bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13143: Genetic Testing Referral Patterns Among Women With Peripartum Cardiomyopathy
Authors: Packard Elizabeth , Reza Nosheen , Owens Anjali , Arany Zoltan , Lewey Jennifer
Published: June 2023

Introduction:
The genetic architecture of peripartum cardiomyopathy (PPCM) and dilated cardiomyopathy (DCM) overlap, and 15% of patients with PPCM have a disease-causing variant in a DCM-associated gene. Despite the impact of genetics on cascade screening and risk stratification, there are no recommendations for genetic testing in PPCM. We aimed to quantify the percentage of individuals with PPCM referred for genetic testing and to identify factors that may impact the likelihood of referral for genetic testing.

Methods
: We conducted a retrospective cohort study of 205 patients diagnosed with PPCM from 1986-2018 within the University of Pennsylvania Health System who had outpatient follow-up. We determined the referral rate for genetic testing and examined differences in referral based on race, timing of PPCM diagnosis, hypertensive disorders of pregnancy (HDP), NYHA class at diagnosis, LVEF at diagnosis, family history, recurrent PPCM, and referral to a heart failure specialist. We compared continuous variables using the Student
t
test and categorical variables using Pearson’s chi-square test.

Results
: Of 205 patients with PPCM, 23 (11%) were referred for genetic testing. Women referred for genetic testing were more likely to have HDP (61% vs. 37%, p=0.03), LVEF <30% at diagnosis (65% vs. 42%, p=0.04), recurrent PPCM (17% vs. 5%, p=0.04), a first-degree family member with heart failure or cardiomyopathy (70% vs. 17%, p<0.001), and any documented family history at the first cardiology visit (78% vs. 54%, p=0.03). Of those referred, 17 (74%) underwent genetic counseling, and 12 (52%) completed genetic testing. Two patients (17%) had a pathogenic or likely pathogenic variant in
TTN
and were recommended for cascade screening, and 9 (75%) had variants of unknown significance which were predominately missense variants.

Conclusions
: A minority of women with PPCM are referred for genetic testing. Referral is largely driven by family history, which may lead to under-diagnosis of pathogenic mutations. Increasing referral rates may improve the detection of pathogenic mutations which may impact the care provided to affected women and their families.
Abstract 13151: Left Ventricular Hypovolemia Secondary to in Utero Mitral Valve Inflow Obstruction in a Late-Gestation Fetal Lamb Model
Authors: Onohara Daisuke , Hagen Matthew , Louey Samantha , Giraud George , Jonker Sonnet , Padala Muralidhar
Published: June 2023

Introduction:
Hypoplastic left heart syndrome (HLHS) is a congenital heart defect of an underdeveloped left ventricle (LV), necessitating palliative interventions after birth to survive. HLHS often occurs alongside mitral or aortic valve stenosis, lending to the hypothesis that reduced blood flow into and out of the LV in utero could retard LV growth. We have developed a late-gestation fetal lamb model to investigate if in utero mitral inflow obstruction could cause LV hypovolemia.

Methods:
Twelve pregnant ewes with twin fetuses at 82% gestation were used. In the experimental fetuses (EXPT), mitral inflow obstruction was achieved with an inflatable balloon catheter implanted into the left atrium (LA) in a beating heart. Other implants included a flow probe on the ascending aorta to measure cardiac output, and carotid artery and jugular vein catheters to monitor fetal health. After recovery from surgery, progressive LA balloon inflation began at ~86% gestation, and was left inflated for 8 days (92% gestation). Transesophageal fetal ultrasound was performed at baseline and at termination to measure cardiac chamber volumes and function. Hearts were explanted, weighed and prepared for histology.

Results:
Fetal body weights were similar (EXPT: 4.6±0.9kg vs CTRL: 4.5±0.6kg, p=0.8597). Total heart weight was higher in EXPT (31.4±5.6g) than CTRL (26.4±2.4g, p=0.0471), but LV weight was similar (EXPT: 7.4± 1.8g vs. CTRL: 7.9± 1.1g, p=0.5652). LV end-diastolic volume was 2.3± 0.7ml in EXPT vs. 7.1± 0.8ml in CTRL (p<0.0001), and end-systolic volume was 1.01ml (0.95 to 1.95ml) in EXPT vs. 3.38ml (3.28 to 3.57ml) in CTRL (p=0.0025). LV/RV weight ratio was 0.83±0.17 in EXPT and 1.08±0.19 in CTRL (p=0.0209), whereas LV/RV chamber area ratio was 0.21±0.06 in EXPT and 0.56±0.05 in CTRL (p=0.0005).

Conclusions:
In this fetal sheep model, obstructing mitral inflow retarded LV growth, demonstrating a potential mechanistic link between blood inflow and in utero LV volumetric growth.
Abstract 13153: Proteomic Differences in Sarcomere Positive HCM May Explain More Severe Clinical Differences
Authors: Garmany Ramin , Bos Johan M , Tester David J , Giudicessi John , Dos Remedios Cristobal , Dasari Surendra , Johnson Kenneth L , Ryan Zachary C , Maleszewski Joseph J , Ommen Steve R , Dearani Joseph A , Ackerman Michael J
Published: June 2023

Introduction:
Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy. Approximately 40-50% of HCM is caused by pathogenic variants in genes encoding proteins of the cardiac sarcomere. Patients with sarcomeric HCM have earlier expression and more severe disease progression. Herein, we evaluated the proteomic differences between patients with sarcomeric HCM and genotype negative HCM.

