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.

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.

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.

Pre-discharge and early post-discharge management of patients hospitalized for acute heart failure: A scientific statement by the Heart Failure Association of the ESC.

Acute heart failure is a major cause of urgent hospitalizations. These are followed by marked increases in death and rehospitalization rates, which then decline exponentially though they remain higher than in patients without a recent hospitalization. Therefore, optimal management of patients with acute heart failure before discharge and in the early post-discharge phase is critical. First, it may prevent rehospitalizations through the early detection and effective treatment of residual or recurrent congestion, the main manifestation of decompensation. Second, initiation at pre-discharge and titration to target doses in the early post-discharge period, of guideline-directed medical therapy may improve both short- and long-term outcomes. Third, in chronic heart failure, medical treatment is often left unchanged, so the acute heart failure hospitalization presents an opportunity for implementation of therapy. The aim of this scientific statement by the Heart Failure Association of the European Society of Cardiology is to summarize recent findings that have implications for clinical management both in the pre-discharge and the early post-discharge phase after a hospitalization for acute heart failure.

Patient phenotype profiling in heart failure with preserved ejection fraction to guide therapeutic decision making. A scientific statement of the Heart Failure Association, the European Heart Rhythm Association of the European Society of Cardiology, and the European Society of Hypertension.

Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodium-glucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype-based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence-based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy.

Ferric Carboxymaltose in Iron-Deficient Patients with Hospitalized Heart Failure and Reduced Kidney Function.

BACKGROUND: Reduced kidney function is common among patients with heart failure. In patients with heart failure and/or kidney disease, iron deficiency is an independent predictor of adverse outcomes. In the AFFIRM-AHF trial, patients with acute heart failure with iron deficiency treated with intravenous ferric carboxymaltose demonstrated reduced risk of heart failure hospitalization, with improved quality of life. We aimed to further characterize the impact of ferric carboxymaltose among patients with coexisting kidney impairment. METHODS: The double-blind, placebo-controlled AFFIRM-AHF trial randomized 1132 stabilized adults with acute heart failure (left ventricular ejection fraction <50%) and iron deficiency. Patients on dialysis were excluded. The primary end point was a composite of total heart failure hospitalizations and cardiovascular death during the 52-week follow-up period. Additional end points included cardiovascular hospitalizations, total heart failure hospitalizations, and days lost to heart failure hospitalizations or cardiovascular death. For this subgroup analysis, patients were stratified according to baseline eGFR. RESULTS: Overall, 60% of patients had an eGFR <60 ml/min per 1.73 m 2 (the lower eGFR subgroup). These patients were significantly older, more likely to be female and to have ischemic heart failure, and had higher baseline serum phosphate levels and higher rates of anemia. For all end points, event rates were higher in the lower eGFR group. In the lower eGFR group, the annualized event rates for the primary composite outcome were 68.96 and 86.30 per 100 patient-years in the ferric carboxymaltose and placebo arms, respectively (rate ratio, 0.76; 95% confidence interval, 0.54 to 1.06). The treatment effect was similar in the higher eGFR subgroup (rate ratio, 0.65; 95% confidence interval, 0.42 to 1.02; Pinteraction = 0.60). A similar pattern was observed for all end points ( Pinteraction > 0.05). CONCLUSIONS: In a cohort of patients with acute heart failure, left ventricular ejection fraction <50%, and iron deficiency, the safety and efficacy of ferric carboxymaltose were consistent across a range of eGFR values. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency (Affirm-AHF), NCT02937454 .

Worsening of chronic heart failure: definition, epidemiology, management and prevention. A clinical consensus statement by the Heart Failure Association of the European Society of Cardiology.

Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline-recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice.

A patient with heart failure, who is frail: How does this affect therapeutic decisions?

Patients with heart failure (HF) are heterogeneous, not only related to comorbidities but also in the presentation of frailty syndrome. Frailty syndrome also affects patients with HF across the lifespan. Frailty in patients with HF has a significant impact on clinical features, diagnosis, management, adverse medical outcomes and costs. In everyday clinical practice, frail patients with HF require an individualized approach, often imposing the need to modify therapeutic decisions. The aim of this review is to illustrate how frailty and multimorbidity in HF can affect therapeutic decisions. The scientific evidence underlying this publication was obtained from an analysis of papers indexed in the PubMed database. The search was limited to articles published between 1990 and July 2022. The search was limited to full-text papers published in English. The database was searched for relevant MeSH phrases and their combinations and keywords including: "elderly, frail"; "frailty, elderly"; "frail older adults"; "frailty, older adults"; "adult, frail older"; "frailty, heart failure"; "frailty, multimorbidity"; "multimorbidity, heart failure"; "multimorbidity, elderly"; "older adults, cardiovascular diseases". In therapeutic decisions regarding patients with HF, additionally burdened with multimorbidity and frailty, it becomes necessary to individualize the approach in relation to optimization and treatment of coexisting diseases, frailty assessment, pharmacological and non-pharmacological treatment and in the implementation of invasive procedures in the form of implantable devices or cardiac surgery.