bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11681: Engineering of an IPSC Derived Perfusable and Thick Three-Layer Cardiac Tissue
Authors: Miki Kenji , Gershlak Joshua R , Ott Harald
Published: June 2023

Introduction:
The left ventricular wall is an approximately 1 cm thick tissue composing of vascular networks and three distinct layers: the endocardium, the myocardium, and the epicardium. Engineering of a perfusable and thick three-layer cardiac tissue from human induced pluripotent stem cells (hiPSCs) has not been accomplished to date. Here, we describe formation of a perfusable and thick three-layer engineered cardiac tissue (PTTL-ECT) using additive and subtractive manufacturing.

Methods:
hiPSCs were differentiated into endocardial (Endo) cells, cardiomyocytes (CMs) and epicardial (Epi) cells. To create a perfusable vascular network in an engineered cardiac tissue, we used a water-soluble heat extruded material to print a sacrificial pattern that would eventually dissolve and become a vascular lumen. By casting hydrogels and the three types of cells derived from hiPSCs, we stacked the endocardial layer, myocardial layer, and epicardial layer mimicking the architecture of the ventricular wall . We then compared PTTL-ECT with engineered tissues without perfusable vascular channels (TTL-ECT) and single layer perfused tissues (PTSL-ECT).

Results:
Purity of hiPSC derived-Endo cells, -CMs, and -Epi cells reached 96.98±1.33% for NFATC1
+
and CD31
+
Endo-cells, 83.95±1.77% for cTNT
+
CMs, and 97.75±1.75% for WT1
+
Epi-cells, respectively. The PTTL-ECT had 1.2 cm thickness at day 1 after casting. Histological analysis of the TTL-ECT without vascular channel showed a necrotic core with only the outermost cell layer survived after 4 weeks of culture. Addition of the vascular channel enabled cell survival across the thickness of the entire PTTL-ECT, while the three-layered structure remained intact over four weeks of perfusion culture. CMs in the PTTL-ECT showed enhanced maturity in terms of gene expression profiles, sarcomere lengths and contraction force compared with PTSL-ECT.

Conclusions:
By combining additive and subtractive manufacturing methods, we successfully generated a perfused, three layers thick cardiac graft that maintained architecture and viability over extended culture periods. The PTTL-ECT could be an useful in vitro model that mimic the native ventricular tissue in disease modeling and drug testing.
Abstract 11691: Self-Reported Sodium Intake Identifies a Sodium Vulnerable State With Increased Response to Spironolactone in HFpEF
Authors: Martens Pieter , Mullens Wilfried , Fang James C , Tang Wai Hong
Published: June 2023

Introduction:
Asking patients about sodium intake is standard practice in heart failure (HF).

Hypothesis:
Self-reported sodium intake in HF with preserved ejection fraction (HFpEF) reflects a vulnerability to sodium intake driven by aldosterone.

Methods:
The TOPCAT trial registered self-reported sodium intake at baseline. Cox-regression and linear-mixed models were used to assess the relationship between self-reported sodium intake and outcome. Interaction analysis between self-reported sodium intake and the treatment effect of spironolactone on HF-outcome, blood pressure (BP), dyspnea and edema at follow-up were used to assess sodium vulnerability mediated by an aldosterone effect.

Results:
Self-reported sodium intake of 1748 HFpEF patients included in TOPCAT were divided according to tertiles of sodium intake (47% low, 35% moderate and 18% reported high sodium intake). After covariate adjustment lower self-reported sodium intake associated with higher risk for HF-admission (p=0.009). Patients with a lower sodium intake demonstrated higher E-wave and LV-end diastolic volume and higher estimated plasma volume (p<0.001). Lower sodium intake was associated with a larger treatment effect of spironolactone on HF-admission (HR=0.69, 95%CI 0.53-0.91 vs highest tertile HR=1.37 95%CI 0.79-2.38, p-interaction=0.030). Additionally, linear-mixed models indicated larger BP-reduction (Figure) and larger reduction in dyspnea and edema (p-interaction all<0.001) in patients with lower sodium intake receiving spironolactone.

Conclusions:
Low self-reported sodium in HFpEF is associated with volume status and higher risk of HFH. The more pronounced treatment effect with spironolactone on HF-outcome, BP and volume status in patients with the lowest self-reported sodium intake potentially suggests that low self-reported sodium intake is an indicator of a sodium vulnerable, potentially aldosterone driven, state.
Abstract 11693: Improving Angiotensin Receptor-Neprilysin Inhibitor Utilization for Veterans Admitted With Acute Decompensated Heart Failure: A Single-Center Experience
Authors: Underberg Daniel L , Jiang Michael , DUNNE SEAN , Tibrewala Anjan , Kansal Mayank
Published: June 2023

Objective:
Improve angiotensin receptor-neprilysin inhibitor (ARNI) utilization among patients admitted with acute decompensated heart failure (HF) through a multidisciplinary quality improvement (QI) intervention.

Background:
ARNIs reduce mortality and hospitalizations for patients with HF and abnormal systolic function; current guidelines recommend them as first-line agents for Stage C HF. Inpatient initiation of ARNIs during an acute exacerbation is cost-effective and safe. Despite this, ARNI utilization remains low nationally and at our center.

Methods:
We implemented a multidisciplinary QI intervention at a large urban Veterans Affairs (VA) medical center. The intervention included electronic health record system redesign to provide clinical decision support, a new pharmacy-led screening process and recommendation system to the primary inpatient team, and an educational campaign. Our primary outcome metric was monthly ARNI initiation rate, defined as the number of new ARNI initiations divided by the number of eligible patients admitted for an acute HF exacerbation. We used a statistical process control (XmR) chart to measure change.

Results:
We observed a statistically significant, non-random improvement in mean monthly ARNI initiation rate from 8.4% pre-intervention to 35.7% post-intervention. An XmR chart is shown in Figure 1. Split limits analysis showed variation post-intervention was within statistical control, suggesting sustainable change.

