bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 6977: Thrombi Located at the Apex of Left Atrial Appendage Tend to Disappear in Patients with Atrial Fibrillation
Authors: Sugitani Miho , Mine Takanao , Ishihara Masaharu
Published: April 2024

Background:
Catheter ablation (CA) for atrial fibrillation (AF), or left atrial appendage (LAA) occlusion device to prevent stroke are contraindicated in patients with left atrial appendage thrombus (LAAT), and LAAT is required to disappear. However, LAAT do not disappear in some people, and the predictors for LAAT disappearance remains unclear.

Methods:
We retrospectively studied 65 LAAT patients taking anticoagulants out of 1381 consecutive patients who underwent transthoracic echocardiography (TEE) prior to cardioversion or CA for AF. Patients with significant valvular disease and coagulation disorder were excluded. Clinical data were evaluated at the time of TEE. The LAA was divided into three parts (the apex, middle and base), and the position of the LAAT were classified by three independent observers, and the size, shape and movability of LAAT were also evaluated.

Results:
Forty-six of 65 LAAT patients underwent re-TEE during follow-up (6.4±14.4 months), and LAAT disappeared in 20 out of 46 patients. Patients with disappearance of LAAT had LAAT located at the apex of LAA (apex: 16/24, 67%, middle: 2/10, 20%, base 2/12, 17%, p=0.0041), shorter left atrial dimension (LAD) (46.1±5.4 vs. 50.2±5.5 mm, p=0.0264) and longer period to re-TEE (9.6±20.5 vs. 4.0±6.4 months, p=0.0046). On multivariate analysis, LAAT located at the apex of LAA (p=0.0057, OR 6.9844833, 95%CI 1.6144805-30.215916) and smaller LAD (p=0.07614, OR 3.1453251 for each 10 mm decrease in LAD, 95%CI 0.8785845-0.988234) were associated with disappearance of LAAT. Disappearance rate of LAAT in patients with LAAT located at the apex of LAA and small LAD (<48mm) was 82% (9/11) [Figure].

Conclusion:
Thrombi located at the apex of LAA might be easy to disappear in patients with atrial fibrillation.
Abstract 8865: Multilevel Correlates of Received Social Support Among Heart Transplant Recipients in the International Bright Study: A Secondary Analysis
Authors: Abshire Saylor Martha , Denhaerynck Kris , Mielke Juliane , Davidson Patricia , Dobbels Fabienne , Russell Cynthia , De Geest Sabina M
Published: April 2024

Introduction:
Social support is critical in follow-up of patients after heart transplant (HTx) and positively influences well-being and clinical outcomes.

Hypothesis:
The purpose of this secondary analysis was to 1) explore received social support variation in HTx-recipients at country and center level (emotional and practical) and 2) to assess patient-, micro-, meso- and macro-level correlates.

Methods:
We examined data from the multi-level cross-sectional BRIGHT study, conducted in 36 HTx-centers in 11 countries. We used an 11-item instrument to measure received social support related to medication adherence with emotional and practical sub-scales. The Conceptual Model of Social Networks and Health guided selection of patient-, micro-, meso- and macro-level factors. Descriptive statistics for multi-level variables and bivariate analysis for emotional and practical dimensions of social support were conducted. Sequential multiple ordinal mixed logistic regression analysis was used to test multi-level models.

Results:
A total of 1379 adult HTx-recipients were included in this study. We identified variability at country and center level for both, emotional (country: 8.2%; center: 5.3%) and practical (country: 2.1%; center: 3.4%) dimensions of received social support. Independent correlates of emotional support at the micro level were patient-perceived level of chronic illness management and trust in the HTx-team, and at the patient level were female gender, living alone and depressive symptoms. Independent correlates of practical support were patients’ (micro) and clinicians (meso) perceived level of chronic illness management, and at the patient level were age, male gender and living alone.

Conclusions:
Social support in HTx-recipients varies by country, center and was associated with multi-level correlates. Qualitative and longitudinal studies are needed to understand influencing factors of social support for intervention development, improvement of social support and clinical outcomes.
Abstract 8874: Diabetes and Chronic Kidney Disease in Heart Failure With Reduced and Preserved
Authors: Nichols Gregory A , Qiao Qing , Déruaz-Luyet Anouk , Kraus Bettina J
Published: April 2024

Introduction:
Heart Failure (HF) is a major public health burden, but population-based estimates of incidence rates of clinical outcomes by HF category are scarce. We calculated adjusted incidence rates of type 2 diabetes (T2D) and chronic kidney disease (CKD) in patients with HF with preserved (HFpEF) or reduced ejection fraction (HFrEF).

Methods:
We identified adult patients with a HF diagnosis from 2005-2017 in the electronic medical record of Kaiser Permanent Northwest and calculated age/sex adjusted incidence or progression rates per 1,000 person-years using generalized estimating equations over 15 years of follow-up (2005-2019). Patients with their first diagnosis of T2D or with two eGFR values <60ml/min/1.73m
2
per the CKD-EPI equation recorded after a HF diagnosis were counted as incident cases. Progression of CKD was calculated among those with CKD at baseline defined as deteriorating to a lower eGFR category (category 3a, 45-59 ml/min/1.73m
2
; 3b, 30-44; 4, 15-29; 5, <15 or ESKD). Progression to insulin was calculated among those with T2D at baseline not already on insulin.

Results:
Of the 37,773 patients with a HF diagnosis, 36% had no EF available. 46.4% were categorized as HFpEF, 6.7% HFmrEF and 10.9% HFrEF. Compared with HFrEF patients, those with HFpEF were older (72.1 vs. 68.6 years) and more likely to be female (55% vs. 33%). Patients with HFrEF were more likely than HFpEF to develop CKD or have CKD deterioration (Table). However, due to the much larger size of the HFpEF group, HFpEF generated higher absolute numbers of events. Incidence rates and progression of T2D were smaller for both HFrEF and HFpEF.

