New evidence of visual space anisotropy with autostereograms

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Impact of frailty on mortality and hospitalization in chronic heart failure: A systematic review and meta-analysis

© 2018 The Authors. Background-—Although frailty has been associated with increased risks for hospitalization and mortality in chronic heart failure, the precise average effect remains uncertain. We performed a systematic review and meta-analysis to summarize the hazards for mortality and incident hospitalization in patients with heart failure and frailty compared with those without frailty and explored the heterogeneity underlying the effect size estimates. Methods and Results-—MEDLINE, EMBASE, and Cochrane databases were queried for articles published between January 1966 and March 2018. Predefined selection criteria were used. Hazard ratios (HRs) were pooled for meta-analyses, and where odds ratios were used previously, original data were recalculated for HR. Overlapping data were consolidated, and only unique data points were used. Study quality and bias were assessed. Eight studies were included for mortality (2645 patients), and 6 studies were included for incident hospitalization (2541 patients) during a median follow-up of 1.82 and 1.12 years, respectively. Frailty was significantly associated with an increased hazard for mortality (HR, 1.54; 95% confidence interval, 1.34–1.75; P<0.001) and incident hospitalization (HR, 1.56; 95% confidence interval, 1.36–1.78; P<0.001) in chronic heart failure. The Fried phenotype estimated a 16.9% larger effect size than the combined Fried/non-Fried frailty assessment for the end point of mortality (HR, 1.80; 95% confidence interval, 1.41–2.28; P<0.001), but not for hospitalization (HR, 1.57; 95% confidence interval, 1.30–1.89; P<0.001). Study heterogeneity was found to be low (I 2 =0%), and high quality of studies was verified by the Newcastle-Ottawa scale. Conclusions-—Overall, the presence of frailty in chronic heart failure is associated with an increased hazard for death and hospitalization by ≈1.5-fold

Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure : a pilot study

Altres ajuts: This work was supported in part by Fundació La Marató de TV3 (201516-10, 201502-30), Societat Catalana de Cardiologia, "la Caixa" Banking Foundation.Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor developed for the treatment of heart failure with reduced ejection fraction. Its benefits are achieved through the inhibition of neprilysin (NEP) and the specific blockade of the angiotensin receptor AT1. The many peptides metabolized by NEP suggest multifaceted potential consequences of its inhibition. We sought to evaluate the short-term changes in serum endorphin (EP) values and their relation with patients' physical functioning after initiation of sacubitril/valsartan treatment. A total of 105 patients with heart failure with reduced ejection fraction, who were candidates for sacubitril/valsartan treatment, were included in this prospective, observational, multicentre, and international study. In a first visit, and in agreement with current guidelines, treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker was replaced by sacubitril/valsartan because of clinical indication by the responsible physician. By protocol, patients were reevaluated at 30 days after the start of sacubitril/valsartan. Serum levels of α- (α-EP), γ-Endorphin (γ-EP), and soluble NEP (sNEP) were measured using enzyme-linked immunoassays. New York Heart Association (NYHA) functional class was used as an indicator of patient's functional status. Baseline median levels of circulating α-EP, γ-EP, and sNEP were 582 (160-772), 101 (37-287), and 222 pg/mL (124-820), respectively. There was not a significant increase in α-EP nor γ-EP serum values after sacubitril/valsartan treatment (P value = 0.194 and 0.102, respectively). There were no significant differences in sNEP values between 30 days and baseline (P value = 0.103). Medians (IQR) of Δα-EP, Δγ-EP, and ΔsNEP between 30 days and baseline were 9.3 (−34 − 44), −3.0 (−46.0 − 18.9), and 0 units (−16.4 − 157.0), respectively. In a pre-post sacubitril/valsartan treatment comparison, there was a significant improvement in NYHA class, with 36 (34.3%) patients experiencing improvement by at least one NYHA class category. Δα-EP and ΔsNEP showed to be significantly associated with NYHA class after 30 days of treatment (P = 0.014 and P < 0.001, respectively). Δα-EP was linear and significantly associated with NYHA class improvement after 30 days of sacubitril/valsartan treatment. These preliminary data suggest that beyond the haemodynamic benefits achieved with sacubitril/valsartan, the altered cleavage of endorphin peptides by NEP inhibition may participate in patients' symptoms improvement

Rehospitalization burden and morbidity risk in patients with heart failure with mid-range ejection fraction

