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Background: We assessed the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension., Methods: In the double-blind PASSION study (Phosphodiesterase-5 Inhibition in Patients With Heart Failure With Preserved Ejection Fraction and Combined Post- and Pre-Capillary Pulmonary Hypertension), patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension were randomized 1:1 to receive tadalafil at a target dose of 40 mg or placebo. The primary end point was the time to the first composite event of adjudicated heart failure hospitalization or all-cause death. Secondary end points included all-cause mortality and improvements in New York Heart Association functional class or ≥10% improvement in 6-minute walking distance from baseline., Results: Initially targeting 372 patients, the study was terminated early because of disruption in study medication supply. At that point, 125 patients had been randomized (placebo: 63; tadalafil: 62,). Combined primary end-point events occurred in 20 patients (32%) assigned to placebo and 17 patients (27%) assigned to tadalafil (hazard ratio, 1.02 [95% CI, 0.52-2.01]; P =0.95). There was a possible signal of higher all-cause mortality in the tadalafil group (hazard ratio, 5.10 [95% CI, 1.10-23.69]; P =0.04). No significant between-group differences were observed in other secondary end points. Serious adverse events occurred in 29 participants (48%) in the tadalafil group and 35 (56%) in the placebo group., Conclusions: The PASSION trial, terminated prematurely due to study medication supply disruption, does not support tadalafil use in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension, with potential safety concerns and no observed benefits in primary and secondary end points., Registration: URL: https://www.clinicaltrialsregister.eu/; Unique identifier: 2017-003688-37. URL: https://drks.de; Unique identifier: DRKS -DRKS00014595., Competing Interests: Dr Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, AOP Health, Bayer, Ferrer, GossamerBio, Janssen, Keros, and MSD. Max Wissmüller has received lecture fees from Janssen. Hanno Leuchte has received fees for consultations and/or lectures from Acceleron, Jansse-Cilag, Bayer, Boehringer-Ingelheim, Ferrer, MSD, and Pfizer. Michael Halank has received fees for lectures and/or consultations from AstraZeneca, Janssen-Cilag, and MSD. In addition, he has received support for attending meetings and/or travel from AOP Health and Janssen-Cilag. Hans-Jürgen Seyfarth has received fees for lectures and/or consultations from Janssen-Cilag and MSD. Stephan Baldus has received fees for lectures and/or consultations from Abbott, Edwards, Jenavalve, AstraZeneca, Bayer, Daiicho Sankyo, and Amgen, as well as research grants from Abbott, AstraZeneca, and Daiichi Sankyo. Johann Bauersachs has received fees for lectures and/or consultations from Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cardior, Corvia, CVRx, Edwards, Norgine, Novartis, Pfizer, Roche and Vifor. In addition, institutional grants have been provided by Abiomed, CVRx, Norgine, Roche, and Zoll. He holds patents for microRNA and downstream targets for diagnostics and therapeutic purposes (PCT/EP2007/008772 and PCT/EP2009/051986). Michael Böhm is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project No. 322900939) and reports personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, ReCor, Servier and Vifor. Hossein-Ardeschir Ghofrani has received honoraria for consultations and/or speaking at conferences from Bayer HealthCare AG, Actelion, Encysive, Pfizer, Ergonex, Lilly, and Novartis. He is member of the Advisory Board for Acceleron, Bayer HealthCare AG, Pfizer, GSK, Actelion, Lilly, Merck, Encysive, and Ergonex. He has also received governmental grants from the German Research Foundation, Excellence Cluster Cardiopulmonary Research, State Government of Hessen, and the German Ministry for Education and Research. Stavros Konstantinides reports personal lecture/advisory fees and research grants to his institution from Bayer AG, Boston Scientific, Daiichi-Sankyo, LumiraDx, and Penumbra, as well as personal lecture/advisory fees from MSD and Pfizer–Bristol-Myers Squibb. Karen M. Olsson has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, Ferrer, GSK, Janssen, MSD, Pfizer, and United Therapeutics. Rolf Wachter has received fees for lectures and/or consultation from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Medtronic, Novartis, Pfizer, Pharmacosmo, Sciarc, Servier, and Vifor. His institution has received research grants from Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, European Union, and Medtronic. Carolyn S.P. 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, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corp, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as cofounder and non–executive director of Us2.ai. Stephan Rosenkranz has received fees for lectures and/or consultations from Abbott, Acceleron, Actelion, Aerovate, AOP, AstraZeneca, Bayer, Boehringer-Ingelheim, Edwards, Ferrer, Gossamer, Janssen, MSD, and United Therapeutics. His institution has received research grants from Actelion, AstraZeneca, Bayer, Janssen, and Lempo. The other authors report no conflicts.

