bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13112: Theranostic Properties of Porphysome Nanoparticles in Atherosclerotic Cardiovascular Disease
Authors: Nankivell Victoria A , Vidanapathirana Achini , Rajora Maneesha , Psaltis Peter , Tan Joanne T , Tieu William , Zheng Gang , Bursill Christina A
Published: June 2023

Introduction:
‘Porphysome’ nanoparticles contain porphyrin-lipid which permits fluorescent imaging and can be radiolabelled for positron emission tomography (PET) imaging. The outer shell contains the R4F peptide that interacts with scavenger receptor SR-B1, enabling macrophage targeting and therapeutic effects.

Aim:
To investigate anti-atherosclerotic and imaging properties of porphysomes.

Methods:
In vitro,
porphysome or PBS-treated macrophages were assessed for uptake (fluorescence microscopy), [
3
H]-cholesterol efflux and inflammatory responses following lipopolysaccharide stimulation (qRT-PCR/ELISA).
In vivo,
high-fat diet (HFD) fed apolipoprotein (
Apo)e
-/-
mice were infused for 8 weeks with porphysomes (3x/week, 40mg/kg) or PBS.
64
Cu-porphysomes were detected by fluorescence (IVIS)/PET imaging. Aortas were digested for flow cytometry.

Results:
In vitro
, porphysomes were internalised by macrophages and increased cholesterol efflux (80%,
P
<0.05), compared to PBS controls. Porphysomes reduced macrophage mRNA levels of inflammatory factors
Il-1β
(88%),
Il-18
(54%) and
Ccl5
(75%), and protein secretion of IL-1β (69%) and CCL5 (82%),
P
<0.05. Porphysomes suppressed inflammasome components
Rela
(38%),
Nlrp3
(69%) and
Asc
(36%),
P
<0.05. In
Apoe
-/-
mice, porphysomes were detected in aortic sinus plaque by fluorescence, co-localised with CD68
+
macrophages, and by IVIS in aortic arch plaque, with higher fluorescence intensity in HFD (55%) than chow-fed mice. PET imaging found porphysomes localised in hearts. Porphysome uptake was higher in aortic macrophages than endothelial (9-fold) or smooth muscle (4.5-fold) cells (
P
<0.05). Porphysome-treated mice had less aortic macrophages (49%) of the M2-like phenotype (60%), than PBS controls.

Conclusions:
Porphysomes exhibit multi-modal imaging capabilities for identifying plaque and have athero-protective properties, demonstrating theranostic potential for atherosclerosis.
Abstract 13216: Evaluation of Left Ventricular Flow Propagation Velocity From Multi-Dimensional Cardiac Imaging
Authors: Zhang Jiacheng , Meyers Brett , Brindise Melissa , Loke Yue-Hin , Vlachos Pavlos
Published: June 2023

Introduction:
The propagation velocity (Vp) during the left ventricular (LV) early diastole has been proposed as a marker of the diastolic function. However, the measurement of Vp is limited to one-dimensional data from Color M-mode (CMM) echocardiography and does not consider the spatiotemporal variation of Vp.

Methods:
We introduce a new method to evaluate the LV diastolic flow propagation from multi-dimensional cardiac flow imaging. The proposed method estimates the local and instantaneous flow propagation velocity (V
prop
) by fitting the first order wave equation to the velocity gradients with weighted least-squares. The proposed method was validated using the synthetic vortex ring flow data. The method was applied to the LV flow data acquired with two-dimensional phase-contrast magnetic resonance imaging (pc-MRI) and 4D flow MRI.

Results:
The V
prop
estimated from multi-dimensional data has about 50% less error than the V
prop
from one-dimensional data. Fig. 1(a) shows the waveforms of the mitral inflow velocity, the IVPD, and the propagation intensity (I
prop
) during the LV diastole of a normal filling patient. During early diastole, the timing of peak flow propagation coincides with the peak intraventricular pressure difference. Fig. 1(b) presents the fields of the blood flow velocity, the V
prop
, and the relative pressure from the timeframes indicated using the dotted lines in the waveform plots. The flow propagation towards the apex is mainly located at the front of the inflow jet and downstream of the vortex ring formed near mitral valve tips.

Conclusions:
This study introduces a novel propagation velocity measurement method for multi-dimensional cardiac flow imaging and demonstrated the V
prop
’s spatial distribution temporal evolution.
Abstract 13217: Optimizing Longitudinal Retention in Care Among Patients With Hypertension in Primary Healthcare Settings: Findings From the Hypertension Treatment in Nigeria Program
Authors: Ye Jiancheng , ORJI IKECHUKWU ANTHONY A , Baldridge Abigail , Ojo Tunde , Shedul Grace , Ugwuneji Eugenia , EGENTI NONYE , Omitiran Kasarachi , Okoli Rosemary , Eze Helen , Nwankwo Ada , Hirschhorn Lisa , Chopra Aashima , Ale Boni , Shedul Gabriel , Kandula Namratha , Huffman Mark D , Ojji Dike ,   Hypertension Treatment in Nigeria Program investigators
Published: June 2023

Introduction:
Previous hypertension research has evaluated retention using cross-sectional study designs. However, longitudinal analyses are likely more useful to identify areas for improving retention.

Objective:
To describe longitudinal retention patterns among patients with hypertension in primary care in 6 Federal Capital Territory council areas in Nigeria.

Methods:
The Hypertension Treatment in Nigeria Program implemented a multi-level intervention package in 60 centers in Nigeria. Baseline and follow-up data were collected from January 2020 to December 2021. Healthcare workers scheduled patients for a follow-up appointment at each visit, for which one month was recommended. Retention was measured by the patient presenting to the clinic for a follow-up visit within 7 days of the scheduled appointment.