Conclusions:
Our outcomes demonstrate successful implementation of a multidisciplinary intervention to improve ARNI utilization among patients admitted with acute decompensated HF at a large VA medical center. ARNI initiation rate increased significantly post-intervention, and the split limits analysis suggests that our results represent sustainable change. A longer period of data collection will be useful to assess HF readmission and mortality rates in response to this intervention.
Abstract 11698: Family History of Atherosclerotic Cardiovascular Disease and Subclinical Coronary Atherosclerosis Among Asymptomatic Individuals: The Miami Heart Study at Baptist Health South Florida
Authors: Patel Jaideep , Al Rifai Mahmoud , Cainzos Achirica Miguel , Feldman Theodore , Blaha Michael J , Shapiro Michael D , Blankstein Ron , Sharma Garima , Ali Shozab S , Arias Lara , Saxena Anshul , Feldman David , Cury Ricardo C , Budoff Matthew , Fialkow Jonathan , Nasir Khurram
Published: June 2023

Introduction:
We sought to examine whether a positive family history of coronary heart disease and/or stroke (FamHx) is associated with presence of subclinical coronary atherosclerosis, as evaluated using CAC and CCTA, in asymptomatic individuals. We also evaluated whether these associations differ by FamHx type.

Hypothesis:
Coronary atherosclerotic plaque burden by CCTA and baseline CAC score will differ depending on the FamHx domain assessed.

Methods:
We included 2,359 asymptomatic participants free from known ASCVD from the Miami Heart Study, an ongoing, community-based, prospective cohort study where all participants underwent CAC, CCTA, and FHx assessment at baseline. Self-reported FamHx in first-degree relatives was evaluated using 5 definitions: any, premature, parental, sibling, and both parents and siblings. We used multivariable logistic regression models to estimate adjusted the associations between each FamHx definition, CAC>0, and presence of any coronary plaque on CCTA.

Results:
A total of 546 (23%) participants reported any FamHx (mean age 53.5 +/- 6.8 years, 54% female, 45% with CAC >0, and 50% with any coronary plaque). In analyses adjusted for sociodemographics, any FamHx was associated with CAC>0, and FamHx of both parents and siblings showed the strongest association with CAC>0 (OR 2.17; 95% CI 1.01, 4.67), followed by premature FamHx (
Table
). The associations for any and parental FamHx remained statistically significant after further adjusting for traditional risk factors, while the other definitions trended in the same direction, but the confidence intervals included the null value. Associations with any plaque on CCTA were weaker than for CAC>0, and none was statistically significant.

Conclusion:
FamHx, particularly a FamHx in both parents and siblings and premature FamHx, is associated with presence of CAC>0. The number of participants with several definitions of FHx was low, likely limiting statistical power.
Abstract 11725: Exosomes Secreted from TSG6-Rich Adipose-Derived Stem Cells Induce Neovascularization in Ischemic Limb
Authors: Yamaguchi Kosei , Inoue Oto , Usui Soichiro , Nomura Ayano , Hashimuko Daiki , Takeda Yusuke , Goten Chiaki , Takashima Shinichiro , Sakata Kenji , Iino Kenji , Takemura Hirofumi , Takamura Masayuki
Published: June 2023

Introduction:
Therapeutic angiogenesis is attractive for tackling cardiovascular disease. Exosomes, which contain growth factors and micro RNAs, might be useful to develop cell-free therapeutic angiogenesis. Previously we have reported that CD271+ADRCs have excellent angiogenic activity. In this study, we investigated the in vivo angiogenic effects and mechanisms of CD271+ ADSC-derived exosomes (CD271+ Exo) using a mouse model of limb ischemia.

Methods:
We analyzed single-cell RNA-sequencing data of human stromal vascular fraction (SVF) cells. After normalization and clustering, CD271+ and CD271- cells were analyzed in DESeq2. Next, we established CD271+/- ADSCs from human SVF using FACS. After 48 hours of serum deprivation, conditioned media was collected. Exosomes were purified by magnetic isolation using phosphatidylserine/Tim4 interaction and confirmed by ELISA of exosomal markers. We labeled exosomes by PKH26 membrane dye and injected them into a mice model of limb ischemia. After 2 weeks, lectin perfused limb was harvested and analyzed by immunohistochemistry (Fig.A).

Results:
In single-cell transcriptome of human SVF, TSG6 was predominantly expressed in Lineage-CD34+ stromal cells. Furthermore, TSG6 was significantly upregulated in CD271+ SVF cells compared to CD271- SVF cells and other cluster cells (Fig.B). Consistently, TSG6 mRNA expression was upregulated in CD271+ ADSCs (Fig.C). We confirmed exosomal marker expression (CD63, CD9, and CD81) of isolated Exo (Fig.D). In exosome therapy, CD271+ Exo promotes neovascularization compared to CD271- Exo or PBS. Notably, there were more cells containing PKH labeling in the CD271+ Exo-treated group (Fig.E).

Conclusions:
This study reveals a novel mechanism by which CD271+ Exo promotes angiogenesis via TSG6. CD271+ Exo would be useful for cell-free therapeutic angiogenesis.
Abstract 11732: Assessing Efficacy of Post-Acute Heart Failure Discharge Follow-Ups at a Safety-Net Hospital
Authors: Gunta Preetham , Ubaid Aamer , Gupta Kashvi , Lopez-Candales Angel
Published: June 2023

Introduction:
Recent data shows that when adults are discharged after hospitalization for acute heart failure (HF), a clinic follow up with either cardiology or general medicine within 7 days results in significantly lower chances of 30 day readmissions. We sought to analyze the trends of clinic follow up after acute HF hospitalization and the associated barriers and facilitators at our safety net hospital.

Methods:
Data was extracted from the electronic medical records using ICD 9,10 codes for acute HF admissions between Jan 2019 and Dec 2021. Quarterly trends of rates of clinic follow up were analyzed over the past 3 years; t-test was used to assess for statistical significance. Multivariable logistic regression models were constructed to test the association between patient level factors and clinic follow up after adjusting for sociodemographic factors. A p value < 0.05 was used to establish significance.

