bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13838: Smooth Muscle Cells Are the Origin of the Majority of Foam Cells in Atherosclerotic Lesions of Apolipoprotein E-deficient Mice
Authors: Wang Ying , Allahverdian Sima , Dubland Joshua A , Asonye Enyinnaya , Seidman Michael A , Francis Gordon A
Published: April 2024

Background:
Apolipoprotein E-deficient (ApoE
-/-
) mice are the most frequently used model of human atherosclerosis. Foam cells in mouse lesions have been believed to be primarily macrophage-derived using traditional staining with macrophage markers. Recent studies indicated that smooth muscle cells (SMCs) comprise at least 50% of foam cells in human coronary atherosclerosis, and express reduced levels of ATP-binding cassette transporter A1 (ABCA1) when compared to intimal leucocytes. Identification of SMC-derived foam cells is challenging due to the absence of classic SMC markers and expression of macrophage markers by a high percentage of intimal SMCs in mouse and human lesions.

Hypothesis:
Unlike human atherosclerosis, foam cells in ApoE
-/-
mice are primarily macrophage- rather than SMC-derived.

Methods:
8-week-old male and female ApoE
-/-
mice were fed a Western diet for 6 weeks to promote lesion development. Flow cytometry was used to estimate the proportion of leukocyte- and SMC-derived foam cells in cell suspensions from digested ascending aortas. Foam cells were identified by the neutral lipid dye BODIPY, and leukocyte-derived were distinguished from SMC-derived foam cells by expression of CD45 (a pan-leukocyte marker), and I-A/I-E (antigen presenting cell markers), which have not been reported to be expressed by SMCs. SMC origin was confirmed using a SMC-specific epigenetic lineage marker. ABCA1 level was also measured in the two foam cell populations.

Results:
69.47±3.20 % (male) and 73.33±2.35 % (female) (mean ± SEM, n=9 each) of foam cells in ApoE
-/-
mouse lesions were CD45 and I-A/I-E negative, and were confirmed by SMC lineage marker to be predominantly SMC-derived. SMC-derived foam cells were thus significantly greater than leukocyte-derived foam cells in ApoE
-/-
mice (
P
<0.01), and exhibited three times lower ABCA1 protein than leukocyte-derived foam cells in both sexes.

Conclusions:
Contrary to our hypothesis, SMCs contribute the majority of foam cells in ApoE
-/-
mouse atherosclerosis. Impaired ABCA1 expression in SMC foam cells, as seen in human intimal SMC foam cells, suggests a likely mechanism for preferential SMC foam cell development in both species, and a potential target for atherosclerosis treatment and prevention.
Abstract 13841: Transcriptomic Signatures of Atrial- And Ventricular-like Human Induced Pluripotent Stem Cell Derived Cardiomyocytes
Authors: Churko Jared , Treutlein Barbara , Garg Priyanka , Venkatasubramanian Meenakshi , Wu Haodi , Chen Shih-Yu , Chen Wen-Yi , Lee Jaecheol , Termglinchan Vittavat , Mantalas Gary , Neff Norma , Jabart Eric , Nolan Garry , Salomonis Nathan , Wu Joseph
Published: April 2024

Differentiation of cardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) can be used to gain insight into the signaling pathways that regulate human heart development. The resulting hiPSC-CMs formed have been reported to possess either atrial- or ventricular-like characteristics and uncovering the molecular mechanisms which regulate the development of these cardiomyocyte subtypes will be instrumental in drug screening and disease modelling research efforts. To investigate the molecular signatures of atrial- and/or ventricular-like hiPSC-CMs formed after differentiation, we profiled the transcriptomic signatures of day 30 hiPSC-CMs using single-cell RNA-seq. Using unsupervised and supervised clustering approaches, we defined distinct subpopulations of hiPSC-CMs representing different stages of maturity as well as expressing atrial or ventricular markers. Expression of
NR2F2
was found to be specifically enriched within the atrial defined subpopulation while
HEY2
expression was enriched within the ventricular defined subpopulation. To further investigate the role that these transcription factors play in defining each cardiomyocyte subpopulation, we created cell lines deficient in either
HEY2
or
NR2F2
using CRISPR technology. Patch-clamp analysis revealed an increase in atrial-like action potentials within
HEY2
gene-edited cardiomyocytes and single cell Westerns revealed a decrease in the expression of the ventricular marker
MYL2
within these cells. Finally, by assessing the temporal expression of transcription factors during differentiation by RNA-seq (along with CyTOF analysis), we observed that the expression of atrial markers preceded the expression of ventricular markers. By defining the transcriptomic signatures of cardiomyocyte subpopulations using single-cell RNA-seq and additional novel supporting methods, we provide a platform for understanding human heart developmental pathways in vitro, hiPSC-CM heterogeneity, and cardiomyocyte subtype specificity.
Abstract 13847: Impact of the Unzipping Technique on Pulmonary Artery Structure and Growth
Authors: Lamers Luke , Nygard Cole , Luehrs Rachel , Roldan Alejandro , Bates Melissa
Published: April 2024

Introduction:
With the unzipping technique, small diameter stents are implanted to relieve pulmonary artery (PA) stenosis, subsequently dilated, fractured and re-stented with large stents dilatable to adult PA diameters. The unzipping technique is utilized in clinical practice with undefined long term results. This study assessed the impact of unzipping on PA structure and growth.

Methods:
Twelve piglets with left PA (LPA) stenosis underwent the unzipping sequence at 6, 10 and 18 weeks of age and were compared to normal controls and controls with untreated LPA stenosis. 2D and 3D rotational angiography pre/post interventions and PA histology was performed on all animals.

