TRISCEND II: Novel Randomized Trial Design for Transcatheter Tricuspid Valve Replacement.

BACKGROUND: Severe tricuspid regurgitation remains largely undertreated given limited treatment options. Transcatheter tricuspid valve interventions have emerged as a promising therapy for these patients, and the TRISCEND II pivotal trial is the first randomized controlled trial to evaluate transcatheter tricuspid valve replacement (TTVR). OBJECTIVES: The TRISCEND II pivotal trial studies the transcatheter EVOQUE tricuspid valve replacement system using an FDA Breakthrough Device Designation - a program intended to provide timely access to medical devices by speeding up development, assessment, and review. METHODS: The TRISCEND II trial is a prospective, multicenter trial that randomizes patients with symptomatic severe tricuspid regurgitation to treatment with either TTVR in conjunction with optimal medical therapy or optimal medical therapy alone. The trial's novel 2-phase design evaluates 30-day safety and 6-month effectiveness endpoints for the first 150 patients in the initial phase and a 1-year safety and effectiveness endpoint for the full cohort of 400 patients in the second phase. RESULTS: The TRISCEND II trial's 2-phase trial design provided an opportunity for early review and led to the first commercial approval of a TTVR system. CONCLUSIONS: The design of the TRISCEND II trial will likely inform future transcatheter tricuspid device trials. CONDENSED ABSTRACT: The TRISCEND II pivotal trial is the first randomized controlled trial of transcatheter tricuspid valve replacement (TTVR). It was designed under the FDA's Breakthrough Device Program to bring a novel TTVR therapy to patients with limited treatment options. A 2-phase design allowed for early review of safety and effectiveness outcomes followed by a full-cohort safety and effectiveness endpoint in the second phase at 1 year. This approach led to approval of the first commercial transcatheter therapy for tricuspid valve replacement.

10 Years of SYNTAX: Closing an Era of Clinical Research After Identifying New Outcome Determinants.

The SYNTAX trial randomized patients equally eligible for coronary artery bypass grafting or percutaneous coronary intervention using the Heart Team approach. The SYNTAXES study achieved a follow-up rate of 93.8% and reported the 10-year vital status. Factors associated with increased mortality at 10 years were pharmacologically treated diabetes mellitus, increased waist circumference, reduced left ventricular function, prior cerebrovascular and peripheral vascular disease, western Europe and North American descent, current smoking, chronic obstructive pulmonary disease, elevated C-reactive protein, anemia, and an increase in HbA1c. Procedural factors associated with higher 10 years mortality include periprocedural myocardial infarction, extensive stenting, small stents, ≥1 heavily calcified lesion, ≥1 bifurcation lesion, residual SYNTAX score >8, and staged percutaneous coronary intervention. Optimal medical therapy at 5 years, use of statins, on-pump coronary artery bypass grafting, multiple arterial grafts, and higher physical component score and mental component score were associated with lower mortality at 10 years. Numerous scores and prediction models were developed to help individualize risk assessment. Machine learning has emerged as a novel approach for developing risk models.

Minimum Core Data Elements for Transcatheter Mitral Therapies: Scientific Statement by PASSION CV, HVC, and TVTR.

Mitral regurgitation is the most common valvular disease and is estimated to affect over 5 million Americans. Real-world data collection contributes to safety and effectiveness evidence for the U.S. Food and Drug Administration, quality evaluation for the Centers for Medicare and Medicaid Services and hospitals, and clinical best practice research. We aimed to establish a minimum core data set in mitral interventions to promote efficient, reusable real-world data collection for all of these purposes. Two expert task forces separately evaluated and reconciled a list of candidate elements derived from: 1) 2 ongoing transcatheter mitral trials; and 2) a systemic literature review of high-impact mitral trials and U.S multicenter, multidevice registries. From 703 unique data elements considered, unanimous consensus agreement was achieved on 127 "core" data elements, with the most common reasons for exclusion from the minimum core data set being burden or difficulty in accurate assessment (41.2%), duplicative information (25.0%), and low likelihood of affecting outcomes (19.6%). After a systematic review and extensive discussions, a multilateral group of academicians, industry representatives, and regulators established and implemented into the national Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapies Registry 127 interoperable, reusable core data elements to support more efficient, consistent, and informative transcatheter mitral device evidence for regulatory submissions, safety surveillance, best practice development, and hospital quality assessments.