Heart failure with mid-range ejection fraction (HFmrEF) has been proposed as a distinct HF phenotype, but whether patients on this category fare worse, similarly, or better than those with HF with reduced EF (HFrEF) or preserved EF (HFpEF) in terms of rehospitalization risks over time remains unclear. We prospectively included 2961 consecutive patients admitted for acute HF (AHF) in our institution. Of them, 158 patients died during the index admission, leaving the sample size to be 2803 patients. Patients were categorized according to their EF: HFrEF if EF ≤ 40% (n = 908, 32.4%); HFmrEF if EF = 41-49% (n = 449, 16.0%); and HFpEF if EF ≥ 50% (n = 1446, 51.6%). Covariate-adjusted incidence rate ratios (IRRs) were used to evaluate the association between EF status and recurrent all-cause and HF-related admissions. At a median follow-up of 2.6 years (inter-quartile range: 1.0-5.3), 1663 (59.3%) patients died, and 6035 all-cause readmissions were registered in 2026 patients (72.3%), 2163 of them HF related. Rates of all-cause readmission per 100 patients-years of follow-up were 150.1, 176.9, and 163.6 in HFrEF, HFmrEF, and HFpEF, respectively (P = 0.097). After multivariable adjustment, when compared with that of patients with HFrEF and HFpEF, HFmrEF status was not significantly associated with a different risk of all-cause readmissions (IRR = 0.99; 95% confidence interval [CI], 0.77-1.27; P = 0.926; and IRR = 0.93; 95% CI, 0.74-1.18; P = 0.621, respectively) or HF-related readmissions (IRR = 1.06; 95% CI, 0.77-1.46; P = 0.725; and IRR = 1.11; 95% CI, 0.82-1.50; P = 0.511, respectively). Following an admission for AHF, patients with HFmrEF had a similar rehospitalization burden and a similar risk of recurrent all-cause and HF-related admissions than had patients with HFrEF or HFpEF. Regarding morbidity risk, HFmrEF seems not to be a distinct HF phenotype

Right Ventricular Dysfunction Staging System for Mortality Risk Stratifiction in Heart Failure with Preserved Ejection Fraction

Right ventricular dysfunction (RVD) parameters are increasingly important features in heart failure with preserved ejection fraction (HFpEF). We sought to evaluate the prognostic impact of a progressive RVD staging system by combining the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (TAPSE/PASP) ratio with functional tricuspid regurgitation (TR) severity. We prospectively included 1355 consecutive HFpEF patients discharged for acute heart failure (HF). Of them, in 471 (34.7%) patients, PASP could not be accurately measured, leaving the final sample size to be 884 patients. Patients were categorized as Stage 1: TAPSE/PASP ≥ 0.36 without significant TR; stage 2: TAPSE/PASP ≥ 0.36 with significant TR; stage 3: TAPSE/PASP < 0.36 without significant TR; and stage 4: TAPSE/PASP < 0.36 with significant TR. By the 1 year follow-up, 207 (23.4%) patients had died. We found a significant and graded association between RVD stages and mortality rates (15.8%, 25%, 31.2%, and 45.4% from stage 1 to stage 4, respectively; log-rank test, p < 0.001). After multivariable adjustment, and compared to stage 1, stages 3 and 4 were independently associated with mortality risk (HR: 1.8219; 95% CI 1.308-2.538; p < 0.001 and HR = 2.2632; 95% CI 1.540-3.325; p < 0.001, respectively). A RVD staging system, integrating TAPSE/PASP and TR, provides a comprehensive and widely available tool for risk stratification in HFpEF

Role of PCSK9 in the course of ejection fraction change after ST-segment elevation myocardial infarction : a pilot study

Altres ajuts: Conselleria d'Educació, Investigació, Cultura i Esport GV/2018/116Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma low-density lipoprotein cholesterol. Beyond lipid control, recent findings suggest a deleterious effect of this protein in the pathogenesis of postmyocardial infarction left ventricle remodelling and heart failure-related complications. The aim of this study was to assess the relationship between circulating PCSK9 and 6 month cardiac magnetic resonance imaging-derived left ventricular ejection fraction (LVEF) after a first ST-segment elevation myocardial infarction (STEMI). We prospectively evaluated 40 patients with a first STEMI, LVEF < 50% and treated with primary percutaneous coronary intervention in which PCSK9 was measured 24 h postreperfusion. All patients underwent cardiac magnetic resonance imaging 1 week and 6 months after STEMI. Baseline characteristics were compared across median values of PCSK9. The association between PCSK9 levels and LVEF at 6 months was evaluated by analysis of covariance. The mean age of the sample was 60 ± 12 years and 33 (82.5%) were male patients. The infarct location was anterior in 27 patients (67.5%), and 9 patients (22.5%) were Killip class ≥ II. The mean 1 week and 6 month LVEF were 41 ± 7% and 48 ± 10%, respectively. The mean PCSK9 was 1.93 ± 0.38 U/mL. Testing the association between serum PCSK9 and 6 month LVEF with analysis of covariance revealed an inverse relationship (r = −0.35, P = 0.028). After multivariate adjustment, circulating PCSK9 remained significant and inversely associated with 6 month LVEF (P = 0.002). In patients with a first STEMI with reduced ejection fraction at index admission and treated with primary percutaneous coronary intervention, circulating PCSK9 was associated with lower LVEF at 6 months

