bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16374: Perm1 Regulates Mitochondrial Energetics Through O-Glcnacylation in Cardiomyocytes
Authors: SREEDEVI KARTHI , James Amina , Yedla Shreya , Do Sara , arowa sumaita , Shah Riyan , Goode Breanna , Bui Sydney , Olmos Katia , Zaitsev Alexey , Warren Junco S
Published: December 2023

O-GlcNAcylation is a post-translational modification of proteins that plays an important role in cellular homeostasis and stress responses. Two enzymes regulate O-GlcNAcylation: O-GlcNAc transferase (OGT) that adds O-GlcNAc to proteins; O-GlcNAcase (OGA) that removes O-GlcNAc from proteins. While O-GlcNAcylation is necessary to respond to ischemia/reperfusion injury, chronic activation of O-GlcNAcylation in the heart has adverse effects, and excessive O-GlcNAcylation leads to the development of heart failure. However, there is currently no therapy for heart failure that targets O-GlcNAcylation. Perm1 is a striated muscle-specific regulator of mitochondrial bioenergetics. We previously demonstrated that Perm1-knockout mice exhibit reduced cardiac function and myocardial energy reserve, in association with excessive O-GlcNAcylation and upregulation of OGT. Here, we hypothesized that Perm1 maintains mitochondrial energetics by suppressing O-GlcNAcylation. We found that adenovirus-mediated overexpression of Perm1 in cardiomyocytes significantly decreased O-GlcNAcylation (Figure 1A-B) and increased the basal and maximal respiration and ATP production rates as compared with control in Cell Mito Stress Test using a Seahorse 96x flux analyzer (orange vs. green, Figure 1C-D). Furthermore, the increased levels of O-GlcNAcylated proteins (215% of control, p<0.05) via silencing OGA (si-OGA) in cardiomyocytes significantly decreased the basal and maximal respiration capacity and ATP production rates as compared with control (green vs. purple, Figure 1C-D), all which were completely rescued by Perm1 overexpression (blue, Figure 1C-D). These results suggest that Perm1 positively regulates mitochondrial energetics, in part, via suppressing O-GlcNAcylation and that Perm1 might be a new therapeutic target of heart failure that maintains mitochondrial function through preventing excessive O-GlcNAcylation under pathological stress.
Abstract 16382: Inaccuracy of Non-Invasive Brachial Cuff-Measured Blood Pressure During Surgery
Authors: Kim Sungsoo , Kwon Sohee , Cannesson Maxime
Published: December 2023

Introduction:
Blood pressure (BP) is an essential vital sign to be monitored during surgery. BP is measured only by Non-Invasive brachial Cuff-measured Blood Pressure (NICBP) devices in 90% of surgeries in US. However, previous studies demonstrated possible inaccuracy of NICBP. The inaccuracy of BP during surgery is a significant public concern because it can result in missing therapeutic potentials and consequently increasing cardiovascular risks during and after surgery. However, there is no large study to evaluate the accuracy of NICBP measured during surgery.

Method:
It has been known that invasive intra-arterial blood pressure (IABP) measured by an arterial line catheter is an optimal reference for validation of NICBP accuracy given its highest level of accuracy. Our study collected 2,814,154 pairs of BP measurements between NICBP and IABP which were measured at the same time during surgery from 38,706 patients who received surgeries at University of California, Los Angeles from 2016 through 2023.

Result:
We evaluated the accuracy of NICBP compared to IABP using Confusion matrix analysis (Fig 1). We defined predicted BP classification when BP is classified by NICBP. We also defined actual BP classification when BP is classified by IABP. We categorized BP according to Mean Arterial Pressure (MAP; mmHg) into 5 groups; MAP<65, 65≤MAP<75, 75≤MAP<95, 95≤MAP<105, and 105≤MAP. True Positive rates of each classification ranged from 36.7% to 66.7% (Fig 1). It was surprising that 49.9% in actual MAP (aMAP)<65, 56.9% in 65≤aMAP<75, 33.9% in 75≤aMAP<95, 63.4% in 95≤aMAP<105, and 50.6% in 105≤ aMAP was misclassified into the incorrect BP classifications by NICBP.

