Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials.

BACKGROUND: In the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups. METHODS: We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries. In both trials, eligible participants were aged 18 years or older, had heart failure with a left ventricular ejection fraction of at least 45%, a BMI of at least 30 kg/m2, New York Heart Association class II-IV symptoms, and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; a measure of heart failure-related symptoms and physical limitations) of less than 90 points. In STEP-HFpEF, people with diabetes or glycated haemoglobin A1c concentrations of at least 6·5% were excluded, whereas for inclusion in STEP-HFpEF DM participants had to have been diagnosed with type 2 diabetes at least 90 days before screening and to have an HbA1c of 10% or lower. In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks. The dual primary endpoints were change from baseline to week 52 in KCCQ-CSS and bodyweight in all randomly assigned participants. Confirmatory secondary endpoints included change from baseline to week 52 in 6-min walk distance, a hierarchical composite endpoint (all-cause death, heart failure events, and differences in changes in KCCQ-CSS and 6-min walk distance); and C-reactive protein (CRP) concentrations. Heterogeneity in treatment effects was assessed across subgroups of interest. We assessed safety in all participants who received at least one dose of study drug. FINDINGS: Between March 19, 2021 and March 9, 2022, 529 people were randomly assigned in STEP-HFpEF, and between June 27, 2021 and Sept 2, 2022, 616 were randomly assigned in STEP-HFpEF DM. Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group. Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-group difference in bodyweight at week 52 -8·4% [-9·2 to -7·5]; p<0·0001). For the confirmatory secondary endpoints, 6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide group compared with the placebo group (p<0·0001 for all comparisons). For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction. 161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group. INTERPRETATION: In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated. FUNDING: Novo Nordisk.

Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.

BACKGROUND: Obesity and type 2 diabetes are prevalent in patients with heart failure with preserved ejection fraction and are characterized by a high symptom burden. No approved therapies specifically target obesity-related heart failure with preserved ejection fraction in persons with type 2 diabetes. METHODS: We randomly assigned patients who had heart failure with preserved ejection fraction, a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more, and type 2 diabetes to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: A total of 616 participants underwent randomization. The mean change in the KCCQ-CSS was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4; P<0.001), and the mean percentage change in body weight was -9.8% with semaglutide and -3.4% with placebo (estimated difference, -6.4 percentage points; 95% CI, -7.6 to -5.2; P<0.001). The results for the confirmatory secondary end points favored semaglutide over placebo (estimated between-group difference in change in 6-minute walk distance, 14.3 m [95% CI, 3.7 to 24.9; P = 0.008]; win ratio for hierarchical composite end point, 1.58 [95% CI, 1.29 to 1.94; P<0.001]; and estimated treatment ratio for change in CRP level, 0.67 [95% CI, 0.55 to 0.80; P<0.001]). Serious adverse events were reported in 55 participants (17.7%) in the semaglutide group and 88 (28.8%) in the placebo group. CONCLUSIONS: Among patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, semaglutide led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 1 year. (Funded by Novo Nordisk; STEP-HFpEF DM ClinicalTrials.gov number, NCT04916470.).

Epidemiology, pathophysiology, diagnosis and management of chronic right-sided heart failure and tricuspid regurgitation. A clinical consensus statement of the Heart Failure Association (HFA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Right-sided heart failure and tricuspid regurgitation are common and strongly associated with poor quality of life and an increased risk of heart failure hospitalizations and death. While medical therapy for right-sided heart failure is limited, treatment options for tricuspid regurgitation include surgery and, based on recent developments, several transcatheter interventions. However, the patients who might benefit from tricuspid valve interventions are yet unknown, as is the ideal time for these treatments given the paucity of clinical evidence. In this context, it is crucial to elucidate aetiology and pathophysiological mechanisms leading to right-sided heart failure and tricuspid regurgitation in order to recognize when tricuspid regurgitation is a mere bystander and when it can cause or contribute to heart failure progression. Notably, early identification of right heart failure and tricuspid regurgitation may be crucial and optimal management requires knowledge about the different mechanisms and causes, clinical course and presentation, as well as possible treatment options. The aim of this clinical consensus statement is to summarize current knowledge about epidemiology, pathophysiology and treatment of tricuspid regurgitation in right-sided heart failure providing practical suggestions for patient identification and management.

Diagnosis and management of patients with left ventricular hypertrophy: Role of multimodality cardiac imaging. A scientific statement of the Heart Failure Association of the European Society of Cardiology.

