bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11721: Frailty Assessed by a Composite Assessment of Cognitive and Physical Frailty Predicts Long-Term Outcomes in Elderly Pre-Clinical Heart Failure Patients
Authors: Meng Chen , Wang Hua
Published: June 2023

Introduction:
We combined the Fried phenotype and the mini-mental state examination (MMSE) +clock drawing test (CDT) to assess frailty in elderly pre-clinical heart failure (HF) patients, and aimed to evaluated the prevalence and prognostic value of frailty assessed by this simple composite scoring system in this population.

Methods:
we conducted a single-center prospective observational cohort study in which enrolled inpatients≥ 65 years and followed up for 2 years. The primary outcomes were 2-year all-cause mortality or readmission. Multivariate Cox proportional hazard model was used to test the predictive validity.

Results:
Overall, 531 elderly pre-clinical HF inpatients were included in our study (mean age: 75.4±6.47 years, male: 230 [43.3%]). Among them, 11.7% (62/531) were assessed as cognitive impairment without physical frailty, 15.1% (80/531) were assessed as physical frailty without cognitive dysfunction and 13.0% (69/531) were assessed as cognitive frailty with physical frailty and cognitive impairment. The cognitive frailty individuals were older (P<0.05), had shorter time of education (P<0.001), higher level of N-terminal pro-B-type natriuretic peptide (P<0.05), and were more likely to have comorbidities of peripheral arterial disease and the history of stroke (P<0.05) and take ≥5 medications (P<0.05). Physical frailty patients (P=0.019) and cognitive frailty patients (P=0.003) both had a higher incidence of mortality or readmission during 2-year follow-up and had a 1.50-fold (95%CI 1.04-2.18, P=0.03) and 1.84-fold (95%CI 1.19-2.83, P=0.01) higher risk of 2-year adverse events, respectively, after adjusting age, sex, marital status,education years,diabetes and the history of stroke.

Conclusions:
In conclusion, cognitive frailty is common in elderly pre-clinical HF patients. Adding cognitive impairment to physical frailty could predict all-cause mortality or readmission better in this population in the long term.
Abstract 11851: Acetate Rescues the Gut Microbial Metabolites PAA/PAG-induced Vascular Senescence by Epigenetic and SASP Regulation
Authors: Saeedi Soheil , Thomas Aurélien , LeGludic Sylvain , Gergely Karsai , Lettlova Sandra , Osto Elena , Allemann Meret , Lee Pratintip , Beer Juerg H
Published: June 2023

Introduction:
Age-related gut microbiota alteration may underpin vascular disease. Yet, little is known about the role of cardiovascular disease-linked gut microbial metabolite phenylacetyl glutamine (PAG) in vascular aging.

Hypothesis:
1)

PAG promotes endothelial senescence via epigenetic and SASP modulation;

2)

Acetate rescues PAG-induced endothelial senescence and impaired angiogenesis.

Methods:
We quantitated plasma concentrations of PAG and its precursor phenylacetic acid (PAA) in old and young healthy humans (>65
vs.
18-35 years, n=41-45) and mice (24
vs.
3 months, n=6) by LC-MS/MS. Fecal acetate was measured by HPLC-RI. We then treated proliferating human aortic endothelial cells (PEC) with PAA+Glutamine (for PAG production) to examine its effects on cellular senescence, epigenetic and SASP state, mitochondrial respiration, and angiogenesis.

Results:
We showed markedly higher plasma PAA and PAG concentrations in old humans and mice
vs.
young ones. Yet, fecal acetate level was significantly lower in old
vs.
young mice. PAG significantly induced senescence (increased SA-β-gal positive cells and transcripts p16, p19, p21) and mitochondrial ROS production in PEC associated with upregulated SASP (IL1α, IL1β, TNF-α and adhesion molecule VCAM-1), and reduced mitochondrial respiration. PAG markedly reduced angiogenesis (endothelial sprouting and tube formation) accompanied by decreases in CaMKKβ
T286
and histone deacetylase 4 (HDAC4
S632
) phosphorylation, histone 3 (H3) acetylation, and the subsequent Mef2A-mediated eNOS
S1177
phosphorylation. By contrast, acetate (3 μM) rescued senescence and impaired angiogenesis and mitochondrial function and reversed SASP and epigenetic alteration induced by PAG in PEC.

Conclusions:
We conclude that acetate regulates the aging gut microbial metabolite PAG-induced SASP and epigenetic alteration, by which rescues endothelial senescence and represents a potential vascular regenerative strategy.
Abstract 11871: Hypoglossal Nerve Stimulation as a Treatment for Sleep Apnea Does Not Lower Blood Pressure
Authors: Hitt Nathaniel , Hoffmann Adam , Patel Sagar , HAGAU DENISA
Published: June 2023

Introduction:
Obstructive sleep apnea (OSA) effects up to 30% of men and 15% of women in North America. Untreated, OSA is associated with the development of hypertension, heart failure, coronary artery disease, cardiac arrhythmia, and stroke. Treatment reduces these risks. The American Academy of Sleep Medicine outlines the first line treatment of OSA as continuous positive airway pressure (CPAP). However, many patients are unable to tolerate CPAP. One of the newest therapies approved in 2014 is implantation of a hypoglossal nerve stimulator (HNS) which functions by stimulating the tongue protrudor muscles to reduce upper airway obstruction. However, there is minimal research investigating HNS's effects on comorbidities. Currently there are two published studies showing improved blood pressure control and heart rate variability, but each study only included 46 patients. Several factors warrant a comparison including the lack of data, procedural risks, and procedural cost; especially, when considering the proven efficacy and low cost of CPAP. We present a retrospective analysis of blood pressure after HNS implantation.

Hypothesis:
We hypothesize that HNS implantation will improve blood pressure control.