Background: Mitral transcatheter edge-to-edge repair (M-TEER) is a guideline-recommended treatment option for patients with severe symptomatic mitral regurgitation (MR). Outcomes with the PASCAL system in a post-market setting have not been established., Objectives: The authors report 30-day and 1-year outcomes from the MiCLASP (Transcatheter Repair of Mitral Regurgitation with Edwards PASCAL Transcatheter Valve Repair System) European post-market clinical follow-up study., Methods: Patients with symptomatic, clinically significant MR were prospectively enrolled. The primary safety endpoint was clinical events committee-adjudicated 30-day composite major adverse event rate and the primary effectiveness endpoint was echocardiographic core laboratory-assessed MR severity at discharge compared with baseline. Clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year., Results: A total of 544 patients were enrolled (59% functional MR, 30% degenerative MR). The 30-day composite major adverse event rate was 6.8%. MR reduction was significant from baseline to discharge and sustained at 1 year with 98% of patients achieving MR ≤2+ and 82.6% MR ≤1+ (all P < 0.001 vs baseline). One-year Kaplan-Meier estimate for survival was 87.3%, and freedom from heart failure hospitalization was 84.3%. Significant functional and quality-of-life improvements were observed at 1 year, including 71.6% in NYHA functional class I/II, 14.4-point increase in Kansas City Cardiomyopathy Questionnaire score, and 24.2-m improvement in 6-minute walk distance (all P < 0.001 vs baseline)., Conclusions: One-year outcomes of this large cohort from the MiCLASP study demonstrate continued safety and effectiveness of M-TEER with the PASCAL system in a post-market setting. Results demonstrate high survival and freedom from heart failure hospitalization, significant and sustained MR reduction, and improvements in symptoms, functional capacity, and quality of life., Competing Interests: Funding Support and Author Disclosures This work was supported by Edwards Lifesciences. Prof Lurz has received institutional fees and research grants from Abbott Vascular, Edwards Lifesciences, Medtronic, ReCor, and Occlutech. Dr Schmitz has received speaker fees and proctor honorarium from Edwards Lifesciences and Abbott. Dr Geisler has received personal fees (lecture honoraria) and institutional research grants from Edwards Lifesciences. Dr Hausleiter is a consultant and receives speaker fees and institutional research support from Edwards Lifesciences. Prof Eitel has received research grants from Abbott Vascular and speaker fees from Abbott, Edwards Lifesciences, and Boston Scientific. Dr Rudolph has received research grants from Edwards Lifesciences, Abbott, and Boston Scientific. Dr Lubos has received grants from Abbott and personal fees from Abbott, Abiomed, AstraZeneca, Bayer, Edwards Lifesciences, New Valve Technology, and Novartis. Dr von Bardeleben is a principal investigator for Abbott, DZHK, Edwards Lifesciences, JensCare, Medtronic, NeoChord, and the University of Göttingen IIT; and serves as an advisor, proctor, or speaker for Abbott, Edwards Lifesciences, JenaValve, JensCare, Medtronic, NeoChord, Philips, and Siemens. Dr Berti has received honoraria from and is a consultant for Proctor & Gamble, Abbott, and Boston Scientific. Dr De Marco has received honoraria and consultation fees from Edwards Lifesciences. Dr Linke has received grants from Novartis and Edwards Lifesciences; personal fees from Abbott, Abiomed, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Edwards Lifesciences, Medtronic, Novartis, Sanofi Genzyme, and Pfizer; and other fees from Picardia, Filterlex, and Transverse Medical outside the submitted work. Dr Hengstenberg has received institutional research grants from Edwards Lifesciences, Boston Scientific, Abbott, and Medtronic; and serves as a proctor for Edwards Lifesciences and Boston Scientific. Dr Baldus has received a research grant from Abbott; and lecture fees from Abbott and Edwards Lifesciences. Dr Spargias has received honoraria or consultation fees from Edwards Lifesciences, Abbott Vascular, and Medtronic. Dr Denti is a consultant for InnovHeart, Approxima, Picardia, and HRV; and receives speaker fees from Edwards Lifesciences and Abbott. Prof Nickenig has received research funding from the Deutsche Forschungsgemeinschaft, the German Federal Ministry of Education and Research, the EU, Abbott, AGA Medical, AstraZeneca, Bayer, Berlin Chemie, Biosensus, Biotronic, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Edwards Lifesciences, Medtronic, Novartis, Pfizer, Sanofi, and St. Jude Medical; and has received honoraria for lectures or advisory boards from Abbott, AGA Medical, AstraZeneca, Bayer, Berlin, Cardiovalve, Berlin Chemie, Biosensus, Biotronic, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Edwards Lifesciences, Medtronic, Novartis, Pfizer, Sanofi, and St. Jude Medical. Prof Möllmann has receives speaker/proctor fees from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and SMT. Prof Rottbauer is a consultant for and receives speaker honoraria from Edwards Lifesciences. Dr Praz received travel expenses from Edwards Lifesciences, Abbott Vascular, Polares Medical, Medira, and Siemens Healthineers. Dr Butter has received lecture fees from Edwards Lifesciences and Abbott; and educational grants from Boston Scientific. Dr Van Mieghem has received research grants from Abbott Vascular, Boston Scientific, Medtronic, Edwards Lifesciences, Daiichi-Sankyo, AstraZeneca, and Teleflex; and scientific advisory fees from Anteris, JenaValve, Abbott Vascular, Boston Scientific, Medtronic, Amgen, Daiichi-Sankyo, Siemens, Pie Medical, and Teleflex. Dr Sherif is a consultant for and receives speaker honoraria from Edwards Lifesciences. Dr Swaans is a proctor/lecturer for Abbott Vascular, Boston Scientific, Bioventrix, Cardiac Dimensions, Edwards Lifesciences, GE Healthcare, Medtronic, and Philips Healthcare. Dr Witkowski is an advisory board member and has received honoraria from Abbott and Edwards Lifesciences. Dr Buch participates in the Abbott structural heart advisory group; and has received honoraria from Abbott. Prof Seidler has received honoraria for lectures, advisory boards, or travel grants from Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Corvia, Cytokinetics, Edwards Lifesciences, Medtronic, Myocardia, Novartis, Pfizer, and Teleflex. Dr Eißmann has received honoraria or consultation fees from Edwards Lifesciences and Abbott Vascular. Dr Marcoff serves as a member of the echocardiography core laboratory for Edwards Lifesciences and Abbott for which he receives no direct compensation. Dr Koulogiannis is a consultant and advisory board member for Edwards Lifesciences; and a speaker for Abbott. Dr Rassaf has received research funding from the Deutsche Forschungsgemeinschaft and Abbott; and receives honoraria for lectures or advisory boards from AstraZeneca, Bayer, Berlin Chemie, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Novartis, and Pfizer. Dr Luedike received research grants and honoraria for consulting and lectures from Edwards Lifesciences, Novartis, and Pfizer. 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: History of cancer is common in patients undergoing transcatheter mitral valve repair (TMVR)., Objectives: Aim was to examine the impact of cancer history on outcomes after TMVR., Methods: In patients of a monocentric prospective registry of TMVR history of cancer was retrospectively assessed from records. Associations with 6-week functional outcomes and clinical outcomes during a median follow-up period of 594 days were examined., Results: Of 661 patients (mean age 79 years; age-range 37-101 years; 56.1% men), 21.6% had a history of cancer with active disease in 4.1%. Compared with non-cancer patients, cancer patients had a similar procedural success rate (reduction of mitral regurgitation to grade 2 or lower 91.6% vs. 88%; p = 0.517) and similar relevant improvement in 6-min walking distance, NYHA class, Minnesota Living with Heart Failure Questionnaire score and Short Form 36 scores. 1-year survival (83% vs. 82%; p = 0.813) and 1-year survival free of heart failure decompensation (75% vs. 76%; p = 0.871) were comparable between cancer and non-cancer patients. Patients with an active cancer disease showed significantly higher mortality compared with patients having a history of cancer (hazard ratio 2.05 [95% CI 1.11-3.82; p = 0.023]) but similar mortality at landmark analysis of 1 year., Conclusion: TMVR can be performed with equal efficacy in patients with and without cancer and symptomatic mitral regurgitation. Cancer patients show comparable clinical outcome and short-term functional improvement as non-cancer patients. However, longterm mortality was increased in patients with active cancer underlining the importance of patient selection within the heart-team evaluation., (© 2023. The Author(s).)

Objectives: Left ventricular reverse remodeling (LVRR) is associated with improved outcome in patients with heart failure. Factors associated with and predictive of LVRR in patients with low-flow low-gradient aortic stenosis (LFLG AS) after transcatheter aortic valve implantation (TAVI) and its impact on outcome were assessed., Methods: Pre- and postprocedural left ventricular (LV) function and volume were investigated in 219 patients with LFLG. LVRR was defined as an absolute increase of ≥10% in LV ejection fraction (LVEF) and reduction of ≥15% in LV end-systolic volume (LVESV). The primary endpoint was the combination of all-cause mortality and rehospitalization for heart failure., Results: The mean LVEF was 35.0 ± 10.0%, with a stroke volume index (SVI) of 25.9 ± 6.0 mL/m 2 and LVESV of 94.04 ± 46.0 mL. At a median of 5.2 months (interquartile range, 2.7-8.1 months), 77.2% (n = 169) of the patients showed echocardiographic evidence of LVRR. A multivariate model revealed three independent factors for LVRR after TAVI: SVI of <25 mL/m 2 (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.08-3.58; p < 0.01), LVEF of <30% (HR, 2.76; 95% CI, 1.53-2.91; p < 0.01), and valvulo-arterial impedance (Z va ) of <5 mmHg/mL/m 2 (HR, 5.36; 95% CI, 1.80-15.98; p < 0.01). Patients without evidence of LVRR showed a significantly higher incidence of the 1-year combined endpoint (32 [64.0%] vs. 75 [44.4%], p < 0.01)., Conclusions: The majority of patients with LFLG AS show LVRR after TAVI, which is associated with favorable outcomes. An SVI of <25 mL/m 2 , LVEF of <30%, and Z va < 5mmHg/mL/m 2 represent predictors of LVRR., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Patients with left heart disease (LHD) often display pulmonary hypertension (PH), which impacts morbidity and mortality. The pathophysiology of PH is complex and entails pulmonary congestion due to elevated left-sided filling pressures, pulmonary vasoconstriction as well as vascular remodeling. The recent ESC/ERS Guidelines on pulmonary hypertension updated the hemodynamic definitions of pulmonary hypertension in general, and the subclassification of post-capillary PH. This review summarizes recent advances in the diagnostic work-up and management strategies of PH associated with LHD. Specifically, we summarize revisited hemodynamic definitions and the characteristics of isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). Furthermore, we review the current knowledge on the pathogenesis of PH-LHD, the prognostic relevance of hemodynamic parameters, and the management strategies, differentiating between treatment of the underlying left heart disease and therapies targeting the pulmonary circulation. The article emphasises the need for precise diagnostic work-up and individualized treatment strategies in patients with PH-LHD., Competing Interests: MW: Vortragshonorare von Janssen; JA: Vortragshonorare von Janssen und MSD; CH: Honorare für Vorträge und/oder Beratertätigkeiten: Actelion, Bayer, MSD, Pfizer; SR: Honorare für Vorträge und/oder Beratertätigkeiten: Abbott, Acceleron, Actelion, Aerovate, Altavant, AOP Orphan, AstraZeneca, Bayer, Boehringer-Ingelheim, Edwards, Ferrer, Gossamer, Janssen, MSD, United Therapeutics, Vifor; Forschungsunterstützung an Institution: Actelion, AstraZeneca, Bayer, Janssen; JD, LO, TT und SB: keine Interessenkonflikte im Zusammenhang mit diesem Artikel., (Thieme. All rights reserved.)

