bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17091: ARO-APOC3, an Investigational RNAi Therapeutic, Silences APOC3 and Reduces Atherosclerosis-Associated Lipoproteins in Patients With Mixed Dyslipidemia: MUIR Study Results
Authors: Vasas Szilard , Azizad Masoud , Clifton Peter , Gaudet Daniel , Goldenberg Ronald , Modesto Karen , Chang Ting , Melquist Stacey , Fu Ran , San Martin Javier , Ballantyne Christie M
Published: December 2023

Background:
Despite the availability of potent LDL-C-lowering therapies, patients with mixed dyslipidemia (MD) remain at high risk of cardiovascular (CV) disease due to residual risk from triglyceride (TG)-rich atherogenic lipoproteins (TRLs), ie, remnant cholesterol and/or VLDL-C. Inhibition of APOC3 has emerged as a promising therapeutic strategy for reducing this residual CV risk.

Aim:
We report interim results through Week 24 from MUIR, an ongoing, randomized, placebo-controlled, Phase 2b study (NCT04998201) evaluating the effects of ARO-APOC3 in patients with MD (fasting TGs 150 to 499 mg/dL and either LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL).

Methods:
Eligible subjects (n=353) were randomized 3:1 to receive either subcutaneous injections of 10, 25, or 50 mg ARO-APOC3 or matched placebo on Day 1 and at Week 12 or 50 mg ARO-APOC3 on Day 1 and Week 24. Subjects were on a stable diet and optimal lipid-lowering therapies. The primary endpoint was the percent change from baseline in fasting TGs at Week 24. Statistically significant differences were determined using mixed model repeat measures analysis.

Results:
At Week 24, when dosed on Day 1 and Week 12, ARO-APOC3 significantly decreased APOC3 in a dose-dependent manner up to 80% (p<0.0001). Least squares (LS) mean TGs were significantly reduced by 52 to 64% (p<0.0001). Least squares (LS) mean atherogenic lipoproteins were reduced by up to 27% for non-HDL-C, 19% for apolipoprotein B, and 55% for remnant cholesterol. LS mean HDL-C was increased by up to 51%. The most frequent adverse events were COVID-19 infection, worsening of glycemic control, and upper respiratory infection.

Conclusions:
By silencing APOC3 expression, ARO-APOC3 significantly reduced circulating TGs and atherogenic TRLs in patients with MD. The effect of ARO-APOC3 on CV relative risk reduction will be evaluated in an upcoming outcomes trial.
Abstract 17095: Change in Oral Anticoagulant Use for Atrial Fibrillation From 2013 to 2018 Among US Veterans and the Impact of Frailty
Authors: Al-Ani Awsse , Reisman Joel , Hu Wen , Orkaby Ariela R , McManus David D , Ko Darae
Published: December 2023

Introduction:
Direct oral anticoagulants (DOACs) are superior to warfarin in both efficacy and safety regardless of frailty status. Data on prescribing patterns of different oral anticoagulants (OACs) in frail older adults are limited.

Methods:
We utilized the Veterans Health Administration clinical data, to identify those aged 65 and older with a diagnosis of non-valvular atrial fibrillation (AF) who initiated anticoagulation in 2013 and 2018. Frailty was assessed using the 31-item VA Frailty Index (VA-FI). Patients were stratified into 3 categories. VA-FI: frail (frailty index >0.2), pre-frail (frailty index 0.11-0.2), and non-frail (frailty index 0-0.1). Baseline data on prior stroke, CHA
2
DS
2
-VASc score, and bleeding were extracted. Descriptive statistics and logistic regression were used to examine association of frailty with choice of OAC.

Results:
Among 39,647 Veterans included from 2013 and 2018, mean age was between 71 to 76. 99% were male and 88% white race. From 2013 to 2018, DOACs use increased from 21% to 88%, while warfarin use decreased accordingly. Among the OACs, dabigatran was dominant (65%) in 2013 but apixaban was dominant (66%) in 2018. Increasing frailty was associated with reduced use of DOACs (p<0.001 in 2013 and 2018). Regardless of the choice of drug, the prior bleeding and prior stroke/transient ischemic attack were mostly seen in the frail population ranging between 54-60% and 20-21% respectively. CHA
2
DS
2
-VASc score averaged 3 for non-frail, and 4 for prefrail and frail patients regardless of the year. (Figure)

Conclusion:
Prior bleeding and stroke episodes were more common among the frail population. There was significant reduction in use of DOACs in both years with increasing frailty. Studying the impact of anticoagulant choice on clinical outcomes among frail older adults with non-valvular AF are needed.
Abstract 17123: Opioid Withdrawal Causing a Broken Heart!
Authors: Chhabra Karan , Gudipati Swapna , Bloomingdale Richard
Published: December 2023

Introduction:
Takotsubo syndrome is a condition characterized by transient acute left ventricular systolic dysfunction. Although it was previously thought of as a benign self-limiting condition, it is now known to be associated with significant morbidity and mortality.

Case:
A 26-year-old male patient with past medical history of Fentanyl abuse now on methadone, presented with features of opioid withdrawal. ECG on arrival was normal sinus rhythm with QTc 488 ms. with a troponin of 2.63. Due to excessive agitation and vomiting, he was given IV haloperidol and ondansetron. The patient then became unresponsive and sustained a cardiac arrest. He was found to be in polymorphic ventricular tachycardia and was able to be resuscitated. ECG after resuscitation demonstrated new yamaguchi T waves with a QTc 597 ms and troponin of 6.60. Transthoracic echocardiography subsequently revealed a reduced ejection fraction of 35% with apical hypokinesis, and he was referred for an ischemic evaluation with CTA coronary that showed normal coronary arteries. He was diagnosed with takotsubo cardiomyopathy and was initiated on dapagliflozin, metoprolol succinate and losartan. For opioid dependence, he was prescribed buprenorphine/naloxone being mindful of his QTc and was provided a wearable cardioverter defibrillator on discharge. Final ECG demonstrated QTc of 465 ms.

