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Background: Heart failure is a substantial global health concern that severely affects patients' quality of life. We aimed to compare the effects of early integration of palliative care (EIPC) and standard cardiac care on health status and mood of patients with non-terminal heart failure., Methods: EPCHF was a multicentre, parallel, two-arm, open-label, randomised controlled trial carried out at University Hospital Bonn and University Hospital Düsseldorf in Germany. Eligible patients (aged 18 years or older) had heart failure, with New York Heart Association class II or more and NT-proBNP concentrations greater than or equal to 400 pg/mL. Patients were randomly assigned (1:1) to receive EIPC with standard cardiac care or standard cardiac care alone. Randomisation was computer-generated with allocation concealment, variable block sizes, and stratification by investigational site. The primary endpoints were health status and mood, measured every 3 months over 12 months using the Functional Assessment of Chronic Illness Therapy-Palliative Care (FACIT-PAL) and the Kansas City Cardiomyopathy Questionnaire (KCCQ), analysed by intention to treat. This trial is registered with DRKS.de, DRKS00013922., Findings: Between May 21, 2019, and Nov 15, 2021, 843 patients were assessed for eligibility, 205 of whom were enrolled (100 assigned to EIPC and 105 assigned to standard cardiac care). 143 (70%) patients were male and 62 (30%) were female. Over 12 months, both groups significantly improved in FACIT-PAL and KCCQ Overall Summary Score (OSS) with no significant differences between the groups (FACIT-PAL adjusted mean difference 0·98 points [95% CI -1·28 to 3·23]; p=0·40; KCCQ-OSS adjusted mean difference -2·06 points [-7·89 to 3·78]; p=0·49). Nine (9%) patients in the EIPC group and seven (7%) patients in the standard cardiac care group died from any cause, with no significant differences in time to death between the two groups (hazard ratio [HR] 1·32 [95% CI 0·49 to 3·54]; p=0·58). 22 (22%) patients in the EIPC group and 21 (21%) patients in the standard cardiac care group were hospitalised at least once due to heart failure, with no significant differences in time to heart-failure-related hospitalisation between the two groups (HR 1·09 [0·61 to 1·98]; p=0·77). 70 (70%) patients in the EIPC group and 62 (59%) in the standard cardiac care group had any adverse events (p=0·10)., Interpretation: In this open-label, randomised clinical trial, standard cardiac care, featuring guideline-directed optimisation of medical therapy and regular 3-monthly follow-ups was found to be as effective as when combined with EIPC in improving health status and mood in patients with non-terminal heart failure. Future clinical practices should consider EIPC based on individual patient needs., Funding: Federal Ministry of Education and Research., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: The co-occurrence of heart failure (HF) and cancer represents a complex and multifaceted medical challenge. Patients with prevalent cardiovascular disease (CVD), particularly HF, exhibit an increased risk of cancer development, raising questions about the intricate interplay between these two prevalent conditions. This review aims to explore the evolving landscape of cancer development in patients with HF, shedding light on potential mechanisms, risk factors, and clinical implications., Recent Findings: Epidemiological data suggests higher cancer incidences and higher cancer mortality in HF patients, which are potentially more common in patients with HF with preserved ejection fraction due to related comorbidities. Moreover, recent preclinical data identified novel pathways and mediators including the protein SerpinA3 as potential drivers of cancer progression in HF patients, suggesting HF as an individual risk factor for cancer development. The review emphasizes preliminary evidence supporting cancer development in patients with HF, which offers several important clinical interventions such as cancer screening in HF patients, prevention addressing both HF and cancer, and molecular targets to treat cancer. However, there is need for more detailed understanding of molecular and cellular cross-talk between cancer and HF which can be derived from prospective assessments of cancer-related outcomes in CV trials and preclinical research of molecular mechanisms., (© 2024. The Author(s).)

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).)

