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Abstract Aims Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID‐19. Our hypothesis is that in patients with AHF and elevated C‐reactive protein (CRP) levels without symptoms or signs of infection, a 7‐day course of steroid therapy will lead to reduced inflammation and short‐term improvement in quality of life and a reduced risk of worsening HF (WHF) events. Methods and results The study, which is currently ongoing, will include 100 patients with AHF ages 18–85, regardless of ejection fraction, screened within 12 h of presentation. Patients will be included who have NT‐proBNP > 1500 pg/mL and CRP > 20 mg/L at screening. Exclusion criteria include haemodynamic instability and symptoms and signs of infection. After signed consent, eligible patients will be randomized according to a central randomization scheme stratified by centre 1:1 to either treatment once daily for 7 days with 40 mg prednisone orally or to standard care. Patients will be assessed at study day 2, day 4 or at discharge if earlier, and at days 7 and 31 at the hospital; and at day 91 through a telephone follow‐up. The primary endpoint is the change in CRP level from baseline to day 7, estimated from a mixed model for repeated measures (MMRM) including all measured timepoints, in patients without a major protocol violation. Secondary endpoints include the time to the first event of WHF adverse event, readmission for HF, or death through day 91; and changes to day 7 in EQ‐5D visual analogue scale score and utility index. Additional clinical and laboratory measures will be assessed. Conclusions The results of the study will add to the knowledge of the role of inflammation in AHF and potentially inform the design of larger studies with possibly longer duration of anti‐inflammatory therapies in AHF.

Abstract Aims We aim to identify the most accurate marker for early prediction of poor diuretic response in acute heart failure (AHF) patients with signs of congestion requiring intravenous diuretic treatment. Methods In this single‐centre, prospective observational study, AHF patients with signs of congestion received a standardized intravenous furosemide dose (1 mg/kg of body weight; 40 mg in bolus and remaining dose in 2 h continuous infusion). Subsequently, we assessed spot urine composition at 2 h post‐administration, comparing it with total urine output at 6 h. Various potential urine markers were analysed for predicting urine output using receiver operating characteristic (ROC) curves and logistic regression models. We investigated guideline‐recommended markers, including spot urine sodium (UNa+) and its cut‐off, and introduced the UNa+/UCr (urine creatinine concentration) ratio adjusting UNa+ for urine dilution. Results Out of 111 patients (85% males, 66.4 ± 13.9 years old, NTproBNP 7290 [4493–14 582] pg/ml), there were 18 (16%) with a poor diuretic response (cumulative urine output

Abstract Despite improvements over recent years, morbidity and mortality associated with heart failure (HF) are higher in countries in the Central and Eastern Europe and Baltic region than in Western Europe. With the goal of improving the standard of HF care and patient outcomes in the Central and Eastern Europe and Baltic region, this review aimed to identify the main barriers to optimal HF care and potential areas for improvement. This information was used to suggest methods to improve HF management and decrease the burden of HF in the region that can be implemented at the national and regional levels. We performed a literature search to collect information about HF epidemiology in 11 countries in the region (Bulgaria, Croatia, Czechia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Serbia, and Slovenia). The prevalence of HF in the region was 1.6–4.7%, and incidence was 3.1–6.0 per 1000 person‐years. Owing to the scarcity of published data on HF management in these countries, we also collected insights on local HF care and management practices via two surveys of 11 HF experts representing the 11 countries. Based on the combined results of the literature review and surveys, we created national HF care and management profiles for each country and developed a common patient pathway for HF for the region. We identified five main barriers to optimal HF care: (i) lack of epidemiological data, (ii) low awareness of HF, (iii) lack of national HF strategies, (iv) infrastructure and system gaps, and (v) poor access to novel HF treatments. To overcome these barriers, we propose the following routes to improvement: (i) establish regional and national prospective HF registries for the systematic collection of epidemiological data; (ii) establish education campaigns for the public, patients, caregivers, and healthcare professionals; (iii) establish formal HF strategies to set clear and measurable policy goals and support budget planning; (iv) improve access to quality‐of‐care centres, multidisciplinary care teams, diagnostic tests, and telemedicine/telemonitoring; and (v) establish national treatment monitoring programmes to develop policies that ensure that adequate proportions of healthcare budgets are reserved for novel therapies. These routes to improvement represent a first step towards improving outcomes in patients with HF in the Central and Eastern Europe and Baltic region by decreasing disparities in HF care within the region and between the region and Western Europe.

Abstract In our retrospective study, we aimed to investigate the relationship between urinary chloride (uCl−) and selected clinical and laboratory biomarkers, renal function, and patient outcomes in the acute heart failure (AHF) population. We divided 248 adult patients (≥ 18 years) with AHF into two groups: low uCl− (

Abstract Heart failure (HF) poses a significant challenge, often leading to frequent hospitalizations and compromised quality of life. Continuous pulmonary artery pressure (PAP) monitoring offers a surrogate for congestion status in ambulatory HF care. This meta-analysis examines the efficacy of PAP monitoring devices (CardioMEMS and Chronicle) in preventing adverse outcomes in HF patients, addressing gaps in prior randomized controlled trials (RCTs). Five RCTs (2572 participants) were systematically reviewed. PAP monitoring significantly reduced HF-related hospitalizations (RR 0.72 [95% CI 0.6–0.87], p = 0.0006) and HF events (RR 0.86 [95% CI 0.75–0.99], p = 0.03), with no impact on all-cause or cardiovascular mortality. Subgroup analyses highlighted the significance of CardioMEMS and blinded studies. Meta-regression indicated a correlation between prolonged follow-up and increased reduction in HF hospitalizations. The risk of bias was generally high, with evidence certainty ranging from low to moderate. PAP monitoring devices exhibit promise in diminishing HF hospitalizations and events, especially in CardioMEMS and blinded studies. However, their influence on mortality remains inconclusive. Further research, considering diverse patient populations and intervention strategies with extended follow-up, is crucial for elucidating the optimal role of PAP monitoring in HF management.

