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Heart failure (HF) is common and associated with a poor prognosis, despite advances in treatment. Over the last decade cardiovascular outcome trials with sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus have demonstrated beneficial effects for three SGLT2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) in reducing hospitalisations for HF. More recently, dapagliflozin reduced the risk of worsening HF or death from cardiovascular causes in patients with chronic HF with reduced left ventricular ejection fraction, with or without type 2 diabetes mellitus. A number of additional trials in HF patients with reduced and/or preserved left ventricular ejection fraction are ongoing and/or about to be reported. The present position paper summarises recent clinical trial evidence and discusses the role of SGLT2 inhibitors in the treatment of HF, pending the results of ongoing trials in different populations of patients with HF.

BACKGROUND: The assessment of self-care behaviour is important for tailoring care to patients and evaluating the effectiveness of heart failure (HF) disease-management programmes. The European HF Self-care Behaviour (EHFScB) scale is a validated instrument used worldwide. AIM: The purpose of the study was to evaluate psychometric properties of the Hebrew version of the nine-item EHFScB scale in Israeli patients with HF. METHOD: To develop the Hebrew version of the EHFScB scale, forward and back translation was performed. The psychometric evaluation was based on data from 102 patients with HF (mean age 61±12 yr, male 75%, New York Heart Association [NYHA] class II 42% and NYHA class III 51%) included in two cross-sectional studies performed in 2007 and 2015-2017 in an Israeli hospital. Content validity, construct validity, known-groups validity, and discriminant validity were assessed. Reliability was evaluated with internal consistency. RESULTS: Content validity and useability were confirmed by HF experts and patients with HF. Construct validity was tested using factor analysis and two factors were extracted (factor 1: consulting behaviour; factor 2: adherence to the regimen). Known-groups validity testing revealed a significant difference before and after an educational intervention in the total score (n=40 [41.6±23.8] vs [67.6±21.8]; pFunding agencies: Swedish National Science Council [K2013-69X-22302-01-3, 2016-01390]; Swedish National Science Council/Swedish research council for health, working life and welfare (VR-FORTE) [2014-4100]; Swedish Heart and Lung AssociationSwedish Heart-Lung Foundation [E0

To identify predictors and evaluate outcomes of posttransplant diabetes mellitus (PTDM) and to investigate the effect of treatment modalities on outcomes. The database of a tertiary medical center was searched for all adult patients without prior diabetes who underwent lung, liver, or heart transplantation between January 1, 2012 and June 30, 2018. Patients in whom PTDM (defined as HbA1C ≥ 6.5% at least 3 months post transplantation) developed during follow-up (mean 3.32 years) were identified. Risk factors for PTDM, determined by regression analysis and clinical outcomes [all-cause mortality, severe infections, graft loss, and major adverse cardiovascular events (MACE)], were compared between those who developed PTDM and those who did not; in the former, insulin-based therapy was compared with non-insulin regimen. The cohort included 281 transplant recipients: 158 lung, 109 liver, and 14 heart. PTDM was diagnosed in 60 (21.35%) patients at a mean of 11.3 ± 12.89 months post transplantation. The only significant independent risk factor for PTDM was age (HR 1.028, 95% CI = 1.002–1.054, P = 0.0314). PTDM was associated with higher rates of severe infections (HR 2.565, 95% CI = 1.626–4.050, P

Background Left ventricular assist devices (LVADs) support the diseased heart of patients with advanced heart failure and are used as a bridge to heart transplantation or as destination therapy for patients ineligible for heart transplantation. Body image changes, as well as anxiety and depression, are prevalent among patients with an implanted LVAD. Objective The aim of this study was to investigate whether a relationship exists between body image and personal well-being among patients with an implanted LVAD and, if it does, whether it is moderated by anxiety and depression. Methods In this cross-sectional correlational study, a convenience sample of 30 adult patients with an implanted LVAD (mean age, 63 +/- 10; 90% male) from the outpatient facility of a tertiary medical center completed validated instruments including the Body Image Scale, Cosmetic Scale, Hospital Anxiety and Depression Scale, and Personal Well-being Index, from October 2017 to February 2018. Results were subjected to multivariate linear regression and bootstrap moderation analyses. Results Eleven patients (37%) had below-average personal well-being scores, and 14 patients (47%) had below-average body image scores. Seven (23%) had either anxiety or depression, and 11 (37%) had both anxiety and depression. Body image was found to be a significant predictor of personal well-being (t = 2.16, P = .04). When anxiety and depression were present, body image (t = 2.08, P = .049), depression (t = 2.53, P = .018), and the interaction between body image and depression (t = -2.1, P = .047) were significantly associated with personal well-being. Conclusions Body image significantly predicted personal well-being among patients with an implanted LVAD. Depression alone, or depression combined with anxiety, moderated the relationships between body image and personal well-being. The current results may help to heighten healthcare providers awareness of body image perception among patients with an implanted LVAD.

International audience; Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.

Sudden death is a devastating complication of heart failure (HF). Current guidelines recommend an implantable cardioverter-defibrillator (ICD) for prevention of sudden death in patients with HF and reduced ejection fraction (HFrEF) specifically those with a left ventricular ejection fraction

[Abstract] The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of the LVAD-supported patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD-supported patients. The expected and non-expected device-related and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of the LVAD implanting centres. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to experience comorbidities common in the older population. The probability of an LVAD-supported patient presenting with medical emergency to a local emergency department, internal, or surgical ward of a non-LVAD implanting centre is increasing. The purpose of this trilogy is to supply the immediate tools needed by the non-LVAD specialized physician: ambulance clinicians, emergency ward physicians, general cardiologists, internists, anaesthesiologists, and surgeons, to comply with the medical needs of this fast-growing population of LVAD-supported patients. The different issues discussed will follow the patient's pathway from the ambulance to the emergency department and from the emergency department to the internal or surgical wards and eventually to the discharge home from the hospital back to the general practitioner. In this first part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, after the introduction on the assist devices technology in general, definitions and structured approach to the assessment of the LVAD-supported patient in the ambulance and emergency department is presented including cardiopulmonary resuscitation for LVAD-supported patients.

