bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11441: The Smarter Weight Loss Intervention Trial: The Effect of Real-Time Feedback on Weight Loss at 12-Months
Authors: Burke Lora E , Sereika Susan M , Bizhanova Zhadyra , Kariuki Jacob K , Parmanto Bambang , Beatrice Britney , Loar India , Cheng Jess , Pulantra I Wayan , Wang Yuhan , Cedillo Maribel , Conroy Molly
Published: March 2022

Introduction:
Obesity prevalence exceeds 40%, yet availability of standard behavioral treatment to those with overweight/obesity is limited; moreover, its in-person format and intensity is unappealing to some. Evidence indicates that providing feedback (FB) to self-monitoring (SM) of lifestyle behaviors improves outcomes. We tested the efficacy of delivering tailored FB messages remotely compared to no FB on weight loss outcomes.

Hypothesis:
At 12 mos participants receiving feedback (SM+FB) would have greater weight loss than those in the SM only group.

Methods:
We randomized 502 adults with overweight/obesity to either SM+FB (n=251) or SM alone (n=251). We delivered 3 smartphone pop-up messages/day to SM+FB group that were tailored to SM entries and delivered at random during waking hours. SM tools included a smartphone app to self-report diet, Fitbit Charge 2 to monitor physical activity, and a digital scale to track weight. All had a 90-min 1:1 intervention session with a dietitian at baseline that focused on behavioral changes to achieve weight loss. Percent weight loss from baseline and percentage of participants having ≥5% weight loss at 12 mos were compared between treatment groups using an intention-to-treat approach. Missing assessment weights at 12 mos were imputed using participants’ weight tracking data.

Results:
The sample was mostly female (79.5%) and white (84.3%) with a mean BMI of 33.1 ± 3.93 kg/m
2
. Based on the linear mixed modeling of weight, only a significant time main effect was observed (
F
= 61.43,
P
<.0001), suggesting that on average there was significant change in weight over the 12-month period. Both groups had similar percent weight loss at 12 mos, SM+FB group: mean [95% CI] -2.12% [-3.04, -1.20] and SM group: -2.39% [-3.32, -1.47] (P= .679). The percentage achieving ≥5% weight loss at 12 mos was also similar between the groups (26.3% for the SM+FB group and 29.1% for the SM group) (P= 0.485).

Conclusions:
The results did not support our hypothesis that participants in the SM+FB group would show greater weight loss at 12 mos than those in the SM group; however, the data support clinical efficacy for both approaches to a weight loss intervention.
Abstract 11443: Where NO
2
Meets Omega-3 Polyunsaturated Fatty Acids: Health Impact of Short-Term Ambient Air Pollution Exposure in Healthy Adults
Authors: Tong Haiyan , Chen Hao , Zhang Siqi , Shen Wan , Salazar Claudia , Schneider Alexandra , Wyatt Lauren , Rappold Ana , Diaz-Sanchez David , Devlin Robert , Samet James
Published: March 2022

Introduction:
Exposure to ambient nitrogen dioxide (NO
2
) is associated with adverse respiratory and cardiovascular outcomes. Supplementation of omega-3 polyunsaturated fatty acids (PUFA) has shown health benefits against exposure to air pollution.

Hypothesis:
Dietary omega-3 PUFA intake offers cardiovascular and respiratory benefits against short-term exposure to ambient NO
2
in healthy adults.

Methods:
Sixty-two healthy participants were enrolled into low or high omega-3 groups based on their habitual dietary omega-3 PUFA intake. Each participant was repeatedly assessed for blood lipids, markers of coagulation and fibrinolysis, vascular function, heart rate variability (HRV), and lung function up to five times separated by at least 7 days between October 2016 and September 2019. Daily ambient NO
2
concentrations were obtained from nearby air quality monitoring stations. The associations between NO
2
concentrations and the measured biomarkers were evaluated using the linear mixed-effects models stratified by the omega-3 intake levels.

Results:
In the high omega-3 group, an IQR increase in NO
2
concentrations was associated with reductions in total cholesterol at lag2 [-2.6% (-4.4, -0.9)], LDL at lag2 [-3.1% (-5.5, -0.7)], and HDL at lag1 [-2.4% (-4.4, -0.3)] and lag2 [-2.0% (-3.8, -0.1)]; increases in flow-mediated dilatation of brachial artery at lag1[5.7% (0.1, 11.2)] and lag2 [5.7% (0.8, 10.6)]; decreases in plasma levels of endothelin-1at lag3 [-25.6% (-50.0, -1.2)] and lag4 [-22.9% (-45.9, -0.01)]; decreased high frequency (HFn) of HRV [-7.2% (-13.6, -0.8)] and increased LF/HF ratio [13.4% (0.2, 28.3)] at lag3; as well as increased lung function. In the low omega-3 group, blood lipids, vascular function biomarkers and lung function were not significantly associated with NO
2
exposure. However, NO
2
exposure was associated with elevations in coagulation markers (von Willebrand Factor and D-dimer) and a decrease in very-low frequency of HRV at lag0 in the low omega-3 group.

Conclusions:
The results imply that high dietary omega-3 PUFA intake may offer benefits to cardiovascular and respiratory health in response to exposure to low-level ambient NO
2
in healthy adults. THIS ABSTRACT OF A PROPOSED PRESENTATION DOES NOT NECESSARILY REFLECT EPA POLICY.
Abstract 11445: Safety and Efficacy of Cryoballoon Ablation for Atrial Fibrillation Performed at Community Hospitals with Low to Medium Case Numbers: Acute and First Long Term Results of The German "Regional" Registry
Authors: Michaelsen Jochen , Parade Ulli , Bauerle Hansjoerg , Winter Klaus-Dieter , Rauschenbach Ulrich , Mischke Karl , Schaefer Carl , Gutleben Klaus-Juergen , Willich Tobias , Breithardt Ole-Alexander A , Middendorf Stefan , Grove Rainer , Mosa Joerg , Krug Joachim , Hoffmann Rainer ,   REGIONAL Investigators
Published: March 2022

Introduction:
Pulmonary vein isolation (PVI) using cryoballoon ablation (CBA) is a guideline recommended treatment for symptomatic paroxysmal and persistent atrial fibrillation. Little is known on performance data of CBA in low to medium volume hospitals.

