bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5328Clinical and demographic predictors of attenuated LDL-C response to PCSK9 inhibition with bococizumab: Insights from the SPIRE trials
Authors: Siddiqi H , Everett B M , Rose L M , Ridker P M 
Published: October 2019

Abstract

Background
While there exists significant inter-individual variability in low density lipoprotein cholesterol (LDL-C) response to proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition, predictors of this response remain uncertain. The Studies of PCSK9 Inhibition and the Reduction of Vascular Events (SPIRE) randomized control trials evaluated the efficacy of bococizumab, a humanized murine PCSK9 antibody, in patients at high cardiovascular risk.

Purpose
This study's purpose is to determine predictors of attenuated LDL-C response to bococizumab.

Methods
SPIRE 1 and 2 trial subjects allocated to bococizumab (n=13,675) were included. Subjects with an increase in LDL-C or non-compliance to bococizumab, or development of anti-drug or neutralizing antibodies were excluded. The remaining 8281 subjects were divided into quintiles of percent LDL-C reduction from baseline to 14 weeks. The first quintile (Q1) was considered an attenuated response. Multivariate logistic regression was used to discern significant predictors of attenuated response (Q1) compared to robust response (Q5).

Results
Q1 included 1657 subjects with median 35% LDL-C reduction (range 0.4% - 48%), whereas Q5 included 1658 subjects with median 83% LDL-C reduction (range 78% - 99%). Female sex, diabetes, white race, younger age, higher baseline non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein (a) [Lp(a)] and high-sensitivity C-reactive protein (hsCRP) were significantly associated with an attenuated response compared to a robust response (each p<0.05, Table).
Multivariate logistic regression for attenuated percent LDL-C response to bococizumab from baseline to 14 week Baseline characteristic Adjusted odds ratio (95% confidence interval) P-value Female 3.30 (2.72, 4.00) <0.0001 Diabetes 1.57 (1.32, 1.86) <0.0001 White race 1.44 (1.07, 1.93) 0.016 BMI (per 1kg/m2) 1.09 (1.07, 1.11) <0.0001 Age (per year) 0.98 (0.98, 0.99) 0.0005 Ln hs-CRP (per 1mg/L) 1.19 (1.11, 1.29) <0.0001 Lp (a) (per 10mg/dL) 1.11 (1.09, 1.14) <0.0001 Non-HDL-C (per 10mg/dL) 1.05 (1.02, 1.07) <0.0001 Odds ratios mutually adjusted for the listed variables.

Conclusions
In the SPIRE 1 and 2 trials, excluding subjects with anti-drug and neutralizing antibodies, significant predictors of an attenuated LDL-C response to PCSK9 inhibition with bococizumab included female sex, diabetes, younger age and white race.

Acknowledgement/Funding
Pfizer
P5349Platelet/lymphocyte ratio as an inflammatory marker and predictor of short-term neurological outcomes in survivors after cardiac arrest
Authors: Rodriguez L , Martinez L A , Rosillo S O , Martin L , Merino C , Marco I , Velez A , Caro-Codon J , Garcia De Veas J M , Iniesta A M , Rial V , Gonzalez O , Armada E , Lopez-Sendon J L , Lopez-De-Sa E 
Published: October 2019

Abstract

Background
Platelet/lymphocyte ratio (PLR), an inflammatory marker associated with poor outcomes in different clinical situations, may play a role in the proinflammatory state triggered during hypoxic-ischemic brain injury secondary to cardiac arrest.

Purpose
To study PLR dynamics and its relationship with neurologic outcomes in survivors after CA treated with target-temperature-management (TTM).

Methods
Observational retrospective study from a prospective database of survivors of in-hospital and out-of-hospital CA admitted to our Acute Cardiac Care Unit between August 2006 to December 2018. All patients received TTM according to our local protocol.

