Background: Left Ventricle Myocardial Work (LVMW) has shown utility in assessing patients with aortic stenosis (AS) in recent studies. In the present study, we evaluated the predictive value and optimal cut-off values of LVMW parameters measured prior to TAVI that may be associated with increased mortality in AS patients. Methods: A total of 116 consecutive patients who were qualified for TAVI between March 2021 and November 2022 were evaluated. Pre-procedural LVMW indices (GWI, GCW, GWW, and GWE) were assessed and long-term survival was analysed. Survival and influencing factors were evaluated using univariate and multivariate Cox proportional hazard models, with significant factors subsequently included in cut-off analysis. Results: The median survival time following the TAVI procedure was 1404 (1143-1549) days, with a maximum observation period of 1721 days. All-cause mortality during the follow-up period reached 29%. Multivariate analysis revealed that EF, GLS, GWI, GWE and GCW before TAVI were independent predictors of all-cause mortality. We identified 1975 mmHg, 1497 mmHg and 85% as optimal cut-off values for GCW, GWI and GWE, which allow for significant stratification of patients according to risk. Conclusions: In this analysis, baseline-assessed parameters such as GLS, GWI, GWE, and GCW emerged as independent predictors of all-cause mortality. The proposed cut-off values clearly separated patient groups with different survival outcomes.

Background: Sepsis has heterogeneous etiologies. Although bacteria are the most common causative agents, viral and yeast forms of sepsis also occur. Procalcitonin (PCT) is widely used to monitor severe bacterial infections and may support the differential diagnosis of infection etiology. Methods: We evaluated the diagnostic value of PCT in viral sepsis using PCT levels at ICU admission and PCT kinetics during ICU treatment. Results: During the COVID-19 pandemic, 191 adult ICU patients with sepsis and a positive SARS-CoV-2 PCR test at hospital admission were included and classified into two groups according to the presence or absence of bacterial or yeast co-infection. PCT showed a distinct diagnostic pattern influenced by the presence of co-infection. PCT remained low in isolated viral sepsis, whereas elevated concentrations were associated with superimposed bacterial or yeast co-infection and worse clinical outcomes. Overall mortality was significantly lower in patients with isolated viral sepsis compared to those with co-infection (50 vs. 69%, p = 0.009). Conclusions: In viral sepsis, persistently low PCT concentrations argue against bacterial co-infection, whereas elevated or rising values should prompt increased diagnostic evaluation. Although PCT provides clinically relevant diagnostic information, it must be interpreted cautiously and in conjunction with clinical assessment and microbiological data. PCT should serve as an adjunctive, not a standalone, marker of infection etiology in sepsis.

Abstract Aims Cardiogenic shock (CS) is the deadliest manifestation of acute heart failure, with persistently high mortality rates and a lack of recent therapeutic breakthroughs. Accurate risk prediction is crucial in clinical decision‐making and the design of future clinical trials. We aimed to validate the CLIP score, a biomarker‐based risk score comprising cystatin C, lactate, interleukin‐6 and NT‐proBNP, for predicting mortality in acute coronary syndrome (ACS) related CS, and to compare its predictive value with the previously published CardShock risk score. Methods and results The study is a post hoc analysis of the CardShock Study, a prospective, observational European multicentre study on CS. The CLIP score was calculated 12 h after hospital admission, and its ability to predict 90‐day mortality was assessed using are under the curve (AUC) of the receiver‐operating characteristics (ROC) curve analysis. The discriminative ability of the CLIP score was compared with the CardShock risk score by comparing the AUC's. The cohort was dichotomized into low and high risk groups by the optimal cut‐off value derived from the ROC analysis of the CLIP score. Kaplan–Meier curves were constructed to evaluate risk stratification when combining the CLIP and CardShock risk scores. The cohort (n = 121) comprised 77% (n = 93) men and the median age was 67 years (IQR 61–76). A total of 21% (n = 25) of the patients had non‐ACS related CS. The CLIP score demonstrated appropriate predictive accuracy for 90‐day mortality (AUC 0.84, 95% CI 0.77–0.91), comparable with the CardShock risk score (AUC 0.77 [95% CI 0.69–0.85]; P = 0.064 for comparison). A CLIP score cut‐off of 0.28 stratified patients into high risk (65% mortality) and low risk (16% mortality) groups. In addition, incorporating the CLIP score enhanced risk stratification in all CardShock risk score categories. Conclusions The CLIP score, calculated within 12 h of hospital admission, accurately predicted 90‐day mortality in CS and complemented the CardShock risk score. The biomarker‐based score has potential utility in dynamic mortality risk assessment and could inform clinical management and trial design.

