bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13593: Rates of Acute Kidney Injury or Discontinuation After SGLT2 Inhibitor Initiation in a Real-World Cohort of Patients With Heart Failure With Reduced Ejection Fraction
Authors: Perez Martinez Bryan , Adie Sarah , Konerman Matthew C
Published: June 2023

Background:
SGLT2 inhibitors (SGLT2i) decrease mortality and risk of hospitalizations in patients with HFrEF. SGLT2i have a natriuretic effect shortly after initiation, followed by a lasting osmotic diuretic effect. We sought to evaluate real-world rates of acute kidney injury (AKI) in our clinical setting that includes patients concurrently receiving high doses of loop diuretics.

Methods:
We abstracted patient level data on 200 patients with HFrEF initiated on a SGLT2i in the outpatient setting in the University of Michigan (1/7/2016 - 2/7/2022). Our co-primary endpoints were rate of AKI and discontinuation of SGLT2i. Secondary end points consisted of diuretic dose reduction, change in potassium, change in serum creatinine (SCr), and other side effects not requiring discontinuation.

Results:
The majority of patients were male (64%) with a mean LVEF of 27%. A total of 104 (52%) patients had diabetes mellitus. The majority of patients (54%) were taking an angiotensin-receptor neprilysin inhibitor. The mean daily furosemide equivalent diuretic dose was 93.3 mg. Twenty-two (11%) patients had AKI and 18 patients (9%) discontinued their SGLT2i. Yeast infection (3%), hypotension (2.5%), and AKI (2%) were the most common reasons for discontinuation. Using ROC curve analysis, the strongest predictors for AKI were A1C (AUC = 75.8, empirical confidence interval [ECI] 66.5-83.5); baseline SCr (AUC = 72.0 ECI 65.7-78.7); LVEF (AUC = 67.6 ECI 58.4-75.8); and furosemide equivalent diuretic dose (AUC = 66.0 ECI 57.5-74.6). Similarly, the strongest positive predictors for SGLT2i discontinuation were A1C (AUC = 81.1 ECI 74.8-87.2); baseline Scr (AUC = 67.4 ECI 58.7-75.5); LVEF (AUC = 68.7 ECI 58.9-76.5); and furosemide equivalent diuretic dose (AUC = 67.2 ECI 58.2-76.0).

Conclusions:
A1C was the strongest predictor of AKI and SGLT2i discontinuation in HFrEF patients started on SGLT2i. Glucosuria may be related to this effect. SCr, LVEF, and furosemide equivalents also predicted these outcomes.
Abstract 13595:
Lactobacillus
Supplementation Augments Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension
Authors: Prisco Sasha Z , Park Anna , Raveendran Rashmi , Prins Kurt W
Published: June 2023

Introduction:
Gut microbiome dysbiosis induces hyperactivation of the immune systemic in multiple diseases. In pulmonary arterial hypertension (PAH), dysbiosis could therefore regulate right ventricular (RV) function because inflammatory glycoprotein 130 (GP130) signaling pathologically restructures RV microtubules and junctophilin-2 (JPH2) to promote RV dysfunction (RVD) in MCT rats. Interestingly, increases in intestinal
Lactobacillus,
an anti-inflammatory bacteria, by intermittent fasting enhance RV function in monocrotaline (MCT) rats. However, it is unknown if
Lactobacillus
supplementation can restructure the microbiome to suppress GP130-mediated RVD.

Methods:
Male rats were randomly allocated into 3 groups: control, MCT water gavage (MCT-water), and MCT
Lactobacillus rhamnosus
(4x10
7
CFU/day) gavage (MCT-
Lactobacillus
) with treatments starting 2 weeks after MCT injection. Next-generation sequencing evaluated the composition of the bacterial and fungal components of the microbiome. SomaScan proteomics quantified levels of serum GP130 ligands. Immunoblots probed RV microtubule and JPH2 expression. Echocardiography and closed-chest pressure-volume (PV) loops determined RV function.

Results:
Lactobacillus
supplementation restructured the micro/mycobiome, and concomitantly improved jejunal epithelial cell morphology. Serum proteomics revealed
Lactobacillus
treatment decreased circulating GP130 ligand levels which normalized RV microtubule and JPH2 protein expression. Finally,
Lactobacillus
reduced RV hypertrophy and fibrosis and enhanced RV function without changing PAH severity.

Conclusions:
Lactobacillus
supplementation restructured the microbiome, dampened GP130 activation, normalized RV microtubule and JPH2 expression, and augmented RV function. Thus,
Lactobacillus
treatment could be a readily translatable approach to combat RVD in PAH.
Abstract 13599: LX2020, an Adeno Associated Viral-Based Plakophilin 2 Gene Therapy Stabilizes Cardiac Disease Phenotype in a Severe Mouse Model of Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Sheikh Farah , Zhang Jing , Wang Jie , Bradford William H , Nair Anju , Fargnoli Anthony , Selvan Nithya , Gutierrez Sonia , Law Ken , Fenn Tim , McCormac Paul , Barth Jay A , Khanna Richie
Published: June 2023

Introduction:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) increases risk of sudden cardiac death (SCD) and can progress to heart failure. Clinical studies have established 40-50% prevalence of mutations to desmosomal genes, with plakophilin-2 (PKP2) being the most frequent. To date, no effective treatment exists for ARVC. LX2020 is a novel AAV gene therapy that restores cardiac expression of human PKP2. A proof-of-concept study with LX2020 was conducted in a severe novel PKP2 mutant mouse model that exhibits all classic phenotypes of ARVC.

Hypothesis:
LX2020 mediated PKP2 expression is sufficient to scaffold the desmosomal cell-cell complex to promote survival as well as preserving cardiac electrical and mechanical function.

Methods:
A total of N=16 PKP2 Hom mice were randomized for vehicle/formula control (VC), low dose (LD) and high dose (HD). LX2020 was administered at postnatal day 2 and mice were analyzed 4-weeks post administration. Endpoints included survival, EKG, cardiac MRI and desmosomal levels of PKP2, desmoplakin (DSP), desmoglein-2 (DSG2), plakoglobin (JUP), along with fascia-adherens (N-Cad), and gap junction (CX43), using western blot analyses.

