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

Background: 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: 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).)

Background: Functional tricuspid regurgitation (TR) can develop either because of right ventricular (RV) remodeling (ventricular functional TR) and/or right atrial dilation (atrial functional TR)., Objectives: This meta-analysis aimed to investigate the association between right heart remodeling and long-term (>1 year) all-cause mortality in patients with significant TR (at least moderate, ≥2+)., Methods: MEDLINE, ISI Web of Science, and SCOPUS databases were searched. Studies reporting data on at least 1 RV functional parameter and long-term all-cause mortality in patients with significant TR were included. This study was designed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) requirements., Results: Out of 8,902 studies, a total of 14 were included, enrolling 4,394 subjects. The duration of follow-up across the studies varied, ranging from a minimum of 15.5 months to a maximum of 73.2 months. Overall, long-term all-cause mortality was 31% (95% CI: 20%-41%; P ≤ 0.001). By means of meta-regression analyses, an inverse relation was found between tricuspid annular plane systolic excursion (11 studies enrolling 3,551 subjects, -6.3% [95% CI: -11.1% to -1.4%]; P = 0.011), RV fractional area change (9 studies, 2,975 subjects, -4.4% [95% CI: -5.9% to -2.9%]; P < 0.001), tricuspid annular dimension (7 studies, 2,986 subjects, -4.1% [95% CI: -7.6% to -0.5%]; P = 0.026), right atrial area (6 studies, 1,920 subjects, -1.9% [95% CI: -2.5% to -1.3%]; P < 0.001) and mortality., Conclusions: RV dysfunction parameters are associated to worse clinical outcomes in patients with TR, whereas right atrial dilatation is linked to a better prognostic outcome. Further studies are needed to unravel the pathophysiological differences within the functional TR spectrum. (Right heart remodeling and outcomes in patients with tricuspid regurgitation; CRD42023418667)., Competing Interests: Funding Support and Author Disclosures Dr von Roeder has received an institutional research grant from Deutsche Stiftung für Herzforschung. Dr Grayburn has received grant support from Abbott Vascular, Boston Scientific, 4C Medical, Edwards Lifesciences, Medtronic, Restore Medical, and W.L. Gore; and has received consulting fees/honoraria from Abbott Vascular, 4C Medical, Edwards Lifesciences, Medtronic, and W.L. Gore. Dr Sannino has received grant support from Cardiovalve and Edwards Lifesciences. 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.)

Conflicting results from 2 randomized clinical trials of transcatheter mitral valve edge-to-edge repair in secondary mitral regurgitation (SMR) have led to the recognition that SMR is a heterogeneous disease entity presenting with different functional and morphological phenotypes. This review summarizes the current knowledge on SMR caused primarily by atrial secondary mitral regurgitation (aSMR) and ventricular SMR pathology. Although aSMR is generally characterized by severe left atrial enlargement in the setting of preserved left ventricular anatomy and function, different patterns of mitral annular distortion cause different phenotypes of aSMR. In ventricular SMR, the relation of SMR severity to left ventricular dilation as well as the degree of pulmonary hypertension and right ventricular dysfunction are important phenotypic characteristics, which are key for a better understanding of prognosis and treatment response., Competing Interests: Funding Support and Author Disclosures Dr Hausleiter has received research support and speaker honoraria from Edwards Lifesciences. Dr Sannino has received research support from Edwards, Neochord, and Cardiovalve Venus Medtech. Dr Stolz has received speaker honoraria from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The CLASP IID randomized trial (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial) demonstrated the safety and effectiveness of the PASCAL system for mitral transcatheter edge-to-edge repair (M-TEER) in patients at prohibitive surgical risk with significant symptomatic degenerative mitral regurgitation (DMR)., Objectives: This study describes the echocardiographic methods and outcomes from the CLASP IID trial and analyzes baseline variables associated with residual mitral regurgitation (MR) ≤1+., Methods: An independent echocardiographic core laboratory assessed echocardiographic parameters based on American Society of Echocardiography guidelines focusing on MR mechanism, severity, and feasibility of M-TEER. Factors associated with residual MR ≤1+ were identified using logistic regression., Results: In 180 randomized patients, baseline echocardiographic parameters were well matched between the PASCAL (n = 117) and MitraClip (n = 63) groups, with flail leaflets present in 79.2% of patients. Baseline MR was 4+ in 76.4% and 3+ in 23.6% of patients. All patients achieved MR ≤2+ at discharge. The proportion of patients with MR ≤1+ was similar in both groups at discharge but diverged at 6 months, favoring PASCAL (83.7% vs 71.2%). Overall, patients with a smaller flail gap were significantly more likely to achieve MR ≤1+ at discharge (adjusted OR: 0.70; 95% CI: 0.50-0.99). Patients treated with PASCAL and those with a smaller flail gap were significantly more likely to sustain MR ≤1+ to 6 months (adjusted OR: 2.72 and 0.76; 95% CI: 1.08-6.89 and 0.60-0.98, respectively)., Conclusions: The study used DMR-specific echocardiographic methodology for M-TEER reflecting current guidelines and advances in 3-dimensional echocardiography. Treatment with PASCAL and a smaller flail gap were significant factors in sustaining MR ≤1+ to 6 months. Results demonstrate that MR ≤1+ is an achievable benchmark for successful M-TEER. (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial [CLASP IID]; NCT03706833)., Competing Interests: Funding Support and Author Disclosures The CLASP IID trial is funded by Edwards Lifesciences. Dr Marcoff has served as a member of the echocardiography core laboratory for Edwards Lifesciences, Abbott, and Medtronic, with no direct compensation. Dr Koulogiannis has served as a consultant and advisory board member for Edwards Lifesciences; has served as a speaker for Abbott; has served as a member of the echocardiography core laboratory for Edwards Lifesciences, Abbott, and Medtronic, with no direct compensation. Dr Lilian Aldaia has served as a member of the echocardiography core laboratory for Edwards Lifesciences, Abbott, and Medtronic, with no direct compensation. Dr Mediratta has served as a member of the echocardiography core laboratory for Edwards Lifesciences, Abbott, and Medtronic, with no direct compensation. Dr Chadderdon has served as a consultant for Edwards Lifesciences and Medtronic; and has received research grants from GE Healthcare. Dr Makar has served as a consultant for Boston Scientific and Abbott Vascular. Dr Ruf has received speaker, consulting, and proctoring fees from Abbott Laboratories and Edwards Lifesciences. Dr Nabauer has received speaker, consulting, and proctoring fees from Edwards Lifesciences. Dr Grayburn has received research