bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9674: Stroke, Migraine, and Cervical Arterial Dissection: Shared Genetics Reveals Concordant and Opposing Risk Mechanisms
Authors: Chasman Daniel , Daghlas Iyas , Sargurupremraj Muralidharan , Danning Rebecca , Gormley Padhraig , Malik Rainer , Amouyel Philipe , Metso Tiina , pezzini alessandro , Kurth Tobias , Debette Stephanie
Published: April 2022

Introduction:
Migraine, stroke, and cervical artery dissection (CeAD) represent a triad of cerebrovascular disorders with pairwise comorbid relationships and vascular involvement. Systematic exploration of their shared genetics may inform shared and divergent etiology.

Methods:
The largest available GWASs for all three disorders were used, including for subtypes of stroke (ischemic stroke [IS], large artery stroke [LAS], small vessel stroke [SVS], cardioembolic stroke [CE]) and migraine (with aura [MA] and without aura [MO]). For each pair of disorders, genetic correlation was assessed both on a genome-wide basis and within candidate loci for each disorder. Cross-trait meta-analysis was used to identify shared novel candidate loci. Causality of migraine susceptibility on stroke and CeAD was evaluated by Mendelian randomization (MR).

Results:
Among all pairs of disorders, genome-wide genetic correlation was only observed for CeAD and migraine, particularly MO. Local genetic correlations were more extensive between migraine and CeAD than migraine and stroke or CeAD and stroke, identifying novel CeAD associations at rs6693567 (
ADAMTSL4/ECM1
), rs11187838 (
PLCE1
), and rs7940646 (
MRVI1
), while strengthening prior subthreshold evidence at rs9486725 (
FHL5
) and rs650724 (
LRP1
). At known migraine loci, novel associations with stroke had concordant risk alleles for SVS at rs191602009 (
CARF
), and for CE at rs55884259 (
NKX2-5
). However, at other migraine loci, there were novel associations with opposite risk alleles for all stroke, IS, and SVS at rs55928386 (
HTRA1
), for LAS at rs11172113 (
LRP1
), and for all stroke and IS, respectively, at rs1535791 and rs4942561 (both
LRCH1
). rs182923402 (near
PTCH1
) was a novel locus for both migraine and CE with concordant effects. MR supported causal influence of migraine on CeAD (OR [95%CI] per doubling migraine prevalence=1.69 [1.24-2.3], p=0.0009) with concordant risk, but with opposite risk on LAS (0.86 [0.76 - 0.96], p=0.0067).

Conclusions:
Genetic effects between migraine and CeAD had concordant effects on risk, highlighting vascular functions in migraine and novel CeAD loci. Most shared loci for migraine and stroke subtypes had opposite effects on risk. The
LRP1
locus was common to all three disorders.
Abstract 9675: Right Ventricular and Right Atrial Function in Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction: A Comparison With Pulmonary Arterial Hypertension
Authors: Van Wezenbeek Jessie , Kianzad Azar , Van De Bovenkamp Arno , Wessels Jeroen , Mouratoglou Sophia-Anastasia , Braams Natalia , Jansen Samara , Meulblok Eva , Meijboom Lilian J , Marcus J. Tim T , vonk noordegraaf anton , Goumans Marie Jose , Bogaard Harm J , Handoko M L , De Man Frances S
Published: April 2022

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is a prevalent condition for which no treatment exists. Pulmonary hypertension (PH) and right atrial (RA) and right ventricular (RV) dysfunction are frequently observed. The question remains whether PH and the associated RV/RA dysfunction in HFpEF are treatment targets or a mere reflection of disease severity.

Methods:
To study the relative contribution of pressure-overload and left-to-right interaction, we compared RA/RV function in three groups: 1. HFpEF (n=13); 2. HFpEF-PH (n=33), and; 3. pulmonary arterial hypertension (PAH) matched to pulmonary artery pressures of HFpEF-PH (n=47). Patients underwent right heart catheterization and cardiac magnetic resonance imaging. Groups were compared using one-way ANOVA, after which post-hoc analysis with unpaired t-test and Bonferroni correction was performed.

Results:
The right ventricle in HFpEF-PH was less dilated and hypertrophied than in PAH and RV ejection fraction was more preserved (HFpEF-PH: 52±11 vs. PAH: 36±12%). RV filling patterns were altered: vena cava backflow during RA contraction was observed in PAH only. In HFpEF-PH, RA pressure was elevated throughout the

cardiac cycle (HFpEF-PH: 10[8-14] vs. PAH: 7[5-10] mmHg), while RA volume was smaller, reflecting excessive RA stiffness (HFpEF-PH: 0.14[0.10-0.17] vs. PAH: 0.08[0.06-0.11]mmHg/mL). RA stiffness was associated with an increased RA eccentricity index (HFpEF-PH: 1.3±0.2 vs PAH: 1.2±0.1) and transmural pressure gradient (9[5-12] vs 2[-2-5] mmHg).

Conclusions:
Despite similar pressure-overload, RV/RA function was less compromised in HFpEF-PH than in PAH. Increased RA pressure and stiffness in HFpEF-PH were explained by left atrial/RA-interaction. Our results indicate that increased RA pressure is not a sign of overt RV failure, but rather a reflection of HFpEF-severity.
Abstract 9686: Stroke and Thrombosis Risk in Left Ventricular Non-Compaction
Authors: Collins Matthew , Laubham Matthew , Joyce Cara , Yu Mingxi , LIEBO MAX
Published: April 2022

Introduction:
Left ventricular non-compaction (LVNC) is a rare genetic condition affecting 1 in 5000 people in which the myocardium of the left ventricle fails to adequately compact, forming deep recesses within the muscle wall. These recesses have been theorized to contribute to thrombus formation and embolic stroke, though the association has never been firmly established in the limited literature over the last 20 years.

