How to tackle therapeutic inertia in heart failure with reduced ejection fraction. A scientific statement of the Heart Failure Association of the ESC.

Guideline-directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF) reduces morbidity and mortality, but its implementation is often poor in daily clinical practice. Barriers to implementation include clinical and organizational factors that might contribute to clinical inertia, i.e. avoidance/delay of recommended treatment initiation/optimization. The spectrum of strategies that might be applied to foster GDMT implementation is wide, and involves the organizational set-up of heart failure care pathways, tailored drug initiation/optimization strategies increasing the chance of successful implementation, digital tools/telehealth interventions, educational activities and strategies targeting patient/physician awareness, and use of quality registries. This scientific statement by the Heart Failure Association of the ESC provides an overview of the current state of GDMT implementation in HFrEF, clinical and organizational barriers to implementation, and aims at suggesting a comprehensive framework on how to overcome clinical inertia and ultimately improve implementation of GDMT in HFrEF based on up-to-date evidence.

Insulin and Metformin Administration: Unravelling the Multifaceted Association with Mortality across Various Clinical Settings Considering Type 2 Diabetes Mellitus and COVID-19.

Due to the molecular mechanisms of action of antidiabetic drugs, they are considered to be effective in the treatment of both COVID-19 and the post-COVID-19 syndromes. The aim of this study was to determine the effect of administering insulin and metformin on the mortality of patients with type 2 diabetes (T2DM) with symptomatic COVID-19 with the use of logistic regression models. The association between death and insulin and metformin was weak and could not be included in the multivariate model. However, the interaction of both drugs with other factors, including remdesivir and low-molecular-weight heparin (metformin), age and hsCRP (insulin), modulated the odds of death. These interactions hint at multifaceted (anti-/pro-) associations of both insulin and metformin with the odds of death, depending on the patient's characteristics. In the multivariate model, RDW-SD, adjusted with low-molecular-weight heparin treatment, age, sex and K+, was associated with mortality among patients with COVID-19 and T2DM. With a 15% increase in RDW-SD, the risk of death increased by 87.7%. This preliminary study provides the foundations for developing further, more personalized models to assess the risk of death in T2DM patients, as well as for identifying patients at an increased risk of death due to COVID-19.

Impact of Synthesis Parameters upon the Electronic Structure in PVD-Deposited CdxZn1-xO Composite Thin Films: An XPS-XANES Investigation.

The impact of different synthesis parameters, such as thickness, postsynthesis annealing temperature, and oxygen gas flow rate, upon the electronic structure is discussed in detail in the present experimental investigation. X-ray photoelectron spectroscopy (XPS) and X-ray absorption near-edge structure (XANES) spectroscopy techniques are used to evaluate the surface electronic properties along with the presence and stability of the CdO2 surface oxide in CdxZn1-xO (x = 0.4) composite thin films. The thin films were synthesized with varying thicknesses using a Cd0.4Zn0.6O (CZO) ceramic and Cd0.4Zn0.6 (CZ) metallic targets and oxygen gas flow rates during magnetron sputtering. The Zn L3,2 edge and O K edge XANES spectra are affected by the oxygen gas flow rate. For the zero rate, an increase in intensity is observed in the Zn L3,2 edge, and notable changes occur in the overall spectral features of the O K edge. In the films synthesized in the presence of oxygen, highly probable O 2p → antibonding Zn 3d electronic transitions decrease the probability of the Zn 2p1/2 → antibonding Zn 3d electronic transition by filling the vacant antibonding Zn 3d states, leading to the reduction in overall intensity in the Zn L3,2 edge. Scanning electron microscopy reveals grain growth with increasing annealing temperature. The annealing induces orbital hybridization, generating new electronic states with higher transition probabilities and intensity enhancement in both Zn L3,2 and O K edges. The presence of the CdO2 surface phase is confirmed by analyzing the Cd 3d5/2 and O 1s XPS core levels. The CdO2 surface phase is observed in the films synthesized using the CZO target for all thicknesses, while the CZ target is only observed for higher thicknesses. Further postsynthesis annealing treatment results in the disappearance of the CdO2 phase. The CdO2 surface phase can be controlled by varying the film thickness and postsynthesis annealing temperature.

