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Heart failure (HF) is characterized by frequent hospital admissions due to acute decompensation and shortened life span with a progressive clinical course leading to an advanced stage where traditional therapies become ineffective. Due to aging of the population and improved therapies, only a small of proportion of patients with advanced HF are candidates for surgical treatments, such as mechanical circulatory support or heart transplantation. In most cases, prompt identification and management of congestion is paramount to improving symptoms and quality of life and avoiding progression to severe multiorgan dysfunction and death.

Background: Glucocorticoid therapy has emerged as an effective therapeutic option in hospitalized patients with coronavirus disease 2019 (COVID-19). This study aimed to focus on the impact of relevant clinical and laboratory factors on the protective effect of glucocorticoids on mortality. Methods: A sub-analysis was performed of the multicenter Cardio-COVID-Italy registry, enrolling consecutive patients with COVID-19 admitted to 13 Italian cardiology units between 01 March 2020 and 09 April 2020. The primary endpoint was in-hospital mortality. Results: A total of 706 COVID-19 patients were included (349 treated with glucocorticoids, 357 not treated with glucocorticoids). After adjustment for relevant covariates, use of glucocorticoids was associated with a lower risk of in-hospital mortality (adjusted HR 0.44; 95% CI 0.26–0.72; p = 0.001). A significant interaction was observed between the protective effect of glucocorticoids on mortality and PaO2/FiO2 ratio on admission (p = 0.042), oxygen saturation on admission (p = 0.017), and peak CRP (0.023). Such protective effects of glucocorticoids were mainly observed in patients with lower PaO2/FiO2 ratio (100 mg/L). Conclusions: The protective effects of glucocorticoids on mortality in COVID-19 were more evident among patients with worse respiratory parameters and higher systemic inflammation.

Aims: We sought to analyse quality of life (QoL) measures derived from two questionnaires widely used in clinical trials, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQoL 5 dimensions (EQ-5D), and to compare their prognostic value in men and women with heart failure and reduced ejection fraction (HFrEF).Methods and results: From the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) we compared KCCQ and EQ-5D at baseline and after 9 months in 1276 men and 373 women with new-onset or worsening symptoms of HFrEF, who were sub-optimally treated and in whom there was an anticipated up-titration of guideline-derived medical therapies. Women had significantly worse baseline QoL (median) as compared with men, both when assessed with KCCQ overall score (KCCQ-OS, 44 vs. 53, P < 0.001) and EQ-5D utility score (0.62 vs. 0.73, P < 0.001). QoL improved equally in women and men at follow-up. All summary measures of QoL were independently associated with all-cause mortality, with KCCQ-OS showing the most remarkable association with mortality up to 1 year compared to the EQ-5D scores (C-statistic 0.650 for KCCQ-OS vs. 0.633 and 0.599 for EQ-5D utility score and EQ-5D visual analogue scale, respectively). QoL was associated with all outcomes analysed, both in men and women (all P for interaction with sex >0.2).Conclusion: Amongst patients with HFrEF, women reported significantly worse QoL than men. QoL was independently associated with subsequent outcome, similarly in men and women. The KCCQ in general, and the KCCQ-OS in particular, showed the strongest independent association with outcome.

Several risk factors have been identified to predict worse outcomes in patients affected by SARS-CoV-2 infection. Machine learning algorithms represent a novel approach to identifying a prediction model with a good discriminatory capacity to be easily used in clinical practice. The aim of this study was to obtain a risk score for in-hospital mortality in patients with coronavirus disease infection (COVID-19) based on a limited number of features collected at hospital admission.We studied an Italian cohort of consecutive adult Caucasian patients with laboratory-confirmed COVID-19 who were hospitalized in 13 cardiology units during Spring 2020. The Lasso procedure was used to select the most relevant covariates. The dataset was randomly divided into a training set containing 80% of the data, used for estimating the model, and a test set with the remaining 20%. A Random Forest modeled in-hospital mortality with the selected set of covariates: its accuracy was measured by means of the ROC curve, obtaining AUC, sensitivity, specificity and related 95% confidence interval (CI). This model was then compared with the one obtained by the Gradient Boosting Machine (GBM) and with logistic regression. Finally, to understand if each model has the same performance in the training and test set, the two AUCs were compared using the DeLong's test. Among 701 patients enrolled (mean age 67.2 ± 13.2 years, 69.5% male individuals), 165 (23.5%) died during a median hospitalization of 15 (IQR, 9-24) days. Variables selected by the Lasso procedure were: age, oxygen saturation, PaO2/FiO2, creatinine clearance and elevated troponin. Compared with those who survived, deceased patients were older, had a lower blood oxygenation, lower creatinine clearance levels and higher prevalence of elevated troponin (all P 0.001). The best performance out of the samples was provided by Random Forest with an AUC of 0.78 (95% CI: 0.68-0.88) and a sensitivity of 0.88 (95% CI: 0.58-1.00). Moreover, Random Forest was the unique model that provided similar performance in sample and out of sample (DeLong test P = 0.78).In a large COVID-19 population, we showed that a customizable machine learning-based score derived from clinical variables is feasible and effective for the prediction of in-hospital mortality.

Background: Inflammatory responses play an important role in the pathophysiology of cardiogenic shock (CS). The aim of this study was to investigate the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) in CS and to assess their relation to clinical presentation, other biochemical variables, and prognosis. Methods: Levels of PCT, CRP and IL-6 were analyzed in serial plasma samples (0-120h) from 183 patients in the CardShock study. The study population was dichotomized by PCTmax >= and < 0.5 mu g/L, and IL-6 and CRPmax above/below median. Results: PCT peaked already at 24 h [median PCTmax 0.71 mu g/L (IQR 0.24-3.4)], whereas CRP peaked later between 48 and 72 h [median CRPmax 137mg/L (59-247)]. PCT levels were significantly higher among non-survivors compared with survivors from 12 h on, as were CRP levels from 24 h on (p < 0.001). PCTmax >= 0.5 mu g/L (60% of patients) was associated with clinical signs of systemic hypoperfusion, cardiac and renal dysfunction, acidosis, and higher levels of blood lactate, IL-6, growth-differentiation factor 15 (GDF-15), and CRPmax. Similarly, IL-6 > median was associated with clinical signs and biochemical findings of systemic hypoperfusion. PCTmax >= 0.5 mu g/L and IL-6 > median were associated with increased 90-day mortality (50% vs. 30% and 57% vs. 22%, respectively; p < 0.01 for both), while CRPmax showed no prognostic significance. The association of inflammatory markers with clinical infections was modest. Conclusions: Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis. (C) 2020 Elsevier B.V. All rights reserved.