Aims: Takotsubo syndrome (TTS) is associated with a substantial rate of adverse events. We sought to design a machine learning (ML)-based model to predict the risk of in-hospital death and to perform a clustering of TTS patients to identify different risk profiles., Methods and Results: A ridge logistic regression-based ML model for predicting in-hospital death was developed on 3482 TTS patients from the International Takotsubo (InterTAK) Registry, randomly split in a train and an internal validation cohort (75% and 25% of the sample size, respectively) and evaluated in an external validation cohort (1037 patients). Thirty-one clinically relevant variables were included in the prediction model. Model performance represented the primary endpoint and was assessed according to area under the curve (AUC), sensitivity and specificity. As secondary endpoint, a K-medoids clustering algorithm was designed to stratify patients into phenotypic groups based on the 10 most relevant features emerging from the main model. The overall incidence of in-hospital death was 5.2%. The InterTAK-ML model showed an AUC of 0.89 (0.85-0.92), a sensitivity of 0.85 (0.78-0.95) and a specificity of 0.76 (0.74-0.79) in the internal validation cohort and an AUC of 0.82 (0.73-0.91), a sensitivity of 0.74 (0.61-0.87) and a specificity of 0.79 (0.77-0.81) in the external cohort for in-hospital death prediction. By exploiting the 10 variables showing the highest feature importance, TTS patients were clustered into six groups associated with different risks of in-hospital death (28.8% vs. 15.5% vs. 5.4% vs. 1.0.8% vs. 0.5%) which were consistent also in the external cohort., Conclusion: A ML-based approach for the identification of TTS patients at risk of adverse short-term prognosis is feasible and effective. The InterTAK-ML model showed unprecedented discriminative capability for the prediction of in-hospital death., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: About 20-40% of people with Heart failure (HF) suffer from some depression, which is 4-5% greater than the overall population. This depression can lead to undesirable outcomes, including elevated mortality rate and frequent hospitalization., Purpose: The current study aims to evaluate the impact of cognitive behavioural therapy (CBT) on self-care and the symptoms of depression and anxiety in HF patients., Methods: We searched PubMed, Web of Science (WOS), Scopus, and Cochrane Library till 15 October 2022. All relevant randomized controlled trials (RCTs) were included. The data were extracted and pooled using Review Manager software (RevMan 5.4). Continuous data were pooled as mean difference and 95% confidence interval (CI)., Results: Our search retrieved 1146 records, and 7 studies (611 patients) were finally included. We assessed the Beck Depression Inventory-II (BDI-II) as the primary outcome of the study. Hamilton Rating Scale for Depression (HRSD-17), Change in Beck Anxiety Inventory, Kansas City Cardiomyopathy Questionnaire (KCCQ), and Self-Care of Heart Failure Index (SCHFI) were also assessed as secondary outcomes. With CBT, BDI-II showed a significant reduction after 4 to 6 months follow-up (MD = -4.87, 95% CI: [-8.06; -1.69], P = 0.003) as well as 8 to 9 months follow-up (MD = -5.71, 95% CI: [-8.95; -2.46], P = 0.0006). But no significant difference was shown with 3 months follow-up (M.D=-4.34; 95%CI: [-10.70; 2.03], P = 0.18)., Conclusions: CBT has long-term (4-9 months) significant favorable outcomes decreasing anxiety and depression compared to non-CBT groups. No significant short-term (less than 3 months) impact on HF patients' self-care, depression, or anxiety were shown., (© 2023. BioMed Central Ltd., part of 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: Improved imaging modalities contributed to increasing awareness of cardiac amyloidosis. Contemporary data on frequency trends in Germany are lacking., Methods: In a retrospective study using health claims data of a German statutory health insurance, patients with diagnostic codes of amyloidosis and concomitant heart failure between 2009 and 2018 were identified., Results: Prevalence increased from 15.5 to 47.6 per 100,000 person-years, and incidence increased from 4.8 to 11.6 per 100,000 person-years, with a continuous steepening in the slope of incidence trend. In patients with amyloidosis and heart failure age and proportion of men significantly increased, whereas the frequency of myeloma and nephrotic syndrome significantly decreased over time. Median (IQR) survival time after first diagnosis was 2.5 years (0.5-6 years), with a 9% (95% CI 2-15%, p = 0.008) reduced risk of death in the second compared to the first 5 years of observation. In the 2 years prior and 1 year after diagnosis, mean total health care costs were 6568 €, 11,872 € and 21,955 € per person and year., Conclusion: The rise in cardiac amyloidosis has continuously accelerated in the last decade. Considering the adverse outcome and high health care burden, further effort should be put on early detection of the disease to implement available treatment., (© 2022. The Author(s).)

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.)

