bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16739: Tricuspid Regurgitation Following Conduction System Pacing Lead Entanglement in Chordae Tendineae
Authors: Chhetri Chandra , Haseeb Shahan , Ansari Umair A , Goyal Rajat
Published: December 2023

Case Description:
A 62-year-old male with symptomatic sinus bradycardia presented for pacemaker implantation. Conduction system pacing (CSP) was pursued using the Medtronic 3830 lead. The lead was advanced through a C315His sheath and positioned at the basal-mid ventricular septum. Passive pacing demonstrated V1 notching and aVR/aVL discordance. An attempt was made to fixate the lead but despite rapid clockwise turns at the proximal lead tip, no lead penetration was seen in the LAO projection. The lead was removed and the sheath was repositioned. A second attempt was made with similar results. When attempting to remove the lead however, the lead remained adherent to the tissue despite multiple counter-clockwise turns. Increasing traction was applied at the proximal lead tip which resulted in elongation of the fixation screw and eventual disengagement from the tissue. Upon examination of the lead tip, there was fibrinous tissue suggestive of either chordae tendineae or valve remnant. Further attempts at CSP were aborted and the patient underwent traditional RV septal lead placement. Transthoracic echocardiogram (TTE) performed following the procedure demonstrated mild-moderate eccentric tricuspid regurgitation, likely due to chordae injury.

Discussion:
Left bundle branch pacing (LBBP) is becoming an increasingly popular form of CSP and requires deep penetration of the septum to engage the left bundle branch. To our knowledge, this is only the second case describing tricuspid valve chordae tendineae entanglement as a result of a CSP attempt. Most often, tricuspid regurgitation due to LBBP is attributed to entrapment of the septal TV leaflet from a basal position of the pacing lead. In our case, we suspect tricuspid valve injury occurred as a direct result of entanglement of the screw into the chordae. Potential ways to mitigate this complication are to pursue a more distal implantation site or to confirm adequate passive injury current prior to fixation to ensure the screw tip engages the myocardial tissue. Most of all, it is important to recognize that when a lead is not advancing into the septum, one should abort the position early and try an alternative site to avoid complications.
Abstract 16765: Association of Evening or Bedtime Dosing of Antihypertensive Medications With Nighttime Blood Pressure and Cardiovascular Prognoses
Authors: narita keisuke , Hoshide Satoshi , Kario Kazuomi
Published: December 2023

Introduction:
Previous studies suggested that bedtime use of antihypertensive medications does not improve cardiovascular outcomes. However, there is a few studies reporting the association of bedtime dosing of antihypertensives with nighttime blood pressure (BP) and cardiovascular prognoses.

Hypothesis:
Evening/bedtime dosing of antihypertensives may improve cardiovascular outcomes through reductions in nocturnal BP.

Methods:
We used the dataset of nationwide prospective, the Japan Ambulatory Blood Pressure Monitoring Prospective (JAMP) study to assess the association of evening/bedtime dosing with nighttime BP and cardiovascular prognoses. Among whole 6,359 participants underwent 24h ambulatory BP monitoring, participants with pre-history of cardiovascular disease and not use antihypertensives were excluded in this analysis. Evening or bedtime and two occasions (morning and evening/bedtime) use of antihypertensives were defined as the group of evening/bedtime dosing.

Results:
Among 4,085 participants (69.1 years and 45% of male), there was no difference between the group of evening/bedtime and morning/others dosing in 24h systolic BP (SBP) (132.9±14.2 vs. 132.0±14.0, p=0.086). Nighttime SBP was higher in evening/bedtime dosing (123.1±17.5 vs. 121.4±16.8, p=0.004). During the median 4.9-years followed-up, 150 cardiovascular events (coronary artery disease, stroke, heart failure) occurred. The evening/bedtime dosing was not associated with cardiovascular events risk adjusted by 24h ambulatory BP (adjusted HR [95%CI], 1.11 [0.78-1.57]) or nighttime BP (Figure). In stratified analysis of participants with or without nocturnal hypertension (nighttime SBP≥120 mmHg or diastolic BP≥70 mmHg), evening/bedtime dosing was also not associated with cardiovascular outcomes.

Conclusions:
Our study suggested that evening/bedtime dosing of antihypertensives did not give benefit for nighttime BP control and cardiovascular prognoses.
Abstract 16782: Depression and Its Relationship With Uncontrolled Hypertension: A Single Urban Center Experience
Authors: Tieliwaerdi Xiarepati , Amoateng Richard , Shah Aaisha , Bilal Muhammad Ibraiz , Manalo Kathryn , Appiah-Kubi Edmund , Johnston Alexandra , Gadani Mrudula
Published: December 2023

Introduction:
Depression and hypertension (HTN) contribute to cardiovascular risks with studies showing that depression increases the risk of developing HTN. However, the impact of depression on blood pressure control in patients with HTN remains unclear. The study aimed to investigate the incidence of depression in patients with uncontrolled HTN.

Methods:
A matched-pair analysis was conducted on 9,046 patients with diagnosis of HTN at a single-center Internal Medicine clinic between 2019 and 2022. Demographic variables, co-morbidities, blood pressure and PHQ 9 scores were recorded. Uncontrolled HTN was defined as BP ≥140/90 mmHg, and PHQ-9 scores ≥ 4 indicated depression. Age- and gender-matched patients with controlled HTN were included for comparison.

Results:
Among 9,046 patients with HTN, 1,886 (20.4%) had uncontrolled HTN. Patients with uncontrolled HTN were older (57.43 ±17.02 vs 46.68 ± 18.6, p=0.000) and more likely to be black (34.1 % vs 29.1%, p<0.000) compared to those with controlled HTN. In the matched-pair analysis (3,660 patients), no significant difference in incidence of depression was observed in patients between uncontrolled and controlled HTN (389 vs 377, p=0.626). Patients with uncontrolled HTN had a higher prevalence of congestive heart failure (150 vs 113, p=0.018) and chronic kidney disease (211 vs 167, p=0.017).

