bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12386: The Prevalence of Coronary Microvascular Dysfunction Among Patients With Low Pretest Probability of Coronary Artery Disease
Authors: Aljizeeri Ahmed H , Ahmed Amjad M , Zayed Mohammed , AlaliAlfaris Mousa , ELNEAMA AWADELKARIM ABDALLA , Suliman Ihab , Al Harthi Mohsen , Alsaileek Ahmed A , Al-Mallah Mouaz
Published: June 2023

Introduction:
Coronary microvascular dysfunction (CMD) is an underdiagnosed cause of chest pain. The 2021 AHA/ACC guidelines do not advocate for testing in patients with chest pain and low pretest probability (PTP <15%) of coronary artery disease (CAD). The prevalence of CMD among patients with low pretest probability is not known. We sought to estimate the prevalence of CMD among patients with chest pain and a low pretest probability of CAD.

Methods:
We reviewed all the patients referred to positron emission tomography myocardial perfusion imaging (PET-MPI) from May 2011 to January 2022. Patients with chest pain and low PTP of CAD who had normal PET-MPI were included in the analysis. Rest and peak myocardial blood flows (MBF) were measured. Coronary flow reserve (CFR) was calculated as a ratio of peak/rest MBF. CMD was defined as CFR of <2.

Results:
1873 patients (age 53.7 ± 9.3 years, 23.6% males) with low PTP and normal PET-MPI were included in the analysis. 372 (20%) patients had MVD. Patients with CMD had lower use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, aspirin, and statin. Diabetes, hypercholesterolemia, and hypertension did not predict CMD. However, female gender (OR: 1.7 95%CI: 1.1- 2.6, p=0.016), age (OR: 1.02 95%CI: 1.00 - 1.04, p=0.023) and BMI (OR: 1.04 95%CI: 1.02 - 1.07, p=0.001) were associated with higher likelihood of MVD.

Conclusions:
Coronary Microvascular Dysfunction is common among patients with chest pain, low PTP of CAD, and normal myocardial perfusion imaging. Females are more likely to have CMD. Further studies are needed to verify the prognostic value of this population.
Abstract 12437: Characteristics and Prognostic Impact of Concomitant Tricuspid Regurgitation in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation
Authors: Osawa Takumi , Sato Kimi , Kawamatsu Naoto , Yamamoto Masayoshi , Machino Tomoko , Hoshi Tomoya , Ishizu Tomoko , Ieda Masaki
Published: June 2023

Introductions:
Previous studies have shown that concomitant presence of tricuspid regurgitation (TR) was associated with poor prognosis in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI). Nonetheless, another report suggested that impact of TR was affected by mitral regurgitation (MR) severity. We aim to investigate the imaging characteristics of concomitant TR according to the MR severity and its prognostic impact in patients who underwent TAVI.

Methods:
We studied 129 patients with severe AS who underwent TAVI from 2015 to 2020 (mean age 84 years; male 33%). We subdivided patients according to the presence of TR and MR (≥ moderate) and compared the imaging characteristics and prognosis.

Results:
Significant TR was observed in 25 patients (19%); among those with TR, 15 had both MR and TR and remaining 10 had only TR (Figure A). Patients with TR showed impaired right ventricular (RV) systolic function and higher tricuspid annulus area and RV end-diastolic volume (p < 0.05 for all). When we further compare the characteristics of patients with TR according to the MR severity, RV systolic function, tricuspid annulus area, or RV volume were similar regardless of the MR severity, while left ventricular (LV) volume was significantly smaller in patients with significant TR alone. During the follow-up, 15 patients experienced all-cause death. Patients with TR alone showed poorer all-cause mortality (Log-rank p = 0.008; Figure B). In multivariable Cox proportional-hazards model, TR was independently associated with all-cause mortality in the absence of MR (hazard ratio 4.94, p = 0.008).

Conclusions:
In patients undergoing TAVI, significant TR was associated with advanced RV remodeling regardless of MR status, while patients who only exhibited TR had less LV remodeling. Concomitant TR was associated with poorer outcome in the absence of MR, indicating that could be an independent risk factor in patients undergoing TAVI.
Abstract 12439: A Systematic Review on the Management and Outcomes of Patients With Mitral Annular Calcification Thrombus
Authors: Cintosun Amber , Belzile David , Orchanian-Cheff Ani , Tsang Wendy
Published: June 2023

Introduction:
Mitral annular calcification (MAC) is a common chronic degenerative process of the mitral valve. Thrombus formation on MAC is a rare complication that is poorly understood and likely contributes to the increased risk of thromboembolic events. We performed a systematic review (PROSPERO 2022 CRD42022299281) to understand the management and outcomes of patients with thrombus on MAC.

Methods:
Medline, Embase, and Cochrane databases (inception to December 2021) were searched to identify studies with MAC thrombus. Patients with prior mitral valve intervention or prosthesis were excluded. The outcomes of interest were treatment, mortality, and thromboembolic events.

Results:
Fifteen studies with 22 cases of MAC thrombus were included (Table 1). The average age at diagnosis was 69.1±14.8 years and 82% were female. Most patients presented with stroke or transient ischemic event (68%) or myocardial infarction (18%). All patients were diagnosed with either transthoracic (82%) or transesophageal (18%) echocardiography. Seventy-seven percent of patients were treated with anticoagulation alone and 23% required surgery. The most common indication for surgery was prevention of recurrent embolization (14%). No mortality was reported. Thromboembolic events after diagnosis occurred in 27%. For those treated with anticoagulation alone, 23% had persistent thrombus with or without embolization.