Results:
Eleven of twelve animals completed the three catheterizations. One stent (4 mm implant diameter) could not be crossed at the second procedure. Following the interventions, the diameter of the unzipped LPA was similar to the proximal LPA of normal controls (14 mm ± 1.2 vs 14.7 mm ± 1,
p
= 0.19). The diameter of the distal LPA was larger in normal controls, compared to interventions and controls with untreated LPA stenosis (14.6 mm ± 0.9 vs 11.6 mm ± 1.9, vs 10 mm ± 1.2,
p
< .01). Diameters of six 1
st
order LPA branches were similar between normal controls and interventions, and larger than the branch diameters in the stenosis controls. Right PA (RPA) dimensions were larger in controls with untreated stenosis, compared to normal controls and interventions (17.8 mm ± 1.2 vs 16.2 mm ± .9 vs 16 ± 1.7 mm p<0.05). RPA 1
st
order branching diameters were similar for normal controls and interventions. RPA 1
st
order branch diameters in stenosis controls were larger for 3 of 6 branches compared to normal controls and 1 of 6 compared to interventions. Histologically, the distal LPA displayed uniform fibrointimal proliferation and smooth muscle hypertrophy in pigs with both interventions and untreated stenosis. Focal RPA fibrointimal proliferation was noted in stenosis and intervention animals.

Conclusion:
PA growth distal to the unzipped segment is partially compromised, yet 1
st
order branch diameters are normal and significantly larger, compared to untreated stenosis. Histological vascular abnormalities are noted bilaterally in stenosis animals which do not normalize following the unzipping technique.
Abstract 13869: The Usefulness of Echocardiographic Indices of Right Ventricular Systolic Function in Patients With Interstitial Pneumonia
Authors: Amano Masashi , Izumi Chisato , Obayashi Yuki , Fuki Masayuki , Imanaka Miyako , Nishimura Shunsuke , Kuroda Maiko , Imamura Sari , Onishi Naoaki , Sakamoto Jiro , Tamaki Yodo , Enomoto Soichiro , Miyake Makoto , Tamura Toshihiro , Kondo Hirokazu , Kaitani Kazuaki , Nakagawa Yoshihisa
Published: April 2024

Introductions:
It is well known that interstitial pneumonia (IP) may induce pulmonary hypertension, but there have been few studies about right ventricular (RV) function in patients with IP and usefulness of echocardiographic indices in its evaluation.

Methods:
We retrospectively investigated 200 consecutive patients with IP. Patients with left heart failure or emphysema were excluded. Conventional left ventricular (LV) parameters and indices of RV function, such as tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and longitudinal strain of right ventricular free wall (RVLS) were evaluated. As a substitute for pulmonary vascular resistance, pressure gradient calculated by peak velocity of tricuspid regurgitation (TRPG) / cardiac output (CO) was used. Stage of IP was classified as mild, moderate, and severe, based on the degree of fibrosis and involvement area with CT images.

Results:
The mean age was 70.5±8.7 years (122 males (61%)). Stage of IP was graded as mild in 96 patients (48%), moderate in 71 patients (35.5%), and severe in 33 patients (16.5%). All LV parameters were normal at all stages of IP. FAC, which is an index of transverse RV systolic function, has not decreased until IP became severe (42.4±7.9 at mild vs. 40.7±7.5 at moderate vs. 32.7±7.1% at severe stage). On the other hand, TAPSE and RVLS, which are indices of longitudinal RV systolic function, showed graded reduction as stage of IP progressed (TAPSE: 21.1±3.0 vs. 18.0±3.3 vs. 15.2±3.2 mm; p<0.01, RVLS: -20.2±4.2 vs. -18.3±5.0 vs. -15.1±3.9%; p<0.01) and these indices have decreased at earlier stage of IP although TRPG and TRPG/CO were not elevated at this stage. (TRPG: 22.5±3.9 vs. 28.2±10.0mmHg, TRPG/CO: 5.0±1.7 vs. 6.1±2.1; mild vs. moderate). In ROC analysis, TAPSE (AUC=0.82) showed high predictive value for distinguishing between mild and moderate /severe IP, and the optimal cut-off values were 18.4mm (sensitivity: 80.0%, specificity: 70.2%).

Conclusion:
RV dysfunction progressed as stage of IP progressed. TAPSE and RVLS as the indices of longitudinal RV systolic function are useful to detect the earlier stage of RV dysfunction in patients with IP.
Abstract 13877: 5-Year Impact of Catheter Ablation for Atrial Fibrillation in Patients With a Prior History of Stroke
Authors: Bunch Thomas J , May Heidi T , Bair Tami L , Cutler Michael J , Crandall Brian G , Jacobs Victoria , Mallender Charles , Osborn Jeffrey S , Weiss J. P , Day John D
Published: April 2024

Background:
Catheter ablation of atrial fibrillation (AF) is an established therapeutic rhythm approach. Patients with a prior history of a stroke (CVA) represent a unique high-risk population for recurrent thromboembolic events. The role of antiarrhythmic treatment on the long-term natural history of stroke recurrence in these high patients is not fully understood.

Hypothesis:
The process of AF ablation will impact the long-term history of disease progression in high risk CVA patients.

Methods:
3 patient groups with a prior CVA and 5 years of follow-up were matched 1:3:3 by propensity score (±0.01): AF ablation patients receiving their first ablation (n=139), AF patients that did not receive an ablation (n=416), and CVA patients without clinical AF (n=416). Prior CVA was determined by medical chart review using ICD 9/10 codes. Patients were followed for 5-year outcomes of recurrent CVA, heart failure, death.

Results:
The average age of the population was 69±11 years and 51% male. The AF was paroxysmal in 25%, persistent in 34.7%, and longstanding persistent in 41%. AF ablation patients had higher rates of hypertension (p<0.0001), but diabetes prevalence was similar between the groups (p=0.50). Propensity-matched 5-year risk of CVA (HR=2.26, p<0.0001, Figure) and death (HR=2.43, p<0.0001) were higher in the AF, no ablation group compared those that were ablated. When comparing AF, ablation to no AF patients, there was not a significant difference in 5-year risk of for CVA (HR=0.82, p=0.39) and death (HR=0.92, p=0.70), however heart failure risk was increased (HR=3.08, p=0.001).

