bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 12555: The Dual PPAR-α/γ Agonist Aleglitazar Enhances Arteriogenesis, Angiogenesis and Endothelial Function
Authors: Werner Christian , Schirmer Stephan H , Pavlickova Valerie , Böhm Michael , Laufs Ulrich 
Published: July 2021

Objective:
Peroxisome proliferator-activated receptor (PPAR)-α and -γ agonists modify lipid and glucose metabolism. The aim of the study was to characterize the effects of the dual PPAR-α/γ agonist aleglitazar on endothelial function, neoangiogenesis and arteriogenesis in mice and on human endothelial progenitor cells (EPC).

Methods and Results:
Male C57Bl/6 wild-type (WT, normal chow) and apolipoprotein E-deficient (apoE-/-) mice on Western-type diet (WTD) were treated with aleglitazar (10 mg/kg i.p.) or vehicle by daily injection.

Hindlimb ischemia was induced by right femoral artery ligation (FAL). ApoE-/- mice on WTD treated with aleglitazar before FAL were characterized by an improvement of endothelial-dependent laser Doppler perfusion (right/left foot ratio 0.40±0.03) 1 week after FAL compared to controls (R/L foot ratio 0.24±0.01; p<0.001). Collateral-dependent perfusion measured under conditions of maximal vasodilatation 1 week after FAL using fluorescent microspheres was impaired in apoE-/- on WTD compared to WT mice (R/L leg ratio in WT 78±13 vs. apoE-/- 56±6; p<0.001) and was normalized by aleglitazar treatment.
Neoangiogenesis was measured in-vivo by subcutaneously implanting discs covered with cell-impermeable filters. The vascularized area of the discs was quantified after 14 days by perfusion of the animals with space-filling fluorescent microspheres. Aleglitazar increased neoangiogenesis in WT mice by 178±18% compared to vehicle (p<0.05).
Endothelium-dependent relaxation of aortic rings was impaired in apoE-/- mice on WTD for 6 weeks (relaxation to 52±5% of max. contraction) compared to WT animals (relaxation to 18±5% of max. contraction) (p<0.001). Aleglitazar treatment improved endothelial function (relaxation to 39±5% of max. contraction; p<0.05).
In parallel, number and function of EPC were improved in mice. Studies in human EPC showed that 1) aleglitazar’s effects were mediated by both PPAR-α and -γ signalling and Akt and 2) migration and colony forming units were up-regulated by aleglitazar in cultivated EPC from CAD patients.

Conclusion:
The study provides evidence for beneficial effects of the dual PPAR-α/γ agonist aleglitazar on vascular function in addition to or mediated by its metabolic actions.
Abstract 13152: A Novel Link between Energy Expenditure, Plasma Lipid Turnover, and Cardiovascular Health
Authors: Laurila Pirkka-Pekka , Soronen Jarkko , Boon Mariëtte , Taskinen Marja-Riitta , Ripatti Samuli , Rensen Patrick , Kovanen Petri , Jauhiainen Matti 
Published: July 2021

We previously showed that USF1 transcription factor was associated with familial combined hyperlipidemia in Finns. In the current study, we have conducted a detailed metabolic characterization of Usf1 in mice.
We generated a congenic strain of Usf1 knockout mice, fed with high-fat diet for 5 months. The knockouts displayed both elevated cholesterol and phospholipids in their plasma HDL-fractions and lower total and VLDL-triglycerides. This was due to both enhanced TRL clearance linked to elevated LPL activity of the knockouts, and reduced hepatic VLDL secretion. The elevated HDL-C levels were associated with increased efflux capacity of HDL particles derived from Usf1-/- mice. The detailed analysis of Usf1-/- HDL composition revealed an enrichment of phospholipids, known to enhance the efflux capacity of HDL particles.
The Usf1-/- mice were protected against HFD induced obesity despite being physically less active and eating more than Usf1+/+ mice. Furthermore, they were protected against insulin resistance, atherosclerosis, and fatty liver. Multiplex measurements revealed a reduction in the cytokines representing vascular inflammation. While absorption of lipids was similar between Usf1-/- and Usf1+/+ mice, the Usf1-/- mice displayed elevated VO2 and VCO2, even in thermoneutral conditions, suggesting an increased metabolic rate. Analysis of post-injection organ distribution of [3H]triolein and [14C] cholesteryl oleate revealed a selective uptake of TRLs to brown adipose tissue in Usf1-/- mice, mediated by an LPL-dependent mechanism, as inhibiting LPL by tetrahydrolipstatin completely eliminated lipoprotein uptake to BAT. There was a dramatic 8-fold reduction in lipid droplet size as well as lipid content of BAT. The protein levels of mitochondrial complex II were elevated in the BAT of Usf1-/- mice. Furthermore, PET/CT measurements demonstrated an increased glucose uptake to BAT of Usf1-/- mice. Together, these findings demonstrate overall avidity of BAT to process energy substrates.
Our data establish the critical role of Usf1 as a metabolic master-regulator, and demonstrate that Usf1 deficiency leads to a remarkably beneficial metabolic profile in mice. Our discoveries make USF1 appear a particularly attractive therapeutic target.
Abstract 13818: Effect of Gender on Hospital Discharge Survival After an Out-of-hospital Cardiac Arrest - a Systematic Review and Meta-analysis
Authors: Bougouin Wulfran , Mustafic Hazrije , Marijon Eloi , Murad Hassan , Dumas Florence , Barbouttis Anna , Jabre Patricia , Beganton Frankie , Empana Jean-Philippe , Cariou Alain , Jouven Xavier 
Published: July 2021