Minimum Core Data Elements for Evaluation of TAVR: A Scientific Statement by PASSION CV, HVC, and TVT Registry.

Transcatheter aortic valve replacement (TAVR) is the standard of care for severe, symptomatic aortic stenosis. Real-world TAVR data collection contributes to benefit/risk assessment and safety evidence for the U.S. Food and Drug Administration, quality evaluation for the Centers for Medicare and Medicaid Services and hospitals, as well as clinical research and real-world implementation through appropriate use criteria. The essential minimum core dataset for these purposes has not previously been defined but is necessary to promote efficient, reusable real-world data collection supporting quality, regulatory, and clinical applications. The authors performed a systematic review of the published research for high-impact TAVR studies and U.S. multicenter, multidevice registries. Two expert task forces, one from the Predictable and Sustainable Implementation of National Cardiovascular Registries/Heart Valve Collaboratory and another from The Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry convened separately and then met to reconcile a final list of essential data elements. From 276 unique data elements considered, unanimous consensus agreement was achieved on 132 "core" data elements, with the most common reasons for exclusion from the minimum core dataset being burden or difficulty in accurate assessment (36.9%), duplicative information (33.3%), and low likelihood of affecting outcomes (10.7%). After a systematic review and extensive discussions, a multilateral group of academicians, industry representatives, and regulators established 132 interoperable, reusable essential core data elements essential to supporting more efficient, consistent, and informative TAVR device evidence for regulatory submissions, safety surveillance, best practice, and hospital quality assessments.

Minimum Core Data Elements for Evaluation of TAVR: A Scientific Statement by PASSION CV, HVC, and TVT Registry.

Transcatheter aortic valve replacement (TAVR) is the standard of care for severe, symptomatic aortic stenosis. Real-world TAVR data collection contributes to benefit/risk assessment and safety evidence for the U.S. Food and Drug Administration, quality evaluation for the Centers for Medicare and Medicaid Services and hospitals, as well as clinical research and real-world implementation through appropriate use criteria. The essential minimum core dataset for these purposes has not previously been defined but is necessary to promote efficient, reusable real-world data collection supporting quality, regulatory, and clinical applications. The authors performed a systematic review of the published research for high-impact TAVR studies and U.S. multicenter, multidevice registries. Two expert task forces, one from the Predictable and Sustainable Implementation of National Cardiovascular Registries/Heart Valve Collaboratory and another from The Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry convened separately and then met to reconcile a final list of essential data elements. From 276 unique data elements considered, unanimous consensus agreement was achieved on 132 "core" data elements, with the most common reasons for exclusion from the minimum core dataset being burden or difficulty in accurate assessment (36.9%), duplicative information (33.3%), and low likelihood of affecting outcomes (10.7%). After a systematic review and extensive discussions, a multilateral group of academicians, industry representatives, and regulators established 132 interoperable, reusable essential core data elements essential to supporting more efficient, consistent, and informative TAVR device evidence for regulatory submissions, safety surveillance, best practice, and hospital quality assessments.

Prospective Study of TMVR Using Balloon-Expandable Aortic Transcatheter Valves in MAC: MITRAL Trial 1-Year Outcomes.

OBJECTIVES: The aim of this study was to evaluate 1-year outcomes of valve-in-mitral annular calcification (ViMAC) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial. BACKGROUND: The MITRAL trial is the first prospective study evaluating the feasibility of ViMAC using balloon-expandable aortic transcatheter heart valves. METHODS: A multicenter prospective study was conducted, enrolling high-risk surgical patients with severe mitral annular calcification and symptomatic severe mitral valve dysfunction at 13 U.S. sites. RESULTS: Between February 2015 and December 2017, 31 patients were enrolled (median age 74.5 years [interquartile range (IQR): 71.3 to 81.0 years], 71% women, median Society of Thoracic Surgeons score 6.3% [IQR: 5.0% to 8.8%], 87.1% in New York Heart Association functional class III or IV). Access was transatrial (48.4%), transseptal (48.4%), or transapical (3.2%). Technical success was 74.2%. Left ventricular outflow tract obstruction (LVOTO) with hemodynamic compromise occurred in 3 patients (transatrial, n = 1; transseptal, n = 1; transapical, n = 1). After LVOTO occurred in the first 2 patients, pre-emptive alcohol septal ablation was implemented to decrease risk in high-risk patients. No intraprocedural deaths or conversions to open heart surgery occurred during the index procedures. All-cause mortality at 30 days was 16.7% (transatrial, 21.4%; transseptal, 6.7%; transapical, 100% [n = 1]; p = 0.33) and at 1 year was 34.5% (transatrial, 38.5%; transseptal, 26.7%; p = 0.69). At 1-year follow-up, 83.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.1 mm Hg (IQR: 5.6 to 7.1 mm Hg), and all patients had ≤1+ mitral regurgitation. CONCLUSIONS: At 1 year, ViMAC was associated with symptom improvement and stable transcatheter heart valve performance. Pre-emptive alcohol septal ablation may prevent transcatheter mitral valve replacement-induced LVOTO in patients at risk. Thirty-day mortality of patients treated via transseptal access was lower than predicted by the Society of Thoracic Surgeons score. Further studies are needed to evaluate safety and efficacy of ViMAC.

Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes.

OBJECTIVES: The aim of this study was to assess 1-year clinical outcomes among high-risk patients with failed surgical mitral bioprostheses who underwent transseptal mitral valve-in-valve (MViV) with the SAPIEN 3 aortic transcatheter heart valve (THV) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial. BACKGROUND: The MITRAL trial is the first prospective study evaluating transseptal MViV with the SAPIEN 3 aortic THV in high-risk patients with failed surgical mitral bioprostheses. METHODS: High-risk patients with symptomatic moderate to severe or severe mitral regurgitation (MR) or severe mitral stenosis due to failed surgical mitral bioprostheses were prospectively enrolled. The primary safety endpoint was technical success. The primary THV performance endpoint was absence of MR grade ≥2+ or mean mitral valve gradient ≥10 mm Hg (30 days and 1 year). Secondary endpoints included procedural success and all-cause mortality (30 days and 1 year). RESULTS: Thirty patients were enrolled between July 2016 and October 2017 (median age 77.5 years [interquartile range (IQR): 70.3 to 82.8 years], 63.3% women, median Society of Thoracic Surgeons score 9.4% [IQR: 5.8% to 12.0%], 80% in New York Heart Association functional class III or IV). The technical success rate was 100%. The primary performance endpoint in survivors was achieved in 96.6% (28 of 29) at 30 days and 82.8% (24 of 29) at 1 year. Thirty-day all-cause mortality was 3.3% and was unchanged at 1 year. The only death was due to airway obstruction after swallowing several pills simultaneously 29 days post-MViV. At 1-year follow-up, 89.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.6 mm Hg (interquartile range: 5.5 to 8.9 mm Hg), and all patients had MR grade ≤1+. CONCLUSIONS: Transseptal MViV in high-risk patients was associated with 100% technical success, low procedural complication rates, and very low mortality at 1 year. The vast majority of patients experienced significant symptom alleviation, and THV performance remained stable at 1 year.

Prospective Evaluation of TMVR for Failed Surgical Annuloplasty Rings: MITRAL Trial Valve-in-Ring Arm 1-Year Outcomes.

OBJECTIVES: The authors report 1-year outcomes of high-risk patients with failed surgical annuloplasty rings undergoing transseptal mitral valve-in-ring (MViR) with the SAPIEN 3 aortic transcatheter heart valve (THV). BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective study evaluating transseptal MViR with the SAPIEN 3 aortic THV in high-risk patients with failed surgical annuloplasty rings. METHODS: Prospective enrollment of high-risk patients with symptomatic moderate to severe or severe mitral regurgitation (MR) or severe mitral stenosis and failed annuloplasty rings at 13 U.S. sites. The primary safety endpoint was technical success. The primary THV performance endpoint was absence of MR grade ≥2+ or mean mitral valve gradient ≥10 mm Hg (30 days and 1 year). Secondary endpoints included procedural success and all-cause mortality (30 days and 1 year). RESULTS: Thirty patients were enrolled between January 2016 and October 2017 (median age 71.5 years [interquartile range: 67.0 to 76.8 years], 36.7% women, median Society of Thoracic Surgeons score 7.6% [interquartile range: 5.1% to 11.8%], 76.7% in New York Heart Association functional class III or IV). Technical success was 66.7% (driven primarily by need for a second valve in 6 patients). There was no intraprocedural mortality or conversion to surgery. The primary performance endpoint was achieved in 85.7% of survivors at 30 days (24 of 28) and 89.5% of patients alive at 1 year with echocardiographic data available (17 of 19). All-cause mortality at 30 days was 6.7% and at 1 year was 23.3%. Among survivors at 1-year follow-up, 84.2% were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.0 mm Hg (interquartile range: 4.7 to 7.3 mm Hg), and all had ≤1+ MR. CONCLUSIONS: Transseptal MViR was associated with a 30-day mortality rate lower than predicted by the Society of Thoracic Surgeons score. At 1 year, transseptal MViR was associated with symptom improvement and stable THV performance.