Hypothesis:
We assessed the hypothesis that patients with LVNC, as well as those with hypertrabeculation not meeting LVNC criteria, would have increased rates of lifetime incidence of CVA, LV thrombus diagnosis, and distal arterial embolic events.

Methods:
We performed a retrospective control-matched cohort study assessing patients at Loyola University Medical Center diagnosed with LVNC, as well as those with hypertrabeculated left ventricles not meeting LVNC criteria, assembling the largest cohort of adult patients in the literature to date. We matched our study patients to controls based on age, HTN, DM, smoking status, history of atrial fibrillation, and history of DVT/PE.

Results:
Compared to matched controls, neither the LVNC group (n=98) nor the hypertrabeculation group (n=119) showed an increased risk of CVA, but both were associated with an increase in diagnosis of LV thrombus by TTE, TEE, or cMRI (p=0.045, p=0.003, respectively). Furthermore, in the LVNC group, each 10% increase in EF was found to reduce the risk of a composite endpoint of arterial thromboembolism (CVA, LV thrombus, distal arterial embolus) by 50%, while in the hypertrabeculation group, each 10% increase in EF reduced total arterial thromboembolism by 37%.

Conclusions:
These findings suggest that patients with hypertrabeculated left ventricles are either more likely to have LV thrombi that do not result in CVA events, or that due to the ventricle morphology, LV thrombi are being diagnosed when none are actually present. Furthermore, our study supports the existing literature that more severe systolic dysfunction increases risk for CVA and thromboembolic events, though that association seems largely multifactorial. Based on these results we cannot advocate for or against a particular anticoagulation strategy in patients with LVNC.
Abstract 9707: Validation of Japanese High Bleeding Risk Criteria in Patients Undergoing Percutaneous Coronary Intervention and Comparisons With Contemporary Bleeding Risk Scores
Authors: Shimizu Takeshi , Kimishima Yusuke , Misaka Tomofumi , Yoshihisa Akiomi , Yamaki Takayoshi , Kunii Hiroyuki , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika
Published: April 2022

Introduction:
The Japanese version of high bleeding risk (J-HBR) criteria have been established by modifying the Academic Research Consortium criteria for high bleeding risk (ARC-HBR), since East-Asian people have several distinct risk factors that were not included in ARC-HBR. We aimed to validate the J-HBR criteria for bleeding outcomes and compare with contemporary risk scores.

Methods:
Consecutive 1643 patients with coronary artery disease who underwent percutaneous coronary intervention were enrolled. We followed-up bleeding events of Bleeding Academic Research Consortium (BARC) 3 or 5.

Results:
Among 1643 patients, 1143 (69.6%) who met J-HBR criteria had a higher accumulated bleeding rate than those who did not (P < 0.001, left figure). BARC 3 or 5 bleeding event rates at 1 year were 4.8% in patients who met J-HBR criteria and 0.6% in those who did not (P < 0.01). The J-HBR criteria had higher sensitivity than ARC-HBR, PRECISE-DAPT and PARIS bleeding risk score (94.8%, 81.0%, 75.9% and 87.9%, respectively) and lower specificity than those (31.4%, 52.6%, 54.1% and 51.0%, respectively). J-HBR score was calculated by adding 1 point for major criterion and 0.5 point for minor criterion in J-HBR criteria. The bleeding event rate increased with advancing J-HBR score (right figure). The c-statistics of J-HBR score for predicting BARC 3 or 5 bleeding at 1 year was 0.74 (95% CI, 0.67 - 0.80) that was comparable to ARC-HBR score, PRECISE-DAPT score and PARIS bleeding risk score (0.73, 0.73 and 0.72, respectively). In the multivariate analysis, chronic kidney disease, anemia and heart failure were associated with BARC 3 or 5 bleeding (HR 6.39, P < 0.01; HR 3.38, P < 0.01; and HR 2.95, P < 0.01; respectively) among factors included in J-HBR criteria.

Conclusions:
The J-HBR criteria successfully identified patients at high bleeding risk, with high sensitivity and low specificity. The bleeding risk was closely related to J-HBR score and its individual component.
Abstract 9717: Reduction in Arnt/hif1 Beta Mediates Vascular Dysfunction in Mice with Type 2 Diabetes Mellitus
Authors: Wu Rongxue , Nguyen Tu , Zheng Mei , Knapp Maura , Sladojevic Nikola , Sitikov Albert , Liao James K , Wu Rongxue
Published: April 2022

Introduction:
Endothelial dysfunction, especially at the microvasculature level, is one of the most deleterious events in diabetes. ARNT is a transcription factor that functions as a master regulator of glucose homeostasis, but its role in diabetic vascular complications is poorly understood

Hypothesis:
Aberrations in ARNT expression might contribute to the vascular deficiencies associated with diabetes

Methods and Results:
We found a reduction in ARNT expression in microvascular endothelial cells (MVECs) derived from type 2 diabetic mice (db/db). Thus, we generated an inducible, EC-specific ARNT-knockout mutation (ArntΔEC, ERT2) to address the hypothesis that aberrations in ARNT expression might contribute to the vascular deficiencies associated with diabetes. We show here that loss of ARNT in the endothelium mimics diabetic phenotypes, such as impairs blood flow recovery after hindlimb ischemia (n=8-12, p<0.01 vs Control group), delays wound healing, and exacerbates infiltration of pro-inflammatory neutrophils after myocardial infarction. Interestedly, the degree of these impairments in the KO mice was more remarkable in diabetic animals induced with high-fat chow (n=10, P<0.01vs Control) In addition, the siRNA-mediated knockdown of ARNT activity reduced tube formation and cell viability measurements in HUVECs cultured under high-glucose conditions. The ArntΔEC, ERT2 mutation also reduced measures of cell viability while increasing the production of reactive oxygen species (ROS) in MVECs isolated from mouse skeletal muscle, and the viability of ArntΔEC, ERT2 MVECs under high-glucose concentrations increased when the cells were treated with a ROS inhibitor.