Advances in treatment, common cardiovascular (CV) risk factors and the ageing of the population have led to an increasing number of cancer patients presenting with acute CV diseases. These events may be related to cancer itself or cancer treatment. Acute cardiac care specialists must be aware of these acute CV complications and be able to manage them. This may require an individualized and multidisciplinary approach. The management of acute coronary syndromes and acute pericardial diseases in cancer patients was covered in part 1 of a clinical consensus document. This second part focusses on acute heart failure, acute myocardial diseases, venous thromboembolic diseases and acute arrhythmias., Competing Interests: Conflict of interest: P.L.: nothing in relation to this work. A.S.: nothing in relation to this work. G.G.: has received speaker honoraria from Novartis, Orion Pharma, AstraZeneca, and Bristol-Myers Squibb. R.A.: nothing in relation to this work. G.B.: nothing in relation to this work. S.H.: nothing in relation to this work. G.L.: nothing in relation to this work. D.F.: speaker’s honoraria or advisory board fees from Abbott Laboratories, Bayer, Boehringer Ingelheim, Leo Pharmaceuticals, Menarini, Novartis, Orion Pharma, Roche Diagnostics. S.G.: speaker’s and advisory fees (all institutional) from AstraZeneca, Daiichi-Sankyo, Boehringer. P.S.: speaker’s and advisory fees (all institutional) from AstraZeneca, Daiichi-Sankyo, Bayer, Boehringer, Pfizer, BMS, Amgen, Sanofi. P.V.D.M.: consultancy and/or Servier, Novartis, Pfizer, Pharmacosmos, Ionis. Supported by the ERC (StG 715732). A.R.L.: speaker, advisory board, or consultancy fees and/or research grants from Pfizer, Novartis, Servier, Amgen, Takeda, Roche, Janssens-Cilag Ltd., Clinigen, Eli Lily, Eisai, Bristol-Myers Squibb, Ferring Pharmaceuticals, Boehringer Ingelheim, Myocardial Solutions, iOWNA, and Heartfelt Technologies Ltd. A.O.: speaker’s and advisory fees from Seagen, Roche, Diaichi-Sankyo, and Astra Zeneca. Travel support from Lilly, Astra Zeneca, and Leo Pharmaceuticals. A.W.: honorarium, advisory board or consultancy fees: Janssen Cilag, GSK, Alexion, Caelum, Takeda, Celgene., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.)

Heart failure with preserved ejection fraction (HFpEF) is a common and difficult-to-treat heart disease. Approximately half of patients with heart failure suffer from this form, and mortality is between 5% and 7% per year. Previous therapeutic trials for the treatment of HFpEF have been disappointing. However, recent data on therapy with sodium-glucose cotransporter‑2 (SGLT2) inhibitors in HFpEF are encouraging. In addition to numerous experimental studies showing improvement in diastolic dysfunction parameters, the EMPEROR-Preserved study demonstrated for the first time clinically that therapy with the SGLT2 inhibitor empagliflozin significantly reduced hospitalization for heart failure. By contrast, cardiovascular mortality was not affected. Differences for patients with and without type 2 diabetes mellitus were not observed. Thus, for the first time, there is an evidence-based treatment option to reduce hospitalization and improve quality of life in these patients. Further studies will show to what extent these beneficial effects will also lead to an improvement in the prognosis of these patients., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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.)

The progressive nature of heart failure (HF) coupled with high mortality and poor quality-of-life (QoL) mandates greater attention to palliative care (PC) as a routine component of HF management. Limited evidence exists from randomized controlled trials supporting the use of interdisciplinary palliative care in the progressive course of HF. The early palliative care in heart failure trial (EPCHF) is a prospective, controlled, nonblinded, multicenter study of an interdisciplinary palliative care intervention in 200 patients with symptomatic HF characterized by NYHA ≥ 2. The 12-month EPCHF intervention includes monthly consultations by a palliative care team focusing on physical and psychosocial symptom relief, attention to spiritual concerns and advance care planning. The primary endpoint is evaluated by health-related QoL questionnaires after 12 months of treatment. First the functional assessment of chronic illness therapy palliative care (FACIT-Pal) score evaluating QoL living with a chronic disease and second the Kansas City cardiomyopathy questionnaire (KCCQ) measuring QoL living with heart failure will be determined. Secondary endpoints are changes in anxiety/depression (HADS), symptom burden score (MIDOS), spiritual well-being functional assessment of chronic illness therapy spiritual well-being scale (FACIT-Sp), medical resource and cost assessment. EPCHF will help evaluate the efficacy and cost-effectiveness of palliative care in symptomatic HF using a patient-centered outcome as well as clinical and economic endpoints. EPCHF is funded by the Bundesministerium für Bildung und Forschung (BMBF, 01GY17)., (© 2021. The Author(s).)

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.

