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With the recent approval of the transcatheter EVOQUE tricuspid valve replacement system to treat severe, symptomatic tricuspid regurgitation, there is a need to define the appropriate patient population and anatomical considerations for this device. In this consensus document, the authors review these considerations, describe the procedural steps and imaging requirements to ensure technical success, and discuss management of complex intraprocedural circumstances., Competing Interests: Funding Support and Author Disclosures Dr Hahn has received speaker fees from Abbott Vascular, Boston Scientific, Edwards Lifesciences, Philips Healthcare, and Siemens Healthineers; and is chief scientific officer for the echocardiography core laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she receives no direct industry compensation. Dr Makkar has received research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Makkar is a consultant for Abbott Vascular, Boston Scientific, Edwards Lifesciences, GE Healthcare. Dr Davidson has received research grant support from Edwards Lifesciences, Abbott Vascular; is an advisor for Philips Healthcare; and is an uncompensated advisor for Edwards Lifesciences. Dr Puthamana has received speaker honoraria from Edwards Lifesciences and Abbott Structural; and has received consultant fees from Edwards Lifesciences. Dr Zahr has received consulting, research, and educational grants from Edwards Lifesciences, Medtronic, and Philips. Dr Chadderdon is a consultant to Edwards Lifesciences, Medtronic, and Phillips Healthcare. Dr Fam is a consultant to Edwards Lifesciences, Abbott, Medtronic, and Cardiovalve. Dr Ong has received speaker honoraria and consultant fees from Abbott Vascular and Edwards Lifesciences. Dr Yadav has received consultant and speaker fees from Edwards Lifesciences, Abbott, and Boston Scientific; is an advisory board member for and has stock options in Dasi Simulations; has received institutional research funding from Edwards Lifesciences, Abbott Vascular, Medtronic, Boston Scientific, Innovalve, JenaValve, HighLife, Trisol, and CroiValve. Dr Thourani has received research grants from and is an advisor for Edwards Lifesciences. Dr Vannan has received institutional research grants and equipment support from Siemens Healthineers, Philips, GE Healthcare; and has received institutional speaker honoraria from Siemens, Philips, Abbott, and Medtronic (no direct industry compensation). Dr Tchétché has received consulting fees from Edwards Lifesciences. Dr Dumonteil is a consultant for Abbott, Ancora Heart, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Smith has received institutional research grants from Edwards Lifesciences, Medtronic, NeoChord, and Artivion; has received speaker honoraria from Medtronic and Edwards Lifesciences; and is on the advisory board of Edwards Lifesciences. Dr Grayburn has received research grants from Abbott Vascular, Boston Scientific, Cardiovalve, Cardiomech, Edwards Lifesciences, Medtronic, NeoChord, Restore Medical, and 4C Medical; and has received consulting and advisory board fees from Abbott Vascular, Edwards Lifesciences, Medtronic, and 4C Medical. Dr Webb has received research grants from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific; and is a consultant to Edwards Lifesciences. Dr Moss is a consultant to Edwards Lifesciences; and has received speaker fees and travel support from Edwards Lifesciences, Abbott, Medtronic, Boston Scientific. Dr Windecker has received research, travel, or educational grants to the institution without personal remuneration from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, B. Braun, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, Cardiovalve, Cordis Medical, Corflow Therapeutics, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Farapulse, Fumedica, Guerbet, Idorsia, Inari Medical, Infraredx, Janssen-Cilag, Johnson & Johnson, MedAlliance, Medicure, Medtronic, Merck Sharp & Dohme, Miracor Medical, MonarQ, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pharming Tech, Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, and V-Wave; has served as an advisory board member and/or member of the steering or executive groups of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, and V-Wave with payments to the institution but no personal payments; and is a member of the steering or executive committee group of several investigator-initiated trials that receive funding from industry without impact on his personal remuneration. Dr Nabauer has received consultant and speaker fees from Edwards Lifesciences and Abbott Vascular. Dr Hausleiter is a consultant to Edwards Lifesciences; and has received research funding and speaker honoraria from Edwards Lifesciences. Dr Kodali is a consultant for Admedus, TriCares, TriFlo, X-Dot, Micro-Interventional Devices, Supira, Adona, Tioga, Helix Valve Repair, and Moray Medical; has served as an advisory board member for Dura, Biotech, Thubrikar Aortic Valve, Philips, Medtronic, and Boston Scientific; and has received institutional grant support from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Tricuspid regurgitation (TR) is a common valve disease that has a significant impact on patients' quality of life., Objectives: This study sought to report the final 3-year outcomes of tricuspid transcatheter edge-to-edge repair (T-TEER) with the TriClip (Abbott) implant from the TRILUMINATE (TRILUMINATE Study With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater TR) study for the treatment of severe symptomatic TR., Methods: The TRILUMINATE study (N = 98 subjects) is an international, prospective, single-arm, multicenter study to investigate the safety and performance of T-TEER with the TriClip implant in patients with symptomatic moderate or greater TR. Echocardiographic assessments were performed at a core laboratory., Results: At 3 years, TR was reduced to moderate or less in 79% of subjects, and a reduction of at least 1 grade was achieved in 92% of subjects. TR reduction achieved at 1 year was sustained through 3 years. Subjects also experienced an improvement in heart failure symptoms assessed by NYHA functional class and quality of life assessed by the Kansas City Cardiomyopathy Questionnaire at 3 years compared to baseline. The site-reported heart failure hospitalization rate decreased from 0.56 events/patient-year 1 year before device implantation to 0.14 events/patient-year 3 years after device implantation, representing a reduction of 75% (P < 0.0001)., Conclusions: In the longest follow-up to date of any T-TEER therapy, the TRILUMINATE study demonstrated that the TriClip procedure is both safe and effective, with sustained benefits at 3 years in subjects with symptomatic moderate or greater TR. (TRILUMINATE Study With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater TR [TRILUMINATE]; NCT03227757)., Competing Interests: Funding Support and Author Disclosures This study was supported by Abbott Structural Heart. Dr Nickenig has received research funding and honoraria from Abbott, Edwards Lifesciences, and Medtronic; and has participated in clinical trials with Abbott, Edwards Lifesciences, and Medtronic. Dr Lurz has served as a consultant for Abbott Structural Heart, Edwards Lifesciences, Medtronic, ReCor, and Occlutech. Dr Sorajja has served as a consultant for 4C Medical, Abbott Structural, Adona, Boston Scientific, Edwards Lifesciences, Foldax, GE Medical, GLG, Medtronic, Phillips, Siemens, WL Gore, vDyne, and xDot; and has received personal fees from Abbott Vascular (outside the submitted work). Dr von Bardeleben has received institutional research grants and speaker honorarium from Abbott Vascular and Edwards Lifesciences; and has received nonfinancial trial support from Abbott Vascular, Boston Scientific, Edwards Lifesciences, Lifetec, and Medtronic. Dr Sitges has served as a consultant for Abbott, Edwards Lifesciences, Metronic, and General Electric; has received speaker honoraria from Abbott, Edwards Lifesciences, Medtronic, and General Electric; and has received speaker honoraria and travel and grant support from Abbott. Dr Hausleiter has received speaker honoraria and research support from Abbott Vascular and Edwards Lifesciences. Dr Trochu has received speaker honoraria, travel support, and grant support from Abbott and Novartis; has received honoraria for lectures or advisory boards from Amgen, Bayer, and Resmed; and has been an unpaid member of the Corvia Medical Scientific Advisory Group. Dr Näbauer has received speaker honoraria from Abbott. Dr Heitkemper is an employee of Abbott. Dr Hahn has received speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, and Philips Healthcare; and has institutional consulting contracts for which she receives no direct compensation with Abbott Structural, Boston Scientific, Edwards Lifesciences, Medtronic, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Data on procedural and early outcomes after transjugular transcatheter tricuspid valve replacement (TTVR) are limited., Objectives: This study sought to evaluate first-in-man procedural and clinical outcomes after transjugular TTVR with a special focus on patients who received large device sizes in whom TTVR outcomes have been questioned., Methods: The retrospective registry included patients who underwent TTVR using the LuX-Valve Plus system (Jenscare Biotechnology Co Ltd) for symptomatic tricuspid regurgitation (TR) from January 2022 until February 2024 at 15 international centers in a compassionate use setting. The endpoints were procedural TR reduction, in-hospital death, adverse events, and 1-month survival. We further stratified results according to the size of the implanted device (<55 vs ≥55 mm)., Results: The registry included a total of 76 patients at