Conclusions:
Collectively, these observations suggest that declines in endothelial ARNT expression contribute to the suppressed angiogenic phenotype in diabetic mice, and that the cytoprotective effect of ARNT expression in ECs is at least partially mediated by declines in ROS production. Endothelial ARNT might be a critical mediator of endothelial function and could serve as a therapeutic target for diabetic complications.
Abstract 9729: Totum-070 Prevents Diet-induced Hyperlipidemia in High Fat High Cholesterol Fed Hamsters
Authors: Langhi Cedric , Otero Yolanda F , Le Joubioux Florian , Guigas Bruno , PELTIER Sébastien , Sirvent Pascal
Published: April 2022

Low-density lipoprotein cholesterol (LDL-Chol) is a well-established modifiable risk factor for cardiovascular disease. TOTUM-070 (T070) is a clinical stage patented blend of biomolecules extracted from 5 plant extracts with high content of polyphenols. We tested the hypothesis that T070 administration prevents hyperlipidemia in Syrian hamsters and explored the potential mechanisms involved. Hamsters were fed either normal diet (ND) or high fat high cholesterol diet (HFHCD) with or without T070 mixed at 3.5%, 4.25% and 5% in the diet for 12 weeks (n=16 per group). During the study duration, no effect of T070 on food intake was observed. At the end of the study, no effect of T070 on the final body weight was noticed when hamsters were supplemented with T070 in comparison to the HFHCD group. HFHCD feeding led to a 5-fold increase in blood total cholesterol compared to ND (1141± 49mg/dl vs 221.4 ± 8.8 mg/dl, respectively, p<0.0001), and a 13-fold increase in non-HDL Chol compared to ND (866 ± 43 mg/dl
vs
65 ± 9 mg/dl, respectively, p<0.0001). Compared to the HFHCD group, the 3 groups supplemented with T070 at 3.5%, 4.25% and 5% exhibited a dose-dependent decrease in total-Chol (788 ± 61 mg/dl, n.s; 678 ± 41 mg/dl, p<0.01 and 667 ± 37 mg/dl, p<0.01, respectively) and non-HDL Chol (542 ± 61 mg/dl, p<0.05; 455 ± 37 mg/dl, p<0.01 and 455 ± 33 mg/dl, p<0.01, respectively). Serum triglyceride (TG) levels were increased to 1018 ± 103 mg/dl in HFHCD vs. ND (256 ± 24 mg/dl, p<0.0001). T070 had a dose-dependent effect on serum TG levels reduction (709 ± 91 mg/dl T070 3.5%, p<0.05; 605 ± 56 mg/dl T070 4.25%, p<0.001; and 547 ± 57 mg/dl T070 5%, p<0.001) in comparison to the HFHCD group. Analysis of hepatic lipid content revealed strong lipid accumulation in HFHCD (92-fold increase
vs
ND), while lipid content decreased by 36%, 52% and 44% in the 3.5, 4.25 and 5% supplemented groups, respectively. Lipid metabolism-related gene expression in liver and intestine was altered upon HFHCD compared to ND but tended to return to normal levels in T070 groups. Collectively, our results highlight the beneficial effect of T070 in the management of moderate cholesterol levels.
Abstract 9735: Cost Effectiveness of Screening for Valvular Heart Disease Using the Valvenet Deep Learning Electrocardiogram Model
Authors: Poterucha Timothy J , Elias Pierre , Hahn Rebecca T , Nazif Tamim , Maurer Mathew S , Einstein Andrew J , Leon Martin B , Perotte Adler , Cohen David J
Published: April 2022

Background:
Valvular heart disease (VHD) is an important contributor to CVD morbidity and mortality. The ValveNet model uses deep learning analysis of ECGs to detect moderate or severe left sided valve disease (LSVDz) including aortic stenosis (AS), aortic regurgitation (AR), and mitral regurgitation (MR) alone and in combination. A screening program using it may allow cost effective VHD screening.

Methods:
The ValveNet deep learning algorithm was tested on 26,606 ECGs from unique patients (pts) (LSVDz prevalence 8.6%) and demonstrated a sensitivity 81.3% and specificity 70.2% for LSVDz detection. We developed a decision analytic model to examine the cost-effectiveness of VHD screening using 3 approaches: (1) No screening, (2) ValveNet-assisted ECG with TTE in pts with positive ECGs (ValveNet Screen Strategy), and (3) up-front TTE (TTE Up-Front). Cost effectiveness was assessed as the incremental cost to detect a case of LSVDz. Costs were based on Medicare rates and assumed that ValveNet had negligible costs above a standard ECG. Sensitivity analyses were conducted across a range of prevalence levels and costs.

Results:
At a LSVDz prevalence of 5%, the ValveNet strategy was projected to identify significant LSVDz in 81% of prevalent cases at a cost of $175 per pt with an incremental cost-effectiveness ratio (ICER) of $4308/LSVDz detected compared with no screening. Compared with the ValveNet strategy, the ICER for TTE Up-Front was $34,169 per additional case of significant LSVDz detected and was highly prevalence-dependent (Figure). Additional multiway and fully probabilistic sensitivity analyses will be presented.