Conclusions:
This single-center matched-pair analysis suggest that depression is not associated with inadequate blood pressure control, despite its role in increasing the risk of developing HTN in prior studies. Optimal blood pressure control plays a crucial role in preventing development of co-morbid conditions as seen in our study. A holistic approach to HTN management and factors beyond depression should be considered. Further research is warranted to gain a deeper understanding of the relationship between depression, HTN, and cardiovascular outcomes, enabling more targeted interventions and improved patient care.
Abstract 16785: Hypertension Induces Metabolite Content Alterations in Hypoperfused Mouse Brain Cortex
Authors: Carnevale Lorenzo , Perrotta Marialuisa , Mastroiacovo Francesco , Carnevale Raimondo , Pacella Jacopo , Carnevale Daniela , Lembo Giuseppe
Published: December 2023

Introduction and aims:
Hypertension is one of the main risk factors for dementias. To understand the link between vasculature and neuronal dysfunction in hypertension-induced cognitive impairment we leverage MRI, a translational imaging tool that let us concomitantly analyze cerebral structure, function and metabolism.

Methods:
Transverse aortic constriction (TAC) was performed in C57Bl/6J mice to induce cerebral hypertension. The brain was characterized by structural MRI, cerebral blood flow (CBF) was analyzed by perfusion MRI and cortical cerebral metabolism was characterized by point-resolved spectroscopy performed on a small-animal dedicated 7T MRI. Finally, we characterized the microvascular structure in regions impacted by hypertension by immunofluorescence.

Results:
TAC mice shown hemodynamic alterations in cortical CBF compared to sham mice (A). Macroscopic volumetric analyses of the cortex shown no significant alterations, however hypoperfused cortical regions shown local cortical thickening, suggesting a local swelling due to inflammatory processes (B). The histological microvascular analysis evidenced capillary Blood-Brain Barrier loss of integrity (C). Finally, this cortical region shown alterations in glucose and glutamine metabolite concentration measured by MR spectroscopy (D).

Conclusions:
Leveraging MRI we have concomitantly characterized the cortical structure, function and metabolism in TAC-hypertensive mice. These alterations in cerebral blood flow and metabolism of glucose/glutamine are biomarkers of ongoing cerebral injury and are potential targets of further investigation to shed light on the interplay between vascular and neuronal injury in hypertension.
Abstract 16791: Conduction System Response to Cardiac Resynchronization Therapy
Authors: Lee Jiyoung J , Bhatt Raj , Yilmaz Mikael , Boyle Noel G , Do Duc H
Published: December 2023

Background:
Cardiac resynchronization therapy (CRT) can be an effective treatment for cardiomyopathy patients with intraventricular conduction delay. However, significant controversy remains over the effect of QRS duration shortening on CRT outcomes. We hypothesize that reduction in QRS duration following CRT implantation is associated with echocardiographic outcomes.

Methods:
We included all adult patients with structural heart disease and CRT followed at UCLA. We reviewed all available electrocardiograms (ECG) and echocardiograms. We excluded patients with CRT for complete heart block, congenital heart disease, and those without intrinsic QRS ECGs prior to CRT.

Patients were categorized as left bundle branch block (LBBB) if Strauss criteria were met prior to CRT implantation. Other patterns (including right bundle branch block with QRS duration ≥150ms) were classified as IVCD. We evaluated QRS duration before and immediately after CRT implantation. Changes in QRS duration post-CRT implant were calculated in percentage change. Echocardiograms were evaluated for changes in left ventricular end diastolic dimension (LVIDD) and ejection fraction (LVEF) following CRT implantation.

Results:
We included 108 patients (mean age of implant 66.1±12.8 years, 65% male, 63% nonischemic cardiomyopathy). Of these, 44 patients (41%) had LBBB. After CRT, patients with LBBB had significant decrease in QRS duration (-9.3±17.0% vs +16.9±30.9%, p < 0.001), improvement in LVEF (12.1±10.5% vs 1.85±10.7%, p < 0.001) and reduction in LVIDD (-0.6±0.7cm vs 0.1±0.7cm, p < 0.001) compared to patients with IVCD. Decrease in QRS duration was significantly correlated with both improvement in LVEF (Pearson r = 0.21, p = 0.037) and reduction in LVIDD (Pearson r = 0.28, p = 0.006).

Conclusion:
CRT resulted in significantly larger decrease in QRS duration amongst patients with LBBB compared to IVCD. QRS duration reduction was, in turn, significantly correlated with improvements in LVIDD and LVEF. This likely reflects the proximal nature of true LBBB, and the ability of CRT to utilize the remaining distal Purkinje system for impulse propagation. Further research on the electrical and mechanical response to CRT can help guide optimization of target populations.
Abstract 168: Circulating Blood Neutrophils Are the Main Source of Plasma Nampt After Cardiac Arrest
Authors: Zhu Xiangdong , Li Jing , Lin Shaoxia , Vanden Hoek Terry L
Published: December 2023

Introduction:
Nampt functions as a novel extracellular damage-associated molecular pattern. It has been shown to be released from many cell types including neutrophils, adipocytes, and hepatocytes. In a mouse model of cardiac arrest, increased plasma Nampt correlates with inflammation, cardiovascular dysfunction and poor survival. However, the source of plasma Nampt after cardiac arrest is unknown.

Hypothesis:
We hypothesize that plasma Nampt is released from blood neutrophils.

Methods:
Circulating blood neutrophils from C57/BL6 mice were depleted by intraperitoneal injection of 500 μg murinized Ly-6G (1A8) antibody. 48 hours later, mice were subjected to 8 min KCl-induced cardiac arrest followed by resuscitation. Saline-treated mice served as the control group. Blood neutrophil counts were measured at 48 h after injection. Plasma NAMPT concentration at 4 h post-resuscitation was measured by ELISA.

Results:
Ly-6G antibody induces a nearly complete depletion of blood neutrophils at 48 h after injection. Neutrophil counts were 1.17 ± 0.07 for saline control mice and 0.12 ± 0.01 (10
6
/ml) for Ly-6G treated mice (p < 0.01). Plasma eNampt concentrations at 4h post-ROSC were significantly lower in Ly-6G treated mice compared to control mice. Plasma concentration of NAMPT decreased from 12.67 ± 0.39 ng/ml for saline-treated mice to 5.34 ± 1.41 ng/ml for Ly-6G treated mice (p < 0.01).

