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Background: The prognostic role of moderate hyperkalemia in reduced ejection fraction (HFrEF) patients is still controversial. Despite this, it affects the use of renin–angiotensin–aldosterone system inhibitors (RAASi) with therapy down-titration or discontinuation. Objectives: Aim of the study was to assess the prognostic impact of moderate hyperkalemia in chronic HFrEF optimally treated patients. Methods and results: We retrospectively analyzed MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) database, with median follow-up of 4.2 [IQR 1.9–7.5] years. Data on K+ levels were available in 7087 cases. Patients with K+ plasma level ≥ 5.6 mEq/L and < 4 mEq/L were excluded. Remaining patients were categorized into normal >4 and < 5 mEq/L (n = 4826, 68%) and moderately high ≥5.0 and ≤ 5.5 mEq/L (n = 496, 7%) K+. Then patients were matched by propensity score in 484 couplets of patients. MECKI score value was 7% [IQR 3.1–14.1%] and 7.3% [IQR 3.4–15%] (p = 0.678) in patients with normal and moderately high K+ values while cardiovascular mortality events at two years follow-up were 41 (4.2%) and 33 (3.4%) (p = 0.333) in each group respectively. Conclusions: Moderate hyperkalemia does not influence patients' outcome in a large cohort of ambulatory HFrEF patients.

Background The prognostic role of diabetes mellitus (DM) in heart failure (HF) patients is undefined, since DM is outweighed by several DM-related variables when confounders are considered. We determined the prognostic role of DM, treatment, and glycemic control in a real-life HF population. Methods 3927 HF patients included in the Metabolic Exercise Cardiac Kidney Index (MECKI) score database were evaluated with a median follow-up of 3.66 years (IQR 1.70–6.67). Data analysis considered survival between DM (n = 897) vs. non-DM (n = 3030) patients, and, in diabetics, between insulin (n = 304), oral antidiabetics (n = 479), and dietary only (n = 88) treatments. The role of glycemic control was evaluated grouping DM patients according to glycated hemoglobin (HbA1c): 8% (n = 149). All analyses were performed also adjusting for ejection fraction, renal function, hemoglobin, sodium, exercise peak oxygen uptake, and ventilation/carbon dioxide relationship slope. Study primary endpoint was the composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Secondary endpoints were cardiovascular and all causes death. Results For all endpoints, upon adjustment for confounders, DM status and insulin treatment or dietary regimen were not significantly associated with adverse long-term prognosis compared to non-DM and oral antidiabetic treated patients, respectively. A worse prognosis was observed in HbA1c >8% patients (Log-Rank p Conclusion In HF patients, DM, insulin treatment and dietary regimen are not adverse outcome predictors. The only condition related to long-term prognosis, considering potential confounders, is poor glycemic control.

Background: In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O2; V.O2AT) has been reported as an absolute value (V.O2ATabs), as a percentage of predicted peak V.O2 (V.O2AT%peak_pred), or as a percentage of observed peak V.O2 (V.O2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing. Research question: What is the prognostic power of these different ways to report AT? Study design and methods: In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer. Results: This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O2ATabs (mean ± SD, 823 ± 305 mL/min) and V.O2AT%peak_pred (mean ± SD, 39.6 ± 13.9%), but not V.O2AT%peak_obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O2ATabs (0.680) and V.O2AT%peak_pred (0.688) performed similarly, whereas V.O2AT%peak_obs (0.538) was significantly weaker (P < .001). Moreover, the V.O2AT%peak_pred AUC value was the only one performing as well as the AUC based on peak V.O2 (0.710), with an even a higher AUC (0.637 vs 0.618, respectively) in the group with severe HF (peak V.O2 < 12 mL/min/kg). Finally, the combination of V.O2AT%peak_pred with peak V.O2 and V. per CO2 production shows the highest prognostic power. Interpretation: In HF, V.O2AT%peak_pred is the best way to report V.O2 at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O2 and, remarkably, in patients with severe HF.

Cardiopulmonary exercise testing is a prognostic tool in heart failure with reduced left ventricular ejection fraction (HFrEF). Prognosticating algorithms have been proposed, but none has been validated. In 2017, a predictive algorithm, based on peak oxygen consumption (VO2), ventilatory response to exercise (ventilation [VE] carbon dioxide production [VCO2], the VE/VCO2 slope), exertional oscillatory ventilation (EOV), and peak respiratory exchange ratio, was recommended, according treatment with β blockers: patients with HFrEF registered in the metabolic exercise test data combined with cardiac and kidney indexes (MECKIs) database were used to validated this algorithm. According to the inclusion/exclusion criteria, 4,683 MECKI patients with HFrEF were enrolled. At 3years follow-up, the end point was cardiovascular death and urgent heart transplantation (cardiovascular events [CV]). CV events occurred in 25% in patients without β blockers, whereas those with β-blockers had 11% (p 10