Introduction:
Conflicting results exist regarding the impact of gender on survival after Sudden Cardiac Arrest (SCA).

Hypothesis:
Assess association between female gender and survival after SCA

Methods:
An electronic search of Embase, Ovid MEDLINE In-Process & Non-Indexed Citations and EBM Reviews - Cochrane Register of Controlled Trials, EBM Reviews - Cochrane Database of Systematic Reviews and Google was conducted (January 1948 to January 2014) for studies of any study design and language, examining the gender effect on survival at hospital discharge after a SCA.

Two independent reviewers selected studies and extracted data.
The inter-rater agreements kappa were measured at the first and second selection steps.
Moreover, the pooled OR and 95% CI, concerning women vs. men survival at hospital discharge after an OHCA were calculated with a random effect model.
Subgroups analyses were performed, according to the cardiac origin of OHCAs and according to the study quality. Study quality criteria were based on the New Castle Ottawa Scale.

Results:
After a detailed screening of 556 citations, 12 studies were identified involving 404 621 patients.

The inter-rater agreements kappa was high for the 2 study selection steps (0.91 and 1).
In most studies, women were older and had less favorable baseline characteristics including a lower prevalence of witnessed-OHCA, OHCA in a public location, bystander cardio-pulmonary resuscitation and shockable rhythms compared to men. However and after adjustment for these differences, women were more likely to survive at hospital discharge (N=12; OR: 1.11 [1.02-1.21]; p=0.013). This result remains in studies analyzing OHCA of presumed cardiac origin (N=7; OR: 1.17 [1.03-1.34]; p=0.017) and in studies of high quality (N=7; OR: 1.11 [1.02-1.21]; p=0.017).

Conclusion:
Despite less favorable baseline characteristics, women are more likely to survive at hospital discharge after an OHCA. Further studies are needed to explain this paradox.
Abstract 14789: A Rare Case of Primary Cardiac Leiomyosarcoma Involving the Left Ventricle
Authors: Khalid Hafiz D , Grunloh Danielle S , Bhatti Ahsan M , Rhee Benjamin J , Orakzai Sarwar 
Published: July 2021

Case Report:
A 73 year old female was admitted to our hospital with complaints of acute shortness of breath on exertion and chest tightness accompanied with non-exertional left arm pain. Her prior history was significant for hypertension. Vital signs were significant for tachycardia. EKG revealed sinus tachycardia and low voltage QRS complexes. Cardiac Biomarkers were negative. CXR on admission showed massive cardiomegaly.

(A) Echocardiography, Off Axis, Apical long axis view showing a large mass attached to the LV apex surrounded by large pericardial effusion. Pericardiocentesis was performed and 1200ml of bloody fluid was removed.
(B) Cardiac MRI was performed which revealed a mass arising from the inferolateral wall of Left Ventricle measuring 6.5x4.9x6.2 cm
Left thoracotomy, wedge biopsy of left ventricular mass was performed. (C, D)Pathological analysis confirmed well differentiated Leiomyosarcoma (grade 1 of 3) FNCLCC grading system. Tumor was strongly positive for vimentin, smooth muscle myosin and desmin.
Abstract 15378: Mitochondrial Fission Plays a Crucial Role in Cardiomyocyte Adaptation to Energy Stress via Mitophagy
Authors: Ikeda Yoshiyuki , Maejima Yasuhiro , Ohishi Mitsuru , Sadoshima Junichi 
Published: July 2021