Conclusions:
In a large real-world dataset of HF patients, rates of CKD progression were very high in both HFrEF and HFpEF, affecting approximately half of patients with CKD at baseline. Although progression and new incidence of CKD were relatively lower in HFpEF vs. HFrEF, the greater prevalence of HFpEF was driving the majority of heart failure-associated CKD.
Abstract 8881: Comprehensive Assessment of Systemic Atherosclerosis in Relation to the Ocular Resistive Index in Acute Coronary Syndrome Patients
Authors: Ebuchi Yasunari , fukamachi daisuke , Kojima Keisuke , Nagaoka Taiji , Murata Nobuhiro , Ohgaku Akihito , Koyama Yutaka , Fujito Hidesato , Arai Riku , Monden Masaki , Tamaki Takehiro , Kitano Daisuke , Okumura Yasuo , Yamagami Satoru
Published: April 2024

Introduction:
It remains unclear how systemic atherosclerosis can affect ocular microvessels. The abnormality of the ocular microvasculatures can be non-invasively detected by measuring ocular arterial blood flow velocity using laser speckle flowgraphy (LSFG). Among the ocular blood flow parameters obtained by LFSG, the ocular blowout time (BOT) and the ocular resistivity index (RI) are used as the index of retinal vascular resistance. The purpose of this study was to investigate the relationship between ocular vascular resistance evaluated by LSFG and cardiac function evaluated by transthoracic echocardiography in patients with acute coronary syndrome (ACS).

Methods:
We evaluated 53 patients with ACS who were taken to Coronary Care Unit between April 2019 and September 2020. The mean blur rate (MBR), the ocular blowout time (BOT) and the ocular resistivity index (RI) were measured by LSFG. In addition, the age-matched normal subjects were also evaluated the measurement of LSFG in 20 healthy subjects with no ocular disease and no history of cardiovascular disease.

Results:
Among all ACS patients, there were significant positive correlations between ocular RI and systemic parameters, i.e., IMT(r = 0.34, P = 0.01), PWV(r = 0.41, P < 0.01), BUN(r = 0.27, P = 0.047), cystatin C(r = 0.32, P = 0.020), urinary β2 microglobulin(r = 0.30, P = 0.029), L-FABP(r = 0.28, P = 0.046), and E/e’(r = 0.34, P = 0.013). There was also significant negative correlation between ocular BOT and PWV(r = -0.44, P < 0.01). Age-matched comparing the selective ACS (n=20) with healthy group (n=20), the ocular RI was significantly higher in the ACS group (0.34 ± 0.04 vs 0.38 ± 0.07, P = 0.03).

Conclusions:
We found that the ocular resistivity index, which was non-invasively obtained by LSFG, was associated with systemic atherosclerosis, early renal dysfunction and cardiac diastolic dysfunction in ACS patients, suggesting that it might be useful index as an non-invasive comprehensive arteriosclerotic markers.
Abstract 9007: Higher Level of Chronic Illness Management is Associated With Greater Trust in the Heart Transplant Team
Authors: Cajita Mia , Mielke Juliane , Denhaerynck Kris , Dobbels Fabienne , Russell Cynthia , De Geest Sabina M ,   BRIGHT study team
Published: April 2024

Trust is associated with better patient outcomes, such as better medication adherence and improved patient satisfaction. However, the association between trust and level of chronic illness management (CIM) has not yet been addressed.

We assessed the hypothesis that level of CIM will be associated with trust in the HTx team. Additionally, we explored potential meso-level moderators of this relationship (time spent on patient visits, number of visits, multidisciplinarity, CIM competencies, and CIM preparedness of the healthcare team).

A secondary analysis was conducted using the international cross-sectional BRIGHT study, which included 1397 HTx recipients and 100 HTx clinicians from 36 HTx centers across 11 countries. Level of CIM was measured using the Patient Assessment of Chronic Illness Care (PACIC – patients’ report) and the CIMI BRIGHT (clinicians’ reports). Patients’ trust in the HTx team was measured using an adapted Wake Forest Trust scale. Multiple logistic regression was used to test the hypothesis.

1397 patients (mean age 53.6 13.2 years; 72.7% male; 85.9% white; average time post HTx 3.4 1.4 years) and 100 HTx clinicians (mean age 46.2 10.2 years; 87% female; 85% nurses; mean time worked in HTx center 10.0 7.5 years) were included. Even after controlling for patient’s age, gender, race, education, employment, years post HTx, health literacy, language congruency, and comorbidities, level of CIM as assessed by both patients and clinicians was significantly associated with trust in the HTx team (odds ratio (OR)=1.85, p<.001; OR=1.35, p=.012, respectively). Patients from centers with higher levels of CIM were more likely to trust their HTx team. Lastly, only ‘
time spent on patient visits
’ significantly moderated the relationship between level of CIM (PACIC and CIMI) and trust (OR=1.61, p=.037; OR=1.56, p=.048, respectively), wherein the impact of time in fostering trust towards the HTx team was greater when level of CIM was high.

In conclusion, level of CIM (assessed from patients’ and clinicians’ perspectives) was positively associated with trust. Our findings also suggest that allotting more time for patients during follow-up visits is a relevant factor to consider to further optimize the HTx care ecosystem.
Abstract 9038: Success of Online CME at Improving Competence and Confidence Related to Treatment Adherence in Pulmonary Arterial Hypertension
Authors: Harris Margaret , Hanley Kelly , O'Connor Alison , Chang Lih-Fan , Hatcher Victor , Capparelli Catherine
Published: April 2024

Introduction:
Despite treatment advances in PAH, many patients have difficulty adhering to therapy, resulting in decreased persistence and poor outcomes. We sought to determine if online continuing medical education (CME) could improve the competence and confidence of cardiologists related to strategies to improve treatment adherence in PAH.

Methods:
This CME intervention comprised of a 15-minute online video-based rapid-fire discussion between 2 expert faculty. A repeated pairs pre-/post-assessment study design was used and McNemar’s test assessed significance (P <.05 is considered significant), with Cohen’s d being used to assess educational impact (.20-.49 a small effect, .50-.79 a moderate effect, and
>
.80 a large effect). The activity launched October 1, 2020 and data were collected through January 11, 2021.