grants from Abbott Vascular, Boston Scientific, Cardiovalve, Edwards Lifesciences, Medtronic, Neochord, W. L. Gore and Associates, and 4C Medical; and has also served as a consultant and advisory board member for Abbott Vascular, Cardiovalve, Edwards Lifesciences, Medtronic, W. L. Gore and Associates, and 4C Medical. Dr Vannan has received research grants and speaker honoraria from Piedmont Heart Institute for Abbott, Medtronic, Edwards Lifesciences, Philips, Siemens Healthineers, and GE Healthcare. Dr Ender has received institutional honoraria from Edwards Lifesciences, Abbott, and Medela, with no direct compensation. Dr Puthumana has served on the Speakers Bureau and as a training consultant for Abbott Structural and Edwards Lifesciences. Dr Mansoor has served as a consultant for Atricure. Dr Hahn has received speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, and Philips Healthcare; has stock options with Navigate; has held institutional consulting contracts with Abbott Structural, Boston Scientific, Edwards Lifesciences, Medtronic, and Novartis; and has served as a Chief Scientific Officer for the echocardiography core laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, with no direct industry compensation for either. Dr Mahmood has served as a consultant for education materials for Abbott Medical and GE Ultrasound. Dr Haeffele has served as a consultant to Edwards Lifesciences. Dr Ong has received speaker fees from Abbott. Dr Schneider has served as a speaker, proctor, and advisor for Edwards Lifesciences and Abbott; and has served as an advisor for Boehringer and Lilly. Dr D. Wang has served as a consultant to Edwards Lifesciences, Abbott Vascular, Materialise, and Boston Scientific. Dr Koss has served as an educational speaker for Abbott and Edwards Lifesciences. Dr Harb has served as a consultant for Abbott, Boston Scientific, and Mitria. Dr Miyasaka has served as a consultant for Abbott. Dr Ivannikova has received speaker fees from Edwards Lifesciences. Dr Mitchel has served on the Abbott Speakers Bureau. Dr Raissi has served as a consultant for Abbott. Dr Kalbacher has received proctor fees from Edwards Lifesciences and PiCardia Ltd; and has received lecture fees from Edwards Lifesciences and Abbott Medical. Dr Ho has served as an advisor for Neochord, Half Moon Medical, and Valgen; and has held institutional consulting contracts with GE Healthcare and Edwards Lifesciences. Dr Smith has served in clinical trial leadership and has received institutional grant and travel support for device evaluation from Edwards Lifesciences; has received institutional grants from Artivion; and has received speaker honoraria from Artivion and Medtronic. Dr Hausleiter has served as a consultant and has received speaker honoraria and institutional research support from Edwards Lifesciences. Dr Lim has served as a consultant for Ancora, LagunaTech, Nyra, Opus, Philips, Venus, and Valgen; and has received research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Gillam has served as a consultant for Philips, Bracco, Edwards Lifesciences, and Medtronic; and has institutional echocardiography core laboratory contracts from Abbott, Edwards Lifesciences, and Medtronic, with no direct compensation. 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.)

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, a central committee of heart failure (HF) specialists optimized guideline-directed medical therapies (GDMT) and documented medication and goal dose intolerances before patient enrollment., Objectives: The authors sought to assess the rates, reasons, and predictors of GDMT intolerance in the COAPT trial., Methods: Baseline use, dose, and intolerances of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were analyzed in patients with left ventricular ejection fraction (LVEF) ≤40%, in whom maximally tolerated doses of these agents as assessed by an independent HF specialist were required before enrollment., Results: A total of 464 patients had LVEF ≤40% and complete medication information. At baseline, 38.8%, 39.4%, and 19.8% of patients tolerated 3, 2, and 1 GDMT classes, respectively (any dose); only 1.9% could not tolerate any GDMT. Beta-blockers were the most frequently tolerated GDMT (93.1%), followed by ACEIs/ARBs/ARNIs (68.5%), and then MRAs (55.0%). Intolerances differed by GDMT class, but hypotension and kidney dysfunction were most common. Goal doses were uncommonly achieved for beta-blockers (32.3%) and ACEIs/ARBs/ARNIs (10.2%) due to intolerances limiting titration. Only 2.2% of patients tolerated goal doses of all 3 GDMT classes., Conclusions: In a contemporary trial population with HF, severe mitral regurgitation, and systematic HF specialist-directed GDMT optimization, most patients had medical intolerances prohibiting 1 or more GDMT classes and achieving goal doses. The specific intolerances noted and methods used for GDMT optimization provide important lessons for the implementation of GDMT optimization in future clinical trials. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079)., Competing Interests: Funding Support and Author Disclosures Abbott Laboratories has provided funding for this paper. Dr Cox has received grants from AstraZeneca, and Cumberland Pharmaceuticals; and consulting fees from Roche. Dr Udelson has served on steering committees for Abiomed; and has received consulting fees from Imbria Pharmaceuticals. Dr Lim has received grants from Abbott, Edwards, Medtronic, and Gore; consulting fees from Abbott, Edwards, Keystone Heart, Pipeline, Siemens, Valgen, and Venus; has served on advisory boards for Ancora and Venus; and holds equity in 510Kardiac and Venus. Dr Grayburn has received grant support and consulting fees from Edwards Lifesciences and Neochord; and grants from Boston Scientific, Medtronic, and Tendyne. Dr Mack has the following nonfinancial relationships: he has served as co-primary 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 Abraham has received grants and consulting fees from Abbott. Dr Stone has received honoraria from Terumo, Cook, and Infraredx; consulting fees from Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Reva, MAIA Pharmaceuticals, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, and Gore; holds equity/options for Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and MedFocus family of funds. Dr Lindenfeld has received grants from AstraZeneca; and consulting fees from Abbott, CVRx, Edwards Lifesciences, RESMED, Relypsa, BI, 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 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: Transcatheter therapies are a recognized alternative intervention in patients with severe mitral regurgitation who are at high surgical risk. The purpose of this study was to characterize patients screened for transcatheter mitral valve replacement (TMVR), establish the clinical and anatomic reasons for unsuitability, and determine clinical course and early outcomes., Methods: International multicentre registry was conducted of consecutive patients screened for TMVR at 12 centres in Europe, the United States, and Canada between April 2015 and September 2018. Patient-level retrospective data were collected for all