Aims: Exercise oscillatory ventilation (EOV) is a pivotal cardiopulmonary exercise test parameter for the prognostic evaluation of patients with chronic heart failure (HF). It has been described in patients with HF with reduced ejection fraction (50%, HFpEF), but no data are available for patients with HF with mid-range ejection fraction (40–49%, HFmrEF). The aim of the study was to evaluate the prognostic role of EOV in HFmrEF patients. Methods and results: We analysed 1239 patients with HFmrEF and 4482 patients with HFrEF, enrolled in the MECKI score database, with a 2-year follow-up. The study endpoint was the composite of cardiovascular death, urgent heart transplant, and ventricular assist device implantation. We identified EOV in 968 cases (16% and 17% of cases in HFmrEF and HFrEF,. respectively). HFrEF EOV+ patients were significantly older, and their parameters suggested a more severe HF than HFrEF EOV− patients. A similar behaviour was found in HFmrEF EOV+ vs. EOV− patients. Kaplan–Meier analysis, irrespective of ejection fraction, showed that EOV is associated with a worse survival, and that patients with HFrEF and HFmrEF EOV+ had a significantly worse outcome than the EOV− of the same ejection fraction groups. EOV-associated survival differences in HFmrEF patients started after 18 months of follow-up. Conclusion: Exercise oscillatory ventilation has a similar prevalence and ominous prognostic value in both HFmrEF and HFrEF patients, indicating a group of patients in need of a more intensive follow-up and a more aggressive therapy. In HFmrEF, the survival curves between EOV+ and EOV− patients diverged only after 18 months.

Aims: Exercise-derived parameters, specifically peak exercise oxygen uptake (peak VO2) and minute ventilation/carbon dioxide relationship slope (VE/VCO2 slope), have a pivotal prognostic value in heart failure (HF). It is unknown how the prognostic threshold of peak VO2 and VE/VCO2 slope has changed over the last 20 years in parallel with HF prognosis improvement. Methods and results: Data from 6083 HF patients (81% male, age 61 ± 13 years), enrolled in the MECKI score database between 1993 and 2015, were retrospectively analysed. By enrolment year, four groups were generated: group 1 1993–2000 (n = 440), group 2 2001–2005 (n = 1288), group 3 2006–2010 (n = 2368), and group 4 2011–2015 (n = 1987). We compared the 10-year survival of groups and analysed how the overall risk (cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation) changed over time according to peak VO2 and VE/VCO2 slope and to major clinical and therapeutic variables. At 10 years, a progressively higher survival from group 1 to group 3 was observed, with no further improvement afterwards. A 20% risk for peak VO2 15 mL/min/kg (95% confidence interval 16–13), 9 (11–8), 4 (4–2) and 5 (7–4) was observed in group 1, 2, 3, and 4, respectively, while the VE/VCO2 slope value for a 20% risk was 32 (37–29), 47 (51–43), 59 (64–55), and 57 (63–52), respectively. Conclusions: Heart failure prognosis improved over time up to 2010 in a HF population followed by experienced centres. The peak VO2 and VE/VCO2 slope cut-offs identifying a definite risk progressively decreased and increased over time, respectively. The prognostic threshold of peak VO2 and VE/VCO2 slope must be updated whenever HF prognosis improves.

The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned. Background: The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned. Methods and results: We analyzed data from HF patients (958 patients (801 males, 84%, age 67 ± 11 years)) with AF enrolled in the MECKI score database. We evaluated prognosis (composite of cardiovascular death, urgent heart transplant, or left ventricular assist device) of patients receiving β-blockers (n = 777, 81%) vs. those not treated with β-blockers (n = 181, 19%). We also analyzed the role β1-selectivity and the role of daily β-blocker dose. To account for different HF severity, Kaplan-Meier survival curves were normalized for relevant confounding factors and for treatment strategies. Dose was available in 629 patients. Median follow-up was 1312 (577–2304) days in the entire population, 1203 (614–2420) and 1325 (569–2300) days in patients not receiving and receiving β-blockers. 224 (23%, 54/1000 events/year), 163 (21%, 79/1000 events/year), and 61 (34%, 49/1000 events/year) events were recorded, respectively. At 10-year patients treated with β-blockers had a better outcome (HR 0.447, p < 0.01) with no effects as regards β1selective drugs (53%) vs. β1-β2 blockers (47%). Survival improved in parallel with β-blocker dose increase (HR 0.296, 0.496, 0.490 for the high, medium, and low dose vs. no β-blockers, p < 0.0001). Conclusion: HF patients with AF taking a β-blocker have a better outcome (with a survival improvement in parallel with daily dose but no differences as regards β1 selectivity) but this does not mean that β-blockers improve outcomes in these patients as we cannot control for all the potential confounders associated with β-blocker use.