Results:
14,346 patients (68.7% female, mean [SD] age = 49.1 [12.6] years) were included with 61,320 documented visits, among which 14,975 were registration visits and 46,345 were follow-up visits. 9,490 (66.2%) patients had ≥1 follow-up visit.
Fig 1
demonstrates longitudinal patterns for 37-day retention by council area, in which Kuje has the highest follow-up rate (55.6%) while variability was seen across areas. The median (IQR) time to the scheduled appointment was 30 days (28, 31), and observed time to follow-up visit was 32 days (29, 42). 40,759 (66.5%) appointments were scheduled ≤ 30 days, 58,773 (95.8%) appointments were scheduled ≤ 37 days, and 282 appointments (0.5%) were scheduled ≥ 60 days after the previous visit. Among documented follow-up visits, 16,524 (35.7%) occurred within 30 days of the prior visit, 32,145 (69.4%) occurred within 37 days, and 31,344 (67.6%) were within 7 days of the scheduled appointment.

Conclusions:
Retention in hypertension is widely variable within individuals, over time, and across council areas. Longitudinal retention analyses provide robust assessments to develop tailored strategies to improve retention.
Abstract 13288: Relationship Between the Detection of Atrial Fibrillation, Race and Complication Rate
Authors: Misra Gauri , Prinz Nick , Cotton Caroline , Moorman Randall , Monfredi Oliver ,   Cntr for Advanced Med Analytics
Published: June 2023

Earlier work at our institution has shown that identification and treatment of atrial fibrillation (AF) is suboptimal in hospitalized patients. We set out to better characterize delays in the detection and management of AF, and to investigate their consequences We conducted a retrospective review of 425 consecutive clinically significant AF events (episodes lasting >5 mins) generated by automated algorithmic continuous telemetry analysis between 12/25/20 and 9/21/21 for patients admitted to the cardiology floor of UVA Medical Center. Time of onset/duration of episodes were automatically recorded, and detailed chart review was performed. AF events in patients that generated clinical responses were significantly longer (median 2850 secs (SD 3962 secs; n=95)) than events in patients whose event was not identified by care teams (median 480 (SD 9280 secs; n=152), p <.01). In patients who were clinically identified, the median delay to identification was 483 mins (SD 692 mins; n=95). Patients who had AF events identified by clinical care teams and received intervention (anticoagulation, rate limiting medication, anti-arrhythmic, IV fluid bolus or electrical cardioversion) within 60 minutes of the onset of the event had lower rates of subsequent AF-related complications (MI, stroke, heart failure or escalation of care) - those who received intervention within 60 minutes had subsequent AF-related complication rates of 10%, while who were intervened upon after 60 minutes had complication rates of 18%. Non-white patients were more likely to have their incident AF event missed by clinical care teams - among those patients who had AF identified, 85% were white, and 15% were non-white, while among patients who had AF but were not identified, 70% were white and 30% were non-white (p-value <0.05). In conclusion, incident AF detection and management in our hospital is markedly delayed, and these delays are consequential in terms of risk of subsequent AF-related complications. Likelihood of an AF event leading to clinical recognition also appears to depend on race. Our future work will investigate the use of automated clinical team alerting of incident AF events to shorten times to AF detection and management, and effects of that on AF related complications and outcomes.
Abstract 13331: Low Statin Adherence Identified Across Diverse Populations in the All of Us Research Program
Authors: Escobar Gabriela V , de Hond Anne A , Sarraju Ashish , Rodriguez Fatima , Hernandez-Boussard Tina
Published: June 2023

Introduction:
Statins are a cornerstone of primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), the leading cause of death in the US. Despite conclusive evidence to the efficacy and safety of statins, low adherence remains a public health challenge. Although patient, clinician, and health system barriers to statin adherence have been documented, the effect of national policies targeting prescription access remains largely understudied. This study sought to assess the effect of the 2016 US Preventive Services Task Force (USPSTF) recommendation of statins on racial/ethnic disparities in treatment adherence.

Methods:
Utilizing records of the novel All of Us Research Program, a dataset of historically underrepresented groups in health research, we compared statin use in adult ASCVD non-Hispanic White (NHW) patients before (2014-2016) and after (2017-2020) the USPSTF recommendation with Black and Hispanic patients. Statin use was measured as percent days covered (PDC). Trends were compared using a regression model with demographics and an indicator variable for the change in recommendation as covariates. Regression coefficients and p-values were analyzed to assess the effect of the policy.

Results:
The study included 94,883 unique statin prescription records belonging to a patient cohort of which 52% were female, 21% Black and 12% Hispanic, with a mean age of 61.93 years. There was poor statin adherence across all racial/ethinic subgroups (PDC < 0.80). Following the policy, PDC increased 3.1% overall (p<0.01), 12 percentage points in Black patients and no change in Hispanics with respect to NHW.

Conclusion:
Our results provide preliminary evidence that the 2016 USPSTF changes increased statin adherence, yet there were differential effects among racial/ethnic subgroups. To address population adherence disparities, more research is needed to inform policy that will facilitate access for underserved populations in the United States.
Abstract 13357: From Junctional Rhythm to Slow Vt: Flecainide Poisoning
Authors: Shi Hanyuan , Zhang Rui , Gongal Prajesh , Feldman Daniel , Ortengren Alexandra , Rassias Athos , Sangha Rajbir , Moudgal Rohitha , Henkin Stanislav
Published: June 2023

Introduction:
Flecainide is a class IC anti-arrhythmic used to treat atrial fibrillation. Toxicity can cause bradycardia, QRS prolongation, and ventricular tachyarrhythmia (VT) due to blockade of sodium channels. Although most metabolism occurs through the liver, up to 30% excretion is renal but not dialyzable. The case here represents two arrhythmogenic challenges associated with flecainide treated with alkalization and lipid emulsion.

Case:
A 75-year-old woman with atrial fibrillation initially presented with syncope and hematemesis. Initial ECG showed junctional bradycardia with narrow escape in HR 30s. Labs notable for creatinine 2.55 (nl <1.2 mg/dl) and potassium 4.8 (3.5-5.0 mmol/L). pH was 7.28 with bicarbonate 18 (22-31 mmol/L). She was treated with glucagon and atropine for suspected B-blocker toxicity but quickly went into shock. Rhythm then changed to a wide complex tachycardia (Fig) with wide QRS 280ms, VT rates in 100s. Due to development of this slow VT, flecainide toxicity was highly suspected, and a bicarbonate drip was started to maintain pH>7.50 in addition to intralipid infusion. In the span of 12 hours, she was able to wean off her vasopressor support. On hospital day 3, she started metoprolol and remained in sinus bradycardia at the time of discharge.

