Evolution of economic burden of heart failure by ejection fraction in newly diagnosed patients in Spain.

OBJECTIVE: To describe healthcare resource utilization (HCRU) and costs, in patients with newly diagnosed heart failure (HF) according to ejection fraction (EF) in Spain. METHODS: Retrospective cohort study that analyzed anonymized, integrated and computerised medical records in Spain. Patients with ≥ 1 new HF diagnosis between January 2013 and September 2019 were included and followed-up during a 4-year period. Rates per 100 person-years of HCRU and costs were estimated. RESULTS: Nineteen thousand nine hundred sixty-one patients were included, of whom 43.5%, 26.3%, 5.1% and 25.1% had HF with reduced, preserved, mildly reduced and unknown EF, respectively. From year 1 to 4, HF rates of outpatient visits decreased from 1149.5 (95% CI 1140.8-1159.3) to 765.5 (95% CI 745.9-784.5) and hospitalizations from 61.7 (95% CI 60.9-62.7) to 15.7(14.7-16.7) per 100 person-years. The majority of HF-related healthcare resource costs per patient were due to hospitalizations (year 1-4: 63.3-38.2%), followed by indirect costs (year 1-4: 12.2-29.0%), pharmacy (year 1-4: 11.9-19.9%), and outpatient care (year 1-4: 12.6-12.9%). Mean (SD) per patient HF-related costs decreased from 2509.6 (3518.5) to 1234.6 (1534.1) Euros (50% cost reduction). At baseline, 70.1% were taking beta-blockers, 56.3% renin-angiotensin system inhibitors, 11.8% mineralocorticoid receptor antagonists and 8.9% SGLT2 inhibitors. At 12 months, these numbers were 72.3%, 65.4%, 18.9% and 9.8%, respectively. CONCLUSIONS: Although the economic burden of HF decreased over time since diagnosis, it is still substantial. This reduction could be partially related to a survival bias (sick patients died early), but also to a better HF management. Despite that, there is still much room for improvement.

Healthcare resource utilization and costs among patients with heart failure with preserved, mildly reduced, and reduced ejection fraction in Spain.

AIMS: To describe healthcare resource utilization (HCRU) of patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF) in Spain.  METHODS: Adults with ≥ 1 HF diagnosis and ≥ 1 year of continuous enrolment before the corresponding index date (1/January/2016) were identified through the BIG-PAC database. Rate per 100 person-years of all-cause and HF-related HCRU during the year after the index date were estimated using bootstrapping with replacement. RESULTS: Twenty-one thousand two hundred ninety-seven patients were included, of whom 48.5% had HFrEF, 38.6% HFpEF and 4.2% HFmrEF, with the rest being of unknown EF. Mean age was 78.8 ± 11.8 years, 53.0% were men and 83.0% were in NYHA functional class II/III. At index, 67.3% of patients were taking renin angiotensin system inhibitors, 61.2% beta blockers, 23.4% aldosterone antagonists and 5.2% SGLT2 inhibitors. Rates of HF-related outpatient visits and hospitalization were 968.8 and 51.6 per 100 person-years, respectively. Overall, 31.23% of patients were hospitalized, mainly because of HF (87.88% of total hospitalizations); HF hospitalization length 21.06 ± 17.49 days (median 16; 25th, 75th percentile 9-27). HF hospitalizations were the main cost component: inpatient 73.64%, pharmacy 9.67%, outpatient 9.43%, and indirect cost 7.25%. Rates of all-cause and HF-related HCRU and healthcare cost were substantial across all HF subgroups, being higher among HFrEF compared to HFmrEF and HFpEF patients. CONCLUSIONS: HCRU and cost associated with HF are high in Spain, HF hospitalizations being the main determinant. Medication cost represented only a small proportion of total costs, suggesting that an optimization of HF therapy may reduce HF burden.

Clinical relevance of adding intravascular ultrasound to coronary angiography for the diagnosis of extrinsic left main coronary artery compression by a pulmonary artery aneurysm in pulmonary hypertension.

