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Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus., Competing Interests: Conflict of interest: none declared., (© The Authors 2024. Published by John Wiley & Sons Limited and Oxford University Press on behalf of the European Society of Cardiology, and Frontiers Media SA on behalf of the European Society for Organ Transplantation.)

Background and Aims: Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry., Methods: Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes., Results: Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy., Conclusions: Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Conflict of interest statement A.J.S.C.: none related to the present work. Outside the present work: consultancy fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Edwards, Menarini, Novartis, Nutricia, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Gore, Impulse Dynamics, Respicardia. A.P.M.: none related to the present work. Outside the present work: personal fees from Novartis, Bayer, AstraZeneca for participation in study committees. L.H.L.: none related to the present work. Outside the present work: grants: AstraZeneca, Vifor, Boston Scientific, Boehringer Ingelheim, Novartis, MSD; Consulting: Vifor, AstraZeneca, Bayer, Pharmacosmos, MSD, MedScape, Sanofi, Lexicon, Myokardia, Boehringer Ingelheim, Servier, Edwards Life Sciences, Alleviant; Speaker’s honoraria: Abbott, OrionPharma, MedScape, Radcliffe, AstraZeneca, Novartis, Boehringer Ingelheim, Bayer; Patent: AnaCardio. M.F.P.: none related to the present work. Outside the present work: Consultancy, speaker’s, institutional fees from AstraZeneca, Boehringer Ingelheim, CHF solution, Menarini, Novartis, Servier. M.G.C.-L.: none related to the present work. Outside the present work: Speakers honorary and/or consultancy fees from AstraZeneca, Boehringer Ingelheim, Novartis, Rovi, Vifor, Bayer, CareDx, Pfizer, Abbott and Medtronic. M.L.: none related to the present work. Outside the present work: speakers honoraria: AstraZeneca, Vifor, Boehringer Ingelheim, Novartis, Bayer, Sanofi; Consulting: Vifor, Boehringer Ingelheim. P.M.S.: honoraria for lectures from Servier, AstraZeneca, Respicardia, Menarini. Consultancy agreement and honoraria from Boehringer Ingelheim, Novartis, Vifor Pharma and Roche diagnostic. S.D.A.: grants and personal fees from Vifor and Abbott Vascular, and personal fees for consultancies, trial committee work and/or lectures from Actimed, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bioventrix, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Edwards, Farraday, Impulse Dynamics, Janssen, Novartis, Occlutech, Pfizer, Respicardia, Servier, Vectorious, and V-Wave. T.M.: none related to current work. Outside of current work, speaker honoraria; Boehringer Ingelheim, AstraZeneca, Edwards and Abbott. All other authors declare no conflict of interest for this contribution.