Methods:
Mass-spectrometry was performed on cardiac tissue from genotyped patients with HCM obtained after surgical myectomy, followed by differential proteomics (log2fc ≥
Abstract 13156: The Location of Combined High-Risk Low Endothelial Shear Stress and High Plaque Structural Stress is Distant From the Minimal Lumen Area in the Majority of Coronary Plaques Responsible for Major Adverse Cardiac Events
Authors: Ahmed Mona , Gu Sophie Z , Hakim Diaa , Coskun Ahmet U , Cefalo Nicholas , Huang Yuan , Maynard Charles , Costopoulos Charis , Maehara Akiko , Stone Gregg W , Bennett Martin R , Stone Peter H
Published: June 2023

Introduction:
The presence of multiple high-risk prognostic features enhances risk-stratification of plaques prone to destabilization and major adverse cardiac events (MACE). Spatial superimposition of high-risk features (concordance) likely amplifies local risk. Local endothelial shear stress (ESS) and plaque structural stress (PSS) metrics predict MACE, but their spatial concordance and their location relative to the minimal lumen area (MLA) is unknown. If the highest-risk plaque area is distant from the MLA, then PCI of the MLA alone will leave high-risk plaque areas untreated.

Purpose:
To identify the site of high-risk features of low ESS and high PSS heterogeneity (HI) along the course of a plaque in patients who develop MACE, and the site of their spatial concordance relative to the MLA.

Methods:
We examined ESS, PSS, and PSS HI in 22 non-culprit lesions (NCL) leading to MACE, and 64 randomly selected control NCLs without MACE from the PROSPECT study. ESS was calculated by computational fluid dynamics and PSS by finite element analysis on co-registered lesions. We examined high-risk plaques with empirically-derived (ROC curve) ESS < 1.3 Pa and PSS HI > 0.29 in 16 lesions leading to future MACE, and 11 control lesions without MACE.

Results:
MACE outcomes were significantly more frequent in plaques with combined low ESS+high PSS HI vs plaques with low ESS alone (72.7% vs 27.3%, p<0.001) at 3 years follow-up. Of the 16 MACE plaques with both low ESS+high PSS HI, 14 exhibited high-risk values that were spatially concordant vs 2 that were discordant (87.5% v 12.5%, p=0.01). In the 14 plaques with concordant values, there were 26 focal plaque areas with high-risk concordance. The mean distance from the concordant high-risk areas to the MLA was 13.2 ± 11.6 mm (Figure).

Conclusion:
High-risk ESS and PSS measures frequently co-localize in plaques responsible for future MACE, and are substantially distant from the MLA. PCI of the MLA area alone may leave many high-risk areas untreated.
Abstract 13172: Systematic Dissection, Preservation, and Multiomics in Whole Human and Bovine Hearts
Authors: Moreira Jesse D , Gower Adam C , Xue Liying , Alekseyev Yuriy , Smith Karan K , Choi Seung H , Ayalon Nir , Farb Melissa G , Tenan Kenneth , LeClerc Ashley , Levy Daniel , Benjamin Emelia J , Lenburg Marc , Mitchell Richard N , Padera Robert , Fetterman Jessica L , Gopal Deepa M
Published: June 2023

Introduction:
We developed a rigorous, systematic protocol for the dissection and preservation of human hearts for biobanking to advance our understanding of cardiovascular diseases (CVDs). Existing cardiac biobanks consist largely of biopsy tissue in select diseases and are insufficient for correlating whole organ phenotype with clinical data.

Methods:
We demonstrate optimal conditions for multiomics interrogation (ribonucleic acid (RNA) sequencing, untargeted metabolomics) in hearts by evaluating the effect of technical variables (storage solution, temperature) and simulated postmortem interval (PMI) on RNA and metabolite stability. We used bovine (N=3) and human (N=2) hearts fixed in PAXgene or snap-frozen with liquid nitrogen.

Results:
Using a paired Wald test, only two of the genes assessed were differentially expressed between left ventricular samples from bovine hearts stored in PAXgene at 0 and 12 hours PMI (FDR q < 0.05). We obtained similar findings in human left ventricular samples, suggesting stability of RNA transcripts at PMIs up to 12 hours. Different library preparation methods (mRNA poly-A capture vs. rRNA depletion) resulted in similar quality metrics with both library preparations achieving >95% of reads properly aligning to the reference genomes across all PMIs for bovine and human hearts. PMI had no effect on RNA Integrity Number or quantity of RNA recovered at the time points evaluated. Of the metabolites identified (855 total) using untargeted metabolomics of human left ventricular tissue, 503 metabolites remained stable across PMIs (0, 4, 8, 12 hours). Most metabolic pathways retained several stable metabolites.

Conclusions:
Our data demonstrate a technically rigorous, feasible and reproducible protocol that will enhance cardiac biobanking practices and facilitate novel insights into human CVD through the use of multiomics in postmortem human cardiac tissue.
Abstract 13175: The Effect of Impella Placement on Morbidity and Mortality in Cardiogenic Shockcomparing Outcomes of Two Percutaneous Mechanical Circulatory Support Modalities as Bridges to Advanced Heart Failure Therapy
Authors: DeStefano John , Kendsersky Payton , Silkowski Molly , Ramsayer Emily , Minchak Megan , Evans Matt , Mostertz William C , Maran Arasi , Nielsen Chris , Fernandes VALERIAN
Published: June 2023

Objectives:
The use of percutaneous mechanical circulatory support (PMCS) devices offers a means to maintain hemodynamic stability in pre-transplant patients. The Impella Heart Pump and the intra-aortic balloon pump (IABP) are two devices commonly employed for this purpose. We sought to compare the relative safety and efficacy of Impella vs IABP using a retrospective cohort of patients at our institution from 2014-2021.

Methods:
239 patients received Impella support, and 220 patients received IABP. Of these patients, 26 receiving Impella and 49 receiving IABP were identified as pre-transplant/VAD. The incidences of 30-day mortality, major bleeding, hemolysis, limb ischemia, stroke, repositioning, and infection were recorded. The number of patients receiving transplants, VADs, Mechanical Circulatory Support escalation, and ECMO were also recorded. The relative risks of complications were calculated, and an alpha of 0.05 was assigned to identify significance.

