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An abstract of the study "In Chronic Heart Failure Overactive Chemokine System Is Associated With Immune Activation, Low Grade Inflammation and Predicts Loss of Fat Tissue," by H. Bukowska and B. Millo, is presented.

An abstract of the study "The Activation of the NF-kappaB System in Chronic Heart Failure," by E. A. Jankowska and colleagues is presented.

An abstract of the study "Endotoxin in vitro stimulates proliferation of peripheral blood mononuclear cells in patients with mild stable chronic heart failure, whereas in oedematous patients promotes apoptosis," by E. A. Jankowska and colleagues is presented.

An abstract of the article "Periodic breathing is frequent during the daytime in stable patients with heart failure and is related to impaired exercise tolerance and abnormal autonomic reflex control," by T. Witkowski et al., is presented.

An abstract of the study "In Chronic Heart Failure Elevated Homocysteine Level Is Related to Impaired Metabolism and Endothelial Dysfunction," by B. Millo and W. Banasiak, is presented.

An abstract of the study "Anemia Is Independent Predictor of Poor Outcome in Patients With Chronic Heart Failure," by W. Banasiak, is presented.

An abstract of the article "Ergoreflex Contribution to Ventilatory Response Assessed During Exercise of Forearm and Quadriceps Muscles in Patients With Chronic Heart Failure," by A. Kaczmarek and colleagues, is presented.

An abstract of the study "Adrenal and Gonadal Andropenia Is Related to Clinical Severity and Increased Mortality in Men With Chronic Heart Failure," by J. Majda and colleagues is presented.

An abstract of the study "Reduced bone mineral density in men with chronic heart failure and its pathophysiological mechanisms," by E. A. Jankowska and colleagues is presented.

An abstract of the article "Increased number of CD4+ T cells in the peripheral blood in patients with chronic heart failure," by E. A. Jankowska et al., is presented.

An abstract of the article "Body composition and prognosis in 511 chronic heart failure patients: results from three European centers," by M. Cicoira et al., is presented.

The effects of a 6-week treatment with amiodarone on the P-wave triggered signal-averaged electrocardiogram in patients with paroxysmal atrial fibrillation and coronary artery disease have been studied. Amiodarone favorably influences P-wave triggered signal-averaged electrocardiographic parameters, predominantly in patients in whom amiodarone is effective in preventing paroxysmal atrial fibrillation. [ABSTRACT FROM AUTHOR]

In chronic congestive heart failure (CHF) an overactivity of muscle ergoreceptors and peripheral chemoreceptors may lead to an increased ventilatory response to exercise and contribute to the autonomic imbalance. The analysis of heart rate variability (HRV), which is a reliable method of studying autonomic regulations within the cardiovascular system, showed depressed HRV indexes in CHF, but predictors of abnormal HRV pattern in CHF remain controversial. Considering a common mechanism involved in generation of both abnormal ventilation and autonomic dysfunction in CHF, we hypothesized that impaired ventilation may be better than other variables of CHF severity in determining HRV parameters. Seventy-two patients with CHF (57+/-9 years, ejection fraction: 28+/-11%) underwent cardiopulmonary exercise testing; the relation between ventilation and carbon dioxide production (VE/VCO2) was used as an index of the ventilatory response to exercise. Time and frequency-domain measurements of HRV were derived from 24-hour electrocardiographic monitoring. Patients had reduced exercise tolerance with abnormal ventilatory response (peak oxygen consumption [VO2max]: 17.8+/-5.5 ml/kg/min, VE/VCO2: 36.0+/-9.8). Correlations were found between HRV measures and etiology, New York Heart Association (NYHA) functional class, and VO2max, but the strongest relation was observed for VE/VCO2 slope (r values from -0.33 to -0.65, p <0.01). In the multiple regression analysis only VE/VCO2 was found to correlate independently with all HRV measurements. To investigate the role of peripheral chemoreceptor overactivity as the mechanism of autonomic imbalance and the increased ventilatory response to exercise, we assessed peripheral chemosensitivity in 22 patients (mean value of peripheral chemosensitivity: 0.62+/-0.34 L/min/%SaO2, significantly higher than in normal controls, mean value: 0.29+/-0.20 L/min/%SaO2 in our laboratory). The activity of the peripheral chemoreflex inversely correlated with all parameters of HRV. Increased ventilatory response to exercise correlated with depressed HRV measures in patients with CHF better than other clinical variables. An important role of the increased peripheral chemosensitivity in this relation may be relevant, being also a potential link between functional severity and sympathovagal imbalance in CHF. [ABSTRACT FROM AUTHOR]