Conclusions:
A screening strategy using the ValveNet ECG model may detect a large proportion of significant LSVDz while providing cost savings compared with routine TTE screening. If ongoing studies demonstrate benefit of early treatment of asymptomatic valve disease, the ValveNet approach may be a cost-effective approach to community VHD screening.
Abstract 9741: Pharmacokinetics, Pharmacodynamics and Safety of Bempedoic Acid in a Phase 1 Clinical Trial in Healthy Japanese, Chinese and White Subjects
Authors: Amore Benny M , Teng Rujun , Hanselman Jeffrey C
Published: April 2022

This study investigated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of bempedoic acid (BA), an inhibitor of ATP-citrate lyase that significantly lowers LDL-C levels, after single and multiple oral dose administration in White and first-, second-, or third-generation Japanese and Chinese subjects living in the US. This double-blind, placebo-controlled study was conducted at a single US site in a total of 40 healthy subjects randomized (3:1) to receive BA or placebo. The PK, PD, and safety of BA were assessed in Japanese subjects after a single dose of BA 60, 120, or 180 mg; and in Japanese, Chinese, and White subjects (baseline LDL-C 70–190 mg/dL; not receiving a statin) after daily BA 180-mg dosing for 14 days. Enrolled subjects (28% female) ranged 23-59 years of age. In Japanese subjects, single dose maximum BA plasma concentrations increased proportionally, and AUC increased slightly greater than proportional to dose. After 14 days of BA 180 mg, mean estimates of BA elimination half-life were 25.2, 20.0 and 23.9 hours in Japanese, Chinese, and White subjects, respectively. Active metabolite ESP15228 AUC exposures were approximately 20% of BA across subjects. Mean oral clearance (CL/F) in Japanese (0.494 L/h) and Chinese (0.592 L/h) subjects was 29% and 15% less and volume of distribution (V
z
/F) in Japanese (18.0 L) and Chinese (19.2 L) subjects was 32% and 27% less than in White subjects, respectively. Differences in CL/F and V
z
/F were decreased after body weight (BW) normalization, with higher mean BW for White subjects (80.6 kg) observed relative to Japanese (67.4 kg) and Chinese (74.1 kg) subjects. A reduction in fasting LDL-C, non-HDL-C, and hsCRP was observed with BA. The mean (SD) percent change from baseline in LDL-C among subjects (n=6 each) receiving BA 180 mg was –29% (14) for Japanese subjects, –39% (8) for Chinese subjects, and –17% (28) for White subjects compared with +17% (21) for subjects receiving placebo. Results from this study suggest that administration of BA 180 mg once daily over 14 days markedly reduced LDL-C and was well tolerated in all subjects. PK differences, largely explained after normalizing CL/F and V
z
/F by subject BW, are not expected to result in clinically meaningful differences in the efficacy or safety profiles of BA.
Abstract 9743: Experiences of and Factors Associated with Dietary Sodium Adherence in Heart Failure From Patients’ and Their Caregivers’ Perspectives: A Qualitative Study
Authors: Heo Seongkum , Kim JinShil , Shim Jae Lan , Barbe Tammy , Black Vicki , Lee Mee Ok
Published: April 2022

Introduction:
The majority of patients with heart failure (HF) experience high prevalence of HF symptoms, which cause poor health-related quality of life and high rates of hospitalization. Poor dietary sodium adherence is prevalent and adversely affects HF symptoms and hospitalization rates. Support or lack of support from caregivers can affect patients’ dietary sodium adherence. However, experiences in dietary sodium adherence from both patients’ and caregivers’ perspectives have not been fully examined in patients with HF.

Purpose:
The purpose of this study was to explore HF patients’ and their caregivers’ experiences of dietary sodium adherence, including the status and factors associated with it.

Methods:
Qualitative data were collected from 22 patients with HF (67 years old, 72.7% female) and 18 their caregivers (52.2 years old, 33.3% female) using an interview guide with semi-structured questions and were analyzed based on conventional content analysis method.

Results:
Four themes were revealed: 1) lack of adherence to a low sodium diet, 2) barriers to dietary sodium adherence, 3) facilitators of dietary sodium adherence, and 4) distorted perceptions of dietary education from healthcare providers. The majority of patients did not adhere to a low sodium diet for most of the time. There were several barriers to dietary sodium adherence, including distorted perceptions, insufficient knowledge, disadvantages of dietary sodium adherence, and lack of family support. There were a few facilitators of dietary sodium adherence, including family support. The majority of patients received dietary education from their healthcare providers, but they did not recognize it and/or the detailed content.

Conclusions:
More effective interventions reflecting patients’ and caregivers’ knowledge about a low sodium diet and factors affecting patients’ eating habits need to be developed and delivered to patients with HF to improve their dietary sodium adherence. In particular, clinicians and healthcare providers need to provide clear explanations about the purpose and content of dietary recommendations with ways to follow the recommendations to patients and their caregivers to improve dietary sodium adherence more effectively.
Abstract 9757: Frequency of Atrial Fibrillation in a Contemporary Elderly Primary Care Population: A Vital-af Trial Study
Authors: Khurshid Shaan , Ashburner Jeffrey M , Chang Yuchiao , Trisini Lipsanopoulos Ana T , Borowsky Leila H , Guan Wyliena , Ellinor Patrick T , McManus David D , Atlas Steven , Singer Daniel , Lubitz Steven A
Published: April 2022

Introduction:
Reliable estimates of atrial fibrillation (AF) frequency can inform our understanding of population disease burden and shape interventions to reduce AF-related morbidity.

Methods:
We quantified the prevalence and incidence of AF in VITAL-AF (NCT035115057), a cluster-randomized trial of AF screening using single-lead handheld electrocardiograms within 16 primary care practices affiliated with Massachusetts General Hospital. Potential AF events were identified using the electronic health record. AF events satisfying a high specificity electronic algorithm for prevalent AF (positive predictive value 98.4%) were classified as prevalent AF, while all other potential AF events (including all incident AF events) were manually adjudicated. We calculated AF prevalence and incidence overall and within clinical strata, among individuals who were not screened.