Methods:
All cases of HNS implantation at MercyOne North Iowa Mason City, Iowa were retrospectively reviewed. Each case was manually reviewed for pre- and post-surgery blood pressure, heart failure exacerbations, arrhythmia, hemoglobin A1c, stroke, and acute coronary syndrome.

Results:
Fifty-nine patients had a mean change in blood pressure of +1.76 systolic and +0.76 diastolic with a standard error of 2.10 and 1.29 respectively. The mean follow-up time was 5.7 months after the fine-tuning sleep titration study. Five patients needed one less blood pressure medication and 6 patients needed one more. Preliminary regression analysis does not support gender, age, apnea-hypopnea index, or body mass index being predictive of change in blood pressure with HNS implantation. There was no statistically significant effect on other comorbidities.

Conclusion:
This study showed no clinically significant change in blood pressure after HNS implantation. Limitations include the small sample size and only one follow-up blood pressure.
Abstract 11904: Lipoprotein(a) Integrates Monocyte-Mediated Thrombosis and Inflammation in Atherosclerotic Cardiovascular Disease
Authors: Rosenson Robert S , Tate Ashley , CHEN QINZHONG , Grushko Olga , Damodaran Dilna , Mejia Priscilla , Boffa Michael , Koschinsky Marlys L , Narula Jagat , Goonewardena Sascha N
Published: June 2023

Introduction:
Lipoprotein (a) [Lp(a)] drives atherosclerotic cardiovascular disease (ASCVD) through multiple mechanisms including cholesterol accumulation, inflammation, and thrombosis. However, the effects of Lp(a) on monocyte activation and monocyte-mediated thrombosis are unknown.

Hypothesis:
Lp(a) itself can activate monocytes, driving inflammation and thrombosis in parallel.

Methods:
We employed systems biology approaches consisting of proteomics, transcriptomics, and mass cytometry to define the immune cellular and molecular phenotypes in ASCVD subjects with high and low Lp(a) levels and leveraged cell models to define the mechanisms through which Lp(a) drives monocyte inflammation and thrombosis. We included study participants with CHD who were aged 18 to 80 years with Lp(a) concentrations
>
150 nmol/L (cases) and <75 nmol/L (controls).

Results:
Circulating markers of inflammation (CCL3, CD40) and vascular dysfunction (PAR1, tissue factor [TF]) were elevated in subjects with high Lp(a) levels compared with those with low Lp(a) levels. Additionally, although total monocytes levels and hs-CRP levels were similar between the groups, CD14+ monocytes from ASCVD subjects with an elevated Lp(a) were primed and expressed more TF at baseline and in response to stress. Mechanistically, we found that Lp(a) itself can activate monocytes through Toll-like receptors (TLR) and nuclear factor kappa B (NFκB) signaling, driving both TF expression and TF activity (Figure).

Conclusions:
Overall, these studies are the first to link Lp(a) to monocyte-mediated inflammation and thrombosis in ASCVD subjects, demonstrating a novel mechanism through TLR2, NFκB, and monocyte TF through which Lp(a) amplifies immunothrombotic risk.
Abstract 11918: Improving Quality of Care for Patients With Valvular Heart Disease in a Learning Health System
Authors: Baldridge Abigail S , Bindra Parmeen H , Cruz Shruti , Thomas James D , Narang Akhil , Ahmad Faraz S
Published: June 2023

Introduction:
Delayed treatment of valvular heart disease (VHD) is associated with higher mortality and adverse event incidence. In a large, integrated health system, we developed and piloted a digital health solution embedded in the electronic health record (EHR) to identify, triage, and streamline evaluation of patients with VHD.

Methods:
The initiative began May 2021 with agreement of our team members and stakeholders for prioritization of the project and implementation. Structured echocardiographic data were made available in electronic data warehouse. SQL-based disease classification algorithms based on published guidelines were built for aortic stenosis (AS), mitral regurgitation (MR) and tricuspid regurgitation. Echocardiograms with suspected VHD were pushed daily into a reporting dashboard and smartform we built within the EHR. Nurse coordinators responsible for VHD patient care tested the platform, and we iteratively adapted components based on feedback. Performance of AS and MR classification algorithms against historical data were evaluated using kappa statistics. We launched the program in March 2022 and report the initial results.

Results:
Between August and October 2021, 650 echocardiograms were reviewed by a nurse coordinator. Agreement between the guideline-based algorithms and chart review was moderately high (0.64 for AS and 0.86 for MR). Between March and May 2022, 7180 echocardiograms with suspected VHD were surfaced in the EHR for 6588 patients. Among 1501 patients prioritized for review based on disease severity, 341 patients were referred to the valve clinic for procedural intervention, 783 patients are under watchful waiting, and 377 patients were determined to unlikely benefit from valve interventions.

Conclusions:
By leveraging data from echocardiogram repositories, it is feasible to implement a VHD quality improvement program within a learning health system. This requires a diverse and interdisciplinary team for development, implementation, governance, and continued iteration of EHR-embedded digital health tools to improve quality of care. While we focused on VHD, our methodology and infrastructure allow for expansion and leverage into other therapeutic domains within cardiovascular disease and beyond.
Abstract 11960: Right Ventricular Diameter in Risk Stratification of Sudden Cardiac Death
Authors: Huang Hao , Cheng Sijing , Deng Yu , Liu Xi , Yu Yu , Hua Wei
Published: June 2023

Introduction:
Right ventricular (RV) abnormalities have been linked with the risk of sudden cardiac death (SCD) in general population. This study was designed to evaluate the additional value of right ventricular diameter (RVD) in predicting life-threatening ventricular tachycardia (VT)/ventricular fibrillation (VF) in patients with implantable cardioverter-defibrillators (ICD).