INTRODUCTION: The role of sex compared to comorbidities and other prognostic variables in patients with coronavirus disease (COVID-19) is unclear. METHODS: This is a retrospective observational study on patients with COVID-19 infection, referred to 13 cardiology units. The primary objective was to assess the difference in risk of death between the sexes. The secondary objective was to explore sex-based heterogeneity in the association between demographic, clinical and laboratory variables, and patients' risk of death. RESULTS: Seven hundred and one patients were included: 214 (30.5%) women and 487 (69.5%) men. During a median follow-up of 15 days, deaths occurred in 39 (18.2%) women and 126 (25.9%) men. In a multivariable Cox regression model, men had a nonsignificantly higher risk of death vs. women (P = 0.07).The risk of death was more than double in men with a low lymphocytes count as compared with men with a high lymphocytes count [overall survival hazard ratio (OS-HR) 2.56, 95% confidence interval (CI) 1.72-3.81]. In contrast, lymphocytes count was not related to death in women (P = 0.03).Platelets count was associated with better outcome in men (OS-HR for increase of 50 × 103 units: 0.88 95% CI 0.78-1.00) but not in women. The strength of association between higher PaO2/FiO2 ratio and lower risk of death was larger in women (OS-HR for increase of 50 mmHg/%: 0.72, 95% CI 0.59-0.89) vs. men (OS-HR: 0.88, 95% CI 0.80-0.98; P = 0.05). CONCLUSIONS: Patients' sex is a relevant variable that should be taken into account when evaluating risk of death from COVID-19. There is a sex-based heterogeneity in the association between baseline variables and patients' risk of death.

Data concerning the combined prognostic role of natriuretic peptide (NP) and troponin in patients with COVID-19 are lacking. The aim of the study is to evaluate the combined prognostic value of NPs and troponin in hospitalized COVID-19 patients. From March 1, 2020 to April 9, 2020, consecutive patients with COVID-19 and available data on cardiac biomarkers at admission were recruited. Patients admitted for acute coronary syndrome were excluded. Troponin levels were defined as elevated when greater than the 99th percentile of normal values. NPs were considered elevated if above the limit for ruling in acute heart failure (HF). A total of 341 patients were included in this study, mean age 68 +/-& nbsp;13 years, 72% were men. During a median follow-up period of 14 days, 81 patients (24%) died. In the Cox regression analysis, patients with elevated both NPs and troponin levels had higher risk of death compared with those with normal levels of both (hazard ratio 2.94; 95% confidence interval 1.31 to 6.64; p = 0.009), and this remained significant after adjustment for age, gender, oxygen saturation, HF history, and chronic kidney disease. Interestingly, NPs provided risk stratification also in patients with normal troponin values (hazard ratio 2.86; 95% confidence interval 1.21 to 6.72; p = 0.016 with high NPs levels). These data show the combined prognostic role of troponin and NPs in COVID-19 patients. NPs value may be helpful in identifying patients with a worse prognosis among those with normal troponin values. Further, NPs' cut-point used for diagnosis of acute HF has a predictive role in patients with COVID-19.

Aims Acute heart failure (AHF) leads to a drastic increase in mortality and rehospitalization. The aim of the study was to identify prognostic variables in a real‐life population of AHF patients admitted to the emergency department with acute shortness of breath. Methods and results We evaluated potential predictors of mortality in 728 consecutive patients admitted to the emergency department with AHF. Possible predictors of all‐cause and cardiovascular (CV) mortality were investigated by Cox and Fine and Gray models at multivariable analysis. Among the 728 patients, 256 died during the entire follow‐up, 142 of these due to CV cause. The 1 year mortality rate was 20%, with the highest risk of death during the index hospitalization (with 8% estimate in‐hospital mortality at 30 days). A higher risk of events during the index hospitalization was more evident for the CV deaths, for which we found a cumulative 1 year incidence of 12% with a cumulative incidence in the first 30 days of hospitalization of about 5%. At multivariable analysis, age (P

Aim Istaroxime is a first-in-class agent which acts through inhibition of the sarcolemmal Na+ /K+ pump and activation of the SERCA2a pump. This study assessed the effects of a 24 h infusion of istaroxime in patients hospitalised for acute heart failure (AHF). Methods and results We included patients hospitalised for AHF with left ventricular ejection fraction ≤40% and E/e' > 10. Patients were randomised to a 24 h intravenous infusion of placebo or istaroxime at doses of 0.5 μg/kg/min (cohort 1: placebo n = 19; istaroxime n = 41) or 1.0 μg/kg/min (cohort 2: placebo n = 20, istaroxime n = 40). The primary endpoint of change in E/e' ratio from baseline to 24 h decreased with istaroxime vs. placebo (cohort 1: -4.55 ± 4.75 istaroxime 0.5 μg/kg/min vs. -1.55 ± 4.11 placebo, P = 0.029; cohort 2: -3.16 ± 2.59 istaroxime 1.0 μg/kg/min vs. -1.08 ± 2.72 placebo, P = 0.009). Both istaroxime doses significantly increased stroke volume index and decreased heart rate. Systolic blood pressure increased with istaroxime, achieving significance with the high dose. Self-reported dyspnoea and N-terminal pro-brain natriuretic peptide improved in all groups without significant differences between istaroxime and placebo. No significant differences in cardiac troponin absolute values or clinically relevant arrhythmias were observed during or after istaroxime infusion. Serious cardiac adverse events (including arrhythmias and hypotension) did not differ between placebo and istaroxime groups. The most common adverse events were injection site reactions and gastrointestinal events, the latter primarily with istaroxime 1.0 μg/kg/min. Conclusions In patients hospitalised for AHF with reduced ejection fraction, a 24 h infusion of istaroxime improved parameters of diastolic and systolic cardiac function without major cardiac adverse effects.