Conclusions:
This is the first systematic review examining the management and outcomes of patients with MAC thrombus. In patients with MAC who present with a thromboembolic event, careful echocardiographic assessment of MAC to exclude the presence of thrombus should be performed. While most patients can be managed with anticoagulation alone, a significant number will require surgery. Persistent thrombus despite anticoagulation and recurrent embolization are common. Larger studies are needed to elucidate the optimal long-term care for these patients.
Abstract 12442: A Systematic Review And Network Meta-analysis In HfpEF Pharmacologic Treatment
Authors: Zafeiropoulos Stefanos , Farmakis Ioannis , Milioglou Ioannis , Doundoulakis Ioannis , Stavrakis Stavros , Giamouzis Grigorios , Butler Javed , Giannakoulas George
Published: June 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) remains a highly prevalent condition with significant morbidity and mortality but limited treatment options. Sodium glucose cotransporter-2 inhibitors (SGLT2i), angiotensin-receptor neprilysin inhibitors (ARNi) and mineralocorticoid receptor antagonists (MRA) are moderately to weakly guideline supported. Yet, the potential gain with combination therapies has not been elucidated.

Hypothesis:
This study sought to estimate and compare the aggregate treatment benefit of medical therapies for HFpEF.

Methods:
We performed a systematic reviewed and network meta-analysis, using MEDLINE, Cochrane, and the Web of Science databases for randomized controlled studies from inception to May 2022. We included patients with heart failure and left ventricular ejection fraction >40%, treated with any of the following therapies: angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), beta-blockers (BB), MRA, digoxin, ARNi, SGLT2i, and vericiguat. Our analysis assumed additive benefits of each therapy. The primary outcome was a composite of cardiovascular (CV) death and hospitalization for heart failure (HHF); secondary outcome was all-cause mortality.

Results:
We identified 14 studies with a total of 26,556 patients, mean age 71 (±8.8), 49% females and mean ejection fraction of 57% (±8%). Mean follow-up time was 24 months. MRA and SGLT2i, were the individual components that reduced the primary outcome [HR =0.82 (95% CI 0.67-0.99 and 0.78 (95% CI 0.68 - 0.91), respectively], while the combination of ACE-i/ARB, BB, MRA and SGLT2i was the only beneficial [HR 0.53 (95% CI 0.30 - 0.95]. None of the explored combinations or individual components were associated with decreased all-cause mortality.

Conclusions:
In patients with HFpEF, MRA and SGLT2i alone as well as a combination of ACE-i/ARB, BB, MRA and SGLT2i were associated with decreased risk of CV mortality and HHF.
Abstract 12468: Hemodynamic Validation of Echocardiographic Left Ventricular to Left Atrial Volumes Ratio Indices in Heart Failure With Preserved Ejection Fraction
Authors: Palka Przemyslaw , Hilling-Smith Roland , Swann Rohan , Allwood Sean , Moore Alexander , Bian Chris , Lange Aleksandra
Published: June 2023

Introduction:
The assessment of mean left atrial (LA) pressure rather than Left Ventricular (LV) end-diastolic pressure reflects more accurately filling pressure which is pathophysiological landmark of Heart Failure with preserved Ejection Fraction (HFpEF).

Hypothesis:
We sought to test whether the measurement of LV to LA volume ratio at the specific cardiac phases can estimate resting LA pressure in patients with HFpEF.

Methods:
Fifty-three HFpEF patients (mean age 71+-10 years) who underwent cardiac catheterization including direct, at rest, retrograde LA pressure, were analysed. Echocardiographic data was obtained 1.5+-1.0 hours off cardiac catheterization. Patients were divided into: Group 1 (normal filling pressure) and Group 2 (elevated filling pressure, mean LA pressure >12mmHg and/or pulmonary capillary wedge pressure 14mmHg). The ratio of LV/LA volume was measured in end-systole (LV
ES
/LA
max
), end-diastole (LV
ED
/LA
min
), diastasis (LV
dias
/LA
dias
), and as both maximum (LV
ED
/LA
max
), and minimum (LV
ES
/LA
min
).

Results:
All measured LV/LA ratios were lower in Group 2 as compared to Group 1 and correlated inversely with an increased LA pressure (LV
ED
/LA
min
, r=-0.54, p<0.001; LV
ES
/LA
min
, r=-0.53, p<0.001; LV
ED
/LA
max
, r=-0.52, p<0.001; LV
dias
/LA
dias
, r=-0.50, p<0.001; LV
ES
/LA
max
, r=-0.37, p=0.013. The following ratios, LV
dias
/LA
dias
, LV
ED
/LA
max
, LV
ED
/LA
min
, and LV
ES
/LA
min
, were the most accurate echocardiographic indices to differentiate HFpEF patients between Group 2 and Group 1 (independently off the presence atrial fibrillation), with the area under the curve >0.75 and statistically noninferior to the following a new LA function parameters such as: LA reservoir strain, index LA reservoir strain, LA total emptying fraction and LA active emptying fraction. The cut-off values for LV
ES
/LA
min
<1.45 and LV
dias
/LA
dias
<1.30 had the sensitivity 78%, 74% and specificity 71%, 71%, respectively, to differentiate patients between Group 2 and Group 1.

Conclusions:
Among all studied echocardiographic indices the LV
ES
/LA
min
and LV
dias
/LA
dias
were the most accurate parameters to assess the level of LA pressure in HFpEF.
Abstract 12497: Pulmonary Embolism Mortality Prediction With Deep Learning Based on Computed Tomographic Pulmonary Angiography and Clinical Data
Authors: Fayad Fayez H , Zhong Zhusi , Sollee John , jiao zhicheng , Bai Harrison , Atalay Michael
Published: June 2023

Introduction:
Pulmonary embolism (PE) is a significant cause of mortality in the United States. We aimed to develop deep learning models using computed tomographic pulmonary angiography (CTPA) and clinical data to predict mortality in patients with PE.

