bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 10369: Safety of Anatomic versus Functional Diagnostic Testing: Insights From the PROMISE Trial (PROspective Multicenter Imaging Study for Evaluation of Chest Pain)
Authors: Lu Michael T , Douglas Pamela S , Udelson James E , Adami Elizabeth C , Ghoshhajra Brian B , Picard Michael H , Roberts Rhonda , Lee Kerry L , Einstein Andrew J , Mark Daniel B , Velazquez Eric J , Carter William , Ridner Michael , Al-Khalidi Hussein R , Hoffmann Udo 
Published: April 2024

Introduction:
Suspected coronary artery disease (CAD) is a common indication for diagnostic testing. However, a comprehensive, randomized comparison of test safety, including radiation dose, incidental findings, and test complications, of coronary computed tomography angiography (CTA) and functional tests has not been performed.

Methods:
All PROMISE patients completing a diagnostic test were analyzed as tested for differences between CTA vs functional tests in A) 90 day cumulative radiation dose in milliSieverts (mSv), B) index test and cumulative dose for those whose physicians intended referral for nuclear stress before randomization, C) incidental findings (all and prespecified as potentially clinically significant) and D) index test complications.

Results:
Of 9470 eligible patients (mean age 61, 53% women), 4633 had CTA and 4837 had functional testing (3263 nuclear stress, 1083 stress echo and 491 exercise ECG).

As a strategy comparison, CTA had lower median but higher mean cumulative radiation dose than functional testing (median: 10.3 vs 11.5 mSv, p<0.001, mean: 12.5 vs 10.6, p<0.001). In a test to test comparison in 6349 intended for nuclear stress before randomization, CTA had lower index test (mean: 10.5 vs 14.1, p<0.001) and cumulative (mean: 12.4 vs 15.2, p<0.001) dose than nuclear stress.
Incidental findings were more common on CTA than functional tests (43% vs 2%, p<0.001). CTA found more potentially clinically significant incidentals (19% vs 0.7%, p<0.001), including valvular disease (echo), breast uptake (nuclear), and lung nodules, pneumonia or pulmonary embolism (CT).
There were no major index test complications. Minor complications occurred in 0.8% of CTAs and 0.4% of functional tests (p<0.01). In those intended for nuclear stress, complications occurred in 0.8% of CTAs and 0.5% of nuclear stress tests (p=0.17), including hypotension (nuclear) and mild contrast reaction or extravasation (CT). No CTA and 5 functional test complications led to hospitalization.

Conclusions:
CTA had lower median but higher mean radiation dose compared to all functional testing, but lower dose than nuclear stress. CTA had more potentially clinically meaningful incidental findings, and despite very low overall rates, more minor complications.
Abstract 11703: Adipose Angiotensinogen Inactivation Reduces Adipose Tissue Inflammation and Increases Metabolic Activity in Adipose Stroma Vascular cells
Authors: LeMieux Monique J , Ramalingam Latha , Mynatt Randall , Kalupahana Nishan S , Kim Jung Han , Moustaid-Moussa Naima 
Published: April 2024

The adipose renin-angiotensin system (RAS) is an important regulator of blood pressure and fluid balance and has been linked to obesity-induced inflammation, though mechanisms are not completely understood. Previously, we showed that overexpression of the RAS protein precursor, angiotensinogen (Agt) in adipose tissue increases adiposity, insulin resistance, adipose and systemic inflammation in mice fed a low-fat diet (LFD). Accordingly, we hypothesized that Agt inactivation in adipose tissue will protect against obesity-associated inflammation. To test this hypothesis, we generated adipose tissue Agt knockout (Agt-KO) mice using the aP2-Cre-LoxP system. Agt-KO and wild-type (WT) littermates were each fed a LFD or high-fat diet (HFD) to assess metabolic changes. Our results demonstrate that while no significant differences were observed in body weight or fat mass between the two genotypes on either diet, glucose tolerance was improved in the Agt-KO compared to the WT littermates. This was consistent with higher expression of genes involved in insulin signaling, glucose transport and fatty acid metabolism in white adipose tissue from Agt-KO mice. Moreover, Agt inactivation reduced total adipose macrophage infiltration,and gene/protein expression of MCP-1 and other proinflammatory adipokines in Agt-KO mice compared to WT. Lastly, extracellular flux analyses (using Seahorse Xfe) in both differentiated and non-differentiated stromal vascular cells revealed higher glycolytic activity and mitochondrial respiration in Agt-KO compared to WT mice. Overall, our findings indicate that adipose Agt inactivation reduced adipose inflammation and improved glucose tolerance in part via increased metabolic activity of adipose cells. The cellular and molecular changes observed are consistent with previously reported functions of RAS in insulin resistance, and inflammation.
Funded by a GIA from the American Heart Association Southwest Affiliate (NMM)
Abstract 14173: Pharmacologic and Activated Fibroblast-Specific Gβγ-GRK2 Inhibition is Protective Following Ischemia Reperfusion Injury
Authors: Travers Joshua G , Kamal Fadia A , Nieman Michelle L , Blaxall Burns C 
Published: April 2024