AIMS:The Heart Failure Frailty Score (HFFS) is a novel, multidimensional tool to assess frailty in patients with heart failure (HF). It has been developed to overcome limitations of existing frailty assessment tools while being practical for clinical use. The HFFS reflects the concept of frailty as a multidimensional, dynamic and potentially reversible state, which increases vulnerability to stressors and risk of poor outcomes in patients with HF. METHODS AND RESULTS:The HFFS was developed through a Delphi consensus process involving 54 international experts. This approach involved iterative rounds of questionnaires and interviews, where a panel of experts provided their opinions on specific questions prepared by the Steering Committee. The experts were invited to vote and share their views anonymously, using a 5-point Likert scale over iterative rounds. An 80% threshold was set for agreement or disagreement for each statement. Twenty-two variables from four domains (clinical, functional, psycho-cognitive and social) have been selected for inclusion in the HFFS after the third round of the Delphi process. A shorter version (S-HFFS), including 10 variables, has also been developed for daily clinical use. CONCLUSIONS:The HFFS is a new multidimensional tool for the identification of frailty in patients with HF. It should also enables healthcare providers to identify potential 'red flags' for frailty in order to develop personalized care plans. The next step will be to validate the new score in patients with HF.

BACKGROUND:Before the development of disease-modifying therapies for transthyretin amyloidosis cardiomyopathy (ATTR-CM), N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and troponin I/T were recognized as independent prognostic biomarkers of mortality. This study evaluated the prognostic value of these biomarkers in a contemporary patient population and the impact of vutrisiran, an RNA interference therapeutic that rapidly knocks down circulating transthyretin, on biomarker levels. OBJECTIVES:This study sought to evaluate the association between risk of cardiovascular events and all-cause mortality with baseline NT-proBNP and troponin I levels and changes from baseline at month 6 in patients from HELIOS-B and explore how vutrisiran impacts biomarkers over time. METHODS:In HELIOS-B, a double-blind, placebo-controlled study, 655 patients with ATTR-CM were randomized 1:1 to receive vutrisiran or placebo for up to 36 months. The primary endpoint was a composite outcome of all-cause mortality and recurrent cardiovascular events. All-cause mortality through 42 months was a secondary endpoint. NT-proBNP and troponin I were assessed as prespecified exploratory endpoints. RESULTS:Baseline NT-proBNP and troponin I levels were independently associated with risks of the composite outcome and all-cause mortality (P < 0.0001 for both biomarkers and endpoints). At month 6, increases in NT-proBNP from baseline were associated with higher risk of the composite outcome and all-cause mortality, and decreases in troponin I were associated with a lower risk of the composite outcome. At month 30, the median changes from baseline of NT-proBNP and troponin I were 753 pg/mL (Q1-Q3: -8 to 2,573 pg/mL) and 9.7 pg/mL (Q1-Q3: -6.3 to 41.2 pg/mL) in the placebo arm and 118 pg/mL (Q1-Q3: -419 to 911 pg/mL) and -5.8 pg/mL (Q1-Q3: -25.0 to 10.0 pg/mL) in the vutrisiran arm. The geometric mean fold-change ratios (vutrisiran/placebo) were 0.68 (95% CI: 0.61-0.76) for NT-proBNP and 0.68 (95% CI: 0.62-0.75) for troponin I (P < 0.0001 for both). CONCLUSIONS:Patterns of associations between biomarkers and adverse outcomes support the importance of early treatment initiation and the potential for risk reduction in patients with ATTR-CM. Vutrisiran maintained stable or reduced levels of both biomarkers consistent with the benefit of treatment in reducing the risk of cardiovascular events and all-cause mortality. (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149).

PURPOSE:Cardiovascular risk factors, particularly obesity, are strong predictors of poor COVID-19 outcomes, though prognosis remains uncertain for overweight individuals. Identifying new tools to assess obesity's impact on COVID-19 severity is vital for early risk stratification. We evaluated the C2HEST-score system's ability to predict unfavorable outcomes in hospitalized COVID-19 patients. MATERIAL AND METHODS:Consecutive 2183 patients hospitalized due to confirmed COVID-19 were enrolled to this study. Based on the physical examination and past medical history, 332 carefully selected patients were assigned to one of two of the study cohorts, i.e. obese (n ​= ​191) vs. non-obese (n ​= ​141), and allocated to different risk-strata based on the C2HEST score result. RESULTS:A total of 52 in-hospital deaths (27.2 ​%) were reported in the obese cohort, while in the non-obese cohort the in-hospital mortality rate was 17 ​% (24 reported cases). The in-hospital, 3-month and 6-month mortality were the highest in the high-risk C2HEST stratum in both study cohorts, reaching respectively 47.62 ​%, 57.14 ​%, and 57.14 ​% in the obese and 63.64 ​%, 72.73 ​%, and 88.89 ​% in the non-obese cohorts. Among patients with the high-risk C2HEST-score, non-obese individuals were more likely to experience myocardial injury and acute heart failure, whereas obese individuals were more prone to develop acute kidney injury. CONCLUSIONS:This study shows the usefulness and performance of the C2HEST-score in predicting the adverse outcomes of COVID-19 in hospitalized patients with obesity. In the cohort with normal body mass, the C2HEST score revealed to be far more precise in the risk prediction.