Results:
In total, 180 cardiologists were included in the analysis. Overall, there were competence and confidence improvements seen among participants from pre- to post-assessment: • 13% of cardiologists (P<.01) improved at selecting the most appropriate PAH therapy for better adherence for a patient who requires treatment escalation due to intermediate-risk status yet struggles to follow a rigid medication schedule • 27% of cardiologists (P<.001) improved at selecting the most appropriate strategy to manage PAH treatment-related side effects • 36% of cardiologists had a measurable increase in confidence in ability to manage side effects during uptitration of PAH specific therapiesContinued educational gaps:• 61% of cardiologists failed to choose appropriate therapy to improve adherence for an intermediate-risk patient who struggles to follow a rigid medication schedule • 50% of cardiologists failed to select the most appropriate strategy to manage PAH treatment-related side effects

Conclusions:
This study demonstrates the success of online CME on improving competence and confidence of pulmonologists related to treatment adherence in PAH. Continued gaps were identified for future educational targets.
Abstract 9063: Global Longitudinal Strain and Longitudinal Early Diastolic Strain Rate May Identify Those Williams Syndrome Patients at Risk of Cardiomyopathy Development
Authors: Carillo Marie L , Levin Mark D , Spurney Christopher F , Kozel Beth A
Published: April 2024

Introduction:
Williams syndrome (WS) is a rare disease caused by a chromosomal microdeletion at 7q11.23 resulting in elastin insufficiency and vascular disease, most commonly supravalvar aortic stenosis. Previous studies show WS patients are at risk for cardiomyopathy, but, to date, no markers predict such disease. This study was designed to test the hypothesis that WS left ventricular (LV) longitudinal strain and longitudinal early diastolic strain rate differ significantly from controls and may identify those at risk of cardiomyopathy development.

Methods:
Echocardiograms were performed in 43 WS subjects and equal numbers of sex, age and BSA-matched controls enrolled in a prospective cross-sectional NIH study of end organ WS disease (ClinicalTrials.gov Identifier: NCT0284044). Myocardial strain analysis was performed using TomTec software by two independent observers to determine global longitudinal peak systolic strain (GLS) and early diastolic peak strain rate (DSR) in the apical 4 chamber view (A4C). Mann Whitney test was used for all comparisons.

Results:
WS subject mean cohort ages (years) were: group A: 7±2, n=12; group B: 13±2, n=11; group C: 26±2, n=10; group D: 48±9, n=10, and matched control mean age and sample size were not different. All subjects had ejection fraction>55%. Groups C and D WS subjects showed significantly diminished median GLS (%) compared to controls (Fig 1A): C: -20.6 vs. -24.6, P<0.04; D: -22.4 vs. -25.5, P<0.04. DSR (1/s) was significantly decreased in all WS age groups (P<0.02) and decreased with age compared to controls (Fig 1B): 1.25 vs. 2.2 to 0.9 vs. 1.0.

Conclusion:
WS subjects demonstrate decreased DSR indicating diminished diastolic function from childhood. GLS differences appeared in adulthood, possibly indicating early systolic impairment. This data suggests GLS and DSR may be useful in targeting therapies towards those WS patients at greatest risk of cardiomyopathy development.
Abstract 9078: The Bad Bleeding Score: A Simple Score to Assess Bleeding Risk in Atrial Fibrillation Patients With Direct Oral Anticoagulants
Authors: Kawasaki Masato , Yamada Takahisa , Watanabe Tetsuya , Morita Takashi , Kikuchi Atsushi , Seo Masahiro , Nakamura Jun , Kayama Kiyomi , Sakamoto Daisuke , Ueda Kunpei , Kougame Takehiro , Tamura Yuto , Fujita Takeshi , Nishigaki Keisuke , Kokubu Yuki , Fukuda Yuto , Fukunami Masatake
Published: April 2024

Backgrounds:
Therapeutic decisions in atrial fibrillation (AF) are often influenced by assessment of bleeding risk. However, existing bleeding risk scores have limitations.

Methods and Results:
We retrospectively studied 924 AF patients who were prescribed with direct oral anticoagulants (DOAC) in a single center cohort between May 2011 and July 2015. Using Cox proportional hazards regression, 3 factors were identified to be associated with bleeding among those patients over 1.9 year-follow up. The predictive performance of 3-item score (BAD score: the sum of the point values of the following parameters; bleeding history, age (≥75yrs) and dual antiplatelet therapy) and 3 existing risk scores (HAS-BLED, ORBIT, and ATRIA) were then assessed in the sequel cohort between Aug 2015 and Jun 2016. BAD score had good ability to identify those who bled in an external validation population (C-index: BAD score, 0.63; HAS-BLED, 0.61; ORBIT, 0.64; ATRIA, 0.59). The risk of bleeding increased with higher BAD score.

Conclusions:
BAD score might be a useful and simple bleeding risk score in AF patients with DOAC.
Abstract 9091: Care Fragmentation and Health Outcomes Among African Americans: Jackson Heart Study
Authors: Rao Vishal N , Li Zhen , Hammill Bradley G , Mentz Robert J , Sims Mario , OBrien Emily C
Published: April 2024

Introduction:
African American (AA) adults experience high comorbidity burden, yet the association between care fragmentation and outcomes among AA is unknown. We aimed to characterize care fragmentation among AA Medicare beneficiaries in the Jackson Heart Study (JHS) and associated outcomes.

Methods:
We identified 2 cohorts of JHS participants enrolled in Medicare: 1) established cardiovascular disease (CVD), including coronary artery disease, stroke, and heart failure, and 2) complex medical needs, defined as a Charlson Comorbidity Index ≥ 3. Care fragmentation was defined as 1 - Bice-Boxerman index, which was estimated from all ambulatory visits in Medicare claims during 1 year before (pre-baseline) and 1 year after baseline exam. Cox proportional hazard was used to assess associations between pre-baseline exam care fragmentation and cumulative incident all-cause hospitalizations and mortality over 3 years.