Results
A total of 466 patients were included. Mean age was 62.7±14.4 years and 102 (21.9%) were women. Baseline characteristics are shown in Table 1. 430 (92.2%) of CA were witnessed, 312 (67.0%) had ventricular fibrillation as initial cardiac rhythm. Among them, 236 (51.1%) survived until hospital discharge and 208 (45.1%) presented favorable neurological outcomes (a score 1 or 2 on cerebral performance category (CPC)). The mean value of PLR at admission and during targeted temperature was 100.4±5.2 and 224.5±7.3 respectively (mean difference 123.1±7.1, p<0.0001). This increase in PLR was significantly higher among patients with worse neurological outcomes (CPC 3–5, mean DPLR 138.2±5.5) at 3 months compared with survivors with CPC 1–2 (mean DPLR 108.2±6.3, p=0.0348 for paired comparison between both groups).
Table 1 Hypertension, n (%) 235 (54.9) Diabetes, n (%) 113 (26.4) Dyslipidaemia, n (%) 171 (40.0) Smocking habit, n (%) 208 (48.5) Time to ROSC mean ± SD, min 26.6±18.6 Mean arterial pressure at HA mean±DS, mmHg 81.3±22.1 pH at HA mean ± SD 7.18±0.16 Lactic at HA mean ± SD 6.37±4.42 ROSC: return of spontaneus circulation; HA: hospital admission.

Conclusion
Our findings reflect the impact of inflammation in neurological outcomes after OHCA treated with TTM. Major increases of PLR constitute a novel marker of poor prognosis during early assessment of OHCA patients.
P5356NT-proBNP is a valuable diagnostic tool of heart failure even during post partum period
Authors: Squillace M , Gherbesi E , Schiavone M , Gobbi C , Malanchini G , Denora M , Mallia V , Schillaci M , Ossola M W , Bonanomi C , Lombardi F 
Published: October 2019

Abstract

Background
Post-partum period is characterized by complex haemodynamic changes that may lead to heart failure (HF) in a minority of patients. B-type natriuretic peptides inactive amino terminal fragment (NT-proBNP) is an established biomarker in the management of HF. Patients presenting with dyspnea are considered at high risk of HF if NT-proBNP is above 125 pg/ml. Higher levels of NT-proBNP in the post natal period were reported to be associated with increased risk of cardiovascular events, but there is no defined cut-off value established for prediction of HF in this setting.

Purpose
We conducted this study to identify an adequate cut-off value which would predict haemodynamic overload among post-partum women.

Methods
All women who gave informed consent during an obstetric clinical evaluation at our tertiary centre between 01/01/2018 and 30/09/2018 were included in the study. NT-proBNP was measured within 24 hours from delivery. The primary endpoint of the study was the development of signs and symptoms of heart failure (with the need of intravenous diuretics or a cardiological evaluation) within 15 days after delivery. We therefore analyzed the ability of different cut-off of NT-proBNP values in predicting the primary outcome. Confidence intervals (CI) for sensitivity and specificity were calculated with the Wilson score method.

Results
252 women were included in the study. Eleven of them developed in the study timeframe signs and symptoms of HF (4.3%); all of them were treated with diuretics. Nine patients were evaluated with echocardiography and 3 of them required cardiological counseling. The cut-off value of 600 pg/mL was found to have the best sensitivity (73%, CI 95% 0.43–0.9), specificity (98%, CI 95% 0.95–0.98), positive likelihood ratio (29, CI 95% 12–69) and negative likelihood ratio (0.28, IC 95% 0.10–0.70). The diagnostic odds ratio was 104 (CI 95% 22–494, p<0.001). Mean NT-proBNP was 169±121 pg/mL (cutoff <600 pg/mL) versus 852±245 pg/mL.
Different cut-off evaluated NT-proBNP value (pg/mL) Specificity Sensibility Diagnostic Odds ratio 125 42 81 3.4 (95% CI 0.7–16, p=0.1) 300 85 72 14 (95% CI 4–62, p<0.01) 600 98 73 104 (95% CI 22–494, p<0.01) 700 98 66 65 (95% CI 12–341, p<0.01)

