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.
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.
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.
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.
The Cosserat continuum is very effective in regularizing the ill‐posed governing equations of the Cauchy/Maxwell continuum. An elasto‐plastic constitutive model for the linear formulation of the ...Cosserat continuum is here presented, which features non‐associated flow, hardening/softening behaviour and multiple yield and plastic potential surfaces, whilst linear hyper‐elasticity is adopted to reproduce the recoverable response. For the definition of the yield and plastic potential functions, the equivalent von Mises stress is formulated using energy considerations and the theory of representations, the latter being also used to retrieve an expression for the Lode's angle. The recent Generalized classical criterion is then used to define the yield and plastic potential functions so that Lode's angle‐dependent deviatoric sections can be used.
A Finite Element (FE) procedure based on a fully implicit backward Euler predictor/corrector scheme for the Cosserat continuum is here presented. The integration algorithm is suitable for yield and ...plastic potential surfaces with general shape in the deviatoric plane. The key element of the integration scheme is the spectral decomposition of the stress tensor, which is achieved, despite the lack of symmetry, because of the mathematical structure of the yield function and the set of invariants chosen as independent variables. It is also shown that the choice of invariants enables considerable mathematical simplifications, which result in the reduction of the system of equations and unknowns of the elasto‐plastic problem from 19 to 1, and to rigorously handle the discontinuity at the apex of the surfaces. The algorithm has been implemented in a proprietary FE programme, and used for the constitutive model recently proposed by the same authors in this journal for the Cosserat continuum, which allows to set various classical failure criteria as yield and plastic potential surfaces. Numerical analyses have been conducted to simulate a biaxial compression test and a shallow strip footing resting on a Tresca, Mohr–Coulomb, Matsuoka–Nakai and Lade–Duncan soil. The benefits of the Cosserat continuum over the Cauchy/Maxwell medium are discussed considering mesh refinement, non‐associated flow and softening behaviour.
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 χ2=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. (Circ J 2015; 79: 1076–1083)
Background: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).Methods and Results: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, and <30 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 (χ2=0.29; P=0.5928). The adjusted HR for NT-proBNP >5,180 pg/ml was 2.09 (P<0.001) in the highest, 1.7 (P<0.001) 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 (P<0.001), and 3.24 (P=0.002), respectively. The models incorporating NT-proBNP as a dichotomous or categorized variable had equivalent C-statistics.Conclusions: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. (Circ J 2014; 78: 2439–2446)
Summary
Yield and plastic potential surfaces are often affected by problems related to convexity. One such problem is encountered when the yield surface that bounds the elastic domain is itself ...convex; however, convexity is lost when the surface expands to pass through stress points outside the current elastic domain. In this paper, a technique is proposed, which effectively corrects this problem by providing linear homothetic expansion with respect to the centre of the yield surface. A very compact implicit integration scheme is also presented, which is of general applicability for isotropic constitutive models, provided that their yield and plastic potential functions are based on a separate mathematical definition of the meridional and deviatoric sections and that stress invariants are adopted as mechanical quantities. The elastic predictor‐plastic corrector algorithm is based on the solution of a system of 2 equations in 2 unknowns only. This further reduces to a single equation and unknown in the case of yield and plastic potential surfaces with a linear meridional section. The effectiveness of the proposed convexification technique and the efficiency and stability of the integration scheme are investigated by running numerical analyses of a notoriously demanding boundary value problem.
Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated ...prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF.
This study included consecutive outpatients with HF and NVAF treated with edoxaban (
= 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (
= 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation.
Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively,
= 0.452). The two populations' survival appeared non-significantly different at the 2-year follow-up.
this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients.
Summary
Hypo‐elastic relations are often adopted to simulate the recoverable non‐linear behaviour of soils within elasto‐plastic constitutive models. In reality, they are unable to reproduce the ...elastic, ie, recoverable, response of materials; hence, they introduce severe inconsistencies in models based on the decomposition of the total strain tensor into its recoverable and permanent parts. Hyper‐elasticity should then be used. However, existing models developed within this framework do not satisfy a number of fundamental theoretical requirements. A new hyper‐elastic model is proposed, which is rigourously formulated by integrating some of the main relations which emerge from experimental results. The model satisfies all theoretical requirements and also possesses features that are fundamental for its numerical integration. The model can be considered as the correct hyper‐elastic version of the classical hypo‐elastic constitutive relation adopted in models based on the Critical State framework, such as the Modified Cam‐Clay, with a constant Poisson's ratio.
The acute decompensated heart failure/N-terminal pro-B-type natriuretic peptide (ADHF/NT-proBNP) score is a validated risk scoring system that predicts mortality in hospitalized heart failure ...patients with a wide range of left ventricular ejection fractions (LVEFs). We sought to assess discrimination and calibration of the score when applied to patients with advanced decompensated heart failure (AHF).
We studied 445 patients hospitalized for AHF, defined by the presence of severe symptoms of worsening HF at admission, severely depressed LVEF, and the need for intravenous diuretic and/or inotropic drugs. The primary outcome was cumulative (in-hospital and post-discharge) mortality and post-discharge 1-year mortality. Separate analyses were performed for patients aged ≤ 70 years. A Seattle Heart Failure Score (SHFS) was calculated for each patient discharged alive.
During follow-up, 144 patients (32.4%) died, and 69 (15.5%) underwent heart transplantation (HT) or ventricular assist device (VAD) implantation. After accounting for the competing events (VAD/HT), the ADHF/NT-proBNP score's C-statistic for cumulative mortality was 0.738 in the overall cohort and 0.771 in patients aged ≤ 70 years. The C-statistic for post-discharge mortality was 0.741 and 0.751, respectively. Adding prior (≤6 months) hospitalizations for HF to the score increased the C-statistic for post-discharge mortality to 0.759 in the overall cohort and to 0.774 in patients aged ≤ 70 years. Predicted and observed mortality rates by quartiles of score were highly correlated. The SHFS demonstrated adequate discrimination but underestimated the risk. The ADHF/NT-proBNP risk calculator is available at http://www.fsm.it/fsm/file/NTproBNPscore.zip.
Our data suggest that the ADHF/NT-proBNP score may efficiently predict mortality in patients hospitalized with AHF.
Abstract 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.
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