Conclusion:
Circulating blood neutrophils are sufficiently depleted by Ly-6G antibody, and neutrophils are the major contributor to plasma NAMPT during cardiac arrest. The study of neutrophil depletion on post-resuscitation inflammatory cytokine and mouse survival is ongoing.
Abstract 16822: Short Term Outcomes of Endovascular and Surgical Therapies for Critical Limb Ischemia: A Nationwide Analysis
Authors: Naser Ahmad , SAFIRIYU ISRAEL , Akunor Harriet , Fatuyi Michael , Nagraj Sanjana , Flatow Elie , Gashi Eleonora , Sokol Seth I
Published: December 2023

Background:
Endovascular therapy (EVT) and peripheral arterial bypass surgery (PABS) are established revascularization modalities in patients with critical limb ischemia (CLI). However, there is limited data regarding the short term outcomes of both procedures.

Research question:
Is there a difference between the in-hospital outcomes of EVT and PABS for patients with CLI?

Methods:
Patients with a diagnosis of CLI in the National Inpatient Sample database were reviewed from 2018 to 2020, and stratified into EVT and PABS groups. The primary outcome was in-hospital mortality and secondary outcomes included in-hospital complications. Multivariate logistic regression was used to adjust for confounders.

Results:

A total of 14,015 adult patients with CLI were identified (EVT:11,970; PABS: 2045). There was no significant difference in the in-hospital mortality between the two groups (adjusted odds ratio [aOR] 0.43, 95%CI 0.10-1.89 p=0.264). Furthermore, there was no significant difference in the rates of in-hospital complications: septic shock (aOR 0.67, 95%CI 0.18-2.36, p=0.529), acute stroke (aOR 0.54, 95%CI 0.12-2.36, p=0.413), cardiogenic shock (aOR 0.89, 95%CI 0.14-7.84, p=0.973), vascular complications, (aOR 1.66, 95%CI 0.67-4.11, p=0.278), compartment syndrome (aOR 0.24, 95%CI 0.03-1.90, p=0.177), and acute kidney injury (aOR 1.30, 95%CI 0.88-1.90, p=0.184) between the two groups
fig 1
. In addition, the mean length of stay was comparable between the groups 5.95 vs 6.14 days (adjusted mean difference[aMD] 0.23, 95%CI -0.31-0.78, p=0.298. However, the mean hospital costs were significantly lower for the PABS group compared to the EVT group ($24,463 vs $29,400, aMD 0.87 $-3,684, 95%CI $-5,813-$-1,554, p=0.001).

Conclusion:
Endovascular therapy and bypass surgery for CLI had comparable in-hospital mortality and in-hospital complications, although, the hospital cost was significantly higher with endovascular therapy.
Abstract 16825: Brahma Related Gene-1 (BRG1) Protein Mediates Helpful Compensatory Response to Retard Development of Heart Failure
Authors: DeSpain Patrick S , Kuempel Jacob D , Xi Yu , Kidwell Ashley N , Zhang Tianru , Rivera Reed A , Zhang Xiuren , Peng Xu , Tong Carl W
Published: December 2023

Background:
Chromatin remodeling can modulate transcription by changing gene accessibility. Brahma Related Gene-1 (Brg1) protein, which is an adenosine triphosphate catalytic subunit that supports chromatin remodeling, has been implicated in development of hypertrophic cardiomyopathy. However, contribution of Brg1 to the development of heart failure (HF) has not been clearly elucidated.

Hypothesis:
We hypothesize that Brg1 mediates compensatory response to cardiac stress; therefore, loss of Brg1 function will accelerate development of HF.

Methods:
The myosin light chain-2 Cre/loxP system was used to produce cardiac myocyte specific deletion of Brg1(-/-) mouse model with floxed littermates as control.

Results:
At baseline, Brg1(-/-) hearts showed mildly reduced left ventricular ejection fraction (LVEF). Aging to 12 months caused LV dilation and further reduction of LVEF in Brg1(-/-). We used trans-aortic constriction (TAC) for pressure overload challenge and chose similarly severe TAC induced pressure gradient as indicated by similarly fast peak flow velocities across the constriction. At 2-weeks post-TAC, Brg1(-/-) hearts exhibited severely reduced LVEF, severely dilated LV, and decreased ability to thicken LV wall during systole. In contrast, control hearts did not dilate and maintained its LVEF with increased LV wall thickness. Thus, Brg1 deletion greatly diminished the heart’s ability to compensate for aging and pressure challenge, thereby accelerating development of heart failure with reduced ejection fraction (HFrEF). Separately, RNA sequence analyses of 12-months aged hearts showed Brg1 deletion caused upregulation of 810 genes including HF associated long noncoding RNA XIST and down regulation of 50 genes, while 3-months old hearts were not significantly different.

Conclusion:
Brg1 mediates compensatory responses that are helpful to the heart to prevent development of HF; therefore, it is a potential treatment mechanism for HF.
Abstract 16831: Deficiency of Cholesterol Efflux Pathways in Smooth Muscle Cells Enhances Vasoconstriction but Does Not Affect Atherosclerosis
Authors: Halmos Benedek , Westerterp Marit
Published: December 2023

Smooth muscle cells (SMCs) regulate blood flow distribution via vasoconstriction mediated by α-adrenergic receptors (α-ARs). Plasma membrane cholesterol may affect α
1
-AR signaling, but consequences for SMC-mediated vasoconstriction are unclear. Cholesterol loading promotes SMC to macrophage transition
in vitro
, which may enhance atherosclerotic plaque vulnerability. However, the role of ATP Binding Cassette A1 and G1 (ABCA1/G1)-cholesterol efflux pathways in SMC-mediated vasoconstriction and atherogenesis remains poorly understood.