Discussion:
This case represented acute renal failure secondary to flecainide toxicity and gastrointestinal bleed. Toxicity led to QRS widening and slow VT, which diminished contractility. Serum alkalization and sodium load works to displace flecainide from its channel receptor; intralipid sequesters lipophilic toxin in a “lipid sink” mechanism. In extreme cases, ECMO and overdrive pacing are used.

Conclusions:
Early recognition of flecainide-related arrhythmias is key. The subsequent approach to flecainide toxicity includes reducing absorption (charcoal, lipid emulsion), antagonizing drug effect (alkalization), and proving hemodynamic support (phenylephrine, vasopressin).
Abstract 13359: Added Benefit of Parametric Mapping in Anthracycline-Induced Cardiomyopathy - Avoiding a Misdiagnosis
Authors: Garg Rimmy , Barzallo Pablo , Del Cid Fratti Juan , Bhardwaj Chetan , Paleru Vijayasree
Published: June 2023

Case Presentation
A 72 year old man presented with progressive dyspnea on exertion, only able to climb 4 stairs prior to symptom onset. He had a history of diffuse large B-cell lymphoma for which he had completed chemotherapy with cyclophosphamide, doxorubicin, rituximab, vincristine, and prednisone a year prior to presentation with recent PET scan showing complete remission. EKG showed rate-controlled atrial fibrillation. TTE confirmed a severely reduced systolic function with LVEF 25% and global hypokinesis. Coronary angiogram revealed no obstructive disease. Cardiac MRI (CMR) was then performed with no evidence of myocardial infarction, infiltration, or scarring on delayed gadolinium enhancement (DGE). T2 mapping, DIR, and TIR sequencing did not show any myocardial edema. However, baseline pre-contrast T1 relaxation time was increased at 1140-1153ms [Figure 1A] with a calculated ECV [Figure 1B] elevated at 37-40%, concerning for anthracycline-induced cardiomyopathy (AIC).

Discussion
Anthracyclines, such as doxorubicin, are important chemotherapeutic agents; however, their utility is often limited by development of progressive cardiotoxicity. Cumulative dose-dependent exposure can lead to apoptotic myocyte loss, myocardial fibrosis, and dysmotility. DGE usually identifies focal myocardial fibrosis; however, anthracycline-induced fibrosis is frequently diffuse and can be missed by qualitative analysis and DGE burden assessment. Diffuse fibrosis is better demonstrated with use of hematocrit adjusted ECV and pre-/post-T1 mapping. CMR provides additional information about decrease in the LV mass, aortic stiffness, myocardial strain, early fibrosis detection, and myocardial edema that can aid in early detection of cardiotoxicity during anthracycline therapy. Use of CMR parametric imaging is complementary and essential in accurately diagnosing AIC in patients with prior exposure and merits widespread consideration in cardio-oncology.
Abstract 13604: Sodium-Glucose-Cotransporter-2 Inhibitor (SGLT2i) Exposure in the Immediate Post-Acute Kidney Injury Period in Patients Hospitalized With Acute Heart Failure is Associated With Improved Outcomes
Authors: Kumar Sanchit , Aklilu Abinet , Ahmad Tariq , Wilson F. Perry
Published: June 2023

Introduction:
Sodium-Glucose Cotransporter-2 inhibitor (SGLT2i) use during or immediately following Acute Heart Failure (AHF) exacerbation has shown clinical benefit including improved symptoms, lower frequencies of re-hospitalization for heart failure and death. However, effects of SGLT2i use immediately following acute kidney injury (AKI) on mortality and renal recovery in this setting are unknown.

Hypothesis:
Among patients admitted with AHF who sustain in-hospital AKI, exposure to SGLT2i in the immediate post-AKI period would be associated with better outcomes.

Methods:
Adult patients admitted across 5 hospitals between January, 2020 and April, 2022 with acute heart failure (NT-pro-BNP >500ng/L and receipt of IV diuretic within 24 hours of admission) and KDIGO-defined AKI during hospitalization were included. Advanced CKD (eGFR ≤15 ml/min/1.72m2) and those prescribed SGLT2i > 10 days after AKI were excluded. AKI recovery and death were compared between the exposed and unexposed cohorts using a time-varying Cox-regression analysis after adjusting for potential confounders.

Results:
In this retrospective cohort of 3599 individuals admitted with AHF that developed AKI during hospitalization, 293 patients received SGLT2i within the 10 days post-AKI. The median (IQR) time to AKI after admission was 24 (1.41-64.48) hours. 36.52% of the SGLT2i exposed had renal recovery pre-SGLT2i exposure. For the SGLT2i-exposed (pre-renal recovery) vs. unexposed groups, rates of 14-day renal recovery were not significantly different (adj. HR 0.99, 95% CI 0.82-1.19, p=0.90). However, the post-AKI SGLT2i-exposed group had a lower risk of death at 30 days (adj. HR 0.39, 95% CI 0.19-0.79, p=0.009) after adjustment for potential confounders.