Hypothesis:
Deep learning models based on CTPA and clinical data will outperform PE Severity Index (PESI) in predicting PE mortality.

Methods:
A total of 927 patients (163 deceased, median age 64, range 13-99, 52% female) and 3978 total CTPAs were identified via retrospective review across three institutions. Data from one institution were randomly split 7:1:2 into training, validation, and internal testing sets. Data from the two remaining institutions were used as an external testing set. Imaging features extracted from PEnet and clinical data (PESI variables) were used to train Random Survival Forest models. Performance was evaluated with concordance index (c-index) and compared to PESI predictions with the Wilcoxon signed-rank test. Kaplan-Meier analysis was performed by stratifying patients into high- and low-risk groups based on the combined imaging and clinical model prediction.

Results:
Models based on (a) imaging, (b) clinical, and (c) combined imaging and clinical data achieved c-index values of 0.761, 0.774, and 0.843, respectively, on the internal testing set, and 0.660, 0.713, and 0.722 on the external testing set. For both data sets, the combined model outperformed PESI (0.740 and 0.709, respectively, both p<0.001). When stratifying patients into high- and low-risk groups, mortality outcomes were significantly different (p<0.001, Figure).

Conclusions:
Deep learning models based on combined CTPA features and clinical data outperform PESI for mortality prediction in PE. The addition of imaging to clinical features improves performance compared to clinical features alone.
Abstract 125: Kidney-specific Biomarkers For Predicting Acute Kidney Injury Following Cardiac Arrest
Authors: Berlin Noa , Pawar Rahul , Grossestreuer Anne V , Issa Mahmoud S , Silverman Jeremy , Shekhar Aditya , Cole Andrew , Liu Xiaowen , Roessler Lara L , Holmberg Mathias Johan , Donnino Michael , Moskowitz Ari
Published: June 2023

Introduction:
Acute kidney injury (AKI) is a common complication following cardiac arrest (CA) and is associated with poor outcomes. Early detection of AKI is crucial; serum creatinine (sCR) is the most commonly used indicator of AKI, despite low sensitivity and specificity for early detection of AKI.

Hypothesis:
Kidney-specific serum biomarkers neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C could better predict post-CA AKI than sCR.

Methods:
Adult CA patients who had kidney-specific biomarkers of AKI collected shortly after return of spontaneous circulation (ROSC) as part of four randomized trials and one observational study were included. Patients with Kidney Disease Improving Global Outcome (KDIGO) stage III AKI or end-stage renal disease, or renal replacement therapy at the time of enrollment were excluded. The association between renal biomarker levels (sCR, NGAL, KIM-1, cystatin-C) shortly after ROSC and the development of KDIGO stage III AKI within 7 days of enrollment were assessed as well as their predictive value of future AKI development.

Results:
Of 155 patients, 46 (29.7%) developed stage III AKI within 7 days, and 98 (63.2%) died prior to hospital discharge. Patients who developed stage III AKI, compared to those who did not, had higher median levels of sCR (1.4 mg/dL [IQR: 1.2, 1.9] vs. 1.2 [IQR: 1.0, 1.5]; p=0.001), NGAL (868,208 pg/mL [IQR: 412,547.1, 1,341,597] vs. 298,928.3 [IQR: 170,786.6, 594,389.7], p<0.001). and cystatin-C (1,649,202 pg/mL [IQR: 1,184,788, 2,440,583] vs. 1,132,955 [IQR: 795,323.7, 1,580,415]; p<0.001). There was no difference in KIM-1 between groups (150.6 pg/mL [IQR: 150.8, 288.4] vs. 158.9 [IQR: 78.8, 284.7]; p=0.351). There was no significant difference between biomarkers in their ability to predict development of stage III AKI (NGAL AUC=0.75 [95%CI: 0.67-0.83], cystatin-C AUC=0.71 [95%CI: 0.62-0.79], KIM-1 AUC=0.55 [95%CI: 0.45-0.65], sCR AUC=0.67 [95%CI: 0.57-0.76], p>0.05 for all). Both NGAL and cystatin-C performed better than KIM-1 (p<0.01).

Conclusion:
In post-CA patients, sCR, NGAL, and cystatin-C (but not KIM-1) measured shortly after ROSC were higher in patients who subsequently developed AKI. No biomarker was statistically superior to sCR. Comparison was limited by the small number of patients who developed AKI.
Abstract 12544: Sex Differences in Cardiac Catheterization Outcomes Among Black Patients in an Urban Center
Authors: Weze Kelechi O , Asangmbeng Nformbuh , Chang Eric Y , Amah Chidi , Taha Yasir , Echols Melvin
Published: June 2023

Introduction:
Sex disparities persist in the management of CAD. Although between-racial and ethnic group disparities continue to exist, there are limited data regarding intra-race sex differences within African American (AA) populations. Thus, we describe the sex differences in outcomes among Black patients receiving left heart catheterization (LHC) in a large urban medical center (UMC).

Methods:
Using electronic health data, we extracted data of AA patients (pts) undergoing LHC between January 2014 to December 2019 from an UMC. Baseline demographics and management were compared between men and women. The primary outcome of interest was percutaneous coronary intervention (PCI), with secondary outcomes of coronary artery bypass graft (CABG) and Intra-aortic balloon pump (IABP). Outcomes were analyzed with chi-square testing and multivariable regression.