OBJECTIVES: We sought to assess the clinical value of adding intravascular ultrasound (IVUS) evaluation to coronary angiography (CA) to guide extrinsic left main coronary artery (LMCA) compression diagnosis and treatment in pulmonary hypertension (PH). BACKGROUND: LMCA compression due to a pulmonary artery aneurysm (PAA) is a severe complication of PH. Although guidelines encourage the use of IVUS for LMCA disease evaluation, it has hardly been used in this scenario. METHODS: We analyzed morbimortality of type 1 and 4 PH patients with clinically suspected LMCA compression by a PAA between 2010 and 2018 in a reference unit. LMCA compression was prospectively assessed with CA ± IVUS. Angiographic-LMCA compression was considered conclusive when LMCA stenosis>50% was present in four predetermined projections; inconclusive, when LMCA stenosis>50% was present in <4 projections and negative if no stenosis>50% was present. Patients with conclusive and inconclusive CA underwent IVUS. IVUS-LMCA compression was defined as systolic minimum lumen area < 6 mm2 . RESULTS: LMCA compression was suspected in 23/796 patients (3%). CA was conclusive for compression in 7(30.5%), inconclusive in 9(39%), and negative in 7(30.5%). IVUS confirmed LMCA compression in 6/7(86%) patients with conclusive CA and in 2/9(22%) with inconclusive CA. Patients fulfilling IVUS criteria for LMCA compression underwent stent implantation. At 20 months follow-up a composite end-point of death, stent restenosis/thrombosis, or lung transplant was reported in three patients (13%). CONCLUSIONS: CA can misdiagnose LMCA extrinsic compression. IVUS discriminates better whether significant compression by a PAA exists or not, avoiding unnecessary LMCA stenting. Patients treated following this strategy show a low rate of major clinical events at 20 months follow-up.

Impact of the film-forming dispersion pH on the properties of yeast biomass films.

BACKGROUND: Yeast biomass, mainly composed of proteins and polysaccharides (mannans and ß-glucans), has been proposed to develop films. pH can affect the solubility of polysaccharides, the structure of the cell wall, and the interactions between proteins. Considering the potential impact of these effects, the pH of yeast film-forming dispersions was studied from 4 to 11. RESULTS: In tensile tests, samples increased their elongation by increasing pH, from 7 ± 2% (pH 4) to 29 ± 5% (pH 11), but Young's modulus was not significantly modified. Regarding thermal degradation, the maximum degradation rate temperature was shifted 46 °C from pH 4 to 11. Differences in water vapour permeability, colour, opacity, and roughness of films were also found. According to the results of differential protein solubility assay, hydrophobic interactions and hydrogen bonding were promoted at pH 4, but disulfide bonds were benefited at pH 11, in addition to partial ß-glucan dissolution and break-up of the alkali-sensitive linkage in molecules from the cell wall. CONCLUSION: The results lead to the conclusion that film-functional characteristics were greatly benefited at pH 11 in comparison with the regular pH of dispersion (pH 6). These results could help in understanding and selecting the pH conditions to enhance the desired properties of yeast biomass films. © 2021 Society of Chemical Industry.

COVID-19 in solid organ transplant recipients: A single-center case series from Spain.

The clinical characteristics, management, and outcome of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after solid organ transplant (SOT) remain unknown. We report our preliminary experience with 18 SOT (kidney [44.4%], liver [33.3%], and heart [22.2%]) recipients diagnosed with COVID-19 by March 23, 2020 at a tertiary-care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine) was used in 50.0% of patients and had to be prematurely discontinued in 2 of them. Other antiviral regimens included hydroxychloroquine monotherapy (27.8%) and interferon-ß (16.7%). As of April 4, the case-fatality rate was 27.8% (5/18). After a median follow-up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C-reactive protein levels at various points were significantly higher among recipients who experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS-CoV-2 infection has a severe course in SOT recipients.