Antiplatelet therapy prior to COVID-19 infection impacts on patients mortality: a propensity score-matched cohort study.

One of the major pathomechanisms of COVID-19 is the interplay of hyperinflammation and disruptions in coagulation processes, involving thrombocytes. Antiplatelet therapy (AP) by anti-inflammatory effect and inhibition of platelet aggregation may affect these pathways. The aim of this study was to investigate if AP has an impact on the in-hospital course and medium-term outcomes in hospitalized COVID-19 patients. The study population (2170 COVID-19 patients: mean ± SD age 60 ± 19 years old, 50% male) was divided into a group of 274 patients receiving any AP prior to COVID-19 infection (AP group), and after propensity score matching, a group of 274 patients without previous AP (non-AP group). Patients from the AP group were less frequently hospitalized in the intensive care unit: 9% vs. 15%, 0.55 (0.33-0.94), developed less often shock: 9% vs. 15%, 0.56 (0.33-0.96), and required less aggressive forms of therapy. The AP group had more coronary revascularizations: 5% vs. 1%, 3.48 (2.19-5.55) and strokes/TIA: 5% vs. 1%, 3.63 (1.18-11.2). The bleeding rate was comparable: 7% vs. 7%, 1.06 (0.54-2.06). The patients from the AP group had lower 3-month mortality: 31% vs. 39%, 0.69 (0.51-0.93) and didn't differ significantly in 6-month mortality: 34% vs. 41%, 0.79 (0.60-1.04). When analyzing the subgroup with a history of myocardial infarction and/or coronary revascularization and/or previous stroke/transient ischemic attack and/or peripheral artery disease, AP had a beneficial effect on both 3-month: 37% vs. 56%, 0.58 (0.40-0.86) and 6-month mortality: 42% vs. 57%, 0.63 (0.44-0.92). Moreover, the favourable effect was highly noticeable in this subgroup where acetylsalicylic acid was continued during hospitalization with reduction of in-hospital: 19% vs. 43%, 0.31 (0.15-0.67), 3-month: 30% vs. 54%, 044 (0.26-0.75) and 6-month mortality: 33% vs. 54%, 0.49 (0.29-0.82) when confronted with the subgroup who had acetylsalicylic acid suspension during hospitalization. The AP may have a beneficial impact on hospital course and mortality in COVID-19 and shouldn't be discontinued, especially in high-risk patients.

2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC.

Document Reviewers: Rudolf A. de Boer (CPG Review Co-ordinator) (Netherlands), P. Christian Schulze (CPG Review Co-ordinator) (Germany), Elena Arbelo (Spain), Jozef Bartunek (Belgium), Johann Bauersachs (Germany), Michael A. Borger (Germany), Sergio Buccheri (Sweden), Elisabetta Cerbai (Italy), Erwan Donal (France), Frank Edelmann (Germany), Gloria Färber (Germany), Bettina Heidecker (Germany), Borja Ibanez (Spain), Stefan James (Sweden), Lars Køber (Denmark), Konstantinos C. Koskinas (Switzerland), Josep Masip (Spain), John William McEvoy (Ireland), Robert Mentz (United States of America), Borislava Mihaylova (United Kingdom), Jacob Eifer Møller (Denmark), Wilfried Mullens (Belgium), Lis Neubeck (United Kingdom), Jens Cosedis Nielsen (Denmark), Agnes A. Pasquet (Belgium), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Bianca Rocca (Italy), Xavier Rossello (Spain), Leyla Elif Sade (United States of America/Türkiye), Hannah Schaubroeck (Belgium), Elena Tessitore (Switzerland), Mariya Tokmakova (Bulgaria), Peter van der Meer (Netherlands), Isabelle C. Van Gelder (Netherlands), Mattias Van Heetvelde (Belgium), Christiaan Vrints (Belgium), Matthias Wilhelm (Switzerland), Adam Witkowski (Poland), and Katja Zeppenfeld (Netherlands) All experts involved in the development of this Focused Update have submitted declarations of interest. These have been compiled in a report and simultaneously published in a supplementary document to the Focused Update. The report is also available on the ESC website www.escardio.org/guidelines See the European Heart Journal online for supplementary documents that include evidence tables.

