bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10351: Racial Differences in Chronic Stress or Allostatic Load Variation Due to Androgen Deprivation Therapy in Prostate Cancer
Authors: Stabellini Nickolas , Cullen Jennifer , Moore Justin , Cao Lifen , Agarwal Neeraj , Datta Biplab , Garcia Jorge , Shanahan John , Waite Kristin , Hamerschlak Nelson , Montero Alberto , Barnholtz-Sloan Jill , Guha Avirup
Published: June 2023

Introduction:
The cumulative burden of chronic stress and life events can be measured by Allostatic load (AL), whose high values are related to poorer health outcomes and increased risk of cardiovascular disease (CVD). The primary objective of this study is to analyze the impact of androgen deprivation therapy (ADT) on AL variation in patients upon diagnosis of prostate cancer (PC).

Hypothesis:
ADT may increase AL variation in prostate cancer patients.

Methods:
Data were obtained from a Cleveland area integrated health care systems informatics platform. The initial cohort included males ≥18 years diagnosed with PC between 2005 and 2022. AL was calculated using multiple markers representing the cardiovascular, metabolic, and immune systems (
Table 1
) before diagnosis and monthly during the first year. ADT use was captured based on prescribed medications. A linear-mixed-effects model, adjusted for patient demographics, CVD risk factors, and cancer characteristics, and treatment, was used to study AL monthly variation. The analysis was stratified by Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) race.

Results:
We analyzed a total of 7,168 PC adenocarcinoma patients (31.7% NHB vs 68.3% NHW), of which 20.9% received ADT. NHBs had higher AL pre-PC diagnosis than NHWs (p=0.001). AL monthly variation was 0.15 (±0.02) higher in all PC patients on ADT (p<0.001) and these results persisted stratifying by race (0.10 ± 0.04 for NHBs, p=0.01 and 0.16 ± 0.03 for NHW, p<0.001). There was no racial difference between AL increase in those receiving only ADT (0.09 +/- 0.04; p = 0.06). The details of individual AL variable measures pre-PC diagnosis and the mixed-effects model are presented in Table 1.

Conclusion:
Pre-PC-diagnosis chronic stress/AL is higher among NHBs vs. NHWs with the addition of ADT increasing AL in both races after PC diagnosis. This study is hypothesis-generating, offering data that help explain, in part, the racial differences in ADT-mediated CVD.
Abstract 10370: Effects of Tirzepatide on 24-Hour Ambulatory Blood Pressure and Heart Rate in Adults With Obesity - Results From the SURMOUNT-1 Ambulatory Blood Pressure Monitoring Sub-Study
Authors: De Lemos James A , le Roux Carel W , Mao Huzhang , Ahmad Nadia N , zhang shuyu , Bunck Mathijs , Stefanski Adam
Published: June 2023

Background:
Tirzepatide has demonstrated substantial reductions in body weight and in-office blood pressure (BP) in people with obesity with and without type 2 diabetes (T2D). The effects of tirzepatide on ambulatory BP and heart rate (HR) have not been evaluated. We sought to assess the effect of tirzepatide on 24-hour (24h) mean systolic BP (SBP), diastolic BP (DBP) and HR, as measured during 24h ambulatory BP monitoring (ABPM) in people living with obesity without T2D.

Methods:
In the SURMOUNT-1 ABPM sub-study, participants with a body mass index ≥30, or ≥27 kg/m
2
and at least one weight-related complication (excluding diabetes), with SBP/DBP <140/90 mmHg (and stable antihypertensive therapy if used), were randomly assigned 1:1:1:1 to once-weekly subcutaneous tirzepatide 5, 10, or 15 mg or placebo. The randomization was stratified by pre-diabetes status, country, sex, and use of heart rate controlling medicines at baseline. Participants underwent 24h ABPM at baseline and after 36 weeks of treatment.

Results:
Among participants randomized in the SURMOUNT-1 trial, 600 were enrolled in the ABPM substudy (69% female; mean age 46 y, BMI 37 kg/m
2
). No clinically significant between-treatment differences were observed in baseline characteristics. Overall, 494 participants had evaluable ABPM data at baseline and post-baseline. Treatment with all tirzepatide doses was associated with significant reductions in 24h SBP at 36 weeks compared with placebo. Participants who received tirzepatide 5 and 10 mg, but not 15 mg, had significantly reduced 24h DBP at 36 weeks versus placebo. An increase in 24h HR was observed with each tirzepatide dose relative to placebo.

Conclusion:
After 36 weeks of treatment, tirzepatide was associated with statistically significant and clinically meaningful reductions in mean 24h SBP at all doses and of DBP at the two lower doses. Tirzepatide treatment was associated with a dose-dependent increase in the mean 24h HR.
Abstract 10402: Activated Protein C Rescues Sepsis-Associated Cardiac Dysfunction and Renal Injury in Aging
Authors: Krause-Hauch Meredith , Ren Di , Slotabec Lily , Wang Hao , Davitt Kayla , Li Zehui , Zoungrana Linda Ines , Li Ji
Published: June 2023

Introduction:
Sepsis is a progressive life-threatening condition in which mortality has been consistently linked to increasing organ dysfunction. We have found that activated protein C (APC) has cytoprotective and anti-inflammatory properties in cardiovascular disease. Whether APC is critical for maintaining systemic homeostasis under sepsis in aging remains unknown.

Hypothesis:
Administration of recombinant APC ameliorates sepsis-associated renal injury and cardiac dysfunction in aging
via
EPCR (endothelial cell protein C receptor).

Methods:
Young (3-6 months) and aged (18-21 months) C57BL/6J wild type (WT), and EPCR point mutation (EPCR

R84A/R84A

) knock in C57BL/6J mice were subjected to cecal ligation and puncture (CLP) surgery. APC (0.2 μg/g) was injected (i.p.) 1 hour after CLP surgery and every 24 hours to determine the therapeutic effects of APC on CLP-induced sepsis. Cardiac function was assessed daily
via
echocardiogram.