Results:
The average age of the IABP group was 54.8 +/- 12.1 years with 39 males to 10 females. The average age of the Impella group was 44.8 +/- 15 years with 15 males to 11 females. There was no significant difference in pre-placement EF between these two groups (IABP EF = 19.28+/-8.62, Impella EF = 21.15+/-9.69; p = 0.4016). A significantly higher relative risk of mortality (RR = 3.23; 95% CI = 1.45-7.20, p = 0.0041), major bleeding (RR = 8.48; 95% CI = 3.2 - 22.45, p < 0.00001), and hemolysis (RR = 35.2; 95% CI = 2.12-582, p = 0.0128) was noted in patients receiving Impella support. No significant difference in the incidence of limb ischemia, stroke, repositioning, or infection was observed between these two groups. A significantly higher number of patients receiving Impella support also required ECMO (p = 0.0003)

Conclusions:
These data suggest that a higher risk of mortality or major complications may exist for patients receiving Impella support pre-transplant/VAD. Further analysis is needed to correct for baseline differences between these two cohorts.
Abstract 13187: Inhibition of Advanced Glycation End Products Formation and Serum Protein Infiltration in Bioprosthetic Heart Valves: Investigations of Anti-Glycation Agents
Authors: Zakharchenko Andrey , Rock Christopher A , Thomas Tina , Keeney Samuel , Hall Emily J , Takano Hajime , Ferrari Giovanni , LEVY Robert
Published: June 2023

Introduction:
Bioprosthetic heart valves (BHV) fabricated from glutaraldehyde pretreated bovine pericardium (BP), are the most commonly used heart valve replacements. However, BHV durability is limited by structural valve degeneration (SVD) resulting from both calcification and advanced glycation end product (AGE) deposition together with serum protein infiltration. This study investigated, for the first time, the application of anti-glycation agents as a way to mitigate AGE-related structural degeneration of BHV.

Hypothesis:
We investigated the hypothesis that anti-AGE agents (Aminoguanidine (AG), Pyridoxamine (PYR), and N-Acetylcysteine (NAC)) could mitigate BP glycation in model studies, both in vitro and in vivo.

Methods:
To model AGE accumulation in BHV, we used well-established accelerated
in vitro
glycation models using BP incubation with or without inhibitors. Incorporation of AGE in BP was monitored using radiolabeled glycation precursors. Changes in collagen structure were examined by two photon confocal microscopy and differential scanning calorimetry. In vivo studies used a juvenile rat subdermal BP implantation model with drug administration via drinking water. Endpoints were AGE formation, collagen structure, thermal denaturation temperature, serum albumin uptake, calcification, and serum glycation marker levels.

Results:
In vitro studies demonstrated that each of these agents significantly inhibited AGE formation in BP. However, after 28-day rat subdermal BP implantation in vivo, only PYR demonstrated significant inhibition of both AGE and serum albumin accumulation per immunostaining. BHV calcification was not mitigated by PYR, AG or NAC.

Conclusions:
This study is the first to demonstrate the use of AGE inhibitors in mitigating BHV glycation. PYR demonstrated significant efficacy both in vitro and in vivo, mitigating AGE formation and albumin infiltration in BP. Thus, this study provides a rationale for investigating PYR as a possible candidate for improving the durability and biocompatibility of clinically used BHV, providing the solution for this unmet clinical need.
Abstract 13191: Leukocytoclastic Vasculitis and Acute Renal Failure as a Sign of Infective Endocarditis: A Case Report
Authors: Bussa Rahul , Haniff Fiyad , Ahmed Mohammad , Chisty Alia
Published: June 2023

Case Presentation:
Infective endocarditis (IE) can sometimes be a diagnostic challenge because its presentation in its early stages may coincide with that of several other disease processes. It has an incidence of ~7 per 100,000 annually yet has an in-hospital mortality of about 20-25%. We present a case of a 56-year-old immunocompetent male with a recent diagnosis of leukocytoclastic vasculitis (LCV) who was admitted for acute renal failure (ARF). With his history of LCV (Figure 1), renal vasculitis was thought to be contributing to his ARF. On admission, he was afebrile and had a creatinine of 5.25 (baseline of 0.8), hyponatremia, anemia, mild leukocytosis, and mildly elevated lactate. No other infectious sequelae were noted. Nephrology was consulted for workup of renal failure, and a renal biopsy was recommended. Before the biopsy was able to be performed, blood cultures returned positive for Enterococcus faecalis. Transesophageal echocardiogram revealed a large, mobile 1.3-centimeter vegetation attached to the left ventricular outflow tract side of the non-coronary cusp of the aortic valve. Parenteral antibiotics were initiated, and cardiothoracic surgery was consulted for surgical correction. The patient ultimately underwent aortic valve replacement successfully with renal recovery to baseline and resolution of his leukocytoclastic vasculitis soon thereafter.

Discussion:
LCV has been established as a rare, but well-reported sign of IE. Similarly, only a few cases of IE presenting as ARF have been reported. In patients presenting with both LCV and ARF, it is important to maintain a high index of suspicion for IE. Going down the pathway to work up renal vasculitis may unnecessarily expose patients to invasive procedures, incorrect treatment modalities, and other complications.
Abstract 13193: Prevalence of Late Gadolinium Enhancement Following Pediatric Heart Transplantation Increases With Time Since Transplantation
Authors: Lawson Andrew A , Watanabe Kae , Griffin Lindsay , Laternser Christina , Markl Michael , Rigsby Cynthia K , Sojka Melanie , Robinson Joshua D , Husain Nazia
Published: June 2023

Introduction:
Chronic graft failure in pediatric heart transplant recipients (PHT) is associated with myocardial fibrosis on explanted specimens. Cardiac magnetic resonance imaging (CMR) is a validated, non-invasive method to detect myocardial fibrosis via the presence of late-gadolinium enhancement (LGE). In adult heart transplant recipients, LGE is associated with increased risk of hospitalization and death. We describe LGE on CMR among PHT and its associations with clinical and graft characteristics.