a median age of 78 years (Q1-Q3: 72-83 years, 47.4% women). TR was reduced to ≤2+ and ≤1+ in 94.7% and 90.8% of patients (75.0% of patients received TTVR devices ≥55 mm) with well-sustained results at 1-month follow-up (TR ≤2+ in 95.0% and ≤1+ 86.8%). Residual TR was paravalvular in all cases. In-hospital death occurred in 4 patients (5.3%). Four patients (5.3%) underwent cardiac surgery during index hospitalization. Major in-hospital bleeding events occurred in 5 patients (6.6%). New in-hospital pacemaker implantation was required in 3.9% of patients in the overall cohort (5.7% in "pacemaker-naive" individuals). No cases of valve thrombosis, stroke, myocardial infarction, or pulmonary embolism were observed. At 1-month follow-up, survival was 94.4%, and NYHA functional class significantly improved. One further patient received a pacemaker, 1 further bleeding event occurred, and 2 patients underwent reintervention or surgery within the first 30 days after TTVR. No differences in procedural outcomes or adverse events were observed after stratification for valve size., Conclusions: Transjugular TTVR appears to be a safe and effective treatment option for patients with severe TR with comparable outcomes in very large tricuspid anatomies., Competing Interests: Funding Support and Author Disclosures Dr Stolz has received speaker honoraria from Edwards Lifesciences. Dr Cheung has received speaker honoraria from Edwards Lifesciences, Abbott Vascular, and Medtronic; and has served as an eligibility committee member for the TRINITY trial. Dr Boone has served as a consultant for Edwards Lifesciences and Abbott. Dr Fam has served as a consultant for Edwards Lifesciences, Abbott, and Cardiovalve. Dr Villablanca has served as a consultant for Edwards Lifesciences, Medtronic, Angiodynamic, Telflex, and Abiomed. Dr De Backer has received institutional research grants and consulting fees from Abbott, Boston Scientific, and Medtronic. Dr Tchétché has served as consultant for Abbott, Edwards Lifesciences, Boston Scientific, and Medtronic. Dr So has served as a proctor for Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Latib has served on the Advisory Board for Medtronic, Abbott Vascular, Boston Scientific, Edwards Lifesciences, Shifamed, NeoChord Inc, V-dyne, and Philips. Dr Scotti has served as a consultant for NeoChord and Edwards Lifesciences. Dr Estévez-Loureiro has served as a consultant to Abbott Vascular, Edwards Lifesciences, Boston Scientific, Venus Medtech, and Jenscare. Dr Leurent has received speaker and proctoring honoraria from Edwards Lifesciences and Abbott Medical. Dr Hausleiter has received research support and speaker honoraria from Edwards Lifesciences., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Early studies of the Tendyne transcatheter mitral valve replacement (TMVR) showed promising results in a small selective cohort., Objectives: The authors present 1-year data from the currently largest commercial, real-world cohort originating from the investigator-initiated TENDER (Tendyne European Experience) registry., Methods: All patients from the TENDER registry eligible for 1-year follow-up were included. The primary safety endpoint was 1-year cardiovascular mortality. Primary performance endpoint was reduction of mitral regurgitation (MR) up to 1 year., Results: Among 195 eligible patients undergoing TMVR (median age 77 years [Q1-Q3: 71-81 years], 60% men, median Society of Thoracic Surgeons Predicted Risk of Mortality 5.6% [Q1-Q3: 3.6%-8.9%], 81% in NYHA functional class III or IV, 94% with MR 3+/4+), 31% had "real-world" indications for TMVR (severe mitral annular calcification, prior mitral valve treatment, or others) outside of the instructions for use. The technical success rate was 95%. The cardiovascular mortality rate was 7% at 30 day and 17% at 1 year (all-cause mortality rates were 9% and 29%, respectively). Reintervention or surgery following discharge was 4%, while rates of heart failure hospitalization reduced from 68% in the preceding year to 25% during 1-year follow-up. Durable MR reduction to ≤1+ was achieved in 98% of patients, and at 1 year, 83% were in NYHA functional class I or II. There was no difference in survival and major adverse events between on-label use and "real-world" indications up to 1 year., Conclusions: This large, real-world, observational registry reports high technical success, durable and complete MR elimination, significant clinical benefits, and a 1-year cardiovascular mortality rate of 17% after Tendyne TMVR. Outcomes were comparable between on-label use and "real-world" indications, offering a safe and efficacious treatment option for patients without alternative treatments. (Tendyne European Experience Registry [TENDER]; NCT04898335)., Competing Interests: Funding Support and Author Disclosures The TENDER study was carried out without financial support from industry. It was initiated as an academic investigator trial by LMU University Hospital and Universitätsmedizin Mainz. Dr Baldus has received research grants and honoraria from Abbott and Edwards Lifesciences. Dr Rudolph has received speaker honoraria from Abbott. Dr Andreas has received proctoring, consulting, and speaker fees from Edwards Lifesciences, Abbott, Medtronic, Boston, Zoll, and AbbVie; and institutional research grants from Edwards Lifesciences, Abbott, Medtronic, and LSI. Dr Duncan has received consulting fees and honoraria from Abbott, Edwards Lifesciences, Medtronic, NeoChord. Dr Nombela serves as a physician proctor for and has received advisory fees from Abbott Cardiovascular, Edwards Lifesciences, and Products + Features. Dr Ruge serves as a physician proctor for and has received advisory fees from Abbott Medical. Dr Conradi serves as an advisory board member for Abbott, Medtronic, and JenaValve; and is a consultant for Edwards Lifesciences, Boston Scientific, MicroPort, Pi-Cardia. Dr Dumonteil has received consulting and proctoring fees from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Barth has received speaker and advisory fees from Abbott Cardiovascular and Edwards Lifesciences. Dr Adamo has received speaker honoraria from Abbott, Medtronic, and Edwards Lifesciences. Dr Maisano has received grant and/or research institutional support from Abbott, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific, New Valve Technology, Terumo, and Venus; has received consulting fees and personal and institutional honoraria from Abbott, Medtronic, Edwards Lifesciences, Xeltis, Cardiovalve, Occlufit, Simulands, MTEX Cardio, Venus, and Squadra; has received royalty income from and holds intellectual property rights with Edwards Lifesciences; is a shareholder (including share options) in CardioGard, Cardiovalve, Magenta, SwissVortex, Transseptal Solutions, 4Tech, and Perifect. Dr Lurz has received honoraria from ReCor Medical and Innoventric; and has received institutional grants from Edwards Lifesciences and ReCor. Dr Hausleiter has received speaker fees, research support, and advisory fees from Edwards Lifesciences. Dr von Bardeleben has received speaker or advisory fees from Abbott Cardiovascular, Edwards Lifesciences, Medtronic, NeoChord, Philips, and Siemens; and has conducted unpaid trial activity for Abbott Cardiovascular, Edwards Lifesciences, Jenscare Scientific, Medtronic, and NeoChord. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter tricuspid valve replacement (TTVR) abolishes tricuspid regurgitation (TR) and has emerged as a definitive treatment for TR., Objectives: The purpose of this multicenter, observational study was to determine the clinical characteristics and short-term outcomes of patients with TR screened for TTVR., Methods: Patients underwent TTVR screening at 7 centers on a compassionate-use basis. The primary endpoints were NYHA functional class and TR grade at 30-day follow-up. Secondary endpoints included all-cause mortality, heart failure hospitalization, technical success, and reasons for TTVR screening failure., Results: A total of 149 patients (median age 79 years [Q1-Q3: 72-84 years], 54% women) underwent TTVR screening. The TTVR screening failure rate was 74%, mainly related to large tricuspid annular diameter. Patients undergoing TTVR (n = 38) had significant functional improvements (NYHA functional class I or II from 21% to 68%; P < 0.001), with TR ≤1+ in 97% at 30-day follow-up (P < 0.001 from baseline). Technical success was achieved in 91%, with no intraprocedural mortality or conversion to surgery. At 30-day follow-up, mortality was 8%, heart failure hospitalization 5%, major bleeding 18%, and reintervention 9%. Patients who failed screening for TTVR and subsequently underwent "bailout" transcatheter edge-to-edge repair (n = 26) had favorable outcomes (NYHA functional class I or II from 27% to 58%; P < 0.001), with TR ≤1+ in 43% at 30-day follow-up (P < 0.001 from baseline)., Conclusions: This first real-world report of TTVR screening demonstrated a high screening failure rate, mainly related to large tricuspid annular diameter. Patients undergoing TTVR had superior TR reduction and symptom alleviation compared with bailout tricuspid transcatheter edge-to-edge repair, at the cost of greater procedural complications., Competing Interests: Funding Support and Author Disclosures Dr Taramasso has served as a consultant for Abbott Vascular, Boston Scientific, 4Tech, and CoreMedic; and has received speaker honoraria from Edwards Lifesciences. Dr Dumonteil has received consultancy and proctoring fees from Abbott Vascular, Ancora Heart, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Modine has been a consultant for Boston Scientific, Medtronic, Edwards Lifesciences, MicroPort, GE, and Abbott. Dr Latib has served on advisory boards for Medtronic, Abbott Vascular, Boston Scientific, Edwards Lifesciences, Shifamed, NeoChord, VDyne, and Philips. Dr Praz has received travel expense reimbursement from Edwards Lifesciences, Abbott Vascular, and Polares Medical. Dr Hausleiter has received speaker honoraria and research support from Abbott Vascular and Edwards Lifesciences; and is a consultant to Abbott Vascular and Edwards Lifesciences. Dr Fam is a consultant to Edwards Lifesciences, Abbott, and Cardiovalve. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: According to the TRILUMINATE (Clinical Trial to Evaluate Cardiovascular Outcomes in Patients Treated With the Tricuspid Valve Repair System) trial, transcatheter tricuspid edge-to-edge repair (T-TEER) improves quality of life beyond medical treatment, while no effects on heart failure hospitalization (HFH) and survival were observed at 1 year. However, the generalizability of the TRILUMINATE trial to real-world conditions remains a subject of discussion., Objectives: The aim of this study was to apply the clinical TRILUMINATE inclusion and exclusion criteria to a real-world T-TEER patient group and evaluate symptomatic and survival outcome in TRILUMINATE-eligible and TRILUMINATE-ineligible patients., Methods: Clinical TRILUMINATE inclusion and exclusion criteria were applied to a cohort of patients who underwent T-TEER at 5 European centers from 2016 to 2022. Study patients were compared regarding baseline characteristics, survival, HFH, and symptomatic outcomes as measured by NYHA functional class, a quality-of-life questionnaire and 6-minute walk distance., Results: Of 962 patients, 54.8% were classified as TRILUMINATE eligible, presenting with superior left ventricular function and fewer comorbidities compared with the ineligible population. Tricuspid regurgitation reduction, improvement in NYHA functional class, quality of life, and exercise capacity were comparable in both groups. However, the 1-year survival and HFH rates significantly differed (tricuspid regurgitation ≤2+ at discharge, 82% vs 85%; survival, 85% vs 75%; HFH, 14% vs 22% for eligible vs ineligible patients)., Conclusions: The observed differences in survival and HFH outcomes suggest a limited generalizability of TRILUMINATE to real-world conditions and indicate the need for additional studies evaluating the outcomes after T-TEER in less selected patient populations., Competing Interests: Funding Support and Author Disclosures Dr Praz has received travel expenses from Edwards Lifesciences, Abbott Vascular, Polares Medical, Medira, and Siemens Healthineers. Dr Kalbacher has received personal fees from Abbott Medical, Edwards Lifesciences, and Pi-Cardia. Dr Ludwig has received travel compensation from Edwards Lifesciences; has received advisory fees from Bayer; and has received speaker honoraria from Abbott. Dr Stolz has received speaker honoraria from Edwards Lifesciences. Dr Rudolph serves on the advisory boards of Edwards Lifesciences and Abbott Vascular; and has received research grants from Edwards Lifesciences and Abbott Vascular. Dr Kresoja has received travel expenses from Edwards Lifesciences. Dr Lurz has received institutional grants from Edwards Lifesciences; and has received honoraria from Innoventric. Dr Hausleiter has received research grant support and speaker honoraria from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Knowledge about atrial functional tricuspid regurgitation (afTR) in transcatheter aortic valve replacement (TAVR) patients is scarce., Objectives: The aim of the study was to analyze the association between the entity and the development of tricuspid regurgitation (TR) in patients undergoing TAVR for aortic stenosis and concomitant TR., Methods: We analyzed patients undergoing TAVR for severe aortic stenosis from January 2013 to December 2020 and concomitant at least moderate TR at baseline. afTR was defined as enlargement of the right atrium in relation to the right ventricle. TR development after TAVR and 3-year all-cause mortality were evaluated., Results: Out of 3,474 TAVR patients, we identified 420 patients with concomitant at least moderate TR. A total of 363 patients were included in the study, with 178 patients stratified in the afTR and 185 in the non-afTR group based on a receiver-operating characteristic curve cutoff of 1.132 of the right atrial/right ventricular area ratio. TR improvement after TAVR was observed in significantly less patients with afTR compared with non-afTR (31.1% vs 60.6%; P < 0.001). Multivariate regression analysis confirmed afTR as independent predictor for TR persistence (adjusted OR: 2.80; 95% CI: 1.66-4.76; P < 0.001). Moreover, afTR was associated with aggravation of TR after TAVR (17.0% vs 6.8%; P = 0.013). Three-year all-cause mortality was significantly higher in patients with persistence compared with patients with improvement of TR (P < 0.001)., Conclusions: In TAVR patients, afTR is an independent predictor for TR persistence. Moreover, TR persistence is associated with increased 3-year all-cause mortality., Competing Interests: Funding Support and Author Disclosures Drs Steffen and Deseive have received speaker honoraria from AstraZeneca. Dr Orban has received speaker honoraria from Abbott Medical, AstraZeneca, Abiomed, Bayer vital, Biotronik, Bristol-Myers Squibb, CytoSorbents, Daiichi Sankyo Deutschland, Edwards Lifesciences Services, and Sedana Medical. Dr Braun has received speaker honoraria from Abbott Vascular and Edwards Lifesciences. Dr Hausleiter has received research support and speaker honoraria from Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Men and women differ regarding comorbidities, pathophysiology, and the progression of valvular heart diseases., Objectives: This study sought to assess sex-related differences regarding clinical characteristics and the outcome of patients with severe tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI)., Methods: All 702 patients in this multicenter study underwent TTVI for severe TR. The primary outcome was 2-year all-cause mortality., Results: Among 386 women and 316 men in this study, men were more often diagnosed with coronary artery disease (52.9% in men vs 35.5% in women; P = 5.6 × 10 -6 ). Subsequently, the underlying etiology for TR in men was predominantly secondary ventricular (64.6% in men vs 50.0% in women; P = 1.4 × 10 -4 ), whereas women more often presented with secondary atrial etiology (41.7% in women vs 24.4% in men, P = 2.0 × 10 -6 ). Notably, 2-year survival after TTVI was similar in women and men (69.9% in women vs 63.7% in men; P = 0.144). Multivariate regression analysis identified dyspnea expressed as New York Heart Association functional class, tricuspid annulus plane systolic excursion (TAPSE), and mean pulmonary artery pressure (mPAP) as independent predictors for 2-year mortality. The prognostic significance of TAPSE and mPAP differed between sexes. Consequently, we looked at right ventricular-pulmonary arterial coupling expressed as TAPSE/mPAP and identified sex-specific thresholds to best predict survival; women with a TAPSE/mPAP ratio <0.612 mm/mm Hg displayed a 3.43-fold increased HR for 2-year mortality (P < 0.001), whereas men with a TAPSE/mPAP ratio <0.434 mm/mm Hg displayed a 2.05-fold increased HR for 2-year mortality (P = 0.001)., Conclusions: Even though men and women differ in the etiology of TR, both sexes show similar survival rates after TTVI. The TAPSE/mPAP ratio can improve prognostication after TTVI, and sex-specific thresholds should be applied to guide future patient selection., Competing Interests: Funding Support and Author Disclosures Dr Lachmann has received funding from the Technical University of Munich (Clinician Scientist Grant) and from the Else Kröner-Fresenius Foundation (Clinician Scientist Grant). All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Residual mitral regurgitation (MR) is thought to be an important predictor of long-term survival following transcatheter edge-to-edge repair (TEER). Intraprocedural MR assessment using transesophageal echocardiography could be limited by image quality, hemodynamics, and patient sedation. The MitraScore is a validated multimodal approach for intraprocedural MR assessment during TEER., Objectives: This study aimed to assess the impact of residual MR using the MitraScore on 1-year mortality., Methods: Patients undergoing mitral TEER were eligible for inclusion in the prospective, multicenter MITRA-PRO registry (A Prospective Registry Study on 1-Year Mortality and the Prognostic Significance of MitraScore After MitraClip Implantation in Patients With Mitral Regurgitation). Patients with a MitraScore ≤3 were defined as patients with mild residual MR after mitral TEER, whereas a MitraScore ≥4 was considered as relevant residual MR. Mortality, rehospitalization, and major adverse events were assessed 1 year after TEER., Results: A MitraScore ≤3 was found in 1,059 patients (71.0%), whereas 432 patients revealed a MitraScore ≥4 (29.0%). One-year mortality was significantly lower in patients with nonrelevant residual MR (MitraScore ≤3 14.6% vs MitraScore≥4 22.1%). An almost linear relationship between intraprocedural MitraScore after TEER and mortality was observed. The combined clinical endpoint of mortality and rehospitalization within the 1-year follow-up was also significantly lower in the MitraScore ≤3 group (31.5%) than in the MitraScore ≥4 group (40.8%). A subgroup analysis confirmed the predictive value of the MitraScore in patients with primary, secondary, or mixed MR etiologies., Conclusions: Residual MR assessed by intraprocedural MitraScore after TEER predicts 1-year mortality and rehospitalization. Therefore, the multimodal MitraScore improves MR assessment during mitral TEER and might improve patient survival.