Conclusion
Our study suggests that NT-proBNP higher than 600 pg/mL is a high risk marker for developing HF in the post partum period. This value is slightly higher compared to the one adopted among the general population for diagnosis of HF and may reflect the peculiar haemodynamic changes of this setting.
P5386Transplantation of endothelial progenitor cells in the treatment of coronary artery microembolism in rats
Authors: Xue Y , Zhang P , Miao G , Zhou B 
Published: October 2019

Abstract

Objective
As the impairment of myocardial micro-environments due to coronary micro-embolization (CME) compromises the treatment effect of percutaneous coronary intervention and leads to adverse prognosis, we hypothesized that endothelial progenitor cells (EPCs) transplantation could improve cardiac function in the condition of CME.

Materials and methods
Low- (2×105) and high- (2×106) dose rat bone marrow-derived EPCs were transplanted in a model of CME. To develop a CME model, rats were injected with autologous micro-blood clots into the left ventricle. Echocardiography was examined before and 1, 7, and 28 days after EPC transplantation; serum cTNI, vWF,and cardiac microRNA expression were examined one day after EPCs transplantation. Heart morphology and VEGF, vWF, and bFGF expression were examined one day after EPC transplantation.
Figure 1. Results

Results
After 10 days of culture inductions, BM-EPCs have high purity as confirmed by flow cytometry. Cardiac function reflected by LVEF significantly decreased after CME treatment and rescued by low-dose EPC. Compared to the sham group, cTNI, and vWF serum levels increased significantly after CME treatment and rescued by low-dose EPC and high-dose EPC. Low-dose EPC treatment decreased myocardial necrosis and fibrosis and elevated cardiac expression of VEGF and vWF, while decreasing the cardiac expression of bFGF. Low-dose EPC treatment significantly suppressed cardiac expression of microRNA-19a but significantly enhanced microRNA-21, microRNA-214, and microRNA-486-3p expression. In conclusion, our results indicate that low-dose EPC transplantation may play a pro-angiogenic, anti-fibroblast, anti-fibrosis, and anti-necrosis role and enhance cardiac function in a rat model of CME through a microRNA-related pathway.

Acknowledgement/Funding
Supported by the State Key Laboratory of Low-Dimensional Quantum Physics Open Project Fund (No. KF201608)
P5392Epicardium derived cells promote sympathetic ganglionic outgrowth towards myocardium in vitro
Authors: Ge Y , Smits A M , Van Munsteren J C , Van Herwaarden T , Vegh A M D , Goumans M J T H , Schalij M J , De Ruiter M C , Jongbloed M R M 
Published: October 2019

Abstract

Background
The autonomic nerve system is essential to maintain homeostasis in the body. In the heart, autonomic innervation is important for adjusting the physiology to the continuously changing demands such as stress responses. After cardiac damage, excessive neurite outgrowth, referred to as autonomic hyperinnervation, can occur which is related to ventricular arrhythmias and sudden cardiac death. The cellular basis for this hyperinnervation is as yet unresolved. Here we hypothesize a role for epicardium derived cells (EPDCs) in stimulating sympathetic neurite outgrowth.

Purpose
To investigate the potential role of adult EPDCs in promoting sympathetic ganglionic outgrowth towards adult myocardium.

Method
Fetal murine superior cervical ganglia were dissected and co-cultured with activated adult mesenchymal epicardium-derived cells (EPDCs) or/and adult myocardium in a 3D collagen gel culture system. Four experiment groups were included: Group 1: Vehicle cultures (ganglia cultured without EPDC/myocardium) (n=48); Group 2: ganglia co-cultured with EPDCs (n=38); Group 3: ganglia co-cultured with myocardium (n=95); and group 4: ganglia co-cultured with both EPDCs and myocardium (n=96). The occurrence of neurite outgrowth was assessed in each group. The density of neurites that showed directional sprouting (i.e. sprouting towards myocardium) was assessed as well with a semi-automatic quantification method. Finally, sub-analyses were made by taking gender into account.

