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PurposeHER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction.MethodsPatients with stage I-IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40-49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%.ResultsOf 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%.ConclusionThis study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population.

Background: Oral anticoagulation is recommended after ablation for atrial fibrillation among patients at high risk for stroke. Left atrial appendage closure is a mechanical alternative to anticoagulation, but data regarding its use after atrial fibrillation ablation are lacking., Methods: We conducted an international randomized trial involving 1600 patients with atrial fibrillation who had an elevated score (≥2 in men and ≥3 in women) on the CHA 2 DS 2 -VASc scale (range, 0 to 9, with higher scores indicating a greater risk of stroke) and who underwent catheter ablation. Patients were randomly assigned in a 1:1 ratio to undergo left atrial appendage closure or receive oral anticoagulation. The primary safety end point, tested for superiority, was non-procedure-related major bleeding or clinically relevant nonmajor bleeding. The primary efficacy end point, tested for noninferiority, was a composite of death from any cause, stroke, or systemic embolism at 36 months. The secondary end point, tested for noninferiority, was major bleeding, including procedure-related bleeding, through 36 months., Results: A total of 803 patients were assigned to undergo left atrial appendage closure, and 797 to receive anticoagulant therapy. The mean (±SD) age of the patients was 69.6±7.7 years, 34.1% of the patients were women, and the mean CHA 2 DS 2 -VASc score was 3.5±1.3. At 36 months, a primary safety end-point event had occurred in 65 patients (8.5%) in the left atrial appendage closure group (device group) and in 137 patients (18.1%) in the anticoagulation group (P<0.001 for superiority); a primary efficacy end-point event had occurred in 41 patients (5.3%) and 44 patients (5.8%), respectively (P<0.001 for noninferiority); and a secondary end-point event had occurred in 3.9% and 5.0% (P<0.001 for noninferiority). Complications related to the appendage closure device or procedure occurred in 23 patients., Conclusions: Among patients who underwent catheter-based atrial fibrillation ablation, left atrial appendage closure was associated with a lower risk of non-procedure-related major or clinically relevant nonmajor bleeding than oral anticoagulation and was noninferior to oral anticoagulation with respect to a composite of death from any cause, stroke, or systemic embolism at 36 months. (Funded by Boston Scientific; OPTION ClinicalTrials.gov number, NCT03795298.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: The expansion of tricuspid valve (TV) interventions has underscored the need for accurate and reproducible three-dimensional (3D) transthoracic echocardiographic (TTE) tools for evaluating the tricuspid annulus and for 3D normal values of this structure. The aims of this study were to develop new semi-automated software for 3D TTE analysis of the tricuspid annulus, compare its accuracy and reproducibility against those of multiplanar reconstruction (MPR) reference, and determine normative values., Methods: Three-dimensional TTE images of 113 patients with variable degrees of tricuspid regurgitation were analyzed using the new semiautomated software and conventional MPR methodology (as the reference standard), each by three independent readers. For each measured parameter, intertechnique agreement was assessed using linear regression and Bland-Altman analyses, and interreader variability using intraclass correlation coefficients and coefficients of variation. Additionally, 3D TTE data sets of 789 subjects from the WASE (World Alliance Societies of Echocardiography) study were analyzed using this new software to determine normal values for each tricuspid annular (TA) parameter., Results: Semiautomated measurements showed excellent agreement with MPR reference values for all TA measurements: high correlations (all r values >0.8) and minimal biases. All measurements were more reproducible than with MPR: higher intraclass correlation coefficients (0.94-0.96 vs 0.82-0.90) and lower coefficients of variation (5%-12% vs 8%-18%). Sex- and age-related differences were identified in 3D normal values of most TA parameters. Dynamic analysis showed that TA parameters vary throughout the cardiac cycle, reaching minimal values at end-systole and maximum values in late diastole., Conclusions: Novel software for semiautomated analysis of TA geometry and dynamics provides accurate and reproducible measurements. Normal values of TA dimensions, parsed by sex and age, are reported., Competing Interests: Conflicts of Interest Ms. Blitz, Ms. Sauber, Mr. Calvarons, Mr. Degel, Dr. Rucki, Mr. Blankenhagen, and Dr. Schreckenberg are employees of Philips. These authors had no role in study design, conduct, analysis, and interpretation of the findings. Dr. Lang receives grants as a speaker from Philips. Drs. Cotella, Clement, and Tomaselli have received research grants from Philips for unrelated projects., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Functional mitral regurgitation induces adverse effects on the left ventricle and the left atrium. Left atrial (LA) dilatation and reduced LA strain are associated with poor outcomes in heart failure (HF). Transcatheter edge-to-edge repair (TEER) of the mitral valve reduces heart failure hospitalization (HFH) and all-cause death in selected HF patients., Objectives: The aim of this study was to evaluate the impact of LA strain improvement 6 months after TEER on the outcomes of patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial., Methods: The difference in LA strain between baseline and the 6-month follow-up was calculated. Patients with at least a 15% improvement in LA strain were labeled as "LA strain improvers." All-cause death and HFH were assessed between the 6- and 24-month follow-up., Results: Among 347 patients (mean age 71 ± 12 years, 63% male), 106 (30.5%) showed improvement of LA strain at the 6-month follow-up (64 [60.4%] from the TEER + guideline-directed medical therapy [GDMT] group and 42 [39.6%] from the GDMT alone group). An improvement in LA strain was significantly associated with a reduction in the composite of death or HFH between the 6-month and 24-month follow-up, with a similar risk reduction in both treatment arms (P interaction  = 0.27). In multivariable analyses, LA strain improvement remained independently associated with a lower risk of the primary composite endpoint both as a continuous variable (adjusted HR: 0.94 [95% CI: 0.89-1.00]; P = 0.03) and as a dichotomous variable (adjusted HR: 0.49 [95% CI: 0.27-0.89]; P = 0.02). The best outcomes were observed in patients treated with TEER in whom LA strain improved., Conclusions: In symptomatic HF patients with severe mitral regurgitation, improved LA strain at the 6-month follow-up is associated with subsequently lower rates of the composite endpoint of all-cause mortality or HFH, both after TEER and GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079)., Competing Interests: Funding Support and Author Disclosures The COAPT trial was sponsored by Abbott. Dr Delgado received speaker fees from Abbott Vascular, Edwards Lifesciences, Merck Sharp and Dohme, and GE Healthcare. Dr Stassen has received funding from the European Society of Cardiology (European Society of Cardiology Training Grant App000064741). Dr Weissman is associate director of an academic echocardiography core laboratory (MedStar Health Research Institute) with institutional contracts with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. Dr Grayburn has received grant support from Abbott Vascular, Medtronic, Boston Scientific, Cardiovalve, Edwards Lifesciences, W. L. Gore, Medtronic, and NeoChord; and has received consulting fees from Abbott Vascular, Edwards Lifesciences, W. L. Gore, and 4C Medical. Dr Kar has received consulting fees and is an Advisory Board member at Boston Scientific; has received consulting fees and stock equity from Valcare; and has received consulting fees from W.L. Gore and Medtronic. Dr Lim has received research grant support from Abbott, Boston Scientific, Edwards, and Medtronic; has received consultant fees from LagonaTech, Valgen, and Venus; and is an Advisory Board member for Ancora and Philips. Dr Lindenfeld has received research grant support from AstraZeneca; and has received consulting fees from Abbott Vascular, CVRx, Edwards Lifesciences, RESMED, Relypsa, Boehringer Ingelheim, and V-Wave. Dr Abraham has received research grant support from the National Heart, Lung, and Blood Institute (National Institutes of Health 1 UG3/UH3 HL140144-01, 08/01/18-07/31/22, “Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Readmission/Mortality in Patients with Heart Failure and Central Sleep Apnea [LOFT-HF]”); has received consulting income from Abbott Vascular, Boehringer-Ingelheim, and Zoll Respicardia; has received speaker honoraria from Impulse Dynamics; and has received salary support from V-Wave Medical. Dr Mack has served as coprimary investigator for the PARTNER Trial for Edwards Lifesciences and COAPT trial for Abbott; and has served as study chair for the APOLLO trial for Medtronic. Dr Asch is the Director of the Core Laboratories at MedStar Health Research Institute, which has institutional contracts (no personal compensation) with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at Medtronic; and Dr Stone’s employer, Mount Sinai Hospital, has received research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr Bax has received speaker fees from Abbott Vascular. 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: Moderate secondary mitral regurgitation (SMR) represents a subgroup of heart failure (HF) patients with treatment restricted to medical therapy. Outcomes in patients with moderate SMR treated with mitral transcatheter edge-to-edge repair (M-TEER) are less well known., Objectives: The aim of this study was to assess the safety and effectiveness of M-TEER in subjects with moderate SMR using the EXPANDed studies., Methods: One-year outcomes in subjects from the EXPANDed studies (EXPAND [A Contemporary, Prospective Study Evaluating Real-world Experience of Performance and Safety for the Next Generation of MitraClip Devices] and EXPAND G4 [A Post-Market Study Assessment of the Safety and Performance of the MitraClip G4 System] MitraClip studies) with baseline moderate SMR (2+), per echocardiographic core laboratory (ECL) assessment, were compared with subjects with baseline severe SMR (≥3+)., Results: There were 335 subjects with moderate SMR and 525 with severe SMR at baseline per ECL review. Baseline characteristics were similar between the 2 subgroups. After treatment with M-TEER, significant MR reduction was achieved in both groups. Significant left ventricular (LV) reverse remodeling was observed through 1 year, with a >20 mL decrease in LV end-diastolic and end-systolic volumes on average in the moderate SMR group. Significant 1-year improvements in NYHA functional class (>78% NYHA functional class I or II) and quality of life (>20 points on the Kansas City Cardiomyopathy Questionnaire-Overall Summary) were observed in subjects with moderate SMR. Similarly, low rates of major adverse events, all-cause mortality, and HF hospitalizations were observed between the 2 subgroups through 1 year., Conclusions: In the EXPANDed studies, subjects with moderate SMR treated with M-TEER had improvements similar to subjects with severe SMR in quality of life and positive LV remodeling at 1 year. Future studies are needed to evaluate if M-TEER would be beneficial for HF patients with moderate SMR., Competing Interests: Funding Support and Author Disclosures The EXPAND (NCT03502811) and EXPAND G4 (NCT04177394) studies were funded and sponsored by Abbott. Dr Asgar is a consultant to Abbott Structural Heart, Medtronic, Edwards Lifesciences, W.L. Gore, and Anteris Technologies. Dr Tang has received speaker honoraria and served as a physician proctor, consultant, advisory board member, TAVR publications committee member, APOLLO trial screening committee member, and IMPACT MR steering committee member for Medtronic; has received speaker honoraria and served as a physician proctor, consultant, advisory board member, and TRILUMINATE trial anatomic eligibility and publications committee member for Abbott Structural Heart; has served as an advisory board member for Boston Scientific and JenaValve; has served as a consultant and physician screening committee member for Shockwave Medical; has served as a consultant for NeoChord, Peija Medical, and Shenqi Medical Technology; and has received speaker honoraria from Siemens Healthineers. Dr Rogers is a consultant to Abbott Structural Heart, Biosense Webster, and Boston Scientific. Dr Rottbauer has received consulting fees/speaker honoraria from Abbott, Bayer Healthcare, Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, and Medtronic; and is a member of the steering committee of the EXPAND G4 study for Abbott and Encourage AF study for Daiichi Sankyo. Dr Morse is a consultant for Edwards Lifesciences. Dr Denti has received speaker honoraria from Abbott and Edwards Lifesciences; and has been a consultant to InnovHeart, Artiness, and Pi-Cardia. Dr Mahoney is a consultant and proctor for Medtronic, Edwards Lifesciences, and Boston Scientific; is a consultant for Abbott; and has been awarded research grants from Edwards Lifesciences, Medtronic Abbott, and Boston Scientific. Dr Rinaldi has been awarded honoraria and/or consulting fees from Abbott, Boston Scientific, and Edwards Lifesciences. Dr Asch’s work as an academic core laboratory director is performed through institutional research grants (MedStar Health) with Abbott, Boston Scientific, Medtronic, Edwards Lifesciences, Neovasc, Ancora Heart, LivaNova, MVRx, InnovHeart, Polares Medical, and Aria CV. Dr Zamorano has received speaker honoraria from Pfizer, Amgen, and Daiichi Sankyo; and research grants from Abbott and Edwards Lifesciences. Dr Dong and Ms Huang are employees of Abbott Structural Heart. Dr Lindenfeld has been a consultant for Abbott, Alleviant, AstraZeneca, Biotronik, Boston Scientific, CVRx, Edwards Lifesciences, Merck, Medtronic, V-Wave, Vascular Dynamics, WhiteSwell, and Vectorious; and receives research funding from AstraZeneca. Dr Maisano has received grants and/or institutional research support from Abbott, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific, NVT, and Terumo; has received honoraria and consulting fees (personal and institutional) from Abbott, Medtronic, Edwards Lifesciences, Xeltis, and Cardiovalve; has received royalty income and intellectual property rights from Edwards Lifesciences; and is a shareholder (including stock options) of CardioGard, Magenta, SwissVortex, Transseptal Solutions, Occlufit, 4Tech, and Perifect. Dr von Bardeleben has performed nonpaid trial activities for Abbott, Edwards Lifesciences, Medtronic, and the University of Göttingen (IIT); and serves as an advisory board or speaker bureau member for Abbott Cardiovascular Edwards Lifesciences, Medtronic, and NeoChord. Dr Kar has received grants and institutional research support from Abbott, Boston Scientific, and Edwards Lifesciences; has received consulting fees/honoraria from Abbott, Boston Scientific, W.L. Gore, and Medtronic; served as a steering committee member of the TRILUMINATE study (Abbott) and as national principal investigator of the EXPAND study and the REPAIR MR study for Abbott. Dr Rodriguez has been awarded grants and support for research from Abbott, Edwards Lifesciences, Boston Scientific, AtriCure, and CardioMech; and has received honoraria or consulting fees from Abbott, Edwards Lifesciences, Philips, Teleflex, and CardioMech., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Evaluation of left and right ventricular (RV) longitudinal systolic function may enhance risk stratification following aortic valve replacement (AVR). The study objective was to evaluate the changes in left and RV longitudinal systolic function and RV-pulmonary artery (RV-PA) coupling from baseline to 30 days and 1 year after AVR., Methods and Results: Left ventricular (LV) longitudinal strain (LS), tricuspid annulus plane systolic excursion (TAPSE), and RV-PA coupling were evaluated in patients from the PARTNER 2A surgical AVR (SAVR) arm (n = 985) and from the PARTNER 2 SAPIEN 3 registry (n = 719). TAPSE and RV-PA coupling decreased significantly following SAVR, but remained stable following TAVR. Lower LV LS, TAPSE, or RV-PA coupling at baseline was associated with increased risk of the composite of death, hospitalization, and stroke at 5 years [adjusted hazard ratios (HRs) for LV LS < 15%: 1.24, 95% confidence interval (CI) 1.05-1.45, P = 0.001; TAPSE < 14 mm: 1.44, 95% CI 1.21-1.73, P < 0.001; RV-PA coupling < 0.55 mm/mmHg: 1.32, 95% CI 1.07-1.63, P = 0.011]. Reduced TAPSE at baseline was the most powerful predictor of the composite endpoint at 5 years. Patients with LV ejection fraction <50% at baseline had increased risk of the primary endpoint with SAVR (HR: 1.34, 95% CI 1.08-1.68, P = 0.009) but not with TAVR (HR: 1.12, 95% CI 0.88-1.42). Lower RV-PA coupling at 30 days showed the strongest association with cardiac mortality., Conclusion: SAVR but not TAVR was associated with a marked deterioration in RV longitudinal systolic function and RV-PA coupling. Lower TAPSE and RV-PA coupling at 30 days were associated with inferior clinical outcomes at 5 years. In patients with LVEF < 50%, TAVR was associated with superior 5-year outcomes., Competing Interests: Conflict of interest: J.T. is consultant for Abbott, Philips Healthcare, and General Electric. R.T.H. reports speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, Medtronic, and Philips Healthcare; she has institutional consulting contracts for which she receives no direct compensation with Abbott Structural, Edwards Lifesciences, Medtronic, and Novartis; she is Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored tricuspid valve trials, for which she receives no direct industry compensation. M.-A.C. has research grant with Medtronic and core laboratory contract with Edwards Lifesciences without direct compensation. W.J. is consultant for Boston Scientific and BridgeBio. F.M.A. and N.J.W. have institutional research grants as directors of an academic core lab from Edwards, Abbott, Medtronic, Boston Scientific, Biotronik, Corcyn, and Foldax. They have no personal disclosures. N.A. received speakers fees from Abbott Vascular, GE Healthcare, and Philips ultrasound and research grants from Alnylam and Pfizer. H.C.H. reports institutional research funding from Abbott, Boston Scientific, Edwards Lifesciences, Highlife, Medtronic, and WL Gore; consulting fees from Edwards Lifesciences, Medtronic, Wells Fargo, and WL Gore; and equity in Holistick Medical and Micro Interventional Devices. M.J.M. has served as a Co-Pi for clinical trials for Abbott and Edwards Lifesciences and as Study Chair for a trial for Medtronic. All roles were uncompensated. V.T. is consultant or researcher for Abbott Vascular, Boston Scientific, CryoLife, Edwards Lifesciences, Medtronic, and Shockwave. The other authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Age-related changes in left ventricular (LV) structure and function lower the threshold for the onset of heart failure with preserved ejection fraction (HFpEF). LV parameters change also with race; however, the racial differences in age-related changes in LV parameters with and without adjustment for body mass index (BMI), heart rate (HR), and blood pressure (BP) remain unclear., Methods and Results: We performed a subanalysis of the World Alliance Society of Echocardiography Normal Values Study, an international cross-sectional study that examined normal echocardiographic values in 15 countries. The age-related changes in 2-dimensional echocardiographic derived parameters including LV size, systolic function, and mass, were compared between healthy Japanese (n=227) and healthy White (n=98) and Black (n=69) American participants. In men, age-related changes in all parameters did not differ significantly among races. However, compared with Japanese women, White American women had a smaller body surface area (BSA)-indexed LV volume, BSA-indexed LV internal dimension at end-systole, BSA-indexed LV stroke volume, and LV mass index to BSA, and a larger LV ejection fraction with age, even after adjusting for BMI, HR, and BP., Conclusions: Age-related changes in LV structure and function, which are important for the pathophysiology of HFpEF, may differ by race. Therefore, future studies examining echocardiographic reference values for each age group in each race are needed.