Results:
Of 18,812 individuals enrolled but not screened between 7/31/2018-10/8/2019 (mean age 74.6±7.2 years, 56.3% women), 2,503 (13.3%) had prevalent AF. AF prevalence was particularly high among individuals aged ≥85 years (29.1%) and individuals with heart failure (43.4%). The AF incidence rate among 16,309 individuals without prevalent AF was 20.1 per 1,000 person-years (95% CI 20.9-26.4). AF incidence also increased markedly with age (e.g., 13.6 at ages 65-69 to 37.1 at ages ≥85 years, p<0.01), was greater in men versus women (26.9 vs. 15.0, p<0.01), and was particularly high among individuals with heart failure (30.7, 95% CI 43.8-69.0). Detailed estimates of AF prevalence and incidence across clinical strata are shown in the
Table
.

Conclusions:
Using rigorous methodology within a contemporary, elderly primary care population, we observed the highest reported prevalence of diagnosed AF, including nearly a third of individuals aged 85 years and older. The incidence of new AF is also substantial. Preventive efforts are warranted to reduce the risk of AF and associated complications.
Abstract 9768: Relationship of Atherogenic Lipoproteins with Insulin Resistance and Carotid Intimal Thickness in Youth at Risk for Cardiovascular Disease
Authors: Chung Stephanie T , Magge Sheela
Published: April 2022

Introduction:
Youth with obesity and abnormal glucose tolerance (AGT) have an atherogenic lipoprotein (Lp) profile (small dense HDL and small LDL) and an increased risk for atherosclerotic disease, but the relative contributions of hyperglycemia and insulin resistance to the development of subclinical atherosclerosis in youth are not well defined.

Hypothesis:
Atherogenic Lp concentrations (ApoB, small LDLp, small HDLp) are associated with lower insulin sensitivity (Si) and greater carotid intimal thickness (cIMT), irrespective of glycemic status.

Methods:
In 155 youth with obesity (14.5±1.4y (mean±SD), 50% female; 42 lean (LC: BMI 25-85%ile), 44 insulin sensitive (OIS, fasting insulin ≤20μM/mL, BMI≥95%ile), 35 insulin resistant (OIR; fasting insulin>20μM/mL, BMI≥95%ile) and 34 with AGT (23 prediabetes, 11 type 2 diabetes) we compared a standard lipid panel and Lp size and number. Linear regressions were used to test the associations between lipids/ NMR-derived Lp with Si index derived from a minimal model during an intravenous glucose test. cIMT was determined by ultrasonography. In a subset of 56 youth (21 LC, 19 OIS, 10 OIR, and 7 AGT) we explored the change in Si with the change in Lp and cIMT after 2 years.

Results:
OIR and AGT had higher triglycerides and lower HDL compared to LC,
P
<0.01. Total cholesterol, LDL, and cIMT were comparable among all youth. ApoB, total triglyceride-rich Lp, LDLp and small LDLp) were similar in OIS, OIR, and AbGT and higher compared to LC. Among adolescents with obesity, Si was inversely associated with ApoB (β=-0.016), total LDLp (β=-0.91), small HDLp (β=-0.11) and cIMT (β= -2.99), all
P
<0.001. There was no effect modification by obesity group. LnSi was associated with total HDL (β=1.30), large HDLp (β= 0.23) and small HDLp (β=-0.11), all
P
<0.01) with steeper associations between AGT vs OIR and AGT vs OIS. After 2 years, the change in insulin sensitivity was not associated with changes in lipoproteins or cIMT.

Conclusions:
Among youth with obesity, insulin resistance was associated with atherogenic lipoproteins and cIMT, regardless of glucose tolerance status. Alterations in HDL particle number and size were distinct early manifestations that were observed in youth with AGT compared to their peers.
Abstract 9773: Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension
Authors: Prisco Sasha Z , Eklund Megan , Moutsoglou Daphne , Prisco Anthony , Khoruts Alexander , Weir Kenneth K , Thenappan Thenappan , Prins Kurt W
Published: April 2022

Introduction:
Intermittent fasting (IF) confers pleotropic cardiovascular benefits including restructuring the gut microbiome and augmenting metabolism. Pulmonary arterial hypertension (PAH) is a rare and lethal disease characterized by right ventricular (RV) mitochondrial dysfunction and resultant lipotoxicity and microbiome dysbiosis. The effects of IF on RV function in PAH are unexplored.

Hypothesis:
IF restructures the gut microbiome, normalizes the microbiota metabolites in the RV, and improves RV function and survival in monocrotaline (MCT) rats.

Methods:
Male SD rats were randomly allocated into 3 groups: control, MCT-
ad lib
feeding, and MCT-IF (every other day feeding). 16S ribosomal RNA sequencing of stool evaluated the microbiome. Jejunal epithelium was evaluated with H&E staining. RV metabolomics assessed microbiome metabolites. RV Oil Red O, H&E, and trichrome staining evaluated lipotoxicity, cardiomyocyte hypertrophy, and fibrosis, respectively. RV function was determined by echocardiography and closed-chest pressure-volume (PV) loops. Lung H&E staining evaluated pulmonary vascular remodeling.

Results:
IF changed the microbiome, with increased abundance of
Lactobacillus
. IF mitigated the reduction in jejunum villi length and goblet cell abundance when compared to MCT-
ad lib
. Metabolomics profiling revealed IF decreased RV levels of microbiome metabolites (bile acids, aromatic amino acid metabolites, and γ-glutamylated amino acids). When probing RV metabolism, IF prevented RV lipid accrual on Oil Red O staining and ceramide accumulation as determined by metabolomics. IF decreased RV cardiomyocyte hypertrophy and reduced RV fibrosis. Echocardiography and PV loops showed IF improved RV systolic and diastolic function despite no significant change in PAH severity. There was a slight but significant decline in histological pulmonary vascular remodeling (MCT-
ad lib
: 52±11
vs
MCT-IF: 47±12%). IF ultimately prevented premature mortality (30% mortality rate in MCT-
ad lib vs
0% in MCT-IF rats).