Results:
Of 1,037 patients admitted for acute HF between 2019-2021, 29.5% were 65 years or older, 64.7% were males, 48.7% were Black and 16.6% were uninsured. Only 8% and 23.1% had a 7 and 14 day clinic follow up respectively. Of those with scheduled follow up 65% and 56% showed up to their appointments at 7 and 14 days respectively. Overtime we noted an increase in the proportion of encounters with a 7 day follow up although the effective follow up (after accounting for no-shows) remained unchanged. Patients that had an inpatient cardiology consult had higher odds of getting a 7 day follow up (OR=1.42, p value = 0.001) after adjusting for age, gender, insurance status and race (black > white, OR = 1.34, p<0.001).

Conclusions:
Our study showed that the effective 7 day follow up did not improve from 2019 to 2021 likely due to COVID19 pandemic. However, a significantly higher proportion of patients obtained 7 day appointments in the last quarter with room for improvement. Steps to increase follow up rates include intervening on the highlighted modifiable factors to achieve better results.
Abstract 11737: Transhepatic Echocardiographic Approach Compared to the Subcostal Approach for Evaluation of the Inferior Vena Cava in Postoperative Patients With Cardiac Surgery
Authors: Orozco -Sepulveda Dayana , Lomeli Sanchez Oscar , Lin Chen C , Ramos Aguas Diego Alejandro , SANTALO RAMON E , Hernandez del Rio Jorge Eduardo , Miranda - Aquino Tomas
Published: June 2023

Introduction:
In postoperative cardiac surgery patients due to the presence of mediastinal tubes, evaluation of the IVC is complicated with the subcostal view, so the transhepatic view could be an option for its evaluation in these patients.

Methods:
We obtained a validation group of non-surgical patients and later in a group of postoperative cardiac surgery patients with mediastinal tubes. Measurements of the IVC diameter in both views was obtained. Agreement between measurements diameters, the time it took to obtain the images, the degree of pain and the quality of the echocardiographic image were compared. The agreement of the variables was determined by the Pearson test.

Results:
A total of 43 patients were obtained from the validation group and 49 patients from the group of postsurgical patients. In the validation group, no significant difference was found in the maximum diameter in subcostal vs. transhepatic (15.6 (± 6.1) vs 16.0 (± 6.2); p = 0.9, r = 0.93), neither in the minimum diameter (11.2 (± 6.8) vs 11.5 (± 6.8); p = 0.7, r = 0.94), nor at the time of execution of the images (15 (11-23) vs 10 (7 -21); p = 0.09, r = 0.17, neither in pain. The transhepatic view had a good image quality (98 % vs 85 %; p = 0.007). In the group of postsurgical patients, no significant difference was found in the maximum diameter in subcostal vs. transhepatic (18.3 (± 5.2) vs. 18.1 (± 4.8); p = 0.8, r = 0.90), neither in the minimum diameter (14.5 (± 5.4) vs 14.3 (± 7.2); p = 0.9, r = 0.93), the time to acquire the image was superior to the subcostal view (57s (40-83) vs 18s (12-32); p = < 0.0001, r = 0.43); the subcostal view had an analogous visual scale of major pain (8 vs 0; p = < 0.0001), transhepatic view had a better good image quality (96 % vs 40 %; p = < 0.0001).

Conclusions:
In cardiac postoperative patients, it is possible to use the transhepatic view because it has an excellent agreement with the values of the subcostal window, with less time to obtain the images and with better image quality.
Abstract 11762: Increased Body Mass Index/Obesity is Associated With Higher Mortality and Major Adverse Cardiac Events in Patients With Hypertrophic Obstructive Cardiomyopathy (HOCM) on a Long-Term Follow-Up - A Systematic Review and Meta-Analysis
Authors: Edusa Samuel , Sharma Aditya , Naseem Rabia , Patel Yash R , Kang Gurmannat SIngh , Singh Ibadat Anmol , Reddy Shilpa , Reyaz Nafisa , Desai Aakash , Duggirala Sonal Devi , STANIKZAI SAMIR , Prem Anand Dharshana , Desai Rupak
Published: June 2023

Background:
Considering a paucity of pooled data on the influence of Body Mass Index (BMI) on long-term cardiac outcomes in individuals with Hypertrophic Obstructive Cardiomyopathy(HOCM), we conducted this systematic review.

Methods:
PUBMED, Scopus, EMBASE and Google Scholar were used to screen studies reporting Mortality/Major Adverse Cardiac Events (MACE) and Sudden Cardiac Death(SCD) among obese vs nonobese HOCM patients. Pooled odds ratios(OR) and heterogeneity were assessed with random-effects models and I
2
statistics. Subgroup analysis was performed to assess the risk by study type, sample size, country and procedure. The leave-one-study-out method was used for sensitivity analysis.

Results:
Of the 178 titles screened, we included 13 studies published between 2016-2022 with a total of 2,409,397 HOCM patients followed for a median of 6 years (1.8-8.2 year range). The sample had a higher proportion of males (61.33%) with a mean age of 56.3 years (37-78 year range). The unadjusted [OR=1.55(1.09-2.21), I
2
=96%] and adjusted [OR=1.28 (1.06-1.54), I
2
=82.7%] pooled odds of all-cause mortality were significantly higher with increased BMI. On subgroup analyses, prospective studies showed higher odds [n=3, 1.79 (1.23-2.6), p<0.01] vs. retrospective ones [n=10, OR=1.2(0.99-1.46), p=0.06]. US Studies, which had large sample sizes, had higher odds [n>=1000:OR=1.39(1.24-1.57)] but lower sample sizes from other countries [n<1000] failed to show statistical significance. The odds of MACE increased with higher BMI [OR=4.27(3.50-5.21), p<0.01], without a significant impact on the risk of SCD [p=0.10]. In those who underwent septal myectomy, increased BMI was associated with higher post-procedural all-cause mortality [OR=1.12(1.02-1.22), p=0.01].