(A Prospective Registry Study on 1-Year Mortality and the Prognostic Significance of MitraScore After MitraClip Implantation in Patients With Mitral Regurgitation [MITRA-PRO]; DRKS00012288)., Competing Interests: Funding Support and Author Disclosures This study was funded by Zentrum für klinische Studien (ZKS, Witten/Herdecke University), and core lab analysis was funded by Abbott Vascular. Prof Boekstegers has served a proctor and for the Center of Excellence for Abbott Vascular and Edwards Lifesciences. Dr Hausleiter has received speaker honoraria and research support from Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Secondary mitral regurgitation (SMR) is a progressive disease with characteristic pathophysiological changes that may influence prognosis. Although the staging of SMR patients suffering from heart failure with reduced ejection fraction (HFrEF) according to extramitral cardiac involvement has prognostic value in medically treated patients, such data are so far lacking for edge-to-edge mitral valve repair (M-TEER)., Objectives: This study sought to classify M-TEER patients into disease stages based on the phenotype of extramitral cardiac involvement and to assess its impact on symptomatic and survival outcomes., Methods: Based on echocardiographic and clinical assessment, patients were assigned to 1 of the following HFrEF-SMR groups: left ventricular involvement (Stage 1), left atrial involvement (Stage 2), right ventricular volume/pressure overload (Stage 3), or biventricular failure (Stage 4). A Cox regression model was implemented to investigate the impact of HFrEF-SMR stages on 2-year all-cause mortality. The symptomatic outcome was assessed with New York Heart Association functional class at follow-up., Results: Among a total of 849 eligible patients who underwent M-TEER for relevant SMR from 2008 until 2019, 9.5% (n = 81) presented with left ventricular involvement, 46% (n = 393) with left atrial involvement, 15% (n = 129) with right ventricular pressure/volume overload, and 29% (n = 246) with biventricular failure. An increase in HFrEF-SMR stage was associated with increased 2-year all-cause mortality after M-TEER (HR: 1.39; CI: 1.23-1.58; P < 0.01). Furthermore, higher HFrEF-SMR stages were associated with significantly less symptomatic improvement at follow-up., Conclusions: The classification of M-TEER patients into HFrEF-SMR stages according to extramitral cardiac involvement provides prognostic value in terms of postinterventional survival and symptomatic improvement., Competing Interests: Funding Support and Author Disclosures Dr Orban has received speaker fees from Abbott Vascular and Tomtec Imaging Systems. Dr Karam has received consultant fees from Edwards Lifesciences and Medtronic; and has received proctor fees from Abbott. Dr von Bardeleben has received institutional grants and has served as a speaker for Abbott Vascular and Edwards Lifesciences; and has performed trials unpaid for Abbott Vascular, Edwards Lifesciences, Lifetec, Medtronic, and NeoChord. Dr Iliadis has received travel support from Abbott; and has received consultant honoraria from Abbott and Edwards Lifesciences. Dr Pfister has received consultancy and speaker fee from Edwards Lifesciences; and has received speaker fee by Abbott Vascular. The Department of Cardiology of the Leiden University Medical Centre received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, and Medtronic. Dr Higuchi has received lecture fees from Medtronic Japan, Daiichi Sankyo, and Ono Pharmaceutical Company. Dr Petronio has received consulting fees and honoraria for lectures from Abbott and Medtronic; has received consulting fees from Boston; and has received honoraria fees from Daiichi Sankyo. Dr Melica has served as a proctor for Abbott Vascular. Dr Braun has received speaker honoraria from Abbott Vascular. Dr Windecker reports research and educational grants to the institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson and Johnson, Medicure, Medtronic, Merck Sharp and Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave. Dr Windecker serves as an unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis but has not received personal payments by pharmaceutical companies or device manufacturers. Dr Windecker is also member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr Praz has received travel expenses from Abbott Vascular, Polares Medical, and Edwards Lifesiences. Dr Kalbacher has received proctor and lecture fees from Edwards Lifesciences; and has received lecture fees from Abbott Vascular. Dr Lurz has received grants from Abbott Medical and Edwards Lifesciences. Dr Bax has received speaker fees from Abbott Vascular and Edwards Lifesciences. Dr Hausleiter has received research support and speaker honoraria from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The comparative efficacy of percutaneous techniques for the preparation of calcified lesions before stenting remains poorly studied., Objectives: This study sought to compare the performance of up-front rotational atherectomy (RA) or balloon-based techniques before drug-eluting stent implantation in severely calcified coronary lesions as assessed by angiography and optical coherence tomography (OCT)., Methods: Patient-level data from the PREPARE-CALC (Comparison of Strategies to Prepare Severely Calcified Coronary Lesions) and ISAR-CALC (Comparison of Strategies to Prepare Severely Calcified Coronary Lesions) randomized trials were pooled. The primary endpoint was stent expansion as assessed by OCT imaging. The secondary endpoints included stent eccentricity, stent asymmetry, angiographic acute lumen gain, strategy success and in-hospital occurrence of cardiac death, target vessel myocardial infarction, and repeat revascularization., Results: Among 274 patients originally randomized, 200 participants with available OCT data after lesion preparation with RA (n = 63), a modified balloon (MB, n = 103), or a super high-pressure balloon (n = 34) before stenting were analyzed. The use of RA versus MB or a super high-pressure balloon led to comparable stent expansion (73.2% ± 11.6% vs 70.8% ± 13.6% vs 71.8% ± 12.2%, P = 0.49) and stent asymmetry (P = 0.83). Compared with RA or MB, a super high-pressure balloon was associated with less stent eccentricity (P = 0.03) with a numerically higher acute lumen gain, albeit not significantly different (P = 0.08). Strategy success was more frequent with RA versus MB (P = 0.002) and numerically more frequent with RA versus a super high-pressure balloon (P = 0.06). Clinical outcomes did not differ between groups., Conclusions: In patients with severely calcified lesions undergoing drug-eluting stent implantation, lesion preparation with RA, MB, or a super high-pressure balloon was associated with comparable stent expansion. A super high-pressure balloon is associated with less stent eccentricity, whereas strategy success is more frequent with RA., Competing Interests: Funding Support and Author Disclosures The PREPARE-CALC trial was an investigator-initiated trial, which was financed by the Heart Center, Segeberger Kliniken GmbH, Bad Segeberg, Germany. The ISAR-CALC trial was an investigator-initiated trial, which was supported by a research grant from SIS Medical AG and Boston Scientific. Dr Rheude has received speaker fees from SIS Medical AG. Dr Allali has received speaker/proctoring honoraria from Boston Scientific and Biotronik. Dr Cuculi has received speaker and consulting fees from Abbott Vascular and SIS Medical AG. Dr Kufner has received speaker and consulting fees from AstraZeneca, Bristol Myers Squibb, and Translumina not related to the current work. Dr Bossard has received speaker and consulting fees from Abbott Vascular and SIS Medical AG. Dr Joner has received lecture fees and research grants from Edwards Lifesciences and Boston Scientific; and is a consultant for Biotronik and Orbus Neich. Dr Byrne has received research funding to the institution from Abbott Vascular, Biosensors, and Boston Scientific. Dr Cassese has received lectures/proctoring honoraria from SIS Medical AG; and has received research funding to the institution from SIS Medical AG and Boston Scientific for the conduct of the ISAR-CALC trial. Dr Abdel-Wahab reports that his hospital received speaker honoraria and/or consulting fees on his behalf from Medtronic and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter treatment techniques for tricuspid regurgitation (TR) have evolved in recent years, with leaflet repair being the most commonly used, but thus far evidence on the PASCAL and PASCAL Ace system is based mainly on compassionate use data., Objectives: This is the first report on commercial use in a multicenter study with a large patient cohort investigating the safety and efficacy of the PASCAL and PASCAL Ace system in the treatment of TR., Methods: In a retrospective, multicenter, observational setting, data from all consecutive patients undergoing leaflet repair for TR at 8 centers was collected, including a centralized analysis of echocardiographic data., Results: A total of 235 high-risk patients (mean age 78 ± 8 years, 49% women, mean Society of Thoracic Surgeons Predicted Risk of Mortality score 8.6% ± 6.8%) were included. TR was functional in 87% of patients and graded severe or higher in 91%. TR was successfully reduced to moderate or less in 78% of patients (P < 0.001). Procedural success was 78% (n = 153). At the latest available follow-up (median 173 days), TR reduction was sustained (78% with TR moderate or less; P < 0.001), and echocardiography showed indications of right ventricular remodeling (mean right ventricular end-diastolic diameter 56 ± 9 mm vs 53 ± 9 mm; P < 0.001). Patients' symptoms diminished significantly (63% were in New York Heart Association functional class I or II at follow-up; P < 0.001). In a device-specific analysis, the PASCAL and PASCAL Ace showed no difference in TR reduction (postprocedural TR moderate or less