Results:
LX2020 showed dose dependent improvements in ARVC related deficits in PKP2 mice, including survival. HD resulted in 100% survival of PKP2 mutant mice, while LD resulted in 60% survival, when compared to 50% survival with VC. ECG data revealed suppression of ectopic beats in 100% of PKP2 mutant mice at HD and 75% suppression at LD when compared to 60% with VC. MRI HD improved left and right ejection fraction, as well as reduced right and left end-diastolic and systolic volumes, when compared to VC. LD showed a mild impact on left ventricular end-diastolic and end-systolic volumes like HD. Mechanistically, while LD showed limited increase in cardiac PKP2 expression, HD showed substantial cardiac PKP2 expression. Significantly increased levels of other desmosomal proteins, especially DSP and DSG2, were seen suggesting scaffolding functions to PKP2.

Conclusions:
These data indicate that the restoration of cardiac PKP2 expression can halt or slow ARVC disease progression, making LX2020 a promising gene therapy candidate for treating PKP2 mutation patients.
Abstract 13611: Association of Poor Mental Health With Cardiovascular Disease and Suboptimal Cardiovascular Health Among Young U.S. Adults
Authors: Kwapong Yaa A , Boakye Ellen , Khan Safi U , Khan Sadiya S , Honigberg Michael C , Hays Allison G , Nasir Khurram , Blumenthal Roger S , Blaha Michael J , Sharma Garima
Published: June 2023

Introduction:
Depression is a non-traditional risk factor for cardiovascular disease (CVD). Data on the association of depression and poor mental health with CVD and suboptimal cardiovascular health (CVH) among young adults are limited.

Methods:
We utilized data from 593,616 young adults (18-44 years) from the 2017-2020 Behavioral Risk Factor Surveillance System, a nationally representative survey of non-institutionalized US adults. Exposures were self-reported depression and poor mental health days (PMHD, categorized as 0 days, 1-13 days, 14-30 days poor mental health in the past 30 days), and outcomes were self-reported CVD (MI, angina, or stroke) and suboptimal CVH (≥ 2 risk factors: hypertension, hypercholesterolemia, overweight/obesity, current smoker, diabetes, inactivity, and inadequate fruit and vegetable intake). Using logistic regression, we investigated the association of depression and PMHD with CVD and suboptimal CVH adjusted for sociodemographic factors (and CVD risk factors for CVD).

Results:
The weighted prevalence of CVD was 2.5% (95% CI 2.4%-2.6%), and depression was 19.6% (95% CI 19.4%-19.8%). CVD was more common among young adults with depression than those without (fully adjusted odds ratio [aOR]: 2.28, 95% CI: 2.10-2.48, Fig. 1A). There was a graded association of PMHD with CVD. Compared with individuals with 0 PMHD, the odds of CVD in those with 1-13 PMHD and 14-30 PHMD were 1.49 (95% CI:1.36-1.64) and 2.26 (95% CI: 2.06-2.48)(Fig. 1B), respectively after adjusting for sociodemographic and CV risk factors. Individuals with depression had higher odds of suboptimal CVH (aOR: 1.77, 95% CI: 1.67-1.88)(Fig 1C) compared with those without depression, with a similar graded relationship observed between PMHD and CVH
(
Fig 1D).

Conclusion:
Depression and poor mental health are associated with premature CVD and suboptimal CVH in young US adults. Prioritizing mental health may help reduce CVD risk and improve CVH in young adults.
Abstract 13612: Using Pre-Operative Cardiac Computed Tomography and Echocardiography to Predict New-Onset Atrial Fibrillation Following TAVR
Authors: Brahier Mark S , Kochi Shwetha , Huang Julia , Piliponis Emma , Smith Andrew , Johnson Adam , Poian Suraya , Abdulkareem Musa , Ma Xiaoyang , Wu Colin , Thomaides Athanasios X , Waksman Ron , Satler Lowell , Bergquist Peter J , Srichai Monvadi B , Petersen Steffen E , Vargas Jose D
Published: June 2023

Introduction:
New-onset atrial fibrillation (NOAF) following transcatheter aortic valve replacement (TAVR) has been associated with higher morbidity and mortality. Numerous studies have focused on clinical variables for NOAF prediction. In this study, we examine pre-operative cardiac computed tomography (cCT) and echocardiographic measurements for NOAF prediction following TAVR.

Methods:
This retrospective study includes 939 patients without pre-existing atrial fibrillation who underwent transfemoral TAVR between 2015 and 2020. Clinical data and standard pre-operative echocardiographic and cCT measurements were recorded. A machine learning method was used to derive left atrial volume and measures of epicardial adipose tissue from cCT. NOAF by 30-days was determined based on continuous electrocardiographic monitoring prior to hospital discharge and routine ECG at 2 and 4 weeks following TAVR. In a two-step analysis, random survival forest (RSF) was used to select variables of highest importance to NOAF prediction without assuming statistical models, followed by logistic regression analysis of the selected variables.

Results:
Among 939 patients, 47 (5%) experienced NOAF. Patients with NOAF had larger left atrial volume index (68.11 vs 56.96 cm
3
/kg/m
2
; p<0.001) but similar epicardial adipose tissue volume (71.78 vs 70.98 cm
3
; p>0.1) and epicardial adipose tissue attenuation (-81.16 vs -82.77 Hounsfield Units; p>0.1). Among 28 covariates selected by RSF for variable importance, 4 covariates were predictive of NOAF in the multivariable logistic regression, including sinotubular junction short axis >34mm [OR 5.687 (2.271-14.241); p=0.0002], maximum aortic valve pressure gradient [OR 1.037 (1.004-1.072); p=0.0266], mean aortic valve pressure gradient [OR 0.939 (0.894-0.986); p=0.0115], and body mass index < 22kg/m
2
[OR 0.331 (0.150-0.729); p=0.006]. Model concordance was 0.75.