Results:
Among eligible JHS participants, 148 had CVD and 94 had complex medical needs. Pre-baseline care fragmentation was ≥ 0.5 among 78% of Cohort 1 and 84% of Cohort 2. Age, sex, insurance status, and income were similar across care fragmentation quartiles in each cohort. Depression symptom scores were higher in the highest care fragmentation quartile compared to the lowest quartile in Cohort 1 (19.5 vs. 11.0; p=0.006), but not in Cohort 2 (16.0 vs. 16.0; p=0.05). Burden of care fragmentation was similar 1 year before and after baseline exam in each cohort (
Figure
). Pre-baseline care fragmentation was not associated with 3-year incident all-cause hospitalization and mortality in each cohort, even after adjustment for age, sex, Charlson score, and depressive symptoms.

Conclusions:
Care fragmentation was prevalent among AA Medicare beneficiaries with CVD or complex medical needs during 1 year before and after enrollment into JHS. There were no associations between care fragmentation and outcomes in either cohort, though the sample size was limited.
Abstract 9101: RVLM Microinjection to Explain the Role of Metabotropic Glutamate Receptors in the Regulation of Baseline Blood Pressure and Heart Rate in SHRSP
Authors: Hasan Md Zahid , Nabika Toru
Published: April 2024

Introduction:
Glutamate (Glu) is activated by the stimulation of its receptors. The microinjection of Glu in rostral ventrolateral medulla (RVLM) elicited a rapid and large increase in blood pressure (BP) and heart rate (HR), which is inhibited with kynurenic acid (KYN), a selective inhibitor of ionotropic glutamate receptors (iGluR). Further, we showed that the response to Glu was much greater in stroke-prone spontaneously hypertensive rats (SHRSP) than that in Wistar Kyoto (WKY) rats, indicating that iGluR in RVLM played an important role to maintain high BP & HR in SHRSP. Whereas, the role of metabotropic glutamate receptors (mGluR) in RVLM were not fully elucidated in SHRSP yet.

Hypotheses:
Since the different mGluR types, e.g., group I (mGluR1, mGluR5), group II (mGluR2, mGluR3) & group III (mGluR4, mGluR6, mGluR7, mGluR8), are expressed in the various regions of rat’s brain, and several studies reported that mGluR5 is largely expressed in RVLM of rats; in this study we evaluated the pathophysiological role(s) of mGluR5, expecting that mGluR5 in RVLM keeps high baseline (i) BP and (ii) HR in SHRSP.

Method:
MTEP (10 nmole, a highly selective mGluR5 antagonist) and KYN (4 nmole) were microinjected unilaterally in RVLM in SHRSP (n=10) and WKY (n=10) to determine the effects on baseline BP & HR. In addition, the effects of two inhibitors on response to Glu (5 nmole) microinjection were observed.

Results:
MTEP reduced baseline BP & HR significantly in SHRSP when compared to those in WKY (ΔMAP: -30±3 vs. -3±2 mmHg, ΔHR: -35±3 vs. -4±2 bpm, respectively, p< 0.05), but failed to attenuate a response to Glu microinjection. In contrast, KYN had no significant effects on baseline BP & HR in the two strains, whereas it showed an inhibitory effect on the response to microinjected Glu, which was significantly greater in SHRSP than that in WKY.

Conclusions:
This study suggested that mGluR5 in RVLM played a major role in the maintenance of high baseline BP & HR in SHRSP.
Abstract 9109: Patient-Specific Ipsc-Derived Cardiac Fibroblasts Phenotypes in Lmna Cardiomyopathy
Authors: Yang Jiajia , Argenziano Mariana , Burgos Angulo Mariana , McDonald Thomas V
Published: April 2024

Introduction:
Mutations in
LMNA
(encoding lamin A/C) are an important cause of familial Dilated Cardiomyopathy (DCM), characterized by systolic ventricular dysfunction and prominent dysrhythmias. However, little is known about how diverse mutations in
LMNA
can vary in molecular pathways leading to DCM other than affecting cardiomyocytes (CMs). Induced pluripotent stem cells (iPSCs) retain the genetic identity of the individual donor and enable the generation of patient-specific cells to enhance Precision Medicine. We generated CMs and cardiac fibroblasts (CFs) from patient-specific iPSCs harboring various
LMNA
mutations to compare their cellular phenotypes.

Hypothesis:
We hypothesize that different mutation locations within
LMNA
lead to DCM by affecting both CMs and CFs.

Methods:
iPSCs from seven DCM patients with heterozygous mutations in
LMNA
(M1I, R216C/R399H, R216C#1, R216C#2, R335Q, R377H and R541C) were differentiated into CMs and CFs. Nuclear morphology, sarcomere structure, molecular signatures, cell migration rate, and RNA-sequencing were analyzed in CMs and CFs.

Results:
Immunostaining of lamin A/C displayed no discernable nuclear deformity in
LMNA
-mutated CMs, whereas CFs showed dramatic nuclear morphologic defects of varying degrees between patient cell lines. Staining of troponin T revealed pronounced sarcomere disarray due to
LMNA
mutation.
LMNA
-patient lines exhibited dysregulated expression of connexin 43, MMP1, collagen 1 and 3, and fibronectin 1 in CFs assessed by qPCR and immunoblot, and reduced cell migration rate detected by wound healing assay. RNA-sequencing of variant R377H demonstrated differentially expressed genes in both CMs (up:1500, down:2630, padj<0.05) and CFs (up:491, down:783, padj<0.05).
LMNA
R377H CMs showed altered Gene Ontology terms including MAPK pathway, cardiac muscle contraction and calcium signaling pathway. Enrichment analysis of R377H CFs highlighted extracellular matrix constituent and organization pathway.