Conclusions:
IF restructured the microbiome and directly enhanced RV function. These results suggest IF may be a non-pharmacological approach to combat RV dysfunction, a currently untreatable and lethal consequence of PAH.
Abstract 9778: Insertable Cardiac Monitoring in Unexplained Syncope Patients is Cost-Saving Compared to External ECG Monitoring Followed by Insertable Cardiac Monitor
Authors: Witte Klaus K , Reynolds Matthew R , Rosemas Sarah C , Ziegler Paul D , Sawyer Laura M
Published: April 2022

Background:
Insertable cardiac monitors (ICMs) are recommended early in the evaluation of unexplained syncope patients after a non-diagnostic initial evaluation, and have been demonstrated as cost-effective for arrhythmia detection in this population. However, pathways frequently include short-term external cardiac monitors (ECM) prior to ICM.

Objective:
We aimed to evaluate the cost-effectiveness of immediate ICM versus a delayed ICM approach (30-day ECM followed by ICM in patients remaining undiagnosed), in unexplained syncope patients in the U.S.

Methods:
A discrete state Markov model assessed the cost-effectiveness of immediate vs. delayed ICM, from a U.S. payer perspective. Cohort characteristics were informed using the 2008-2016 Optum
®
Clinformatics
®
U.S. claims database. Syncope recurrence was modeled based on the EasyAs trial, with risks of mortality, injury, and quality of life consequences identified from the literature. ICM data capture was based on data for Reveal LINQ™ ICM. Diagnostic success with ECM was simulated based on the likelihood of monitoring occurring simultaneously to syncopal recurrence and patient adherence. Cost inputs were derived from claims and national average payment data. All diagnostic and arrhythmia-related treatment costs and benefits were modeled over a lifetime horizon, and future costs/effects were discounted at 3% per annum.

Results:
Immediate ICM was associated with lower lifetime per-patient costs compared to delayed ICM ($36,348 vs.$36,826), and a gain of 0.013 quality-adjusted life-years. This was largely driven by the cost of ECMs in the delayed ICM strategy, totaling $616,600 per 1,000 patients but with a small diagnostic yield such that 92.8%of patients required an ICM. The immediate ICM approach remained the dominant strategy when the assumed patient adherence to prescribed ECM was increased to 100%, and regardless of the choice of initial ECM (1, 2, 14, or 30-day monitor). Cost savings with immediate ICM increased further in scenarios assuming some delayed ICM patients are loss to follow-up after the initial ECM.

Conclusions:
A strategy of immediate ICM was cost-saving compared to delayed ICM, due to the cost and low diagnostic yield of ECM and the delay in arrhythmia detection and treatment.
Abstract 9793: Walking Performance, Quality of Life, and Hemodynamic Characteristics in Patients with Peripheral Artery Disease and End-Stage Kidney Disease (PAD-ESKD)
Authors: Hamburg Naomi , Farber Alik , Bonaca Marc P , Patel Manesh R , Marston William A , Miller Stephan , Padgett Claire , Keller Laurence H , Perelló Joan , Gold Alex , Chertow Glenn M
Published: April 2022

Background:
Patients with peripheral artery disease and end-stage kidney disease (PAD-ESKD) have poor outcomes that may be related to the presence of medial arterial calcification. These patients have been excluded from prior studies of medical interventions; thus, there is a need to better understand baseline functional capacity to aid design of interventional studies.

Methods:
Patients receiving hemodialysis (HD) who met the following inclusion criteria: age ≥55 OR ≥45 with diabetes, PAD as defined by ankle-brachial index (ABI) <0.90 and/or toe-brachial index (TBI) <0.70, and described symptoms with walking were enrolled at 7 US sites in a cross-sectional study of functional status. Patients with chronic limb-threatening ischemia, recent revascularization, or a non-PAD condition limiting walking were excluded. We measured walking with the 6-minute walk distance (6MWD), repeated after a 1-week interval, and the Walking Impairment Questionnaire (WIQ). We assessed claudication symptoms with the San Diego Claudication Questionnaire (SDCQ).

Results:
Of 67 patients who were screened, 36 (54%) met eligibility criteria, and 30 have completed the ongoing study: 43% women, mean (SD) age 69 (8) years, and mean (range) time since initiation of HD 53 (1-219) months. All patients had abnormal TBI with mean 0.46 (0.15). Consistent with the presence of medial arterial calcification, 10 patients (33%) had ABI ≥1.2 in one or both legs. Ten patients (33%) had intermittent claudication (IC). Overall mean (SD) 6MWD was 357 (261) meters (range 60-975). Test-retest reliability of 6MWD was good with an intraclass correlation of 0.97. The 6MWD was <350 meters in 19 patients (63%). Mean (SD) WIQ overall score was 32 (26), range 0-92, out of a possible 100 max. Patients who reported IC, as well as those who did not, had walking impairment as assessed by 6MWD and WIQ.

Conclusion:
We demonstrate the high prevalence of impaired walking ability in patients with PAD-ESKD, a previously poorly characterized population. The PAD-ESKD population has high clinical need, supporting a planned randomized, placebo-controlled trial to evaluate the effects of SNF472, a novel investigational inhibitor of vascular calcification.
Comparative Efficacy of 5 Exercise Types on Cardiometabolic Health in Overweight and Obese Adults: A Systematic Review and Network Meta-Analysis of 81 Randomized Controlled Trials
Authors: Batrakoulis Alexios , Jamurtas Athanasios Z. , Metsios Georgios S. , Perivoliotis Konstantinos , Liguori Gary , Feito Yuri , Riebe Deborah , Thompson Walter R. , Angelopoulos Theodore J , Krustrup Peter , Mohr Magni , Draganidis Dimitrios , Poulios Athanasios , Fatouros Ioannis G.
Published: April 2022

Background:

Although regular exercise is recommended for preventing and treating overweight/obesity, the most effective exercise type for improving cardiometabolic health in individuals with overweight/obesity remains largely undecided. This network meta-analysis aimed to evaluate and rank the comparative efficacy of 5 exercise modalities on cardiometabolic health measures in individuals with overweight/obesity.