in 77% vs 78%; P = 0.82)., Conclusions: In early clinical experience, the PASCAL (Ace) leaflet repair system has high technical and procedural success rates with efficient TR reduction and significant clinical and echocardiographic improvement at follow-up., Competing Interests: Funding Support and Author Disclosures Dr Praz has received travel expenses from Abbott Vascular, Polares Medical, and Edwards Lifesciences. Dr Higuchi has received lecture fees from Medtronic Japan, Daiichi-Sankyo, and Ono Pharmaceutical Company. Dr Luedike has received speaker fees from Edwards Lifesciences. Dr Rassaf has received speaker fees from AstraZeneca, Daiichi-Sankyo, Bayer, Novartis, and Abiomed outside the submitted work. Dr Braun has received speaker honoraria from Abbott Vascular. Dr Lurz has received grants from Abbott Vascular, Edwards Lifesciences, and ReCor Medical. Dr Hausleiter has received research support and speaker honoraria from Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to improve echocardiographic assessment of pulmonary hypertension (PH) in patients presenting with severe tricuspid regurgitation (TR)., Background: Echocardiographic assessment of PH in patients with severe TR carries several pitfalls for underestimation, hence concealing the true severity of PH in very sick patients in particular, and ultimately obscuring the impact of PH on survival after transcatheter tricuspid valve intervention (TTVI)., Methods: All patients in this study underwent TTVI for severe TR between 2016 and 2020. To predict the mean pulmonary artery pressure (mPAP) solely based on echocardiographic parameters, we trained an extreme gradient boosting (XGB) algorithm. The derivation cohort was constituted by 116 out of 162 patients with both echocardiography and right heart catheterization data, preprocedurally obtained, from a bicentric registry. Moreover, 142 patients from an independent institution served for external validation., Results: Systolic pulmonary artery pressure was consistently underestimated by echocardiography in comparison to right heart catheterization (40.3 ± 15.9 mm Hg vs 44.1 ± 12.9 mm Hg; P = 0.0066), and the assessment was most discrepant among patients with severe defects of the tricuspid valve and impaired right ventricular systolic function. Using 9 echocardiographic parameters as input variables, an XGB algorithm could reliably predict mPAP levels (R = 0.96, P < 2.2 × 10 -16 ). Moreover, patients with elevations in predicted mPAP levels ≥29.9 mm Hg showed significantly reduced 2-year survival after TTVI (58.3% [95% CI: 41.7%-81.6%] vs 78.8% [95% CI: 68.7%-90.5%]; P = 0.026). Importantly, the poor prognosis associated with elevation in predicted mPAP levels was externally confirmed (HR for 2-year mortality: 2.9 [95% CI: 1.5-5.7]; P = 0.002)., Conclusions: PH in patients with severe TR can be reliably assessed based on echocardiographic parameters in conjunction with an XGB algorithm, and elevations in predicted mPAP levels translate into increased mortality after TTVI., Competing Interests: Funding Support and Author Disclosures Dr Lachmann has received funding from the Technical University of Munich (clinician scientist grant) and from the Else Kröner-Fresenius Foundation (clinician scientist grant). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the prevalence and prognostic implications of cardiohepatic syndrome (CHS) in patients with tricuspid regurgitation (TR) treated with tricuspid transcatheter edge-to-edge valve repair (T-TEER)., Background: The role of CHS in patients undergoing T-TEER for severe TR has not been studied., Methods: This study included patients who underwent T-TEER for TR between 2016 and 2020 at 2 high-volume academic centers. CHS was defined as elevation of at least 2 of 3 cholestatic hepatic enzymes. The impact of CHS on 1-year all-cause mortality and clinical outcomes after T-TEER was investigated., Results: T-TEER reduced TR severity to ≤2+ in 257 of 305 included patients (86.2%). CHS was present in 45.2% of patients and was associated with a higher rate of mortality and of first hospitalization for heart failure (HHF) (CHS vs no CHS: estimated 1-year mortality, 34.0% vs 15.9% [P < 0.01]; HHF, 23.0% vs 12.2% [P = 0.01]). CHS was identified as an independent predictor of 1-year all-cause mortality (HR: 1.86; 95% CI: 1.10-3.14; P < 0.05). Irrespective of CHS, T-TEER improved New York Heart Association functional class and 6-minute walk distance in the majority of patients. In patients with impaired baseline hepatic function, laboratory liver parameters improved after T-TEER., Conclusions: CHS is a strong predictor of mortality and HHF after T-TEER and should be evaluated in the process of procedural decision making for T-TEER. Nevertheless, T-TEER is associated with relevant symptomatic alleviation irrespective of CHS., Competing Interests: Funding Support and Author Disclosures Drs Näbauer and Braun have received speaker honoraria from Abbott Vascular. Dr Orban has received speaker fees from Abbott Vascular and TomTec Imaging Systems; and has received speaker honoraria from Abbott Medical, AstraZeneca, Abiomed, Bayer Vital, Biotronik, Bristol Myers Squibb, CytoSorbents, Daiichi-Sankyo Deutschland, Edwards Lifesciences Services, and Sedana Medical. Dr Higuchi has received lecture fees from Medtronic Japan, Daiichi-Sankyo, and Ono Pharmaceutical Company. Dr Lurz has been a consultant to Abbott Structural Heart, Edwards Lifesciences, and Medtronic. Dr Hausleiter has received speaker honoraria and research support from and serves as consultant for Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this retrospective analysis was to categorize patients with severe aortic stenosis (AS) according to clinical presentation by applying unsupervised machine learning., Background: Patients with severe AS present with heterogeneous clinical phenotypes, depending on disease progression and comorbidities., Methods: Unsupervised agglomerative clustering was applied to preprocedural data from echocardiography and right heart catheterization from 366 consecutively enrolled patients undergoing transcatheter aortic valve replacement for severe AS., Results: Cluster analysis revealed 4 distinct phenotypes. Patients in cluster 1 (n = 164 [44.8%]), serving as a reference, presented with regular cardiac function and without pulmonary hypertension (PH). Accordingly, estimated 2-year survival was 90.6% (95% CI: 85.8%-95.6%). Clusters 2 (n = 66 [18.0%]) and 4 (n = 91 [24.9%]) both comprised patients with postcapillary PH. Yet patients in cluster 2 with preserved left and right ventricular structure and function showed a similar survival as those in cluster 1 (2-year survival 85.8%; 95% CI: 76.9%-95.6%), whereas patients in cluster 4 with dilatation of all heart chambers and a high prevalence of mitral and tricuspid regurgitation (12.5% and 14.8%, respectively) died more often (2-year survival 74.9% [95% CI: 65.9%-85.2%]; HR for 2-year mortality: 2.8 [95% CI: 1.4-5.5]). Patients in cluster 3, the smallest (n = 45 [12.3%]), displayed the most extensive disease characteristics (ie, left and right heart dysfunction together with combined pre- and postcapillary PH), and 2-year survival was accordingly reduced (77.3% [95% CI: 65.2%-91.6%]; HR for 2-year mortality: 2.6 [95% CI: 1.1-6.2])., Conclusions: Unsupervised machine learning aids in capturing complex clinical presentations as observed in patients with severe AS. Importantly, structural alterations in left and right heart morphology, possibly due to genetic predisposition, constitute an equally sensitive indicator of poor prognosis compared with high-grade PH., Competing Interests: Funding Support and Author Disclosures Dr Lachmann has received funding from the Technical University of Munich (clinician scientist grant) and from the Else Kröner-Fresenius Foundation (clinician scientist grant). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs)., Background: The outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined., Methods: Patients (n = 4,012) were categorized into 3 groups: low eGFR (<60 mL/min/1.73 m 2 ), intermediate eGFR (≥60 and <90 mL/min/1.73 m 2 ), and high eGFR (≥90 mL/min/1.73 m 2 ). The primary endpoint was a composite of all-cause death, myocardial infarction, and stroke; the secondary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding, both at 1 year., Results: Patients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95% CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95% CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95% CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95% CI: 1.04-2.08; P = 0.029); there was no significant difference in bleeding., Conclusions: These results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800)., Competing Interests: Funding Support and Author Disclosures This research was supported by a grant (FKZ 81X1600501) from the German Center for Cardiovascular Research and Deutsches Herzzentrum München. Dr Angiolillo has received grants and personal fees from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Janssen, Merck, Sanofi, and CeloNova; has received personal fees from Haemonetics, PhaseBio, PLx Pharma, Pfizer, The Medicines Company, and St. Jude Medical; and has received grants from CSL Behring, Eisai, Gilead, Idorsia Pharmaceuticals, Matsutani Chemical Industry, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr Hochholzer has received personal fees from Bayer Vital, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Novartis, AstraZeneca, and The Medicines Company. Dr Kufner has received personal fees from Bristol Myers Squibb, AstraZeneca, and Translumina. Dr Sager has received grants from the European Research Council, Else-Kröner-Fresenius-Stiftung, Deutsche Herzstiftung, and Deutsche Forschungsgemeinschaft. Dr Neumann has