Results:
There were 3,379 LHC performed (42% in women). Men were relatively younger compared to women (63±11 vs 65±12, p<0.001), had lower BMI (29±8 vs 33±9, p<0.001), EF (45±15 vs 50±15, p<0.001), and rates of health insurance (59% vs 66%, p<0.001). Women had higher rates of dyslipidemia (42% vs 33%, p<0.001), hypertension (87% vs 83%, p=0.001), and Type II DM (43.6% vs 33.6%, p<0.001), but lower rates of smoking (30.5% vs 45%, p<0.001). Men also had higher rates of STEMI 12.8% vs 5.2% and NSTEMI 29.6% vs 28.7% (P<0.001). Men were more likely to receive PCI (40.5% vs 34.5%, p<0.001), CABG (4.6% vs 2.3%, p=0.001), and IABP (2.1% vs 0.5%, p=0.001). After multivariable regression, men had higher odds of PCI (OR=1.15, p=0.15), CABG (OR=2.4, p=0.001), and IABP (OR=5.5, p=0.002).

Conclusions:
In this cohort of AA pts receiving LHC at an urban center, men were more likely to undergo interventions including PCI, CABG, and IABP as compared to women. Even among AA populations, significant sex differences occur. More work is needed to understand underlying factors and address healthcare disparities in this high-risk population.
Abstract 12556: Prevalence of Hypertension and Left Ventricular Hypertrophy in Adolescents Following Left Ventricular Outflow Tract Obstruction Repair
Authors: Walsh Aaron , Hor Kan N , Lee Marc , Lee Simon , Tran Andrew H
Published: June 2023

Introduction:
Left ventricular outflow tract obstructions predispose patients to increased lifetime risk of cardiovascular events even after successful repair (rLVOTO). Left ventricular hypertrophy (LVH) is an adaptive response to elevated afterload and is a predictor of cardiovascular events in adulthood. The prevalence of elevated blood pressure (SBP) and LVH in youths with rLVOTO is limited.

Methods:
Retrospective analysis of rLVOTO patients between 2012-2019, age 13-17 years with documented body mass index (BMI), SBP, LVOT velocity and left ventricular mass indexed to height (LVMi). Moderate LVOTO was defined as peak velocity ≥ 3 m/s. Patients categorized into normotensive (NT, SBP < 120 mm Hg), elevated (E-BP, 120 ≤ SBP < 130 mm Hg), Stage 1 HTN (HTN-1, 130 ≤ SBP < 140 mm Hg) and Stage 2 HTN (HTN-2, SBP ≥ 140 mm Hg). Prevalence of LVH

was reported in each group (pediatric cutoff of LVMi-HT
2.7
≥ 38.6 g/ht
2.7
).

Results:
A total of 193 patients met criteria (age 15.6 ± 1.4 years), 135/193 (70%) male, SBP 120±13 mm Hg, and LVMi-HT
2.7
36.2±9.8 g/ht
2.7
. Half were in the NT group (93/193 (48%)), 55/193 (28%) in E-BP, 32/193 (17%) in HTN-1, and 13/193 (7%) in HTN-2 with no difference in BMI. Prevalence of LVH increased with higher SBP with 24/93 (26%) in NT, 21/55 (38%) in E-BP, 14/32 (43%) in HTN-1, and 4/13 (31%) in HTN-2. 124/193 (64%) had no residual LVOT gradient, 69/193 (36%) with residual LVOT gradient. 52/69 (75%) had LVOT < 3 m/s, of these 12/52 (23%) had ≥ HTN-1. 17/69 (25%) had residual LVOTO ≥ 3 m/s, of these 6/17 (35%) had ≥ HTN-1. No difference in LVMi found between no or mild LVOTO groups (35.9±13 vs 35.6±10 g/ht
2.7
, p = NS). Higher LVMi was found in the LVOTO ≥ 3 m/s group (41.5±13 g/ht
2.7
, p = 0.01 compared to both no or mild LVOTO).

Conclusions:
Youths with rLVOTO have a high prevalence of elevated BP, HTN, and LVH. When stratified by LVOTO severity, presence of ≥ HTN-1 was common with increased LVMi. No difference in BMI was observed among abnormal SBP groups suggesting BMI is not solely responsible for the increased LVMi. Longitudinal studies are needed to define the impact of rLVOTO and HTN on LVH over time. Our findings support early surveillance and management of hypertension in patients following LVOTO repair to help minimize the risk of future cardiovascular events related to LVH.
Abstract 12584: The Role of Toll-Like Receptor 3 in the Development of Aortic Valve Stenosis
Authors: Willemsen Nicola , Niepmann Sven , Boucher Ann Sophie , Nickenig Georg , Zimmer Sebastian
Published: June 2023

Background:
Our current concept of aortic valve stenosis (AS) development suggests that local chronic inflammation drives fibrosis and calcification of the valve cusps. This remodeling is driven by endothelial to mesenchymal transition (EndMT) of valvular endothelial cells (VECs) and by calcification of valvular interstitial cells (VICs). In a preliminary screening, we found Toll-like receptor 3 (TLR3) expression increased in human AS samples. Therefore, aim of this study was to investigate the role of TLR3 in the pathogenesis of AS.

Methods/Results:
We confirmed TLR3 expression in cultured human VICs and VECs. Upon specific TLR3 stimulation with PolyI:C, both VICs and VECs displayed a positive feedback with increased TLR3 expression. Concomitant treatment of PolyI:C-stimulated VICs and VECs with the TLR3/RNA complex inhibitor (C4a) significantly blunted this response. Importantly, the TLR3-mediated pro-inflammatory and calcifying response of VICs and EndMT by VECs was significantly reduced by TLR3-inhibtion with C4a.To examine the role or TLR3 in AS development, a wire injury induced AS mouse model was used. Valves were explanted and stained with hematoxylin/eosin, Sirius red, von Kossa, or anti CD68. PolyI:C treatment promoted AS, as demonstrated by increased valve cusp thickness and pronounced valvular inflammation. Interestingly, AS development was nearly absent in TLR3 deficient mice suggesting a critical role of endogenous TLR3 ligands in this model. Treatment of mice with C4a after wire-injury of the aortic valve significantly reduced both morphological and functional parameters of AS development.