Discussion:
Opioid withdrawal is known to cause a high adrenergic state and this catecholamine excess can result in cardiac stunning, creating transient left ventricular dysfunction along with wall motion abnormalities. Patients with takotsubo cardiomyopathy typically have normal coronary arteries. Approximately 4.5% of these patients can die during their hospitalization and 4% can die within 30 days of discharge. So, clinicians must keep a high index of suspicion for this syndrome in patients with history of substance use disorder, especially in the setting of troponin elevation.
Abstract 17131: Association of Objectively Measured Sleep With 6-minute Walk Distance in Older Adults
Authors: Chapagai Swaty , Harrington Katharine , Alexandria Shaina , Vu Thanh-Huyen T , Khan Sadiya S , Carnethon Mercedes R , Knutson Kristen
Published: December 2023

Background:
Decline in physical function in older adults is associated with higher risk of cardiovascular diseases. While disturbances in sleep may contribute to declines in physical function with aging, prior research is limited by the use of subjective sleep measures.

Hypothesis:
Older adults with sleep disturbance will have impaired functional capacity measured via 6-minute walk test.
Aim:
This study aimed to examine the association between objectively measured sleep parameters and 6-minute walk distance (6MWD), a marker of functional capacity, in a diverse sample of older adults aged ≥55 years.

Methods:
This analysis included 96 participants who were enrolled in the Disparities in Sleep and Cognitive Outcomes (DISCO) study, a prospective cohort study of older adults with objective measurement of sleep and functional capacity. Sleep duration (minutes), efficiency (%), and fragmentation (%) were measured using 7 days-wrist actigraphy. Sleep stages including non-REM stage 3 (N3) duration (minutes) and REM duration (minutes) were measured using an overnight home sleep monitor. Total distance (meters) completed in 6-minutes was the primary outcome. Covariates included age, sex, race, ethnicity, body mass index, smoking status, and pain/ inflammation. Linear regression models were used for analysis.

Results:
Mean age of participants was 69.1 ± 5.4 years (range 56-82 years), 69.8% were women, 72% were White and 97% were Non-Hispanic/Latino. The average 6MWD was 495.6 ± 87 meters. Sleep duration, N3 duration, and REM duration were not statistically associated with total distance walked. In the fully adjusted models, higher sleep efficiency was associated with higher total 6MWD (p<0.001), and greater sleep fragmentation was associated with lower total 6MWD (p=0.016) (see Table 1).

Conclusions:
Less favorable sleep quality, as indicated by lower sleep efficiency and more fragmented sleep, was associated with poorer functional capacity in older adults.
Abstract 17134: Mycn is a Regulator of Cardiomyocyte Proliferation and Regeneration in the Mammalian Heart
Authors: Larson Thijs A , Sierra-Pagan Javier E , Das Satyabrata , Alexy Tamas , li qinglu , Ma Xiao , Gong Wuming , Zhang Jianyi J , Garry Mary G , Garry Daniel J
Published: December 2023

The adult mammalian heart has limited regeneration in response to injury. Therefore, we focused on defining new factors and mechanisms that could enhance repair and regeneration in the adult mouse heart. MYCN is a protooncogene that regulates embryonic heart development. We identified MYCN as a downstream effector of the sonic hedgehog (SHH) signaling cascade during cardiomyocyte proliferation. However, its role in heart regeneration is unknown and warrants further investigation. Here, we describe a novel role for MYCN as a regulator of cardiomyocyte (CM) proliferation and regeneration using genetic mouse models and in vivo modified RNA (modRNA) delivery. By crossing
Mycn
floxed mice with the
Myh6
-MerCreMer mice (
Mycn
CKO), we conditionally deleted
Mycn
in the neonatal heart following administration of 4-hydroxy-tamoxifen (4-OHT) starting at P0. Successful deletion of
Mycn
was demonstrated by qPCR analysis of P2 isolated CMs. Immunohistochemical (IHC) analyses of P3 neonatal hearts in the absence of MYCN demonstrated a significant decrease in Ki67 expression and pH3 detection. This observation was validated in isolated P7 CMs and hearts pulsed with EdU which demonstrated a significant decrease in EdU+ CMs in the absence of MYCN compared to control. We then performed LAD coronary artery ligation surgeries in control and
Mycn
CKO P2 neonatal mice. Echocardiography one month following LAD coronary artery ligations demonstrated that the
Mycn
CKO failed to recover baseline cardiac function compared to their control counterparts who achieved complete recovery measured by ejection fraction (EF) and fractional shortening (FS). RNAseq analysis of control and
Mycn
CKO hearts one month following LAD ligations demonstrated that muscle developmental pathways were significantly downregulated in the
Mycn
CKO group compared to the control. We then delivered either GFP (control) or
Mycn
modRNA intramuscularly into the border zone following LAD coronary artery ligation injuries in adult (2-6 month old) mice. We observed that the
Mycn
modRNA treated mice had significantly improved cardiac function at one month and two months following injury/delivery compared to controls. These results identify MYCN as a regulator of CM proliferation and heart regeneration.
Abstract 17155: Lipoprotein (a) Testing in an Academic Medical System
Authors: Hamed Marwan , Sherafati Alborz , Alhalabi Lubna , Naderian Mohammadreza , Teymourzadeh Azin , Saadatagah Seyedmohammad , Nur Yakub , Kullo Iftikhar J
Published: December 2023

Introduction:
Lp(a) is a causal risk factor for ASCVD that is often elevated in patients with personal or family history (FHx) of ASCVD. The 2019 ESC guidelines recommend universal Lp(a) testing, while the 2019 AHA/ACC guidelines include Lp(a) as a ‘risk enhancer’. We used electronic health records (EHR) to assess utilization of Lp(a) testing in patients with ASCVD, premature ASCVD, and FHx of ASCVD at Mayo Clinic sites in Rochester MN, Phoenix AZ and Jacksonville FL and the Mayo Clinic Health System (MCHS) from 1999-2021.