Background: Prognosis of patients with end-stage heart failure is known to be impacted by the aetiology of heart failure (HF). Ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the most frequent pathologies necessitating ventricular assist device (VAD) support in these patients. However, the specific impact of ICM and DCM in clinical outcomes after VAD implantation remains unclear. Therefore, this study aimed to analyse clinical differences in ICM and DCM patients after LVAD surgery from the current institution., Methods: All consecutive patients from the LVAD centre were included in this retrospective study. To analyse specific differences in in-hospital outcomes, patients were divided into two groups: ICM and DCM. Long-term follow-up was calculated by Kaplan-Meier estimation of survival., Results: Between January 2010 and July 2020, 60 consecutive patients underwent LVAD implantation at the institution: 36 patients (60%) were supported due to end-stage ICM and 24 patients (40%) in regard of therapy-refractory DCM. Baseline characteristics showed no between-group differences. The ICM patients showed a clear trend to higher amount of additional cardiac procedures during VAD surgery (36% ICM vs 12% DCM; p=0.052). In-hospital mortality was comparable between ICM and DCM patients (36% ICM vs 21% DCM; p=0.206). A trend towards higher frequency of pump thrombosis was seen in DCM patients (p=0.080). Long-term survival was comparable between the groups., Conclusion: The aetiology of heart failure did not impact short-term or long-term clinical outcomes after VAD surgery. Multicentre registry data are necessary to substantiate these findings., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

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.)

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.)

Aims: Attenuating exercise-induced elevated left atrial pressure with an atrial shunt device is under clinical investigation for treatment of symptomatic heart failure (HF)., Methods and Results: PRELIEVE was a prospective, non-randomised, multicentre, first-in-man study in symptomatic HF patients with reduced (HFrEF) or preserved (HFpEF) ejection fraction and pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg during exercise. Here, we provide follow-up data up to 1 year after implantation of the Atrial Flow Regulator (AFR) device. The AFR was successfully implanted in 53 patients (HFrEF n = 24 and HFpEF n = 29). Two patients were not enrolled due to an unsuccessful transseptal puncture. There was one device embolisation into the left atrium, which required surgical removal. One patient experienced a serious procedure-related adverse event (post-procedural bleeding and syncope). All patients with sufficient echocardiography readout confirmed device patency with left-right shunt both at 3 (n = 47/51, 92%) and 12 (n = 45/49, 92%) months. At 3 months, rest PCWP decreased by 5 (-12, 0) mmHg (P = 0.0003, median Q1, Q3). No patient developed a stroke, worsening of right heart function or significant increase of pulmonary artery pressure. Six (6/53, 11%) patients were hospitalised for worsening of HF and three (3/53, 6%) patients died. We observed improvements in New York Heart Association functional class, 6-min walking distance and quality of life (Kansas City Cardiomyopathy Questionnaire) in certain patients., Conclusions: Implantation of the AFR device in HF patients was feasible. No shunt occlusion, stroke or new right HF was observed during the 1-year follow-up, with clinical improvements in certain patients., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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.)

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.)

Aims: Reducing elevated left atrial pressure with an atrial septum shunt device is a possible treatment option in symptomatic heart failure patients. This study aimed to investigate the safety and feasibility of the Atrial Flow Regulator (AFR) in heart failure patients., Methods and Results: AFR-PRELIEVE is a prospective, non-randomised, open-label, multicentre study in patients with symptomatic heart failure NYHA Class III or IV and pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg at exercise irrespective of left ventricular ejection fraction (EF ≥15%). Here we report on procedural and three-month follow-up data for a total of thirty-six enrolled patients. Sixteen (44.5%) patients with reduced EF (HFrEF: EF 15-39%) and twenty (55.5%) patients with preserved EF (HFpEF: EF ≥40%) were enrolled. Implantation success rate and device patency with left-right shunt was 100% (post procedure and at three months) in both patient groups, with one SADE in the HFpEF group which completely resolved. Three (3/36, 8.3%) patients were hospitalised for worsening of heart failure (two HFrEF patients, one HFpEF patient). Individual patients from both the HFrEF and HFpEF groups showed improvement in symptoms and surrogate parameters of heart failure (NYHA class, six-minute walking distance, Kansas City Cardiomyopathy Questionnaire, PCWP, NT-proBNP)., Conclusions: Implantation of the AFR device in heart failure patients is feasible and safe; shunt patency at three months was confirmed in the study. The atrial shunt improved symptoms and surrogate parameters of heart failure in some but not all patients in both the HFpEF and HFrEF groups.