Conclusions:
Pre-operative cardiac computed tomography and echocardiographic measurements including sinotubular junction enlargement and aortic valve pressure gradient predict new-onset atrial fibrillation following TAVR.
Abstract 13618: Day Time vs Night Time Extubation After Elective Tetralogy of Fallot Repair
Authors: Smerling Jonathan , Kulkarni Aparna
Published: June 2023

Background:
Daytime extubation post cardiac surgery has been associated with improved hospital outcome in adults. However, data in pediatrics are lacking. We hypothesized that daytime extubations are associated with shorter critical care time (CCT) and investigated the NIH/NHLBI Pediatric Heart Network Collaborative Learning Study (PHN CLS) open database with this goal.

Methods:
The PHN CLS was designed as a quality improvement project to implement early extubation guidelines in patients (pts) with Tetralogy of Fallot (ToF) and coarctation of the aorta across 10 centers. We included all ToF pts who had complete repair and excluded pts with coarctation, significant comorbidities and who were a part of the clinical practice guideline. Time to extubation (TTE) was assessed by duration and as day (8 am - 5 pm) vs. night (5 pm - 8 am). CCT was defined as the number of hours from ICU handoff to time the pt was medically ready to leave the ICU. Two sample t-tests were used to compare CCTs between day and night extubations. The relationship of TTE in hours and CCT was assessed using linear regression analysis. A sensitivity analysis was performed after exclusion of pts > median CCT of 50 hours.

Results:
A total of 144 pts (mean age 155 days, range 28-365 days; 59% males) were included. There was no difference in mean CCT for day (n=70) vs. night (n=74) extubations (104.3
+
18.8 vs. 76.0
+
9.2 hrs, p= 0.17). Overall, there was a strong correlation between TTE and CCT (r
2
0.88, p<0.001), for day extubations (r
2
0.94, p< 0.001) and night extubations (r
2
0.75, p<0.001). On the sensitivity analysis at <50 hours CCT, there was no difference in the mean CCT time for the day (n=30) vs. night (n=32) extubations (36.5
+
2.0 vs. 33.9
+
2.1 hrs, p= 0.39). Day extubations continued to have moderate correlation with CCT in <50 hrs (r
2
0.57, p<0.001) with a weaker correlation for the night group (r
2
0.34, p<0.001). There were 5 reintubations in the overall cohort (3.5%), 1 from the day (0.7%) and 4 from the night (2.8%).

Conclusions:
In this PHN CLS selective cohort of pts with ToF, our findings suggest that daytime vs nighttime extubation did not affect CCT. We also confirmed that those extubated earlier had shorter CCT. Further study into expanded pt groups is needed to assess impact on outcomes.
Abstract 13626: The Glycolytic Enzyme Pyruvate Kinase M2 Regulates Deep Vein Thrombosis
Authors: Nayak Manasa K , Flora Gagan , Doddapattar Prakash , Chauhan Anil K
Published: June 2023

Introduction:
Current treatment regimen for deep vein thrombosis (DVT) includes anticoagulants or surgical intervention. While effective, anticoagulants exhibit a bleeding risk that limits their use. Activated platelets release pro-thrombotic chemokines such as platelet factor 4 (PF4) from their α-granules and are known to potentiate DVT via promoting neutrophil extracellular traps (NETs). Recently, we have shown that dimeric pyruvate kinase M2 (PKM2) regulates platelet function and arterial thrombosis without affecting hemostasis. However, the role of platelet-specific PKM2 in modulating NETosis and DVT remains unexplored.

Methods:
Susceptibility to DVT was evaluated in the flow-restricted inferior vena cava (IVC) stenosis model in PKM2
fl/fl
PF4Cre
+/-
mice. The littermate PKM2
fl/fl
PF4Cre
-/-
(abbreviated as PKM2
fl/fl
) was used as control. Next, we evaluated whether wild-type mice infused with a specific inhibitor of dimeric-PKM2, ML265, reduced DVT susceptibility in the IVC stenosis model.

Results:
The platelet-specific PKM2
-/-
mice were less susceptible to DVT in the IVC stenosis model. The PF4 secretion from α-granules was significantly inhibited in agonist-stimulated platelets from PKM2
fl/fl
PF4Cre+ mice compared to the platelets from PKM2
fl/fl
mice. SNAP-23 phosphorylation regulates SNARE protein complex-mediated mediated secretion from α granules. Therefore, we determined the mechanistic role of PKM2 in modulating SNAP-23-mediated PF4 secretion in platelets. In agonist-stimulated PKM2-/- platelets, SNAP23 phosphorylation and PF4 secretion were reduced compared to agonist-stimulated WT platelets. In addition, neutrophils treated with stimulated platelet releasates from PKM2
fl/fl
PF4Cre+ mice exhibited significantly reduced NET formation in contrast to PKM2
fl/fl
mice. Finally, we demonstrate that ML265-treated mice showed reduced susceptibility to DVT in the IVC stenosis model.

Conclusions:
Our results suggest an essential role of PKM2 in regulating SNAP-23 mediated α-granule release, NETosis, and subsequent development of DVT.
Abstract 13632: The Optimization of Mechanical Circulatory Support Device Combination Considering Ventricular Load in Biventricular Failure Condition: A Simulation Study
Authors: Matsushita Hiroki , Nishikawa Takuya , Yokota Shohei , Kakuuchi Midori , Yokoi Aimi , Nishiura Akitsugu , Uemura Kazunori , Kawada Toru , Li Meihua , Saku Keita
Published: June 2023

Backgrounds:
Recently, the combination of Impella, a percutaneous transvalvular left ventricular assist device, and veno-arterial extracorporeal membrane oxygenation (ECMO) have improved the survival rate of cardiogenic shock by its powerful hemodynamic support effect. Meanwhile, the optimal flow control of those devices remains unclear, especially in biventricular failure (BVF). In this study, we established the mathmatical cardiovasular simulation model, and evaluated how the combination therapy impacts both right (RV) and left (LV) ventricular loading.