Methods:
We performed a retrospective chart review of all PHT who underwent CMR over a 6-year period at a single center (81 CMR studies, 59 unique patients). Two independent reviewers assessed the presence and distribution of LGE using the AHA 17-segment model. Clinical history and CMR-derived volumetry/ejection fraction were obtained; differences between LGE+ and LGE- PHT were evaluated.

Results:
Mean age at CMR was 14.8±4.6y; mean time since transplant was 7.3±5.0y. CMR indication was routine surveillance (without active rejection or history of cardiac allograft vasculopathy) in 63% (51/81) of studies. LGE was present in 36% (29/81). LGE patterns included: posterior hinge-point 27% (22/81), lateral wall 15% (12/81), and extensive, involving >4 AHA segments, 7% (6/81) (Figure). Reviewing initial CMR per PHT (n=59), LGE+ patients were older (17 vs. 13y; p=0.001), with greater time since transplant (8.3 vs. 5.7y; p= 0.041). They demonstrated increased indexed LV end-systolic volume (35 vs. 29 ml/m2; p=0.011) and decreased LV ejection fraction (56.2 vs 60.6%; p=0.015). There were no significant differences in history of moderate/severe rejection or cardiac allograft vasculopathy.

Conclusions:
LV LGE was seen in about a third of PHT patients, more commonly in older patients with longer time since transplantation. Grafts with LGE show remodeling with lower LV ejection fraction. CMR-derived LGE may improve surveillance of chronic graft failure in PHT.
Abstract 13201: Sex Difference Following Cardiac-Targeted Irradiation in Mice
Authors: Dierdorff Jason M , Mehdi Haider , Elmonzer Mohamed , Greiner Alexander , Kutschke William J , Yoon Jin-young , Prathivadhi-Bhayankaram Sruti , Morgan Gina M , Wipf Peter , Epperly Michael W , Greenberger Joel S , London Barry
Published: June 2023

Introduction:
Acute exposure of the heart to ionizing radiation (IR) can damage myocardium, coronary arteries, valves, and pericardium. Long term sequelae include fibrosis, heart failure, arrhythmias and sudden death. We previously reported a protective effect of the oxetanyl sulfoxide radiation mitigator MMS350 in mice treated acutely with 20 Gy total body IR. Here, we assess the long-term effects of cardiac targeted irradiation (CTI) and MMS350 treatment on cardiac structure and function.

Methods:
Ten week-old C57BL/6J mice (50% male) were exposed to 20 Gy CTI with (+R+D, n=20) or without (+R-D, n=20) MMS350 using an Xstrahl Small Animal Radiation Research Platform and followed for 9 months (mo); a parallel cohort was not irradiated (-R+D, n=10; -R-D, n=10). MMS350 was given in drinking water (0.087 mg/ml) for 10 days before to 9 mo after CTI with one IV injection (20 mg/kg) 30 minutes prior to CTI. Echocardiography (echo) was performed at baseline, 3, 6 and 9 mo. At euthanasia, heart weight (HW), lung weight (LW), body weight (BW) and histology were assessed.

Results:
CTI led to radiation dermatitis in 3 female mice requiring euthanasia. MMS350 treatment had no significant effect on any parameters. 9 mo after CTI, HW/BW was increased in male but not female mice, while LW/BW was increased in both sexes (Fig 1A-D). Echo showed a significant increase in EDV with CTI in male (p=0.006) but not female mice (Fig 1E-F), along with a trend towards a decrease in EF in male (79±3 vs 86±2%, p=0.11) but not female mice (85±1 vs 86±1%, p=0.59). Trichrome staining demonstrated fibrosis in both male and female hearts (Fig 1G-N).

Conclusions:
High dose CTI led to cardiac hypertrophy and ventricular dilation after 9 mo in male but not female mice. Both sexes developed cardiac fibrosis and lung congestion. Thus, sex may influence radiation-induced cardiac pathology through currently unknown mechanisms and may have important implications for radiotherapy of thoracic tumors in humans.
Abstract 13223: Calcium/Calmodulin-Dependent Protein Kinase II Decreases KCNH2-Related Current During Sustained Adrenergic Receptor Stimulation
Authors: Amarh Enoch , Assiri Abdullah A , Sahoo Firoj K , Hudmon Andy , Tisdale James E , Skaar Todd C , Overholser Brian R
Published: June 2023

Introduction:
KCNH2
codes for a potassium channel that mediates the primary cardiac repolarizing current, I
Kr
. Calcium/calmodulin-dependent protein kinase II (CaMKII) modulates several ion channels, is enhanced during sustained β-adrenergic receptor (βAR) stimulation, and is proarrhythmic. Furthermore, states of enhanced βAR stimulation/CaMKII activity, such as heart failure, alter microRNA (miR) expression profiles that suppress protein expression.

Hypothesis:
CaMKII decreases KCNH2-related current during sustained βAR stimulation through miR regulation.

Methods:
Putative miR binding sites (n=327) on KCNH2 3′-UTR were identified with bioinformatic tools. Binding sites were then constructed into a pIS0 plasmid, amplified, and transfected into hiPSC-cardiomyocytes. Cells were subjected to sustained βAR stimulation (Isoproterenol: 100 nM, 1 μM), constitutively active δCaMKII (Thr287Asp), or control conditions. Next-generation sequencing was used to identify altered miR binding sites expression and endogenous miR alterations. Whole-cell, voltage-clamp experiments were performed in HEK293 cells expressing KCNH2 and δCaMKII
T287D
. Cells were treated with isoproterenol, and miR mimics were used for validation of the bioassay.