Background: Only a few previous studies have focused on the interaction between pretransplant psychological variables, survival on the waiting list, and adherence to therapy after heart transplantation (HTx)., Methods: This work combined two studies: Study 1 monitored survival of patients on a HTx waiting list (n = 50) and study 2 examined barriers to adherence after HTx (subgroup of n = 20). All patients were evaluated immediately after listing for HTx (T0). Those in study 2 were also evaluated immediately after HTx (T1) and after 6 months (T2). Psychosocial functioning was measured by the Transplant Evaluation Rating Scale (TERS), and depression and anxiety by Patient Health Questionnaire and Hospital Anxiety and Depression Scale. Barriers to immunosuppressive adherence post-HTx were measured by the Medication Experience Scale for Immunosuppressants (MESI)., Results: According to the TERS classification of Rothenhäusler et al, patients were divided into three groups in study 1. Compared with inconspicuous patients (n = 23) and risk patients (n = 21), high-risk patients (n = 6) demonstrated a higher mortality (log-rank test of trend, P = 0.002). In study 2, there was a strong correlation between the TERS (T0) and the MESI (T2) (r = 0.84, P = 0.001)., Conclusions: The TERS may serve as a predictor of survival on the waiting list. There is need for further longitudinal data with larger sample sizes., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The determination of the cardiac preload is still a challenge for intensive care physicians. In addition to clinical assessment, both non-invasive and invasive methods exist for evaluating fluid responsiveness. The following article demonstrates one possible approach for systematic assessment of fluid responsiveness using a practical algorithm for critical care patients., Competing Interests: C. Adler gibt an, dass kein Interessenkonflikt besteht.S. Treskatsch erhielt Honorare für Vortragstätigkeiten von Edwards, Carinopharm, Orion Pharma und Smith & Nephews.R. Pfister erhielt Honorare für Vortragstätigkeiten von Medtronic, Abbott, Orion Pharma.G. Michels erhielt Honorare für Vortragstätigkeiten von Pfizer, Novartis, Servier, Zoll, Getinge und Orion Pharma.Anmerkung: Die Interessenkonflikte stehen in keinem Zusammenhang mit der vorliegenden Arbeit., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aims: Structured management programmes deliver optimized care in heart failure patients and improve outcome. We examined the feasibility of including patients with migration background speaking little or no German in a heart failure management programme., Methods and Results: After adaption of script material and staff to Turkish language we aimed to recruit 300 Turkish and 300 German (control group) patients within 18 months using the operational basis of a local heart failure management programme for screening, contact and inclusion. Of 488 and 1,055 eligible Turkish and German patients identified through screening, 165 Turkish (34%) and 335 German (32%) patients consented on participation (p = 0.46). General practitioners contributed significantly more of the Turkish (84%) than of the German patients (16%, p<0.001). Contact attempts by programme staff were significantly less successful in Turkish (52%) than in German patients (60%, p = 0.005) due to significantly higher rate of missing phone numbers (36% vs 25%), invalid address data (28% vs 7%) and being unreachable by phone more frequently (39% vs 26%, all p<0.001). Consent rate was significantly higher in successfully contacted Turkish (63%) compared to German patients (50%, p<0.001)., Conclusion: The inclusion of Turkish minority patients into a heart failure management programme is feasible with higher consent rate than in Germans. However, effort is high due to inherent logistic adaptions and barriers in identification and contacting of patients., Trial Registration: DRKS00007780.

Aims: This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS-986231, a novel second-generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF)., Methods and Results: Forty-six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose-escalation cohorts in this double-blind, randomized, placebo-controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.5 L/min/m 2 received one 6-h i.v. infusion of BMS-986231 (at 3, 5, 7 or 12 µg/kg/min) or placebo. BMS-986231 produced rapid and sustained reductions in PCWP, as well as consistent reductions in time-averaged pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure and right atrial pressure. BMS-986231 increased non-invasively measured time-averaged stroke volume index, cardiac index and cardiac power index values, and decreased total peripheral vascular resistance. There was no evidence of increased heart rate, drug-related arrhythmia or symptomatic hypotension with BMS-986231. Analyses of adverse events throughout the 30-day follow-up did not identify any toxicities specific to BMS-986231, with the potential exception of infrequent mild-to-moderate headaches during infusion. There were no treatment-related serious adverse events., Conclusions: BMS-986231 demonstrated a favourable safety and haemodynamic profile in patients hospitalized with advanced heart failure. Based on preclinical data and these study's findings, it is possible that the haemodynamic benefits may be mediated by inotropic and/or lusitropic as well as vasodilatory effects. The therapeutic potential of BMS-986231 should be further assessed in patients with heart failure., (© 2017 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminal-prohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

