bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5343The presence of anti-apolipoprotein A1 autoantibodies is associated with a pro-atherogenic profile in HIV-infected patients
Authors: Frias M , Pagano S , Fetaud-Lapierre V , Lecour S , Kamau F , Strijdom H , Vuilleumier N 
Published: October 2019

Abstract

Background
With the access to antiretroviral therapy (ART), the mortality related to the human immunodeficiency virus (HIV) has dropped, shifting the clinical challenges towards chronic disease management, including cardiovascular disease (CVD) risk assessment. Factors that potentially contribute to the physiopathology of HIV-related CVD include the HI-virus itself, adverse effects of ART, and processes such as dyslipidemia, inflammation, immune/autoimmune activation and endothelial injury. Among autoantibodies of possible cardiovascular relevance, those directed against apolipoprotein A-1 (anti-apoA-1 IgG) were shown to predict major adverse cardiovascular events and promote atherogenesis.

Purpose
The aim of the study was to evaluate the prevalence of anti-apoA1 IgG in HIV-free and ART experienced and naïve HIV-infected patients as well as the association between anti-apoA1 IgG levels and, indices of viral suppression, clinical parameters (10 year Framingham Risk Score (FRS)) and inflammatory biomarkers, known to underlie atherosclerosis burden in these patients.

Methods
Anti-apoA1 IgG serum levels were assessed by a homemade ELISA assay in 144 participants from a South African cohort divided in three groups: HIV-free (n=50), HIV-infected/ART experienced (n=50) and HIV-infected/ART naïve (n=44). Inflammatory biomarkers were measured.

Results
HIV-infected patients displayed an increased pro-atherogenic biomarker profile compared to HIV-free subjects, but not difference in the FRS was observed between these two groups. Regarding anti-apoA1 IgG, 24% of HIV-free patients tested positive compared to 40% and 70% in HIV-infected/ART experienced and naïve groups, respectively. HIV-infected, anti-apoA1 IgG positive patients showed a significant decrease in CD4+ counts (p=0.003) and a significant increase in viremia (p=0.0130), mean heart rate (p=0.0243), albuminuria (p=0.0155), pro-inflammatory biomarkers (IFNγ, IL-10, TNFα, MIPα; all p<0.05), circulating levels of intercellular adhesion molecule (ICAM-1) (p=0.0217) and vascular cell adhesion molecule (VCAM-1) (p=0.003) compared to anti-apoA1 IgG negative ones. Of note, while this profile was maintained in HIV-infected/ART experienced, these significant differences were lost in HIV-infected/ART naïve patients. No significant difference in FRS was observed between anti-apoA1 IgG positive vs negative individuals in all groups.

Conclusions
HIV-infected patients presented with an increased prevalence of anti-apoA1 IgG compared to HIV-free subjects. In HIV-infected/ART experienced patients, anti-apoA1 IgG levels were associated with low CD4+ counts, levels of adhesion molecules and pro-inflammatory responses, features associated with increased cardiovascular events. ART highlighted pro-atherogenic differences between HIV-infected anti-apoA1 IgG negative and positive patients.
P5368The prevalence and management of familial hypercholesterolemia in patients with acute coronary syndrome in Poland: results of the TERCET registry
Authors: Dyrbus K , Gasior M , Desperak P , Nowak J , Osadnik T , Banach M 
Published: October 2019

Abstract

Background
Prevalence of familial hypercholesterolemia (FH) is high among patients with coronary artery disease (CAD). However, data on FH among patients with acute coronary syndrome (ACS) are still scarce.

Purpose
Therefore, we aimed to assess the prevalence, lipid-lowering therapy and short- and long-term outcomes in patients with FH among patients with ACS.