Takotsubo syndrome is an acute heart failure syndrome with a pathogenesis that is attributed to sympathetic stimulation. This case report describes a unique case of a 5 month heart‐transplanted female patient who developed apical ballooning on an echocardiography exam performed following an emotional stress event. Detailed clinical investigations and imaging techniques confirmed the diagnosis of Takatsubo syndrome. Our case indicates that Takatsubo's cardiomyopathy should be included in the differential diagnosis of heart‐transplanted patients presenting with sudden graft dysfunction mimicking acute graft rejection or acute coronary syndrome.

Aims Cognitive impairment (CI) in heart failure (HF) patients has mostly been studied in single countries in specific health care settings. Sociodemographic and clinical predictors of the global CI and CI dimensions are still unclear. We described CI in a diverse HF population recruited in several countries and in different health care settings and investigated sociodemographic and clinical factors associated with the global and specific CI dimensions in HF patients. Methods and results A secondary analysis from the baseline data of the Wii-HF trial. Patients (n = 605) were enrolled in Sweden, Italy, Israel, The Netherlands, Germany, and the United States. We used the Montreal Cognitive Assessment to evaluate CI and the 6 minute walk test (6MWT) to measure exercise capacity. Patients were on average 67 years old (SD, 12), and 86% were in New York Heart Association Class II and III. The mean Montreal Cognitive Assessment score was 24 (SD, 4), and 67% of patients had at least a mild CI. The item evaluating short-term memory had a considerable proportion of low scoring patients (28.1%). Worse CI was associated with patients older age, lower education, and lower 6MWT scores (R-2 = 0.27). CI dimension scores were differently associated with specific clinical and demographic variables, but the 6MWT scores were associated with five out of seven CI dimension scores. Conclusions CI is an important problem in HF patients, with specific challenges in regard to memory. Exercise capacity is a modifiable factor that could be improved in HF patients with the potential to improve cognition and other outcomes in this population. Funding Agencies|Swedish National Science Council [K2013-69X-22302-01-3, 2016-01390]; Swedish National Science Council/Swedish Research Council for Health, Working Life and Welfare (VR-FORTE) [2014-4100]; Swedish Heart and Lung AssociationSwedish Heart-Lung Foundation [E085/12]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20130340, 20160439]; Vardal Foundation [2014-0018]; Medical Research Council of Southeast Sweden [FORSS 474681]

OBJECTIVES The immunogenicity of two-dose severe acute respiratory syndrome coronavirus 2 vaccine is lower among heart transplant (HTx) recipients, compared with the general population. Our aim was to assess the immunogenicity of a third-dose vaccine in HTx recipients. METHODS This is a prospective cohort study of HTx recipients who received a third dose of the BNT162b2 vaccine. Immunogenicity was assessed by serum levels of anti-spike immunoglobulin G (S-IgG), taken at baseline and 14–28 days after the third dose. Titres above 50 U/ml were interpreted positive. RESULTS We Included 42 HTx recipients at a median age of 65 years [interquartile range (IQR) 58–70]. At baseline, the median of 27 days (IQR 13–42) before the third dose and the median titre of the whole group was 18 U/ml (IQR 4–130). Only 14 patients (33%) were S-IgG seropositive. After the third dose, the proportion of seropositive patients increased significantly to 57% (P = 0.05) and the median titre increased significantly to 633 U/ml (IQR 7–6104, P < 0.0001). Younger age at HTx (OR per 1-year decrease 1.07, P = 0.05), low tacrolimus serum level (OR per 1-unit decrease 2.28, P = 0.02), mammalian target of rapamycin use (OR 13.3, P = 0.003), lack of oral steroids use (OR 4.17, P = 0.04) and lack of calcineurin inhibitor use (71% of responders vs 100% non-responders received calcineurin inhibitors, P = 0.01) were predictors of seropositive result after the third dose. However, no significant association was detected following adjustment for baseline S-IgG titre. CONCLUSIONS Third-dose booster of BNT162b2 vaccine significantly increased immunogenicity among HTx recipients who previously received a two-dose vaccine.

Background We report the first use of Heartmate 3 (HM3) in a Congenitally corrected Transposition of the Great Arteries (ccTGA) as a Systemic Ventricular Assist Device (SVAD) to treat HF. Case presentation A 55 years old man with a Congenitally corrected Transposition of the Great Arteries (ccTGA) a rare condition in which Heart Failure (HF) is a common presentation in adult life and survival without heart transplantation is hardly an option. Systemic Ventricular Assist Device (SVAD) can be an option if an organ does not become available. We present the first ever implantation of HM3 LVAD (Abbott Inc, Chicago IL) implanted to this patient as a bridge to transplantation, demonstrating the safety and feasibility of the procedure. Due to the unique mediastinal configuration, 3D cardiac CT reconstruction should be used for planning the procedure—intra ventricular placement of the inflow as well as mediastinal placemat of the outflow and pump. Conclusions This successful first use of HM3 as a SVAD for ccTGA patients, opens a novel treatment option for these patients as a bridge for heart transplant or as definitive treatment.

[Abstract] The improvement in left ventricular assist device (LVAD) technology and scarcity of donor hearts have increased dramatically the population of the LVAD-supported patients and the probability of those patients to present to the emergency department with expected and non-expected device-related and patient-device interaction complications. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to suffer from other co-morbidities common in the older population. In this second part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the LVAD-supported patient presenting to the emergency department with bleeding, neurological event, pump thrombosis, chest pain, syncope, and other events are presented. The very challenging issue of declaring death in an LVAD-supported patient, as the circulation is artificially preserved by the device despite no other signs of life, is also discussed in detail.

Endothelial microvascular dysfunction is a known mechanism of vascular pathology in cardiac amyloidosis (CA). Scientific evidence regarding the possible protective role of the amyloid transthyretin (ATTR) stabilizer, tafamidis, is lacking. Circulating endothelial progenitor cells (cEPCs) have an important role in the process of vascular repair. We aimed to examine the effect of tafamidis on cEPCs.Study population included patients with ATTR-CA. cEPCs were assessed using flow cytometry by the expression of CD34Tafamidis induced the activation of the cEPCs pathway, possibly promoting endothelial repair in ATTR-CA.