Introduction: The growing population of heart failure (HF) patients places a burden on the healthcare system. Patient-centered outcomes such as health-related quality of life (HRQoL) and self-care behaviors are key elements of modern HF management programs. Thus, optimized strategies to improve these outcomes are sought., Purpose: To assess the effects of a new model of medical telecare on HRQoL and self-care in patients with HF (the AMULET study)., Methods: The study was prospective, randomized, open-label, and controlled with two parallel groups: telecare and standard care. In the telecare group, HF nurses performed patient clinical assessments with telemedical support by a cardiologist and provided education focused on the prevention of HF exacerbation. In the standard care group, patients were followed according to standard practices in the existing healthcare system. At the baseline and at 12 months, HRQoL was assessed using the Short Form 36 (SF-36) questionnaire and the Minnesota Living with Heart Failure Questionnaire (MLwHF). The level of self-care was assessed with the 12-item standardized European Heart Failure Self-care Behavior Scale (EHFScBS-12)., Results: In the overall study group, 79% of the subjects were male, the mean age was 67 ± 14 years, and 59% of the subjects were older than 65 years of age. The majority of the subjects (70%) had a left ventricular ejection fraction below 40%. After 12 months, statistically significant increases in physical component of the SF-36 (43.3 vs. 47.4 for telecare vs. 43.4 vs. 46.6 for standard care) and mental component of SF-36 (58.4 vs. 62 for telecare vs. 60.4 vs. 64.2 for standard care) were noted, with no intergroup differences. However, patients receiving telecare showed improvement in specific domains, such as physical functioning, role-physical, bodily pain, vitality, social functioning, role-emotional, and mental health. There was a significant decrease in MLwHF (29 vs. 35.0; lower is better) at follow-up for both groups. Telecare patients had a statistically significant decrease in EHFScBS-12 (lower is better) at 12 months., Conclusion: AMULET outpatient telecare, which is based on nurse-led non-invasive assessments supported by specialist teleconsultations, improved the HRQoL and self-care of HF patients after an episode of acute HF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Piotrowicz, Krzesiński, Galas, Stańczyk, Siebert, Jankowska, Siwołowski, Gutknecht, Murawski, Szalewska, Banasiak, Ponikowski and Gielerak.)

Background : Heart failure (HF) patients experience reduced functional fitness level (determining the performance of routine, daily activities) and diminished exercise capacity (linked to more effortful activities). Aim : The aim of the study is to assess this relationship using functional fitness tests compared to peak VO2 and VE/VCO2 slope in the context of exercise capacity and ventilatory response to exercise. Methods : A total of 382 men with stable HFrEF (age: 61 ± 10, NYHA class I/II/III/IV: 16/50/32/2%, LVEF: 30.5 ± 8.3%) underwent cardiopulmonary exercise testing (CPX) and a Senior Fitness Test (SFT). Afterwards, the patients were divided according to the 2capacity with peak VO2 ≥ 18 mL/kg/min, those with higher or lower ventilatory responses (VE/VCO2 slope ≥ 35 vs. <35) to the exercise were compared. Results : Patients who covered shorter distances in the 6 min walking test showed worse results in the functional tests ('stand up and go', 'chair stand' and 'arm curl') and CPX (lower peak VO2, shorter exercise time and higher VE/VCO2 slope). Subjects classified into Class D demonstrated the worst results in all elements of SFT; those in Class A demonstrated the best results. Significant differences that were analogous occurred also between classes B and C. Among the participants who reached peak VO2 ≥ 18 mL/kg/min (n = 170), those with VE/VCO2 slope ≥ 35 were characterized by worse physical fitness as compared to those with VE/VCO2 < 35. Conclusion : Reduced exercise tolerance led to worsening physical function in patients with HFrEF. Moreover, limitations in physical fitness seem to be distinctive for those patients showing excessive ventilatory response to exercise slope VE/VCO2 (≥35). The Senior Fitness Test may be considered as a useful tool for assessing comprehensive functional and clinical status and risk stratification in patients with HFrEF, especially those with extremely low exercise capacity.