Hypothesis:
We hypothesized that higher value of RVD would be an easily accessible predictor in decision-making of ICD implantation.

Methods and Results:
We enrolled 954 chronic heart failure patients, with quantitative measurements of echocardiograms obtained before ICD implantation, and then divided them according to the median level of RVD. Fine-Gray subdistribution and Cox proportional hazard regression analyses were performed to estimate the predictive value of RVD in sustained VT/VF vs. non-arrhythmic mortality (defined as death without prior sustained VT/VF), respectively. Patients with higher median level of RVD had a significantly higher incidence of VT/VF (32.9% versus 26.7%; P=0.041) over the median follow-up of 2.83 years (interquartile range: 1.33-5.27 years). After adjustment for multiple clinically relevant variables, high RVD levels were significantly associated with an increased risk of VT/VF (per 1 SD increase, hazard ratio=1.16; 95% CI, 1.05-1.27; P=0.003), but not non-arrhythmic mortality (per 1 SD increase, hazard ratio=0.97; 95% CI, 0.82-1.14; P=0.680). When adding RVD to the Seattle Proportional Risk Model (SPRM) and the MADIT-ICD VT/VF risk score, the combined models yielded significant improvement in discrimination for VT/VF. Elevated RVD also contributed to residual risk beyond left ventricular parameters including left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF). The restricted mean survival time measure indicated that life gained with ICD implantation in RVD higher group were 11.0, 28.4 and 29.1 days more than their lower counterparts in one, two, and three years’ time.

Conclusions:
RVD is associated with a significantly increased risk of sustained VT/VF in chronic heart failure patients, and provides greater prognostic power when combined with current risk assessment tools.
Abstract 11977: Dapagliflozin Downregulates Adrenal G Protein-Coupled Receptor-Kinase-2 to Exert Sympatholysis in Heart Failure
Authors: Lymperopoulos Anastasios , Maning Jennifer , Cora Natalie , Pollard Celina M , Desimine Victoria L , Iacobellis Gianluca
Published: June 2023

Introduction:
Dapagliﬂozin is a sodium-glucose co-transporter (SGLT)-2 inhibitor exerting several cardiorenal protective effects independently of blood glucose regulation. Adrenal G protein-coupled receptor kinase (GRK)-2 upregulation is a major driver of circulating catecholamine (CA) elevation and sympathetic nervous system (SNS) hyperactivity, especially in heart failure (HF). GRK2 severely dysregulates adrenal sympatho-inhibitory α
2
-adrenergic receptors (ARs), leading to unchecked, chronically elevated CA secretion.

Hypothesis:
SGLT2 inhibition with dapagliﬂozin lowers SNS hyperactivity in part by opposing adrenal GRK2 actions.

Methods:
We used the rat pheochromocytoma PC12 cell line expressing human α
2A
AR, as well as freshly isolated adrenal glands from rats treated with dapagliﬂozin in vivo.

Results:
Dapagliﬂozin treatment for 7 consecutive days (20 mg/kg/d in drinking water) led to a signiﬁcant reduction in blood circulating NE levels (217+67 pg/ml, n=6), compared to control, vehicle-treated rats (363+77 pg/ml, n=6, p<.05), suggesting reduced SNS activity. This was accompanied by reduced GRK2 and tyrosine hydroxylase (TH) mRNA and protein levels in dapagliﬂozin-treated rat adrenals vs. vehicle-treated animal-derived glands, indicating reduced adrenal CA synthesis and secretion. Finally, adrenal α
2
AR density was higher in dapagliﬂozin- vs. vehicle-treated rats(51.3+7.3 vs. 26.1+8.1 fmol/mg of protein, respectively; n=12 glands from 6 animals per group, p<.05). GRK2 and TH downregulation were also observed in PC12 cells treated with 5 μM dapagliﬂozin for 24 hours. Importantly, α
2
AR-dependent inhibition of CA secretion was markedly enhanced 24 hrs post-dapagliﬂozin application. This was due to reduced GRK2-dependent receptor desensitization induced by dapagliflozin, since this effect was abolished in PC12 cells overexpressing GRK2.

Conclusions:
Dapagliﬂozin exerts a sympatholytic action in the adrenal medulla via downregulation of both TH, thus reducing CA biosynthesis, and GRK2, thus reducing α
2
AR desensitization to lower CA secretion. This adrenal-mediated sympatholysis may be part of the increasingly apparent cardiovascular benefits of SGLT2 inhibitors in human HF irrespective of diabetic status.
Abstract 12006: Lipoprotein(a), Coronary Atherosclerotic Plaque, and High-Risk Plaque in Asymptomatic Individuals: The Miami Heart Study at Baptist Health South Florida
Authors: Mszar Reed , Cainzos Achirica Miguel , Valero Elizondo Javier , Quispe Renato , Ali Shozab S , Arias Lara , Saxena Anshul , Cury Ricardo C , Budoff Matthew , Feldman Theodore , Lahan Shubham , Blaha Michael J , Shapiro Michael D , Sharma Garima , Santos Raul D , Fialkow Jonathan , Nasir Khurram
Published: June 2023

Introduction:
Affecting approximately 1 in 5 adults, elevated lipoprotein(a) [Lp(a)] levels are independently associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events, however, the mechanisms driving this association are not fully understood. Therefore, we examined the association between Lp(a) and coronary plaque characteristics in a diverse U.S. cohort free of clinical ASCVD.

Methods:
We examined cross-sectional data from the Miami Heart Study, a prospective cohort study in South Florida conducted among asymptomatic adults 40-65 years of age who underwent CCTA. Those taking any lipid-lowering therapies were excluded. High Lp(a) was defined as ≥125 nmol/L. Outcomes included the following: any plaque on CCTA, coronary artery calcium score >0, maximal stenosis ≥50%, presence of any high-risk plaque feature (positive remodeling, spotty calcification, low-attenuation plaque, napkin ring), and the presence of ≥2 high-risk plaque features. Logistic regression models were adjusted for demographics and other cardiovascular risk factors.