We generated mice with SMC-specific
Abca1/g1
deficiency on the low-density lipoprotein receptor deficient (

Ldlr
-/-

) background by crossbreeding

Abca1
fl/fl
Abcg1
fl/fl
Ldlr
-/-

mice with

Myh11-Cre
ERT2

transgenic mice and feeding them tamoxifen-diet. To induce SMC cholesterol accumulation and atherogenesis, we fed

Myh11-Cre
ERT2
Abca1
fl/fl
Abcg1
fl/fl
Ldlr
-/-

and

Myh11-Cre
ERT2
Ldlr
-/-

mice Western-type diet (WTD) for 16 weeks.

Combined
SMC-Abca1/g1
deficiency increased vasoconstriction in aortic rings induced by the α
1
-AR agonist phenylephrine, with reversal by methyl-β-cyclodextrin, substantiating its cholesterol-dependency. Unexpectedly,
SMC
-
Abca1/g1
deficiency induced urinary bladder enlargement by >20-fold, resembling bladder outlet obstruction (BOO). This was reversed by the α
1
-AR antagonist tamsulosin, indicating its dependence on SMC constriction. Moreover,
SMC
-
Abca1/g1
deficiency decreased SMC markers and increased macrophage- and fibroblast-markers in the bladder wall, enhancing collagen deposition, consistent with SMC transdifferentiation. However, after 16 weeks WTD,
SMC
-
Abca1/g1
deficiency did not affect atherosclerotic lesion size, fibrous cap thickness, necrotic core, collagen, or macrophage content, suggesting that SMCs in atherosclerotic plaques were not affected. This may be due to low
Abca1/g1
expression in intimal SMCs.

We uncover a new role of SMC cholesterol efflux pathways in suppressing α
1
-AR mediated vasoconstriction and bladder SMC transdifferentiation, decreasing BOO. Our data may provide a mechanistic link for the association between BOO and diabetes in humans, particularly because diabetes is associated with decreased cholesterol efflux.
Abstract 16832: Biomarker Enhanced Risk Prediction of Incident Heart Failure in Low-Risk Patients: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Chunawala Zainali , Khan Sadiya S , Qamar Arman , Arora Sameer , Fudim Marat , Vaduganathan Muthiah , Mentz Robert J , Bhatt Deepak , Grodin Justin L , Pandey Ambarish , Caughey Melissa C
Published: December 2023

Background:
Primary prevention strategies to reduce heart failure (HF) burden are urgently warranted. The Pooled Cohort equations to Prevent HF (PCP-HF) risk score is a validated risk tool that integrates readily available parameters obtained in primary care setting to estimate the 10-year risk for incident HF. Although PCP-HF performs well for high-risk individuals, the model’s predictive utility for low-risk individuals may potentially be enhanced by integration of biomarkers.

Methods:
In this study, the PCP-HF risk score was derived from data collected at visit 5 (2011-2013) of the ARIC cohort study and its 5-year predictive accuracy was investigated using surveillance data up to 2019. Participants with <10% PCP-HF risk probability of incident HF were classified as low-risk. Incremental improvement in predicting incident HF by including laboratory and imaging-based biomarkers in the low-risk population was analyzed by logistic regression, by calculating the area under the curve (AUC) from receiver operating characteristics.

Results:
Of 4980 study participants with 5 years of follow up, 47% had a low PCP-HF risk score (mean age 73 years, 71% women, 32% Black). Of these, 3% developed HF within 5 years. Compared to those with a high PCP-HF risk score, individuals with low PCP-HF risk score were younger, more often female and Black; had lower left ventricular (LV) mass index and left atrial volume index, higher magnitude of LV global longitudinal strain, and lower levels of NT-proBNP and hs-TnT. On further analysis, the model incorporating laboratory and imaging-based biomarkers exhibited greater predictive accuracy for incident HF compared to the original PCP-HF risk score in this low-risk population (AUC: 0.85 vs 0.62).

Conclusion:
The integration of laboratory and imaging-based biomarkers with the PCP-HF risk score enhances the predictive accuracy of risk modeling for incident HF, especially in individuals identified as low-risk by the 10-year risk prediction tool.
Abstract 16844: Identifying Splenic Radiomics Features Associated With Risk of Coronary Artery Disease
Authors: Kamineni Meghana , Yu Zhi , Raghu Vineet , Alaa Ahmed M , Schuermans Art , Friedman Sam F , Reeder Christopher , Ellinor Patrick T , Maddah Mahnaz , Philippakis Anthony A , Hornsby Whitney , Natarajan Pradeep
Published: December 2023

Introduction:
Inflammation is a validated mechanism for residual coronary artery disease (CAD) risk via clinical trials and analysis of germline and somatic genetic variation in blood cells. While the spleen plays an important role in regulating inflammation, the role it plays in CAD is unclear.

Hypothesis:
We aim to test the hypothesis that radiographic splenic biomarkers may offer novel insights for CAD.

Methods:
We used deep learning to segment spleens from the abdominal MRIs of 38,474 patients in the UK Biobank. CAD was defined as history of coronary artery bypass grafting, myocardial infarction (MI), coronary artery angioplasty, or billing codes (OPCS-4: K40, K41, K45, K49, K50.2, K75). We extracted image features using the
pyradiomics
package. To identify image features associated with CAD, we used L1-regularized logistic regression models with the splenic features and clinical features used in the Pooled Cohort Equations (PCE) for outcomes of CAD and cardiovascular disease (CVD) events (defined as a composite of CAD, MI, and stroke outcomes). We computed the area under the receiver operating characteristic (AUROC) on a held-out 30% of the patient population and determined 95% confidence intervals using 1,000 Monte-Carlo resampled bootstraps.

Results:
Study participants had mean (SD) age 55.1 (7.5) years, 19,921 (51.8%) were women, 1,412 (3.7%) had CAD, and 2,473 (6.4%) had CVD events. The model to predict CAD using the splenic and PCE features had an AUROC of 0.84 (95% CI, 0.84-0.85), and 3 out of 10 significant covariates were splenic features. 1-SD increases in sphericity, minor axis length, and entropy in neighboring voxel gray levels were associated with 5.4% (95% CI, 5.1-5.7) higher, 13.3% (95% CI, 13.0-13.6) lower, and 10.5% (95% CI, 10.2-10.8) higher odds of CAD after adjustment. Results were consistent in the model to predict CVD events, and decreased minor axis length and increased texture variation were associated with increased risk. Model performance was lower for older age groups, who had higher incidences of CAD.