IntroductionThe 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.PurposeTo assess the effects of a new model of medical telecare on HRQoL and self-care in patients with HF (the AMULET study).MethodsThe 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).ResultsIn 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.ConclusionAMULET 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.

Abstract Background Frailty is a severe, common co‐morbidity associated with heart failure (HF) with preserved ejection fraction (HFpEF). The impact of frailty on HFpEF outcomes may affect treatment choices in HFpEF. The impact of frailty on HFpEF patients and any impact on the clinical benefits of sodium glucose co‐transporter 2 (SGLT2) inhibition in HFpEF have been described in only a limited number of trials. Whether the SGLT2 inhibitor empagliflozin would improve or worsen frailty status when given to HFpEF patients is also not known. The aims of this study were, therefore, to evaluate, in HFpEF patients enrolled in the EMPEROR‐Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), the impact of frailty on clinical outcomes, and on the effects of empagliflozin, as well as the effect of empagliflozin on frailty status during treatment period. Methods We calculated a cumulative deficit‐derived frailty index (FI) using 44 variables including clinical, laboratory and quality of life parameters recorded in EMPEROR‐Preserved. Patients were classified into four groups: non‐frail (FI

Abstract The decongestion ability in response to diuretic treatment plays a crucial role in the treatment of acute heart failure. This effectiveness is evaluated through the assessment of sodium concentration and urine volume, which are also treatment goals themselves. However, the bidirectional interconnection between these factors remains not fully understood. The objective of this study is to provide mechanistic insights into the correlation between spot urine sodium concentrations (UNa+) and urine dilution. This aims to better understand of the decongestive abilities in acute heart failure (AHF). The study was single-center, prospective, conducted on a group of 50 AHF patients. Each participant received a standardized furosemide dose of 1 mg per kg of body weight. Hourly diuresis was measured in the first 6 h of the study, and urine composition was assessed at predefined timepoints. The study group presented the exponential (rather than linear) pattern of relationship between UNa+ and 6-h urine volume, whereas relationship between eGFR and 6-h urine volume was linear (r = 0.61, p

Abstract The COVID-19 pandemic has had a significant impact on global public health, with long-term consequences that are still largely unknown. This study aimed to assess the data regarding acute cardiovascular hospital admissions in five European centers before and during the pandemic. A multicenter, multinational observational registry was created, comparing admissions to the emergency departments during a 3-months period in 2020 (during the pandemic) with the corresponding period in 2019 (pre-pandemic). Data on patient demographics, COVID-19 test results, primary diagnosis, comorbidities, heart failure profile, medication use, and laboratory results were collected. A total of 8778 patients were included in the analysis, with 4447 patients in 2019 and 4331 patients in 2020. The results showed significant differences in the distribution of cardiovascular diseases between the two years. The frequency of pulmonary embolism (PE) increased in 2020 compared to 2019, while acute heart failure (AHF) and other cardiovascular diseases decreased. The odds of PE incidence among hospitalized patients in 2020 were 1.316-fold greater than in 2019. The incidence of AHF was 50.83% less likely to be observed in 2020, and the odds for other cardiovascular diseases increased by 17.42% between the 2 years. Regarding acute coronary syndrome (ACS), the distribution of its types differed between 2019 and 2020, with an increase in the odds of ST-segment elevation myocardial infarction (STEMI) in 2020. Stratification based on sex revealed further insights. Among men, the incidence of AHF decreased in 2020, while other cardiovascular diseases increased. In women, only the incidence of STEMI showed a significant increase. When analyzing the influence of SARS-CoV-2 infection, COVID-positive patients had a higher incidence of PE compared to COVID-negative patients. COVID-positive patients with ACS also exhibited symptoms of heart failure more frequently than COVID-negative patients. These findings provide valuable information on the impact of the COVID-19 pandemic on acute cardiovascular hospital admissions. The increased incidence of PE and changes in the distribution of other cardiovascular diseases highlight the importance of monitoring and managing cardiovascular health during and post pandemic period. The differences observed between sexes emphasize the need for further research to understand potential sex-specific effects of COVID-19 on cardiovascular outcomes.

Abstract 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).

Objective This study aimed to assess the prognostic significance of residual (discharge) dyspnoea in acute heart failure (AHF) patients.Design Single-centre, prospective observational study.Setting Patients hospitalised for decompensated AHF in a single cardiology centre, in Poland.Participants All patients (n=202) who survived the hospitalisation with the primary diagnosis of AHF and were discharged from the hospital.Primary and secondary outcome measures 1-year all-cause mortality; and the composite endpoint of 1-year all-cause mortality and rehospitalisation for the HF (whichever occurred first).Results On admission, 159 (78.7%) AHF patients presented dyspnoea at rest, while residual resting dyspnoea at discharge was present in 16 patients (7.9%). There were 48 (24%) patients with moderate/severe exertional dyspnoea at discharge. In the multivariable model, the resting dyspnoea at discharge was related to a higher risk of both 1-year mortality and composite outcome, with HR (95% CI) 8.0 (3.7 to 17.3) and 5.1 (2.6 to 10.2), respectively, both p

ABSTRACT Acute heart failure is a common and increasingly prevalent condition, affecting >10 million people annually. For those patients who survive to discharge, early readmissions and death rates are >30% everywhere on the planet, making it a malignant condition. Beyond these adverse outcomes, it represents one of the largest drivers of health care costs globally. Studies in the past 2 years have demonstrated that we can induce remissions in this malignant process if therapy is instituted rapidly, at the first acute heart failure episode, using full doses of all available effective medications. Multiple studies have demonstrated that this goal can be achieved safely and effectively. Now the urgent call is for all stakeholders, patients, physicians, payers, politicians, and the public at large to come together to address the gaps in implementation and enable health care providers to induce durable remissions in patients with acute heart failure.

