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Abstract Aims In low‐risk patients with severe aortic stenosis (AS), sutureless surgical aortic valve replacement (SU‐SAVR) may be an alternative to transcatheter aortic valve implantation (TAVI). The risk of heart failure hospitalization (HFH) after aortic valve replacement (AVR) in this population is incompletely characterized. This study aims to investigate the incidence, predictors, and outcomes of HFH in patients undergoing SU‐SAVR versus TAVI. Methods and results Patients referred for AVR between 2013 and 2020 at two centres were consecutively included. The decision for SU‐SAVR or TAVI was determined by a multidisciplinary Heart Team. Cox regression and competing risk analysis were conducted to assess adverse events. Of 594 patients (mean age 77.5 ± 6.4, 59.8% male), 424 underwent SU‐SAVR, while 170 underwent TAVI. Following a mean follow‐up of 34.1 ± 23.1 months, HFH occurred in 112 (27.8%) SU‐SAVR patients and in 8 (4.8%) TAVI patients (P

The main goals of the pharmacological treatment of Heart failure with reduced ejection fraction (HFrEF) are the reduction of mortality and the prevention of hospitalizations. However, other outcomes such as improvements in cardiac remodeling and clinical status, functional capacity and quality of life, should be taken into account. Also, given the significant inter-individual and intra-individual variability of HF, and the fact that patients usually present with comorbidities, an appropriate treatment for HFrEF should exert a clinical benefit in most patient profiles irrespective of their characteristics or the presence of comorbidities, while providing organ protection beyond the cardiovascular system. The aim of this narrative review is to determine which are the proven effects of the guideline-directed treatments for HFrEF on five key clinical outcomes: cardiovascular mortality and hospitalization due to HF, sudden death, reverse cardiac remodeling, renal protection and evidence in hospitalized patients. Publications that fulfilled the pre-established selection criteria were selected and reviewed. Renin-angiotensin system (RAS) inhibitors, namely angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), sodium-glucose co-transporter 2 inhibitors (SGLT2i) show a benefit in terms of mortality and hospitalization rates. ARNI, BB, and MRA have demonstrated a significant positive effect on the incidence of sudden death. ARB, ARNI, BB and SGLT2i have been associated with clear benefits in reverse cardiac remodeling. Additionally, there is consistent evidence of renal protection from ARB, ARNI, and SGLT2i in renal protection and of benefits for hospitalized patients from ARNI and SGLT2i. In conclusion, the combination of drugs that gather most beneficial effects in HFrEF, beyond cardiovascular mortality and hospitalization, would be ideally pursued.

Abstract Aims Natriuretic peptide (NP) uptake varies in Emergency Departments (EDs) across Europe. The ‘Peptide for Life’ (P4L) initiative, led by Heart Failure Association, aims to enhance NP utilization for early diagnosis of heart failure (HF). We tested the hypothesis that implementing an educational campaign in Western Balkan countries would significantly increase NP adoption rates in the ED. Methods and results This registry examined NP adoption before and after implementing the P4L‐ED study across 10 centres in five countries: Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, and Serbia. A train‐the‐trainer programme was implemented to enhance awareness of NP testing in the ED, and centres without access received point‐of‐care instruments. Differences in NP testing between the pre‐P4L‐ED and post‐P4L‐ED phases were evaluated. A total of 2519 patients were enrolled in the study: 1224 (48.6%) in the pre‐P4L‐ED phase and 1295 (51.4%) in the post‐P4L‐ED phase. NP testing was performed in the ED on 684 patients (55.9%) during the pre‐P4L‐ED phase and on 1039 patients (80.3%) during the post‐P4L‐ED phase, indicating a significant absolute difference of 24.4% (95% CI: 20.8% to 27.9%, P

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients’ physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients.