Conclusion:
In a retrospective cohort of patients hospitalized with AHF with in-hospital AKI, exposure to SGLT2i within 10 days post-AKI was associated with decreased mortality and no significant delay in renal recovery.
Abstract 13606: Deletion of CD47
Specifically
in Lymphatic Endothelium Augments Arterial Lymphangiogenesis and Attenuates Atherosclerosis
Authors: Singla Bhupesh , Aithabathula Ravi Varma , Ahn Wonmo , Csanyi Gabor
Published: June 2023

Thrombospondin-1 (TSP1), an extracellular glycoprotein mediates differential physio- or pathological effects via interacting with cell surface receptors including CD36 and CD47. TSP1 is a well-known angiogenesis inhibitor, however, its role in regulating lymphangiogenesis is not clear. We recently reported that global CD47-deficient mice are protected from atherosclerosis, however, myeloid cell-specific CD47 loss augments lesion formation suggesting the importance of cell-specific CD47 blockade in atherosclerosis. Our experiments revealed CD47 as a dominant TSP1 receptor in lymphatic endothelial cells (LECs). As the lymphatic vasculature is functionally linked to atherosclerosis, we herein investigated the effects of LEC TSP1-CD47 signaling inhibition on lymphangiogenesis and atherosclerotic lesion formation. Our immunoblotting data demonstrated elevated TSP1 expression in human and mouse atherosclerotic aortic tissue compared to non-atherosclerotic control tissue. TSP1 at pathological concentrations inhibited VEGF-C-stimulated
in vitro
lymphangiogenesis. Mechanistically, TSP1 inhibited VEGF-C-induced Akt activation in LECs, leading to decreased eNOS phosphorylation and attenuated nitric oxide production. Further, TSP1-treated CD47-silenced LECs proliferate faster and have higher Akt and eNOS activation than TSP1-treated control cells. AAV8-PCSK9-injected LEC-specific CD47 knockout (
Cd47
f/f
Lyve-1 Cre
+/-
) mice had reduced atherosclerosis in both aorta and aortic root compared with control (
Cd47
f/f
) mice. Additional immunostaining experiments performed on aortic root cross-sections indicated improved lymphatic vessel density in
Cd47
f/f
Lyve-1 Cre
+/-
mice. These results demonstrate that TSP1-mediated LEC CD47 activation inhibits lymphangiogenesis and blockade of LEC CD47 signaling suppresses atherosclerosis. Altogether, these findings identify LEC CD47 as a potential therapeutic target in atherosclerosis.
Abstract 13660: Lp(a) is Associated With Coronary Artery Calcification in a Population With Exceptionally Low Cardiovascular Disease Risk
Authors: Trumble Benjamin C , Thompson Randall C , Elizalde Caden A , Miyamoto Michael , Stieglitz Jonathan , Wann Samuel S , Allam Adel , Rowan Chris , Cummings Daniel , Sutherland M Linda , Sutherland James , Eid Rodriguez Daniel , Michalik David E , Lombardi Guido , Seabright Edward , Alami Sarah , Garcia Angela R , Beheim Bret , Hooper Paul , Finch Caleb , Buetow Kenneth , Gurven Michael , Kaplan Hillard , Thomas Gregory S ,   Horus Team,   Tsimane Health and Life History Project
Published: June 2023

Introduction:
The Tsimane forager-horticulturalists of Bolivia are highly physically active, carry high infectious disease burdens, and have the lowest reported population levels of coronary artery calcium (CAC), as well as relatively low cholesterol (LDL, HDL, total) levels. In industrialized populations, lipoprotein(a)—Lp(a)— is strongly predictive of coronary artery and aortic valve calcification (AVC). However, these relationships have not been assessed in this non-urban population.

Hypothesis:
We hypothesize that, despite the very low levels of CAC seen in the Tsimane, Lp(a) is higher in those with CAC and AVC but overall lower in Tsimane compared to a US comparator population (CARDIA).

Methods:
CAC and AVC were measured by non-contrast cardiac CT in 917 Tsimane (15.5% CAC positive, 21.0% AVC positive). A subset of 98 Individuals with and without CAC or AVC had serum Lp(a) analyzed (median age 63 yrs, range 41-91 yrs, 67% male) using a standard double monoclonal antibody ELISA at the Northwest Lipid Metabolism and Diabetes Research Laboratory (University of Washington). Individuals with CAC and AVC were oversampled (45.9% CAC positive, and 76.7% with AVC; 10% with neither) to ensure statistical power.

Results:
Overall, Tsimane had significantly lower levels of Lp(a) than CARDIA white males (Tsimane male median 16.5 nmol/L vs US median 19.4 nmol/L; p<0.001) and CARDIA white females (Tsimane female median 11.5 nmol/L vs US median 21.9 nmol/L; p<0.001), despite oversampling Tsimane with CAC and AVC. While Tsimane Lp(a) was low, individuals with CAC had significantly higher Lp(a) (p=0.030) controlling for age, sex, and body fat. Tsimane with no CAC had a median Lp(a) of 12.2 nmol/L, while those with any CAC signal had a median Lp(a) of 17.7 nmol/L. There was no association between AVC and Lp(a).

Conclusions:
While the Tsimane have lower levels of both CAC and Lp(a) than US adults, Lp(a) is significantly higher in Tsimane with CAC. The absence of association between Lp(a) and AVC may indicate that among the Tsimane, the etiology of AVC may be less tied to Lp(a) than in industrial populations. These results suggest that Lp(a) is associated with arterial calcification even in patients with low overall cardiovascular disease risk.
Abstract 13674: Optimal Hounsfield Threshold for Lipid-Rich Plaque by Artificial Intelligence-Enabled Quantitative CT Using Near-Infrared Spectroscopy
Authors: Omori Hiroyuki , Matsuo Hitoshi , Earls James , Sobue Yoshihiro , Fujimoto Shinichiro , Nozaki Yui , Nakazawa Gaku , Takahashi Kuniaki , Osawa Kazuhiro , Okubo Ryo , Kaneko Umihiko , Sato Hideyuki , Kajiya Takashi , Miyoshi Toru , Ichikawa Keishi , Abe Mitsunori , Kitagawa Toshiro , Ikenaga Hiroki , Saji Mike , Iguchi Nobuo , Ijichi Takeshi , Mikamo Hiroshi , Kurata Akira , Moroi Masao , iijima raisuke , Crabtree Tami , Min James K , Nakanishi Rine
Published: June 2023

Introduction:
By near-infrared spectroscopy (NIRS), plaques with 4-mm maximum lipid-core burden index (maxLCBI4
mm
) ≥ 400 are lipid-rich plaque. By CCTA, the optimal Hounsfield threshold (HU) for lipid-rich plaques defined by presence of low-density non-calcified plaque (LD-NCP) is still unclear.

Hypothesis:
Artificial intelligence-enabled quantitative CT (AI-QCT) will enable identification of HU for lipid-rich plaques when compared to NIRS reference standard.