Patients with heart failure (HF) are at an increased risk of hospital admissions. The aim of this report is to describe the feasibility, safety and accuracy of a novel wireless left atrial pressure (LAP) monitoring system in patients with HF.The V-LAP Left Atrium Monitoring systEm for Patients With Chronic sysTOlicDiastolic Congestive heart Failure (VECTOR-HF) study is a prospective, multicenter, single-arm, open-label, first-in human clinical trial to assess the safety, performance and usability of the V-LAP system (Vectorious Medical Technologies) in patients with New York Heart Association class III HF. The device was implanted in the interatrial septum via a percutaneous, trans-septal approach guided by fluoroscopy and echocardiography. Primary endpoints included the successful deployment of the implant, the ability to perform initial pressure measurements and safety outcomes.To date, 24 patients have received implants of the LAP-monitoring device. No device-related complications have occurred. LAP was reported accurately, agreeing well with wedge pressure at 3 months (Lin concordance correlation coefficient = 0.850). After 6 months, New York Heart Association class improved in 40% of the patients (95% CI = 16.4%-63.5%), while the 6-minute walk test distance had not changed significantly (313.9 ± 144.9 vs 232.5 ± 129.9 meters; P = 0.076).The V-LAP left atrium monitoring system appears to be safe and accurate.

OBJECTIVES In this study, we aimed to determine the comparative outcomes of patients supported with continuous-flow left ventricular assist devices (LVADs): HeartMate 2 (HM2), HeartWare (HW) and HeartMate 3 (HM3) in a real-world setting. METHODS The study was an investigator-initiated comparative retrospective analysis of patients who underwent continuous-flow LVAD implantation at our institution between 2008 and 2017. The follow-up duration was 18 months after implantation. RESULTS The study included 105 continuous-flow LVAD-supported patients of whom 51% (n = 54), 24% (25) and 25% (26) underwent implantation of HM2, HW and HM3, respectively. During follow-up, patients who were supported with HM3 versus either HM2 or HW LVADs demonstrated a lower risk of stroke (0% vs 26%, P CONCLUSIONS HM3 device currently presents better prognostic and adverse events profiles when compared with the HM2 or the HW LVADs. A larger-scale head-to-head comparison between the devices is warranted in order to confirm our findings.

A 53-year-old female patient, an active smoker, received a diagnosis in early 2019 of poor-risk, metastatic renal cell carcinoma with invasion of the inferior vena cava and hepatic veins. Pre-treatment transthoracic echocardiography (TTE) revealed thrombotic involvement of the right atrium with

The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re-interpretation of information already considered in the 2016 ESC/HFA guidelines. Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium-glucose co-transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter-defibrillators in non-ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta-analyses have given us the chance to provide refined recommendations in selected other areas. Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure.

Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion. Jaarsma, T (corresponding author), Univ Linkoping, Fac Hlth Sci, Kungsgatan 40, S-60174 Norrkoping, Sweden. tiny.jaarsma@liu.se

[Abstract] The growing population of left ventricular assist device (LVAD)-supported patients increases the probability of an LVAD- supported patient hospitalized in the internal or surgical wards with certain expected device related, and patient-device interaction complication as well as with any other comorbidities requiring hospitalization. In this third part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the hospitalized LVAD-supported patient are presented including blood pressure assessment, medical therapy of the LVAD supported patient, and challenges related to anaesthesia and non-cardiac surgical interventions. Finally, important aspects to consider when discharging an LVAD patient home and palliative and end-of-life approaches are described.

Patients with heart failure (HF) who contract SARS-CoV-2 infection are at a higher risk of cardiovascular and non-cardiovascular morbidity and mortality. Regardless of therapeutic attempts in COVID-19, vaccination remains the most promising global approach at present for controlling this disease. There are several concerns and misconceptions regarding the clinical indications, optimal mode of delivery, safety and efficacy of COVID-19 vaccines for patients with HF. This document provides guidance to all healthcare professionals regarding the implementation of a COVID-19 vaccination scheme in patients with HF. COVID-19 vaccination is indicated in all patients with HF, including those who are immunocompromised (e.g. after heart transplantation receiving immunosuppressive therapy) and with frailty syndrome. It is preferable to vaccinate against COVID-19 patients with HF in an optimal clinical state, which would include clinical stability, adequate hydration and nutrition, optimized treatment of HF and other comorbidities (including iron deficiency), but corrective measures should not be allowed to delay vaccination. Patients with HF who have been vaccinated against COVID-19 need to continue precautionary measures, including the use of facemasks, hand hygiene and social distancing. Knowledge on strategies preventing SARS-CoV-2 infection (including the COVID-19 vaccination) should be included in the comprehensive educational programmes delivered to patients with HF. This article is protected by copyright. All rights reserved. [Abstract copyright: This article is protected by copyright. All rights reserved.]

Aims Exergaming is a new tool to increase physical activity. This study aimed to determine the effects of access to a home-based exergame (Nintendo Wii) in patients with heart failure (HF) on exercise capacity, self-reported physical activity and patient-reported outcome measures. Methods and results We enrolled 605 HF patients in New York Heart Association functional class I-IV, independent of ejection fraction, in an international multicentre randomized controlled trial. Patients were randomized to exergame (intervention) or motivational support (control). The primary endpoint was change in submaximal aerobic exercise capacity as measured by the distance walked in 6 min (6MWT) between baseline and 3 months. Secondary endpoints included long-term submaximal aerobic exercise capacity, muscle function, self-reported physical activity, exercise motivation, exercise self-efficacy at 3, 6 and 12months. At baseline, patients on average walked 403142m on the 6MWT. Patients in the exergame group walked further compared to controls at 3 months (454123 vs. 420 +/- 127m, P = 0.005), at 6 months (452 +/- 123 vs. 426 +/- 133m, P = 0.015) and 12months (456 +/- 122 vs. 420 +/- 135m, P = 0.004). However, correcting for baseline 6MWT values by means of a linear mixed-effects model revealed no main effect for the intervention on 6MWT. Small significant effects on muscle function were found. Statistically significant treatment effects were found for muscle function but after correction for baseline and confounders, only the treatment effect for the heel-rise left at 6 months was significant (PFunding Agencies|Swedish National Science Council [K2013-69X-22302-01-3, 2016-01390]; Swedish National Science Council/Swedish Research Council for Health, Working Life and Welfare, VR-FORTE [2014-4100]; Swedish Heart and Lung AssociationSwedish Heart-Lung Foundation [E085/12]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20130340, 20160439]; Vardal Foundation [2014-0018]; Medical Research Council of Southeast Sweden [FORSS 474681]

