bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic role of clinical features and biomarkers in patients hospitalized with cardiorenal syndromes
Authors: Theofilis P , Vordoni A , Volis N , Doumani-Korka G , Kampourelli A , Xanthopoulou E , Kalaitzidis R G 
Published: November 2023

Abstract

Background
Cardiorenal syndromes (CRS), involving the heart-kidney cross-talk and the activation of neurohumoral and inflammatory pathways, is an entity characterized by high morbidity and mortality.

Objective
To evaluate the prognostic role of risk factors and biomarkers in patients hospitalized for CRS.

Methods
In this prospective, observational cohort study, 113 consecutive patients hospitalized for CRS were enrolled. Socio-demographic characteristics, personal medical history, and prior medication use were recorded upon admission, and echocardiography was performed. Moreover, an array of blood markers were measured. The endpoint of interest was a composite of death or dialysis dependence at discharge.

Results
Patients were classified into two groups; Group 1 (N = 59): discharged being dialysis-independent, Group 2 (N = 54): death/dialysis dependence at discharge. No major differences were detected in baseline characteristics between the two groups. Group 2 patients used renin-angiotensin-aldosterone system blockers (RAASb) less often (Group 1: 69.5% vs. Group 2: 46.3%, p = 0.01) and more frequently presented with oliguria/anuria (Group 1: 28.8% vs. Group 2: 70.4%, p&lt;0.001) and any infection (Group 1: 33.9% vs. Group 2: 55.6%, p = 0.02). No dissimilarities were noted in echocardiographic markers. Group 2 patients had significantly lower hemoglobin, serum albumin, bicarbonate, and 25-hydroxy-vitamin D (25OHD) (Figure 1). At the same time, N-terminal prohormone brain natriuretic peptide, serum potassium, and parathyroid hormone (PTH) were significantly higher in Group 2 patients (Figure 1). In a multivariate regression analysis, lack of RAASb was independently associated with a 17.7-fold increased risk of death or dialysis dependence at discharge, while the decreasing 25OHD/PTH ratio (β coefficient -0.01, p = 0.007) and increasing admission serum potassium levels (β coefficient 0.82, p = 0.03) increased the possibility of facing the composite endpoint. Following a receiver operating characteristic curve analysis, 25OHD/PTH ratio emerge as the most accurate predictor of facing the composite endpoint, with an ideal cutoff of 103.7 (sensitivity 81%, specificity 74%) (Figure 2).

Conclusion
Lack of prior RAASb use, high admission serum potassium, and a low 25OHD/PTH ratio are associated with poor prognosis in patients hospitalized for CRS.Figure 1Figure 2
Association between triglyceride with all-cause mortality and cardiovascular outcomes in heart failure patients
Authors: Ren Q W , Chan H C , Tsang T W , Tse Y K , Wu M Z , Xu X , Yiu K H 
Published: November 2023

Abstract

Background
Remnant cholesterol, identified by triglyceride-rich lipoprotein, is increasingly acknowledged as a significant causal risk factor for ischemic heart diseases. The association with cause-specific outcomes in heart failure (HF) settings remains unexplored. This study aims to determine the association between triglyceride levels with all-cause mortality and cardiovascular outcomes in patients with HF.

Methods
Using a previously validated territory-wide clinical information registry, all eligible patients with HF (N = 127124) from 1996 to 2020 were enrolled. Triglyceride levels associated with risk of mortality were evaluated on a continuous scale using restricted cubic spline curves and by categories of triglyceride using Cox proportional hazards regression model with competing risks as appropriate. The primary outcomes were all-cause mortality and cardiovascular death (CVD). Secondary outcomes included ASCVD (a composite of myocardial infarction, unstable angina, arterial revascularization or ischemic stroke) and HF readmission or death.

Results
The mean age of the study population was 71.4±12.2 years and 65869 (51.8%) were male. Notably, when we investigated the association of triglyceride levels with admission or death for ASCVD, a positive relationship was seen in high triglyceride levels and ASCVD admission or death while neutral in low triglyceride levels. Conversely, when we investigated the association with readmission or death for HF, an inverse relationship was found where lower triglyceride levels were associated with higher risks of HF readmission. Together, the association between triglyceride levels and the risk of all-cause mortality and CVD was an U-shaped curve. The risk of all-cause mortality reached a nadir between triglyceride levels of 1.12 mmol/L and 3.28 mmol/L and was lowest at 1.95 mmol/L.