Conclusion:
Our study demonstrated noticeable inaccuracy of BP by NICBP compared to IABP during surgery. Given high reliability solely on NICBP in measuring BP during the majority of surgery cases, the inaccuracy of NICBP may cause significant public health concerns due to unoptimized BP management during surgery.
Abstract 16384: Interaction of Socioeconomic Status With Polygenic Risk for Coronary Artery Disease in a Novel Biobank
Authors: Pandya Lekha , Ledru Nicolas , Stitziel Nathan O
Published: December 2023

Introduction:
Socioeconomic status (SES) has a measurable and significant impact on cardiovascular disease incidence and outcomes. Study of its potential interactions with other known risk factors, such as genetics, remains an area for further research.

Aim:
To examine the interaction of polygenic risk for coronary artery disease (CAD) with socioeconomic status, as represented by income bracket.

Methods:
We utilized the NIH
All of Us
biobank, which integrates whole genome sequencing, electronic health record, and survey data. A previously-validated PRS for CAD (Inouye et al., 2018) was calculated for each patient. We subsetted the sample into high, medium, and low genetic risk groups per z-scores for the PRS: z-score >1, between 1 and -1, and <-1 respectively. Income information was derived from the survey data. Multivariable logistic regression was used to assess the performance of the PRS in this sample, with outcome defined as presence of CAD. The model was adjusted for PRS, age, gender, and the first 4 principal components of ancestry. Both income and the interaction of PRS by income were included as covariates.

Results:
In this sample of 97,405 individuals, this PRS is strongly associated with CAD prevalence: adjusted odds ratio for CAD per SD of the PRS was 1.96 (95% CI, 1.83-2.10). We then observed a differential effect of income on CAD. In the low and medium genetic risk groups, increasing income was associated with lower CAD prevalence. In the high genetic risk group, this protective effect was lost and CAD prevalence was overall similar across income brackets.

Conclusions:
These findings suggest a complex interaction between genetic risk of CAD and SES. High risk individuals may not derive the same benefit of improved SES and its material benefits. This unique subgroup will require uniquely targeted interventions, highlighting the need for deeper study of genetic risk in order to actualize the promises of precision medicine.
Abstract 16387: Speckle-Tracking Echocardiographic Features of Cardiac Amyloidosis in Patients With HFrEF
Authors: Csecs Ibolya , Katamreddy Adarsh , Flatow Elie , Mangeshkar Shaunak , Singh Nikita , Nazarenko Natalia , Barillas Lara Maria-Irene , Schenone Aldo L , Slipczuk Leandro , Garcia Mario J
Published: December 2023

Introduction:
The role of speckle-tracking echocardiography (STE) for establishing the diagnosis of cardiac amyloidosis (CA) has been primarily studied in patients with preserved EF (HFpEF).

Hypothesis:
We sought to determine the prevalence of abnormal STE indices among HF patients with CA who have reduced EF (HFrEF).

Methods:
We reviewed electronic health records to identify patients consecutively referred for the evaluation of CA by Tc99m PYP imaging between December 2014 to December 2020. Only patients with LVEF < 40% were included. Left ventricular (LV) and atrial (LA) global and segmental strain, relative apical sparing (RELAPS), and end-diastolic wall stress (EDWS) were measured using STE (TomTec).

Results:
Among 138 patients, 65 (47%) were identified with CA+; they were older compared to amyloid negative group (CA-). LV-GLS was similar in both groups. However, basal segments LV strain, LA strain, and LA fractional area change (LA-FAC) were significantly lower, and RELAPS was higher in CA+ patients (Figure). End-diastolic wall stress was also lower in CA+ (for all p< 0.01, Figure). After adjusting for age and sex, impaired basal segment strain, EDWS, and LA-FAC remained independent predictors of identifying CA+ patients (p< 0.05).

Conclusions:
The presence of CA among HFrEF patients is associated with regional variability in LV strain, greater impairment of LA function, and lower EDWS.
Abstract 16395: Caregiver Challenges, Needs, and Health Outcomes After Left Ventricular Assist Device Implantation
Authors: Auld Jonathan , Streur Megan M , Thompson Elaine , Beckman Jennifer , Dougherty Cynthia M
Published: December 2023

Introduction:
Caregivers of patients with left ventricular assist devices (LVAD) experience significant strain in caring for patients after device implant, yet few studies have captured underlying caregiver needs and the impact on caregiver health.

Aim:
To describe caregiver challenges, needs, and health outcomes at three distinct time points following LVAD implant.