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.

Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.

Influence of long-standing pulmonary arterial hypertension and its severity on pulmonary artery aneurysm development.

Pulmonary artery aneurysm (PAA) is a common finding in patients with long-term pulmonary arterial hypertension (PAH). The influence of PAH severity in the development of PAA remains unclear. We sought to determine whether PAA development is related to PAH severity and whether treatment optimization based on risk profile estimation is effective to stop pulmonary artery (PA) enlargement. This is a retrospective study of 125 PAH patients who underwent an imaging test (computed tomography or magnetic resonance) combined with a right heart catheterization within a six-month period. A multivariate analysis was performed to identify independent risk factors for PAA. Patients who underwent an additional imaging-test and RHC during follow-up were analyzed to evaluate changes on PA dimensions. PAA was diagnosed in 42 (34%) patients. PAA was more frequent in patients with congenital heart disease and toxic oil syndrome. PAH time-course showed to be an independent risk factor for PAA (HR 1.051, 95% CI 1.013-1.091, p = 0.008) whereas PAH severity did not. Twenty-six patients underwent a follow-up imaging-test and catheterization. After treatment optimization, a non-significant reduction of mean PA pressure was observed (58.5 mmHg [43.5-70.8] vs. 55.5 mmHg [47.5-66.3], p = 0.115) and a higher proportion of patients achieved a low-risk profile (19% vs. 35%, p = 0.157). However, the PA diameter significantly increased (40.4 ± 10.1 mm vs. 42.1 ± 9.6 mm; p = 0.003). PAA is a common condition in long-standing PAH but its development is not necessarily related to PAH severity. Despite stabilization after treatment optimization, a progressive PA dilatation was observed.

Potential Molecular Pathways Related to Pulmonary Artery Aneurysm Development: Lessons to Learn from the Aorta.

Pulmonary arterial hypertension (PAH) is a rare disease caused by pulmonary vascular remodeling. Current vasodilator treatments have substantially improved patients' survival. This improved survival has led to the appearance of complications related to conditions previously underdiagnosed or even ignored, such as pulmonary artery aneurysm (PAA). The presence of a dilated pulmonary artery has been shown to be related to an increased risk of sudden cardiac death among PAH patients. This increased risk could be associated to the development of left main coronary artery compression or pulmonary artery dissection. Nevertheless, very little is currently known about the molecular mechanisms related to PAA. Thoracic aortic aneurysm (TAA) is a well-known condition with an increased risk of sudden death caused by acute aortic dissection. TAA may be secondary to chronic exposure to classic cardiovascular risk factors. In addition, a number of genetic variants have been shown to be related to a marked risk of TAA and dissection as part of multisystemic syndromes or isolated familial TAA. The molecular pathways implied in the development of TAA have been widely studied and described. Many of these molecular pathways are involved in the pathogenesis of PAH and could be involved in PAA. This review aims to describe all these common pathways to open new research lines that could help lead to a better understanding of the pathophysiology of PAH and PAA and their clinical implications.

Fibroblast growth factor-23 promotes rhythm alterations and contractile dysfunction in adult ventricular cardiomyocytes.