Conclusions:
A higher BMI/obesity in HOCM is associated with increased all-cause mortality, MACE and mortality after septal myectomy on a long-term follow-up (>5 years), without an association with SCD risk.
Abstract 11766: Impact of Increasing Stent Length on Long-Term Clinical Outcomes Undergoing Intracoronary Imaging-Guided Percutaneous Coronary Intervention With New-Generation Drug-Eluting Stents
Authors: Kurosawa Yuta , Shimizu Takeshi , Sakuma Yuya , Ohara Himika , Muto Yuki , Sato Yu , Kiko Takatoyo , Sato Akihiko , Misaka Tomofumi , Yoshihisa Akiomi , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika
Published: June 2023

Background:
While longer stent length of first-generation drug-eluting stents (DES) has been associated with stent-related adverse events, the association between stent length of new-generation DES and clinical outcomes remains controversial.

Methods and Results:
Consecutive 1403 patients including 2277 lesions who underwent intracoronary imaging-guided percutaneous coronary intervention with 2nd- and 3rd-generation DES were enrolled. Patients were divided into two groups according to total stent length (TSL), and followed up for major adverse cardiovascular events (MACE), defined as a composite of cardiac death, non-fatal myocardial infarction and target lesion revascularization (TLR) for patients. Lesions were divided into two groups according to TSL as well, and followed up for TLR and stent thrombosis. In the per patient analysis, long TSL group (TSL ≥ 32 mm, n = 703) had higher prevalence of diabetes (54.5% vs. 45.2%, P < 0.001), anemia (48.4% vs. 43.0%, P = 0.042), peripheral artery disease (<% vs. 10.6%, P = 0.003), multi-vessel disease (64.7% vs. 36.2%, P < 0.001) and chronic total occlusion (9.5% vs 3.4%, P 0.001) than short TSL group (TSL < 32 mm, n = 691). In the follow up period (mean of 1528 days), MACE and TLR were significantly higher in long TSL group than in short TSL group (P = 0.009 and P = 0.037, respectively). In the multivariate analysis after adjusting for confounding factors, the long TSL was an independent predictor of MACE and TLR (hazard ratio [HR] 1.59, P = 0.002 and HR 1.74, P = 0.047). In the per lesion analysis, Kaplan-Meier curve revealed that TLR was significantly higher in long TSL group (TSL ≥ 26 mm, n = 1160) than short TSL group (TSL < 26mm, n = 1117) (P = 0.017), while stent thrombosis was comparable between the two groups. In the multivariate analysis, TLR was an independent predictor of TLR (HR 1.62, P = 0.029).

Conclusion:
Longer stent length of new-generation DES was associated with MACE and TLR, but not with stent thrombosis.
Abstract 11768: Reducing the Burden of the Opioid Epidemic by Adopting a Novel Pain Control Strategy Utilizing Pectoral Nerve Block in Adults Undergoing Transvenous Cardiac Device Implants
Authors: Brider Jamarcus , Lee Bridget , Doty Brandon , Al-Hindi Feross , Nair Devi
Published: June 2023

Introduction:
Despite early mitigation efforts, the opioid pandemic in the United States has persisted and affected many Americans. A public health emergency was declared regarding opioid prescriptions. Alternative approaches to postoperative pain control after transvenous cardiac device implants (TCDI) in adults have not been described.

Methods:
We report a single center retrospective analysis of 153 consecutive patients that underwent TCDI from January to August 2021 with ultrasound guided pectoral nerve block (PNB) using liposomal bupivacaine prior to implant for postoperative pain control. Pain scores (0-10) were recorded systematically during recovery, at discharge, and at wound check follow up. Opioid use in the postoperative period was recorded as well.

Results:
A total of 153 patients were evaluated, 50% female with a mean age of 71.2 years. All patients received PNB successfully with no device site infection or hematoma. The mean Visualized Analog Scale (VAS) pain scores at 1, 3, and 5 hours after the procedure, at discharge, and at follow up were 1.93, 1.22, 1.10, 1.05, and 0.125 respectively. No patients required opioids for pain control throughout the average postoperative period of 14 days.

Conclusion:
Pectoral nerve block with liposomal bupivacaine can be administered safely before TCDI and provides adequate pain control without need for opioid use postoperatively. Further research is needed to assess broad scale implications of this approach to larger patient populations.

Figure 1: Ultrasound Guided PNB, pectoralis major (PM), pectoralis minor (Pm)

Graph of the average postoperative pain score and opioid use during follow up visit over time
Abstract 11793: Rates and Causes of Readmission in Patients With Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis of 17,860 Index Hospitalizations
Authors: Mondal Avilash , Katukuri Nishanth , Kanagala Sai Gautham , Mohammed Adil S , Gurram Priyatham , Ashfaque Mariam , Sofia Amara , Kauser Humaira , Sayyeda Qudsia , Arepalli Satya Sai Venkata Lakshmi , Desai Rupak
Published: June 2023

Background:
The risk of fatal and recurrent cardiovascular complications in Hypertrophic Cardiomyopathy (HCM) warrant data to identify the rate, causes and predictors of readmission on a large scale. We conducted the first-ever meta-analysis to evaluate the pooled rate of short-term and long-term readmissions after index HCM admissions.

Methods:
PubMed/Medline, EMBASE and SCOPUS databases were systematically reviewed to find studies through May 2022 reporting rates and causes of readmission following index HCM admissions. Random effects models were used to estimate pooled rates and causes of readmissions and I
2
statistics were used to report inter-study heterogeneity.

Results:
This meta-analysis included 17860 index HCM admissions (Mean age: 46-67 years, median follow up duration: 321.6 days, Female 53.11%) from 17 studies, which revealed a 14.8% [95% CI 12.2%-17.4%, I
2
=96%] pooled rate of readmission
(Fig. 1)
. Studies published from China (23.5% vs. 10.5%) had a higher readmission rate than the USA
(Fig. 2)
. The long-term readmission rate was highest within 1-3 years (26.6%) and in patients who underwent alcohol septal ablation procedure (10% vs 7.6%) compared to those who underwent surgical myectomy
(Fig. 3)
. The readmission rate was higher in cohorts with smaller sample sizes (19.2% vs 10.2%) (n<1000 vs. n>1000). Among the readmission events, congestive heart failure, and acute decompensated heart failure were the leading causes of readmission, accounting for up to 66% of the readmission cases [95%CI 32.5%-100.4%, p<0.001] following index admissions.