Results:
Among 1,795 participants, 291 (16.2%) had Lp(a) ≥125 nmol/L. In unadjusted analyses, Lp(a) ≥125 nmol/L was associated with a higher prevalence of all outcomes compared with Lp(a) <125 nmol/L, however, differences were only statistically significant for any coronary plaque and the presence of ≥2 high-risk features (
Figure, Panel A
). In multivariable regression models, high Lp(a) was independently associated with the presence of any coronary plaque and ≥2 high-risk features (
Panel B
). Associations for the other outcomes trended in the same direction, however, the confidence intervals included the null.

Conclusion:
In this contemporary analysis of nearly 1,800 middle-aged asymptomatic adults undergoing CCTA, high Lp(a) was independently associated with any coronary plaque and the presence of multiple high-risk plaques.
Abstract 12062: Additional Burden of Esophageal and Gastric Varices on Hospitalized Patients With Moderate or Severe Congenital Heart Disease
Authors: Culbert Hunter , June Ciara , Meziab Omar , Caryl Natalie E , Klewer Scott E , Seckeler Michael D
Published: June 2023

Introduction:
Elevated central venous pressure (CVP) occurs in many forms of congenital heart disease (CHD) which may result in esophageal or gastric varices. We sought to describe the incidence of varices and acute outcomes for hospital admissions with moderate or severe CHD compared to those without CHD.

Methods:
Vizient Clinical Database was queried from 10/2018-12/2021 for admissions aged 1-89 years with ICD-10 codes for moderate or severe CHD with and without ICD-10 codes for esophageal (I85-I85.11) or gastric (I86.4) varices. For comparison (NO-CHD), admissions with no CHD codes with and without varices were queried. Data included demographics, hospital outcomes, principal procedure and costs.

Results:
There were 54,979 CHD admissions, 489 (0.9%) with varices and 28,282,750 NO-CHD admissions, 231,633 (0.8%) with varices (
p
= 0.069); summary in Table 1. Compared to the NO-CHD population, admission with CHD and varices were younger, had longer lengths of stay, higher complication rates and hospital costs with no difference in in-hospital mortality. Table 2 shows the top 5 principal procedures for each group.

Conclusions:
Hospitalized patients with moderate or severe CHD and varices have worse acute hospital outcomes and higher costs compared to those without CHD. These findings suggest a potential additional disease burden in this already fragile population. Future work to identify and potentially treat modifiable factors could improve care for these patients.
Abstract 12248: Decreased Left Ventricular Hemodynamic Forces As A Novel Biomarker Of Myocardial Dysfunction In Duchenne Muscular Dystrophy
Authors: Kollar Sarah E , Capuano Francesco , Udine Michelle , Soslow Jonathan , Loke Yue-Hin , Spurney Christopher
Published: June 2023

Introduction:
Patients with Duchenne muscular dystrophy (DMD) develop progressive cardiomyopathy. Cardiac magnetic resonance (CMR) imaging is used to identify global and regional function, as well as myocardial fibrosis in DMD. Unique left ventricular (LV) biomechanics cannot be assessed through conventional CMR techniques. Thus, we investigated hemodynamic force (HDF) through cine derived wall motion in the LV as a novel biomarker of myocardial dysfunction in DMD patients.

Methods:
This retrospective study consisted of CMR studies from DMD patients and age-matched controls. Feature-tracking (Qstrain, Medis) was performed on short-axis and long-axis cine imaging to capture LV wall motion. A novel technique based on diffeomorphic mapping was used to calculate three-dimensional LV kinematic models and HDF vectors throughout the cardiac cycle (Figure 1A). The apical-basal, lateral-septal, and anterior-posterior HDF vectors were correlated with global and regional functional parameters.

Results:
Eleven DMD and 11 controls were enrolled with LV EF 51 ± 6 vs 56 ± 6 (p = 0.09). DMD patients had decreased apical-basal and lateral-septal HDF across multiple points in the cardiac cycle compared to controls (Figure 1B). Six DMD patients with LV EF < 55% were compared to 5 DMD patients with normal EF, demonstrating significant decrease in apical-basal systolic root mean square (RMS) HDF (p = 0.015), lateral-septal systolic RMS HDF (p = 0.009), anterior-posterior diastolic RMS HDF (p = 0.011), and magnitude systolic RMS HDF (p = 0.011) in patients with dysfunction. Absolute magnitude RMS HDF in all axes correlated with LV global longitudinal strain, LV global circumferential strain, and LV EF (r = 0.59 to 0.81, p < 0.05).

Conclusions:
Cine derived HDF may be a more sensitive measure of LV dysfunction in DMD patients. Apical-basal HDF has potential as a novel biomarker for progression of disease.
Abstract 12254: In-Hospital Or Out-of-Hospital Cardiac Arrest is Associated With Worse Outcomes in Cardiogenic Shock
Authors: Yin Michael Yaoyao , Hernandez-Montfort Jaime , Kanwar Manreet , Kataria Rachna , Blumer Vanessa , LI BORUI , Abraham Jacob , Garan Arthur Reshad , Sinha Shashank , Zhang Yijing , Hall Shelley , Baca Paulina , Dieng Fatou , Harwani Neil , Hickey Gavin W , Wencker Detlef , Khalife Wissam , Li Song , Kim Ju H , Vorovich Esther , Burkhoff Daniel , Kapur Navin K
Published: June 2023

Background:
Patient outcomes after cardiac arrest (CA) complicated by cardiogenic shock (CS) not related to acute myocardial infarction (non-AMI) remain poorly understood. The aim of our study was to assess differences in outcomes between non-AMI CS related to in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrest (OHCA) using a real-world, multi-institutional registry.