Abstract Aims Treatment response to vericiguat, based on baseline N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) subgroups specified in the protocol, was evaluated in the heart failure (HF) VICTORIA trial population by post hoc analysis of combined lower three quartiles [Q1–Q3] vs. the upper quartile [Q4]. Methods and results VICTORIA participants with available baseline NT‐proBNP levels (n = 4805; 95.1% of total) were included. Compared with patients in Q1–Q3 (NT‐proBNP: Q1, ≤1556 pg/mL; Q2, >1556–2816 pg/mL; and Q3, >2816–5314 pg/mL), patients in Q4 (NT‐proBNP: >5314 pg/mL) were older (69.2 ± 12.0 vs. 66.6 ± 12.1 years), had lower mean ejection fraction (27.2 ± 8.3% vs. 29.5 ± 8.2%; P

Abstract Aims Insulin like growth factor binding protein 7 (IGFBP7) is a marker of senescence secretome and a novel biomarker in patients with heart failure (HF). We evaluated the prognostic value of IGFBP7 in patients with heart failure and examined associations to uncover potential new pathophysiological pathways related to increased plasma IGFBP7 concentrations. Methods and results We have measured plasma IGFBP7 concentrations in 2250 subjects with new‐onset or worsening heart failure (BIOSTAT‐CHF cohort). Higher IGFBP7 plasma concentrations were found in older subjects, those with worse kidney function, history of atrial fibrillation, and diabetes mellitus type 2, and in subjects with higher number of HF hospitalizations. Higher IGFBP7 levels also correlate with the levels of several circulating biomarkers, including higher NT‐proBNP, hsTnT, and urea levels. Cox regression analyses showed that higher plasma IGFBP7 concentrations were strongly associated with increased risk of all three main endpoints (hospitalization, all‐cause mortality, and combined hospitalization and mortality) (HR 1.75, 95% CI 1.25–2.46; HR 1.71, 95% CI 1.39–2.11; and HR 1.44, 95% CI 1.23–1.70, respectively). IGFBP7 remained a significant predictor of these endpoints in patients with both reduced and preserved ejection fraction. Likelihood ratio test showed significant improvement of all three risk prediction models, after adding IGFBP7 (P

Abstract The aim of this research was to examine the prevalence of hyperventilation (defined by pCO2 value) among acute heart failure (AHF) patients and to link it with potential triggers and prognosis. All patients underwent dyspnea severity assessment and capillary blood examination on hospital admission and during hospitalization. Out of 241 AHF patients, 57(24%) were assigned to low pCO2 group (pCO2 ≤ 30 mmHg) and 184 (76%) to normal pCO2 group (pCO2 > 30 mmHg). Low pCO2 group had significantly lower HCO3 - (22.3 ± 3.4 vs 24.7 ± 2.9 mmol/L, p

Introduction: The most common side effect of ticagrelor is dyspnea, which leads to premature withdrawal of this life-saving medication in 6.5% of patients. Increased chemoreceptors’ sensitivity was suggested as a possible pathophysiological explanation of this phenomenon; however, the link between oversensitization of peripheral and/or central chemosensory areas and ticagrelor intake has not been conclusively proved.Methods: We measured peripheral chemoreceptors’ sensitivity using hypoxic ventilatory response (HVR), central chemoreceptors’ sensitivity using hypercapnic hyperoxic ventilatory response (HCVR), and dyspnea severity before and 4 ± 1 weeks following ticagrelor initiation in 11 subjects with chronic coronary syndrome undergoing percutaneous coronary intervention (PCI). The same tests were performed in 11 age-, sex-, and BMI-matched patients treated with clopidogrel. The study is registered at ClinicalTrials.com at NCT05080478.Results: Ticagrelor significantly increased both HVR (0.52 ± 0.46 vs. 0.84 ± 0.69 L min-1 %−1; p < 0.01) and HCVR (1.05 ± 0.64 vs. 1.75 ± 1.04 L min−1 mmHg−1; p < 0.01). The absolute change in HVR correlated with the change in HCVR. Clopidogrel administration did not significantly influence HVR (0.63 ± 0.32 vs. 0.58 ± 0.33 L min-1%−1; p = 0.53) and HCVR (1.22 ± 0.67 vs. 1.2 ± 0.64 L min−1 mmHg−1; p = 0.79). Drug-related dyspnea was reported by three subjects in the ticagrelor group and by none in the clopidogrel group. These patients were characterized by either high baseline HVR and HCVR or excessive increase in HVR following ticagrelor initiation.Discussion: Ticagrelor, contrary to clopidogrel, sensitizes both peripheral and central facets of chemodetection. Two potential mechanisms of ticagrelor-induced dyspnea have been identified: 1) high baseline HVR and HCVR or 2) excessive increase in HVR or HVR and HCVR. Whether other patterns of changes in chemosensitivities play a role in the pathogenesis of this phenomenon needs to be further investigated.

Abstract Background A higher protein intake has been associated with a higher muscle mass and lower mortality rates in the general population, but data about protein intake and survival in patients with heart failure (HF) are lacking. Methods We studied the prevalence, predictors, and clinical outcome of estimated protein intake in 2516 patients from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT‐CHF) index cohort. Protein intake was calculated in spot urine samples using a validated formula [13.9 + 0.907 * body mass index (BMI) (kg/m2) + 0.0305 * urinary urea nitrogen level (mg/dL)]. Association with mortality was assessed using multivariable Cox regression models. All findings were validated in an independent cohort. Results We included 2282 HF patients (mean age 68 ± 12 years and 27% female). Lower estimated protein intake in HF patients was associated with a lower BMI, but with more signs of congestion. Mortality rate in the lowest quartile was 32%, compared with 18% in the highest quartile (P

IntroductionThe research examines the relationship between marathon performance and muscle stiffness changes from pre to marathon in recreational runners aged 50+ years.MethodsThirty-one male long-distance runners aged 50–73 years participated in the experiment. The muscle stiffness of quadriceps and calves was measured in two independent sessions: the day before the marathon and 30 min after the completed marathon run using a Myoton device.Results and DiscussionThe 42.195-km run was completed in 4.30,05 h ± 35.12 min, which indicates an intensity of 79.3% ± 7.1% of HRmax. The long-term, low-intensity running exercise (marathon) in older recreational runners and the low level of HRmax and VO2max showed no statistically significant changes in muscle stiffness (quadriceps and calves). There was reduced muscle stiffness (p = 0.016), but only in the triceps of the calf in the dominant (left) leg. Moreover, to optimally evaluate the marathon and adequately prepare for the performance training program, we need to consider the direct and indirect analyses of the running economy, running technique, and HRmax and VO2max variables. These variables significantly affect marathon exercise.