Conclusions:
In this global meta-analysis, the pooled rate of readmission following index HCM hospitalizations was nearly 15% over a year's follow-up, with heart failure accounting for two-thirds of the readmissions.
Abstract 11820: A Meta-Analysis of Efficacy and Safety of the New Generation Watchman FLX Device Compared to the Watchman 2.5
Authors: Zaalouk Mostafa R , Eid Mohamed , Al-Abdouh Ahmad , Ismayl Mahmoud , Mohamed Sarah , Mannumbeth renjithlal Sarath lal , Mubasher Mahmood , Mamas Mamas
Published: June 2023

Introduction:
The first-generation Watchman 2.5 (W2.5) is associated with several limitations, including the difficulty of implantation in complex LAA anatomies, peri device leak, device recapture and device-related thrombosis. The second-generation Watchman FLX (W-FLX) addressed those limitations with proven safety and efficacy of the device.

Hypothesis:
This meta-analysis compares the safety and efficacy of the Watchman FLX and 2.5 devices.

Methods:
The meta-analysis was conducted according to PRISMA guidelines. Studies were located through a search strategy utilizing PubMed, Google scholar and MEDLINE from inception to March 20, 2022, with a primary objective to compare the safety and efficacy of the W-FLX and W2.5. After setting inclusion and exclusion criteria, we identified three recently published observational studies.

Results:
Our analysis included 3 studies comprising 401 patients. New generation W- FLX is associated with less incidence of major-leak compared to the first-generation W 2.5, OR: 0.08 CI (0.06-0.12) P <0.01
(Figure 1).
There was no difference in mortality OR: 1.38 CI (0.00-152360) P .78, procedure success OR: 16.07 CI (0.06-4676.83) P 0.1 or post-procedural complications (Bleeding OR: 0.63 CI (0.03-13.07) P 0.31, device embolization OR: 0.12 CI (0.00-3.79) P 0.08, pericardial effusion OR: 0.14 CI (0.00-12.23) P 0.11 or stroke OR: 0.7 CI (0.00-9170) P 0.71) across the two devices.

Conclusions:
The new generation Watchman FLX has a superior sealing capacity than the Watchman 2.5 with a similar safety profile.
Abstract 11822: Pivotal Trial of a Deep-Learning-Based Retinal Biomarker (Reti-CVD) in the Prediction of Cardiovascular Disease: Data From CMERC-HI
Authors: Rim Tyler Hyungtaek , Lee Chan Joo , Yi Joseph , Lee Geunyoung , Yu Marco , Tham Yih-Chung , Wong Tien Y , Cheng Ching-Yu , Kim Dong Wook , Kim Sung Soo , Park Sung Ha
Published: June 2023

Introduction:
The Korean Ministry of Food and Drug Safety (K-MFDS) has authorized over 110 artificial intelligence (AI)-software as medical devices (AI-SaMDs) for diagnostic purposes. Herein, we clinically validate the efficacy of a three-tier cardiovascular disease (CVD) risk stratification system developed using Reti-CVD, an AI-SaMD that utilizes retinal images to estimate CVD risk. The aim of this study is to evaluate the efficacy of RetiCVD in predicting future CVD risk based on retrospective analysis of a prior prospective cohort study.

Methods:
This clinical study was a single-center, retrospective, conformity-design, confirmatory analysis of prior prospective cohort study. For primary endpoint, retinal images were evaluated by Reti-CVD to validate its three-tier CVD risk stratification system. For secondary endpoints, cardiac CT-measured coronary artery calcium (CAC, 0, >0-100, and >100), carotid intima-media thickness (CIMT, <90
th
and ≥90
th
percentile), and brachial-ankle pulse wave velocity (baPWV, <1800 and ≥1800 cm/s) were also measured as independent variables for future CVD risk. The cumulative incidence of non-fatal and/or fatal CVD events was evaluated. Cox proportional hazards models were used to estimate the hazard ratios (HR) trends.

Results:
In this clinical cohort (n=1106), 33 (3.0%) participants had non-fatal or fatal CVD events over 5 years, and RetiCVD scores were significantly associated with increased CVD risk (HR trend=2.02, 95% CI, 1.26-3.24). In a multivariable Cox model incorporating RetiCVD scores, CAC, CIMT, baPWV, and other traditional risk factors, RetiCVD scores for the high-risk tier were significantly associated with increased CVD risk (low risk as a reference; HR=3.56 [1.34-9.51] in high risk), while other biomarkers showed trends toward association: CAC showed a HR of 2.45 [0.88-6.84] in CAC of >100 compared to zero CAC (reference); CIMT showed a HR of 1.50 (0.64-3.51) in CIMT of ≥90
th
percentile compared to <90
th
percentile; and baPWV showed a HR of 1.27 (0.53-3.03) in baPWV of ≥1800 compared to <1800 cm/s.

Conclusions:
This is the first K-MFDS approved AI-software that can potentially stratify future risk as biomarkers, which can have major implications such as identifying high-risk individuals.
Abstract 11895: Decreased Heart Rate Variability Associated With Hopelessness in Patients With Ischemic Heart Disease
Authors: Goodyke Madison , Baynard Tracy , Bronas Ulf G , Tintle Nathan , Dunn Susan L
Published: June 2023

Hopelessness, a negative outlook and sense of helplessness toward the future, is present in 27-52% of patients with ischemic heart disease (IHD) and is associated with increased morbidity and mortality. Physiologic dynamics of hopelessness in patients with IHD are largely unknown.

Purpose
: To examine how stress adaptation, measured by high frequency (HF) heart rate variability (HRV), following an IHD event may be associated with hopelessness. Subgroup differences focusing on characteristics known to be associated with hopelessness and/or HRV will also be examined (i.e., IHD event, marital status, sex).