Methods
We finally included 19,582 consecutive patients from the Hyperlipidaemia Therapy in the tERtiary Cardiological cEnTer (TERCET) Registry for years 2006–2018. Among them, there were 7,319 patients admitted with ACS: 3,085 due to ST-segment elevation acute coronary syndrome (STEMI), 2,256 due to NSTEMI, and 1,978 due to unstable angina (UA). Stable CAD [sCAD] group n=12,462 that was treated as a reference one. Based on the personal and familial history of premature cardiovascular disease and low-density lipoprotein cholesterol (LDL-C) concentration, the Dutch Lipid Clinic Network (DLCN) algorithm was used for FH diagnosis.

Results
At the time of hospitalization, the overall occurrence of probable/definite FH and possible FH were 1.2% and 13.5% respectively. In patients with ACS, 1.6% had probable/definite FH and 17.0% possible FH. The highest occurrence of FH was observed in STEMI subgroup, where 20.6% of the patients had ≥3 points according to the DLCN criteria. There were significant differences in hypolipemic treatment between the FH subpopulations. In patients with definite/probable FH 92.3% and 91.5% were administered statins at discharge, respectively (including 52.9% prescribed intensive statin therapy). Patients with definite and probable FH had higher 30-day mortality than patients without FH (8.2% and 3.8% vs 2.0%, respectively; p=0.0052). However, no significant differences were observed between the FH groups in the 12-, 36- and 60-month follow-up (Figure). Propensity-score matching analysis showed that definite/probable FH patients had significantly higher all-cause mortality at the 36- and 60-month follow-up in comparison to non-FH subjects (11.4% vs 4.8% and 19.2% vs 7.2%, respectively; p≤0.021 for both).
Outcomes depending on DCLN FH diagnosis.

Conclusions
The prevalence of FH according to the DLCN criteria in the Polish very high-risk population is even 14.7% and is significantly higher in patients with ACS than in patients with sCAD. Among patients included in the Registry, the occurrence of FH rises to 20.6% in the STEMI subgroup, and to 17.2% in the NSTEMI subgroup. Propensity-score matching analysis confirmed that FH itself is a cause of increased all-cause mortality in the long-term follow-up.

Acknowledgement/Funding
None
P5387CRISPR/dCas9 Activated Expression of Cardiomyocyte Differentiation Factors in CDCs in Myocardial Infarctions
Authors: Sano T , Ishigami S , Bandaru S , Ito T , Sano S 
Published: October 2019

Abstract

Background
Existing therapies against myocardial infarction (MI) involve disease management by preventing additional damage to the heart muscle. However, new treatment strategies are in greater demand, which deems to focus on restoring cardiac function by replacing the damaged cells after MI, rather than merely manage the disease. Cardiosphere-derived cells (CDCs) have emerged as a potential source of cardiac regenerative therapy. In spite of being a promising option, the poor differentiation potential of CDCs to develop into a functional population of cardiomyocytes has always been a significant setback.

Purpose
The purpose of the present study centers to overcome the aforementioned setback by enhancing the efficiency of rat CDCs to develop into a large population of cardiomyocytes by intrinsic activation of cardio-specific differentiation factors (TNNT2, GATA4, Mef2c) by Crispr/dcas9 assisted transcriptional enhancement system.

Methods
In the foremost step, an exhaustive screening was performed to identify the specific sequences in endogenous regulatory regions (enhancers and promoters) responsible for transcriptional activation of the TNNT2 gene. Once, potential regulatory regions at proximal and distal end of TNNT2 were identified, crRNAs were designed complementing these regions for recruiting Crispr/dcas9 system fused with transcriptional activator like VP64 (CRISPR-dCas9-VP64). Two distinct plasmids were constructed with crRNA (RFP fused) inserts and CRISPR-dCas9-VP64 (GFP fused) followed by transfection in CDCs those isolated from the heart of a neonatal rat. Post transfection, CDCs were then analyzed for the quantitative expression of cardiomyocyte differentiation factors as well as for fibroblast differentiation factors in comparison with un-transfected CDCs.