Background: Considering the high prevalence of mitral regurgitation (MR) and the highly subjective, variable MR severity reporting, an automated tool that could screen patients for clinically significant MR (≥ moderate) would streamline the diagnostic/therapeutic pathways and ultimately improve patient outcomes., Objectives: The authors aimed to develop and validate a fully automated machine learning (ML)-based echocardiography workflow for grading MR severity., Methods: ML algorithms were trained on echocardiograms from 2 observational cohorts and validated in patients from 2 additional independent studies. Multiparametric echocardiography core laboratory MR assessment served as ground truth. The machine was trained to measure 16 MR-related parameters. Multiple ML models were developed to find the optimal parameters and preferred ML model for MR severity grading., Results: The preferred ML model used 9 parameters. Image analysis was feasible in 99.3% of cases and took 80 ± 5 seconds per case. The accuracy for grading MR severity (none to severe) was 0.80, and for significant (moderate or severe) vs nonsignificant MR was 0.97 with a sensitivity of 0.96 and specificity of 0.98. The model performed similarly in cases of eccentric and central MR. Patients graded as having severe MR had higher 1-year mortality (adjusted HR: 5.20 [95% CI: 1.24-21.9]; P = 0.025 compared with mild)., Conclusions: An automated multiparametric ML model for grading MR severity is feasible, fast, highly accurate, and predicts 1-year mortality. Its implementation in clinical practice could improve patient care by facilitating referral to specialized clinics and access to evidence-based therapies while improving quality and efficiency in the echocardiography laboratory., Competing Interests: Funding Support and Author Disclosures Mr Jiang is an employee of Us2.ai. Mr Hummel is an employee of Us2.ai. Mr Frost is an employee of Us2.ai. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from NovoNordisk and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, CardioRenal, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research and Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; has served as cofounder and non-executive director of Us2.ai; has a patent pending (PCT/SG2016/050217; Method for diagnosis and prognosis of chronic heart failure); and holds U.S. Patent No. 10,702,247 for automated clinical workflow that recognizes and analyses 2-dimensional and Doppler echo images for cardiac measurements and the diagnosis, prediction, and prognosis of heart disease. Dr Shah is supported by grants from the U.S. National Institutes of Health (National Heart, Lung, and Blood Institute; U54 HL160273, R01 HL140731, and R01 HL149423), AstraZeneca, Corvia Medical, and Pfizer; and has received consulting fees from Abbott, AstraZeneca, Alleviant, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer-Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, Metabolic Flux, MyoKardia, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, Ultromics, and United Therapeutics. Dr Lund is supported by Karolinska Institutet, the Swedish Research Council (grant 523-2014-2336), the Swedish Heart Lung Foundation (grants 20150557, 20190310), and the Stockholm County Council (grants 20170112, 20190525); and unrelated to the present work, Dr Lund has received grants, consulting, and honoraria from Abbot, Alleviant, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Edwards, Merck/Merck Sharp & Dohme, Novartis, Novo Nordisk, Owkin, Pharmacosmos, Vifor Pharma; and has stock ownership in AnaCardio. Dr Stone has received Speaker or other honoraria from Cook, Terumo, QOOL Therapeutics, and Orchestra Biomed; is a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, Matrizyme, Cardiomech; and has equity/options from Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, MedFocus family of funds, and Valfix. Dr Swaminathan has received consulting fees from US2.ai. Dr Weissman is the Associate Director of an academic core laboratory with research institutional grants/agreements (MedStar Health) with Us2.ai, Ultromics, TOMTEC, GE, Caption Health, egnite, Abbott, Edwards, Medtronic, Boston Scientific, Corcym, Ancora Heart, Neovasc, InnovHeart, and Polares Medical. Dr Asch is the director of an academic core laboratory with research institutional grants/agreements (MedStar Health) with Us2.ai, Ultromics, TOMTEC, GE, Caption Health, egnite, Abbott, Edwards, Medtronic, Boston Scientific, Corcym, Ancora Heart, Neovasc, InnovHeart, Polares Medical, and Foldax; and is on the Scientific Advisory Board (unpaid) for Us2.ai, Ultromics, and Abbott. 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.)

The frequency and effectiveness of repeat mitral valve interventions (RMVI) after transcatheter edge-to-edge repair (TEER) for secondary mitral regurgitation (MR) are unknown. We aimed to examine the rate of and outcomes after RMVI after TEER in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial. Only 3.9% of COAPT trial patients required a repeat mitral valve intervention during 4-year follow-up which was successful in 90% of cases but was associated with an increased rate of heart failure (HF) hospitalizations (HFH). The COAPT trial randomized HF patients with severe secondary MR to TEER with the MitraClip device plus guideline-directed medical therapy (GDMT) versus GDMT alone. We evaluated the characteristics and outcomes of patients who had an RMVI during 4-year follow-up. A MitraClip implant was attempted in 293 patients randomized to TEER+GDMT, 10 of whom underwent an RMVI procedure (9 repeat TEER and 1 surgical mitral valve replacement) after 4 years of follow-up (cumulative incidence 3.90%, 95% confidence interval [CI] 2.08 to 7.08; median 182 days after the initial procedure). Patients with RMVI had larger mitral annular diameters, fewer clips implanted, and were more likely to have ≥3+MR at discharge compared with those without RMVI. Reasons for RMVI included failed index procedure because of difficult transseptal puncture (n = 2) or tamponade (n = 1); residual or recurrent severe MR after an initially successful procedure (n = 5); partial clip detachment (n = 1); and site-assessed mitral stenosis (n = 1). RMVI was successful in 8/10 (80%) patients. Patients who underwent RMVI had higher 4-year rates of HFH but similar mortality compared with those without RMVI. The annualized incidence rates of all HFH in patients who underwent RMVI were 234 events per 100 person-years (95% CI 139 to 395) pre-RMVI and 46 per 100 person-years (95% CI 25 to 86) post-RMVI as compared with 32 events per 100 patient-years (95% CI 28 to 36) in patients without RMVI. The rate ratio of HFH was reduced after RMVI in patients who underwent RMVI (0.20, 95% CI 0.09 to 0.45). In conclusion, the cumulative incidence of RMVI after 4 years was 3.9% in patients who underwent TEER for severe secondary MR in the COAPT trial. Patients who underwent RMVI were at increased risk of HFH which was reduced after the RMVI procedure. Clinical Trial Registration: Clinical Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier: NCT01626079 URL:https://clinicaltrials.gov/ct2/show/NCT01626079., Competing Interests: Declaration of competing interest Dr. Shahim is supported by Region Stockholm clinical postdoctoral appointment (FoUI- FoUI-969615), Swedish Heart-Lung Foundation (Grants 20220524 and 20190322) and the Swedish Research Council (grant 2022-01472). Dr. Cohen reports grant funding and consulting income from Edwards Lifesciences, Medtronic, Abbott, and Boston Scientific. Dr. Asch is the Director of the Core Laboratories at MedStar Health Research Institute, which has institutional contracts (no personal compensation) with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. Dr. Bax reports that his institution, The Department of Cardiology (LUMC, The Netherlands), has received research grants from Medtronic, Biotronik, Edwards Lifesciences, and Boston Scientific; and has received speaker fees from Abbott Vascular. Dr. George reports consultant fees for Edwards Lifesciences. Dr. Ben-Yehuda has received grants to the Cardiovascular Research Foundation from Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden for core laboratory and data center analyses. Dr. Kar has received consulting fees from and is an advisory board member for Boston Scientific; has received consulting fees from and has stock equity options in Valcare; and has received consulting fees from WL Gore and Medtronic. Dr. Lim has received research grant support from Abbott, Boston Scientific, Edwards, and Medtronic; has received consultant fees from Philips, Valgen, Venus, and WL Gore; and is an advisory board member for Ancora and Venus. Dr. Saxon is a speaker and proctor for Abbott Vascular. Dr. Lindenfeld reports research grant support from AstraZeneca; and consultant fees from Abbott Vascular, CVRx, Edwards Lifesciences, ResMed, Relypsa, Boehringer Ingelheim and V-Wave. Dr Abraham reports research grant support from Abbott Vascular, and National Institutes of Health – National Heart, Lung, and Blood Institute (National Institutes of Health 1 UG3/UH3 HL140144-01, 8/1/2018–7/31/2022), “Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Readmission/Mortality in Patients with Heart Failure and Central Sleep Apnea (LOFT-HF)”; consulting income from Abbott Vascular; and speaker honoraria from Impulse Dynamics. Dr. Mack served as co-primary investigator for the PARTNER Trial for Edwards Lifesciences and COAPT trial for Abbott; served as study chair for the Apollo trial for Medtronic. Dr. Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Abbott; has served as a consultant to Daiichi Sankyo, Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, Millennia BioPharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, BioStar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, Xenter. Dr. Stone's daughter is an employee at IQVIA. Institutional disclosure: Dr. Stone's employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo and V-wave., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The implications of pulmonary vein (PV) flow patterns in patients with heart failure (HF) and mitral regurgitation (MR) are uncertain. We examined PV flow patterns in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) trial (NCT01626079), in which patients with HF and moderate-to-severe or severe functional MR were randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip device plus guideline-directed medical therapy (GDMT) vs. GDMT alone. We sought to evaluate the prognostic utility of baseline PV systolic flow reversal (PVSFR) in HF patients with severe MR and to determine whether the presence of PVSFR can discriminate patients most likely to benefit from TEER in COAPT trial patients., Methods: Patients were categorized by the echocardiographic core laboratory-assessed baseline presence of PVSFR. Two-year outcomes were examined according to PVSFR and treatment., Results: Baseline PV flow patterns were evaluable in 526/614(85.7%) patients, 48.9% of whom had PVSFR. Patients with PVSFR had more severe MR, reduced stroke volume and cardiac output, greater right ventricular dysfunction, and worse hemodynamics. By multivariable analysis, PVSFR was not an independent predictor of 2-year all-cause death, or heart failure hospitalization (HFH). The reductions in the 2-year rates of all-cause death and HFH with TEER compared with GDMT alone were similar in patients with and without PVSFR (P interaction = 0.40 and 0.12, respectively). The effect of TEER on improving Kansas City Cardiomyopathy Questionnaire scores and 6-minute walk distance were also independent of PVSFR., Conclusions: In the COAPT trial, PVSFR identified HF patients with severe MR and more advanced heart disease. Patients with and without PVSFR had consistent reductions in mortality, HFH, and improved quality-of-life and functional capacity after TEER., Clinical Trial Registration: ClinicalTrial.gov IdentifierNCT01626079., (© 2024 The Author(s).)