Aims: To investigate the impact of patiromer on the serum potassium level and its ability to enable specified target doses of renin-angiotensin-aldosterone system inhibitor (RAASi) use in patients with heart failure and reduced ejection fraction (HFrEF)., Methods and Results: A total of 1642 patients with HFrEF and current or a history of RAASi-related hyperkalemia were screened and 1195 were enrolled in the run-in phase with patiromer and optimization of the RAASi therapy [≥50% recommended dose of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, and 50 mg of mineralocorticoid receptor antagonist (MRA) spironolactone or eplerenone]. Specified target doses of the RAASi therapy were achieved in 878 (84.6%) patients; 439 were randomized to patiromer and 439 to placebo. All patients, physicians, and outcome assessors were blinded to treatment assignment. The primary endpoint was between-group difference in the adjusted mean change in serum potassium. Five hierarchical secondary endpoints were assessed. At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13-43) weeks, the adjusted mean change in potassium was +0.03 mmol/l in the patiromer group and +0.13 mmol/l in the placebo group [difference in the adjusted mean change between patiromer and placebo: -0.10 mmol/l (95% confidence interval, CI -0.13, 0.07); P < 0.001]. Risk of hyperkalemia >5.5 mmol/l [hazard ratio (HR) 0.63; 95% CI 0.45, 0.87; P = 0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P = 0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P < 0.001) were lower with patiromer. Hyperkalemia-related morbidity-adjusted events (win ratio 1.53, P < 0.001) and total RAASi use score (win ratio 1.25, P = 0.048) favored the patiromer arm. Adverse events were similar between groups., Conclusion: Concurrent use of patiromer and high-dose MRAs reduces the risk of recurrent hyperkalemia (ClinicalTrials.gov: NCT03888066)., Competing Interests: Conflict of interest: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. T.F. reported consulting fees from Vifor Pharma, Bayer, Biosense Webster, CSL Behring, Galapagos, Minoryx, Novartis, LivaNova, Janssen, Roche, and honoraria from Fresenius Kabi. J.B. reported consulting fees from Abbott, Adrenomed, Amgen, Applied Therapeutics, Array, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, G3 Pharma, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Sequana Medical, and Vifor Pharma. G.F. reported honoraria from Bayer and Boehringer Ingelheim, committee membership for Medtronic, Vifor Pharma, Amgen, Servier, and Novartis, and grants from the European Commission. M.R.W. reported consulting fees from Vifor Pharma and AstraZeneca, and honoraria from Vifor Pharma. P.V.d.M. reported grants from Vifor Pharma, Pfizer, AstraZeneca, and Ionis, consulting fees from Vifor Pharma, Novartis and AstraZeneca, and honoraria from Vifor Pharma and Pharmacosmos. L.H.L. reported grants from AstraZeneca, Vifor, Boston Scientific, Boehringer Ingelheim, and Novartis, consulting fees from Merck, Vifor Pharma, AstraZeneca, Bayer, Pharmacosmos, MedScape, Sanofi, Lexicon, Myokardia, Boehringer Ingelheim, and Servier, honoraria from Abbott, MedScape, Radcliffe, AstraZeneca, and Novartis, and stock options and patents with AnaCardio. F.D. reported support and stock options from Vifor Pharma as a Vifor employee. F.P. reported consulting fees from Vifor Pharma and Novo Nordisk, honoraria from Servier, Pfizer, Novartis, and Boehringer Ingelheim, and presidency (unpaid) of the World Heart Federation. S.D.A. reports consulting fees from Abbott, Bayer, Boehringer Ingelheim, Cardiac Dimension, Cordio, Impulse Dynamics, Novartis, Occlutech, Servier, and Vifor Pharma, and grant support from Abbott and Vifor Pharma. M.M. reported consulting fees from Actelion, Amgen, AstraZeneca, Abbott Vascular, Bayer, Servier, Edwards Therapeutics, Livanova, Vifor Pharma, and WindTree Therapeutics. UMG reports grants, support and stock options from Vifor Pharma. M.K. reported consulting fees from Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Merck, Novo Nordisk, Sanofi, and Vifor Pharma, grants from AstraZeneca and Boehringer Ingelheim, and grant support from Abbott and Vifor Pharma, and honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. A.C. reported honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Menarini, Novartis, Nutricia, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Gore, Impulse Dynamics, Respicardia, and Viatris. P.R. reported grants from AstraZeneca, Bayer, Fresenius, Novartis, Vifor Fresenius Medical Care Renal Pharma, Relypsa, and Vifor, consulting fees from Bayer, Idorsia, G3P, KBP, and Sanofi, honoraria from Sequana medical, AstraZeneca, Bayer, Fresenius, Novartis, Grünenthal, Stealth Peptides, Vifor Fresenius Medical Care Renal, Novo Nordisk, Ablative Solutions, Corvidia, Relypsa, and Vifor CardioRenal, and non-financial support from Servier, Fresenius, and G3P. I.L.P. serves on an advisory board for Vifor Pharma Ltd and on the Steering Committee of the DIAMOND clinical trial. B.P. reported consulting fees from AstraZeneca, Boehringer Ingelheim/Lilly, Sanofi/Lexicon, SCPharmaceuticals, SQinnovations, G3 Pharmaceuticals, Sarfez, KBP biosciences, Cereno scientific, Phase bio, Proton Intel, and Vifor Pharma, stock options from SCPharmaceuticals, SQinnovations, G3 Pharmaceuticals, Sarfez, Cereno scientific, KBP biosciences, Proton Intel, and Vifor Pharma, US Patent 9931412- site specific delivery of eplerenone to the myocardium, and US Patent pending 63/045,783—Histone-modulating agents for the treatment and prevention of organ damage. No other authors reported disclosures., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Background: Diagnostic tools available to support general practitioners diagnose heart failure (HF) are limited., Objectives: (i) Determine the feasibility of the novel cardiac output response to stress (CORS) test in suspected HF patients, and (ii) Identify differences in the CORS results between (a) confirmed HF patients from non-HF patients, and (b) HF reduced (HFrEF) vs HF preserved (HFpEF) ejection fraction., Methods: Single centre, prospective, observational, feasibility study. Consecutive patients with suspected HF (N = 105; mean age: 72 ± 10 years) were recruited from specialized HF diagnostic clinics in secondary care. The consultant cardiologist confirmed or refuted a HF diagnosis. The patient completed the CORS but the researcher administering the test was blinded from the diagnosis. The CORS assessed cardiac function (stroke volume index, SVI) noninvasively using the bioreactance technology at rest-supine, challenge-standing, and stress-step exercise phases., Results: A total of 38 patients were newly diagnosed with HF (HFrEF, n = 21) with 79% being able to complete all phases of the CORS (91% of non-HF patients). A 17% lower SVI was found in HF compared with non-HF patients at rest-supine (43 ± 15 vs 51 ± 16 mL/beat/m2, P = 0.02) and stress-step exercise phase (49 ± 16 vs 58 ± 17 mL/beat/m2, P = 0.02). HFrEF patients demonstrated a lower SVI at rest (39 ± 15 vs 48 ± 13 mL/beat/m2, P = 0.02) and challenge-standing phase (34 ± 9 vs 42 ± 12 mL/beat/m2, P = 0.03) than HFpEF patients., Conclusion: The CORS is feasible and patients with HF responded differently to non-HF, and HFrEF from HFpEF. These findings provide further evidence for the potential use of the CORS to improve HF diagnostic and referral accuracy in primary care., (© The Author(s) 2022. Published by Oxford University Press.)

