bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5332Magic mirror on the wall, can we reach our LDL-C goal? Comparison of calculated LDL-C and direct measured LDL-C levels in atherogenic dyslipidemia condition
Authors: Reiber I , Mark L , Paragh G Y 
Published: October 2019

Abstract

Background
LDL-C represents the primary lipoprotein target for reducing cardiovascular risk. LDL-C can either be calculated or measured directly. Friedewald equation has certain limitations especially with high triglyceride and low LDL-C levels. Although a number of automated direct LDL-C assays are commercially available, non of them is considered to be equivalent to the “gold standard” of direct LDL-C, beta quantitation, a complex and expensive process that is unavailable in routine clinical practice. In atherogenic dyslipidemia condition (ADC) (triglycerides≥2.3 mmol/L and HDL-C<1.0 mmol/L) non-HDL-C and remnant cholesterol are proven additional risk factors.

Purpose
We compared one of the direct homogeneous assays with the widely used Friedewald's and the new Martin/Hopkins methods of estimation of LDL-C to see the differences in average LDL-C, remnant cholesterol and non-HDL-C levels and in availability of less than 1.8 mmol/L of LDL-C in atherogenic dyslipidemia condition.

Methods
We investigated 14 906 lipid profiles from fasting blood samples of Hungarian individuals with triglycerides <4.5 mmol/L. Total cholesterol (TC), HDL-C, triglycerides (TG) and direct LDL-C (D-LDL-C) were measured directly by the enzimatic assays. We also estimated calculated LDL-C by the Friedewald's formula (F-LDL-C) and by using the new Martin/Hopkins estimation (MH-LDL-C). We have now prepared first a variant of Martin/Hopkins table in mmol/L, in which the modified adjustable factors of 2.2 are included. We determined also non-HDL-C and remnant cholesterol (RC) as a difference of non-HDL-C and F-LDL-C (F-RC), MH-LDL-C (MH-RC), D-LDL-C (D-RC).

Results
In the investigated population 19.25% was F-LDL-C, 15.48% MH-LDL-C and 7.92% D-LDL-C below 1.8 mmol/L. ADC occurred at 8.12%. For ADC, when F-LDL-C<1.8 mmol/L (A), mean values for F-LDL-C, MH-LDL-C, D-LDL-C and non-HDL-C were 1.23±0.4; 1.65±0.39; 2.06±0.4 and 2.46±0.5 mmol/L respectively. These mean levels were 1.01±0.36; 1.4±0.3; 1.83±0.3 and 2.15±0.34 mmol/L for MH-LDL-C<1.8 mmol/L (B). For D-LDL-C<1.8 mmol/L (C), mean values were 0.79±0.35; 1.13±0.26; 1.54±0.19 and 1.83±0.25 mmol/L respectively. The average RC values (in mmol/L) for A were F-RC: 1.23±0.36; MH-RC: 0.81±0.18; D-RC: 0.4±0.17, for B 1.14±0.33; 0.74±0.14; 0.32±0.13, and for C 1.04±0.27; 0.70±0.1; 0.29±0.12 respectively.

Conclusions
The Friedewald equation tends to underestimate and the homogeneous enzimatic direct LDL-C assays to overestimate the LDL-C levels compared to the new, accurate, calculated LDL-C values in atherogenic dyslipidemia condition. Based on the data presented in our investigation we should like to propose that more realistic vasculo-protective lipid status can be attained if we calculate LDL-C using the Martin/Hopkins estimation.
P5369Alpha-V integrin regulates the contribution of PW1+ cells to cardiac fibrosis
Authors: Bouvet M , Claude O , Roux M , Mougenot N , Duval V , Nadaud S , Delacroix C , Perret C , Yaniz-Galende E , Lemitre M , Tregouet D A , Marazzi G , Silvestre J S , Sassoon D , Hulot J S 
Published: October 2019

Abstract

Background
Activated cardiac fibroblasts produce extracellular matrix proteins that accumulate during cardiac fibrosis. We have recently shown that PW1 is expressed in a subset of cardiac stromal cells and that cardiac PW1+ cells represent a cellular source of fibroblasts in the ischemic hearts.