The pathophysiology and the management of patients with acute right heart failure are very complex. The bed-side focused echocardiography is the basis of differential diagnosis and acute diagnosis. Individual therapy monitoring is complex due to the strong preload dependence of the right ventricle and the limitation of non-invasive estimation of pulmonary-vascular hemodynamics, so that the indication for a pulmonary artery catheter should be liberal in acute right heart failure. The treatment goals of acute right heart failure are the treatment of the underlying disease or triggering factors in combination with individualized optimization of hemodynamic tailored to current right-ventricular function., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Progression of heart failure with reduced ejection fraction (HFrEF) is promoted by sympathovagal imbalance. Baroreflex activation therapy, i.e., electrical stimulation of baroreceptors at the carotid sinus, can restore sympathovagal balance. Large animal studies of baroreflex activation therapy revealed improvements in cardiac function, susceptibility to ventricular arrhythmias, and a survival benefit as compared to untreated controls. Recently, the first randomized and controlled trial of optimal medical and device therapy alone or plus baroreflex activation therapy in patients suffering from HFrEF was published. It demonstrated a reasonable safety profile in this severely ill patient population. Moreover, the study found significant improvements in New York Heart Association class, quality of life, 6-min walk distance, and NT-proBNP levels. This review provides an overview on baroreflex activation therapy for the treatment of HFrEF-from the concept and preclinical findings to most recent clinical data and upcoming trials.

Objectives: It is unknown whether bone mineral density as a measure of osteoporosis is associated with development of heart failure., Background: Recent evidence suggests shared risk factors between heart failure and osteoporosis. Additionally, patients with osteoporosis are at increased risk for cardiovascular disease., Methods: We examined the prospective association of bone mineral density measured as broadband ultrasound attenuation by quantitative ultrasound of the heel with incident heart failure events in 13,666 apparently healthy persons 42 to 82 years of age participating in the EPIC (European Prospective Investigation into Cancer and Nutrition) study in Norfolk, United Kingdom., Results: During a mean follow-up of 9.3 years, 380 incident cases of heart failure occurred. The risk of heart failure decreased with increasing bone mineral density. The hazard ratios comparing each quartile with the lowest were 0.40 (95% confidence intervals [CI]: 0.27 to 0.59), 0.54 (95% CI: 0.37 to 0.79), and 0.46 (95% CI: 0.32 to 0.68) in analysis adjusting for age, sex, smoking, alcohol consumption, physical activity, occupational social class, educational level, systolic blood pressure, diabetes, cholesterol concentration, and body mass index (p for trend = 0.002), with a 23% risk decrease associated with every increase in 1 standard deviation of bone mineral density (hazard ratio [HR]: 0.77; 95% CI: 0.66 to 0.89). The association was stronger with heart failure without (HR: 0.75; 95% CI: 0.63 to 0.89) than with antecedent myocardial infarction (HR: 0.82; 95% CI: 0.62 to 1.09)., Conclusions: We observed an inverse association between bone mineral density and the risk of heart failure in apparently healthy individuals. Our findings give support for cardiac assessment in people with reduced bone mineral density and warrant further exploration of underlying biological mechanisms linking osteoporosis and heart failure., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Interventional trials provide evidence for a beneficial effect of reduced dietary sodium intake on blood pressure. The association of sodium intake with heart failure which is a long-term complication of hypertension has not been examined., Methods and Results: Hazard ratios [HRs, 95% confidence interval (CI)] of heart failure comparing quintiles of estimated 24 h urinary sodium excretion (USE) were calculated in apparently healthy men (9017) and women (10,840) aged 39–79 participating in the EPIC study in Norfolk. During a mean follow-up of 12.9 years, 1210 incident cases of heart failure occurred. Compared with the reference category (128 mmol/day≤USE≤148 mmol/day), the top quintile (USE≥191 mmol/day) was associated with a significantly increased hazard of heart failure (1.32, 1.07–1.62) in multivariable analysis adjusting for age, sex, body mass index, diabetes, cholesterol, social class, educational level, smoking, physical activity, and alcohol consumption, with a marked attenuation (1.21, 0.98–1.49) when further adjusting for blood pressure. The bottom quintile (USE≤127 mmol/day) was also associated with an increased hazard of heart failure (1.29, 1.04–1.60) in multivariable analysis without relevant attenuation by blood pressure adjustment (1.26, 1.02–1.56), but with substantial attenuation when adjusting for interim ischaemic heart disease and baseline C-reactive protein levels and exclusion of events during the first 2 years (1.18, 0.96–1.47)., Conclusion: We demonstrate a U-shaped association between USE and heart failure risk in an apparently healthy middle-aged population. The risk associated with the high range of USE was attenuated after adjustment for blood pressure, whereas the risk associated with the low range of USE was attenuated after adjustment for pre-existing disease processes., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