patients screened., Results: From a total of 294 patients, 87 (30%) patients were suitable for and underwent TMVR, whereas 207 (70%) patients were unsuitable for TMVR. There was no difference in Society of Thoracic Surgeons predicted risk of mortality (6.3% ± 4.3% vs 6.7 ± 6.1%, P = 0.52) for mitral valve replacement between the groups. The most common reasons for TMVR unsuitability were mitral annular size outside therapeutic range (28%) and small predicted neo-LVOT (25%). Preprocedural multidetector computed tomographic demonstrated that patients unsuitable for TMVR had smaller predicted neo-left ventricular outflow tract (LVOT) area (318 ±192 mm 2 vs 495 ± 202 mm 2 , P = 0.04). At 30 days, there was no difference in rates of rehospitalization (8% vs 8%, P = 0.21), stroke (1% vs 2%, P = 0.42), or mortality (4% vs 10%, P = 0.10), unadjusted for procedural risk, between unsuitable for TMVR and TMVR groups, respectively., Conclusions: Two-thirds of patients failed screening as anatomically unsuitable for TMVR. The findings of this study have important clinical implications, highlighting an unmet clinical need and provide a target for design innovation in future iterations of TMVR devices., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: There are limited data on the predictors of death or heart failure hospitalization (HFH) in patients with heart failure (HF) with functional mitral regurgitation (FMR)., Objectives: The aim of this study was to develop a predictive risk score using the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial database., Methods: In COAPT, 614 symptomatic patients with HF and moderate to severe or severe FMR were randomized to MitraClip implantation plus guideline-directed medical therapy (GDMT) or GDMT alone. A risk score for the 2-year rate of death or HFH was generated from Cox proportional hazards models. The predictive value of the model was assessed using the area under the curve of receiver-operating characteristic plots. Kaplan-Meier curves were generated to estimate the proportion of patients experiencing death or HFH across quartiles of risk., Results: During 2-year follow-up, 201 patients (64.4%) in the GDMT-alone group and 133 patients (44.0%) in the MitraClip group experienced death or HFH (P < 0.001). A risk score containing 4 clinical variables (New York Heart Association functional class, chronic obstructive pulmonary disease, atrial fibrillation or flutter, and chronic kidney disease) and 4 echocardiographic variables (left ventricular ejection fraction, left ventricular end-systolic dimension, right ventricular systolic pressure, and tricuspid regurgitation) in addition to MitraClip treatment was generated. The area under the curve of the risk score model was 0.74, and excellent calibration was present. The relative benefit of MitraClip therapy in reducing the 2-year hazard of death or HFH was consistent across the range of baseline risk., Conclusions: A simple risk score of clinical, echocardiographic, and treatment variables may provide useful prognostication in patients with HF and severe FMR., Competing Interests: Funding Support and Author Disclosures The COAPT trial was sponsored by Abbott. The funder had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. Dr Madhavan has received an institutional grant from the National Institutes of Health/National Heart, Lung, and Blood Institute to Columbia University Irving Medical Center (T32 HL007854). Dr Gray is a consultant for Boston Scientific. Dr Brener is a Speakers Bureau member for AstraZeneca. Dr Lindenfeld has received research grant support from AstraZeneca; and has received consulting income from Abbott Vascular, CVRx, Edwards Lifesciences, RESMED, Relypsa, Boehringer Ingelheim, and V-Wave. Dr Abraham has received research grant support from Abbott Vascular; and has received consulting income from Abbott Vascular. Dr Grayburn has received grant support and consulting fees from Edwards Lifesciences and NeoChord; and has received grant support from Boston Scientific, Medtronic, and Tendyne. Dr Lim has received research grant support from Abbott, Edwards Lifesciences, Medtronic, and Gore; is a consultant for Abbott, Edwards Lifesciences, Keystone Heart, Pipeline, Siemens, Valgen, and Venus; is an advisory board member for Ancora and Venus; and holds equity in 510Kardiac and Venus. Dr Whisenant is a consultant for Edwards Lifesciences, Boston Scientific, Gore, and NeoChord. 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 Stone has received speaker or other honoraria from Terumo, Cook, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Reva, MAIA Pharmaceuticals, Vascular Dynamics, Shockwave, V-Wave, CardioMech, and Gore; and has equity and options with Ancora, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and the MedFocus family of funds. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Tricuspid regurgitation (TR) is prevalent and undertreated, with mortality and morbidity increasing with TR severity. Given poor outcomes with medical therapy and high in-hospital mortality for isolated tricuspid valve surgery, emerging transcatheter repair devices offer a promising alternative., Objectives: The Edwards Cardioband Tricuspid Valve Reconstruction System Early Feasibility study (NCT03382457) evaluates the treatment of functional TR via annular reduction with the Cardioband Tricuspid Valve Reconstruction System (Edwards Lifesciences)., Methods: Patients with ≥ moderate functional TR were eligible for this prospective, single-arm multicenter study. At 1 year, patients were evaluated for echocardiographic parameters, clinical and quality-of-life measures, and major adverse events., Results: The 37 patients enrolled had a mean age of 78 years; 76% were female; and they had ≥ severe functional (97.3%) or mixed (2.7%) TR, atrial flutter/fibrillation (97%), and New York Heart Association functional class III/IV (65%). At 1 year, 73.0% achieved ≤ moderate TR (P < 0.0001), and 73.1% had ≥2 grade reductions. Echocardiography showed significant reductions in the tricuspid annulus diameter (P < 0.0001), mean vena contracta (P < 0.0001), proximal isovelocity surface area effective regurgitant orifice area (P < 0.0001), right ventricular end-diastolic diameter (P < 0.0001), and inferior vena contracta (P = 0.0006). New York Heart Association functional class improved significantly (P < 0.0001), with 92.3% achieving class I/II, and Kansas City Cardiomyopathy Questionnaire scores improved by 19.0 points (P < 0.0001). One-year cardiovascular mortality was 8.1%, reinterventions were necessary in 5.4%, major access site complications occurred in 8.1%, and severe bleeding was noted in 35.1% of patients. Kaplan-Meier estimates of survival and freedom from heart failure rehospitalization were 85.9% and 88.7%, respectively., Conclusions: One-year experience using the Cardioband system for tricuspid valve repair shows high survival and low rehospitalization rates with durable outcomes in TR reduction and echocardiographic, clinical, and quality-of-life outcomes., Competing Interests: Funding Support and Author Disclosures This study was funded by Edwards Lifesciences. Dr Gray consults for Edwards Lifesciences. Dr Lim has received