Conclusions:
This study leverages deep-learning methods across a population based cohort to highlight splenic features correlated with CAD and offers new opportunities to understand the role of the hematopoietic system in CAD.
Abstract 16873: Takotsubo Variant is Associated With Worse Right and Left Ventricular Systolic Function Than Other Stress Cardiomyopathy Variants
Authors: Chedid Maroun , Buda Kevin , Simegn Mengistu , iqbal omer
Published: December 2023

Introduction:
Stress cardiomyopathy (SCM) is usually associated with reduced systolic function on echocardiogram. However, the prevalence of systolic dysfunction between different variables of SCM has not been established.

Hypothesis:
Whether Takotsubo variant SCM is associated with worse systolic function compared to other SCM variants.

Methods:
We conducted a retrospective cohort study evaluating echocardiograms of all patients with SCM between 2010 and 2022 at Hennepin Healthcare, MN, USA. The diagnosis of SCM was made based on the International Takotsubo (InterTak) diagnostic criteria.

Results:
Between January 2010 and December 2022, 296 patients presented with SCM. The majority of patients (N= 173, 58.4%) had the apical (Takotsubo) variant, compared to 78 (26.3%) patients with the midventricular variant and 45 (15.2%) with the basal variant. The three groups had no significant difference in the left ventricular outflow tract and septal diameters. Patients with the apical variant had a lower ejection fraction on presentation compared to mid-ventricular and basal variants (28.1% vs. 36.8% and 35.7%, respectively, p<0.001). Patients with Takotsubo CM had the lowest cardiac output and cardiac index among the three groups (
table 1
). Right ventricular systolic function, evaluated by Tricuspid Annular Plane Systolic Excursion (TAPSE), was lowest in patients with apical SCM (mean TASPE 1.58 cm, p=0.027). All patients had similar ejection fraction recovery at follow-up (mean EF > 55%, p=0.793, mean follow-up time < 4 weeks, p=0.913).

Conclusion:
Takotsubo variant is associated with worse right and left ventricular systolic function compared to other SCM variants, with similar systolic function recovery at follow-up.
Abstract 16875: Prothrombin Complex Concentrate is Superior to Fresh Frozen Plasma for the Management of Bleeding in Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis
Authors: Viana Patricia , Hoffmann Relvas Jessica , Zanchi Persson Marina , Dias Delfino Cabral Thamiris , Sales de Oliveira Jessica , Zanchi Persson Jorge Eduardo , Bonow Paulo A , Souza Freire Camila Veronica , Velasquez Camilo , Amaral Sara
Published: December 2023

Introduction:
Prothrombin Complex Concentrate (PCC) and Fresh Frozen Plasma (FFP) are commonly used for management of bleeding in cardiac surgery patients. However, the relative efficacy and safety of these two strategies remain uncertain.

Hypothesis:
We conducted a meta-analysis to compare outcomes of PCC vs. FFP in patients who undergo cardiac surgery complicated by bleeding.

Methods:
PubMed, Embase, and Cochrane were searched for studies comparing PCC vs. FFP in patients who have cardiac surgery complicated by bleeding. Review Manager 5.4 was used for statistical analysis. Binary and continuous outcomes were compared with pooled odds-ratio and mean differences, respectively. The meta-analysis protocol was registered prospectively in PROSPERO.

Results:
We included 8 studies with 1,500 patients, of whom 613 (40.9%) received PCC. The mean follow-up period ranged from 28-90 days. The PCC group had significantly lower chest tube drainage at 24 hours (MD -148.50 mL; 95% CI -253.02 to -43.99 mL; p = 0.005; I
2
= 42%; Figure 1A). Also, there were fewer units of RBC transfusion within the first 24 hours (MD -1.02 units; 95% CI -1.81 to -0.24 units; p = 0.01; I
2
= 56%; Figure 1B) and fewer patients requiring RBC transfusion within the first 24 hours (OR 0.38; 95% CI 0.28-0.52; p < 0.001; I
2
= 3%) in the PCC group. There was no significant difference between groups in all-cause mortality, thromboembolic events, stroke, or length of hospital stay. A subgroup analysis restricted to RCTs showed a significant reduction in the number of patients requiring RBC transfusion within 24 hours with PCC relative to FFP (OR 0.51; 95% CI 0.27-0.95; p = 0.04; I
2
= 0%).

Conclusion:
These findings suggest that PCC is an effective strategy compared with FFP in reducing chest tube drainage and the need for RBC transfusion within the first 24 hours in patients who undergo cardiac surgery complicated by bleeding, without a significant difference in mortality or thromboembolic events between groups.
Abstract 16881: Endothelial KLF11 is a Novel Endogenous Protectant Against Diabetic Atherosclerosis
Authors: Zhao Guizhen , Zhao Yang , zhu tianqing , Chen Eugene , ZHANG Jifeng
Published: December 2023

Background:
Atherosclerosis is the leading cause of cardiovascular diseases, which is also the primary cause of mortality among diabetic patients. Endothelial cell (EC) dysfunction is a critical early step in the development of atherosclerosis and aggravated in the presence of concurrent diabetes. Krüppel like factor 11 (KLF11), a transcription factor involved in diabetes, inhibits EC inflammation via regulation of NF-κB signaling. However, the potential function of KLF11 in pathogenesis of diabetic atherosclerosis remains undefined.