Background: Implantable cardioverter-defibrillators (ICD)/cardiac resynchronization therapy with defibrillation (CRT-D) recipients may be susceptible to the arrhythmic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Aims: We aimed to evaluate characteristics and outcomes of patients hospitalized for ICD/CRT-D shocks during the pandemic compared to the pre-pandemic period., Methods: This retrospective study analyzed medical records of patients hospitalized for ICD/CRT-D shock in the pre-pandemic (January 1, 2018-December 31, 2019) and pandemic periods (March 4, 2020-March 3, 2022). Survival data were obtained on October 24, 2022., Results: In total, 198 patients (average age 65.6 years) had 138 pre-pandemic and 124 pandemic visits. Of these patients, 115 were hospitalized during pre-pandemic, 108 during the pandemic, and 25 in both periods. No significant differences were noted in age, sex, number of shocks, or appropriateness of therapy between these periods. During the pandemic, during 14 hospital stays of patients with SARS-CoV-2, 8 (57.1%) received electrical shocks, compared to 12 (10.9%) with negative SARS-CoV-2 tests (P <0.001). The in-hospital mortality rate was 2 of 115 patients hospitalized during the pre-pandemic and 7 of 108 during pandemic periods (4 patients with and 3 without SARS-CoV-2 [P = 0.10]). During the follow-up, there were 66 deaths. Cox regression analysis showed that survival decreased with age and heart failure decompensation in medical history but increased with higher ejection fraction. The pandemic alone was not a survival predictor. However, SARS-CoV-2 infection, older age, and heart failure decompensation in medical history predicted worse outcomes during the pandemic period., Conclusions: The pandemic did not increase the number of hospital visits due to ICD/CRT-D discharges. SARS-CoV-2 infection predicts increased mortality in patients with ICD/CRT-D shocks.

Since the arrival of leadless pacemakers (LPs), they have become a cornerstone in remedial treatment of bradycardia and atrioventricular (AV) conduction disorders, as an alternative to transvenous pacemakers. Even though clinical trials and case reports show indisputable benefits of LP therapy, they also bring some doubts. Together with the positive results of the MARVEL trials, AV synchronization has become widely available in LPs, presenting a significant development in leadless technology. This review presents the Micra AV (MAV), describes major clinical trials, and introduces the basics of AV synchronicity obtained with the MAV and its unique programming options.

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.

Introduction: Redox imbalance and oxidative stress are involved in the pathogenesis of arrhythmias. They also play a significant role in pathogenesis of heart failure (HF). In patients with HFand implanted cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D), the direct current shocks may be responsible for additional redox disturbances and additionally increase arrhythmia risk. However, the precise role of oxidative stress in potentially fatal arrhythmias and shock induction remains unclear. Methods: 36 patients with diagnosed HF and implanted ICD/CRT-D were included in this study. Patients were qualified to the study group in case of registered ventricular arrhythmia and adequate ICD/CRT-D intervention. The control group consisted of patients without arrhythmia with elective replacement indicator (ERI) status. Activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) in erythrocyte (RBC), SOD, GPx activity and reactive oxygen/nitrogen species (ROS/RNS) concentration in plasma were determined. The values were correlated with glucose, TSH, uric acid, Mg and ion concentrations. Results: In the perishock period, we found a significant decrease in RBC and extracellular (EC) SOD and RBC CAT activity ( p = 0.0110, p = 0.0055 and p = 0.0002, respectively). EC GPx activity was also lower ( p = 0.0313). In all patients, a decrease in the concentration of all forms of glutathione was observed compared to the ERI group. Important association between ROS/RNS and GSH, Mg, TSH and uric acid was shown. A relationship between the activity of GSH and antioxidant enzymes was found. Furthermore, an association between oxidative stress and ionic imbalance has also been demonstrated. The patients had an unchanged de Haan antioxidant ratio and glutathione redox potential. Conclusion: Here we show significant redox disturbances in patients with HF and ICD/CRT-D interventions. Oxidative stress may be an additional risk factor for the development of arrhythmia in patients with HF. The detailed role of oxidative stress in ventricular arrhythmias requires further research already undertaken by our team., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Szyller, Antoniak, Wadowska, Bil-Lula, Hrymniak, Banasiak and Jagielski.)