Aims: Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity-induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b-3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF., Methods: In phase 2b, approximately 660 patients with heart failure and ejection fraction >40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6-min walk distance (6MWD) of 30-400 m with a <50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ-TSS. The sample size provides 85% power to detect placebo-adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ-TSS at overall two-sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo., Conclusion: ENDEAVOR is the first phase 2b-3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF., (© 2023 AstraZeneca. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Pulmonary hypertension (PH) is a common condition in patients with left heart disease (LHD) that is highly relevant for morbidity and mortality. While post-capillary in nature, the pathophysiology of PH in patients with LHD (heart failure/cardiomyopathy, valvular heart disease; other: congenital/acquired) is complex, and decisions about management strategies are challenging. Recently, the updated European Society of Cardiology/European Respiratory Society guidelines on the diagnosis and treatment of PH revisited hemodynamic definitions and the sub-classification of post-capillary PH, and provided numerous new recommendations on the diagnosis and management of PH associated with various types of LHD. Here, we review several novel aspects that focus on: (a) updated hemodynamic definitions, including the distinction between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH); (b) the pathogenesis of PH-LHD, considering various components contributing to PH, such as pulmonary congestion, vasoconstriction, and vascular remodeling; (c) the prognostic relevance of PH and hemodynamic markers; (d) the diagnostic approach to PH-LHD; (e) management strategies in PH-LHD, distinguishing between targeting the underlying left heart condition, the pulmonary circulation, and/or impaired right ventricular function. In conclusion, precise clinical and hemodynamic characterization and detailed phenotyping are essential for prognostication and the management of patients with PH-LHD., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Frailty and heart failure share pathophysiology and clinical characteristics., Objectives: The aim of this study was to analyze the contribution of heart failure to the physical frailty phenotype by examining patients with heart failure before and after percutaneous mitral valve repair (PMVR)., Methods: Frailty according to the Fried criteria (weight loss, weakness, exhaustion, slowness, and low activity) was assessed in consecutive patients before and 6 weeks after PMVR., Results: A total of 118 of 258 patients (45.7%) (mean age: 78 ± 9 years, 42% female, 55% with secondary mitral regurgitation) were frail at baseline, which significantly decreased to 74 patients (28.7 %) at follow-up (P < 0.001). The frequency of frailty domains slowness, exhaustion, and inactivity significantly decreased, whereas weakness remained unchanged. Baseline frailty was significantly associated with comorbidities, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and functional capacity, whereas frailty after PMVR was not associated with NT-proBNP levels. Predictors of postprocedural reversibility of frailty were NYHA functional class 

Background: Guideline-directed medical therapy (GDMT) optimization is mandatory before transcatheter edge-to-edge mitral valve repair (M-TEER) in patients with secondary mitral regurgitation (SMR) and heart failure (HF) with reduced ejection fraction (HFrEF). However, the effect of M-TEER on GDMT is unknown., Objectives: The authors sought to evaluate frequency, prognostic implications and predictors of GDMT uptitration after M-TEER in patients with SMR and HFrEF., Methods: This is a retrospective analysis of prospectively collected data from the EuroSMR Registry. The primary events were all-cause death and the composite of all-cause death or HF hospitalization., Results: Among the 1,641 EuroSMR patients, 810 had full datasets regarding GDMT and were included in this study. GDMT uptitration occurred in 307 patients (38%) after M-TEER. Proportion of patients receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists was 78%, 89%, and 62% before M-TEER and 84%, 91%, and 66% 6 months after M-TEER (all P < 0.001). Patients with GDMT uptitration had a lower risk of all-cause death (adjusted HR: 0.62; 95% CI: 0.41-0.93; P = 0.020) and of all-cause death or HF hospitalization (adjusted HR: 0.54; 95% CI: 0.38-0.76; P < 0.001) compared with those without. Degree of MR reduction between baseline and 6-month follow-up was an independent predictor of GDMT uptitration after M-TEER (adjusted OR: 1.71; 95% CI: 1.08-2.71; P = 0.022)., Conclusions: GDMT uptitration after M-TEER occurred in a considerable proportion of patients with SMR and HFrEF and is independently associated with lower rates for mortality and HF hospitalizations. A greater decrease in MR was associated with increased likelihood for GDMT uptitration., Competing Interests: Funding Support and Author Disclosures Dr Adamo has received speaker fees from Abbott Vascular and Medtronic. Dr Baldus has received lecture fees and research support from Abbott and Edwards Lifesciences. Dr Kalbacher has received speaker honoraria from Abbott; and has received travel expenses and proctor fees from Edwards Lifesciences. Dr Lurz has received institutional research grants from Edwards Lifesciences and Abbott Vascular. Dr Petronio has been a consultant for Abbott Vascular, Boston Scientific, and Medtronic. Dr von Bardeleben has served on trial steering committees (unpaid) for Abbott, Edwards Lifesciences, Medtronic, and Neochord; and has served on advisory boards for and received speaker fees from Abbott, Edwards Lifesciences, Medtronic, Neochord, Philips, and Siemens. Dr Windecker has received institutional research, travel, or educational grants from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, and V-Wave; has served as advisory board member and/or member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis with payments to his institution; and has been an unpaid member of the steering/executive committee groups of several investigator-initiated trials that receive funding by industry. Dr Hausleiter has received speaker honoraria from Abbott Vascular. Prof Metra has received consulting honoraria for participation in steering committees or advisory boards or for speeches from Abbott Vascular, Amgen, AstraZeneca, Bayer, Edwards Lifesciences, Fresenius, Novartis, and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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