Conclusions:
CFs exhibit mutation-specific molecular and cellular pathophysiology in
LMNA
related DCM. Further functional studies may uncover novel therapeutic targets in cardiac fibroblasts for the treatment of laminopathies.
Abstract 9125: Prognostic Implications of Coronary Revascularization With Diagnostic Imaging Tests
Authors: Kato Takao
Published: April 2024

Introduction:
The differences in the prognostic impact of coronary revascularization with non-invasive diagnostic imaging tests (SPECT versus coronary CT) remain to be elucidated.

Hypothesis:
We aimed to test the hypothesis that the association of the prognostic impact of coronary revascularization with physician-referred non-invasive diagnostic imaging tests (single photon emission computed tomography [SPECT] versus [vs.] coronary computed tomography (CT) angiography) for coronary artery disease was not different.

Methods:
From the multicenter data of 2780 patients with stable angina, enrolled prospectively between January 2006 and March 2008 in Japan, who had undergone physician-referred imaging tests, 1205 patients in SPECT as an initial strategy and 625 patients in CT as an initial strategy were analyzed. We assessed the effect of revascularization (within 90 days) in each diagnostic imaging stratum and the interaction between the two strata.

Results:
A total of 210 (17.4%) patients in the SPECT stratum and 149 (23.8%) in the CT stratum underwent revascularization. Although in each stratum, the cumulative 1-year incidence of MACEs was significantly higher in patients who underwent revascularization than in those who did not (SPECT stratum: 9.1 vs. 1.2%, log-rank P<0.0001; CT stratum: 6.1 vs. 0.8%, log-rank P=0.0001), there was no interaction between the risk of revascularization and the imaging strata (SPECT stratum: adjusted hazard ratio [95% confidence interval], 4.25 [1.86-9.72]; CT stratum: 4.13 [1.16-14.73]; interaction: P=0.97).

Conclusions:
The association of revascularization with the outcomes of patients with suspected coronary artery disease was not different between SPECT-first and CT-first strategies in a physician-referred fashion.
Abstract 9137: Isolated Liver Perfusion and Electron Microscopy Reveal Defect in Vldl Lipidation Associated With Inactivation of Tm6sf2
Authors: Luo Fei , Fletcher Justin A , Smagris Eriks , Burgess Shawn C , Cohen Jonathan C , Hobbs Helen H
Published: April 2024

Background:
A missense variant (E167K) in Transmembrane 6 Superfamily Member 2 (TM6SF2) is associated with lower plasma lipid levels and protection from coronary artery disease. Inactivation of
Tm6sf2
in mice results in increased hepatic triglyceride (TG) content associated with a reduced rate of secretion of very low-density lipoprotein (VLDL)-TG, but not VLDL-Apolipoprotein B (ApoB). To determine the mechanism responsible for the hypolipidemic effect of
Tm6sf2
inactivation, we performed liver perfusion and electron microscopy studies in wildtype (WT) and
Tm6sf2
-/-
mice.

Methods:
Ad libitum
chow-fed male mice (11-13 weeks old, n=4/group)
Tm6sf2
-/-
and age- and sex-matched WT mice (C57BL/6N background) were anaesthetized with ketamine/xylazine and treated with heparin (4U/g body weight). Livers were harvested and perfused for 60 min without recirculation with buffer contained free fatty acids (0.8 mM). VLDL was isolated from the perfusate by ultracentrifugation (
d
=1.006 g/ml) and VLDL-lipids were assayed using enzymatic assays (Sigma-Aldrich) and liquid chromatography mass-spectrometry (LC-MS). Amounts of VLDL-ApoB and -ApoE were compared between strains by immunoblotting. Electron microscopy was performed on liver sections that had been stained with imidazole/osmium tetroxide to visualize lipoproteins.

Results:
The secretion rates of VLDL-ApoB and -ApoE did not differ between the
Tm6sf2
-/-
and WT mice. Hepatic secretion of VLDL lipids (TG, cholesterol, phosphatidylcholine) per ApoB was reduced by 53%, 63% and 67%, respectively, in
Tm6sf2
-/-
mice compared to WT controls. Electron microscopy showed that the VLDL particles in the secretory pathway of
Tm6sf2
-/-
mice were smaller than those in the WT animals.

Conclusions:
Taken together these findings are consistent with TM6SF2 reducing plasma TG and cholesterol levels through limiting addition of neutral lipids to nascent VLDL particles in the hepatocyte prior to secretion.
Abstract 9138: Thioredoxin-Interacting Protein is a Regulator of Redox Homeostasis in Diabetic Cardiomyopathy
Authors: Yoshioka Jun
Published: April 2024

Introduction:
Although the precise pathogenesis of diabetic cardiac damage remains unclear, potential mechanisms include increased oxidative stress. Thioredoxin-interacting protein (Txnip) is a binding partner and an endogenous inhibitor of antioxidative thioredoxin. Txnip is a highly glucose-responsive gene that mediates cellular damage.

Hypothesis:
This study was designed to provide direct in vivo evidence that the specific molecular interaction between Txnip and thioredoxin controls redox balance in the diabetic heart.

Methods and Results:
High glucose increased Txnip expression, leading to decreased thioredoxin activities and oxidative stress in mouse embryonic fibroblasts. The Txnip-thioredoxin complex was observed in cells overexpressing wild-type Txnip but not in cells overexpressing Txnip Cys247-to-Ser mutant (C247S), showing that Txnip C247 is an essential cysteine for this interaction. Then, the role of the Txnip-thioredoxin interaction was evaluated in the diabetic heart, using our newly-developed cardiomyocyte-specific Txnip C247S “knock-in” mutant mice. Injections of streptozotocin in these animals induced type 1 diabetes. Prolonged hyperglycemia upregulated myocardial expression of Txnip both in Txnip C247S mutant mice and their littermate wild-type controls. Interestingly, loss of Txnip’s inhibition of thioredoxin in Txnip C247S mutant hearts increased reduced/oxidized glutathione (GSH/GSSG) ratio and decreased TUNEL-positive cardiomyocytes, indicative of less oxidative stress and apoptosis within the diabetic myocardium in Txnip C247S mutant animals. Echocardiographic assessments did not detect any functional differences in left ventricular (LV) parameters between genotypes both at baseline and under diabetic conditions. However, hemodynamic analyses with beta-adrenergic stimulation revealed a masked functional phenotype that Txnip C247S diabetic hearts had a higher LV contractile reserve than wild-type diabetic hearts.