Results:
Nine and eight predicted miR binding sites were downregulated in the CaMKII group (Δlog fold: -0.287 to -0.59, p<0.05) and sustained βAR group (Δlog fold: -0.29 to -0.72, p<0.05), respectively. Thirty miRs were predicted to bind to these sites on KCNH2 3′-UTR, of which seven were selected for validation based on a Δlog fold < -0.6 in one group (n=4) or < -0.5 in both treatment groups (n=3). Mimics of all seven miRs reduced KCNH2 protein expression, and three decreased KCNH2 currents compared to control (p<0.05). Sustained βAR stimulation decreased peak activation current in cells expressing both KCNH2 and δCaMKII
T287D
by 25% (17±7 pA/pF, p = 0.03) and tail current density by 27% (21±9 pA/pF, p = 0.03), but had no effect on currents in cells expressing only KCNH2.

Conclusions:
CaMKII hyperactivity alters miR expression profiles and decreases KCNH2 function during sustained βAR activation. The effect of the identified miRs on arrhythmia susceptibility with enhanced CaMKII activity warrants further study.
Abstract 13228: Cannabis Inhalation Reduces Muscle Sympathetic Nerve Activity in Humans
Authors: Cheung Christian P , Nardone Massimo , Lee Jordan B , Baker Ryleigh E , Millar Philip J , Burr Jamie F
Published: June 2023

Introduction:
Despite widespread use, the neuro-cardiovascular responses associated with cannabis use remain incompletely understood. Acute increases in heart rate, which are abolished under beta-adrenoreceptor blockade, suggest cannabis increases cardiac sympathetic activity; however, its effects on peripheral sympathetic outflow have not been measured. The objective of this work was to quantify direct recordings of efferent post-ganglionic muscle sympathetic nerve activity (MSNA) following cannabis inhalation.

Hypothesis:
MSNA would be increased following cannabis inhalation.

Methods:
Blood pressure (BP), heart rate, and MSNA measured from the fibular nerve, were recorded in seventeen young, healthy participants (22±3y: 8F) for a 10-minute epoch before and after inhalation of aerosolized dry cannabis flower (100mg, 13.6% THC). Cardiac output was estimated from finger photoplethysmography (Modelflow method). Arterial baroreflex control of MSNA was quantified using the slope of the weighted linear regression between diastolic BP and MSNA.

Results:
Mean BP (79±7 vs. 84±8mmHg), heart rate (61±7 vs. 81±14bpm), cardiac output (4.8±1.1 vs. 6.8±2.5L/min), and total vascular conductance (50±11 vs. 71±26mL/min/mmHg) were increased, while MSNA burst frequency (17±7 vs. 8±6bursts/min), incidence (29±11 vs. 11±9bursts/100hb), and amplitude (38.6±6.4% vs. 23.8±8.3%), and sympathetic baroreflex sensitivity (-3.9±1.8 vs. -1.5±1.5bursts/100hb/mmHg) were decreased following cannabis inhalation (all
P
<0.01). The rise in cardiac output was negatively associated with the reduction in MSNA burst frequency (r
2
=0.40;
P
<0.01).

Conclusions:
These data demonstrate that MSNA is reduced following acute cannabis inhalation in humans and is mediated, in part, through a baroreflex mechanism.
Abstract 13251: A Meta-Analysis of Effects of Acetaminophen on Blood Pressure and Heart Rate
Authors: Zaalouk Mostafa R , Eid Mohamed , Ismayl Mahmoud , Al-Abdouh Ahmad , Motawea Karam , AbdelQadir Yossef H , Mohamed Sarah , Mannumbeth renjithlal Sarath lal , Mamas Mamas
Published: June 2023

Introduction:
Acetaminophen-induced hypotension has been reported previously. It is uncertain whether acetaminophen directly impacts blood pressure and heart rate.

Hypothesis:
The meta-analysis investigates the effects of acetaminophen on the blood pressure and heart rate, and whether there is a dose-response relationship.

Methods:
This meta-analysis was conducted according to PRISMA guidelines. A search strategy was designed to utilize PubMed/Medline, EMBASE, and Google scholar for studies showing the effects of acetaminophen on blood pressure and heart rate from inception to February 20, 2022. After screening, 14 clinical trials were included in the analysis. Dichotomous data were pooled as relative risk (RR) and continuous data as mean difference (MD) or standardized mean difference (SMD) using the inverse-variance method. Heterogeneity was assessed using the Cochrane Q test, and its extent was determined by I-square (A value of more than 50% was considered a significant heterogeneity).

Results:
No statistically significant difference between acetaminophen and control for the overall effect on SBP (MD= -1.52, 95% CI = -4.66 to 1.61, p-value = 0.34) was observed. The findings remained consistent in subgroup analysis by dose, across one gram or less (p-value = 0.54), and more than one gram (p-value = 0.43). Similarly, no statistically significant difference was found for the overall effect on DBP (p-value = 0.61) although we found a statistically significant difference in DBP in the one gram or less subgroup (p-value = 0.02). Finally, we report no statistically significant difference between acetaminophen and control on the MAP (p-value = 0.32) and HR (p-value = 0.18).

Conclusions:
Acetaminophen has no significant effect on SBP, DBP, MAP, and HR. This effect is consistent with different doses except for a possible increase in DBP after using one gram or less. Further studies are needed to investigate the relevance of this effect.
Abstract 13268: Associations Between Plant-Based Dietary Patterns and Risks of Type 2 Diabetes, Cardiovascular Disease, Cancer, and Mortality - A Systematic Review and Meta-Analysis
Authors: Wang Yeli , Hu Yang , Zhu Lu , Sun Qi
Published: June 2023

Introduction: Plant-based dietary patterns
that emphasize foods derived from plant sources and limit consumption of animal products have the potential to prevent and manage major chronic diseases. We aim to assess the existing prospective observational evidence on associations between adherence to plant-based dietary patterns and risk of developing type 2 diabetes (T2D), cardiovascular disease (CVD), cancer, and mortality.