Rotational atherectomy (RA) is an established technique for modifying heavily calcified and fibrotic coronary artery lesions. Despite its efficacy, the use of a high-speed rotating burr can provoke platelet activation and endothelial injury, thereby increasing thrombotic risk, promoting inflammation, and impairing vascular healing. This study investigated the effects of RA and its procedural characteristics on endothelial function and platelet activation by assessing circulating biomarkers. We prospectively analyzed 34 patients undergoing elective RA at a tertiary center. Blood samples were obtained before and 12–24 h after the procedure. Plasma levels of soluble E-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), platelet factor 4 (PF4), P-selectin, and cluster of differentiation 40 ligand (CD40L) were measured. The study population had a mean age of 71 ± 8.9 years, and 73.8% were male. Cardiovascular comorbidities were prevalent, including diabetes (61.9%), hypertension (92.9%), hypercholesterolemia (42.9%), heart failure (45.2%), atrial fibrillation (21.4%), prior PCI (81%), and prior CABG (11.9%). RA significantly increased levels of P-selectin (55.5 ± 26.1 vs. 68.9 ± 26.5, p < 0.001), CD40L (2261.3 ± 2489.9 vs. 3602.0 ± 2428.5, p = 0.01), and PF4 (6054.7 ± 5751.8 vs. 10,877.6 ± 4979.7, p < 0.001). Moreover, mean burr speed correlated with CD40L elevation, while burr-to-artery ratio correlated with E-selectin increase (all p < 0.05). RA induces significant platelet activation and endothelial injury, with biomarker changes suggesting correlation with procedural parameters. These findings highlight the biological impact of RA and may inform strategies to optimize the safety of complex PCI.

In the 2021 European Society of Cardiology (ESC) heart failure (HF) guidelines, sodium-glucose cotransporter 2 (SGLT2) inhibitors were recommended for the prevention of HF in patients with type 2 diabetes mellitus (T2DM) and for the treatment of HF with reduced ejection fraction (HFrEF). Further trials showed efficacy of empagliflozin and dapagliflozin in patients with HF with preserved ejection fraction (HFpEF). These results prompted a broadened recommendation for the SGLT2 inhibitors dapagliflozin or empagliflozin across the whole left ventricular ejection fraction (LVEF) spectrum in the 2023 Focused Update of the ESC HF guidelines and in other international guidelines. In SOLOIST-WHF and EMPULSE, sotagliflozin (enrolling only patients with T2DM) and empagliflozin, respectively, were beneficial when initiated at the end or soon after an episode of decompensated HF. Based on these results and on the early appearance of their beneficial effects, the administration of SGLT2 inhibitors should start early in patients hospitalized for acute HF. Analyses after study drug withdrawal in randomized clinical trials have shown that their benefits may decline rapidly after discontinuation, and thus, persistence of treatment is advised. In EMPACT-MI, empagliflozin did not reduce the primary outcome of cardiovascular (CV) death/HF hospitalization but reduced first/recurrent HF hospitalizations. Potential benefits of SGLT2 inhibitors in further specific conditions (i.e., cardiac amyloidosis, grown-up congenital heart disease and paediatric patients with HF) have been reported in observational studies but need confirmation from prospective trials. This scientific statement summarizes current evidence regarding the effects of SGLT2 inhibitors for the prevention and treatment of HF.