Purpose
We aimed to further identify new cell surface markers expressed by cardiac PW1+ cells and to investigate their role in the fibrogenic behavior of these cells.

Methods and results
We first performed transcriptomic and proteomic profiling of FACS-isolated cardiac PW1+ from normal and ischemic hearts. RNA-sequencing output files were processed with bioinformatics algorithms to identify 378 specific cell-surface markers for cardiac PW1+ cells. By comparing these candidates with the proteomic profile, we then cross-identified 9 cell surface proteins primarily involved in cell motility, adhesion to the matrix, inflammatory response and response to wounding. One of these candidates (i.e., aV-integrin or CD51) was expressed in almost all cardiac PW1+ cells (93±1%), and was predominantly found in cells expressing PW1 in the myocardium. Cardiac PW1+ cells showed a predominant expression of aVβ1 complex which is known to mediate fibrosis through TGF-beta activation in a number of tissues. The transfer of isolated cardiac PW1+CD51+ cells into ischemic hearts was associated with fibrosis development. We further demonstrated that inhibition of aV-integrin in cardiac PW1+ cells reduces their profibrotic gene expression profile and their ability to differentiate into fibroblasts. Lastly, a pharmacological blockade of aV-integrin improved cardiac function and animal survival following myocardial infarction coupled with a reduced infarct size and fibrotic lesion.

Conclusions
These data identify a targetable pathway that regulates cardiac fibrosis in response to an ischemic injury and demonstrate that pharmacological inhibition of aV-integrin leads to reduced pathological outcomes following cardiac ischemia.

Acknowledgement/Funding
Fondation Leducq (grant 13CVD01, CardioStemNet project), Fédération Française de Cardiologie and Era-CVD (ANR-16-ECVD-0011-03, Clarify project)
P5379Modification with CREKA improves cell retention of myocardial ischemia reperfusion
Authors: Chen J , Song Y N , Huang Z Y 
Published: October 2019

Abstract

Background
Poor cell homing limits efficacy of cardiac cellular therapy. The cysteine–arginine–glutamic acid–lysine–alanine (CREKA) homing peptide binds with high specificity to fibrin which is involved in repair of tissue injury.

Purpose
We assessed if CREKA-modified stem cells had enhanced fibrin-mediated homing ability resulting in better functional recovery and structural preservation in a rat myocardial injury model.

Methods
CREKA-modified mesenchymal stem cells (CREKA-MSCs) were obtained via membrane fusion with CREKA-modified liposomes. The fibrin targeting ability of CREKA-MSCs was examined both in vitro and in vivo.

Results
Under both static and flow conditions in vitro, CREKA significantly enhanced MSCs binding ability to fibrin clots. CREKA-MSCs showed much more higher accumulation than unmodified MSCs in injured rat myocardium, colocalizing with fibrin and resulting in better cardiac function.
Stem cell-CREKA-fibrin targeting system

Conclusions
Modification of MSCs with the homing peptide CREKA favored their migration and retention in the infarcted area, resulting in better structural preservation and functional recovery. Fibrin is therefore a novel target for enhancing homing of transplanted cells to injured myocardium and the fibrin-targeting delivery system represents a generalizable platform technology for regenerative medicine.
P5381Lack of sirtuin 5 aggravates myocardial ischemia reperfusion injury
Authors: Witt C N , Koentges C , Pfeil K , Vogelbacher L , Pusdrowski T , Bode C , Zirlik A , Bugger H 
Published: October 2019