Aims: Although impaired left ventricular (LV) global longitudinal strain (GLS) with apical sparing is a feature of cardiac amyloidosis (CA), its diagnostic accuracy has varied across studies. We aimed to determine the ability of apical sparing ratio (ASR) and most common echocardiographic parameters to differentiate patients with confirmed CA from those with clinical and/or echocardiographic suspicion of CA but with this diagnosis ruled out., Methods and Results: We identified 544 patients with confirmed CA and 200 controls (CTRLs) as defined above (CTRL patients). Measurements from transthoracic echocardiograms were performed using artificial intelligence software (Us2.AI, Singapore) and audited by an experienced echocardiographer. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance and optimal cut-offs for the differentiation of CA patients from CTRL patients. Additionally, a group of 174 healthy subjects (healthy CTRL) was included to provide insight on how patients and healthy CTRLs differed echocardiographically. LV GLS was more impaired (-13.9 ± 4.6% vs. -15.9 ± 2.7%, P < 0.0005), and ASR was higher (2.4 ± 1.2 vs. 1.7 ± 0.9, P < 0.0005) in the CA group vs. CTRL patients. Relative wall thickness and ASR were the most accurate parameters for differentiating CA from CTRL patients [area under the curve (AUC): 0.77 and 0.74, respectively]. However, even with the optimal cut-off of 1.67, ASR was only 72% sensitive and 66% specific for CA, indicating the presence of apical sparing in 32% of CTRL patients and even in 6% healthy subjects., Conclusion: Apical sparing did not prove to be a CA-specific biomarker for accurate identification of CA, when compared with clinically similar CTRLs with no CA., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: The conceptual framework of proportionate vs. disproportionate mitral regurgitation (MR) translates poorly to individual patients with heart failure (HF) and secondary MR. A novel index, the ratio of MR severity to left atrial volume (LAV), may identify patients with 'disproportionate' MR and a higher risk of events. The objectives, therefore, were to investigate the prognostic impact of MR severity to LAV ratio on outcomes among HF patients with severe secondary MR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip™ device plus guideline-directed medical therapy (GDMT) vs. GDMT alone in the COAPT trial., Methods and Results: The ratio of pre-procedural regurgitant volume (RVol) to LAV was calculated from baseline transthoracic echocardiograms. The primary endpoint was 2-year covariate-adjusted rate of HF hospitalization (HFH). Among 567 patients, the median RVol/LAV was 0.67 (interquartile range 0.48-0.91). In patients randomized to GDMT alone, lower RVol/LAV was independently associated with an increased 2-year risk of HFH (adjHR: 1.77; 95% CI: 1.20-2.63). RVol/LAV was a stronger predictor of adverse outcomes than RVol or LAV alone. Treatment with TEER plus GDMT compared with GDMT alone was associated with lower 2-year rates of HFH both in patients with low and high RVol/LAV (Pinteraction = 0.28). Baseline RVol/LAV ratio was unrelated to 2-year mortality, health status, or functional capacity in either treatment group., Conclusion: Low RVol/LAV ratio was an independent predictor of 2-year HFH in HF patients with severe MR treated with GDMT alone in the COAPT trial. TEER improved outcomes regardless of baseline RVol/LAV ratio., Clinical Trial Registration: Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier NCT01626079URL https://clinicaltrials.gov/ct2/show/NCT01626079., Competing Interests: Conflict of interest: A.C. has served as a consultant for Abbott and received speaker fees from Abbott and GE Healthcare. A.S. has served as a consultant and received consulting fees from NeoChord Inc. J.F.G. is the co-founder of Cephea Valve Technologies (Abbott). P.A.G. has received consulting fees from Abbott Vascular, Edwards Lifesciences, W.L. Gore, Medtronic, and 4C Medical and has received grant support from Abbott Vascular, Boston Scientific, Cardiovalve, Edwards Lifesciences, W.L. Gore, Medtronic, and Neochord. M.J.M. served as co-primary investigator for the PARTNER Trial for Edwards Lifesciences and COAPT trial for Abbott; served as study chair for the APOLLO trial for Medtronic; all activities unpaid. D.J.C. has received institutional research grants and consulting fees from Abbott, Edwards LifeSciences, Medtronic, and Boston Scientific. S.K. has received grants from Abbott, Boston Scientific, Edwards Lifesciences, and 4TECH; has been a consultant for Boston Scientific, Edwards Lifesciences, Medtronic, and 4TECH; and holds stock options in 4TECH. D.S.L. has received research grant support from Abbott, Boston Scientific, Corvia, Edwards, Medtronic, Trisol, and V Wave; consultant fees from Ancora, Philips, Valgen, and Venus. J.L. has received research grant support from AstraZeneca; consulting income from Abbott Vascular, Alleviant, AstraZeneca, Cordio, CVRx, Edwards Lifesciences, Boehringer Ingelheim, Merck, Medtronic, Vascular Dynamics, and V-Wave. J.B.’s institution has received research grants from Medtronic, Biotronik, Edwards Lifesciences, and Boston Scientific; he has also received speaker fees from Abbott Vascular. F.M.A. and N.J.W. report institutional contracts with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. G.W.S. has received speaker honoraria from Medtronic, Pulnovo, Infraredx, and Abiomed; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. G.W.S.’s daughter is an employee at IQVIA. Institutional disclosure: G.W.S.’s employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc., Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. The other authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: New echocardiographic definitions have been proposed for hemodynamic structural valve deterioration. We aimed to study their consistency in classifying structural valve deterioration after surgical aortic valve replacement., Methods: Data were used of patients undergoing surgical aortic valve replacement in a multicenter, prospective cohort study with a 5-year follow-up. All patients received the same stented bioprosthesis. Echocardiographic parameters were assessed by an independent core laboratory. Moderate or greater stenotic hemodynamic structural valve deterioration was defined according to Capodanno and colleagues, Dvir and colleagues, and the Valve Academic Research Consortium 3; regurgitation data were not considered in this analysis. Consistency was quantified on the basis of structural valve deterioration classification at subsequent time points., Results: A total of 1118 patients received implants. Patients' mean age was 70 years, and 75% were male. Hemodynamic structural valve deterioration at any visit was present in 51 patients (4.6%), 32 patients (2.9%), and 34 patients (3.0%) according to Capodanno, Dvir, and Valve Academic Research Consortium 3. A total of 1064 patients (95%) were never labeled with structural valve deterioration by any definition. After the first classification with structural valve deterioration, 59%, 59%, and 65% had no subsequent structural valve deterioration classification according to Capodanno, Dvir, and Valve Academic Research Consortium 3, respectively., Conclusions: The current definitions of hemodynamic structural valve deterioration are strong negative predictors but inconsistent positive discriminators for the detection of stenotic hemodynamic structural valve deterioration. Although the diagnosis of structural valve deterioration may be categorical, echocardiographic indices lack this degree of precision in the first 5 years after surgical aortic valve replacement. The inconsistency of current structural valve deterioration definitions impedes the detection of true valve degeneration, which challenges the clinical usefulness of these definitions., Competing Interests: Dr Velders: institutional research grant and speaker’s honorarium paid to his department by Medtronic. Dr Vriesendorp: institutional research grant and reimbursement of travel expenses from Medtronic. Dr Asch: no personal conflicts of interest, but his organization receives grants or research contracts from Medtronic, Abbott, Edwards Lifesciences, Boston Scientific, Biotronik, Corcym, and HLT Medical. Dr Reardon: consultant to Medtronic, Abbott Medical, Boston Scientific, Gore Medical, and Transverse Medical; the fees are paid to his department. Dr Dagenais: proctor and speaker for Medtronic and COOK Medical. Dr Moront: trainer and consultant for Medtronic, trainer and speaker for AtriCure, and speaker and consultant for Haemonetics. Dr Sabik: Principal Investigator, PERIGON Pivotal Trial for Medtronic. Prof Klautz: research support, consultation fees, and Principal Investigator, PERIGON Pivotal Trial for Medtronic. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Background: Transcatheter edge-to-edge repair (TEER) improved outcomes in patients with heart failure (HF) and severe secondary mitral regurgitation (SMR) compared with guideline-directed medical therapy (GDMT) alone regardless of the severity of baseline left ventricular ejection fraction (LVEF). The study aimed to evaluate the effect of early changes in LVEF after TEER and GDMT alone in patients with HF and severe SMR., Methods: Within the COAPT trial, we evaluated outcomes according to changes in LVEF from baseline to 30 days. The primary outcome was all-cause death or HF hospitalization (HFH) between 30 days and 2 years., Results: Among 432 patients with paired echocardiographic data, 182 (42.1%) had increased LVEF (LVEF change 6.0% ± 4.9%) and 250 (57.9%) had a decrease or no change in LVEF (LVEF change -6.6% ± 5.6%) from baseline to 30 days. LVEF at 30 days increased more frequently with GDMT alone compared with TEER plus GDMT (51.4% vs 33.0%; P = .0001). Between 30 days and 2 years, there were no significant differences in death or HFH in the increase LVEF and the decrease LVEF groups (58.8% vs 51.4%; multivariable-adjusted HR, 0.97; 95% CI, 0.87-1.08; P = .59). TEER plus GDMT reduced the 30-day to 2-year rate of death or HFH compared with GDMT alone consistently in patients with increase LVEF and decrease LVEF (P int = 0.75)., Conclusions: Among patients with HF and severe SMR, early improvements in LVEF were more frequent with GDMT alone compared with TEER plus GDMT but were not associated with subsequent outcomes at 2 years. TEER reduced death or HFH during 2-year follow-up irrespective of early LVEF changes., (© 2024 The Author(s).)

