bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kynurenine as a potential biomarker in detecting reduced muscle endurance: metabolomic profiling of patients with heart failure and exercise intolerance
Authors: Bekfani T , Bekhite M , Neugebauer S , Derlien S , Hamadanchi A , Haase D , Kretzschmar T , Wu M.F , Lichtenauer M , Kiehntopf M , Von Haehling S , Braun-Dullaeus R.C , Franz M , Moebius-Winkler S , Schulze P.C 
Published: October 2021

Abstract

Aims
Reduced muscle endurance (RME) in patients with HFpEF and HFrEF is associated with structural and metabolic changes in skeletal muscle. We investigated the role of kynurenine (Kyn) as a potential marker in detecting RME. Additionally, we described the likely distorted metabolic pathways in serum in patients with RME and both preserved (HFpEF) and reduced (HFrEF) ejection fraction.

Methods
Fifty-five participants were prospectively recruited (17 HFpEF, 18 HFrEF outpatients and 20 healthy controls, HC). All participants underwent echocardiography, CPET, isokinetic muscle function tests. Quantification of metabolites in serum was performed using liquid chromatography tandem mass spectrometry.

Results
In a linear regression, Kyn was an independent predictor for RME after adjusting for alanine, glutamate, ornithine, spermine and short-chain-ACs (B: −8.2 per 1μM increase, 95% CI: −13.01, −3.30, p=0.001). Kyn showed 83% sensitivity and 70% specificity (area under the curve 0.83) in detecting RME. Patients with RME and HFpEF showed reduced levels of long-chain-, medium-chain-, medium-/long-chain-ACs ratios and alanine (p&lt;0.05). In patients with RME and HFrEF we observed reduced concentrations of AAs (p&lt;0.05). Compared to HC, patients with HFpEF and HFrEF had reduced amino acid (AA)-concentrations except for branched-chain and aromatic AAs, and higher concentrations of acylcarnitines (ACs) and Kyn (p&lt;0.05).

Conclusions
Kyn shows high potential as biomarker for detecting RME. RME was associated with impaired fatty acid oxidation rates in HFpEF patients and with reduced concentrations of AAs in those with HFrEF.

Funding Acknowledgement
Type of funding sources: None.
Mortality among patients hospitalized with heart failure and type 2 diabetes mellitus: results from United States national inpatient sample 2008 to 2018
Authors: Almani M , Zhang Y , Usman M , Qudrat Ullah M , Yousuf M , Fatima N 
Published: October 2021

Abstract

Background
Type 2 diabetes mellitus (T2DM) is an important risk factor for, and a frequent co-existing condition with heart failure (HF). With increasing prevalence of heart failure and type 2 diabetes, patients with concomitant HF and T2DM have worse clinical outcomes.

Purpose
We sought to determine the in-patient mortality for type 2 diabetics admitted for heart failure in the U.S hospitals from 2008 to 2018.

Methods
Data were extracted from the National Inpatient Sample (NIS) 2008 to 2018 Database. The NIS was searched for hospitalizations for adult patients with heart failure as principal discharge diagnosis with type 2 diabetes mellitus as a secondary diagnosis using ICD-9 and ICD-10 codes. The primary outcome was inpatient mortality. Multivariate logistic regression analysis was used determine the impact of evolving demographic characteristics (age, sex and race/ethnicity) on in-hospital mortality. STATA software was used to for analysis.

Results
Hospitalization with a primary discharge diagnosis of heart failure steadily decreased from 1,011,094 in 2008 to 807,764 in 2016 and 139,315 in 2018. The patient characteristics of hospitalizations for heart failure in type 2 diabetics are shown in table 1. Adjusted in-hospital mortality in HF with T2DM decreased significantly from 2008 to 2018 (3.6% in 2008 to 2.0% in 2018, P trend 0.003) as shown in graph 1.

Conclusion
Hospitalization for heart failure decreased steadily from 2008 to 2018 in the United States. In-hospital mortality rate for type 2 diabetics admitted for heart failure decreased significantly from 2008 to 2018.

Funding Acknowledgement
Type of funding sources: None.
Prognostic advantage of optimal medical therapy is not cancelled in hospitalized heart failure patients receiving regular hemodialysis
Authors: Takada T , Jujo K , Kishihara M , Shirotani S , Watanabe S , Abe T , Yoshida A , Minami Y , Hagiwara N 
Published: October 2021

Abstract

Background
As the first-line medications, renin-angiotensin-aldosterone system inhibitor (RAASi) and β-blocker provide prognostic benefits in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). However, the negative inotropic effect of these drugs may destabilize the hemodynamics during hemodialysis (HD) and become prognostically controversial in patients receiving regular HD. Indeed, prior studies have reported the cancellation of the favorable prognostic effects of RAASi and β-blocker in patients with HD. However, it is totally unknown whether the guideline-directed medical therapy affects the prognosis in HF patients receiving regular HD.