The aim of this study was to evaluate and update the effects of immunosuppressive therapy on heart failure outcomes in patients aged 16 years or older with biopsy-proven inflammatory myocardial disease. We performed a systematic review and an aggregate data meta-analysis of studies evaluating the effects of such therapy in acute and chronic myocarditis or inflammatory dilated cardiomyopathy. Studies were chosen based on criteria related to clinical relevance for therapeutic decisions and measured outcomes in left ventricular ejection fraction (LVEF) and New York Heart Association classification (NYHA) at 3, 6, and 12 months. Data sources included PubMed, Embase, Ovid, and ClinicalTrials.gov, with manual reference checks. Data extraction and risk-of-bias assessments were performed by two independent reviewers. We used a random-effects model and assessed heterogeneity with I2 and τ2 statistics. . Seven eligible studies with a total of 594 patients were included, that investigated clinical course of acute and chronic myocarditis and inflammatory dilated cardiomyopathy. At 3 months, the pooled standardized mean difference (SMD) for LVEF was 0.97 (95% CI –0.05 to 1.99; p > 0.05). At 6 months, the pooled SMD was 0.48 (95% CI –1.31 to 2.28), and at 12 months, –0.01 (95% CI –1.65 to 1.62). For NYHA classification, pooled SMDs were 0.02 (95% CI –0.21 to 0.25) at 3 months and –0.22 (95% CI –1.56 to 1.11) at 12 months. In all cases, confidence intervals crossed zero. Heterogeneity remained high (I2 = 92–97%), reflecting substantial variability across studies. In patients with acute or chronic myocarditis or inflammatory dilated cardiomyopathy, immunosuppressive therapy does not improve key echocardiographic or clinical parameters when adding new data from randomized controlled trials (RCTs). High heterogeneity suggests variability in patient populations and protocols, highlighting the need for well-designed RCTs. There is still no evidence to support routine endomyocardial biopsy in non-severe disease, as it will not impact symptomatic treatment, even if inflammation is present.

Introduction:During the SARS-CoV-2 pandemic, intensive efforts have been made to identify COVID-19 outcome predictors. The C2HEST score, used to predict the atrial fibrillation risk, reflects the presence of comorbidities. This study aimed to demonstrate the usefulness of this score in predicting COVID-19 outcomes in hospitalized individuals. Material and methods:2184 medical records of subjects hospitalized due to COVID-19 between February 2020 and June 2021 were analyzed. Subjects were categorized into low/medium/high-risk categories according to the C2HEST score. Outcomes included: in-hospital-, 3- and 6-month-all-cause-mortality, non-fatal hospitalization endpoints, and other in-hospital events. Results:598 deaths (27.4%), including 326 in-hospital (15%), were reported. All types of mortality were highest in the high-risk stratum (35.4%, 54.4%, 56.9%, respectively), and lowest in the low-risk stratum (8.4%, 15%, 37.5%, respectively). The ROC revealed that C2HEST allows one to predict 1-month mortality (AUC30 70.7) and remained at a similar level after 3- and 6-month observation (AUC90 = 72.0 and AUC180 = 67). The p-value for the log-rank test comparing survival curves was < 0.0001. An increase of one C2HEST point raised the overall death rate 1.4-fold. A change from the low- to medium-risk increased the death rate 3.4 times, while between the low- and high-risk-stratum the hazard ratio was 5.0. The C2HEST score also revealed predictive value for pneumonia, sepsis, cardiogenic shock, myocardial injury, acute heart failure, kidney/liver injury, stroke, and gastrointestinal bleeding. Conclusions:The C2HEST score can predict COVID-19 outcomes in hospitalized subjects. This simple score, based on comorbidities, may address medical needs in the risk stratification of COVID19 patients.

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.

Iron deficiency (ID) is present in approximately 50% of patients with heart failure (HF) and even higher prevalence rate up to 80% in post-acute HF setting. The current guidelines for HF recommend intravenous (IV) iron replacement in HF with reduced or mildly reduced ejection fraction and ID based on clinical trials showing improvements in quality of life and exercise capacity, and an overall treatment benefit for recurrent HF hospitalization. However, several barriers cause challenges in implementing IV iron supplementation in practice due, in part, to clinician knowledge gaps and limited resource availability to protocolize routine utilization in appropriate patients. Thus, the current review will discuss practical considerations in ID treatment, implementation of evidence-based ID treatment to improve regional health disparities with toolkits, inclusion/exclusion criteria of IV iron supplementation, and clinical controversies in ID treatment, as well as gaps in evidence and questions to be answered.

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.

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.