Methods:
We used SimulinkⓇ (Mathworks, Inc.) for the simulation. Both the systemic and pulmonary circulation were modeled by using 5-element resistance-capacitance net-work. Four cardiac chambers were represented by time-varying elastance with unidirectional valves (Fig. 1). In LV dysfunction (LV end-systolic elastace was set at low level: 0.4 mmHg/ml), we compared the changes of right (RAP) and left (LAP) atrial pressure, as the marker of ventricular loading, under various RV function and Impella and ECMO flows.

Results:
Impella slightly increased RAP and reduced LAP regardless of RV systolic function (Fig. 2). In high pulmonary vascular resistance (PVR), the increase of Impella flow augumented RAP, while Impella could not be up-titrated more than 2.8 L/min due to LV suction (Fig. 3). In BVF with high PVR, ECMO decreased RAP and increased LAP in each Impella flow (Fig. 4). Higher ECMO and Impella flows rendered LV extremely small, induced suction, and increased RV preload and RAP.

Conclusion:
PVR is the major determinant of stable Impella support without inducing RV loading and LV suction. In BVF with high PVR, ECMO reduced RV loading, while decreased LV filling and induced LV suction by Impella. The preemptive simulation study for an individual patient may help the optimal use of mechanical circulatory support device to maximize RV and LV unloading with improving hemodynamics.
Abstract 13642: Post-Operative Bleeding Risk in TAVR Patients With Atrial Fibrillation
Authors: Brahier Mark S , Kochi Shwetha , Riskin Jeffrey , Kopera Ann , Lawrence Luke , Patel Jay B , Thomaides Athanasios X , Waksman Ron , Satler Lowell , Srichai Monvadi B , Vargas Jose D
Published: June 2023

Introduction:
Antithrombotic medications are the subject of multiple transcatheter aortic valve replacement (TAVR) randomized control trials. Pragmatically, decisions are complicated by conditions such as atrial fibrillation (AF) that also require lifetime anticoagulation. Our study examines antithrombotic medications in a real-world cohort to identify risk factors for bleeding by 1-year post-TAVR.

Methods:
This retrospective study includes 844 patients undergoing transfemoral TAVR between 2015 and 2020. Pre- and post-operative medications, comorbidities, and 1-year outcomes were recorded based on review of the medical record. Antithrombotic regiment decisions were made on a case-by-case basis. Bleeding classification followed VARC2 definitions. Patients were stratified into two groups based on history of AF. Multivariable logistic regression was used to determine independent predictors of bleeding.

Results:
Among the 844 patients, 290 had comorbid AF (34%). Patients with AF were older (80.3 vs 77.8 years; p<0.001), more frequently had cardiovascular comorbidities, and had lower LVEF (52.4% vs 56.8%; p<0.001). Patients with AF were more likely to experience major or life-threatening bleeding (10% vs 5%; p<0.001), but there were no differences in rates of myocardial infarction, cerebrovascular accident, nor death by 1-year follow-up. After controlling for risk factors including anticoagulation and increases to antithrombotic regiment post-operatively, the independent risk predictors of major or life-threatening bleed included female sex [OR 1.522 (1.118-1.741); p=0.018], severe baseline anemia [2.938 (1.146-7.533); p=0.025], and atrial fibrillation [2.195 (1.206-3.997); p=0.010].

Conclusions:
Female sex, severe baseline anemia, and comorbid atrial fibrillation are predictors of major or life-threatening bleed by 1 year in patients undergoing transfemoral TAVR, independent of antithrombotic regiment.
Abstract 13644: Hospitalization Outcomes for Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: Analysis of National Inpatient Sample
Authors: Soon-Shiong Raquel , Karki Sadichhya , Kumi Dennis , Shrestha Prajwal , Asemota Iriagbonse , Zhang Yaqi , KANG CYRA-YOONSUN , Nissan Ninos , Patel Birju
Published: June 2023

Introduction:
Iron deficiency (ID) is associated with worse exercise tolerance in patients with HFrEF regardless of hemoglobin level. Intravenous iron replacement in these patients increases functional capacity, improves quality of life, and reduces recurrent hospitalizations. We examined a large inpatient database to explore the relationship between ID without anemia and outcomes in HFrEF patients.

Methods:
We queried the National Inpatient Sample (2016-2018) for adults with HFrEF as the principal diagnosis and ID as a secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality and secondary outcomes were length of stay, total hospital charges, combined supraventricular and ventricular tachycardia, and cardioversion. STATA software was used for analysis. Multivariate logistic and linear regression analyses were used accordingly to compare groups while adjusting for confounders.

Results:
Of 446,539 patients hospitalized with HFrEF, 0.16% had concomitant ID without anemia. There was no difference in mortality in HFrEF patients with ID compared to those without ID (2.8% vs 2.9%; aOR 0.97; p=0.94). Length of stay was significantly higher (8.0 vs 5.4 days; CI 0.46-4.5; p=0.02) and there was a non-significant increase in hospital charges ($80,292 vs $57,072; CI -$3,043-$39,821; p=0.09) for HFrEF patients with ID. Tachycardia occurred more frequently in HFrEF patients with ID (18.8% vs 10.3%; aOR 1.93; p=0.004), but there was no significant difference in cardioversion (1.39% vs 1.68%; aOR 0.82; p=0.78).

Conclusions:
We did not find an association between ID and inpatient mortality in HFrEF patients. Symptomatic improvement is an important factor for determining time of discharge in patients admitted for HFrEF and our analysis demonstrates significantly longer hospitalization in patients with ID. Further studies may elaborate on the effect of iron replacement on duration of hospitalization for patients admitted with HFrEF.
Abstract 13648: Risk Profile and Prognostic Implications of Premature Advanced Atherosclerotic Disease Among Young Adults: The Coronary Artery Calcium Consortium
Authors: Boakye Ellen , Dardari Zeina A , Osuji Ngozi , Erhabor John , Obisesan Olufunmilayo , Osei Albert , Dzaye Omar , Jha Kunal , Rosanski Alan , Berman Daniel S , Budoff Matthew , Miedema Michael D , Nasir Khurram , Rumberger John A , Shaw Leslee J , Blaha Michael J
Published: June 2023

Introduction:
Advanced atherosclerotic disease among young adults is an under-recognized and unique disease phenotype that has not been well characterized.