Hypothesis:
To determine safety and efficacy of PVI using CBA performed at community hospitals with limited annual case numbers.

Methods:
This prospective registry included 1004 consecutive patients (pts) who had CBA performed for symptomatic paroxysmal (n=563) or persistent AF (n=441) at 20 hospitals, each with <100 PVI / year. CBA procedures were performed according to local standards. Procedural data, efficacy and complication rates were determined.

Results:
The mean number of CBA / year / center was 59±25. CBA was performed by a total of 22 operators (1.1/center), 12/20 operators were board certified for invasive electrophysiology. Average procedure time was 90.1±31.6 min, fluoroscopy time was 19.2±11.4 min. Isolation of all pulmonary veins was reached in 97.9% of pts, the most frequent reason for not achieving complete isolation was development of phrenic nerve palsy (PNP). No hospital deaths were observed. 2 pts (0.2%) suffered a clinical stroke. Pericardial effusion occurred in 6 pts (0.6%), 2 (0.2%) required pericardial drainage. Vascular complications occurred in 24 pts (2.4%), 2 pts (0.2%) underwent vascular surgery. PNP occurred in 48 pts (4.8%) and persisted up to discharge in 6 pts (0.6%). The results were independant for board certification status of the operator and independant for the number of enrolled patients per center (if > or < 60 pts).

Follow up data at 12 months were available from 14 centers and 75,2 % of their pts so far. Recurrent atrial arrhythmias after a 3 months blanking period were found in 177/536 pts. (33%), 152 (85,9%) were symptomatic. 71 (40%) pts with recurrence were still on antiarrhythmic drugs, 42 (23.7%) underwent Re-PVI. One phrenic nerve palsy persisted, there were no further access site complications and no esophago-atrial fistula.

Conclusions:
PVI for paroxysmal or persistant AF using CBA can be safely performed at community hospitals with high acute efficacy, low complication rates and good recurrence data after 1 year despite low and moderate annual case numbers.
Abstract 11446: The Role of Heart Rate Recovery in Chronic Heart Failure - Results from the Myovasc Study
Authors: Velmeden David , Söhne Jakob , Schuch Alexander , Zeid Silav , Schulz Andreas , Troebs Sven-Oliver , Müller Felix , Heidorn Marc , Buch Gregor , Dinh Wilfried , Lackner Karl J , Gori Tomaso , Muenzel Thomas , Wild Philipp S , Prochaska Juergen
Published: March 2022

Background:
Reduced heart rate recovery (HRR) has been associated with cardiac autonomic dysfunction, particularly the parasympathetic nervous system, and all-cause mortality in patients with heart failure (HF).

Methods:
In the present study, data of the MyoVasc study (NCT04064450; N=3,289), a prospective cohort study on chronic HF, were analyzed. Participants received a comprehensive 5-hour examination in a dedicated study center including cardiopulmonary exercise testing (CPET) using modified WHO protocols. HRR
60
was defined as the decrease in heart rate in beats per minute one minute after cessation of CPET peak strain. Information on clinical outcome (i.e. all-cause mortality, worsening of HF (wHF)) was derived from structured follow-up with subsequent validation and independent adjudication of endpoints.

Results:
The analysis sample comprised N=1,179 individuals (mean age: 65.0±10.4 years; 28.2% females) with data on HRR
60
. In a multivariable linear regression analysis, age (β-estimate -0.171 ([95% confidence interval -0.226; -0.116]; P<0.0001), sex (β -0.189 [-0.311;-0.0678]; P=0.0023), diabetes mellitus (β -0.300 [-0.424; -0.175]; P<0.0001), smoking (β -0.236 [-0.361; -0.111]; P= 0.00021), obesity (β: -0.266 [-0.380; -0.151]; P <0.0001), peripheral artery disease (β -0.432 [-0.640; -0.224]; P<0.0001), chronic obstructive pulmonary disease (β -0.179 [-0.304;-0.0542]; P=0.0050) and chronic kidney disease (β -0.322 [-0.474; -0.170]; P<0.0001) were identified as clinical determinants of HRR
60
. In Cox regression analysis, HRR
60
≤15 bpm (1
st
tertile vs. 2
nd
/3
rd
tertile of HRR
60
) demonstrated an increased risk for all-cause death (hazard ratio (HR) 1.90 [1.29; 2.79]; P=0.0011). HRR
60
was also a strong predictor of w HF (HR
T1vsT2-3
1.58 [1.17; 2.13]; P=0.0031) independent of clinical determinants and medication. The results remained robust for all-cause mortality (HR
T1vsT2-3
1.61 [1.10; 2.38]; P =0.016) and wHF (HR
T1vsT2-3
1.36 [1.01; 1.84]; P= 0.045) after additional adjustment for NT-proBNP.

Conclusion:
HRR
60
- a measure associated with cardiac autonomic function - was identified as a strong predictor of clinical outcome of HF patients independent of NT-proBNP, suggesting a potential to advance risk stratification in HF.
Abstract 11451: Use of Mechanical Circulatory Support in Chronic Total Occlusion Percutaneous Coronary Intervention: Insights from the PROGRESS-CTO Registry
Authors: Karacsonyi Judit , Deffenbacher Karen , Benzuly Keith H , Flaherty James D , Alaswad Khaldoon , Jaffer Farouc A , Poomipanit Paul , Khatri Jaikirshan , Patel Mitul , Riley Robert , Sheikh Abdul , Wollmuth Jason R , Korngold Ethan , Uretsky Barry F , Yeh Robert W , Chandwaney Raj H , Wyman R M , Potluri Srinivasa , Doing Anthony , Elguindy Ahmed M , Tammam Khalid , Abi Rafeh Nidal , Schmidt Christian , Vemmou Evangelia , Nikolakopoulos Ilias , Kostantinis Spyridon , Xenogiannis Iosif , Rangan Bavana V , Ungi Imre , Brilakis Emmanouil S , Schimmel Daniel R
Published: March 2022

Introduction:
The use of mechanical circulatory support (MCS) in complex percutaneous coronary intervention (PCI) is the subject of ongoing investigation, but the role of MCS in chronic total occlusion (CTO) PCI is not well studied.