Conclusion:
In patients with a prior CVA, the system and approach towards the management of AF in patients that undergo ablation is associated with lower rates of recurrent stroke compared to AF patients that do not undergo ablation. The CVA rates are similar to a non AF population to suggest the potential of altering the natural history of disease progression.
Abstract 13929: Cardiopulmonary Fitness Index a Novel Index That Improves Prognostic Assessment of Patients With Idiopathic Pulmonary Arterial Hypertension
Authors: Tang Yi , Luo Qin , Zhao Zhihui , Gao Liu , Jin Qi , Xiong Changming , Liu Zhihong
Published: April 2024

Background:
Peak oxygen consumption or ventilator efficiency, which can better provide prognostic information in patients with idiopathic pulmonary arterial hypertension (IPAH) remains controversial, and studies showed circulatory power and ventilatory power were both variables predictive of prognosis in patients with left heart failure. This study was aimed to assess whether circulatory power and ventilatory power were also variables predictive of prognosis in patients with IPAH, and whether a new variable that was defined as peak oxygen consumption (peak VO
2
) divided by minute ventilation/carbon dioxide production at anaerobic threshold (VE/VCO
2
@AT), which we labeled cardiopulmonary fitness index, can better predict prognosis in patients with IPAH.

Methods:
Patients with newly diagnosed IPAH underwent symptom-limited cardiopulmonary exercise testing from 1 January 2011 to 1 January 2014 in Fuwai hospital and were followed for up to 66 months for major cardiac events (mortality and lung transplantation). Prognostic value was assessed by survival curves (Kaplan-Meier method) and uni- and multivariate Cox analyses.

Results:
One hundred forty-two patients with IPAH (105 female, mean age, 33±11years) were studied. During follow-up (mean: 43±14 months), 25 patients died and 1 patient underwent lung transplantation. In a univariate analysis, peak VO
2
, VO
2
@AT , VE/VCO
2
@AT, cardiopulmonary fitness index , circulatory power, ventilatory power, peak heart rate , NT-ProBNP, pulmonary vascular resistance (PVR), cardiac index (CI ) , WHO functional class were all predictive of cardiac events (all
P<
0.05). Multivariate analysis demonstrated that only NT-ProBNP and cardiopulmonary fitness index were the indicators of prognosis (chi-square=7.51,
P
=0.006; chi-square=7.26,
P
=0.007, respectively).The mortality rates of 1- , 2- and 3-year for patients with cardiopulmonary fitness index≤0.29 mL·kg
–1
·min
–1
were 8.3%, 16.6% and 23.3% respectively.

Conclusions:
Cardiopulmonary fitness index, rather than circulatory power or ventilatory power provides prognostic information in patients with IPAH.

ClinicalTrials.gov: NCT02061787.
Abstract 13933: A Comparative Analysis of 30-day Readmission Rates, Etiologies and Resource Utilization Following Transcatheter and Surgical Aortic Valve Replacement From the Nationwide Readmission Database
Authors: Arora Shilpkumar , Panaich Sidakpal , Patel Viralkumar , Patel Nilay , Bambhroliya Chirag , Dhaduk Kartik , Shah Harshil , Patel Smit , Lahewala Sopan , Tripathi Byomesh , Patel Prashant , Deshmukh Abhishek , Grines Cindy , Badheka Apurva
Published: April 2024

Background:
There is sparse comparative data on short-term readmissions following Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR).

Methods:
The study cohort was derived from the National Readmission Data (NRD) 2013, a subset of the Healthcare Cost and Utilization Project (HCUP) sponsored by AHRQ. TAVR and SAVR were identified using appropriate ICD-9-CM codes (TAVR - 35.05, 35.06 & SAVR - 35.21, 35.22) as either primary or secondary procedural codes. Variables which could affect treatment assignment, were adjusted with propensity score match analysis and Match (1:1) cohort was generated. Readmission causes were identified by ICD 9 code in primary diagnosis.

Results:
Our analysis included 3,886 TAVR and SAVR procedures each in the propensity matched cohorts. There was no significant difference in terms of readmission rates amongst patients who underwent TAVR vs. SAVR [21.41% vs. 21.07% (OR: 1.02, 95% CI: 0.92 - 1.14) p = 0.702]. Cardiac etiologies were more likely to be responsible for readmissions following SAVR (42.66% vs. 35.91%, p = 0.006). Atrial fibrillation (AF) was a much more common cause of readmission following SAVR (7.81% vs. 3.37%, p <0.001). Overall vascular (3.24% vs. 1.32%, p = 0.006) and bleeding complications (9% vs. 6.2%, p = 0.025) were more likely to result in readmission in patients undergoing TAVR. Cost of care of index admission and readmission was similar in both groups. Readmission mortality was higher amongst patient with TAVR vs. SAVR (6.49 vs. 3.91, p = 0.02). 50% of TAVR and SAVR readmission occur within 11 days post discharge.

Conclusion:
In our study from a large nationwide database, there was no significant difference in readmission rate, median readmission rate and resource utilization between TAVR and SAVR. Arrhythmias especially AF accounted for more SAVR readmission and Bleeding/vascular complications were more commonly responsible for readmissions following TAVR.
Abstract 13939: Cardiac Resynchronization Improves Cardiac Sodium Channel mRNA Splicing Most in Patients With Severe Heart Failure
Authors: Jiang Ning , Zhou Anyu , Imran Hafiz , Shi Guangbin , Kaseer Bahaa , Siu Vincent , Rijal Jharendra , Chu Antony , Donaldson David , Kim Michael , Kirk Malcolm , Philips Binu , Orlov Michael , Dudley Samuel C
Published: April 2024

Introduction:
Heart failure (HF) downregulates full-length cardiac sodium channel (SCN5A) mRNA and upregulates the splicing variant D (VD), which encodes a prematurely truncated, nonfunctional channel. Recently, we have shown that the ratio of circulating VD to full-length mRNA can predict the risk of sudden death. Cardiac resynchronization therapy (CRT) improves heart function and decreases arrhythmic events. Nevertheless, the mechanisms are unclear.