received personal fees from Amgen, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, and Ferrer; has received grants and personal fees from Pfizer, Biotronik, Edwards Lifesciences, Bayer Healthcare, and Boston Scientific; and has received grants from Medtronic and GlaxoSmithKline outside the submitted work. Dr Schüpke has received the Else Kröner memorial grant from Else Kröner-Fresenius Stiftung; has received financial support from the German Center for Cardiovascular Research; has received consulting fees from Bayer Vital; and has received lecture fees from Daiichi-Sankyo and Biopas Laboratories. Dr Sibbing has received personal fees from Daichi-Sankyo, Sanofi, AstraZeneca, Bayer, Pfizer, and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objectives: The aim of this study was to assess the impact of residual mitral regurgitation (resMR) on mortality with respect to left ventricular dilatation (LV-Dil) or right ventricular dysfunction (RV-Dys) in patients with secondary mitral regurgitation (SMR) who underwent mitral valve transcatheter edge-to-edge repair (TEER)., Background: The presence of LV-Dil and RV-Dys correlates with advanced stages of heart failure in SMR patients, which may impact the outcome after TEER., Methods: SMR patients in a European multicenter registry were evaluated. Investigated outcomes were 2-year all-cause mortality and improvement in New York Heart Association functional class with respect to MR reduction, LV-Dil (defined as LV end-diastolic volume ≥159 ml), and RV-Dys (defined as tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure ratio of <0.274 mm/mm Hg)., Results: Among 809 included patients, resMR ≤1+ was achieved in 546 (67%) patients. Overall estimated 2-year mortality rate was 32%. Post-procedural resMR was significantly associated with mortality (p = 0.031). Although the improvement in New York Heart Association functional class persisted regardless of either LV-Dil or RV-Dys, the beneficial treatment effect of resMR ≤1+ on 2-year mortality was observed only in patients without LV-Dil and RV-Dys (hazard ratio: 1.75; 95% confidence interval: 1.03 to 3.00)., Conclusions: Achieving optimal MR reduction by TEER is associated with improved survival in SMR patients, especially if the progress in heart failure is not too advanced. In SMR patients with advanced stages of heart failure, as evidenced by LV-Dil or RV-Dys, the treatment effect of TEER on symptomatic improvement is maintained, but the survival benefit appears to be reduced., Competing Interests: Funding Support and Author Disclosures This work was supported by Klinikum der Universität München. Dr. Higuchi has received lecture fees from Medtronic Japan, Daiichi-Sankyo, and Ono Pharmaceutical Company. Dr. Orban has received speaker fees from Abbott Vascular and Tomtec Imaging Systems. Dr. Karam has received consultant fees from Abbott Vascular. Dr. Kalbacher has received lecture fees and travel expenses from Abbott; and has received proctor fees and travel expenses from Edwards Lifesciences. Dr. Schofer has received personal fees from Boston Scientific; and has received travel compensation from Abbott Vascular and Edwards Lifesciences. Dr. Ludwig has received travel compensation from Abbott Vascular. Dr. Braun has received speaker honoraria from Abbott Vascular. Dr. Windecker has received research and educational grants from Abbott, Amgen, Bristol Myers Squibb, Bayer, Boston Scientific, Biotronik, CSL, Medtronic, Edwards, Sinomed, and Polares. Dr. Pfister has received financial support for attending symposia from Abbott Vascular. Dr. von Bardeleben has received speaker fees from Abbott Vascular and Edwards Lifesciences. Dr. Hausleiter has received research support and speaker honoraria from Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The authors sought to assess sex-based differences in characteristics and outcomes of patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) for secondary mitral regurgitation (SMR)., Background: Subgroup analysis from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial indicated potential sex-related differences in outcomes after TMVR. The impact of sex on results after TMVR in a real-world setting is unknown., Methods: The authors assessed clinical outcomes and echocardiographic parameters in women and men undergoing TMVR for SMR between 2008 and 2018 who were included in the large, international, multicenter real-world EuroSMR registry (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation)., Results: A total of 1,233 patients, including 445 women (36%) and 788 men (64%), were analyzed. Although women were significantly older and had fewer comorbidities than men, TMVR was equally effective in women and men (mitral regurgitation [MR] grade ≤2+ at discharge: 93.2% vs. 94.6% for women vs. men; p = 0.35). All-cause mortality at 1 year (17.9% vs. 18.9%, adjusted hazard ratio: 0.806; p = 0.46) and at 2-year follow-up (26.5% vs. 26.4%, adjusted hazard ratio: 0.757; p = 0.26) were similar in women versus men after multivariate regression analysis. Durability of MR reduction, improvement in symptoms, quality of life, and functional capacity did also not differ during follow-up., Conclusions: Results from the EuroSMR registry confirmed effective and similar MR reduction with TMVR in women and men. There were no sex-related differences in clinical outcomes up to 2 years of follow-up., Competing Interests: Funding Support and Author Disclosures This work was supported by Klinikum der Universität München. Dr. Orban has received speaker honoraria from Abbott Vascular. Dr. Karam has received consultant fees from Abbott Vascular. Dr. Kalbacher has received travel expenses and lecture fees from Abbott Vascular. Dr. Pfister has received financial support for attending symposia by Abbott Vascular. Dr. Lurz has been a consultant to Abbott Vascular, Edwards Lifesciences, and Medtronic. Dr. Windecker has received research and educational grants to his institution from Abbott, Amgen, Bayer, Bristol Myers Squibb, Biotronik, Boston Scientific, CSL Behring, Medtronic, Edwards Lifesciences, Polares, and Sinomed. Prof. Hausleiter has received speaker honoraria from and has served as consultant for Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this observational first-in-human experience was to investigate the feasibility and safety of the EVOQUE tricuspid valve replacement system and its impact on short-term clinical outcomes., Background: Transcatheter tricuspid intervention is a promising option for selected patients with severe tricuspid regurgitation (TR). Although transcatheter leaflet repair is an option for some, transcatheter tricuspid valve replacement (TTVR) may be applicable to a broader population., Methods: Twenty-five patients with severe TR underwent EVOQUE TTVR in a compassionate-use experience. The primary outcome was technical success, with NYHA (NYHA) functional class, TR grade, and major adverse cardiac and cerebrovascular events assessed at 30-day follow-up., Results: All patients (mean age 76 ± 3 years, 88% women) were at high surgical risk (mean Society of Thoracic Surgeons risk score 9.1 ± 2.3%), with 96% in NYHA functional class III or IV. TR etiology was predominantly functional, with mean tricuspid annular diameter of 44.8 ± 7.8 mm and mean tricuspid annular plane systolic excursion of 16 ± 2 mm. Technical success was 92%, with no intraprocedural mortality or conversion to surgery. At 30-day follow-up, mortality was 0%, 76% of patients were in NYHA functional class I or II, and TR grade was ≤2+ in 96%. Major bleeding occurred in 3 patients (12%), 2 patients (8%) required pacemaker implantation, and 1 patient (4%) required dialysis., Conclusions: This first-in-human experience evaluating EVOQUE TTVR demonstrated high technical success, acceptable safety, and significant clinical improvement. Larger prospective studies are needed to confirm durability and safety and the impact on long-term clinical outcomes., Competing Interests: Funding Support and Author Disclosures Dr. Fam has received speaker honoraria from Abbott Vascular; and is a consultant to Edwards Lifesciences. Dr. von Bardeleben received speaker honoraria from Abbott Vascular and Edwards Lifesciences. Dr. Ye is a consultant to Edwards Lifesciences, JC Medical, and CryoLife. Dr. Moss is a consultant to Edwards Lifesciences. Dr. Hausleiter has received speaker honoraria and research support from Abbott Vascular and Edwards Lifesciences; and is a consultant to Abbott Vascular and Edwards Lifesciences. Dr. George is consultant to VDyne, CardioMech, Atricure, MitreMedical, Neptune Medical, and W.L. Gore. Dr. Nabauer has received speaker honoraria from Abbott Vascular. Dr. Mack is co–principal investigator of the PARTNER (Placement of Aortic Transcatheter Valves) 3 trial for Edwards Lifesciences; is co–principal investigator of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial for Abbott; and is study chair of the APOLLO (Transcatheter Mitral Valve Replacement With the Medtronic Intrepid™ TMVR System in Patients With Severe Symptomatic Mitral Regurgitation) trial for Medtronic (all uncompensated). Dr. Hahn has received speaker fees from Edwards Lifesciences; is a consultant for Abbott Vascular, Boston Scientific, Gore & Associates, and Medtronic; holds equity with Navigate; and is the chief scientific officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she receives no direct industry compensation. Dr. Webb is a consultant to and has received research funding from Edwards Lifesciences, Abbott Vascular, Boston Scientific, Becton Dickinson, and ViVitro Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study was designed to assess hemodynamic changes in response to transcatheter tricuspid valve edge-to-edge repair (TTVR) and to identify hemodynamic predictors associated