Background: The complex clinical status of modern day patients hospitalized due to acute heart failure (AHF) results from their advanced age, comorbidities, frailty, heart failure symptoms (including massive swelling of the lower limb), and dramatic reduction of exercise tolerance. Hence, there is a need to implement physiotherapeutic procedures as early as possible, aiming to both accelerate the restoration of clinical stabilization and prevent post-hospital disability., Objectives: We investigated whether assisted lower limb exercises have an impact on perfusion and oxygenation in skeletal muscle and if they are feasible in patients with AHF., Material and Methods: We examined 34 men (age: 66 ±11 years; left ventricular ejection fraction (LVEF): 34 ±11%; clinical presentation: 31 wet-warm and 3 wet-cold). The intervention (carried out on the 2nd day of hospitalization) included: 1) a 3-minute rest period; 2) an exercise phase (45 repetitions of assisted flexion and extension of the lower limb; and 3) a 10-minute relaxation period. We analyzed blood pressure (BP), heart rate (HR), respiratory rate (RR), tissue oxygenation (reflected by oxygen saturation measured with a pulse oximeter), and changes in peripheral tissue perfusion (reflected by the tissue oxygenation index (TOI) measured with near-infrared spectroscopy (NIRS))., Results: The hemodynamic parameters (both ΔHR and Δsystolic BP) and oxygen saturation did not change (all p > 0.05), whereas the RR declined (p < 0.001). The exercises improved venous outflow (reflected by decreased oxygenated, deoxygenated and total hemoglobin, all p < 0.05) and increased peripheral tissue perfusion, as reflected by the TOI (p < 0.05). The patients reported relief and lack of dyspnea during and after the assisted exercises., Conclusions: The physiotherapeutic intervention improved both venous outflow and muscle oxygenation in men with AHF. The presented protocol was safe, feasible and well-tolerated, and resulted in relief for the patients. We believe that such procedures might be recommended for the initial period of rehabilitation in this challenging subgroup of patients.

Spontaneous day-time periodic breathing (sPB) constitutes a common phenomenon in systolic heart failure (HF). However, it is unclear whether PB during wakefulness could be easily induced and what are the physiological and clinical correlates of patients with HF in whom PB induction is possible. Fifty male HF patients (age 60.8 ± 9.8 years, left ventricle ejection fraction 28.0 ± 7.4%) were prospectively screened and 46 enrolled. After exclusion of patients with sPB the remaining underwent trial of PB induction using mild hypoxia (stepwise addition of nitrogen gas to breathing mixture) which resulted in identification of inducible (iPB) in 51%. All patients underwent assessment of hypoxic ventilatory response (HVR) using transient hypoxia and of hypercapnic ventilatory response (HCVR) employing Read's rebreathing method. The induction trial did not result in any adverse events and minimal SpO 2 during nitrogen administration was ∼85%. The iPB group (vs. non-inducible PB group, nPB) was characterized by greater HVR (0.90 ± 0.47 vs. 0.50 ± 0.26 L/min/%; p <0.05) but comparable HCVR (0.88 ± 0.54 vs. 0.67 ± 0.68 L/min/mmHg; p = NS) and by worse clinical and neurohormonal profile. Mean SpO 2 which induced first cycle of PB was 88.9 ± 3.7%, while in sPB mean SpO 2 preceding first spontaneous cycle of PB was 96.0 ± 2.5%. There was a reverse relationship between HVR and the relative variation of SpO 2 during induced PB ( r = -0.49, p = 0.04). In summary, PB induction is feasible and safe in HF population using simple and standardized protocol employing incremental, mild hypoxia. Pathophysiology of iPB differs from sPB, as it relies mostly on overactive peripheral chemoreceptors. At the same time enhanced HVR might play a protective role against profound hypoxia during iPB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Niewinski, Tubek, Paleczny, Banasiak and Ponikowski.)