Conclusion:
These findings not only support the role of endogenous TLR3 activation in the development of AS but suggest that specific TLR3 inhibition might be beneficial for the treatment or prevention of AS. Further studies are required to decipher the exact mechanisms how TLR3 contributes to AS.
Abstract 12625: Genome-Wide Analysis Revealed Genetic Control of the Renin-Angiotensin-Aldosterone System in the General Population
Authors: Arisido Maeregu Woldeyes , Foco Luisa , König Eva , Zennaro Maria-Christina , Poglitsch Marko , Pramstaller Peter P , Fuchsberger Christian , Pattaro Cristian
Published: June 2023

Introduction:
The Renin-Angiotensin Aldosterone system (RAAS) is the major player in the long-term blood pressure (BP) regulation. The RAAS is targeted by commonly used anti-hypertensive drugs, but despite its importance, little is still known about its genetics, partially due to the technical difficulties in the quantification of the involved biomarkers.

Methods:
Using mass-spectrometry, we simultaneously quantified in serum equilibrium angiotensin I, angiotensin II and aldosterone on 2105 participants to the Cooperative Health Research In South Tyrol study (CHRIS), who were either normotensive or under documented anti-hypertensive drug (AHD) treatment. We derived proxies of renin activity (PRA-S= angiotensin I + angiotensin II), angiotensin-converting enzyme activity (ACE-S= angiotensin I / angiotensin II) and adrenal gland function (AA2-ratio =aldosterone/ angiotensin II). We tested association of these biomarkers with 1,085,897 SNPs imputed against a population specific whole-exome-sequencing-based panel, adjusting for age, sex, AHD, and assuming an additive genetic model using Regenie v3.1.1.

Results:
Study participants were 21 to 95 years old, and 52% were females. Most participants (86%) received specific AHD treatments. ACE-S was associated with variants spanning the ACE gene. The top association was seen at rs4363 (p=2.8E-18), already associated with serum ACE level, and replicating previous findings in an Asian population sample. We found strong evidence of association of angiotensin II and AA2-ratio with the stop gained rs27044 (p=8.2E-10) in the ERAP1, involved in angiotensin II degradation. We observed a borderline association between aldosterone and the synonymous rs7275 at SMARCA4/LDLR (p=5.85E-8), previously related to lipid metabolism. We also report a novel suggestive association between angiotensin I and rs2274978 in the Xaa-Pro aminopeptidase I (XPNPEP1; p=9.49E-6).

Conclusions:
While some results await replication in an independent cohort, findings are consistent with known physiology, and shed light on genetic background of BP regulation.
Abstract 12628: Evaluation of Time From Pre-Hospital Symptom Onset to Angiography on Coronary Artery Occlusion Status and Outcomes in Patients Presenting With NSTE-ACS
Authors: Suba Sukardi , Carey Mary G , Pelter Michele M
Published: June 2023

Introduction:
Current guidelines for invasive coronary angiography (ICA) in patients presenting with NSTE-ACS outline two treatment pathways: early (within 24 hours [hrs]); or late (>24 hrs). Time of hospital admission is used as the start time, however, we hypothesize that pre-hospital time of symptom onset may be a more optimal starting time. This study was designed to test optimal symptom onset-to-angiography time (OAT) and its association with the presence of coronary occlusion and adverse outcomes.

Methods:
Secondary data analysis in NSTE-ACS patients (pre-COVID-19) who underwent ICA. We tested the optimal cutoff point of OAT in classifying coronary occlusion using Youden-index analysis. We tested the association of OAT and in-hospital complication (i.e., myocardial infarction [MI] after admission, unplanned transfer to the cardiac intensive care unit, pulmonary edema, cardiogenic shock, dysrhythmia with intervention) and hospital length of stay [LOS]) using regression models.

Results:
In 163 patients: 124 (76%) had an occluded artery; 37 (23%) had an in-hospital complication. Overall, the mean OAT was 26±22 hrs (24±22 vs. 31±21, with and without occluded artery, respectively), and the median LOS was 55 hrs. The Youden-index optimum OAT cutoff point was 13.4 hrs. In the two logistic models, the adjusted OAT was associated with the presence of coronary occlusion (Figure A). OAT, as a continuous variable, was associated with LOS (
β
=0.64, 95% CI 0.08-1.21,
p
=0.025), no other in-hospital complications were significant (Figure B).

Conclusions:
In patients presenting with NSTE-ACS, OAT at both 13.4 and <24 hrs is a significant predictor of the presence of coronary artery occlusion. Every hour of delayed OAT was associated with a prolonged hospital LOS 0.64 hrs (38 min). Symptom onset appears to be an important starting point in determining optimal timing of ICA in patients with NSTE-ACS, but requires further study with a large sample of patients.
Abstract 12642: Protamine Administration in Patients Undergoing Percutaneous Left Atrial Appendage Occlusion
Authors: Alex Jacob , Nicholson Chad , Aina Deborah , Banthiya Sukriti , Mckenna Shane , Machado Christian
Published: June 2023

Introduction:
Intravenous protamine sulfate is widely used to reverse anticoagulation after structural heart interventions. Protamine is currently designated as in shortage by the US FDA, and its use has potential adverse events such as anaphylaxis, thrombosis, and stroke. There is limited data on the safety and efficacy of heparin reversal with protamine after left atrial appendage occlusion (LAAO).

Hypothesis:
We hypothesize that patients who received protamine for heparin reversal after percutaneous LAAO have no changes in bleeding complication rates versus patients who did not receive protamine.