Methods: A s
ystematic review and meta-analysis on prospective observational studies of plant-based dietary patterns and outcomes of T2D, CVD, cancer, and mortality was conducted. We searched PubMed and MEDLINE, Embase, and Web of Science, and screened references.

Results:
A total of 67 studies were identified, including 3,826,137 participants with 40,885 cases of incident T2D, 145,187 CVD cases, 25,510 cancer cases, and 75,412 deaths. An inverse association was observed between higher adherence to a plant-based dietary pattern and lower risks of T2D (RR, 0.80 [95% CI: 0.74-0.85]), CVD (0.89 [0.84-0.94]), and all-cause mortality (0.85 [0.76-0.95]) with a modest heterogeneity across studies (
I
2
ranged: 62.8%-96.2%), whereas a non-significant inverse association was observed for cancer risk (0.94 [0.87-1.01];
I
2
=49.2%). The inverse association with cancer was strengthened and became significant when healthy plant-based foods, such as vegetables, fruits, whole grains, and legumes, were included in the definition of plant-based dietary patterns (0.90 [95% CI: 0.81-0.99;
I
2
=41.0%]). Among seven studies with measurements of changes in dietary patterns, increased adherence to a plant-based dietary pattern was significantly associated with lower risks of T2D (0.82 [0.71-0.95];
I
2
=72.2%) and mortality (0.95 [0.91-1.00];
I
2
=0%).

Conclusions:
Higher adherence to a plant-based dietary patterns, especially from healthy resources, may be beneficial for the primary prevention of T2D, CVD, cancer, and mortality.
Abstract 13270: Seasonal Variation in In-Hospital Outcomes of Takotsubo-Syndrome-Related Admissions: A National Inpatient Analysis, 2019
Authors: Desai Rupak , Edusa Samuel , Naseem Rabia , Sharma Aditya , Desai Aakash , Patel Yash , Singh Ibadat Anmol , Kang Gurmannat SIngh , Reddy Shilpa , Duggirala Sonal Devi , STANIKZAI SAMIR , Jain Akhil
Published: June 2023

Background:
Contemporary literature lacks data on the impact of climatic variations on the etiopathogenesis and outcomes of Takotsubo Syndrome (TTS)-related hospitalization in the U.S.

Methods:
Seasonal variation was identified based on meteorological classification of the northern hemisphere Spring, Summer, Fall and Winter using data from the National Inpatient Sample (2019) and odds of outcomes were assessed using multivariable regression models.

Results:
The TTS cohort (n=41830) in 2019 was mostly caucasian (80.6%), female (82.1%), and median age ≥65yrs (61.9%). Fall (25.9%) admissions were the highest, followed by summer (25%), spring (24.6%) and winter (24.5%). Despite a similar median length of stay (4-days; p<0.001), winter hospitalization expenditures (USD56763) were the highest and fall lowest (USD51649). Winter admissions had greater all-cause mortality (7.3%vs.6.7%) and dysrhythmias (29.8%vs.28.5%), including Atrial fibrillation (AF) (20.7%vs. 19.7%). Admissions in spring had a higher cardiac arrest (4.8%vs.4.1%) and Acute Venous Thromboembolism (VTE) (4.7%vs.3.5%) compared to overall TTS-related admissions. When adjusted for confounders, a higher risk of dysrhythmias was noted for [winter (OR:1.20; 95%CI:1.03-1.39), Spring (OR:1.15;95%CI:1.00-1.33) and Fall (OR:1.18;95%CI:1.03-1.36) vs. summer; p=0.063]. A higher risk was also noted for AF in winter (OR:1.22;95%CI:1.02-1.45), Spring (OR:1.20;95%CI:1.02-1.42) and Fall (OR:1.28;95%CI:1.08-1.51) when compared to summer; p=0.028]. Spring admissions had a greater risk of VTE than summer admissions [(OR:1.54;95%CI:1.09-2.16) vs. summer; p=0.067]. Other outcomes, such as all-cause mortality and cardiogenic shock, had an association after controlling for confounding variables.

Conclusions:
Compared to Summer, Winter hospitalizations increased the risk of dysrhythmia and AF, while Spring admissions revealed a higher risk of VTE.
Abstract 13289: Risk of QT Interval Prolongation Associated With Dofetilide and Sotalol in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Huang Chien-Yu , Overholser Brian R , Sowinski Kevin M , Jaynes Heather A , KOVACS Richard , Tisdale James E
Published: June 2023

Introduction:
Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced QT interval prolongation. It is unknown if HF with preserved ejection fraction (HFpEF) also increases the risk. Dofetilide (D) and sotalol (S) are potent QT interval-prolonging agents that are commonly used in patients with HFpEF, in whom atrial fibrillation is a common comorbidity.

Hypothesis:
The risk of QTc prolongation associated with D or S (D/S) is increased in patients with HFpEF.

Methods:
The data source was electronic health records from the Indiana Network for Patient Care (February 2010 to May 2021). After removing patients with overlapping diagnoses of HFpEF and HFrEF, no diagnosis code, absence of QT interval records, and no validated record of using D/S, we identified patients taking D/S among three groups: HFrEF (n=138), HFpEF (n=109), and no HF (n=729). Cochran-Mantel-Haenszel statistics were used to compare baseline characteristics. QT interval prolongation was defined as heart rate-corrected QT (QTc) > 500 ms during D/S therapy. Unadjusted odds ratios (OR) of QT interval prolongation were determined by univariate analysis, and adjusted ORs were determined by generalized estimating equations (GEE) with logit link to account for an individual cluster with different times of hospitalization and covariates.