Methods:
We used data from 23,706 participants aged 30-50 years (mean age 43.9 ± 4.6 years; 74.7% men) from the Coronary Artery Calcium (CAC) Consortium, a cohort of individuals with no prior CVD history referred for CAC scanning. We defined advanced disease as CAC ≥ 90
th
percentile for age, sex, and race, and compared risk factor profile of persons with advanced disease to those without CAC and those with CAC < 90
th
percentile. Using multivariable-adjusted Cox proportional hazard and competing risks regression, we assessed the association of advanced disease with all-cause, cardiovascular (CV), and CHD mortality.

Results:
Of the 23,706 participants, 8,289 (35%) had CAC. Among them, 3,549 (43%) had CAC ≥ 90
th
percentile. Compared to persons without CAC and those with CAC < 90
th
percentile, those with CAC ≥ 90
th
had higher prevalence of all the traditional CVD risk factors. Notably, 56% of those with CAC ≥ 90
th
percentile had ≥ 2 risk factors, and 68% already had multivessel CAC compared to 34% of those with CAC < 90
th
percentile. After a mean follow-up of 12.6 ± 3.6 years, the incidence of all-cause, CV, and CHD mortality was highest in those with advanced disease. Persons with CAC ≥ 90
th
percentile had a higher multivariable-adjusted risk of all-cause (HR 2.11 [1.62 - 2.73]), CV (SHR 2.88 [1.74 - 4.78]), and CHD mortality (SHR 4.41 [2.16 - 8.98]), compared to those without CAC. When compared to those with CAC < 90
th
percentile, only those with CAC ≥ 90
th
percentile had significantly higher risk of all-cause, CV, and CHD mortality (
Figure
).

Conclusions:
Premature advanced atherosclerosis is a distinct clinical phenotype that strongly predicts all-cause and cause-specific mortality. Among persons with CAC at young age, those with scores ≥ 90th percentile have the highest risk of early death and should be a focus of clinical prevention.
Abstract 13653: Leveraging Natural Language Processing and Machine Learning to Predict Worsening Heart Failure Events
Authors: Parikh Rishi V , Ambrosy Andrew P , Tan Thida , Sung Sue Hee , Bhatt Ankeet , Fitzpatrick Jesse K , Feng Kent Y , Lee Keane , Adatya Sirtaz , Sax Dana R , Shen Xian , Cristino Joaquim , Go Alan S
Published: June 2023

Background:
Prior risk models in patients with heart failure (HF) have focused on hospitalizations for worsening HF (WHF) and have not evaluated for differences in predictors by left ventricular ejection fraction (LVEF). We used natural language processing (NLP) and machine learning methods with access to longitudinal electronic health record (EHR) data to develop risk prediction models for WHF events across practice settings and by LVEF category.

Methods:
We identified all adults with HF and known LVEF on January 1
st
of each year from 2011-2019 in an integrated health care system. WHF events within 1 year were defined as any hospitalization, emergency department, or outpatient encounter with ≥1 symptom, ≥2 objective findings including ≥1 sign, and ≥1 change in HF-related therapy. Signs and symptoms were ascertained using rule-based NLP. We conducted boosted decision tree-based ensemble models for any WHF event within each LVEF category: HF with reduced EF (HFrEF; LVEF ≤40%), HF with mildly reduced EF (HFmrEF; LVEF 41-49%), and HF with preserved EF (HFpEF; LVEF ≥50%). We evaluated model discrimination using area under the curve (AUC) and model calibration using Brier scores.

Results:
Among 359,298 patients from 2011-2019, 65,838 (18%) had HFrEF, 52,491 (15%) had HFmrEF, and 240,969 (67%) had HFpEF. Mean age was 75±12, 47% were women, and 37% were minorities including 10% Black, 11% Asian/Pacific Islander, and 12% of Hispanic ethnicity. WHF events occurred in 22% of patients with HFrEF, 17% with HFmrEF, and 16% with HFpEF. The models displayed an AUC of 0.75 and Brier score of 0.15 for HFrEF and an AUC of 0.77 and Brier scores of 0.12 for both HFmrEF and HFpEF. Clinical predictors were similar across LVEF categories (
Table
).

Conclusions:
Longitudinal EHR data can be leveraged using NLP and machine learning for accurate risk estimation that reliably identifies clinical predictors across a range of LVEF. These findings may provide novel insight into the natural history of HF.
Abstract 13657: Evaluating Outcomes of Half-Dose Tissue Plasminogen Activator on Patients With Intermediate-Risk Pulmonary Embolism: A Single Center Study
Authors: Shahrori Zaid M , Alhuneafat Laith , Sallam Sherin , jabri ahmad , Al-Abdouh Ahmad , Mhanna Mohammed , Yousaf Adnan , Abu omar Yazan , Nasser Mohamed Farhan , Siraj Aisha
Published: June 2023

Introduction:
In the absence of hypotension, pulmonary embolism (PE) causing right ventricular dysfunction or strain whether confirmed by imaging or cardiac biomarkers is deemed to be an intermediate-risk category. Urgent treatment of intermediate-risk PE can prevent progression to hemodynamic instability and death. Management options include thrombolysis, thrombectomy, or systemic anticoagulation. We aim to evaluate the short-term outcomes of a half-dose tissue plasminogen activator(tPA) for the management of intermediate-risk PE.

Methods:
We retrospectively identified adult patients diagnosed with intermediate-risk PE between the years 2000 and 2021. Demographic data, lab values, imaging, treatment choice, and outcomes were all obtained through chart review. Patients on standard systemic anticoagulation without thrombolysis or thrombectomy served as controls. Data analysis was done through SAS® Software (version 9.4; Cary, NC) to compare those that received half-dose tPA with controls and statistical significance was set at a p-value of 0.05.