Results
We identified a panel of specific crRNA targeting the enhancers and promoters which demonstrated significantly higher expression of differentiation factors like troponin, GATA4, and Mef2c. Further, the fluorescent visualization with GFP and RFP was prominent in the CDCs confirming that these panel of crRNA enhanced the expression of differentiation factors compared to the un-transfected counterparts. Interestingly, the same panel crRNA, in contrast, demonstrated diminished expression of fibroblast differentiation factors like Col1A1, clearly emphasizing that the CRISPR dCas9 system recruitment at regulatory regions forms an efficient molecular targeting system for enhancing the differentiation potential of CDCs into cardiomyocytes.

Conclusion
We have identified endogenous regulatory regions responsible for an intrinsic activation of cardio-specific differentiation factors assisted by Crispr/dcas9 gene transcriptional system. We anticipate the method developed herein can enhance and cardiomyogenic efficiency of CDCs to differentiate into a large population of cardiomyocytes to treat Ischemic heart diseases.
P5399microRNA-486 mediates exercise-induced cardiac growth and prevents cardiac ischemia-reperfusion injury
Authors: Bei Y , Lu D , Meng X , Zhu Y , Liang X , Xiao J 
Published: October 2019

Abstract

Background
Molecules mediating exercise-induced physiological cardiac growth may be beneficial to prevent cardiac injury and remodeling. MicroRNA-486 (miR-486) is a muscle-enriched microRNA which was found to be increased in exercised heart. However, the role of miR-486 in exercise-induced cardiac growth is largely unknown.

Purpose
We aimed to study the function of miR-486 in exercise-induced cardiac growth, and to investigate its potential role in protection against cardiac ischemia/reperfusion (I/R) injury.

Methods
Male C57BL/6 adult mice were subjected to 3-week swimming exercise to induce physiological cardiac growth. Knockdown of miR-486 was performed by intramyocardial injection of miR-486 sponge to evaluate the role of miR-486 in exercise-induced cardiac growth. Moreover, intramyocardial injection of miR-486 overexpression lentivirus was performed to investigate whether miR-486 could reduce infarct size in mice suffered from acute I/R injury (30 min ligation and 24 hr reperfusion of left anterior descending coronary artery). Meanwhile, the functional role of miR-486 was evaluated in neonatal rat cardiomyocytes (NRCMs) treated with oxygen glucose deprivation/reperfusion (OGDR) using Tunel staining. Finally, function-rescue assays were performed to identify target genes of miR-486.

Results
Exercise significantly upregulated miR-486 in the heart, which was reduced by intramyocardial injection of miR-486 sponge. Exercise induced-cardiac growth was abolished in mice with intramyocardial injection of miR-486 sponge, as evidenced by reduced heart weight/body weight ratio and heart weight/tibia length ratio compared to control exercised-mice, suggesting a potential role of miR-486 in mediating exercise-induced cardiac growth. Meanwhile, we found that intramyocardial injection of miR-486 overexpression lentivirus was able to reduce the infarct size as determined by TTC staining. Moreover, in OGDR-induced apoptosis of NRCMs, miR-486 mimics was able to reduce cardiomyocyte apoptosis, while miR-486 inhibitor performed the opposite. Finally, PTEN and FoxO1 were identified as target genes of miR-486 in the control of cardiomyocyte apoptosis.

Conclusions
miR-486 mediates exercise-induced cardiac growth and protects against cardiac I/R injury. Increasing miR-486 might serve as a potential target to reduce myocardial apoptosis upon I/R injury.