Methods:
We analyzed the patient and angiographic characteristics and procedural outcomes of 7,171 CTO PCIs performed between 2012 and June 2021 at 35 international centers.

Results:
Mean patient age was 64.5±10 years, mean left ventricular ejection fraction was 50 ± 13 % and 82% were men. MCS was used in 4.5% of the overall cases, MCS use was elective in 78.7% and urgent in 21.3%. The most common type of MCS was Impella CP (55.5%) followed by intra-aortic balloon pump (14.8%), Tandem Heart (10.0%) and Impella 2.5 (8.7%). Diabetes mellitus (51.0% vs. 42.4%, p=0.003), prior congestive heart failure (60.6% vs. 27.9%, p<0.001) and prior myocardial infarction (52.3% vs. 45.3%, p=0.020) were more common in MCS patients. Left ventricular ejection fraction was lower in the patients with MCS use compared to patients without (Mean±standard deviation, 51.0 ± 12 vs. 34.0 ± 15 %, p<0.001). Cases in which MCS was used were more complex with higher J-CTO score compared with cases without MCS (2.94 ± 1.19 vs. 2.39 ± 1.27, p<0.001). Cases performed with MCS had lower technical (81.6% vs. 86.7%, p=0.011) and procedural (71.3% vs. 85.6%, p<0.001) success rates with higher rates of periprocedural major cardiac adverse events compared to no MCS use (12.6% vs. 1.68%, p<0.001).

Conclusions:
In a contemporary, multicenter registry MCS was used in 4.5% of CTO PCI. Cases where MCS was used were associated with lower technical and procedural success with higher periprocedural major complication rates. Further investigation is required to see if elective use of MCS can improve outcomes in patients with increased comorbidities and higher lesion complexity.
Abstract 11452: Full 3D Single Heartbeat Electromechanical Wave Imaging of the Heart in Vivo with Coherent Compounding of Diverging Waves
Authors: Grondin Julien , Weber Rachel , Konofagou Elisa E
Published: March 2022

Introduction:
Electromechanical wave imaging (EWI) is a new ultrasound-based technique that can noninvasively map myocardial activation of all four chambers at high temporal resolution (500-2000 frames per second). Localization of atrial and ventricular arrhythmias with 3D-rendered EWI maps has been demonstrated and validated in heart rhythm disorders using multiple 2D echocardiographic views at different heartbeats.

Objective:
The objective of this study was to assess the in vivo performance of single heartbeat 3D EWI using coherent compounding of high volume-rate 3D anatomical echocardiography.

Methods:
A 32x32-element matrix array (Vermon, France) was connected to four synchronized research ultrasound scanners (Vantage 256, Verasonics, WA). High volume rate acquisitions were performed with diverging wave imaging at a compounded imaging rate of 840 volumes per second. Three healthy volunteers were imaged during normal sinus rhythm and one open chest canine was imaged during left ventricular pacing. Timing of zero-crossing of temporal inter-volume axial strain curves, corresponding to local onset of contraction, was determined for EWI activation.

Results:
A normal activation sequence was consistently observed in all volunteers (Figure 1). Early activation was mapped in the right atrium, followed by the left atrium, followed by the ventricles. Epicardial ventricular pacing was performed alternatively in the basal anterior-lateral region and in the apical anterior-septal region. The earliest activated region with 3D EWI was observed in the same location as the pacing electrode (Figure 1). Good agreement between 3D EWI and electro-anatomical mapping was obtained.

Conclusions:
Ultrasound-based full 3D EWI is capable of consistently mapping myocardial activation of the full heart in a single heartbeat in healthy volunteers noninvasively and is capable of identifying early activation during epicardial ventricular pacing in an open-chest canine.
Abstract 11455: Does Caregiver Burden Change from Before to 24 Months After Surgery: Findings from the Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Support (
Sustain-it
) Study
Authors: Wu Tingqing , Andrei Adin-cristian , Baldridge Abigail S , Warzecha Anna , Petty Michael , Kao Andrew , Spertus John , hsich eileen , Dew Mary Amanda , Pham Duc , LaRue Shane , Cotts William , Pamboukian Salpy , Pagani Francis D , Lampert Brent , Johnson Maryl R , Hartupee Justin , Takeda Koji , Yuzefpolskaya Melana , Silvestry Scott , Kirklin James , Yancy Clyde , Grady Kathleen L
Published: March 2022

Purpose:
Caregivers (CGs) provide essential support to older (60-80 years) patients with advanced heart failure (HF), yet caregiving may be burdensome. Understanding the caregivers time spent and difficulty in caring for patients may inform CG support needs before and after cardiac surgery. We compared CG burden before and 24 months after heart transplantation (HT), with or without baseline mechanical circulatory support (MCS), and long-term MCS as destination therapy (DT).

Methods:
Between 10/1/15-12/31/18, we enrolled 301 CGs of HF patients from 13 U.S. hospitals: 193 awaiting HT (92 with and 101 without MCS), and 108 scheduled for long-term MCS. At baseline (pre-surgery) and 24 months post-surgery, CGs completed the Oberst Caregiving Burden Scale (OCBS), which has 15 items with 2 subscales: (1) time: range=1-5, higher score=more time spent on task and (2) difficulty: range=1-5, higher score=higher task difficulty. Statistical analyses included t-tests and baseline-adjusted linear regression models.

Results:
CGs’ average age was 60.9±10 years, 83% were spouses, 85% female, and 85% white. Across all groups and both time points, time spent on caregiving tasks was moderate and task difficulty was rated low. Time spent on caregiving decreased significantly from baseline to 24-months for all groups (p-value <0.05 for all; Figure 1A) but task difficulty did not (Figure 1B). At 24-months, mean OCBS time and difficulty scores were significantly higher among CGs of DT patients compared with CGs of HT MCS and HT non-MCS patients.