Results:
The Kaplan-Meier survival curve showed that the survival rate of young mice is 90% and of aged mice is 0% on day 7 of post-CLP. Moreover, the spleens were significantly enlarged in both young and aged CLP WT mice. Intriguingly, administration of recombinant APC can keep all young animals' survival and increased survival rate of aged animals to 65% on day 7 of post-CLP. The spleen size of young/aged CLP groups were significantly reduced by APC treatment. However, the beneficial effects of APC on the survival rate and spleen enlargement caused by CLP were abolished in EPCR

R84A/R84A

mice versus EPCR

WT/WT

littermates. The renal tubules necrosis score and cardiac dysfunctions caused by CLP were worse in aged versus young mice, but APC treatment significantly rescued CLP-caused renal pathology and cardiac dysfunctions of young/aged mice and the rescuing capacity of APC for both renal pathology and cardiac dysfunctions in aged versus young mice was stronger. In addition, APC treatment reduced circulating inflammatory monocytes and neutrophils during CLP-induced sepsis in young/aged WT but not EPCR

R84A/R84A

mice

Conclusions:
Sepsis associated mortality is increased in aging. APC treatment can ameliorate age-related sepsis renal injury and cardiac dysfunctions through receptor EPCR to reduce sepsis related mortality.
Abstract 10406: Longitudinal Trends in Cardiovascular Complications Among Patients Hospitalized for Covid-19 Infection: A National Multi-Center Analysis
Authors: Hall Eric J , Das Sandeep R , Ayers Colby , Bradley Steven M , Elkind Mitchell , Hall Jennifer L , Kolkailah Ahmed A , Mallya Pratheek , Morrow David , Rodriguez Fatima , Roth Gregory A , Rutan Christine , Stevens Laura , Wang Tracy Y , Walchok Jason , Williams Joseph H , De Lemos James A
Published: June 2023

Introduction:
COVID-19 is associated with multiple cardiovascular disease (CVD) complications, while pre-existing CVD and CVD risk factors increase the risk of severe COVID. The COVID-19 pandemic has evolved through multiple phases characterized by new viral variants, vaccine development, and changes in therapies. It is unknown whether rates of CVD complications or risk factor profiles of hospitalized patients have changed over the course of the pandemic.

Methods:
We analyzed the AHA COVID-19 CVD registry, a national multi-center registry of hospitalized adults with active COVID-19 infection. Data from March 2020 were excluded, and subsequent periods from April 2020 to December 2021 were divided into 3-month epochs. Trends in CVD risk factors and CVD outcomes, including a composite primary outcome of CVD death, cardiogenic shock, new heart failure (HF), stroke, and MI, were evaluated across epochs.

Results:
39,961 patients were included. Mean age was 62±18 years during the first epoch and remained consistent through March 2021, after which it decreased and remained stable (55±18 years by the last epoch; p
trend
<0.001). Patients admitted later in the pandemic were more likely to be obese and less likely to have existing CVD (p
trend
<0.001 for each). The incidence of the primary outcome (Figure) increased from 7.2% to 9.8% from the first to the last epoch (p
trend
<0.001). This was driven by an increase in the diagnosis of MI and stroke. Diagnosed pulmonary embolism also rose from 1.9% to 4.7% over the study period (p
trend
<0.001). There was no consistent trend in the rates of new HF, cardiogenic shock, or CVD mortality, all of which were uncommon, occurring in ≤2% of the overall study population.

Conclusions:
Despite a shifting risk factor profile towards a younger population with lower rates of established CVD, the incidence of diagnosed CVD complications among patients hospitalized for COVID-19 increased over the course of the pandemic.
Abstract 10409: Performance of the Hart Cve Panel for Prediction of Cardiovascular Events in Patients With Chronic Kidney Disease
Authors: Mohebi Reza , McCarthy Cian , van Kimmenade Roland , Gaggin Hanna K , Rhyne Rhonda F , Magaret Craig , Barnes Grady , Januzzi James L
Published: June 2023

Background:
Patients with chronic kidney disease (CKD) are at increased risk for cardiovascular events (CVE: incident myocardial infarction [MI], stroke, or cardiovascular death) following an angiographic procedure.

Methods:
Among 446 patients undergoing coronary or peripheral angiography, we applied a previously-developed biomarker panel to predict incident cardiovascular events (HART CVE, Prevencio, Kirkland WA); the panel consists of 4 biomarkers (N-terminal pro-B type natriuretic peptide, kidney injury molecule-1, osteopontin, and tissue inhibitor of matrix metalloproteinase-1) with results expressed in 2 risk levels (CVE high risk and low risk). Patients were followed for 2 years for incident cardiovascular events.

Results:
During the 2-year follow-up, 74 CVE occurred. Participants were categorized into four groups based on CKD stages (Stage 1-2 vs Stage 3-5) and CVE risk level (high risk and low risk). In our multivariable model, considering patients at CKD stage 1-2/CVE low-risk as a reference, the hazard ratio (95 % confidence interval) of cardiovascular events was 2.28 (1.53-5.22) for CKD stage 1-2/CVE high-risk, 0.50 (0.07-3.73) for CKD stage 3-5/CVE low-risk and 4.56 (2.54-8.18) for CKD stage 3-5/CVE high-risk (
Table
). The C-statistic for predicting 2-years cardiovascular events in all 446 patients was 0.77 (0.72, 0.82).

Conclusion:
Patients with CKD are at high risk for incident MI, stroke, and CV death. Utilizing a multiple-protein biomarker panel can assist clinicians in identifying patients at higher risk of CVE, particularly among those at high stages of CKD.
Abstract 10414: Sesn2/AMPK Signaling Medicates Metformin's Pharmacological Action on Cardiac Mitochondrial Functional Integrity in Response to Ischemic Insults
Authors: Li Zehui , Bates Lauryn , Krause-Hauch Meredith , Wang Hao , Zoungrana Linda Ines , Chen Qun , Ren Di , Lesnefsky Edward J , Li Ji
Published: June 2023

Introduction:
Metformin activates AMP-activated protein kinase (AMPK) to limit cardiac damage caused by ischemia and reperfusion (I/R). We found that a stress inducible protein Sesn2 is associated with AMPK to maintain mitochondrial oxidative phosphorylation (OXPHOS) during I/R. But the role of Sesn2/AMPK complex in the beneficial effects of metformin on ischemic insults remain unknown.