institutional research grants with Abbott Vascular, Boston Scientific, Edwards Lifesciences, and Medtronic; and has received consulting fees from Venus Medtech and WL Gore. Dr Smith has received institutional grant support and serves as a speaker for Edwards Lifesciences, Abbott, and Artivion; is on the advisory board for Edwards Lifesciences; and is a speaker for Medtronic. Dr Grayburn has received research grants from Abbott, Edwards Lifesciences, Medtronic, Gore, Neochord, and Cardiovalve; and serves as a consultant/advisory board for Abbott, Edwards Lifesciences, Medtronic, and 4C Medical. Dr Kodali has received research support from Edwards Lifesciences, Medtronic, Boston Scientific, JenaValve, and Abbott Vascular; has received honoraria from Admedus, TriFlo, and Dura Biotech; and is on the advisory board and received equity from MicroInterventional Devices, Dura Biotech, Supira, Adona Medical, Thubrikar Aortic Valve, Inc, and TriFlo. Dr Hahn has received fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, and Philips Healthcare; has institutional consulting contracts for which she receives no direct compensation with Abbott Structural, Boston Scientific, Edwards Lifesciences, Medtronic, and Novartis; and has stock options with Navigate and is Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials for which she receives no direct industry compensation. Dr Whisenant consults for Edwards Lifesciences. Dr McCabe consults for Edwards Lifesciences, Medtronic, Boston Scientific, and Cardiovascular Systems, Inc. Dr Puthumana is on the Speakers Bureau for Abbott Structural. Dr Davidson has received research grant funding and is a consultant for Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is an established relationship between the degree of mitral regurgitation (MR) and prognosis. Quantitation of MR severity guides therapeutic approaches. Inconsistent definitions and categorization of MR severity in clinical studies limit meaningful comparisons among trials and compromise development of an effective evidence base. The purpose of this study was to quantify heterogeneity in grading systems for MR severity in the contemporary literature., Methods: This was a systematic review of randomized controlled trials and propensity score-adjusted clinical studies of mitral valve interventions (surgical or percutaneous). A total of 35 articles from 2015 to 2020 were included (15 randomized controlled trials and 20 propensity score-adjusted clinical studies)., Results: There were 22 studies that reported MR severity in numeric categories, either values from the historical "plus" system or numeric MR grades, whereas 9 studies reported MR severity using text-only descriptive categories. Among the studies that used numeric categories, 2+ MR was defined as moderate in 64% of studies, mild in 27%, and mild-moderate in 9%, and 3+ MR was defined as moderate in 14%, moderate-severe in 52%, and severe in 14%., Conclusions: There was substantial variability in MR severity definition and reporting in contemporary clinical studies of mitral valve interventions. We recommend that the historical plus numeric grading system be abandoned and that inclusion and outcome criteria in MR clinical trials be based on US and European guideline-recommended categories as none or trace, mild, moderate, and severe. Adoption of these simple recommendations will improve the consistency and quality of MR clinical trial design and reporting., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The TRISCEND study (Edwards EVOQUE Tricuspid Valve Replacement: Investigation of Safety and Clinical Efficacy after Replacement of Tricuspid Valve with Transcatheter Device) is evaluating the safety and performance of transfemoral transcatheter tricuspid valve replacement in patients with clinically significant tricuspid regurgitation (TR) and elevated surgical risk., Background: Transcatheter valve replacement could lead to a paradigm shift in treating TR and improving patient quality of life., Methods: In the prospective, single-arm, multicenter TRISCEND study, patients with symptomatic moderate or greater TR, despite medical therapy, underwent percutaneous transcatheter tricuspid valve replacement with the EVOQUE system. A composite rate of major adverse events, echocardiographic parameters, and clinical, functional, and quality-of-life measures were assessed at 30 days., Results: Fifty-six patients (mean age of 79.3 years, 76.8% female, 91.1% TR severe or greater, 91.1% atrial fibrillation, and 87.5% New York Heart Association functional class III or IV) were treated. At 30 days, TR was reduced to mild or less in 98%. The composite major adverse events rate was 26.8% at 30 days caused by 1 cardiovascular death in a patient with a failed procedure, 2 reinterventions after device embolization, 1 major access site or vascular complication, and 15 severe bleeds, of which none were life-threatening or fatal. No myocardial infarction, stroke, renal failure, major cardiac structural complications, or device-related pulmonary embolism were observed. New York Heart Association significantly improved to functional class I or II (78.8%; P < 0.001), 6-minute walk distance improved 49.8 m (P < 0.001), and Kansas City Cardiomyopathy Questionnaire score improved 19 points (P < 0.001)., Conclusions: Early experience with the transfemoral EVOQUE system in patients with clinically significant TR demonstrated technical feasibility, acceptable safety, TR reduction, and symptomatic improvement at 30 days. The TRISCEND II randomized trial (NCT04482062) is underway., Competing Interests: Funding Support and Author Disclosures This work was funded by Edwards Lifesciences. Dr Kodali has received research support from Edwards Lifesciences, Medtronic, Boston Scientific, JenaValve, and Abbott Vascular; has received honoraria from Admedus, TriFlo, and Dura Biotech; and has served on the advisory board and received equity from MicroInterventional Devices, Dura Biotech, Supira, Adona Medical, Thubrikar Aortic Valve, Inc, and TriFlo. Dr Hahn has received speaker fees from Abbott Structural, Edwards Lifesciences, and Philips Healthcare; has received institutional educational and consulting contracts for which she receives no direct compensation from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic; owns equity in Navigate; and is Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she receives no direct industry compensation. Dr George has served as a consultant for CardioMech, Vdyne, Durvena, MITRx, Neptune Medical, Johnson and Johnson, Atricure, and Mitre Medical. Dr Wang has served a consultant for Edwards Lifesciences, Abbott, Boston Scientific, and Neochord; and has received research grant support from Boston Scientific assigned to her employer, the Henry Ford Health System. Dr Elmariah has received institutional research support from Edwards Lifesciences, Medtronic, and Abbott; and has received consulting fees from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Competing Interests: Funding Support and Author Disclosures This study was funded by Edwards Lifesciences. Drs. Davidson, Smith, Grayburn, Gray, and Lim have received grant support/consulting fees from Edwards