Conclusions:
CG time on tasks decreased from baseline to 24-months post-surgery in all groups, and both time and difficulty scores were persistently higher for CGs of DT patients. These results may inform identification of support options to reduce time and difficulty of CG tasks, particularly for those who care for destination therapy HF patients.
Abstract 11458: Temporal Changes in Mitral Regurgitation After Percutaneous Mitral Valve Repair with MitraClip for Functional Mitral Regurgitation in Patients with Atrial Fibrillation
Authors: Uno Goki , Omori Taku , Kagawa Shunsuke , Shiota Takahiro
Published: March 2022

Background:
Recently, percutaneous mitral valve (MV) repair has been increasingly performed for functional mitral regurgitation (FMR). However, few studies have examined the effectiveness of percutaneous MV repair for atrial FMR (AFMR). The aim of this study is to compare the effectiveness of MitraClip implantation between patients with AFMR and ventricular FMR (VFMR).

Methods:
We retrospectively reviewed 113 grade 3 to 4+ FMR patients with persistent atrial fibrillation or atrial flutter who underwent MitraClip implantation. We classified the patients into 2 groups; 43 patients with preserved left ventricular (LV) ejection fraction (LVEF) ≥ 50% and normal LV wall motion were defined as AFMR. 70 patients with LV dysfunction (LVEF < 50 %) or LV wall motion abnormality were defined as VFMR. Transthoracic echocardiography (TTE) follow-up was performed at approximately 1-day, 1-month and 1-year after the procedure.

Results:
The percentage of grade 4+ mitral regurgitation (MR) was 53% in AFMR and 49% in VFMR at baseline (P=0.61). Acute procedural success rate was similar between AFMR and VFMR (95.3% vs. 97.1%, P=0.49). The median period of 1-month and 1-year follow-up TTE were 33 [interquartile range (IQR): 28-36] days and 356 (IQR: 248-399) days in AFMR, and 34 (IQR: 30-38) days and 366 (IQR: 336-415) days in VFMR, respectively. The percentage of grade 3 or 4+ MR at 1-day, 1-month, and 1-year after the procedure were 4.7% (2/43), 10% (3/30), and 5.6% (1/18) in AFMR, and 2.9% (2/70), 7.3% (4/55), and 2.9% (1/35) in VFMR (P=0.49, 0.48, and 0.57, respectively, AFMR vs. VFMR at the same follow-up point). The rates of redo MitraClip or MV surgery for recurrent MR within 1-month and between 1-month/1-year were 0% and 9.3% in AFMR, and 1.4% and 1.4% in VFMR. The percentage of New York Heart Association functional class III or IV at baseline, 1-month, and 1-year after the procedure were 90.7% (39/43), 23.3% (7/30), and 33.3% (6/18) in AFMR and 97.1% (68/70), 27.3% (15/55), and 22.9% (8/35) in VFMR (P=0.15, 0.69, and 0.41, respectively, AFMR vs. VFMR at the same follow-up point).

Conclusions:
In our series, MitraClip implantation had comparable therapeutic effect on both MR severity and heart failure symptoms between patients with AFMR and VFMR.
Abstract 11466: Deficiency of Microrna-1 Induces Cardiac Electrical and Metabolic Remodeling of the Heart
Authors: Yang Dandan , Wan Xiaoping , Cavus Omer , Firoozi Saman , Uttarwar Lalita , Schwieterman Neill , Laurita Kenneth R , Bradley Elisa A , Wold Loren E , Mohler Peter J , Deschenes Isabelle , Fu Jidong
Published: March 2022

Introduction:
MicroRNA-1 (miR1) is an evolutionarily conserved, striated muscle-enriched microRNA and plays critical roles in regulation of the development and physiology of the heart. It has been found that miR1 was downregulated in various types of cardiac diseases. We observed that, compared to that in young mice (age 3-4 months), the expression of miR1 was significantly decreased to the level of 12.5±4.0% in the heart of aged animals (age 18 months).

Hypothesis:
We hypothesized that miR1 deficiency is a major etiology in diseased and/or aged hearts. In the mammalian genome, two distinct genes, miR1-1 and miR1-2 that are located on two chromosomes, generate identical mature miR1.

Methods and Results:
To study the hypothesis, we generated miR1-75% knockdown (75%KD) mice by crossbreeding miR1-1 knockout (KO) and miR1-2 KO animals and found that miR1-75%KD mice could survive to adult age with a relatively higher mortality, while miR1-100%-KO is postnatal lethal. The ejection fraction and fraction shortening of 75%KD hearts was significantly decreased than that of WT animals. Electrocardiogram showed that, compared to the WT group, 75%KD hearts had significantly slower heart rates with shorter PR interval and prolonged QRS interval with observed premature ventricular contractions. Optical mapping of
ex vivo
hearts revealed significantly slower ventricular conduction velocity in 75%KD hearts. Compared to WT cells, 75%KD ventricular cardiomyocytes had hyperpolarized RMPs with prolonged action potentials, and showed significantly decreased sarcomere shortening. Proteomic assays found that proteins of mitochondrial ATP synthesis and electron transport were significantly downregulated in 75%KD hearts.

Conclusions:
We conclude that the deficiency of miR1 is a major etiological factor of cardiac electrical and metabolic remodeling in the heart. Restoring the normal level of miR1 in the heart could be a critical and effective therapeutic strategy to prevent and/or treat heart diseases.
Abstract 11467: Biomimetic Microrna-Laden Small Extracellular Vesicle-Derived Vehicles Increase Pro-Reparative Phenotype in Cardiac Endothelial Cells
Authors: Bheri Sruti , Kassouf Brandon P , Davis Michael E
Published: March 2022

Introduction:
Ckit+ progenitor cells (CPCs) release small extracellular vesicles (sEVs) which are vital for CPC-based recovery after myocardial infarction (MI). sEVs transport RNA cargo within a complex lipid/protein bilayer required for sEV trafficking and endocytosis. However, being cell-derived, sEV yield, cargo content and concentration are often variable. Synthetic sEV-mimics allow for cargo control, but their basic phospholipid membrane often results in rapid clearance. Here, we use thin film hydration (TFH) and electroporation to develop sEV-like vesicles (ELVs) with an sEV membrane and mimic-like cargo control. We

hypothesize

that (1) ELVs with cardioprotective microRNA (miR) cargo will improve functional outcomes from cardiac endothelial cells (CECs) compared to sEVs alone and (2) electroporated ELVs will functionally outperform TFH ELVs.