Iron Deficiency in Heart Failure: A Korea-Oriented Review.

Iron deficiency (ID) occurs at high frequency across the spectrum of heart failure (HF), with HF severity and race being potentially important predictors for its development. ID, irrespective of anaemia status, leads to poor outcomes in patients with HF, including exacerbated reduction in exercise capacity, poor quality of life (QoL) and increased risk of HF hospitalisation. As ID has a large public health and economic burden in Asia, and patients hospitalised with acute HF in the Asia Pacific vs. other regions commonly present with more severe clinical symptoms, there is a clear need to identify and treat ID promptly in Asian patients with HF. The biomarkers serum ferritin and transferrin saturation are used for ID diagnosis, and periodic screening is recommended in all patients with HF. The intravenous iron treatments, ferric carboxymaltose (FCM) and ferric derisomaltose, have demonstrated efficacy and tolerability in patients with acute or chronic HF and ID, with FCM shown to be cost-effective (and in some cases cost-saving). Meta-analyses support the likely benefits of intravenous FCM for improving QoL and reducing HF hospitalisation, without reducing mortality risk in patients with HF and ID. Accordingly, European Society of Cardiology guidelines recommend considering intravenous FCM for patients with symptomatic HF with left ventricular ejection fraction ≤50% who were recently hospitalised for HF and have ID. Although analyses of Asian patients with HF and ID are limited, the effects of intravenous iron would be expected to be similar to that in White populations; further clarifying studies may be of interest.

Usefulness of the Veterans Health Administration COVID-19 (VACO) Index for Predicting Short-Term Mortality among Patients of the COLOS Study.

Advanced age is known to be a predictor with COVID-19 severity. Understanding of other disease progression factors may shorten the time from patient admission to applied treatment. The Veterans Health Administration COVID-19 (VACO index) was assumed to additionally anticipate clinical results of patients hospitalized with a proven infection caused by the SARS-CoV-2 virus. METHODS: The medical records of 2183 hospitalized patients were retrospectively analyzed. Patients were divided into four risk-of-death categories: low risk, medium risk, high-risk, and extreme risk depending on their VACO index calculation. RESULTS: Significant differences in the mortality at the hospital after three months of discharge and six months after discharge were noticed. For the patients in the extreme-risk group, mortality reached 37.42%, 62.81%, and 78.44% for in-hospital, three months of discharge, and six months of discharge, respectively. The mortality marked as high risk reached 20.38%, 37.19%, and 58.77%. Moreover, the secondary outcomes analysis acknowledged that patients classified as extreme risk were more likely to suffer from cardiogenic shock, myocardial infarction, myocardial injury, stroke, pneumonia, acute kidney injury, and acute liver dysfunction. Patients at moderate risk were more often admitted to ICU when compared to other patients. CONCLUSIONS: The usage of the VACO index, combined with an appropriate well-defined medical interview and past medical history, tends to be a helpful instrument in order to predict short-term mortality and disease progression based on previous medical records.

Intravenous iron supplementation improves energy metabolism of exercising skeletal muscles without effect on either oxidative stress or inflammation in male patients with heart failure with reduced ejection fraction.