BACKGROUND: Cardiac dysfunction and arrhythmia are common and onerous cardiovascular events in end-stage renal disease (ESRD) patients, especially those on dialysis. Fibroblast growth factor (FGF)-23 is a phosphate-regulating hormone whose levels dramatically increase as renal function declines. Beyond its role in phosphorus homeostasis, FGF-23 may elicit a direct effect on the heart. Whether FGF-23 modulates ventricular cardiac rhythm is unknown, prompting us to study its role on excitation-contraction (EC) coupling. METHODS: We examined FGF-23 in vitro actions on EC coupling in adult rat native ventricular cardiomyocytes using patch clamp and confocal microscopy and in vivo actions on cardiac rhythm using electrocardiogram. RESULTS: Compared with vehicle treatment, FGF-23 induced a significant decrease in rat cardiomyocyte contraction, L-type Ca2+ current, systolic Ca2+ transients and sarcoplasmic reticulum (SR) load and SR Ca2+-adenosine triphosphatase 2a pump activity. FGF-23 induced pro-arrhythmogenic activity in vitro and in vivo as automatic cardiomyocyte extracontractions and premature ventricular contractions. Diastolic spontaneous Ca2+ leak (sparks and waves) was significantly increased by FGF-23 via the calmodulin kinase type II (CaMKII)-dependent pathway related to hyperphosphorylation of ryanodine receptors at the CaMKII site Ser2814. Both contraction dysfunction and spontaneous pro-arrhythmic Ca2+ events induced by FGF-23 were blocked by soluble Klotho (sKlotho). CONCLUSIONS: Our results show that FGF-23 reduces contractility and enhances arrhythmogenicity through intracellular Ca2+ mishandling. Blocking its actions on the heart by improving sKlotho bioavailability may enhance cardiac function and reduce arrhythmic events frequently observed in ESRD.

Patient-Associated Predictors of 15- and 30-Day Readmission After Hospitalization for Acute Heart Failure.

BACKGROUND: Identifying readmission predictors in heart failure (HF) patients may help guide preventative efforts and save costs. We aimed to identify 15- and 30-day readmission predictors due to cardiovascular reasons. METHODS AND RESULTS: A total of 1831 patients with acute HF admission were prospectively followed during a year. Patient-associated variables were gathered at admission/discharge and events during follow-up. A multivariate Fine and Gray competing risk regression model and a cumulative incidence function were used to identify predictors and build a risk score model for 15- and 30-day readmission. The 15- and 30-day readmission rates due to cardiovascular reasons were 7.1% and 13.9%. Previous acute myocardial infarction, congestive signs at discharge, and length of stay > 9 days were predictors of 15- and 30-day readmission, while much weight loss and large NT-ProBNP reduction were protective factors. The NT-ProBNP reduction was larger at 30 days (> 55%) vs 15 days (> 40%) to protect from readmission. Glomerular filtration rate at discharge < 60 mL/min/1.73m2 and > 1 previous admissions due to HF were predictors of 30-day readmission, while first post-discharge control at an HF unit was a protective factor. CONCLUSIONS: Previous identified factors for early readmission were confirmed. The NT-ProBNP reduction should be increased (> 55%) to protect from 30-day readmission.

PTH, vitamin D, and the FGF-23-klotho axis and heart: Going beyond the confines of nephrology.

BACKGROUND: Profound disturbances in mineral metabolism are closely linked to the progression of chronic kidney disease. However, increasing clinical and experimental evidence indicates that alterations in phosphate homoeostasis could have an even stronger impact on the heart. AIM: The aim of this review is to provide the reader with an update of how alterations in mineral metabolism are related to direct and indirect cardiotoxic effects beyond the nephrology setting. RESULTS: Evidence exists that alterations in mineral metabolism that are related to changes in parathyroid hormone (PTH), vitamin D, and the FGF-23-klotho axis have direct pathological consequences for the heart. Alterations in plasma PTH levels are associated with cardiac dysfunction and detrimental cardiac remodelling. Several clinical studies have associated vitamin D deficiency with the prevalence of cardiovascular disease (CV) and its risk factors. Recent evidences support deleterious direct and nonphosphaturic effects of FGF-23 on the heart as hypertrophy development. In contrast, reduced systemic klotho levels are related to CV damage, at least when advanced age is present. In addition, we discuss how these mineral metabolism molecules can counteract each other in some situations, in the context of failed clinical trials on cardiac protection as is the case of vitamin D supplementation. CONCLUSIONS: Among all mineral components, an increase in systemic FGF-23 levels is considered to have the greatest CV impact and risk. However, it is quite possible that many intracellular mechanisms mediated by FGF-23, especially those related to cardiomyocyte function, remain to be discovered.