Lifesciences. Dr. Hahn is a speaker and consultant for Edwards Lifesciences and is the Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she receives no direct industry compensation. Drs. Deuschl and Feldman are employees of Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objectives: The aim of this study was to assess the impact of age on outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial., Background: In the COAPT trial, TEER with the MitraClip device in patients with heart failure (HF) and moderate to severe or severe secondary mitral regurgitation (SMR) reduced the risk for HF hospitalization (HFH) and all-cause mortality compared with maximally tolerated guideline-directed medical therapy (GDMT) alone. There are limited data regarding the effectiveness of MitraClip therapy in elderly patients., Methods: Patients (n = 614) were grouped by median age at randomization (74 years) and by MitraClip treatment vs GDMT alone. The primary endpoint was the 2-year rate of death or HFH assessed by multivariable Cox regression., Results: Death or HFH within 2 years occurred less frequently after treatment with the MitraClip vs GDMT alone in patients <74 years of age (37.3% vs 64.5%; adjusted HR: 0.41; 95% CI: 0.29-0.59) and ≥74 years of age (51.7% vs 69.6%; adjusted HR: 0.58; 95% CI: 0.42-0.81) (P int  = 0.17). Mortality was also consistently reduced with MitraClip treatment in young and elderly patients (P int  = 0.42). In contrast, elderly patients treated with the MitraClip vs GDMT alone tended to have a lesser reduction of HFH than younger patients (P int  = 0.03). Younger and older patients had similar improvements in quality of life after treatment with the MitraClip compared with GDMT alone., Conclusions: In the COAPT trial, MitraClip treatment of moderate to severe and severe SMR reduced the composite risk for death or HFH and improved survival and quality of life regardless of age. As such, young and elderly patients with HF and severe SMR benefit from TEER, although elderly patients may not have as great a benefit from the MitraClip device in reducing HFH., Competing Interests: Funding Support and Author Disclosures The COAPT trial was funded by Abbott. Dr Madhavan has received an institutional grant from the National Institutes of Health/National Heart, Lung, and Blood Institute to Columbia University Irving Medical Center (T32 HL007854). Dr Lindenfeld has received research grant support from AstraZeneca; and has received consulting income from Abbott Vascular, CVRx, Edwards Lifesciences, RESMED, Relypsa, Boehringer Ingelheim, and V-Wave. Dr Abraham has received research grant support from Abbott Vascular; and has received consulting income from Abbott Vascular. Dr Kar has received consulting fees from and is an advisory board member for Abbott Vascular and Boston Scientific; has received consulting fees from and holds stock equity in Valcare; and has received consulting fees from W.L. Gore and Medtronic (national co–principal investigator, Repair-MR trial and EXPAND registry; steering committee member for TRILUMINATE trial). Dr Lim has received research grant support from Abbott, Edwards Lifesciences, Medtronic, and Gore; is a consultant for Abbott, Edwards Lifesciences, Keystone Heart, Pipeline, Siemens, Valgen, and Venus; is an advisory board member for Ancora and Venus; and holds equity in 510Kardiac and Venus. Dr Grayburn has received grant support and consulting fees from Edwards Lifesciences and NeoChord; and has received grant support from Boston Scientific, Medtronic, and Tendyne. Dr Kapadia holds stock options with Navigate Cardiac Structures. Dr Mack has served as co–primary investigator for the PARTNER (Placement of Aortic Transcatheter Valve) trial for Edwards Lifesciences and the COAPT trial for Abbott; and has served as study chair for the APOLLO trial for Medtronic. Dr Stone has received speaker honoraria from Cook 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, Reva, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, Gore, and Amgen; has equity or options in Ancora, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, Xenter, and the MedFocus family of funds; and receives institutional research support (to Mount Sinai Hospital) from Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Plaque elasticity and intraplaque neovascularisation are strongly suggestive of vulnerable plaque. This study aimed to investigate the relationship between intraplaque neovascularisation and plaque elasticity, and to compare the ultrasound findings with histopathological changes., Methods: Patients enrolled in this study presented with symptomatic carotid stenosis (> 70%) and later underwent both pre-operative ultrasonography and endarterectomy. Contrast enhanced ultrasound (CEUS) and shear wave elastography (SWE) were used to measure the neovascularisation and elasticity of the plaque, respectively. After removal, plaques were histologically assessed to determine the microvessel density (MVD), matrix metalloproteinase (MMP)-9 expression, and type I/type III collagen ratio using immunohistochemistry staining and morphometry. A correlation analysis was used to establish the relationship among the aforementioned quantitative parameters. Inter- and intra-observer consistency evaluations were performed using the intraclass correlation coefficient and Bland-Altman plots., Results: Ninety-four symptomatic patients with 98 plaques were included. The area under the curve (AUC) of the carotid plaque detected using CEUS correlated with its shear wave velocity (SWV) (r = -.714; p < .001), MVD (r = .842; p < .001), collagen type I/III ratio (r = -.833; p < .001), and MMP-9 (r = .738; p < .001). SWE was positively correlated with the type I/III collagen ratio (r = .805; p < .001). The overall interexaminer consistency of the SWE was acceptable (r = .638; p < .001). The interobserver correlation coefficient of the AUC, time to peak (TP), mean transit time (MTT), and SWV were .719, .756, .733, and .686, respectively. The intra-observer variability values of the AUC, TP, MTT, and SWV were .826, .845, .633, and .748, respectively., Conclusion: SWE and CEUS can comprehensively evaluate the vulnerability of the carotid plaque by assessing the elasticity of the plaque and neovascularisation within it. The negative correlation between the intraplaque neovascularisation and elasticity, further validated by histological findings, suggests that the more abundant the neovascularisation, the less elasticity., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Objectives: The authors sought to evaluate the association between mean mitral valve gradient (MVG) and clinical outcomes among patients who underwent MitraClip treatment for secondary mitral regurgitation (SMR) in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial., Background: In the COAPT trial, patients with heart failure (HF) and severe SMR who remained symptomatic despite guideline-directed medical therapy had marked 2-year reductions in mortality and HF hospitalizations after treatment with MitraClip., Methods: MitraClip-treated patients were divided into quartiles (Q) based on discharge echocardiographic MVG (n = 250). Endpoints including all-cause mortality, HF