with mortality., Background: Severe tricuspid regurgitation (TR) is associated with high mortality. TTVR effectively alleviates heart failure symptoms, but comprehensive hemodynamic characterization of patients undergoing TTVR is currently lacking., Methods: This international, multicenter study included 236 patients undergoing TTVR. Data from clinical assessment, echocardiography, intraprocedural right heart catheterization, and noninvasive cardiac output measurement were analyzed. Hemodynamic predictors for mortality were identified using linear Cox regression analysis and were used for stratification of patients with subsequent analysis of survival time., Results: Patients (median age 78 years, 53% women) were symptomatic (89% in New York Heart Association functional class III or IV) because of severe TR (grade ≥3+ in 100%). TTVR significantly reduced TR at discharge (grade ≥3+ in 16%; p < 0.001), with a corresponding 19% reduction of the right atrial v wave (21 mm Hg vs. 16 mm Hg; p < 0.001) and an improvement in cardiac output (from 3.5 to 4.0 l/min; p < 0.01). Invasive mean pulmonary artery pressure, transpulmonary gradient, pulmonary vascular resistance, and right ventricular stroke work were significant predictors of 1-year mortality (p < 0.05 for all). Hemodynamic stratification by mean pulmonary artery pressure and transpulmonary gradient best predicted 1-year survival (p < 0.001). Although patients with pre-capillary dominant pulmonary hypertension showed an unfavorable prognosis (1-year survival 38%), patients without or with post-capillary pulmonary hypertension had favorable outcome (1-year survival 92% or 78%, respectively)., Conclusions: Invasive assessment of cardiopulmonary hemodynamic status predicts survival after TTVR. Invasive hemodynamic characterization may help identify patients profiting most from TTVR., Competing Interests: Author Disclosures Dr. Braun has received speaker honoraria from Abbott Vascular. Dr. Fam is a consultant for Edwards Lifesciences; and has received speaker honoraria from Abbott Vascular. Dr. von Bardeleben has received speaker honoraria from Abbott Vascular and Edwards Lifesciences. Dr. Lurz has received research grants from Edwards Lifesciences and Abbott Vascular; and is a consultant to Edwards Lifesciences and Abbott Vascular. Dr. Hausleiter has received speaker honoraria and research support from and serves as a consultant for Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: The aim of this study was to compare outcomes after transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 Ultra (Ultra) and SAPIEN 3 (S3) transcatheter heart valves (THVs)., Background: The latest generation balloon-expandable Ultra THV incorporates new technical features and might improve outcomes following TAVR., Methods: This registry included all consecutive patients who underwent TAVR with either the Ultra or S3 between January 2014 and January 2020. One-to-one propensity score matching was performed to account for differences in baseline characteristics. In-hospital and 30-day Valve Academic Research Consortium-2-defined outcomes were investigated., Results: A total of 310 patients (n = 155 Ultra, n = 155 S3) were included. There were no significant differences in baseline characteristics after propensity score matching. Procedures were significantly more often performed under conscious sedation with Ultra compared with S3 (97.4% vs. 71.6%; p < 0.001). Pre-dilatation was more frequent with S3 compared with Ultra (85.2% vs. 42.6%; p < 0.001). In-hospital outcomes, including device success (91.6% vs. 95.5%; p = 0.165), major vascular complications (12.3% vs. 11.0%; p = 0.723), and new pacemaker implantation (5.8% vs. 4.5%; p = 0.608), were comparable between S3 and Ultra patients, respectively. Post-procedural mean transprosthetic gradients (13.2 ± 5.7 mm Hg vs. 13.1 ± 4.7 mm Hg; p = 0.829) and rate of moderate or greater paravalvular leakage (PVL) (1.3% vs. 2.7%; p = 0.414) were comparable, whereas mild PVL was more frequent with S3 compared with Ultra (43.0% vs. 18.7%; p < 0.001)., Conclusions: Device success rates were high with both balloon-expandable THVs, with overall low rates of adverse events up to 30 days after TAVR. Despite a lower frequency of pre-dilatation, significant reduction of mild PVL confirms improved annular sealing properties of the novel Ultra THV., Competing Interests: Author Relationship With Industry Dr. Joner has received lecture fees and research grants from Edwards Lifesciences and Boston Scientific; and is a consultant for Biotronik and Orbus Neich. Dr. Kasel is a consultant and proctor for Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to assess the efficacy and safety of ticagrelor versus prasugrel in patients with diabetes mellitus (DM) presenting with acute coronary syndromes (ACS) in whom invasive therapy was planned., Background: The efficacy and safety of ticagrelor versus prasugrel in patients with ACS with DM undergoing invasive treatment remain unknown., Methods: This pre-specified analysis of the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial included 892 patients with ACS with DM and 3,124 patients with ACS without DM randomized to prasugrel or ticagrelor. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding (both assessed 12 months after randomization)., Results: The primary endpoint occurred in 51 patients (11.2%) in the ticagrelor group and 55 patients (13.0%) in the prasugrel group in the DM cohort (hazard ratio: 0.84; 95% confidence interval: 0.58 to 1.24; p = 0.383) and in 132 patients (8.6%) in the ticagrelor group and 81 patients (5.2%) in the prasugrel group in the non-DM cohort (hazard ratio: 1.70; 95% confidence interval: 1.29 to 2.24; p < 0.001). There was a significant treatment arm-by-diabetic status interaction (p int  = 0.0035). Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 27 patients (6.9%) in the ticagrelor group and 19 patients (5.5%) in the prasugrel group (p = 0.425) in the DM cohort and in 68 patients (5.2%) in the ticagrelor group and 60 patients (4.6%) in the prasugrel group in the non-DM cohort (p = 0.500)., Conclusions: DM seems to affect the efficacy of ticagrelor and prasugrel in patients with ACS. In patients with DM, the efficacy of ticagrelor was comparable with that of prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800)., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: The aim of this study was to evaluate the prognostic impact of target lesion revascularization (TLR) of the unprotected left main coronary artery (ULMCA) after stent failure., Background: Although drug-eluting stents are safe and effective for treatment of the ULMCA, increased rates of repeat revascularization have been observed., Methods: This is a patient-level pooled analysis of the randomized ISAR-LEFT-MAIN (Drug-Eluting-Stents for Unprotected Left Main Stem Disease) and ISAR-LEFT-MAIN-2 (Drug-Eluting Stents to Treat Unprotected Coronary Left Main Disease) trials, in which patients underwent stenting of the ULMCA. The present analysis includes patients who underwent angiography during follow-up. Patients with TLR were compared with those without. Additional long-term clinical follow-up after TLR was conducted, and its influence on mortality was evaluated. Mortality was calculated using the Kaplan-Meier method. Predictors of mortality were assessed in a multivariate analysis., Results: A total of 1,001 patients were eligible, of whom 166 experienced TLR. The 5-year mortality rate was 30.2% in patients with TLR compared with 17.3% in those without TLR (p < 0.001). In the multivariate analysis, glomerular filtration rate (-30 ml/min; hazard ratio [HR]: 2.25; 95% confidence interval [CI]: 1.54 to 3.27; p < 0.001), chronic obstructive pulmonary disease (HR: 4.95; 95% CI: 1.33 to 18.42; p = 0.02), and body mass index (+5 kg/m 2 ; HR: 1.61; 95% CI: 1.12 to 2.32; p = 0.01) were independent predictors of mortality after TLR due to left main stent failure. The type of repeat revascularization and the underlying stent did not influence the mortality after TLR of the ULMCA., Conclusions: Mortality after TLR for left main stent failure is high. Patient-related factors seem to have a greater impact on mortality after TLR than other variables., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to assess the value of echocardiographic right ventricular (RV) and systolic pulmonary artery pressure (sPAP) assessment in predicting transcatheter tricuspid edge-to-edge valve repair (TTVR) outcome., Background: RV dysfunction and pulmonary hypertension are associated with poor prognosis and are systematically sought during tricuspid regurgitation evaluation. The value of echocardiographic assessment in predicting TTVR outcome is unknown., Methods: Data were taken from the TriValve (Transcatheter Tricuspid Valve Therapies) registry, which includes patients undergoing TTVR at 14 European and North American centers. The primary outcome was 1-year survival free from hospitalization for heart failure, and secondary outcomes were 1-year survival and absence of hospital admission for heart failure at 1 year., Results: Overall, 249 patients underwent TTVR between June 2015 and 2018 (mean tricuspid annular plane systolic excursion [TAPSE] 15.8 ± 15.3 mm, mean sPAP 43.6 ± 16.0 mm Hg). Tricuspid regurgitation grade ≥3+ was found in 96.8% of patients at baseline and 29.4% at final follow-up; 95.6% were in New York Heart Association functional class III or IV initially, compared with 34.3% at follow-up (p < 0.05). Final New York Heart Association functional class did not differ among TAPSE and sPAP quartiles, even when both low TAPSE and high sPAP were present. Rates of 1-year survival and survival free from hospitalization for heart failure were 83.9% and 78.7%, respectively, without significant differences