BACKGROUND: Skeletal muscle dysfunction is a feature of heart failure (HF). Iron deficiency (ID) is prevalent in patients with HF associated with exercise intolerance and poor quality of life. Intravenous iron in iron deficient patients with HF has attenuated HF symptoms, however the pathomechanisms remain unclear. The aim of study was to assess whether intravenous iron supplementation as compared to placebo improves energy metabolism of skeletal muscles in patients with HF. METHODS: Men with heart failure with reduced ejection fraction (HFrEF) and ID were randomised in 1:1 ratio to either intravenous ferric carboxymaltose (IV FCM) or placebo. In vivo reduction of lactates by exercising skeletal muscles of forearm was analyzed. A change in lactate production between week 0 and 24 was considered as a primary endpoint of the study. RESULTS: There were two study arms: the placebo and the IV FCM (12 and 11 male patients with HFrEF). At baseline, there were no differences between these two study arms. IV FCM therapy as compared to placebo reduced the exertional production of lactates in exercising skeletal muscles. These effects were accompanied by a significant increase in both serum ferritin and transferrin saturation in the IV FCM arm which was not demonstrated in the placebo arm. CONCLUSIONS: Intravenous iron supplementation in iron deficient men with HFrEF improves the functioning of skeletal muscles via an improvement in energy metabolism in exercising skeletal muscles, limiting the contribution of anaerobic reactions generating ATP as reflected by a lower in vivo lactate production in exercising muscles in patients with repleted iron stores.

Diagnosis and treatment of transthyretin amyloidosis cardiomyopathy: A position statement of the Polish Cardiac Society.

Considering the rare incidence of transthyretin amyloidosis cardiomyopathy (ATTR-CM) in Poland, patients encounter difficulties at the stages of diagnosis and treatment. For successful diagnosis, it is vital to raise the suspicion of ATTR-CM, that is, to identify typical clinical scenarios such as heart failure with preserved ejection fraction or the red flags of amyloidosis. In most cases, it is possible to establish the diagnosis on the basis of noninvasive tests. This article presents the recommended diagnostic algorithms including laboratory workup, imaging tests (in particular, isotope scanning), and genetic tests. Since ATTR-CM should be differentiated from light chain amyloidosis, we also discuss aspects related to hematological manifestations and invasive diagnosis. We describe neurological signs and symptoms in patients with amyloidosis and present therapeutic options, including the causative treatment of ATTR-CM with the only currently approved drug, tafamidis. We also discuss drugs that are being assessed in ongoing clinical trials. We outline differences in the symptomatic treatment of heart failure in ATTR-CM and recommendations for nonpharmacological treatment and monitoring of the disease. Finally, we underline the need for providing access to the causative treatment with tafamidis as part of a drug program, as in other rare diseases, so that patients with ATTR-CM can be treated according to the European Society of Cardiology guidelines on heart failure and cardiomyopathy.

Association of serum vitamin D concentration with the final course of hospitalization in patients with COVID-19.

Background: Vitamin D deficiency is a substantial public health problem. The present study evaluated the association between vitamin D concentration and hospitalization and mortality risk in patients with coronavirus disease 19 (COVID-19). Methods: This study used the COronavirus in LOwer Silesia (COLOS) dataset collected between February 2020 and June 2021. The medical records of 474 patients with confirmed severe acute respiratory syndrome 2 (SARS-CoV-2) infection, and whose vitamin D concentration was measured, were analyzed. Results: We determined a significant difference in vitamin D concentration between discharged patients and those who died during hospitalization (p = 0.0096). We also found an effect of vitamin D concentration on the risk of death in patients hospitalized due to COVID-19. As vitamin D concentration increased, the odds ratio (OR) for death slightly decreased (OR = 0.978; 95% confidence interval [CI] = 0.540-0.669). The vitamin D concentration cutoff point was 15.40 ng/ml. In addition, patients with COVID-19 and serum 25-hydroxyvitamin D (25(OH)D) concentrations < 30 ng/ml had a lower survival rate than those with serum 25(OH)D ≥ 30 ng/ml (log-rank test p = 0.0018). Moreover, a Cox regression model showed that patients with an estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 and higher vitamin D concentrations had a 2.8% reduced risk of mortality (hazard ratio HR = 0.972; CI = 0.95-0,99; p = 0.0097). Conclusions: The results indicate an association between 25(OH)D levels in patients with COVID-19 and the final course of hospitalization and risk of death.

Iron Status and Short-Term Recovery after Non-Severe Acute Myocarditis: A Prospective Observational Study.