Hypothesis:
Metformin modulates Sesn2/AMPK signaling cascade to maintain mitochondrial integrity and respiration functions during I/R stress.

Methods:
Cardiomyocyte specific Sesn2 knock out (cSesn2

-/-

) and wildtype littermates (Sesn2

f/f

) C57BL/6J mice were subjected to
in vivo
regional ischemia of 45 min followed by injection of metformin (2 mM, i.v.) 5 min before 24 hr of reperfusion. Mitochondrial functions were determined by a Seahorse XF24 Analyzer. The sarcomere shortening and calcium transients of cardiomyocytes were measured with IonOptix Calcium and Contractility System.

Results:
Echocardiography data showed that I/R versus sham operations significantly reduced ejection fraction (EF) and fractional shortening (FS) in both Sesn2

f/f

and cSesn2

-/-

mice. Metformin treatment improved cardiac function under I/R and reduced myocardial infarct size by I/R in Sesn2

f/f

but not cSesn2
-/-
mice. Immunoblotting data showed metformin activated AMPK signaling and augmented mitochondrial OXPHOS Complex II levels in Sesn2

f/f

but not cSesn2

-/-

hearts under I/R stress conditions. Transmission electronic microscopy with immuno-gold labeling showed that Sesn2 is primarily located in the mitochondrial membrane and metformin treatment stabilized mitochondrial Sesn2 in Sesn2

f/f

versus cSesn2
-/-
hearts under I/R conditions. IonOptix measurements showed that metformin rescues contractile dysfunctions and impaired calcium flux by I/R in Sens2

f/f

but not cSesn2
-/-
cardiomyocytes. In addition, metformin treatment reduced reactive oxygen species (ROS) levels and improved mitochondrial respiration rate under I/R conditions in Sesn2

f/f

but not cSesn2

-/-

hearts.

Conclusions:
Administration of metformin benefits cardiac functions under I/R stress. Sesn2/AMPK signaling mediates mitochondrial functional integrity during I/R with metformin treatment.
Abstract 105: High-dose Intranasal Insulin In A Dose-escalation Study For Healthy Human Subjects
Authors: Schmitzberger Florian F , Fowler Jennifer , Hsu Cindy H , Pai Manjunath , Neumar Robert W , Meurer William J , Silbergleit Robert
Published: June 2023

Introduction:
Intranasal insulin is a putative neuroprotective therapy that could be easily delivered very early after cardiac arrest, but safety at doses extrapolated from animal models have not been studied in humans. We hypothesized that high-dose intranasal insulin can be safely delivered to healthy human subjects.

Methods:
This was a phase 1, open label dose-finding study of intranasal insulin in healthy participants.The primary objective was to determine the maximum tolerated dose of intranasal insulin in healthy subjects. Placebo and insulin were given intranasally to supine healthy volunteers intranasally at escalating doses from 0 to 1000 units on repeated weekly visits. Serum glucose, insulin, and C-peptide levels were measured serially at 0, 15, 30, 60, 120, 180 and 240 minutes after administration.

Results:
Twenty four participants (12 female, median age 53.5, IQR 35.75-61) were enrolled. There was no change in average serum glucose after administration of intranasal insulin. Average serum insulin increased slightly in a dose-dependent manner, peaking at 15 minutes. C-peptide went down over time from administration in all groups. One participant had severe hypoglycemia (minimum 24 mg/dL 45 min after receiving 600U intranasal insulin) that was corrected with oral intake and intravenous dextrose. Another participant had transient hypoglycemia (minimum 51 mg/dL at 30 min) also after 600U intranasal insulin with mild symptoms that was corrected with oral intake. Hypoglycemic episodes were associated with increases in serum insulin. Both participants continued in the study without hypoglycemia after additional doses. One participant dropped out for reasons unrelated to the intervention.

Discussion:
High-dose intranasal insulin up to 1000U was well tolerated, without changes in mean glucose, but with small measurable systemic absorption. Idiosyncratic hypoglycemia requires further study. Delivery of intranasal insulin to the brain at these doses, and efficacy of high-dose intranasal insulin as a neuroprotective therapy after cardiac arrest require further study.
Abstract 10550: Higher Endocardial Viability Ratio is Associated With Improved Left Ventricular Function After Transcatheter Aortic Valve Replacement
Authors: Selinski Christian , Strickling Jarred , Katz Stephanie , Breathett Khadijah , Mehta Nishaki M , Kwon Younghoon , Lim David S , Sodhi Nishtha , Ragosta Michael , Bilchick Kenneth C , Taylor Angela , Mazimba Sula
Published: June 2023

Introduction:
Both LV dysfunction and AS lead to an increase in LVEDP, a decrease in oxygen delivery to cardiac muscle, and ultimately a decrease in the EVR.

Hypothesis:
We hypothesized that patients with low EVR would have less significant recovery of LV function after TAVR.

Methods:
Patients with LVEF <40% and severe AS undergoing TAVR at the University of Virginia (UVA) between 2012 and 2019 were retrospectively reviewed. EVR was calculated by dividing the diastolic pressure time index (DPTI) [(Diastolic blood pressure – LVEDP) x (60seconds/ heart rate – 0.2 seconds)] by the tension time index (TTI) [systolic pressure x 0.2 seconds] using catheter-derived hemodynamics prior to TAVR. LVEF and mAG values were obtained from TTE measurements done for procedural planning and at, or closest to, 1-year follow-up. The patients were divided into cohorts based on EVR above or below 0.7, a value indicative of subendocardial ischemia. Mean change in LVEF was evaluated between these two groups (Figure [1] and Table [1]) and multivariable regression was performed using pre-procedural LVEF, EVR, and change in mean aortic gradient as shown in Table [2].