Background: Body surface area (BSA) has been reported to be the stronger predictor for prognosis than body mass index in heart failure (HF) patients. The sex-specific association of BSA with mortality has been unclear., Methods: EuroSMR, a European multicenter registry, included patients who underwent edge-to-edge repair (TEER) for secondary mitral regurgitation (SMR). The outcome was two-year all-cause mortality., Results: The present cohort included 1594 HF patients (age, 74 ± 10 years; male, 66%). Association of calculated BSA with two-year all-cause mortality was evaluated. Patients were classified into three BSA groups: the lowest 10% (S), the highest 10% (L), and intermediate between S and L (M). Mean BSA was 1.87 ± 0.21 m 2 (male, 1.94 ± 0.18 m 2 ; female, 1.73 ± 0.18 m 2 ). The association of BSA with the endpoint in females showed a U-shaped curve, indicating worse prognosis for both S and L. The association in males followed a linear regression, demonstrating better prognosis for L. Hazard ratio (HR) of L to S in males was 0.43 (95% confidence interval [CI], 0.25-0.74; p = 0.002), whereas HR of L to M in females was 1.76 (95% CI, 1.11-2.78; p = 0.016) (p for interaction = 0.003)., Conclusions: Sex-specific association patterns demonstrate the complex influence of anthropomorphic factors in HF patients scheduled for TEER. Further investigation beyond simple evaluation of weight and height is needed for better comprehension of the obesity paradox and better prediction of the results of transcatheter therapy in HF patients., Competing Interests: Conflicts of interest Dr. Higuchi has received lecture fees from Medtronic Japan, Daiichi Sankyo, and Ono Pharmaceutical Company. Dr. Orban has received speaker fees from Abbott Vascular and Tomtec Imaging Systems. Dr. Adamo has received payment from Abbott and Medtronic. Dr. Melica has received consulting fee and honoraria for lectures from Abbott and honoraria for lectures from Edwards. Dr. Karam has received consultant fees from Abbott Vascular. Dr. Praz has received travel expenses from Abbott Vascular, Polares Medical and Edwards. LifesciencesDr. Kalbacher has received lecture fees and travel expenses by Abbott and proctor and lecture fees as well as travel expenses by Edwards Lifesciences. Dr. Schofer has received personal fees from Boston Scientific and travel compensation from Abbott Vascular and Edwards Lifesciences. Dr. Ludwig has received travel compensation from Abbott Vascular. Dr. Braun has received speaker honoraria from Abbott Vascular. Dr. Windecker has received grants from Abbott, Amgen, Astra Zeneca, BMS, Bayer, Biotronik, Boston Scientific, Cardinal Health, CardioValve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Johnson & Johnson, Medicure, Medtronic, Novartis, Polares, OrPha Suisse, Pfizer, Regeneron, Sanofi-Aventis, Sinomed, Terumo, and V-wave. Dr. Pfister has received consulting fees from Edwards Lifesciences, honoraria for lectures and financial support for attending symposia by Abbott Vascular, and honoraria for lectures from Edwards Lifesciences. Dr. von Bardeleben has received speaker fees from Abbott Vascular and Edwards Lifesciences. Dr. Lurz has received grants from Abbott Vascular, Edwards Lifesciences, and ReCor Medical. Dr. Petronio has received consulting fees and honoraria for lectures from Abbott and Medtronic, consulting fee from Boston, and honoraria fee from Daiichi Sankyo. Dr. Hausleiter has received research support and speaker honoraria from Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: Guideline-directed medical therapy (GDMT), based on the combination of beta-blockers (BB), renin-angiotensin system inhibitors (RASI), and mineralocorticoid receptor antagonists (MRA), is known to have a major impact on the outcome of patients with heart failure with reduced ejection fraction (HFrEF). Although GDMT is recommended prior to mitral valve transcatheter edge-to-edge repair (M-TEER), not all patients tolerate it. We studied the association of GDMT prescription with survival in HFrEF patients undergoing M-TEER for secondary mitral regurgitation (SMR)., Methods and Results: EuroSMR, a European multicentre registry, included SMR patients with left ventricular ejection fraction <50%. The outcome was 2-year all-cause mortality. Of 1344 patients, BB, RASI, and MRA were prescribed in 1169 (87%), 1012 (75%), and 765 (57%) patients at the time of M-TEER, respectively. Triple GDMT prescription was associated with a lower 2-year all-cause mortality compared to non-triple GDMT (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.60-0.91). The association persisted in patients with glomerular filtration rate <30 ml/min, ischaemic aetiology, or right ventricular dysfunction. Further, a positive impact of triple GDMT prescription on survival was observed in patients with residual mitral regurgitation of ≥2+ (HR 0.62; 95% CI 0.44-0.86), but not in patients with residual mitral regurgitation of ≤1+ (HR 0.83; 95% CI 0.64-1.08)., Conclusion: Triple GDMT prescription is associated with higher 2-year survival after M-TEER in HFrEF patients with SMR. This association was consistent also in patients with major comorbidities or non-optimal results after M-TEER., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: A sizeable proportion of patients with secondary mitral regurgitation (SMR) do not receive guideline-directed medical therapy (GDMT) for heart failure (HF). We investigated the association between the use of GDMT and mortality in patients with SMR who underwent transcatheter edge-to-edge repair (TEER)., Methods: We retrospectively analysed patients with SMR and a left ventricular ejection fraction of <50% who underwent TEER at three centres. According to current HF guidelines, GDMT was defined as triple therapy consisting of beta-blockers, renin-angiotensin system (RAS) inhibitors and mineralocorticoid receptor antagonists (MRAs). Patients were divided into two groups: GDMT and non-GDMT groups. We calculated the propensity scores and carried out inverse probability of treatment weighting (IPTW) analyses to compare 2-year mortality between the two groups., Results: Of 463 patients, 228 (49.2%) were treated with GDMT upon discharge. IPTW-adjusted Kaplan-Meier curve showed patients with GDMT had a lower incidence of mortality than those without GDMT (19.8% vs 31.1%, p=0.011). In IPTW-adjusted Cox proportional hazards analysis, GDMT was associated with a reduced risk of 2-year mortality (HR: 0.58; 95% CI: 0.35 to 0.95; p=0.030), which was consistent among clinical subgroups. Moreover, patients with GDMT had a higher rate of left ventricular reverse remodelling at 1 year after TEER than those without GDMT., Conclusion: GDMT, defined as triple therapy consisting of beta-blockers, RAS inhibitors and MRAs, was associated with a reduced risk of 2-year mortality after TEER for SMR. Optimisation of medical therapy is crucial to improve clinical outcomes in patients undergoing TEER for SMR., Competing Interests: Competing interests: RP has received speaker and consultant honoraria from Abbott and Edwards Lifesciences, outside the submitted work. GN has received research funding from the Deutsche Forschungsgemeinschaft, the German Federal Ministry of Education and Research, the European Union, Abbott, Edwards Lifesciences, Medtronic and St Jude Medical; and has honoraria for lectures or advisory boards from Abbott, Edwards Lifesciences, Medtronic and St Jude Medical. SB has received lecture honoraria from Edwards Lifesciences, Bayer Vital, CVRx, MSD Sharp&Dome, JenaValve Technology and Abbott; and research grants from IcoVifor, Symetis SA, Pfizer, JenaValve Technology, Valtech, OptumInsight, Biotronik and Abbott, outside the submitted work. CI has received travel support from Abbott and speaker and consultant honoraria from Abbott and Edwards Lifesciences, outside the submitted work. TT has been financially supported in part by a fellowship from the Japanese College of Cardiology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The change in right-ventricular function (RVF) after transcatheter mitral valve repair is still poorly understood. We assessed the early response of RVF to the MitraClip procedure and its clinical relevance., Methods: We analyzed consecutive patients who underwent a MitraClip procedure to treat MR between August 2010 and March 2019 in the Heart Failure Network Rhineland registry. RVF was assessed before and after the procedure. Impaired RVF was defined as an RV fractional area change (RVFAC) < 35% or tricuspid annular plane systolic excursion (TAPSE) < 16 mm., Results: 816 eligible patients (77 ± 9 years, 58.5% male) were included in the analysis. Baseline values of RVF were: RVFAC 38.6 (IQR 29.7-46.7) % and TAPSE 17.0 (IQR 14.0-21.0) mm. At a median time of 3 (IQR 2-5) days after the procedure, the RVF remained normal in 34% (n = 274), normalized in 17% (n = 140), deteriorated in 15% (n = 125), and was persistently impaired in 34% (n = 277) of patients. The RVF response was significantly associated with a composite outcome of all-cause mortality and hospitalization due to heart failure within a 2-year follow-up. Compared to stable/normal RVF, the adjusted hazard ratios for the outcome were 1.78 (95% CI 1.10-2.86) for normalized RVF, 1.89 (95% CI 1.34-3.15) for deteriorated RVF, and 2.25 (95% CI 1.47-3.44) for persistently impaired RVF. Changes in TAPSE and RVFAC as continuous variables were significantly correlated with the outcome., Conclusion: An early change in RVF following transcatheter mitral valve repair is predictive of mortality and hospitalization due to heart failure during follow-up. Early response of RVF after MitraClip and its clinical significance. An acute, early change in RVF can be observed following the MitraClip procedure, which is associated with the risk of mortality and hospitalization for HF., (© 2021. The Author(s).)

Aims: To investigate the role of left atrial volume index (LAVi) in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (TEER)., Methods and Results: Outcomes were evaluated in SMR patients of a European multicentre registry according to baseline LAVi. Main analysis was performed for all-cause mortality; residual mitral regurgitation (MR) and New York Heart Association (NYHA) class improvement were analysed for patients available. A total of 1074 patients were included with a median LAVi (interquartile range) of 58 ml/m 2 (46-73). Postprocedural reduction of MR grade to ≤2+ was similar across LAVi quintiles, ranging 91%-96% (p = 0.26). Symptomatic benefit (≥1 NYHA class improvement) also did not differ by LAVi quintiles (61%-68% of patients) (p = 0.66). The risk of mortality increased by 23%-42% in the four upper quintiles compared to the bottom quintile (LAVi <42 ml/m 2 ). The hazard ratio (HR) of mortality was 1.35 (95% confidence interval [CI] 1.02-1.78, p = 0.035) associated with a LAVi >42 ml/m 2 , which was attenuated after multivariable adjustment (HR 1.18, 95% CI 0.83-1.67, p = 0.36). A significant interaction was found for MR severity and pulmonary hypertension, with an increased risk of death associated with enlarged LAVi in patients with inframedian effective regurgitant orifice area (HR 1.99, 95% CI 1.06-3.74, p = 0.032) and in patients with systolic pulmonary pressure ≤50 mmHg (HR 1.67, 95% CI 1.02-2.75, p = 0.042) in multivariable analysis., Conclusion: Procedural success and symptomatic benefit were high throughout the whole range of LAVi. The prognostic impact of left atrial enlargement was relevant in patients with less severe SMR and without pulmonary hypertension, reinforcing the need to identify patients in the early course of backward congestion to achieve good long-term outcome after TEER., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Transcatheter mitral valve implantation (TMVI) is a new treatment option for patients with symptomatic mitral valve (MV) disease. Real-world data have not yet been reported. This study aimed to assess procedural and 30-day outcomes of TMVI in a real-world patient cohort., Method and Results: All consecutive patients undergoing implantation of a transapically delivered self-expanding valve at 26 European centres from January 2020 to April 2021 were included in this retrospective observational registry. Among 108 surgical high-risk patients included (43% female, mean age 75 ± 7 years, mean STS-PROM 7.2 ± 5.3%), 25% was treated for an off-label indication (e.g. previous MV intervention or surgery, mitral stenosis, mitral annular calcification). Patients were highly symptomatic (New York Heart Association [NYHA] functional class III/IV in 86%) and mitral regurgitation (MR) was graded 3+/4+ in 95% (38% primary, 37% secondary, and 25% mixed aetiology). Technical success rate was 96%, and MR reduction to ≤1+ was achieved in all patients with successful implantation. There were two procedural deaths and 30-day all-cause mortality was 12%. At early clinical follow-up, MR reduction was sustained and there were significant reductions of pulmonary pressure (systolic pulmonary artery pressure 52 vs. 42 mmHg, p < 0.001), and tricuspid regurgitation severity (p = 0.013). Heart failure symptoms improved significantly (73% in NYHA class I/II, p < 0.001). Procedural success rate according to MVARC criteria was 80% and was not different in patients treated for an off-label indication (74% vs. 81% for off- vs. on-label, p = 0.41)., Conclusion: In a real-world patient population, TMVI has a high technical and procedural success rate with efficient and durable MR reduction and symptomatic improvement., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: In patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) and heart failure with severely reduced ejection fraction, prediction of postprocedural left ventricular ejection fraction (LVEF) improvement is challenging. Decision-making and timing for implantable cardioverter defibrillator (ICD) treatment are difficult and benefit is still unclear in this patient population., Objective: Aims of the study were to analyse long-term overall mortality in TAVI-patients with a preprocedural LVEF ≤ 35% regarding LVEF improvement and effect of ICD therapy., Methods and Results: Retrospective analysis of a high-risk TAVI-population suffering from severe AS and heart failure with a LVEF ≤ 35%. Out of 1485 TAVI-patients treated at this center between January 2013 and April 2018, 120 patients revealed a preprocedural LVEF ≤ 35% and had sufficient follow-up. 36.7% (44/120) of the patients suffered from persistent reduced LVEF without a postprocedural increase above 35% within 1 year after TAVI or before death, respectively. Overall mortality was neither significantly reduced by LVEF recovery above 35% (p = 0.31) nor by additional ICD treatment in patients with persistent LVEF ≤ 35% (p = 0.33)., Conclusion: In high-risk TAVI-patients suffering from heart failure with LVEF ≤ 35%, LVEF improvement to more than 35% did not reduce overall mortality. Patients with postprocedural persistent LVEF reduction did not seem to benefit from ICD treatment. Effects of LVEF improvement and ICD treatment on mortality are masked by the competing risk of death from relevant comorbidities., (© 2021. The Author(s).)