Aims Several risk factors have been identified to predict worse outcomes in patients affected by SARS-CoV-2 infection. Prediction models are needed to optimize clinical management and to early stratify patients at a higher mortality risk. Machine learning (ML) algorithms represent a novel approach to identify a prediction model with a good discriminatory capacity to be easily used in clinical practice. Methods and results The Cardio-COVID is a multicentre observational study that involved a cohort of consecutive adult Caucasian patients with laboratory-confirmed COVID-19 [by real time reverse transcriptase—polymerase chain reaction (RT-PCR)] who were hospitalized in 13 Italian cardiology units from 1 March to 9 April 2020. Patients were followed-up after the COVID-19 diagnosis and all causes in-hospital mortality or discharge were ascertained until 23 April 2020. Variables with more than 20% of missing values were excluded. The Lasso procedure was used with a λ = 0.07 for reducing the covariates number. Mortality was estimated by means of a Random Forest (RF). The dataset was randomly divided in two subsamples with the same percentage of death/alive people of the entire sample: training set contained 80% of the data and test set the remaining 20%. The training set was used in the calibration procedure where a RF models in-hospital mortality with the covariates selected by Lasso. Its accuracy was measured by means of the ROC curve, obtaining AUC, sensitivity, specificity, and related 95% confidence interval (CI) computed with 10 000 stratified bootstrap replicates. From the RF the relative Variable Importance Measure (relVIM) was extracted to understand which of the selected variables had the greatest impact on outcome, providing a ranking from the most (relVIM = 100) to the less important variable. The model obtained was compared with the Gradient Boosting Machine (GBM) and with the logistic regression, where the predictions were cross validated. Finally, to understand if each model has the same performance in sample (training) and out of sample (test), the two AUCs were compared by means of the DeLong’s test. Among 701 patients enrolled (mean age 67.2 ± 13.2 years, 69.5% males), 165 (23.5%) died during a median hospitalization of 15 (IQR, 9–24) days. Variables selected by the Lasso were: age, Oxygen saturation, PaO2/FiO2, Creatinine Clearance and elevated Troponin. Compared with those who survived, deceased patients were older, had a lower blood oxygenation, a lower creatinine clearance levels and higher prevalence of elevated Troponin (all P Conclusions In a large COVID-19 population, we showed that a customizable ML-based score derived from clinical variables, is feasible and effective for the prediction of in-hospital mortality.

Purpose of Review The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function, and it is disrupted in heart failure (HF), resulting in decreased protection against myocardial injury. Impaired NO-sGC-cGMP signaling in HF is secondary to reduced NO bioavailability and altered redox state of sGC, which becomes less responsive to NO. The sGC activator cinaciguat increases cGMP levels by direct NO-independent activation of sGC and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and therefore reduced NO levels, at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, thus exerting a more physiological action. Recent Findings Clinical trials have suggested the benefit of vericiguat in patients with high-risk HF; in particular, a lower incidence of death from cardiovascular causes or HF hospitalization. Summary Adding vericiguat may be considered in individual patients with HF, and reduced left ventricular ejection fraction (HFrEF) particularly those at higher risk of HF hospitalization.

Background Pulmonary embolism (PE) has been described in coronavirus disease 2019 (COVID-19) critically ill patients, but the evidence from more heterogeneous cohorts is limited. Methods Data were retrospectively obtained from consecutive COVID-19 patients admitted to 13 Cardiology Units in Italy, from March 1st to April 9th, 2020, and followed until in-hospital death, discharge, or April 23rd, 2020. The association of baseline variables with computed tomography-confirmed PE was investigated by Cox hazards regression analysis. The relationship between d-dimer levels and PE incidence was evaluated using restricted cubic splines models. Results The study included 689 patients (67.3 ± 13.2 year-old, 69.4% males), of whom 43.6% were non-invasively ventilated and 15.8% invasively. 52 (7.5%) had PE over 15 (9–24) days of follow-up. Compared with those without PE, these subjects had younger age, higher BMI, less often heart failure and chronic kidney disease, more severe cardio-pulmonary involvement, and higher admission d-dimer [4344 (1099–15,118) vs. 818.5 (417–1460) ng/mL, p p p = 0.06). In multivariate regression, only d-dimer was associated with PE (HR 1.72, 95% CI 1.13–2.62; p = 0.01). The relation between d-dimer concentrations and PE incidence was linear, without inflection point. Only two subjects had a baseline d-dimer Conclusions PE occurs in a sizable proportion of hospitalized COVID-19 patients. The implications of bleeding events and the role of d-dimer in this population need to be clarified. Graphic abstract

Aims Myocardial injury (MI) in coronavirus disease‐19 (COVID‐19) is quite prevalent at admission and affects prognosis. Little is known about troponin trajectories and their prognostic role. We aimed to describe the early in‐hospital evolution of MI and its prognostic impact. Methods and results We performed an analysis from an Italian multicentre study enrolling COVID‐19 patients, hospitalized from 1 March to 9 April 2020. MI was defined as increased troponin level. The first troponin was tested within 24 h from admission, the second one between 24 and 48 h. Elevated troponin was defined as values above the 99th percentile of normal values. Patients were divided in four groups: normal, normal then elevated, elevated then normal, and elevated. The outcome was in‐hospital death. The study population included 197 patients; 41% had normal troponin at both evaluations, 44% had elevated troponin at both assessments, 8% had normal then elevated troponin, and 7% had elevated then normal troponin. During hospitalization, 49 (25%) patients died. Patients with incident MI, with persistent MI, and with MI only at admission had a higher risk of death compared with those with normal troponin at both evaluations (P

Aims To assess the clinical relevance of a history of atrial fibrillation (AF) in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods and results We enrolled 696 consecutive patients (mean age 67.4 ± 13.2 years, 69.7% males) admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. One hundred and six patients (15%) had a history of AF and the median hospitalization length was 14 days (interquartile range 9–24). Patients with a history of AF were older and with a higher burden of cardiovascular risk factors. Compared to patients without AF, they showed a higher rate of in-hospital death (38.7% vs. 20.8%; P 0.05 for both) and was not related to stroke or bleeding events. Conclusion Among hospitalized patients with COVID-19, a history of AF contributes to worse clinical course with a higher mortality and in-hospital events including new-onset AF, acute HF, and multiorgan failure. The mortality risk remains significant after adjustment for variables associated with COVID-19 severity and comorbidities.