Methods:
We ascertained Lp(a) testing using LOINC codes and ASCVD status using validated ICD/CPT-based algorithms. ASCVD included coronary heart disease (CHD), cerebrovascular disease (CVD) (ischemic stroke and/or carotid artery stenosis), peripheral artery disease, and abdominal aortic aneurysm. Premature ASCVD was defined as occurring in males < 55 years and females < 65 years. We ascertained FHx using EHR survey data from 2017-2021. We estimated the proportion of patients with ASCVD, premature ASCVD, or FHx of ASCVD who underwent Lp(a) testing.

Results:
Between 1999-2021, we identified 310,760 patients with at least 1 ASCVD subtype of whom 66,710 had premature disease. FHx data was available starting 2017. For the timeframe 2017-2021, we identified 267,177 patients with FHx of ASCVD and 90,269 ASCVD patients. As summarized in Table 1, Lp(a) was tested only in a small proportion of patients; 7% of ASCVD patients, 11% of premature ASCVD patients, and 6% of patients with FHx of ASCVD. Premature CHD patients had the highest testing proportion (17%).

Conclusions:
Our results demonstrate underutilization of Lp(a) testing in patients with personal or FHx of ASCVD. Lp(a) is one of the mediators of “ASCVD residual risk” in patients on statins, and with new Lp(a)-lowering medications in phase III clinical trials, patient and provider education will be needed to increase awareness of Lp(a) as a modulator of ASCVD risk.
Abstract 17158: Effects of Human Monoclonal Antibodies on ADAMTS13 in Immune Thrombotic Thrombocytopenic Purpura
Authors: Halkidis Konstantine , Meng Chan , Siegel Donald L , Zheng X. Long
Published: December 2023

Introduction:
Immune thrombotic thrombocytopenic purpura (iTTP) is caused by antibody-mediated deficiency of the metalloprotease ADAMTS13, which cleaves VWF. Myocardial infarction and ischemic strokes are common and often fatal sequelae of iTTP. Inhibitory anti-ADAMTS13 antibodies appear to affect catalytic turnover more than apparent substrate binding affinity (PMID 37023370). Exploring how antibodies affect VWF cleavage by ADAMTS13 in physiologic conditions is needed to better understand the pathophysiology of iTTP.

Hypothesis:
Anti-ADAMTS13 antibodies may influence ADAMTS13 function by affecting catalytic turnover and/or apparent substrate binding affinity differently in physiologic conditions than in standard assay conditions.

Aims:
Characterize how single chain fragments of the variable loop (scFv’s) previously identified from a phage display library derived from several iTTP patients’ antibodies affect ADAMTS13-mediated VWF cleavage in conditions that more closely represent plasma and see if/how they differ from scFv-mediated effects in standard conditions.

Methods:
ADAMTS13 in normal human plasma was titrated with increasing concentrations of the substrate FRETS-VWF73 to derive maximum velocity (

V
max

) and apparent Michaelis constant (

K
M,app

) in standard assay conditions (pH 6.0) and conditions closer to physiologic (pH 7.0). The same parameters were derived in the presence of saturating concentrations of scFv’s.

Results:
Compared to VWF cleavage by ADAMTS13 in the absence of scFv, the inhibitory scFv4-20 decreased

V
max

at both pH 6.0 and pH 7.0;

K
M,app

decreased at pH 6.0 and increased at pH 7.0. The stimulatory scFv3-3 and scFv4-41 increased

V
max

at each pH, while

K
M,app

in the presence of each scFv decreased only at pH 7.0.

Conclusions:
Anti-ADAMTS13 antibody-mediated effects on VWF cleavage differ when comparing standard and more physiologic pH conditions, guiding future investigative directions into iTTP pathophysiology.
Abstract 17172: Paradoxical QRS Narrowing After Transcatheter Aortic Valve Replacement Concealing New Left Bundle Branch Block
Authors: Kolansky Matthew A , Kolansky Daniel M , Smietana Jeffrey J , Whitman Isaac R
Published: December 2023

Introduction:
Left bundle branch block (LBBB) after transcatheter aortic valve replacement (TAVR) is common and is a risk factor for high-grade atrioventricular (AV) block. We report a case of paradoxical QRS narrowing after TAVR in a patient with pre-existing incomplete right bundle branch block (iRBBB). Such QRS narrowing, masquerading as improved AV conduction, may conceal the development of new LBBB.

Case Presentation:
An 81-year-old man with severe aortic stenosis underwent TAVR with a 29mm Medtronic Evolut transcatheter self-expanding bioprosthetic valve. Post-operative TEE showed a well-seated valve without paravalvular leak. Preoperative ECG demonstrated sinus rhythm, 1
st
degree AV delay (230 ms), and iRBBB (QRS 110 ms) (Fig. 1A). Immediately after TAVR, ECG showed a narrowed QRS (90 ms) with normal morphology (Fig. 1B). A narrowed QRS was sustained on post-operative day 2, with prolongation of the PR interval (260 ms; Fig. 1C). Electrophysiology study (EPS) showed a prolonged HV interval (65 ms) but no inducible block (Fig. 1D), and an implantable loop recorder (ILR) was placed.

Discussion:
Damage to the infranodal cardiac conduction system after TAVR is common, and approximately 15% of post-TAVR patients require pacemaker, with a higher occurrence in self-expanding valves as compared to balloon-expandable valves. Pre-existing RBBB as well as new-onset LBBB after TAVR increase the risk for heart block. Here, QRS normalization of an iRBBB concealed the development of new LBBB, by way of balanced delay in both the right and left bundles. This balanced delay is evident in the slightly longer PR interval post-operatively. Such a finding may be falsely reassuring and requires increased scrutiny (such as EPS and ILR placement).