Aims: Transcatheter mitral valve implantation (TMVI) represents a novel treatment option for patients with mitral regurgitation (MR) unsuitable for established therapies. The CHOICE-MI registry aimed to investigate outcomes of patients undergoing screening for TMVI., Methods and Results: From May 2014 to March 2021, patients with MR considered suboptimal candidates for transcatheter edge-to-edge repair (TEER) and at high risk for mitral valve surgery underwent TMVI screening at 26 centres. Characteristics and outcomes were investigated for patients undergoing TMVI and for TMVI-ineligible patients referred to bailout-TEER, high-risk surgery or medical therapy (MT). The primary composite endpoint was all-cause mortality or heart failure hospitalization after 1 year. Among 746 patients included (78.5 years, interquartile range [IQR] 72.0-83.0, EuroSCORE II 4.7% [IQR 2.7-9.7]), 229 patients (30.7%) underwent TMVI with 10 different dedicated devices. At 1 year, residual MR ≤1+ was present in 95.2% and the primary endpoint occurred in 39.2% of patients treated with TMVI. In TMVI-ineligible patients (n = 517, 69.3%), rates of residual MR ≤1+ were 37.2%, 100.0% and 2.4% after bailout-TEER, high-risk surgery and MT, respectively. The primary endpoint at 1 year occurred in 28.8% of patients referred to bailout-TEER, in 42.9% of patients undergoing high-risk surgery and in 47.9% of patients remaining on MT., Conclusion: This registry included the largest number of patients treated with TMVI to date. TMVI with 10 dedicated devices resulted in predictable MR elimination and sustained functional improvement at 1 year. In TMVI-ineligible patients, bailout-TEER and high-risk surgery represented reasonable alternatives, while MT was associated with poor clinical and functional outcomes., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Recurrent mitral regurgitation (MR) following MitraClip has not been thoroughly investigated. We aimed to examine the predictive factors, morphology, and long-term outcome of recurrent MR after MitraClip., Methods: We assessed data from the Heart Failure Network Rhineland registry from August 2010 to October 2018. Competing risk analyses were performed using the Fine and Gray model to assess the risk of recurrent MR., Results: Among 685 MitraClip patients with a reduction in MR to ≤2+, 61 patients developed recurrent MR within the first 12 months. Flail leaflet (hazard ratio, 3.68; P =0.002) and residual MR (MR grade 2+ versus ≤1+: hazard ratio, 2.56; P =0.03) were the predictors of recurrent MR in primary MR patients, while left atrial volume (per 10 mL increase: hazard ratio, 1.11; P <0.001) and residual MR (hazard ratio, 2.45; P =0.01) were independently associated with recurrent MR in secondary MR patients. In primary MR patients, loss of leaflet insertion or leaflet tear were the predominant morphologies with recurrent MR. In secondary MR patients, more than half of the patients with recurrent MR did not show any disorder of the clip or leaflets. Patients with recurrent MR were more likely to experience unplanned heart failure hospitalization or heart failure symptom with New York Heart Association scale III/IV (54.1% versus 37.8%; P =0.018) and undergo a repeat mitral valve intervention (9.8% versus 2.2%; P =0.005) during the follow-up. In the landmark survival analysis, patients with recurrent MR tended to have lower long-term survival (58.7% versus 83.9%; P =0.08) than patients without recurrent MR., Conclusions: Flail leaflet and residual MR were the predictors of recurrent MR in primary MR patients, while a larger left atrial volume and residual MR were associated with recurrent MR in secondary MR patients, which may be associated with long-term clinical outcomes of patients after MitraClip.

Purpose: Baroreflex activation therapy has favorable effects in heart failure patients. We report the results of a single-center study of baroreflex activation therapy in heart failure with reduced ejection fraction including cardiopulmonary exercise testing for the first time to show the effect on exercise capacity., Methods: A total of 17 patients were treated with baroreflex activation therapy. Eligibility criteria were the New York Heart Association class ⩾III and ejection fraction ⩽35% on guideline-directed medical and device therapy. The New York Heart Association class, quality of life, and 6-min hall walk distance were assessed in all patients. Twelve patients underwent cardiopulmonary exercise testing before and 8.9 ± 6.4 months after initiation of baroreflex activation therapy., Results: The New York Heart Association class and 6-min hall walk distance improved after baroreflex activation therapy, while quality of life remained stable. Weight-adapted peak oxygen uptake increased significantly from 10.1 (8.2-12.9) ml/min/kg to 12.1 (10.4-14.6) ml/min/kg ( p = 0.041). Maximal heart rate was stable. Maximal oxygen pulse increased from 9.7 (5.5-11.3) to 9.9 (7.1-12.1) ml/heartbeat ( p = 0.047) in 10 patients with low maximal oxygen pulse at baseline (<16.5 ml/heartbeat). There was no significant change in maximal oxygen pulse in the whole cohort. Ventilatory efficiency remained stable., Conclusion: Weight-adapted peak oxygen uptake improved after baroreflex activation therapy, pointing to an enhanced exercise capacity. Ventilatory efficiency and heart rate did not change, while oxygen pulse increased in patients with low oxygen pulse at baseline, indicating an improvement in circulatory efficiency, that is, a beneficial effect on stroke volume and peripheral oxygen extraction.