Conclusions:
These data demonstrate that hyperglycemia-induced Txnip is responsible for cardiomyocyte damage in the diabetic heart through the direct inhibition of thioredoxin and increased oxidative stress.
Abstract 9167: Relationship Between Dietary Vitamin D Intake, Obesity, and Twenty Lipoprotein Subclasses: Results from the Kyushu and Okinawa Population Study
Authors: Ikezaki Hiroaki , Nakashima Ryoko , Furusyo Norihiro , Ai Masumi , Okazaki Mitsuyo , HAYASHI JUN , Polisecki Eliana J
Published: April 2024

Introduction:
The correlation between serum vitamin D deficiency, obesity, and various diseases has been reported, however, there were few investigations on the role of dietary vitamin D intake on obesity and dyslipidemia.

Objective:
To examine whether dietary vitamin D intake affects obesity and dyslipidemia.

Methods:
Dietary vitamin D intake amounts calculated using obtained data of food frequency questionnaire and 20 lipoprotein cholesterol and triglycerides subclasses using gel permeation high performance liquid chromatography were analyzed in 945 men and women (mean age 58.3 years, free of thyroid or chronic liver diseases and off osteoporosis, cholesterol lowering, or adrenocorticosteroid medications). Univariate and multivariate regression, and partial correlation analyses were performed to examine the associations between dietary vitamin D intake, obesity, and lipoprotein subclasses.

Results:
Dietary vitamin D intake had a significant negative association with body mass index in both post- and pre-menopausal women groups (
r
= -0.1053 and -0.1761,
P
= 0.02 and 0.04, respectively). Regarding 20 lipoprotein subclasses, dietary vitamin D intake were negatively associated with very low-density lipoprotein-3 cholesterol in premenopausal women (
r
= -0.2099,
P
=0.02) and positively associated with total high-density lipoprotein (HDL) cholesterol in men (
r
= 0.1159,
P
= 0.04). In addition, dietary vitamin D intake also showed a marginally positive correlation with total HDL cholesterol in premenopausal women (
r
= 0.1323,
P
= 0.13). Those association were also found in the frequency of fish intake, a major source of vitamin D in Japan.

Conclusions:
Our results indicate that proactive dietary vitamin D intake may help prevent or eliminate obesity and dyslipidemia.
Abstract 9177: Prognostic Value of Chronic Kidney Disease and Cardiac Sympathetic Dysfunction Assessed by
123
I-metaiodobenzylguanidine Scintigraphy for Lethal Arrhythmic Events in Chronic Heart Failure
Authors: Amami Kazuaki , Yamada Shinya , Kaneshiro Takashi , Yoshihisa Akiomi , Hijioka Naoko , Nodera Minoru , Takeishi Yasuchika
Published: April 2024

Introduction:
Clinical implication of chronic kidney disease (CKD) and cardiac sympathetic nerve activity (CSNA) for lethal arrhythmic events has not been fully elucidated in patients with chronic heart failure (CHF).

Hypothesis:
The combination of CKD and abnormal CSNA, assessed by
123
I-metaiodobenzylguanidine (
123
I-MIBG) scintigraphy, may provide useful prognostic information for the incidence of lethal arrhythmic events.

Methods:
We studied 165 consecutive hospitalized CHF patients without dialysis. In a clinically stable condition, cardiac
123
I-MIBG scintigraphy was performed. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m
2
, and abnormal CSNA was defined as late heart to mediastinum ratio <1.6. We then investigated the incidence of lethal arrhythmic events (sustained ventricular arrhythmia, appropriate implantable cardioverter-defibrillator therapy, or sudden cardiac death).

Results:
During a median follow-up of 5.3 years, lethal arrhythmic events were observed in 40 patients (24.2%). The patients were divided into 4 groups according to the presence of CKD and CSNA abnormality: non-CKD/ normal CSNA (
n
= 52), CKD/ normal CSNA (
n
= 39), non-CKD/ abnormal CSNA (
n
= 33), and CKD/ abnormal CSNA (
n
= 41).The Kaplan-Meier analysis showed that CKD/ abnormal CSNA had the highest event rate (log-rank
p
= 0.004). In addition, the multivariable Cox proportional hazard analysis after the adjustment of multiple confounders showed that CKD/ abnormal CSNA was an independent predictor for lethal arrhythmic events compared to non-CKD/ normal CSNA (HR, 4.667,
p
= 0.006). However, the other two groups did not show significant differences compared to non-CKD/ normal CSNA.

Conclusions:
The combination of CKD and abnormal CSNA, assessed by cardiac
123
I-MIBG scintigraphy, had a significant prognostic value for the incidence of lethal arrhythmic events in patients with CHF.
Abstract 9207: Safety and Efficacy of Catheter Ablation of Atrial Fibrillation in Octogenarians: Insights from the UC San Diego AF Ablation Registry
Authors: Aldaas Omar M , Darden Douglas J , Mylavarapu Praneet , Han Frederick , Hoffmayer Kurt S , Krummen David E , Ho Gordon , Raissi Farshad , Feld Gregory K , Hsu Jonathan C
Published: April 2024

Introduction:
Catheter ablation improves outcomes in symptomatic atrial fibrillation (AF) patients. However, it’s safety and efficacy in the very elderly (≥80 years old) is not well described.

Hypothesis:
Catheter ablation of atrial fibrillation in the very elderly is safe and effective.

Methods:
We performed a retrospective study of all patients who underwent radiofrequency catheter ablation enrolled in the University of California, San Diego AF Ablation Registry. The primary outcome was freedom from atrial arrhythmias on or off antiarrhythmic drugs (AAD).