Purpose
We aimed to evaluate the prognostic impact of RAASi and β-blocker on the cardiovascular (CV) events in HF patients on regular HD.

Methods
This observational study initially included 1,930 consecutive patients who were hospitalized due to HF and discharged alive. Of these, 151 patients who received regular HD were ultimately analyzed. They were classified into 3 groups depending on the prescribing medications at discharge; patients who received none of RAASi or β-blocker (None group: N=19), either RAASi or β-blocker (Either group: N=56), and both RAASi and β-blocker (Both group: N=76). The primary endpoint was a composite of CV death and readmission due to HF.

Results
During the observation period of median 501 (interquartile range: 197–954) days, the primary endpoint occurred in 61 patients (40%). Kaplan-Meier analysis showed the highest rate of composite endpoint in the None group (log-rank for trend: p&lt;0.001, Figure). After adjusting for covariates of age, sex, LVEF, and systolic blood pressure and heart rate at discharge, the hazard ratio (HR) for a composite endpoint was significantly lower in the Either group or Both group than that in the None group [HR: 0.19, 95% confidence interval (CI): 0.08–0.45; HR: 0.16, 95% CI: 0.06–0.42, respectively].

Conclusions
The prescription of RAASi or β-blocker at discharge was associated with lower adverse CV event rates in patients on regular HD who were hospitalized for HF. In order to improve long-term prognosis of HF patients on HD, we should consider the prescription of RAASi or β-blocker for them if hemodynamics during HD is affordable.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Impact of changes in weight and haematocrit on the reduction in systolic office and ambulatory blood pressure with empagliflozin in patients with type 2 diabetes
Authors: Sharma A , Wanner C , Ofstad A P , Mattheus M , Kraus B J , Zinman B , Ferreira J P 
Published: October 2021

Abstract

Background
There is uncertainty on how empagliflozin (EMPA) reduces blood pressure (BP), and in particular the potential role for changes in weight and haematocrit in mediating these effects.

Purpose
To assess the contributions of changes in weight and haematocrit on EMPA induced changes in BP in patients with type 2 diabetes mellitus (T2DM) in the EMPA-BP and EMPA-REG OUTCOME trials.

Methods
Patients received placebo (PBO), EMPA 10 mg or EMPA 25 mg. In EMPA-BP (12-week study), 823 patients with T2DM and hypertension (mean [SD] age 60.2 [9.0] years, HbA1c 7.90 [0.74] %, BMI 32.6 [5.1] kg/m2) were studied. In EMPA-REG OUTCOME, of the 7,020 treated patients with T2DM and cardiovascular disease (mean [SD] age 63.1 [8.6] years, HbA1c 8.07 [0.85] %, BMI 30.6 [5.3] kg/m2), 95.0% were on anti-hypertensive treatment at baseline. ANCOVA/MMRM models were applied to assess changes in systolic BP (SBP) at week 12 associated with, and independent of, changes in weight and haematocrit (Hct). SBP measurements are based on mean 24-h measurements from an ambulatory blood pressure monitoring (ABPM) device in EMPA-BP and seated office measurements in EMPA-REG OUTCOME.

Results
Mean (SD) baseline SBP was 131.7 (11.8), 131.3 (13.0) and 131.2 (12.1) mmHg in the PBO, EMPA 10 mg and EMPA 25 mg groups, respectively in EMPA-BP (mean 24-h SBP) and 135.8 (17.2), 134.9 (16.8) and 135.6 (17.0) mmHg (office SBP), respectively in EMPA-REG OUTCOME. In these relatively young patients with T2DM and mildly elevated mean SBP, EMPA reduced mean SBP by 3.4–4.2 mmHg compared with PBO (table) at week 12. Mean (SE) weight was reduced with EMPA (10 and 25mg) vs PBO treatment by −1.5 (0.2) kg and −2.0 (0.2) kg in EMPA-BP and by −1.2 (0.1) kg and −1.5 (0.1) kg in EMPA-REG OUTCOME at week 12. Mean (SE) haematocrit was increased by 2.1 (0.2) % and 1.8 (0.2) % versus placebo in EMPA-BP and by 2.2 (0.1) % and 2.5 (0.1) % in EMPA-REG OUTCOME with EMPA 10 mg and EMPA 25 mg, respectively. Weight loss accounted for 21–24% of the SBP reduction with EMPA treatment in EMPA-BP and 9–11% in EMPA-REG OUTCOME. Changes in Hct accounted for negligible (between −10% to 1%) SBP reduction with EMPA.