Conclusion
In the HF population, low and high levels of triglyceride were associated with increased risks of all-cause mortality and CVD compared with those with midrange levels. Triglyceride was positively associated with ASCVD while inversely associated with HF admission or death. The lowest risk of all-cause mortality was found at a triglyceride concentration of 1.95 mmol/L.TG and mortalityTG and CVD
Effects of empaglifozin on collagen biomarkers in patients with heart failure. Results from the EMPEROR trials
Authors: Ferreira J , Sumin M , Butler J , Zannad F 
Published: November 2023

Abstract

Background
Extracellular matrix remodeling is one of the key pathways in progression of Heart Failure (HF). Clinical trials demonstrated that SGLT-2 inhibitors improved cardiovascular outcomes in HF patients, which may be partly explained by an effect on cardiac remodeling. Supporting data from preclinical studies suggested effects of SGLT-2 inhibitors on collagen synthesis and attenuation of fibrosis. However, the effect of SGLT-2 inhibitors on collagen turnover in HF patients is not fully elucidated.

Purpose
In patients of the EMPEROR-Preserved and EMPEROR-Reduced trials, across a wide spectrum of ejection fraction and renal function, the effect of empagliflozin on serum markers of collagen turnover was investigated.

Methods
1084 patients (545 in empagliflozin and 539 in placebo) were included in the analysis. Biomarkers measured from serum samples at baseline, 12 and 52 weeks included PICP (a collagen type I formation marker; ELISA), PRO-C3 (a collagen type III formation marker; ECLIA), PINP (a collagen type I formation marker; ECLIA, Roche Diagnostics), PRO-C6 (a collagen type VI formation marker; ECLIA), C1M and C3M (markers of collagen type I and III degradation CLIA). A mixed model repeated measurements model (MMRM) was used to evaluate the treatment effects on the analysed biomarkers.

Results
Treatment with empagliflozin vs. placebo reduced PICP levels at week 12 and week 52, and reduced PRO-C3 at week 52. In contrast, no significant effect was observed on PINP, PRO-C6, C1M or C3M levels (Table 1).

Conclusion
Among patients with chronic HF, across a wide range of EF and of renal function, treatment with empagliflozin reduced the serum levels of PICP, a collagen type I formation marker, both at weeks 12 and 52 and PRO-C3, a collagen type III formation marker, at week 52. These results add support for an anti-fibrotic effect of empagliflozin and may help to explain the clinical effect of SGLT-2 inhibitors on cardiac remodeling.
Redox state of human serum albumin predicts 1-year prognosis in patients with heart failure: a single center prospective cohort study
Authors: Nishikawa T , Ueyama J , Miyata S , Shimizu S , Shibata Y , Yamada S 
Published: November 2023

Abstract

Background
As chronic inflammation would be a fundamental underlying mechanism in the pathogenesis in patients with heart failure (HF), oxidative stress has a possibility to closely associate with the prognosis. However, little is known about the association of oxidative stress with the prognosis in HF patients.

Purpose
In this study, we assessed the association of the fraction of human mercapto-albumin [f(HMA)], an index of the redox state of human serum albumin, with prognosis in patients hospitalized for HF with the aim to find the possible biomarker available on the prediction for adverse events in HF patients.

Methods
A single-center prospective cohort study was conducted. In the cohort, 290 ambulate patients admitted for acute HF or exacerbation of chronic HF were registered. Of these, 182 who were successfully followed-up patients were analyzed (median age: 79 years, men: 68.3%. median follow-up: 365 days). The primary outcome was a composite of HF rehospitalization and all-cause mortality. The high-performance liquid chromatography postcolumn bromocresol green method was used to part human serum albumin into human nonmercaptalbumin (oxidized form) and human mercaptalbumin (HMA, reduced form). We divided patients into two groups by median f(HMA) level. Kaplan-Meier Curve and the Cox proportional hazards model was used to examine the significance of f(HMA) as a prognostic indicator of HF patients, adjusting for potential confounding factors.

Results
Median level of f(HMA) was 57.2%. During 50,965 person-days of follow-up, 52 patients (28.6%) were re-hospitalized due to HF exacerbation, and 25 patients (13.7%) died due to cardiac or noncardiac reasons. Log-rank analysis showed that a high f(HMA) group reduced adverse events (Fig. 1). In the Cox proportional hazards model, a high level of f(HMA) was associated with a reduced risk of composite outcomes (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.39-1.07). In the subgroup analysis, high f(HMA) showed an event-reducing effect in HF rehospitalizations (HR 0.53; 95% CI 0.30-0.94), but not in all-cause mortality (HR 0.61; 95%CI 0.27-1.38).