Aims Treatment with angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptors blockers (ARBs) and beta‐blockers is frequently suboptimal at discharge in patients hospitalized for acute heart failure (AHF). We investigated the prognostic significance of medical treatment at discharge and its changes during hospitalization. Methods and results In a retrospective analysis, we included 623 patients hospitalized for AHF with reduced left ventricular ejection fraction (

Heart failure (HF) is characterized by frequent hospital admissions due to acute decompensation and shortened life span with a progressive clinical course leading to an advanced stage where traditional therapies become ineffective. Due to aging of the population and improved therapies, only a small of proportion of patients with advanced HF are candidates for surgical treatments, such as mechanical circulatory support or heart transplantation. In most cases, prompt identification and management of congestion is paramount to improving symptoms and quality of life and avoiding progression to severe multiorgan dysfunction and death.

Background Geographical differences may impact the treatment of heart failure (HF) and the results of clinical trials. We have investigated the differences between geographical areas across Europe in the BIOSTAT-CHF program. Methods Patients with worsening HF enrolled in BIOSTAT-CHF were subdivided, according to the European geographical areas, into those from Northern countries (The Netherlands, Norway, Sweden, UK), Central countries (Germany, Poland, Serbia, Slovenia), and Mediterranean countries (France, Greece, Italy). Patients were compared for baseline characteristics, treatment, and outcomes. The primary endpoint was a composite of all-cause mortality or HF hospitalization. Results Among 2516 patients enrolled in BIOSTAT-CHF, 814 (32.3%) were from Northern European centers, 816 (32.4%) from Central European centers, and 886 (35.2%) from Mediterranean centers. Patients from Northern European centers were older, had more severe signs and symptoms of HF, and with lower incidence of non-cardiac comorbidities such as chronic kidney dysfunction, diabetes and, hypertension, compared to those from the Central and Mediterranean centers. Patients receiving >= 50% of the target dose of both ACE-I/ARB after the up-titration phase were higher in the Northern European centers compared with the other regions (60% versus 58.7% in the Central European centers and 46.5% in the Mediterranean ones; p 0.05). Conclusion The BIOSTAT-CHF study showed significant differences in the clinical features, treatment and prognosis in European patients with HF. Patients from the Mediterranean centers less often had the HF treatments up-titrated; however, the treatment up-titration benefited patients irrespective of their geographical region and should be part of the "default" clinical practice.

Aims: To assess the prognostic value of a history of heart failure (HF) in patients with coronavirus disease 2019 (COVID-19). Methods and results: We enrolled 692 consecutive patients admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. Mean age was 67.4± 13.2 years, 69.5% of patients were males, 90 (13.0%) had a history of HF, median hospitalization length was 14 days (interquartile range 9–24). In-hospital death occurred in 37 of 90 patients (41.1%) with HF history vs. 126 of those with no HF history (20.9%). The increased risk of death associated with HF history remained significant after adjustment for clinical variables related to COVID-19 and HF severity, including comorbidities, oxygen saturation, lymphocyte count and plasma troponin [adjusted hazard ratio (HR) for death: 2.25; 95% confidence interval (CI) 1.26–4.02; P= 0.006 at multivariable Cox regression model including 404 patients]. Patients with a history of HF also had more in-hospital complications including. acute HF (33.3% vs. 5.1%, P< 0.001), acute renal failure (28.1% vs. 12.9%, P< 0.001), multiorgan failure (15.9% vs. 5.8%, P= 0.004) and sepsis (18.4% vs. 8.9%, P= 0.006). Other independent predictors of outcome were age, sex, oxygen saturation and oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen ratio (PaO2/FiO2). In-hospital treatment with corticosteroids and heparin had beneficial effects (adjusted HR for death: 0.46; 95% CI 0.29–0.74; P= 0.001; n= 404 for corticosteroids, and adjusted HR 0.41; 95% CI 0.25–0.67; P< 0.001; n= 364 for heparin). Conclusions: Hospitalized patients with COVID-19 and a history of HF have an extremely poor outcome with higher mortality and in-hospital complications. HF history is an independent predictor of increased in-hospital mortality.

Importance: Myocardial injury, detected by elevated plasma troponin levels, has been associated with mortality in patients hospitalized with coronavirus disease 2019 (COVID-19). However, the initial data were reported from single-center or 2-center studies in Chinese populations. Compared with these patients, European and US patients are older, with more comorbidities and higher mortality rates. Objective: To evaluate the prevalence and prognostic value of myocardial injury, detected by elevated plasma troponin levels, in a large population of White Italian patients with COVID-19. Design, Setting, and Participants: This is a multicenter, cross-sectional study enrolling consecutive patients with laboratory-confirmed COVID-19 who were hospitalized in 13 Italian cardiology units from March 1 to April 9, 2020. Patients admitted for acute coronary syndrome were excluded. Elevated troponin levels were defined as values greater than the 99th percentile of normal values. Main Outcomes and Measures: Clinical characteristics and outcomes stratified as elevated or normal cardiac troponin levels at admission, defined as troponin T or troponin I at a level greater than the 99th percentile of normal values. Results: A total of 614 patients with COVID-19 were included in this study (mean age [SD], 67 [13] years; 70.8% male), of whom 148 patients (24.1%) died during the hospitalization. Elevated troponin levels were found in 278 patients (45.3%). These patients were older (mean [SD] age, 64.0 [13.6] years vs 71.3 [12.0] years; P