Results:
QTc prolongation associated with D/S occurred in 51.2% of patients with HFpEF, 70.1% of patients with HFrEF, and 29.4% of patients with no HF. After adjusting for age, sex, race, serum potassium and magnesium concentrations, kidney function, concomitant drug therapy, and comorbid conditions, the adjusted odds of QTc prolongation were significantly higher in patients with HFpEF, as well as in those with HFrEF, compared to those with no evidence of HF (Table).

Conclusions:
The odds of QT interval prolongation among inpatients receiving D/S were increased in patients with HFpEF and HFrEF compared to those who did not have HF.
Abstract 13300: Cardiac Structural and Functional Characteristics Are Associated With Left Atrial Appendage Thrombus Formation in Non-Valvular Atrial Fibrillation
Authors: Castellani Carson , Kim Hyun , Thompson Colton , Ning John , Lu Kaiwei , Lohr Nicole L , Tyagi Sudhi , Welsh Aimee C , Berger Marcie
Published: June 2023

Introduction:
Non-valvular atrial fibrillation (NVAF) is a highly prevalent arrhythmia where loss of synchronized atrial contraction increases the risk of intracardiac thrombus particularly within the left atrial appendage (LAA). Anticoagulation is the mainstay of stroke prevention based on the CHA2DS2-VASc score that does not account for LAA structural characteristics.

Methods:
The research comprises a retrospective case-control study of 196 subjects with NVAF who underwent TEE. The control group, without thrombus (n=117), was selected from two different groups, both pools had: NVAF and CHA2DS2-VASc score ≥ 3. One group underwent screening TEE prior to Watchman closure device placement from January 2015 to December 2019 (n=74) the second underwent TEE for any indication from February to October 2014 (n=43). The study group, with thrombus (n=79), included patients with NVAF, a TEE study performed between February 2014 and December 2020, and LAA thrombus. LAA ostial areas (calculated from orthogonal measurements 0, 90° or 45, 135°), maximal depth, and peak outflow velocity were measured, and the rhythm during TEE was interpreted. The control and study groups were compared using Student’s or Welch’s t-test based on variance ratios.

Results:
Patient characteristics and TEE data were collected (Table 1). Patients in the control group compared to the study group had significantly greater LV EF, LAA exit velocities, LAA ostial areas, and maximal LAA depth, and were more likely to be in sinus rhythm at the time of TEE. There were no significant differences between the groups in overall CHA2DS2-VASc scores.

Conclusion:
Cardiac structural and functional characteristics are associated with left atrial appendage thrombus among patients with NVAF.
Abstract 13309: Specific Deletion of Microrna1’S Biophysical Action Causes a Functional Deterioration of the Heart and Increases the Vulnerability to Arrhythmias
Authors: Tang Feng , Wan Xiaoping , Yang Dandan , Kacira Ege , xu Xianyao , Schwieterman Neill , Ponce Daniela , Wold Loren E , Hund Thomas , Mohler Peter J , Deschenes Isabelle , Fu Jidong A
Published: June 2023

MicroRNAs (miRs) are involved in most biological events via a broadly-recognized RNA interference (RNAi) mechanism. miR1, encoded by miR1-1 and miR1-2 genes, is the predominant miRs of the heart and plays a critical role in heart development and cardiac diseases. Previous studies of miRs have focused on the canonical RNAi mechanism. Recently, we discovered a novel biophysical action of miR and found that miR1 physically binds to Kir2.1 and directly suppresses the inward rectifier potassium current (I
K1
). However, the physiological significance of this newly-discovered biophysical action of miR remains unknown. Importantly, we found that a human single nucleotide polymorphism (hSNP)-hSNP14A/G (rs776480338), in which the 14th nucleotide of miR1 is mutated from A to G, specifically disrupts this biophysical action while maintaining its RNAi function. We then created a single nucleotide mutation of hSNP14A/G on mouse miR1-1 and miR1-2 genes by CRISPR/Cas9 technology and have successfully developed 14G-mutated homozygous transgenic mice (14G-Homo), in which the biophysical function of miR1 is specifically removed while the RNAi function is maintained. We found that 14G-Homo mice had higher mortality than wild-type (WT) mice. Echocardiogram showed that, compared to WT hearts, adult 14G-homo heart (2-month age) had significantly lower ejection fraction and fractional shortening with a thinner wall of the left ventricle, which became more severe at the age of 6 months; some mice developed severe heart failure. Surface ECG showed that 14G-Homo hearts had a slower heart rate and the prolonged QRS interval and QT interval. Optical mapping revealed a slower conduction velocity in the 14G-Homo heart with high inducibility of ventricular arrhythmias. Patch clamping of isolated ventricular cardiomyocytes showed that, compared to WT cells, 14G-homo cardiomyocytes had an increased amplitude and prolonged duration of action potential with bigger I
K1
and L-type calcium currents. In conclusion, our discoveries demonstrate that the biophysical action of miR1 is deeply involved in maintaining the homeostasis of the heart. Specific deletion of the biophysical function causes a functional deterioration of the heart and increases the vulnerability to arrhythmias.
Abstract 13315: Differences in Infarct Size and No-Reflow by Sex in Young Adult Rats in an Electronic Cigarette Exposure Study
Authors: Dai Wangde , Shi Jianru , Zhao Lifu , Carreno Juan , Kleinman Michael T , Herman David , Arechavala Rebecca J , Renusch Samantha , Hasen Irene , Ting Amanda , Kloner Robert A
Published: June 2023

Purpose:
We investigated the effects of chronic exposure to electronic cigarettes (e-cig) on myocardial infarct size and the size of the no-reflow zone in a rat model of both sexes.