Methods:
128 atherosclerotic plaques from 47 patients were enrolled prospectively. MaxLCBI
4mm
(cutoff was defined as 400) and LD-NCP derived from AI-QCT (Cleerly LABS, Denver CO) were compared. LD-NCP using 3 different thresholds (<30, <50, and <70 HU) were analyzed by sensitivity, specificity, positive and negative predictive value, accuracy, and area Under the Curve (AUC).

Results:
Amongst 128 atherosclerotic plaques evaluated, 26 (20.3%) met NIRS criteria for lipid rich plaque (maxLCBI
4mm
≥400). The volume of LD-NCP was measure using three different thresholds, <30, <50, and <70 HU as well as criteria of PR > 1.1 and LD-NCP volume >1.8 mm
3
(LD-NCP volume

threshold identified from AUC). This yielded a sensitivity, specificity, positive and negative predictive value, accuracy, and AUC of 92%, 88%, 67%, 98%, 89%, and 0.944 at <30HU, 96%, 79%, 53%,99% 82%, 0.921 at <50HU, and 96% 72%, 46%, 99%, 77%, and 0.907 respectively at <70HU (30 vs. 50 HU: p=0.008; 30 vs. 70HU: p=0.002 (Figure 1).

Conclusions:
A <30 HU threshold for definition of LD-NCP on AI-QCT correlates optimally with NIRS proven lipid-rich plaques.
Abstract 13709: Cardioprotective Mechanisms of FTO-Regulated m
6
A in Heart Failure
Authors: Phan Anh , Mathiyalangan Prabhu , Sahoo Susmita
Published: June 2023

Introduction:
Post-transcriptional modifications of mRNA play an important role in cardiac remodeling. We recently reported an aberrant increase in global N6-methyladenosine (m
6
A) in failing hearts associated with reduction in expression of m
6
A eraser, fat and obesity-associated protein (FTO). Overexpression of FTO increased m
6
A, and improved cardiomyocyte and cardiac function in both
in vitro
and
in vivo
models for myocardial infarction (MI). Here, we investigated the mRNA targets of FTO and mechanism of FTO-dependent cardiac protein expression in failing hearts.

Hypothesis:
We
hypothesized
that FTO mediates cardioprotection via demethylation of selective mRNA transcripts in the nucleus and cytoplasm of cardiomyocytes.

Methods and Results:
To identify subcellular localization of FTO-mRNA interaction, we examined FTO expression in human left ventricular cardiomyocytes under hypoxia
in vitro
and in mouse and human failing hearts
in vivo
. FTO was detected in both nucleus and cytoplasm of healthy cardiomyocytes and tissues, but not in hypoxic cardiomyocytes and MI mouse and human heart tissues. To reveal functional targets of FTO, we performed m
6
A RNA sequencing of nuclear and cytoplasmic RNA in cultured human cardiomyocytes. We identified distinct sets of RNA transcripts in nucleus and cytoplasm of cardiomyocytes involved in cardiac contraction, angiogenesis, cardiomyogenesis, hypermethylated by FTO. Methylated RNA immunoprecipitation experiments revealed that SERCA2a (involved in cardiomyocytes contraction) and FSTL1 (pro-angiogenic) mRNAs directly bind to FTO. Loss of FTO resulted in decreased nuclear export of SERCA2a and FSTL1 mRNAs. Our stable isotope labeling (SILAC) experiment confirmed that FTO regulates de-novo synthesis of SERCA2A and FSTL1 proteins.

Conclusion:
We
conclude
that FTO selectively targets the cardioprotective transcripts, regulates their nuclear export and protein expression. Our study will reveal FTO binding sites on cardiac transcripts and a novel mechanism of FTO-dependent protein expression in cardiomyocytes.
Abstract 13740: Cumulative Social Disadvantage and Cost-Related Medication Non-Adherence Among US Adults With Hypertension: The National Health Interview Survey 2014-2017
Authors: Kesiena Onoriode , Hagan Kobina , Mszar Reed , Hyder Syed , Makram Omar M , Lahan Shubham , Ogunmola Isaac , Singireddy Shreyas , Seffah Kofi , Parekh Tarang , Yahya Tamer , Cainzos-Achirica Miguel , Murrow Jonathan , Nasir Khurram
Published: June 2023

Introduction:
Less than 50% adherence is reported 1 year after initiating antihypertensives. We examined social disparities in cost-related medication non-adherence (CRN) by insurance and family income categories in adults with hypertension.

Methods:
We used National Health Interview Survey 2014-2017 data from adults who reported hypertension and were taking antihypertensive medications. Respondents reported their insurance plan and family income. A cumulative SDoH index was created by aggregating 45 determinants from 6 domains, and respondents were grouped by quartiles (SDoH-Q1 to Q4). Higher SDoH quartiles indicated greater disadvantage. CRN was present if an individual skipped medication to save money, took less medicine to save money, or delayed filling a prescription to save money in the last 12 months.

Results:
A total of 35,893 adults managed for hypertension were surveyed, with a mean age 62.48 [SD 14.24] years, female 51.3%). The prevalence of CRN was 9.5%. The uninsured (34.6%) and those with low income were most likely to report CRN. Regardless of insurance or income, higher SDoH quartile groups were more likely to report CRN. This trend was accentuated among the uninsured and the middle-income group. Adjusting for demographics and comorbidities, the least increment in the odds of CRN with SDoH quartiles was seen among Medicare beneficiaries and low-income: SDoH-Q4 was associated with OR = 8.47 (95%CI, 2.11, 33.93) for Medicare beneficiaries, and OR = 17.80 (95%CI, 7.91, 40.03) for low-income. The highest increment in the odds of CRN with SDoH quartiles were observed with the uninsured (OR = 22.89; 95%CI [4.91, 106.81]), and the middle-income group (OR = 21.57; 95%CI [13.78, 33.77]).