Relation of Institutional Mitral Valve Surgical Volume to Surgical and Transcatheter Outcomes in Medicare Patients.

There are limited data to support proposed increases to the minimum institutional mitral valve (MV) surgery volume required to begin a transcatheter mitral valve repair (TMVr) program. The current study examined the association between institutional MV procedure volumes and outcomes. All 2017 Medicare fee-for-service patients who received a TMVr or MV surgery procedure were included and analyzed separately. The exposure was institutional MV surgery volume: low (1 to 24), medium (25 to 39) or high (40+). Outcomes were in-hospital mortality and 1-year postdischarge mortality and cardiovascular rehospitalization. For MV surgery patients, in-hospital mortality rates were 6.4% at low-volume, 8.7% at medium-volume and 9.8% at high-volume facilities. Rates were significantly higher for low-volume [OR = 1.50, 95% CI (1.23 to 1.84)] and medium-volume [OR = 1.33, 95% CI (1.06 to 1.67)] compared with high-volume facilities. There was no statistically significant relationship between institutional MV surgery volume and in-hospital mortality for TMVr patients, either at low-volume [OR = 1.52, 95% CI (0.56, 4.13)] or medium-volume [OR = 1.58, 95% CI (0.82, 3.02)] facilities, compared with high-volume facilities. Across all volume categories, in-hospital mortality rates for TMVr patients were relatively low (2.3% on average). For both cohorts, the rates of 1-year mortality and cardiovascular rehospitalizations were not significantly higher at low- or medium-volume MV surgery facilities, as compared with high-volume. In conclusion, among Medicare patients, there was a relation between institutional MV surgery volume and in-hospital mortality for MV surgery patients, but not for TMVr patients.

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).

Management and Outcome of Patients Admitted With Tricuspid Regurgitation in France.

BACKGROUND: Growing evidence shows a major outcome impact and undertreatment of tricuspid regurgitation (TR), but large and comprehensive contemporary reports of management and outcome at the nationwide level are lacking. METHODS: We gathered all consecutive patients admitted with a diagnosis of likely functional TR in 2014-2015 in France from the Programme de Médicalisation des Systèmes d'Information national database and collected rate of surgery, in-hospital mortality, 1-year mortality, or heart failure (HF) readmission rates. RESULTS: In 2014-2015, 17,676 consecutive patients (75 ± 14 years of age, 51% female) were admitted with a TR diagnosis. Charlson index was ≥ 2 in 56% of the population and 46% presented with HF. TR was associated with prior cardiac surgery, ischemic/dilated cardiomyopathy, or mitral regurgitation in 73% of patients. Only 10% of TR patients overall and 67% of those undergoing mitral valve surgery received a tricuspid valve intervention. Among the 13,654 (77%) conservatively managed patients, in-hospital mortality, 1-year mortality, and 1-year mortality or HF readmission rates were 5.1%, 17.8%, and 41%, respectively, overall, and 5.3%,17.2%, and 37%, respectively, among those with no underlying medical conditions (8-fold higher than predicted for age and gender). CONCLUSIONS: This nationwide cohort of patients admitted with TR included elderly patients with frequent comorbidities/underlying cardiac diseases. In patients conservatively managed, mortality and morbidity were considerably high over a short time span. Despite this poor prognosis, only 10% of patients underwent a tricuspid valve intervention. These nationwide data showing a considerable risk and potential underuse of treatment highlight the critical need to develop strategies to improve the management and outcomes of TR patients.

Balloon Aortic Valvuloplasty Followed by Impella®-Assisted Left Main Coronary Artery Percutaneous Coronary Intervention in Patients With Severe Aortic Stenosis as a Bridge to Transcatheter Aortic Valve Replacement.