Background Outcomes and treatment effects of therapy may vary according to the cause of heart failure (HF). Methods and Results In this post hoc analysis of the EMPEROR‐Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) trial, the effect of empagliflozin on cardiovascular and renal outcomes was assessed according to the cause of HF. The cause of HF was investigator reported and stratified as ischemic or nonischemic. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs. Of the 3730 patients enrolled, 1929 (51.7%) had ischemic cause. In the placebo arm, patients with ischemic cause of HF did not have a significantly higher risk of cardiovascular mortality (HR, 1.21 [95% CI, 0.90–1.63]) and hospitalization for HF (HR, 0.90 [95% CI, 0.72–1.12]) compared with nonischemic cause. Empagliflozin compared with placebo significantly reduced the risk of cardiovascular death or hospitalization for HF in patients with ischemic and nonischemic cause (HR, 0.82 [95% CI, 0.68–0.99] for ischemic and HR, 0.67 [95% CI, 0.55–0.82] for nonischemic cause; P interaction=0.15). The benefit of empagliflozin on HF hospitalization, the renal composite end point, estimated glomerular filtration slope changes, and health status scores were also consistent in both groups without treatment by cause modification. Conclusions Empagliflozin offers cardiovascular and renal benefits in patients with heart failure with reduced ejection fraction regardless of the cause of HF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.

Abstract The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of the LVAD‐supported patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD‐supported patients. The expected and non‐expected device‐related and patient–device interaction complications impose a significant burden on the medical system exceeding the capacity of the LVAD implanting centres. The ageing of the LVAD‐supported patients, mainly those supported with the ‘destination therapy’ indication, increases the risk for those patients to experience comorbidities common in the older population. The probability of an LVAD‐supported patient presenting with medical emergency to a local emergency department, internal, or surgical ward of a non‐LVAD implanting centre is increasing. The purpose of this trilogy is to supply the immediate tools needed by the non‐LVAD specialized physician: ambulance clinicians, emergency ward physicians, general cardiologists, internists, anaesthesiologists, and surgeons, to comply with the medical needs of this fast‐growing population of LVAD‐supported patients. The different issues discussed will follow the patient's pathway from the ambulance to the emergency department and from the emergency department to the internal or surgical wards and eventually to the discharge home from the hospital back to the general practitioner. In this first part of the trilogy on the management of LVAD‐supported patients for the non‐LVAD specialist healthcare provider, after the introduction on the assist devices technology in general, definitions and structured approach to the assessment of the LVAD‐supported patient in the ambulance and emergency department is presented including cardiopulmonary resuscitation for LVAD‐supported patients.

Abstract The improvement in left ventricular assist device (LVAD) technology and scarcity of donor hearts have increased dramatically the population of the LVAD‐supported patients and the probability of those patients to present to the emergency department with expected and non‐expected device‐related and patient–device interaction complications. The ageing of the LVAD‐supported patients, mainly those supported with the ‘destination therapy’ indication, increases the risk for those patients to suffer from other co‐morbidities common in the older population. In this second part of the trilogy on the management of LVAD‐supported patients for the non‐LVAD specialist healthcare provider, definitions and structured approach to the LVAD‐supported patient presenting to the emergency department with bleeding, neurological event, pump thrombosis, chest pain, syncope, and other events are presented. The very challenging issue of declaring death in an LVAD‐supported patient, as the circulation is artificially preserved by the device despite no other signs of life, is also discussed in detail.

Abstract Aims We assessed the outcome of hospitalized coronavirus disease 2019 (COVID‐19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. Methods and results International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID‐19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF‐COVICAV). The primary endpoint was in‐hospital mortality. Of 1974 patients hospitalized with COVID‐19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62–81] years, 58% male), with HF being present in 256 [20%] patients. Overall in‐hospital mortality was 25% (n = 323/1282 deaths). In‐hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non‐HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44–2.59], P

Abstract The growing population of left ventricular assist device (LVAD)‐supported patients increases the probability of an LVAD‐ supported patient hospitalized in the internal or surgical wards with certain expected device related, and patient‐device interaction complication as well as with any other comorbidities requiring hospitalization. In this third part of the trilogy on the management of LVAD‐supported patients for the non‐LVAD specialist healthcare provider, definitions and structured approach to the hospitalized LVAD‐supported patient are presented including blood pressure assessment, medical therapy of the LVAD supported patient, and challenges related to anaesthesia and non‐cardiac surgical interventions. Finally, important aspects to consider when discharging an LVAD patient home and palliative and end‐of‐life approaches are described.

Abstract Aims Weight excess and insulin resistance predispose to heart failure. High sodium consumption may contribute to the development of cardiac impairment in insulin‐resistant individuals by promoting inadequate skeletal muscle microvascular perfusion response to insulin. We sought to investigate the association of dietary sodium reduction with muscle perfusion, insulin sensitivity, and cardiac function in overweight/obese insulin‐resistant (O‐IR) normotensive subjects. Methods and results Fifty O‐IR individuals with higher than recommended sodium intake were randomized to usual or reduced sodium diet for 8 weeks; 25 lean, healthy subjects served as controls for pre‐intervention measurements. Echocardiography and muscle perfusion were performed during fasting and under stable euglycaemic–hyperinsulinaemic clamp conditions. O‐IR patients demonstrated subclinical cardiac dysfunction as evidenced by lower left ventricular global longitudinal strain (GLS), e′ tissue velocity, and left atrial strain and reduced muscle perfusion. The intervention arm showed improvements in insulin resistance [glucose infusion rate (GIR)], GLS, e′, atrial strain, and muscle perfusion in fasting conditions, as well as improved responses of GLS and muscle perfusion to insulin during clamp. Significant interactions were found between the allocation to low‐salt diet and improvement in muscle perfusion on change in GIR at follow‐up (P = 0.030), and between improvement in muscle perfusion and change in GIR on change in GLS response to insulin at follow‐up (P = 0.026). Mediation analysis revealed that the relationship between the reduction of sodium intake and improvement in GLS was mediated by improvements in muscle perfusion and GIR (decrease in beta coefficient from −0.29 to −0.16 after the inclusion of mediator variables to the model). Conclusions The reduction of dietary sodium in the normotensive O‐IR population improves cardiac function, and this effect may be associated with the concomitant improvements in skeletal muscle perfusion and insulin resistance. These findings might contribute to refining heart failure preventive strategies.

