR (NMT Medical Inc, Boston, MA) and Amplatzer PFO occluders (Abbott Vascular, Plymouth, MN). BACKGROUND: PFO closure with a biodegradable device represents an attractive alternative to permanent devices. Long-term effectiveness and morphology after biodegradation remain unknown. METHODS: Between February 2008 and June 2014, 49 patients received BioSTAR and 48 Amplatzer PFO occluder. TOE was performed after closure, at 6 months and beyond 2 years. RESULTS: PFO features were comparable between the groups. Immediate effective closure (<5 bubbles on Valsalva) was obtained in 96% by BioSTAR and 88% by Amplatzer PFO occluder (p = .16). Except for transient fever after BioSTAR (10.8 vs. 0%; p = .08), there was no adverse events. TOE at 6 months revealed comparable effective closure (93 vs. 89%; p = .74), all devices in correct position and no thrombus/pericardial effusion. In the BioSTAR group, a peri-device left-to-right color Doppler shunt was documented in one patient (2.2%), protrusion of the nitinol framework strut(s) into the atrial cavity in two patients (4.3%), and both events in one patient (2.2%). TOE beyond 2 years showed comparable effective closure (92 vs. 96%; p = 1.00) and again BioSTAR-associated peri-device left-to-right shunt and metal framework strut(s) protrusion. There was no stroke or peripheral embolization in either group while TIA was numerically greater in BioSTAR patients (6.8 vs. 2.5%; p = .61). CONCLUSION: BioSTAR provided similar PFO closure rate as Amplatzer PFO occluder. As yet unreported BioSTAR-associated peri-device left-to-right shunt and metal framework strut(s) protrusion may have practical implications for further development of biodegradable devices.

Outcomes of transcatheter mitral valve replacement for degenerated bioprostheses, failed annuloplasty rings, and mitral annular calcification.

Aims: We sought to evaluate the outcomes of transcatheter mitral valve replacement (TMVR) for patients with degenerated bioprostheses [valve-in-valve (ViV)], failed annuloplasty rings [valve-in-ring (ViR)], and severe mitral annular calcification [valve-in-mitral annular calcification (ViMAC)]. Methods and results: From the TMVR multicentre registry, procedural and clinical outcomes of ViV, ViR, and ViMAC were compared according to Mitral Valve Academic Research Consortium (MVARC) criteria. A total of 521 patients with mean Society of Thoracic Surgeons score of 9.0 ± 7.0% underwent TMVR (322 patients with ViV, 141 with ViR, and 58 with ViMAC). Trans-septal access and the Sapien valves were used in 39.5% and 90.0%, respectively. Overall technical success was excellent at 87.1%. However, left ventricular outflow tract obstruction occurred more frequently after ViMAC compared with ViR and ViV (39.7% vs. 5.0% vs. 2.2%; P < 0.001), whereas second valve implantation was more frequent in ViR compared with ViMAC and ViV (12.1% vs. 5.2% vs. 2.5%; P < 0.001). Accordingly, technical success rate was higher after ViV compared with ViR and ViMAC (94.4% vs. 80.9% vs. 62.1%; P < 0.001). Compared with ViMAC and ViV groups, ViR group had more frequent post-procedural mitral regurgitation ≥moderate (18.4% vs. 13.8% vs. 5.6%; P < 0.001) and subsequent paravalvular leak closure (7.8% vs. 0.0% vs. 2.2%; P = 0.006). All-cause mortality was higher after ViMAC compared with ViR and ViV at 30 days (34.5% vs. 9.9% vs. 6.2%; log-rank P < 0.001) and 1 year (62.8% vs. 30.6% vs. 14.0%; log-rank P < 0.001). On multivariable analysis, patients with failed annuloplasty rings and severe MAC were at increased risk of mortality after TMVR [ViR vs. ViV, hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.27-3.12; P = 0.003; ViMAC vs. ViV, HR 5.29, 95% CI 3.29-8.51; P < 0.001]. Conclusion: The TMVR provided excellent outcomes for patients with degenerated bioprostheses despite high surgical risk. However, ViR and ViMAC were associated with higher rates of adverse events and mid-term mortality compared with ViV.

Mitral valve repair in an octogenarian with symptomatic severe mitral regurgitation: First use of MitraClip in India.

Percutaneous mitral valve repair is an accepted treatment of choice in Europe and North America for severe primary or secondary mitral regurgitation, in highly symptomatic patients for whom surgical repair is prohibitively high risk. We describe the first use of the MitraClip in India in a frail elderly female with symptomatic heart failure from severe primary mitral regurgitation who was considered high risk for surgical repair. She had substantial improvement in her symptoms as well as quality of life following the procedure.

Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes.