Aims: This multicentre study investigated the association of periprocedural changes in the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with clinical outcomes after transcatheter edge-to-edge mitral valve repair (TMVR)., Methods and Results: Patients were retrospectively analysed who underwent TMVR with the MitraClip system (Abbott Vascular, Santa Clara, CA, USA) and had available sequential NT-proBNP testing at baseline and 2 months after TMVR. Periprocedural changes in NT-proBNP following TMVR were assessed as the percent change in NT-proBNP between baseline and the 2 month follow-up, and the significant reduction in NT-proBNP was defined as a decrease of >30% in the follow-up NT-proBNP compared with the pre-procedural NT-proBNP level. Primary outcome was defined as a composite outcome consisting of all-cause mortality and hospitalization due to heart failure from 2 months to 2 years after TMVR. Additionally, we identified the cut-off value of pre-procedural NT-proBNP to predict the composite outcome using a receiver operating characteristic analysis (cut-off: 2485 pg/mL). Of 485 patients undergoing TMVR (age: 76.2 ± 9.2 years, female: 42.1%, secondary mitral regurgitation: 67.2%), 150 patients (30.9%) had the significant reduction in NT-proBNP (>30%) following the procedure. Patients with the NT-proBNP reduction had a lower incidence of the composite outcome, compared with those without the reduction in NT-proBNP (31.4% vs. 40.2%; log-rank P = 0.03). The significant reduction in NT-proBNP was also associated with a lower risk of the composite outcome [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.45-0.97; P = 0.04], independently of pre-procedural NT-proBNP levels and other clinical parameters. The percent change in NT-proBNP was associated with a linear trend of the incidence of the composite outcome (adjusted HR per 10% decrease: 0.96; 95% CI: 0.94-0.98; P < 0.001). A stratified analysis revealed that the prognostic impact of the significant reduction in NT-proBNP was consistent among clinical subgroups, including aetiology of mitral regurgitation (P for interaction = 0.99). Higher pre-procedural NT-proBNP level (>2485 pg/mL) was associated with the increased risk of the composite outcome (adjusted HR: 1.50; 95% CI: 1.03-2.17; P = 0.03); however, patients with a higher pre-procedural NT-proBNP who achieved the significant reduction in NT-proBNP had a similar risk of the composite outcome to those with a lower pre-procedural NT-proBNP., Conclusions: Changes in sequential NT-proBNP measurements were associated with clinical outcomes within 2 years after TMVR. The assessment of NT-proBNP dynamics may be valuable to assess the residual risk for patients undergoing TMVR and could assist with post-procedural management after TMVR., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: The number of transcatheter mitral valve repair (TMVr) procedures has increased substantially during the last years. A better understanding of the relationship between hospital volume of transcatheter transvenous mitral valve repairs using MitraClip® and patient outcomes may provide information for future policy decisions to improve patient management., Methods and Results: We analysed patient characteristics and in-hospital outcomes for all TMVr procedures using MitraClip® performed in Germany from 2011 to 2017. Hospitals were stratified according to centre volumes and patients were compared for baseline characteristics and adverse in-hospital events. Overall, 24 709 inpatients were treated during the observational period. Patients treated in centres with a volume of ≤10 procedures annually developed more often pulmonary embolism (odds ratio 2.22, 95% confidence interval 1.19-4.13; P = 0.012) compared to those treated in centres with a volume of >10 procedures annually, whereas no association of centre volume (≤10 or >10) was found with in-hospital mortality (P = 0.728). Although patients treated in centres with an annual volume >25 TMVr procedures had higher numbers of comorbidities compared to those treated in centres with an annual volume of ≤25 TMVr procedures, in-hospital mortality did not differ (3.6% vs. 3.5%, P = 0.485). Similarly, when centre volumes were stratified for ≤50 vs. >50 procedural volumes, no association with in-hospital mortality was recorded (P = 0.792). A lower rate of mitral valve surgery after MitraClip® was observed over time, particularly in high-volume centres., Conclusion: Annual numbers of MitraClip® implantations increased from 2011 to 2017 in Germany, whereas in-hospital mortality remained stable. Although patients treated in high-volume centres had a more unfavourable risk profile, in-hospital mortality was comparable to that of low-volume centres., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background Optimizing risk stratification in patients undergoing transcatheter mitral valve repair is an ongoing challenge. The Mitral Regurgitation International Database (MIDA) score represents a user-friendly mortality risk stratification tool that is validated on a large-scale registry of patients with degenerative mitral regurgitation (MR). We here assessed the potential benefit of the MIDA risk score for patients with functional or degenerative MR undergoing transcatheter mitral valve repair. Methods and Results In total, 680 patients undergoing MitraClip implantation were stratified according to MIDA score tertiles into a low (0-7), intermediate (8-9), and a high (10-12) MIDA score group. MR was assessed in follow-up echocardiograms in 416 patients at 323±169 days after transcatheter mitral valve repair. During 2-year follow-up, 8.2% (15/182) of patients with low, 21.3% (64/300) with intermediate, and 26.3% (52/198) with high MIDA score died (log-rank test P <0.001). Hazard of all-cause mortality increased by 13% (95% CI, 3%-25%) with every additional point of the MIDA score. Subanalysis of 431 patients with functional MR showed similar results. Furthermore, rates of a combined end point of mortality and hospitalization for heart failure were higher with increasing MIDA score (30% [54/182], 38% [113/300] and 48% [94/198], respectively, log-rank test P =0.001). Frequency of residual MR ≥II at follow-up increased with increasing MIDA score group (33%, 44%, and 59%, respectively, P <0.001). Conclusions The MIDA mortality risk score maintains its predictive utility in patients undergoing transcatheter mitral valve repair, regardless of MR cause. Moreover, it was predictive of worse event-free survival regarding a combined end point of mortality and hospitalization for heart failure, and was associated with postprocedural residual MR ≥II and MR recurrence.

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

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

Purpose of Review: Pulmonary hypertension is a common phenomenon in heart failure patients that is highly relevant for morbidity and outcome. Although postcapillary in nature, the pathophysiology of pulmonary hypertension in patients with heart failure with reduced or preserved ejection fraction is complex, and decisions about management strategies remain challenging., Recent Findings: Recently, the hemodynamic definitions and subclassification of postcapillary pulmonary hypertension have been revisited. The distinction between isolated postcapillary pulmonary hypertension (IpcPH) and combined post and precapillary pulmonary hypertension (CpcPH) and their definition are essential. Novel data on the prognostic impact of hemodynamic variables and right ventricular function highlight the importance of cardiopulmonary interaction in patients with left-sided heart failure (LHF). Furthermore, the impact of management strategies including medical therapy, remote hemodynamic monitoring, and interventional approaches on hemodynamics and outcome has recently been investigated. Here, we critically review recent developments and future considerations in this field, and highlight distinct treatment strategies targeting the underlying left heart condition, the pulmonary circulation, and/or impaired right ventricular function., Summary: Detailed hemodynamic characterization and proper phenotyping are essential for prognostication and the management of patients with pulmonary hypertension associated with LHF, both in clinical practice and when addressing research questions.

Background: Left atrial (LA) dimension is a marker of disease severity and outcome in primary and secondary mitral regurgitation. In transcatheter mitral valve repair, LA enlargement might additionally impact on device handling and technical success through an altered anatomy and atrial annular dilatation., Methods and Results: Data from the multicentre German TRAnscatheter Mitral valve Interventions registry (TRAMI) were used to analyse the association of baseline LA diameter by tertiles with efficacy, safety and long-term clinical outcome in patients undergoing edge-to-edge repair with MitraClip. In 520 of 843 patients prospectively enrolled in TRAMI, baseline LA diameter were reported [median (interquartile range) LA diameter in tertiles: 44 (40-46) mm, 51 (48-53) mm and 60 (55-66) mm]. Larger LA diameters were significantly associated with secondary aetiology of mitral regurgitation, lower ejection fraction, larger left ventricle, male sex and atrial fibrillation (all P < 0.05). Technical success was not different across tertiles (96%, 95.4% and 98.4%, respectively; P = 0.43) as were major in-hospital cardiovascular and cerebral adverse events (mortality, myocardial infarction or stroke: 1.8%, 1.2% and 4.4%, respectively; P = 0.11 across tertiles). However, 4-year mortality significantly increased with larger LA diameter (32.9%, 46.4% and 51.7%, respectively; P < 0.01), as did hospitalization in survivors (60%, 67.6% and 78.9%, respectively; P < 0.05). The association between LA diameter and outcome remained significant after multivariable adjustment including baseline left ventricular end-diastolic diameter., Conclusion: Left atrial enlargement is a strong and independent predictor of adverse long-term outcome after transcatheter mitral valve repair. Further study is warranted to examine whether timely intervention may have the potential to modify outcome., (© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Mitral regurgitation (MR) is one of the most common valvular defects in the eldery. In patients suffering from heart failure, secondary MR is common and associated with worse prognosis. Due to the usually very high operative risk these patients are immensely under-treated. This leads to an increased need for interventional treatment strategies. Until now there were no randomized data regarding the prognostic impact of interventional treatment of secondary MR. This article is supposed to sum up evidence derived from recent studies regarding this issue. Finally we will provide an outlook on catheter-based mitral valve prothesis., Competing Interests: Dr. Körber gibt an, dass kein Interessenkonflikt besteht.Prof. Pfister erhielt Reisekostenerstattung und Vortragshonorar von Abbott.Prof. Baldus hat educational grants und research grants von Abbott und Edwards erhalten., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Heart failure with preserved ejection fraction (HFpEF) is frequently associated with pulmonary hypertension (PH), which substantially impacts survival. Based on pulmonary vascular resistance (PVR) and the diastolic pressure gradient (DPG), current guidelines distinguish between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). However, the therapeutic consequences of this sub-classification remain entirely unclear. We specifically investigated the efficacy and safety of PDE5i in patients with HFpEF and CpcPH., Methods: In 40 hemodynamically precisely characterized patients with HFpEF and Cpc-PH who were treated with a PDE5i for at least 12 months, the therapeutic effect on 6-minute walk distance (6MWD), WHO functional class (FC), NTproBNP levels, right ventricular function, and hospitalization rates was evaluated., Results: Patients' mean age was 73 ± 9 years, and comorbidities were frequent (78% hypertension, 58% atrial fibrillation, 35% diabetes). Initially, 38 patients (95%) were in WHO-FC III and 2 patients (5%) in WHO-FC II. Prior to PDE5i initiation, mean PAPm was 46.2 ± 10.3 mmHg, PAWP 21.2 ± 4.7 mmHg, DPG 5.5 ± 7.2 mmHg, and PVR 6.2 ± 3.0 WU. After 12 months of PDE5i therapy, the 6MWD increased from initially 277 ± 17 to 340 ± 18 m (p < 0.001), and the proportion of patients in WHO-FC I/II increased from 5% to 37.5%. NTproBNP levels decreased by 33% (p = 0.004), and TAPSE improved from 16.8 ± 0.7 mm at baseline to 18.2 ± 0.6 mm (p = 0.01). The rate of HF-associated hospitalizations was substantially lower in the 12 months post PDE5i initiation compared to the prior 12 months. The DPG had no impact on the response to therapy. No deaths occurred, and typical side effects of PDE5i were observed., Conclusion: These data indicate that at least a subset of precisely characterized patients with HFpEF and CpcPH who tolerate PDE5i may benefit from targeted therapy. A randomized study in this particular sub-population is warranted., (Copyright © 2018. Published by Elsevier B.V.)