Abstract 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.

Abstract 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.

Abstract Aims Most studies examined spot urine sodium's (sUNa+) prognostic utility during the early phase of acute heart failure (AHF) hospitalization. In AHF, sodium excretion is related to clinical status; therefore, we investigated the differences in the prognostic information of spot UNa+ throughout the course of hospitalization for AHF (admission vs. discharge). Methods and results The study population were AHF patients (n = 172), who survived the index hospitalization. We compared the relationship between early (on admission, at 24 and 48 h) and discharge sUNa+ measurements with post‐discharge study endpoints: composite of 1 year all‐cause mortality and AHF rehospitalization (with time to first event analysis) as well as with each event in separation. There were 49 (28.5%) deaths, 40 (23.3%) AHF rehospitalizations, while the composite endpoint occurred in 69 (40.1%) during 1 year follow‐up. The sUNa+ had prognostic significance for the composite endpoint when assessed on admission, at 24 and at 48 h: hazard ratios (HRs) with 95% confidence intervals (CIs) (per 10 mmol/L) were 0.88 (0.82–0.94); 0.87 (0.81–0.91); 0.90 (0.84–0.96), all P

Peripheral chemoreceptors (PChRs) play a significant role in maintaining adequate oxygenation in the bloodstream. PChRs functionality comprises two components: tonic activity (PChT) which regulates ventilation during normoxia and acute reflex response (peripheral chemosensitivity, PChS), which increases ventilation following a specific stimulus. There is a clear link between augmented PChS and exercise intolerance in patients with heart failure with reduced ejection fraction. It has been also shown that inhibition of PChRs leads to the improvement in exercise capacity. However, it has not been established yet: 1) whether similar mechanisms take part in heart failure with preserved ejection fraction (HFpEF) and 2) which component of PChRs functionality (PChT vs. PChS) is responsible for the benefit seen after the acute experimental blockade. To answer those questions we enrolled 12 stable patients with HFpEF. All participants underwent an assessment of PChT (attenuation of minute ventilation in response to low-dose dopamine infusion), PChS (enhancement of minute ventilation in response to hypoxia) and a symptom-limited cardiopulmonary exercise test on cycle ergometer. All tests were placebo-controlled, double-blinded and performed in a randomized order. Under resting conditions and at normoxia dopamine attenuated minute ventilation and systemic vascular resistance (p = 0.03 for both). These changes were not seen with placebo. Dopamine also decreased ventilatory and mean arterial pressure responses to hypoxia (p < 0.05 for both). Inhibition of PChRs led to a decrease in V˙E/V˙CO2 comparing to placebo (36 ± 3.6 vs. 34.3 ± 3.7, p = 0.04), with no effect on peak oxygen consumption. We found a significant relationship between PChT and the relative decrement of V˙E/V˙CO2 on dopamine comparing to placebo (R = 0.76, p = 0.005). There was a trend for correlation between PChS (on placebo) and V˙E/V˙CO2 during placebo infusion (R = 0.56, p = 0.059), but the relative improvement in V˙E/V˙CO2 was not related to the change in PChS (dopamine vs. placebo). We did not find a significant relationship between PChT and PChS. In conclusion, inhibition of PChRs in HFpEF population improves ventilatory efficiency during exercise. Increased PChS is associated with worse (higher) V˙E/V˙CO2, whereas PChT predicts an improvement in V˙E/V˙CO2 after PChRs inhibition. This results may be meaningful for patient selection in further clinical trials involving PChRs modulation.

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

Acute coronary syndrome is a factor for poor prognosis and recurrent cardiovascular events. Adequate antiplatelet therapy is crucial in patients with the acute coronary syndrome for risk reduction. Such treatment is well described in four documents issued by the European Society of Cardiology, which precisely illustrate the use of antiplatelets in the settings of ST-elevated and non-ST elevated myocardial infarction. Despite its unquestioned role in the treatment of acute coronary syndrome, recent real-world-data from Polish registries reveal poor adherence to the guidelines-recommended antiplatelet treatment in Poland. Thus, we present here a comprehensive review of the use of antiplatelets in the settings of the acute coronary syndrome. Each phase of the treatment, i.e. pre-hospital, in-hospital and post-hospital, is discussed separately for a better understanding of the decision-making process at each step. We also present unpublished data from Polish registries (e.g. PL-ACS 2019, National Registry of Procedures of Invasive Cardiology, RECEPTOmetrPEX panel) regarding adherence to the guidelines-recommended treatment in Poland, thus highlighting the points of care which should be immediately improved. It has to be stressed here that careful assessment of ischaemic and bleeding risk has to be performed in each patient with acute coronary syndrome individually and repeated at successive phases of the treatment. Only such an approach allows for appropriate antiplatelet therapy tailoring.