according to baseline echocardiographic RV characteristics (TAPSE, fractional area change, and end-diastolic area) and sPAP (p > 0.05 for all)., Conclusions: TTVR provides clinical improvement, with 1-year survival free from hospital readmission >75% in patients with severe tricuspid regurgitation. Conventional echocardiographic parameters used to assess RV function and sPAP did not predict clinical outcome after TTVR., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to retrospectively compare the characteristics, procedural courses, and outcomes of patients presenting with concomitant mitral regurgitation (MR) and tricuspid regurgitation (TR) in the TriValve (Transcatheter Tricuspid Valve Therapies) and TRAMI (Transcatheter Mitral Valve Interventions) registries., Background: Transcatheter mitral edge-to-edge valve repair (TMVR) has been shown to be successful in patients with severe MR. Lately, edge-to-edge repair has also emerged as a possible treatment for severe TR in patients at high risk for cardiac surgery. In patients with both severe MR and TR, the yield of concomitant transcatheter mitral and tricuspid valve repair (TMTVR) for patients at high surgical risk is unknown., Methods: The characteristics, procedural data, and 1-year outcomes of all patients in the international multicenter TriValve registry and the German multicenter TRAMI registry, who presented with both severe MR and TR, were retrospectively compared. Patients in TRAMI (n = 106) underwent isolated TMVR, while those in TriValve (n = 122) additionally underwent concurrent TMTVR in compassionate and/or off-label use., Results: All 228 patients (mean age 77 ± 8 years, 44.3% women) presented with significant dyspnea at baseline (New York Heart Association functional class III or IV in 93.9%), without any differences in the rates of pulmonary hypertension and chronic pulmonary disease. The proportion of patients with left ventricular ejection fraction <30% was higher in the TMVR group (34.9% vs. 18.0%; p < 0.001), while patients in the TMTVR group had lower glomerular filtration rates. At discharge, MR was comparably reduced in both groups. At 1 year, overall all-cause mortality was 34.0% in the TMVR group and 16.4% in the TMTVR group (p = 0.035, Cox regression). On multivariate analysis, TMTVR was associated with a 2-fold lower mortality rate (hazard ratio: 0.52; p = 0.02). The rate of patients in New York Heart Association functional class ≤II at 1 year did not differ (69.4% vs. 67.0%; p = 0.54)., Conclusions: Concurrent TMTVR was associated with a higher 1-year survival rate compared with isolated TMVR in patients with both MR and TR. Further randomized trials are needed to confirm these results., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: The aim of this study was to develop a risk score integrating cytochrome P450 2C19 loss-of-function genotypes with clinical risk factors influencing clopidogrel response that would allow the identification with more precision of subjects at risk for high platelet reactivity (HPR) and adverse clinical outcomes., Background: Clopidogrel is the most broadly used platelet P2Y 12 inhibitor. However, a considerable number of patients achieve inadequate platelet inhibition, with persistent HPR, an established marker of increased thrombotic risk, underscoring the need for tools to help identify these subjects. Although carriers of loss-of-function alleles of the cytochrome P450 2C19 enzyme have reduced clopidogrel metabolism leading to increased rates of HPR and thrombotic complications, this explains only a fraction of the pharmacodynamic response to clopidogrel, and a number of clinical factors have also been shown to have contributing roles., Methods: Three prospective and independent studies were used to: 1) develop a risk score integrating genetic and clinical factors to identify patients with HPR while on clopidogrel; 2) investigate the external validity of the risk score; and 3) define clinical outcomes associated with the risk score in a cohort of patients with myocardial infarction treated with clopidogrel., Results: A risk score ABCD-GENE (Age, Body Mass Index, Chronic Kidney Disease, Diabetes Mellitus, and Genotyping) was developed incorporating 5 independent predictors of HPR: 4 clinical (age >75 years, body mass index >30 kg/m 2 , chronic kidney disease [glomerular filtration rate <60 ml/min], and diabetes mellitus) and 1 genetic (cytochrome P450 2C19 loss-of-function alleles). The C-statistics for the score as an integer variable were 0.71 (95% confidence interval [CI]: 0.68 to 0.75) and 0.64 (95% CI: 0.60 to 0.67) in the pharmacodynamic derivation and validation cohorts, respectively. A cutoff score ≥10 was associated with the best sensitivity and specificity to identify HPR status. The C-statistics for the score were 0.67 (95% CI: 0.64 to 0.71) for all-cause death and 0.66 (95% CI: 0.63 to 0.69) for the composite of all-cause death, stroke, or myocardial infarction at 1 year. Using multiple models for adjustment, the ABCD-GENE score consistently and independently correlated with all-cause death, as well as with the composite of all-cause death, stroke, or myocardial infarction, both as a continuous variable and by using the cutoff of ≥10. The score did not predict bleeding., Conclusions: The ABCD-GENE score is a simple tool to identify patients with HPR on clopidogrel and who are at increased risk for adverse ischemic events, including mortality, following an acute myocardial infarction. In patients with a high ABCD-GENE score, long-term oral P2Y 12 inhibitors other than clopidogrel should be considered., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to compare angiographic and optical coherence tomography findings following subintimal as opposed to intraplaque recanalization of chronic total occlusions (CTOs)., Background: There is ongoing controversy regarding outcomes of intraplaque versus subintimal CTO recanalization., Methods: Consecutive patients undergoing angiography and intravascular optical coherence tomography following CTO recanalization were included in the ISAR-OCT-CTO (Intracoronary Stenting and Angiographic Results - Optical Coherence Tomography for Chronic Total Occlusions) registry. The study endpoints were percent diameter stenosis and late lumen loss as well as rate of uncovered and malapposed struts. Independent correlates of uncovered and malapposed struts were assessed by multivariate analysis., Results: The study included 75 patients. Intraplaque and dissection and re-entry techniques (DART) were used in 46 and 29 patients, respectively. There were no differences in terms of in-segment percent diameter stenosis (median 36.9 [interquartile range (IQR): 26.4 to 43.1] vs. 31.2 [IQR: 23.2 to 49.5]; p = 0.656), in-stent late lumen loss (0.215 mm [IQR: 0.063 to 0.495 mm] vs. 0.230 mm [IQR: 0.060 to 0.645 mm]; p = 0.837), or in-segment late lumen loss (0.030 mm [IQR: -0.278 to 0.510 mm] vs. 0.130 mm [IQR: -0.120 to 0.500 mm]; p = 0.395) at follow-up between the 2 techniques. Optical coherence tomography analysis showed comparable strut coverage (79.9% vs. 71.3%; p = 0.255) but significantly higher strut malapposition (6.6% vs. 13.6%; p < 0.001) following DART. Use of DART independently correlated with presence of strut malapposition (odds ratio: 3.41; 95% confidence interval: 1.24 to 9.36; p = 0.017) but not of strut coverage (odds ratio: 0.65; 95% confidence interval: 0.28 to 1.49; p = 0.314)., Conclusions: Intraplaque and subintimal recanalization techniques are associated with comparable mid-term angiographic results. Although the rate of uncovered struts is high following CTO recanalization, the recanalization technique does not independently correlate with presence of uncovered struts. There is a high rate of strut malapposition following CTO recanalization, particularly if achieved by means of DART., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the impact of the ACURATE neo (NEO) (Boston Scientific, Marlborough, Massachusetts) versus SAPIEN 3 (S3) (Edwards Lifesciences, Irvine, California) on permanent pacemaker implantation (PPI) in patients with pre-existing right bundle branch block (RBBB) after transcatheter aortic valve replacement., Background: Pre-existing RBBB is the strongest patient-related predictor for PPI after transcatheter aortic valve replacement. No comparison of newer-generation transcatheter heart valves with regard to PPI in these patients exists., Methods: This multicenter registry includes 4,305 patients; 296 (6.9%) had pre-existent RBBB and no pacemaker at baseline and formed the study population. The primary endpoint was new PPI at 30 days. The association of NEO versus S3 with PPI was assessed using binary logistic regression analyses and inverse probability treatment weighting in a propensity-matched population., Results: The 30-day PPI rate was 39.2%. The S3 and NEO were used in 66.9% and 33.1%, respectively. The NEO was associated with lower rates of PPI compared with the S3 (29.6% vs. 43.9%; p = 0.025; odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.32 to 0.89; p = 0.018), after multivariable adjustment (OR: 0.48; 95% CI: 0.26 to 0.86; p = 0.014), and in the inverse probability treatment weighting analysis (OR: 0.37; 95% CI: 0.25 to 0.55; p < 0.001). There was no difference in device failure (8.2% vs. 6.6%; p = 0.792) or in-hospital course. In the propensity-matched population, PPI rate was also lower in the NEO versus S3 (23.1% vs. 44.6%; p = 0.016; OR: 0.37; 95% CI: 0.17 to 0.78; p = 0.010), with no difference in device failure (9.2% vs. 6.2%; p = 0.742)., Conclusions: In patients with RBBB, risk of PPI was significantly lower with the NEO compared with the S3, suggesting the possibility of a patient tailored transcatheter heart valve therapy., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)