Methods:
sEVs were isolated from CPC conditioned media with ultracentrifugation. ELVs were synthesized from sEVs by removing inherent miR cargo and then loading endothelial specific miR126 through TFH or electroporation. For TFH, sEVs were dissolved in an organic solvent to form a lipid bilayer and then loaded with miR126 to initiate ELV self-assembly. For electroporation, miR126 was added to sEVs by varying voltage pulses. ELVs were characterized for size and concentration. Both cargo clearance and miR126 loading were quantified with a Quant-iT miR kit. Functionality of both ELV designs was assessed by delivering miR126+ ELVs to CECs for angiogenesis and proliferation.

Results:
ELVs on a similar scale to sEVs were successfully formed using both methods, despite variability in concentration. ELV miR126 loading capacity after cargo removal was higher and tunable with electroporation compared to TFH. Electroporation also preserved more membrane proteins than TFH. When delivered to CECs, electroporated miR126+ ELVs increased angiogenesis and proliferation compared to sEVs over 24 hours, in a dose-dependent manner.

Conclusion:
Using an sEV-like membrane with customizable miR cargo allows for improved functional outcomes from cardiac cells, with electroporated samples having more cargo tunability. Beyond miR126, this work highlights a delivery vehicle for combination miR therapy after MI.
Abstract 11473: Renal and Cardiac Effects of Remote Ischemic Preconditioning in Children Undergoing Cardiopulmonary Bypass Surgery
Authors: Law Yuk M , Hsu Christine , Katz Ronit , hingorani sangeeta , MCMULLAN David , Richards Michael , Jeffries Howard , Tian Rong , Himmelfarb Jonathan
Published: March 2022

Introduction:
Children undergoing cardiac surgery are at risk for AKI and cardiac dysfunction affecting outcome. Improved surgical techniques and post-operative care allow better outcomes in complex repairs and at-risk patients. Opportunity exists in further protecting multiple end organ function with remote ischemic preconditioning (RIPC) given promising but mixed data in adults and children.

Hypothesis:
A non-invasive technique of inducing reversible lower extremity ischemia with inflation of pressure cuff lessens renal and myocardial injury.

Methods:
A single center randomized, placebo controlled, double blinded trial of RIPC in children undergoing cardiac surgery of RACHS-1 category 2 or greater. RIPC was performed in the operating room after anesthesia and before sternotomy. Pre-specified end points are change in creatinine, eGFR, development of AKI, B-type natriuretic peptide and Troponin I at 6, 12, 24, 48, 72 hours post separation from bypass. Secondary end points included select clinical outcomes.

Results:
There were 45 in the RIPC and 39 patients in the control group: age was 3.5 and 3.8 years, respectively; 57 patients below 1 year of age; 35 patients below 1 month of age. There was no difference between groups in creatinine, cystatin C, eGFR at each time points. There was a trend for a larger rate of decrease, especially for cystatin C (p=0.042) in the RIPC group but the magnitude was small. AKI was observed in 21 (54%) of control and 16 (36%) of RIPC group (p=0.094). Adjusting for baseline creatinine, the odds ratio for AKI in in RIPC compared to control group was 0.31 (p=0.037). Adjusted for clinical characteristics, the odds ratio was 0.34 (p=0.056). Peak troponin occurred at 6 hrs. Compared to control, the RIPC group had a lower troponin at 6 hrs (p=0.140). However, no difference in other analyses of troponin and B-type natriuretic peptides between the groups. Length of stay, all-cause mortality, systolic function by echocardiography and composite clinical end points of advanced renal and heart failure were not different between groups.

Conclusions:
There is suggestion of RIPC delivering renal protection in an at-risk pediatric population. Additional larger, higher risk population studies will be required to fully determine its efficacy.
Abstract 11475: A Genetically Modified pH Resistant NCX1 Mouse Prevents Calcium Overload During Acidosis and is Cardioprotective
Authors: Zhang Rui , Wu Xiaokang , Xie Catherine , Gonzalez Devina , Lotteau Sabine , Thomas Gavali Joice , Li Liang , John Scott , Philipson Kenneth D , Ottolia Michela , Goldhaber Joshua I
Published: March 2022

Acidosis inhibits the cardiac sodium(Na)/calcium(Ca) exchanger (NCX1), allegedly contributing to elevated cytoplasmic Na and Ca concentrations during ischemia. Upon reperfusion and restoration of normal pH, a reactivated NCX1 abruptly shifts into reverse (Ca influx) mode because of the abnormally high cellular Na concentration, thus producing massive Ca overload and cell damage. To test the dependence of ischemia/reperfusion (I/R) injury on NCX1’s pH sensitivity, we used CRISPR/Cas9 technology to create mice with a pH-resistant NCX1 by substituting Alanine for Histidine at position 165 (H165A). These mice live into adulthood with slightly reduced LV function (EF% H165A: 50 ± 5; Wildtype (WT): 67 ± 2; p<0.025, N=4-6). In enzymatically isolated adult ventricular myocytes, we used the patch clamp technique and voltage ramps from +80 to -120 mV to confirm that NCX1 current in H165A mice is resistant to pH reduction (from 7.4 to ~pH 6.4 by substituting 80 mM Na-Acetate for equimolar NaCl) when compared to WT animals (% reduction at +80mV: WT 77.7± 2.8, P<0.027 in 3 cells from 2 mice; H165A 0.21 ± 11.35, P=0.31 in 7 cells from 3 mice). We then performed I/R studies in explanted hearts perfused in Langendorff fashion with oxygenated Tyrode’s containing (in mM): 136 NaCl, 1.8 CaCl
2
, 5.4 KCl, 0.33 NaH
2
PO
4
, 1.0 MgCl
2
, 10 HEPES, and 10 glucose, pH 7.4, 37
o
C. 20 minutes of stop-flow ischemia were followed by reperfusion for 120 minutes. Necrosis area (pixels
2
) in WT was 26 ± 3 (N=11), compared to only 9 ± 1 (N=7) in H165A mice (P<0.0004). To compare effects of lower pH on isolated cardiomyocyte Ca, we used a photometric epifluorescence detection system to measure cytosolic Ca in enzymatically isolated ventricular myocytes loaded with the Ca indicator fura-2 AM (2 μM). When pH was lowered to ~6.4, Ca transients (ΔF340/F380) increased in WT from 0.6 to 0.9 (P < 0.0004, N=19 cells from 3 mice) but notably did not change in H165A (0.5 ± 0.03 @ pH 7.4, 0.5 ± 0.04 @ pH 6.4, P=0.307, N=21 cells from 3 mice). pH changes were verified in separate cells using the pH indicator SNARF-AM (10 μM). We conclude that eliminating pH sensitivity in NCX1 has major effects on intracellular Ca regulation, is cardioprotective, and a potential strategy for therapies in patients with prolonged ischemia prior to reperfusion.
Abstract 11483: A 7-Year Arterial Stiffness and Carotid Intima-Media Thickness Progression Predict Obesity, High Lean Mass, and Incident Hypertension from Age 17.7 to 24.5 Years: the ALSPAC Study
Authors: Agbaje Andrew O , Barker Alan R , Tuomainen Tomi-Pekka
Published: March 2022