Method:
Using a cross-sectional, concurrent mixed methods design, patients were interviewed at 1 of 3 time points during LVAD recovery: at hospitalization after LVAD implant (n=3), at 1 month (n=9) , or 3 months (n=7) after returning home. Key health outcomes (measures) included caregiver Roles and Responsibilities (CRRS), mental health (SF-12 MCS), and physical function (Duke Activity Status Index, DASI). Qualitative interviews were transcribed verbatim and analyzed using thematic analysis; qualitative and quantitative findings were integrated using matrix displays across time points.

Results:
Caregivers (N=19) were 60.0±9.6 years old, 68% married, 88% female, 56% with 2 or more comorbidities, and 56% caring for Destination Therapy patients. Three phases of caregiving were characterized. At 1 month, caregiver burden was highest (CRRS: hospitalization after implant= 32±12.7; 1 mo = 51.6±7.8; 3 mo = 47.3±8.9); physical function lowest (DASI: hospitalization after implant = 53.7±5.3; 1 mo = 38.1±9.7; 3 mo = 42.1±15.6); and mental health highest (SF-12: hospitalization after implant = 43.4±7.8; 1 mo = 55.8±25.9; 3 mo = 48.3±26.8). Qualitative analyses validated caregiving challenges and health impact at 1 month (isolation, constant caregiving, uncertainty) and low physical function (work of caregiving, disrupted sleep), while simultaneously underscoring positive mental health effects (gratitude for a second chance, establishing routines, experiencing support).

Conclusion:
The characterization of three phases of caregiving after LVAD implantation provides important new insights necessary for targeted interventions for LVAD caregivers. Identified targets to relieve caregiver burden and improve adjustment after patients are discharged home include the need for relief from isolation and 24/7 caregiving, promotion of sleep and routines, and social support.
Abstract 16400: Development of Deep Neural Network Models for Identification of Pulmonary Vein Potentials From Body Surface Electrocardiograms of Patients With Atrial Fibrillation
Authors: Tanaka Munekazu , Kohjitani Hirohiko , Inoue Tomoyuki , Morinaga Akifumi , Yoneda Fumiya , Nishiwaki Shushi , Shizuta Satoshi , Okuno Yasushi , Ono Koh
Published: December 2023

[Background]
Pulmonary vein (PV) potential is essential as the origin of atrial fibrillation (AF). However, no established method exists to evaluate PV potentials on a body surface ECG (BS-ECG).

[Objective]
To develop a method to identify PV potentials from BS-ECGs using state-of-the-art deep neural network (DNN) technology.

[Methods and results]
A cohort of 799 consecutive paroxysmal AF patients, who underwent Pulmonary Vein Isolation (PVI), were enrolled, and pre- and post-PVI 12-lead ECGs (12ECGs) were collected, amounting to a dataset of 1598 ECGs. Four DNN models were constructed, each employing distinct architectures: 1D-ResNet, 1D-DenseNet, 1D-EfficientNet-b3, and 1D-ViT (Vision Transformer). These models were rigorously trained and evaluated for the identification of PV potentials. The 1D-EfficientNet-b3-based model exhibited optimal performance, achieving an accuracy of 89.4% in the training set and 89.1% in the test set. The Gradient-weighted Class Activation Mapping (Grad-CAM) effectively demonstrated that the segments 200-300ms before the P-wave is crucial for identifying PV potentials. Furthermore, DNN models were developed for each single-lead ECG. While there were variations in the accuracy of PV potential identification among single-lead models, the V6-lead model demonstrated superior performance with an accuracy of 83.2%.

[Conclusions]
The findings of this research strongly suggest that our DNN-based model can accurately differentiate PV potentials from BS-ECGs. Additionally, Grad-CAM visualizations indicate that pertinent features for the identification of PV potentials are predominantly clustered in the P-wave frontal region. This signifies a promising advancement in the non-invasive detection and analysis of PV potentials, paving the way for improved management of paroxysmal AF.
Abstract 16414: Prognostic Value of Exercise Tolerance and Exercise-Associated Diastolic Dysfunction in Elderly Patients Referred for Exercise Stress Echocardiography
Authors: Elias Joseph , Konje Swiri , Munoz Alba , Kim Ga Hee , Gandhi Kruti , Moras Errol C , Perez Lizardo Christopher , Kaur Arpanjeet , Omar Alaa , Argulian Edgar
Published: December 2023

Aim:
We studied the prognostic value of exercise tolerance, measured in metabolic equivalents of tasks (METs), and exercise-associated diastolic dysfunction (Ex-DD) in elderly patients referred for exercise stress echocardiography (ExE).