Abstract The aim of this study was to test the utility of haemodynamic and autonomic variables (e.g. peripheral chemoreflex sensitivity [PCheS], blood pressure variability [BPV]) for the prediction of individual performance (marathon time and VO2max) in older men. The post-competition vasodilation and sympathetic vasomotor tone predict the marathon performance in younger men, but their prognostic relevance in older men remains unknown. The peripheral chemoreflex restrains exercise-induced vasodilation via sympathetically-mediated mechanism, what makes it a plausible candidate for the individual performance marker. 23 men aged ≥ 50 year competing in the Wroclaw Marathon underwent an evaluation of: resting haemodynamic parameters, PCheS with two methods: transient hypoxia and breath-holding test (BHT), cardiac barosensitivity, heart rate variability (HRV) and BPV, plasma renin and aldosterone, VO2max in a cardiopulmonary exercise test (CPET). All tests were conducted twice: before and after the race, except for transient hypoxia and CPET which were performed once, before the race. Fast marathon performance and high VO2max were correlated with: low ventilatory responsiveness to hypoxia (r = − 0.53, r = 0.67, respectively) and pre-race BHT (r = − 0.47, r = 0.51, respectively), (1) greater SD of beat-to-beat SBP (all p

From a physiological point of view, peripheral chemoreceptors (PCh) are the main sensors of hypoxia in mammals and are responsible for adaptation to hypoxic conditions. Their stimulation causes hyperventilation—to increase oxygen uptake and increases sympathetic output in order to counteract hypoxia-induced vasodilatation and redistribute the oxygenated blood to critical organs. While this reaction promotes survival in acute settings it may be devastating when long-lasting. The permanent overfunctionality of PCh is one of the etiologic factors and is responsible for the progression of sympathetically-mediated diseases. Thus, the deactivation of PCh has been proposed as a treatment method for these disorders. We review here physiological background and current knowledge regarding the influence of widely prescribed medications on PCh acute and tonic activities.

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 SpO2 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

Abstract Aims Failure to prescribe key medicines at evidence‐based doses is associated with increased mortality and hospitalization for patients with Heart Failure with reduced Ejection Fraction (HFrEF). We assessed titration patterns of guideline‐recommended HFrEF medicines internationally and explored associations with patient characteristics in the global, prospective, observational, longitudinal registry. Methods and results Data were collected from September 2013 through December 2014, with 7095 patients from 36 countries [>18 years, previous HF hospitalization within 1–15 months, left ventricular ejection fraction (LVEF) ≤ 40%] enrolled, with dosage data at baseline and up to 18 months from 4368 patients. In 4368 patients (mean age 63 ± 17 years, 75% male) ≥ 100% target doses at baseline: 30.6% (ACEIs), 2.9% (ARBs), 13.9% (BBs), 53.8% (MRAs), 26.2% (ivabradine). At final follow‐up, ≥100% target doses achieved in more patients for ACEI (34.8%), BB (18.0%), and ivabradine (30.5%) but unchanged for ARBs (3.2%) and MRAs (53.7%). Adjusting for baseline dosage, uptitration during follow‐up was more likely with younger age, higher systolic blood pressure, and in absence of chronic kidney disease or diabetes for ACEIs/ARBs; younger age, higher body mass index, higher heart rate, lower LVEF, and absence of coronary artery disease for BBs. For ivabradine, uptitration was more likely with higher resting heart rate. Conclusions The international QUALIFY Registry suggests that few patients with HFrEF achieve target doses of disease‐modifying medication, especially older patients and those with co‐morbidity. Quality improvement initiatives are urgently required.

Abstract 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.

Abstract Aims Several different diagnostic parameters can be used to assess left ventricular (LV) longitudinal systolic function, but no studies comparing their predictive value have been conducted. We sought to compare the prognostic value of LV long‐axis function parameters at rest and exercise using the population with heart failure with preserved ejection fraction (HFpEF). Methods and results Clinical and biochemical variables were collected at baseline in 201 patients with HFpEF. Echocardiography was performed at rest and immediately after exercise, with measurement of mitral annular plane systolic excursion, systolic tissue velocity (s′), global longitudinal strain (GLS), and global longitudinal strain rate (GLSR). Participants were followed for 48 (24–60) months for heart failure hospitalization and cardiovascular death. Seventy‐four patients (36.8%) met the study endpoint. Cox regression analysis revealed that after adjustment for Meta‐Analysis Global Group in Chronic Heart Failure risk score, brain natriuretic peptide (BNP), and peak VO2, heart failure hospitalization and cardiovascular death were significantly associated with GLS at rest [hazard ratio (HR) 0.91; 95% confidence interval (CI) 0.84–0.98; P = 0.016], GLS after exercise (HR 0.84; 95% CI 0.77–0.91; P

Abstract Aims Heart failure (HF) remains a major public health challenge worldwide. Contemporary epidemiological data on HF hospitalization rates and related in‐hospital mortality are scarce also in Poland. The aim of the study was to determine the trends in hospitalization rates due to HF and related in‐hospital mortality in Poland in the recent decade. Methods and results Data on HF hospitalizations and in‐hospital mortality in patients aged >17 years in Poland between 2010 and 2019 were obtained from the central database of the Polish National Health Fund. Hospitalizations with either primary or secondary diagnosis of HF were identified using the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes (I50, I42, J81 with extensions, and R57.0). There were 4 259 698 HF hospitalizations and 608 577 in‐hospital deaths (14% in‐hospital mortality) reported during 2010–2019 in Poland. During this period, there was a steady increase in the number of HF hospitalizations per 1000 inhabitants in subsequent years, being more pronounced in men than in women (in 2019: 16 and 13 HF hospitalizations per 1000 inhabitants in men and women, respectively). The relative risk of HF hospitalization was higher in men than in women, and this gender‐related difference steadily increased from 9% in 2010 to 25% in 2019. During 2010–2019, there was an increase in the number of HF hospitalizations per 1000 inhabitants in subsequent age groups, with a trend being more pronounced in men than in women (129 and 99 HF hospitalizations per 1000 inhabitants in men and women aged ≥80 years, respectively). During this period, there was a slight increase in in‐hospital mortality during HF hospitalization in subsequent years, being more pronounced in women than in men (in 2019: 16% and 14% of in‐hospital mortality in women and men, respectively). The relative risk of in‐hospital mortality during HF hospitalization was higher in women than in men, and this gender‐related difference steadily increased from 8% in 2010 to 18% in 2019. During this period, in‐hospital mortality during HF hospitalization was ~12% for women and men aged 18–29 years, whereas the highest values of in‐hospital mortality reached ~19% for patients aged ≥80 years. Conclusions We have observed steady growing trends in HF hospitalization rates and related in‐hospital mortality in Poland over the last decade. Both age and gender have differentiated the reported epidemiological patterns.