Conclusion:
While cumulative social disadvantage was associated with higher cost-related medication non-adherence among adults on medications for hypertension, this association was stronger in the uninsured, Medicaid beneficiaries, and the middle-income group.
Abstract 13959: Role of METTL3 in Regulating Pulmonary Hypertension via Controlling GLUT4 mRNA Translation
Authors: Arumugam Paramasivam , Jayaseelan Vijayashree Priyadharsini , Karthik Ganesh M
Published: June 2023

Introduction:
N6-methyladenosine (m6A) modification is one of the most prevalent internal modifications of eukaryotic mRNAs, which plays a crucial role in cardiovascular disease via regulating mRNA splicing, stability, and translation. However, the potential role of m6A modification and its regulatory proteins in pulmonary hypertension (PH) remain largely unexplored.

Hypothesis:
To investigate the role of m6A modification and its regulatory proteins in the pathogenesis of PH.

Methods:
m6A level and its regulatory proteins were measured in PH rat models after monocrotaline administration or hypoxia-induced. The global mRNA m6A level was measured by an m6A-RNA methylation quantification kit in lung tissues from PH rats. Western blot was used for m6A regulatory proteins expression analysis. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was performed to analyze the target genes of m6A master regulator METTL3. Pulmonary artery smooth muscle cells (PASMCs) were used for function analysis.

Results:
m6A level and its regulatory proteins expression including METTL3 were increased in lung tissues from PH rats. m6A RNA immunoprecipitation analysis revealed that GLUT4 as an m6A-regulated gene in PH. Functionally, knockdown of
METTL3
reduced expression of GLUT4 and PASMC proliferation.

Conclusions:
METTL3 promotes PASMC proliferation and PH via enhancing GLUT4 translation in an m6A-dependent manner. This study identified a novel RNA epigenetic mechanism that enhances PASMC proliferation, vascular remodeling, and PH. Thus, m6A modification and its regulatory proteins represent promising therapeutic targets for PH.
Abstract 13966: The Effect of Diabetes-Associated Adiposomes in Promoting Caveolar Loss and Endothelial Dysfunction
Authors: Mirza Imaduddin , Naquiallah Dina , Hassan Chandra , MAsrur MArio , Bianco Francesco M , Ali Mohamed , Mahmoud Abeer M
Published: June 2023

Introduction:
Our recent findings revealed that
ex vivo
cultured human adipose tissues (AT) release extracellular vesicles (adiposomes) that are efficiently captured by endothelial cells. These adiposomes are lipid-enclosed structures that carry bioactive cargos and mediate signaling between the AT and remote cells and tissues. Under hyperglycemia, ceramides could be glycosylated into glycosphingolipids (GSLs), selectively packed in adiposomes to be cleared away from adipocytes.

Hypothesis:
We hypothesize that the AT from obese, diabetic patients (OB-T2D) creates excess GSL-rich adiposomes, which are incorporated into endothelial cells causing alterations in endothelial cell properties and function.

Methods:
AT samples were collected from OB-T2D and non-OB subjects (n=10, each). Nanoparticle tracking and electron microscopy were used to analyze and visualize these adiposomes, and mass spectrometry was used to study their content. Adiposome uptake, lipid fusion, and changes in endothelial membrane structure and signaling pathways were also assessed.

Results:
Compared to non-obese controls, adiposomes isolated from OB-T2D were higher in number and contained higher levels of GSLs. When added to cultured endothelial cells, GSL-rich adiposomes tended to accumulate in an endothelial structure known as caveolae, which concentrate signaling molecules such as endothelial nitric oxide synthase (eNOS) and others. Electron microscopy showed a caveolar loss from the cell surface, and live TIRF microscopy indicated increased caveolar detachment. We observed induced phosphorylation of the key caveolar protein, caveolin-1, by GSL-rich adiposomes known to cause caveolar fission. This effect was mediated via activation of Src kinase (induced phosphorylation), as it was inhibited by the Src kinase inhibitor, PP2. These molecular events were accompanied by reductions in endothelial nitric oxide synthase (eNOS) activation and nitric oxide production, disturbances in endothelial gap junction, and increased permeability.

Conclusion:
we conclude that dysfunctional AT in OB-T2D produces GSL-loaded adiposomes that fuse with endothelial cells and activate the Src kinase pathway resulting in caveolar fission and endothelial cell dysfunction
Abstract 13972: Intermittent Occlusion of the Superior Vena Cava Improves Urine Sodium Excretion in Patients With Acutely Decompensated Heart Failure
Authors: Abraham Jacob , Yousefzai Rayan , Kiernan Michael S , Tedford Ryan J , Benzuly Keith , Karas Richard , Burkhoff Daniel , Kapur Navin K
Published: June 2023

BACKGROUND:
Urine sodium excretion identifies risk for short and long-term adverse events in acutely decompensated heart failure (ADHF). The VENUS HF Early Feasibility Study is testing whether intermittent occlusion of the superior vena cava (SVC) with the preCARDIA system, a catheter mounted balloon and pump console, improves decongestion in ADHF. We hypothesized that preCARDIA therapy increases natriuresis in ADHF.

Methods:
In a multicenter, prospective, single-arm exploratory safety and feasibility trial, 32 patients with ADHF were assigned to preCARDIA therapy for 24 hours. Urine output and urine electrolytes were measured from a spot urine sample before, immediately after, and for 24 hours after preCARDIA treatment in 13 patients.

Results:
32 patients were enrolled and received the preCARDIA system. Thirteen patients had complete urine electrolytes available for analysis. Compared to pre-treatment values, total daily urine output increased (1.9±0.8 vs. 4.2±1.5 L/day, p<0.001) and net fluid balance improved (-1.2±0.8 vs. -2.6±1.4 L/day, p=0.01) with treatment. Compared to pre-treatment, urine sodium (U-Na: 64±26 vs 97±24 mEq/L, p=0.0008) and U-Na/urine creatinine (U-Na/U-Cr: 1.7±1.3 vs 5.3±3.9 mmol/mg p=0.024) increased with treatment (Figure). Improved daily urine output and net fluid balance persisted 24 hours after treatment (1.9±0.8 vs 4.4±1.5 L p=0.0001; -1.2±0.8 vs -3.2±1.5 L/24h p=0.0003, respectively). Both U-Na and U-Na/U-Cr remained increased 24 hours after device removal (90 mEq/L, p=0.01; 3.93±2.8 p=0.026). Treatment increased fractional excretion of U-Na (2.08±1.87% vs. 4.22±2.72% p=0.05). No change in potassium excretion was observed.