The right ventricle has become increasingly studied in cardiovascular research. In this article, we describe specific pathophysiological characteristics of the right ventricle, with special focus on functional and molecular modifications as well as therapeutic strategies in right ventricular dysfunction, underlining the differences with the left ventricle. Then we analyze the main imaging modalities to assess right ventricular function in different clinical settings. Finally, we acknowledge main therapeutic advances for treatment of right heart diseases.

The authors regret that the Author Dr. Bussotti Maurizio appears with the following affiliation: Unità Operativa Cardiologia Riabilitativa, Multimedica IRCCS, Milano, Italy. But that was a mistake, the right affiliation of Dr. Bussotti Maurizio is instead: Department of Cardiology, Istituti Clinici Scientifici Maugeri IRCCS, Milano, Italy. The authors kindly ask you to correct this affiliation also with all abstracting partners as PubMed. The authors would like to apologise for any inconvenience caused. DOI of original article: .

The increasing number of patients with heart failure HF and comorbidities is due to aging population and increase of life expectancy of patients with cardiovascular disease. Encouraging results derived by recent trials may suggest some comorbidities as new targets for new drugs, highlighting the need for a better understanding of the comorbidities’ effects in HF patients and the need of a multidisciplinary approach for the management of chronic HF with comorbidities. We report a brief review about main cardiovascular and non-cardiovascular comorbidities in HF patients in order to update physicians and researchers engaged in the HF research or in “fight against heart failure.”

Background Heart failure with midrange ejection fraction (HFmrEF) represents a heterogeneous category where phenotype, as well as prognostic assessment, remains debated. The present study explores a specific HFmrEF subset, namely those who recovered from a reduced EF (rec-HFmrEF) and, particularly, it focuses on the possible additive prognostic role of cardiopulmonary exercise testing. Methods and Results We analyzed data from 4535 patients with HFrEF and 1176 patients with rec-HFmrEF from the Metabolic Exercise combined with Cardiac and Kidney Indexes database. The end point was cardiovascular death at 5 years. The median follow-up was 1343 days (25th–75th range 627–2403 days). Cardiovascular death occurred in 552 HFrEF and 61 rec-HFmrEF patients. The multivariate analysis confirmed an independent role of the MECKI score's variables in HFrEF (C-index = 0.744) whereas, in the rec-HFmrEF group, only age and peak oxygen uptake (pVO2) remained associated to the end point (C-index = 0.745). A peak oxygen uptake of ≤55% of predicted and a ventilatory efficiency of ≥31 resulted as the most accurate cut-off values in the outcome prediction. Conclusions: Present data support the cardiopulmonary exercise test and, particularly, the peak oxygen uptake, as a useful tool in the rec-HFmrEF prognostic assessment. A peak VO2 of ≤55% predicted and ventilatory efficiency of ≥31 might help to identify a high-risk rec-HFmrEF subgroup.

Background: The prognostic role of diabetes mellitus (DM) in heart failure (HF) patients is undefined, since DM is outweighed by several DM-related variables when confounders are considered. We determined the prognostic role of DM, treatment, and glycemic control in a real-life HF population. Methods: 3927 HF patients included in the Metabolic Exercise Cardiac Kidney Index (MECKI) score database were evaluated with a median follow-up of 3.66 years (IQR 1.70–6.67). Data analysis considered survival between DM (n = 897) vs. non-DM (n = 3030) patients, and, in diabetics, between insulin (n = 304), oral antidiabetics (n = 479), and dietary only (n = 88) treatments. The role of glycemic control was evaluated grouping DM patients according to glycated hemoglobin (HbA1c): 8% (n = 149). All analyses were performed also adjusting for ejection fraction, renal function, hemoglobin, sodium, exercise peak oxygen uptake, and ventilation/carbon dioxide relationship slope. Study primary endpoint was the composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Secondary endpoints were cardiovascular and all causes death. Results: For all endpoints, upon adjustment for confounders, DM status and insulin treatment or dietary regimen were not significantly associated with adverse long-term prognosis compared to non-DM and oral antidiabetic treated patients, respectively. A worse prognosis was observed in HbA1c >8% patients (Log-Rank p < 0.001), even after correction for confounding factors. All results were replicated by hazard ratio analysis. Conclusion: In HF patients, DM, insulin treatment and dietary regimen are not adverse outcome predictors. The only condition related to long-term prognosis, considering potential confounders, is poor glycemic control.

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

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 (

Objectives To assess the incremental prognostic utility of discharge serum creatinine (SCr), systolic blood pressure (SBP), and NT-proBNP and sodium concentrations in hospitalized patients with acutely decompensated chronic heart failure. Background Whether key prognostic variables at discharge provide incremental prognostic information beyond that provided by a model based on admission variables (referent) remains incompletely defined. Methods The primary outcome was a composite of death, urgent heart transplantation, or ventricular assist device implantation at 1 year. The gain in predictive performance was assessed using C index, Bayesian Information Criterion, and Net Reclassification Improvement. Results The best fit was obtained when discharge NT-proBNP was added to the referent model. No interaction between admission and discharge NT-proBNP was found. Discharge SCr, SBP, and sodium did not improve goodness-of-fit. Conclusions Admission and discharge NT-proBNP provide complementary and independent prognostic information; as such, they should be taken into account concurrently.