Abstract
Sirtuin 5 (SIRT5) is a mitochondrial NAD+-dependent protein deacylase which regulates the enzymatic activity of numerous mitochondrial proteins due to increased succinylation and malonylation, including enzymes of energy substrate oxidation and mitochondrial antioxidant enzymes. Since energy depletion and mitochondrial oxidative stress contribute to myocardial IR injury, it was our objective to evaluate the potential role of SIRT5 in IR injury. In regular Langendorff heart perfusions, 8 week-old cardiomyocyte-selective SIRT5−/− mice showed no difference in LV developed pressure or dp/dt max compared to wildtype mice. However, recovery of LV developed pressure and dp/dt max following 25 min of ischemia was lower by 34% and 20% in SIRT5−/− mice compared to WT mice, respectively. In contrast, postischemic recovery of cardiac function was not impaired and even improved in mice with cardiomyocyte-selective overexpression of SIRT5 compared to WT mice undergoing IR. Mitochondrial H2O2 generation was significantly increased in SIRT5−/− mice compared to WT mice following IR, and mitochondria-targeted antioxidant treatments (MnTBAP or SS-31) during heart perfusion completely normalized recovery of contractile parameters in SIRT5−/− mice following IR. In conclusion, SIRT5 is not required to maintain cardiac function under physiological conditions. However, lack of SIRT5 aggravates myocardial IR injury, likely by increasing mitochondrial oxidative stress. SIRT5 agonism may thus represent a potential therapeutic strategy to attenuate myocardial IR injury.
P5383Autologous adipose-derived stromal cell treatment for patients with refractory angina (MyStromalCell Trial) - 3-years follow-up results
Authors: Qayyum A A , Mathiasen A B , Helqvist S , Joergensen E , Haack-Soerensen M H , Ekblond A , Kastrup J 
Published: October 2019

Abstract

Background
Improvements in medical and interventional therapies have transformed ischemic heart disease into a chronic illness for lot of patients. The disease is in progress and by time patients suffer from cardiac symptoms, reduced work capacity and decline in quality of life. Stem cell therapy is investigated as a treatment option for these patients.

Purpose
In this study, long-term safety and efficacy of autologous intra-myocardial injections of adipose-derived stromal cells (ASCs) were studied in patients with refractory angina.

Methods
Sixty patients were double-blinded 2:1 randomised to ASC or saline injections and followed for three years. The patients had significant angina due to ≥1 coronary artery stenosis but preserved left ventricular ejection fraction. ASCs were obtained from abdomen, ex vivo culture expanded and VEGF-A165 stimulated before delivery into the ischemic myocardium.

Results
The cardiac symptoms, CCS and NYHA classification, were significantly reduced in the ASC group during the three years follow-up period (2.5±0.9 to 1.8±1.2, P=0.002 and 2.4±0.6 to 2.2±0.8, P=0.007, respectively). However, no significant change was observed in CCS or NYHA in the placebo group during the follow-up period (2.5±0.8 to 2.1±1.3, P=0.186 and 2.7±0.6 to 2.4±0.8, P=0.314, respectively).
Moreover, the number of weekly angina attacks reported was significantly reduced in the ASC group (P=0.017), but not in the placebo group (P=0.425).
For patients in the ASC group, the bicycle exercise time (383±30s to 370±44s, P=0.052) and the exercise performance in watt were un-changed (81±6 to 78±10, P=0.123), but the performance in METs was reduced significantly (4.2±0.3 to 4.0±0.4, P=0.027) during the follow-up period.
At the same time in the placebo group, there was a significant decline in bicycle exercise time (437±53s to 383±58s, P=0.001), the exercise performance measured in watt (87±12 watt to 80±12 watt, P=0.019) and in METs (4.5±0.4 to 4.1±0.4, P=0.002).
In both groups, significant improved quality-of-life, angina stability, angina frequency and physical limitation score was observed but not for overall satisfaction score.

Conclusion
Patients receiving ASCs had improved cardiac symptoms during the three years follow-up period, which was not the case for patients in the placebo group. Moreover, patients receiving ASCs had unchanged exercise capacity, in opposition to deterioration in the placebo group.