Left ventricular (LV) hypertrophy consists in an increased LV wall thickness. LV hypertrophy can be either secondary, in response to pressure or volume overload, or primary, i.e. not explained solely by abnormal loading conditions. Primary LV hypertrophy may be due to gene mutations or to the deposition or storage of abnormal substances in the extracellular spaces or within the cardiomyocytes (more appropriately defined as pseudohypertrophy). LV hypertrophy is often a precursor to subsequent development of heart failure. Cardiovascular imaging plays a key role in the assessment of LV hypertrophy. Echocardiography, the first-line imaging technique, allows a comprehensive assessment of LV systolic and diastolic function. Cardiovascular magnetic resonance provides added value as it measures accurately LV and right ventricular volumes and mass and characterizes myocardial tissue properties, which may provide important clues to the final diagnosis. Additionally, scintigraphy with bone tracers is included in the diagnostic algorithm of cardiac amyloidosis. Once the diagnosis is established, imaging findings may help predict future disease evolution and inform therapy and follow-up. This consensus document by the Heart Failure Association of the European Society of Cardiology provides an overview of the role of different cardiac imaging techniques for the differential diagnosis and management of patients with LV hypertrophy.

Prevention of sudden death in heart failure with reduced ejection fraction: do we still need an implantable cardioverter-defibrillator for primary prevention?

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 ≤35% after at least 3 months of optimized HF treatment. The benefit of ICD in patients with symptomatic HFrEF caused by coronary artery disease has been well documented; however, the evidence for a benefit of prophylactic ICD implantation in patients with HFrEF of non-ischaemic aetiology is less strong. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers (BB), and mineralocorticoid receptor antagonists (MRA) block the deleterious actions of angiotensin II, norepinephrine, and aldosterone, respectively. Neprilysin inhibition potentiates the actions of endogenous natriuretic peptides that mitigate adverse ventricular remodelling. BB, MRA, angiotensin receptor-neprilysin inhibitor (ARNI) have a favourable effect on reduction of sudden cardiac death in HFrEF. Recent data suggest a beneficial effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in reducing serious ventricular arrhythmias and sudden cardiac death in patients with HFrEF. So, in the current era of new drugs for HFrEF and with the optimal use of disease-modifying therapies (BB, MRA, ARNI and SGLT2i), we might need to reconsider the need and timing for use of ICD as primary prevention of sudden death, especially in HF of non-ischaemic aetiology.

Heartmate 3 as a bridge to heart transplantation in a patient with congenitally corrected transposition of the great arteries: a case report.

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.

Improved immunogenicity following the third dose of BNT162b2 mRNA vaccine in heart transplant recipients.

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.

The Effect of Tafamidis on Circulating Endothelial Progenitor Cells in Patients with Transthyretin Cardiac Amyloidosis.

AIMS: 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. METHODS AND RESULTS: Study population included patients with ATTR-CA. cEPCs were assessed using flow cytometry by the expression of CD34(+)/CD133(+) and vascular endothelial growth factor receptor (VEGFR)-2(+) and by the formation of colony-forming units (CFUs) and production of VEGF. Tests were repeated at pre-specified time-points up to 12 months following the initiation of tafamidis. Included were 18 ATTR-CA patients at a median age of 77 (IQR 71, 85) years and male predominance (n = 15, 83%). Following the initiation of tafamidis and during 12 months of drug treatment, there was a gradual increase in the levels of CD34(+)/VEGFR-2(+) (0.43 to 2.42% (IQR 1.53, 2.91)%, p = 0.002) and CD133(+)/VEGFR-2(+) (0.49 to 1.64% (IQR 0.97, 2.90)%, p = 0.004). Functionally, increase in EPCs-CFUs was microscopically evident following treatment with tafamidis (from 0.5 CFUs (IQR 0.0, 1.0) to 3.0 (IQR 1.3, 3.8) p < 0.001) with a concomitant increase in EPC's viability as demonstrated by an MTT assay (from 0.12 (IQR 0.03, 0.16) to 0.30 (IQR 0.18, 0.33), p < 0.001). VEGF levels increased following treatment (from 54 (IQR 52, 72) to 107 (IQR 62, 129) pg/ml, p = 0.039). CONCLUSIONS: Tafamidis induced the activation of the cEPCs pathway, possibly promoting endothelial repair in ATTR-CA.