Background Chronic obstructive pulmonary disease (COPD) is among the most common comorbidities in patients hospitalized with heart failure and is generally associated with poor outcomes. However, the results of previous studies with regard to increased mortality and risk trajectories were not univocal. We sought to assess the prognostic impact of COPD in patients admitted for acutely decompensated heart failure (ADHF) and investigate the association between use of β-blockers at discharge and mortality in patients with COPD. Methods We studied 1530 patients. The association of COPD with mortality was examined in adjusted Fine-Gray proportional hazard models where heart transplantation and ventricular assist device implantation were treated as competing risks. The primary outcome was 5-year all-cause mortality. Results After adjusting for establisked risk markers, the subdistribution hazard ratios (SHR) of 5-year mortality for COPD patients compared with non-COPD patients was 1.25 (95% confidence intervals [CIs] 1.06–1.47; p = .007). The relative risk of death for COPD patients increased steeply from 30 to 180 days, and remained noticeably high throughout the entire follow-up. Among patients with comorbid COPD, the use of β-blockers at discharge was associated with a significantly reduced risk of 1-year post-discharge mortality (SHR 0.66, 95%CIs 0.53–0.83; p ≤.001). Conclusions Our data indicate that ADHF patients with comorbid COPD have a worse long-term survival than those without comorbid COPD. Most of the excess mortality occurred in the first few months following hospitalization. Our data also suggest that the use of β-blockers at discharge is independently associated with improved survival in ADHF patients with COPD.

Objective The Kaplan–Meier method may overestimate absolute mortality risk (AMR) in the presence of competing risks. Urgent heart transplantation (UHT) and ventricular assist device implantation (VADi) are important competing events in heart failure. We sought to quantify the extent of bias of the Kaplan–Meier method in estimating AMR in the presence of competing events and to analyze the effect of covariates on the hazard for death and competing events in the clinical model of decompensated chronic heart failure with reduced ejection fraction (DCHFrEF). Study Design and Setting We studied 683 patients. We used the cumulative incidence function (CIF) to estimate the AMR at 1 year. CIF estimate was compared with the Kaplan–Meier estimate. The Fine–Gray subdistribution hazard analysis was used to assess the effect of covariates on the hazard for death and UHT/VADi. Results The Kaplan–Meier estimate of the AMR was 0.272, whereas the CIF estimate was 0.246. The difference was more pronounced in the patient subgroup with advanced DCHF (0.424 vs. 0.338). The Fine–Gray subdistribution hazard analysis revealed that established risk markers have qualitatively different effects on the incidence of death or UHT/VADi. Conclusion Competing risks analysis allows more accurately estimating AMR and better understanding the association between covariates and major outcomes in DCHFrEF.

Background Still there is conflicting evidence about gender-related differences in prognosis among patients with heart failure. This prognostic uncertainty may have implications for risk stratification and planning management strategy. The aim of the present study was to explore the association between gender and one-year mortality in patients admitted with acute decompensated heart failure (ADHF). Methods We studied 1513 patients. The Cumulative Incidence Function (CIF) method was used to estimate the absolute rate of mortality, heart transplantation (HT)/ventricular assist device (VAD) implantation, and survival free of HT/VAD implantation at 1 year. An interaction analysis was performed to assess the association between covariates, gender, and mortality risk. Propensity score matching and Cox regression were used to compare mortality rates in the gender subgroups. Results The CIF estimates of 1-year mortality, HT/VAD implantation, and survival free of HT/VAD implantation at 1 year were 33.1%, 7.0%, and 59.9% for women and 30.2%, 10.2%, and 59.6% for men, respectively. Except for diabetes, there was no significant interaction between gender, covariates, and mortality risk. In the matched cohort, the hazard ratio of death for women was 1.19 (95% confidence intervals [CIs]: 0.90–1.59; p = .202). After adjusting for age and baseline risk, the hazard ratio of death for women was 1.18 (95% CIs: 0.95–1.43; p = .127). The use of gender-specific predictive models did not allow improving the accuracy of risk prediction. Conclusions Our data strongly suggest that women and men have comparable outcome in the year following a hospitalization for ADHF.