This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

Aims: Right ventricular (RV) functional assessment is mainly limited to its longitudinal contraction. Dedicated three-dimensional echocardiography (3DE) software enabled the separate assessment of the non-longitudinal components of RV ejection fraction (EF). The aims of this study were (i) to establish normal values for RV 3D-derived longitudinal, radial, and anteroposterior EF (LEF, REF, and AEF, respectively) and their relative contributions to global RVEF, (ii) to calculate 3D RV strain normal values, and (iii) to determine sex-, age-, and race-related differences in these parameters in a large group of normal subjects (WASE study)., Methods and Results: 3DE RV wide-angle datasets from 1043 prospectively enrolled healthy adult subjects were analysed to generate a 3D mesh model of the RV cavity (TomTec). Dedicated software (ReVISION) was used to analyse RV motion along the three main anatomical planes. The EF values corresponding to each plane were identified as LEF, REF, and AEF. Relative contributions were determined by dividing each EF component by the global RVEF. RV strain analysis included longitudinal, circumferential, and global area strains (GLS, GCS, and GAS, respectively). Results were categorized by sex, age (18-40, 41-65, and >65 years), and race. Absolute REF, AEF, LEF, and global RVEF were higher in women than in men (P < 0.001). With aging, both sexes exhibited a decline in all components of longitudinal shortening (P < 0.001), which was partially compensated in elderly women by an increase in radial contraction. Black subjects showed lower RVEF and GAS values compared with white and Asian subjects of the same sex (P < 0.001), and black men showed significantly higher RV radial but lower longitudinal contributions to global RVEF compared with Asian and white men., Conclusion: 3DE evaluation of the non-longitudinal components of RV contraction provides additional information regarding RV physiology, including sex-, age-, and race-related differences in RV contraction patterns that may prove useful in disease states involving the right ventricle., Competing Interests: Conflict of interest: A.K. serves as the Chief Medical Officer of Argus Cognitive, Inc. and received financial compensation for his work, outside the submitted paper. No direct conflicts of interest related to this study have been reported by other authors. All authors have been involved in the design of the WASE study, patient enrolment, and/or data analysis, and all have critically reviewed and approved the final manuscript prior to submission. A full list of WASE investigators is provided in the footnote., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Recent randomized studies have broadened the indication of transcatheter aortic valve replacement (TAVR) to also include low-surgical-risk patients. However, the data on self-expanding (SE) and balloon-expandable (BE) valves in low-risk patients remain sparse., Methods: The current study is a post hoc analysis of combined data from both LRT 1.0 and 2.0 trials comparing BE and SE transcatheter heart valves., Results: A total of 294 patients received a BE valve, and 102 patients received an SE valve. The 30-day clinical outcomes were similar across both groups except for stroke (4.9% vs. 0.7%, p = 0.014) and permanent pacemaker implantation (17.8% vs. 5.8%, p < 0.001), which were higher in the SE cohort than the BE cohort. No difference was observed in terms of paravalvular leak (≥moderate) between the groups (0% vs. 1.5%, p = 0.577). SE patients had higher aortic valve area (1.92 ± 0.43 mm 2 vs. 1.69 ± 0.45 mm 2 , p < 0.001) and lower mean gradient (8.93 ± 3.53 mmHg vs. 13.41 ± 4.73 mmHg, p < 0.001) than BE patients. In addition, the rate of subclinical leaflet thrombosis was significantly lower in SE patients (5.6% vs. 13.8%, p = 0.038)., Conclusion: In this non-randomized study assessing SE and BE valves in low-risk TAVR patients, SE valves are associated with better hemodynamics and lesser leaflet thrombosis, with increased rates of stroke and permanent pacemaker implantation at 30 days; however, this could be due to certain patient-dependent factors not fully evaluated in this study. The long-term implications of these outcomes on structural valve durability remain to be further investigated., Clinical Trial Registry: LRT 1.0: NCT02628899 LRT 2.0: NCT03557242., Competing Interests: Declaration of Competing Interest Ron Waksman reports serving on the advisory boards of Abbott Vascular, Boston Scientific, Medtronic, Philips IGT, and Pi-Cardia Ltd.; being a consultant for Abbott Vascular, Biotronik, Boston Scientific, Cordis, Medtronic, Philips IGT, Pi-Cardia Ltd., Swiss Interventional Systems/SIS Medical AG, Transmural Systems Inc., and Venous MedTech; receiving institutional grant support from Amgen, Biotronik, Boston Scientific, Chiesi, Medtronic, and Philips IGT; and being an investor in MedAlliance and Transmural Systems. Puja Parikh – Consultant: Medtronic, Inc. Federico Asch – No personal disclosures. Director of the MedStar Health Academic Echocardiography Core Laboratory which has institutional contracts with Medtronic, Edwards Lifesciences, Abbott, Boston Scientific, Biotronik, LivaNova, and Foldax. Gaby Weissman – No personal disclosures. Director of an academic cardiac computed tomography core lab with institutional contracts with Ancora Heart and LivaNova. Toby Rogers – Consultant: Edwards Lifesciences, Medtronic, Boston Scientific, Abbott; Advisory board: Medtronic, Boston Scientific; Equity: Transmural Systems; Intellectual property: co-inventor on patents, assigned to NIH. All other authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Transcatheter aortic valve implantation is an effective treatment for patients with aortic stenosis; however, complications related to paravalvular leakage (PVL) persist, including increased risk of mortality, cardiovascular mortality, and rehospitalisation., Aims: We sought to evaluate the clinical outcomes and valve performance at 1 year in patients with severe aortic stenosis treated with the ACURATE neo2 valve in a post-market clinical setting., Methods: Valve Academic Research Consortium-2 safety events were assessed up to 1 year. Independent core laboratories evaluated echocardiographic measures of valve performance and hypoattenuated leaflet thickening (HALT; as measured by four-dimensional computed tomography)., Results: The study enrolled 250 patients (64% female; mean age: 81 years; baseline Society of Thoracic Surgeons risk score: 2.9±2.0%); 246 patients were implanted with ACURATE neo2. All-cause mortality was 0.8% at 30 days and 5.1% at 1 year. The 1-year rates for stroke and disabling stroke were 3.0% and 1.3%, respectively. Overall, HALT of >50% leaflet involvement of at least one leaflet was present in 9% of patients at 30 days and in 12% of patients at 1 year. No association was observed between the presence of HALT and 1-year clinical or haemodynamic outcomes. Early haemodynamic improvements were maintained up to 1 year (mean aortic valve gradient: 47.6±14.5 mmHg at baseline, 7.6±3.2 mmHg at 1 year; mean aortic valve area: 0.7±0.2 cm 2 at baseline, 1.7±0.4 cm 2 at 1 year). At 1 year, 99% of patients had mild or no/trace PVL (<1% had moderate PVL; no patient had severe PVL)., Conclusions: The study outcomes confirm favourable performance and safety up to 1 year in patients treated with ACURATE neo2 in routine clinical practice. (ClinicalTrials.gov: NCT04655248).

Aims: While transthoracic echocardiography (TTE) assessment of left ventricular end-diastolic pressure (LVEDP) is critically important, the current paradigm is subject to error and indeterminate classification. Recently, peak left atrial strain (LAS) was found to be associated with LVEDP. We aimed to test the hypothesis that integration of the entire LAS time curve into a single parameter could improve the accuracy of peak LAS in the noninvasive assessment of LVEDP with TTE., Methods and Results: We retrospectively identified 294 patients who underwent left heart catheterization and TTE within 24 h. LAS curves were trained using machine learning (100 patients) to detect LVEDP ≥ 15 mmHg, yielding the novel parameter LAS index (LASi). The accuracy of LASi was subsequently validated (194 patients), side by side with peak LAS and ASE/EACVI guidelines, against invasive filling pressures. Within the validation cohort, invasive LVEDP was elevated in 116 (59.8%) patients. The overall accuracy of LASi, peak LAS, and American Society of Echocardiography/European Association for Cardiovascular Imaging (ASE/EACVI) algorithm was 79, 75, and 76%, respectively (excluding 37 patients with indeterminate diastolic function by ASE/EACVI guidelines). When the number of LASi indeterminates (defined by near-zero LASi values) was matched to the ASE/EACVI guidelines (n = 37), the accuracy of LASi improved to 87%. Importantly, among the 37 patients with ASE/EACVI-indeterminate diastolic function, LASi had an accuracy of 81%, compared with 76% for peak LAS., Conclusion: LASi allows the detection of elevated LVEDP using invasive measurements as a reference, at least as accurately as peak LAS and current diastolic function guideline algorithm, with the advantage of no indeterminate classifications in patients with measurable LAS., Competing Interests: Conflict of interest: R.M.L. is in the speaker’s bureau and receives grant support from Philips Medical Systems. J.L.S. and D.P. are employed by Philips Medical Systems. No other authors have anything to disclose that could be perceived as potential conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In patients with cardiac amyloidosis (CA), left ventricular ejection fraction (LVEF) is frequently preserved, despite commonly reduced global longitudinal strain (GLS). We hypothesized that nonlongitudinal contraction may initially serve as a mitigating mechanism to maintain cardiac output and studied the relationship between global circumferential (GCS) and radial (GRS) strain with LVEF and extracellular volume (ECV), a marker of amyloid burden., Methods: Patients with CA who underwent cardiac magnetic resonance (CMR; n = 140, 70.7 ± 11.5 years, 66% male) or echocardiography (n = 67, 71 ± 13 years, 66% male) and normal controls (CMR, n = 20; echocardiography, n = 45) were retrospectively identified, and GCS, GLS, and GRS were quantified using feature-tracking CMR or speckle-tracking echocardiography and compared between CA patients with preserved and reduced LVEF (CA HFpEF , CA HFrEF ) and controls. The prevalence of impaired strain (magnitudes <2.5th percentile of the controls) was compared between CA HFpEF and CA HFrEF and between ECV quartiles., Results: While echocardiography-derived GLS was impaired in both CA HFpEF (-13.4% ± 3.1%, P < .003) and CA HFrEF (-9.1% ± 3.2%, P < .003), compared with controls (-20.8% ± 2.4%), GCS was more impaired in CA HFrEF compared with both controls (-15.6% ± 5.0% vs -32.3% ± 3.3%, P < .003) and CA HFpEF (-30.4% ± 5.7%, P < .003) and did not differ between CA HFpEF and controls (P = .24). The prevalence of abnormal CMR-derived GCS (P < .0001) and GRS (P < .0001) but not GLS (P = .054) varied significantly across ECV quartiles., Conclusions: Among CA patients with preserved LVEF, preserved GCS and GRS, despite near-universally impaired GLS, may be explained by an initial predominantly subendocardial involvement, where mostly longitudinal fibers are located. If confirmed in future studies, these findings may facilitate identification of patients with early stages of CA, when treatments may be most effective., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Machine learning techniques designed to recognize views and perform measurements are increasingly used to address the need for automation of the interpretation of echocardiographic images. The current study was designed to determine whether a recently developed and validated deep learning (DL) algorithm for automated measurements of echocardiographic parameters of left heart chamber size and function can improve the reproducibility and shorten the analysis time, compared to the conventional methodology. The DL algorithm trained to identify standard views and provide automated measurements of 20 standard parameters, was applied to images obtained in 12 randomly selected echocardiographic studies. The resultant measurements were reviewed and revised as necessary by 10 independent expert readers. The same readers also performed conventional manual measurements, which were averaged and used as the reference standard for the DL-assisted approach with and without the manual revisions. Inter-reader variability was quantified using coefficients of variation, which together with analysis times, were compared between the conventional reads and the DL-assisted approach. The fully automated DL measurements showed good agreement with the reference technique: Bland-Altman biases 0-14% of the measured values. Manual revisions resulted in only minor improvement in accuracy: biases 0-11%. This DL-assisted approach resulted in a 43% decrease in analysis time and less inter-reader variability than the conventional methodology: 2-3 times smaller coefficients of variation. In conclusion, DL-assisted approach to analysis of echocardiographic images can provide accurate left heart measurements with the added benefits of improved reproducibility and time savings, compared to conventional methodology., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Although various hemodynamic parameters to assess prosthetic performance are available, prosthesis-patient mismatch (PPM) is defined exclusively by effective orifice area (EOA) index thresholds. Adjusting for the Society of Thoracic Surgeons predicted risk of mortality (STS PROM), we aimed to explore the added value of postoperative hemodynamic parameters for the prediction of all-cause mortality at 5 years after aortic valve replacement., Methods: Data were obtained from the Pericardial Surgical Aortic Valve Replacement (PERIGON) Pivotal Trial, a multicenter prospective cohort study examining the performance of the Avalus bioprosthesis. Candidate predictors were assessed at the first follow-up visit; patients who had no echocardiography data, withdrew consent, or died before this visit were excluded. Candidate predictors included peak jet velocity, mean pressure gradient, EOA, predicted and measured EOA index, Doppler velocity index, indexed internal prosthesis orifice area, and categories for PPM. The performance of Cox models was investigated using the c-statistic and net reclassification improvement (NRI), among other tools., Results: A total of 1118 patients received the study valve, of whom 1022 were eligible for the present analysis. In univariable analysis, STS PROM was the sole significant predictor of all-cause mortality (hazard ratio, 1.40; 95% confidence interval, 1.26-1.55). When extending the STS PROM with single hemodynamic parameters, neither the c-statistics nor the NRIs demonstrated added prognostic value compared to a model with STS PROM alone. Similar findings were observed when multiple hemodynamic parameters were added., Conclusions: The STS PROM was found to be the main predictor of patient prognosis. The additional prognostic value of postoperative hemodynamic parameters for the prediction of all-cause mortality was limited., Competing Interests: Dr Velders reported institutional research grant and speaker fees paid to his department by 10.13039/100004374Medtronic. Dr Vriesendorp reported institutional research support and reimbursement of travel expenses from 10.13039/100004374Medtronic. Dr Asch reported institutional grants or research contracts from Medtronic, Abbott, Edwards Lifesciences, Boston Scientific, 10.13039/501100005035Biotronik, Corcym, and HLT Medical. Dr Dagenais reported serving as a lecturer, consultant, and proctor for Cook Medical; a proctor and lecturer for Medtronic; and a lecturer for Edwards Lifesciences. Dr Lange reported serving as a consultant for Medtronic, being a stockholder in and receiving royalties from Medtronic, and consulting for HighLife Medical. Dr Reardon reported consulting for Medtronic, Abbott Medical, Boston Scientific, Gore Medical, and Transverse Medical, with fees paid to his department. Dr Rao reported consulting for Medtronic, Gore, and Abbott and serving on an advisory board for Medtronic. Dr Sabik was the North American Principal Investigator for the PERIGON Pivotal Trial, Medtronic. Dr Groenwold reported no conflicts of interest. Dr Klautz was European Principal Investigator of the PERIGON Pivotal Trial and reported research support and consultation fees from 10.13039/100004374Medtronic. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2023 The Author(s).)