Conclusion
The findings of this study support that f(HMA) could be a novel prognostic biomarker for HF patients.Fig. 1
Contribution of the left atrial speckle tracking in the evaluation of left ventricule filling pressure in acute coronary syndromes
Authors: Brahim A S M A , Mghaieth Zghal F A T H I A 
Published: November 2023

Abstract

Introduction
A non invasive estimation of diastolic function with echocardiography according to consensual methods, ie American society of Echocardiography (ASE) / European association of cardiovascular imaging (EACVI) algorithm 2018, is considered an integral essential part of the clinical evaluation of patients presenting with symptoms of acute coronary syndrome (ACS). Left atrial (LA) longitudinal strain in the frame of speckle tracking echocardiography (STE) was reported recently to have additive diagnostic value to assess left ventricle (LV) filling pressures (LVFP) in a large spectrum of cardiovascular diseases.
Our study aim is to assess the accuracy of LA strain in evaluating LVFP in patients with ACS, as a single parameter.

Methods
Our study was monocentric in our cardiology department led prospectively between April 20, 2022, and June 30, 2022. We included all patients admitted to our department for evolving ST elevation (STEMI) or non-ST elevation (NSTEMI) myocardial infarction (&lt;48 hours from onset of symptoms). Echocardiographic measurements were performed according to ASE/EACVI in less than 24 hours. They were divided into two groups according to the elevation of LVFP group 1 with non-elevated LVFP vs group with elevated LVF. LA-GS was assessed using images obtained in apical 4- and 2-chamber views , with attention to optimal visualization of the LA. The endocardial border of the LA was traced manually. Left atrial reservoir strain (LARS) was calculated from LV-end diastole, and pump strain (LAPS) after the onset of the p-wave in the electrocardiogram.

Results
Fifty patients were included in our study. The mean age was 59 ± 12 years. 72%(36) of our population was men. 34%(17) of the population had elevated LVFP (Group2) with a male predominance of 82% (14). They were active smokers in 64% (11), 52%(9) had hypertension, 70% (12) had diabetes mellitus, 47%(8) had dyslipidemia and 35% (6) were hospitalized for NSTEMI.
The mean LARS and LAPS were 26.9%, and 15.2% in group 1 vs 15.1%, and 7.1% respectively in group 2 with a difference statically significative p = 0.001, and p = 0.002 respectively.
The area under the curve was 0.910 (LARS) and 0.850 (LAPS).
The best cut-off for the LAPS was 11.5% with 100% of sensibility and 63% of specificity, for the LARS the best cut-off was 18% with 95% of sensibility and 66% of specificity.

Conclusion
LA-GS includes a reproducible and simple method for LVFP assessment in ACS. it provides an additional variable that can contribute when one of the other parameters is missing.
Left ventricular longitudinal myocardial function in heart failure patients with transition to preserved ejection fraction from reduced ejection fraction and those with preserved ejection fraction
Authors: Nagai S , Nishimori M , Todo S , Oota E , Odajima S , Takeuchi K , Ichikawa Y , Kintsu M , Yamauchi Y , Shiraki H , Yamashita K , Fukuda T , Hisamatsu E , Hirata K , Tanaka H 
Published: November 2023

Abstract

Background
Left ventricular (LV) longitudinal myocardial dysfunction is considered the first marker of a preclinical form of heart failure (HF) with preserved ejection fraction (HFpEF), and is strongly associated with poor outcomes. LV ejection fraction (LVEF) may improve over time during treatment or follow-up in some patients with HF with reduced ejection fraction (HFrEF). Furthermore, it has been reported that patients with HF with improved EF, known as HFimpEF, which was defined as current LVEF &gt; 40% but any previously documented LVEF ≤ 40%, had favorable outcomes compared to those with HFpEF. However, LV longitudinal myocardial function in patients with previously reduced LVEF who had improved LVEF to normal range (≥ 50%), and its association with cardiovascular events remains unclear.

Purpose
The purpose of this study was the comparison of LV longitudinal myocardial function in patients with HFpEF and those with previously reduced LVEF who had improved LVEF to normal range (reduced LVEF-HFpEF), and to investigate whether LV longitudinal myocardial function was associated with cardiovascular events.