Trends in Kaposi's Sarcoma Morbidity: A Retrospective Cohort Study of Heart and Lung Transplant Recipients.

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.

Health-related quality of life in left ventricular assist device-supported patients.

AIMS: This study aimed to evaluate the different health-related quality of life (HR-QoL) aspects in patients with both short-term and long-term duration LVAD support at pre-specified time intervals. METHODS AND RESULTS: We performed a single-centre HR-QoL analysis of short-term and long-term LVAD-supported patients using the short version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) and the Changes in Sexual Functioning Questionnaire along with a survey to evaluate patients' social and driving routines. Data were collected at baseline and at 6 or 12 month follow-up. Included were 46 patients with a median time from LVAD implantation of 1.1 [inter-quartile range (IQR) 0.5, 2.6] years. The median KCCQ-12 summary score was 56 (IQR 29, 74) with most favourable scores in the symptom frequency domain [75 (IQR 50, 92)] and worse scores in the physical limitation [42 (IQR 25, 75)] and QoL [44 (IQR 25, 75)] domains. No significant changes were apparent during study follow-up [KCCQ-12 summary score 56 (IQR 35, 80)], and no significant correlation between the KCCQ-12 summary score and ventricular assist device-support duration was detected (r = -0.036, P = 0.812). Sexual dysfunction was noted across all domains with a cumulative score of 31 (IQR 22, 42). Seventy-six per cent of patients resumed driving after LVAD implantation, and 43% of patients reported they socialize with family and friends more frequently since surgery. CONCLUSIONS: Short-term and long-term LVAD-supported patients had impaired HR-QoL and sexual function at baseline and at follow-up yet reported an improvement in social interactions and independency. A broader spectrum of patient's reported HR-QoL measures should be integrated into the pre-LVAD implantation assessment and preparation.

Self-care of heart failure patients: practical management recommendations from the Heart Failure Association of the European Society of Cardiology.

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.

Integration of a palliative approach into heart failure care: a European Society of Cardiology Heart Failure Association position paper.

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.

Abdominal Surgery in Patients with a Ventricular Assist Device: A Single Center Experience in Israel.

BACKGROUND: 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. OBJECTIVES: To determine the outcomes of the management of LVAD-supported patients who underwent elective and urgent abdominal surgical procedures in our institution. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

An 18-month comparison of clinical outcomes between continuous-flow left ventricular assist devices.

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 < 0.001 and 0% vs 40%, P < 0.001, respectively) and lower rates of thrombosis (0% vs 31%, P < 0.001 and 0% vs 12%, P < 0.001, respectively), findings that were consistent with their calculated haemocompatibility scores (cumulative score 5, 89 and 56 for HM3, HM2 and HW, respectively, P < 0.001). Moreover, patients supported with HM3 versus HW had fewer unplanned hospitalizations [median 1 (25th-75th interquartile range 0-2) vs 3 (interquartile range 2-4), P = 0.012]. Importantly, survival free from stroke or device exchange was higher in patients supported with HM3 compared with either the HM2 or the HW LVADs [hazard ratio (HR) 2.77, confidence interval (CI) 1.13-6.78; P = 0.026 and HR 2.70, CI 1.01-7.20; P = 0.047, respectively]. 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.

Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology.

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.

Heart failure in cardiomyopathies: a position paper from the Heart Failure Association of the European Society of Cardiology.

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 ∼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.

Video capsule endoscopy is safe and effective in suspected small bowel bleeding among left ventricular assist device recipients.

INTRODUCTION:: Suspected small bowel bleeding is frequently encountered in left ventricular assist device recipients and the identification of the culprit lesion may be challenging. Data regarding the safety and yield of small bowel capsule in the investigation of suspected small bowel bleeding are limited. We aimed to evaluate the safety and efficacy of small bowel video capsule endoscopy for the investigation of suspected small bowel bleeding among left ventricular assist device recipients. METHODS:: Patients with left ventricular assist device who underwent video capsule endoscopy for the investigation of suspected small bowel bleeding were identified. Suspected small bowel bleeding was defined as the presence of overt bleeding at least 30 days following left ventricular assist device implantation with no identifiable cause in upper and lower endoscopy. RESULTS:: A total of 10 patients with left ventricular assist device associated suspected small bowel bleeding performed 12 small bowel capsule endoscopies between January 2008 and December 2015 at our tertiary medical care facility. There were no cases of capsule retention or any other serious adverse events during the exams. A significant finding was identified in 8 out of 10 patients, including 3 cases of small bowel angioectasia, 2 cases of small bowel ulcers, 1 case of cecal polyp, and 2 cases of active bleeding with no apparent bleeding source. Small bowel enteroscopy identified and treated bleeding angioectasia in the latter two cases. CONCLUSION:: Small bowel capsule endoscopy is safe and effective in the investigation of left ventricular assist device associated suspected small bowel bleeding.