Background: The fourth-generation mitral transcatheter edge-to-edge repair (M-TEER) device introduced an improved clip deployment sequence, independent leaflet grasping, and 2 wider clip sizes to tailor the treatment of patients with mitral regurgitation (MR) for a broad range of anatomies. The 30-day safety and effectiveness of the fourth-generation M-TEER device were previously demonstrated., Objectives: The aim of this study was to evaluate 1-year outcomes in a contemporary, real-world cohort of subjects treated with the MitraClip G4 system., Methods: EXPAND G4 is an ongoing prospective, multicenter, international, single-arm study that enrolled subjects with primary and secondary MR. One-year outcomes included MR severity (echocardiographic core laboratory assessed), heart failure hospitalization, all-cause mortality, functional capacity (NYHA functional class), and quality of life (Kansas City Cardiomyopathy Questionnaire)., Results: A total of 1,164 subjects underwent M-TEER from 2020 to 2022. At 1 year, there was a durable reduction in MR to mild or less in 92.6% and to none or trace in 44.2% (P < 0.0001 vs baseline). Few subjects had major adverse events through 1 year (<2% for myocardial infarction, surgical reintervention, or single-leaflet device attachment). The 1-year Kaplan-Meier estimates for all-cause mortality and heart failure hospitalization were 12.3% and 16.9%. Significant improvements in functional capacity (NYHA functional class I or II in 82%; P < 0.0001 vs baseline) and quality of life (18.5-point Kansas City Cardiomyopathy Questionnaire overall summary score improvement; P < 0.0001) were observed., Conclusions: M-TEER with the fourth-generation M-TEER device was safe and effective at 1 year, with durable reductions in MR severity to ≤1+ in more than 90% of patients and concomitant improvements in functional status and quality of life., Competing Interests: Funding Support and Author Disclosures The EXPAND G4 study (NCT04177394) was funded and sponsored by Abbott. Dr von Bardeleben has performed unpaid trial activities for Abbott, Edwards Lifesciences, Medtronic, and the University of Göttingen (IIT); and serves as an advisory board or Speakers Bureau member for Abbott Cardiovascular, Edwards Lifesciences, Medtronic, and NeoChord. Dr Mahoney is a consultant and proctor for Medtronic, Edwards Lifesciences, and Boston Scientific; is a consultant for Abbott; and has been awarded research grants from Edwards Lifesciences, Medtronic, Abbott, and Boston Scientific. Dr Morse is a consultant for Edwards Lifesciences. Dr Denti has received speaker honoraria from Abbott and Edwards Lifesciences; and has been a consultant to InnovHeart, Artiness and Pi-Cardia. Dr Maisano has received grants and/or institutional research support from Abbott, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific, New Valve Technology, and Terumo; has received honoraria and consulting fees (personal and institutional) from Abbott, Medtronic, Edwards Lifesciences, Xeltis, and Cardiovalve; has received royalty income and intellectual property rights from Edwards Lifesciences; and is a shareholder (including stock options) in CardioGard, Magenta, SwissVortex, Transseptal Solutions, Occlufit, 4Tech, and Perifect. Dr Rinaldi has been awarded honoraria and/or consulting fees from Abbott, Boston Scientific, and Edwards Lifesciences. Dr De Marco is a consultant and has provided paid expert testimony for Abbott and Boston Scientific. Dr Chehab has received study and consulting grants from Abbott, Edwards Lifesciences, and BioTronics. Dr Price has received consulting fees from Alleviant Medical, Medtronic, Boston Scientific, Abbott, W.L. Gore, Philips Medical, and InnovHeart. Dr Williams has received funding for research from Abbott, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr Leurent has received proctoring, lecture, and consulting fees from Abbott. Dr Rogers has received consulting fees from Abbott and Boston Scientific. Dr Asch’s work as an academic core laboratory director is performed through institutional research grants (MedStar Health) with Abbott, Boston Scientific, Medtronic, Edwards Lifesciences, Neovasc, Ancora Heart, LivaNova, MVRx, InnovHeart, Polares Medical, and Aria CV. Dr Rodriguez has been awarded grants and support for research from Abbott, Edwards Lifesciences, Boston Scientific, AtriCure, and CardioMech; and has received honoraria or consulting fees from Abbott, Edwards Lifesciences, Philips, Teleflex, and CardioMech. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although accurate assessment of right ventricular (RV) morphology and function is clinically important, data regarding reference values for echocardiographic measurements of the right ventricle in the Japanese population are limited. Methods and Results: The World Alliance Society of Echocardiography (WASE) Normal Values Study was conducted to examine normal echocardiographic values in 15 countries. Using the WASE study database, we analyzed 2-dimensional echocardiographic parameters of RV size and systolic function in 192 healthy Japanese individuals and compared them with those obtained from 153 healthy American individuals. In the Japanese population, the absolute values of RV dimensions were smaller for women than men, although the difference disappeared after the data were adjusted for body surface area. RV dimensions, RV length and RV area were smaller in the elderly, but age did not affect RV systolic function. The absolute value, but not the adjusted value, of RV size tended to be smaller in Japanese than American individuals for both sexes. For men, RV systolic function parameters were lower in the Japanese population. This trend was not seen in women. Conclusions: The present study identified normal reference values for RV size and systolic function in a healthy Japanese population. Sex, age, and race had a significant impact on RV size; however, this trend was weak for RV systolic function., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023, THE JAPANESE CIRCULATION SOCIETY.)

Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogenic COL3A1 variant diagnosed at age <50 years were included from 2 institutions and the GenTAC Registry (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions). Height-adjusted vertebral artery tortuosity index (VTI-h) using magnetic resonance or computed tomography angiography was calculated. Associations between VTI-h and outcomes of (1) cardiovascular events (arterial dissection/rupture, aneurysm requiring intervention, stroke), or (2) hollow organ collapse/rupture at age <50 years were evaluated using receiver operator curve analysis (using outcome by age 30 years) and mixed-effects Poisson regression for incidence rate ratios. Of 65 subjects (54% male), median VTI-h was 12 (interquartile range, 8-16). Variants were missense in 46%, splice site in 31%, and null/gene deletion in 14%. Thirty-two subjects (49%) had 59 events, including 28 dissections, 5 arterial ruptures, 4 aneurysms requiring intervention, 4 strokes, 11 hollow organ ruptures, and 7 pneumothoraces. Receiver operator curve analysis suggested optimal discrimination at VTI-h ≥15.5 for cardiovascular events (sensitivity 70%, specificity 76%) and no association with noncardiovascular events (area under the curve, 0.49 [95% CI, 0.22-0.78]). By multivariable analysis, older age was associated with increased cardiovascular event rate while VTI-h ≥15.5 was not (incidence rate ratios, 1.79 [95% CI, 0.76-4.24], P =0.185). However, VTI-h ≥15.5 was associated with events among those with high-risk variants <40 years (incidence rate ratios, 4.14 [95% CI, 1.13-15.10], P =0.032), suggesting effect modification by genotype and age. Conclusions Increased arterial tortuosity is associated with a higher incidence rate of cardiovascular events in Vascular Ehlers-Danlos syndrome. Vertebral tortuosity index may be a useful biomarker for prognosis when evaluated in conjunction with genotype and age.

Background: Left atrial volume (LAV) has prognostic value. Guidelines propose indexation to body surface area (BSA), however studies demonstrate this can overcorrect for body size. Limited studies investigate indexation across different ethnicities. We sought to evaluate the effect of ethnicity on indexation., Methods: Using data from the World Alliance of Societies of Echocardiography (WASE) cohort, healthy subjects were classified by race as White, Black, Asian, or Other. Biplane LAV was indexed to traditional isometric measurements (BSA, height, weight, ideal body weight (IBW) and IBW derived BSA (IBSA)), as well as previously-derived allometric height exponents (2.7 and 1.72). Additionally, an allometric height exponent for our cohort was derived (linear regression of the logarithmic transformation of LAV = a(height) b ) as 1.87. All indices were then assessed using Spearman correlation, with a good index retaining correlation of LAV/index to raw LAV (r∼1), while avoiding overcorrection by the index (r∼0)., Results: There were 1366 subjects (White: 524, Black: 149, Asian: 523, Other: 170; median age 44 years, 653 females (47.8%)). In the entire group, BSA, IBSA, height 1.87 and height 1.72 performed well with retaining correlation to raw LAV (r > 0.9 for all), and minimising overcorrection to body size (r < 0.1 for all). On race-specific analysis, BSA overcorrected for body size in the White population (r = 0.128). Height 1.72 minimised overcorrection for body size in all populations (r ≤ 0.1 for all races)., Conclusion: Despite a cohort with normal BMI, there was still disparity in LAV indexation with BSA across races. Allometric height indexation, particularly using height 1.72 , is a possible solution, although further validation studies in BMI extremes are required., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Objectives: A flow-gradient classification is used to determine the indication for intervention for patients with severe aortic stenosis (AS) with discordant echocardiographic parameters. We investigated the agreement in flow-gradient classification by stroke volume (SV) measurement at the left ventricular outflow tract (LVOT) and at the left ventricle., Methods: Data were used from a prospective cohort study and patients with severe AS (aortic valve area index ≤0.6 cm 2 /m 2 ) with preserved ejection fraction (>50%) were selected. SV was determined by an echocardiographic core laboratory at the LVOT and by subtracting the 2-dimensional left ventricle end-systolic from the end-diastolic volume (volumetric). Patients were stratified into 4 groups based on SV index (35 mL/m 2 ) and mean gradient (40 mm Hg). The group composition was compared and the agreement between the SV measurements was investigated using regression, correlation, and limits of agreement. In addition, a systematic LVOT diameter overestimation of 1 mm was simulated to study flow-gradient reclassification., Results: Of 1118 patients, 699 were eligible. The group composition changed considerably as agreement on flow state occurred in only 50% of the measurements. LVOT SV was on average 15.1 mL (95% limits of agreement -24.9:55.1 mL) greater than volumetric SV. When a systematic 1-mm LVOT diameter overestimation was introduced, the low-flow groups halved., Conclusions: There was poor agreement in the flow-gradient classification of severe AS as a result of large differences between LVOT and volumetric SV. Furthermore, this classification was sensitive to small measurement errors. These results stress that parameters beyond the flow-gradient classification should be considered to ensure accurate recommendations for intervention., Competing Interests: B.V.: institutional research grant and speaker's honorarium paid to his department from Medtronic. M.V.: institutional research grant and reimbursement of travel expenses from Medtronic. F.A.: no personal conflicts of interest, but his organization receives grants or research contracts from Medtronic, Abbott, Edwards Lifesciences, Boston Scientific, Biotronik, Corcym, and HLT Medical. M.M.: trainer and consultant for Medtronic; a trainer and speaker for AtriCure; and a speaker and consultant for Haemonetics. F.D.: proctor and speaker for Medtronic and Cook Medical. M.R.: consultant to Medtronic, Abbott Medical, Boston Scientific, Gore Medical, and Transverse Medical; the fees are paid to his department. J.S.: Principal Investigator, PERIGON Pivotal Trial for Medtronic. R.K.: research support, consultation fees, and Principal Investigator, PERIGON Pivotal Trial for Medtronic. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2023 The Author(s).)

Background Left ventricular (LV) global longitudinal strain (GLS) provides incremental prognostic information over LV ejection fraction in patients with heart failure (HF) and secondary mitral regurgitation. We examined the prognostic impact of LV GLS improvement in this population. Methods and Results The COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial randomized symptomatic patients with HF with severe (3+/4+) mitral regurgitation to transcatheter edge-to-edge repair with the MitraClip device plus maximally tolerated guideline-directed medical therapy (GDMT) versus GDMT alone. LV GLS was measured at baseline and 6-month follow-up. The relationship between the improvement in LV GLS from baseline to 6 months and the composite of all-cause death or HF hospitalization between 6- and 24-month follow-up were assessed. Among 383 patients, 174 (45.4%) had improved LV GLS at 6-month follow-up (83/195 [42.6%] with transcatheter edge-to-edge repair+GDMT and 91/188 [48.4%] with GDMT alone; P =0.25). Improvement in LV GLS was strongly associated with reduced death or HF hospitalization between 6 and 24 months ( P <0.009), with similar risk reduction in both treatment arms ( P interaction =0.40). By multivariable analysis, LV GLS improvement at 6 months was independently associated with a lower risk of death or HF hospitalization (hazard ratio [HR], 0.55 [95% CI, 0.36-0.83]; P =0.009), death (HR, 0.48 [95% CI, 0.29-0.81]; P =0.006), and HF hospitalization (HR, 0.50 [95% CI, 0.31-0.81]; P =0.005) between 6 and 24 months. Conclusions Among patients with HF and severe mitral regurgitation in the COAPT trial, improvement in LV GLS at 6-month follow-up was associated with improved outcomes after both transcatheter edge-to-edge repair and GDMT alone between 6 and 24 months. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