Conclusion
The reduction in SBP is modestly mediated through a reduction in weight. There was no meaningful effect of EMPA induced changes in Hct on SBP. Results were consistent using ABPM or office SBP. These findings suggest that EMPA's effects on SBP are likely mediated through other mechanisms such as natriuresis or reduction in arterial stiffness.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim and Eli Lilly and Company. Table 1
Clinical outcomes and death associated with cardiorenal syndromes. A comprehensive nationwide cohort study
Authors: Fauchier L , Gatault P , Bisson A , Gueguen J , Gouin N , Sautenet B , Herbert J , Angoulvant D , Halimi J M 
Published: October 2021

Abstract

Background
Cardiorenal syndromes (CRS) are associated with increased risks of all-cause and cardiovascular death, end-stage kidney disease (ESKD), myocardial infarction (MI), heart failure (HF) and ischemic stroke. Whether subtypes of CRS are more prone to develop specific complications is unclear.

Methods
This longitudinal cohort study was based on the national hospitalisation database covering hospital care from the entire French population. The analysis focused on those with at least 5 years of complete follow-up (or dead earlier) as described by others. We identified 385,687 consecutive patients hospitalized in France in 2012 who had heart failure (HF), chronic kidney disease (CKD) and/or CRS. We estimated incidence of cardiovascular and all-cause death, MI, hospitalization for HF, ischemic stroke, ESKD (chronic dialysis or transplantation). Analysis were adjusted for 1) age and sex and 2) all baseline characteristics except cardiac and renal comorbidities.

Results
Overall, 57.7% were male, 67.3% had hypertension, 31.1% had diabetes mellitus and their mean age was 75.3±13.2; 34,217 had isolated CKD, 324,141 had HF, 11,162 had acute concomitant CRS (which could be type 1, 3 or 5 CRS), 12,198 had type 2 CRS and 3,969 had type 4 CRS.
Type 2 CRS was associated with the highest 5-year incidence of all-cause (30.3/100 patient-years [29.7–30.9]) and cardiovascular (10.7 [10.4–11.1]) death and HF (46.9 [45.9–47.9]), type 4 CRS with the highest incidence of MI (2.50 [2.21–2.83]) and patients with acute CRS with the highest incidence of ischemic stroke (2.05 [1.89–2.21]). The incidence of ESKD was 7.43/100 patient-years [6.92–7.99] for type 4 and 6.31 [6.03–6.61] for type 2 CRS, 6.16 [5.88–6.45] for aCRS, 6.00 [5.87–6.14] for CKD and 1.17 [1.15–1.19] for HF.
As compared to CKD, the adjusted risk of ESKD was higher in type 4 (HR: 1.18 [1.10–1.28]) and aCRS (1.07 [1.02–1.13]) and similar for type 2 (HR: 0.99 [0.94–1.04]) CRS. The adjusted risk of all-cause and cardiovascular death and HF was higher in patients with type 2 CRS vs all other groups, and higher in aCRS and 4 CRS than isolated CKD.

Conclusion
The long-term prognosis of CRS subtypes is poor but varies widely, some CRS subtypes being more closely associated with specific complications than others.

Funding Acknowledgement
Type of funding sources: None. All-cause deathCardiovascular death
Prognostic value of the combination of pulmonary-systemic pressure ratio and a new systemic inflammation-nutrition index in patients admitted for acute decompensated heart failure
Authors: Yamada T , Watanabe T , Morita T , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakamura J , Kayama K , Fukunami M 
Published: October 2021

Abstract

Background
Concomitant presence of pulmonary hypertension in heart failure (HF) is associated with increased adverse events and may be related to interventricular uncoupling and impaired cardiac efficiency. It has recently been shown that an increased mean pulmonary artery pressure to mean systemic arterial pressure ratio (MPS ratio), a marker of interventricular coupling and efficiency, is associated with worse clinical outcomes in patients with advanced HF. On the other hand, systemic inflammation plays a critical role in the outcomes of heart failure, and malnutrition is also associated with poor outcome in heart failure patients It has been recently reported that advanced lung cancer inflammation index (ALI), which is calculated as body mass index × serum albumin / neutrophil to lymphocyte ratio (NLR), is an independent prognostic marker in several types of cancer. However, there is no information available on the prognostic value of the combination of MPS ratio and ALI in patients with acute decompensated HF (ADHF).