Results:
We included 57 patients in our final analysis with 19 receiving tPA. Patient characteristics and comorbidities were comparable between both groups. There was a significant difference between PE location, presence of acute deep vein thrombosis, and peak troponin level between both groups (Table 1). The thrombolytic cohort was more likely to have a 60/60 sign and a thrombus in transit on echocardiography than controls. The thrombolytic group was more likely to have major bleeding (17% vs 7.9%, p= 0.4) and in-hospital mortality (5.3% vs 0%, p=0.3), however, this was not statistically significant.

Conclusion
Patients who received half-dose tPA had non-significant higher rates of major bleeding and in-hospital mortality. Larger scale, randomized control trials are needed to establish the benefit and safety of thrombolytics in patients with intermediate-risk PE.
Abstract 13675: Patient Awareness and Provider Counseling on Adverse Pregnancy Outcomes and Cardiovascular Risk - Insights From American Heart Association Research Goes Red Registry
Authors: Boakye Ellen , Kwapong Yaa A , Khandelwal Abha , Roger Veronique L , Ouyang Pamela , Mallya Pratheek , Zhao Juan , Akel William , Blumenthal Roger , Mehta Laxmi S , Hall Jennifer L , Sharma Garima
Published: June 2023

Introduction:
Adverse pregnancy outcomes (APOs) are associated with long-term cardiovascular (CV) risk. This study aimed to identify awareness of the association of APOs with CV risk among patients and to determine whether care providers assessed pregnancy history and counseled on the association of APOs with CV risk during patient visits.

Methods:
We used data from participants enrolled in the AHA Research Goes Red Registry, an online research platform powered by Verily, who responded to the Fertility and Pregnancy Survey. Among them, 1,499 were postmenopausal (mean age 54.7 ± 7.8 years). We focused on three specific questions related to the goals of this study. We summarized responses using proportions, for the overall sample and by race and income, and tested differences using the Chi-squared test. Significance was set at p<0.05.

Results:
A total of 828 participants answered the question on awareness of the association of APOs with CV health. Of them, 35% were unaware of this association, with significant differences by race (p=0.019) (
Fig 1A
). Among 815 women who responded to the question on whether their care providers took pregnancy history during visits, 35% stated that their providers did not. The percentage varied significantly by income level, with highest percentage among women with an annual income <$50,000 and the lowest in those with an income ≥$200,000 (p=0.037) (
Fig 1B
). Notably, pregnancy history was not taken by providers in 1 in 2 Asian women (
Fig 1C
). Among 813 women who answered the question on provider counseling on the association of APOs with CV risk, 71% reported that their care providers did not educate them on this association, with no significant differences by race or income.

Conclusions:
In this contemporary cohort, considerable knowledge gaps exist on the association of APOs with CV risk, with disparities by race. Also, most women are not educated on this association by their care providers. These data suggest the need for more education on APOs and CV.
Abstract 13688: Low-Affinity Insulin-Like Growth Factor Binding Protein 7 and Its Association With Pulmonary Arterial Hypertension Severity and Survival
Authors: Torres-Viera Guillermo , Lancaster Andrew , Yang Jun , Griffiths Megan , Brandal Stephanie , Damico Rachel L , Everett Allen D , Ivy Dunbar D , Austin Eric , Simpson Catherine , Vaidya Dhananjay , Nichols Bill
Published: June 2023

Introduction:
Insulin like growth factor binding proteins (IGFBPs) are a family of growth factor modifiers, some of which are known to be independently associated with PAH survival. IGFBP7 is a unique low-affinity IGFBP that, independent of IGF, stimulates prostacyclin production.

Hypothesis:
Elevated IGFBP7 is associated with worse disease severity and survival in PAH.

Methods:
Using enzyme-linked immunosorbent assays (ELISA), we evaluated serum IGFBP7 in a multicenter PAH cohort, the NHLBI PAHBiobank (N=2583), and healthy controls (N=99). Hemodynamic and functional measures were used to assess IGFBP7’s association to PAH severity and survival. Kruskal Wallis was used for comparison and Spearman’s rank correlation for correlations. Linear and logistic regressions performed for associations. IGFBP7 was dichotomized at the median and analyzed by Kaplan-Meier survival and Cox proportional Hazard regression.

Results:
Serum IGFBP7 levels were significantly elevated in patients with PAH compared to controls. After adjustment, logarithmic increases in IGFBP7 were associated with a 38 meter shorter six-minute walk distance (6MWD; -37.7, 95%CI -54 to -21, p=<0.001), a higher mean right atrial pressure (2.18mmHg, 95%CI 1.51-2.89, p<0.001) and a higher REVEAL risk score (1.10, 95%CI 0.88-1.33, p <0.001). Logarithmic increases in IGFBP7 were also associated with a two-times higher likelihood of having PAH associated with Portopulmonary disease (2.39, 95%CI 1.95-2.84, p<0.001). Kaplan Meier analysis demonstrated significant survival effects of IGFBP7 above the median (see Figure 1) and an adjusted (age, sex, functional class, and 6MWD) Cox proportional hazards model (HR 3.1, 95% CI 2.2-4.4, p<0.001).