Methods:
The CS Working Group (CSWG) registry is a retrospective dataset of patients hospitalized with CS from 17 clinical sites. A standardized set of data elements were collected between 2016 and 2021. Patients were identified as having either AMI or non-AMI related CS, and non-AMI related CS was further classified by acuity of etiology as acute-on-chronic heart failure (ACHF) and
de novo
HF. IHCA or OHCA were defined based on location of CA. The outcomes of this analysis were in-hospital mortality, renal replace therapy (RRT) and mechanical ventilation (MV).

Results:
There were 1767 patients (age 60.3 ± 14.6 years, 72.4% male) with non-AMI CS enrolled, of whom 1371 (77.6%) had ACHF and 349 (19.7%) had
de novo
HF. There were 152 (8.6%) IHCA and 103 (5.8%) OHCA. Mortality was higher for ACHF and
de novo
HF patients with IHCA compared with patients without IHCA, and was higher for ACHF patients with OHCA compared with patients without OHCA
(Figure 1A-B).
Rates of RRT were higher for ACHF and
de novo
HF patients with IHCA compared with patients without IHCA and was similar between ACHF and
de novo
HF patients with and without OHCA
(Figure 1C-D).
Rates of MV were higher for ACHF and
de novo
HF patients with IHCA or OHCA compared with ACHF and
de novo
HF patients without IHCA or OHCA
(Figures 1E-F)
.

Conclusion:
Outcomes are worse among patients with CA, irrespective of HF etiology or whether CA occurs in or out of the hospital. Further investigation is needed to better understand mechanisms contributing to these poor outcomes and to identify therapeutic targets for improvement.
Abstract 12272: Pericardial Decompression Syndrome Following Low Volume Pericardiocentesis for Malignant Cardiac Tamponade
Authors: Clarke Kregor Alexandria , Deleveaux Spencer , Fernandes Nerissa , Patel Samir , Joshi Anjali
Published: June 2023

Introduction:
Cardiac tamponade is a life-threatening condition requiring emergent intervention. Pericardial decompression syndrome (PDS) is a rare complication that presents as acute ventricular dysfunction following pericardiocentesis with a mortality rate up to 29%. In this case, we present a patient with PDS who developed cardiogenic shock following pericardiocentesis for cardiac tamponade.

Clinical course:
A 58-year-old female with no significant cardiac history presented with chest pain and dyspnea. Computed topography revealed a mediastinal mass and large pericardial effusion. Transthoracic echocardiogram (TTE) demonstrated the effusion with tamponade physiology. Left ventricular (LV) systolic function was preserved at this time. A total of 450ml of serosanguinous fluid was removed by pericardiocentesis, with minimal residual volume around the RV and a large effusion remaining around the LV. Repeat TTE 14 hours later revealed severe global hypokinesis and biventricular failure with an LV EF of 15%. The patient was started on inotropic therapy and transferred to our tertiary care center. Continuous diuresis and vasopressor therapy were initiated. Once stable, the patient was taken for pericardial window with further removal of 600ml of fluid. Subsequent TTE demonstrated recovery of LV systolic function to 47%.

Discussion:
Our patient developed cardiogenic shock secondary to biventricular heart failure following pericardiocentesis. This presentation is concerning for pericardial decompression syndrome. While the exact mechanism of PDS is not known, the current hypothesis postulates that drainage of fluid compressing the RV leads to a sudden increase in venous return. This abrupt change causes septal bowing and decreased LV systolic function. Some sources recommend draining pericardial fluid in smaller quantities; however, PDS may still occur at smaller volumes as was seen in our patient. PDS is a rare but life-threatening complication that requires vigilance post-pericardiocentesis regardless of volume removed.
Abstract 12319: Open-Heart Surgeries Leading to Unexpected Latent Disease - A Rare Case of Disseminated Mycobacterium Chimaera
Authors: Vellanki Shaitalya , Lee Maximillian , Zerbe Christa
Published: June 2023

Global reports describe several cases of disseminated
Mycobacterium chimaera
related to surgical field contamination by specific 3T heater-cooler units utilized in open cardiothoracic procedures. Eventual diagnosis leads to aggressive multidrug regimens and possible surgery, resulting in a high, yet potentially avoidable overall mortality rate. A years-long latency period between a patient’s initial exposure and clinical presentation can make this infection extremely challenging to diagnose. A 68-year-old-male with coronary artery disease (CAD) and a bicuspid aortic valve (BAV) suffered from shortness of breath and palpitations for eight years. An extensive cardiac work-up, including a cardiac MRI, revealed aortic root dilatation and significant CAD involving the left anterior descending coronary artery. The patient underwent an elective BAV repair, aortic root replacement, and single vessel coronary artery bypass surgery without any acute post-operative complications. Approximately four years later, he began experiencing fevers, night sweats, and vision changes. Eventually, he was ultimately diagnosed with disseminated
M. chimaera
confirmed by tissue biopsy. His treatment course of linezolid, moxifloxacin, ethambutol, and rifabutin, was complicated by adverse effects and complex resistance patterns. The complications he experienced secondary to this disease would eventually include long-standing bacteremia, encephalitis, splenic lesions, and aortic root abscess, which ultimately required open sternotomy for AV replacement and aortic root exchange. This patient remains the sole survivor from his home hospital among several other patients who also underwent cardiac surgeries and subsequently developed disseminated
M. chimaera.
He has since developed additional spinal involvement described as destructive osteomyelitis/discitis and confirmed via biopsy. As he continues to combat this clinically devastating bacterial pathogen, his multi-system complications with such an insidious presentation serve as a reminder to maintain a high clinical suspicion for the possibility of disseminated mycobacterial and other similar infectious processes in the differential diagnoses of all cardiothoracic surgical patients.
Abstract 12383: Large Field-of-View Intravascular Ultrasound for Peri-Procedural Assessment of Stent Frame Expansion After Transcatheter Heart Valve-in-Valve
Authors: KALINCZUK LUKASZ , Skotarczak Wiktor , Chmielak Zbigniew , Dabrowski Maciej , Wolny Rafal , Stoklosa Patrycjusz , Wozniak Olgierd , Hoffman Piotr , Michalowska Ilona , Demkow Marcin , Mintz Gary S , Sondergaard Lars , Witkowski Adam R
Published: June 2023