Background Obesity has been suggested to confer a survival benefit in acute heart failure. The concentrations of NT-proBNP may be reduced in patients with high body mass index (BMI). Objectives To investigate the relationship among BMI, NT-proBNP, and mortality risk in decompensated chronic heart failure (DCHF). Methods This was a retrospective study. We studied 1001 patients with DCHF. Hazard ratios (HR) were calculated with Cox regression analysis. Results During the 1-year follow-up, 295 patients died. Compared with normal-weight patients, the unadjusted HR for death were 1.02 (95% CIs 0.79–1.33; p = 0.862) for patients with a BMI of 25.0–29.9 kg/m2 and 0.83 (95% CIs 0.61–1.12; p = 0.213) for patients with a BMI ≥ 30 kg/m2. NT-proBNP remained independently associated with mortality across the BMI categories. There was no statistically significant interaction between BMI and NT-proBNP levels for risk prediction. Conclusions Obesity was not associated with mortality risk. NT-proBNP remained an independent prognostic factor across the BMI categories.

This paper presents a new yield function, defined in terms of stress invariants and suitable for isotropic geomaterials. It is a generalisation of that of the modified Cam-Clay (MCC) model and as s...

This paper presents an approach to use the method of characteristics in plane strain problems with failure criteria other than the Mohr–Coulomb and Tresca. Although the method is of general validity, an instance of application is presented for the evaluation of the vertical plastic collapse load of a rigid shallow strip footing resting on a purely frictional material with no lateral surcharge. A comparison with results from finite-element analyses confirms the correctness of the approach.

Renal dysfunction may confound the clinical interpretation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. This study investigated whether renal dysfunction influences the prognostic accuracy of NT-proBNP in acute decompensated heart failure (ADHF).We studied 908 ADHF patients. The primary outcome was 12-month mortality. Interaction between estimated glomerular filtration rate (eGFR) and NT-proBNP in predicting mortality was tested with the likelihood ratio test. The patients were classified into 3 eGFR strata: ≥60, 30-59, and30 ml·min(-1)·1.73 m(-2). Cox models were used to calculate the adjusted hazard ratios (HR) for NT-proBNP, modeled as a dichotomous or categorized variable, within each level of eGFR. NT-proBNP was categorized using optimal cut-offs defined in ROC analysis for each eGFR level. A total of 234 patients (25.8%) died. Testing for interaction was not significant (χ(2)=0.29; P=0.5928). The adjusted HR for NT-proBNP5,180 pg/ml was 2.09 (P0.001) in the highest, 1.7 (P0.001) in the intermediate, and 3.33 (P=0.010) in the lowest eGFR level. The adjusted HR for NT-proBNP above the optimal cut-offs defined on ROC analysis were 1.5 (P=0.239), 2.2 (P0.001), and 3.24 (P=0.002), respectively. The models incorporating NT-proBNP as a dichotomous or categorized variable had equivalent C-statistics.There was no evidence of interaction between eGFR and NT-proBNP in predicting mortality. The NT-proBNP cut-off of 5,180 ng/L provided independent prognostic information, irrespective of the level of residual renal function.

Background Circulating microRNAs (miRs) are promising biomarkers for heart failure (HF). Previous studies have provided inconsistent miR "signatures." The phenotypic and pathophysiologic heterogeneity of HF may have contributed to this inconsistency. In this study we assessed whether advanced HF (AHF) patients present a distinct miR signature compared with healthy subjects (HS) and mild to moderate HF (MHF) patients. Methods The study consisted of 2 phases: a screening phase and a validation phase. In the screening phase, 752 miRs were profiled in HS and MHF and AHF patients ( N = 15), using the real-time quantitative polymerase chain reaction (RT-qPCR) technique and global mean normalization. In the validation phase, the miRs found to be significantly dysregulated in AHF patients compared with both HS and MHF patients were validated in 15 HS, 25 patients with MHF and 29 with AHF, using RT-qPCR, and normalizing to exogenous (cel-miR-39) and endogenous controls. Results In the screening phase, 5 miRs were found to be significantly dysregulated: -26a-5p; -145-3p; -150-5p; -485-3p; and -487b-3p. In the validation phase, miR-150-5p was confirmed to be significantly downregulated in AHF patients when compared with both HS and MHF patients, irrespective of the normalization method used. miR-26a-5p was confirmed to be significantly dysregulated only when normalized to cell-miR-39. Dysregulation of the other miRs could not be confirmed. miR-150-5p was significantly associated with maladaptive remodeling, disease severity and outcome. Conclusions Our data suggest miR-150-5p as a novel circulating biomarker for AHF. The association of miR-150-5p with maladaptive remodeling, disease severity and outcome supports the pathophysiologic relevance of downregulated miR-150-5p expression to AHF.