Acknowledgement/Funding
This work was supported by the grants from National Natural Science Foundation of China 81722008, 91639101 and 81570362 to JJ Xiao, 81770401 to Y Bei
P5412Prevalence of RV failure assessed by echocardiography in acute dyspnoea cohort
Authors: Cerlinskaite K , Bugaite J , Gabartaite D , Verikas D , Krivickiene A , Motiejunaite J , Zaliaduonyte-Peksiene D , Zakarkaite D , Mebazaa A , Kavoliuniene A , Celutkiene J 
Published: October 2019

Abstract

Introduction
Recently more attention has been placed on right ventricle (RV) parameters in acute settings. The present study investigates echocardiographic RV parameters in patients with acute heart failure (AHF) or non-AHF acute dyspnoea.

Purpose
To determine the patterns of RV injury in different profiles of acute dyspnoea.

Methods
Prospective multicentre observational study included 1455 acutely dyspnoeic patients from 2015 to 2017. RV focused echocardiography was performed during the first 48 hours in 452 (31%) patients. They were compared in three patient profiles based on cause of dyspnoea and history of chronic HF (CHF): 1) AHF; 2) Non-AHF with CHF (Non-AHF+CHF); 3) other non-AHF patients (Non-AHF+other).

Results
Significant differences in RV morphology and function were observed in the study groups (Table 1). RV global function assessed by tricuspid annular plane systolic excursion (TAPSE) and RV longitudinal shortening was mostly affected in AHF patients. This was accompanied by more enlarged RV and increased right atrial pressure (RAP), assessed by the inferior vena cava diameter and respiratory collapse. Less severely impaired RV function and increased RAP were also observed in non-AHF+CHF patients indicating RV involvement in the chronic disease. Normal RV parameters dominated in Non-AHF+other group, however pulmonary artery systolic pressure >40 mmHg was observed in all profiles, suggesting similar severity of pulmonary hypertension in cardiac or pulmonary causes of acute dyspnoea.
Table 1. RV parameters in acute dyspnoea profiles Parameter AHF (n=291) Non-AHF + CHF (n=73) Non-AHF + other (n=88) p value LVEF, % 38 [25–55] 50 [40–55] 55 [50–55] <0.001 RV basal diameter, cm 4.5 [3.9–5.2] 4 [3.5–4.5] 4 [3.5–4.55] <0.001 TAPSE, cm 1.5 [1.2–1.8] 1.8 [1.6–2] 2 [1.5–2.4] <0.001 RV free wall strain, -% −15.3 [−19; −11.24] −19.3 [−24.5; −15.78] −23 [−24.5; −19.69] <0.001 Entire RV strain, -% −12.03 [−15.17; −9.11] −16.4 [−19.31; −10.5] −18 [−18.75; −16.9] <0.001 PASP >40, % 66% 51% 50% 0.039 IVC diameter, cm 2.4 [2–2.8] 2 [1.7–2.4] 1.8 [1.4–2.3] <0.001 IVC collapse, % 34.9 [19.7–50.2] 44.1 [28.7–59.3] 52.6 [35–72.7] <0.001 LVEF, left ventricular ejection fraction; RV, right ventricle; TAPSE, tricuspid annular plane systolic excursion; PASP, pulmonary artery systolic pressure; IVC, inferior vena cava; AHF, acute heart failure; CHF, chronic heart failure.

Conclusions
Our data confirm more pronounced acute failure of right ventricle in acute heart failure patients than in chronic heart failure patients admitted due to other causes of dyspnoea. Pulmonary hypertension is present in a majority of the acute dyspnoea patients.

Acknowledgement/Funding
The work was supported by the Research Council of Lithuania, grant Nr. MIP-049/2015 and approved by Lithuanian Bioethics Committee, Nr. L-15-01.
P5414Factors influencing mortality in a long-term follow-up after heart transplantation; role of immunomonitoring
Authors: Alyaydin E , Welp H , Pogoda C , Pistulli R , Reinecke H , Tuleta I 
Published: October 2019

Abstract

Background
Despite relevant improvements in the last years, increased mortality limits the success of heart transplantation therapy. Although many factors influencing mortality have been identified, the most studies analyzed relatively short follow-up time following heart transplantation.