© 2021 European Society of Cardiology, Despite guideline recommendations and available evidence, implementation of treatment in heart failure (HF) is poor. The majority of patients are not prescribed drugs at target doses that have been proven to positively impact morbidity and mortality. Among others, tolerability issues related to low blood pressure, heart rate, impaired renal function or hyperkalaemia are responsible. Chronic kidney disease plays an important role as it affects up to 50% of patients with HF. Also, dynamic changes in estimated glomerular filtration rate may occur during the course of HF, resulting in inappropriate dose reduction or even discontinuation of decongestive or neurohormonal modulating therapy in clinical practice. As patients with HF are rarely naïve to pharmacologic therapies, the challenge is to adequately prioritize or select the most appropriate up-titration schedule according to patient profile. In this consensus document, we identified nine patient profiles that may be relevant for treatment implementation in HF patients with a reduced ejection fraction. These profiles take into account heart rate (70 bpm), the presence of atrial fibrillation, symptomatic low blood pressure, estimated glomerular filtration rate (30 mL/min/1.73 m2 ) or hyperkalaemia. The pre-discharge patient, frequently still congestive, is also addressed. A personalized approach, adjusting guideline-directed medical therapy to patient profile, may allow to achieve a better and more comprehensive therapy for each individual patient than the more traditional, forced titration of each drug class before initiating treatment with the next.

Background Endothelial microvascular dysfunction is a known mechanism of injury in cardiac amyloidosis (CA), but evidence regarding the level and function of endothelial progenitor cells (EPCs) in patients with CA is lacking. Methods Study population included patients with light-chain or transthyretin (ATTR) CA. Patients with diagnosed heart failure and preserved ejection fraction (HFpEF) without monoclonal gammopathy and a 99mTc-DPD scan incompatible with TTR were used as controls. Blood circulating EPCs were assessed quantitatively by the expression of VEGFR-2(+), CD34(+) and CD133(+) using flow cytometry, and functionally by the formation of colony forming units (CFUs). MTT assay was used to demonstrate cell viability. Tests were repeated 3 months following the initiation of amyloid-suppressive therapies (either ATTR-stabilizer or targeted chemotherapy) in CA patients. Results Our preliminary cohort included 14 CA patients (median age 74 years, 62% ATTR CA). Patients with CA vs. patients with HFpEF (n=8) demonstrated lower expression of CD34(+)/VEGFR-2(+) cells [0.51% (IQR 0.4, 0.7) vs. 1.03% (IQR 0.6, 1.4), P=0.043] and CD133(+)/VEGFR-2(+) cells [0.35% (IQR 0.23, 0.52) to 1.07% (IQR 0.6, 1.5), P=0.003]. Functionally, no differences were noted between groups. Following the initiation of amyloid-suppressive therapies in CA patients, we observed the up-regulation of CD34(+)/VEGFR-2(+) cells [2.47% (IQR 2.1, 2.7), P Conclusions These preliminary results demonstrate reduced EPCs levels in CA patients indicating significant microvascular impairment. Amyloid-targeted therapies induce the activation of EPCs, thus possibly promoting endothelial regeneration. These findings may represent a novel mechanism of action of amyloid-suppressive therapies EPCs in CA patients and during therapy Funding Acknowledgement Type of funding source: None

The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) has recently issued a position paper on the role of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF). The present document provides an update of the position paper, based of new clinical trial evidence. Accordingly, the following recommendations are given: • Canagliflozin, dapagliflozin empagliflozin, or ertugliflozin are recommended for the prevention of HF hospitalization in patients with type 2 diabetes mellitus and established cardiovascular disease or at high cardiovascular risk. • Dapagliflozin or empagliflozin are recommended to reduce the combined risk of HF hospitalization and cardiovascular death in symptomatic patients with HF and reduced ejection fraction already receiving guideline-directed medical therapy regardless of the presence of type 2 diabetes mellitus.

Background: Self-care is important in chronic diseases such as heart failure. The cultural background of health care providers might influence their view on self-care behaviour and education they provide. The aim of this study was to describe health care providers&rsquo, perceptions of the role of culture in self-care and how those perceptions shape their experiences and their practices. Methods: A qualitative study was performed in Israel, a country with a culturally diverse population. Data were collected using semi-structured interviews with 12 healthcare providers from different cultural backgrounds. Interviews were recorded and transcribed verbatim and analysed using content analysis. Results: Healthcare providers experienced cultural background influenced their patients&rsquo, self-care behaviour. Perceived culture-specific barriers to self-care such as dietary traditions interfering with the recommended diet, willingness to undertake self-care and beliefs conflicting with medical treatment were identified. Healthcare providers described that they adapted patient education and care based on the cultural background of the patients. Shared cultural background, awareness and knowledge of differences were described as positively influencing self-care education, while cultural differences could complicate this process. Conclusions: Cultural-specific barriers for self-care were perceived by health care providers and they identified that their own cultural background shapes their experiences and their practices.