Results
Cervical ganglia cultured with EPDCs alone (group 2) showed increased neurite outgrowth compared to vehicle cultures (group 1), however the neurites did not show directional sprouting towards EPDCs. When co-cultured with myocardium (group 3), directional neurite outgrowth towards myocardium was observed. Compared to the ganglia-myocardium co-cultures, directional outgrowth was significantly increased in co-cultures combining myocardium and EPDCs (group 4), and the neurite density was also significantly augmented. Comparison between males and female ganglia demonstrated that more neurite outgrowth occurred in female-derived ganglia than in male-derived ganglia under the same co-culture conditions.

Conclusion
Activated adult EPDCs promote sympathetic ganglionic outgrowth in vitro. Sex differences exist in the response of ganglia to EPDCs, and female-derived ganglia appear more sensitive to EPDC-signalling. Results support a role of EPDCs in cardiac autonomic innervation and open avenues for exploring of their role in ventricular hyperinnervation after cardiac damage.
P5397Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210
Authors: Cheng H , Song X Y , Chen L , Xu R D , Qin Q , Fu M Q , Qian J Y , Zou Y Z , Ma J Y , Ge J B 
Published: October 2019

Abstract

Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210

Background
A paracrine effect was regarded as the key mechanism involved in the MSC (mesenchymal stem cell)-based treatment for myocardial infarction. In our pilot experiments, hypoxia remarkably promotes MSC to paracrine exosomal miR-210, which could significantly enhance the cardiomyocytes survival in hypoxic incubation, suggesting that exosomal miR-210 played critical roles in the favorable paracrine effect of MSC on cardiomyocytes.

Purpose
The aim of this study was to investigate the important mechanism by which MSCs promote the tolerance of cardiomyocytes to hypoxia by secreting exosomal miR-210.

Methods and results
The exosomes were isolated from MSCs conditioned medium through ultracentrifugation, and we detected that miR-210 was the most abundant in MSC-exosome and increased most prominently in the hypoxia. The extracted exosomes were prepared for conditioned medium and the effect on myocardial protection was examined. The viability of control group was much better than the cardiomyocytes treated with hypoxia, but it was further increased in the presence of MSC-exosome, however, measurement was significantly lower in cardiomyocytes in hypoxia with exosomes derived from MSCs treated with GW4869. Subsequently, the co-localization of miR-210 with exosome-specific surface markers CD81 and CD63 were observed by immunofluorescence technique. Continuous magnetic live cell imaging was used to observe the uptake of exosome by cardiomyocytes, and fluorescence localization was used to observe the localization of miR-210 with Cy3 fluorescence in cardiomyocytes. Then, we demonstrated that MSCs exosomal miR-210 exerts the cardioprotective effect by regulating the AIFM3 (apoptosis-inducing factor mitochondria-associated protein 3), and we directly overexpressed miRNA-210 in cardiomyocytes and the results showed that the regulatory activity of the intake of exosomal miR-210 was consistent with that of the biological exosomal miR-210. Finally, we verified the protective effect on the ischemic myocardium by constructing rat myocardial infarction models. The level of apoptosis was detected at 1 week after myocardial infarction. The left ventricular ejection fraction and ventricular remodeling were measured at 4 weeks. In vivo, we demonstrated that explanted miR-210 from transplanted MSCs significantly reduced myocardial necrosis and apoptosis induced by ischemia and improved cardiac function and myocardial remodeling.

Conclusion
Here, we show that the exosomal miR-210 secreted by MSCs significantly increase the viability of cardiomyocytes and cardiac function. These findings suggest that exosomal miR-210 is a key effector that mediates the protection against hypoxia.

Acknowledgement/Funding
National Natural Science Foundation of China (Grant Nos. 81470467)
P5402Inhibition of microRNA-210 as a novel therapeutic strategy to protect against atherosclerosis development
Authors: Alexandru N , Safciuc F , Tanko G , Constantin A , Nemecz M , Filippi A , Dragan E , Georgescu A 
Published: October 2019

Abstract

Background
MicroRNAs are involved in many processes such as cell proliferation and differentiation, angiogenesis, apoptosis, mitochondrial metabolism and DNA damage repair. Circulating levels of microRNA-210 (miR-210) are associated with the risk for cardiovascular mortality at patients with coronary artery disease.