Transluminal lead extraction (TLE) is a well-established procedure for the removal of damaged or infected pacing systems. Despite its high efficacy, the procedure is associated with significant risks, some of which may contribute to severe life-threatening complications. Herein, we present the case of a 90-year-old female who was 100% pacemaker-dependent (PM-dependent) and had ventricular lead fragmentation after the TLE procedure. In this elderly patient, after taking into account the whole clinical context-age, frailty syndrome, infection, and high peri- and postprocedural risks-we decided on MICRA VR implantation as well as leaving the remains of the ventricular lead in the right heart chambers. A Leadless pacemaker (LP) is an excellent alternative to PM-dependent individuals, in whom implantation of permanent transvenous PM is precluded due to multiple infectious and non-infectious issues.

Aim: Prevention of heart failure (HF) hospitalisations and deaths constitutes a major therapeutic aim in patients with HF. The role of telemedicine in this context remains equivocal. We investigated whether an outpatient telecare based on nurse-led non-invasive assessments supporting remote therapeutic decisions (AMULET telecare) could improve clinical outcomes in patients after an episode of acute HF during 12-month follow-up., Methods and Results: In this prospective randomised controlled trial, patients with HF and left ventricular ejection fraction (LVEF) ≤49%, after an episode of acute HF within the last 6 months, were randomly assigned to receive either an outpatient telecare based on nurse-led non-invasive assessments (n = 300) (AMULET model) or standard care (n = 305). The primary composite outcome of unplanned HF hospitalisation or cardiovascular death occurred in 51 (17.1%) patients in the telecare group and 73 (23.9%) patients in the standard care group up to 12 months after randomization [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.48-0.99; P = 0.044]. The implementation of AMULET telecare, as compared to standard care, reduced the risk of first unplanned HF hospitalisation (HR 0.62, 95% CI 0.42-0.91; P = 0.015) as well as the risk of total unplanned HF hospitalisations (HR 0.64, 95% CI 0.41-0.99; P = 0.044).There was no difference in cardiovascular mortality between the study groups (HR 1.03, 95% CI 0.54-1.67; P = 0.930)., Conclusions: AMULET telecare as compared to standard care significantly reduced the risk of HF hospitalisation or cardiovascular death during 12-month follow-up among patients with HF and LVEF ≤49% after an episode of acute HF., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Peripheral chemoreceptors' (PCh) hyperactivity increases sympathetic tone. An augmented acute ventilatory response to hypoxia, being a marker of PCh oversensitivity, was also identified as a marker of poor prognosis in HF. However, not much is known about the tonic (chronic) influence of PCh on cardio-respiratory parameters. In our study 30 HF patients and 30 healthy individuals were exposed to 100% oxygen for 1 min during which minute ventilation and hemodynamic parameters were non-invasively recorded. Systemic vascular resistance (SVR) and mean arterial pressure (MAP) responses to acute hyperoxia differed substantially between HF and control. In HF hyperoxia caused a significant drop in SVR in early stages with subsequent normalization, while increase in SVR was observed in controls. MAP increased in controls, but remained unchanged in HF. Bilateral carotid bodies excision performed in two HF subjects changed the response to hyperoxia towards the course seen in healthy individuals. These differences may be explained by the domination of early vascular reaction to hyperoxia in HF by vasodilation due to the inhibition of augmented tonic activity of PCh. Otherwise, in healthy subjects the vasoconstrictive action of oxygen remains unopposed. The magnitude of SVR change during acute hyperoxia may be used as a novel method for tonic PCh activity assessment., (© 2021. The Author(s).)