Abstract Aims Patients with acute heart failure (AHF) are included into clinical trials regardless of differences in baseline clinical characteristics. The aim of this study was to assess patients with AHF according to the presence of central and/or peripheral congestion at hospital admission and evaluate treatment response and outcomes in studied phenotypes. Methods and results We investigated retrospectively 352 patients (mean age: 68 ± 13 years, 77% men) hospitalized due to AHF with the signs of congestion on admission. Patients were divided according to the type of signs of congestion into three groups: A, isolated pulmonary congestion (n = 52, 15%); B, isolated peripheral congestion (n = 31, 9%); and C, signs of mixed (peripheral and central) congestion (n = 269, 76%). Patients from Group A had lower concentration of urea, bilirubin, and gamma‐glutamyl transferase whereas higher level of haematocrit, albumin, and leukocytes on admission. The highest baseline N‐terminal pro‐B‐type natriuretic peptide level (median: 4113 vs. 3634 vs. 6093 pg/mL) and percentage of patients with chronic heart failure (56 vs. 58 vs. 74%; A vs. B. vs. C, respectively, all P

Abstract Aims Endothelin‐1 (ET‐1) is a potent vasoconstrictor, which regulates renal and vascular function. We aimed to relate plasma levels of ET‐1 with the clinical picture and outcomes in acute heart failure (AHF). Methods and results We studied 113 patients with AHF [mean age 65 ± 13 (years), median (upper and lower quartiles) N‐terminal pro‐B‐type natriuretic peptide, 5422 (2689; 8582) (pg/mL)], in whom plasma levels of ET‐1 were serially measured at admission (10.8 ± 5.2), Day 1 (9.5 ± 3.4), and Day 2 (8.9 ± 3.8) (pg/mL). The population was divided into tertiles across baseline ET‐1 levels. Patients in the highest ET‐1 tertile had predominant clinical signs of peripheral congestion; however, no difference was observed in pulmonary congestion and severity of dyspnoea. They also presented lower spot urine sodium at admission (75 ± 35 vs. 99 ± 43 vs. 108 ± 30), 6 h (84 ± 34 vs. 106 ± 43 vs. 106 ± 35), and Day 1 (75 ± 38 vs. 96 ± 36 vs. 100 ± 35) (mmol/L), when compared with the second and first tertile, respectively (all P

Peripheral chemoreceptors (PChRs), because of their strategic localization at the bifurcation of the common carotid artery and along the aortic arch, play an important protective role against hypoxia. Stimulation of PChRs evokes hyperventilation and hypertension to maintain adequate oxygenation of critical organs. A relationship between increased sensitivity of PChRs (hyperreflexia) and exercise intolerance (ExIn) in patients with heart failure (HF) has been previously reported. Moreover, some studies employing an acute blockade of PChRs (e.g., using oxygen or opioids) demonstrated improvement in exercise capacity, suggesting that hypertonicity is also involved in the development of ExIn in HF. Nonetheless, the precise mechanisms linking dysfunctional PChRs to ExIn remain unclear. From the clinical perspective, there are two main factors limiting exercise capacity in HF patients: subjective perception of dyspnoea and muscle fatigue. Both have many determinants that might be influenced by abnormal signalling from PChRs, including: exertional hyperventilation, oscillatory ventilation, ergoreceptor oversensitivity, and augmented sympathetic tone. The latter results in reduced muscle perfusion and altered muscle structure. In this review, we intend to present the milieu of abnormalities tied to malfunctioning PChRs and discuss their role in the complex relationships leading, ultimately, to ExIn.

Abstract Aims Episodes of acute heart failure (AHF) may lead to end‐organ dysfunction. In this post hoc analysis of the Relaxin in Acute Heart Failure trial, we used the MELD‐XI (Model of End‐Stage Liver Dysfunction) score to examine hepatorenal dysfunction in patients with AHF. Methods and results On admission, the MELD‐XI score was elevated (abnormal) in 918 (82%) patients, with 638 (57%) having isolated renal dysfunction (creatinine > 1 mg/dL), 73 (6.5%) isolated liver dysfunction (bilirubin > 1 mg/dL), and 207 (18.5%) coexisting dysfunction of the kidneys and the liver (both creatinine and bilirubin > 1 mg/dL). The percentage of patients with elevated MELD‐XI score remained constant through a 60 day follow‐up, as we observed a gradual decrease of liver dysfunction prevalence, counterbalanced by an increase in renal dysfunction. Serelaxin treatment was associated with a lower MELD‐XI score on Day 2 and Day 5 (both P

Viral respiratory infections (VRI) are the most prevalent type of infectious diseases and constitute one of the most common causes of contact with medical care. Regarding the pathophysiology of the cardiovascular system, VRI can not only exacerbate already existing chronic cardiovascular disease (such as coronary artery disease or heart failure) but also trigger new adverse events or complications (e.g., venous thromboembolism), the latter particularly in subjects with multimorbidity or disease-related immobilization. In the current paper, we provide a narrative review of diverse cardiovascular complications of VRI as well as summarize available data on the pathology of the circulatory system in the course of coronavirus disease 2019 (COVID-19).

Acute heart failure (AHF) is a common and severe condition with a poor prognosis. Its course is often complicated by worsening renal function (WRF), exacerbating the outcome. The population of AHF patients experiencing WRF is heterogenous, and some novel possibilities for its analysis have recently emerged. Clustering is a machine learning (ML) technique that divides the population into distinct subgroups based on the similarity of cases (patients). Given that, we decided to use clustering to find subgroups inside the AHF population that differ in terms of WRF occurrence. We evaluated data from the three hundred and twelve AHF patients hospitalized in our institution who had creatinine assessed four times during hospitalization. Eighty-six variables evaluated at admission were included in the analysis. The k-medoids algorithm was used for clustering, and the quality of the procedure was judged by the Davies–Bouldin index. Three clinically and prognostically different clusters were distinguished. The groups had significantly (p = 0.004) different incidences of WRF. Inside the AHF population, we successfully discovered that three groups varied in renal prognosis. Our results provide novel insight into the AHF and WRF interplay and can be valuable for future trial construction and more tailored treatment.