BACKGROUND: In patients with atrial fibrillation, left atrial appendage closure with the Watchman device prevents thromboembolism from the left atrial appendage; however, thrombus may form on the left atrial face of the device, and then potentially embolize. Herein, we studied the incidence, predictors, and clinical outcome of device-related thrombus (DRT) using a large series of clinical trial cohorts of patients undergoing Watchman implantation. METHODS: We studied the device arms of 4 prospective Food and Drug Administration trials: PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) (n=463); PREVAIL (Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) (n=269); CAP (Continued Access to PROTECT AF registry) (n=566); and CAP2 (Continued Access to PREVAIL registry) (n=578). Surveillance transesophageal echocardiographs were performed at 45 days and 12 months in all patients, and also at 6 months in the randomized control trials. We assessed both the incidence of DRT during these transesophageal echocardiographs (and other unscheduled transesophageal echocardiographs), and clinical outcomes of postprocedure stroke or systemic embolism (SSE) and adjusted for CHA2DS2-VASC and HAS-BLED scores. RESULTS: Of 1739 patients who received an implant (7159 patient-years follow-up; CHA2DS2-VASc=4.0), DRT was seen in 65 patients (3.74%). The rates of SSE with and without DRT were 7.46 and 1.78 per 100 patient-years (adjusted rate ratio, 3.55; 95% confidence interval [CI], 2.18-5.79; P<0.001), and ischemic SSE rates were 6.28 and 1.65 per 100 patient-years (adjusted rate ratio, 3.22; 95% CI, 1.90-5.45, P<0.001). On multivariable modeling analysis, the predictors of DRT were as follows: history of transient ischemic attack or stroke (odds ratio [OR], 2.31; 95% CI, 1.26-4.25; P=0.007), permanent atrial fibrillation (OR, 2.24; 95% CI, 1.19-4.20; P=0.012); vascular disease (OR, 2.06; 95% CI, 1.08-3.91; P=0.028); left atrial appendage diameter (OR, 1.06 per mm increase; 95% CI, 1.01-1.12; P=0.019); left ventricular ejection fraction (OR, 0.96 per 1% increase; 95% CI, 0.94-0.99; P=0.009). DRT and SSE both occurred in 17 of 65 patients (26.2%). Of the 19 SSE events in these patients with DRT, 9 of 19 (47.4%) and 12 of 19 (63.2%) occurred within 1 and 6 months of DRT detection. Conversely, after left atrial appendage closure, most SSEs (123/142, 86.62%) occurred in patients without DRT. CONCLUSIONS: After left atrial appendage closure with Watchman, DRT (≈3.7%) is not frequent but, when present, is associated with a higher rate of stroke and systemic embolism.

Cleft mitral leaflets and severe mitral regurgitation: Testing the limits of percutaneous mitral valve repair.

Repair of mitral regurgitation (MR) with the MitraClip device (Abbot Vascular, Menlo Park, CA) to treat degenerative MR is associated with improved acute and long-term outcomes. There is an increasing adoption of the device and operators are now testing the limits of the therapy even for unfavorable anatomies. Isolated cleft mitral leaflets are rare but represent a challenge to percutaneous repair. We present two cases of successful repair of severe MR and cleft mitral leaflets. In the first case, a 52-year-old male with a dilated cardiomyopathy and an ejection fraction (EF) of 15% presented in decompensated heart failure. Workup revealed a pseudo-cleft anterior mitral leaflet and a cleft posterior leaflet. A strategy to treat the restricted posterior leaflet lateral of the posterior cleft with a provisional second clip resulted in trace residual MR with only one clip, and an EF improvement to 50% at 2-month follow-up. In the second case, an 80-year-old male with a history of obstructive CAD with a normal EF but severe MR and a restricted anterior leaflet presented with severe shortness of breath. An initial strategy to grasp the middle of the valve was unsuccessful due to the cleft. Instead, two clips were placed side-by-side on either side of the cleft resulting in trivial residual MR. Despite challenging anatomy percutaneous repair can allow for dramatic reduction in MR, resulting in significant left ventricular remodeling and improvement of EF and cardiac output.

Prevalence of Coronary Endothelial and Microvascular Dysfunction in Women with Symptoms of Ischemia and No Obstructive Coronary Artery Disease Is Confirmed by a New Cohort: The NHLBI-Sponsored Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD).

OBJECTIVE: In a separate, contemporary cohort, we sought to confirm findings of the original Women's Ischemia Syndrome Evaluation (WISE). BACKGROUND: The original WISE observed a high prevalence of both invasively determined coronary endothelial and coronary microvascular dysfunction (CMD) that predicted adverse events in follow-up. METHODS: We comparatively studied the WISE-Coronary Vascular Dysfunction (CVD) cohort (2009-2011), with signs and symptoms of ischemia but without significant CAD, to the original WISE (1997-2001) cohort. CMD was defined as coronary flow reserve (CFR) ≤2.5, or endothelial dysfunction as epicardial coronary artery constriction to acetylcholine (ACH), or <20% epicardial coronary dilation to nitroglycerin (NTG). RESULTS: In WISE (n=181) and WISE-CVD (n=235) women, mean age in both was 54 years, and 83% were white (WISE) vs 74% (WISE-CVD, p=0.04). Use of hormone replacement therapy was less frequent in WISE-CVD vs WISE (46% vs 57%, p=0.026) as was presence of hypertension (40% vs 52%, p=0.013), hyperlipidemia (20% vs 46%, p<0.0001), and smoking (46% vs 56%, p=0.036). Similar rates were observed in WISE-CVD and WISE cohorts for CMD (mean CFR 2.7±0.6 vs 2.6±0.8, p=0.35), mean change in diameter with intracoronary ACH (0.2±10.0 vs 1.6±12.8 mm, p=0.34), and mean change in diameter with intracoronary NTG (9.7±13.0 vs 9.8±13.5 mm, p=0.94), respectively. CONCLUSIONS: This study confirms prevalence of CMD in the contemporary WISE-CVD cohort similar to that of the original WISE cohort, despite a lower risk factor burden in WISE-CVD. Because these coronary functional abnormalities predict major adverse cardiac events, clinical trials of therapies targeting these abnormalities are indicated.