Hypothesis:
We tested whether CRT altered circulating full-length SCN5A mRNA and VD and further investigated its correlation with clinical parameters in HF.

Methods:
HF patients with new implantable cardioverter-defibrillators (ICDs) for primary prevention were enrolled. Circulating SCN5A and VD levels at baseline and at a follow-up visit were measured and compared using the ratio of VD to total SCN5A transcripts. The change of VD was expressed as the difference between the proportion of VD levels at baseline and at a follow-up visit.

Results:
A total of 81 HF patients were enrolled. At enrollment, patients with lower ejection fraction (EF) (≤30%) had higher circulating VD levels (0.80±0.11 vs. 0.73±0.07, P<0.05). After a median follow-up of 235 days, the VD ratio significantly improved (0.84±0.08 vs. 0.74±0.10, P<0.01) in patients receiving CRT. In patients without CRT, the VD ratio had significantly increased (0.77±0.07 vs 0.84±0.05, P<0.05). In patients with CRT, the change of the VD ratio significantly correlated with left ventricular end systolic diameter (r=0.853, p<0.01), EF (r=-0.643, p<0.05) and ischemic cardiomyopathy (r=0.645, p<0.05).

Conclusions:
CRT decreased the proportion of nonfunctional sodium channels, which may explain the lower arrhythmic risk with CRT therapy. Furthermore, the improvement was more prominent in patients with left ventricular dilation, lower EF and ischemic cardiomyopathy.
Abstract 13948: High Intraprocedural Atrial Fibrillation Termination Rate by Large Area Rotor Ablation Combined With Pulmonary Vein Isolation
Authors: Kis Zsuzsanna , Bhagwandien Rohit , Theuns Dominic , Wijchers Sip , Szili-Torok Tamas
Published: April 2024

Introduction:
There remains contradictory data about the optimal ablation technique and the type of termination of atrial fibrillation (AF) ablation particularly in patient (pt) with persistent AF. The aim of this study was to determine the type of the termination of persistent AF during combined conventional and rotor ablation.

Method:
This is a single-center, prospective, observational study enrolled thirty-eight pts (24/63% male, mean age 63 years) with AF (mean left atrial size: 46,2 ± 7 mm), who underwent focal impulse and rotor modulation (FIRM) mapping and large area ablation around the core of the identified rotor(s), followed by conventional pulmonary vein isolation(PVI) using contact force catheter aiming 10-20 gr depending on the location. Two distinctive types of the AF termination were defined: sub-acute termination related to rotor elimination, furthermore acute termination due to PVI. Electric cardioversion (ECV) was executed only in the absence of spontaneous conversion to sinus rhythm (SR).

Result:
In 10(26%) pts acute AF termination after PVI was observed. In further 12 (31%) pts sub-acute termination of the AF could be observed after the identified rotor ablation. The combined technique of conventional and rotor ablation of pts with persistent AF resulted in 57,8% of termination rate. Spontaneous cardioversion could not be reached in 16 (42%) pts however 15 out of them were converted to SR by ECV. Procedural complication occurred in 3 pts presenting with groin hematoma, in one patient left atrial appendage (LAA) thrombus was revealed by transoesophageal echocardiography performed right after the ablation for guiding the planned LAA closure.

Conclusion:
Large area rotor ablation drag technique combined with contact force sensing technique results in a high termination rate of persistent AF. More studies are warranted to define the clinical significance and long term success rate of rotor ablation in pts with persistent atrial fibrillation.
Abstract 13962: Goals of Care Intervention in Advanced Heart Failure
Authors: Dougherty Cynthia M , Doorenbos Ardith Z , Levy Wayne C , Curtis J R
Published: April 2024

Introduction:
Guidelines for care in Stage D advanced heart failure (HF) include discussions of prognosis, advance care planning, and deactivation of the implantable defibrillator, along with symptom management and quality of life. The
purpose
of this study was to evaluate, among adults with advanced HF and their HF providers, the effect of a communication intervention designed to improve patient-provider communication about goals of care (GoC) that incorporated prognostic information from the Seattle HF Model (SHFM).

Hypothesis:
Patients in the GoC intervention will demonstrate increased numbers of GoC conversations, quality of communication, quality of life, with reduced depression and anxiety compared to usual care (UC).

Methods:
Eighty patients (40/group) with a diagnosis of HFrEF (EF%< 40%), mean age 58.2±11.2 years, 76.3% male, 82.5% Caucasian, EF%=30.3±9.7%, 1 year SHFM scores of 95.1% participated in a RCT comparing GoC to UC. HF providers were physicians and APRNs (N=9) in a tertiary care academic medical center. The GoC intervention: HF education, ICD deactivation information, and the Five Wishes directive, delivered in a nurse-led telephone discussion that preceded a subsequent HF clinic visit. At baseline and after the HF visit, the Quality of Communication (QOC), Kansas City Cardiomyopathy Questionnaire (KCCQ), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder (GAD-7) scales were completed. Numbers of GoC conversations are verified with medical records. Analysis of variance will be used to determine effects on study outcomes.

Results:
There was a significant increase in goals-of-care conversations (73% vs, 2.6%,
p
<0.001) and quality of end-of-life communication (
p
=0.03) in the GoC group compared to UC after the intervention. There were no significant differences between groups on quality of life, anxiety, or depression. HF providers noted that having a GoC conversation within a regular HF clinic visit took additional clinic time.