Aims: Abnormal endogenous erythropoietin (EPO) constitutes an important cause of anaemia in chronic diseases. We analysed the relationships between iron deficiency (ID) and the adequacy of endogenous EPO in anaemic heart failure (HF) patients, and the impact of abnormal EPO on 12-month mortality., Methods and Results: We investigated 435 anaemic HF patients (age: 74 ± 10 years; males: 60%; New York Heart Association class I or II: 39%; left ventricular ejection fraction: 43 ± 17%). Patients with EPO higher than expected for a given haemoglobin were considered EPO-resistant whereas those with EPO lower than expected - EPO-deficient. ID was defined as serum ferritin <100 µg/L or 100-299 µg/L with transferrin saturation <20%. EPO-resistant patients (22%) had more advanced HF whereas those with EPO deficiency (57%) were more frequently females and had worse renal function. Lower serum ferritin (indicating depleted body iron stores) was related to higher EPO observed/predicted ratio when adjusted for significant clinical confounders, including C-reactive protein. One year all-cause mortality was 28% in patients with EPO resistance compared to 17% in patients with EPO deficiency and 10% in patients with adequate EPO (log-rank test for the comparison EPO resistance vs. adequate EPO: P = 0.02). When adjusted for other prognosticators, there was still a trend towards increased 12-month mortality in patients with higher EPO level., Conclusion: Anaemic HF patients with endogenous EPO deficiency vs. resistance have different clinical and laboratory characteristics. In such patients, ID contributes to EPO resistance independently of inflammation., (© 2021 European Society of Cardiology.)

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a major health burden worldwide due to high mortality rates and hospital bed shortages. SARS-CoV-2 infection is associated with several laboratory abnormalities. We aimed to develop and validate a risk score based on simple demographic and laboratory data that could be used on admission in patients with SARS-CoV-2 infection to predict in-hospital mortality., Methods: Three cohorts of patients from different hospitals were studied consecutively (developing, validation, and prospective cohorts). The following demographic and laboratory data were obtained from medical records: sex, age, hemoglobin, mean corpuscular volume (MCV), platelets, leukocytes, sodium, potassium, creatinine, and C-reactive protein (CRP). For each variable, classification and regression tree analysis were used to establish the cut-off point(s) associated with in-hospital mortality outcome based on data from developing cohort and before they were used for analysis in the validation and prospective cohort. The covid-19 score was calculated as a sum of cut-off points associated with mortality outcome., Results: The developing, validation, and prospective cohorts included 129, 239, and 497 patients, respectively (median age, 71, 67, and 70 years, respectively). The following cut of points associated with in-hospital mortality: age > 56 years, male sex, hemoglobin < 10.55 g/dL, MCV > 92.9 fL, leukocyte count > 9.635 or < 2.64 10 3 /µL, platelet count, < 81.49 or > 315.5 10 3 /µL, CRP > 51.14 mg/dL, creatinine > 1.115 mg/dL, sodium < 134.7 or > 145.4 mEq/L, and potassium < 3.65 or > 6.255 mEq/L. The AUC of the covid-19 score for predicting in-hospital mortality was 0.89 (0.84-0.95), 0.850 (0.75-0.88), and 0.773 (0.731-0.816) in the developing, validation, and prospective cohorts, respectively (P < 0.001The mortality of the prospective cohort stratified on the basis of the covid-19 score was as follows: 0-2 points,4.2%; 3 points, 15%; 4 points, 29%; 5 points, 38.2%; 6 and more points, 60%., Conclusion: The covid-19 score based on simple demographic and laboratory parameters may become an easy-to-use, widely accessible, and objective tool for predicting mortality in hospitalized patients with SARS-CoV-2 infection., (© 2021. The Author(s).)