Introduction.
It is unknown whether large field-of-view intravascular ultrasound (IVUS) can be a valid peri-procedural imaging tool to assess actual expansion of transcatheter heart valve (THV) during valve-in-valve procedures.

Hypothesis.
To compare % expansion of SAPIEN 3 THV measured with peri-procedural IVUS versus post-procedural cardiac gated contrast multi-slice computer tomography (MSCT). Expansion was defined as actual outer frame area/nominal area x 100%.

Methods.
Studied were patients with successful valve-in-valve for failed surgical mitral and tricuspid bioprosthetic valves. All underwent peri-procedural IVUS using 10MHz Vision PV035 (Philips North America Corporation, Andover, USA) and post-procedural MSCT (SOMATOM Definition Flash, Dual Source, SIEMENS). IVUS and MSCT (Syngo Via, Siemens, Germany) measurements were
off
-line and done at 1-mm step along the entire height of SAPIEN 3 THV (height 18, 20 and 22 mm for the Sapien THV 23, 26 and 29 mm, respectively).

Results.
Five patients (68.8±11.2 years, 3 female) were treated for failed surgical mitral (n=3) and tricuspid (2) bioprosthetic valves using SAPIEN 3 THV size 23mm (n=1), 26mm (n=1), and 29mm (n=3). Mean peri-procedural and pre-discharge residual transvalvular gradient differed substantially (1.9±0.9 vs 7.9±1.1mmHg, p=0.001). In total, 104 corresponding cross-sections of the THVs were measured with both IVUS and MSCT. Actual outer-frame SAPIEN 3 expansion was smaller within the lengths of inflow and mid segment (overlapping the ring) than in the outflow, being substantially smaller than nominal (Fig 1). Overall, there was very good agreement between % expansion of THV stent frame assessed in IVUS and MSCT (93.5%±13.3% vs 96.3%±11.3%;
r
=0.976 and p<0.001).

Conclusions.
Peri-procedural use of large field-of-view IVUS offers an accurate insight into actual THV expansion deployed valve-in-valve.
Figure 1.
% expansion of SAPIEN 3 measured in IVUS and MSCT.
Abstract 12815: High Throughput Variant Identification in the S3-S5 Helices of
KCNH2
(hERG)
Authors: Ullah Rizwan , Ng Chai A , Vanags Loren , Mitchell Devyn , Vandenberg Jamie , Kroncke Brett
Published: June 2023

Introduction:
LQTS is a multi-factorial cardiac repolarization disorder characterized by a prolonged corrected QT interval (QTc) that predisposes individuals to sudden death. Variants in
KCNH2
account for ~30% of LQTS cases. Variants in a ‘hotspot’ domain of
KCNH2
are of concern, as variant location in
KCNH2
is strongly associated with increased risk of cardiac events. Here, we determined the trafficking phenotype of all possible variants in the S3 and S4 helices (Voltage sensor) and S5 helix and p-loop (pore domain), both ‘hotspot’ domains, of
KCNH2
.

Method:
We used a HA tagged
KCNH2
construct containing mCherry to enable massively parallel characterization of channel trafficking of missense
KCNH2
variants. We studied a total of 3315/3381 possible variants for residues 477-637.

Results:
Our preliminary data revealed a heterogenous distribution of trafficking defects (range: 0-157% of WT). Some regions (e.g. 562-566) were largely intolerant to substitution (trafficking scores ~0% for all variants) whereas other regions (e.g. 509-521) were very permissive of substitution (trafficking ranged from 78-146% of WT). For 51 clinically identified variants, we compared trafficking results with peak tail current density data and found that 4/6 were correctly classified as functionally normal and 42/44 correctly classified as loss of function.

Conclusion:
Massively parallel trafficking assay can identify
KCNH2
defects and illuminate important channel biophysics. Massively parallel trafficking assays will enable prospective and accurate variant assessment for any missense variant in
KCNH2
and subsequently other proteins where misfolding is a major loss-of-function mechanism.
Abstract 12816: Single High-Sensitivity Point of Care Whole Blood Cardiac Troponin I Measurement to Rule Out Acute Myocardial Infarction at Low Risk
Authors: Apple Fred S , Smith Stephen W , Greenslade Jaimi , Sandoval Yader , Parsonage William , Ranasinghe Isuru , Gaikwad Niranjan , Schulz Karen , Stephensen Laura , Schmidt Christian , Okeson Brynn , Cullen Louise
Published: June 2023

Introduction:
High-sensitivity cardiac troponin (hs-cTn) laboratory assays are used to rule out myocardial infarction (MI) on presentation, but prolonged result turn-around times can delay patient management.

Hypothesis:
Our aim was to identify patients at low risk of index MI using a rapid, point of care (POC), whole blood hs-cTnI assay at presentation, with potential early patient discharge, with
<
1% risk of adverse events.