SUMMARY This paper presents a novel formulation for defining soil failure. It plots in the principal stress space as a surface with the shape ranging between an approximation of the Matsuoka–Nakai and of the Mohr–Coulomb criteria depending on the value of a single parameter. The new function can be used as a replacement of the original equations of these well-established criteria for implementing in a program for numerical analyses, and it is particularly effective for approximating the Matsuoka–Nakai criterion. Both the Mohr–Coulomb and the Matsuoka–Nakai failure criteria present numerical difficulties during implementation and also at run-time. In the case of the Matsuoka–Nakai, the new formulation plots in the first octant only, whereas the original criterion plots in all octants, which causes severe convergence problems particularly for those Gauss points with low stress state, such as those on the side of a shallow footing. When the shape parameter is set to reproduce the Mohr–Coulomb failure criterion, on the other hand, the new formulation plots as a pyramid with rounded edges. Moreover, as the new function is at least of class C2, the second derivatives are continuous, thus ensuring quadratic convergence of the Newton's method used within the integration scheme of the constitutive law. The proposed formulation can also provide both sharp and rounded apex of the surface at the origin of the stress space by setting accordingly one additional parameter. Copyright © 2013 John Wiley & Sons, Ltd.

Purpose: According to the literature, estradiol has a direct vasodilator action by means of endothelium-derived relaxing factor synthesis. The present study aims to evaluate the acute hemodynamic effects of intranasal 17-β-estradiol on cerebral and lower limb arterial circulation in postmenopausal women. Methods: Sixteen healthy women in natural menopause (mean age: 54 ± 3 years) were investigated for at least 6 months, each receiving 300 µg of intranasal 17-β-estradiol. We evaluated the heart rate, systolic/diastolic blood pressure, peak systolic velocity, end-diastolic velocity, and velocity–time integral (VTI) at the level of internal carotid and posterior tibial arteries, before and after 30, 60, and 180 minutes of drug administration. Results: After intranasal 17-β-estradiol administration, the internal carotid artery VTI showed statistically significant ( P < .05) variations at all the time intervals after administration of the drug (30, 60, and 180 minutes) when compared with “time zero” (T0, ie, the speed recorded at baseline before drug administration). No significant variation was found at the posterior tibial artery. The systolic/diastolic blood pressure and heart rate did not significantly differ before and after drug administration. Conclusions: The administration of a single intranasal dose of 17-β-estradiol in healthy postmenopausal women increased cerebral perfusions, whereas the effect on peripheral circulation was much more limited.

In this paper, it is mathematically demonstrated that classical yield and failure criteria such as Tresca, von Mises, Drucker–Prager, Mohr–Coulomb, Matsuoka–Nakai and Lade–Duncan are all defined by the same equation. This can be seen as one of the three solutions of a cubic equation of the principal stresses and suggests that all such criteria belong to a more general class of non-convex formulations which also comprises a recent generalization of the Galileo–Rankine criterion. The derived equation is always convex and can also provide a smooth approximation of continuity of at least class C 2 of the original Tresca and Mohr–Coulomb criteria. It is therefore free from all the limitations which restrain the use of some of them in numerical analyses. The mathematical structure of the presented equation is based on a separate definition of the meridional and deviatoric sections of the graphical representation of the criteria. This enables the use of an efficient implicit integration algorithm which results in a very short machine runtime even when demanding boundary value problems are analysed.

Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) has been associated with prognosis in heart failure. The aim of this study was to assess whether NT-proBNP enhances risk prediction in acute decompensated heart failure (ADHF). The authors enrolled 453 patients hospitalized for ADHF. The primary outcome was 12-month mortality. Two separate multivariable predictive models were built by using standard variables-only and NT-proBNP concentrations. The models were internally validated using the bootstrapping method. Twelve-month mortality was 28.3%. There was no statistical evidence of overfit. Compared with the standard variables-only model, the NT-proBNP model had a better predictive performance as judged by the Nagelkerke R(2) (0.410 vs 0.374) and the Brier score (0.136 vs 0.141), which are measures of overall performance; the Akaike Information Criterion (399.2 vs 415.0), which is a tool for model selection; and the C index (0.844 vs 0.831), which is a measure of the discriminative ability. Both models were well calibrated, as judged by the Hosmer-Lemeshow chi-square test. Both models predicted 12-month mortality significantly better than the Enhanced Feedback for Effective Cardiology Treatment risk score. In conclusion, the NT-proBNP model improved risk prediction compared with the standard variables-only model.

To assess the impact of comorbidities on long-term all-cause mortality in patients hospitalized with exacerbated signs/symptoms of previously chronic stable HF (AE-CHF).1119 patients admitted for AE-CHF and with NT-proBNP levels900pg/mL were enrolled. Univariable and multivariable Cox analyses were performed to assess the association of age, gender, hypertension, diabetes, obesity, atrial fibrillation, coronary heart disease (CHD), chronic obstructive pulmonary disease, previous cerebrovascular accidents, chronic liver disease (CLD), thyroid disease, renal impairment (RI), and anemia with 3-year all-cause mortality.During the follow-up, 441 patients died and 126 underwent heart transplantation (HT) or ventricular assist device (VAD) implantation. 45.8% of the fatal events and 52.4% of HT/VAD implantations occurred within 180days after admission. Increasing age (p=.012), obesity (p=.037), atrial fibrillation (p=.030), CHD (p=.015), CLD (p=.001), RI (p.001), and anemia (p.001) were independently associated with 3-year all-cause mortality. Most of the prognostic impact of CHD, took place within the first 180days after admission. Male gender was associated with mortality beyond 180days. Compared with normal weight, obesity was associated with better overall survival. Obese patients, however, had significantly lower NT-proBNP concentrations and less frequently presented with hypotension, hyponatremia, and severe left ventricular systolic dysfunction, despite a similar prevalence of severe dyspnea at admission.Several comorbidities are associated with long-term risk of death in hospitalized patients with worsening HF, although the nature of this association does appear to be complex. Our data may help to raise awareness about the clinical relevance of comorbid conditions.