Hypothesis
: Decreased HF HRV will be associated with greater levels of hopelessness.

Methods
: Participants were enrolled while hospitalized for an IHD event after being identified as appropriate for HRV analysis (n=69). Two weeks after hospital discharge, participants wore a Polar H7 heart rate monitor for 10 minutes while supine for HRV data collection. A demographic questionnaire and State-Trait Hopelessness Scale were then completed. From the 10-minutes of HRV data, a 5-minute HRV segment with the least amount of artifact (<5%) was used for analysis. HRV data was log transformed to account for non-normality. Linear regression was used to assess the relationship between HRV and state hopelessness.

Results
: There was a moderate negative correlation between HF HRV and state hopelessness (r= -0.35, p=0.004). This remained significant in multivariable regression models when controlling for history of depression and factors known to influence HRV (i.e., time of day, age, and smoking status). No sex differences (Cohen’s d=-0.04, p=0.78) were observed for HF HRV, but persons who underwent bypass surgery had lower HF compared to those that did not (Cohen’s d=0.63, p=0.04). Due to high correlation with HF and root mean square of successive differences between normal heartbeats (rMSSD) and SD1 (r=0.85), patterns of association with hopelessness and those variables were similar throughout.

Conclusion
: Decreased HF was moderately correlated with increased state hopelessness following an IHD event. Assessing HRV in patients following an IHD event could provide promising evidence of a biomarker to assist in identifying patients at risk for hopelessness.
Abstract 11920: Positive Hiv Status Increases Length of Stay And Cost of Hospitalization Among Hospitalized Patients With Acute Myocardial Infarction and Heart Failure: An Analysis of National Inpatient Sample 2016 to 2019
Authors: Shoar Saeed , Sharma Samin K
Published: June 2023

Introduction:
Due to dramatic advance in the development of highly active antiretroviral therapy, patients living with human immunodeficiency virus (HIV) (PLWH) have gained a near-normal life expectancy. As a result, cardiovascular diseases are now the most common causes of mortality among PLWH.

Objectives:
We aimed to investigate if HIV positive status affect the outcomes of PLWH hospitalized with acute myocardial infarction (AMI) or heart failure (HF) in the United States.

Methods:
Using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), we queried the national inpatient sample database to identify admission cases with AMI or HF between 2016 and 2019. Then, we stratified the AMI and HF cases according to their HIV status. Weighted data was analyzed to compare mortality rate, frequency of home disposition (HD), length of stay, and total hospital charges between HIV positive and HIV negative patients for AMI and HF admission cases.

Results:
Data pertaining to a total of 28,484,087 admissions was analyzed. Of this, there were 896,702 cases of AMI and 4,154,918 cases of HF. HIV status was positive in 0.24% and 0.32% of AMI and HF patients, respectively.

Conclusion:
HIV positive status is associated with a longer length of stay and total hospital charged among hospitalized patients with AMI or HF. While PLWH admitted with AMI have a higher mortality rate than HIV negative counterparts, the HIV status does not seem to impact the outcome of HF patients. Additionally, PLWH seem to be more frequently discharged home than HIV negative patients.
Abstract 11939: Phosphorylation of Serca2 at Serine 663, a Physiological and Clinical Event in Ischemic Heart Diseases, That Regulates Intracellular Ca
2+
and Cell Death
Authors: GONNOT FABRICE , Dia Maya , GOURIOU Yves , Bidaux Gabriel , Chouabe Christophe , Crola Da Silva Claire , Ducreux Sylvie , PILLOT Bruno , Kaczmarczyk Andrea , Leon Christelle , Perret Coralie , Sciandra Franck , Farhat Fadi , Sebbag laurent , Bochaton Thomas , Thibault Helene , Ovize Michel , Paillard Melanie , Gomez Ludovic
Published: June 2023

Introduction:
Despite advances in cardioprotection, new therapeutic strategies capable of preventing acute myocardial ischemia-reperfusion injury and reducing secondary event of patients are still needed.

Hypothesis:
We hypothesized that limitation of SERCA2 phosphorylation on a serine/threonine residue at reperfusion could provide protection against reperfusion injury, via the activation of the Ca
2+
reuptake into SR/ER which confers detoxification of the cytosolic and mitochondrial Ca
2+
overload during reperfusion
.
Methods:
Combining
in silico
analysis with
in vitro
and
in vivo
genetic approaches, we discovered that the phosphorylation of SERCA2 at serine 663 is a clinical and pathophysiological event of cardiac function.

Results:
We demonstrated that the phosphorylation level of SERCA2 at serine 663 is increased with heart damage in both patient and mouse ischemic hearts. Mechanistically, we demonstrated that preventing serine 663 phosphorylation significantly increased SERCA2 Ca
2+
pumping activity into the reticulum and protected against hypoxia/reoxygenation-induced cell death, by counteracting the cytosolic and mitochondrial Ca
2+
overload. To link this specific residue event to a physiological role of SERCA2 in heart, we demonstrated that gene therapy for the phosphoresistant form of SERCA2 at serine 663 improved the excitation/contraction coupling of cardiomyocytes and significantly reduced infarct size in an
in vivo
myocardial infarction model, whereas mice expressing a phosphomimetic form of SERCA2 developed a larger infarct size.

Conclusions:
Together, these findings establish the pathophysiological role and the therapeutic potential of SERCA2 modulation in acute myocardial infarction, based on the hotspot phosphorylation level of SERCA2 on its serine 663 residue.
Abstract 11968: Association Between Reduction in Inflammation and Change in Cardiovascular Risk: Results From the Liira Study
Authors: Weber Brittany N , Weisenfeld Dana , Seyok Thany , Massarotti Elena , Barrett Leanne , Solomon Daniel , Plutzky Jorge , Bolster Marcy , DI CARLI MARCELO , Liao Katherine P
Published: June 2023

Background:
Coronary microvascular disease (CMD) is associated with increased cardiovascular (CV) risk in rheumatoid arthritis (RA). Studies suggest that higher RA disease activity is associated with a higher degree of CMD, as measured by coronary flow reserve (CFR). However, it is not known whether reducing inflammation results in improvement in CMD or other CV correlates. The objective of this study was to determine the association between reducing inflammation with changes in CV risk.