Mitochondria are dynamic organelles that undergo fusion and fission. This study aims to clarify the role of mitochondrial dynamics on energetic stress resistance in cardiomyocytes (CMs).
Dynamin-related protein 1 (Drp-1) which mediates mitochondrial fission was localized primarily in the cytosol in CMs. Glucose deprivation (GD) induced modest mitochondrial accumulation of Drp1 in CMs within 4 hours. Four-hour GD increased the proportion of CMs with fused mitochondria (23.5±6.9 to 35.0±10.8%, p<0.05), but also increased that of CMs with fission (2.1±0.3 to 15.5±4.8%, p<0.05) in Ad-shScr-transduced CMs, whereas mitochondria with fission did not increase after GD in Ad-shDrp1-transduced CMs (0.3±0.6 to 0.8±0.5%). These results suggest that GD induces both mitochondrial fusion and fission, and Drp1 plays an essential role in mitochondrial fission in response to GD. Transduction with Ad-shDrp1 significantly increased TUNEL-positive CMs and reduced cell viability after 4 hours of GD compared to transduction with Ad-shScr, suggesting that endogenous Drp1 protects CMs against cell death during GD. We evaluated the role of Drp1 in mediating mitophagy using mitochondria-targeted Keima fluorescence. Keima has a bimodal excitation spectrum peaking at 440 and 560 nm, corresponding to the neutral and acidic pH states, respectively. Puncta with high 560/440, indicating the presence of mitochondria in lysosomes, were significantly increased after 4 hours of GD in CMs transduced with Ad-shScr, but not in CMs transduced with Ad-shDrp, suggesting that Drp1 is necessary for stimulating autophagic mitochondrial degradation. Next, we examined the role of fission on energy stress in vivo using cardiac specific Drp1 hetero knockout (Drp1-hetCKO) mouse. Translocation of Drp1 from cytosol to mitochondria significantly increased in response to 48-hour fasting in control mice but not in Drp1-hetCKO mice. Left ventricular ejection fraction did not change after fasting in control mice (79.8±6.4 to 78.6±8.3%). However that in Drp1-hetCKO mice decreased after GD (79.4±9.7 to 48.3±11.6%, p<0.05), suggesting that Drp1 acts to preserve cardiac function during fasting.
In conclusion, mitochondrial fission is crucial to adapt CMs to energy stress through mitophagy.
Abstract 15689: Activation of PKR-Like Endoplasmic Reticulum Kinase is Required for Autophagy Stimulation and Cardiomyocyte Survival During Acute Myocardial Ischemia
Authors: Sciarretta Sebastiano , Nagarajan Narayani , Yee Derek , Zhai Peiyong , Umapathi Priya , Brady Christopher D , Volpe Massimo , Frati Giacomo , Sadoshima Junichi 
Published: July 2021

PKR-like endoplasmic reticulum (ER) kinase (PERK) is an ER-resident serine/threonine kinase that regulates the cellular response to ER stress and energy deprivation. Under stress, PERK activation can be either protective or detrimental. We studied for the first time whether PERK regulates cardiomyocyte (CM) survival and death during myocardial ischemia, which is characterized by both ER and energy stress.
We found that PERK is significantly activated after 30 minutes of myocardial ischemia (2.4 ± 0.04-fold, p<0.001), as shown by its increased phosphorylation status. After 3 hours of ischemia, mice with cardiac-specific overexpression of dominant-negative PERK (Tg-DN-PERK) displayed a significant increase in infarct size/area at risk with respect to non-transgenic (NTg) mice (66.4 ± 4.1% vs. 38.5 ± 6.8%, p<0.05), indicating that ischemia-induced PERK activation is cardioprotective.
PERK signaling regulates autophagy in cancer cells. Autophagy is an intracellular degradation mechanism that promotes CM survival during ischemia by relieving both energy and ER stress. We found that autophagy activation during ischemia is abrogated in the hearts of Tg-DN-PERK with respect to NTg, as indicated by reduced LC3-II accumulation (0.71 ± 0.05-fold, p<0.01). Consistently, CMs with adenovirus-mediated overexpression of DN-PERK displayed reduced LC3-II accumulation (0.69 ± 0.1-fold vs. control CMs, p<0.05) after 4 hours of glucose deprivation (GD) in vitro, a condition that mimics ischemia-induced energy stress. A similar result was also observed after bafilomycin A1 treatment to test autophagic flux. These data indicate that PERK is required for autophagy activation and flux during CM ischemia and GD.
Finally, we saw that DN-PERK overexpression significantly promotes CM death after GD, as shown by propidium iodide assay (2.01 ± 0.25-fold vs. control CMs, p<0.05). However, co-overexpression of Atg7, which activates autophagy, significantly reduced cell death induced by DN-PERK (-61%, p<0.05). These data suggest that autophagy inhibition partly mediates the detrimental effects of PERK inhibition during energy stress.
In conclusion, our study demonstrates that PERK activation is required for autophagy activation and CM survival during ischemia.
Abstract 17420: First Clinical Experience of Novel MRI Artifact Suppression Sequence in ICD Patients Undergoing Scar Delineation for Ventricular Tachycardia (VT) Ablation
Authors: Abdulghani Mohammed S , Asoglu Ramazan , Shin T. , Gullpalli R. , Huang Rui , Remo Benjamin , Klein Tommas , Hussien Ayman , Saliaris Anastasios , See Vincent , Synowski Stephen , Shorofsky Stephen , Jeudy Jean , Dickfeld Timm 
Published: July 2021