Aims: Red cell distribution width (RDW) is associated with increased risk of heart failure (HF). We examined in a healthy population (1) whether this association is independent of cardiovascular risk factors and iron metabolism and (2) whether RDW associates with physical activity., Methods and Results: Hazard ratios (HRs, highest quartile versus lowest quartile of RDW) for the risk of HF were calculated in 17,533 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. During a follow-up of 11.2±2.2 years 640 participants developed a HF event. The HR for HF events was 1.44 (95%CI 1.15-1.80, p<0.001). There was a non-linear increase in HF risk across RDW quartiles. Adjustment for established risk factors (sex, age, diabetes, smoking, systolic blood pressure, total and high-density lipoprotein cholesterol) attenuated the HR for HF to 1.40 (95%CI 1.11-1.77, p=0.001). Adjustment for CRP, iron and ferritin levels did not affect the HR for HF. RDW levels are inversely associated with physical activity (per category β=-0.37, 95%CI -0.053 to -0.021, p<0.0001), independent of iron metabolism. However, the association between HF and RDW levels was not changed by physical activity., Conclusions: This study confirms that RDW is associated with HF events in an apparently healthy middle-aged population. More importantly, we show that the underlying pathophysiology linking HF with anisocytosis is not reflected by conventional risk factors, nor it is explained by iron metabolism or inflammation. Furthermore, RDW levels were associated with physical inactivity, but this did not influence the RDW-associated-risk of heart failure., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Aims: BNP has important effects on haemodynamics and myocardial remodelling which are protective from development and progression of heart failure. The aim of this study was to examine whether three common genetic variants (rs198389, rs5068, and rs198358) within or adjacent to the BNP gene locus which were shown to be associated with BNP blood levels are associated with risk of heart failure in the pospective population-based EPIC-Norfolk cohort., Methods and Results: The hazard ratio on heart failure was calculated in 23 192 participants in the EPIC-Norfolk study with Cox proportional regression analyses. During a mean follow-up of 12.6 years, 1673 (7.2%) participants had a heart failure event. There was no significant association between genotypes of rs198389, rs5068, and rs198358 and heart failure risk. Results did not differ materially in analyses stratified by hypertension, obesity, and coronary heart disease., Conclusions: Common genetic variants reported to be associated with BNP levels were not associated with a relevant risk of heart failure in our population-based cohort. However, we cannot exclude a small association with risk of heart failure or an association with individual subtypes of the heart failure syndrome.

Background: Diabetes mellitus is associated with a high risk for heart failure, which is further increased in the presence of coronary heart disease. So far no clinical risk score for development of heart failure exists for patients with type 2 diabetes and macrovascular disease., Methods: Independent clinical predictors for heart failure events were identified by Cox regression in a post-hoc analysis of the PROactive trial and were used for calculating a risk prediction score., Results: 233 of 4951 patients with available baseline data suffered a serious adverse heart failure event during a mean follow-up of 34.5 (±2.3) months. Age, renal dysfunction, diuretic use, HbA1c, duration of diabetes, LDL-cholesterol, heart rate, right and left bundle branch block, microalbuminuria, previous myocardial infarction and pioglitazone treatment were independent predictors of heart failure. The risk score showed a good calibration and moderate discrimination (AUC 0.75). Patients were accurately stratified with an actual risk of 1.0%, 3.2% and 9.7% in the bottom, middle and top tertile of the score, respectively, with corresponding hazard ratios of 3.5 (95% CI 2.0-6.2) and 10.5 (95% CI 6.3-17.6) for the middle and top tertile compared to the bottom tertile (both p<0.0001). The score stratified well in subgroups defined by pioglitazone treatment, prior myocardial infarction, obesity, poor glycemic control and microalbuminuria., Conclusion: A risk score based on routinely assessed clinical variables proved a good stratification for future heart failure events in diabetic patients with macrovascular disease. Strategies targeting specific interventions and monitoring of high risk patients need further evaluation., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aims: Increasing levels of resting heart rate are associated with increased risk of developing hypertension and cardiovascular disease, and seem to play a role in the progression of heart failure. The shape of the association between resting heart rate and risk of developing heart failure has not been examined in healthy individuals of the general population., Methods and Results: Hazard ratios (HRs) of heart failure comparing categories of resting heart rate [51-60 b.p.m. (reference), 61-70 b.p.m., 71-80 b.p.m., 81-90 b.p.m., and 91-100 b.p.m.] were calculated in apparently healthy men (9805) and women (12 321) aged 39-79 participating in the 'European Prospective Investigation into Cancer and Nutrition' (EPIC) study in Norfolk. During a mean follow-up of 12.9 years, 1356 incident cases of heart failure occurred. In participants without potential heart rate-modifying medication, age- and sex-adjusted incidence rates of heart failure were 3.3, 3.7, 4.0, 5.1, and 5.5 per 1000 person-years for increasing categories of resting heart rate; compared with the reference category, HRs and 95% confidence intervals (CI) for increasing categories of resting heart rate were 1.08 (0.88-1.34), 1.17 (0.94-1.46), 1.39 (1.08-1.79), and 1.42 (1.00-2.03), respectively, in multivariable analysis adjusting for age, sex, body mass index, systolic blood pressure, prevalent diabetes, cholesterol concentration, social class, educational level, smoking, and physical activity. Within the reference range of resting heart rate (50-100 b.p.m.) each 10 b.p.m. increase was associated with an 11% increase in hazard of heart failure in multivariable analysis. The results did not change materially after adjusting for myocardial infarction and coronary heart disease events during follow up (1.12, 1.06-1.18)., Conclusion: Resting heart rate shows a graded association with hazard of heart failure in apparently healthy men and women which is not mediated by coronary heart disease. Further study is needed to examine the underlying mechanisms.