Introduction:
An American Heart Association’s statement recommended investigating the natural history of arterial stiffness and blood pressure (BP) vis-à-vis the rate at which arterial stiffness and BP increase with age.

Hypothesis:
To test whether carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT) progression independently predict increased fat mass and BP.

Methods:
We studied 3862 participants from the Avon Longitudinal Study of Parents and Children birth cohort. cfPWV and cIMT were measured by ultrasound scan, total and trunk fat mass, and lean mass by dual-energy Xray absorptiometry scan, body mass index (BMI), BP, heart rate, fasting insulin, glucose, high sensitivity C-reactive protein, and lipid profile were measured at ages 17.7 and 24.5 years. Participants at >75th percentile of total and trunk fat mass or having >24.9 kg/m
2
BMI were classified as overweight and obese, >75th percentile as high lean mass, and >120/80 mm Hg as elevated BP and hypertension. Data were analysed with logistic regression and linear mixed models, adjusting for cardiometabolic and lifestyle factors.

Results:
Among 1719 [44.5%] male and 2143 [55.5%] female participants, cfPWV at 17.7 years independently predicted systolic hypertension [Odds ratio (OR) 1.19 (1.01 - 1.40); p=0.043], diastolic hypertension [OR 1.77 (1.32 - 2.38); p<0.0001], BMI-obesity [OR 1.19 (1.01 - 1.41); p=0.041], and trunk fat mass-obesity [OR 1.24 (1.03 - 1.49); p=0.023] at age 24.5 years. cIMT at 17.7 years predicted high lean mass [OR 54.29 (0.73 - 4053.52); p=0.069] at 24.5 years with borderline significance. A 7-year increase in cfPWV was directly associated with the 7-year increase in lean mass [Effect estimate 0.09 kg (0.05 - 0.13); p<0.0001], systolic BP [21.58 mmHg (14.32 - 28.84); p<0.0001] and diastolic BP [31.74 mmHg (24.90 - 38.57); p<0.0001], but inversely associated with BMI [-0.03 kg/m
2
(-0.06 - -0.01); p=0.039]. cIMT progression from age 17.7 - 24.5 years was directly associated with the 7-year increase in total fat mass, trunk fat mass, lean mass, BMI, and diastolic BP.

Conclusions:
Arterial stiffness and cIMT progression independently predicted obesity, high lean mass, and incident hypertension among young adults.
Abstract 11489: Oral Rhamnan Sulfate Reduces Vascular Inflammation and Atherosclerotic Plaque Formation
Authors: Patil Nikita , Gómez-Hernández Almudena , Zhang Fuming , Cancel Limary , Feng Xu , Yan Lufeng , Xia Ke , Takematsu Eri , Yang Emily , Le Victoria , Fisher Megan , Gonzalez-Rodriguez Agueda , Garcia-Monzon Carmelo , Tunnell James , Tarbell John , Linhardt Robert , Baker Aaron
Published: March 2022

Introduction:
The glycocalyx, an interior lining of blood vessels, forms a barrier against inflammation and atherosclerotic risk factors. It is degraded during plaque development, allowing fat deposition in the intima. Rhamnan sulfate (RS), a polysaccharide from green seaweed, resembles GAGs such as heparan sulfate in the glycocalyx.

Hypothesis:
We hypothesize that RS can replace and rejuvenate the glycocalyx to enhance barrier function and prevent plaque formation.

Methods:
In vitro, we tested the effects of RS on proliferation, migration and permeability to LDL. We used western blots to measure the efficacy of RS in inhibiting the NF-κb pathway. We also performed atomic force microscopy on endothelial cells to test effects of RS on glycocalyx stiffness and thickness post-inflammation. In vivo, we conducted a study in female and male ApoE
-/-
mice on a high fat diet for 13 weeks where RS treatment was provided orally (n = 10 per group).

Results:
Rhamnan sulfate decreased growth factor induced proliferation and migration of endothelial and vascular smooth muscle cells. It increased heparan sulfate coverage and decreased the permeability of endothelial cells to LDL. It also decreased the activation of NF-κb in response to TNF-α treatment while also binding to NF-κb subunits. In ApoE
-/-
mice, oral consumption of RS decreased cholesterol levels in the plasma by 22.5% in female mice. En face analysis of aorta showed that plaque area decreased by 45.2% in female and 36.4% in male mice. In female mice, lipid deposition and stenosis decreased in the aortic arches and thoracic aortas while only lipid deposition was reduced in the aortic arches of male mice. Inflammatory factors were also decreased in the aortic arches of female mice. In livers of these mice, RS treatment reduced NAFLD activity scores and lipid deposition in females and unsaturated lipid content in males. RNA sequencing showed significant differences in genes related to metabolism, circadian rhythm and lipid regulation between high fat diet and RS groups and male and female mice.