Methods and results
We studied 219 patients admitted for ADHF, who underwent right heart catheterization at the admission and were discharged with survival. During a follow up period of 5.1±4.2 yrs, 57 had cardiovascular death (CVD). MPS ratio was significantly greater (0.401±0.107 vs 0.346±0.105, p=0.0009) and ALI was significantly smaller (34.2±18.7 vs 52.0±27.1, p&lt;0.0001) in patients with than without CVD At multivariate Cox analysis, MPS ratio and ALIwere significantly associated with CVD, independently of eGFR and prior heart failure hospitalization, after the adjustment with left ventricular end-diastolic dimension and serum sodium level. The patients with both greater MPS ratio&gt;0.350 (AUC 0.652 [0.569–0.735]) and smaller ALI &lt;35.767 (AUC 0.714 [0.636–0.792]) had a significantly increased risk of CVD than those with either greater MPS or smaller ALI and none of them (67% vs 22% vs 11%, p&lt;0.0001, respectively).

Conclusion
The combination of MPS ratio and ALI might be useful for stratifying ADHF patients at higher risk for CVD.

Funding Acknowledgement
Type of funding sources: None.
A human arterial transcriptomic signature predicts major adverse cardiac events and identifies novel, redox-related therapeutic targets within the vascular wall
Authors: Kotanidis C P , Lockstone H , Polkinghorne M , Badi I , Akoumianakis I , Siddique M , Antonopoulos A , Evans T , Farid S , Srivastava V , Krasopoulos G , Sayeed R , Channon K M , Antoniades C 
Published: October 2021

Abstract

Background
The transcriptomic profile of the human vascular wall is implicated in a range of pathologies. RNA sequencing technologies allow for interrogation of gene expression patterns that are associated with clinical outcomes and can guide future research and drug development.

Purpose
To apply discovery network transcriptomics to internal mammary arteries (IMAs) obtained from patients undergoing cardiac surgery, in order to identify redox-related molecular pathways within the vascular wall that can be treated therapeutically.

Methods
Arm 1 included 377 patients in whom segments of IMA were used for ex-vivo quantification of NADPH-stimulated superoxide production by lucigenin-enhanced chemiluminescence. Arm 2 included 205 patients in whom bulk RNA sequencing was performed in RNA isolated from IMA, and the WGCNA package used for the analyses. The association with future incidence of major adverse cardiac events (MACE: cardiovascular death, non-fatal myocardial infarction, and stroke) was assessed using Cox regression models (adjusted for age, sex, hypertension, dyslipidaemia, diabetes mellitus, body mass index, smoking, and plasma TNFa).

Results
Over a median follow-up of 4.84 years [IQR: 2.03–7.14], 38 (11.2%) MACE occurred in Arm 1. High arterial NADPH-stimulated superoxide was independently associated with MACE risk (Adj. HR [95% CI]: 2.62 [1.13–6.07] high group, p=0.02). Unsupervised transcriptomic analysis in Arm 2 allowed identification of 10 coexpressed gene “modules”. Eigengenes summarising modular coexpression signatures were then correlated with NADPH-stimulated superoxide revealing the red module (a) as the most significant (rho=0.19, p=0.01). In survival analysis the red module showed significant correlation with MACE (Adj. HR [95% CI]: 1.40 [1.00–1.95] per SD, p=0.04). For an optimal cut-off, patients with high eigengene values for the red module showed a 4-fold higher risk of MACE (b), and significantly higher arterial oxidative stress (c). Enrichment analysis (performed with Enrichr) of genes in the red module revealed “Electron Transport Chain”, “Oxidative phosphorylation”, “Striated Muscle Contraction Pathway”, and “Glycolysis and Gluconeogenesis” amongst the top enriched pathways (d).

Conclusion
We present for the first time a novel human arterial transcriptomic signature reflecting changes in redox state, which identifies long-term cardiovascular risk. Targeting pathways in the vasculature related with the mitochondrial electron transport chain, the contractile mechanism, or glucose metabolism may lead to the development of novel therapeutics in cardiovascular disease.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): EPSRC-EP/N509711/1-2119518British Heart Foundation Figure 1
Degree of peripheral Thyroxin Deiodination and recurrent cardiovascular events in euthyroid patients undergoing PCI: five-year findings from a large single-center cohort study
Authors: Yuan D S , Jia S D , Zhang C , Liu Y , Zhao X Y , Yang Y J , Gao R L , Xu B , Gao Z , Yuan J Q 
Published: October 2021

Abstract

Background
In euthyroid patients undergoing percutaneous coronary intervention (PCI), it is still unclear whether thyroxin deiodination level can predict the recurrence of cardiovascular events (CVEs). Using free triiodothyronine to free thyroxine (FT3/FT4) ratio, a marker of peripheral thyroxin deiodination, we aim to investigate its association with recurrent long-term adverse events in this population.