Conclusion:
This case illustrates that paradoxical normalization of AV conduction following TAVR may belie an increased risk of high-grade AV block. Structural heart teams should be aware of this potential post-operative complication.
Abstract 17187: The Relationship Between N-Terminal Pro-Brain Natriuretic Peptide Levels and Poor Outcomes in Covid-19 Patients
Authors: Soney Hywel , Sidhu Manavjot S
Published: December 2023

Introduction:
N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker reflecting increased cardiac stress. It is a key variable in assessing patients with various pathologies. However, assessment of NT-proBNP as a variable in the prognostication of poor outcomes in COVID-19 patients is lacking. In addition, COVID-19 has brought its own variables and sequelae along with overlapping pathologies in a variety of systems.

Hypothesis:
With the systemic impact that COVID-19 can have, NT-proBNP represents a variable that will aid in identifying patients at higher risk of poor outcomes. We aim to assess the utility of NT-proBNP to help predict the incidence of major adverse cardiovascular events (MACE) and mortality in patients hospitalized with COVID-19.

Methods:
Using a multi-center observational database, we analyzed 1,692 hospitalized COVID-19 PCR-positive patients at Methodist Health System from March to July 2020. We examined NT-proBNP levels, in-hospital death or hospice referral rates, and incidence of MACE in the cohort. MACE was defined as congestive heart failure (CHF) exacerbation, pericardial effusion, cardiac tamponade, myocarditis, pericarditis, myocardial infarction (MI), stroke, pulmonary embolism/deep vein thrombosis, or shock. The incidence of mortality and MACE were compared between patients with and without elevated NT-proBNP levels. Elevated NT-proBNP levels were those >900 pg/mL. A chi-square (
X
2
) and odds ratio (OR) test were used to analyze observed variables.

Results:
Of the 1,692 hospitalized patients, 576 patients (34.0%) arrived with elevated NT-proBNP levels. Patients with elevated NT-proBNP had a higher incidence of mortality (OR=3.2559, 95% CI=2.522-5.203, p<0.0001) and MACE (OR=6.564, 95% CI=5.255-8.199, p<0.0001) compared to patients with NT-proBNP levels <900 pg/mL. Additionally, the elevated NT-proBNP patients had a higher incidence of CHF exacerbation, MI, and shock compared to patients with NT-proBNP levels <900 pg/mL.

Conclusions:
NT-proBNP levels can be a vital tool in recognizing COVID-19 patients who are at higher risk of poor outcomes. The use of NT-proBNP can further aid in prognostication in patients presenting to the hospital with COVID-19.
Abstract 17195: Sex-Specific Differences in Outcomes Following Alcohol Septal Ablation or Septal Myectomy for Hypertrophic Obstructive Cardiomyopathy: A Systematic Review and Meta-Analysis
Authors: Saravanabavanandan Ragavendar , Jaimalani Aniket , Khan Muhammad Ahsan Naseer , Riaz Sania , Mangas Gabriel , Ahsan Syed Muhammad , Posani Sarojini , Patel Tirath , Fawad Moiz , Al-Tawil Mohammed
Published: December 2023

Introduction:
Clinical evidence and emerging studies suggest that the clinical heterogeneity observed in hypertrophic obstructive cardiomyopathy (HOCM) could be due to sex-based differences. However, definite evidence to guide sex-specific treatment is not yet available. We aim to explore the sex-related differences in treatment outcomes following alcohol septal ablation (ASA) and septal myectomy (SM).

Methods:
We searched PUBMED/MEDLINE, EMBASE, and SCOPUS to identify studies that report sex-stratified comparison of outcomes in adults undergoing ASA or SM. The primary outcomes were the short-term/ 30-day mortality, post-operative permanent pacemaker (PPM) requirement, and the length of in-hospital stay.

Results:
Fifteen studies totaling 31,907 patients (47% men and 53% women) met our eligibility criteria. Among patients undergoing ASA (n=13357) or SM (n=18550), females were found to be significantly older at the time of intervention (ASA - mean difference (MD): 7.55 years; 95% CI [4.83, 10.28]; p < 0.00001; SM - MD: 4.41; 95% CI [2.79, 6.03]; p < 0.00001).In both the ASA and SM treatment arms, females had a significantly higher risk of short-term all-cause mortality (ASA - RR: 0.48, 95% CI [0.32, 0.71]; p = 0.0003; SM - RR: 0.63; 95% CI [0.44, 0.90]; p = 0.01), greater PPM implantation rate (ASA - p = 0.002; SM - p = 0.05), and longer in-hospital stay (ASA - MD: 1.00 days; p < 0.00001; SM - MD: 0.69; p < 0.00001). Among those undergoing ASA, females had a significantly higher rate of atrioventricular (AV) block (p < 0.00001). However, the 30-day re-admission rate following SM was similar in both sexes.

Conclusions:
This is the first meta-analysis to compare sex differences in HOCM treatment outcomes. Female patients were older, had higher short-term mortality, and required more PPM implants compared to males, regardless of whether they received ASA or SM. This emphasizes the critical need for a sex-specific treatment approach in managing HOCM.
Abstract 17214: Sex Difference in Outcomes of Redo-Surgical Aortic Valve Replacement (redo-SAVR) for Failed Bioprosthetic Aortic Valves: Insights From the National Inpatient Sample
Authors: Rivera Frederick B , Yan Linjie , Zhao Jiahe , Choi Sarang , Priela Lia Veronique , Collado Fareed Moses M
Published: December 2023

Introduction:
Redo surgical aortic valve replacement (SAVR) remains the gold standard for the management of failed bioprosthetic valves (BV). We aim to determine if there are sex differences in in-hospital outcomes among patients who underwent redo-SAVR for failed BV.

Methods:
We obtained the data from the National Inpatient Sample from 2013-2020. Our primary outcome was in-hospital mortality. Secondary outcomes included acute stroke, acute myocardial infarction (MI), acute kidney injury post-operative bleeding and blood transfusion. (See figure 1). Multivariable regression analyses were done to adjust for confounders.