Methods:
This retrospective study included 242 atrial fibrillation patients with a high risk of stroke and bleeding who received percutaneous LAAO between January 2020 and November 2021. The primary outcome assessed was life-threatening, disabling, or major bleeding within 48 hours following the procedure. Secondary outcomes included major adverse cardiac events (MACE) within 48 hours, minor bleeding events, MACE, device-related thrombosis or pericardial effusion within 45 days, and RBC transfusions. Patients with peri-procedure complications including pericardial effusion and/or thrombosis were excluded. Baseline characteristics were compared between both cohorts.

Results:
No significant difference in the primary outcome was observed between patients who received protamine compared to those who did not (5.8% vs 4.9%, p-value 0.57). There was significantly more minor bleeding in patients who did not receive protamine (0.6% vs 4.9%, p-value 0.05). MACE within 48h following the procedure, MACE, device-related thrombosis or pericardial effusion within 45 days, and RBC transfusions were comparable between the two cohorts, as described in table 2.

Conclusions:
Protamine administration for heparin reversal did not affect rates of life-threatening, disabling, or major bleeding complications in patients who underwent percutaneous LAAO.
Abstract 12644: Multiple Spontaneous Coronary Artery Dissections in a Middle-Aged Man With Acute Chest Pain
Authors: sharma arushi , Sharma Nitish , Alampoondi Venkatarmanan Sai Vikram , shah neeta
Published: June 2023

Introduction:
Previously considered rare, spontaneous coronary artery dissection (SCAD) has emerged as an important cause of chest pain, acute coronary syndrome, and sudden cardiac death. Due to hormonal factors, SCAD often affects seemingly healthy women. SCAD in men remains little understood and under-recognized. We report a case of a 61-year-old gentleman who presented with NSTE-ACS and was found to have SCAD.

Patient Presentation:
A 61-year-old male with history of untreated hyperlipidemia presented with acute substernal chest pressure radiating to bilateral arms and back. On presentation, vitals and physical examination was normal.His labs showed troponin I at 0.015 ng/mL which later up trended to 21.7 ng/ml. ECG demonstrated sinus bradycardia with no ischemic changes. Decision was made to take him for cardiac catheterization.It demonstrated right coronary artery (RCA) was ecstatic. Distally, there was a a right conus branch fistula draining into pulmonary artery. There was evidence of microvascular dysfunction. An echocardiogram showed mid and basal inferolateral akinesis, normal EF.He was started on dual anti platelets (DAPT) and GDMT. At the time of discharge, he started having recurrence of his chest pain with exertion. Cardiac CT showed multiple spontaneous coronary artery dissections with healing dissections and remodeling throughout the ecstatic RCA and its distal branches with additional contour irregularities and non-obstructive dissection flaps in the diagonal branch of the left anterior dissecting artery. He was enrolled into cardiac rehabilitation.

Conclusion:
SCAD occurs by the formation of an intramural hematoma or intimal disruption causing a coronary obstruction. Coronary angiography remains the primary tool in the diagnosis. Alternative imaging modalities, such as intravascular ultrasound and optical coherence tomography, CT coronary angiography can be used to confirm the diagnosis. It is managed medically with DAPT and adequate control of blood pressure. Cardiac rehabilitation appears to be beneficial in preventing recurrence. We would also like to emphasize that SCAD can occur in any age group and gender, it’s crucial to recognize it early and is a condition that can be managed conservatively.
Abstract 12655: Lipomatous Metaplasia in Chronic Infarcts is Associated With Prolonged Activation Recovery Interval Within Ventricular Tachycardia Corridors
Authors: Xu Lingyu , Zahid Sohail , Pourmousavi Khoshknab MirMilad , Moss Juwann , Berger Ronald D , Chrispin Jonathan , Callans David J , Marchlinski Francis E , Zimmerman Stefan , Han Yuchi , Desjardins Benoit , Trayanova Natalia , Nazarian Saman
Published: June 2023

Introduction:
We studied the association of infarct scar versus lipomatous metaplasia (LM) with the activation recovery interval (ARI) in putative ventricular tachycardia (VT) corridors traversing the infarct zone.

Methods:
The cohort included 32 patients from the prospective Intra-Myocardial Fat Deposition and Ventricular Tachycardia in Ischemic Cardiomyopathy (INFINITY) study. We defined myocardial scar, border zone (BZ) and potential viable corridors through infarct by late gadolinium enhancement (LGE)-cardiac magnetic resonance (CMR), and LM by computed tomography (CT). The images were registered with electroanatomic maps wherein the ARI of each point (1,530 within LM, 4,946 within scar) was calculated using a custom Python code as the time interval from the minimum derivative within the QRS to the maximum derivative within the T wave. ARI dispersion was defined as the standard deviation (SD) of ARI per AHA segment. Multilevel random effects linear regression models, clustered by patient, were used to evaluate the association between ARI (or ARI dispersion) with tissue types.

Results:
LM exhibited higher myocardial ARI than normal myocardium, BZ, scar [regression coefficient: 35.5 vs. 0, 11.4, and 25.4,
P
<0.001]. Of 100 corridors computed from LGE-CMR and electrophysiologically confirmed to participate in VT reentry, 97 traversed through or near LM, and displayed prolonged ARI compared to 123 non-critical corridors distant from LM [356 (319, 396) vs. 283 (266, 316) ms, P <0.001, Figure 1]. The association of LM with Log(ARI
SD
) was more robust than that of scar (likelihood ratio χ
2
47.5 vs. 23.4, and 5.9% vs. 1.6% increase in Log(ARI
SD
) /1 cm
2
increase per AHA segment, respectively). Additionally, LM and scar exhibited interaction (p<0.001) in their association with Log(ARI
SD
).