Background Accurate identification of renal dysfunction (RD) is crucial to risk stratification in chronic heart failure (CHF). Patients with CHF are at special risk of having RD despite normal serum creatinine (SCr), owing to a decreased Cr generation. At low levels of SCr, the equations estimating renal function are less accurate. This study was aimed to assess and compare the prognostic value of formulas estimating renal function in CHF patients with normal SCr. Methods We studied 462 patients with systolic CHF and normal SCr. Creatinine clearance was estimated by the Cockcroft–Gault (eCrCl) and glomerular filtration rate by the 4-variable MDRD equation (eGFR); eCrCl normalized for body-surface area (eCrCl BSA ) was calculated. The primary outcome was all-cause mortality at 2years. Results Seventy five patients died. At multivariate Cox regression analysis, only eCrCl BSA was significantly associated with mortality ( p =0.006); eGFR ( p =0.24), eCrCl ( p =0.09) and BUN ( p =0.14) were not statistically significant predictors. The patients in the lowest eCrCl BSA quartile had an adjusted 2.1-fold (CI: 1.06–4.1) increased risk of mortality, compared with those in the referent quartile. Two-year survival was 70.4% in the lowest eCrCl BSA quartile and 89.7% in the referent quartile. Other independent predictors of mortality were ischemic etiology (RR: 2.16 [CI: 1.3–3.5], p =0.0017), NYHA III/IV class (RR: 2.45 [CI: 1.51–3.97], p =0.0003), LVEF p =0.014), and anemia (RR: 1.86 [CI: 1.16–2.99], p =0.009). Conclusions A sizeable proportion of CHF patients have prognostically significant RD despite normal SCr. Such patients represent a high-risk subgroup and can more accurately be identified by the CG formula corrected for BSA than the MDRD.

Background The first few months after admission are the most vulnerable period in patients with acute decompensated heart failure (ADHF). Methods and results We assessed the association of the updated ADHF/N-terminal pro-B-type natriuretic peptide (NT-proBNP) risk score with 90-day and in-hospital mortality in 701 patients admitted with advanced ADHF, defined as severe symptoms of worsening HF, severely depressed left ventricular ejection fraction, and the need for i.v. diuretic and/or inotropic drugs. A total of 15.7% of the patients died within 90 days of admission and 5.2% underwent ventricular assist device (VAD) implantation or urgent heart transplantation (UHT). The C-statistic of the ADHF/NT-proBNP risk score for 90-day mortality was 0.810 (95% CI: 0.769-0.852). Predicted and observed mortality rates were in close agreement. When the composite outcome of death/VAD/UHT at 90 days was considered, the C-statistic decreased to 0.741. During hospitalization, 7.6% of the patients died. The C-statistic for in-hospital mortality was 0.815 (95% CI: 0.761-0.868) and Hosmer-Lemeshow χ(2)=3.71 (P=0.716). The updated ADHF/NT-proBNP risk score outperformed the Acute Decompensated Heart Failure National Registry, the Organized Program to Initiate Lifesaving Treatment in Patients Hospitalized for Heart Failure, and the American Heart Association Get with the Guidelines Program predictive models. Conclusions Updated ADHF/NT-proBNP risk score is a valuable tool for predicting short-term mortality in severe ADHF, outperforming existing inpatient predictive models.

Objectives The purpose of this study was to investigate the prognostic value of change in distance walked in 6 min in chronic heart failure (CHF). Background The strongest indication for the 6-min walking test (6MWT) is for measuring the response to therapeutic interventions in patients with CHF. Whether the increase in distance walked after a therapeutic intervention translates into improved clinical outcome is largely unknwon. Methods We studied 476 CHF patients with left ventricular systolic dysfunction who were referred to our institution for adjustment of heart failure therapy because of persisting or worsening symptoms. Adjustment of therapy involved four classes of drugs: angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, beta-blockers, loop diuretics, and aldosterone antagonists. A standardized 6MWT was performed at baseline and at discharge. Results After 15.2 ± 8 days, the distance walked increased from 326 ± 107 m to 408 ± 109 m (+25%; p = 0.001). During a mean follow-up of 23.9 months, 94 patients died and 12 patients underwent cardiac transplantation. Among a set of variables, New York Heart Association functional class (p = 0.02), serum creatinine concentration (p = 0.01), left ventricular ejection fraction (p = 0.002), distance walked at baseline (p = 0.0002), and change in distance walked (p = 0.002) were significant independent predictors of survival. When the patients were divided into two subgroups according to the median value of the distance walked at baseline, the increase in walking distance was significantly associated with survival only in the subgroup of patients who walked Conclusions Our data indicate that repeating a 6MWT after drug intervention provides independent prognostic information in CHF patients with more compromised exercise capacity.