AIMS Mineralocorticoid receptor antagonists (MRAs) have been demonstrated to improve outcomes in reduced ejection fraction heart failure (HFrEF) patients. However, MRAs added to conventional treatment may lead to worsening of renal function and hyperkalaemia. We investigated, in a population-based analysis, the long-term effects of MRA treatment in HFrEF patients. METHODS AND RESULTS We analysed data of 6046 patients included in the Metabolic Exercise Cardiac Kidney Index score dataset. Analysis was performed in patients treated (n = 3163) and not treated (n = 2883) with MRA. The study endpoint was a composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Ten years' survival was analysed through Kaplan-Meier, compared by log-rank test and propensity score matching. At 10 years' follow-up, the MRA-untreated group had a significantly lower number of events than the MRA-treated group (P

Low relative lymphocyte count is an important prognostic marker in acute heart failure (AHF); however, it could be influenced by other abnormalities in white cells count. Our purpose is to evaluate if low absolute lymphocyte count (ALC) is an independent predictor of events in patients with AHF. In a retrospective analysis, we included 309 patients with AHF, divided into two groups according to the median value of ALC at admission (1410 cells/μl). The primary end point was all-cause mortality or urgent heart transplantation within 1 year. Patients with low ALC were older and had more comorbidity, namely atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease and anemia. Low ALC was associated with higher all-cause mortality or urgent heart transplantation at 1 year (24.3 vs 13.0%; P = 0.012). In a multivariable model, the independent predictors of mortality at 1 year were ALC 1410 cells/μl or less at admission [hazard ratio 2.04; CI (confidence interval) 95% (1.06–3.95); P = 0.033], age [hazard ratio 1.08; CI 95% (1.04–1.12); P

Aims Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction. Methods and results We collected data on 6112 HF patients and compared the prognostic accuracy of MECKI score, HFSS, and SHFM at 2- and 4-year follow-up for the combined endpoint of cardiovascular death, urgent cardiac transplantation, or ventricular assist device implantation. Patients were followed up for a median of 3.67 years, and 931 cardiovascular deaths, 160 urgent heart transplantations, and 12 ventricular assist device implantations were recorded. At 2-year follow-up, the prognostic accuracy of MECKI score was significantly superior [area under the curve (AUC) 0.781] to that of SHFM (AUC 0.739) and HFSS (AUC 0.723), and this relationship was also confirmed at 4 years (AUC 0.764, 0.725, and 0.720, respectively). Conclusion In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2- and 4-year follow-up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed.

Aims: The use of β-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared β-blockers in HFrEF, and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients (MECKI score database) the association of β-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of β-selectivity and dosage regimens. Methods and results: In 5242 HFrEF patients, we investigated the role of: (i) β-blocker treatment vs. non-β-blocker treatment, (ii) β1-/β2-receptor-blockers vs. β1-selective blockers, and (iii) daily β-blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on β-blockers, while 807 (13.2%) were not. At 5 years, β-blocker-patients showed a better outcome than non-β-blocker-subjects [hazard ratio (HR) 0.48, P 2 5 mg carvedilol equivalent daily dose, n = 1005) patients than in both medium dose (12.5–25 mg, n = 1431) and low dose (

Background: Critically ill patients often present with hyperglycemia, regardless of previous history of diabetes mellitus (DM). Hyperglycemia has been associated with adverse outcome in acute myocardial infarction and acute heart failure. We investigated the association of admission blood glucose level with the clinical picture and short-term mortality in cardiogenic shock (CS). Methods: Consecutively enrolled CS patients were divided into five categories according to plasma glucose level at the time of enrolment: hypoglycemia (glucose = 16.0 mmol/L) hyperglycemia. Clinical presentation, biochemistry, and short-term mortality were compared between the groups. Results: Plasma glucose level of 211 CS patients was recorded. Glucose levels were distributed equally between normoglycemia (26% of patients), mild (27%), moderate (19%) and severe (25%) hyperglycemia, while hypoglycemia (2%) was rare. Severe hyperglycemia was associated with higher blood leukocyte count (17.3 (5.8) E9/L), higher lactate level (4.4 (3.3-8.4) mmol/L) and lower arterial pH (7.23 (0.14)) compared with normoglycemia or mild to moderate hyperglycemia (p

Introduction: Cardiogenic shock complicating acute myocardial infarction has a very high mortality. Our present study focuses on serial measurement of lactate during admission due to cardiogenic shock and the prognostic effect of lactate and a relative change in lactate in patients after admission and the institution of intensive care treatment. Methods and Results: This is a secondary analysis of the CardShock study. Data on lactate at baseline were available on 217 of 219 patients. In the study population, the median baseline lactate was 2.8 mmol/L (min-max range, 0.5-23.1 mmol/L). At admission, lactate was predictive of 30-day mortality with an adjusted Hazard ratio (HR) of 1.20 mmol/L (95% confidence interval, CI 1.14-1.27). Within the first 24 h of admission, baseline lactate remained predictive of 30-day mortality. Lactate at 6 h had a HR of 1.14 (95% CI 1.06-1.24) and corresponding values at 12 and 24 h had a HR of 1.10 (1.04-1.17), and of HR 1.19 (95% CI 1.07-1.32), respectively. A 50% reduction in lactate within 6 h resulted in a HR of 0.82 (95% CI 0.72-0.94). Corresponding hazard ratios at 12 and 24 h, were 0.87 (95% CI 0.76-0.98) and 0.74 (95% CI 0.60-0.91), respectively. Conclusion: The main findings of the present study are that baseline lactate is a powerful predictor of 30-day mortality, lactate at 6, 12, and 24 h after admission are predictors of 30-day mortality, and a relative change in lactate is a significant predictor of survival within the first 24 h after instituting intensive care treatment adding information beyond the information from baseline values.