Results:
There were more men who underwent the procedure compared to women. (62.3% versus 37.7%, p<0.001) Hypertension, coronary artery disease and smoking were commonly seen among men. Obesity is more common among women. There was no difference in in-hospital mortality. Men were less likely than women to have vascular complications (adjusted odd ratio (aOR) 0.63, p<0.005; acute kidney injury aOR 0.63, p< 0.01, and acute stroke (aOR 0.6, p< 0.002).

Conclusions:
Men underwent more redo-SAVR procedures than women. There were no sex difference in in-hospital outcomes, however, men were less likely to have AKI, stroke and vascular complications from the procedure. Further research is needed to explore these sex disparities.
Abstract 17240: Preoperative Pectoralis Muscle Area Index is Associated With Increased Post-LVAD Length of Stay and 90-day Readmission
Authors: Carey Matthew R , Ladanyi Annamaria , Nishikawa Mia , Bordon Abraham , Pinsino Alberto , Latif Farhana , Sayer Gabriel T , Takeda Koji , Uriel Nir , Colombo Paolo C , Yuzefpolskaya Melana
Published: December 2023

Background:
In LVAD pts, preoperative sarcopenia, as measured by pectoralis muscle area index (PMI), has been associated with mortality and GI bleed; however, the association with length of stay (LOS) and readmission is unknown.

Methods:
This was a single-center retrospective cohort study of pts who underwent LVAD 01/2015-10/2018. Preoperative pectoralis muscle area was measured on CT chest prior to implant using Tera Recon, adjusted for height squared to give the PMI. Multivariable negative binomial regressions were used to assess the association between PMI and LOS. Subhazard ratios (SHR) and cause-specific hazard ratios (CSHR) were used to assess the association between PMI and freedom from 90-day readmission.

Results:
Of 254 LVAD pts, 95 had a preop CT chest and were included (median days CT to LVAD: 7 [IQR 3-13]). Pts with PMI in the lowest quartile (PMI < 4.86 cm
2
/m
2
) constituted the low PMI cohort; all others served as the reference cohort. Baseline characteristics are shown in the Table. During index hospitalization, 2 low PMI pts died vs 7 reference; 0 low PMI pts were transplanted vs 2 reference. Low PMI was associated with longer post-LVAD LOS (adjusted incidence rate ratio 1.31 [95% CI 1.03-1.66],
p
=0.03) and increased risk of 90-day readmission (aSHR, accounting for risk of death and transplantation, 3.77 [1.17-12.1],
p
=0.03; aCSHR 3.67 [1.35-9.96],
p
=0.01) (Fig). The most common reason for readmission in low PMI pts was infection (n=3).

Conclusions:
Low PMI is associated with longer LOS and higher likelihood of 90-day readmission after LVAD. PMI could be used to identify sicker patients at risk for more intensive medical intervention and potentially higher health care cost.
Abstract 17244: Association of Remnant Lipoprotein Cholesterol, Type 2 Diabetes Mellitus, and Major Adverse Cardiovascular Events: Insights From the UK Biobank
Authors: Gabani Mohanad , Kingsley Jeffrey , Rikhi Rishi , Chevli Parag A , Herrington David M , Shapiro Michael D
Published: December 2023

Background:
Remnant lipoprotein-cholesterol (RLP-C) has emerged as a potential contributor to adverse cardiovascular events. While the association of low-density lipoprotein- cholesterol and atherosclerotic cardiovascular disease is well-established, the joint association of RLP-C and type 2 diabetes mellitus (T2DM) in driving major adverse cardiovascular events (MACE) remains less explored.

Methods:
We included a total of 118,004 participants from the UK Biobank with nuclear magnetic resonance-measured RLP-C. Participants were categorized into four groups based on their RLP-C levels and T2DM status: Group 1 (RLP-C below the median and no T2DM), Group 2 (RLP-C above the median and no T2DM), Group 3 (RLP-C below the median and T2DM), and Group 4 (RLP-C above the median and T2DM). Cox proportional hazards regression was employed to assess the association of these four categories with the time to incident MACE. The model was adjusted for age, sex, race, BMI, smoking, systolic blood pressure, anti-hypertensive and lipid-lowering therapy, and physical activity.

Results:
Our analysis revealed significant associations between RLP-C levels, T2DM, and the risk of MACE. Compared to the reference group (Group 1), Groups 2-4 had hazard ratio for the MACE outcome of 1.27 (95% CI: 1.18-1.37, p < .0001), 1.43 (95% CI: 1.29-1.59, p < .0001), and 2.04 (95% CI: 1.78-2.32, p < .0001), respectively (see Figure).

Conclusion:
This analysis from individuals in UK Biobank free from cardiovascular disease at baseline demonstrated a significant joint association between elevated RLP-C levels and T2DM, with the risk of major adverse cardiovascular events.
Keywords:
remnant lipoprotein cholesterol, type 2 diabetes mellitus, major adverse cardiovascular events, UK Biobank, nuclear magnetic resonance
Abstract 17254: Myocardial Functional Recovery Following Durable Ventricular Assist Device in Children
Authors: Langanecha Bhavikkumar , Honjo Osami , Power Alyssa , Mazwi Mjaye , Zaulan Oshri , Lynch Aine , Haller Christoph , George Kristen , Fazari Linda , Maurich Andrea , Chiasson David , Jeewa Aamir
Published: December 2023

Introduction:
Ventricular Assist Device (VAD) explantation following myocardial functional recovery (MFR) for heart failure (HF) is uncommon and associated with a risk of recurrence of HF.

Research Question:
What are the patient characteristics and outcomes for VAD explantation in children following MFR?

Methods:
Retrospective, single centre study of patients who were supported with durable VADs, both intracorporeal continuous flow devices (CFD) and paracorporeal pulsatile flow devices (PFD) between 2004 to 2022.