A device is presented for reconstituting sand specimens directly onto the triaxial apparatus by pluviation in air, water or under vacuum. The sand is delivered by means of an uniform rain covering the whole specimen cross section and target density is achieved by changing fall height and depositional intensity. The apparatus was calibrated using Ticino River sand, for which water and vacuum pluviations provided the lowest and highest densities, respectively. Whilst the density of loose samples was similar to that obtained using Kolbuszewski (1948) and ASTM minimum density methods, much denser specimens were obtained with vacuum pluviations as compared to vibration compaction methods (similar to ASTM maximum density method). The resulting maximum relative density, referred to the limits from standard tests, was as high as 140%. Water pluviation density is independent of both depositional intensity and fall height. For other target density best results in terms of sample uniformity are achieved by vacuum pluviation with an appropriate selection of depositional intensity and fall height. This also provides an extremely high reproducibility of target density.

C l i n M e d International Library Citation: Ciccone MM, Scicchitano P, Cortese F, Gesualdo M, Fornarelli F (2014) Endothelial Function in Obese and Overweight Patients: The Role of Olive Oil, Fish and Nuts. Int J Diabetes Clin Res 1:004 Received: September 29, 2014: Accepted: October 18, 2014: Published: October 22, 2014 Copyright: © 2014 Ciccone MM. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Ciccone, et al. Int J Diabetes Clin Res 2014, 1:1

Pietro Scicchitano,1 Francesca Cortese,1 Gabriella Ricci,1 Santa Carbonara,1 Michele Moncelli,1 Massimo Iacoviello,1 Annagrazia Cecere,1 Michele Gesualdo,1 Annapaola Zito,1 Pasquale Caldarola,2 Domenico Scrutinio,3 Rocco Lagioia,3 Graziano Riccioni,4 Marco Matteo Ciccone1 1Section of Cardiovascular Diseases, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Policlinico, Bari, Italy; 2Section of Cardiovascular Diseases, Policlinic, San Paolo Hospital, Bari, Italy; 3Section of Cardiovascular Diseases, Fondazione Maugeri, Cassano Murge, Italy; 4Intensive Cardiology Care Unit, San Camillo de Lellis Hospital, Manfredonia, Foggia, Italy Abstract: Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies. Keywords: chronic heart failure, heart rate reduction, cardiac ischemic disease, heart-rate lowering drugs, funny current

The paper presents a new tension failure criterion which generalizes the so-called Galileo–Rankine formulation. The criterion can be used as a component of the so-called perfectly no-tension model for masonry and cements as well as for establishing a tension cut-off in complex constitutive models for soils, granular materials and powders. The criterion is described by means of a very concise equation based on the third invariant of the stress tensor, approximating the boundaries of the compressive octant of the principal stress space. This sheds new light on the physical significance of the third invariant of the stress tensor. The new criterion has been validated against two known analytical solutions for no-tension materials and also effectively applied for solving two geotechnical and structural engineering problems. The proposed formulation allows for an efficient implementation in finite-element programmes, removing some of the numerical difficulties associated with the Galileo–Rankine criterion.

To investigate whether percent achieved of predicted peak exercise oxygen uptake (%VO2max) and recovery of oxygen consumption after exercise may provide prognostic information in chronic heart failure (CHF), we prospectively studied 196 patients with mild to moderate CHF. The following variables were examined: age, etiology of CHF, functional class, ejection fraction (EF), peak exercise oxygen uptake normalized for body weight (VO2max), %VO2max, time to reach 50% of the peak oxygen uptake after exercise (T1/2VO2max), presence of nonsustained ventricular tachycardia (NSVT) and inability to take ACE-inhibitors. VO2max was the most powerful predictor of cardiac death (P

In any elasto-plastic constitutive model there are three main ingredients, namely a yield surface, a plastic potential surface and a hardening/ softening rule. In this paper a versatile mathematical expression is presented which can be used to describe the yield and plastic potential surfaces. The expression is defined completely by a maximum of only four parameters. These parameters can easily be obtained from observable soil behaviour in simple triaxial tests. A major advantage of the expression is that by suitable adjustment of the parameters a wide range of surface shapes can be achieved. For example, it is possible to reproduce the so called “bullet shape” typical of the plastic potential used in the original Cam clay model and the “tear shape” yield surfaces employed in the more recent models. In fact the expression is capable of accurately reproducing the shapes of many of the yield and plastic potential surfaces currently in use. The expression is also shown to be in good agreement with experimental data.