Treatment of decompensated heart failure often includes administration of levosimendan. Myeloperoxidase (MPO) is released during polymorphonuclear neutrophil (PMN) degranulation, and mediates dysregulation of vascular tone in heart failure. We evaluated the effects of levosimendan-treatment on MPO in patients with acute decompensation of chronic heart failure over a one week course. Plasma MPO levels were significantly decreased after levosimendan treatment (from 252.1 ± 31.1 pmol/l at baseline to 215.02 ± 27.96 pmol/l at 6 h, p < 0.05). Ex vivo incubation of whole blood with levosimendan decreased MPO release after PMN-stimulation (8.2 ± 1.4-fold increase at baseline vs. 6.0 ± 1.1-fold increase with levosimendan). MPO levels also significantly correlated with diastolic blood pressure over the time course. In a multivariate linear model, the main contributor to systolic, diastolic and mean blood pressure was level of PMN elastase. MPO contributed only in heparin-treated patients, suggesting a more significant role for endothelial-bound MPO than for circulating MPO or elastase with respect to blood pressure regulation. We here provide the first evidence that levosimendan treatment inhibits MPO release by PMNs in decompensated heart failure patients. This mechanism may regulate endothelial function and vascular tone in heart failure patients.

Myeloperoxidase (MPO) is a heme enzyme abundantly expressed in polymorphonuclear neutrophils. MPO is enzymatically capable of catalyzing the generation of reactive oxygen species (ROS) and the consumption of nitric oxide (NO). Thus MPO has both potent microbicidal and, upon binding to the vessel wall, pro-inflammatory properties. Interestingly, MPO - a highly cationic protein - has been shown to bind to both endothelial cells and leukocyte membranes. Given the anionic surface charge of red blood cells, we investigated binding of MPO to erythrocytes. Red blood cells (RBCs) derived from patients with elevated MPO plasma levels showed significantly higher amounts of MPO by flow cytometry and ELISA than healthy controls. Heparin-induced MPO-release from patient-derived RBCs was significantly increased compared to controls. Ex vivo experiments revealed dose and time dependency for MPO-RBC binding, and immunofluorescence staining as well as confocal microscopy localized MPO-RBC interaction to the erythrocyte plasma membrane. NO-consumption by RBC-membrane fragments (erythrocyte "ghosts") increased with incrementally greater concentrations of MPO during incubation, indicating preserved catalytic MPO activity. In vivo infusion of MPO-loaded RBCs into C57BL/6J mice increased local MPO tissue concentrations in liver, spleen, lung, and heart tissue as well as within the cardiac vasculature. Further, NO-dependent relaxation of aortic rings was altered by RBC bound-MPO and systemic vascular resistance significantly increased after infusion of MPO-loaded RBCs into mice. In summary, we find that MPO binds to RBC membranes in vitro and in vivo, is transported by RBCs to remote sites in mice, and affects endothelial function as well as systemic vascular resistance. RBCs may avidly bind circulating MPO, and act as carriers of this leukocyte-derived enzyme., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aims: To assess, and identify predictors of 2-year adverse outcomes of surgical high-risk patients after successful MitraClip therapy (MC), differentiated by the aetiology of mitral regurgitation (MR)., Methods and Results: Kaplan-Meier analysis was used to assess survival free from death, heart failure rehospitalization, and reintervention up to 2 years in 202 successfully treated patients [74 ± 9 years, 132 men (65%); secondary MR aetiology in 140 patients, primary MR in 62]. Predictors for study endpoints were determined using Cox regression analyses. Mortality was 20% at 1 year and 33% at 2 years in both primary and secondary MR patients; independent predictors of death were reduced forward stroke volume, impaired LV function, and renal failure in primary MR, yet only an increased logistic EuroSCORE in functional MR patients. The rate of rehospitalizations was not different between the patient subgroups for 6 months, but then diverged significantly in favour of primary MR patients (estimated 2-year incidence, primary MR 40% vs. secondary MR 66%). No predictor was found for primary MR patients, but increased LV end-diastolic volume significantly increased the risk of rehospitalization in functional MR patients. Reinterventions were overall rare (7.4% at 1 year, 9.7% at 2 years); primary MR patients required all except one reintervention within 2 months of MC, with again no predictors found, whereas secondary MR patients (all except one with discharge MR of 2+) exhibited a steadily declining freedom from reintervention curve throughout follow-up., Conclusion: MR aetiology affects rehospitalization and reintervention, but not mortality, differently after successful MC.

Aims: To assess the feasibility, short-term durability and clinical outcomes of MitraClip® therapy for mitral regurgitation (MR) in patients with end-stage heart failure and a severely reduced left ventricular (LV) ejection fraction., Methods and Results: We analysed retrospectively collected data from seven European centres. Included in the study were 50 heart failure patients [mean age 70 ± 11 years, 38 men (76%)] with a LV ejection fraction ≤25% and MR of at least grade 3+. All patients had functional MR, were in New York Heart Association (NYHA) functional class III or IV, and their mean logistic EuroSCORE was 34%. The patients underwent a total of 53 MitraClip® procedures; one or more clips were implanted in 50 procedures (48 patients), for an acute procedural success rate of 94%. Severity of MR was reduced in all successfully treated patients, 44 (92%) were discharged with MR ≤2+. Thirty-day mortality was 6%; cumulative survival at 6 months was 81.2%. Clinical and echocardiographic 6-month follow-up data were obtained from 32 and 31 successfully treated patients, respectively. At 6 months, MR ≤2+ was present in 27 (87%) of 31 patients, and 23 (72%) of 32 patients were in NYHA functional class I or II. Six-minute walk distance improved significantly, and significant reductions in LV volumes indicative of reverse LV remodelling were concordant with significant reductions in N-terminal pro-brain natriuretic peptide plasma levels., Conclusion: MitraClip® therapy reduces functional MR in patients with end-stage heart failure and marked LV dysfunction and entails clinical benefit at 6 months.

Objective: In the present study, we sought to identify mechanisms underlying increased oxidative stress in vascular tissue in an experimental animal model of chronic congestive heart failure (CHF)., Methods and Results: Superoxide and nitric oxide (NO) was measured in vessels from cardiomyopathic hamsters (CHF hamsters) and golden Syrian hamsters. We also determined expression of endothelial nitric oxide synthase (NOSIII), the soluble guanylyl cyclase, the cGMP-dependent kinase, and the NADPH oxidase. To analyze the contribution of the renin-angiotensin system to oxidative stress, CHF hamsters were treated with the angiotensin-converting enzyme inhibitor captopril for 200 days (120 mg . kg(-1) . d(-1)). CHF led to increased superoxide production by NOSIII and the NADPH oxidase. Decreased NO production in CHF was associated with a decrease in the expression of NOSIII and an inhibition of NO downstream signaling in the aorta. NOSIII expression was increased within the left ventricle. Captopril treatment normalized NOSIII expression in vessels and the myocardium, reduced superoxide levels, and prevented NOSIII uncoupling. Accordingly, endothelial function, NO production, and downstream signaling were improved in CHF vessels., Conclusions: Oxidative stress in CHF is mediated by NADPH oxidase and an uncoupled NOSIII secondary to an activation of the renin-angiotensin system leading to impaired NO downstream signaling.