Impact of diabetes on the predictive value of heart failure biomarkers

Altres ajuts: This study was funded by the Redes Temáticas de Investigación Cooperativa en Salud (RETICS); Red Cardiovascular (RD12/0042/0047) as part of the Plan Nacional de I+D+I.Patients with diabetes mellitus (DM) have an increased risk of developing heart failure (HF). Further, DM is associated with poor prognosis in patients with HF. Our aim was to determine whether DM has any impact on the predictive value of a multi-biomarker panel in patients with HF. We included 1069 consecutive ambulatory HF patients in the study: age 66.2 ± 12.8 years, 33.5 ± 13.3 left ventricular ejection fraction, 36% diabetic patients. We measured serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), ST2, galectin-3, high-sensitivity C reactive protein (hs-CRP), cystatin-C, soluble transferrin receptor (sTfR), and neprilysin and followed patients for 4.9 ± 2.8 years. Primary endpoints were all-cause and cardiovascular death. During follow-up, 534 patients died; 283 died of cardiovascular causes. Diabetic subjects had higher mortality (57.7 vs. 45.6%, p < 0.001). NTproBNP (p = 0.07), hs-TnT (p < 0.001), galectin-3 (p < 0.001), and cystatin-C (p = 0.001) concentrations were higher in diabetic patients, whereas sTfR levels were lower (p = 0.005). There were no interactions between DM and NTproBNP, hs-TnT, galectin-3, hs-CRP, cystatin-C, sTfR, and neprilysin relative to risk prediction for all-cause or cardiovascular death. By contrast, ST2 significantly interacted with DM for all-cause (p = 0.02) and cardiovascular (p = 0.03) death. In diabetic patients, HRs for ST2 were 1.27 (95% CI 1.16-1.40, p < 0.001) and 1.23 (95% CI 1.09-1.39, p = 0.001) for all-cause and cardiovascular death, respectively. In nondiabetic patients, HRs for ST2 were 1.53 (95% CI 1.35-1.73, p < 0.001) and 1.64 (95% CI 1.31-2.05, p < 0.001) for all-cause and cardiovascular death, respectively. The multivariable Cox regression analysis showed that hs-TnT and ST2 were the only markers that were independently associated with both all-cause and cardiovascular mortality in patients with HF and diabetes. Moreover, in these patients, the combination of these two markers significantly increased discrimination as assessed by the area under the curve. Biomarkers used in the general population to predict the clinical course of heart failure are also useful in patients with diabetes. In these patients, among all the biomarkers analysed only hs-TnT and ST2 were independently associated with both all-cause and cardiovascular mortality

Meteorin-like/ Meteorin-b protects heart against cardiac dysfunction

Meteorin-like/Meteorin-β (Metrnl/Metrnβ) is a secreted protein produced by skeletal muscle and adipose tissue that exerts metabolic actions that improve glucose metabolism. The role of Metrnβ in cardiac disease is completely unknown. Here, we show that Metrnβ-null mice exhibit asymmetrical cardiac hypertrophy, fibrosis, and enhanced signs of cardiac dysfunction in response to isoproterenol-induced cardiac hypertrophy and aging. Conversely, adeno-associated virus-mediated specific overexpression of Metrnβ in the heart prevents the development of cardiac remodeling. Furthermore, Metrnβ inhibits cardiac hypertrophy development in cardiomyocytes in vitro, indicating a direct effect on cardiac cells. Antibody-mediated blockage of Metrnβ in cardiomyocyte cell cultures indicated an autocrine action of Metrnβ on the heart, in addition to an endocrine action. Moreover, Metrnβ is highly produced in the heart, and analysis of circulating Metrnβ concentrations in a large cohort of patients reveals that it is a new biomarker of heart failure with an independent prognostic value

The PCSK9-LDL Receptor Axis and Outcomes in Heart Failure:BIOSTAT-CHF Subanalysis

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis progression. Objectives: The aim of this study was to determine whether the PCSK9-LDLR axis could predict risk in patients with heart failure (HF). Methods: The BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure) is a multicenter, multinational, prospective, observational study that included patients with worsening HF signs and/or symptoms. The primary endpoints were all-cause mortality and the composite of mortality or unscheduled hospitalizations for HF. We implemented Cox proportional hazard regression to determine the simultaneously adjusted effect of PCSK9 and LDLR on both outcomes when added to the previously validated BIOSTAT-CHF risk scores. Results: This study included 2,174 patients (mean age: 68 ± 12 years; 53.2% had a history of ischemic heart disease). Median (interquartile range) PCSK9 and LDLR levels were 1.81 U/ml (1.45 to 2.18) and 2.98 U/ml (2.45 to 3.53), respectively. During follow-up, 569 deaths (26.2%) and 896 (41.2%) composite endpoints were ascertained. A multivariable analysis, which included BIOSTAT-CHF risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.49; p = 0.020) and the composite endpoint (HR: 1.21; 95% CI: 1.05 to 1.40; p = 0.010). A similar analysis for LDLR revealed a negative association with mortality (HR: 0.86; 95% CI: 0.76 to 0.98; p = 0.025) and the composite endpoint (HR: 0.92; 95% CI: 0.83 to 1.01; p = 0.087). Including PCSK9 and LDLR improved risk score performance. Conclusions: The PCSK9-LDLR axis was associated with outcomes in patients with HF. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF