bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15810: Direct Evidence of Functional Coupling of β2 Adrenergic Receptors With L-type Calcium Channels in Rat Cardiomyocytes and its Loss in Heart Failure
Authors: Sanchez-Alonso Jose L , Gorelik Julia
Published: April 2024

Introduction:
L-type calcium channels (LTCCs) are crucially involved in excitation-contraction coupling. β1 and β2 adrenergic receptors (βARs) are important mediators of LTCC function via production of the second messenger cAMP. Stimulation of LTCCs through β2AR happens only in the close proximity of the channel suggesting a coupling between LTCC with β2AR rather than with β1AR. We wanted to find out if this coupling is exclusive of the channels located in the t-tubules (TTs) or it can be found in other areas of cell plasma membranes (crests). We also wanted to look at failing cardiomyocytes and see if the coupling is impaired.

Method:
We applied super-resolution scanning patch-clamp to record functional LTCCs from control and 16-weeks post-MI heart failure rat ventricular cardiomyocytes. Stimulation of β1AR (ISO 1.0μM + ICI 50nM) or β2AR (ISO 1.0μM + CGP 0.3μM), on specific microdomains (TTs or crests) was applied locally though the pipette (350nm tip diameter) in cell-attached mode.

Results:
In control cells, local stimulation of β2AR increased the occurrence (from 30% to 50% on TTs and from 13% to 27% on crests) and the open probability of LTCCs (0.045±0.007 vs. 0.066±0.007 on TTs, p<0.05 and 0.026±0.008 vs 0.046±0.002 on crest, p<0.05). Surprisingly, local stimulation of β1AR did not increase neither occurrence nor open probability of LTCC both in the TTs and in the crests. In failing cells, a microdomain-specific disruption of signalling was observed, with β2AR stimulation only increasing the occurrence (from 33% to 56%) and the open probability (0.079±0.011 vs 0.0107±0.009, p<0.05) of LTCCs in the crests but not in the TTs.

Conclusions:
This study provides first direct evidence of the specific coupling of β2ARs with LTCCs that is also dependent on the location and is disrupted in failing cardiomyocytes.
Abstract 15814: Novel Protective Mechanism of Cu Transporter ATP7A for Extracellular SOD Against Endothelial Dysfunction in Type2 Diabetes Vascular Complications
Authors: Varadarajan Sudhahar , Okur Nazir , O'Bryan John , Minshall Richard , Phillips Shane , Ushio-Fukai Masuko , Fukai Tohru
Published: April 2024

Endothelial dysfunction induced by oxidative stress is the major vascular complication in diabetes mellitus (DM). Extracellular SOD (ecSOD), a secretory copper (Cu) enzyme, preserves endothelial function by scavenging extracellular superoxide, and its full activity requires Cu transporter ATP7A. We reported that reduced ATP7A-ecSOD pathway in vascular smooth muscle cells (VSMCs) is involved in endothelial dysfunction in type1 DM with hypoinsulinemia, but its role and mechanism in type2 DM with impaired insulin-Akt signaling is entirely unknown. Here we show that in VSMC, insulin increases ATP7A protein expression (1.8 fold) without affecting transcription by reducing ATP7A ubiquitination in a PI3K/Akt dependent manner. In organoid culture of mouse aorta, insulin increases ecSOD specific activity (47%) and ATP7A expression (1.9-fold). Insulin stimulation (2 hrs) promotes ATP7A translocation from TGN to caveolin (Cav) enriched lipid raft (C/LR) where it binds to ecSOD in PI3K/Akt dependent manner, reflecting Cu delivery to ecSOD through ATP7A at C/LR. Mechanistically, insulin increases pAkt binding to ATP7A to induce pSer-ATP7A, which is required for ATP7A translocation to C/LR. Mass spectrometry analysis identified Akt phosphorylation site of ATP7A at S1424/S1432/S1466. Of note, vascular ATP7A protein expression, ecSOD specific activity and endothelial function are impaired in Cav1 KO or Akt2 KO or ATP7Amut mice, but not Akt1 KO mice, suggesting the importance of Akt2-mediated ATP7A protein stabilization and its translocation to C/LR for ecSOD activation. Moreover, in aorta or VSMCs of high fat diet-induced type2 DM mice with impaired insulin-Akt pathway, ATP7A expression (57%) and ecSOD specific activity (53%), but not Cu/Zn SOD, are decreased. Acetylcholine-induced vasorelaxation is significantly impaired in resistant vessels of type2 DM mice, which is rescued in ATP7A-Tg/Type2 DM mice. In summary, insulin-Akt dependent ATP7A protein stabilization and translocation to C/LR promotes ecSOD activation, which prevents endothelial dysfunction in type2 DM. Thus, enhancing Akt2-ATP7A-ecSOD axis is potential therapeutic strategy for protecting against endothelial dysfunction in diabetes vascular complications.
Abstract 15835: Cold Air Inhalation Induces Differential Effects on Coronary Microvascular Resistance and Flow Depending on Presence of Significant Coronary Artery Disease
Authors: Williams Rupert , Asrress Kaleab , Lumley Matthew , Arri Satpal , Patterson Tiffany , Manou-Stathopoulou Vasiliki , Macfarlane Catherine , Ellis Howard , Khawaja Zeeshan , Briceno Natalia , Clapp Brian , Perera Divaka , Chiribiri Amedeo , Plein Sven , Marber Michael , Redwood Simon
Published: April 2024

Introduction:
Cold temperatures increase the incidence of myocardial infarction. Precise mechanisms remain unclear. Sudden severe myocardial oxygen supply/demand mismatch may be responsible. We measured coronary flow and myocardial work during cold air inhalation (CAI), invasively and with cardiac magnetic resonance imaging (CMR), aiming to elucidate the dominant mechanisms.

Methods:
All data were acquired at rest and peak stress during CAI: 5minutes -15oC via a face-mask. Simultaneous intracoronary pressure and flow velocity data were acquired in a target artery from 20 patients (10 with normal coronary arteries, 10 with a significant stenosis (CAD). Coronary flow average peak velocity (APV), microvascular resistance (MVR) and buckberg index (BI: a surrogate for subendocardial ischemia) were calculated. Wave intensity analysis also differentiated waves that accelerate and decelerate coronary flow. Separately CMR perfusion was performed in 7 patients with a significant stenosis to quantify myocardial perfusion reserve (MPR) and transmural perfusion gradients (TPG).

Results:
At rest MVR is lower in CAD patients, maintaining APV (1a,b). During CAI, although myocardial work increased similarly in normal and CAD patients (rate pressure product mean difference 2312 and 2651mmHg.min-1 respectively), there was a differential response in coronary flow, with a significant increase and a downward trend in APV respectively (1a). Relative hypoperfusion of stenosed segments was also noted on MPR (2a). This inability of CAD patients to augment APV is explained by a significant increase in MVR (1b) collaborating with a reduction in accelerating flow waves (1c). These cause a relative subendocardial perfusion deficit, demonstrated by a significant decrease in BI (1d) and increase in TPG (2b).

Conclusions:
CAI increases myocardial work but CAD patients are unable to augment flow due to microvascular vasoconstriction and adverse ventricular-vascular coupling.
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 11175: The Effects of LCZ696 on Left Ventricular Remodeling in Hypertensive Patients - Results of a Double Blind, Randomized, Multicenter Trial
Authors: Schmieder Roland E , Wagner Frank , Mayr Michael , Delles Christian , Ott Christian , Keicher Christian , Aichner Solveig , Khder Yasser , Yates Denise , Albrecht Diego , Langenickel Thomas , Freyhardt Patrick , Janka Rolf , Bremerich Jens
Published: April 2024

Background:
Arterial hypertension and the resulting reduction in aortic distensibility impose increased hemodynamic load to the left ventricle and, if untreated may lead to left ventricular hypertrophy (LVH) and heart failure.

Purpose:
We analyzed the effects of LCZ696 on LV-structure and function as well as on regional and global aortic distensibility.

Methods:
We conducted a prospective, randomized, double-blind, parallel-group, multicenter study in 114 patients with mild to moderate hypertension. Patients were randomized to LCZ696 200/400mg o.d. or olmesartan (OLM) 20/40mg o.d. At baseline, 12 and 52 weeks left ventricular mass (LVM) index as well as local and global aortic distensibility were evaluated by 3 T magnetic resonance imaging (MRI) and pulse wave analysis, respectively.

Results:
Baseline characteristics, office BP (155.1±9.0/92.2±8.7 mmHg) and LVM index (72±15 g/m
2
) were similar between treatment groups at baseline. After 52 weeks of treatment, decrease in office systolic BP was greater in the LCZ696 group than in the OLM group (-4.99 [95% CI -9.46 to -0.53] mmHg, p=0.029). Compared to OLM, treatment with LCZ696 resulted in a greater decrease in LVM index at 12 weeks (-4.05 [95% CI -7.9 to -0.2] g/m
2
, p=0.039) and at 52 weeks (-3.27 [95% CI -6.2 to -0.34] g/m
2
, p=0.029). After adjustment for office SBP at follow-up, the change in LVM index at 12 weeks (p=0.0356) and at 52 weeks (p=0.0189) remained significantly greater in the LCZ696 group. Local aortic distensibility measured by MRI in the ascending, proximal and distal descending aorta did not show any significant difference between groups. LCZ696 was associated with a larger decrease of central pulse pressure compared to OLM (-3.50 [95% CI: -6.15 to -0.85] mmHg, p=0.01) at 52 weeks. Both treatments were safe and well tolerated.

Conclusion:
In patients with hypertension, LCZ696 reduced LVM to significantly greater extent than OLM. Since reduction of LVM is associated with improved cardiovascular prognosis, the observed effect of LCZ696 on LVM is of clinical relevance.
Abstract 11235: Improvement of Defective Channel Function on RyR2 Mediated by CaMKII Activation Suppresses Arrhythmogenesis in TnT-related Hypertrophic Cardiomyopathy
Authors: Okuda Shinichi , Sufu-Shimizu Yoko , Kato Takayoshi , Okamoto Yoko , Nishimura Shigehiko , Oda Tetsuro , Kobayashi Shigeki , Yamamoto Takeshi , Yano Masafumi
Published: April 2024

Backgrounds:
In Familial Hypertrophic Cardiomyopathy (FHC) caused by cardiac troponin T (cTnT) mutations, Ca
2+
sensitivity in myofilaments is increased, results in leading to sudden cardiac death. The activation of calcium/calmodulin-dependent protein kinase II (CaMKII) is known to be one of the key elements for the alteration of calcium handling in heart failure, presumably mediated through defective channel function of cardiac ryanodine receptor (RyR2). However, how cTnT mutations lead to lethal arrhythmias and abnormal calcium handling through defective RyR2 remains elusive. Here, we investigated the pathogenic role of CaMKII on aberrant Ca
2+
release through RyR2 for arrhythmogenesis in FHC hearts and therapeutic effects of dantrolene, which was found to correct inter-domain interactions between N-terminal and central domain of RyR2 in FHC-related cTnT-mutated transgenic mouse (TG; cTnT-delta160E). TG have been reported myocardial disarray in histology and increased Ca
2+
sensitivity in myofilaments.

Methods and results:
On confocal Ca
2+
imaging by fluo4-AM exposed to isoproterenol (ISO; 10 nmol/L), the Ca
2+
spark frequency (SpF:s-1·100μm-1) was much higher in TG cardiomyocytes (ISO-TG: n=11: 7.8±0.6; p<0.05) than in non-TG (n=8: 3.4±0.4). It was largely reversed by CaMKII inhibitor {KN-93(1μM), n=7: 5.2±0.5; p<0.05}, but not by PKA inhibitor (PKI){H-89(1μM), n=7: 7.3±0.4}. The significant increase of spontaneous Ca
2+
transient (sCaT), which was measured after sequential pacing at 5 Hz was appeared in ISO-TG (42.1%; p<0.05 vs ISO-treated non-TG 14.0%), whereas it was again attenuated by CaMKII inhibitor (15.8%), but not by PKI (33.0%). These abnormal events in ISO-TG were reproduced by adding EGTA-AM into ISO-treated non-TG, suggesting that increased Ca
2+
buffering capacity, causing an increase in diastolic [Ca
2+
], predisposes to aberrant Ca
2+
release events. Moreover, after the treatment of dantrolene (1μM), ISO-induced SpF (n=6: 5.2±0.3; p<0.05 vs ISO-TG) and sCaT (25.9%) were decreased in TG.

Conclusions:
CaMKII activation may play a role in the development of abnormal calcium handling in FHC-linked cTnT mutated hearts, possibly through defective inter-domain interaction between N-terminal and central domain of RyR2.
Abstract 11237: Safety and Efficacy of Radiofrequency versus Second-Generation Cryoballoon Ablation for Treatment of Atrial Fibrillation - A Meta-analysis of Current Evidence
Authors: Pandya Bhavi , Parikh Valay , Kenigsberg David , O’Neill Padraig Gearoid , Koo Charles H , Aryana Arash , Kowalski Marcin
Published: April 2024

Background:
To compare the strategies of point-by-point radiofrequency ablation (RFA) to second-generation cryoballoon ablation (CBA) in terms of safety and efficacy, we pooled data for systematic review and meta-analyses from all available literature comparing their clinical performance.

Methodology:
The Cochrane Library, PubMed, Google Scholar and studies presented at various meetings were searched for any published literature comparing safety and efficacy of the CBA with RFA. A total of 7published studies, with 2,969 patients were included in this meta-analysis with 1322 patients in RFA group and 1647 patients in CBA group.

Results:
The pooled analysis showed non-significant differences in procedure time (SMD=4.04, [CI: -16.16, 24.23], p=0.7, I
2
=97%), fluoroscopic time (SMD=-2.49, [CI: -5.82, 0.84], p=0.14, I
2
=93%) and access site complication (OR=1.44, [CI: 0.82, 2.54], p=0.2, I
2
=0%) between the two techniques of ablation. While RFA was found to have lower odds of phrenic nerve palsy (OR=0.04, [CI: 0.01, 0.15], p<0.00001, I
2
=0%) and higher odds of cardiac tamponade (OR=2.67, [CI: 1.17, 6.08], p=0.02, I
2
=0%) compared to CBA. Comparing efficacy amongst two groups, there was no statistically significant difference in terms of arrhythmia recurrences (OR=1.35, [CI: 0.94, 1.93], p=0.1, I
2
=69%).

Conclusion:
Point-by-point radiofrequency ablation was found to have less incidences of phrenic nerve palsy and higher incidences of cardiac tamponade compared to second-generation cryoballoon ablation. However efficacy profiles were similar in both groups.
Abstract 11277: Computational Fluid Dynamics Characterization of Pulsatile Flow in Patient Specific Central and Sano Shunts: Relevance to Shear-Stress Induced, Platelet-Mediated Thrombosis
Authors: Ascuitto Robert , Ross-Ascuitto Nancy , Celestin Carey , Guillot Martin
Published: April 2024

Introduction:
Central shunts (aorta) and Sano shunts (right ventricle) connected to the pulmonary arteries (PAs) are vital operations for infants with complex heart defects. However, they can become thrombosed.

Hypothesis:
At sites of prominent angulation, flow augments wall shear stress (WSS), a determinate of platelet-mediated thrombosis.

Methods:
We employed a patient-based computational model (Fluent) of pulsatile flow (viscosity 5 cPa-s), using a finite volume method and cardiac catheterization data, and geometric simulations (Autodesk Inventor), using angiography, to study flow behavior and WSS. Two central (4.0 and 3.5 mm) and Sano (5 and 6 mm) shunts were assessed. At the inlet to the central and Sano shunts, ascending aorta (AAo, 87/40 and 93/35 mmHg) and right ventricle (RV, 99/10 and 84/10 mmHg) pressures were used, respectively. At the outlets, measured PA pressures were used.

Results:
For central shunts, Fig 1, WSS reached 245 Pa and 123 Pa, peak systole. For Sano shunts, Fig 2, WSS attained 203 Pa and 133 Pa, peak systole. At sites of angulation, we identified flow vortices augmenting WSS (>100 Pa), and downstream regions of flow stagnation and recirculation, which are conducive to platelet aggregation and thrombus formation. Shunt burden, assessed by averaging WSS over the luminal surface of the shunts and the cardiac cycle, was 73.0 Pa and 67.2 Pa for central shunts, and 34.9 Pa and 19.6 Pa for Sano shunts.

Conclusions:
Our results indicate central shunts present a higher risk for thrombosis than Sano shunts. Importantly, WSS induced, platelet-mediated thrombosis is insensitive to aspirin, as the process does not involve the cyclooxygenase pathway.
Abstract 11315: Ideal Cardiovascular Health, Cardiometabolic Remodeling, and Heart Failure in African-Americans: The Jackson Heart Study
Authors: Spahillari Aferdita , Talegawkar Sameera , Correa Adolfo , Carr J. J , Terry James G , Lima Joao , Freedman Jane E , Das Saumya , Kociol Robb , de Ferranti Sarah , Mohebali Donya , Mwasongwe Stanford , Tucker Katherine L , Murthy Venkatesh L , Shah Ravi V
Published: April 2024

Background:
Though African-Americans are at disproportionately high risk for heart failure (HF) and cardiometabolic disease, few studies have evaluated the association between ideal cardiovascular health metrics and cardiometabolic diseases or incident HF in African-Americans.

Hypothesis:
Ideal cardiovascular health is associated with adverse cardiometabolic phenotypes and incident HF.

Methods:
A total of 4195 African-American participants without prevalent coronary heart disease with 7 ideal cardiovascular health (ICVH) metrics measured at baseline (2000-2004) underwent evaluation by cardiac magnetic resonance (CMR; n=1188) and/or abdominal computed tomography (CT; n=2352). 3661 (87%) participants were followed for incident HF.

Results:
Mean age at baseline was 54.4 years (65% women). A lower composite score of ICVH at baseline was associated with greater LV hypertrophy, greater LV concentric remodeling, worse LV strain, and greater visceral and subcutaneous adipose tissue in follow-up (all P <0.0001). Ideal BMI, absence of smoking, controlled blood pressure and normoglycemia were associated with improved cardiac and adiposity phenotypes. Relative to individuals with 0-2 ideal ICVH factors, African-Americans with 3 factors had 48% lower incident HF risk (HR 0.52, 95% CI 0.35-0.75, P=0.0006) and those with ≥ 4 factors had 58% lower HF risk (HR 0.42, 95% CI 0.24-0.76, P=0.004). Of the 7 components of ICVH, non-ideal physical activity, smoking, and impaired glucose control were associated with incident HF risk.

Conclusions:
In African-Americans, lower ideal cardiovascular health in mid-life is associated with later adverse cardiometabolic remodeling and incident HF. Lack of physical activity, smoking and impaired glucose control are associated with incident HF risk and represent potential targets for prevention of cardiometabolic disease and HF in African-Americans.
Abstract 11362: The Riser Pattern, a Novel Marker of Adverse Prognosis in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Komori Takahiro , Eguchi Kazuo , Saito Toshinobu , Hoshide Satoshi , Kario Kazuomi
Published: April 2024

Introduction:
The cardiovascular prognosis of heart failure with preserved ejection fraction (HFpEF) has been shown to be similar to that of heart failure with reduced ejection fraction (HFrEF). It is unknown which factors predict cardiovascular outcomes in HFpEF.

Hypothesis:
The abnormal pattern of circadian BP rhythm known as riser BP pattern is associated with adverse outcomes in HFpEF.

Methods:
We enrolled 516 hospitalized HF patients who underwent ambulatory BP monitoring (ABPM) (age, 69±13 yrs; 61% males [n=314] and 39% females [n=200]), and were followed up for 23±16 months. The combined endpoints consisted of all-cause mortality and cardiovascular events.

Results:
Combined endpoints were observed in 220 cases. In a Kaplan-Meier analysis, the riser BP pattern subgroup had a significantly higher incidence of combined endpoints than the other subgroups of the HFpEF patients (Figure). In a Cox regression analysis adjusted for significant variables, the riser BP pattern was a significant predictor of adverse outcomes in the HFpEF group (HR 3.01, 95%CI 1.54-6.08, p<0.01), but not in the HFrEF group.

Conclusions:
The riser BP pattern was found to be a novel predictor of cardiovascular outcomes in patients with HFpEF.
Abstract 11365: Bioelectrical Impedance Analysis is Useful for the Management of Heart Failure and Prediction of Cardiac Events in Adult Patients With Congenital Heart Disease
Authors: Sato Masaki , Inai Kei , Shimizu Mikiko , Takeuchi Daiji , Ishii Testuko , Toyohara Keiko , Shinohara Tokuko , Sugiyama Hisashi , Tomimatsu Hirofumi , Nakanishi Toshio , Park In-Sam
Published: April 2024

Introduction:
Since decompensated heart failure generally leads to fluid volume overload, the ability to recognize and quantify fluid retention is critical for the treatment of heart failure. Bioelectrical impedance analysis (BIA) is a safe, non-invasive, and rapid assessment method, but little has been reported on the role of BIA in the management of patients with congenital heart disease (CHD).

Hypothesis:
We assessed the hypothesis that BIA is useful for the management of heart failure in adult patients with congenital heart disease.

Methods:
We performed a retrospective single-center study of 173 consecutive adult patients with congenital heart disease who were admitted to our institute between April 2013 and December 2015. We retrospectively reviewed the medical records of the patients to evaluate the relationship between the BIA parameters (intracellular water, extracellular water, protein, mineral, fat, edema index (EI, ratio of extracellular water to total body water)) and the laboratory values, echocardiographic parameters, and prevalence of cardiac events.

Results:
The patients in functional classes 3 and 4 had a higher EI compared with the patients in functional classes 1 and 2 (0.395 vs. 0.384, p < 0.001). In the multivariate analysis, the EI was significantly related to serum albumin, BUN, and BNP. In addition, the reduction in body weight (BW) achieved during the hospitalization was significantly related to the reduction in EI; using a generally defined upper limit of EI as 0.39, we developed this model equation: Required BW reduction (kg) = 98.1(EI - 0.39) + 2.26(Protein) - 4.14(Mineral) - 0.04(BUN) - 1.86. During the median follow-up period of 36 months, the Kaplan-Meier analysis revealed that an EI of more than 0.39 was significantly associated with an increased prevalence of cardiac events. Using the Cox hazard model, we determined that the hazard ratio of cardiac events in patients with an EI ≧0.39 compared to patients with an EI <0.39 was 3.9 (95%CI 2.0-7.9). In patients who had undergone a Fontan operation, the hazard ratio was 7.0(95%CI 1.4-77.1).

Conclusions:
The Edema index determined by BIA is a useful marker for the treatment of heart failure and the prediction of cardiac events in adult patients with congenital heart disease.
Abstract 11366: Retained Cardiac Implantable Electronic Device Fragments After Incomplete Extraction Do Not Adversely Affect Magnetic Resonance Imaging Quality or Safety
Authors: Austin Christopher , Landolfo Kevin , Parikh Pragnesh , Kusumoto Fred
Published: April 2024

Introduction:
The prevalence of cardiac implantable electronic devices (CIED) is steadily increasing. Accordingly, the frequency of CIED extraction has also increased. Occasionally, safe retrieval of all CIED components is not feasabile and lead fragments are left behind. Little is known about the safety and diagnostic accuracy of MRI in patients with retained CIED fragments.

Methods:
Two hundred consecutive patients were identified as having undergone orthotopic heart transplantation (OHT) at our institution between April 2006 and December 2014. Chest x-rays immediately prior to OHT were reviewed for presence of CIED and chest x-rays immediately following OHT were reviewed for retained CIED fragments. MRI performed after OHT in patients with retained CIED fragments were inspected for image quality and procedural safety. The most recent chest x-ray in patients with retained CIED fragments subjected to MRI was reviewed for change in fragment position.

Results:
One hundred seventy-eight of 200 patients (89%) had CIED prior to OHT. All patients with CIED had surgical device extraction at the time of OHT. Of these, 29 patients (12%) had retained CIED fragments after OHT, the majority of which (23/29) were ICD coil fragments located in the superior vena cava, brachiocephalic or subclavian vein. Ten patients with retained CIED fragments underwent a total of 28 MRI after OHT. No patient safety issues were identified during MRI acquisition, and all MRI images were of diagnostic quality. There were no changes in the position of CIED fragments following MRI.

Conclusions:
Diagnostic MRI can be safely performed in patients with retained CIED fragments after incomplete device extraction. Adherence of the ICD coil to the vessel wall due to fibrosis has been well described and is a common impediment to complete device extraction. Retrieval of these fragments prior to MRI does not appear warranted given the demonstrated safety and preserved MRI image quality in this population.
Abstract 11368: Pre-operative Endothelin Levels Predict Post-operative Acute Kidney Injury in Cardiac Surgery
Authors: Ghashghaei Roxana , Wetterson Nick , Coletta Joelle , Golts Eugene , Patel Minal , Lee Elizabeth , Clopton Paul , Mehta Ravinder , Maisel Alan S , Taub Pam
Published: April 2024

Introduction:
Acute kidney injury (AKI) occurs in up to 40% of patients undergoing cardiac surgery and is associated with substantial morbidity and mortality, prolonged hospitalizations, and increased costs. AKI is clinically characterized by by a rapid reduction in kidney function resulting in a failure to maintain fluid, electrolyte and acid-base homoeostasis. Thus, there is a critical need to identify patients at increased risk for developing AKI when undergoing cardiac surgery. Endothelin is a locally produced vasoactive and natriuretic peptide with pro-inflammatory and pro-fibrotic properties that serves an important role in the regulation of renal hemodynamics and hemofiltration.

Hypothesis:
In this study, we hypothesize that endothelin will predict post-operative AKI in patients undergoing cardiac surgery.

Methods:
105 patients undergoing cardiac surgery (either coronary bypass surgery and/or valve surgery) were recruited from the Veterans Affairs San Diego Health Care System and their plasma samples pre-operatively and at 2, 6, 12, 24, and 48 hours post-operatively were collected. A post-hoc analysis was then performed to determine the ability of pre-operative endothelin levels to predict post-operative AKI.

Results:
Of 105 patients, 18 patients (17%) developed AKI post-operatively. Endothelin levels were elevated at baseline in patients who had a RIFLE score of at least 1, which is indicative of baseline renal injury. Preoperative endothelin was elevated in patients with post-operative AKI vs. no AKI (4.03 pg/mL [3.43-5.49] vs. 3.14 pg/mL [2.56-4.10], p=0.003). Interestingly, it was also determined that endothelin was superior to baseline creatinine in predicting AKI. Preoperative endothelin was predictive of post-operative AKI (AUC=0.721 (0.611-0.830), p=0.003) while there was no significant association between preoperative creatinine and post-operative AKI; p=0.953 (95% CI = 0.320-0.689).

Conclusions:
Elevation of pre-operative endothelin levels predicts post-operative AKI in patients undergoing cardiac surgery. Future studies are needed to understand mechanisms by which elevations in endothelin levels can predict future renal injury.
Abstract 11383: Reversal of Post-stroke Cerebral Microvascular Dysfunction by Neuroprotective and Hyperdynamic Therapy for Experimental Subarachnoid Hemorrhage
Authors: Mutoh Tatsushi , Sasaki Kazumasu , Mutoh Tomoko , Nakamura Kazuhiro , Taki Yasuyuki , Ishikawa Tatsuya
Published: April 2024

Introduction:
Early brain injury characterized by microvascular dysfunction in cerebral vessels may play an important role in the development of delayed cerebral ischemia (DCI) or vasospasm after subarachnoid hemorrhage (SAH). However, little is known as to the microcirculatory mechanism(s) to treat post-SAH DCI.

Hypothesis:
To clarify the utility of neuroprotective and hyperdynamic therapy in relieving cerebral microcirculatory dysfunction affected by vasospasm after experimental SAH.

Methods:
Male C57BL/6 mice were subjected to SAH by endovascular perforation and minocycline for antibiotic and anti-inflammatory use was started. Closed cranial bone window was then made over the left somatosensory cortex. In vivo real-time imaging was performed using 2-photon laser-scanning microscopy at postoperative day 3 to record alterations on the level of cerebral microvessels and the effects of dobutamine hyperdynamic therapy at clinical dose were evaluated. Comparison was made with a group without minocycline administration.

Results:
According to the 3-dimentional observation, >50% of pial and penetrating arteries constricted moderately (25-50%) from day 2 to 3 after SAH, which was greater in number in a group without minocycline pretreatment (p>0.05). In areas close to the microvasospasm, blood cell flow as measured by line scan increased by 24% (range, from 7 to 39%) following dobutamine infusion. Reversal of flow stagnation by dobutamine was more prominently observed in animals with minocycline pretreatment in pial and penetrating arteries (1.2 ± 0.5 vs. 1.8 ± 1.0 mm/s, p<0.05). Diameters of the microvessels or location of microthrombi in precapillary arterioles were not affected in any of the groups (p>0.05).

Conclusions:
The data suggest that early neuroprotection followed by inotropic hemodynamic therapy can improve microcirculation in specific areas affected by microvasospasm, which may in part, explain novel therapeutic targets for the early treatment of DCI after SAH.
Abstract 11400: Targeting Coagulation Factor Xa With Rivaroxaban Reduces the Onset and Progression of Atherosclerosis and Enhances Plaque Stability in ApoE Null Mice
Authors: Posthuma Jelle , Posma Jens , van Oerle Rene , Schurgers Leon , Heitmeier Stefan , ten Cate Hugo , Spronk Henri
Published: April 2024

Objective:
Atherosclerosis is a progressive chronic inflammatory vascular disease, complicated by plaque rupture and subsequent thrombus formation.
In vitro
studies indicate that coagulation proteases such as thrombin and factor Xa (FXa) may contribute to pro-atherosclerotic mechanisms mediated through activation of protease-activated receptors (PARs). Whereas experimental thrombin inhibition reduced development and progression of atherosclerosis, the contribution of FXa to atherogenesis has not been elucidated. To assess the involvement of FXa in atherosclerosis, we investigated the effects of direct FXa inhibition by rivaroxaban on experimental atherosclerosis.

Approach and Results:
Female ApoE
-/-
mice (age 8-9weeks) received high-fat diet (HFD) or HFD supplemented with rivaroxaban for 8 or 14 weeks (n=10/group). In the second arm, ApoE
-/-
mice received HFD for 14 weeks, followed by either continuation with HFD or switched to HFD supplemented with rivaroxaban for 6 weeks (n=10/group). Inhibition of FXa decreased the onset of atherosclerosis in the aortic arch after 8 weeks (-36.92%, p<0.05) and 14 weeks (-46.47%, p<0.05) as well as in the carotid artery; 8 weeks (-38.14%, p<0.05) and 14 weeks (-23.38%, p<0.05). Furthermore, progression of pre-existing plaque after 14 weeks was reduced in the aortic arch (-20.85%, p<0.05) and carotid artery (-30.26%, p<0.05). Immunohistochemical staining revealed reduced plaque vulnerability, as reflected by diminished macrophage infiltration (-38.28%, p<0.05), enhanced collagen (+45.30%, p<0.05) and reduced necrotic core (-37.49%, p<0.05). These findings were associated with elevated collagen-producing vascular smooth muscle cells and reduced collagen degradation proteins MMPs. The qualitative and quantitative improvements were accompanied by reduced expression of PARs and their activators, thrombin and FXa.

Conclusions:
Pharmacological inhibition of FXa with rivaroxaban impedes the onset and progression of atherosclerosis and increased plaque stability, which is possibly mediated through reduced activation of PARs. These data suggest that direct targeting of FXa may be beneficial in treatment of atherosclerosis; to demonstrate clinical relevance further studies are required.
Abstract 11401: Exercise and Cardiac Function by Tissue Doppler Imaging. The Copenhagen City Heart Study
Authors: Joseph Gowsini , Sogaard Peter , Nielsen Gitte , Biering-Sorensen Tor , Schnohr Peter , Skov Jensen Jan , Mogelvang Rasmus
Published: April 2024

Introduction:
TDI (Tissue Doppler Imaging) is a sensitive marker of myocardial dysfunction and mortality in heart disease and in the general population. Regular physical activity is associated with risk reduction in coronary heart disease and mortality. There is a need for studies to clarify whether exercise has beneficial effects on cardiac function.

Hypothesis:
Regular physical exercise is associated with better cardiac function measured by TDI in the general population

Methods:
2,162 persons from the general population were examined by echocardiography and TDI. Peak systolic (s′), early diastolic (e′) and late diastolic (a′) velocities were measured by color TDI. Longitudinal displacement (LD) was calculated from the velocity curve during ejection. Statistical tests were performed by linear univariate and multivariable regression analyses, in relation to age groups (<50years, 50-65 years, >65 years) and physical activity level: I (inactivity), II (light activity), III (moderate activity) and IV (high-level activity). These levels were graded from the physical activity questionnaire, which contained information about activity level at work and in leisure time.

Results:
Participants aged<50 years had a significantly higher level of e′ and LD in the most active group: e′=11.0 (± standard deviation, SD=2.0), p<0.001; LD=12.8 (SD=2.1), p<0.003. This pattern remained significant after adjusting for sex, hypertension, diabetes, and ischaemic heart disease and after Bonferroni correction. For e′, there was significant interaction between age and activity level (p<0.001), which supports the findings of better cardiac function with increasing activity among the young age group.

Conclusion:
In the general population, the association between increasing level of exercise and better cardiac function was found only in the youngest age group ( <50 years old). Among the elder age groups higher level of activity was not correlated to better cardiac function.
Abstract 11411: Parental Age of Hypertension Onset and Risk of Hypertension in the Offspring: The Framingham Heart Study
Authors: Niiranen Teemu J , McCabe Elizabeth L , Larson Martin G , Vasan Ramachandran S , Cheng Susan
Published: April 2024

Introduction:
Parental hypertension (HTN) is known to predict HTN in offspring. However, the relative impact of objectively diagnosed early- vs. late-onset parental HTN on risk of HTN in the community is unknown.

Hypothesis:
We hypothesized that parental early- vs. late-onset HTN is associated with a substantially greater risk of HTN in offspring.

Methods:
We analyzed serially collected blood pressure data in the Original cohort (since 1948) and in the Offspring cohort (since 1971) of Framingham Heart Study participants. We identified 1635 non-hypertensive Offspring (32±9 years, 54% women) with longitudinal blood pressure data available for both parents. We defined HTN onset as blood pressure ≥140/90 mmHg or taking antihypertensive medication at ≥2 consecutive exams, and early-onset HTN as onset age <55 years. We analyzed the risk for HTN in Offspring in relation to their parental HTN status: (1) no parents with HTN (N=107); (2) ≥1 parent with late-onset HTN (N=480); (3) 1 parent with early-onset HTN (N=721); and, (4) both parents with early-onset HTN (N=327).

Results:
Incident HTN was most common in Offspring whose both parents had early-onset HTN (Figure, log-rank p<0.0001). Incidence rates for HTN per 1000 person-years increased across the 4 groups: 5.9 in group 1, 8.3 in group 2, 11.0 in group 3, and 18.9 in group 4. In a multivariable-adjusted discrete logistic model, Offspring HTN risk increased from group 1 (referent) to group 2 (hazard ratio [HR] 1.50, 95% confidence interval [CI] 0.85-2.68), and from group 3 (HR 2.04, 95% CI 1.18-3.54) to group 4 (HR 3.45, 95% CI 1.93-6.14). In 463 Offspring who developed HTN, a 10-year lower parental age of HTN onset was associated with a 1.28-fold (95% CI 1.02-1.61) greater odds of early-onset HTN.

Conclusions:
Early-onset and not late-onset HTN in parents is a strong risk factor for HTN in offspring. It may be important to differentiate between early- and late-onset parental HTN when estimating an individual’s HTN risk.
Abstract 11434: Air Pollution is Associated With Ischemic Stroke via Cardiogenic Embolism
Authors: Chung Jong-Won , Bang Oh Young , Ahn Kangmo , Park Sang-Soon , Park Tai Hwan , Kim Jae Guk , Ko Youngchai , Lee SooJoo , Lee Kyung Bok , Lee Jun , Kang Kyusik , Park Jong-Moo , Cho Yong-Jin , Hong Keun-Sik , Nah Hyun-Wook , Kim Dae-Hyun , Cha Jae-Kwan , Ryu Wi-Sun , Kim Dong-Eog , Kim Joon-Tae , Choi Jay Chol , Oh Mi-Sun , Yu Kyung-Ho , Lee Byung-Chul , Lee Ji Sung , Lee Juneyoung , Park Hong-Kyun , Kim Beom Joon , Han Moon-Ku , Bae Hee-Joon
Published: April 2024

Introduction:
Both individual and environmental factors influence stroke risk and the effect might differ across stroke subtypes. The prevalence of cardioembolic stroke is increasing in Asian and other developing countries, which may be associated with the ambient air pollution as well as an aging population. However, the association between air pollution and stroke subtype remains unclear.

Hypothesis:
This study investigated the impact of short-term exposure to air pollution on ischemic stroke subtype, while focusing on stroke caused via cardioembolism.

Methods:
From a nationwide multicenter prospective stroke registry database, 13,535 acute ischemic stroke patients hospitalized to 12 participating centers were enrolled in this study. Data on the hourly concentrations of particulate matter <10μm (PM
10
), nitrogen dioxide (NO
2
), sulfur dioxide (SO
2
), ozone (O
3
), and carbon monoxide (CO) were collected from 181 nationwide air pollution surveillance stations. The average values of these air pollutants over the 7 days prior to stroke onset from nearest air quality monitoring station in each patient were used to determine association with stroke subtype.

Results:
PM
10
and SO
2
concentrations were independently associated with an increased risk of cardioembolic stroke, as compared to large artery atherosclerosis and non-cardioembolic stroke. In sensitivity analyses, the proportion of cases of cardioembolic stroke was positively correlated with the PM
10
, NO
2
, and SO
2
quintiles. Moreover, seasonal (including Asian dust storms in spring and winter) and geographic (including polluted mid-sized cities) factors were related to an increased proportion of cardioembolic stroke, which may be attributed to the high levels of air pollution.

Conclusions:
Our findings suggest that the short-term exposure to air pollutants is associated with cardioembolic stroke subtype, and greater care should be taken for those susceptible to cerebral embolism during peak pollution periods. Public and environmental health policies to reduce air pollution could help slow down global increasing trends of cardioembolic stroke.
Abstract 11521: Circulating Thymosin Beta-4 is Elevated in Women With Heart Failure
Authors: Tan Warren K , Chan Siew Pang , Pakkiri Leroy S , Chong Jenny P , Chen Zhaojin , Liew Oi Wah , Ng Tze Pin , Ling Lieng Hsi , Sim David K , Leong Gerard K , Yeo Daniel P , Ong Hean-Yee , Jaufeerally Fazlur R , Wong Raymond C , Chai Ping , Low Adrian F , Davidsson Pia , Gan Li-Ming , Ratan Bhat , Purnamawati Kristy , Lam Carolyn S , Richards Arthur M , Drum Chester L
Published: April 2024

Background:
Heart failure with preserved ejection (HFpEF) predominates in females, is often difficult to diagnose, has no specific circulating biomarkers, and no proven therapeutic options. Thymosin beta-4 (TB4) is an endogenously produced peptide with cardioprotective properties. In animal models, exogenously delivered TB4 was reported to reduce apoptosis, attenuate inflammation, minimize fibrosis, activate stem cells, preserve ejection fraction, and promote angiogenesis. Measurements of circulating TB4 in humans are limited, and its levels in heart failure (HF) relative to controls is not known.

Hypothesis:
We hypothesized that TB4 is upregulated in HF as a compensatory mechanism, and may be a plasma marker of HF with either preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF). Because TB4 is an X-linked gene, sex-specific regulation is suspected.

Methods:
To measure plasma levels of TB4, we developed a quantitative and targeted liquid chromatography mass spectroscopy (LCMS) assay. The assay was applied to age- and sex- matched HFpEF (n=219), HFrEF (n=219) and controls (n=219) from a prospective nationwide study.

Results:
Compared to controls, plasma TB4 was elevated in HFpEF [985(421-1723) ng/mL vs. 1401(720-2379) ng/mL, p<0.001], but not in HFrEF [1106(556-1955) ng/mL, p=0.642]. Stratifying by sex, only women [1623(1040-2625) ng/mL vs. 942(386-1891) ng/mL, p<0.001], but not men [1238.5(586-1967) ng/mL vs 1004(451-1538) ng/mL, p=1.0], had elevated TB4 in the setting of HFpEF. Over 2 years, there were 60 deaths among patients with HF. TB4 predicted time to all-cause mortality in women (p=0.046) but not men (p=0.454) with HF, independent of clinical risk factors and N-terminal pro-B-type natriuretic peptide (adjusted hazards ratio for LnTB4=1.64; 95% CI, 1.01-2.67).

Conclusion:
Circulating TB4 is a novel marker of HFpEF in women. The independent prognostic impact of plasma TB4 in women with HFpEF suggests the presence of sex-specific mechanisms in HFpEF.
Abstract 11546: The Potential Beneficial Effects of Dyad Training on Medical Students’ Cardiopulmonary Resuscitation Performance
Authors: Huang Chin-Chou , Chen Jaw-Wen , LIN Shing-Jong
Published: April 2024

Introduction:
Dyad training, which entails cooperative learning in pairs, has shown to improve student learning experiences. Cardiopulmonary resuscitation (CPR) is a team effort during which team members must cooperate to perform various tasks at the same time. Whether or not dyadic training—training two teams together—is beneficial for CPR education and simulations is still unknown.

Hypothesis:
Dyadic training is beneficial for CPR training.

Methods:
We enrolled 267 medical students (164 male and 103 female) in the study. We provided these students with a 2-hour training session on CPR for simulated cardiac arrest. Student teams were split into double groups (Dyad training groups: Groups A and B) or Single Groups. All groups received two CPR simulation rounds. CPR simulation training began with peer demonstration for Group A, and peer observation for Group B. Then the two groups switched roles. Single Groups completed CPR simulation without peer observation or demonstration. Teams were then evaluated based on leadership, teamwork, and team member skills.

Results:
Group B had the highest first simulation round scores overall (P= 0.004) and in teamwork (P= 0.001) and team member skills (P= 0.031). Group B also had the highest second simulation round scores overall (P< 0.001) and in leadership (P= 0.033), teamwork (P< 0.001) and team member skills (P< 0.001). In the first simulation, there were no differences between Dyad training groups with those of Single Groups in overall scores, leadership scores, teamwork scores, and team member scores. In the second simulation, Dyad training groups scored higher in overall scores (P= 0.002), leadership scores (P= 0.044), teamwork scores (P= 0.005), and team member scores (P= 0.008). Dyad training groups also displayed higher improvement in overall scores (P= 0.010) and team member scores (P= 0.022).

Conclusions:
Dyad training was effective for CPR training. Both peer observation and demonstration for peers in dyad training can improve student resuscitation performance.
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.