BACKGROUND: The use of Impella® to provide hemodynamic support during unprotected left main coronary artery (LMCA) percutaneous coronary intervention (PCI) has been shown to be feasible, but severe AS is a relative contraindication for its use. Balloon aortic valvuloplasty (BAV) may facilitate the use of Impella® in these patients. OBJECTIVE: To assess the feasibility of BAV followed by Impella®-assisted LMCA PCI in patients with severe AS as bridge to TAVR. METHODS: Patients with symptomatic severe AS with LMCA stenosis ≥70% requiring PCI prior to TAVR were included. Outcomes were retrospectively collected. RESULTS: Seven patients underwent BAV followed by Impella®-assisted LMCA PCI. Five patients were male; mean age 86 (75-91; SD ± 5.5). Mean STS score was 6.5% (4.3-13.8; SD ± 3.4). Impella® 2.5 L was used in all cases. The procedure was successful in all patients without peri-procedure complications. At 30-day post-BAV/PCI follow up, all patients had experienced improvement in NYHA class (N = 2 NYHA IV to III, N = 5 NYHA III to II). At such interval, mean EF was 54% (30-77; SD ± 17.7). The post BAV change in AVA [0.8 cm2 (0.4-1.5; SD ± 0.3; P = 0.07)], and AV mean gradient [30.8 mmHg (21-45; SD ± 8.9; P = 0.95)] after the procedure were not statistically significant. All patients underwent TAVR after a median PCI-to-TAVR interval of 62 days (33-339; SD ± 96.7). CONCLUSIONS: BAV followed by Impella®-assisted LMCA PCI appears to be a feasible strategy for intermediate and high surgical risk patients with severe AS undergoing LMCA PCI as bridge to TAVR.

Tricuspid valve repair with the Cardioband system: two-year outcomes of the multicentre, prospective TRI-REPAIR study.

AIMS: Tricuspid regurgitation (TR) is associated with high morbidity and mortality rates with limited treatment options. We report one- and two-year outcomes of the Cardioband tricuspid valve reconstruction system in the treatment of ≥moderate functional TR in the TRI-REPAIR study. METHODS AND RESULTS: Thirty patients were enrolled in this single-arm, multicentre, prospective study. Patients were evaluated as having ≥moderate, symptomatic functional TR and deemed inoperable due to unacceptable surgical risk. Clinical, functional, and echocardiographic data were prospectively collected up to two years (mean duration 604±227 days). At baseline, 83% were in NYHA Class III-IV, and the mean LVEF was 58%. Technical success was 100%. At two years, there were eight deaths. Echocardiography showed a significant reduction in septolateral annular diameter of 16% (p=0.006) and 72% of patients (p=0.016) with ≤moderate TR grade; 82% of patients were in NYHA Class I-II (p=0.002). Six-minute walk distance and KCCQ score improved by 73 m (p=0.058) and 14 points (p=0.046), respectively. CONCLUSIONS: These results demonstrate that the Cardioband tricuspid system showed favourable results in patients with symptomatic, ≥moderate functional TR. Annular reduction and TR severity reduction remained significant and sustained at two years. Patients experienced improvements in quality of life and exercise capacity. ClinicalTrials.gov Identifier: NCT02981953.

1-Year Outcomes for Transcatheter Repair in Patients With Mitral Regurgitation From the CLASP Study.

OBJECTIVES: The authors report the CLASP (Edwards PASCAL Transcatheter Mitral Valve Repair System Study) expanded experience, 1-year outcomes, and analysis by functional mitral regurgitation (FMR) and degenerative mitral regurgitation (DMR). BACKGROUND: The 30-day results from the CLASP study of the PASCAL transcatheter valve repair system for clinically significant mitral regurgitation (MR) have been previously reported. METHODS: Eligible patients had symptomatic MR ≥3+, were receiving optimal medical therapy, and were deemed candidates for transcatheter mitral repair by the local heart team. Primary endpoints included procedural success, clinical success, and major adverse event rate at 30 days. Follow-up was continued to 1 year. RESULTS: One hundred nine patients were treated (67% FMR, 33% DMR); the mean age was 75.5 years, and 57% were in New York Heart Association functional class III or IV. At 30 days, there was 1 cardiovascular death (0.9%), MR ≤1+ was achieved in 80% of patients (77% FMR, 86% DMR) and MR ≤2+ in 96% (96% FMR, 97% DMR), 88% of patients were in New York Heart Association functional class I or II, 6-min walk distance had improved by 28 m, and Kansas City Cardiomyopathy Questionnaire score had improved by 16 points (p < 0.001 for all). At 1 year, Kaplan-Meier survival was 92% (89% FMR 96% DMR) with 88% freedom from heart failure hospitalization (80% FMR, 100% DMR), MR was ≤1+ in 82% of patients (79% FMR, 86% DMR) and ≤2+ in 100% of patients, 88% of patients were in New York Heart Association functional class I or II, and Kansas City Cardiomyopathy Questionnaire score had improved by 14 points (p < 0.001 for all). CONCLUSIONS: The PASCAL transcatheter valve repair system demonstrated a low complication rate and high survival, with robust sustained MR reduction accompanied by significant improvements in functional status and quality of life at 1 year. (The CLASP Study Edwards PASCAL Transcatheter Mitral Valve Repair System Study [CLASP]; NCT03170349).