Objective: Endothelial dysfunction is an early event in the natural progression of heart failure. Increased oxidative stress has been linked to impaired endothelial function and both may play a prognostic role., Methods and Results: Endothelium-dependent and endothelium-independent vasodilatation were determined in 289 patients with mild left ventricular dysfunction by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography. Vascular effects of the coadministration of the antioxidant vitamin C at pharmacological doses (24 mg/min) were assessed. Occurrence of death, heart transplantation, and readmission with worsening heart failure were recorded as clinical outcome parameters during a follow-up period of 4.8 years. Patients experiencing adverse events (n=79) had lower vasodilator responses to acetylcholine (P<0.001) and to sodium nitroprusside (P=0.03) compared with patients without events. However, beneficial effects of vitamin C did not differ between both groups. Cox proportional hazards model demonstrated that age (P=0.001), renal function (P=0.001), and blunted acetylcholine-induced vasodilatation (P=0.007) remained independent predictors of adverse outcome., Conclusions: Impaired peripheral endothelial function independently predicts long-term adverse outcome in patients with early-stage heart failure. The findings suggest that assessment of peripheral endothelial function may represent an additional mean for risk stratification and therapy management in these patients.

Aims: While invasively determined congestion holds mechanistic and prognostic significance in acute heart failure (HF), its role in patients with tricuspid regurgitation (TR)‐related right‐ heart failure (HF) undergoing transcatheter tricuspid valve intervention (TTVI) is less well established. A comprehensive understanding of congestion patterns might aid in procedural planning, risk stratification, and the identification of patients who may benefit from adjunctive therapies before undergoing TTVI. The aim of this study was to investigate the role of congestion patterns in patients with severe TR and its implications for TTVI. Methods and results: Within a multicentre, international TTVI registry, 813 patients underwent right heart catheterization (RHC) prior to TTVI and were followed up to 24 months. The median age was 80 (interquartile range 76–83) years and 54% were women. Both mean right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) were associated with 2‐year mortality on Cox regression analyses with Youden index‐derived cut‐offs of 17 mmHg and 19 mmHg, respectively (p < 0.01 for all). However, RAP emerged as an independent predictor of outcomes following multivariable adjustments. Pre‐interventionally, 42% of patients were classified as euvolaemic (RAP <17 mmHg, PCWP <19 mmHg), 23% as having left‐sided congestion (RAP <17 mmHg, PCWP ≥19 mmHg), 8% as right‐sided congestion (RAP ≥17 mmHg, PCWP <19 mmHg), and 27% as bilateral congestion (RAP ≥17 mmHg, PCWP ≥19 mmHg). Patients with right‐sided or bilateral congestion had the lowest procedural success rates and shortest survival times. Congestion patterns allowed for discerning specific patient's physiology and specifying prognostic implications of right ventricular to pulmonary artery coupling surrogates. Conclusion: In this large cohort of invasively characterized patients undergoing TTVI, congestion patterns involving right‐sided congestion were associated with low procedural success and higher mortality rates after TTVI. Whether pre‐interventional reduction of right‐sided congestion can improve outcomes after TTVI should be established in dedicated studies. [ABSTRACT FROM AUTHOR]

Heart failure is a significant burden among the multiple complications that adults with congenital heart disease (CHD) may encounter. There is an increasing need to address the long-term implications of heart failure in affected patients, as the diagnosis and treatment of heart failure in CHD are particularly challenging due to the complexity of the various underlying congenital cardiac anomalies and the residual cardiac defects. Moreover, management strategies for CHD often differ from those for acquired heart disease. Therefore, the development of a comprehensive database is crucial to enhance the understanding and improve the care of adults with heart failure due to CHD. The prospective Pathfinder-CHD Registry is tailored to capturing and analyzing data on heart failure in ACHD, encompassing all key aspects of heart failure management, including demographic details, medical history, laboratory results, electrocardiographic and other cardiac imaging findings, as well as information on medical, surgical or interventional treatment, and clinical outcomes. As data privacy and security are paramount considerations in this endeavor, robust measures are implemented to ensure that patient confidentiality is upheld, with adherence to relevant ethical guidelines and data protection regulations. In conclusion, the Pathfinder-CHD Registry is designed to improve the care, management, and outcomes of these complex diseases, and to enable longitudinal studies to examine prevalence, disease progression, risk factors, and the effectiveness of various treatment strategies. By identifying patterns and trends within the ACHD population, this database can support the development of evidence-based strategies, tailored therapeutic approaches, and prognostic models to improve the care and outcomes of adults with CHD and heart failure. The ultimate goal of this registry is to serve as a platform for collaborative research, fostering multidisciplinary efforts and facilitating the evaluation of new, targeted therapies, interventions, and guidelines specifically designed for managing this growing population of adults with heart failure due to CHD. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to evaluate the impact of proportionality of secondary mitral regurgitation (SMR) in a large real-world registry of transcatheter edge-to-edge mitral valve repair (TMVr) Differences in the outcomes of recent randomized trials of TMVr for SMR may be explained by the proportionality of SMR severity to left ventricular (LV) volume. The ratio of pre-procedural effective regurgitant orifice area (EROA) to LV end-diastolic volume (LVEDV) was retrospectively assessed in patients undergoing TMVr for severe SMR between 2008 and 2019 from the EuroSMR registry. A recently proposed SMR proportionality scheme was adapted to stratify patients according to EROA/LVEDV ratio in 3 groups: MR-dominant (MD), MR-LV-co-dominant (MLCD), and LV-dominant (LD). All-cause mortality was assessed as a primary outcome, secondary heart failure (HF) outcomes included hospitalization for HF (HHF), New York Heart Association (NYHA) functional class, N-terminal pro–B-type natriuretic peptide (NT-proBNP), 6-min-walk distance, quality of life and MR grade. A total of 1,016 patients with an EROA/LVEDV ratio were followed for 22 months after TMVr. MR was reduced to grade ≤2+ in 92%, 96%, and 94% of patients (for MD, MLCD, and LD, respectively; p = 0.18). After adjustment for covariates including age, sex, diabetes, kidney function, body surface area, LV ejection fraction, and procedural MR reduction (grade ≤2+), adjusted rates of 2-year mortality in MD patients did not differ from those for MLCD patients (17% vs. 18%, respectively), whereas it was higher in LD patients (23%; p = 0.02 for comparison vs. MD+MLCD). The adjusted first HHF rate differed between groups (44% in MD, 56% in MLCD, 29% in LD; p = 0.01) as did the adjusted time for first death or HHF rate (66% in MD, 82% in MLCD, 68% in LD; p = 0.02). Improvement of NYHA functional class was seen in all groups (p < 0.001). Values for 6-min-walk distances, quality of life and NT-proBNP improved in most patients. MD and MLCD patients had a comparable, adjusted 2-year mortality rate after TMVr which was slightly better than that of LD patients. Patients treated with TMVr had symptomatic improvement regardless of EROA/LVEDV ratio. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Tricuspid regurgitation (TR) is the most frequent valvular complication after cardiac transplantation. As in native hearts, the role of surgical therapy particularly in secondary TR is unclear due to high procedural risk and unsatisfying results. Currently, percutaneous techniques are under development for TR repair with less procedural risk and promising preliminary results. Case summary We present a 67-year-old man who underwent heart transplantation (biatrial anastomosis) because of ischaemic heart disease 15 years ago and aortic valve replacement in 2010. Because of progressive severe dyspnoea (New York Heart Association Class III) in 2018 and signs of right heart failure with ascites he underwent transthoracic echocardiography which showed normal graft function, but massive TR of functional aetiology. The heart team decision was an interventional approach using the Cardioband System (Edwards Lifesciences) to treat TR based on the high risk associated with a third cardiac surgery and impaired right ventricular function. The procedure was performed in general anaesthesia with transoesophageal echocardiography and fluoroscopic guidance. Tricuspid regurgitation improved from massive to mild with a mean pressure gradient of 2.9 mmHg. Discussion This is the first case report of Cardioband implantation in tricuspid position in a heart transplant patient with the good technical and clinical result, suggesting that this technique might offer a treatment option to highly selected post-transplant patients with secondary severe TR and high surgical risk. [ABSTRACT FROM AUTHOR]

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