Results:
128 patients that underwent TAVR had a LVEF <40%. 85 patients (32.5% female) had complete invasive hemodynamic and echocardiographic data. The mean change in post-TAVR LVEF in the lower subgroup was <5% with a standard deviation of 12.5. In patients with EVR >0.7 there was improvement of LVEF of >10% with a standard deviation of 10.8. Two-tailed t-testing was performed with a corresponding p-value of 0.0181. Multivariable regression on pre-procedural LVEF, pre-procedural EVR, and change in mean AG were all statistically significant.

Conclusion:
EVR >0.7 is associated with greater improvement in LV function in advanced heart failure patients after TAVR.
Abstract 10706: Transnitrosation From the NO-Receptor Soluble Guanylyl Cyclase to Oxidized Thioredoxin-1 Has a Potential Cardiovascular Protective Effect Against Oxidative Stress
Authors: YOUNIS WAQAS , Cui Chuanlong , shu Ping , Qin Yong , Beuve Annie V
Published: June 2023

Soluble guanylyl cyclase (GC1) is an α/β heterodimer producing cGMP when stimulated by nitric oxide (NO). The NO-GC1-cGMP pathway is essential for cardiovascular homeostasis. Oxidative stress is known to disrupt the NO-GC1-cGMP pathway via oxidation of GC1 cysteines, which makes it unresponsive to NO stimulation. Under these conditions, GC1-α subunit “moonlights” by increasing cellular S-nitrosation via specific transfer of its nitrosothiols to cysteines of other proteins (transnitrosation). One of the SNO-targets identified by Mass Spectrometry (MS) was the oxidized form of Thioredoxin1 (oTrx1), which is unidirectionally transnitrosated by GC1 with αC610 as a SNO-donor and C73 of Trx1 as the SNO-recipient. Because oTrx1 itself drives transnitrosation, we sought and MS-identified SNO-proteins targeted by both GC1 and Trx1, suggesting a SNO-GC1→oTrx1→targets cascade. We investigated the (patho)physiological relevance of GC1-dependent transnitrosation activity by creating a knock-in (KI) mice with replacement of αC610 to a serine (αC610S). Biotin switch assays confirm that, under oxidative stress (Angiotensin II (AngII) treatment), global and Trx1 levels of S-nitrosation (SNO) were drastically reduced in lungs and hearts of KI mice compared to WT but the NO-stimulated GC1 activity was similar between WT and KI. Importantly, telemetry recordings indicated that 2 weeks of AngII treatment led to a more severe increase in BP and a more prolonged QTc in KI mice. The AngII-induced rise in MBP was 27.6 ± 2.5 mmHg in KI vs 21.6 ± 1.2mmHg in WT, while AngII-increase in QTc, reflecting delayed repolarization, was 12.53 ± 2.30ms in KI vs. 8.713 ± 2.72ms for the WT. The elevated BP with AngII treatment correlated with higher increase in cardiac hypertrophy, oxidation (measured by DHE staining) and fibrosis (picric acid staining) in KI mice. The AngII-induced increase in a) hypertrophy in KI was 0.63 ± 0.07 vs. 0.24 ± 0.08 mg/g in WT, b) cardiac oxidation was 0.19 ± 0.07 in KI and negligible in WT, and c) fibrosis was 1.75 (A.U) in KI vs. 1.31 in WT. These more severe cardiovascular dysfunctions in KI mice in response to AngII suggest that transnitrosation by GC1, potentially using oTrx1 as a nitrosothiol relay, is a mechanism of protection against oxidative stress.
Abstract 10710: Plasma Proteomic Profiles of the Blood Pressure Response During Exercise Are Associated With Incident Hypertension
Authors: Rao Prashant , Keyes Michelle , Mi Michael , Barber Jacob , Tahir Usman A , Deng Shuliang , Clish Clary , Shen Dongxiao , Farrell Laurie , Xanthakis Vanessa , Ramachandran Vasan S , Bouchard Claude , Sarzynski Mark A , Gerszten Robert E , Robbins Jeremy
Published: June 2023

Introduction:
The blood pressure (BP) response during acute exercise (acute exercise blood pressure (AEBP)) is related to future risk of hypertension (HTN) and cardiovascular disease (CVD). Biochemical characterization of AEBP could identify novel biomarkers of CVD risk and inform understanding of its biology.

Methods:
We applied an aptamer-based proteomics platform to assay ~5000 proteins at rest in 681 healthy individuals of the HERITAGE Family Study (mean age 34y, 54% women) who underwent an acute exercise perturbation. AEBP was measured during submaximal exercise on a cycle ergometer. We then performed a proteomic association study of resting BP and AEBP. Top protein associations with acute exercise SBP and DBP were analyzed for their association with incident HTN and CVD in the Framingham Heart Study (FHS). Putative causal effects of AEBP-related proteins were investigated by Mendelian randomization (MR), using cis-protein quantitative loci genetic instruments.

Results:
We identified new markers of AEBP, many of which are secreted proteins that span biological processes relevant to vascular function including transforming-growth factor beta-receptor 3 (β = -3.39, p = 2.33e-6), prostaglandin D2-synthase (β = -2.50, p = 1.18e-10-9), and angiopoietin-related protein 4 (β = 2.44, p = 1.05e-4). The addition of 12 AEBP-associated proteins to clinical information informed future risk of HTN and CVD among normotensive community-dwelling individuals (clinical model, clinical proteomic model AUCs: incident HTN 0.69, 0.73; coronary heart disease 0.73, 0.76; heart failure 0.83, 0.87). MR analysis of AEBP-associated proteins supported a potential causal relationship between 5 proteins and BP regulation (TGFBR3, ANGPTL4, CGA FSHB, PTGDS, KLK8).