Summary: Background: In preclinical studies, the use of double allogeneic grafts has shown promising results in promoting tissue revascularization, reducing infarct size, preventing adverse remodelling and fibrosis, and ultimately enhancing cardiac function. Building upon these findings, the safety of PeriCord, an engineered tissue graft consisting of a decellularised pericardial matrix and umbilical cord Wharton's jelly mesenchymal stromal cells, was evaluated in the PERISCOPE Phase I clinical trial (NCT03798353), marking its first application in human subjects. Methods: This was a double-blind, single-centre trial that enrolled patients with non-acute myocardial infarction eligible for surgical revascularization. Seven patients were implanted with PeriCord while five served as controls. Findings: Patients who received PeriCord showed no adverse effects during post-operative phase and one-year follow-up. No significant changes in secondary outcomes, such as quality of life or cardiac function, were found in patients who received PeriCord. However, PeriCord did modulate the kinetics of circulating monocytes involved in post-infarction myocardial repair towards non-classical inflammation-resolving macrophages, as well as levels of monocyte chemoattractants and the prognostic marker Meteorin-like in plasma following treatment. Interpretation: In summary, the PeriCord graft has exhibited a safe profile and notable immunomodulatory properties. Nevertheless, further research is required to fully unlock its potential as a platform for managing inflammatory-related pathologies. Funding: This work was supported in part by grants from MICINN (SAF2017-84324-C2-1-R); Instituto de Salud Carlos III (ICI19/00039 and Red RICORS-TERAV RD21/0017/0022, and CIBER Cardiovascular CB16/11/00403) as a part of the Plan Nacional de I + D + I, and co-funded by ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) and AGAUR (2021-SGR-01437).

Abstract Aims The prevalence of advanced heart failure (HF) is increasing due to the growing number of patients with HF and their better treatment and survival. There is a scarcity of data on the accuracy of HF web‐based risk scores in this selected population. This study aimed to assess mortality prediction performance of the Meta‐Analysis Global Group in Chronic HF (MAGGIC‐HF) risk score and the model of the Barcelona Bio‐HF Risk Calculator (BCN‐Bio‐HF) containing N terminal pro brain natriuretic peptide in HF patients receiving intermittent inotropic support with levosimendan as destination therapy. Methods and results Four hundred and three advanced HF patients from 23 tertiary hospitals in Spain receiving intermittent inotropic support with levosimendan as destination therapy were included. Discrimination for all‐cause mortality was compared by area under the curve (AUC) and Harrell's C‐statistic at 1 year. Calibration was assessed by calibration plots comparing observed versus expected events based on estimated risk by each calculator. The included patients were predominantly men, aged 71.5 [interquartile range 64–78] years, with reduced left ventricular ejection fraction (27.5 ± 9.4%); ischaemic heart disease was the most prevalent aetiology (52.5%). Death rate at 1 year was 26.8%, while the predicted 1‐year mortality by BCN‐Bio‐HF and MAGGIC‐HF was 17.0% and 22.1%, respectively. BCN‐Bio‐HF AUC was 0.66 (Harrell's C‐statistic 0.64), and MAGGIC‐HF AUC was 0.62 (Harrell's C‐statistic 0.61). Conclusions The two evaluated risk scores showed suboptimal discrimination and calibration with an underestimation of risk in advanced HF patients receiving levosimendan as destination therapy. There is a need for specific scores for advanced HF.