Methods:
Consecutive emergency department patients from two prospective, observational studies with suspected acute coronary syndrome were enrolled. A POC hs-cTnI assay (Siemens Atellica
®
VTLi) threshold using whole blood at presentation, that resulted in a negative predictive value (NPV) of ≥99.5% and sensitivity of
>
99% for index MI, was derived (SEIGE) and validated using plasma (SAMIE). Event adjudications were established using hs-cTnI assay results from usual clinical care. The primary outcome was MI at 30-days.

Results:
1086 patients (8.1% MI) were enrolled in a US derivation cohort (SEIGE) and 1486 (5.5% MI) in an Australian validation cohort (SAMIE). A derivation whole blood POC hs-cTnI concentration of <4ng/L provided a NPV of 99.5% (95% CI: 97.2-100%) and sensitivity of 98.9% (93.8-100%) for ruling out MI. In the validation cohort, NPV was 99.8% (99.1-100%) and sensitivity 98.8% (93.3-100%). 17.8% and 41.8%, respectively, were defined as low risk for discharge. 30-day adverse cardiac events were 0.1% (n=1) for SEIGE and 0.8% (n=5) for SAMIE.

Conclusions:
A point-of-care, whole blood hs-cTnI assay permits an accessible, rapid and safe exclusion of MI, and expedites discharge from the emergency department.
Abstract 12929: Association of Posttraumatic Stress Disorder With Stroke in Women Veterans
Authors: Ebrahimi Ramin , dennis paul , Shroyer Annie L , Alvarez Carlos , beckham jean , Sumner Jennifer
Published: June 2023

Introduction:
Posttraumatic stress disorder (PTSD) has been associated with ischemic heart disease in women veterans. To date, the evidence for the potential association of PTSD with other cardiovascular disorders remains limited. Furthermore, the overwhelming majority of the research in this area has been conducted predominately in men. The goal of this investigation was to evaluate the association of PTSD with incident stroke in a large cohort of women veterans.

Methods:
Veterans Affairs (VA) electronic health records were used to identify women veterans aged ≥18 years who visited any VAs nationwide from 1/1/2000-12/31/2017. Diagnosis of each risk factor and disorder was based on administrative billing codes (International Classification of Disease versions 9 and 10). The final study cohorts included 1:2 matched group of patients with and without PTSD respectively. The cohorts were matched for age, traditional risk factors such as diabetes, hypertension, hyperlipidemia and smoking, as well as obesity, chronic kidney disease, psychiatric disorders (depression, anxiety), female specific risk factors (e.g., pre-eclampsia), drug and alcohol dependence, neuroendocrine disorders (e.g., hypo or hyperthyroidism), and number of visits. Cox regression was used to model incident stroke as a function of PTSD.

Results:
The study population included 398,769 patients, including 132,293 with PTSD and 265,846 matched patients without PTSD. The cox regression analysis revealed that PTSD was significantly associated with greater rates of incident stroke (hazard ratio [HR]=1.64, 95% confidence interval: 1.43-1.86, p<.001).

Conclusion:
These results point to a strong association of PTSD with incident stroke in women veterans. Further research is indicated to assess the association of PTSD with a broader range of cardiovascular disorders.
Abstract 12982: Between a Rock and a Hard Place: Stiff Left Atrial Syndrome in a Patient With Hereditary Rickets
Authors: Hourmozdi Jonathan N , Mylvaganam Ruben , Akhter Nausheen
Published: June 2023

Introduction:
Stiff left atrial syndrome (SLAS) is an uncommon cause of pulmonary hypertension (PH) that has been described as a complication of ablation for atrial fibrillation; here we describe a unique case of SLAS in the setting of extensive left atrial calcification from the treatment of hereditary hypophosphatemia (HH).

Case Presentation:
A 44-year-old woman with a history of HH presented for evaluation of progressive exertional dyspnea. Previous treatment with calcitriol and phosphate had been complicated by severe calcific mitral and aortic stenosis requiring aortic and mitral valve replacement eight years prior. She reported initial improvement in her symptoms after surgery, but more recently had noted worsening dyspnea and edema despite escalating her home diuretic dose. TTE was notable for moderately severe PH with no evidence of valvular or ventricular dysfunction. Chest CT showed extensive left atrial mural calcification (Figure A) with corresponding calcium visible in the wall of the left atrium on TTE (Figure B). The patient was admitted and underwent IV diuresis followed by RHC confirming mPAP of 41mmHg with a PCWP of 20mmHg and prominent V waves to 33mmHg (Figure C-D). PCWP was confirmed by wedge oxyhemoglobin saturation. Symptoms were improved but not resolved with additional diuresis.

Discussion:
In this patient with metastatic calcinosis related to the treatment of her HH, we believe her PH is most likely secondary to SLAS due to marked circumferential left atrial calcification. SLAS is characterized by decreased left atrial compliance, leading to large V waves in the absence of mitral regurgitation or an elevated LVEDP. Beyond diuresis, there are no proven treatments for PH due to SLAS.
Abstract 13097: Safety, Pharmacokinetics, and Pharmacodynamics of AZD3366 Alone and in Combination With Aspirin and Ticagrelor in Healthy Subjects
Authors: Kardassis Dimitris , Egnell Ann-Charlotte , Åstrand Magnus , Daniels Samuel J , Frickleton Celeste , Whatling Carl , Fjellstrom Ola , Gabrielsen Anders
Published: June 2023

Introduction:
Despite reperfusion in patients with ST-elevation myocardial infarction and acute ischemic stroke; reperfusion injury, microvascular dysfunction, thrombosis, and obstruction remain important causes of persistent ischemia and infarct expansion leading to poor clinical outcome. AZD3366, a recombinant human apyrase engineered to enhance hydrolysis of extracellular adenosine tri-/diphosphate (ATP/ADP) to adenosine monophosphate and subsequently adenosine, has exhibited anti-thrombotic, anti-inflammatory, and tissue protective properties in preclinical studies.