Conclusions:
Rhamnan sulfate reduces inflammation in endothelial cells and proliferation of vSMCs. It also reduces plaque formation in aorta of ApoE
-/-
mice.
Abstract 11500: General Evaluation of the Aorta by Computed Tomography in a Latin Population
Authors: Henriques Mickael , Gouveia e Melo Ryan , Peixoto André , Fernandes e Fernandes Ruy , Ministro Augusto A , Leitão João , Caldeira Daniel , Mendes Pedro Luis
Published: March 2022

Introduction:
The normal diameter values of the aorta are controversial, dictate when aneurysmal disease develops and when it should be treated. They differ between populations implicating that the indications for treatment are not universal. The need arises for regional registries so that treatment may be personalized. However, there are no previous registries in a latin population. Therefore, we performed a population based study on aortic diameters based on CTs measures.

Methods:
Cross-sectional study based on retrospective analysis of random CTs performed during 2018 in the largest Portuguese hospital. Patients with aneurysms were excluded. Diameter was presented in millimeters using outer to outer wall measurements, in an anterior-posterior or transverse plane, perpendicular to the lumen center line. Diameter was adjusted for age and sex, and measured in the locations specified in table 1. Age was categorized in 3 groups: >=50; 50-75; >75. This project was submitted and approved by the Ethics Committee of our institution (ref336/20).

Results:
The mean age of the population analyzed was 64 years old (SD 17; min-max 18-98) and 53.3% were male. A total of 396 CTs were analyzed, and of these 45% had thorax, 97% had abdominal and 83% had pelvic imaging. Mean aortic and iliac diameter are presented in table 1 and were adjusted for age and sex. In all locations of the aorta, the diameter was significantly higher in men than in women, except for the ascending aorta in women under 50 (p<0.001). Diameters increased with age and were significant for all age groups and measured locations (p<0.001). We found intra and interobserver measures to be fairly agreeable (Cohen
k
: 0.21 and 0.24, respectively).

Conclusions:
We defined a set of normal values at key aortic locations. Age and sex significantly influenced these measures, while the dimensions follow a similar pattern through the vessel regardless of these factors.

Table 1. Mean aortic diameter by location, age and sex.
Abstract 11501: Morbid Obesity Eliminates the Obesity Paradox in Patients Hospitalized for Heart Failure
Authors: Aguilar-gallardo Jose S , ROMEO Francisco , Correa Ashish A , Contreras Johanna P
Published: March 2022

Introduction:
For reasons unclear, obesity has been paradoxically associated with reduced mortality in patients hospitalized for heart failure. In this study, we analyze if this paradox extends to patients with morbid obesity.

Methods:
This was a retrospective cohort study using the 2018 Nationwide Inpatient Sample that included adult patients hospitalized with a primary diagnosis of heart failure. Patients with morbid obesity and non-morbid obesity were compared to those without obesity as a comorbidity. The primary outcome was mortality. Secondary outcomes included length of stay, total charges, and cardiogenic shock. Multivariate regression analysis was used to adjust for age, race, Charlson Comorbidity Index, and other relevant comorbidities with a p-value <0.2 in univariate screen. Statistical analysis was performed using Stata 17.0.

Results:
A total of 1,248,490 (weighted) heart failure hospitalizations were included. Multivariate regression analysis revealed a trend for increased mortality in the morbidly obese with an odds ratio (OR) 1.10 (p=0.056). It also revealed paradoxically decreased mortality in patients with non-morbid obesity with an OR 0.73 (p=0.000), confirming the presence of the obesity paradox in this population. In the subgroup with reduced ejection fraction, morbid obesity was associated with increased mortality, with an OR 1.68 (p=0.029). Morbid obesity was also associated with increased length of stay and total hospitalization charges, but decreased incidence of cardiogenic shock.

Conclusions:
Morbid obesity eliminates, and in some cases reverses the obesity paradox in patients hospitalized for heart failure. More research is required to clarify the mechanisms behind this counterintuitive phenomenon.
Abstract 11504: Socioeconomic Factors Including Neighborhood SES Leading to Gaps in Care for Patients with Significant Congenital Heart Disease
Authors: Zaidi Abbas H , Gauvreau Kimberlee , Bucholz Emily M , Saleeb Susan F , Jenkins Kathy J , Deferranti Sarah
Published: March 2022

Introduction:
Lifelong continuity of care is crucial for patients with significant congenital heart disease (CHD). Unfortunately, gaps in care (GIC) are common and may be attributed to vulnerable developmental periods, changes in insurance status, lack of symptoms or knowledge regarding follow-up, and inability to access specialty care. There is limited understanding of socioeconomic and demographic factors that contribute to GIC in CHD.

Hypothesis:
Socioeconomic factors including U.S. neighborhood socioeconomic score(SES) are associated with GIC in patients with significant CHD.

Methods and Results:
A total of 8674 patients followed at Boston Children's Hospital (BCH) with moderate to severe CHD(as defined by AHA/ACC 2008 guidelines) were seen in clinic between January 2013 and December 2015. Socioeconomic characteristics including language, race, ethnicity, and U.S. neighborhood socioeconomic score (SES) were analyzed. GIC of > 3.25-years were identified in 33% (2829) of patients. GIC were associated with being an adolescent or young adult (13-23 years) (P<0.001), non-English speaking (P<0.002), non-white (P<0.001), Hispanic ethnicity (P = 0.02), and a low SES (P <0.001).

Conclusions:
A third of patients with significant CHD experienced a substantial GIC (>3.25 years). Adolescent young adult age and socioeconomic factors, including race, ethnicity, language, and a low SES were associated with GIC in patients with significant CHD. Interventions to identify and support these vulnerable populations could improve patient continuity of care and overall outcomes. Further studies are needed to understand the reasons for such GIC in vulnerable populations.
Abstract 11510: Associations of Cardiovascular Health in Young Adulthood with Long-Term Blood Pressure Trajectories: Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Guo James W , Ning Hongyan , Allen Norrina , Liu Kiang , Reges Orna , Lloyd-jones Don
Published: March 2022

Introduction:
Cardiovascular health (CVH) in young adulthood (YA) has been associated with cardiovascular outcomes in older age. However, little is known about the relationship between YA CVH and mid-life BP trajectories.