Methods and results:
Diet-induced type 2 diabetic atherosclerosis model is established in LDLR
-/-
mice by feeding a diabetogenic high-fat diet with cholesterol (DDC). KLF11 expression was increased in ECs from ascending aorta of LDLR
-/-
mice fed DDC diet. Moreover, EC specific KLF11 gain- (transgenic) and loss-of-function (knockout) mice in a LDLR
-/-
background were fed a DDC for 16 weeks. Endothelial KLF11 deficiency (Klf11
ECKO
-LDLR
-/-
) markedly increased atherogenesis, while EC-selective KLF11 overexpression significantly inhibited DDC-induced atherogenesis. Single cell RNA sequencing profiling the ECs isolated from DDC-fed Klf11
ECKO
-LDLR
-/-
mice and littermate controls showed that KLF11 depletion increased endothelial-to-mesenchymal transition (EndMT) during atherogenesis.
In vitro
studies showed that KLF11 not only inhibited EC inflammation and oxidative stress, but also diminished EndMT in response to high glucose. Conversely, knockdown of KLF11 augmented the EC dysfunction and EndMT.

Conclusions:
Our study indicates that endothelial KLF11 protects against diabetic atherosclerosis through inhibition of EC inflammation, oxidative stress and EndMT.
Abstract 16882: Comparison of Regadenoson and Adenosine in First Pass Quantitative Perfusion Cardiovascular Magnetic Resonance in Subjects With Suspected Coronary Microvascular Disease
Authors: Rodriguez-Lozano Patricia , Wang Shuo , Wang Haonan , Ng Ming-Yen , Kim Paul , Singh Amita , Mushtaq Saima , Tsun Hei Sin , Tada Yuko , Hillier Elizabeth , Mariager Christian Østergaard , Salerno Michael , Pontone Gianluca , Urmeneta Javier , Saeed Ibrahim M , Patel Hena , Madsen Simon , Martinez Vicente , Maceira Alicia , Monmeneu Jose , Pazhenkottil Aju P , Benovoy Mitchel , Amir-Khalili Alborz , Janich Martin A , Arai Andrew E , Friedrich Matthias G , Patel Amit R
Published: December 2023

Introduction:
Regadenoson and adenosine are commonly used vasodilators in myocardial perfusion imaging for detection of coronary artery disease. There are no comparative studies of the vasodilator properties of two agents in subjects with suspected coronary microvascular disease (CMD). We aimed to compare the potency of two vasodilators by quantifying myocardial perfusion in subjects with suspected CMD.

Methods:
Subjects with angina and more than two risk factors for CMD (females, or males with diabetes, metabolic syndrome, HTN, hyperlipidemia, and smoking) who had no obstructive coronary disease by invasive coronary angiography or CT angiography were enrolled for first-pass perfusion images using dual sequence. Stress perfusion images were acquired on 1.5T or 3.0T GE Healthcare during adenosine infusion or regadenoson. Rest perfusion images were acquired either 10 minutes following the cessation of adenosine or reversal with aminophylline. Myocardial blood flow (MBF) in ml/min/g and myocardial perfusion reserve (MPR) were quantified using Fermi deconvolution.

Results:
A total of thirty-two subjects were recruited with a mean age of 62±11 years, 53% men, history of hypertension in 91%, diabetes in 72%, hyperlipidemia in 75%, and tobacco use in 16%. Twenty (63%) of subjects underwent adenosine, while twelve (38%) of subjects underwent regadenoson. Regadenoson produced similar stress MBF compared to adenosine (2.30 ± 0.54 vs. 2.35 ± 0.61 ml/min/g, p = 0.66). Rest MBF was higher in the regadenoson group compared to adenosine group (1.35±0.35 vs. 1.12±0.26 ml/min/g, p=0.07). MPR was non-significantly lower in regadenoson compared to adenosine 1.72±0.70 vs.1.89±0.53 ml/g/min, p=0.13).

Conclusions:
Based on fully quantitative perfusion using CMR, regadenoson and adenosine have similar vasodilator efficacy in subjects with risk factors for CMD. However, resting blood flows are slightly higher when regadenoson is used which may impact quantification of MPR.
Abstract 16970: Acetyl-CoA Metabolism: A Catalyst for Improved Vascular Recovery in Limb Ischemia via Transdifferentiation Mechanisms
Authors: Li Shuang , Lu Alexander J , Carter Kaylee N , Nagueh Eric S , Cooke John P , Lai Li
Published: December 2023

Background:
Angiogenic transdifferentiation, the process by which resident fibroblasts transform into endothelial cells, contributes to restoring perfusion and preserving ischemic tissue. The metabolic shift is essential for transdifferentiation in vitro. Acetyl-CoA, a metabolite involved in histone acetylation, is a key substrate, and ATP Citrate Lyase (ACL) is the enzyme responsible for converting citrate to acetyl-CoA. We hypothesized that acetyl-CoA metabolism may regulate vascular recovery in limb ischemia through angiogenic transdifferentiation.

Methods:
We employed
in vivo
Matrigel plug assays, a murine hindlimb ischemia model, fibroblast lineage tracing mice, and ACL fibroblast-specific knockout mice to investigate the function of acetyl-CoA in vascular recovery and transdifferentiation. Isotope tracing assays were conducted to identify the primary carbon sources of acetyl-CoA during transdifferentiation, and pharmacological interventions targeting the corresponding transporters were used to confirm the findings.

Results:
In our hindlimb ischemia model, we observed a significant increase in ACL expression, particularly in fibroblasts, in the ischemic tissue on day 3 after surgery, coinciding with the peak of vascular flow recovery. Subcutaneous administration of Matrigel in mice revealed that ACL knockdown in fibroblasts reduced plug vascularity and the number of induced endothelial cells. Furthermore, both pharmacological inhibition of global ACL expression and genetic suppression of ACL in fibroblasts significantly impaired limb vascular recovery following ischemia. Importantly, inhibition of ACL in lineage-tracing mice resulted in a significant reduction in the population of induced endothelial cells, indicating that ACL ablation in fibroblasts blocked angiogenic transdifferentiation. In addition, we demonstrated that glucose and glutamine were the primary carbon sources for accumulated acetyl-CoA, and inhibition of glucose transporter (Glut1) or glutamine transporter (Slc1a5) significantly impaired transdifferentiation.