Results:
A total of 75 children, of which 43 were female, underwent VAD implantation (PFD = 61 and CFD = 14) at a median (IQR) age of 5.6 (0.8, 13.5) years and with a weight of 16.2 (7.5, 40.7) kg. From this cohort, we identified 8/75 (11%) children who underwent VAD explantation for MFR after a median duration of 56 (22, 115) days. All were supported with durable PFD. Five were listed for transplantation as a part of their HF management strategy following VAD implantation and four patients had dilated cardiomyopathy (DCM). Of those, 7/8 (88%) children with MFR were under 2 years of age and 5/8 (63%) were supported for > 90 days. The pathological findings on the LV core samples were variable in severity and no patient had any evidence of active inflammation (see Table). After explant, 7/8 patients remained in HF remission with no symptoms and stable LV function. One patient had a recurrence of HF following explantation after demonstrating MFR while on VAD support. This patient was 5 years old at implant and was in HF remission for ~9 months following explant before HF recurrence, requiring VAD re-implantation and eventual heart transplantation.

Conclusions:
MFR resulting in VAD explantation is feasible in children with chronic HF especially for those < 2 years of age. Further work is needed to help better identify the features that promote MFR and maintain it after explant.
Abstract 17260: Endothelium-Targeted Nanoparticle Delivery of FOXM1 Reactivates Aging-Impaired Endothelial Regeneration for Vascular Repair and Inflammatory Lung Injury Resolution: Precision Gene Therapy of Acute Respiratory Distress Syndrome
Authors: Huang Xiaojia , Zhang Xianming , Machireddy Narsa , Evans Colin , Zhao Youyang
Published: December 2023

Introduction:
Aging is a major risk factor of high incidence and increased mortality of acute respiratory distress syndrome (ARDS). However, the underlying molecular mechanisms remain elusive and there is no effective therapy for ARDS.

Hypothesis:
Impaired endothelial regeneration and vascular repair in aged lungs causes persistent lung injury leading to high incidence of ARDS and high mortality in elderly patients following sepsis challenge.

Methods:
Genetic lineage tracing was employed to determine the cell origin of endothelial regeneration. Aged Foxm1Tg mice was used for assessing the role of FoxM1 in activating endothelial regeneration. Endothelium-targeted nanoparticles were employed to deliver FOXM1 gene selectively to endothelial cells (ECs) in aged mice. Methylation analysis was employed to determine how aging impairs FoxM1 expression.

Results:
Genetic lineage tracing study showed that endothelial regeneration was mediated by lung endothelial proliferation in adult mice whereas this intrinsic regenerative program was impaired in aged mice. Expression of FoxM1, an important mediator of endothelial regeneration in young adult mice, was not induced in lungs of aged mice due to aging-induced hypermethylation of the Foxm1 promoter. Transgenic
FOXM1
expression or
in vivo
endothelium-targeted nanoparticle delivery of
FOXM1
gene reactivated endothelial regeneration, normalized vascular repair and promoted survival of aged mice following sepsis. Furthermore, nanoparticle delivery of FoxM1 gene selectively in lung ECs also reactivated endothelial regeneration in aged mice, supporting the novel concept of precision gene therapy. In COVID-19 lung autopsy samples, FOXM1 expression was not induced in vascular ECs of elderly patients in contrast to mid-age patients, validating the clinical relevance of our findings.

Conclusions:
We have demonstrate that persistent lung injury and high mortality in aged mice following sepsis challenge is ascribed to impaired endothelial regeneration and vascular repair. Therapeutic reactivation of FoxM1-dependent endothelial regeneration and vascular repair represents a potential effective therapy for elderly ARDS patients by endothelium-targeted nanoparticle delivery of FOXM1 gene.
Abstract 17273: Phenotypic Clustering of Patients With Heterotaxy Syndrome Predicts Outcomes of Mortality and Transplantation
Authors: Bucholz Emily M , Sompolinsky Tehila , Beroukhim Rebecca S , Castellanos Daniel A , Dewitt Elizabeth S , Geva Tal , Ghelani Sunil J , Hoganson David , Marx Gerald R , Roberts Amy E , Teele Sarah A , Schidlow David N
Published: December 2023

Background:
Current classifications of heterotaxy syndrome (HS) (e.g. left/right isomerism, polysplenia/asplenia) do not capture the heterogeneity of cardiac anomalies observed nor provide insight on risk stratification. We aimed to improve these classifications using cluster analysis to identify anatomic phenotypes in HS patients.

Methods:
Using a retrospective database of all HS patients seen at Boston Children’s Hospital from 1985-2014 (n=264), we performed principal component and cluster analyses on 47 cardiac anatomic variables and compared rates of mortality/transplantation across clusters.

Results:
Five clusters were identified ranging in size from 19 to 91 patients. Cluster #1 had a high prevalence of right-dominant complete atrioventricular canal defects (CAVC), double-outlet right ventricle (DORV), pulmonary stenosis/atresia (PS/PA), and total anomalous pulmonary venous connection (TAPVC); Cluster #2 of left-dominant CAVC, DORV, and TAPVC; Cluster #3 of left-sided obstructive lesions and interrupted IVC; Cluster #4 of transposition of the great arteries with PS/PA; and Cluster #5 of interrupted IVC with miscellaneous cardiac anomalies (Table). Over 80% of patients in clusters 1 and 2 underwent single ventricle palliation compared with only 16% of patients in cluster 5. Transplant-free survival was lowest in clusters 1, 2, and 3 but differed by single versus biventricular repair (Figure).

Conclusions:
Cluster analysis of cardiac anatomic variables identified 5 phenotypes of HS including 3 higher risk and 2 lower risk phenotypes. These findings highlight the need for improved phenotyping of HS to account for the high degree of disease heterogeneity.
Abstract 17327: Heterogenous Shared Decision-Making Approaches to Sports Eligibility Decisions for Athletes With Cardiovascular Disease
Authors: Montembeau Sarah , Kim Jonathan H , Baugh Christine , Dickert Neal W
Published: December 2023

Background:
Historically, almost all pathologic cardiovascular (CV) diagnoses led to complete restriction from competitive sports. In 2015, the American College of Cardiology (ACC) and American Heart Association began to embrace a more nuanced, patient-centered approach to sports eligibility using shared decision-making (SDM). While SDM is a conceptually defensible approach to sports eligibility, operationalization is complex, and we know very little about how physicians understand and deploy it.