Methods:

A database search was conducted in MEDLINE, Embase, Scopus, and Web of Science from inception up to September 2020. The review focused on randomized controlled trials involving exercise interventions consisting of continuous endurance training, interval training, resistance training, combined aerobic and resistance training (combined training), and hybrid-type training. Exercise interventions aimed to improve somatometric variables, body composition, lipid metabolism, glucose control, blood pressure, cardiorespiratory fitness, and muscular strength. The Cochrane risk of bias tool was used to evaluate eligible studies. A random-effects network meta-analysis was performed within a frequentist framework. The intervention ranking was carried out using a Bayesian model where mean and SD were equal to the respective frequentist estimates.

Results:

A total of 4331 participants (59% female; mean age: 38.7±12.3 years) from 81 studies were included. Combined training was the most effective modality and hybrid-type training the second most effective in improving cardiometabolic health-related outcomes in these populations suggesting a higher efficacy for multicomponent exercise interventions compared to single-component modalities, that is, continuous endurance training, interval training, and resistance training. A subgroup analysis revealed that the effects from different exercise types were mediated by gender.

Conclusions:

These findings corroborate the latest guidelines on exercise for individuals with overweight/obesity highlighting the importance of a multicomponent exercise approach to improve cardiometabolic health. Physicians and healthcare professionals should consider prescribing multicomponent exercise interventions to adults with overweight/obesity to maximize clinical outcomes.

Registration:

URL:https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42020202647
DPP4 Promotes Human Endothelial Cell Senescence and Dysfunction via the PAR2–COX-2–TP Axis and NLRP3 Inflammasome Activation
Authors: Valencia Inés , Vallejo Susana , Dongil Pilar , Romero Alejandra , San Hipólito-Luengo Álvaro , Shamoon Licia , Posada María , García-Olmo Damián , Carraro Raffaelle , Erusalimsky Jorge D. , Romacho Tania , Peiró Concepción , Sánchez-Ferrer Carlos F.
Published: April 2022

Background:

Abnormal accumulation of senescent cells in the vessel wall leads to a compromised vascular function contributing to vascular aging. Soluble DPP4 (dipeptidyl peptidase 4; sDPP4) secretion from visceral adipose tissue is enhanced in obesity, now considered a progeric condition. sDPP4 triggers vascular deleterious effects, albeit its contribution to vascular aging is unknown. We aimed to explore sDPP4 involvement in vascular aging, unraveling the molecular pathway by which sDPP4 acts on the endothelium.

Methods:

Human endothelial cell senescence was assessed by senescence-associated β-galactosidase assay, visualization of DNA damage, and expression of prosenescent markers, whereas vascular function was evaluated by myography over human dissected microvessels. In visceral adipose tissue biopsies from a cohort of obese patients, we explored several age-related parameters in vitro and ex vivo.

Results:

By a common mechanism, sDPP4 triggers endothelial cell senescence and endothelial dysfunction in isolated human resistance arteries. sDPP4 activates the metabotropic receptor PAR2 (protease-activated receptor 2), COX-2 (cyclooxygenase 2) activity, and the production of TXA
2
(thromboxane A
2
) acting over TP (thromboxane receptor) receptors (PAR2–COX-2–TP axis), leading to NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3) inflammasome activation. Obese patients exhibited impaired microarterial functionality in comparison to control nonobese counterparts. Importantly, endothelial dysfunction in obese patients positively correlated with greater expression of DPP4, prosenescent, and proinflammatory markers in visceral adipose tissue nearby the resistance arteries. Moreover, when DPP4 activity or sDPP4-induced prosenescent mechanism was blocked, endothelial dysfunction was restored back to levels of healthy subjects.

Conclusions:

These results reveal sDPP4 as a relevant mediator in early vascular aging and highlight its capacity activating main proinflammatory mediators in the endothelium that might be pharmacologically tackled.
New species and new records of Reteporella (Bryozoa: Cheilostomatida) from Greenland waters
Authors: DENISENKO NINA V.
Published: April 2022

New species and new records of the cheilostome bryozoan family Phidoloporidae are reported from the poorly studied shelf and continental slope of Greenland. Reteporella vitta n. sp. differs from congeners in the shape and size of fenestrulae, the size of autozooids and their arrangement within the colony, features of the orificial complex, including the indistinctly denticulate distal rim, shape of the condyles and height of the peristome, as well as the shape and location of the suboral avicularium, and the morphology of the ovicell. Reteporella obscura n. sp. differs from other Reteporella species in a unique combination of the following characters: colony surface texture, shape of orifice and condyles, shape of the suboral avicularium, and the morphology of the ovicell. Other specimens of Reteporella from Greenland were identified as R. watersi (Nordgaard, 1907), firstly recorded in southern and western parts of the study area, and as R. grimaldii (Jullien, 1903) and R. beaniana (King, 1846), previously known only from some localities of western and eastern Greenland and recorded abundantly in 2016. Reteporella watersi specimens from Greenland differ from conspecific material from the Faroe Islands in lacking oral spines and in the size of zooidal characters.
Prototype of a Warn-on-Forecast System for Smoke (WoFS-Smoke)
Authors: Jones Thomas , Ahmadov Ravan , James Eric , Pereira Gabriel , Freitas Saulo , Grell Georg
Published: April 2022