Left ventricular assist devices (LVADs) are used more commonly in patients with advanced-stage heart failure. Some of these patients may require elective or urgent abdominal surgical procedures.To determine the outcomes of the management of LVAD-supported patients who underwent elective and urgent abdominal surgical procedures in our institution.A retrospective review was conducted on 93 patients who underwent LVAD implantation between August 2008 and January 2017. All abdominal surgeries in these patients were studied, and their impact on postoperative morbidity and mortality Ten patients underwent abdominal surgical procedures. Of these procedures, five were emergent and five were elective. The elective cases included one bariatric surgery for morbid obesity, one hiatal hernia repair, two cholecystectomies, and one small bowel resection for a carcinoid tumor. The emergency cases included suspected ischemic colitis, right colectomy for bleeding adenocarcinoma, laparotomy due to intraabdominal bleeding, open cholecystectomy for gangrenous cholecystitis, and laparotomy for sternal and abdominal wall infection. All patients undergoing elective procedures survived. Of the five patients who underwent emergency surgery, three died (60%, P = 0.16) and one presented with major morbidity. One of the two survivors required reintervention. In total, 12 interventions were performed on this group of patientswas evaluated.Ten patients underwent abdominal surgical procedures. Of these procedures, five were emergent and five were elective. The elective cases included one bariatric surgery for morbid obesity, one hiatal hernia repair, two cholecystectomies, and one small bowel resection for a carcinoid tumor. The emergency cases included suspected ischemic colitis, right colectomy for bleeding adenocarcinoma, laparotomy due to intraabdominal bleeding, open cholecystectomy for gangrenous cholecystitis, and laparotomy for sternal and abdominal wall infection. All patients undergoing elective procedures survived. Of the five patients who underwent emergency surgery, three died (60%, P = 0.16) and one presented with major morbidity. One of the two survivors required reintervention. In total, 12 interventions were performed on this group of patients.It is safe to perform elective abdominal procedures for LVAD-supported patients. The prognosis of these patients undergoing emergency surgery is poor and has high mortality and morbidity rates.

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Background: Self-care is recognized as important behaviour in chronic diseases such as heart failure (HF). The cultural background of patients with HF is one of the factors that can be considered to affect their adherence to self-care. The cultural background of the health care providers might also influence their view on self-care behaviour and the education they provide. The aim of this study was to describe health care providers' perceptions of the role of culture in self-care and how those perceptions shape their experiences and their practices.Methods: A qualitative study was performed in Israel, a country with a culturally diverse population. Data was collected using semi-structured interviews with 12 healthcare providers from different cultural backgrounds, selected by purposeful sampling, from two hospitals in Israel. Interviews were audio recorded and transcribed verbatim. Data was analysed using content analysis.Results: Healthcare providers experienced cultural background influenced their patients’ self-care behaviour. Perceived cultural-specific barriers to self-care such as: dietary traditions interfering with the recommended HF diet, willingness to undertake self-care and beliefs conflicting with medical treatment were identified. Healthcare providers described that they adapted their patient education and care based on the cultural background of the patients. Shared cultural background, awareness and knowledge of differences were described as positively influencing self-care education, while cultural differences could complicate this process. These findings are encapsulated within four categories regarding perceptions of health care providers: ‘Culture permeates self-care behaviours’, ‘Culture influence the way care is provided’, ‘Mutual cultural background impacts the mindset to address self-care’ and ‘Culture is only a small piece of the puzzle...’Conclusions: Cultural-specific barriers for self-care were perceived by health care providers and they identified that their own cultural background shapes their experiences and their practices.

To identify predictors and evaluate outcomes of posttransplant diabetes mellitus (PTDM) and to investigate the effect of treatment modalities on outcomes.The database of a tertiary medical center was searched for all adult patients without prior diabetes who underwent lung, liver, or heart transplantation between January 1, 2012 and June 30, 2018. Patients in whom PTDM (defined as HbA1C ≥ 6.5% at least 3 months post transplantation) developed during follow-up (mean 3.32 years) were identified. Risk factors for PTDM, determined by regression analysis and clinical outcomes [all-cause mortality, severe infections, graft loss, and major adverse cardiovascular events (MACE)], were compared between those who developed PTDM and those who did not; in the former, insulin-based therapy was compared with non-insulin regimen.The cohort included 281 transplant recipients: 158 lung, 109 liver, and 14 heart. PTDM was diagnosed in 60 (21.35%) patients at a mean of 11.3 ± 12.89 months post transplantation. The only significant independent risk factor for PTDM was age (HR 1.028, 95% CI = 1.002-1.054, P = 0.0314). PTDM was associated with higher rates of severe infections (HR 2.565, 95% CI = 1.626-4.050, P 0.0001), MACE (HR 1.856, 95% CI = 1.013-3.401, P = 0.0454) and death (HR 1.840, 95% CI = 1.024-3.304, P = 0.0413). Recipients treated with insulin-based regimens had a higher risk of severe infections (HR 2.579, 95% CI = 1.640-4.055, P 0.0001), MACE (1.925, 95% CI = 1.074-3.451, P = 0.0278) and death (HR 1.960, 95% CI = 1.071-3.586, P = 0.0291).PTDM is associated with increased mortality and poor outcomes in lung, liver, and heart transplant recipients. Early identification and aggressive treatment of PTDM and its associated cardiometabolic risk factors may improve outcomes.

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus-driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high-quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in-hospital management. Chioncel, O (corresponding author), Univ Med & Pharm Carol Davila, Inst Emergency Cardiovasc Dis Prof CC Iliescu, Bucharest 950474, Romania. ochioncel@yahoo.co.uk

The Heart Failure Association of the European Society of Cardiology has published a previous position paper and various guidelines over the past decade recognizing the value of palliative care for those affected by this burdensome condition. Integrating palliative care into evidence-based heart failure management remains challenging for many professionals, as it includes the identification of palliative care needs, symptom control, adjustment of drug and device therapy, advance care planning, family and informal caregiver support, and trying to ensure a good death. This new position paper aims to provide day-to-day practical clinical guidance on these topics, supporting the coordinated provision of palliation strategies as goals of care fluctuate along the heart failure disease trajectory. The specific components of palliative care for symptom alleviation, spiritual and psychosocial support, and the appropriate modification of guideline-directed treatment protocols, including drug deprescription and device deactivation, are described for the chronic, crisis and terminal phases of heart failure. Funding Agencies|Patient Forum of the European Society of Cardiology

Objectives This was a first-in-human study to assess the feasibility, safety, and exploratory efficacy of interatrial shunting for treating high-risk heart failure (HF) in patients with reduced and preserved ejection fraction. Methods A single-arm open-label study of patients with New York Heart Association functional class III or IV HF on optimal therapy was performed at 6 centers. The V-Wave shunt, an hourglass-shaped implant containing a 1-way bioprosthetic valve, was implanted by transseptal catheterization. Clinical, functional, echocardiographic, and hemodynamic evaluations were performed at baseline, 3 and 12 months, and annually (clinical follow-up) thereafter (median follow-up 28 months; interquartile range: 21 to 31 months). Results A total of 38 patients were enrolled (30 with HF with reduced ejection fraction and 8 with HF with preserved ejection fraction; mean age 66 ± 9 years; 97% and 3% in New York Heart Association functional classes III and IV, respectively), and the shunt device was successfully implanted in all cases without periprocedural mortality. The rate of major device- or procedure-related complications during the first 12 months was 2.6% (periprocedural cardiac tamponade in 1 patient). At 3- and 12-month follow-up, there were improvements in New York Heart Association functional class (classes I and II in 78% and 60% of patients, respectively), quality of life (improvements ≥5 points in 74% and 73% of patients, respectively), and 6-min walk distance (mean increases of 41 ± 63 m and 28 ± 83 m, respectively) (p Conclusions Interatrial shunting with the V-Wave system was feasible and safe in patients with HF with reduced and preserved ejection fraction. Improvements in clinical and functional status were observed early and at 12 months despite attenuation of shunt patency in one-half of the patients. Patients with preserved shunt patency tended to maintain clinical benefit during longer term follow-up. Device modification that improves the durability of patency is likely worthwhile before confirmation of these findings in a randomized trial.

Objective We tested whether remote dielectric sensing (ReDS)-directed fluid management reduces readmissions in patients recently hospitalized for heart failure (HF). Background Pulmonary congestion is the most common cause of worsening HF leading to hospitalization. Accurate remote monitoring of lung fluid volume may guide optimal treatment and prevent re-hospitalization. ReDS technology is a quantitative non-invasive method for measuring absolute lung fluid volume. Methods Patients hospitalized for acute decompensated HF were enrolled during their index admission and followed at home for 90days post-discharge. Daily ReDS readings were obtained using a wearable vest, and were used as a guide to optimizing HF therapy, with a goal of maintaining normal lung fluid content. Comparisons of the number of HF hospitalizations during ReDS-guided HF therapy were made, both to the 90days prior to enrollment and to the 90days following discontinuation of ReDS monitoring. Results Fifty patients were enrolled, discharged, and followed at home for 76.9±26.2days. Patients were 73.8±10.3years old, 40% had LVEF above 40%, and 38% were women. Compared to the pre- and post-ReDS periods, there were 87% and 79% reductions in the rate of HF hospitalizations, respectively, during ReDS-guided HF therapy. The hazard ratio between the ReDS and the pre-ReDS period was 0.07 (95% CI [0.01–0.54] p =0.01), and between the ReDS and the post-ReDS period was 0.11 (95% CI [0.014–0.88] p =0.037). Conclusions These findings suggest that ReDS-guided management has the potential to reduce HF readmissions in acute decompensated HF patients recently discharged from the hospital.

Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but—per definition—causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio-and vasoactive drugs used in the hospitalization phase to stabilize the patient’s hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g. catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents., SCOPUS: re.j, info:eu-repo/semantics/published

Physical activity is an essential part of managing heart failure. However, adherence to activity recommendations is low, especially in female patients. The aim of this study was to investigate the perceptions of healthcare providers regarding sex differences in physical activity, motivation, barriers, and whether adaptations in care based on sex might be meaningful.This is a qualitative study; data were collected in semi-structured interviews with healthcare providers. The data were analysed using qualitative content analysis.The major overarching theme was that healthcare providers feel that "Men and women are equal, but different". This theme was explained in terms of 7 sub-themes with associated categories, as follows: "Men and women prefer and perform different physical activity regardless of health status", "Male and female heart failure patients have different motivations for, and barriers to, being active", "Factors related to differences in physical activity and physical capacity between male and female heart failure patients", "Heart failure has more impact on physical activity and physical capacity than patient's sex", and "Tailoring activity advice for heart failure patients based on sex."Healthcare providers had clear opinions regarding the existence of sex differences that might affect patients' care. Several differences were identified in male and female heart failure patients in terms of physical activity. There seems to be a conflict between fear of discriminating and the value of personalizing care.

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and similar to 10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies.

Background:Successful long-term left ventricular assist device (LVAD) therapy necessitates a high degree of self-care. We aimed to develop an instrument that measures self-care behaviors in adult patients living with an LVAD.Methods:We used the method to develop patient-reported outcomes recommended by the US Food and Drug Administration. Prior to developing the instrument, a literature review was conducted to generate items using the middle-range theory of self-care of chronic illness as a guiding framework. A 2-round Delphi method, involving 17 clinicians with expertise in heart failure and assist devices from the Netherlands, Israel, United States, Canada, and Japan, was used to generate and select items. In the first Delphi survey, the levels of importance, relevance, and clarity of items in the instrument were evaluated. The second Delphi survey was performed to gain consensus on the final selection of items. We also examined face validity.Results:A preliminary 37-item version of the Self-Care Behavior Scale was produced. The first panel judged 33 items as important and relevant, taking out 4 items due to vague wording and duplication and adding in 4 items. In the final 33-item version, 19 items address self-care maintenance behaviors, 10 items address self-care monitoring behaviors, and 4 items address self-care management behaviors. Patients (N = 25) did not have any difficulties understanding items and report any missing items.Conclusion:The 33-item Self-Care Behavior Scale for patients with heart failure having an LVAD has been developed and is ready for further psychometric testing.

Data on post-transplant Kaposi's sarcoma in heart and lung transplant recipients are sparse. This study examined the incidence of biopsy-proven post-transplant Kaposi's sarcoma in thoracic organ recipients over a period of 20 years. As mammalian target of rapamycin inhibitors were introduced in 2006 as optional maintenance immunosuppressive therapy, the overall results were analysed and stratified into 2 groups: 1996 to 2005 and 2006 to 2016. A total of 867 transplant recipients met the study criteria. Post-transplant Kaposi's sarcoma was diagnosed in 7 (0.81%) patients. Five cases (0.19% of transplant recipients) were recorded in 1996 to 2005 and 2 (0.03% of transplant recipients) in 2006 to 2016 (p = 0.04). Multivariable logistic regression analyses identified the following as risk factors: period of transplantation (odds ratio (OR) 4.844, 95% confidence interval (95% CI) 1.156-20.291), age at transplantation (OR 1.066, 95% CI 0.992-1.145), and North African origin (OR 7.282, 95% CI 12.55-42.254). This study found a decreased incidence of post-transplant Kaposi's sarcoma over the last 20 years, mainly attributed.