Background: Iron deficiency has been implicated in the pathophysiology of heart failure and myocardial ischemia and reperfusion injury. Moreover, reperfused heart seems to lose iron, thus even subjects with normal iron status could benefit from iron therapy. Impaired mitochondrial respiration and energy starvation may be among possible consequences of myocardial iron deficiency. So far no attempts have been made to treat acute coronary syndromes with iron. Thus our aim was to verify the hypothesis that intravenous iron therapy given during reperfusion of an acute myocardial infarction will reduce left ventricular remodeling and hemodynamic abnormalities in a 2-month follow-up as well as early mitochondrial dysfunction and mortality, in the rat with normal iron status. Methods and results: A single dose of ferric carboxymaltose was administered intravenously at 30 min of reperfusion following 30 min of ischemia in the rat model of myocardial infarction. Ventricular arrhythmias were monitored using a telemetric system, activity of mitochondrial enzymes was assessed using spectrophotometry, serum markers of oxidative stress and inflammation were determined and left ventricular function and remodeling were monitored using echocardiography and pressure-volume loops. Intravenous iron therapy did not affect post-myocardial infarction mortality, left ventricular size or function, ventricular arrhythmias, activity of mitochondrial respiratory chain, oxidative stress or markers of inflammation, but was not associated with any adverse effects. Conclusions: Although ferric carboxymaltose given at reperfusion was safe, it was ineffective in this model of reperfused myocardial infarction in the rat with normal iron status.

Neurohormone activation plays an important role in Acute Heart Failure (AHF) pathophysiology. Serum osmolarity can affect this activation causing vasopressin excretion. The role of serum osmolarity and vasopressin concentration and its interaction remain still unexplored in AHF. The objective of our study was to evaluate the relationship of serum osmolarity with clinical parameters, vasopressin concentration, in-hospital course, and outcomes in AHF patients. The study group consisted of 338 AHF patients (male (76.3%), mean age of 68 ± 13 years) with serum osmolarity calculated by the equation: 1.86 × sodium [mmol/L] + (glucose [mg/dL]/18) + (urea [mg/dL]/2.8) + 9 and divided into osmolarity quartiles marked as: low: 304 mOsm/L. There was an increasing age gradient in the groups and patients differed in the occurrence of comorbidities and baseline clinical and laboratory parameters. Importantly, analysis revealed that vasopressin presented a linear correlation with osmolarity (r = −0.221, p = 0.003) and its concentration decreased with quartiles (61.6 [44.0–81.0] vs. 57.8 [50.0–77.3] vs. 52.7 [43.1–69.2] vs. 45.0 [30.7–60.7] pg/mL, respectively, p = 0.034). This association across quartiles was observed among de novo AHF (63.6 [55.3–94.5] vs. 58.0 [50.7–78.6] vs. 52.0 [46.0–58.0] vs. 38.0 [27.0–57.0] pg/mL, respectively, p = 0.022) and was not statistically significant in patients with acute decompensated heart failure (ADHF) (59.5 [37.4–80.0] vs. 52.0 [38.0–74.5] vs. 57.0 [38.0–79.0] vs. 50.0 [33.0–84.0] pg/mL, respectively, p = 0.849). The worsening of renal function episodes were more frequent in quartiles with higher osmolarity (4 vs. 2 vs. 13 vs. 11%, respectively, p = 0.018) and patients that belonged to the quartiles with low and high osmolarity were characterized more often by incidence of worsening heart failure (20 vs. 9 vs. 10 vs. 22%, respectively, p = 0.032). There was also a U-shape distribution in relation to one-year mortality (31 vs. 19 vs. 23 vs. 37%, respectively, p = 0.022). In conclusion, there was an association of serum osmolarity with clinical status and both in-hospital and out-of-hospital outcomes. Moreover, the linear dependence between vasopressin concentration and serum osmolarity in the AHF population was identified and was driven mainly by patients with de novo AHF which suggests different pathophysiological paths in ADHF and AHF de novo.

Abstract Aims Iron deficiency worsens symptoms, quality of life, and exercise capacity in chronic heart failure (CHF) and might do so by promoting fluid retention. We assessed whether iron repletion improved congestion in CHF and appraised the prognostic utility of calculated plasma volume status (PVS), a novel index of congestion, in the FAIR‐HF data set. Methods and results In FAIR‐HF, 459 iron deficient CHF patients were randomized to intravenous ferric carboxymaltose (FCM) or saline and assessed at 4, 12, and 24 weeks. Using weight and haematocrit, we calculated PVS in 436 patients. At baseline, PVS and weight were −5.5 ± 7.7% and 76.9 ± 14.3 kg, with peripheral oedema evident in 35% of subjects. Higher PVS values correlated to other congestion surrogates such as lower serum albumin. At 4 weeks, FCM was associated with greater reductions in weight (0.02) and PVS (P −4% at baseline predicted worse outcomes even after adjustment for treatment assignment (hazard ratio 1.88, 95% confidence interval 1.01–3.51, 0.046). Conclusions Intravenous iron therapy with FCM is associated with early reductions in PVS and weight, implying that decongestion might be one mechanism via which iron repletion aids CHF patients. Calculated PVS is of prognostic utility in this cohort.

Nitric oxide (NO)-soluble guanylate cyclase(sGC)-cGMP signalling is impaired in HF syndromes, which could predispose to vascular oxidative stress. Nitrates directly stimulate cGMP, but are limited by tolerance. Therapeutic targets that aim at increasing cGMP concentrations have therefore been explored. Recently, two classes of drugs have been discovered, the sGC activators and the sGC stimulators, which target two different redox states of sGC: the NO-sensitive reduced (ferrous) sGC and NO-insensitive oxidized (ferric) sGC, respectively. Cinaciguat is an activator and riociguat and vericiguat are sGC stimulators. Vericiguat is the most advanced agent in its clinical trial programme with two completed phase IIb studies, SOCRATES -REDUCED in HFrEF and SOCRATES-PRESERVED in HFpEF, with mixed results on NT-proBNP. The ongoing VICTORIA trial in HFrEF will study 4,872 participants with a mortality/morbidity end-point and VITALITY HFpEF trial will study 735 participants, with a quality of life end-point.