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present consensus document aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing HF are listed., (The article has been co-published with permission in the European Journal of Preventive Cardiology and European Journal of Heart Failure. All rights reserved. © The Author(s) 2022. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article.)

Aims: Cardiac magnetic resonance (CMR) is recommended in the diagnosis of cardiomyopathies, but it is time-consuming, expensive, and limited in availability in some European regions. The aim of this study was to determine the use of CMR in cardiomyopathy patients enrolled into the European Society of Cardiology (ESC) cardiomyopathy registry [part of the EURObservational Research Programme (EORP)]., Methods and Results: Three thousand, two hundred, and eight consecutive adult patients (34.6% female; median age: 53.0 ± 15 years) with cardiomyopathy were studied: 1260 with dilated (DCM), 1739 with hypertrophic (HCM), 66 with restrictive (RCM), and 143 with arrhythmogenic right ventricular cardiomyopathy (ARVC). CMR scans were performed at baseline in only 29.4% of patients. CMR utilization was variable according to cardiomyopathy subtypes: from 51.1% in ARVC to 36.4% in RCM, 33.8% in HCM, and 20.6% in DCM (P < 0.001). CMR use in tertiary referral centres located in different European countries varied from 1% to 63.2%. Patients undergoing CMR were younger, less symptomatic, less frequently had implantable cardioverter-defibrillator (ICD)/pacemaker implanted, had fewer cardiovascular risk factors and comorbidities (P < 0.001). In 28.6% of patients, CMR was used along with transthoracic echocardiography (TTE); 67.6% patients underwent TTE alone, and 0.9% only CMR., Conclusion: Less than one-third of patients enrolled in the registry underwent CMR and the use varied greatly between cardiomyopathy subtypes, clinical profiles of patients, and European tertiary referral centres. This gap with current guidelines needs to be considered carefully by scientific societies to promote wider availability and use of CMR in patients with cardiomyopathies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)-presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Randomized clinical trials initially used heart failure (HF) patients with low left ventricular ejection fraction (LVEF) to select study populations with high risk to enhance statistical power. However, this use of LVEF in clinical trials has led to oversimplification of the scientific view of a complex syndrome. Descriptive terms such as 'HFrEF' (HF with reduced LVEF), 'HFpEF' (HF with preserved LVEF), and more recently 'HFmrEF' (HF with mid-range LVEF), assigned on arbitrary LVEF cut-off points, have gradually arisen as separate diseases, implying distinct pathophysiologies. In this article, based on pathophysiological reasoning, we challenge the paradigm of classifying HF according to LVEF. Instead, we propose that HF is a heterogeneous syndrome in which disease progression is associated with a dynamic evolution of functional and structural changes leading to unique disease trajectories creating a spectrum of phenotypes with overlapping and distinct characteristics. Moreover, we argue that by recognizing the spectral nature of the disease a novel stratification will arise from new technologies and scientific insights that will shape the design of future trials based on deeper understanding beyond the LVEF construct alone., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aim: To investigate the characteristics long-term prognostic implications (up to ∼2.2 years) of atrial fibrillation (AF) compared to sinus rhythm (SR), between acute and chronic heart failure (HF) with reduced (HFrEF < 40%), mid-range (HFmrEF 40-49%), and preserved (HFpEF ≥ 50%) ejection fraction (EF)., Methods and Results: Data from the observational, prospective, HF long-term registry of the European Society of Cardiology were analysed. A total of 14 964 HF patients (age 66 ± 13 years, 67% male; 53% HFrEF, 21% HFmrEF, 26% HFpEF) were enrolled. The prevalence of AF was 27% in HFrEF, 29% in HFmrEF, and 39% in HFpEF. Atrial fibrillation was associated with older age, lower functional capacity, and heightened physical signs of HF. Crude rates of mortality and HF hospitalization were higher in patients with AF compared to SR, in each EF subtype. After multivariable adjustment, the hazard ratio of AF for HF hospitalizations was: 1.036 (95% CI 0.888-1.208, P = 0.652) in HFrEF, 1.430 (95% CI 1.087-1.882, P = 0.011) in HFmrEF, and 1.487 (95% CI 1.195-1.851, P < 0.001) in HFpEF; and for combined all-cause death or HF hospitalizations: 0.957 (95% CI 0.843-1.087, P = 0.502), 1.302 (95% CI 1.055-1.608, P = 0.014), and 1.365 (95% CI 1.152-1.619, P < 0.001), respectively. In patients with HFrEF, AF was not associated with worse outcomes in those presenting with either an acute or a chronic presentation of HF., Conclusions: The prevalence of AF increases with increasing EF but its association with worse cardiovascular outcomes, remained significant in patients with HFpEF and HFmrEF, but not in those with HFrEF.