hospitalization, and health status measures at 2 years were compared between quartiles., Results: Mean MVG after MitraClip was 2.1 ± 0.4 mm Hg, 3.0 ± 0.2 mm Hg, 4.2 ± 0.5 mm Hg, and 7.2 ± 2.0 mm Hg in Q1 (n = 63), Q2 (n = 61), Q3 (n = 62), and Q4 (n = 64), respectively. There was no difference across quartiles in the 2-year composite endpoint of all-cause mortality or HF hospitalization (43.2%, 49.2%, 40.6%, and 40.9%, respectively; p = 0.80), nor in improvements in New York Heart Association functional class, Kansas City Cardiomyopathy Questionnaire score, or 6-min walk time. Results were similar after adjustment for baseline clinical and echocardiographic characteristics, post-procedure MR grade, and number of clips (all-cause mortality or HF hospitalization Q4 [44.6%] vs. Q1 to Q3 [40.3%]; adjusted hazard ratio: 1.23, 95% confidence interval: 0.60 to 2.51; p = 0.57)., Conclusions: Among HF patients with severe SMR, higher MVGs on discharge did not adversely affect clinical outcomes following MitraClip. These findings suggest that in select patients with HF and SMR otherwise meeting the COAPT inclusion criteria, the benefits of MR reduction may outweigh the effects of mild-to-moderate mitral stenosis after MitraClip., Competing Interests: Funding Support and Author Disclosures The COAPT Trial was sponsored by Abbott, which also provided funding to the Cardiovascular Research Foundation to support statistical analysis and administrative/editorial assistance for this paper. Dr. Herrmann has received institutional grant support from Abbott Vascular, Ancora, Boston Scientific, Edwards Lifesciences, and Medtronic; and consulting fees from Abbott Vascular, Edwards Lifesciences, and Medtronic. Dr. Lim has received research grant support and consulting fees from Abbott Vascular. Dr. Kar has received research grant support from Abbott, Boston Scientific, Edwards Lifesciences, and Mitralign; and has received consulting income from Abbott and Boston Scientific. Dr. Lindenfeld has received consulting fees from Abbott, Edwards Lifesciences, Boston Scientific, Relypsa, Boehringer Ingelheim, V-Wave, CVRx, and Impulse Dynamics; and research grant support from AstraZeneca. Dr. Abraham has received research grant support from Abbott; and consulting fees from Abbott and Edwards Lifesciences. Dr. Grayburn has received research grant support from Abbott, Edwards Lifesciences, Medtronic, W.L. Gore, and Boston Scientific; has consulted for Abbott, Edwards, Medtronic, and Neochord; and has imaging core laboratory contracts with Edwards Lifesciences, Neochord, W.L. Gore, and Cardiovalve. Drs. Asch and Weissman are director and associate director, respectively, of an academic echocardiography core laboratory with institutional contracts with Abbott, Neovasc, Ancora, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. Dr. Mack has served as coprincipal investigator for the Edwards Lifesciences–sponsored PARTNER 3 trial and the Abbott-sponsored COAPT trial; and has served as study chairman for the Medtronic-sponsored APOLLO trial. Dr. Stone has received speaker or other honoraria from Cook, Terumo, Qool Therapeutics, and Orchestra Biomed; has served as a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, Matrizyme, and Cardiomech; and has equity/options from Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, MedFocus family of funds, and Valfix. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Mitral regurgitation (MR) is a common form of valvular heart disease that is associated with significant morbidity and mortality. Treatment decisions are completely dependent on accurate diagnosis of both mechanism and severity of MR, which can be challenging and is often done incorrectly. Transthoracic echocardiography is the most commonly used imaging test for MR; transesophageal echocardiography is often needed to better define morphology and MR severity, and is essential for guiding transcatheter therapies for MR. Multidetector computed tomography has become the standard to assess whether transcatheter valve replacement is an option because of its ability to assess valve sizing, access, and potential left ventricular outflow tract obstruction. Finally, cine cardiac magnetic resonance has been recommended by recent guidelines to quantify MR severity when the distinction between moderate and severe MR is indeterminate by echocardiography. This paper focuses on the main questions to be answered by imaging techniques and illustrates some common tips, tricks, and pitfalls in the assessment of MR., Competing Interests: Funding Support and Author Disclosures Dr. Grayburn has been a consultant for Abbott Vascular, Edwards Lifesciences, Gore, Medtronic, and 4C Medical. Dr. Thomas has been a consultant for Abbott, Edwards Lifesciences, GE Healthcare, and Bay Labs., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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

Objectives: The aim of this study was to evaluate the outcomes of MitraClip implantation versus guideline-directed medical therapy (GDMT) in patients with secondary mitral regurgitation (SMR) according to baseline functional status as assessed by the widely used New York Heart Association (NYHA) functional classification., Background: Patients with heart failure (HF) and impaired functional status at baseline have poor prognosis. Whether the effects of transcatheter repair of secondary SMR in patients with HF are influenced by baseline functional status is unknown., Methods: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, patients with HF with moderate to severe or severe SMR who remained symptomatic despite maximally tolerated GDMT were randomized to MitraClip implantation versus GDMT alone. Outcomes were evaluated according to baseline functional status as assessed using the NYHA functional classification. The primary endpoint of interest was the rate of death or HF-related hospitalization (HFH) at 2 years in time-to-first-event analyses., Results: Among 613 randomized patients, 240 were in NYHA functional class II (39.2%), 322 were in NYHA functional class III (52.5%), and 51 were in ambulatory NYHA functional class IV (8.3%). Rates of death or HFH were progressively higher with increasing NYHA functional class. Compared with GDMT alone, MitraClip implantation resulted in lower 2-year rates of death or HFH consistently in patients in NYHA functional class II (39.7% vs. 63.7%; hazard ratio [HR]: 0.54; 95% confidence interval [CI]: 0.37 to 0.77), NYHA functional class III (46.6% vs. 65.5%; HR: 0.60; 95% CI: 0.45 to 0.82), and NYHA functional class IV (66.7% vs. 85.2%; HR: 0.55; 95% CI: 0.28 to 1.10; p interaction  = 0.86). Greater improvements in quality of life at 2 years were observed in patients treated with the MitraClip compared with GDMT irrespective of baseline functional status., Conclusions: The NYHA functional classification provides prognostic utility in patients with HF and moderate to severe or severe SMR. In the COAPT trial, the benefits of MitraClip implantation were consistent in patients with better or worse functional status as assessed by NYHA functional class. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079)., (Copyright © 2020. Published by Elsevier Inc.)