Methods:
To assess sports cardiologists’ understandings of SDM and approaches to eligibility decisions, in-depth interactive interviews were conducted with (N=20) self-identified sports cardiologists. Participants were sampled at random from the ACC Sports and Exercise Cardiology Section. Interviews were conducted using video conference or telephone, and transcripts were analyzed for qualitative description of key domains.

Results:
Analysis revealed heterogeneity regarding core elements of SDM. All 20 clinicians endorsed SDM, but conceptions of what SDM means varied. Some emphasized communication between physicians rather than with patients, and there was variation in describing the clinician’s role primarily as a provider of information or a more active driver of the decision. Furthermore, even though lifestyle considerations are a key component of SDM for sports eligibility, few clinicians (n=6) specifically referenced elicitation of a patient’s preferences as part of the SDM process. Clinicians also stated highly variable thresholds for prohibitive annual risk of sudden cardiac death during sports participation ranging from <1% to >10%, and they expressed heterogenous views of how athletes interpret risk. Some believed athletes can interpret risk in similar ways as other people; others felt they are largely blind to risk.

Conclusions:
These data collectively demonstrate heterogenous views of and approaches to SDM for sports eligibility decisions that likely result in very different encounters and decision outcomes. There is a need to develop a more robust understanding of how SDM is operationalized in this context and determine an evidence-based approach to SDM for sports and exercise eligibility in the context of CV disease.
Abstract 17328: A Case of Reversible Severe Systolic Cardiomyopathy; Thinking Outside the Box
Authors: Shaw Joshua , Dhar Kalyani , Dianati Maleki Neda
Published: December 2023

Introduction:
Non-ischemic systolic cardiomyopathy is associated with significant morbidity and mortality. Prompt evaluation and timely removal of the potential insult may lead to reverse remodeling and recovery of the left ventricular (LV) systolic function.

Case:
A 39-year-old female with BMI 40 presented with dyspnea and bilateral lower extremity edema. Vital signs significant for mild tachycardia and hypertension. ECG showed sinus tachycardia. Physical exam revealed bibasilar crackles and 3+ pitting edema of the lower extremities. Laboratory significant for NTpro BNP 563 pg/dL and TSH <0.005 IU/mL with a free T4 of 2.73 ng/dL. Chest x-ray showed pulmonary vascular congestion. Echocardiogram showed severely reduced LV systolic function with ejection fraction (EF) of 27%, global LV hypokinesis and diastolic LV diameter of 6.85 cm. No significant atrial or ventricular arrhythmias noted on Telemetry. A CT angiography of the coronary arteries showed no evidence of calcification or obstructive coronary disease. Additional labs revealed severely elevated TSH receptor antibody and thyroid stimulating immunoglobulin. Diffuse thyroid enlargement noted on ultrasound. Patient was diagnosed with Grave’s disease (GD) with Burch-Wartofsky score of 30 indicating an impending thyroid storm. She was treated with Metoprolol and Methimazole. She underwent intravenous diuresis and was started on guideline-directed medical therapy for systolic cardiomyopathy. In follow-up after 6 months, her TSH had normalized. On repeat imaging, her LVEF improved to > 50% with diastolic LV diameter of 5.6 cm.

Discussion:
This patient was diagnosed with non-ischemic dilated systolic cardiomyopathy due to severe hyperthyroidism from GD. Thyrotoxicosis-induced systolic cardiomyopathy occurs in about 1% of patients with GD and is associated with increased morbidity and mortality. Excess thyroid hormones in thyrotoxicosis can affect multiple regulatory and structural genes of cardiac myocytes resulting in abnormal intracellular calcium regulation and impaired LV systolic and diastolic function. Our experience is consistent with literature demonstrating the importance of timely diagnosis and treatment of this reversible cause of systolic cardiomyopathy.
Abstract 17336: A Hepato-Cardiac FGF21 Signaling Axis Promotes Cardiac Hypertrophy
Authors: Mia Sobuj , Sidiropoulou Rafailia , Hoffman Matthew , Markopoulou Eftychia , Fragkiadakis Konstantinos , Siokatas Georgios , Ganesh Yerra Veera , Selzman Craig H , Drakos Stavros , Chaudhuri Dipayan , Molkentin Jeff , Marketou Maria , Drosatos Konstantinos
Published: December 2023

FGF21 is expressed mainly in the liver and other organs, including the heart. The role of FGF21 is controversial, with potential benefits for obesity and certain heart conditions, but also associations with heart failure and increased mortality. We found higher serum FGF21 levels (2.5-fold) in left ventricular hypertrophy patients (N=31) compared to those without hypertrophy (N=45). Similarly, mice subjected to Transverse Aortic Constriction (TAC) had elevated plasma FGF21 levels and hepatic expression. Surprisingly, a time course experiment showed that liver FGF21 production peaked 3 days post-TAC (prior to the onset of hypertrophy), while an unexpected increase of cardiac FGF21 expression was observed 2 weeks post-TAC, coinciding with hypertrophy and dysfunction. FGF21 expression in skeletal muscle did not change. As in mice, hypertensive individuals (N=6) showed a 14-fold increase in cardiac FGF21 mRNA levels compared to normotensive (N=6). To delineate the role of hepatic and cardiac FGF21 in hypertrophy, TAC was performed on mice with hepatocyte- (HEP-FGF21-KO) or cardiomyocyte-specific (CM-FGF21-KO) FGF21 ablation. Both HEP-FGF21-KO and CM-FGF21-KO mice were protected from hypertrophy, pro-hypertrophic signaling, fibrosis, and cardiac dysfunction. Notably, hepatocyte FGF21 deletion prevented cardiac FGF21 upregulation with TAC, suggesting control of CM FGF21 expression by liver-derived FGF21 and highlighting the role of CM FGF21 in driving cardiac hypertrophy. This was confirmed by treatment of AC16 human cardiomyocytes with recombinant FGF21 that increased endogenous FGF21 expression and cell size. RNAseq analysis revealed attenuation of cardiac fibrosis- and hypertrophy-related transcriptome in both HEP-FGF21-KO and CM-FGF21-KO mice. To explore if FGF21 increase is a cause and not a consequence of cardiac hypertrophy, we developed anti-sense oligonucleotides against FGF21 and administered them in C57BL/6 mice with TAC. ASO-FGF21 treatment attenuated cardiac hypertrophy and fibrosis and improved cardiac function. Thus, FGF21 emerges as a therapeutic target for pathological cardiac hypertrophy.
Abstract 17349: Independent and Joint Effect of Central and Brachial Systolic Blood Pressure on Incident Stroke in Hypertensive Adults
Authors: Ding Congcong , Cao Tianyu , Huang Xiao
Published: December 2023