José Ramón González-Juanatey,1 Josep Comín-Colet,2 Domingo Pascual Figal,3 Antoni Bayes-Genis,4 Jose Maria Cepeda,5 José M García-Pinilla,6,7 Antonio García-Quintana,8 Luis Manzano,9 Jose Luis Zamorano10 1Cardiology Department, Hospital Clínico Universitario Santiago de Compostela, Centro de investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Santiago de Compostela, Spain; 2Cardiology Department, Hospital Universitario de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain; 3Cardiology Department, Hospital Virgen de la Arrixaca, University of Murcia, Murcia, Spain; 4Cardiology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; 5Department of Internal Medicine, Hospital Vega Baja, Orihuela, Alicante, Spain; 6Cardiology Department, Hospital Universitario Virgen de la Victoria, IBIMA, Málaga, Spain; 7Department of Medicine and Dermatology, Universidad de Málaga, Málaga, Spain; 8Cardiology Department, Hospital Universitario de Gran Canaria Doctor Negrín, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain; 9Department of Internal Medicine, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain; 10Cardiology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainCorrespondence: José Ramón González-Juanatey, Email Jose.Ramon.Gonzalez.Juanatey@sergas.esAbstract: Heart failure (HF) is a progressive condition with periods of apparent stability and repeated worsening HF events. Over time, unless optimization of HF treatment, worsening HF events become more frequent and patients enter into a cycle of recurrent events with high morbidity and mortality. In patients with HF there is an activation of deleterious neurohormonal pathways, such as the renin angiotensin aldosterone system and the sympathetic system, and an inhibition of protective pathways, including natriuretic peptides and guanylate cyclase. Therefore, HF burden can be reduced only through a holistic approach that targets all neurohormonal systems. In this context, vericiguat may play a key role, as it is the only HF drug that activates the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate system. On the other hand, it has been described relevant disparities in the management of HF population. Consequently, it is necessary to homogenize the management of these patients, through an integrated patient-care pathway that should be adapted at the local level. In this context, the development of new technologies (ie, video call, specific platforms, remote control devices, etc.) may be very helpful. In this manuscript, a multidisciplinary group of experts analyzed the current evidence and shared their own experience to provide some recommendations about the therapeutic optimization of patients with recent worsening HF, with a particular focus on vericiguat, and also about how the integrated patient-care pathway should be performed.Keywords: heart failure, worsening heart failure, patient-care pathway, vericiguat

Abstract Aims Venoarterial extracorporeal membrane oxygenation (VA‐ECMO) is currently one of the most used devices in refractory cardiogenic shock. However, there is a lack of evidence on how to set the ‘optimal’ flow. We aimed to describe the evolution of VA‐ECMO flows in a cardiogenic shock population and determine the risk factors of ‘high‐ECMO flow’. Methods and results A 7 year database of patients supported with VA‐ECMO was used. Based on the median flow during the first 48 h of the VA‐ECMO run, patients were classified as ‘high‐flow’ or ‘low‐flow’, respectively, when median ECMO flow was ≥3.6 or

Aims: In low‐risk patients with severe aortic stenosis (AS), sutureless surgical aortic valve replacement (SU‐SAVR) may be an alternative to transcatheter aortic valve implantation (TAVI). The risk of heart failure hospitalization (HFH) after aortic valve replacement (AVR) in this population is incompletely characterized. This study aims to investigate the incidence, predictors, and outcomes of HFH in patients undergoing SU‐SAVR versus TAVI. Methods and results: Patients referred for AVR between 2013 and 2020 at two centres were consecutively included. The decision for SU‐SAVR or TAVI was determined by a multidisciplinary Heart Team. Cox regression and competing risk analysis were conducted to assess adverse events. Of 594 patients (mean age 77.5 ± 6.4, 59.8% male), 424 underwent SU‐SAVR, while 170 underwent TAVI. Following a mean follow‐up of 34.1 ± 23.1 months, HFH occurred in 112 (27.8%) SU‐SAVR patients and in 8 (4.8%) TAVI patients (P < 0.001). The SU‐SAVR cohort exhibited higher all‐cause mortality (138 [32.5%] patients compared with 30 [17.6%] in the TAVI cohort [P < 0.001]). These differences remained significant after sensitivity analyses with 1:1 propensity score matching for baseline variables. SU‐SAVR with HFH was associated with increased all‐cause mortality (61.6% vs. 23.1%, P < 0.001). Independent associates of HFH in SU‐SAVR patients included diabetes, atrial fibrillation, chronic obstructive pulmonary disease, lower glomerular filtration rate and lower left ventricular ejection fraction. SU‐SAVR patients with HFH had a 12‐month LVEF of 59.4 ± 12.7. Conclusions: In low‐risk AS, SU‐SAVR is associated with a higher risk of HFH and all‐cause mortality compared to TAVI. In patients with severe AS candidate to SU‐SAVR or TAVI, TAVI may be the preferred intervention. [ABSTRACT FROM AUTHOR]

The co-occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre-clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time.