Methods
We retrospectively studied 70 patients with HFpEF and 45 patients with reduced LVEF-HFpEF. Reduced LVEF-HFpEF was defined as current LVEF ≥ 50% but any previously documented reduced LVEF &lt; 50% (mean: 34 ± 10%). HFpEF was defined as current and all previous LVEF reports ≥ 50%, and met the HFA-PEFF diagnostic algorithm criteria. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS) by means of two-dimensional speckle-tracking strain. The primary endpoint was defined as cardiovascular death over a median follow-up period of 5.0 (0.5-9.0) years.

Results
As expected, the Kaplan-Meier curve indicated that patients with reduced LVEF-HFpEF experienced fewer cardiovascular death than those with HFpEF (Figure A). GLS in patients with HFpEF was significantly lower than that in patients with reduced LVEF-HFpEF (13.6 ± 3.5% vs. 14.8 ± 2.2%, P = 0.03) regardless of similar LVEF (55.7 ± 3.3% vs 56.8 ± 5.0%, P = 0.15). An important finding of the multivariate Cox proportional hazards analysis showed that GLS was an independently associated with cardiovascular death (Figure B).

Conclusion
Impaired LV longitudinal myocardial function was observed in patients with HFpEF compared to those with reduced LVEF-HFpEF regardless of similar LVEF. Moreover, LV longitudinal myocardial function was independently associated with cardiovascular death HF patients with current LVEF ≥ 50%. Our findings may provide new insights for the management of HF patients.FigureAFigureB
Synchrotron-based X-ray phase contrast imaging of transmural cardiac tissue in patients treated for advanced heart failure
Authors: Li K Y C , Loncaric F , Skreb N , Bonnin A , Dejea H , Garcia-Canadilla P , Ilic I , Gasparovic H , Milicic D , Bijnens B , Cook A C , Planinc I , Cikes M 
Published: November 2023

Abstract

Background
Cardiac imaging is essential for identifying structural changes in advanced heart failure (HF) and understanding underlying pathophysiology. Synchrotron radiation-based X-ray phase contrast imaging (X-PCI) is a non-destructive imaging modality that can provide high resolution three-dimensional (3D) visualisation of cardiac tissue on the microstructural level. Thus far, such analyses including the quantification of myocyte aggregates ranging from the epicardium to the endocardium, have been confined to animal models and human fetal tissue. We aimed to explore the feasibility of using X-PCI to quantify and compare structural organisation and orientation of myocyte aggregates in the myocardium across different advanced HF aetiologies.

Methods and design
Four adult patients were included - two receiving a left ventricular assist device (LVAD), and two undergoing heart transplantation (HTx). Aetiology of advanced HF in both the LVAD and HTx group was ischaemic heart disease and dilated cardiomyopathy (DCM), respectively. Transmural tissue samples were obtained by left ventricular apical coring (LVAD) and from the explanted hearts (HTx). The tissue specimens were imaged by X-PCI at the TOMCAT beamline using an effective pixel size of 5.8 µm. Orientation of aggregates of cardiomyocytes was assessed using a structure tensor-based method and morphological parameters were derived - the helical angle (HA), or the angle between the circumferential left ventricular plane and myocyte aggregates, and fractional anisotropy (FA), the degree of anisotropy or disorganisation of the local myocardium.

Results
The general patient characteristics are shown in Table 1. X-PCI enabled 3D visualisation of transmural myocardial tissue samples showing differences in organisation of myocardial structure in different HF aetiologies (Figure 1). The epicardial adipose layer was thicker in DCM, paired with a thinner epicardial myocyte layer (yellow arrows). Furthermore, the epi-to-endocardial HA transition was clearly visualized in ICM (double arrows), whereas there was clear disruption of the HA gradient in DCM samples – a finding further quantified via FA (green arrows).

Conclusion
X-PCI allows non-destructive advanced imaging of ex-vivo tissue. By harnessing the power of digital 3D imaging on a cellular level, it provides a novel insight to differential information on tissue organisation in different aetiologies of advanced heart failure.Table 1Figure 1
Myocardial structural and functional changes in cardiac amyloidosis - insights from a prospective observational patient registry
Authors: Duca F , Rettl R , Binder C , Dachs T M , Camuz Ligios L , Agis H , Kain R , Koschutnik M , Dona C , Badr Eslam R , Nitsche C , Loewe C , Hengstenberg C , Kammerlander A A , Bonderman D 
Published: November 2023

Abstract

Background
Within the last decade, cardiac amyloidosis (CA) has been acknowledged as a significant cause of heart failure and patients who are affected face a dismal prognosis, especially in later stages of the disease. The pathophysiological hallmark of cardiac amyloidosis (CA) is the deposition of amyloid within the myocardium. Consequently, extracellular volume (ECV) of affected patients increases. However, studies on ECV progression over time and its' impact on prognosis are lacking.