Methods:
In this phase 1 randomized single-blind placebo-controlled study in healthy subjects (
NCT04588727
), 7 cohorts of 8 subjects received a single short IV infusion of AZD3366 (2-640 mg [n=6]) or placebo (n=2). A further 3 cohorts of 5 healthy Japanese/1 cohort of 8 healthy Chinese subjects were included within this dose range. A separate group of 24 subjects received 160 mg of AZD3366 in combination with aspirin and ticagrelor (n=12) or aspirin and ticagrelor alone (n=12). The primary objective was to assess safety and tolerability; secondary objectives included assessment of pharmacokinetics (PK) and pharmacodynamics of AZD3366.

Results:
Overall, 103 subjects were randomized; mean age 37.2 (± 9) years, 100 were male. AZD3366 treatment alone or in combination with ticagrelor and aspirin did not result in any clinically relevant safety or tolerability findings. Peak AZD3366 plasma concentrations were reached within 0.5 h post-dosing, followed by monophasic or biphasic decline with a terminal PK half-life of approximately 140 h. Complete ADP-stimulated platelet aggregation inhibition was reached within 10 mins post-dosing; duration ranged from 4 h at 2 mg to ~35 days at 640 mg (Figure).

Conclusions:
AZD3366 alone or in combination with aspirin and ticagrelor was generally safe, well tolerated, and achieved complete platelet inhibition with a dose-dependent duration.
Abstract 13142: Development of a 30-Day Health Status Prediction Model for High-Risk Transfemoral Carotid Artery Stenting Using a Simple Machine Learning Algorithm
Authors: Harris Kristie M , Romain Gaelle , Cleman Jacob , Mena-Hurtado Carlos , Smolderen Kim G
Published: June 2023

Introduction:
Individualized prediction models for transfemoral carotid artery stenting (TF-CAS) health status outcomes have not been developed. We applied a machine learning algorithm to identify the most robust pre-procedural predictors of 30-day TF-CAS health status, and validated models across different health status measures to maximize generalizability.

Methods:
The 390-center SAPPHIRE registry enrolled high-risk patients undergoing TF-CAS from 2006-2014, containing two cohorts with pre-procedural and 30-day health status assessments: Cohort 1 (n=4,667) had EQ-5D-3L (Index and Visual Analog Scale [VAS]); Cohort 2 (n=3,594) had SF-36 (Mental [MCS] and Physical [PCS] Component Summary scores). A random forest algorithm ranked the importance of 50 pre-procedural variables (pre-procedural health status, modified Rankin and NIH stroke scores, demographics, comorbidities, and disease characteristics) for 30-day health status in each cohort. Selection thresholds were based on visual inspection of the importance plots to evaluate the information gain value of each variable considered. Overlapping variables across health status measures were retained to develop a multivariable linear regression model to predict 30-day health status in each cohort.

Results:
Importance plot (
Figure
) inspection yielded 23 variables, each of which had importance values >15% for ≥2 of the 4 health status measures. From these, 7 overlapping variables were ultimately retained in the linear regression analyses that predicted ~40% of the variance (R
2
=.39-.45) for 30-day TF-CAS health status, including pre-procedural health status, age, heart failure, history of stroke, Rankin stroke score, renal disease, and pulmonary disease.

Conclusions:
Seven easily assessed pre-procedural variables robustly predicted TF-CAS health status. This model can inform the risk-benefit analysis underlying the TF-CAS medical decision-making process for patients and clinicians.
Abstract 13168: Benefits of Apixaban Over Warfarin are Preserved Independent of Warfarin Time in Therapeutic Range: Insights From the AUGUSTUS Trial
Authors: Harrington Josephine , Hellkamp Anne S , Alexander John H , Mehran Roxana , Granger Christopher B , Goodman Shaun G , Aronson Ron , Windecker Stephan , Lopes Renato D
Published: June 2023

Introduction:
In the AUGUSTUS trial, patients randomized to apixaban had lower rates of major or clinically relevant non-major (CRNM) bleeding, lower rates of death or hospitalization, and similar rates of death or ischemic events compared with warfarin. Patients randomized to aspirin (ASA) had higher rates of bleeding with similar rates of death or hospitalization, and death or ischemic event. The impact of warfarin time-in-therapeutic-range (TTR) on these outcomes is not known; however, it is plausible that sites achieving better TTR might have better outcomes with warfarin use.

Methods:
Using average site TTR, we assessed the hazard of bleeding, ischemic events, and death/hospitalization across quartiles of site-based TTR. These analyses were performed for both randomized strategies: apixaban vs warfarin and ASA vs placebo.

Results:
This analysis included data from 4420 patients at 399 sites. Site TTR was separated into quartiles of TTR (Q1: 0-49%, Q2: 42-55%, Q3: 56-69%, Q4: 70-100%). Sites with higher TTR tended to have fewer female patients (32.4% Q1 vs 25.4% Q4), more White patients (88.5% Q1 vs 97.1% Q4), and more patients previously prescribed oral anticoagulants (44.5% Q1 vs 52.5% Q4). There was no significant interaction between site TTR quartile and the hazard ratio (HR) for bleeding, death or hospitalization, or death or ischemic event with apixaban vs warfarin, or on the HR for bleeding, or death or hospitalization with ASA vs placebo (Figure). There was a borderline significant interaction (p<0.047) between site TTR quartile and the HR for death or ischemic events with ASA vs placebo, such that patients at sites with higher TTR were more likely to derive a benefit from ASA compared with placebo.

Conclusion:
The benefits of apixaban over warfarin seen previously in AUGUSTUS are consistent across the spectrum of quartiles of site TTR. Patients at sites with higher average TTR may be more likely to derive a benefit from aspirin use to prevent death or ischemic events.