Methods:
CVH (defined by 6 of AHA’s 7 metrics, excluding BP) was measured twice in YA and defined as poor, intermediate, and ideal for each metric, scored as 0, 1, or 2 points respectively, then summed as a composite CVH score (range 0 to 12). Categorical CVH status was defined as ≥10 points = high, 6-9 = moderate, 0-5 = low. Latent-class modeling (SAS Proc Traj) was used to identify trajectories of mid-BP (mean of SBP and DBP) from ages 35 to 55 years. Multinomial logistic regression was used to estimate the association of YA CVH status with mid-life BP trajectory group membership.

Results:
There were 3,358 CARDIA participants (56% female, 46% Black; mean age 25 years) in YA with follow-up data for BP trajectories. We observed 3 BP trajectory groups, labeled as low, middle, and higher (Figure). A 1-point higher CVH score in YA was associated with adjusted odds ratios (aORs) of 0.84 (95% CI, 0.80-0.89) for being in the middle and 0.73 (0.67-0.79) for being in the higher mid-life BP trajectory groups. Compared with high CVH status at baseline, those with low and moderate CVH were significantly more likely to be in the middle and higher BP trajectory groups (Table). Among the CVH metrics, only BMI was significantly associated with BP trajectory group.

Conclusions:
Moderate or low CVH status in YA is associated with elevated mid-life BP trajectory. These data suggest that early life CVH status, and particularly BMI, may be important to manage for primordial prevention of hypertension.
Abstract 11511: Long-Term Outcomes of Transcatheter Aortic Valvuloplasty in Infants: A Study from the Pediatric Cardiac Care Consortium
Authors: Greene Ryan T , Weinmeister Kristi , Claxton J’Neka , Kochilas Lazaros , Hiremath Gurumurthy
Published: March 2022

Introduction:
Long-term outcomes of aortic stenosis (AS) after balloon aortic valvuloplasty (BAV) in infancy are scarce. Here, we report the 25-year outcomes after the first BAV in infants enrolled in the Pediatric Cardiac Care Consortium (PCCC), a US-based registry of pediatric cardiac interventions.

Methods:
We queried the PCCC for patients undergoing BAV in infancy between 1982 and 2003. Outcomes were tracked through 2019 in the PCCC and by linkage with the National Death Index and the Organ Procurement and Transplantation Network. Cases dependent on ductus arteriosus at the time of BAV were deemed critical and procedural outcomes were defined as optimal if residual valve gradient was <30mmHg and no more than mild insufficiency reported. Reinterventions were tracked in PCCC through 2011. Transplant-free survival (TFS) post initial BAV is described by Kaplan-Meier plots
.

Results:
The cohort included 316 patients: males 75.3%, median age 0.6 months (IQR: 0.1 - 2) at the time of the BAV. Of them, 95 had critical AS and 187 had optimal procedural outcome. A total of 289 (91.5%) survived to hospital discharge. Over a median follow-up time of 21.7 years (IQR: 18.9, 24.6), 3 patients underwent transplantation and 17 died, with a 25-year TFS of 92.4% (95%CI: 89.0-96.0%). Presence of critical AS and procedural outcome did not affect long-term outcomes (Figure 1). One hundred thirteen patients underwent at least one transcatheter or surgical reintervention through 2011: 48 (42%) had critical AS and 59 (52%) had suboptimal outcome after the first BAV (relative risk of reintervention 1.26 (95%CI: 0.94, 1.69) and 1.98 (95%CI: 1.48, 2.64) respectively).

Conclusions:
Infants undergoing BAV have favorable 25-year survival independent of the critical nature of the AS and the lack of optimal outcome at discharge. Patients with suboptimal result were more likely to require reintervention.
Abstract 11513: Impact of Family History of Coronary Artery Disease on Clinical Outcomes in Takotsubo Cardiomyopathy
Authors: Li Pengyang , Jin Chengyue , Cui Can , CAI Peng , Manohar Shamita A , Jin Ling , wei xin , Pan Su , Dixon Richard A , Liu Qi
Published: March 2022

Introduction:
Family history of coronary artery disease (CAD) is a critical risk factor for CAD, underscoring the contribution of genetic factors to disease pathogenesis and susceptibility. Takotsubo cardiomyopathy (TCM) simulates the clinical features of and frequently coexists with CAD. However, the association between family history of CAD (FHxCAD) and TCM is unclear.

Aim:
We examined the impact of FHxCAD on in-hospital clinical outcomes of TCM patients.

Methods:
This retrospective cohort study was conducted using the National Inpatient Sample database [2016-2018]. We identified 4,733 patients admitted to hospital with a primary diagnosis of TCM (ICD-10 coding system); 648 (13.7%) had a FHxCAD. We performed propensity score matching at 1:1 ratio (n=646, matched TCM with FHxCAD; n=646, matched TCM without FHxCAD), and we compared in-hospital outcomes and complications between TCM patients with or without a FHxCAD.

Results:
In the unmatched cohort, the TCM with FHxCAD group had a reduced incidence of cardiogenic shock, acute kidney injury (AKI) and acute respiratory failure (ARF); lower mortality rates; shorter length of stay (LOS); and decreased total charge compared to the TCM without FHxCAD group (p<0.05). After propensity score matching, the TCM with FHxCAD group, when compared with the TCM without FHxCAD group, also had a lower incidence of cardiogenic shock (2.2% vs. 6.3%, p<0.001; odds ratio [OR] 0.33, 95% confidence interval [CI], 0.18-0.61), AKI (5.1% vs. 8.7%, p=0.016; OR 0.57, 95% CI, 0.36-0.88), and ARF (5.7% vs. 12.7%, p<0.001; OR 0.42, 95% CI, 0.28-0.63); decreased in-hospital mortality (<11 vs. 3.1%, p=0.002; OR 0.2, 95% CI, 0.07-0.57); shorter LOS (2.66 ± 1.96 days vs. 3.40 ± 3.05 days, p<0.001); and a reduced total charge (p=0.001), respectively. The incidence of cardiac arrest and ventricular arrhythmias did not differ significantly based on FHxCAD in the unmatched or matched cohorts.

Conclusions:
Family history of CAD was associated with favorable clinical outcomes in both unmatched and propensity-matched cohorts of in-hospital TCM patients. Further studies are necessary to identify mechanisms contributing to the association between in-hospital TCM outcomes and FHxCAD.