Acknowledgement/Funding
Arvid Nilssons Foundation; Rigshospitalets Research Foundation; Aase and Ejnar Danielsens Foundation
P5395Exercise-induced miR-17-3p Prevents Pathological Myocardial Dysfunction
Authors: Zhou Q , Xiao J 
Published: October 2019

Abstract

Background
Exercise is beneficial for pathological myocardial dysfunction and heart failure. We previously reported that miR-17-3p contributed to exercise-induced cardiac growth and protected against cardiac ischemia/reperfusion injury. However, if exercise-induced miR-17-3p can prevent pathological myocardial dysfunction is undetermined.

Purpose
To investigate if exercise-induced miR-17-3p can prevent pathological myocardial dysfunction.

Methods
The miR-17-3p expression was examined in phenylephrine (PE, 50μmol/L, 48 h) and angiotensin II (Ang II, 1μmol/L, 48 h) treated primary neonatal rat ventricular cardiomyocytes (NRCM), and the myocardium of thoracic aortic constriction (TAC, 4weeks) or angiotensin II (1.3 mg/kg/day, 4weeks) induced cardiac hypertrophy murine model. miR-17-3p transgenic mice were generated and subjected to TAC or Ang II to investigate the effect of miR-17-3p overexpression in attenuating pathological cardiac dysfunction by echocardiography. Cell area and hypertrophic genes were determined by Wheat Germ Agglutinin (WGA) staining and qRT-PCRs. In addition, cell area and hypertrophic genes (ANP, BNP, β-MHC) were determined by immunolabeling and qRT-PCR in NRCM after the transfection of miR-17-3p mimic or inhibitor. Furthermore, functional rescue assays were performed to identify phosphatase and tensin homolog (PTEN) as a target gene of miR-17-3p, and myocyte enhancer factor 2C (MEF2C) as an upstream regulator of miR-17-3p in pathological cardiac hypertrophy.

Results
The expression of miR-17-3p was significantly decreased in the heart from TAC or Ang II mouse model, and in PE or Ang II-induced cardiomyocyte hypertrophy model. miR-17-3p overexpression mice displayed improved cardiac function and reduced cardiac hypertrophy after TAC or Ang II treatment in vivo. miR-17-3p mimic significantly attenuated PE or Ang II-induced cardiomyocyte hypertrophy in vitro. Based on functional rescue experiments, PTEN was identified as a direct target of miR-17-3p that mediated its protective effects in cardiac hypertrophy. Moreover, MEF2C was identified as a negative upstream regulator of miR-17-3p involved in the control of cardiac hypertrophy.
Proposed mechanism of miR-17-3p

Conclusion
Exercise-induced miR-17-3p can prevent pathological myocardial dysfunction by targeting PTEN. MEF2C was an upstream regulator of miR-17-3p. Targeting MEF2C/miR-17-3p/ PTEN represents a novel therapeutic strategy for pathological myocardial dysfunction.

Acknowledgement/Funding
The grants from National Natural Science Foundation of China (81722008, 91639101 and 81570362 to JJ Xiao)
P5405Clinical and prognostic relevance of increased liver stiffness coupled with abnormal liver function tests in decompensated heart failure
Authors: Soloveva A , Bayarsaikhan M , Lukina O , Troitskaya E , Bondari S , Khruleva Y , Arisheva O , Garmash I , Villevalde S , Kobalava Z 
Published: October 2019

Abstract

Objective
Recent studies have demonstrated associations of either abnormal liver function tests (LFT) or liver stiffness (LS) increase with negative outcomes in decompensated heart failure (DHF). We aimed to assess incidence, clinical and prognostic relevance of combined increase of LS and LFT in DHF.