The inodilator levosimendan in repetitive doses in the treatment of advanced heart failure.

Inotropes may be an appropriate response for some patients with advanced heart failure who remain highly symptomatic despite optimization of evidence-based therapy. These patients need to be supported waiting for a heart transplant or ventricular assist device, or may be candidates for inotropy as an intervention in its own right to maintain a patient in the best achievable circumstances. Objectives in such a situation include relieving symptoms, improving quality of life and reducing unplanned hospitalizations and the costs associated with such admissions. Levosimendan, a calcium sensitizer and potassium channel opener with inotrope and vasodilator actions, has emerged as a potentially valuable addition to the armamentarium in this context, used in repeated or intermittent cycles of therapy. Detailed proposals and guidance are offered for the identification of candidate patients with good prospects of a beneficial response to levosimendan, and for the safe and effective implementation of a course of therapy.

Role of mTOR inhibitors for the control of viral infection in solid organ transplant recipients.

Appropriate post-transplant immunosuppressive regimens that avoid acute rejection, while reducing risk of viral reactivation, have been sought, but remain a chimera. Recent evidence suggesting potential regulatory and antiviral effects of mammalian target of rapamycin inhibitors (mTORi) is of great interest. Although the concept of an immunosuppressive drug with antiviral properties is not new, little effort has been made to put the evidence together to assess the management of immunosuppressive therapy in the presence of a viral infection. This review was developed to gather the evidence on antiviral activity of the mTORi against the viruses that most commonly reactivate in adult solid organ recipients: cytomegalovirus (CMV), polyomavirus, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and hepatitis C virus (HCV). A rapid review methodology and evaluation of quality and consistency of evidence based on the GRADE system was used. The existing literature was variable in nature, although indicating a potential advantage of mTORi in CMV, polyomavirus, and HHV8 infection, and a most doubtful relation with EBV and HCV infection. Several recommendations about the management of these infections are presented that can change certain current patterns of immunosuppression and help to improve the prognosis of the direct and indirect effects of viral infection in solid organ recipients.

Donor/recipient sex mismatch and survival after heart transplantation: only an issue in male recipients? An analysis of the Spanish Heart Transplantation Registry.

The results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 ± 4.1 vs. 24.3 ± 3.7; P < 0.01), and male donors were younger than female donors (33.4 ± 12.7 vs. 38.2 ± 12.3; P < 0.01). No further relevant differences related to donor sex were detected. In the univariate analysis, mismatch was associated with mortality in men (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.06-1.32; P = 0.003) but not in women (HR, 0.91; 95% CI 0.74-1.12; P = 0.4). A significant interaction was detected between sex mismatch and recipient gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with long-term mortality (HR, 1.14; 95% CI 1.01-1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women.

Paediatric celiac patients carrying the HLA-DR7-DQ2 and HLA-DR3-DQ2 haplotypes display small clinical differences.

AIM: The aim of this study was to determine the relevance of HLA-DR7-DQ2 typing in a prospective cohort of paediatric coeliac disease patients from Southern Europe. METHODS: This cross-sectional study tested 249 paediatric patients with coeliac disease. HLA-DR3-DQ2 was typed in combination with HLA-DR7-DQ2 to screen for the HLA-DQ2 haplotype. The histological, analytical and clinical characteristics of the subjects were recorded. RESULTS: A total of 91 coeliac patients were diagnosed: 96.7% carried HLA-DQ2 and 4.4% carried HLA-DQ8. In percentage terms, 80.2% of patients carried HLA-DR3-DQ2 and 34.1% carried HLA-DR7-DQ2. We did not find significant differences between HLA-DR7-DQ2 and HLA-DR3-DQ2 paediatric patients with respect to histological damage and clinical characteristics, except for irritability and weight loss. These characteristics were more frequent in HLA-DQ2trans than in HLA-DQ2cis (22.2% vs. 0.0% [p = 0.035] and 55.6% vs. 21.4% [p = 0.017], respectively). Coeliac-specific autoantibody levels were higher in HLA-DQ2cis than one half of HLA-DQ2trans patients (105.5 vs. 19.2 U/mL, p = 0.014). CONCLUSION: Small clinical differences were found between paediatric coeliac patients carrying HLA-DR7-DQ2 and HLA-DR3-DQ2. For a correct screening of HLA-DQ2, at least in our geographical population, the HLA-DR7-DQ2 haplotype should be typed due to its frequency and clinical presentation.