Purpose
Therefore, the aim of our present study was to evaluate risk factors for enhanced mortality with emphasis on quantitative changes in immunological blood cells late after heart transplantation.

Methods
174 patients with a mean time after heart transplantation of 13.1±6.5 years were retrospectively analyzed using data collected during follow-up visits in our center. Clinical examinations, results of laboratory tests, including immunomonitoring of CD4+, CD8+, CD19+ cells and natural killer cells, ultrasound vessel visualization and coronary angiography were evaluated with respect to the all-cause mortality.

Results
In patients who were still alive at the time of data analysis (group 1, n=134), glomerular filtration rate, erythrocyte count, hemoglobin and mean corpuscular hemoglobin concentration were significantly increased compared to the group encompassing patients who died before this time point (group 2, n=40) (p<0.05 for all). In contrast, c- reactive protein (CRP), leukocyte count, triglycerides and N-terminal pro-brain natriuretic peptide were significantly decreased in group 1 versus group 2 (p<0.05 for all). In the first group the patients were relevantly less frequently on dialysis, presented lower NYHA classes, later onset of cardiac allograft vasculopathy and received hearts from donors with lower body mass (p<0.05 for all). Additionally, patients from the first group were characterized by significantly higher CD4 and lower CD8 percentages as well as a tendency towards higher CD19 cell count. In a multivariate cox regression analysis CD4 percentage (hazard ratio (HR): 0.454, confidence interval (CI): 0.236–0.871; p=0.018), onset of cardiac allograft vasculopathy (HR: 0.422, CI: 0.190–0.941; p=0.035) and CRP (HR: 0.325, CI: 0.170–0.621; p=0.018) were independent risk factors for increased mortality.

Conclusions
Increased inflammation, anemia, renal and heart insufficiency, early onset of cardiac allograft vasculopathy, worse functional status and donor associated factors such as higher body mass correlated significantly with enhanced mortality among patients after heart transplantation. In contrast to the early phase following heart transplantation, where the suppression of CD4+ cell number contributes to the decrease in the frequency of acute rejections, aggressive reduction of CD4+ cells by high doses of immunosuppressive agents late after cardiac transplantation may augment risk of mortality. It may be explained due to the creation of a subclinical chronic immunosuppressive condition and potentiation of side effects of immunosuppressive drugs.
P5415Sleep disordered breathing in patients before and after heart transplantation: association with biomarkers and clinical parameters
Authors: Medvedeva E , Korostovtseva L S , Simonenko M A , Sazonova Y V , Sviryaev Y V 
Published: October 2019

Abstract

Background
Sleep-disordered breathing (SDB) is highly frequent in patients with severe heart failure (HF). SDB, and predominantly central sleep apnea (CSA), may improve after recovery of cardiac function, but available data are limited and inconclusive, especially in patients who have undergone heart transplantation. The assessment of the severity of sleep apnea is mainly based on the apnea-hypopnea index (AHI), but this event-based parameter alone may not sufficiently reflect the complex pathophysiological mechanisms underlying SDB potentially contributing to adverse outcomes in patients with heart failure.

Purpose
To assess SDB in patients with severe HF before and after heart transplantation, their relationship with biomarkers and clinical parameters.

Methods
We included 117 patients (mean age 52.4±4.7 years) with HF NYHA class II-IV in the prospective cohort study, follow-up period was 5 years. The left ventricular ejection fraction (LVEF) was 28.05±9.57%. All patients underwent a comprehensive clinical examination, echocardiography, polysomnography (PSG, Embla N7000, Natus, USA). The plasma level of NT-proBNP, was analyzed by immunoassay (ELISA). The SPSS statistical software (version 23.0) was used.