Conclusions:
We report for the first time that intermittent SVC occlusion using the preCARDIA system to reduce congestion may increase urinary sodium excretion in ADHF. Future studies will further test the clinical utility of the preCARDIA system.
Abstract 13977: The Impact of Left Atrial Functional Changes on Clinical Outcomes Following Transcatheter Aortic Valve Replacement
Authors: Saeed Sahrai , Mannina Carlo , Ramanujam Sushmita , Gibson Gregory , Gill Harminder , Chehab Omar , Grigoryan Karine , Hancock Jane , Patterson Tiffany , Niederer Steven A , Redwood Simon R , Prendergast Bernard , Rajani Ronak
Published: June 2023

Background:
In patients with aortic stenosis (AS) and preserved left ventricular (LV) function, pre-intervention left atrial (LA) enlargement is common and predicts adverse events. Changes in LA function are appropriate markers of LV response to AS but have not been well explored in patients undergoing TAVI. The objectives of the current study were to evaluate changes in LA function following TAVI and their impact upon clinical outcomes.

Methods:
A total of 313 consecutive patients undergoing TAVI were included. There were 160 (51%) paired echocardiographic datasets with a median time of 1 (range 0-57) days pre-TAVI and a median time of 120 (1.2-810) days post-TAVI. All studies were evaluated for LA maximum volume index (LAVI
max
), LA minimum volume index (LAVI
min
), total emptying volume (LAEV), total emptying fraction (LAEF) and expansion index (LAEI). The pre-defined endpoints were cardiac-related hospitalization and all-cause death.

Results:
During a mean follow-up of 18 (±9.7) months, there were 58 deaths (18.5%) and 35 (11.2%) hospitalizations for heart failure, whereas 9 (2.9%) patients continued to report symptoms (NYHA 3). The prevalence of atrial fibrillation was 16.3% and coronary artery disease 52.7%. In a multivariate cox regression analysis, lower body surface area (HR 3.79; 95% CI 1.07-13.33, p=0.038), higher serum creatinine (HR 1.004; 95% CI 1.002-1.006, p<0.001) and LV ejection fraction (EF) <50% (HR 1.94; 95% CI 1.08-3.48, p=0.027) were predictors of all-cause mortality, independent of age, aortic valve area, the presence of coronary artery disease and time from index echocardiography to TAVI procedure. All LA function parameters demonstrated an improvement following TAVI (Fig. 1). In univariate cox regression analyses, baseline LA functional parameters were not associated with all-cause mortality alone or a composite of all-cause mortality and cardiac related hospitalization.

Conclusions:
In patients undergoing TAVI, lower body surface area, higher serum creatinine and LVEF <50% were independent predictors of all-cause mortality. TAVI led to successful reverse LA functional and structural remodeling and LV functional recovery. However, pre-TAVI LA functional and structural parameters were not predictors of survival.
Abstract 13990: Even the Perfect Face Can Break Your Heart: A Case of Variant Takotsubo Cardiomyopathy After Facial Reconstruction Surgery
Authors: Haji Mohammed , Mitsuyama Rei , Parulkar Anshul , Ovide Gerry
Published: June 2023

Introduction:
Mid and basal akinesia of the left ventricular wall is a rare variant of Takotsubo cardiomyopathy (TTC). This form of cardiomyopathy is commonly associated with severe emotional and physical triggers in post-menopausal women, but not typically in younger patients undergoing minimally invasive surgical interventions.
Case Description:
A 45-year-old female with prior breast augmentation surgery presented to the emergency room after an elective facial reconstruction procedure, complicated by shock. At the end of the procedure, she received a planned phenylephrine challenge by her surgeon to assess the risk of post-op bleeding, after which she developed persistent hypotension. On arrival, the patient was hypotensive, tachycardic, and requiring oxygen. The patient was started on norepinephrine and vasopressin infusions. Initial labs were notable for a troponin of 4,611. EKG showed sinus arrhythmia and diffuse ST depressions. Transthoracic echocardiogram (TTE) showed a left ventricle with moderately reduced systolic function with akinesia of mid and basal segments with preserved contractility of the apex. Left heart catheterization showed no coronary disease and an elevated left ventricular end diastolic pressure. Right heart catheterization on vasopressors revealed elevated pulmonary pressures and a Fick cardiac output/cardiac index of 4/2.3. Given elevated filling pressures, the patient received diuresis as pressors and oxygen were weaned. Prior to discharge, minimal guideline directed management therapy was started due to low blood pressures and a repeat TTE was unchanged.

Discussion:
This is a rare case of variant TTC associated with facial reconstruction surgery and exposure to an adrenergic agent, both atypical triggers. One hypothesized mechanism of TTC is linked to a catecholamine surge and therefore, adrenergic agonists, such as phenylephrine, and general anesthetics have been reported as contributing to the risk of developing TTC. This case further creates awareness for this syndrome as a post-procedural complication and cause of shock, despite minimal invasiveness and prior tolerance to similar interventions. Additionally, further research of catecholamine drugs as possible risk factors is needed.
Abstract 14057: Detection of Left Ventricular Systolic Dysfunction From Electrocardiographic Images
Authors: Sangha Veer , Aghajani Nargesi Arash , Dhingra Lovedeep , Mortazavi Bobak , Ribeiro Antonio H , Banina Evgeniya , Brandt Cynthia , Miller Edward J , Ribeiro Antonio , Velazquez Eric J , Krumholz Harlan M , Khera Rohan
Published: June 2023

Background:
Left ventricular systolic dysfunction (LVSD) is associated with an over 8-fold risk of heart failure and 2-fold risk of premature death. Echocardiographic screening is limited by access to the technology, and artificial intelligence-based tools have been limited to ECG signals, precluding access by end users.