Background:
Recent studies have suggested that CMR imaging can be safely performed in selected patients with implanted ICDs. However, metal artifacts significantly impact the evaluation of myocardial fibrosis when using standard late gadolinium enhanced (LGE) protocols.

Methods:
10 continuous patients scheduled for VT ablation underwent LGE CMR imaging (1.5T Siemens Avanto) for scar delineation using either the standard clinical late gadolinium enhancement (LGE) sequences (n=5) or a novel MR pulse sequence that used an inversion preparation pulse with a wide inversion bandwidth of 2.4kHz (n=5).

Results:
Standard LGE MR sequences produced a large central signal void with surrounding hyperintensity due to voxel dephasing. The new wide inversion bandwidth sequence reduced the artifact in the right ventricle from 21±7% to 1.2±1.3% (p<.001). Similarly, the new MRI sequence reduced the artifact in the LV from 44±9% to 4.5±5.7% (p<.001).

LV artifact location changed from 100% (inferior), 100% (septal), 100% (lateral) and 100% (anterior) to 0%, 0%, 0% and 60%, respectively. Similarly, the LV artifact present was present in the basal, mid and apical segment in 100%, 100%, and 100% in the old sequence but was reduced to 0%, 60%, and 20% in the new sequence (Fig.1).
While the artifact of the standard sequence prevented the reliable predictions of the voltage-defined scar during VT ablation, no significant low voltage area outside the imaged LGE areas were found in the patients imaged with the new MRI sequence.

Conclusions:
Widening the inversion bandwidth achieves a dramatic reduction in ICD metal artifact during LGE CMR imaging and allows a near completely evaluation of the whole myocardium. This allowed the reliable prediction of low voltage areas during VT ablation despite presence of ICD.
Abstract 18989: Periprocedural Heparin Requirement in Patients Undergoing Atrial Fibrillation Ablation Stratified by Different Baseline Anticoagulation Regimens: Evidence for a Prothrombotic State With Interrupted Dabigatran
Authors: Benhayon Daniel , Santangeli Pasquale , Zado Erica , Ryan John , Callans David , Marchlinski Francis 
Published: July 2021

Introduction:
Thromboembolic (TE) and bleeding complications represent the most common adverse events during atrial fibrillation (AF) ablation. In order to prevent TE, unfractionated heparin (UFH) is recommended throughout the procedure, with a target ACT of 350-400 sec.

In this study we compared periprocedural heparin requirements during different pre-procedure anticoagulation regimens and the potential clinical implications.

Methods:
We retrospectively analyzed every case of AF ablation performed at our institution over the last 2 years, including only first time ablations, and collected the amount of UFH per kilogram needed to achieve the target ACT.

The groups were compared based on the periprocedural anticoagulation strategy (warfarin vs. dabigatran vs. rivaroxaban), and the number of doses held before the procedure.
Patients on warfarin were all on uninterrupted warfarin, but for comparison we further subdivided this group into INR tertiles, based on INR at time of procedure.

Results:
We included 584 patients. Of those 391 (67%) were on warfarin, 162 (28%) were receiving dabigatran and 31 (5%) rivaroxaban. Baseline characteristics were not significantly different

between the groups, including procedural duration and baseline creatinine. 54.1% had paroxysmal AF and 5.3% had a prior TIA/stroke.
Patients that held ≥2 doses of dabigatran needed significantly more UFH-per-kilogram-per-procedure, as compared to patients on warfarin with INR <1.5. (15% more; p=0.029). See figure.
No differences were observed between those on warfarin with INR ≤1.5 and those holding ≥2 doses rivaroxaban (p=0.56).
No significant differences were observed in the rate of bleeding or TE complications between groups (P=0.18).