Conclusions:
Acetyl-CoA accumulation through ACL-mediated metabolism improves vascular recovery in limb ischemia by promoting angiogenic transdifferentiation.
Abstract 16975: Wheel-Running Exercise Abrogates Enhanced Sympathetic Neural-Immune Interface in Aortic Adventitia of Angiotensin II-Infused Hypertensive Mice
Authors: Cho Jae Min , Zhu Enbo , Roustaei Mehrdad , Vu Khoa , Nahoul Jonah , Chapleau Mark W , Hsiai Tzung K
Published: December 2023

Background:
Artery stiffness causes cardiovascular pathology. Although mechanisms underlying endothelial dysfunction and arterial stiffness are well characterized, it is unknown if neural-immune interaction in aortic adventitia (AA) influences arterial stiffness. We hypothesized that sympathetic innervation and CD68
+
macrophages are increased in AA of Angiotensin II (Ang II)-infused mice leading to increased arterial fibrosis and stiffness, and that voluntary wheel-running exercise (VWR) mitigates these effects.

Methods and Results:
In eight-week-old C57BL/6 male mice, Ang II was infused at 1.5 μg/g/day for 4 weeks with and without VWR. Mean arterial blood pressure [MAP] measured by tail-cuff averaged 135±11 mmHg in Ang II-infused mice (n=5) and 90±10 mmHg in vehicle-infused mice (n=4). Staining for markers of nerve fibers/bundles with Neurofilament A (NF200), sympathetic nerves with tyrosine hydroxylase (TH), nerve endings in AA with synapsin, and CD68
+
macrophages were all increased in AA removed from Ang II-infused mice compared with vehicle-infused mice. The increases in CD68
+
macrophages and extracellular matrix (ECM) were associated with elevated pulse wave velocity (PWV), an index for arterial stiffness (Ang II:
p < 0.05
vs. vehicle). scRNA-seq analyses further corroborated that Ang II infusion promoted fibrosis and macrophage-associated genes in AA. VWR significantly attenuated the Ang II-induced increases in MAP, sympathetic innervation, CD68
+
expression, ECM, and PWV (Ang II+VWR: all
p<0.05
vs. Ang II). To chemically “denervate” the sympathetic nervous system, we injected 6-hydroxydopamine (6-OHDA, 100 mg/kg on day 0 and 250 mg/kg on day 2, then weekly for 4 weeks) or vehicle in Ang II-infused mice. 6-OHDA decreased MAP, sympathetic innervation, macrophage expression, ECM accumulation, and PWV (Ang II+6-OHDA:
p<0.05
vs. Ang II+vehicle, n=3).

Conclusion:
Ang II-induced hypertensive mice develop increases in sympathetic innervation and macrophages in close proximity within AA that define an enhanced sympathetic neural-immune interface in association with vascular fibrosis, arterial stiffness, and hypertension. VWR significantly mitigates these pathophysiological responses.
Abstract 16991: Rare Variants in BMP10 Confer Risk of Pulmonary Arterial Hypertension
Authors: Zhang XueJia , Jiang Rui , Li TianQi , Lv TingTing , Ye MengTing , Ma MingJie , Yang WeiXian , Wang Xiaojian
Published: December 2023

Background:
Genetic mutations in the genes of BMPR2 pathway are the most crucial cause of pulmonary arterial hypertension. BMP10 is the major ligand of BMPR2, but it remains elusive that whether BMP10 mutation are associated with pulmonary arterial hypertension (PAH).

Methods:
Whole exome sequencing was applied to screen the BMP10 mutations in 378 patients with congenital heart disease associated with pulmonary arterial hypertension (CHD-PAH). The pathogenicity of variants was assessed by ACMG guideline. Pedigree structures and familial transmission of variants were analyzed for the case who carried the BMP10 mutation. The deleterious function of BMP10 mutations were analyzed via
in vitro
experiments.

Results:
Five rare and pathogenic BMP10 variants were identified in five patients with CHD-PAH, including three missense mutations (p.Q74R, p.R96Q, p.I335S) and two nonsense mutations (p.Q116Ter, p.R313Ter). These five cases did not carry mutation in other known PAH risk genes. Five BMP10 mutations were classified as uncertain significance(UVS) or likely pathogenic(LP) variants according to ACMG guideline. It was notworthy that the high impact likely loss-of-function variants in BMP10 were found in 0.53% (2 out of 378) of cases, which was significiantly hihger than those of 0.002% (4 out 251106) in the general population from the GnomAD database (P<10
-4
). Familial analysis revealed that a case had inherited the heterozygous BMP10 p.I335S missense variant from her affected mother, strongly indicating the co-segregation of BMP10 mutaiton and PAH phenotype. Functional experiments implied that the missense mutation p.I335S and the nonsense mutation p.Q116Ter both resulted in reduced BMP10 protein expression in 293T cells.

Conclusion:
We identified strong association between rare damaging variants in BMP10 and PAH. The novel BMP10 mutations found in this study will provide new insights into the genetic mechanism of PAH.
Abstract 17005: Brugada Syndrome: Is There a Difference Between Probands and Relatives?
Authors: Scicluna James , Scerri Jeanesse , Debattista Jessica , Scerri Christian , Sammut Mark A , Abela Mark
Published: December 2023

Introduction:
Brugada syndrome (BrS) is an inherited arrhythmic disease that is rarely linked to sudden cardiac death (SCD), often associated with SCN5A mutations.

Hypothesis:
The main objective of this study was to report the demographic, clinical findings and outcomes of a BrS registry in the Maltese Islands, comparing probands and relatives.

Methods:
Data was collected prospectively in all BrS patients. BrS was defined as per the latest European Society of Cardiology SCD guidelines published in 2022. Patients were placed in two groups (proband vs relative).

Results:
120 individuals were included (2.7 per 10,000 individuals) (56.7% male, mean age 44.0±16.5 years at diagnosis, 7.5% athletes). 54 (45.0%) were probands. 61 (50.8%) reported cardiac symptoms. A relevant family history of SCD was present in 55 (46.6%). Follow up period of 49.8 ± 33.3 months.