Aims: Heart failure (HF) is characterized by high mortality and hospital readmission rates. Limited access to cardiologists restricts the application of guideline-directed, patient-tailored medical therapy. Some telemedicine solutions and novel non-invasive diagnostic tools may facilitate real-time detection of early HF decompensation symptoms, prompt initiation of appropriate treatment, and optimal management of medical resources. We describe the rationale and design of the AMULET trial, which investigates the effect of comprehensive outpatient intervention, based on individualized haemodynamic assessment and teleconsultations, on cardiovascular mortality and unplanned hospitalizations in HF patients., Methods and Results: The AMULET trial is a multicentre, prospective, randomized, open-label, and controlled parallel group trial (ClinicalTrials.gov Identifier: NCT03476590). Six hundred and five eligible patients with HF (left ventricular ejection fraction ≤49%, at least one hospitalization due to acute HF decompensation within 6 months prior to enrolment) were randomly assigned in a 1:1 ratio to either an intervention group or a standard care group. The planned follow-up is 12 months. The AMULET interventions are performed in ambulatory care points operated by nurses, with the remote support of cardiologists. The comprehensive clinical evaluation comprises measurements of heart rate, blood pressure, body mass, thoracic fluid content, and total body water. A recommendation support module based on these objective parameters is implemented in remote therapeutic decision-making. The primary complex endpoints are cardiovascular mortality and unplanned HF hospitalization., Conclusions: The AMULET trial will provide a prospective assessment of the effect of comprehensive ambulatory intervention, based on telemedicine and haemodynamically guided therapy, on mortality and readmissions in HF patients., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Iron deficiency (ID) is frequent in heart failure (HF), linked with exercise intolerance and poor prognosis. Intravenous iron repletion improves clinical status in HF patients with left ventricular ejection fraction (LVEF) ≤45%. However, uncertainty exists about the accuracy of serum biomarkers in diagnosing ID. The aims of this study were (i) to identify the iron biomarker with the greatest accuracy for the diagnosis of ID in bone marrow in patients with ischaemic HF, and (ii) to establish the prevalence of ID using this biomarker and its prognostic value in HF patients., Methods and Results: Bone marrow was stained for iron in 30 patients with ischaemic HF with LVEF ≤45% and 10 healthy controls, and ID was diagnosed for 0-1 grades (Gale scale). A total of 791 patients with HF with LVEF ≤45% were prospectively followed up for 3 years. Serum ferritin, transferrin saturation, soluble transferrin receptor (sTfR) were assessed as iron biomarkers. Most patients with HF (n = 25, 83%) had ID in bone marrow, but none of the controls (P < 0.001). Serum sTfR had the best accuracy in predicting ID in bone marrow (area under the curve 0.920, 95% confidence interval 0.761-0.987, for cut-off 1.25 mg/L sensitivity 84%, specificity 100%). Serum sTfR was ≥1.25 mg/L in 47% of HF patients, in 56% and 46% of anaemics and non-anaemics, respectively (P < 0.05). The reclassification methods revealed that serum sTfR significantly added the prognostic value to the baseline prognostic model, and to the greater extent than plasma N-terminal pro B-type natriuretic peptide. Based on internal derivation and validation procedures, serum sTfR ≥1.41 mg/L was the optimal threshold for predicting 3-year mortality, independent of other established variables., Conclusions: High serum sTfR accurately reflects depleted iron stores in bone marrow in patients with HF, and identifies those with a high 3-year mortality., (© 2020 European Society of Cardiology.)

Aims: In acute heart failure (AHF), assessment of renal function comprises estimation of glomerular filtration rate (eGFR), which does not provide any information about renal sodium/water handling. We describe the interactions between urinary sodium concentration and eGFR to better characterize AHF patients., Methods and Results: In 219 patients with AHF, spot urine sodium (UNa + ) and eGFR were assessed on admission, day 1 and day 2 of hospitalization. We found no correlation between UNa + and eGFR (calculated on each consecutive day, as an average of all three values, and as changes from baseline; all P > 0.05). The population was subsequently divided into four profiles based on eGFR (preserved vs. impaired; cutoff of 60 mL/min/1.73 m 2 ) and UNa + (sodium excreter vs. non-excreter; cutoff of 60 mmol/L). At day 1, there were 70 (31.9%) patients classified as preserved eGFR/sodium excreter, 37 (16.8%) as impaired eGFR/sodium non-excreter, 72 (32.9%) as impaired eGFR/sodium excreter, and 40 (18%) as preserved eGFR/sodium non-excreter. Both sodium non-excreter profiles were associated with an increased risk of in-hospital heart failure worsening [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.3-6.4], inotrope use (OR 2.6, 95% CI 1.1-6.7) and rehospitalization due to AHF (OR 3.2, 95% CI 1.6-6.2; all P < 0.05). The preserved eGFR/sodium non-excreter profile was associated with highest 1-year mortality (52.5%) and remained an independent prognosticator after adjustment for other prognosticators (hazard ratio 2.9, 95% CI 1.7-5.2; P < 0.0005)., Conclusions: In AHF, values of spot UNa + and eGFR are not interrelated. Concomitant assessment of eGFR and spot UNa + may be useful for better clinical and therapeutic profiling of patients., (© 2020 European Society of Cardiology.)