Triple vasodilator therapy in pulmonary arterial hypertension associated with congenital heart disease.

OBJECTIVE: This study assessed the long-term effects of triple therapy with prostanoids on patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD), as there is limited information on the safety and efficacy of this treatment approach. METHODS: A retrospective cohort study was conducted on patients with PAH-CHD who were actively followed up at our centre. All patients were already receiving dual combination therapy at maximum doses. Clinical characteristics, including functional class (FC), 6-minute walking test distance (6MWTD) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, were documented before initiating triple therapy and annually for a 2-year follow-up period. RESULTS: A total of 60 patients were included in the study, with a median age of 41 years and 68% being women. Of these, 32 had Eisenmenger syndrome, 9 had coincidental shunts, 18 had postoperative PAH and 1 had a significant left-to-right shunt. After 1 year of triple combination initiation, a significant improvement in 6MWTD was observed (406 vs 450; p=0.0027), which was maintained at the 2-year follow-up. FC improved in 79% of patients at 1 year and remained stable in 76% at 2 years. NT-proBNP levels decreased significantly by 2 years, with an average reduction of 199 ng/L. Side effects were experienced by 33.3% of patients but were mostly mild and manageable. Subgroup analysis showed greater benefits in patients without Eisenmenger syndrome and those with pre-tricuspid defects. CONCLUSIONS: Triple therapy with prostanoids is safe and effective for patients with PAH-CHD, improving FC, 6MWTD and NT-proBNP levels over 2 years. The treatment is particularly beneficial for patients with pre-tricuspid defects and non-Eisenmenger PAH-CHD.

N-terminal pro-B-type natriuretic peptide post-discharge monitoring in the management of patients with heart failure and preserved ejection fraction - a randomized trial: The NICE study.

AIMS: There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post-discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) into the post-discharge management of HFpEF patients. METHODS AND RESULTS: Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open-label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT-proBNP monitoring (n = 79) or no access to NT-proBNP (control group, n = 78) during pre-scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT-proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47-2.81, p = 0.760). Regarding secondary endpoints, the NT-proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02-0.98; p = 0.048), whereas non-HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance [Correction added on 29 April 2024, after first online publication: In the preceding sentence, "95% CI 0.02 - 0.09" has been corrected to "95% CI 0.02 - 0.98; p = 0.048" in this version.]. Awareness of NT-proBNP levels were associated with higher doses of diuretics and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers) in the NT-proBNP monitoring group. CONCLUSIONS: Post-discharge monitoring of NT-proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.

Multi-Component Biodegradable Materials Based on Water Kefir Grains and Yeast Biomasses: Effect of the Mixing Ratio on the Properties of the Films.

The use of biopolymeric materials is restricted for some applications due to their deficient properties in comparison to synthetic polymers. Blending different biopolymers is an alternative approach to overcome these limitations. In this study, we developed new biopolymeric blend materials based on the entire biomasses of water kefir grains and yeast. Film-forming dispersions with varying ratios of water kefir to yeast (100/0, 75/25, 50/50 25/75 and 0/100) underwent ultrasonic homogenisation and thermal treatment, resulting in homogeneous dispersions with pseudoplastic behaviour and interaction between both biomasses. Films obtained by casting had a continuous microstructure without cracks or phase separation. Infrared spectroscopy revealed the interaction between the blend components, leading to a homogeneous matrix. As the water kefir content in the film increased, transparency, thermal stability, glass transition temperature and elongation at break also increased. The thermogravimetric analyses and the mechanical tests showed that the combination of water kefir and yeast biomasses resulted in stronger interpolymeric interactions compared to single biomass films. The ratio of the components did not drastically alter hydration and water transport. Our results revealed that blending water kefir grains and yeast biomasses enhanced thermal and mechanical properties. These studies provided evidence that the developed materials are suitable candidates for food packaging applications.