Methods
The study included 130 patients (73% male, 68±11 years [M±SD], myocardial infarction 49%, atrial fibrillation 63%, diabetes mellitus 39%, chronic kidney disease 24%, EF 39±14%, EF<40% 54%, NT-proBNP 3601 [1905; 6220] pg/ml, alcohol abuse 26.2%) hospitalized with DHF, in whom levels of alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin (TB) and LS (using transient elastography) were assessed in the first 48 hours of admission. Patients with previous liver disease or acute hepatitis were excluded. Higher then upper normal limit levels of either AST/ ALT/ TB were considered as LFT increase; LS >5.9 kPa – as abnormal. Outcomes were assessed by phone contacts in 1, 3, 6 and 12 months. Kruskal–Wallis test, Pearson's chi-squared test and Kaplan-Meier survival analysis were used. P<0.05 was considered significant.

Results
Median LS was 11.1 (6.8; 24.5) kPa, median ALT 20.1 (14.9; 30.7) U/l, AST 26 (20; 36.3) U/l, TB 19 (13.2; 27) μmol/l. LS and ALT, AST, TB increase occurred in 79.2 and 15.4, 13.1, 40.8% patients.
Based on combination of LS and LFT increase subjects were divided into 3 groups: without LS and LFT increase (G1, 16.2%), with only LS increase (G2, 33.1%) and both LS and LFT increase (G3, 46.1%). Isolated LFT increase was noted only in 6 (4.6%) patients.
G3 compared to G2 and G1 was characterized by lower EF (33±14 vs 41±13 and 45±11%, p<0.001) and inferior vena cava (IVC) collapsibility (23.3 vs 41.9 and 61.9%, p=0.003), higher IVC diameter (2.4 [2; 2.6] vs 2.2 [2; 2.4] and 2 [1.95; 2.2] cm, p<0.001), right ventricular diameter (3.5 [3.2; 3.9] vs 3.2 [3; 3.6] and 3 [2.9; 3.1] cm, p<0.001), pulmonary artery pressure (56 [45; 66] vs 50 [37; 65] and 40 [33; 49] mmHg, p=0.014), higher rate of tricuspid regurgitation (70 vs 44.2 and 28.6%, p=0.001). Groups did not differ by alcohol abuse rate (p=0.152).
Kaplan–Meier analysis of groups for all-cause death probability showed significant differences (figure): event-free survival for G3 vs G1 and G2 was 64.9 vs 81 and 95% (log rank p=0.011, χ2=6.5 for G3 vs G1; log rank p=0.081, χ2=3.1 for G3 vs G2). HF readmission probability was significantly higher in G3 vs G2 and G1: corresponding event-free survival was 50.9 vs 66.7 and 80% (log rank p=0.012, χ2=6.3 for G3 vs G1; log rank p=0.036, χ2=4.4 for G3 vs G2).

Conclusions
Combination of abnormal LFT and increased LS was observed in 46.1% of DHF patients and was associated with lower EF, more serious right-sided dysfunction and higher probability of negative long-term outcomes.
P5406Impact of the albumin level on the prognostic value of diuretic response in patients admitted for acute decompensated heart failure: a prospective study
Authors: Yamamoto K , Yamada T , Morita T , Furukawa Y , Tamaki S , Iwasaki Y , Kawasaki M , Kikuchi A , Kawai T , Seo M , Abe M , Nakamura J , Fukunami M 
Published: October 2019

Abstract

Background
The reduced diuretic response (DR) has been shown to be associated with poor clinical outcome in patients with acute decompensated heart failure (ADHF). In addition, hypoalbuminemia, which is related to DR, has been also reported to predict poor prognosis in ADHF patients. However, there is no information available on the impact of albumin level on the prognostic value of DR in patients with ADHF.

Methods
We prospectively studied 296 consecutive patients who were admitted for ADHF and survived to discharge. The patients were divided into 2 groups according to the presence or absence of hypoalbuminemia at the admission, defined as the serum level of albumin at admission <3.5g/dl, and DR was defined as weight loss per 40mg intravenous dose and 80mg oral dose of furosemide up to day 4. The endpoint was a composite of all-cause mortality and unplanned hospitalization for worsening heart failure.