Introduction:
It is unclear whether central systolic blood pressure (cSBP) is an independent predictor of stroke above and beyond brachial systolic blood pressure (bSBP).

Hypothesis:
This study aimed to investigate the difference between cSBP and bSBP in predicting first stroke and the joint effect of cSBP and bSBP on the risk of first stroke in hypertensive adults.

Methods:
A total of 8,122 hypertensive adults without stroke history were included in this study. cSBP was measured noninvasively using A-Pulse CASPro device. The outcome was first stroke.

Results:
During a median follow-up of 4.4 years, 579 first stroke were identified. The per SD increment of cSBP (HR: 1.16, 95% CI: 1.07, 1.26) and bSBP (HR: 1.16, 95% CI: 1.07, 1.26) was significantly associated with higher risk of first stroke. The differences in areas under the curves, continuous net reclassification indices, and integrated discrimination indices of bSBP and cSBP models for predicting first stroke were 0.003 (95% CI: -0.003, 0.008), 0.007 (95% CI: -0.058, 0.071), and -0.0002 (95% CI: -0.0028, 0.0013), respectively. When cSBP and bSBP were evaluated jointly, participants in the highest tertiles of both cSBP and bSBP had the highest risk of first stroke compared with their counterparts (HR: 1.59, 95% CI: 1.29, 1.96; P-interaction = 0.034). Similar results were found for ischemic stroke and hemorrhagic stroke.
Conclusions:
Although cSBP was not found to be superior to bSBP in predicting first stroke, cSBP and bSBP were jointly associated with the risk of first stroke among hypertensive adults.
Abstract 17353: Health Literacy and Hypertension: A Systematic Review
Authors: Horde Gaither W , Huang Edward , Hammock James , Levitan Emily B , Zhu Aowen , Hansen Ross , Carroll Travis , Siddiqui Mohammed , Jackson Elizabeth A
Published: December 2023

Introduction:
Low health literacy (HL) is highly prevalent in the United States. Despite the potential for low HL to be a major barrier to effective self-management of blood pressure (BP), data on HL among adults with hypertension (HTN) is scarce.

Goals:
We conducted a systematic review to examine the prevalence and factors associated with low HL among adults with HTN. Additionally, we examined intervention trials which sought to modify the impact of low HL among participants with HTN.

Methods:
A comprehensive search of 6 databases was performed to identify studies which measured HL using a validated survey and included adults with HTN. After removing duplicate citations, two authors independently reviewed the references for eligibility, data extraction, and risk of bias assessment.

Results:
A total of 1,046 studies were identified of which 44 met eligibility criteria. The prevalence of low HL was 33% among the 31,507 participants included across the 44 studies. In the studies that reported associations between social determinants of health factors and HL, lower education levels, non-white race, and lower HTN knowledge were found to be significantly associated with lower HL among adults with HTN. Among the 15 observational studies which examined BP, lower HL was associated with higher BP in 8 studies. Six randomized control trials included an intervention to modify HL and measure its effect on BP control. Two of these trials demonstrated significant reductions in BP among the intervention group compared to control.

Conclusion:
Among studies which measured HL in adults with HTN, education, HTN knowledge and race were associated with HL; however, interventions to address HL were not consistently associated with improvements in BP control. A more detailed examination of methods to address HL among adults with HTN is warranted.
Abstract 17358: Persistent Pericardial Effusion Secondary to Dasatinib Successfully Treated With Colchicine
Authors: Espinoza Joaquin , Lecompte Paola , Quintero Martinez Juan , Mustafa Mohammed , akbar fatemah , Colombo Rosario
Published: December 2023

Introduction:
Dasatinib is one of the first-line therapies for CML. A large pericardial effusion requiring drainage has rarely been documented among its adverse effects, and its treatment is still a subject of study.

Case Presentation:
A 44-year-old female with history of chronic myeloid leukemia (CML) in remission on Dasatinib for the past 10 years presented to the emergency with complaints of chest pain and palpitations for 3 weeks. Physical examination was remarkable for muffled heart sounds and tachycardia. No JVD, pulsus paradoxus, or hypotension were noted. A 12-lead EKG showed low voltage QRS in limb leads (A), and transthoracic echo (TTE) reported a moderate to large pericardial effusion with features concerning for early tamponade (B). A pericardiocentesis was performed with 500 mL of hemorrhagic fluid removed with a drain placed. Dasatinib was held but pericardial output remained elevated (>100 mL/day) for the following 12 days. Colchicine 0.6mg twice a day was then initiated. Cardiothoracic surgery recommended against a pericardial window. On day 15, the drain was able to be removed after a marked reduction in fluid output. Patient was discharged to complete 3 weeks of colchicine therapy. Two weeks later, the patient remained asymptomatic with no signs of recurrent pericardial effusion on a repeat TTE.

Discussion:
Dasatinib is associated with a range of reported side effects including development of pericardial effusions in a limited number of cases. Nonetheless, there is a dearth of information regarding their optimal treatment approach. Our case highlights the use of colchicine as a potential strategy for patients with persistent Dasatinib-related pericardial effusions.