Background: Normal values for three-dimensional (3D) right ventricular (RV) size and function are not well established, as they originate from small studies that involved predominantly white North American and European populations, did not use RV-focused views, and relied on older 3D RV analysis software. The World Alliance Societies of Echocardiography study was designed to generate reference ranges for normal subjects around the world. The aim of this study was to assess the worldwide capability of 3D imaging of the right ventricle and report size and function measurements, including their dependency on age, sex, and ethnicity., Methods: Healthy subjects free of cardiac, pulmonary, and renal disease were prospectively enrolled at 19 centers in 15 countries, representing six continents. Three-dimensional wide-angle RV data sets were obtained and analyzed using dedicated RV software (TomTec) to measure end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume, and ejection fraction (EF). Results were categorized by sex, age (18-40, 41-65, and >65 years) and ethnicity., Results: Of the 2,007 subjects with attempted 3D RV acquisitions, 1,051 had adequate image quality for confident measurements. Upper and lower limits for body surface area-indexed EDV, ESV, and EF were 48 and 95 mL/m 2 , 19 and 43 mL/m 2 , and 44% and 58%, respectively, for men and 42 and 81 mL/m 2 , 16 and 36 mL/m 2 , and 46% and 61%, respectively, for women. Men had significantly larger EDVs, ESVs, and stroke volumes (even after body surface area indexing) and lower EFs than women (P < .05). EDV and ESV did not show any meaningful differences among age groups. Three-dimensional RV volumes were smallest in Asians., Conclusions: Reliability of 3D RV acquisition is low worldwide, underscoring the importance of future improvements in imaging techniques. Sex and race must be taken into consideration in the assessment of both RV volumes and EF., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Although malnutrition is associated with poor prognosis in several diseases, its prognostic impact in patients with heart failure (HF) and secondary mitral regurgitation (SMR) is not understood., Objectives: The purpose of this study was to assess the prevalence and impact of malnutrition in HF patients with severe SMR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip plus guideline-directed medical therapy (GDMT) vs GDMT alone in the COAPT trial., Methods: Baseline malnutrition risk was calculated using the validated geriatric nutritional risk index (GNRI) score. Patients were categorized as having "malnutrition" (GNRI ≤98) vs "no malnutrition" (GNRI >98). Outcomes were assessed through 4 years. The primary endpoint of interest was all-cause mortality., Results: Among 552 patients, median baseline GNRI was 109 (IQR: 101-116); 94 (17.0%) had malnutrition. All-cause mortality at 4 years was greater in patients with vs those without malnutrition (68.3% vs 52.8%; P = 0.001). Using multivariable analysis, both baseline malnutrition (adjusted-HR [adj-HR]: 1.37; 95% CI: 1.03-1.82; P = 0.03) and randomization to TEER plus GDMT compared with GDMT alone (adj-HR: 0.65; 95% CI: 0.51-0.82; P = 0.0003) were independent predictors of 4-year mortality. In contrast, GNRI was unrelated to the 4-year rate of heart failure hospitalization (HFH), although TEER treatment reduced HFH (adj-HR: 0.46; 95% CI: 0.36-0.56). The reductions in death (adj-P interaction  = 0.46) and HFH (adj-P interaction  = 0.67) with TEER were consistent in patients with and without malnutrition., Conclusions: Malnutrition was present in 1 of 6 patients with HF and severe SMR enrolled in COAPT and was independently associated with increased 4-year mortality (but not HFH). TEER reduced mortality and HFH in patients with and without malnutrition. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079)., Competing Interests: Funding Support and Author Disclosures The COAPT trial was sponsored by Abbott. Dr Scotti has served as a consultant for and has received consulting fees from NeoChord Inc. Dr Coisne has served as a consultant for Abbott; and has received speaker fees from Abbott and GE Healthcare. Dr Granada is the Co-Founder of Cephea Valve Technologies (Abbott); and is the CEO of the Cardiovascular Research Foundation. Dr Kar has received grants from Abbott, Boston Scientific, Edwards Lifesciences, and 4TECH; has been a consultant for Boston Scientific, Edwards Lifesciences, Medtronic, and 4TECH; and holds stock options in 4TECH. Dr Lim has received research grant support from Abbott, Boston Scientific, Corvia, Edwards, Medtronic, Trisol, and V Wave; and has received consultant fees from Ancora, Philips, Valgen, and Venus. Dr Cohen has received institutional research grants and consulting fees from Abbott, Edwards Lifesciences, Medtronic, and Boston Scientific. Dr Lindenfeld has received research grant support from AstraZeneca; and has received consulting income from Abbott Vascular, Alleviant, AstraZeneca, Cordio, CVRx, Edwards Lifesciences, Boehringer Ingelheim, Merck, Medtronic, Vascular Dynamics, and V-Wave. Dr Abraham has received research grant support from the National Institutes of Health – National Heart, Lung, and Blood Institute (National Institutes of Health 1 UG3/UH3 HL140144-01, 08/01/18 - 07/31/22, “Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Readmission/Mortality in Patients with Heart Failure and Central Sleep Apnea [LOFT-HF])”; has received consulting income from Abbott Vascular, Boehringer Ingelheim, and Zoll Respicardia; has received speaker honoraria from Impulse Dynamics; and has received salary support from V-Wave Medical. Dr Mack has served as co-primary investigator for the PARTNER trial for Edwards Lifesciences and the COAPT trial for Abbott; and has served as study chair for the APOLLO trial for Medtronic. Dr Asch has received institutional contracts with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; his employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave; and his daughter is an employee at Medtronic. 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 fourth-generation MitraClip G4 System builds on the previous NTR/XTR system with additional wider clip sizes (NTW and XTW), an independent grasping feature, and an improved clip deployment sequence., Objectives: The primary objective of this study was to assess the safety and performance of the MitraClip G4 System within a contemporary real-world setting., Methods: EXPAND G4 is a prospective, multicenter, international, single-arm, postapproval study that enrolled patients with primary (degenerative) mitral regurgitation (MR) and secondary (functional) MR at 60 centers. Follow-up of the full cohort has been conducted through 30 days. Echocardiograms were analyzed by an echocardiography core laboratory. Study outcomes included MR severity, functional capacity measured by NYHA functional class, quality of life measured using the Kansas City Cardiomyopathy Questionnaire, major adverse event rates, and all-cause mortality., Results: In EXPAND G4, 1,141 subjects with primary MR and secondary MR were treated from March 2021 to February 2022. Implantation and acute procedural success rates were 98.0% and 96.2%, respectively, with a mean of 1.4 ± 0.6 clips implanted per subject. MR was significantly reduced at 30 days compared with baseline (98% achieved MR ≤ 2+, and 91% achieved MR ≤ 1+; P < 0.0001). Functional capacity and quality of life were substantially improved, with 83% of patients achieving NYHA functional class I or II. Likewise, an 18-point improvement was observed in Kansas City Cardiomyopathy Questionnaire summary scores compared with baseline. The composite major adverse event rate was 2.7%, and the all-cause death rate was 1.3% at 30 days., Conclusions: This study demonstrates for the first time the effectiveness and safety of MitraClip G4 System at 30 days in a cohort of >1,000 patients with MR in a contemporary, real-world setting., Competing Interests: Funding Support and Author Disclosures The EXPAND G4 study was funded and sponsored by Abbott. Dr von Bardeleben has served in unpaid trial activities for Abbott, Edwards Lifesciences, Medtronic, and the University of Göttingen (IIT); and is an advisory board or Speakers Bureau for Abbott Cardiovascular, Edwards Lifesciences, Medtronic, and NeoChord. Dr Rogers is a consultant and proctor for Abbott and has received honoraria. Dr Mahoney serves as consultant and proctor for Medtronic, Edwards Lifesciences, and Boston Scientific; is a consultant for Abbott; and has received research support from Edwards Lifesciences, Medtronic, Abbott, and Boston Scientific. Dr Denti has received speaker honoraria from Abbott and Edwards Lifesciences; and has served as a consultant for InnovHeart, Artiness, and Pi-Cardia. Prof Maisano has received grant and/or institutional research support from Abbott, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific, NVT, and Terumo; has received consulting fees and honoraria (personal and institutional) from Abbott, Medtronic, Edwards Lifesciences, Xeltis, and Cardiovalve; has received royalty income and intellectual property rights from Edwards Lifesciences; and is a shareholder (including share options) in CardioGard, Magenta, SwissVortex, Transseptal Solutions, Occlufit, 4Tech, and Perifect. Dr Rinaldi has received honoraria or consulting fees from Abbott, Boston Scientific, and Edwards Lifesciences. Dr Chehab has received study grants and consulting fees from Abbott, Edwards Lifesciences, and BioTronics. Dr Zamorano has received speaker honoraria from Pfizer, Amgen, and Daiichi Sankyo; and has received research grants from Abbott and Edwards Lifesciences. Dr Price has received consulting fees from Acist Medical, Medtronic, Boston Scientific, Abbott, W.L. Gore, Philips Medical, and InnovHeart (outside of the submitted work). Dr Williams has received research funding from Abbott, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr Asch’s work as director of an academic core laboratory is through institutional research grants (MedStar Health) with Abbott, Boston Scientific, Medtronic, Edwards Lifesciences, Neovasc, Ancora Heart, LivaNova, MVRx, InnovHeart, Polares Medical, and Aria CV. Dr Rodriquez has received grant and research support from Abbott, Edwards Lifesciences, Boston Scientific, AtriCure, and CardioMech; and has received honoraria or consultating fees from Abbott, Edwards Lifesciences, Philips, Teleflex, and CardioMech. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter mitral valve replacement (TMVR) is an emerging therapeutic alternative for patients with secondary mitral regurgitation (MR). Outcomes of TMVR versus guideline-directed medical therapy (GDMT) have not been investigated for this population. This study aimed to compare clinical outcomes of patients with secondary MR undergoing TMVR versus GDMT alone., Methods: The CHOICE-MI registry (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency) included patients with MR undergoing TMVR using dedicated devices. Patients with MR pathogeneses other than secondary MR were excluded. Patients treated with GDMT alone were derived from the control arm of the COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation). We compared outcomes between the TMVR and GDMT groups, using propensity score matching to adjust for baseline differences., Results: After propensity score matching, 97 patient pairs undergoing TMVR (72.9±8.7 years; 60.8% men; transapical access, 91.8%) versus GDMT (73.1±11.0 years; 59.8% men) were compared. At 1 and 2 years, residual MR was ≤1+ in all patients of the TMVR group compared with 6.9% and 7.7%, respectively, in those receiving GDMT alone (both P <0.001). The 2-year rate of heart failure hospitalization was significantly lower in the TMVR group (32.8% versus 54.4%; hazard ratio, 0.59 [95% CI, 0.35-0.99]; P =0.04). Among survivors, a higher proportion of patients were in the New York Heart Association functional class I or II in the TMVR group at 1 year (78.2% versus 59.7%; P =0.03) and at 2 years (77.8% versus 53.2%; P =0.09). Two-year mortality was similar in the 2 groups (TMVR versus GDMT, 36.8% versus 40.8%; hazard ratio, 1.01 [95% CI, 0.62-1.64]; P =0.98)., Conclusions: In this observational comparison, over 2-year follow-up, TMVR using mostly transapical devices in patients with secondary MR was associated with significant reduction of MR, symptomatic improvement, less frequent hospitalizations for heart failure, and similar mortality compared with GDMT., Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT04688190 (CHOICE-MI) and NCT01626079 (COAPT)., Competing Interests: Disclosures Dr Ludwig reports travel compensation from Edwards; speaker honoraria from Abbott; and advisory fees from Bayer. Dr Conradi reports being on the advisory board at Abbott, Medtronic, and Boston Scientific and personal fees from Edwards. Dr Cohen reports research grant and consulting fees from Abbott, Edwards Lifesciences, Boston Scientific, and Medtronic AC; is a proctor at Abbott; and is a speaker at Abbott and General Electric Healthcare. Dr Scotti is a consultant for NeoChord. Dr Abraham reports research grant from the National Institutes of Health–National Heart, Lung, and Blood Institute (National Institutes of Health 1 UG3/UH3 HL140144-01, 08/01/18-07/31/22, LOFT-HF [Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Readmission/Mortality in Patients With Heart Failure and Central Sleep Apnea]); consulting at Abbott, Boehringer Ingelheim, and Zoll; honoraria from Impulse Dynamics; and salary from V-Wave Medical. Dr Ben Ali reports grants from Medtronic and Edwards. Dr Kar reports grants and consulting from Abbott, Boston Scientific, Edwards, and 4TECH and stock at 4TECH. Dr Scott Lim reports grants from Abbott, Boston Scientific, Corvia, Edwards, Medtronic, Trisol, and V-Wave and is a consultant at Ancora, Philips, Valgen, and Venus. Dr Duncan is a consultant at Abbott, Edwards, and Medtronic. Dr Adamo reports personal fees from Edwards and Boston Scientific and grants and honoraria from Medtronic. Dr Muller is on the advisory board at Abbott, Medtronic, and Edwards. Dr Petronio is a consultant at Medtronic, Boston Scientific, and Abbott. Dr Ruge is on the advisory board at Abbott and is a proctor at Abbott and Edwards. Dr Sondergaard reports grants and consulting at Edwards and Medtronic. Dr Adam reports grants and honoraria from Medtronic and personal fees from Boston Scientific and Edwards. Dr Dahle is a proctor/speaker at Abbott and Edwards. Dr Kempfert reports honoraria from Edwards, Medtronic, Abbott, and CryoLife. Dr Garatti is a proctor at Abbott. Dr Schmidt reports honoraria and travel support from Abbott and Cardiovalve. Dr Tang is a proctor/consultant at Medtronic; consultant/advisory board at Abbott; consultant at NeoChord; advisory board at JenaValve; and honoraria from Siemens and EastEnd Medical. Dr Redwood is a proctor at and reports personal fees from Edwards and is on the advisory board at Medtronic. Dr Taramasso is a consultant at Abbott, Edwards, Boston Scientific, Shenqi Medical, Simulands, Occlufit, MTEx, Medira, 4tech, and CoreMedic and reports personal fees from Cardiovalve. Dr Praz is a consultant at Edwards. Dr Fam is a consultant at Edwards, Abbott, and Cardiovalve. Dr Dumonteil is a consultant/proctor at Abbott, Boston Scientific, Edwards, and Medtronic. Dr von Bardeleben reports consulting/honoraria from Abbott, Edwards, and Medtronic and research grants to the university from Abbott and Edwards. Dr Rudolph reports honoraria from Abbott. Dr Reardon is a consultant at Medtronic, Boston, Abbott, and Gore (all funds to the department). Dr Metra reports personal fees from Actelion, Amgen, Livanova, Servier, Vifor Pharma as member of the Executive or Data Monitoring Committees of sponsored clinical trials, AstraZeneca, Abbott, Bayer, Boheringer Ingelhelm, and Edwards Therapeutics for participation to advisory boards and speeches at sponsored meetings. Dr Denti reports personal fees from Abbott and Edwards. Dr Mack reports being a co-Principal Investigator for the PARTNER trial (Placement of Aortic Transcatheter Valve Trial; Edwards) and COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation; Abbott) and is a study chair for the APOLLO trial (Transcatheter Mitral Valve Replacement With the Medtronic Intrepid TMVR System in Patients With Severe Symptomatic Mitral Regurgitation; Medtronic). Dr Hausleiter reports consulting fees, speaker honoraria, and research support to the institution from Abbott and Edwards. Dr Asch reports institutional contracts from Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. Dr Latib is on the advisory board at Medtronic, Boston Scientific, Philips, Edwards, and Abbott. Dr Lindenfeld reports grant support from AstraZeneca and consulting at Abbott, Alleviant, AstraZeneca, Cordio, CVRx, Edwards, Boehringer Ingelheim, Merck, Medtronic, Vascular Dynamics, and V-Wave. Dr Modine is a consultant at Abbott, Edwards, and Medtronic. Dr Stone reports honoraria from Medtronic, Pulnovo, and Infraredx; is a consultant at Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and reports equity/options at Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at Medtronic. Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Inc, Phillips, Biosense Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr Granada is the President and Chief Executive Officer of Cardiovascular Research Foundation. The other authors report no conflicts.