Results
There were 144 patients with hypoalbuminemia and 152 patients without hypoalbuminemia. During a mean follow-up period of 2.2±1.5 years, 88 patients with hypoalbuminemia and 53 patients without hypoalbuminemia reached the endpoint. In group with hypoalbuminemia, DR was significantly smaller in patients with than without the endpoint (0.85 [0.50–1.50] vs 1.60 [0.76–2.70] kg/40mg furosemide, p=0.003), while there was no significant difference in DR between them in group without hypoalbuminemia (1.17 [0.59–1.66] vs 1.07 [0.75–1.88] kg/40mg furosemide, p=0.381). At multivariate Cox analysis, in group with hypoalbuminemia, DR was significantly associated with the endpoint, independently of age, left ventricular ejection fraction, and serum creatinine and plasma BNP levels. On the other hand, in group without hypoalbuminemia, DR showed no significant association with the endpoint at univariate Cox analysis. Kaplan-Meier analysis showed that patients with poor DR (≤1.08 kg/40mg furosemide: median value) had a significantly higher risk of the endpoint in group with hypoalbuminemia, but not in group without hypoalbuminemia (Figure).
Figure 1

Conclusion
Our results suggested that prognostic value of DR in ADHF patients is affected by the presence or absence of hypoalbuminemia.
P5416A single-center, thirty-year experience of heart transplantation: analysis of the evolution of patients profile and long term outcomes
Authors: Turco A , Totaro P , Pellegrini C , Guida S , Cattadori B , Di Matteo A , Seminari E , Camporotondo R , Riccardi M , Ghio S , Raineri C , Scelsi L , D'Armini A M , Oltrona Visconti L , Pelenghi S 
Published: October 2019

Abstract

Background
Heart Transplantation is still the gold standard therapy for patients suffering from end-stage cardiomyopathy and has been successfully performed in our center since 1985. Over this 30 years period there has been a significant evolution in patients characteristics and in candidate selection (either as a donor and as recipient) as shown by the recent benchmark from International Society of Heart and Lung Transplantation (ISHLT). Here we analyze the evolution of patients profile in our population and we correlated such evolution to the clinical outcomes and to the overall data from ISHLT.

Materials and methods
Overall 1122 patients underwent heart transplantation at our center from November 19th1985 to date. To analyze the evolution patients profile and donor criteria, patient population was divided in 4 groups according era of transplantation following ISHLT model (Group A from 1985 to 1991; Group B from 1992 to 2003; Group C from 2004 to 2008 and Group D from 2009 to date). Patients characteristics at time of transplantation, donor criteria ad clinical outcomes were analyzed and compared within 4 groups. An overall comparison of our results to the data from ISHLT was also performed.

Results
Overall Kaplan-Meier survival curve correlates favourably with ISHLT data showing a 20 years survival approaching 40%. Patients age at transplantation changed significantly among 4 groups from a median of 49 years (95% CI 47 to 51) in Group A to 54 years (95% CI 50 to 57) in Group D (p<0.001). Likewise donor age also changed significantly from a median of 24 years (95% CI 22 to 28) in Group A to 43 years (95% CI 39 to 47) in group D (p<0.001). Time on waiting list also changed significantly from a median of 115 days (95% CI 94 to 137) in Group A to 293 (95% CI 200 to 401) in Group D (p<0.001). As a marker of evolution of accepted donor criteria also ischemic time changed from 125±52 minutes of Group A to 153±61 minutes of Group D (p<0.001). As showed in Fig 1, Kaplan-Meier survival curves demonstrated a worse 1-year survival in Group D compared to others 3 Group.
Figure 1

Conclusions
The significant changing characteristics of both recipients and donors, over 30 years of activity, had a significant impact in early (1 year) postoperative survival following heart transplantation. Although medium/long term outcomes are still satisfactory in patients surviving at least 1 year, these data clearly suggest a more accurate patients selection and the need of alternative treatment before patients conditions deteriorate while on waiting list for heart transplantation