Presentation and outcomes of mitral valve surgery in France in the recent era: a nationwide perspective.

OBJECTIVES: Unbiased information regarding the surgical management of patients with mitral regurgitation (MR) at the nationwide level are scarce and mainly US-based. The Programme de Médicalisation des Systèmes d'Information, a mandatory national database, offers the unique opportunity to assess the presentation and outcomes of all consecutive mitral valve (MV) surgeries performed in France in the contemporary era. METHODS: We collected all MV surgeries performed for MR in France in 2014-2016. MR aetiology was classified as degenerative (DMR), secondary (SMR) or Other (rheumatic or congenital disease and infective endocarditis). RESULTS: During the 3-year period, 18 167 MV surgeries were performed in France (55% repair and 45% replacement; 52% isolated). Age was 66±12 years and 59% were male. Aetiology was DMR in 42%, SMR in 16% and other in 42% including 19% with uncertain aetiologies. Overall, in-hospital mortality was 6.5% and increased with age, female gender, Charlson Comorbidity Index, type of surgery (replacement vs repair), associated surgery (combined vs isolated) and MR aetiology (all p<0.01). In-hospital mortality and rate of death/readmission for heart failure (HF) at 1 year were 3.4% and 13%, respectively for DMR (2.4% and 11% for isolated DMR) and 7.8% and 27%, respectively for SMR (5.5% and 23% for isolated SMR). Repair rate was 55% overall, 68% in DMR and 72% for isolated DMR surgery (70% of all DMR). Repair rates decreased with age, Charlson Comorbidity Index and female sex (all p<0.0001). CONCLUSION: In this cross-sectional contemporary prospective nationwide database, in-hospital mortality and 1 year rate of death and HF readmission were considerable overall and in all subsets. Repair rates were suboptimal overall especially in the elderly and women subsets. These results underline the need to develop strategies to improve management and outcomes of patients with both DMR and SMR.

Dismal Outcomes and High Societal Burden of Mitral Valve Regurgitation in France in the Recent Era: A Nationwide Perspective.

Background Although US recent data suggest that mitral regurgitation (MR) is severely undertreated and carries a poor outcome, population-based views on outcome and management are limited. We aimed to define the current treatment standards, clinical outcomes, and costs related to MR at the nationwide level. Methods and Results In total, 107 412 patients with MR were admitted in France in 2014 to 2015. Within 1 year, 8% were operated and 92% were conservatively managed and constituted our study population (68% primary MR and 32% secondary MR). The mean age was 77±15 years; most patients presented with comorbidities. In-hospital and 1-year mortality rates were 4.1% and 14.3%, respectively. Readmissions were common (63% at least once and 37% readmitted ≥2 times). Rates of 1-year mortality or all-cause readmission and 1-year mortality or heart failure readmission were 67% and 34%, respectively, and increased with age, Charlson index, heart failure at admission, and secondary MR etiology; however, the event rate remained notably high in the primary MR subset (64% and 28%, respectively). The mean costs of hospital admissions and of readmissions were 5345±6432 and 10 080±10 847 euros, respectively. Conclusions At the nationwide level, MR was a common reason for admission and affected an elderly population with frequent comorbidities. Less than 10% of patients underwent a valve intervention. All subsets of patients who were conservatively managed incurred high mortality and readmissions rates, and MR represented a major societal burden with an extrapolated annual cost of 350 to 550 million euros (390-615 million US dollars). New strategies to improve the management and outcomes of patients with both primary and secondary MR are critical and warranted.