Aims: Markers of inflammation are associated with increased risk of heart failure, but data on differential white blood cell (WBC) count are lacking. We examined the prospective association between differential WBC count and incident heart failure events., Methods and Results: Hazard ratios (HRs) (per increase of 1000 cells/μL, 95% confidence interval) of total WBC count and individual components on heart failure were calculated in apparently healthy 7195 men and 8816 women aged 39-79 participating in the 'European Prospective Investigation into Cancer and Nutrition' (EPIC) study in Norfolk. During a mean follow-up of 12.4 years, 935 incident cases of heart failure occurred. In women, neither total WBC count (1.02, 0.96-1.09) nor individual components were associated with HR of heart failure after accounting for known risk factors. In men, HR of heart failure increased with increasing levels of total WBC count (1.09, 1.04-1.15) after accounting for established risk factors; analysis of WBC components showed increased hazard with increasing levels of granulocyte count (1.16, 1.09-1.24) and, independently of this, decreased hazard with increasing levels of monocyte count (0.71, 0.53-0.93); lymphocyte count was not significantly associated with heart failure (0.97, 0.83-1.13). Results did not change materially after excluding smokers, adjusting for intermediate myocardial infarction and coronary heart disease and C-reactive protein., Conclusion: Inflammation as measured by WBC count was independently associated with incident heart failure in apparently healthy men but not women. The association observed in men was driven by granulocyte count, but there was an independent inverse association between monocyte count and incident heart failure.

Background: Fruit and vegetable intake has been associated with lower risk for cardiovascular risk factors and disease, but data on heart failure are sparse and inconsistent. The association of plasma vitamin C, a biomarker reflecting fruit and vegetable intake, with heart failure has not been studied., Methods: We examined the prospective association of plasma vitamin C concentrations with incident fatal and nonfatal heart failure events in apparently healthy 9,187 men and 11,112 women aged 39 to 79 years participating in the "European Prospective Investigation into Cancer and Nutrition" study in Norfolk., Results: The risk of heart failure decreased with increasing plasma vitamin C; the hazard ratios comparing each quartile with the lowest were 0.76 (95% CI 0.65-0.88), 0.70 (95% CI 0.60-0.81), and 0.62 (95% CI 0.53-0.74) in age- and sex-adjusted analyses (P for trend <.0001). Every 20 μmol/L increase in plasma vitamin C concentration (1 SD) was associated with a 9% relative reduction in risk of heart failure after adjustment for age, sex, smoking, alcohol consumption, physical activity, occupational social class, educational level, systolic blood pressure, diabetes, cholesterol concentration, and body mass index, with similar result if adjusting for interim coronary heart disease., Conclusions: Plasma vitamin C, a biomarker reflecting fruit and vegetable intake, was inversely associated with the risk of heart failure in this healthy population. This observation should be regarded as hypothesis generating for further prospective trials aimed at examining the effect of a diet rich in fruit and vegetables for prevention of heart failure., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Heart failure is a common complication of type 2 diabetes and bears a poor prognosis. For patients with diabetes and heart failure the commonly accepted standards for diagnosis and treatment of heart failure are to be applied, although prospective diabetes- specific trials are lacking. The optimum HbA(1c) target value as well as the optimum blood glucoselowering treatment are not known. Due to an absence of prospective randomized trials the treatment should follow general therapeutic principles (low incidence of side effects, combination therapy, patient-friendly dosage, costs).