Conclusions:
The GoC intervention resulted in more GoC conversations and higher quality communication between HF patients and HF providers without increased anxiety or depression. Further studies are needed to assess impact on longer-term quality of care and patient outcomes.
Abstract 13974: Loss of Endothelial Primary Cilia Promotes Thrombus Formation in Mice
Authors: Yau Jonathan W , Singh Krishna K , Lei Xi , Quan Adrian , Teoh Hwee , Al-Omran Mohammed , Ni Heyu , Verma Subodh
Published: April 2024

Introduction:
Recent evidence suggest that endothelial cilia may suppress anti-inflammatory signaling and protect against atherosclerosis. Given that atherosclerosis predisposes to thrombosis, we hypothesized that endothelial cilia may also play a fundamental role in thrombogenesis.

Hypothesis:
We hypothesize that endothelial cilia is important for protection against thrombosis, and that loss of endothelial cilia promotes thrombus formation in mice.

Methods:
We focused on the intraflagellar transport 88 (IFT88) gene since endothelial deletion of IFT88 has been associated with decreased atherosclerotic lesions in a murine model of atherosclerosis. Key thrombosis-associated molecules were evaluated in IFT88-silenced human umbilical vein endothelial cells (HUVECs). Thrombi formation were monitored in the laser-injured cremasteric arteries of 8 week old male endothelial cell (EC) specific IFT88 knockout (EC-IFT88
-/-
) mice.

Results:
Compared to scrambled siRNA-treated HUVECs, those exposed to siIFT88 exhibited lower mRNA and protein levels of tissue factor pathway inhibitor (TFPI) and thrombomodulin, two key regulators of blood coagulation (-27% and -20%, respectively; N=3; p < 0.05). We next examined the effect of IFT88 loss on thrombosis in mice. Upon laser-induced injury, we determined, via mean fluorescence intensity, that although the thrombi formed in the cremasteric arteries of EC-IFT88
-/-
mice were similar in size to those produced in the wild type (WT) mice (2.2 ± 0.6 and 2.0 ± 0.3 AU, respectively; x10
6
; N=32 thrombi; p=0.8), the average rate at which thrombi developed was significantly faster in the EC-IFT88
-/-
mice relative to that in WT mice (97 ± 11 and 57 ± 3 AU/s, respectively; N=32 thrombi; p<0.001).

Conclusions:
Loss of endothelial IFT88 results in decreased TFPI mRNA and protein expression in HUVECs. EC-IFT88
-/-
mice exhibited earlier thrombi formation in our laser injury model of thrombosis. These results collectively suggest that endothelial cilia intricately regulates thrombus formation in a TFPI-dependent manner and represents a previously unrecognized target to modulate thrombosis susceptibility.
Abstract 13986: Beta-blocker Therapy Reduces Adverse Aorta-Related Events in Patients With Type B Acute Aortic Intramural Hematoma
Authors: Nakashima Masaki , Kaji Shuichiro , Murai Ryosuke , Sasaki Yasuhiro , Ota Mitsuhiko , Kim Kitae , Yamane Takafumi , Kitai Takeshi , Kobori Atsushi , Kinoshita Makoto , Furukawa Yutaka
Published: April 2024

Background:
Optimal medical therapy is widely accepted as a first line therapy for patients with type B acute aortic intramural hematoma (B-IMH). Beta-blocker therapy is supposed to be effective for prevention of aortic dilatation by decreasing aortic wall stress. However, benefits of beta-blocker therapy have not been rigorously shown in B-IMH compared with type B acute aortic dissection with patent false lumen. The purpose of this study was to assess the association of beta-blocker therapy and clinical outcomes in B-IMH patients.

Methods and Results:
A total of 193 consecutive acute B-IMH patients admitted to our hospital and discharged alive were retrospectively analyzed. The mean age was 71±10 years and 124 (64%) patients were men. Of the 193 patients, 165 patients (85%) were treated with beta-blocker therapy at discharge. We compared the incidence of aorta-related adverse events, a composite of end-organ or limb ischemia, aortic rupture, recurrent dissection, aortic expansion ≥5 mm, and aortic surgery, between the patients with and without beta-blocker therapy. During a mean follow up of 4.2years, 16 of 165 (9.7%) patients with beta-blocker therapy developed aorta-related adverse events, whereas 8 of 28 (29%) patients without beta-blocker therapy developed aorta-related adverse events (p<0.001). A multivariate Cox regression analysis adjusted for age, gender and prevalence of hypertension indicated that beta-blocker therapy was associated with a significantly reduced risk for aorta-related adverse events (hazard ratio=0.33, 95% confidence interval: 0.14-0.83, p=0.02).

Conclusions:
Beta-blocker therapy was associated with a significantly reduced risk for aorta-related adverse events in patients with type B acute aortic intramural hematoma.
Abstract 13987: Comparative Effectiveness and Clinical Safety Between Dabigatran, Rivaroxaban, and Warfarin
Authors: Lai Chao-Lun , Chen Ho-Min , Lin Ting-Tse , Liao Min-Tsun , Chan K. Arnold
Published: April 2024

Background:
Several new oral anticoagulants have been developed for prevention of stroke/systemic embolism in atrial fibrillation (AF) patients. This retrospective cohort study aimed to provide real world data concerning the comparative effectiveness and clinical safety between dabigatran, rivaroxaban, and warfarin.

Methods:
Incident adult users of oral anticoagulants with a diagnosis of AF at prescription were extracted from the National Health Insurance claims database in Taiwan from between Jun. 1 2012 and Dec. 31 2013. Two propensity scores were derived using multinomial logistic regression to model the probability of receipt of three study medications as a function of baseline characteristics. The proportional hazards models with adjustment of the quintiles of the propensity scores were used to estimate the relative hazards of specific outcomes between study groups.