Background: Surgical repair of primary mitral regurgitation (MR) is considered an indicator of quality performance. Therefore, accurate data reporting is critical for quality assessment. During an institutional quality review, MR etiology could not be determined in 40% of operations in The Society of Thoracic Surgeons database entries, and therefore our true repair rate could not be reliably ascertained. Therefore, we reviewed all source documents and echocardiograms to assess our true disease etiology and repair rate., Methods: Source records and echocardiograms of all operations performed in a single health care system for a 1-year period were reviewed by an experienced mitral valve surgeon, an echocardiographic core laboratory, and a data manager. Disease etiology and operation were compared with data previously entered in the database by post hoc chart abstraction., Results: In all, 314 isolated mitral valve operations were performed. The MR was originally classified as primary, 163 (52%); secondary, 22 (7%); rheumatic, 37 (12%); endocarditis, 24 (8%); other, 33 (10%); and unknown, 35 (11%). Reported repair rate for primary MR was 142 of 163 (87.1%). After review, etiology was determined to be primary, 177 (56%); secondary, 33 (11%); rheumatic, 61 (20%); endocarditis, 25 (8%); and others, 18 (5%)-resulting in a change of classification in 99 of 314 patients (31.5%) and a true repair rate for primary MR of 165 of 177 (93.2%)., Conclusions: Source document and imaging review of mitral valve surgery revealed significant discordance with post hoc chart abstraction methods. A more detailed data entry methodology is necessary to accurately report the true disease etiology and repair rates for primary MR., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Surgery for isolated tricuspid valve (TV) disease remains relatively infrequent because of significant patient comorbidities and poor surgical outcomes. This study reviewed the experience with isolated TV surgery in the current era to determine whether outcomes have improved., Methods: From 2007 through 2017, 685 TV operations were performed in a single institution, of which 95 (13.9%) operations were isolated TV surgery. Patients were analyzed for disease origin, risk factors, operative mortality and morbidity, and long-term survival., Results: A total of 95 patients underwent isolated TV surgery, an average of 9 patients per year increasing from an average of 5 per year to 15 per year during the study period. Surgery was reoperative in 41% (38 of 95) of patients, including 11.6% (11 of 95) with prior coronary artery bypass grafting and 29.4% (28 of 95) with prior valve surgery (9 TV, 11 mitral, 2 aortic, 5 mitral and aortic, and 1 mitral and TV). Repair was performed in 71.6% (68 of 95) of patients, and replacement was performed in 28.4% (27 of 95). Operative mortality was 3.2% (3 of 95), with no mortality in the most recent 73 patients over the last 6 years. Stroke occurred in 2.1% (2 of 95) of patients, acute kidney injury requiring dialysis in 5.3% (5 of 95), and the need for new permanent pacemaker in 16.8% (16 of 95)., Conclusions: In the current era with careful patient selection and periprocedural management, isolated TV surgery can be performed with lower morbidity and mortality than has traditionally been reported with good long-term survival. These outcomes can also serve as a benchmark for catheter-based TV intervention outcomes., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Traditional approaches to the characterization of secondary or functional mitral regurgitation (MR) have largely ignored the critical importance of the left ventricle (LV). We propose that patients with secondary MR represent a heterogenous group, which can be usefully subdivided based on understanding that the effective regurgitant orifice area (EROA) is dependent on left ventricular end-diastolic volume (LVEDV). According to the Gorlin hydraulic orifice equation, patients with heart failure, an LV ejection fraction of 30%, an LVEDV of 220 to 250 ml, and a regurgitant fraction of 50% would be expected to have an EROA of ≈0.3 cm 2 independent of specific tethering abnormalities of the mitral valve leaflets. The MR in these patients is proportionate to the degree of LV dilatation and can respond to drugs and devices that reduce LVEDV. In contrast, patients with EROA of 0.3 to 0.4 cm 2 but with LVEDV of only 160 to 200 ml exhibit degrees of MR that are disproportionately higher than predicted by LVEDV. These patients appear to preferentially benefit from interventions directed at the mitral valve. Our proposed conceptual framework explains the apparently discordant results from 2 recent randomized controlled trials of mitral valve repair. The MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial enrolled patients who had MR that was proportionate to the degree of LV dilatation, and during long-term follow-up, the LVEDV and clinical outcomes of these patients did not differ from medically-treated control subjects. In comparison, the patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial had an EROA ≈30% higher but LV volumes that were ≈30% smaller, indicative of disproportionate MR. In these patients, transcatheter mitral valve repair reduced the risk of death and hospitalization for heart failure, and these benefits were paralleled by a meaningful decrease in LVEDV. Thus, characterization of MR as proportionate or disproportionate to LVEDV appears to be critical to the selection of an optimal treatment for patients with chronic heart failure and systolic dysfunction., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: This study examined the impact of mitral valve repair (MVRe) on survival of patients with moderate or severe (≥2+) MR and ischemic cardiomyopathy randomized to coronary artery bypass grafting (CABG) versus CABG+surgical ventricular reconstruction (SVR) in the STICH trial., Methods: Among patients with moderate or severe MR and ischemic cardiomyopathy undergoing CABG or CABG+SVR, the impact of MVRe on mortality between the two treatment arms was compared., Results: Among 867 patients with assessment of baseline MR severity, 211 had moderate or severe MR. After excluding 7 patients who underwent mitral valve replacement, 50, 44, 62, and 48 patients underwent CABG, CABG+MVRe, CABG+SVR, and CABG+SVR+MVRe, respectively. Four-year mortality rates were lower following CABG+MVRe than CABG alone (16% vs. 55%; adjusted hazard ratio [HR] 0.30; 95% CI 0.13-0.71). In contrast, the CABG+SVR+MVRe and CABG+SVR groups had similar 4-year mortality of 39% vs. 39% (adjusted HR 0.88; 95% CI 0.46-1.70). MVRe had a more favorable effect on survival in patients undergoing CABG alone compared to CABG+SVR ( p =0.013). Baseline MR severity was similar between patients that received CABG+MVRe and those that underwent CABG+SVR+MVRe. A larger proportion of patients demonstrated a reduction in MR between 4 and 24 months after CABG+MVRe compared to CABG+SVR+MVRe (50.0% versus 25.0%, p =0.023)., Conclusion: In patients with moderate or severe MR and ischemic cardiomyopathy undergoing CABG, MVRe appears to have a favorable effect on survival. The addition of SVR to CABG may attenuate the anticipated benefits of MVRe by limiting the long-term reduction of MR with MVRe.