Methods and Results:
Sprague Dawley rats (6 weeks old) were randomized to 4 exposure groups: (1) Purified air (n=16 male/16 female); (2) e-cig vapor with 15mg/mL nicotine (n=13 male/15 female); (3) e-cig vapor without nicotine (n=16 male/12 female); and (4) Standard nicotine-containing combustion cigarette smoke (n=16 male/16 female). All rats were exposed to inhalation exposure for 8 weeks, prior to being subjected to 30 minutes of left coronary artery occlusion followed by 3 hours of reperfusion. Two-way analysis of variance (that factors sex and treatment) demonstrated that chronic exposure to e-cig vapor (with or without nicotine) or to standard cigarettes did not alter myocardial infarct or no-reflow size compared to air. However, as shown in the figure, infarct size was significantly smaller (40.7 ± 2.7% vs 54.5 ± 2.6%; p=0.0004) and no-reflow size was smaller (18.1 ± 2.0% vs 26.8 ± 2.2%; p=0.0042) in female rats compared to male rats.

Conclusions:
Long-term e-cig exposure did not affect the cardiac sensitivity to ischemia/reperfusion injury in young rats. Female rats are more tolerance to ischemia/reperfusion injury than males. This sex difference phenomena was not observed in our previous study [Li et al. J Thromb Thrombolysis. 1995;2(3):221-225.] that examined the tolerance between males and females subjected to 90 mins of left coronary artery occlusion followed by 4 hours of reperfusion in 1-year-old SD rats and found the myocardial infarct size to be similar between the sexes. The different findings between the 2 studies may be due to the age difference (which implies possible hormonal effects in the younger rats) or different coronary artery occlusion and reperfusion times.
Abstract 13323: A Survey Study of the Adherence to the 2020 Acc/aha Heart Failure Guideline in Low-Middle Income Countries (Gaza Strip as an Example)
Authors: Alsaiqali Mahmoud , Al-Saikaly Ghassan , AboAbdo Mohammad , Mezeid Mohammed , Mansour Zakaria , Al Zaharna Alaa , Al-Sadawi Mohammed , Habib Mohammed , Mhanna Mohammed
Published: June 2023

Introduction:
Acute heart failure is associated with higher post-discharge mortality, especially in low-middle income countries (LMIC). There are limited studies on adherence to the recommended post-discharge care guidelines in these settings. The study assessed adherence to the 2020 ACC/AHA inpatient heart failure performance and quality measure in Gaza Strip, Palestine.

Methods:
The study was a cross-sectional survey study. We chose a stratified random sample from the three different geographical areas across Gaza Strip with numbers proportional to the size of each region. Patients selected were adults (>18 years) admitted to the various hospitals for acute decompensated heart failure between 4/2021 and 12/2021. We collected data through chart review. Measures were β blockers, ACEi/ARB and MRA prescription, and outpatient follow-up. Results reported as proportion with 95% CI.

Results:
The sample size was 155 patients. The mean age was 64 years. 59% were males. The mean length of stay was 2.8 days. β blockers were prescribed to 85.1% [79.5,90.8] of patients. For ACEi/ARB use, it was 42.7% [34.9,50.5]. For MRA, after excluding ineligible patients, it was prescribed in 48.5% [39.9, 57.2]. None of the patients were prescribed hydralazine/nitrate. Only 30.1% [ 23.6, 38.1] of patients had an outpatient appointment. The median time between discharge and appointment date was 22 days. Only 9.7% [5.0,14.3] of patients were discharged with all quality measures fulfilled.

Conclusions:
There are considerable gaps in the post-discharge care of heart failure patients in the Gaza Strip. There is a need to develop local care guidelines to improve care.
Abstract 13338: Clinical Profile of Patients Hospitalized for Heart Failure With Severely Reduced Ejection Fraction: From the GWTG-HF Registry
Authors: Harrington Josephine , sun jie-lena , Felker Michael , Binder Gary , Kociol Robb , Divanji Punag , Allen Larry A , Alhanti Brooke , Yancy Clyde W , Albert Nancy M , Fonarow Gregg C , Devore Adam D , Greene Stephen J
Published: June 2023

Introduction:
Many patients with heart failure (HF) have severely reduced ejection fraction but do not meet threshold for consideration of advanced therapies (i.e., stage D HF). The clinical profile, outcomes, and management of these patients in US practice is not well described.

Methods:
We studied patients hospitalized for worsening chronic HF with reduced ejection fraction (HFrEF) ≤40% across 423 sites in the Get With The Guidelines® (GWTG)-HF registry admitted 2014 -2019. We excluded patients with heart transplantation or durable mechanical circulatory support, severe kidney disease (eGFR<20 mL/min/1.73 m
2
or dialysis), or missing critical data elements. Patients were grouped by EF (≤30% vs. 31-40%) and data were compared using absolute standardized differences.

Results:
Among 113,348 patients with HFrEF ≤40%, 78,589 (69%) had an EF≤30%. Compared with EF 31-40%, patients with EF≤30% tended to be younger, were less likely to be female, and more likely to be Black
(Table).
Patients with EF ≤30% had lower systolic blood pressure, but modestly higher eGFR and lower rates of atrial fibrillation and diabetes. Rates of guideline-directed medical therapy (GDMT) use at discharge were generally higher among those with EF≤30%, including greater use of triple therapy (ACEI/ARB/ARNI + beta-blocker + MRA). Among 20,387 patients age ≥65 years linked to Medicare, compared with patients with EF 31-40%, patients with EF≤30% faced higher rates of 12-month mortality and HF hospitalization, but similar rates of all-cause hospitalization.

Conclusions:
Among patients hospitalized for worsening chronic HFrEF in US clinical practice, most patients have severely reduced EF≤30%. Despite modestly higher use of GDMT at discharge and younger age, patients with severely reduced EF face heightened post-discharge risk of death and HF hospitalization.