Conclusions:
Higher circulating IGFBP7 levels were significantly associated with worse PAH severity and decreased survival. Given its role of as a prostacyclin stimulant, IGFBP7 may also serve as a therapeutic target for disease modulation.
Abstract 13700: LncRNA
MERRICAL
Controls Macrophage Chemotaxis and Vascular Inflammation by
In-cis
Regulation of CCL3/4 via H3k4me3 in Diabetes-Associated Atherosclerosis
Authors: Chen Jingshu , Jamaiyar Anurag , Zhuang Rulin , Sausen Grasiele , Cheng Henry S. , Perez-Cremades Daniel , TZANI ASPASIA , McCoy Michael , Assa Carmel , Eley Samuel , Plutzky Jorge , Feinberg Mark W
Published: June 2023

Introduction:
Diabetes-associated atherosclerosis is characterized by excessive vascular wall inflammation, including impaired lipid deposition, increased immune cell infiltration and plaque formation in the vessel wall. Macrophages are instrumental for lesion formation, however the mechanisms underlying their impaired functional capacity remain poorly understood in diabetes. Herein, we identify a unique role of a macrophage-enriched lncRNA
MERRICAL
(Macrophage Enriched lncRNA Regulates Inflammation, Chemotaxis, and AtheroscLerosis) in the development of diabetes-associated atherosclerosis.

Methods:
Transcriptomic analysis of the aortic intima from

Ldlr
-/-

mice was performed at 4 time points along the continuum of lesion progression and regression under a high fat, high sucrose-containing (HFSC) or chow diet, respectively, to identify differentially expressed lncRNAs. Gain- and loss-of-function cell-based assays, RNA-protein interactions, and
in vivo
knockdown were performed to uncover the role of a top lncRNA candidate.

Results:
LncRNA
MERRICAL
is nuclear localized and increased by 249% in intimal lesions during progression. Transcriptomic analysis of
MERRICAL
-deficient bone marrow-derived macrophages showed decreased chemokine and inflammatory gene expression for
Ccl3, Ccl4, and Il1β,
with reduced chemotaxis and inflammatory-associated gene ontology pathways. Gain- and loss-of-function studies demonstrated the role of lncRNA
MERRICAL
in
cis
-regulation of its neighboring genes
Ccl3 and Ccl4,
an effect that is mediated in part via interaction with the histone modification enzyme H3K4me3. Remarkably, systemic knockdown of
MERRICAL
in HFSC-fed mice strongly reduced lesion formation by 73% in the aortic sinus by inhibiting the pro-inflammatory and
Ccl3
- and
Ccl4
-associated chemotactic response and decreasing the recruitment of leukocytes into the aortic wall.

Conclusions:
These findings establish a
cis
-regulatory mechanism by which a macrophage-specific lncRNA,
MERRICAL
, potently inhibits pro-inflammatory and chemotactic responses to alleviate lesion progression in diabetes, with implications for a broad range of diabetes-associated vascular disease states.
Abstract 13703: Sex Differences on Cardiovascular Outcomes of Pcsk9-Inhibitors: A Meta-Analysis
Authors: Rivera Frederick B , De Luna Deogracias V , Ansay Marie Francesca M , Rocimo Aubrey Melody , Alfonso Pia Gabrielle I , Ong Bradley Ashley , Golbin Jem Marie P , Shah Nishant , Santos Volgman Annabelle
Published: June 2023

Background:
LDL-Cholesterol (LDLC) lowering therapies have been proven to significantly lower major adverse cardiovascular events (MACE) in patients with cardiovascular disease. Ideal LDL-C target levels are often not achieved using a high-dose statin and ezetimibe. The proprotein convertase subtilisin/kexin type-9 (PCSK-9) inhibitors can further reduce LDL-C and MACE, yet gender differences in LDL-C reduction remains unclear. We sought to determine if there are sex differences in efficacy outcomes of PCSK-9 inhibitors.

Method:
A comprehensive literature search was performed, and ongoing studies were identified using ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We used a PRISMA, Preferred Reporting Items for a Review and Meta-analysis and RevMan version 5.4 software to conduct a meta-analysis, heterogeneity test, and sensitivity analysis on the included studies. We established the significance level for all outcomes at a P-value of <0.05. Statistical heterogeneity was identified through forest plots and a standard Chi-squared test with a significant level of p<0.1. The extent of heterogeneity was based on the I
2
statistic, wherein a value of more than 50% was interpreted as substantial heterogeneity. Fixed-effects analysis was applied in this meta-analysis.

Results:
There was a significant reduction in MACE in PCSK9 inhibitor arm vs. placebo in both males (HR 0.85, 95% CI 0.80 to 0.91, p<0.0001, and females (HR 0.86, 95% CI 0.76 to 0.96, p=0.009) (Figure). Furthermore, there was a similar significant reduction in LDLC with PCSK-9 inhibitors compared to placebo and ezetimibe for both sexes. Lastly, there was a significant reduction in LDL-C seen in both sexes when analyzed as to the frequency of PCSK9 inhibitor administration and the type of PCSK9 inhibitor given.

Conclusion:
This meta-analysis found no sex differences and similar efficacy in women and men in reducing MACE using PCSK-9 inhibitors.
Abstract 13714: Clinical Characteristics and Comparative Outcomes of Patients Undergoing Angiovac Endovascular Debulking of Tricuspid Valve Endocarditis versus Medical Therapy in Patients Considered Non-Surgical Candidates
Authors: Tanveer Ud Din Mian , Fu Sheng , Radhakrishnan Srikanth , Joseph Namita , Khalif Adnan , Hughes-doichev Rachel A , lasorda david , Chakravarthy Mithun , Radhakrishnan Anita U , raina Amresh
Published: June 2023

Introduction:
There remains a paucity of research regarding clinical characteristics and comparative outcomes of patients with tricuspid valve (TV) endocarditis, considered non-surgical candidates, undergoing debulking of TV vegetations using the AV(AngiVac) device compared to medical therapy.

Methods:
We conducted a retrospective cohort study at a single tertiary referral center comparing patients with TV endocarditis who were not considered surgical candidates. We compared clinical characteristics and outcomes in patients who underwent debulking of TV vegetations with AV vs those who were treated with medical therapy.