Methods:
Retrospectively, 583 patients (70±6 years, 57% women, EF: 61±5%) who underwent ExE using the Bruce protocol and were ≥60 years of age were included and followed for death or cardiac hospitalization. Ex-DD was defined as the presence of abnormal resting tissue Doppler mitral annular velocity (e') and post-exercise E/e' ratio.

Results:
During a median follow-up period of 3.7 years, 13 patients died, 70 were hospitalized, and 77 had combined outcome. 151 (26%) patients had Ex-DD and had more combined outcome compared to no Ex-DD (29 [19%] vs. 48 [11%], p=0.01). The average workload during ExE was 8.3±2.8 METs. Receiver operating characteristic curve identified that METs <8.5 best predicts the combined outcome. As such, patients were classified into 260 with METs ≥ 8.5 and 323 with METs < 8.5. Patients with METs < 8.5 were older, had worse risk profiles, poorer resting and post-exercise diastolic variables, more Ex-DD (32% vs. 19%, p<0.001), and more outcomes (55 [17%] vs. 22 [9%], p=0.002) compared to METs ≥ 8.5. Both Ex-DD (HR: 1.9, 95% CI: 1.2-2.9) and METs < 8.5 (HR: 1.9, 95% CI: 1.1-3.1) independently predicted the combined outcome. The presence of both METs < 8.5 and Ex-DD conferred the highest risk (HR: 2.9, 95% CI: 1.5-5.6) and remained significant after adjustment and propensity score matching, while the presence of either alone carried an intermediate risk (HR: 1.9, 95% CI: 1.1-3.5), which became non-significant after adjustment and matching.

Conclusions:
poor exercise capacity is associated with an adverse prognosis, irrespective of resting or Ex-DD. METs < 8.5 had particularly poor prognosis when combined with Ex-DD, while either alone did not predict outcomes.
Abstract 16437: An Infectious Rise in Fats - Severe Hypertriglyceridemia Secondary to SARS-CoV-2 Infection
Authors: Katsadouros Vasili , Hoffman Erik C
Published: December 2023

Intro
There are many complications because of COVID-19 infections. These have ranged from organ dysfunctions to severe disease states. The global nature of SARS-CoV-2 pandemic has allowed clinicians to discover new pathophysiology associated with infections. We present a case of a patient with severe hypertriglyceridemia (HTG) after a SARS COVID-19 infection and propose a correlation between his infection and elevated triglyceride (TG) levels.

Case
A 64 y/o man living with a history of HFpEF, COPD, and HLD presented to our clinic after being diagnosed with SARS-CoV-2 infection two days prior. He had upper respiratory symptoms of a productive cough, fevers, decreased appetite, and mild dyspnea with exertion not requiring supplemental oxygen. He was prescribed paxlovid and discharged home. On follow up his symptoms had improved. He was due for a repeat lipid level and this was drawn during his visit. His last lipid panel results were normal. His repeat TG was 2,186 mg/dL. It was thought his levels were elevated because of his SARS-CoV-2 infection. His fasting TG levels were repeated and found to have normalized with a low-fat diet alone and had no further interventions.

Discussion
There have been few reports demonstrating a rise in TG levels after SARS-CoV-2 infections. Hepatic injury secondary to the infection or medications prescribed for treatment may lead to elevated TGs levels. When these are excluded, it is unknown what leads to HTG. Studies have evaluated lipoprotein lipase (LPL) activity levels and how they were decreased after SARS-CoV-2 infections. LPL assists in the metabolism of TG’s and activity is decreased in many disease states. It is thought that the COVID-19 infection causes HTG secondary to acquired LPL deficiency. These patients require close monitoring to decrease complications.