A spontaneous type 1 brugada pattern was the primary method of diagnosis in probands (71.1%), ajmaline provocation in relatives (71.6%) (p<0.001). Probands reported more symptoms (33.1% vs 17.8%, p<0.0001), documented arrhythmias during holter monitoring (29.0% vs 9.3%, p=0.028), and manifested J /ST elevation during stress testing (14.0% vs 5.3%, p=-0.039). The age at diagnosis was similar for probands and relatives. Similar proportions of atrioventricular block (15.7%), prolonged QRS (10.2%), early repolarisation (12.8%), QRS fragmentation (5.6%), low QRS voltages (5.6%) and pathological TWI (8.3%) were observed in both groups. 18 (20.4%) were identified with a SCN5A mutation (P, LP, VUS as per ACMG criteria). 5 patients (4.2%) had a novel variant. 17 (15.3%) were referred for a VT study. 20 (16.7%) had an ICD implanted, more frequent in probands (34.0% vs 3.1%) (p<0.001). 3 were implanted because of OHCA. 27 (22.5%) were implanted with an ILR, commoner in probands (33.3% vs 16.4%, p=0.047). Two patients (10% of ICD subgroup) had an appropriate ICD therapy. One patient is on quinidine because of refractory shocks.

Conclusions:
The prevalence of BrS in Malta is comparable to other studies. 20.4% (probands) had a SCN5A mutation. The higher incidence of symptoms, arrhythmias, abnormal response during exercise and ICD implantation in probands (vs relatives) may suggest they are a higher risk group.
Abstract 17013: CTX320: An Investigational in vivo CRISPR-Based Therapy Efficiently and Durably Reduces Lipoprotein (a) Levels in Non-Human Primates After a Single Dose
Authors: Morrow Phuong Khanh , D'Souza Sanjay , Wood Tess , Gowda Vivek , Lee Nicolette , Lei Zhang Maria , Pandji Jeremy , Serwer Laura , Steiger Keith , Sula Erisa , Thorstensen Erin , Urbaez Kayla , Usadi Jacob
Published: December 2023

Background:
Genetic and epidemiological studies have identified elevated levels of lipoprotein (a) (Lp(a)) as a direct cause of atherosclerosis and related diseases. CTX320™ is an investigational
in vivo
CRISPR/Cas9 gene editing therapy designed to knock out the apolipoprotein (a) component of Lp(a) in the liver. CTX320 contains Cas9 mRNA and guide RNA (gRNA) formulated for efficient encapsulation into LNPs for
in vivo
administration
.
Here we assessed the efficacy, safety, and durability of CTX320 in primary human cells and non-human primates (NHPs).

Methods:
For
in vitro
studies, primary human hepatocytes were plated and dosed with CTX320 one day later. Cells were harvested after three days and analyzed via Sanger and next-generation sequencing. For NHP studies, cynomolgus monkeys were dosed with either vehicle control or CTX320 at doses ranging from 0.5 to 3 mg/kg. Baseline levels of plasma Lp(a) were established via ELISA prior to dosing and plasma Lp(a) levels were measured at multiple intervals after dosing until the end of each study.

Results:
In primary human hepatocytes, potent, dose-dependent editing of up to >80% was observed with CTX320. In NHPs, dose-dependent editing in the liver of ~10%, ~45%, and ~65% at the 0.5, 1.5, and 3 mg/kg doses, respectively, was observed after treatment with CTX320. Plasma Lp(a) levels were reduced by ~20%, ~80%, and ~90% from baseline in each of these respective groups. These reduced Lp(a) levels were attained by Day 15 and lasted for the duration of the study (Day 84). As is commonly observed with LNP delivery, transient elevation in liver enzymes was observed and resolved within 14 days without intervention. In a separate durability study in NHPs, a single infusion of CTX320 at 2 mg/kg led to significant and durable decreases in plasma Lp(a) levels. By Day 14, plasma Lp(a) levels had decreased by an average of 94% from baseline, which persisted through Day 224. The study is ongoing.

Conclusion:
CTX320 was well-tolerated in NHPs and resulted in high levels of editing in the liver that led to long-lasting reduction in plasma Lp(a). This data suggests CTX320 could be used to reduce plasma Lp(a) levels in humans.
Abstract 17020: Education of Children Improves Awareness of Hypertension, a Novel Method to Improve Health Equity
Authors: Rocha Cherylann , Ladd Amy C , Olson Kristine C , Davis Unice , Smith Grace , Martinez Arianna , Neely Sarah , Dagostino Ralph , Hundley Greg G , Duncan Phillip , Shah Sangeeta
Published: December 2023

Introduction:
Approximately 45% of the U.S. population has hypertension (HTN), with increased prevalence in Black adults in urban areas. HTN is a risk factor for heart disease, stroke, and renal failure. Increasing awareness of HTN during early education may improve health equity.

Hypothesis:
We hypothesized that a science-based educational program administered to primary school students can increase knowledge of HTN with the objective of increasing awareness and health equity.

Methods:
We engaged 95 4th graders in an urban, public school system (44% White, 43% Black, 13% Other) with an innovative, experiential educational program administered across four, one-hour sessions as part of their curriculum. We taught and assessed students’ awareness of HTN across four topics: (1) knowledge of BP & HTN, (2) organ systems impacted by HTN, (3) habits to maintain a healthy BP, and (4) their competence to operate a BP monitor according to AHA recommendations. Assessments were completed via surveys of 21 individual data points and administered pre-and post-program with each child as their own control. Paired t-tests were used to analyze the pre- and post-survey data.

Results:
Of the 95 students who underwent the program, 71 children had both pre- and post-program results. Comparison of pre-and post-program data showed a statistically significant improvement in students’ knowledge about healthy nutrition, organs affected by HTN, and understanding of blood pressure/HTN (53% to 90%, 20% to 75%, and 40% to 77%, respectively)[p<0.001 for all; Table below]

Conclusions:
Implementing an educational program focused on knowledge of nutrition, organ systems, and BP to 4th-grade students significantly raised awareness of HTN. This innovative program in an urban public school is feasible and may be the first step to decreasing the morbidity of a highly prevalent and modifiable disease in a community.