Burden of Illness beyond Mortality and Heart Failure Hospitalizations in Patients Newly Diagnosed with Heart Failure in Spain According to Ejection Fraction.

OBJECTIVE: The objective of this study was to describe the rates of adverse clinical outcomes, including all-cause mortality, heart failure (HF) hospitalization, myocardial infarction, and stroke, in patients newly diagnosed with HF to provide a comprehensive picture of HF burden. METHODS: This was a retrospective and observational study, using the BIG-PAC database in Spain. Adults, newly diagnosed with HF between January 2013 and September 2019 with ≥1 HF-free year of enrolment prior to HF diagnosis, were included. RESULTS: A total of 19,961 patients were newly diagnosed with HF (43.5% with reduced ejection fraction (EF), 26.3% with preserved EF, 5.1% with mildly reduced EF, and 25.1% with unknown EF). The mean age was 69.7 ± 19.0 years; 53.8% were men; and 41.0% and 41.5% of patients were in the New York Heart Association functional classes II and III, respectively. The baseline HF treatments included beta-blockers (70.1%), renin-angiotensin system inhibitors (56.3%), mineralocorticoid receptor antagonists (11.8%), and SGLT2 inhibitors (8.9%). The post-index incidence rates of all-cause mortality, HF hospitalization, and both combined were 102.2 (95% CI 99.9-104.5), 123.1 (95% CI 120.5-125.7), and 182 (95% CI 178.9-185.1) per 1000 person-years, respectively. The rates of myocardial infarction and stroke were lower (26.2 [95% CI 25.1-27.4] and 19.8 [95% CI 18.8-20.8] per 1000 person-years, respectively). CONCLUSIONS: In Spain, patients newly diagnosed with HF have a high risk of clinical outcomes. Specifically, the rates of all-cause mortality and HF hospitalization are high and substantially greater than the rates of myocardial infarction and stroke. Given the burden of adverse outcomes, these should be considered targets in the comprehensive management of HF. There is much room for improving the proportion of patients receiving disease-modifying therapies.

Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period: The multinational randomized LeoDOR trial.

AIM: The LeoDOR trial explored the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute heart failure (HF). METHODS AND RESULTS: In this prospective multicentre, double-blind, two-armed trial, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or matching placebo for 12 weeks. All patients had left ventricular ejection fraction (LVEF) ≤30% during index hospitalization. Levosimendan was administered according to centre preference either as 6 h infusion at a rate of 0.2 µg/kg/min every 2 weeks, or as 24 h infusion at a rate of 0.1 µg/kg/min every 3 weeks. The primary efficacy assessment after 14 weeks was based on a global rank score consisting of three hierarchical groups. Secondary clinical endpoints included the composite risk of tiers 1 and 2 at 14 and 26 weeks, respectively. Due to the COVID-19 pandemic, the planned number of patients could not be recruited. The final modified intention-to-treat analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm), which reduced the statistical power to detect a 20% risk reduction in the primary endpoint to 60%. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint: the mean rank score was 72.55 for the levosimendan group versus 73.81 for the placebo group (p = 0.863). However, there was a signal towards a higher incidence of the individual clinical components of the primary endpoint in the levosimendan group versus the placebo group both after 14 weeks (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.12-7.68; p = 0.021) and 26 weeks (HR 1.64, 95% CI 0.87-3.11; p = 0.122). CONCLUSIONS: Among patients recently hospitalized with HF and reduced LVEF, intermittent levosimendan therapy did not improve post-hospitalization clinical stability.