Heart failure is a devastating disease characterized by chamber remodeling, interstitial fibrosis and reduced ventricular compliance. Cardiac fibroblasts are largely responsible for extracellular matrix homeostasis, however upon injury or pathologic stimulation, these cells transition to a myofibroblast phenotype and play a fundamental role in myocardial fibrosis and remodeling. Chronic sympathetic overstimulation induces excess signaling through G protein βγ subunits and ultimately results in pathologic G protein-coupled receptor kinase 2 (GRK2)-mediated β-adrenergic receptor downregulation. We hypothesized that Gβγ-GRK2 inhibition plays an important role in the cardiac fibroblast to attenuate pathologic myofibroblast differentiation, interstitial fibrosis and the overall progression of heart failure.
To investigate this hypothesis, mice were subjected to ischemia/reperfusion injury and treated with the small molecule Gβγ-GRK2 inhibitor gallein for 4 weeks. Animals receiving vehicle demonstrated severe cardiac dilatation and deterioration in overall cardiac function as measured by percent fractional shortening and ejection fraction. Remarkably, mice treated with gallein exhibited nearly complete preservation of cardiac function, along with reduced scar formation and fibrotic marker expression, suggesting a direct effect within the cardiac fibroblasts. To further explore possible mechanisms, activated fibroblast-restricted GRK2 knockout mice (GRK2fl x PeriostinMCM) were subjected to 4 weeks of ischemia/reperfusion injury. These animals displayed preserved myocardial function and reduced eccentric hypertrophy and collagen deposition compared to GRK2fl littermate controls. Finally, systemic Gβγ-GRK2 inhibition by gallein may not confer further protection over activated fibroblast-specific GRK2 ablation alone.
In summary, these findings suggest a potential therapeutic role for Gβγ-GRK2 inhibition in limiting pathologic myofibroblast activation, interstitial fibrosis and heart failure progression. We believe this fibroblast-targeted approach will lead to the refinement of existing targets and compounds, and possibly the generation of novel therapeutics for the treatment of heart failure.
Abstract 15209: Endotoxemia as Mechanism for Platelet Aggregation in Patients With Pneumonia
Authors: Nocella Cristina , Carnevale Roberto , Bartimoccia Simona , Pastori Daniele , Pignatelli Pasquale , Violi Franecesco 
Published: April 2024

Introduction:
Patients with community-acquired pneumonia (CAP) are at increased risk of cardiovascular events; platelet activation has been suggested to play a role but the underlying mechanism is still unclear.

Hypothesis:
Our study hypothesis was that endotoxins (bacterial lipopolysaccharide, LPS) might play a role.

Methods:
Patients (n=100) with diagnosis of community-acquired pneumonia (CAP) through the emergency department (ED) and healty subjects (n=50) were consecutively recruited.

Categorical variables were reported as counts (percentage) and continuous variables as means ± standard deviation (SD).
The study was comprised 3 parts: 1) analysis of serum endotoxins in CAP patients versus controls; 2) ex vivo platelets aggregation in CAP patients and controls; 3) in vitro experiments to assess if LPS, in a range of concentrations detected in the blood of CAP patients, was capable of activating platelets.

Results:
CAP patients showed higher serum LPS and ex vivo platelet aggregation (PA) compared to controls. In in vitro study LPS, in a concentration (15-100 pg/ml) similar to that detected in human circulation of CAP patients, no changes of PA were detected. Conversely, LPS elicited PA if incubated with platelets stimulated with sub-threshold concentration of collagen or ADP; this effect was blunted in platelets pre-incubated with an inhibitor of toll-like receptor 4 (TLR4bp). LPS-mediated PA was associated with over-production of thromboxane (Tx) A2 and 8-iso-PGF2α-III, and was inhibited by aspirin or a TxA2 receptor antagonist. Platelet oxidative stress as assessed by measuring reactive oxygen species such as H
2
O
2
, and Nox2 activation was enhanced in LPS-treated platelets and reduced by the TLR4bp. Similarly, TLR4bp blunted the up-regulation of PLA2 phosphorylation, which was observed in LPS-treated platelets. Analysis of up-stream signaling potentially responsible for Nox2 and PLA2 activation demonstrated that LPS-mediated PA was associated with phosphorylation of AKT, p38 and p47
phox
translocation.

Conclusion:
Together these data show that LPS amplifies the platelet response to common agonists via TLR4-mediated eicosanoid production and suggest endotoxemia as a potential trigger for PA in patients with pneumonia.
Abstract 15847: Inhibition of Drp1-mediated Mitochondrial Fission Improves Diastolic Function in Right Ventricular Ischemia-reperfusion Injury
Authors: Tian Lian , Feng Ming-Guo , Hong Zhigang , Sharp Willard W , Kutty Shelby , Archer Stephen L 
Published: April 2024

Introduction:
Mitochondrial fission, regulated by the GTPase dynamin-related protein 1 (Drp1), contributes to impairment of left ventricular function following ischemia-reperfusion (IR) injury or cardiac arrest. Drp1 inhibition improves LV function in IR. The effects of IR on the right ventricle (RV) and the contribution of mitochondrial fission to impaired RV function following IR are unknown. We hypothesize that: a) IR activates Drp1 in RV myocytes leading to mitochondrial fission and RV dysfunction b) inhibiting Drp1 will improve RV function.

Methods:
RV-IR was compared in control rats versus rats with monocrotaline-induced pulmonary arterial hypertension (MCT PAH). PAH was confirmed by measuring pulmonary artery acceleration time (PAAT), RV diastolic and systolic thickness (RVFW), and tricuspid annular plane systolic excursion (TAPSE) via ultrasound.

IR was created in RV Langendorff preparation using two cycles of 15 min of ischemia followed by 15 min of reperfusion. We investigated the effects of two Drp1 inhibitors on RV function following IR: Mdivi-1, an inhibitor of Drp1’s GTPase activity and P110, a peptide inhibitor of the interaction between Drp1 and its binding partner, fission protein 1 (Fis1).
Immunoblotting was performed on mitochondrial and cytosolic protein extracted from RV after Langendorff experiment to measure total and active Drp1 (defined as Drp1 in the mitochondria or phosphorylated at serine 616).

Results:
Compared to control, MCT produced severe PAH in week 4 as indicated by reduced PAAT and TAPSE and increased RVFW thickness. IR increased RV end diastolic pressure (RVEDP) without impairing developed systolic RV pressure. Both Mdivi-1 and P110 reduced the rise of RVEDP in the PAH RV following IR, with P110 being more effective. At baseline, cytosolic Drp1 expression was lower and mitochondrial Drp1 expression was higher in PAH vs. control RV. With IR, mitochondrial Drp1 expression increased in normal RV.

Conclusions:
The RV-IR response is characterized by isolated diastolic dysfunction and it results from Drp1 activation. Inhibition of mitochondrial fission, particularly by blocking the Drp1-Fis1 interaction, preserves RV diastolic function and may be a promising therapeutic strategy to improve RV function in PAH.
Abstract 11553: Percutaneous Coronary Intervention Outcomes in the Elderly: A Single Regional Centre Experience
Authors: Mohamed Mohamed O , Khan Hamid S , Zaphiriou Alex , Townend John N , Doshi Sagar N , Ludman Peter F , Khan Sohail Q 
Published: April 2024

Background:
Ischaemic heart disease is responsible for a significant health care burden in the elderly. The benefit from coronary revascularization with PCI in very elderly patients remains unclear.

Purpose:
We sought to assess the morbidity and mortality of very elderly patients (VEP; age ≥80 years) undergoing PCI, and compare outcomes to elderly patients (EP; 70-79 years).

Methods:
820 consecutive patients (age ≥70 years) undergoing PCI over a three-year period were included (Jan 2012 to Jan 2015). Baseline characteristics, procedural details and clinical outcomes at three points of follow up (in-hospital, 30-day and 1-year) were recorded and patients were classified in to two groups, EP (n=508, 65% males) and VEP (n=312, 67% males).

Results:
875 PCI procedures were evaluated, 553 (62%) in the EP group and 322 (38%) performed in VEP group. Baseline characteristics were similar in both groups. All comparative data are expressed as VEP vs. EP with p<0.05 unless otherwise stated.

VEP were more likely than EP to undergo PCI for ACS [STEMI (35.3% vs. 22.0%), NSTEMI (47.9% vs. 44.7%)]. EP were more likely to have PCI for stable angina.
VEP were more likely to receive three or more stents than EP (19.6% vs. 13.1%). Uni-variable relative risk analyses of mortality and post-procedural complications are shown in Figure 1. Global unadjusted in-hospital mortality was higher in the VEP group (9.1% vs. 4.9%). Global mortality was also higher in the VEP group at 30-day follow up (10.3% vs. 7.5%) and 1-year end point (18.6% vs. 8.7%).
Among the post procedure complications, major bleeding requiring transfusion and renal failure were higher in the VEP, whilst stroke rates were not statistically different.

Conclusions:
Very elderly patients undergoing PCI have higher mortality and complication rate compared to elderly patients. The higher risk of complications may in part be explained by their higher likelihood to present with an ACS and more complex anatomy.
Abstract 13431: Safety And Efficacy of Angioseal Deployment in Patients With Common Femoral Artery Access During Electrophysiological Procedures Performed With Uninterrupted Oral Anticoagulation
Authors: Gianni Carola , Engel Jason T , Powers Brent M , Mohanty Sanghamitra , Trivedi Chintan , Bai Rong , Al-Ahmad Amin , Burkhardt J D , Gallinghouse G J , Hranitzky Patrick M , Horton Rodney P , Sanchez Javier E , Beheiry Salwa , Di Biase Luigi , Natale Andrea 
Published: April 2024

Introduction:
Retrograde access is commonly used during EP procedures to access the aortic root as well as the LV. Many patients who undergo these procedures are under uninterrupted oral anticoagulation (OAC), therefore it is important to find a way to minimize arterial access-site complications.

Hypothesis:
Femoral arterial access closure devices can be safely used to achieve hemostasis after common femoral artery access in EP procedures performed with uninterrupted OAC.

Methods:
Consecutive patients who underwent femoral arterial access closure with the AngioSeal device in two centers were included in this retrospective analysis. All patients were systemically heparinized with ACT between 300 and 500 s. Success was defined as hemostasis achieved in < 5 minutes.

Results:
Over a 2-year period, 62 patients underwent femoral arterial access closure. 52% were PVC/VT ablations, 40% AF (NCC), and 8% SVT (NCC/WPW). 53% of the patients were female, with a mean age of 59 ± 13 years and BMI 30.0 ± 5.2; sheath size was 8F for all.

40% on uninterrupted OAC (24% factor Xa inhibitors, 16% warfarin), whereas 23% were on ASA, 5% on dual antiplatelet therapy, and 32% were not receiving any antithrombotic therapy at the time of the procedure. In all patients with uninterrupted OAC, femoral arterial access was ultrasound-guided to ensure that the arteriotomy was located above the bifurcation but below the external iliac artery.
Femoral arterial closure was successful in all, without any device-related complication. There were 2 (3%) access-related complications requiring prolonged hospitalization, both related to the additional venous access, as determined by ultrasound: 1 superficial bleeding in a patient with NCC tachycardia during AF ablation who was on uninterrupted rivaroxaban and 1 large hematoma in a patient who underwent VT ablation and was on ASA. The incidence of complications was not significantly different between patients with uninterrupted OAC compared to those with uninterrupted antiplatelet thereapy or no antithrombotic therapy (Fischer’s exact test P = NS).