Conclusions:
We identified new blood biomarkers of BP regulation that were elicited only by an acute exercise perturbation and highlight novel potential causal pathways.
Abstract 10724: Use of Right Heart Catheterization and Length of Stay in Patients With Acute Right Heart Failure: A National Inpatient Database Analysis
Authors: Naik Riddhima , Jha Samir
Published: June 2023

Background:
Right Heart Catheterization (RHC) is an important tool in the assessment of hemodynamic status in patients with right heart failure (RHF), however is underutilized.
Objective:
To evaluate the use of RHC in RHF with the primary outcome as mortality and secondary outcome as length of stay (LOS) using the National Inpatient Sample (NIS).

Methods:
Using 2018 NIS database, we queried for adults over 18 years with the diagnosis of acute RHF and RHC as a procedure using the ICD-10 code via STATA program. Multivariate logistic regression method was used to adjust for age, gender, race, Charlson comorbidity index, cardiogenic shock, septic shock, respiratory failure, acute coronary syndrome, heart failure, atrial fibrillation/flutter, acute kidney injury, chronic kidney disease, end-stage renal disease. Using a 95% confidence interval (CI), a p-value less than 0.05 was considered statistically significant.

Results:
A total of 49010 admissions was recorded for acute RHF of which 4795 underwent RHC. 360 patients (7.5%) died in the RHC group versus 4615 (10.4%) in the non-RHC group.16.9% of patients in the RHC group had cardiogenic shock versus 7.3% in the non-RHF group. On univariate analysis, patients undergoing RHC had decreased odds of mortality compared to patients without RHC [Odds ratio (OR) = 0.69, p=0.003] and patients undergoing RHC had increased LOS compared to patients without RHC [OR= 3.15, p=0.012]. The mean LOS for the RHF group was 13.3 days versus 7.5 days in the non-RHF group. On multivariate analysis, those undergoing RHC had decreased odds of mortality compared to those without RHC [OR= 0.47, p=0.000] and LOS was longer for those undergoing RHC [OR= 3.15, p=0.008]. All the outcomes were statistically significant.

Conclusion:
Right heart catheterization, when used in acute right failure, showed decreased odds of mortality when compared to patients receiving non-invasive medical management only however, no difference in length of stay was observed.
Abstract 10736: Statistical Shape Modeling Reveals Anatomic Shape Features Associated With the Outcome of Optimal Medical Therapy in Uncomplicated Type B Aortic Dissection
Authors: Liu Minliang , Dong Hai , Wu Yuxuan , Mazlout Adam , Oshinski John N , Sun Wei , Elefteriades John A , Leshnower Bradley G , Gleason Rudolph L
Published: June 2023

Introduction:
Currently, Type B aortic dissection (TBAD) without the presence of either organ malperfusion or aortic rupture is managed with optimal medical therapy (OMT) consisting of an aggressive anti-hypertensive medical regimen and surveillance imaging. Although OMT achieves excellent early survival, the long-term outcomes with OMT alone remain poor. In this study, we identified anatomic shape features that correlate with OMT failure and aortic growth rates in uncomplicated TBAD via statistical shape modeling (SSM).

Methods:
Contrast CT scans of patients with acute uncomplicated TBAD were analyzed from 25 patients who were initially treated with OMT. OMT failure was defined as aortic intervention (surgical or endovascular repair, n = 8). Statistical shape models were constructed using principal component analysis (PCA) and partial least square regression (PLSR) to extract anatomic shape features from the aorta and flap geometries. For 14 of the 25 patients, additional follow-up CT scans (5 to 117 months) were used to quantify the rate of aortic expansion.

Results:
Four PCA (feature 5: p = 0.048, 12: p = 0.005, 14: p = 0.047, 24: p = 0.038) and two PLSR (feature 1: p = 0.000, 2: p = 0.004) shape features were effective at separating OMT failure patients and patients who were adequately treated with OMT. Two PCA features were moderately correlated with aortic growth rate (correlation coefficient, feature 11; r = 0.579, 21: r = 0.503). A PLSR feature was correlated with the growth rate (r = 0.867). Representative shape features are shown in Figure 1.

Conclusions:
Anatomic shape features extracted from SSM were correlated with the outcomes of OMT and aortic growth rate. SSM shape features may provide additional anatomic risk factors in addition to aortic diameter that predicts aneurysmal degeneration and the need for surgical intervention. Future investigations will incorporate the SSM shape features to determine the risk of OMT failure in uncomplicated TBAD patients.
Abstract 10913: Causes of Early Mortality After Catheter Ablation of Atrial Fibrillation
Authors: Tan Min Choon , Rattanawong Pattara , Deshmukh Abhishek , Srivathsan Komandoor , Scott Luis , McLeod Christopher J , Asirvatham Samuel J , Noseworthy Peter A , Cha Yong-Mei , Mulpuru Siva K , Lee Justin Z
Published: June 2023

Background:
Recognition of the causes of early mortality after atrial fibrillation (AF) catheter ablation is essential for the improvement of patient safety.

Objective:
This study sought to determine the causes of early mortality (≤90-days) after AF ablation and to further understand the circumstances surrounding death after the procedure.

Methods:
We performed a retrospective analysis of AF ablation from January 1, 2013, to December 1, 2021 at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). Causes of death were identified through a comprehensive chart review of the electronic health record from within the Mayo Clinic system and outside records when available.

Results:
A total of 6,723 patients were included in the study. The 30-day and 90-day all-cause mortality rates were 0.09% and 0.22%, respectively. Among all 90-day deaths, majority of the deaths (73.3%) did not have a direct relationship with the procedure. Sudden death was the most common cause of early death (20%), followed by peri-procedural stroke (13%), respiratory failure (13%), atrioesophageal fistula (13%), infection (7%), heart failure (7%), and traumatic brain injury (7%). The 90-day mortality rate directly due to AF ablation procedural complications was 0.06%. Most of the early deaths (93.3%) occurred after discharge from index hospitalization, among which 64.3% were readmitted before their death, 14% died at home, and 7% were discharged on comfort care and died in hospice. The main reason for readmission leading to death was respiratory failure (33%).