Methods:
A total of 393,910 12-lead ECGs from patients undergoing echocardiography at Yale were used to develop a model identifying LV ejection fraction < 40% in printed ECG images, using a EfficientNet-B3 convolutional neural network with transfer learning. The algorithm was validated using real-world ECG images. To allow interpretability, gradient-weighted class activation mapping (Grad-CAM) was used to localize class-discriminating signals in the images.

Results:
A total of 60,293 ECGs (15.3%) were performed in patients with LVSD. The ECG-based image identified LVSD accurate across multiple image formats in the held-out test set (AUROC 0.91, AUPRC 0.69), and in two external sets of real-world ECG images from an outpatient academic center (AUROC 0.93, AUPRC 0.69) and a rural hospital system (AUROC 0.91, AUPRC 0.89). An ECG suggestive of LVSD portended over 24-fold higher odds of LVSD in the held-out set (OR 24.4, 95% CI, 22.4-26.6). Regardless of the ECG layout, class-discriminative patterns from Grad-CAM localized to leads V2 and V3, corresponding to the left ventricle. Moreover, a positive ECG screen in individuals with LV ejection fraction > 40% at the time of initial assessment was associated with 4-fold increased risk of developing incident LV systolic dysfunction in the future (HR 4.3, 95% CI 3.9-4.7, median follow up 2.3 years).

Conclusions:
We developed and validated a layout-independent deep learning model that identifies LVSD from images of ECGs. This approach represents an automated and accessible screening strategy for LVSD, particularly in low resource settings.
Abstract 14068: Reduced Left Atrial Conduction Velocity in Patients With Hypertrophic Cardiomyopathy and Normal Left Atrial Voltage Presenting for Paroxysmal Atrial Fibrillation Ablation
Authors: Zahid Sohail , Malik Tahir , Peterson Connor , Dai Matthew , Katz Moshe , Bernstein Scott , Barbhaiya Chirag , Park David S , Knotts Robert , Holmes Douglas , Kushnir Alexander , Aizer Anthony , CHINITZ LARRY A , Jankelson Lior
Published: June 2023

Introduction:
Patients with hypertrophic cardiomyopathy (HCM) exhibit abnormal cardiac tissue arrangement characterized as myocardial disarray. The incidence of atrial fibrillation (AF) is increased 4-fold in patient with HCM and confers a 4-fold increased risk of death. Catheter ablation is less effective in HCM, with a 2-fold increased risk of AF recurrence. The mechanisms of AF perpetuation and recurrence in HCM are poorly understood. We sought to investigate the left atrial conduction characteristics in patients with HCM, paroxysmal AF and normal left atrial bipolar voltage.

Methods:
We analyzed 24 consecutive patients with HCM and 24 consecutive controls, all presenting for radiofrequency (RF) ablation of paroxysmal atrial fibrillation. Only patients with normal left atrial voltage (mean voltage >0.8 mV) were included in the study. Intracardiac electrograms were extracted from CARTO (Biosense Webster Inc.) mapping system and analyzed using custom Matlab/Python code interfacing with Core OpenEP software. Conduction velocity was calculated using local activation time gradients.

Results:
There was no difference in baseline demographic characteristics or atrial size measured by echocardiography between HCM and control patients. Patients with HCM had significantly reduced atrial conduction velocity and conduction velocity dispersion compared to controls (Fig A,C) [0.62±0.03 m/s vs 0.44±0.04 m/s, p=0.002], despite no differences in bipolar voltage (Fig B,D) or voltage dispersion. Patients with HCM had significantly less freedom from AF than controls after catheter ablation [OR for recurrence 3.3 (1.02-10.90), p<0.05 vs control].

Conclusion:
Atrial conduction velocity and dispersion is significantly reduced in patients with HCM and paroxysmal AF, possibly contributing to arrhythmia perpetuation and persistence after catheter ablation. This finding may be useful in characterizing left atrial properties beyond bipolar voltage.
Abstract 14083: Prognostic Utility of Neutrophil Gelatinase-Associated Lipocalin in Predicting Cardiovascular Events in Patients With Stable Coronary Artery Disease Treated With Percutaneous Coronary Intervention
Authors: Hsu Chien-Yi , LEU HSIN-BANG , Chen Jaw W
Published: June 2023

Introduction:
Neutrophil gelatinase-associated lipocalin (NGAL) modulates matrix metalloproteinase-9 thereby affecting the stability of the atherosclerotic plaque. Accumulating evidence showed that high NGAL levels were independently associated with major adverse cardiac events (MACE) and mortality in patients with acute myocardial infarction (MI). However, only few studies have measured NGAL in stable coronary artery disease (SCAD) patients, and no significant prognostic predicting value between NGAL and SCAD has been established yet.

Hypothesis:
The aim of this study was to investigate the prognostic role of NGAL in a prospective cohort study of patients with SCAD treated with percutaneous coronary intervention (PCI).

Methods:
In total, 2296 SCAD patients with previous PCI were enrolled in a multi-center prospective observational study. The primary outcome was the occurrence of MACE (cardiovascular death, nonfatal MI and ischemic stroke). The secondary outcome was the occurrence of combined cardiovascular events (including all-cause death, nonfatal MI, nonfatal stroke, revascularization and hospitalization for heart failure).

Results:
During the mean follow-up period of 4.6 ±1.7 years, 384 patients reached the primary endpoints and 746 patients reached the secondary endpoints. Kaplan-Meier analysis showed that the event-free survival was significantly different in the first tertile and third tertile groups (log-rank test, p<0.001) in subjects categorized by NGAL levels. In multivariate Cox proportional hazard regression analysis, plasma NGAL was independently associated with MACE (adjusted hazard ratio [aHR] 1.24; 95% confidence interval [CI] 1.03-1.50, p=0.02) and the risk of developing combined cardiovascular events (aHR 1.31; 95% CI 1.14-1.51, p<0.001) during follow-up.

Conclusions:
High plasma NGAL independently associated with the occurrence of MACE and combined cardiovascular events in SCAD patients treated with PCI.