Results:
Of 847 patients, 42 (5.0%) were 80 years of age or greater with a median age of 81.5 (80,82.3) and 805 (95.0%) were less than 80 years of age with a median age of 64.4 (57.6,70.2). Among those who were ≥80 years old, 29 were undergoing de novo ablation (69.0%) whereas in the younger cohort, 518 (64.5%) were undergoing de novo ablation (p=0.548). There were no statistically significant differences in fluoroscopy (p=0.406) or procedure times (p=0.076), antiarrhythmic drug use (p=0.611), or procedural complications (p=0.500) between groups. After multivariable adjustment, there were no statistically significant differences in recurrence of atrial arrhythmias on or off AAD (Adjusted Hazard Ratio (AHR) 0.75 (95% CI 0.45-1.23); p=0.252] (
Figure 1)
, all-cause hospitalizations [AHR 0.86 (95% CI 0.46-1.60); p=0.626] or all-cause mortality [AHR 4.48 (95% CI 0.59-34.07); p=0.147] between octogenarians and the younger cohort.

Conclusion:
In this registry analysis, catheter ablation of AF appears similarly effective and safe in patients 80 years or older when compared to a younger cohort.
Abstract 9218: The Long Non-Coding Rna
Caren
Improves Cardiac Dysfunction in Aged Mice
Authors: Sato Michio , Miyata Keishi , Kadomatsu Tsuyoshi , Node Koichi , Oike Yuichi
Published: April 2024

Background:
Heart failure (HF) is the predominant cause of hospitalization and amongst the leading causes of death in developed countries. Especially, the prevalence of HFpEF is increasing and its prognosis is not improving. Our understanding of HFpEF pathophysiology is incomplete and optimal treatment remains uncertain. Under such circumstance, recently, it has been reported that some lncRNAs expressed in heart play important roles in cardiac development and disease.

Methods and Results:
Using a gene trapping approach in mouse embryonic stem cells, we identified
Caren
(for

car

diomyocyte-

en

riched noncoding transcript), a cytoplasmic lncRNA abundantly expressed in cardiomyocytes.
Caren
overexpression in cardiomyocytes activated mitochondrial biogenesis by upregulating of Tfam protein and attenuated TAC-induced activation of Ataxia Telangiectasia Mutated (ATM), a key regulator of DNA Damage Response (DDR). Moreover, TAC operated mice treated with AAV6-
Caren
relieved reduction of fractional shortening (%FS) and improved dilatation of left ventricular. Next, proteomics analysis revealed that Histidine triad nucleotide-binding protein1 (Hint1) which activates the ATM-DDR pathway was reduced in
Caren
transgenic mice. Moreover, 24-month-old WT mice treated with AAV6-
Caren
diminished systolic and dilatation capacity were improved. And electron microscopy analysis revealed that mitochondrial cristae were restored and the numbers of mitochondria were increased in the heart of 24-month-old WT mice treated with AAV6-
Caren
compared with the mice treated with
AAV6-GFP
as control.

Conclusion:
A cytoplasmic lncRNA
Caren
improves not only systolic function but also diastolic function in failing / aged heart by suppressing the ATM-DDR pathway and activating mitochondrial bioenergetics.
Abstract 9221: Long-Term Risk of New-Onset Arrhythmia in Patients With ST-Segment Elevation Myocardial Infarction According to Revascularization Status
Authors: Thomsen Anna Foged , Jons Christian , Jabbari Reza , Ravn Jacobsen Mia R , Stampe Niels K , Butt Jawad H , Olsen Niels T , Kelbæk Henning , Torp-Pedersen Christian , Fosbol Emil , Pedersen Frants , Kober Lars , Engstrom Thomas , Jacobsen Peter Karl K
Published: April 2024

Introduction:
Emerging data show that complete revascularization reduces cardiovascular death and recurrent myocardial infarction in ST-segment elevation myocardial infarction (STEMI). The influence of revascularization status on development of arrhythmia in the chronic post-STEMI phase is poorly described.

Hypothesis:
We hypothesized that incomplete compared with complete revascularization in STEMI is associated with an increased long-term risk of new-onset arrhythmia.

Methods:
Using unique Danish registries, the risk of new-onset arrhythmia was assessed in STEMI with complete or incomplete revascularization after primary percutaneous coronary intervention (PPCI) at Rigshospitalet University Hospital, Denmark, from 2009-2016. The primary outcome was new-onset arrhythmia defined as a composite of atrial fibrillation/flutter, sinoatrial dysfunction, advanced 2nd- or 3rd-degree atrioventricular block, ventricular tachycardia/fibrillation, cardiac arrest, or pacemaker/ICD implantation, with presentation >7 days post-PPCI. Secondary outcome was all-cause mortality.

Results:
A total of 5,062 patients (median age: 62.0 years; 76% men) were included, of which 3,985 and 1,077 patients underwent complete and incomplete revascularization, respectively. During a median follow-up of 4.9 years, 580 (15%) patients in the complete and 217 (20%) patients in the incomplete revascularization group were diagnosed with new-onset arrhythmia (Figure 1). Compared with complete revascularization, incomplete revascularization was associated with a higher risk of new-onset arrhythmia (adjusted hazard ratio [HR] 1.3; 95% CI, 1.1-1.5; P=0.004) and higher all-cause mortality (adjusted HR 1.3; 95% CI, 1.0-1.5; P=0.02).

Conclusions:
Incomplete revascularization in STEMI was associated with an increased long-term risk of new-onset arrhythmia and all-cause mortality compared with complete revascularization.
Abstract 9299: Associations Between Precipitation and Racial/Ethnic-Specific Adult Cardiovascular Disease Mortality During Wintertime in Northeast United States
Authors: Majeed Haris
Published: April 2024

Introduction:
Minority (i.e. non-Hispanic (NH) Blacks) populations tend to have higher rates of chronic diseases in comparison to NH Caucasians, leading to early cardiovascular disease (CVD) death. Studies suggest that winter precipitation (rain/snow) is associated with an increased risk of adult CVD mortality. Whether winter precipitation is associated with race/ethnic (RE)-specific CVD mortality remains unknown.