This research begins the process of creating an ensemble-based forecast system for smoke aerosols generated from wildfires using a modified version of the National Severe Storms Laboratory (NSSL) Warn-on-Forecast System (WoFS). The existing WoFS has proven effective in generating short-term (0–3 h) probabilistic forecasts of high-impact weather events such as storm rotation, hail, severe winds, and heavy rainfall. However, it does not include any information on large smoke plumes generated from wildfires that impact air quality and the surrounding environment. The prototype WoFS-Smoke system is based on the deterministic High-Resolution Rapid Refresh-Smoke (HRRR-Smoke) model. HRRR-Smoke runs over a continental United States (CONUS) domain with a 3-km horizontal grid spacing, with hourly forecasts out to 48 h. The smoke plume injection algorithm in HRRR-Smoke is integrated into the WoFS forming WOFS-Smoke so that the advantages of the rapidly cycling, ensemble-based WoFS can be used to generate short-term (0–3 h) probabilistic forecasts of smoke. WoFS-Smoke forecasts from three wildfire cases during 2020 show that the system generates a realistic representation of wildfire smoke when compared against satellite observations. Comparison of smoke forecasts with radar data show that forecast smoke reaches higher levels than radar-detected debris, but exceptions to this are noted. The radiative effect of smoke on surface temperature forecasts is evident, which reduces forecast errors compared to experiments that do not include smoke.
Nationwide Analysis of Hospital Admissions Prior to Hartmann’s Procedure for Acute Diverticulitis
Authors: Qafiti Fred N. , Marsh Amanda M. , Yi Slee , Rosenthal Andrew , Parreco Joshua , Lopez-Viego Miguel A. , Buicko Jessica L.
Published: April 2022

Introduction

Diverticular disease is one of the most common gastrointestinal diseases that require hospital admission. This study aims to identify trends in prior hospital admissions for patients that ultimately require a Hartmann’s procedure for complicated diverticulitis.

Methods

The Nationwide Readmissions Database for 2010–2014 was queried for all patients aged 18 years or older admitted with an ICD-9 code for colonic diverticulitis and end colostomy creation. Patients with prior hospital admissions were identified. The primary outcome was mortality after Hartmann’s procedure. Secondary outcomes were prior hospital admission and previous percutaneous drain placement. Multivariable logistic regression was performed to control for confounding factors for each outcome and results were weighted for national estimates.

Results

There were 90,162 patients admitted with complicated diverticulitis requiring end colostomy creation. Prior hospital admissions were found in 28.1% (n = 25,307) and 14.4% (n = 12,947) had a previous percutaneous drain placed during a prior admission. The overall mortality rate was 5.9% (n = 5314) after Hartman’s procedure. The mortality rate for patients with prior hospital admissions was 8.7% ( P < .001), and the mortality rate for patients with previous percutaneous drain placement was 4.3% ( P < .001). After controlling for confounding factors including comorbidities, patients with prior admission had an increased risk of mortality (OR 1.48 [1.40–1.58], P < .001) and patients with previous percutaneous drain placement had a decreased risk of mortality (OR .66 [.60-.72], P < .001).

Conclusions

Hospitalizations for complications of diverticulitis are a costly burden to our healthcare system. By identifying those patients at high risk for readmission and emergency surgery, perioperative outcomes may be improved.
Does Metabolic Syndrome Effect the Perioperative Course and Costs of Patients With Hepatocellular Carcinoma Undergoing Robotic Hepatectomy? A Propensity Score-Matched Analysis
Authors: Rayman Shlomi , Sucandy Iswanto , Ross Sharona B. , Crespo Kaitlyn , Syblis Cameron , App Samantha , Rosemurgy Alexander
Published: April 2022

Background

This study was undertaken to examine the postoperative outcomes, costs, and survival after robotic hepatectomy for hepatocellular carcinoma (HCC) in patients with or without metabolic syndrome.

Methods

Following IRB approval, we prospectively followed 56 patients undergoing robotic hepatectomy for HCC from 2016-2020. Patients with metabolic syndrome were compared to patients without metabolic syndrome regarding postoperative clinical outcomes, costs, and survival. Propensity score matching of a 1:1 ratio matched patients with and without metabolic syndrome according to 6 variables.

Results

17 patients were matched to each arm. Mean age was 64 ± 14.0 years and 30 patients (88%) had operations that were classified as advanced (IWATE 7-9) or expert (IWATE 10-12). There were no differences between patients with metabolic syndrome versus patients without metabolic syndrome in terms of operative duration (306 [301 ± 76.2] vs 239 [260 ± 116.9] minutes; P = 0.23), estimated blood loss (300 [321 ± 195.5] vs 200 [214 ± 151.4] ml; P = 0.08), conversion to “open” operation (1 [6%] vs 1 [6%]; p = 1.00), tumor size (5 [5 ± 3.0] vs 3 [4 ± 2.2] cm; P = 0.28), postoperative complications with Clavien-Dindo Score (≥III) (0 vs 1; P = 1.00), in-hospital mortality (0 [0%] vs 1 [6%]; P = 1.00), length of stay (5 [5 ± 1.7] vs 4 [5 ± 4.4] days; P = 1.00), and 30-day readmissions (1 [6%] vs 1 [6%]; P = 1.00). There were no differences in overall costs and profit. There was no difference in 1-year, 2-year, and 3- year overall survival in patients with or without metabolic syndrome after robotic HCC resection (84% vs 77%, 84% vs 61%, and 45% vs 61%, P = 0.42).

Conclusion

For patients with and without metabolic syndrome, robotic advanced/expert hepatectomy for HCC resulted in similar intra-operative metrics, postoperative outcomes, costs, and survival.