Purpose
The aim was to investigate the effects and involved mechanisms of a novel treatment, miR-210 inhibitor (antagomiR-210), on the activation of inflammation and immune system, and overproduction of reactive oxygen species in atherosclerosis.

Methods
Golden Syrian hamsters were divided into: (1) simultaneously hypertensive - hyperlipidemic (HH) by combining two feeding conditions for 4 months, that mimic atherosclerosis; (2) HH with subcutaneous injection at months 1,2,3 containing antagomiR-210, or scramble (Scr)-miR negative control, or vehicle (phosphate-buffered saline, PBS) alone; (3) controls (C), age-matched normal healthy animals.

Results
The results showed that atherosclerosis significantly increased miR-210 levels in circulation, liver and thoracic aorta, which were abolished by antagomiR-210 administration. The preventive treatment of atherosclerosis with antagomiR-210 induced the following effects: (i) reduced the cholesterol, triglyceride and hepatic enzyme levels in plasma; (ii) increased the levels of circulating endothelial progenitor cells and reduced circulating microvesicle concentrations; (iii) improved endothelial cell functions; (iv) lowered inflammation by the reduction of TNF-α levels in plasma and infiltrated macrophage number into liver and thoracic aorta; (v) diminished immune system activation by decreasing the PD-1 levels in circulation, PD-L1/PD-L2 expression in liver/thoracic aorta and T cell number infiltrated into liver/thoracic aorta; (vii) reduced oxidative stress by decreasing O2·− generation into liver/thoracic aorta; (viii) lowered the expression of miR-210 target protein, protein tyrosine phosphatase 1B (PTP1B), in plasma/liver/thoracic aorta, and of its downstream molecules (PI3K, AKT1/2/3, eNOS, ERK1/2) in liver and thoracic aorta.

Conclusion
The results revealed the antagomiR-210 ability to modulate the pro-inflammatory, immune-stimulatory and pro-oxidant microenvironment within the atherosclerotic animal model, via direct targeting to PTP-1B and PI3K/AKT/eNOS and MAPK/ERK/ROS as downstream pathways.
In summary, our data provide new insight in molecular basis of an encouraging therapeutic strategy based on miR-210 inhibition for the treatment of atherosclerosis and cardiovascular disease.

Acknowledgement/Funding
CNCS-UEFISCDI, projects no. PN-III-P1-1.2-PCCDI-2017-0527 and no. PN-III-P1-1.2-PCCDI-2017-0797, and by the Romanian Academy
P5413Effect of empagliflozin as add-on therapy on serum uric acid level in patients with type 2 diabetes hospitalized for acute decompensated heart failure: a prospective randomized controlled study
Authors: Tamaki S , Yamada T , Morita T , Furukawa Y , Iwasaki Y , Kawasaki M , Kikuchi A , Kawai T , Seo M , Abe M , Nakamura J , Yamamoto K , Fukunami M 
Published: October 2019

Abstract

Background
Elevated serum uric acid (UA) level has been shown to be associated with reduced survival among patients (pts) with heart failure. Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower serum uric acid level in pts with type 2 diabetes mellitus (T2D). Empagliflozin, one of the SGLT2 inhibitors, has been shown to reduce the risk of cardiovascular mortality in T2D pts with cardiovascular disease, and involvement of UA lowering effect by empagliflozin in the reduction of cardiovascular mortality has been suggested. However, little is known about the effect of empagliflozin as add-on therapy on serum UA level in T2D pts with acute decompensated heart failure (ADHF).

Purpose
We sought to elucidate the effect of empagliflozin as add-on therapy on serum UA level in T2D pts with ADHF.