Conclusion
HTG is known to cause increased incidence of pancreatitis and ASCVD events. While treating these, one must assess the underlying etiology that led to the disease state. In patients found to have elevated TG levels it is important to include questions pertaining to recent infectious processes. Further research is needed to deduce how infectious processes can lead to elevated TG levels. Treatment consists of initiating a low-fat diet and may include fibrates.
Abstract 16499: Social Determinants and Racial Disparities Among Hospitalized Individuals With Hypertensive Crisis; a Retrospective Population-Based Cohort Analysis
Authors: Evbayekha Endurance O , Idowu Abiodun , Shamaki Garba Rimamskep R , Nriagu Bede , Okorare Ovie , Aiwuyo Henry , Ouedraogo Faizal , Adabale Olanrewaju , Antia Akanimo , Bolaji Olayiwola , Jaiswal Vikash , Okoh Alexis K , Bob-Manuel Tamunoinemi
Published: December 2023

Introduction:
Hypertensive crisis (HC) encompasses hypertensive emergencies (HE) and urgencies (HU). Recent literature on HC's social determinants (SD) and racial disparities (RD) of the inpatient population is scarce. We aimed to examine these factors.

Hypothesis:
We hypothesized that there would be variations in the RD and SD of hospitalized individuals with HC.

Methods:
A retrospective analysis of the 2016-2020 National Inpatient Sample was conducted, and all hospitalizations for HC were identified with their ICD-10 codes. A multivariate logistic regression analysis was performed to account for confounders and estimate the probability of outcomes. Our primary outcomes were SDs of HC. Secondary outcomes were myocardial infarction (MI), stroke, acute kidney injury (AKI), and transient ischemic attack (TIA).

Results:
Of the 32,355,827 of all hospitalizations, 2.4% (762,185) had a diagnosis of HC (48.5% (369735) HU, 37.3% (284350) HE, and 14.2% (108100) ‘HC unspecified’), with 49.8% (285,634) Caucasians, 34% (188,255) Blacks, 11.2% (63,952) Hispanics and 2.8% (16,173) were Asians. When stratified by age, the Black population was the youngest of all the races; 57.6 years ±15.6 vs. 67.9 years ±15.5 Caucasians, vs. 60.5 years ±17 Hispanics, vs. 65.2 years ±17 Asians, p<0.0001. The minority populations were more likely than the Caucasians to be diagnosed with HCs; Blacks 2.7 (2.6-2.9), Hispanics 1.2 (1.2-1.3), and Asians 1.4 (1.3-1.5),(p<0.0001, all). Furthermore, being male 1.1 (1.09-1.2, p<0.0001), those with ‘self-pay’ insurance type 1.02 (1.01-1.03, p<0.0001), and those in the <25th percentile of median household income 1.3 (1.2-1.3, p<0.0001), were more likely to be diagnosed with HCs.The Black population had the highest likelihood of end-organ damage; MI 2.7 (2.6-2.9), Stroke 3.2 (3.1-3.4), AKI 2.4 (2.2-2.5), and TIA 2.8 (2.7-3.0), (p<0.0001, all), compared to their Caucasian counterpart.

Conclusions:
Being of a minority population, male sex, low-income status, and uninsured were associated with a higher likelihood of hypertensive crisis. Blacks were the youngest and had the highest risk of end-organ damage. Targeted interventions and healthcare policies should be implemented to address these disparities and improve patient outcomes.
Abstract 165: Immediate Internalization of Transplanted Mitochondria in Circulatory Immune Cells After Cardiac Arrest Resuscitation in Rats
Authors: Aoki Tomoaki , Becker Lance B , Endo Yusuke , Nakamura Eriko , Hayashida Kei
Published: December 2023

Background:
Mitochondrial transplantation (MTx) is an innovative technology that has the potential effect for attenuating ischemia reperfusion injury. We previously demonstrated that MTx significantly improves survival and neurological outcomes after cardiac arrest (CA) and resuscitation in rats. However, the underlying mechanism by which MTx enhances CA outcomes remains unclear.

Aim:
To investigate the hypothesis that injected donor mitochondria are rapidly internalized by circulatory immune cells, particularly monocytes/macrophages, which play crucial roles in post-CA inflammatory signaling.

Methods and Results:
Adult male Sprague-Dawley rats underwent sham operation or 10 minutes of asphyxial CA followed by resuscitation with CPR. Either a respiration buffer as a vehicle or donor mitochondria labeled with MitoTracker Deep Red (MTDR) was intravenously injected to animals of both groups. In the CA groups, the injection was performed upon achieving spontaneous circulation. Serial blood samples were collected at 30, 75, and 150 seconds after injection. Flow cytometry analysis revealed that a marked increase of MTDR-positive ratios, peaking at 30 seconds, in CD45
+
leukocytes, CD3
+
T lymphocytes, and CD11b/c
+
monocytes/macrophages in the MTx-treated CA group compared to the other groups (Figure A). Notably, in sham-operated rats with donor mitochondrial injection, only minimal donor mitochondria were found in the circulating immune cells at those time points. Brain and spleen 1 h post-CA with MTx showed enhanced signals of MTDR measured using an in vivo imaging system, indicating successful transfer of injected mitochondria to organs (Figure B).