Pathomechanisms responsible for recovery from acute myocarditis (MCD) or progression to non-ischemic cardiomyopathy have not been comprehensively investigated. Iron, positioned at the crossroads of inflammation and the energy metabolism of cardiomyocytes, may contribute to the pathophysiology of inflammatory myocardial disease. The aim of this study was to evaluate whether systemic iron parameters are related to myocardial dysfunction in MCD patients. We prospectively enrolled 42 consecutive patients hospitalized for MCD. Their iron status and their clinical, laboratory, and echocardiographic indices were assessed during hospitalization and during ambulatory visits six weeks after discharge. A control group comprising healthy volunteers was recruited. The MCD patients had higher serum ferritin and hepcidin and lower serum iron concentration and transferrin saturation (TSAT) than the healthy controls (all p < 0.01). Six weeks after discharge, the iron status of the MCD patients was already comparable to that of the control group. During hospitalization, lower serum iron and TSAT correlated with higher NT-proBNP (both p < 0.05). In-hospital lower serum iron and TSAT correlated with both a lower left ventricular ejection fraction (LVEF) and worse left ventricular global longitudinal strain at follow-up visits (all p < 0.05). In conclusion, in patients with acute MCD, iron status is altered and normalizes within six weeks. Low serum iron and TSAT are related to greater in-hospital neurohormonal activation and subtle persistent left ventricular dysfunction.

Telemedicine in Heart Failure in the COVID-19 and Post-Pandemic Era: What Have We Learned?

Numerous studies showed that patients with heart failure (HF) and COVID-19 are at high risk of in-hospital complications and long-term mortality. Changes in the organisation of the medical system during the pandemic also worsened access to standard procedures, increasing the general mortality in HF and forcing the systems to be reorganised with the implementation and development of telemedical technologies. The main challenges for HF patients during the pandemic could be solved with new technologies aimed to limit the risk of SARS-CoV-2 transmission, optimise and titrate the therapy, prevent the progression and worsening of HF, and monitor patients with acute HF events in the course of and after COVID-19. Dedicated platforms, phone calls or video conferencing and consultation, and remote non-invasive and invasive cardiac monitoring became potential tools used to meet the aforementioned challenges. These solutions showed to be effective in the model of care for patients with HF and undoubtedly will be developed after the experience of the pandemic. However, the multitude of possibilities requires central coordination and collaboration between institutes with data protection and cost reimbursement to create effective mechanisms in HF management. It is crucial that lessons be learned from the pandemic experience to improve the quality of care for HF patients.

Efficacy of ferric carboxymaltose in heart failure with iron deficiency: an individual patient data meta-analysis.

BACKGROUND AND AIMS: Whereas a beneficial effect of intravenous ferric carboxymaltose (FCM) on symptoms and exercise capacity among patients with iron deficiency and heart failure (HF) has been consistently demonstrated, the effects of treatment on clinical events remain the subject of research. This meta-analysis aimed to characterize the effects of FCM therapy on hospitalizations and mortality. METHODS: Patient-level data from randomized, placebo-controlled FCM trials including adults with HF and iron deficiency with ≥52 weeks follow-up were analysed. The co-primary efficacy endpoints were (i) composite of total/recurrent cardiovascular hospitalizations and cardiovascular death and (ii) composite of total HF hospitalizations and cardiovascular death, through 52 weeks. Key secondary endpoints included individual composite endpoint components. Event rates were analysed using a negative binomial model. Treatment-emergent adverse events were also examined. RESULTS: Three FCM trials with a total of 4501 patients were included. Ferric carboxymaltose was associated with a significantly reduced risk of co-primary endpoint 1 (rate ratio 0.86; 95% confidence interval 0.75-0.98; P = .029; Cochran Q: 0.008), with a trend towards a reduction of co-primary endpoint 2 (rate ratio 0.87; 95% confidence interval 0.75-1.01; P = .076; Cochran Q: 0.024). Treatment effects appeared to result from reduced hospitalization rates, not improved survival. Treatment appeared to have a good safety profile and was well tolerated. CONCLUSIONS: In iron-deficient patients with HF with reduced left ventricular ejection fraction, intravenous FCM was associated with significantly reduced risk of hospital admissions for HF and cardiovascular causes, with no apparent effect on mortality.