Results
PSG showed the following types of SDB in the studied cohort: obstructive sleep apnoea (OSA) was diagnosed in 48 patients (41%), central - in 20 (17%), mixed - in 26 (22%). Among them mild SDB was diagnosed in 29 cases, moderate in 32 and severe in 33 patients. SDB was not found in 23 patients. The following correlations were identified: NT-proBNP and obstructive apnea index (OAI) (r=−0.44, p=0.007), NT-proBNP and sleep efficiency (r=−0.71, p=0.006), AHI and body mass index (BMI) (r=0.32, p=0.01), OAI and BMI index (r=0.34, p<0.001), desaturation index and BMI (r=0.43, p<0.001), average saturation oxygen and BMI (r=−0,6, p<0,001). Twenty-three patients underwent heart transplantation. According PSG-data 1 year after transplantation we observed decrease of central apnea index (CAI) (p=0,04). On the other hand, OAI increased (p=0,01) independently of the significant change in BMI (p=0,08).

Conclusion
We found very high rate of SDB (80%) in patients with severe HF, the predominant type was OSA. AHI, OAI and indicators of oxygen saturation correlate with BMI and biomarkers before heart transplantation. After 1 year after transplantation CAI decreased, assessment of the dynamics of obstructive sleep apnea requires further study.
P5428QRS narrowing more than 15 ms after CRT implantation is strongly associated with the long-term survival
Authors: Hameli E , Theuns D A M J , Lenzen M J , Yap S C , Szili-Torok T , Caliskan K 
Published: October 2019

Abstract

Background
Cardiac resynchronization therapy (CRT) is used in selected heart failure patients with electrical cardiac dyssynchrony with a prolonged QRS duration and a left ventricle ejection fraction (LVEF) ≤35%. QRS duration post CRT implantation can probably predict responders and survivors. The aim of our study is to investigate the effect of QRS change on long-term survival post CRT implantation.

Methods
We performed a retrospective cohort study in patients receiving a CRT device in our tertiary referral center between January 2009 and January 2018. Clinical and electrocardiographic (ECG) data were collected at baseline, one week after CRT implantation, six months, and yearly during follow-up. The primary endpoint was death, left ventricle assisting device implantation, or heart transplantation. At the end, the cohort was dichotomized to the cut-off value of ≥15ms according current literature.

Results
The study population consisted of 219 patients of whom 145 (66%) patients were survivors and 74 (34%) non-survivors. Non-survivors were significantly older (63 vs. 68 years, p=0.001), male gender (67% vs. 82%, p=0.015), had more often diabetes mellitus (20% vs. 39%, p=0.002), chronic obstructive pulmonary disease (12% vs. 28%, p=0.003), an ischemic etiology of heart failure (42% vs. 61%, p=0.009) with previous myocardial infarction (29% vs 53%, p=0.001), previous revascularization (32% vs. 49%, p=0.019), atrial fibrillation (21% vs. 39%, p=0.004), worser NYHA class (p=0.008), and amiodarone use (10% vs. 22%, p=0.024). Blood urea nitrogen (BUN) (8.1 mmol/L vs. 10.4 mmol/L, p<0.001) and creatinine levels (96 μmol/L vs. 114 μmol/L, p=0.001) were also higher in the non-survivors group. Median QRS duration (168 ms IQR [154 to 182]) at baseline was comparable between survivors and non-survivors (170 ms vs. 166 ms, p=0.17). However, median QRS change one week after CRT implantation was significantly better in the survivors (−19 ms IQR [−30 to −2] vs. −6 ms IQR [−24 to +12], p=0.004). The QRS change at the last FU (median 5.1 years IQR [2.9 to 7.8] was consistently higher in the survivor group (−16 ms IQR [−29 to 0] vs. +1 ms IQR [−27 to +20], p=0.004). Dichotomized to ΔQRS narrowing of ≥15 ms after CRT implantation showed significantly better long-term survival (figure).
Kaplan-Meier curve

Conclusion
QRS narrowing cut-off of ≥15 ms post CRT implantation is strongly associated with the long term survival in chronic heart failure patients with reduced LVEF.