Abstract Background and Aims Although decreased exercise capacity (due to dyspnea or angina-like symptoms) constitutes the fundamental characteristics of hypertrophic cardiomyopathy (HCM), the pathophysiology of these symptoms remains only partly understood. We investigated clinical and functional determinants of decreased exercise capacity in a broad range of HCM patients irrespective of primary disease aetiology (either genetic disorder or e.g. infiltrative phenocopies in the course of cardiac amyloidosis), overt heart failure (HF) and the presence of haemodynamically significant left ventricular outflow tract obstruction (LVOTO). Further, we deterimined the contribution of skeletal and respiratory muscle weakness to decresed exercise capacity. Methods We analyzed clinical data and functional assessments (skeletal and respiratory muscle strength, physical fitness) in relation to symptomatology and sub-maximal exercise capacity in 82 clinically stable patients with HCM (females: 32 %; age: 62±16 years; left ventricular ejection fraction [LVEF] 59±7%; intraventricular septum wall thickness [IVS] 19±4 mm; median plasma N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 818 pg/mL [lower and upper quartile: 208-1917]; New York Heart Association [NYHA] class 0/I/II/III: 38/18/33/11 % [0 indicates no HF]; significant LVOTO: 29%). Results HCM patients with more severe symptomatology (NYHA class II-III vs 0-I) were older, had more frequently significant LVOTO and greater comorbidity burden, and had higher NT-proBNP and worse estimated renal function (all p≤0.03). Gender distribution, percentage of beta-blocker therapy and implanted device, body mass index, major echocardiography parameters (including LVEF, left ventricular end-diastolic diameter and IVS), high-sensitive (hs) cardiac troponin type I and hs-C-reactive protein were comparable in these 2 groups of subjects (all p>0.05). In multivariable linear regression models more advanced age, higher circulating natriuretic peptides (NT-proBNP) and previous coronary revascularization were independent predictors of more advanced NYHA class (standardized β-coefficient=0.30, p<0.01; β=0.27, p<0.01; and β=0.22, p<0.05; respectively). Similarly, more advanced age, female sex and higher NT-proBNP were independent correlates of shorter distance in 6-minute walking test (6MWT) (β=-0.46, p<0.001; β=-0.26, p<0.001; and β=-0.36, p<0.001; respectively). All analyzed muscle parameters (including respiratory muscle strength parameters) and objective measures of physical fitness (Functional Fitness Test for older adults) remained independently associated with 6MWT distance (all p<0.001) when adjusted for aforementioned clinical and laboratory correlates of 6MWT. Conclusions Muscle weakness and low physical fitness are related to decreased exercise capacity in HCM and may be potential therapeutic targets to alleviate disease symptoms also in non-obstructive HCM phenotype.

The COVID-19 pandemic has revealed that viruses can have multiple receptor properties, penetrating various tissues and causing mutations in various genes, thus promoting a range of metabolic disorders. The purpose of this study was to investigate the connection between three factors: diabetic status, pre-hospitalization oxygen therapy, and saturation levels, to the values of morphological, inflammatory, and biochemical parameters in the blood serum of COVID-19 patients. The study group consisted of 2139 patients, 1076 women (50.30%) and 1063 men (49.70%), with an average age of 63.73 ± 15.69 years. The population was divided into three groups based on a three-stage scale, taking into account patients with either type 2 diabetes/prediabetes (473 patients), those who received oxygen therapy before hospitalization, and those with a saturation value of below 95% (cut-off value). Among patients who did not receive pre-hospitalization oxygen therapy, those with diabetes and a SpO2 level < 95% had significantly higher levels of D-dimers, procalcitonin, albumin, lymphocytes, RDW-SD ≥ 47, potassium, creatinine, and troponin T when compared to diabetic patients with a SpO2 level ≥ 95%. Similarly, in the same group of patients without pre-hospitalization oxygen therapy, those without diabetes but with a SpO2 level < 95% showed significantly increased levels of IL-6, CRP, albumin, lymphocytes, RDW-SD ≥ 47, glucose, potassium, sodium, creatinine, and ALT, compared to patients without diabetes and with a SpO2 level ≥ 95%. The findings suggest that lower saturation levels may result in increased potassium and glucose levels in patients who did not receive any oxygen therapy before hospitalization due to COVID-19. It is hypothesized that this may be caused by damage to pancreatic β-cells by SARS-CoV-2, and disturbances in the potassium channel, leading to cell membrane depolarization and insulin secretion.

Physicians' adherence to guideline-recommended heart failure (HF) treatment remains suboptimal, especially regarding the target doses. In particular, there is evidence that non-cardiologists are less compliant with HF guideline recommendations. This is likely to have a detrimental impact on patients' survival, readmissions and quality of life. Thus, the present document aims to address the reasons underlying low implementation and under-dosing of guideline-directed medical therapy in HF and to update a guidance for the initiation and rapid titration of HF drugs. In particular, aim of this document is to provide practical indications for drug implementation, to be applied not only by cardiologists but also by GPs and internal medicine doctors.