Methods
We enrolled 38 consecutive T2D pts admitted for ADHF. On admission, enrolled pts were randomly assigned in a 1:1 ratio to either empagliflozin add-on therapy (EMPA(+)) or conventional glucose-lowering therapy (EMPA(−)). All pts in EMPA(+) group received empagliflozin (10 mg/day) throughout the study period. Left ventricular ejection fraction (LVEF) was measured at baseline using echocardiography. Body weight and vital signs, such as blood pressure and heart rate, were measured, and blood and urine samples were collected at baseline and 1, 2, 3 and 7 days after randomization. Renal handling of UA was evaluated by fractional excretion of UA (FEUA).

Results
Twenty pts were assigned to the EMPA(+) group, and 18 pts were assigned to the EMPA(−) group. There were no significant baseline differences in LVEF, plasma brain natriuretic peptide level, body mass index, or serum creatinine level between the EMPA(+) and EMPA(−) groups. In addition, prevalence rate of hyperuricemia, serum UA level, and FEUA did not significantly differ between the two groups at baseline. However, there was significant difference in the change in serum UA level from baseline at 2, 3 and 7 days after randomization between the two groups (Figure A). As a result, serum UA level was significantly lower in the EMPA(+) group than in the EMPA(−) group at 7 days after randomization (6.2±1.8 mg/dL vs 7.8±1.8 mg/dL, p=0.0127). Moreover, FEUN of the EMPA(+) group was significantly higher at 1, 2 and 7 days after randomization (Figure B), which suggested that serum UA level was lowered in the EMPA(+) group by increased urinary excretion of UA.
Figure 1

Conclusions
This study demonstrated that empagliflozin as add-on therapy can lower serum UA level in T2D pts with ADHF through the effect on the urinary excretion rate of UA.
P5421Prevalence of electromagnetic interference from left ventricular assist devices in patients with implantable cardioverter defibrillator/pacemakers
Authors: Kooij C , Yalcin Y C , Theuns D A M J , Constantinescu A A , Brugts J J , Manintveld O C , Yap S C , Szili-Torok T , Bogers A J J C , Caliskan K 
Published: October 2019

Abstract

Background
Many patients eligible for left ventricular assist device (LVAD) therapy already have an implantable cardioverter defibrillator (ICD) and/or pacemaker (PM). However, electromagnetic interference (EMI) between the LVAD and ICD/PM devices could be cumbersome.

Purpose
The aim of this study was to investigate the prevalence of EMI between different types of ICD/PM in patients implanted with an LVAD.

Methods
Data was obtained through a retrospective electronic patient database analysis of all LVAD patients (including HeartMate II (HMII) and HeartMate 3 (HM3)), from our tertiary referral center, from December 2006 to February 2019. Device switches have also been taken into account due to elective replacement. Electromagnetic interference was defined as ICD/PM telemetry interference (i.e. the inability to interrogate ICD/PM)

Results
In total, 109 patients received an LVAD (mean age 52±12, 83% male), Of these, 86 (79%) patients had an ICD/PM at LVAD implantation. One patient with ICD/PM was excluded from further analysis because of missing follow-up data. Among the 85 patients (45 HM II and 40 HM3), 11 (13%) experienced EMI; 5 (11%) with a HM II and 6 (15%) with a HM3 (p=0.59). The implanted ICD/PM devices were from Medtronic (n=25), Abbott (n=23), Biotronik (n=18), Boston Scientific (n=18), and Microport (n=1). EMI with the HM II was present in St Jude/Abbott devices (type 1 Atlas, 1 Unify, 1 Fortify, and 2 Promote). In HM 3 LVAD patients, EMI was observed in Biotronik devices (1 Lumax, 1 Ilivia, 1 Ilesto, and 2 Iperia) and Medtronic (Claria).

Conclusion
In our cohort of HM II and HM 3 LVAD patients, at least one in seven patients experienced EMI from either the HM II or HM3 LVAD with the ICD/PM. Electromagnetic interference from HM II LVADs was mainly present in patients with St Jude/Abbott ICD/PM devices However, in the HM3 patients, EMI was mainly present in patients with Biotronik devices, which is not yet widely known!