Angiogenic Imbalance and Residual Myocardial Injury in Recovered Peripartum Cardiomyopathy Patients.

BACKGROUND: Recent studies suggest that angiogenic imbalance during pregnancy may lead to acute peripartum cardiomyopathy (PPCM). We propose that angiogenic imbalance and residual cardiac dysfunction may exist even after recovery from PPCM. METHODS AND RESULTS: Twenty-nine women at least 12 months after presentation with PPCM, who exhibited recovery of left ventricular (LV) ejection fraction (≥50%), were included in the study (mean age 35±6 years, LV ejection fraction 61.0±3.9%). The number of circulating endothelial progenitor cells (EPCs) and plasma levels of proangiogenic vascular endothelial growth factor and of soluble vascular endothelial growth factor receptor Flt1 (sFlt1) were measured. All patients underwent comprehensive cardiac function assessment, including tissue Doppler imaging and 2-dimensional (2D) strain echocardiography. All measurements were compared with healthy controls. Patients with a history of PPCM have significantly higher sFlt1 concentrations (median [25th-75th percentile]; 149.57, [63.14-177.89] versus 20.29, [15.00-53.89] pg/mL, P<0.001) and significantly decreased vascular endothelial growth factor/sFlt1 ratio (P=0.012) compared with controls, with a trend toward lower concentration of circulating CD34+/KDR+ levels. In addition, patients with PPCM had lower early velocities E' septal (9.9±2.1 versus 11.0±1.5 cm/s, P=0.02), with a significantly lower systolic velocity S' septal (7.6±1.2 versus 8.5±1.2 cm/s, P=0.003) by tissue Doppler imaging. Significantly lower LV global longitudinal (-19.1±3.3 versus -22.7±2.2%, P<0.001) and apical circumferential 2D strain (-16.6±4.9 versus -21.2±7.9, P=0.02) were present in patients with PPCM compared with controls. CONCLUSIONS: Higher concentration of sFlt1 with concomitant decreased circulating endothelial progenitor cell levels along with inappropriate attenuated vascular endothelial growth factor levels may imply an angiogenic imbalance that exists even after recovery and may thus predispose to PPCM. In addition, tissue Doppler imaging and 2D strain were able to identify residual myocardial injury in post-PPCM women with apparent recovery of LV systolic function. Both angiogenic imbalance and residual myocardial injury may play an important role in the recurrence of LV dysfunction during subsequent pregnancies.

[LAPAROSCOPIC "SLEEVE" GASTRECTOMY POST HEART TRANSPLANTION].

Morbid obesity affects the function of the transplanted heart either directly, by damaging many elements that affect cardiac function or indirectly, by the initial appearance or worsening of co-morbidities that affect the heart. Bariatric surgery is the most effective treatment for a significant and sustained decrease in weight and it leads to the disappearance of co-morbidities such as diabetes, hypertension and dyslipidemia in high rates. These diseases can damage the blood vessels of the graft and impair its function. We report a case study of a 47-year-old morbidly obese male (BMI 36 kg/m2] who underwent heart transplantation three years previously, developed gradual weight gain and symptoms of aggravating heart failure. Coronary artery disease in the implanted heart was diagnosed. Clinically, he started suffering from shortness of breath and chest pain during minimal effort. In addition, he also suffered from high blood pressure and kidney failure. Laparoscopic sleeve gastrectomy was successfully performed and he was discharged four days later. On follow-up the patient has lost 35 kg. His present weight is 74 kg (BMI 25.7). All symptoms of heart failure improved and oral medications for hypertension and heart failure were withdrawn. Our conclusion is that it is justified to consider bariatric surgery in heart transplant recipients suffering from morbid obesity, as long as the long-term benefit outweighs the surgical risk. The decision to perform bariatric surgery should be made by a multidisciplinary team and the operation should take place at a center with extensive experience in bariatric surgery.