Hypothesis:
RE-specific associations between winter precipitation and CVD mortality would be strongest for NH Blacks.

Methods:
Using a population-based design, CDC data was obtained for Northeast US (New York, New Jersey, Pennsylvania). Region- and RE-specific (NH Blacks & Whites, Asian, Latino) adult (35-74 years) CVD mortality for winter months (December-February) from 2011-2019 were recorded based on ICD-10 codes (I00-I99). With population estimates, winter CVD rates were derived. Adjusting for the trend, temperatures, percent inactivity, obesity, college education, income, and region; negative binomial regression was used to associate winter precipitation and CVD rates.

Results:
From 2011-2019, 84,100 winter CVD adult deaths were recorded in Northeast US. A 1-inch rise in winter precipitation was significantly associated with an increased risk in CVD deaths only for NH Blacks (adjusted rate ratio [RR] 1.02; 95% CI 1.01-1.05) in Northeast US (Fig 1). Whereas the covariate, winter temperatures (per 1
o
C rise) was significantly associated with a decrease in CVD only for NH Blacks (RR 0.99; 95% CI 0.98-0.99) and NH Whites (RR 0.99; 95% CI 0.98-0.99). Insignificant interactions were observed between winter precipitation and temperature.

Conclusions:
Winter rainy/snowy conditions are associated with increased risk of CVD events among NH Black adults. This suggests that climate effects on CVD may differ by RE and highlights the importance for incorporating RE diversity in combination with climatological influences when studying CVD risks.
Abstract 9320: Biological Sex as a Modifier of the Natural History of Dilated Cardiomyopathy
Authors: Tayal Upasana , Owen Ruth , Buchan Rachel , Halliday Brian , Lota Amrit S , Jarman Julian , Baruah Resham , Ware James S , Barton Paul J , Cleland John , Frenneaux Michael , Pennell Dudley J , Gregson John , Prasad Sanjay K
Published: April 2024

Introduction:
Dilated cardiomyopathy (DCM) has a ~20% 5-year mortality rate. Understanding the impact of biological sex offers scope to improve outcomes.

Objective:
Investigate potential sex specific differences in the outcome of DCM.

Methods:
Prospective longitudinal observational cohort study of 604 patients (n=206 women, 398 men) with DCM confirmed by cardiac MRI. The median follow up for cardiovascular death, major heart failure and arrhythmic events was 3.9 years.

Results:
At baseline women had higher left ventricular ejection fraction (LVEF), smaller left ventricular volumes, less myocardial fibrosis and lower serum troponin concentrations (all p<0.05, Table 1), with no difference in age at study enrolment or medication. Despite this favourable profile, within 2 years women had more primary outcome events than men (Figure) with Kaplan Meier estimates of 10.7% vs 5.1%; adjusted* hazard ratio 3.47, 95% CI 1.81 to 6.65, [*age, LVEF, troponin,
LMNA
, left atrial volume and myocardial fibrosis]. Between 2-5 years, men and women had similar outcomes (adjusted* HR 0.55; 0.17,1.78). An LVEF <35% in men (HR 3.21, 1.67 to 6.18, C-statistic 0.647) but <40% in women (HR 2.37, 1.05 to 5.36, C statistic 0.602) had the greatest discrimination for predicting outcome.

Conclusions:
Female sex is an adverse modifier of the early natural history of DCM. There is evidence for sex specific risk stratification thresholds. Sex should be considered a determining variable in DCM care.
Abstract 9321: Cardiac Work and End-Organ Perfusion During Biventricular Compared to Left Ventricular Impella and Norepinephrine Support in a Porcine Model of Severe Cardiogenic Shock
Authors: Junker Udesen Nanna L , Josiassen Jakob , Helgestad Ole K , Banke Ann B , Frederiksen Peter H , Jensen Lisette O , Schmidt Henrik , Ravn Hanne B , Moller Jacob E
Published: April 2024

Background:
Vasopressors are often combined with left ventricular (LV) mechanical support in severe cardiogenic shock to increase end-organ perfusion. Biventricular mechanical support might improve end-organ perfusion at lower cardiac workload compared to LV mechanical support and vasopressor infusion in severe cardiogenic shock.

Aim:
To compare LV and right ventricular (RV) total cardiac work (pressure-volume area x heart rate x 10
3
) and organ-specific venous oxygen saturations from the pulmonary artery (SvO
2
), kidney- and cerebral- veins in pigs with cardiogenic shock treated with biventricular (Bipella) versus ImpellaCP + norepinephrine 0.10 μg/kg/min (Imp+NE).

Methods:
Cardiogenic shock was induced by injections of microspheres into the left main coronary artery in eight pigs (approx. 70 kg). From conductance catheters in both ventricles, cardiac workload was calculated, and oxygen saturations were attained from the pulmonary artery, internal jugular- and kidney vein. Pigs were allocated in a crossover model to Bipella for 60 minutes (n=4) or Imp+NE for 30 minutes (n=4) and after completion shifted to the opposite treatment. Results are presented as median(Q1;Q3).

Results:
Bipella effectively unloaded the LV with reduction in LV work compared to Imp+NE (569[410-685] vs 357[206-509] 10
3
ml x mmHg/min, p=0.0078) while RV work was comparable (p=0.74). A significant increase in SvO
2
(66[63-73] vs 49[44-58]%, p=0.01) and cerebral venous oxygen saturations (71[63-77] vs 62[48-66]%, p=0.016) was observed during Imp+NE compared to Bipella, whereas no difference in kidney oxygen saturations was demonstrated (p=0.31).

Conclusion:
In this porcine study of cardiogenic shock due to left main coronary ischemia, Bipella decreased LV workload, but systemic oxygen delivery was not optimal (Figure). Imp+NE provided a higher LV workload balanced by an improvement in cerebral- and mixed venous oxygen saturation.