Conclusion:
Atrial fibrillation ablation procedure has a 90-day mortality of 0.22% and the most common cause of early mortality was sudden death. The majority (73.3%) of early mortality was not

directly associated with a procedural complication, and the mortality rate due to complications associated with the AF ablation procedure was 0.06%.
Abstract 10920: Efficacy of Cilostazol After Endovascular Therapy for Peripheral Artery Disease: A Meta-Analysis
Authors: Saballo Darlene Pearl , Yumena Marc Jusenn , Gonzales Lea Arceli
Published: June 2023

Introduction.
Endovascular therapies (EVT) for peripheral arterial disease (PAD) have been useful in improving quality of life outcomes; however, rates of restenosis after EVT remain high and lead to worse clinical outcomes. Use of cilostazol with antiplatelet therapy following EVT has been shown to improve clinical outcomes, although its role remains debatable. This meta-analysis aims to examine the clinical outcome of cilostazol use post-EVT in randomized controlled trials, and provide some basis for recommending this as a useful adjunct post-EVT in PAD patients.

Objectives.
This study aims to assess the efficacy of cilostazol as added therapy with antiplatelets after EVT in terms of decreasing restenosis, revascularization incidence, and incidence of bleeding and adverse effects.

Methods.
An electronic literature search for randomized controlled trials published up to June 2021 was conducted. Four randomized control trials which compared the efficacy of adding cilostazol to antiplatelet therapy in decreasing the risk of restenosis in patients with PAD who underwent EVT were selected. Data from all included studies were entered, compiled and analyzed using the Review Manager version 5.3 software.

Results.
A total of 589 patients from the four randomized controlled trials were analyzed in this meta-analysis. The efficacy of addition cilostazol post-EVT showed benefit of cilostazol in lowering restenosis (SMD 0.39 [95% CI 0.26, 0.57] P < 0.00001), revascularization (SMD 0.44 [95% CI 0.30, 0.64] P < 0.0001), and no significant differences between groups in preventing major cardiac cardiac events (SMD 0.80 [95% CI 0.51, 1.24] P=0.32) for post-EVT patients occurrence for post-EVT patients.

Conclusion.
The addition of Cilostazol to antiplatelet therapy post-EVT in patients with PAD may decrease rates of restenosis and revascularization.

Keywords:
cilostazol, EVT, restenosis, revascularization, major adverse cardiac events
Abstract 10947: A Polygenic Risk Score Added to a QRISK2 Cardiovascular Risk Calculator Demonstrated Robust Clinical Acceptance in the Primary Care Setting
Authors: Fuat Ahmet , Adlen Ella , Monane Mark , Coll Ruth , Groves Sarah , Little Elizabeth , Wild Jonathan , Kamali Farzan J , soni yusuf , Haining Shona , Riding Helen , Giner Delgado Carla , Riveros-Mckay Fernando , Weale Michael , Plagnol Vincent , Harrison Seamus , Donnelly Peter
Published: June 2023

Introduction:
We have previously shown that combining a polygenic risk score (PRS) for cardiovascular disease (CVD), a numerical summary of an individual’s genetic predisposition to CVD, with standard clinical risk calculators such as ASCVD-PCE and QRISK results in improved estimates of CVD risk. Implementation of such a cardiovascular integrated risk tool (CVD IRT) into real world clinical practice is a key focus for further study.

Hypothesis:
We assessed the hypothesis that a CVD IRT can be incorporated into routine primary care.

Methods:
The Healthcare Evaluation of Absolute Risk Testing Study (NCT05294419) is a prospective trial recruiting up to 1,000 healthy participants undergoing health checks across 12 UK NHS general practices. Both QRISK2 and CVD IRT scores were generated and returned to clinicians, who then communicated the results to participants. The primary outcome of this study is operational success as well as feedback from health care providers (HCPs) and participants. The study also measures the impact of the CVD IRT on clinical decision making.

Results:
These are interim analyses. As of April 2022, 624 eligible participants (62% female, mean age 55) have been recruited. A total of 371 CVD IRT reports have been generated, with 100% of blood samples generating scores that were all returned within the designated time frame. Among the primary care HCPs, 89% (8/9) agreed that the incorporation of CVD IRT into routine care could be done in a straightforward manner. Among the participants who have completed a survey to date, 93% (125/135) would likely or very likely recommend the CVD IRT to friends and family. Average QRISK2 (6.3%) and CVD IRT (6.6%) risk scores did not differ significantly, but there were broad changes in risk among individual patients, with 5% (19/371) of patients crossing above the risk threshold to treat according to NICE guidelines (10-year risk ≥ 10%) as well as 3% (11/371) of patients reclassified as very high risk (10-year risk ≥ 20%).

Conclusions:
The rollout of an integrated risk tool combining polygenic risk into a standardized CVD risk calculator within primary care is feasible and well accepted by clinicians and participants. The CVD IRT results suggest clinically actionable changes in a substantial proportion of this population.
Abstract 11005: The Impact of Time Censoring on Machine Learning Models Which Identify Patients With Undiagnosed Cardiac Amyloidosis
Authors: Lee Greg , Fielden Sam , Carry Brendan , Ulloa Cerna Alvaro , Jing Linyuan , Nemani Arun , Rocha Daniel , Flick Kyle , Ruhl Jeffrey , Venkataraman Jagadish , Zimmerman Noah , Chen Ruijun , Fornwalt Brandon , Haggerty Christopher M
Published: June 2023

Introduction:
Cardiac amyloidosis (CA) is a common cause of progressive heart failure. New therapies can improve outcomes but most CA patients remain undiagnosed and untreated. Machine learning models deployed on electronic health record (EHR) data may be able to find patients with undiagnosed CA. To date, most models have focused on identification of undiagnosed amyloid from uncensored data modalities (Fig 1).