Background: Cardiogenic shock (CS) is the most life-threatening manifestation of acute heart failure. Its complexity and high in-hospital mortality may justify the need for invasive monitoring with a pulmonary artery catheter (PAC). Methods: Patients with CS included in the CardShock Study, an observational, prospective, multicenter, European registry, were analyzed, aiming to describe the real-world use of PAC, evaluate its impact on 30-day mortality, and the ability of different hemodynamic parameters to predict outcomes. Results: Pulmonary artery catheter was used in 82 (37.4%) of the 219 patients. Cardiogenic shock patients who managed with a PAC received more frequently treatment with inotropes and vasopressors, mechanical ventilation, renal replacement therapy, and mechanical assist devices ( P < .01). Overall 30-day mortality was 36.5%. Pulmonary artery catheter use did not affect mortality even after propensity score matching analysis (hazard ratio = 1.17 [0.59-2.32], P = .66). Cardiac index, cardiac power index (CPI), and stroke volume index (SVI) showed the highest areas under the curve for 30-day mortality (ranging from 0.752-0.803) and allowed for a significant net reclassification improvement of 0.467 (0.083-1.180), 0.700 (0.185-1.282), 0.683 (0.168-1.141), respectively, when added to the CardShock risk score. Conclusions: In our contemporary cohort of CS, over one-third of patients were managed with a PAC. Pulmonary artery catheter use was associated with a more aggressive treatment strategy. Nevertheless, PAC use was not associated with 30-day mortality. Cardiac index, CPI, and SVI were the strongest 30-day mortality predictors on top of the previously validated CardShock risk score.

Cardiovascular diseases affect adult population but risk factors develop as a result of known or assumed behavior since childhood. In Italy, up to 22.2% of children are overweight, 10.6% are obese, and 2.5% have severe obesity.We performed a systematic review of the literature to identify studies and initiatives addressing health promotion among children in Italy. Given the high heterogeneity of interventions and outcomes assessed we opted to perform a qualitative synthesis of the results. We described also nonrandomized trial where the intervention of primary prevention was very innovative, explained in detail, and reached an improving outcome for participants.We identified 11 projects since 1983, only five were randomized control trials. Three involved children and teachers of primary and secondary schools and were based on specific curricular lectures about health. One was based on a game developed for high schools with the purpose to promote healthy lifestyle and physical activity. The fifth project was based on an enhanced physical activity program.Our results show that school and family should be considered as the privileged places for health promotion. In Italy, the development of scientific-validated lifestyle interventions for children is still an unmet need.

Chronic heart failure (CHF) may be associated with an energy deficit in cardiac muscle. As levo-carnitine (LC) is involved in the production of myocardial energy, it is hypothesized that LC supplementation may ameliorate CHF symptoms. This multicentre, randomized, double-blind, and placebo-controlled study included 265 patients with CHF. Patients were randomized to receive either LC or placebo, twice a day. Endpoints were measured after 7 days of treatment. Primary endpoint was a reduction of at least one NYHA class. Secondary endpoints were changes in 6-min walk distance (6-MWD) compared with baseline, either alone or in combination with NYHA class decrease, left ventricular ejection fraction, and NT-proBNP level, together with adverse events. The primary endpoint was reached in 60.9% of patients treated with LC, compared with only 44.7% of the placebo group ( P = 0.012). Among the secondary endpoints, 6-MWD, alone or in combination with NYHA class, improved significantly in the LC group compared with placebo ( P = 0.0497 and P = 0.003, respectively). l-Carnitine was well tolerated. The lowest baseline values of plasma-free carnitine were observed in patients with NYHA classes III and IV where the effect of LC supplementation was greatest ( P = 0.002). Treatment with LC significantly improved CHF symptoms in Chinese patients, probably by correcting a status of carnitine insufficiency.

Background: There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals. Methods: A total of 684 patients with suspected AM and recent onset of symptoms (70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance. Results: At presentation, 118 patients (26.6%) had left ventricular ejection fraction P P P =0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction Conclusions: In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction

Chronic kidney disease (CKD) is one of the most prevalent comorbidities in HF, and no specific treatment is still available for the so-called cardiorenal syndrome. Areas covered: The aim of this review is to describe the interaction of heart and kidney function and the consequences of cardiorenal syndrome, focusing on the use of available therapeutics. Expert commentary: The presence of CKD has been associated with adverse outcomes in HF regardless of ejection fraction. On the other hand, cardiovascular events are the most common causes of morbidity and mortality among CKD patients, reflecting the close pathophysiological crosstalk between these organs. Multiple mechanisms are involved in the development of cardiorenal syndrome, including hemodynamic, neurohormonal and inflammatory mediators. The management of several HF drugs is a challenge in the presence of CKD mainly due to blunted diuretic response and increased risk of worsening of kidney function. Therefore, finding a balance between the optimization of cardiac and renal outcomes is a real negotiation in the everyday clinical practice.

Since increased heart rate (HR) is associated with higher mortality in several cardiac disorders, HR is considered not only a physiological indicator but also a prognostic and biological marker. In heart failure (HF), it represents a therapeutic target in chronic phase. The use or up-titration of beta-blockers, a milestone in HF with reduced left ventricular ejection fraction (LVEF) treatment, is at times limited by patients' hemodynamic profile or intolerance. Ivabradine, a HR-lowering drug inhibiting the f-current in pacemaker cells, has been shown to improve outcome in patients with chronic HF, in sinus rhythm with increased HR beyond beta-blocker therapy. The rationale for this review is to update the role of HR as a prognostic biomarker and a potential therapeutic target in other scenarios than chronic HF; namely, in patients with coexisting atrial fibrillation (AF), in HF with preserved LVEF (HFpEF), in acute HF, and in patients discharged after an episode of acute HF. Preliminary studies and case reports that evaluated the use of ivabradine in the setting of acute HF will be summarized. Recent results of HR reduction in the setting of HFpEF with ivabradine will be presented. Finally, data from large registries and trials that evaluated the prognostic impact of HR in patients with acute HF and sinus rhythm or AF will be reviewed, showing that only patients in sinus rhythm may benefit from HR reduction.