Results:
A total of 75 patients with TV endocarditis were included in the study. At baseline, patients in the medical therapy group were younger (34.4 years ± 10.5 vs 48.6 years ± 21, p < 0.0003), more frequently male in gender (55.9% vs 44%, p < 0.39) and had higher incidence of intravenous drug use (93.2% vs 56%, p < 0.0002). Patients were more likely to have history of malignancy (6% vs 1.7%, p < 0.32), cardiac implantable electronic device (31% vs 8.5%, p = 0.02) and central venous access (19% vs 1.7%, p = 0.01) if they underwent AV. Medical therapy was more commonly used for relatively smaller TV vegetations (1.68 cm vs 2.9 cm, p < 0.0001). Medical therapy was also associated with higher complication rates including distal embolization (81.4% vs 0%, p < 0.0001) and cerebrovascular accidents (5.1% vs 0% p = 0.36). In hospital mortality was similar for both groups and length of stay remained unchanged.

Conclusions:
Debulking of TV endocarditis with AV is feasible in patients not deemed to be surgical candidates and is not associated with higher inpatient mortality or length of stay. There was a lower rate of distal embolization and cerebrovascular accident in patients undergoing AV. Larger, multi center studies are needed to evaluate whether AV might improve outcomes in patients with TV endocarditis and large vegetations not deemed surgical candidates.
Abstract 13742: Left Atrial Appendage Closure versus Direct Oral Anticoagulant Outcomes Among High Risk Atrial Fibrillation: A Meta-Analysis
Authors: Jaiswal Vikash , Attia Abdelrahman , Shrestha abhigan babu , Joshi Amey , Jaiswal Akash , Kalra Kriti , Pasam Chetana , Biswas Monodeep
Published: June 2023

Introduction:
Relevant data comparing the beneficial approach towards atrial fibrillation (AF) patients with left atrial appendage closure (LAAC) and direct oral anticoagulation therapy (DOAC) is limited and not well known.

Hypothesis:
We aim to evaluate the clinical outcomes among AF patients who received LAAC and DOAC therapy.

Methods:
We systematically searched all electronic databases from inception until May 30th 2022 comparing cardiovascular outcomes among LAAC versus DOAC. Unadjusted odds ratios (OR) were pooled using a random-effect model, and a p-value of <0.05 was considered statistically significant.

Results:
A total of 6315 patients (LACC: 2703, DOACs: 3612) from six studies consisting of one RCT and five propensity-score-matched studies were included in our analysis. Compared with DOAC, LAAC cohort was associated with a significant reduction in primary composite outcome of ischemic stroke, major bleeding and all-cause mortality [OR 0.62, (95% CI 0.45 to 0.84), p=0.002]. Similarly, LAAC cohort showed a significantly reduced all-cause mortality [OR 0.61, (95% CI 0.43 to 0.87), p=0.006], CV mortality [OR 0.56, (95% CI 0.44 to 0.71), p<0.001] and post-procedural bleeding [OR 0.57, (95% CI 0.40 to 0.83), p=0.003]. There were no significant differences in terms of ischemic stroke/TIA [OR 1.15, (95% CI 0.88 to 1.52), p=0.31] and systemic embolism [OR 1.01, (95% CI 0.49 to 2.07), p=0.97] between patients receiving LAAC or DOAC.

Conclusions:
LAAC shows superiority over DOAC in terms of reducing the all-cause mortality, cardiovascular mortality and major bleeding events among patients with high risk atrial fibrillation, however large multicenter randomised trials are warranted to further justify these findings among large sample size.
Abstract 13745: Electronic Cigarette-Derived Aerosols Induce Endothelial Dysfunction: Role of Aldehydes and Transient Receptor Potential Ankyrin-1 in Mice
Authors: Jin Lexiao , Richardson Andre , Fryar Laura , Lorkiewicz Pawel , Riggs Daniel , Srivastava Sanjay , Bhatnagar Aruni , Conklin Daniel J
Published: June 2023

Introduction:
Electronic cigarettes (e-cigs) threaten to reverse the decline in rates of nicotine dependence and smoking. While some believe that e-cigarettes are less harmful than combustible cigarettes, e-cig use is associated with respiratory symptoms (cough, wheeze) and endothelial dysfunction (ED) indicating a potential to increase the risk of cardiovascular disease (CVD) with chronic use. ED is
sine qua non
of multiple CVD, yet the mechanism of e-cig-induced ED is unknown.

Hypothesis:
E-cigs generate levels of irritants that activate the Transient Receptor Potential Ankyrin-1 (TRPA1) to trigger nocifensive reflexes and induce ED in mice.

Methods:
Wild type (WT) and TRPA1-null C57BL/6J male and female mice were exposed to: filtered air (control), aerosols of JUUL e-cig liquid, e-cig solvents without nicotine (propylene glycol:glycerin, PG:G), or irritant gases alone (acrolein, formaldehyde). Urinary levels of nicotine and aldehyde metabolites were measured by UPLC-MS/MS. During acute exposures, respiratory irritant responses were monitored by radiotelemetry. Following short-term exposure (4d), aortic endothelial function, blood/plasma markers of organ toxicity, and platelet activation were measured.

Results:
Exposure of WT mice to e-cig aerosols increased urine levels of the acrolein, but not formaldehyde, metabolite (3HPMA), to that of exposures to 1 ppm acrolein alone. In WT mice, exposure to either PG:G (30:70), formaldehyde (5 ppm), or acrolein (1 ppm) induced respiratory braking. In female WT mice (n=5-18), exposure to PG:G (-61.8±4.2 % ACh relaxation) and formaldehyde (–56.3 ± 4.5 %) but not acrolein (-80.0±3.2 %) induced ED vs control group (-77.8±1.5 %). In female TRPA1-null mice (n=5-14), neither PG:G (-77.6±3.6 %), formaldehyde (-85.9±7.8 %) nor acrolein (-86.6±2.8 %) exposure induced ED vs control (-81.3±5.4 %). Acrolein exposure enhanced aortic sensitivity to an NO donor similarly in female WT and TRPA1-null mice.

Conclusions:
Formaldehyde and acrolein generated from the PG:G in e-cigs provoked pulmonary irritant reflexes, and formaldehyde exposure alone induced ED in female mice. Irritant aldehydes in e-cig-derived aerosols activate the TRPA1 receptor to promote ED that could increase CVD risk.