Conclusions:
Interrupted dabigatran is associated with significantly increased need for UFH compared to those functionally off warfarin, which may suggest a slight rebound procoagulant effect due to dabigatran interruption.
Abstract 19514: Race and Willingness to Participate in Cardiovascular Clinical Research
Authors: Zhang Xiaotao , Bazzano Lydia A , Gavin Stephen G , Gaudreau Stephanie , Breault Joseph 
Published: July 2021

African Americans (AA) are underrepresented in clinical trials in the United States for a variety of reasons. The majority of studies examining this issue were conducted >10 years ago and since then, efforts have been implemented to improve AA enrollment in research. We took advantage of the cardiovascular research data of a large community academic center in New Orleans, Louisiana to examine whether race was associated with participation in cardiovascular research. We used a nested case control design with 80% power to detect a doubling in odds of non-participation. Individuals could be included if they were offered participation in any of the 4 largest studies conducted in 2012, were White or AA and were American citizens (n=974). Median income household income was inferred using postal codes. Cases were defined as individuals who declined to participate and did not sign a consent form. Controls were defined as individuals who agreed to participate and signed a consent form. We identified 100 cases and selected 200 controls matched on age (within 1 year) and sex using a random selection algorithm. Of the 974 eligible for analysis, mean (SD) age was 65 (14)
years, median household income in thousands was 51.92 (19.9), and 65.3% were men. Of those who agreed to participate, 32.2% were AA while of those who refused, 31.0% were AA. The unadjusted Mantel-Haenszel odds ratio for non-participation by race was 1.06 (95% CI: 0.60 to 1.94) for AA individuals compared to their White age and sex matched counterparts. Using multivariable conditional logistic regression, the odds ratio for participation in a study was 1.04 (95% CI: 0.56 to 1.92) for AA as compared to their White age and sex matched counterparts, after adjustment for median household income, employment, and marital status. Our findings suggest that, at a large community academic center, race does not significantly affect willingness to participate in cardiovascular research independent of age, gender, socioeconomic and marital status.
Abstract 40: Should Bilateral Internal Thoracic Artery Grafting Be Used in Emergency Patients?
Authors: Ben-Gal Yanai , Mohr Rephael , Pevni Dimitri , Ganiel Amir , Kramer Amir , Nesher Nahum , Nevo Avner , Paz Yossi , Medalion Benjamin 
Published: July 2021

HYPOTHESIS:
Bilateral Internal Thoracic Artery (BITA) grafting is not often used in emergency coronary artery bypass grafting (CABG) due to questionable survival benefit ,relative complexity and increased risk of sternal infection compared to operations incorporating Single Internal Thoracic Artery (SITA).

The purpose of this study is to compare early and long term outcome of emergent patients undergoing BITA grafting, to that of emergent patients undergoing CABG with SITA

METHODS:
Four hundred thirty eight emergency patients underwent BITA grafting between 1996 and 2008. They were compared with 339 emergency patients who underwent CABG with SITA

RESULTS:
Occurrence of female gender (18.5% vs. 29.5%, P< 0.001, in the BITA and SITA groups, respectively), diabetes (25.3% vs. 38.6%, P< 0.001), age 70+ (61.0% vs.39.7%, P< 0.001), chronic obstructive pulmonary disease (5.7% vs.13.9%, P< 0.001) EF <30% (12.1% vs. 17.1%, P< 0.001), and chronic renal failure (7.1% vs. 17.1%, p< 0.001) was lower in the BITA group. On the other hand critical preoperative state (35.4% vs. 26.0%, P= 0.003), and recent myocardial infarction (39.5% vs. 32.7%, P= 0.031) were more prevalent among BITA patients. Euro score I of SITA patients was significantly higher (10.58 ± 4.1 vs.8.65 ± 3.5, P= 0.016).

Operative mortality (5.3% vs 7.4%, BITA vs. SITA), and sternal wound infections (2.7% vs. 2.1%) were not significantly different between groups.
Mean follow-up was 8.75 ± 4.75 years. Ten year survival (Kaplan-Meier) of SITA patients with euro score 11+ was similar to that of BITA patients with euro score 11+. (34% vs. 37%, log rank test) .However, Kaplan-Meier 10 year survival of BITA patients with euro score I of 10 or lower was significantly better(80% vs. 68%, , BITA and SITA groups, respectively , P= 0.012 ).Assignment to the BITA group in the subset with lower euro score was also associated with better propensity adjusted survival ( HR 4.8 p < 0.001, compared to the SITA group, COX model)

CONCLUSIONS:
This large cohort study shows that,BITA grafting may be used in emergency patients., In medium and low risk emergency patients long term outcome is better than that of patients treated with SITA