Background: To contribute to the protocol development of exercise training in LVAD supported patients by reviewing the exercise programs for those patients in the ESC affiliated countries. Methods: A subset of data from 77 (26 countries) LVAD implanting centers that participated in the Extra-HF survey (170 centers) was analyzed. Results: Of the 77 LVAD implanting centers, 45 (58%) reported to have a functioning exercise training program (ETP) for LVAD patients. In 21 (47%) of the 45 ETP programs in LVAD implanting centers, patients begin their ETP during their in-hospital post-operative recovery period. Most centers (71%) have an early post-discharge program for their patients, and 24% of the centers offer a long-term maintenance program. The professionals involved in the ETPs are mainly physiotherapists (73%), psychologists, cardiac rehab nurses (22%), or cardiologists specialized in rehabilitation (22%). Not all programs include the treating cardiologist or surgeons. Most of the ETPs (84%) include aerobic endurance training, mostly cycling (73%), or walking (62%) at low intensity intervals. Some programs apply resistance training (47%), respiratory muscle training (55%), or balance training (44%). Reasons for the absence of ETPs are referral of patients to another center (14 centers) and lack of resources (11 centers). Conclusion: There is a great variance in ETPs in LVAD implanting centers. Not all the implanting centers have an ETP, and those that do have adopted a local protocol. Clear guidance on ETP supplied by LVAD implanting centers to LVAD supported patients and more evidence for optimal modalities are needed. (C) 2015 Elsevier Ireland Ltd. All rights reserved. Funding Agencies|Heart Failure Association of the ESC

Introduction Prevention of acute decompensated heart failure (ADHF) hospitalizations has both medical and economic implications, yet remains an unmet need. Increases in pulmonary and perhaps upper airway fluid content may be detectable remotely by voice analysis. The Cordio HearO™ system is a mobile application with cloud-based computing, designed to identify distinct speech measures (SM) in standard audio recordings which may be indicative of HF clinical status and provide early warning of impending decompensation. Hypothesis Cordio HearO™ speech analysis can identify clinical worsening of heart failure (HF) patients prior to hospitalization. Methods In this ongoing multicenter, observational study, we recruited 173 New York Heart Association Class II-III, stable stage C chronic heart failure patients. The patients recorded five sentences (2-5 sec each) each day in their native language (English, Hebrew, Arabic or Russian), using Cordio HearO™ operating on standard smartphone devices. Patients have been followed for 3 to 23 months. The current analysis explored the association between different SM parameters and episodes of HF decompensation requiring hospitalization. Results A total of 196,610 recordings, collected over 47,376 patient days of follow up were analyzed during which 13 patients required hospitalization for ADHF. 10 (76.9%) (95% CI: 54.02% - 99.83%) of these episodes were detected by Cordio HearO™ software an average of 12.2 (range 8 to 17 days) days prior to admission. The estimated false-positive event rate per year was 1.47 (95% CI: 1.28 - 1.68). Conclusions Cordio HearO™ novel speech analysis technology may be a useful tool in remote monitoring of HF patients, providing an early warning of impending episodes of decompensation, thus having the potential to reduce ADHF hospitalizations and improve patient quality of life and economic outcomes. Ongoing and future studies will continue to define the role of speech measures in the management of heart failure patients.

We initiated this study to evaluate the prevalence and clinical significance of tricuspid regurgitation in patients with left ventricular dysfunction.A single-center analysis of all echocardiographic studies between 2000 and 2013 was performed. Patients with ejection fraction35% were included, and those with mechanical valves, mitral stenosis, or significant aortic valve pathology were excluded. Patients were grouped based on tricuspid regurgitation severity (nonsignificant, moderate, and severe). Demographic and echocardiographic findings and survival were compared.The study included 3943 patients (74% male, age 69 ± 14 years); 70% had nonsignificant, 24% had moderate, and 6% had severe tricuspid regurgitation. In a multivariate model, tricuspid regurgitation was independently associated with older age (odds ratio [OR] 1.009; 95% confidence interval [CI], 1.001-1.017; P = .022), female sex (OR 1.644; 95% CI, 1.329-2.035; P.001), atrial fibrillation (OR 1.764; 95% CI, 1.429-2.134; P.001), tricuspid regurgitation gradient (OR 1.051; 95% CI, 1.045-1.058; P.001 per mm Hg), right ventricular dysfunction (OR 3.492; 95% CI, 2.870-4.248; P.001), left atrial area (cmSignificant tricuspid regurgitation is common in patients with left ventricular dysfunction. It is linked to various cardiac pathologies and independently associated with increased mortality.

Circulating endothelial progenitor cells have an important role in the process of vascular repair. Impaired recruitment and function of endothelial progenitor cells is related to the pathophysiology of congestive heart failure. Endothelial progenitor cells have been shown to express the mineralocorticoid receptor.To investigate the effect of mineralocorticoid receptor antagonists on endothelial progenitor cells in patients with heart failure.Twenty-four patients with compensated heart failure, who were not under mineralocorticoid receptor antagonist therapy, were recruited. Either eplerenone (n=8) or spironolactone (n=16) therapy was initiated. Circulating endothelial progenitor cell level, identified as the proportion of mononuclear cells expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34, was evaluated by flow cytometry at baseline and after 8 weeks. Following 7 days of culture, colonies were counted by microscopy and MTT assay was performed on randomly selected patients (n=12) to estimate viability.Both median CD34+/VEGFR2+ and median CD133+/VEGFR2+ increased significantly (P = 0.04 and 0.02, respectively). However, the number of colonies and viability of the cells after therapy (as assessed by the MTT assay) was not significantly different compared with the baseline.These preliminary results suggest that mineralocorticoid receptor blockade may enhance endothelial progenitor cells recruitment in patients with compensated heart failure.