Background: Left ventricular (LV) circumferential strain has received less attention than longitudinal deformation, which has recently become part of routine clinical practice. Among other reasons, this is because of the lack of established normal values. Accordingly, the aim of this study was to establish normative values for LV circumferential strain and determine sex-, age-, and race-related differences in a large cohort of healthy adults., Methods: Complete two-dimensional transthoracic echocardiograms were obtained in 1,572 healthy subjects (51% men), enrolled in the World Alliance Societies of Echocardiography Normal Values Study. Subjects were divided into three age groups (<35, 35-55, and >55 years) and stratified by sex and by race. Vendor-independent semiautomated speckle-tracking software was used to determine LV regional circumferential strain and global circumferential strain (GCS) values. Limits of normal for each measurement were defined as 95% of the corresponding sex and age group falling between the 2.5th and 97.5th percentiles. Intergroup differences were analyzed using unpaired t tests., Results: Circumferential strain showed a gradient, with lower magnitude at the mitral valve level, increasing progressively toward the apex. Compared with men, women had statistically higher magnitudes of regional and global strain. Older age was associated with a stepwise increase in GCS despite an unaffected ejection fraction, a decrease in LV volume, and relatively stable global longitudinal strain in men, with a small gradual decrease in women. Asian subjects demonstrated significantly higher GCS magnitudes than whites of both sexes and blacks among women only. In contrast, no significant differences in GCS were found between white and black subjects of either sex. Importantly, despite statistical significance of these differences across sex, age, and race, circumferential strain values were similar in all groups, with variations of the order of magnitude of 1% to 2%. Notably, no differences in GCS were found among brands of imaging equipment., Conclusion: This study established normal values of LV regional circumferential strain and GCS and identified sex-, age-, and race-related differences when present., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Gender and racial differences in cardiac chamber size are vital to establish normal ranges of cardiac chamber size in healthy subjects. Many studies report either nonindexed raw measurements or measurements indexed to isometric body surface area (BSA) when establishing normal reference values. Other studies advocate allometric indexation for standardization of heart size. We compared several allometric methods on gender and racial differences in left ventricular end-diastolic volume (LVEDV) measured on three-dimensional echocardiography., Methods: Three-dimensional echocardiographic LVEDV data from the World Alliance Societies of Echocardiography normal values study were indexed to isometric BSA, BSA 1.5 , BSA 1.8 , isometric height, height 2.3 , height 2.9 , and estimated lean body mass. Gender, racial, national, and regional differences in indexed and nonindexed LVEDV were assessed using Cohen's d statistic or Cohen's f statistic, according to the number of groups being compared. Cohen's d < 0.20 and Cohen's f < 0.10 were regarded as very small relative magnitudes of difference., Results: Differences in LVEDV among White, Black, and Asian races were smallest when BSA 1.5 or BSA 1.8 was used for indexation, followed by estimated lean body mass. LVEDV/BSA 1.5 was nearly identical for men and women (very small, d = 0.05). However, both LVEDV/BSA 1.5 and LVEDV/BSA 1.8 still provided moderate relative magnitudes of difference (f = 0.22-0.37) among geographic regions. Specifically, among Asians, Indians had the smallest LVEDV/BSA 1.5 (1.8) . Brazilians had the smallest LVEDV/BSA 1.5 (1.8) among Whites., Conclusions: Gender and racial differences in LVEDV became smaller when LVEDV was indexed to BSA 1.5 or BSA 1.8 . However, differences in LVEDV among nations remain even after applying allometric scaling. This finding suggests that differences in body composition and/or hemodynamics are potentially more important determinants of heart size than race or gender., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Data from a 5-year follow-up of outcomes after transcatheter edge-to-edge repair of severe mitral regurgitation, as compared with outcomes after maximal doses of guideline-directed medical therapy alone, in patients with heart failure are now available., Methods: We randomly assigned patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy to undergo transcatheter edge-to-edge repair plus receive medical therapy (device group) or to receive medical therapy alone (control group) at 78 sites in the United States and Canada. The primary effectiveness end point was all hospitalizations for heart failure through 2 years of follow-up. The annualized rate of all hospitalizations for heart failure, all-cause mortality, the risk of death or hospitalization for heart failure, and safety, among other outcomes, were assessed through 5 years., Results: Of the 614 patients enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of hospitalization for heart failure through 5 years was 33.1% per year in the device group and 57.2% per year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.41 to 0.68). All-cause mortality through 5 years was 57.3% in the device group and 67.2% in the control group (hazard ratio, 0.72; 95% CI, 0.58 to 0.89). Death or hospitalization for heart failure within 5 years occurred in 73.6% of the patients in the device group and in 91.5% of those in the control group (hazard ratio, 0.53; 95% CI, 0.44 to 0.64). Device-specific safety events within 5 years occurred in 4 of 293 treated patients (1.4%), with all the events occurring within 30 days after the procedure., Conclusions: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite guideline-directed medical therapy, transcatheter edge-to-edge repair of the mitral valve was safe and led to a lower rate of hospitalization for heart failure and lower all-cause mortality through 5 years of follow-up than medical therapy alone. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: The relationship between left ventricular (LV) remodeling and clinical outcomes after treatment of severe mitral regurgitation (MR) in heart failure (HF) has not been examined., Objectives: The aim of this study was to evaluate the association between LV reverse remodeling and subsequent outcomes and assess whether transcatheter edge-to-edge repair (TEER) and residual MR are associated with LV remodeling in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial., Methods: Patients with HF and severe MR who remained symptomatic on guideline-directed medical therapy (GDMT) were randomized to TEER plus GDMT or GDMT alone. Baseline and 6-month core laboratory measurements of LV end-diastolic volume index and LV end-systolic volume index were examined. Change in LV volumes from baseline to 6 months and clinical outcomes from 6 months to 2 years were evaluated using multivariable regression., Results: The analytical cohort comprised 348 patients (190 treated with TEER, 158 treated with GDMT alone). A decrease in LV end-diastolic volume index at 6 months was associated with reduced cardiovascular death between 6 months and 2 years (adjusted HR: 0.90 per 10 mL/m 2 decrease; 95% CI: 0.81-1.00; P = 0.04), with consistent results in both treatment groups (P interaction  = 0.26). Directionally similar but nonsignificant relationships were present for all-cause death and HF hospitalization and between reduced LV end-systolic volume index and all outcomes. Neither treatment group nor MR severity at 30 days was associated with LV remodeling at 6 or 12 months. The treatment benefits of TEER were not significant regardless of the degree of LV remodeling at 6 months., Conclusions: In patients with HF and severe MR, LV reverse remodeling at 6 months was associated with subsequently improved 2-year outcomes but was not affected by TEER or the extent of residual MR. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079)., Competing Interests: Funding Support and Author Disclosures The COAPT trial was sponsored by Abbott Vascular. Dr Lindman has received investigator-initiated research grants from Edwards Lifesciences. Dr Asch is the director of an academic echocardiography core laboratory (MedStar Health Research Institute) with institutional contracts with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, Foldax, InnovHeart, Polares Medical, and Corcyn. Dr Grayburn has received consulting fees from Abbott Vascular, Edwards Lifesciences, W.L. Gore, Medtronic, and 4C Medical; and has received grant support from Abbott Vascular, Boston Scientific, Cardiovalve, Edwards Lifesciences, W.L. Gore, Medtronic, and NeoChord. Dr Mack has served as a co–primary investigator for the PARTNER trial for Edwards Lifesciences and the COAPT trial for Abbott; and has served as study chair for the APOLLO trial for Medtronic. Dr Bax’s employer, the Department of Cardiology (Leiden University Medical Center), has received research grants from Medtronic, Biotronik, Edwards Lifesciences, and Boston Scientific; and Dr Bax has received speaker fees from Abbott Vascular. Dr Gonzales has received speaker honoraria from Abbott. Dr Barker has received consultant honoraria from Edwards Lifesciences; and is an advisory board member for Medtronic and Boston Scientific. Dr Weissman is the associate director of an academic echocardiography core laboratory (MedStar Health Research Institute) with institutional contracts with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. Dr Abraham has received research grant support from Abbott Vascular and the National Heart, Lung, and Blood Institute; has received consulting income from Abbott Vascular; and has received speaker honoraria from Impulse Dynamics. Dr Lindenfeld has received research grant support from AstraZeneca and VoluMetrix; and has received consulting income from Abbott Vascular, AstraZeneca, Alleviant, Bayer, CVRx, Cytokinetics, Edwards Lifesciences, Boehringer Ingelheim, Merck, Medtronic, Vascular Dynamics, VoluMetrix, and V-Wave. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical; and has equity or options in Ancora, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee of Medtronic. Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Phillips, Biosense Webster, Shockwave, Vascular Dynamics, and V-Wave. 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 LRT trial (Low-Risk Transcatheter Aortic Valve Replacement [TAVR]) demonstrated the safety and feasibility of TAVR in low-risk patients, with excellent 1- and 2-year outcomes. The objective of the current study is to provide the overall clinical outcomes and the impact of 30-day hypoattenuated leaflet thickening (HALT) on structural valve deterioration at 4 years., Methods: The prospective, multicenter LRT trial was the first Food and Drug Administration-approved investigational device exemption study to evaluate feasibility and safety of TAVR in low-risk patients with symptomatic severe tricuspid aortic stenosis. Clinical outcomes and valve hemodynamics were documented annually through 4 years., Results: A total of 200 patients were enrolled, and follow-up was available on 177 patients at 4 years. The rates of all-cause mortality and cardiovascular death were 11.9% and 3.3%, respectively. The stroke rate rose from 0.5% at 30 days to 7.5% at 4 years, and permanent pacemaker implantation rose from 6.5% at 30 days to 11.7% at 4 years. Endocarditis was detected in 2.5% of the cohort, with no new cases reported between 2 and 4 years. Transcatheter heart valve hemodynamics remained excellent post-procedure and were maintained (mean gradient 12.56±5.54 mm Hg and aortic valve area 1.69±0.52 cm 2 ) at 4 years. At 30 days, HALT was observed in 14% of subjects who received a balloon-expandable transcatheter heart valve. There was no difference in valve hemodynamics between patients with and without HALT (mean gradient 14.94±5.01 mm Hg versus 12.3±5.57 mm Hg; P =0.23) at 4 years. The overall rate of structural valve deterioration was 5.8%, and there was no impact of HALT on valve hemodynamics, endocarditis, or stroke at 4 years., Conclusions: TAVR in low-risk patients with symptomatic severe tricuspid aortic stenosis was found to be safe and durable at 4 years. Structural valve deterioration rates were low irrespective of the type of valve, and the presence of HALT at 30 days did not affect structural valve deterioration, transcatheter valve hemodynamics, and stroke rate at 4 years., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02628899., Competing Interests: Disclosures Dr Waksman reports serving on the advisory boards of Abbott Vascular, Boston Scientific, Medtronic, Philips IGT, and Pi-Cardia Ltd; being a consultant for Abbott Vascular, Biotronik, Boston Scientific, Cordis, Medtronic, Philips IGT, Pi-Cardia Ltd, Swiss Interventional Systems/SIS Medical AG, Transmural Systems Inc, and Venous MedTech; receiving institutional grant support from Amgen, Biotronik, Boston Scientific, Chiesi, Medtronic, and Philips IGT; and being an investor in MedAlliance and Transmural Systems Inc. Dr Parikh is Consultant at Medtronic Inc. Dr Asch is director of the MedStar Health Academic Echocardiography Core Laboratory, which has institutional contracts with Medtronic, Edwards Lifesciences, Abbott, Boston Scientific, Biotronik, and LivaNova. Dr Weissman is director of an academic cardiac computed tomography core laboratory with institutional contracts with Ancora Heart and LivaNova. Dr Garcia-Garcia reports receiving institutional grants from Medtronic, Biotronik, Neovasc, Boston Scientific, Abbott, Shockwave, Chiesi, and Philips. Dr Rogers reports being a proctor and consultant for Boston Scientific, Edwards Lifesciences, and Medtronic; serving on the Advisory Board of Medtronic; and holding equity interest in Transmural Systems Inc. All other authors have no conflicts of interest to disclose.