Conclusion:
Our findings demonstrate rapid internalization of injected mitochondria by circulatory immune cells after MTx in post-CA rats, suggesting a pivotal role for circulating immune cells in the mechanism underlying the beneficial effects of MTx in CA resuscitation.
Abstract 16512: Significant Sociodemographic Disparities and the Burden of Major Adverse Cardiac and Cerebrovascular Events Among Cancer Survivors Hospitalized With COVID-19: A Nationwide Analysis
Authors: Gurram Priyatham , Mohammed Adil S , Guntuku Sandeep , Lingamsetty Shanmukh sai pavan , Medarametla Ravi Venkata Sai Krishna , Baskara Salian Rishabh , Yadav Vikas , Nawab Shariq , Mohammed Zaki Ur Rahman , SAEED ERUM , SAEED IRFAN , Jahan Rawnak , Jain Akhil , Desai Rupak
Published: December 2023

Background:
Cancer survivors are at an increased risk of cardiovascular disease due to various treatment modalities, and COVID-19 can further complicate their cardiovascular health. Therefore, we aimed to study the burden of major adverse cardiac and cerebrovascular events (MACCE) among cancer survivors hospitalized with COVID-19 and associated sociodemographic disparities.

Methods:
We analyzed the National Inpatient Sample Database (2020) to identify COVID-19 related adult (≥18 years old) hospitalizations among cancer survivors and associated MACCE (all-cause mortality, acute myocardial infarction, cardiac arrest, and stroke) using ICD-10 codes. A multivariable regression analysis of MACCE based on disparities like age, sex, race, and household income was done.

Results:
Of 112,270 COVID-19 related admissions in cancer survivors (51.8% males, 68% white, 14.7% black, and 9.8% Hispanic), 17.8% (n = 19935) patients experienced in-hospital MACCE. All MACCE events were higher among patients aged ≥ 65 years and 45-64 years compared with the 18-44 year age group, with ORs of 5.61 (95% CI: 3.43-9.19) and 2.30 (95% CI: 1.41-3.76) respectively. Males have higher odds of MACCE than females (OR 1.33, 95% CI: 1.23-1.43). The odds of MACCE were higher in Hispanics (OR 1.23, 95% CI: 1.08-1.39) and Native Americans (OR 1.71, 95% CI: 1.08-2.73) compared to Whites. Lowest income quartile patients had a higher MACCE than highest-income quartile patients (OR 1.13, 95% CI: 1.00-1.28). For all the above-mentioned ORs, the level of significance was p<0.05.

Conclusion:
Among COVID-19 related admissions in cancer survivors, elderly patients, males, Hispanics, Native Americans, and those in the lowest income quartile are prone to have increased MACCE. Factors like age, sex, race, and socioeconomic status seem to play a role in MACCE incidence. Understanding these factors may help emphasize improving patient care, address health equity issues, and inform healthcare policymakers.
Abstract 16573: Orthostatic Blood Pressure Changes and Cognitive Function: Insights From the SPRINT MIND Trial
Authors: Yang Ruixue , Cai Jun
Published: December 2023

Introduction:
The association between orthostatic blood pressure (BP) changes and cognitive function has not been thoroughly investigated. Moreover, whether orthostatic hypotension or hypertension modifies the effects of intensive BP control on cognitive outcomes is unknown.

Hypothesis:
We hypothesized that orthostatic BP changes were associated with cognitive function and the effects of intensive BP control on cognitive outcomes might be different among individuals with/without orthostatic hypotension or hypertension.

Methods:
We performed a post hoc analysis of SPRINT MIND, a randomized controlled trial evaluating the effects of intensive vs. standard SBP control on cognitive outcomes in hypertensive patients. The relationships between baseline orthostatic BP changes (defined as baseline standing systolic BP [SBP]–baseline seated SBP) and probable dementia (PD) and mild cognitive impairment (MCI) were analyzed. The competing risk proportional hazards regression and cubic spline regression were used in analysis.