Transcatheter InterAtrial Shunt Device for the treatment of heart failure: Rationale and design of the pivotal randomized trial to REDUCE Elevated Left Atrial Pressure in Patients with Heart Failure II (REDUCE LAP-HF II).

BACKGROUND: A randomized, sham-controlled trial in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) ≥40% demonstrated reductions in pulmonary capillary wedge pressure (PCWP) with a novel transcatheter InterAtrial Shunt Device (IASD). Whether this hemodynamic effect will translate to an improvement in cardiovascular outcomes and symptoms requires additional study. STUDY DESIGN AND OBJECTIVES: REDUCE Elevated Left Atrial Pressure in Patients with Heart Failure II (REDUCE LAP HF-II) is a multicenter, prospective, randomized, sham-controlled, blinded trial designed to evaluate the clinical efficacy of the IASD in symptomatic HF and elevated left atrial pressures. Up to 608 HF patients age ≥ 40 years with LVEF ≥40%, PCWP ≥25 mm Hg during supine ergometer exercise, and PCWP ≥5 mm Hg higher than right atrial pressure will be randomized 1:1 to the IASD versus sham control. Key exclusion criteria include hemodynamically significant valvular disease, evidence of pulmonary arterial hypertension, and right heart dysfunction. The primary endpoint is a hierarchical composite, analyzed by the Finkelstein-Schoenfeld methodology, that includes (1) cardiovascular mortality or first nonfatal ischemic stroke through 12 months; (2) total (first plus recurrent) HF hospitalizations or healthcare facility visits for intravenous diuretics up to 24 months, analyzed when the last randomized patient completes 12 months of follow-up; and (3) change in Kansas City Cardiomyopathy Questionnaire overall summary score from baseline to 12 months. Follow-up echocardiography will be performed at 6, 12, and 24 months to evaluate shunt flow and cardiac chamber size/function. Patients will be followed for a total of 5 years after the index procedure. CONCLUSIONS: REDUCE LAP-HF II is designed to evaluate the clinical efficacy of the IASD device in patients with symptomatic HF with elevated left atrial pressure and LVEF ≥40%.

Impact of tricuspid regurgitation on survival in patients with heart failure: a large electronic health record patient-level database analysis.

AIMS: More evidence is needed to quantify the association between tricuspid regurgitation (TR) and mortality in patients with heart failure (HF). METHODS AND RESULTS: Between 2008-2017, using the Optum longitudinal database, a patient-level database that integrates multiple US-based electronic health and claim records from several health care providers, we identified 435 679 patients with new HF diagnosis and both an assessment of the left ventricular ejection fraction and at least 1 year of history. TR was graded as mild, moderate or severe and classified as prevalent (at the time of the initial HF diagnosis) or incident (subsequent new cases thereafter). For prevalent TR, the analysis was performed using a Cox proportional hazards model with adjustment for patient covariates. Incident TR was modelled as a time-updated covariate, as were other non-fatal events during follow-up. Prevalence of mild, moderate and severe TR at baseline was 10.1%, 5.1% and 1.4%, respectively. Over a median follow-up of 1.5 years, 121 273 patients (27.8%) died and prevalent TR was independently associated with survival. Compared to patients with no TR at baseline, the adjusted hazard ratios for mortality were 0.99 [95% confidence interval (CI) 0.97-1.01], 1.17 (95% CI 1.14-1.20) and 1.34 (95% CI 1.28-1.39) for mild, moderate and severe TR, respectively. In the 363 270 patients free from TR at baseline, incident TR (at least mild, at least moderate, or severe) developed during follow-up in 12.1%, 5.1% and 1.1%, respectively. Adjusted mortality hazard ratios for such new cases were 1.48 (95% CI 1.44-1.52), 1.92 (95% CI 1.86-1.99) and 2.44 (95% CI 2.32-2.57), respectively. Findings were consistent across all patient subgroups based on age, gender, rhythm, associated comorbidities, prior cardiac surgery, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide, and left ventricular ejection fraction. CONCLUSIONS: In this large contemporary patient-level database of almost half-million US patients with HF, TR was associated with a marked increases in mortality risk overall and in all subgroups. Future randomized controlled trials will evaluate the impact of TR correction on clinical outcomes and the causal relationship between TR and mortality.