Conclusion:
LM is closely associated with prolonged local action potential duration of corridors and ARI dispersion, which may facilitate the propensity of VT circuit reentry.
Abstract 12671: Weight Loss Improves Cardiometabolic Health as Measured by Plasma Proteins in Individuals With Type 2 Diabetes
Authors: Sattar Naveed , Taheri Shahrad , Welsh Paul , Astling David , Chadwick Jessica , Hinterberg Michael , Troth Emma , Ostroff Rachel , Zaghloul Hadeel , Chagoury Odette , Taylor Roy , Lean Michael , Williams Stephen A
Published: June 2023

Introduction:
The DiRECT (UK cohort) and DIADEM-1 (Middle Eastern/North Africian cohort) trials in patients with type 2 diabetes demonstrated average weight loss of >10kg spurred by dietary intervention led to 46-61% diabetes remission at 12 months. Here we investigated cardiometabolic outcomes of these cohorts using predictive proteomic SomaSignal
®
tests.

Methods:
Eight cardiometabolic SomaSignal tests (each derived from ~5000 plasma proteins measurements using aptamer-based proteomics assay) related to cardiometabolic health were assessed in baseline and 1-year samples in intervention (DiRECT n=118, DIADEM-1 n=66) and control (DiRECT n=144, DIADEM-1 n=76) participants.

Results:
Despite differences in baseline characteristics (age, ethnicity, diabetes duration, cardiovascular (CV) risk factors), both intervention groups showed similar improvements in overall cardiometabolic outcomes (Figure). Seven SomaSignal tests in DiRECT and six SomaSignal tests in DIADEM-1 significantly improved in the intervention groups compared to respective control arms. Liver fat, glucose intolerance, body fat percentage, resting metabolic rate, visceral fat, and cardiorespiratory fitness predictions significantly improved in intervention arms of both trials with greater relative improvements seen in individuals that lost >10kg. Additionally, CV risk improved significantly in the DiRECT intervention arm (which had higher baseline CV risk compared to DIADEM-1), as well as in both trials among individuals lost >10kg.

Conclusion:
Proteomic changes suggest widespread improvement in cardiometabolic traits, including CV risk, across both trials of intentional weight loss in individuals with type 2 diabetes. Notably, greater relative improvements in all traits including CV risk were seen in individuals that lost >10kg. These data suggest large intentional weight loss will improve future CV outcomes.
Abstract 12678: Steroids versus Steroid-Sparing Agents in Cardiac Sarcoidosis: A Retrospective Analysis of Clinical Outcomes
Authors: Montes Angela , James Walter , Burt Jeremy R , Rieter William , Rissmiller Richard , Winterfield Jeffrey , Griffin Jan , Houston Brian
Published: June 2023

Introduction:
Equipoise remains on whether initial therapy for cardiac sarcoidosis (CS) should consist of corticosteroids alone or include steroid-sparing agents (SSAs). This study retrospectively assessed outcomes of CS patients initially treated with prednisone only versus SSAs +/- prednisone.

Hypothesis:
We hypothesized that initial therapy inclusive of SSAs would be associated with reduced adverse outcomes.

Method:
We performed a retrospective review of CS patients seen at the MUSC Pearlstine Sarcoidosis Center of Excellence in the preceding year. The patients were divided into two cohorts: the prednisone group was defined as patients taking only prednisone for
>
3 months as initial therapy of CS. The SSA group was defined as patients taking SSAs (methotrexate or MMF) +/- prednisone within three months of initial therapy for CS. Cardiovascular outcomes after CS diagnosis were compared between the groups.

Results:
We included 107 patients for analysis (37 prednisone; 70 SSA (53% methotrexate, 47% MMF)). Patients in the SSA group were 77% less likely to develop heart failure with reduced ejection fraction (RR 0.23, p=0.0001), 72% less likely to develop heart failure with preserved ejection fraction (RR 0.28, p=0.001), 62% less likely to be hospitalized for heart failure (RR 0.38, p=0.02), 77% less likely to be hospitalized for ventricular tachycardia (RR 0.23, p=0.01), 60% less likely to develop ventricular arrhythmias (RR 0.4, p=0.003), 80% less likely to experience an ICD shock (RR 0.2, p=0.005), and 50% less likely to develop heart block requiring a pacemaker (RR 0.5, p=0.01) than the prednisone group (see Figure).

Conclusions:
In this study of CS patients, early therapy inclusive of SSAs was associated with significantly reduced heart failure and arrhythmia risks. Our study suggests that early therapy for CS should include SSAs. Future investigations in these cohorts will focus on between-group comparisons to assess for potential confounding factors.
Abstract 12692: Central Sensitization in Women With Ischemia and No Obstructive Coronary Artery Disease: A Pilot Study
Authors: Dave Esha K , Thandra Sneha , Harper Daniel E , singh vinita , Ahuja Avni , Leon Ana , Schwartz Arielle , Rashid Fauzia , Kimble Laura P , Mehta Puja K
Published: June 2023

Introduction:
Myocardial ischemia with no obstructive coronary arteries (INOCA) is more common in women and associated with adverse cardiovascular outcomes. INOCA patients have recurrent chest pain and reduced quality of life, and therapeutic strategies are poorly defined. Central nervous system factors can promote and maintain spontaneous clinical pain. We explored central sensitization in INOCA.

Methods:
Twenty-nine women diagnosed with INOCA based on coronary angiography were enrolled. Baseline demographics, risk factors, and angina burden by the Seattle Angina Questionnaire (SAQ) was assessed. Generalized pain hypersensitivity was assessed using the validated Central Sensitization Inventory (CSI), with scores ≥40 indicating the presence of central sensitization. Functional capacity was determined by Duke Activity Status Index (DASI). A DASI score ≤34 is prognostic of major adverse cardiac events. Depressive symptoms were assessed using the Beck Depression Inventory. Descriptive statistics and Pearson correlations were performed; p-value ≤.05 was considered significant.