Results:
Totally, 16930 subjects including 4280 with dabigatran, 1499 with rivaroxaban, and 11151 with warfarin were identified. The mean age was 72.7 years and the median follow-up duration 8.7 months. Both dabigatran group (adjusted hazard ratio [aHR] 0.37, 95% confidence interval [CI] 0.30-0.46) and rivaroxaban group (aHR 0.50, 95% CI 0.37-0.66) possessed a lower risk of all-cause death in comparison with warfarin group. Comparing with warfarin group, dabigatran group and rivaroxaban group were also associated with lower risks of ischemic stroke (aHR 0.48, 95% CI 0.39-0.59 for dabigatran and aHR 0.50, 95% CI 0.36-0.69 for rivaroxaban), arterial embolism/thrombosis (aHR 0.42, 95% CI 0.26-0.68 for dabigatran and aHR 0.38, 95% CI 0.18-0.83 for rivaroxaban), and intracranial hemorrhage (aHR 0.29, 95% CI 0.16-0.51 for dabigatran and aHR 0.48, 95% CI 0.25-0.95 for rivaroxaban). In addition, we found no statistically significant difference between dabigatran and rivaroxaban in the risks of all the clinical outcomes studied.

Conclusions:
Both dabigatran and rivaroxaban were associated with significant reductions in risks of all-cause death, ischemic stroke, arterial embolism/thrombosis, and intracranial hemorrhage, compared with warfarin. Besides, no significant difference could be found in the risks of various clinical outcomes between dabigatran and rivaroxaban.
Abstract 13990: Early Clinical Experience of Trans-Catheter Closure of Patent Ductus Arteriosus in Extremely Premature Neonates
Authors: Philip Ranjit , Balduf Kaitlin , Washington Kristin , Chilakala Sandeep , Arevalo Alejandro , Fagan Thomas , Waller B. Rush , Sathanandam Shyam
Published: April 2024

Introduction:
Children born prematurely often have a patent ductus arteriosus (PDA). Surgical ligation of the PDA is standard when pharmacologic therapy fails. Trans-catheter closure of PDA (TCCPDA) in premature neonates is a relatively new technique.

Hypothesis:
To describe our early clinical experience of TCCPDA in premature neonates who require positive pressure ventilation (PPV) and to identify risk factors for poor respiratory outcomes.

Methods:
A retrospective review was performed. A respiratory severity score (RSS) was calculated for all patients. The change in the RSS post-procedure and the time taken for return to pre-procedure RSS were used as outcome variables. Patients with pulmonary artery systolic pressure >50% of the systolic blood pressure were considered to have pulmonary hypertension (PHT).

Results:
Thirty premature neonates (25.7±2.8 weeks’ gestation, birth weight=756±284 g) that were PPV dependent with or without PHT were referred for TCCPDA at 55.5±32.2 days of age, weighing 1.67±0.54 Kg. Procedures were performed using only femoral venous access under echo and fluoroscopic guidance. The device used for closure included the 4mm Amplatzer Vascular Plug-II (AVP-II) in 10, 6 mm AVP-II in 10, 8mm AVP-II in 3, 4mm AVP-4 in 1 and MVP-5Q device in 6 patients. The procedure and fluoroscopic times were 83.7±56.8 and 12.8±11.6 minutes respectively. The radiation and contrast doses were 52.8±34.2 mGy and 2.8±1.5 mL/Kg respectively. The baseline RSS and QP:QS ratio were 3.9±3.3 and 2.2±0.8 respectively. The presence of PHT was the only predictor for a longer time to return to pre-procedure RSS (18 vs. 87 hours; OR=5.4, 95% CI:2.2-9.4, P<0.001) with a 68.8±32.6% increase in RSS (P<0.01). There was one procedure-related mortality. One patient, weighing1.06 Kg, developed left pulmonary artery stenosis following device closure. The device embolized in another patient 6 hours post-procedure. Both these devices were snared and retrieved. No other complications were noted during the procedure or on follow-up (mean 1.8 ± 0.8 years). No patients had residual PDA on follow-up echocardiogram.

Conclusions:
It is feasible to perform trans-catheter closure of PDAs in premature neonates. Presence of PHT prolongs the need for PPV after PDA closure.
Abstract 13994: Anti-cellular Proliferation Therapy Reduces Atherosclerotic Plaques and Vascular Inflammation in Experimental Hypercholesterolemia
Authors: Gomes Fernando L , Maranhao Raul C , Tavares Elaine R , Oliveira Priscila C , Machado Thiago V , Soeiro Alexandre M , Higuchi Maria de Lourdes , Kalil-Filho Roberto , Serrano Carlos V
Published: April 2024

Introduction:
The lipid nanoemulsion (LDE) binds intensely to LDL receptors due to similarity in molecular composition. Anti-proliferative agents paclitaxel (PTX) and methotrexate (MTX) may have beneficial effects on atherosclerosis by preventing proliferation of inflammatory cells and vascular smooth muscle cells.

Hypothesis:
By combining LDE to PTX and MTX, effective regression of hypercholesterolemic atherosclerosis and vascular inflammation occurs.

Methods:
Rabbits underwent induction of atherosclerosis by consuming a cholesterol diet for 8 weeks. Afterwards, 7 rabbits were sacrificed and had their aortas analyzed (Control group). The other rabbits had diet replaced by regular diet, and were divided into 3 groups (n=7 each), according to the 8-week treatment offered: LDE-PTX, LDE-PTX+MTX and Diet (no agent). The rabbits were then sacrificed and the aortas analyzed. Vascular tumor necrosis factor-α (TNF) gene expression was determined in all aorta samples.

Results:
See graph. LDE-PTX and LDE-PTX+MTX treatments presented marked gross regressions of plaque areas when compared to Control. Diet treatment alone did not reduce significantly plaque area. Regarding TNF gene expression, Control group presented 1.70±1.01 mRNA levels while LDE-PTX, LDE-PTX+MTX and diet alone groups presented 1.01±0.03, 0.31±0.10 and 0.20±0.09 levels (p<0.01 ANOVA). All 3 treatment groups produced significant decrease in LDL blood levels.