Hypothesis:
We hypothesized that lack of post-diagnosis censoring when training CA models leads to poor performance in predicting patients with undiagnosed CA whereas training with appropriate time censoring improves performance.

Methods:
We used 41 EHR features (demographics, labs, electrocardiogram/echocardiography measurements, vitals) to train a boosted decision tree model with and without time censoring. This was applied to 112 patients with confirmed CA and 22,400 controls matched on age, sex, encounter frequency and timespan of EHR. We also compared our findings to a web-based CA algorithm that was publicly available in 2020.

Results:
The EHR algorithm had modestly higher performance on at-risk, time-censored patients when trained with and without time censoring (area under the receiver operating characteristic curve (AUROC) 0.84±0.09 vs 0.79±0.07). Testing on temporally uncensored data showed higher performance (AUROC: 0.91±0.05) which may be unrepresentative of deployment scenarios where post-diagnostic features are unavailable for model use. The publicly available algorithm demonstrated a similar trend when tested on uncensored data (AUROC: 0.67±0.03) as compared to an appropriately censored feature set (AUROC: 0.54±0.04).

Conclusions:
EHR algorithms can be trained to find patients with high risk of undiagnosed cardiac amyloidosis. These models should be evaluated on temporally censored data so that post-diagnostic features do not artificially inflate performance estimates and negatively impact real-world deployment.
Abstract 11055: Outcomes and Progression of Rasopathy-Associated Hypertrophic Cardiomyopathy
Authors: Ho Michael , Whitt Zachary , Meisner Joshua
Published: June 2023

Background:
RASopathy associated hypertrophic cardiomyopathy (HCM) is a frequent cause of pediatric onset HCM. RAS pathway inhibitors are a precision therapeutic option for RASopathy associated HCM. However, limited understanding of HCM progression and correlation with clinical outcomes currently restrict use to a compassionate basis, primarily in infancy. We hypothesize review of RASopathy associated HCM progression and outcomes will demonstrate burden of disease throughout childhood with the goal to identify high risk populations who may benefit from targeted therapies.

Methods:
A single-center retrospective review identified 59 patients with a diagnosis of HCM and a RASopathy. Echocardiographic, clinical, and molecular data were collected through chart review with echocardiographic measurements at set time points from neonate to young adult.

Results:
There was high overall mortality in our cohort (20.3%, n = 12). Cardiac arrest, transplant, or death was significantly higher in patients with heart failure in infancy (defined by need for diuretic use) (p<0.001) (Fig 1A). There were no differences by syndrome or genotype. Pulmonary valve (PV) intervention was 16.9% (n = 10) and largely limited to infancy with median age 0.79 years (IQR 0.34-1.63) at first intervention. Incidence of atrial arrhythmias was 13.6% (n = 8) with median age of onset 0.44 years (IQR 0.35-0.88). Rates of septal myectomy were high (23.7%, n = 14). Myectomies, however, were not limited to infancy with median age at first myectomy 3.10 years (IQR 1.09-10.49) (Fig 1B). 21.4% (n = 3) required repeat myectomy.

Conclusions:
In contrast to previous research, our data suggest there is significant continued HCM growth outside of infancy as evidenced by high incidence of myectomy throughout childhood and young adulthood with frequent need for repeat myectomy. These suggest potential use of targeted therapies outside of infancy with further study needed to identify high-risk populations.
Abstract 11062: Temporal Change of Severity of Atrial Functional Mitral Regurgitation
Authors: Hasegawa Hiroko , Kagawa Shunsuke , Kuwajima Ken , Yamane Takafumi , Shiota Takahiro
Published: June 2023

Introduction:
Left atrial (LA) remodeling due to long burden of atrial fibrillation can cause atrial functional mitral regurgitation (A-FMR). However, longitudinal echocardiographic follow-up of patients with A-FMR has rarely been reported.

Methods:
We retrospectively identified 23 outpatients diagnosed with significant (≥ moderate) A-FMR on transthoracic echocardiography (TTE), with at least two studies performed more than one year apart. A-FMR was defined as 1) left ventricular ejection fraction ≥ 50% without regional wall motion abnormalities; 2) absence of primary valvular pathology; and 3) presence of atrial fibrillation. We excluded patients with significant aortic valve disease or mitral stenosis, treated valvular or congenital disease, any form of cardiomyopathy or carditis, or previous heart transplant. Follow-up was censored at the time of any interventions for valvular disease. The mitral regurgitation (MR) severity was graded based on the current guidelines, and classified as none (0); mild (1+); moderate (2+); moderate-to-severe (3+); or severe (4+). The change (Δ) of the echocardiographic variables between baseline and latest follow-up was assessed.

Results:
The median observation period was 3.4 [interquartile range: 2.6-6.6] years. At baseline, the mean LA diameter was 51 ± 7 mm and MR vena contracta width was 4.4 ± 1.1 mm. As shown in
Figure 1a, 1b
, there was a moderate positive correlation between observation period and Δ LA diameter (r = 0.504, P = 0.014). However, there was no significant correlation between observation period and Δ MR vena contracta width (r = -0.041, P = 0.85). During the observation period, guideline-based MR severity progressed in 4 (17%), unchanged in 12 (52%), and decreased in 7 (30%). The MR severity was not significantly different between baseline and follow-up (P = 0.60) (
Figure 1c
).

Conclusion:
In patients with A-FMR, LA size increased over time, whereas the severity of A-FMR did not progress significantly over time.
Abstract 11087: Impact of Frailty on Short-Term and Long-Term Outcomes Among St-Elevation Myocardial Infarction Patients Receiving Primary Percutaneous Coronary Intervention
Authors: Hosseini Farshad , Pitcher Ian , Kang Mehima , MacKay Martha , Singer Joel , Lee Terry , Madden Kenneth , CAIRNS John A , Wong Graham C , Fordyce Christopher
Published: June 2023

Introduction:
The impact of frailty on short-term and long-term outcomes in a contemporary STEMI population is unclear. We hypothesized that in STEMI patients undergoing primary percutaneous coronary intervention (pPCI) frailty would be independently associated with adverse in-hospital and 1-year outcomes.