Results:
Mean age was 55.4±10 years and body mass index (BMI) was 30.1±7 kg/m
2
.
Cardiac risk factors were prevalent with 59% hypertension, 55% hyperlipidemia, and 21% diabetes. SAQ scores indicated a high angina burden: 49.3±25.7 (angina frequency) and 39.3±27.6 (angina stability). Mean CSI score was 40.5±17, and 62% had CSI scores ≥40, indicating central sensitization. Mean DASI score was 33.3±18.6. A majority (52%) had a DASI score ≤34, indicative of guarded prognosis. CSI scores correlated positively with depression (r=0.78, p=0.00001) and BMI (r=0.39, p=0.04), and negatively with DASI (r=-0.36, p=0.05), indicating impaired physical functioning in those with higher levels of central pain sensitivity.

Conclusions:
Nearly two-thirds of women with INOCA have central sensitization. Central pain amplification is associated with angina, depression, obesity, and a limited functional capacity in mid-life INOCA women. The role of the central nervous system in persistent chest pain should be further investigated and may lead to novel therapeutic strategies.
Abstract 12703: Transthyretin Amyloid Cardiomyopathy Among Patients Hospitalized for Heart Failure and Performance of an Adapted Wild-Type ATTR-CM Machine Learning Model: Findings From GWTG-HF
Authors: Peters Anthony , Solomon Nicole , Chiswell Karen , Fonarow Gregg C , Khouri Michel G , Schepart Alex , Baylor Lori , Alvir Jose , Bruno Marianna , Huda Ahsan , Allen Larry A , Sharma Kavita , Devore Adam D , Greene Stephen J
Published: June 2023

Introduction:
An 11-factor random forest model has been previously developed among ambulatory patients for identifying potential wild-type amyloidogenic TTR cardiomyopathy (wtATTR-CM), but model performance in a large sample of patients hospitalized for HF has not been evaluated.

Methods:
This study included Medicare beneficiaries hospitalized for HF in the Get With The Guidelines-HF® Registry from 2008-2019. Patients with and without a diagnosis of wtATTR-CM were compared. ICD9/10 codes were used as proxies to identify wtATTR-CM patients on inpatient/outpatient claims within ±6 months of hospitalization. Within a cohort matched 1:1 by age and sex, univariable logistic regression was used to evaluate relationships between each of the 11 factors of the established ATTR-CM model and wtATTR-CM. Discrimination and calibration of the 11-factor model was assessed.

Results:
Among 205,545 patients hospitalized for HF across 608 US hospitals, 627 patients (0.31%) had a diagnosis code for wtATTR-CM. wtATTR-CM patients were more likely to be male (69% vs 47%), Black race (23% vs 9%), and had lower systolic blood pressure (median 124 vs 139 mmHg). Univariable analysis within the 1:1 matched cohort of each of the 11-factors in the wtATTR-CM model found pericardial effusion, carpal tunnel syndrome, lumbar spinal stenosis, and elevated serum enzymes (e.g., troponin elevation) to be strongly associated with wtATTR-CM (
Figure, Panel A
). The 11-factor model showed modest discrimination with c-statistic of 0.65 (
Figure, Panel B
), with good calibration within the matched cohort (
Figure, Panel C
).

Conclusions:
Among patients hospitalized for HF in US practice, the number of wtATTR-CM as defined by diagnosis codes was low. Patients with a diagnosis of wtATTR-CM have a distinct clinical profile, and most factors within the prior 11-factor model were associated with greater odds of wtATTR-CM diagnosis. In this population, the wtATTR-CM model demonstrated modest discrimination.
Abstract 12704: Race And Quality of Life Among Patients With Heart Failure—A Serial Multiple Mediator Model
Authors: Wu Jiarong , Moser Debra K , Lin Chin-Yen , Chiang Ambrose A , Riegel Barbara J
Published: June 2023

BACKGROUND:
Black patients have worse quality of life than Whites. Depression and sleep quality are associated with quality of life (QoL). However, the manner in which depression and sleep quality influence the relationship between race and QoL in patients with HF is unclear.

Objective:
To explore whether depressive symptoms and/or sleep quality mediate the relationship between race and QoL among patients with HF.

METHOD:
We performed a secondary analysis of data from 271 adults with HF in this descriptive study. Participants were enrolled from out-patient settings in the Northeastern US. Self-reported race (White or Black), depressive symptoms (Patient Health Questionnaire), sleep quality (Pittsburgh Sleep Quality Index), and QoL (Kansas City Cardiomyopathy Questionnaire) were collected at baseline. A serial multiple mediator analysis was conducted with a regression framework, using the PROCESS macro for SPSS.

Results:
Ninety-six patients (35.4%) were Black. Race was directly associated with depressive symptoms and sleep quality. Black patients had more depressive symptoms and poorer sleep quality than White patients. Depressive symptoms were directly associated with sleep quality and QoL. Sleep quality was directly associated with QoL. Race was not directly associated with QoL; but indirectly associated with QoL through the following three paths: 1) depressive symptoms; 2) sleep quality; 3) depressive symptoms and sleep quality. Due to more depressive symptoms and/or poorer sleep quality, Black patients had poorer QoL than Whites (Figure).

Conclusion:
Depressive symptoms and sleep quality independently and in combination mediated the relationship between race and QoL. These findings suggest that screening for depressive symptoms and sleep quality could identify patients at risk for poor QoL, especially in racial minority groups.