Key Points: Five years after bilateral carotid body resection (bCBR) performed in four patients, the absence of the hypoxic ventilatory response persisted, suggesting no compensatory regrowth. Breathing hypoxic gas mixtures (15% and 12%) results in a lower (by ∼10%) minimal blood oxygen saturation ( S p O 2 ) in bCBR patients compared to heart failure subjects (CHF) with intact peripheral chemoreceptors. After bCBR, patients were characterized by a greater short-term variability in S p O 2 during mild hypoxia in comparison to the CHF group. The ventilatory response to hypercapnia was preserved following bCBR and was sufficient to maintain minimal S p O 2 at levels comparable to controls when combined with hypoxia. Bilateral CBR - a novel treatment modality for sympathetically mediated diseases - should be used with caution due to the risk of significant desaturation even during mild hypoxia equivalent to that experienced during long-haul air travel and high altitude., Abstract: Carotid body resection has been proposed as a novel treatment for sympathetically mediated diseases but the safety of bilateral carotid body resection (bCBR) for blood oxygenation during hypoxic stress (long-haul flights or high altitude) remains uncertain. Also unknown is whether central ventilatory drive is sufficient to maintain adequate oxygen saturation when exposed to hypercapnia with concomitant hypoxia. Thus, we administered: 15% O 2 , 12% O 2 , 5% CO 2 /12% O 2 and 5% CO 2 /95% O 2 to a group of four patients with congestive heart failure (65 ± 2.9 years) in whom bCBR was performed 5 years earlier. Ventilatory, haemodynamic and blood oxygen saturation ( S p O 2 ) responses were recorded non-invasively and compared to control groups with intact peripheral chemoreceptors (both healthy and heart failure patients). First, we confirmed that the ventilatory response to hypoxia was eliminated in patients with bCBR, although the increase in cardiac output was preserved. Second, administration of hypoxic gas mixtures resulted in a larger decrease in S p O 2 and greater short-term variability of the S p O 2 leading to a lower minimal S p O 2 for both hypoxia levels in the bCBR group compared to heart failure controls (82.5 ± 1.2% vs. 91.6 ± 2.3% for 15% O 2 and 73.8 ± 4.0% vs. 83.7 ± 3.1% for 12% O 2 ). Third, in bCBR patients the ventilatory response to hypercapnia was present and sufficient to maintain a minimal S p O 2 at a level comparable to heart failure controls following administration of 5% CO 2 /12% O 2 (88.7 ± 4.2% vs. 91.1 ± 2.8%). We conclude that bCBR carries a risk of significant oxygen desaturation even during mild hypoxia. Despite preservation of central chemosensitivity, future studies should focus on unilateral CBR or on pharmacological modulation of peripheral chemosensitivity., (© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.)

Heart failure (HF) is characterized by frequent decompensation and an unpredictable trajectory. To prevent early hospital readmission, coordinated discharge planning and individual therapeutic approach are recommended., Aims: We aimed to assess the effect of 1 month of ambulatory care, led by nurses and supported by non-invasive haemodynamic assessment, on the functional status, well-being, and haemodynamic status of patients post-acute HF decompensation., Methods and Results: This study had a multicentre, prospective, and observational design and included patients with at least one hospitalization due to acute HF decompensation within 6 months prior to enrolment. The 1 month ambulatory care included three visits led by a nurse when the haemodynamic state of each patient was assessed non-invasively by impedance cardiography, including thoracic fluid content assessment. The pharmacotherapy was modified basing on haemodynamic assessment. Sixty eight of 73 recruited patients (median age = 67 years; median left ventricular ejection fraction = 30%) finished 1 month follow-up. A significant improvement was observed in both the patients' functional status as defined by New York Heart Association class (P = 0.013) and sense of well-being as evaluated by a visual analogue score (P = 0.002). The detailed patients' assessment on subsequent visits resulted in changes of pharmacotherapy in a significant percentage of patients (Visit 2 = 39% and Visit 3 = 44%)., Conclusions: The proposed model of nurse-led ambulatory care for patients after acute HF decompensation, with consequent assessment of the haemodynamic profile, resulted in: (i) improvement in the functional status, (ii) improvement in the well-being, and (iii) high rate of pharmacotherapy modifications., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)