Objectives
We aimed to investigate the progression of ECV and its prognostic impact in CA patients.

Methods
Serial cardiac magnetic resonance (CMR) examinations, including ECV quantification were performed in consecutive CA patients.

Results
Between 2012 and 2021, 103 CA patients underwent baseline and follow-up CMR, including ECV quantification.
Median ECVs at baseline of the total (n = 103), transthyretin [(ATTR) n = 80], and [light chain (AL) n = 23] CA cohorts were 48.0%, 49.0%, and 42.6%. During a median follow-up period of 12 months, ECV increased significantly in all cohorts (48.0% to 50.5%, p&lt;0.001; 49.0% to 50.5%, p&lt;0.001; 42.6% to 50.6%, p = 0.026). Separate analyses for treatment-naïve (n = 14) and treated (n = 66) ATTR patients revealed that the median change of ECV from baseline to follow-up was significantly higher among untreated patients (5.5% versus 2.7%, p = 0.035).
Survival analyses demonstrated that median change of ECV was an independent (adjusted for troponin t and NT-proBNP) predictor of outcome in all CA cohorts [total: hazard ratio (HR): 1.114, 95% confidence-interval (CI): 1.045 – 1.189, p&lt;0.001; ATTR: HR: 1.099, 95% CI: 1.014 – 1.192, p = 0.022; AL: HR: 1.142, 95% CI: 1.006 – 1.297, p = 0.040].

Conclusions
The present study demonstrates that ECV, quantified by CMR T1 mapping, increases significantly in CA patients over the course of 12 months. While ECV increased, irrespective of amyloid type our analyses showed the highest increase among untreated ATTR patients. Moreover, the change of ECV was an independent predictor of adverse outcomes in AL, as well as ATTR patients emphasizing the usefulness of CMR T1 mapping in the management of CA patients.Figure 1.Dot PlotsFigure 2.Kaplan Meier Curves
Dietary sodium intake and outcomes: a secondary analysis from SODIUM - HF
Authors: Colin-Ramirez E , Saldarriaga C I , Alemayehu W , Ezekowitz J 
Published: November 2023

Abstract

Background
Sodium restriction is common advice provided to patients with heart failure, however, evidence from the SODIUM-HF trial and a subsequent meta-analysis failed to show a beneficial effect of dietary sodium restriction on outcomes.

Purpose
This secondary analysis of SODIUM HF is aimed to assess association between baseline dietary sodium intake, the change in dietary sodium at 6 months and a composite of cardiovascular hospitalization, emergency department visit, and all-cause death at 12 and 24 months.

Methods
Multivariable Cox proportional hazard regression model was used to assess association of dietary sodium level measured at randomization with primary and secondary endpoints. Adjusted Hazard ratios and 95% confidence intervals were presented. A responder analysis also explored the achieved dietary sodium at 6 months with subsequent risk for clinical outcomes.

Results
792 participants were included. At baseline, sodium intake was ≤ 1500 mg/day in 19.9% (n = 158), &gt;1500-3000 mg/day in 56.5% (n = 448) and &gt;3000 mg/day in 23.4% (n= 186) of the participants. Women, older patients, and those with lower glomerular filtration rate and higher ejection fraction were more often represented in the group with sodium intake ≤1500 mg/day; conversely, diabetes, prior smoking, use of mineralocorticoid receptor antagonists, and ICD were observed in the groups of higher sodium intake levels (&gt;3000 mg/day)(Table 1). Cox proportional hazard regression analysis showed no association between sodium level (per doubling) at baseline with clinical outcomes (all associations p=ns), however, adjusted models exhibited a trend towards a decreased risk of CV hospitalizations at 2 years. In the responder analysis, a trend towards a decreased adjusted risk for composite outcome and CV hospitalizations at 1 year in those achieving a sodium level &lt;1500 mg at 6 months was observed (Table 2). Adjusted Cox proportional hazard regression analysis showed no association for 1- and 2-year outcomes per 500 mg increase in absolute difference in sodium level between baseline and 6 months.

Conclusion
In SODIUM HF, there was no association between sodium level at baseline with clinical outcomes at any time point but there is a trend towards a decreased risk of CV hospitalizations at 2 years and in patients achieving &lt;1500 mg / day by 6 months, a trend towards fewer subsequent clinical events was present. This finding should be explored via a prospective clinical trial.Baseline characteristics of populationOutcomes