Conclusions:
Common femoral artery access closure with the AngioSeal device is safe and effective in achieving hemostasis in patients undergoing EP procedures performed with uninterrupted OAC.
Abstract 16773: Ablation of Cardiac Myosin Binding Protein-C in Human iPSC- Engineered Cardiac Tissue Model Causes Increased Calcium Sensitivity and Accelerated Contractile Kinetics
Authors: Ralphe John C , de Lange Willem J , Hernandez Jonathan J , Jacobs Derek R , Kreitzer Caroline R 
Published: April 2024

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease that can cause sudden cardiac arrest, diastolic dysfunction and heart failure. Mutations in cardiac myosin binding protein-C (cMyBP-C), a regulator of contractility, are among the most prevalent causes of HCM. cMyBP-C truncation mutations may affect as many as 1 in 1,600 Americans. Though murine models of cMyBP-C ablation have aided in understanding the role of cMyBP-C in health and disease, they are limited by differences in cardiac physiology between mice and humans. iPSC technology now allows researchers to study the effect of HCM mutations in iPSC-derived cardiomyocytes from HCM patients and controls, however differences in genetic background between patients and controls and clonal variation remain confounders.
We hypothesized that cMyBP-C ablation in human cardiomyocytes would primarily alter cardiac contractility.
CRISPR/Cas9 was used to introduce frame shift mutations in cMyBP-C in the well characterized DF19-9-11T human iPSC line. Human iPSCs were differentiated into cardiomyocytes and then cast into an integrated 3D engineered cardiac tissue (ECT) model for functional testing against non-targeted isogenic controls.

Homozygous cMyBP-C ablation significantly accelerated contraction (CT
100
= 219±3 vs. 235±5ms; p = 0.02) and early relaxation (RT
50
= 144±2 vs. 167±4ms; p <0.001), while late relaxation was slowed (RT
50-90
= 127±2 vs. 112±2ms; p <0.001; n=6 for each group). These accelerated contractile kinetics were accompanied by a significantly blunted response to adrenergic stimulation and an increase in Ca
2+
sensitivity. Heterozygous cMyBP-C ablation resulted in acceleration in relaxation kinetics (RT
50
= 148±7 vs. 167±4ms; p = 0.04 and RT
50-90
= 96±4 vs. 112±2ms; p = 0.002), without significantly affecting the rate of contraction.

The accelerated kinetics of contraction and early relaxation in cMyBP-C null ECT provides important human evidence that cMyBP-C acts as a brake on cardiac contractility. These data provide strong evidence that the human model system can be used to study the function of cMyBP-C and provide a platform to test therapies that may rectify the contractile defects caused by cMyBP-C haploinsufficiency.
Abstract 14203: Implications of Atrial Fibrillation on Clinical Outcomes of Patients With Heart Failure With Preserved Ejection Fraction
Authors: Shafi Irfan , Alhusain Rashid , Awadelkarim Abdalaziz , Tidwell Chad , Mumm Tyler , Mishra Tushar , Ali Mohammed , Manmohan Singh , AFONSO Luis , Kottam Anupama 
Published: April 2024

Background:
Atrial fibrillation and heart failure with preserved ejection fraction(HFpEF) are closely interrelated, and atrial fibrillation confer poor prognosis in HFpEF patients.

Objective:
We sought to study outcomes and implications of atrial fibrillation among patients hospitalized with HFpEF.

Methods:
Patients with a principal discharge diagnosis of HFpEF between 2016 and 2018 were identified in the National Readmissions Database. Among those, patients with and without a secondary diagnosis of atrial fibrillation were categorized. HFpEF hospitalizations with atrial fibrillation were matched 1:1 fashion to HFpEF without atrial fibrillation using age, sex, and Charlson comorbidity index.

Results:
Of the 195,110 HFpEF hospitalizations, 66,584 had HFpEF with a secondary diagnosis of atrial fibrillation. Propensity score-matched comparison between HFpEF with and without atrial fibrillation showed higher in-patient mortality (3.18% vs. 2.58%, P=0.00), Cardiogenic shock (0.62% vs. 0.39%, P=0.00) and bleeding (2.09% vs. 1.08%, P=0.00) as compared with HFpEF without atrial fibrillation. Total charges were higher in HFpEF with atrial fibrillation compared to patients without atrial fibrillation ($ 46018.97 vs. $ 43692.16). The 30 days all-cause readmission rate among patients admitted with HFpEF and survived index hospitalization was 20.14% (95% CI 19.96 - 20.31%).

Conclusion:
In patients with HFpEF presence of atrial fibrillation was associated with higher inpatient mortality.

Figure 1: Patient selection flow diagram
Table 1: Outcomes of HFpEF Patients with and without Atrial Fibrillation in Propensity-Matched Groups.