Intravenous ferric carboxymaltose for iron repletion following acute heart failure in patients with and without diabetes: a subgroup analysis of the randomized AFFIRM-AHF trial.

BACKGROUND: In AFFIRM-AHF, treatment of iron deficiency with intravenous ferric carboxymaltose (FCM) reduced the risk of heart failure (HF) hospitalization and improved quality of life (QoL) vs placebo in patients stabilized following an acute HF (AHF) episode, with no effect on cardiovascular (CV) death. Diabetes and iron deficiency frequently accompany AHF. This post hoc analysis explored the effects of diabetes on outcomes in AFFIRM-AHF patients. METHODS: Patients were stratified by diabetes yes/no at baseline. The effects of FCM vs placebo on primary (total HF hospitalizations and CV death) and secondary (total CV hospitalizations and CV death; CV death; total HF hospitalizations; time to first HF hospitalization or CV death; and days lost due to HF hospitalizations or CV death) endpoints at Week 52 and change vs baseline in disease-specific QoL (12-item Kansas City Cardiomyopathy Questionnaire [KCCQ-12]) at Week 24 were assessed by subgroup. For each endpoint, the interaction between diabetes status and treatment outcome was explored. RESULTS: Of 1108 AFFIRM-AHF patients, 475 (FCM: 231; placebo: 244) had diabetes and 633 (FCM: 327; placebo: 306) did not have diabetes. Patients with diabetes were more commonly male (61.5% vs 50.9%), with a higher frequency of ischemic HF etiology (57.9% vs 39.0%), prior HF history (77.7% vs 66.5%), and comorbidities (including previous myocardial infarction [49.3% vs 32.9%] and chronic kidney disease [51.4% vs 32.4%]) than those without diabetes. The annualized event rate/100 patient-years with FCM vs placebo for the primary endpoint was 66.9 vs 80.9 in patients with diabetes (rate ratio [RR]: 0.83, 95% CI 0.58-1.81) and 51.3 vs 66.9 in patients without diabetes (RR: 0.77, 95% CI 0.55-1.07), with no significant interaction between diabetes status and treatment effect (pinteraction = 0.76). Similar findings were observed for secondary outcomes. Change from baseline in KCCQ-12 overall summary score was numerically greater with FCM vs placebo at almost all time points in both subgroups, with no interaction between diabetes and treatment effect at Week 24. CONCLUSIONS: The clinical and QoL benefits observed with intravenous FCM in patients with iron deficiency following stabilization from an AHF episode are independent of diabetes status. Trial registration Clinicaltrials.gov, NCT02937454 (registered 10.18.2016).

Expert opinion of the Heart Failure Association of the Polish Society of Cardiology, the College of Family Physicians in Poland, and the Polish Society of Family Medicine on the peri discharge management of patients with heart failure.

Despite advances in the treatment of heart failure (HF), the rate of hospitalisation for exacerbations of the disease remains high. One of the underlying reasons is that recommended guidelines for the management of HF are still too rarely followed in daily practice. Disease exacerbation requiring inpatient treatment is always afactor that worsens the prognosis, and thus signals disease progression. This is also akey moment when therapy should be modified for HF exacerbation, or initiated in the case of newly diagnosed disease. Inpatient treatment and the peri­discharge period is the time when the aetiology and mechanism of HF decompensation should be established. Therapy should be individualised based on aetiology, HF phenotype, and comorbidities; it should take into account the possibilities of modern treatment. According to the recommendations of the European Society of Cardiology (ESC), patients with HF should receive multidisciplinary management. Cooperation between the various members of the multidisciplinary team taking care of patients with HF improves the efficiency and quality of treatment. This document expands and details the information on the peri­discharge management of HF contained in the 2021 ESC guidelines and the 2022 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of America (HFSA) guidelines.