Methods:
The Lipids, Inflammation and CV risk in RA (LiiRA) study recruited RA patients age ≥18 yrs with active RA about to initiate a TNFi as part of clinical care. All subjects underwent a stress myocardial perfusion PET scan to quantify CFR at baseline and after 24 weeks. A lower CFR in the absence of obstructive CAD is indicative of CMD, CFR< 2.5 defined CMD. Inflammatory markers and hs-cTnT were performed at baseline and 24 weeks. Primary and secondary outcomes was change in CFR and hs-cTnT, respectively, and tested by Spearman correlations.

Results:
A total of 66 subjects completed the study, 80% female, mean RA duration 7.7 yrs. Baseline estimated ASCVD risk was 5.6%, yet 47% had evidence of CMD. We observed a significant reduction in all inflammatory markers between baseline and follow-up, along with improvements in RA disease activity; however, no change in the mean CFR or hs-cTnT was observed. A reduction in hsCRP and IL-1beta was associated with a reduction in hs-cTnT. A non-significant trend for correlation of reduced IL-1beta with higher CFR was observed among subjects with CMD at baseline (Figure).

Conclusion:
There was a high prevalence of CMD at baseline, but CFR did not significantly improve. Reducing inflammation was correlated with improvements in measures of CV risk, mainly in the subset of patients with detectable hs-cTnT, particularly via the IL-1beta pathway. These data suggest that hs-cTnT may be a useful marker when considering targeting inflammation to reduce CV risk in RA.
Abstract 11971: Identification of Response Biomarkers and Signaling Pathways Associated With the LOX-1 Blockade by MEDI6570 in Type 2 Diabetes
Authors: Varma Vijayalakshmi , Sinibaldi Dominic , Ongstad Emily L , Vavere Andrea L , Gabrielsen Anders , Schiopu Alexandru , George Richard T , Gan Li-ming , Nilsson Jan , Collen Anna
Published: June 2023

Introduction
: Elevated circulating soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) levels are associated with risk of MACE and heart failure following acute coronary syndrome (ACS), implying that LOX-1 signaling is a culprit in cardiovascular risk. MEDI6570 is a human monoclonal antibody in clinical trials that binds to LOX-1, antagonizing the interaction with ligands including oxLDL.

Methods:
To determine LOX-1 risk-related biomarkers and associated pathways in response to MEDI6570, we performed Sparse Partial-Least-Squares Discriminant Analysis on transcriptomics (PBMC) and serum proteomics (OLINK) in strong versus weak responders to MEDI6570 treatment, defined by a decrease in sLOX-1, in patients with type 2 diabetes (T2D) in a single ascending dose, placebo-controlled study (NCT03654313). Biomarkers that showed concordance at three or more timepoints during treatment were further tested in an independent high-risk (T2D and/or CVD) cohort (SUMMIT; n=1231), for correlation with sLOX-1.

Results:
We identified biomarkers of inflammation that predominated among others, including oxidative stress, apoptosis, cellular adhesion, and migration. Of these, IL-16 and IL-18 showed significant correlation to sLOX-1 (IL-16 r=0.43, p<0.001; IL-18 r=0.44, p<0.001) in the independent SUMMIT cohort. Additionally, in a subset of the SUMMIT cohort, significant correlations were observed between baseline and 20-year follow-up levels for sLOX-1 (r=0.271, p=0.012), IL-16 (r=0.243, p=0.025), and IL-18 (r=0.459, p<0.0001), demonstrating persistent long-term elevation of these inflammatory markers in patients. We also identified neutrophil-related markers (CEACAM8, PRTN3, PGLYRP1, CPB1, GRN, LTBR) in response to MEDI6570, which have not been previously associated with LOX-1.

Conclusions:
Findings indicate that IL-16 and IL-18 may be potential links between LOX-1 signaling and cardiovascular risk, being modified by treatment with MEDI6570. This study also identified neutrophil-related markers in response to MEDI6570 treatment, implicating a potential role for neutrophils in LOX-1-mediated effects. A phase 2 study in patients with recent ACS and treatment with MEDI6570 or placebo is ongoing (NCT04610892).
Abstract 12056: Angiopoietin-Like Protein 3 Blood Levels and Cardiometabolic Traits and Diseases: A Mendelian Randomization Study
Authors: Gobeil Emilie , Bourgault Jerome , Gagnon Eloi , Arsenault Benoit J
Published: June 2023

Introduction:
Angiopoietin-like 3 (ANGPTL3) is a key regulator of blood lipid levels. ANGPTL3 inhibitors are currently under investigation for their impact on metabolic and cardiovascular health. Our objective was to investigate the causal effect of genetically-predicted blood ANGPTL3 levels on cardiometabolic traits and diseases using Mendelian randomization (MR).

Methods:
We performed a series of two-sample MR studies using cis-acting variants on ANGPTL3 blood levels measured using aptamers in 35,559 participants of the deCODE study. We used inverse-variance weighted-MR to assess the effect of genetically-predicted blood ANGPTL3 levels on lipid and apolipoprotein B levels (from the UK Biobank, n = 441,016 participants), non-alcoholic fatty liver disease (from a genome-wide association meta-analysis [GWAS] of 8434 cases and 770,614 controls of European ancestry), type 2 diabetes (from the DIAGRAM consortium, 74,124 cases and 824,006 controls), acute pancreatitis (from a GWAS of 7832 cases and 793,427 controls of European ancestry) and coronary artery disease (from the CARDIoGRAMplusC4D and UK Biobank GWAS meta-analysis [34,541 cases and 261,984 controls of European ancestry]).