Background: Site selection is critical in acute heart failure trials. We assessed whether the enrollment rate per site affects patients' characteristics, outcomes and treatment response. Methods and results: A total of 1161 patients enrolled at 96 sites in the RELAX-AHF trial (serelaxin vs placebo) were included. Annualized enrollment rate was calculated as the total number of patients enrolled at each site divided by time that the site was open (patients per year). Sites were classified in low (20 patients per site/year) and were compared for prognosis and serelaxin effect. High enrolling sites were more prevalent in Eastern Europe and Israel. Time from hospital admission to randomization was shorter in high enrolling sites (6.3 +/- 4.4 h >20 patients sites versus 8.7 +/- 4.5 h for

AIM Heart rate (HR) is an important prognostic factor in patients affected by chronic heart failure (CHF); ivabradine has been demonstrated to significantly reduce nonfatal myocardial infarction and hospitalization rate for acute heart failure and to improve left ventricular (LV) reverse remodeling, quality of life, exercise capacity, and arterial elastance (Ea) in these patients. We aimed at evaluating the short-term effects of ivabradine on ventricular-arterial coupling (VAC), aortic stiffness, and endothelial function in stable patients with CHF. METHODS We evaluated 30 consecutive CHF patients (LVEF≤ 35%, NYHA class II) with sinus rhythm and HR ≥ 70 bpm on optimized pharmacological therapy. All of them underwent both transthoracic echocardiogram to assess aortic elastic properties (aortic distensibility, AD; aortic stiffness index, ASI; systolic aortic strain, SAS) and VAC, and peripheral arterial tonometry to measure endothelial function. Therapy with ivabradine 5 mg bid was added and each patient was evaluated with the same examinations after 4 months. RESULTS At the baseline, 73% of patients had impaired VAC and 63% endothelial dysfunction. After 4 months, there was a significant improvement in the VAC value (ΔVAC -0.10 ± 0.18, P = .021), mainly linked to Ea (ΔEa -0.40 ± 0.23 mm Hg/mL; P = .003). All the parameters of aortic elasticity underwent significant improvement (ΔAD 1.82 ± 1.43 cm² × dyn- ¹, P = .004; ΔASI -4.73 ± 6.07, P = .033; ΔSAS -7.98 ± 4.37%, P = .003). Lastly, we also noted a significant improvement of endothelial function (Δ RHI 0.35 ± 0.35; P

AimsThe aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short-term mortality. Methods and resultsThe CardShock study was a multicentre, prospective, observational study conducted between 2010 and 2012. Patients with either acute coronary syndrome (ACS) or non-ACS aetiologies were enrolled within 6h from detection of cardiogenic shock defined as severe hypotension with clinical signs of hypoperfusion and/or serum lactate >2mmol/L despite fluid resuscitation (n = 219, mean age 67, 74% men). Data on clinical presentation, management, and biochemical variables were compared between different aetiologies of shock. Systolic blood pressure was on average 78 mmHg (standard deviation 14 mmHg) and mean arterial pressure 57 (11) mmHg. The most common cause (81%) was ACS (68% ST-elevation myocardial infarction and 8% mechanical complications); 94% underwent coronary angiography, of which 89% PCI. Main non-ACS aetiologies were severe chronic heart failure and valvular causes. In-hospital mortality was 37% (n = 80). ACS aetiology, age, previous myocardial infarction, prior coronary artery bypass, confusion, low LVEF, and blood lactate levels were independently associated with increased mortality. The CardShock risk Score including these variables and estimated glomerular filtration rate predicted in-hospital mortality well (area under the curve 0.85). ConclusionAlthough most commonly due to ACS, other causes account for one-fifth of cases with shock. ACS is independently associated with in-hospital mortality. The CardShock risk Score, consisting of seven common variables, easily stratifies risk of short-term mortality. It might facilitate early decision-making in intensive care or guide patient selection in clinical trials.

Background: Acute heart failure (HF) is common in the elderly, but the association of age with clinical outcomes and prognostic factors has not been examined thoroughly.Methods and Results: We analyzed the clinical and laboratory characteristics and the outcomes of 1,347 patients with acute HF enrolled in the VERITAS trial. Subjects were subdivided based on their median age of 72 years. Older patients had a higher prevalence of comorbidities and a higher prevalence of hypertension and atrial fibrillation. During a mean follow-up of 149 +/- 61 days, 432 patients (32.1%) reached the composite end point of death, in-hospital worsening HF, or HF rehospitalization by 30 days, and 135 patients (10.4%) died by 90 days, with a worse outcome in elderly patients in both cases. At multivariable analysis, different variables were related with each of these outcomes in elderly compared with younger patients. Regarding deaths at 90 days, plasma urea nitrogen and hemoglobin levels were predictive only in the younger patients, whereas respiratory rate and albumin levels were associated with mortality only in the older patients.Conclusions: Elderly patients with acute HF have different clinical characteristics and poorer outcomes. Prognostic variables differ in elderly compared with younger patients.

Objective: Chronic heart failure (CHF) is characterized by several micronutrient deficits. Amino acid supplementation may have a positive effect on nutritional and metabolic status in patients with CHF. Levo-carnosine (b-alanyl-L-histidine) is expressed at a high concentration in myocardium and muscle. Preliminary studies with L-carnosine in healthy individuals have suggested a potential role in improving exercise performance. To our knowledge, no study has been conducted in patients with heart failure. The aim of this study was to test the oral supplementation of L-carnosine and its effects on quality of life and exercise performance in patients with stable CHF. Methods: Fifty patients with stable CHF and severe left-ventricular systolic dysfunction on optimal medical therapy were randomized 1:1 to receive oral orodispersible L-carnosine (500 mg OD) or standard treatment. Left-ventricular ejection fraction (LVEF) was measured by echocardiography. Cardiopulmonary stress test, 6-minute walking test (6MWT) and quality-of-life (visual analog scale score and the EuroQOL five dimensions questionnaire [EQ-5D]) were performed at baseline and after 6 mo. Results: Patients receiving orodispersible L-carnosine had an improvement in 6MWT distance (P ¼ 0.014) and in quality-of-life (VAS score) (P ¼ 0.039) between baseline and follow-up. Compared with controls, diet supplementation with orodispersible L-carnosine was associated with an improvement in peakVO2 (P < 0.0001), VO2 at anaerobic threshold, peak exercise workload, 6MWT and quality-of-life assessed by the EQ-5D test and the VAS score. Conclusion: This study suggests that L-carnosine, added to conventional therapy, has beneficial effects on exercise performance and quality of life in stable CHF. More data are necessary to evaluate its effects on left-ventricular ejection fraction and prognosis in CHF.