Aims: Evidence suggests an excess risk of non-thromboembolic major adverse cardiac events (MACE) associated with atrial fibrillation (AF), particularly in individuals free of overt coronary artery disease (CAD). Metabolic syndrome (MetS) increases cardiovascular risk in the general population, but less is known how it influences outcomes in AF patients. We aimed to assess whether MetS affects the risk of MACE in AF patients without overt CAD., Methods and Results: This prospective, observational study enrolled 843 AF patients (mean-age, 62.5 ± 12.1 years, 38.6% female) without overt CAD. Metabolic syndrome was defined according to the National Cholesterol Education Program. The 5-year composite MACE included myocardial infarction (MI), coronary revascularization, and cardiac death. Metabolic syndrome was present in 302 (35.8%) patients. At 5-year follow-up, 118 (14.0%) patients experienced MACE (2.80%/year). Metabolic syndrome conferred a multivariable adjusted hazard ratio (aHR) of 1.98 for MACE [95% confidence interval (CI), 1.23-3.16; P = 0.004], and for individual outcomes: MI (aHR, 2.00; 95% CI, 1.69-5.11; P < 0.001), revascularization (aHR, 2.33; 95% CI, 1.40-3.87; P = 0.001), and cardiac death (aHR, 2.59; 95% CI, 1.25-5.33; P = 0.011). Following the propensity score (PS)-adjustment for MetS, the association between MetS and MACE (PS-aHR, 1.87; 95% CI, 1.21-3.01; P = 0.012), MI (PS-aHR, 1.72; 95% CI, 1.54-5.00; P = 0.008), revascularization (PS-aHR, 2.18; 95% CI, 1.69-3.11; P = 0.015), and cardiac death (PS-aHR, 2.27; 95% CI, 1.14-5.11; P = 0.023) remained significant., Conclusion: Metabolic syndrome is common in AF patients without overt CAD, and confers an independent, increased risk of MACE, including MI, coronary revascularization, and cardiac death. Given its prognostic implications, prevention and treatment of MetS may reduce the burden of non-thromboembolic complications in AF.

Aims: Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort., Methods and Results: This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein-Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann-Whitney estimator 0.54, 95% confidence interval [CI] 0.47-0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200-370 mL (60% of patients) (Mann-Whitney estimator 0.61, 95% CI 0.52-0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death., Conclusion: The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)

In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Aims: Ularitide is a synthetic form of urodilatin, a natriuretic peptide produced in the kidney with vasodilating, natriuretic, and diuretic effects, that offers promise for the management of decompensated heart failure (DHF). We assessed the efficacy and safety of ularitide in treating patients with DHF., Methods and Results: In this Phase II randomized, double-blind, placebo-controlled trial, 221 DHF patients received either placebo (n=53) or ularitide at 7.5 ng/kg/min (n=60), 15 ng/kg/min (n=53), or 30 ng/kg/min (n=55) as a 24-h continuous infusion. At 6 h, ularitide demonstrated a significant decrease in pulmonary capillary wedge pressure (P=0.052, P=0.000004, P=0.000002, respectively) and improved dyspnoea score in the 7.5, 15, and 30 ng/kg/min ularitide group (P=0.0026, P=0.0026, P=0.0013, respectively). Ularitide reduced systemic vascular resistance and increased cardiac index for the 15 and 30 ng/kg/min groups (P=0.017, P=0.00002, respectively). Systolic blood pressure (BP) decreased dose dependency. Heart rate and serum creatinine were unchanged through day 3. Most frequently reported drug-related adverse events through day 3 in all ularitide groups were dose-dependent BP decrease and hypotension., Conclusion: Ularitide lowered cardiac filling pressures and improved dyspnoea without apparent early deleterious effects on renal function in DHF patients. These results suggest that ularitide may play a role in the management of DHF.