Results:
We selected 27 independent variants near or in the ANGPTL3 region associated with ANGPTL3 blood levels (R2<0.1, p<5x10
-08
). Genetically-predicted ANGPTL3 levels were strongly and significantly associated with triglyceride and apolipoprotein B levels (beta [SE] = 0.156 [0.032], p-value = 1.05x10
-06
, and beta [SE] = 0.058 [0.013], p-value = 8.16x10
-06
, respectively) but were not associated with non-alcoholic fatty liver disease, type 2 diabetes or coronary artery disease (all p-values > 0.05). Genetically-predicted ANGPTL3 levels were however significantly associated with acute pancreatitis (beta [SE] = 0.071 [0.025], and p-value = 0.004).

Conclusions:
Our two-sample MR study revealed that blood ANGPTL3 levels may be causally-related to lipid-lipoprotein levels, but not with cardiometabolic diseases. Blood ANGPTL3 levels were however associated with acute pancreatitis, thereby suggesting that ANGPTL3 inhibition might warrant further investigation in the prevention of acute pancreatitis.
Abstract 12087: Improving Characterization of Abdominal Aortic Aneurysms by Modeling Thrombosis
Authors: Rezaeitaleshmahalleh Seyedmostafa , Lyu Zonghan , King Kristin , Hofer Jan M , Liedl David , Zhang Xiaoming , Rasmussen Todd , McBane Robert D , Jiang Jingfeng
Published: June 2023

Introduction:
In seniors, the prevalence of abdominal aortic aneurysms (AAA) is high (9-10%). We aim to characterize AAA growth rates (slow vs. rapid) to help inform management strategies, including individualized imaging surveillance frequency.

Hypothesis:
Modeling thrombosis may improve the characterization of AAAs' growth status.

Methods:
3D geometrical AAA models with and without thrombosis (vessel lumen only) were generated for 70 human subjects using available contrast-enhanced CTA data. AAA growth rates were categorized as slow (< 5 mm/year) or rapid (≥ 5 mm/year) based on serial imaging. Python scripts were used to calculate geometrical parameters (83) with and without thrombosis. Patient-specific relevant health information was retrieved through a review of medical records. Support vector machine (SVM), a well-established machine learning method, was run with 10-fold cross-validation (100 iterations) to assess the predictive accuracy.

Results:
Among 70 AAAs studied, the ratio between rapidly-growing and slowly-growing was nearly 1:2. The combination of antihypertensive medication, coronary artery disease, juxta-aneurysm aortic size, and five geometrical parameters quantifying the extent of thrombosis provided the best accuracy for AAA's growth status. The area under receiving operating curve (AUROC) was 0.85, and total accuracy was 0.81, with 57% and 93% of rapidly- and slowly-growing AAAs correctly identified, respectively. Excluding patients with aneurysm thrombus, the AUROC and accuracy in predicting rapidly-growing AAAs decreased to 0.82 and 48%, respectively.

Conclusions:
machine-learning-based predictive modeling appears feasible for characterizing AAA's growth rate status. Manual aortic image segmentation, required for data analytics, is labor-intensive (on average, 1 hour). Leveraging artificial intelligence-based segmentation methodology may provide an automated solution to improve workflow and feasibility.
Abstract 12104: Pediatric Hypertrophic Cardiomyopathy With Left Ventricular Systolic Dysfunction: Insights From the Sarcomeric Human Cardiomyopathy Registry (SHaRe)
Authors: Abou Alaiwi Sarah , Roston Thomas M , Vissing Christoffer , Marstrand Peter , Claggett Brian , Nauffal Victor , Parikh Victoria N , Helms Adam S , Ingles Jodie , Jacoby Daniel L , Lakdawala Neal K , Michels Michelle , Owens Anjali T , Ashley Euan A , Pereira Alexandre , Rossano Joseph , Saberi Sara , Semsarian Christopher , Ware James S , Miller Erin , Wittekind Samuel , Russell Mark W , Day Sharlene , olivotto iacopo , Ho Carolyn
Published: June 2023

Introduction:
Left ventricular systolic dysfunction (LVSD, LV ejection fraction (LVEF) <50), occurs in ~8% of adults with hypertrophic cardiomyopathy (HCM) and is associated with poor prognosis. However, the incidence and prognosis of LVSD in pediatric patients with HCM (<18 years old) is poorly understood.

Methods:
Patients in SHaRe with pediatric HCM were included. Time-to-event analyses were performed to estimate 1) cumulative incidence of LVSD in pediatric vs adult HCM (Kaplan Meier), 2) predictors of incident LVSD in pediatric HCM (Cox-proportional hazards) and 3) a composite outcome of all-cause mortality, heart transplant and left ventricular assist device implant in pediatric HCM.

Results:
In total, 1296 pediatric HCM patients (34% females, median 12.2 years at diagnosis, median 8.3 years follow-up) were included. LVSD occurred in 155 (12%) of patients with 29% (n=45) having LVSD at the first SHaRe visit and 22% (n=34) developing LVSD <18 years old. At 5-year follow-up, the cumulative incidence of LVSD was 9% [8-11%]. Predictors of incident pediatric LVSD included HCM before age 12 (HR 2.0 [1.3-3.0]), female sex (HR 0.49 [0.32-0.77]), P/LP variants in thick filament genes (HR 2.6 [1.1-4.2], multiple P/LP variants (HR 9.1 [CI 2.9-29.1]) and baseline LVEF (HR 0.63 [0.58-0.68], per 5 %-points increase). Pediatric HCM was associated with higher rate of LVSD compared to adult-onset HCM (n=6428, median HCM at age 49 years, median follow-up of 7.1 years), p=0.05 (Figure 1). The composite endpoint occurred in 41% (n= 63/155) of children with HCM and subsequent LVSD. In patients with LVSD, female sex (HR 2.44 [1.41-4.17]) and baseline LVEF <35% (HR 4.0 [2.4-6.9]) were independently associated with the composite outcome.

Conclusion:
Females were less likely to develop LVSD but more likely to have adverse outcomes once they do. Clinical outcomes are adverse, and greater recognition of and surveillance for LVSD in pediatric HCM are warranted.