This was a first-in-human study to assess the feasibility, safety, and exploratory efficacy of interatrial shunting for treating high-risk heart failure (HF) in patients with reduced and preserved ejection fraction.A single-arm open-label study of patients with New York Heart Association functional class III or IV HF on optimal therapy was performed at 6 centers. The V-Wave shunt, an hourglass-shaped implant containing a 1-way bioprosthetic valve, was implanted by transseptal catheterization. Clinical, functional, echocardiographic, and hemodynamic evaluations were performed at baseline, 3 and 12 months, and annually (clinical follow-up) thereafter (median follow-up 28 months; interquartile range: 21 to 31 months).A total of 38 patients were enrolled (30 with HF with reduced ejection fraction and 8 with HF with preserved ejection fraction; mean age 66 ± 9 years; 97% and 3% in New York Heart Association functional classes III and IV, respectively), and the shunt device was successfully implanted in all cases without periprocedural mortality. The rate of major device- or procedure-related complications during the first 12 months was 2.6% (periprocedural cardiac tamponade in 1 patient). At 3- and 12-month follow-up, there were improvements in New York Heart Association functional class (classes I and II in 78% and 60% of patients, respectively), quality of life (improvements ≥5 points in 74% and 73% of patients, respectively), and 6-min walk distance (mean increases of 41 ± 63 m and 28 ± 83 m, respectively) (p 0.02 for all, data available for 36 patients), without changes in objective measures of left- or right-sided function. All shunts were patent at 3 months, but 5 of 36 (14%) had occluded, and another 13 of 36 (36%) were stenotic at the valve by 12 months. Patients with widely patent shunts had lower long-term rates of death, left ventricular assist device placement or heart transplantation (p = 0.001), and HF hospitalization (p = 0.008), along with a reduction of pulmonary capillary wedge pressure (from 23.3 ± 5.4 mm Hg at baseline to 18.0 ± 4.0 mm Hg at 12 months; p = 0.011).Interatrial shunting with the V-Wave system was feasible and safe in patients with HF with reduced and preserved ejection fraction. Improvements in clinical and functional status were observed early and at 12 months despite attenuation of shunt patency in one-half of the patients. Patients with preserved shunt patency tended to maintain clinical benefit during longer term follow-up. Device modification that improves the durability of patency is likely worthwhile before confirmation of these findings in a randomized trial.

Introduction: Heart failure places a significant economic burden on health care. Acute heart failure requires hospitalization and often frequent re-hospitalization in expensive wards where vasoactive rescue therapy is often added on top of standard medications. In these lean times, there is a growing need for cost-effective therapeutic options that supply superior support and in addition shorten the length of stay in hospital and reduce re-hospitalization rates. The inodilator levosimendan represents the latest addition to the vasoactive treatments of acute heart failure patients, and it appears to meet these expectations. Our aim was to answer the question whether the treatment efficacy of levosimendan - when selected as therapy for patients hospitalized for acute heart failure - brings savings to hospitals in various European countries representing different economies. Methods and results: We took a conservative approach and selected some a fortiori arguments to simplify the calculations. We selected seven European countries to represent different economies: Italy, Spain, Greece, Germany, Sweden, Finland and Israel. Data on the costs of medications and on the cost per day were collected and fed in a simple algorithm to detect savings. These saving varied from country to country, from a minimum of (sic)0.50 in Germany to a maximum of (sic)354.64 in Sweden. Conclusions: The use of levosimendan as a therapy for patients hospitalized for acute heart failure provides a net saving to hospitals driven by a reduction in the length of hospital stay. This finding is true in each of the countries considered in this study.

We describe a Bedouin family with a novel autosomal recessive syndrome characterized by dilated cardiomyopathy and septo-optic dysplasia. Genetic analysis revealed a homozygous missense mutation in TAX1BP3, which encodes a small PDZ domain containing protein implicated in regulation of the Wnt/β-catenin signaling pathway, as the causative mutation. The mutation affects a conserved residue located at the core of TAX1BP3 binding pocket and is predicted to impair the nature of a crucial hydrophobic patch, thereby interrupting the structure and stability of the protein, and its ability to interact with other proteins. TAX1BP3 is highly expressed in heart and brain and consistent with the clinical findings observed in our patients; a knockdown of TAX1BP3 causes elongation defects, enlarged pericard, and enlarged head structures in zebrafish embryos. Thus, we describe a new genetic disorder that expands the monogenic cardiomyopathy disease spectrum and suggests that TAX1BP3 is essential for heart and brain development.

The treatment of patients hospitalized with heart failure (HHF) and ambulatory chronic heart failure (CHF) differs in various countries.To evaluate the management and outcomes of patients with HFF and CHF in Israel compared to those in other European countries who were included in the ESC-HF Long-Term Registry.From May 2011 to April 2013, heart failure patients - 467 Israelis and 11,973 from other countries - were evaluated. The Israeli patients included 178 with HHF and 289 with CHF. One year outcomes, including all-cause and cardiovascular mortality as well as HHF, were evaluated.The HHF Israeli patients were older than their CHF Israeli counterparts, had more co-morbidities, included more women, and were treated less frequently with medications suggested by European guidelines. The Israeli HHF patients had similar all-cause 1 year mortality rates compared to HHF patients from other participating countries, but their cardiovascular (CV) mortality was lower, while a significantly higher rate of all-cause and HHF was noted. The Israeli CHF patients were older, suffered from more co-morbidities and had prior cardio-electronic implantable devices. In addition, they had higher mortality rates, especially non-CV, and were more frequently hospitalized, compared to CHF patients from other countries.The Israeli patients with heart failure differed in their baseline characteristics and the therapeutic approach. Despite high usage of treatments recommended by official guidelines, especially among CHF patients, mortality, particularly in HHF patients, remained high.

Background High admission blood glucose (ABG) level has been associated with a poor short-term outcome among non-diabetic patients with heart failure (HF). We aimed to investigate the association between ABG levels and long-term (10 years) mortality in patients with or without pre-existing diabetes mellitus (DM) admitted with HF. Methods We analyzed data on 1811 patients with DM and 2182 patients without pre-existing DM who were hospitalized with HF during a prospective national survey. The relationship between ABG and 10-year mortality was assessed using the Cox proportional hazard model adjusting for multiple variables. ABG was analyzed both as a categorical (200 mg/dL) and as a continuous variable. Results At 10 years of follow-up the cumulative probability of mortality was 85 and 78% among patients with DM and patients with no pre-existing DM (p 200 mg/dL had an increased mortality risk (>200 mg/dL versus 200 mg/dL is associated with increased mortality risk.