Conclusions:
Therefore, this study demonstrates that anti-cellular proliferation by PTX+MTX, combined to LDE, produces marked gross atherosclerotic regression and beneficial effect on vascular inflammation.
Abstract 14005: Beat-to-beat Variability of Hemodynamic Parameters Predict the Outcomes of Head Up Tilt Table Test in Patients With Vasovagal Syncope
Authors: Zhang Chunying , Zhang Qing , Chu Yanpeng , Ren Lu , Tong Lin , Wu Lin
Published: April 2024

Introduction:
The risk of severe syncopal episodes during head up tilt table test (HUTT) in patients with vasovagal syncope (VVS) limits its use in clinic. The objective of this study was to identify the early hemodynamic predictors of positive results during HUTT.

Methods:
HUTT was conducted prospectively in 82 consecutive patients with suspicious VVS and 19 normal control. Continuous noninvasive hemodynamic monitor was used to monitor the beat-to-beat changes of heart rate (HR) and blood pressure (BP). Values of short-term heart rate variability (HRV) and blood pressure variability (BPV) were calculated using formula of HR(BP)V= Σ ∣ HR(BP)n+1-HR(BP)n ∣ /(n x √2). Receiver-operating characteristic (ROC) curve analysis was used to test the predictive values.

Results:
Fifty-six out of 82 patients were HUTT positive. The results indicated that four parameters, including percentage of HR increment (ΔHR%) and systolic BPV increment (ΔSBPV%) were early (5 minutes after tilt-up), the ΔSBPV% and percentage of mean arterial pressure variability increment (ΔMAPV%) were late (30 minutes after tilt-up) predictors of a syncopal episode during HUTT. The detailed predictive information of these parameters were listed in table 1.

Conclusion:
Beat-to-beat variability of HR, SBPV and MAPV increment during early and late tilt-up period are valuable pre-syncopal parameters to predict the outcome of HUTT in patients with VVS.
Abstract 14011: Safety of Balloon Pulmonary Angioplasty in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension -Detail Analyses of Procedure Related Complications
Authors: Aoki Tatsuo , Sugimura Koichiro , Miura Masanobu , Tatebe Shunsuke , Yamamoto Saori , Yaoita Nobuhiro , Suzuki Hideaki , Sato Haruka , Kozu Katsuya , Satoh Kimio , Shimokawa Hiroaki
Published: April 2024

Background:
Although balloon pulmonary angioplasty (BPA) is an emerging therapeutic strategy to improve hemodynamics of patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), the original study in 2001 reported that BPA frequently induced pulmonary edema requiring mechanical ventilation. In this study, to evaluate the safety of BPA in CTEPH patients, we examined not only hemodynamics but also complications associated with latest BPA procedures by using imaging modalities.

Methods and Results:
From July 2009 to May 2016, we performed BPA in 78 patients with inoperable CTEPH, in whom we performed 393 sessions with combined use of imaging modalities, including optical computed tomography to select balloon size and 3D reconstructed computed tomography to determine target lesions of pulmonary arteries (PA). Mean age of the patients was 65 year-old and 65 of them were female (82%). In 72 patients (92%) who completed the treatment, hemodynamics and 5-year survival were examined after BPA. Mean follow-up period was 21 ± 15 months. After the completion of BPA treatments, mean PA pressure (38±10 to 25±7 mmHg, P<0.01), pulmonary vascular resistance (7.0±3.1 to 3.7±1.7 Wood unit) and 6-min walk distance (383±156 to 489±113 meters) were all significantly improved (all P<0.01). In the 393 sessions, hemoptysis was noted in 64 sessions (16%), and non-invasive positive pressure ventilation (NPPV) was used for hemoptysis and/or hypoxemia in 32 sessions (8.1%). In last 4 years, the incidence of hemoptysis and the use of NPPV have progressively decreased (Figure). Furthermore, there were no peri-procedural deaths, and 5-year survival after 1st BPA session was 94% (only one patient died for colon cancer).

Conclusions:
These results indicate that BPA improves hemodynamics and exercise capacity, resulting in good long-term prognosis in inoperable CTEPH patients with acceptable complication risk.
Abstract 16611: Higher Total Ultrafiltration Volume During Infant Cardiac Surgery is Associated With Acute Kidney Injury
Authors: Zanaboni Dominic B , Seshadri Roopa , Gaynor J. William , Dreher Molly , Blinder Joshua J
Published: April 2024

Introduction:
Many congenital heart centers use intraoperative ultrafiltration (UF) for fluid removal during and after infant cardiopulmonary bypass (CPB) surgery to reduce fluid overload. Excessive UF may result in intravascular hypovolemia. Postoperative acute kidney injury (AKI) is multifactorial, but little is understood about the role of UF on hypovolemia and postoperative AKI.

Methods:
This is a single center, retrospective review of infants receiving UF associated with CPB surgery. Patients requiring ECMO were excluded. UF volume (ml) was indexed to weight (kg). AKI was determined using the serum creatinine ‘Kidney Disease Improving Global Outcome (KDIGO)’ criteria or neonatal KDIGO (≤ 30 days of age) criteria. Multivariable logistic regression was used to adjust for multiple covariates associated with AKI.

Results:
From 6/2013 to 4/2015, 532 subjects <1 year of age underwent CPB-assisted congenital heart surgery with UF. Sixty-four (12%) subjects developed postoperative AKI. No patients required renal replacement therapy. Higher total indexed UF volume was associated with AKI (median 119 ml/kg [IQR 92-164 ml/kg] versus 97 ml/kg [72-128 ml/kg], p=0.001). Other univariate associations with AKI are listed in table 1. After adjusting for multiple covariates, higher indexed total UF volume was associated with increased AKI risk (OR 1.1, CI 1.03 - 1.17, p=0.005) for each additional 10 ml/kg UF volume. The only additional independently associated factor with AKI was higher vasoactive inotrope score on post-operative day 2 (OR 1.1, [1.04-1.17], p<0.001).