Methods
3549 euthyroid patients with prior CVEs history undergoing PCI were consecutively enrolled in our study and subsequently divided into three FT3/FT4 ratio tertiles (T1&lt;2.41, n=1170; 2.41≤T2&lt;2.75, n=1198; T3&gt;2.75, n=1181). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of all-cause death, myocardial infarction, stroke and revascularization. The secondary endpoints were all-cause death and cardiac death.

Results
The median follow-up time was 5 years. The incidence of all-cause death, cardiac death and MACCE were significantly higher among patients in the lowest FT3/FT4 tertile (P&lt;0.05). After adjustment of confounding factors, decreased FT3/FT4 ratio was independently associated with an increased risk of all-cause death (HR 1.82, 95% CI 1.13–2.93, P=0.014), cardiac death (HR 1.90, 95% CI 1.04–3.46, P=0.036) and MACCE (HR 1.33, 95% CI 1.10–1.60, P=0.003).

Conclusions
In euthyroid patients undergoing PCI, FT3/FT4 ratio, a surrogate marker of peripheral thyroxin deiodination, demonstrates a strong association with long-term recurrent cardiovascular events. Routine assessment of FT3/FT4 ratio might be a simple and effective tool for risk stratification in this specific patient population.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Key Research and Development Program of China (No. 2016YFC1301300, 2016YFC1301301); National Natural Science Foundation of China (No. 81770365)
Association between distance to tertiary hospital and cardiovascular outcomes in coronary artery disease patients
Authors: Gonzalez-Manzanares R , Carmona-Artime L , Ruiz-Moreno M , Perea-Armijo J , Piserra A , Rodriguez-Nieto J , Flores G , Pericet-Rodriguez C , Ojeda S , Hidalgo F J , Suarez De Lezo J , Mazuelos F , Segura J M , Romero M , Pan M 
Published: October 2021

Abstract

Background
The impact of distance from residence to Tertiary Referral Hospital and cardiovascular (CV) outcomes in patients with coronary artery disease (CAD) is unknow. Despite longer travel distances hinder access to healthcare and may worsen CV outcomes, we hypothesize that Mediterranean lifestyle and behaviors in distant rural areas may be associated with a reduced risk of CV death and events.

Purpose
To investigate the association between travel distance to Tertiary Hospital and mid-term cardiovascular outcomes in a population of CAD patients in Southern Spain.

Methods
Retrospective study including all patients discharged after percutaneous coronary intervention (PCI) at a high-volume center in Southern Spain during 2018. Those belonging to another healthcare area were excluded. One-way driving distances from residence to hospital were computed using Google Maps Distance Matrix API with R package “gmapsdistance”. Patients were stratified into tertiles according to travel distance (short, STD; intermediate, ITD; and long, LTD). Kaplan-Meier (KM) and Multivariable Cox regression (adjusted for age, sex, atrial fibrillation, cancer history, prior revascularization and clinical presentation) were used to assess the impact of travel distance on CV death and a composite outcome of MACE (Myocardial Infarction, unplanned PCI and CV death).

Results
Of 1005 patients discharged after PCI during the study period, 966 met the selection criteria. Flowchart and baseline characteristics by distance groups are presented in Figure 1. Median travel distance tertiles were 6.1 (STD), 41.7 (ITD) and 78.4 (LTD). During a median follow-up of 31 (IQR 28–35) months, 50 cardiovascular deaths [STD 27 (8.4%), ITD 13 (4%), LTD 10 (3.1%), p=0.006)] and 63 MACE occurred [STD 45 (13.9%), ITD 37 (11.5%), LTD 26 (8.1%), p=0.060)]. KM curves for the three distance groups are shown in Figure 2. In univariable and multivariable Cox models, longer travel distances were associated with better outcomes, as for every 10 Km increase, there was a 11% and 7% decrease in the hazards of CV death (HR adj: 0.89, CI 0.82–0.98, p=0.029) and of MACE (HR adj: 0.93, CI 0.87–0.99, p=0.025), respectively.

Conclusion
Travel distance was inversely associated with CV events in a population of CAD patients in Southern Spain. Patients in the first tertile of distance had a higher rate of CV death. Multicenter studies involving other Mediterranean regions are needed to confirm these findings and to look for explanations.

Funding Acknowledgement
Type of funding sources: None. Flowchart and baseline characteristicsSurvival curves by distance groups