Methods:
We retrospectively identified 1,579 STEMI patients aged ≥ 65 years who had received pPCI (2007 - 2020). A frailty index (FI) was determined using the health deficit accumulation model (Table 1). Frail patients were defined as those with a FI > 0.25. The primary outcome was 1-year all-cause mortality. The composite adverse outcome comprised in-hospital all-cause mortality, cardiogenic shock, heart failure, re-infarction, major bleeding, or stroke. A multivariable model adjusting for age, sex, heart failure on presentation, infarct territory, prolonged reperfusion time, initial heart rate, and systolic blood pressure was performed.

Results:
There were 228 (14.4%) frail patients. Compared to non-frail patients, frail patients were older (mean 80.3 vs. 75.3 years, p < 0.001) and had a higher comorbidity burden. After multivariable adjustment, baseline frailty was independently associated with increased 1-year all-cause mortality, in-hospital all-cause mortality, and the composite adverse outcome (Figure 1).

Conclusions:
In conclusion, among STEMI patients receiving pPCI, frailty was common and was independently associated with increased in-hospital and long-term adverse outcomes. These findings raise the need for early recognition of frailty and implementation of a comprehensive care model towards the management of frail patients.
Abstract 11101: Q Fever Endocarditis Combined With Thrombus and Antiphospholipid Syndrome
Authors: Lee Jieun , Yong Hwan Seok , Baek Man-Jong , Na Jin O , Choi Jah Yeon Y
Published: June 2023

A 63-year-old-man presented to our institution with dyspnea. Transthoracic echocardiography (TTE) showed severe degenerative aortic stenosis with regurgitation and decreased left ventricular contractility. Subsequent transesophageal echocardiography (TEE) and cardiac computed tomography (CT) revealed an outpouching structure at aortomitral intervalvular fibrosa (AMIVF) (Fig A to D), which was compatible with pseudoaneurysm and suggested sequelae of previous infective endocarditis. On surgery, thickened AV leaflets were noted, especially on NCC and LCC (Fig E). When extracting the AV leaflets, subannular pouching was seen without evidence of active inflammation or infection (Fig F). AV replacement with 25-mm Sorin Mitroflow was performed.One-year TTE follow-up showed markedly increased transAV pressure gradient. TEE and cardiac CT revealed symmetric nodular thickening of bioprosthetic AV leaflets with opening limitation (Fig G to J). The patient was admitted on the diagnosis of subclinical bioprosthetic valve thrombosis, and anticoagulation with warfarin and aspirin was started. During the hospitalization, the patient had persistent fever with bicytopenia and hepatosplenomegaly, but repetitive blood cultures were negative. There was no definite fever focus even in 18F-FDG PET CT (Fig K). Since the patient worked on a farm in Dangjin, Chungcheongnam-Do, South Korea, where Q fever is prevalent, an indirect immunofluorescence assay for
Coxiella burnetii
was conducted and the result turned out to be positive. Additional coagulopathy laboratory findings showed positive for lupus anticoagulant, anti-cardiolipin IgM, and anti-beta2 GPI IgM. Finally, the patient was diagnosed with Q fever endocarditis combined with antiphospholipid syndrome and treated with doxycycline with hydroxychloroquine and maintained anticoagulation. Recent follow-up of TTE and cardiac CT showed complete resolution of prosthetic AV thrombus.
Abstract 11144: Cardiac Imaging Procedural Volume and Reimbursement Among Medicare Beneficiaries During Covid-19 Pandemic: An Observational Study From 2018 to 2020
Authors: Fath Ayman R , Aglan Amro , Olagunju Abdulbaril , Abraham Bishoy , Eldaly Abdullah S , Kamar Juan , Mihyawi Nawfal , Khurana Aditya
Published: June 2023

Introduction:
The COVID-19 pandemic has had major impacts on all healthcare services, including cardiac imaging. In this study, we investigate annual changes in cardiac imaging procedural volume and reimbursement among Medicare Beneficiaries (MB) from 2018 to 2020.

Methods:
We used the Center of Medicare and Medicaid Services database to identify a 100% sample of MB who underwent cardiac imaging procedures from 2018 to 2020. Using the Current Procedural Terminology (CPT) codes, we identified transthoracic echocardiogram (TTE), transesophageal echocardiogram (TEE), stress echocardiogram, and nuclear stress test procedures. We examined each procedure’s total, inpatient (facility), and outpatient (non-facility) annual volumes per 1,000 MB. We also examined the total annual Medicare reimbursement per imaging type during that period. We compared annual changes in volumes and total reimbursement between two-time intervals: 2018-2019 and 2019-2020.

Results:
All annual cardiac imaging procedural volumes decreased significantly in 2020 compared to 2019 (
P<0.001
). The biggest change was observed in TEE, which decreased by 29.20%, followed by stress echocardiography (26.01%), nuclear stress test (22.96%), and TTE (10.68%). The decrease was more evident in the inpatient setting. Inpatient stress echocardiography decreased by 27.04% (vs 23.82% in the outpatient setting), nuclear stress test decreased by 24.82% (vs 20.66%), and TTE decreased by 11.03% (vs 9.58%). There was also a significant reduction in total annual reimbursement for all procedures in 2020 compared to 2019 (
P=0.0015
). Stress echocardiogram, nuclear stress test, TEE, and TTE reimbursement decreased by 28.08%, 24.00%, 21.11%, and 15.79%, respectively.

Conclusions:
The COVID-19 pandemic was associated with a significant and abrupt reduction in annual cardiac imaging procedural volumes and total reimbursement among MB in both inpatient and outpatient settings.