Background: The incidence of leaflet thrombosis after transcatheter aortic valve replacement (TAVR) with active surveillance by four-dimensional computed tomography (4DCT) ranges from 7% to 14%. The incidence of leaflet thrombosis when 4DCT is performed for clinical and echocardiographic indications is unknown., Methods: All patients with prior TAVR or surgical aortic valve replacement (SAVR) who underwent evaluation between October 2015 and January 2017 at our institution and had clinical or echocardiographic indications of leaflet thrombosis were evaluated by 4DCT. Indications for 4DCT by echocardiography included (1) interval increase in mean gradient of 10 mm Hg or more, (2) interval decrease in ejection fraction of 10% or more, (3) thrombus seen on transthoracic echocardiography, (4) persistent or increasing paravalvular leak, or (5) valve dehiscence or thickened leaflets seen on transthoracic echocardiography. Clinical indicators were (1) stroke, (2) transient ischemic attack, or (3) new or worsening heart failure., Results: During the study period, 612 patients underwent TAVR, and 101 patients (55 TAVR; 46 SAVR) met the criteria for 4DCT imaging. Leaflet thrombosis was seen in 17 of 55 TAVR patients (30.9%) and 15 of 46 SAVR patients (32.6%). Follow-up imaging with 4DCT after treatment with anticoagulation showed improvement or resolution in thrombus burden and leaflet excursion in all TAVR patients and in two-thirds of SAVR patients., Conclusions: One-third of patients with clinical or echocardiographic indications suggestive of leaflet thrombosis were found to have evidence of leaflet thrombosis using 4DCT. This allowed tailored anticoagulation therapy with resolution of the thrombus in most patients and avoiding unnecessary anticoagulation in the remaining two-thirds of patients., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to show safety and efficacy of the Cardioband system during 6 months after treatment., Background: Current surgical and medical treatment options for functional mitral regurgitation (FMR) are limited. The Cardioband system (Valtech Cardio, OrYehuda, Israel) is a novel transvenous, transseptal direct annuloplasty device., Methods: Thirty-one patients (71.8 ± 6.9 years of age; 83.9% male; EuroSCORE II: 8.6 ± 5.9) with moderate to severe FMR, symptomatic heart failure, and depressed left ventricular function (left ventricular ejection fraction 34 ± 11%) were prospectively enrolled., Results: Procedural success rate, defined as delivery of the entire device, was 100%. There were no periprocedural deaths (0%), and mortality rate at 1 month or prior to hospital discharge and at 7 months was 5% and 9.7% respectively. Cinching of the implanted Cardioband reduced the annular septolateral dimension by >30% from 3.7 ± 0.5 cm at baseline to 2.5 ± 0.4 cm after 1 month and to 2.4 ± 0.4 cm after 6 months, respectively (p < 0.001). Percentage of patients with FMR ≥3 was reduced from 77.4% to 10.7% 1 month after the procedure (p < 0.001) and 13.6% (p < 0.001) at 7 months. Percentage of patients with New York Heart Association functional class III/IV decreased from 95.5% to 18.2% after 7 months (p < 0.001); exercise capacity as assessed by 6-min walking test increased from 250 ± 107 m to 332 ± 118 m (p < 0.001) and quality of life (Minnesota Living With Heart Failure Questionnaire) was also significantly improved (p < 0.001)., Conclusions: In this feasibility trial in symptomatic patients with FMR, transcatheter mitral annuloplasty with the Cardioband was effective in reducing MR and was associated with improvement in heart failure symptoms and demonstrated a favorable safety profile. (Cardioband With Transfemoral Delivery System; NCT01841554)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control., Methods and Results: We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation. UTMD-GLP-1 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Nuclear overexpression of GLP-1 by inducing phosphorylation of FoxO1-S256 and translocation of FoxO1 from the nucleus to the cytoplasm significantly inactivated FoxO1 and activated the expression of cyclin D1 in nuclei of cardiac muscle cells. Reversal of adriamycin cardiomyopathy appeared to be mediated by dedifferentiation and proliferation of nuclear FoxO1-positive cardiac muscle cells with evidence of embryonic stem cell markers (OCT4, Nanog, SOX2 and c-kit), cardiac early differentiation markers (NKX2.5 and ISL-1) and cellular proliferation markers (BrdU and PHH3) after UTMD with GLP-1 gene therapy., Conclusions: Intranuclear myocardial delivery of the GLP-1gene can reverse established adriamycin cardiomyopathy by stimulating myocardial regeneration., (Copyright © 2015 Elsevier Inc. All rights reserved.)