Background: Although increased left ventricular (LV) mass is associated with adverse outcomes, measured values vary widely depending on the specific technique used. Moreover, the impact of sex, age, and race on LV mass remains controversial, further limiting the clinical use of this parameter. Accordingly, the authors studied LV mass using a variety of two-dimensional and three-dimensional echocardiographic techniques in a large population of normal subjects encompassing a wide range of ages., Methods: Transthoracic echocardiograms obtained from 1,854 healthy adult subjects (52% men) enrolled in the World Alliance Societies of Echocardiography (WASE) Normal Values Study, were divided into three age groups (young, 18-35 years; middle aged, 36-55 years; and old, >55 years). LV mass was obtained using five conventional techniques, including linear and two-dimensional methods, as well as direct three-dimensional measurement. All LV mass values were indexed to body surface area, and differences according to sex, age, and race were analyzed for each technique., Results: LV mass values differed significantly among the five techniques. Three-dimensional measurements were considerably smaller than those obtained using the other techniques and were closer to magnetic resonance imaging normal values reported in the literature. For all techniques, LV mass in men was significantly larger than in women, with and without body surface area indexing. These technique- and sex-related differences were larger than measurement variability. In women, age differences in LV mass were more pronounced and depicted significantly larger values in older age groups for all techniques, except three-dimensional echocardiography, which showed essentially no differences. LV mass was overall larger in black subjects than in white or Asian subjects., Conclusions: Significant differences in LV mass values exist across echocardiographic techniques, which are therefore not interchangeable. Sex-, race-, and age-related differences underscore the need for separate population specific normal values., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: Aortic valve area (AVA) used for echocardiographic assessment of aortic stenosis (AS) has been traditionally interpreted independently of sex, age and race. As differences in normal values might impact clinical decision-making, we aimed to establish sex-, age- and race-specific normative values for AVA and Doppler parameters using data from the World Alliance Societies of Echocardiography (WASE) Study., Methods and Results: Two-dimensional transthoracic echocardiographic studies were obtained from 1903 healthy adult subjects (48% women). Measurements of the left ventricular outflow tract (LVOT) diameter and Doppler parameters, including AV and LVOT velocity time integrals (VTIs), AV mean pressure gradient, peak velocity, were obtained according to ASE/EACVI guidelines. AVA was calculated using the continuity equation. Compared with men, women had smaller LVOT diameters and AVA values, and higher AV peak velocities and mean gradients (all P < 0.05). LVOT and AV VTI were significantly higher in women (P < 0.05), and both parameters increased with age in both sexes. AVA differences persisted after indexing to body surface area. According to the current diagnostic criteria, 13.5% of women would have been considered to have mild AS and 1.4% moderate AS. LVOT diameter and AVA were lower in older subjects, both men and women, and were lower in Asians, compared with whites and blacks., Conclusion: WASE data provide clinically relevant information about significant differences in normal AVA and Doppler parameters according to sex, age, and race. The implementation of this information into clinical practice should involve development of specific normative values for each ethnic group using standardized methodology., Competing Interests: Conflict of interest: M.S., M.B. and N.H. are employees of TOMTEC Imaging Systems. No other direct conflicts of Interest related to this study have been reported by any of the authors., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The third-generation MitraClip NTR/XTR transcatheter edge-to-edge repair system was introduced to assist in leaflet grasping with the longer clip arms of MitraClip XTR and to improve ease of use with the modified delivery catheter., Objectives: The EXPAND study evaluated contemporary real-world outcomes in subjects with mitral regurgitation (MR) treated with the third-generation MitraClip NTR/XTR transcatheter edge-to-edge repair system., Methods: EXPAND is a prospective, multicenter, international, single-arm study that enrolled patients with primary MR and secondary MR at 57 centers. Follow-up was conducted through 12 months. Echocardiograms were analyzed by an echocardiographic core laboratories. Study outcomes included: MR severity, functional capacity measured by New York Heart Association functional class, quality of life measured by Kansas City Cardiomyopathy Questionnaire, heart failure hospitalizations, all-cause mortality., Results: 1,041 patients were enrolled from April 2018 through March 2019, of which 50.5% had primary or mixed etiology. Implant success was 98.9%; 1.5 ± 0.6 clips were implanted per subject. Significant MR reduction from baseline (≥MR 3+: 56.0%) to 30 days (≤MR 1+:88.8%) was maintained through 1 year (MR ≤1+: 89.2%). A total of 84.5% and 93.0% of subjects in primary MR and secondary MR, respectively, had ≤1+ MR at 1 year. Significant improvements were observed in clinical outcomes (New York Heart Association functional class I/II in 80.3%, +21.6 improvement in Kansas City Cardiomyopathy Questionnaire score) at 1 year. All-cause mortality and heart failure hospitalizations at 1 year were 14.9% and 18.9%, respectively, which was significantly lower than previous studies., Conclusions: The study demonstrates treatment with the third-generation system resulted in substantial reduction of MR in a contemporary real-world practice, compared with the results of earlier EVEREST and COAPT trials.(The MitraClip® EXPAND Study of the Next Generation of MitraClip® Devices [EXPAND]; NCT03502811)., Competing Interests: Funding Support and Author Disclosures The EXPAND study was funded and sponsored by Abbott. Dr Kar has received grants and institutional research support from Abbott, Boston Scientific, and Edwards Lifesciences; has received consulting fees/honoraria from Abbott, Boston Scientific, W.L. Gore, and Medtronic; served as a steering committee member of the TRILUMINATE study (Abbott); and served as national principal investigator of the EXPAND study and the REPAIR MR study for Abbott. Dr von Bardeleben has served in unpaid trial activities for Abbott, Edwards Lifesciences, and University of Göttingen (IIT); and has served on an advisory or Speakers Bureau for Abbott Cardiovascular, Bioventrix, Boston Scientific, Cardiac Dimensions, Edwards Lifesciences, and Neochord. Prof Rottbauer has received consulting fees/speaker honoraria from Abbott, Bayer Healthcare, Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, and Medtronic; and is a member of the steering committee of the EXPAND G4 study for Abbott and Encourage AF study for Daiichi Sankyo. Dr Mahoney has served as proctor for Medtronic, Edwards Lifesciences, and Boston Scientific; has been a consultant for Abbott, Medtronic, Edwards Lifesciences, and Boston Scientific; and has received research support from Edwards Lifesciences, Medtronic, Abbott, and Boston Scientific. Dr Price has received consulting fees from AstraZeneca, Chiesi USA, Medtronic, Boston Scientific, Abbott, and WL Gore outside of the submitted work. Dr Grasso has served as a proctor for Abbott and Boston Scientific; and has received speaker fees from Edwards Lifesciences. Dr Williams has received research funding from Abbott, Medtronic, BSC, and Edwards Lifesciences. Prof Lurz has served as a consultant and received institutional fees and research grants from Abbott, Edwards Lifesciences, Medtronic, ReCor, and Occlutech. Dr Ahmed has served as a proctor and advisor, and received consulting fees and research grants from Abbott, Edwards Lifesciences, and Medtronic. Prof Hausleiter has received research support from Abbott Vascular and Edwards Lifesciences. Dr Chehab has received study grants and consulting fees from Abbott, Edwards Lifesciences, and Biotronics. Dr Zamorano has received speaker honoraria from Pfizer, Amgen, and Daiichi Sankyo; and research grants from Abbott and Edwards Lifesciences. Dr Asch’s work as director of an academic core laboratory is paid by institutional research grants (MedStar Health) from Abbott, Boston Scientific, Medtronic, Edwards Lifesciences, Neovasc, Ancora Heart, Livanova, MVRx, InnovHeart, Polares Medical, and Aria CV. Prof Maisano has received grant and/or institutional research support from Abbott, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific Corporation, NVT, and Terumo; and has received consulting fees, personal and institutional honoraria from Abbott, Medtronic, Edwards Lifesciences, Xeltis, and Cardiovalve; has received royalty income/IP rights from Edwards Lifesciences; and is a shareholder (including share options) of Cardiogard, Magenta, SwissVortex, Transseptalsolutions, Occlufit, 4Tech, and Perifect., (Copyright © 2023. Published by Elsevier Inc.)

Background: Assessment of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) plays a key role in the diagnosis of cardiac amyloidosis (CA). However, manual measurements are time consuming and prone to variability. We aimed to assess whether fully automated artificial intelligence (AI) calculation of LVEF and GLS provide similar estimates and can identify abnormalities in agreement with conventional manual methods, in patients with pre-clinical and clinical CA., Methods: We identified 51 patients (age 80 ± 10 years, 53% male) with confirmed CA according to guidelines, who underwent echocardiography before and/or at the time of CA diagnosis (median (IQR) time between observations 3.87 (1.93, 5.44 years). LVEF and GLS were quantified from the apical 2- and 4-chamber views using both manual and fully automated methods (EchoGo Core 2.0, Ultromics). Inter-technique agreement was assessed using linear regression and Bland-Altman analyses and two-way ANOVA. The diagnostic accuracy and time for detecting abnormalities (defined as LVEF ≤ 50% and GLS ≥ -15.1%, respectively) using AI was assessed by comparisons to manual measurements as a reference., Results: There were no significant differences in manual and automated LVEF and GLS values in either pre-CA (p = .791 and p = .105, respectively) or at diagnosis (p = .463 and p = .722). The two methods showed strong correlation on both the pre-CA (r = .78 and r = .83) and CA echoes (r = .74 and r = .80) for LVEF and GLS, respectively. The sensitivity and specificity of AI-derived indices for detecting abnormal LVEF were 83% and 86%, respectively, in the pre-CA echo and 70% and 79% at CA diagnosis. The sensitivity and specificity of AI-derived indices for detecting abnormal GLS was 82% and 86% in the pre-CA echo and 100% and 67% at the time of CA diagnosis. There was no significant difference in the relationship between LVEF (p = .99) and GLS (p = .19) and time to abnormality between the two methods., Conclusion: Fully automated AI-calculated LVEF and GLS are comparable to manual measurements in patients pre-CA and at the time of CA diagnosis. The widespread implementation of automated LVEF and GLS may allow for more rapid assessment in different disease states with comparable accuracy and reproducibility to manual methods., (© 2023 Wiley Periodicals LLC.)

Aims: Mitral valve transcatheter edge-to-edge repair is a guideline-recommended treatment option for patients with secondary mitral regurgitation (SMR). The purpose of this analysis was to report contemporary real-world outcomes in SMR patients treated with third-generation MitraClip systems., Methods and Results: EXPAND is a prospective, multicentre, international, single-arm study with 1041 patients treated for mitral regurgitation (MR) with MitraClip NTR/XTR, with 30-day and 1-year follow-up. All echocardiograms were analysed by an independent echocardiographic core lab. Study outcomes included procedural outcomes, durability of MR reduction, and major adverse events including all-cause mortality and heart failure hospitalizations (HFH). A subgroup of 413 symptomatic patients (age 74.7 ± 10.1 years, 58% male) with severe SMR were included. MR reduction to MR ≤ 1+ and MR ≤ 2+ was achieved in 93.0% and 98.5% of patients, respectively, which was sustained at 1-year follow-up. All-cause mortality was 17.7% at 1-year- follow-up, and the combined endpoint of all-cause mortality or first HFH occurred in 34% of patients. This combined endpoint was significantly less frequently observed in MR ≤ 1+ patients (Kaplan-Maier estimates: 29.7% vs. 69.6% for MR ≤ 1+ vs. MR  ≥ 2 +; p < 0.0001). New York Heart Association (NYHA) functional class improved significantly from baseline (NYHA ≤ II: 17%) to 1-year follow-up (NYHA ≤ II: 78%) (p < 0.0001). While MR reduction was comparable between NTR-only vs. XTR-only treated patients, less XTR clips were required for achieving MR reduction., Conclusions: Under real-world conditions, optimal sustained MR reduction to MR ≤ 1+ was achieved in a high percentage of patients with third-generation MitraClip, which translated into symptomatic improvement and low event rates. These results appear to be comparable with recent randomized clinical trials., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background The current standard of care for the treatment of patients with primary mitral regurgitation (MR) is surgical mitral valve repair. Transcatheter edge-to-edge repair with the MitraClip device provides a less invasive treatment option for patients with both primary and secondary MR. Worldwide, >150 000 patients have been treated with the MitraClip device. However, in the United States, MitraClip is approved for use only in primary patients with MR who are at high or prohibitive risk for mitral valve surgery. The REPAIR MR (Percutaneous MitraClip Device or Surgical Mitral Valve Repair in Patients With Primary Mitral Regurgitation Who Are Candidates for Surgery) trial is designed to compare early and late outcomes associated with transcatheter edge-to-edge repair with the MitraClip and surgical repair of primary MR in older or moderate surgical risk patients. Methods and Results The REPAIR MR trial is a prospective, randomized, parallel-controlled, open-label multicenter, noninferiority trial for the treatment of severe primary MR (verified by an independent echocardiographic core laboratory). Patients with severe MR and indications for surgery because of symptoms (New York Heart Association class II-IV), or without symptoms with left ventricular ejection fraction ≤60%, pulmonary artery systolic pressure >50 mm Hg, or left ventricular end-systolic diameter ≥40 mm are eligible for the trial provided they meet the moderate surgical risk criteria as follows: (1) ≥75 years of age, or (2) if <75 years of age, then the subject has a Society of Thoracic Surgeons Predicted Risk Of Mortality score of ≥2% for mitral repair (or Society of Thoracic Surgeons replacement score of ≥4%), or the presence of a comorbidity that may introduce a surgery-specific risk. The local surgeon must determine that the mitral valve can be surgically repaired. Additionally, an independent eligibility committee will confirm that the MR can be reduced to mild or less with both the MitraClip and surgical mitral valve repair with a high degree of certainty. A total of 500 eligible subjects will be randomized in a 1:1 ratio to receive the MitraClip device or to undergo surgical mitral valve repair (control group). There are 2 co-primary end points for the trial, both of which will be evaluated at 2 years. Each subject will be followed for 10 years after enrollment. The study has received approval from both the Food and Drug Administration and the Centers for Medicare and Medicaid Services, and enrolled its first subject in July 2020. Conclusions The REPAIR MR trial will determine the safety and effectiveness of transcatheter edge-to-edge repair with the MitraClip in patients with primary MR who are at moderate surgical risk and are candidates for surgical MV repair. The trial will generate contemporary comparative clinical evidence for the MitraClip device and surgical MV repair. Registration https://clinicaltrials.gov/ct2/show/NCT04198870; NCT04198870.