Background: Altered mental status is among the signs of hypoperfusion in cardiogenic shock, the most severe form of acute heart failure. The aim of this study was to investigate the prevalence of altered mental status, to identify factors associating with it, and to assess the prognostic significance of altered mental status in cardiogenic shock. Methods: Mental status was assessed at presentation of shock in 215 adult cardiogenic shock patients in a multinational, prospective, observational study. Clinical picture, biochemical variables, and short-term mortality were compared between patients presenting with altered and normal mental status. Results: Altered mental status was detected in 147 (68%) patients, whereas 68 (32%) patients had normal mental status. Patients with altered mental status were older (68 vs. 64 years, p=0.04) and more likely to have an acute coronary syndrome than those with normal mental status (85% vs. 74%, p=0.04). Altered mental status was associated with lower systolic blood pressure (76 vs. 80 mmHg, p=0.03) and lower arterial pH (7.27 vs. 7.35, pConclusions: Altered mental status is a common clinical sign of systemic hypoperfusion in cardiogenic shock and is associated with poor outcome. It is also associated with several biochemical findings that reflect inadequate tissue perfusion, of which low arterial pH is independently associated with altered mental status.

Congestion is a fundamental clinical sign in patients with chronic heart failure (CHF). Diuretics are the mainstay treatment for congestion but, so far, no randomized trial has ever shown any beneficial effect of diuretics on mortality in patients with CHF. It is also unclear how and when diuretics should be up, or down titrated, or when their use can be safely stopped. In this review, we discuss current evidence regarding the clinical use of diuretics. We also highlight the need for more clinical trials to explore the short- and long-term safety, efficacy and clinical benefits of different classes of diuretics, used alone or in combination, in patients with CHF.

Background The clinical CardShock risk score, including baseline lactate levels, was recently shown to facilitate risk stratification in patients with cardiogenic shock (CS). As based on baseline parameters, however, it may not reflect the change in mortality risk in response to initial therapies. Adrenomedullin is a prognostic biomarker in several cardiovascular diseases and was recently shown to associate with hemodynamic instability in patients with septic shock. The aim of our study was to evaluate the prognostic value and association with hemodynamic parameters of bioactive adrenomedullin (bio-ADM) in patients with CS. Methods CardShock was a prospective, observational, European multinational cohort study of CS. In this sub-analysis, serial plasma bio-ADM and arterial blood lactate measurements were collected from 178 patients during the first 10 days after detection of CS. Results Both bio-ADM and lactate were higher in 90-day non-survivors compared to survivors at all time points (P < 0.05 for all). Lactate showed good prognostic value during the initial 24 h (AUC 0.78 at admission and 0.76 at 24 h). Subsequently, lactate returned normal (≤2 mmol/L) in most patients regardless of later outcome with lower prognostic value. By contrast, bio-ADM showed increasing prognostic value from 48 h and beyond (AUC 0.71 at 48 h and 0.80 at 5–10 days). Serial measurements of either bio-ADM or lactate were independent of and provided added value to CardShock risk score (P < 0.001 for both). Ninety-day mortality was more than double higher in patients with high levels of bio-ADM (>55.7 pg/mL) at 48 h compared to those with low bio-ADM levels (49.1 vs. 22.6%, P = 0.001). High levels of bio-ADM were associated with impaired cardiac index, mean arterial pressure, central venous pressure, and systolic pulmonary artery pressure during the study period. Furthermore, high levels of bio-ADM at 48 to 96 h were related to persistently impaired cardiac and end-organ function. Conclusions Bio-ADM is a valuable prognosticator and marker of impaired hemodynamics in CS patients. High levels of bio-ADM may show shock refractoriness and developing end-organ dysfunction and thus help to guide therapeutic approach in patients with CS., published version, peerReviewed

Background: Despite scarce data, invasive mechanical ventilation (MV) is widely recommended over noninvasive ventilation (NIV) for ventilatory support in cardiogenic shock (CS). We assessed the real-life use of different ventilation strategies in CS and their influence on outcome focusing on the use of NIV and MV. Methods: 219 CS patients were categorized by the maximum intensity of ventilatory support they needed during the first 24 h into MV (n= 137; 63%), NIV(n= 26; 12%), and supplementary oxygen (n= 56; 26%) groups. We compared the clinical characteristics and 90-day outcome between the MV and the NIV groups. Results: Mean age was 67 years, 74% were men. The MV and NIV groups did not differ in age, medical history, etiology of CS, PaO2/FiO(2) ratio, baseline hemodynamics or LVEF. MV patients predominantly presented with hypoperfusion, with more severe metabolic acidosis, higher lactate levels and greater need for vasoactive drugs, whereas NIV patients tended to be more often congestive. 90-day outcome was significantly worse in the MV group (50% vs. 27%), but after propensity score adjustment, mortality was equal in both groups. Confusion, prior CABG, ACS etiology, higher lactate level, and lower baseline PaO2 were independent predictors of mortality, where as ventilation strategy did not have any influence on outcome. Conclusions: Although MV is generally recommended mode of ventilatory support in CS, a fair number of patients were successfully treated with NIV. Moreover, ventilation strategy was not associated with outcome. Thus, NIV seems a safe option for properly chosen CS patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.