Conclusions:
While few patients developed postoperative AKI, higher intraoperative UF volume is associated with AKI risk. Postoperative hypovolemia due to excessive UF may be a modifiable AKI risk factor. Judicious use of postoperative UF may reduce AKI risk.
Abstract 16623: Wnt Signaling Inhibits T-Type Calcium Channels in Cardiomyocytes
Authors: Florczak Kaya
Published: April 2024

Introduction:
The Wnt/β-catenin pathway plays a critical role in embryonic heart development but is mostly inactive in adult hearts. Recent studies have shown that the pathway is re-activated in many heart diseases including myocardial infarction, cardiac hypertrophy and heart failure. Previous work from our laboratory demonstrated that activation of the Wnt/β-catenin pathway reduces the voltage-gated Na
+
current (I
Na
) in neonatal rat ventricular myocytes (NRVMs). In this study, we examined the effects of Wnt signalling on T-type calcium channels (Ca
v
3.1), which play a key role in the pacemaker function of the sinoatrial node (SAN).

Methods:
NRVMs were treated with Wnt3a protein or CHIR-99021, which activates the Wnt/β-catenin pathway by GSK-3β inhibition. PCR array assays, RT-qPCR, and western blot were used to examine changes in mRNA and protein levels of ion channels. To investigate the impact of ion channel alterations on SAN function, a protocol was developed to isolate SAN tissue from mouse hearts and maintain it ex vivo during ECG recording and drug perfusion.

Results:
PCR array assays showed a 72% reduction in mRNA of
Cacna1g
(encoding Ca
v
3.1) by treatment with Wnt3a protein (130.4±13.2 in control cells vs. 37.4±2.4 in Wnt3a-treated cells, n=4, p<0.05). RT-qPCR and western blot analyses showed a dose-dependent reduction (p<0.05, n=4) in
Cacna1g
mRNA and Ca
v
3.1 protein levels in NRVMs treated with CHIR-99021. Patch-clamp recording also revealed recued T-type calcium current in NRVMs treated with CHIR. Ex vivo perfusion of mouse SANs with a small molecule inhibitor of I
Na
, flecainide, led to slowed conduction velocity and sinus-exit block in a dose-dependent manner (p<0.05, n=5).

Conclusion:
The Wnt/β-catenin pathway regulates the expression of both T-type Ca
2+
channels and voltage-gated Na
+
channels, which are important for impulse generation and conduction in the SAN. Thus, the Wnt pathway may play a role in sinoatrial node dysfunction.
Abstract 16646: Inositol 1,4,5-Trisphosphate Receptor Regulation in Atrial Myocyte Microdomains
Authors: DeSantiago Jaime , Varma Disha , Blatter Lothar , Banach Kathrin
Published: April 2024

Introduction:
InsP
3
receptor type 2 (InsP
3
R2) is up-regulated in patients with atrial fibrillation (AF) and InsP
3
-induced Ca release (IICR) is linked to an increase in premature atrial contractions (PACs). Nevertheless, knowledge of the physiological and pathophysiological relevance and regulation of InsP
3
Rs in the atria is limited.

Hypothesis:
We hypothesized that InsP
3
R and NADPH oxidase 2 (NOX2) form a functional signaling domain where NOX2 derived reactive oxygen species (ROS) regulate InsP
3
R agonist affinity and contractile strength.

Method:
Atrial myocytes (AM) were isolated from wild type and NOX2 (gp91
phox-/-
) deficient mice. Changes in cytoplasmic Ca concentration [Ca]
i
; fluo-4/AM) or ROS (2’,7’-dichlorofluorescein, DCF) were monitored by confocal microscopy.

Results:
We demonstrate for the first time in AMs that agonist angiotensin II (AngII) induced IICR and PACs depend on ROS production in a signaling domain of InsP
3
R and NOX2. Superfusion of AMs with AngII (1 μM) significantly increased diastolic [Ca]
i
(ΔF/F
0
, Ctrl
20’
: 1.0±0.01, AngII
20’
: 1.2±0.03; n=7; p<0.05), the field stimulation induced Ca transient amplitude (ΔF/F
0
, Ctrl: 2.0±0.17, AngII: 2.39±0.22, n=7; p<0.05), and spontaneous Ca releases resulting in PACs (Ctrl: 0 s
-1
, AngII: 0.15±0.05 s
-1
; n=7; p<0.05). These effects, were suppressed by InsP
3
R2 blocker 2-aminoethoxydiphenyl-borate (2APB; 1 μM)) and phopholipase C inhibitor, U73122 (10 μM), demonstrating their dependence on IICR. Simultaneously, AngII induced an increase in ROS production that was sensitive to the NOX2 specific inhibitor gp91ds-tat (1 μM). In AMs deficient for NOX2 (gp91
phox-/-
) AngII failed to increase [Ca]
i
and to induce PACs indicating a sensitization of InsP
3
R by NOX2/ROS. In saponin (0.005%) permeabilized AMs InsP
3
(5 μM) induced spatially defined Ca release events (sparks) that increased in frequency in presence of exogenous ROS (tert-Butyl hydroperoxide: tBHP: 5 μM; InsP
3
: 9.65±1.44 sparks*s
-
1
(100 μm
-1
); InsP3 + tBHP: 10.77±1.5 sparks*s
-1
(100 μm
-1
), n=5, p<0.05). The combined effect of InsP
3
+ tBHP was entirely suppressed by 2-APB suggesting a ROS dependent sensitization of the ryanodine receptor through IICR.

Conclusion:
Our data show a novel mechanism of InsP
3
R regulation in the atrial muscle that consisting of a functional signaling domain where InsP
3
R and NOX2 closely interact. This mechanism could have relevance in a stretch dependent increase in atrial contractile force.