Results:
A total of 8547 participants (mean [SD] age, 67.9 [9.3] years; 5543 [64.9] men) were included in this analysis. In the crude model, the restricted cubic spline analysis showed L-shaped associations between orthostatic SBP change and new-onset PD and MCI (all P for nonlinearity<0.05). However, these associations all disappeared after adjustment for covariates. Moreover, orthostatic diastolic BP change was not associated with the PD or MCI incidence. Intensive BP control did not alter the risk of PD or MCI in patients with/without orthostatic hypotension or hypertension.

Conclusions:
Orthostatic BP changes were not associated with the risk of PD or MCI; baseline orthostatic hypotension or hypertension did not influence the effects of intensive BP control on cognitive outcomes. These results are hypothesis-generating and merit further study.
Abstract 16617: Effects of Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors on Inflammatory and Haemostatic Parameters in Coronary Artery Disease Patients
Authors: Ugovšek Sabina , Rehberger Likozar Andreja , SEBESTJEN Miran
Published: December 2023

Background and aims:
Despite progress in treatment, elevated levels of low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) represent a significant part of the residual risk. Both are associated with inflammation and the coagulation fibrinolytic system. The purpose of our research was to evaluate the effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on lipid parameters and indicators of inflammation, coagulation and fibrinolysis.

Methods:
We included 100 patients after a myocardial infarction with insufficiently controlled LDL-C values despite the maximum dose of statin, and highly elevated Lp(a). Patients received alirocumab or evolocumab (150mg sc or 140g sc every two weeks; respectively) or placebo for 6 months.

Results:
In the group receiving PCSK9i, a significant decrease in total cholesterol (TC), LDL-C, triglycerides (TG) and Lp(a), and an increase in high density lipoprotein cholesterol (p<0.001 for all) was found. Before treatment concentrations of TC, LDL-C and TG correlated with the concentration of thrombin activatable fibrinolysis inhibitor (r=0.41, p<0.001; r=0.353, p<0.001; r=0.311, p=0.003; respectively), and plasminogen activator inhibitor-1 (r=0.302, p=0.007; r=0.218, p=0.049; r=0.278; p=0.013; respectively). The concentration of TC and LDL-C correlated with overall fibrinolytic potential (r=-0.220, p=0.034; r=-0.207, p=0.047; respectively). The concentration of TG was related to the concentration of interleukin 6 (r=0.290, p=0.004) and interleukin 8 (r=0.332, p=0.001). No correlations between Lp(a) and inflammatory or haemostatic variables were found. No associations were found after treatment.

Conclusion:
Our results show that fibrinolytic parameters and inflammatory cytokines are related to the concentration of LDL-C and not Lp(a) before and with neither of them after treatment with PCSK9i.
Abstract 16623: Extra-Cellular Volume Fraction Analysis on Cardiac CT is Useful for Predicting the Prognosis of Hypertrophic Cardiomyopathy
Authors: Aoki Shuhei , Takaoka Hiroyuki , Asada Kazunari , Kinoshita Makiko , Yashima Satomi , Suzuki Katsuya , Yoshida Kazuki , Sasaki Haruka , Eguchi Noriko , Kobayashi Yoshio
Published: December 2023

Introduction:
Extra-Cellular volume fraction (ECV) analysis on MRI helps predict ventricular arrhythmia in hypertrophic cardiomyopathy (HCM). But the performance of cardiac MRI takes time, and there are also several contraindications. Cardiac CT is more versatile than cardiac MRI and is also helpful in screening coronary artery disease. We investigated the usefulness of ECV analysis on CT for the prognosis of HCM.Aim: To determine the utility of ECV analysis on CT to predict the prognosis in patients with HCM.

Methods:
Eighty-five HCM patients who underwent cardiac CT from December 2008 to March 2022 were analyzed. Left ventricular (LV) ECV (LV-ECV) on CT was measured, and we investigated the relationship between LV-ECV on CT and the major adverse cardiac events (MACEs) (cardiac death, fatal arrhythmia, and heart failure hospitalization) after CT.

Results:
All patients were followed for 69 ± 58 months after cardiac CT and 14 patients (16%) had MACEs. They had a significantly higher LV-ECV and lower ejection fraction (LVEF) than those without MACEs(42.4 ± 8.4% vs. 34.0 ± 7.0%, P=0.003, and (56.7 ± 11.8% vs. 66.7 ± 7.0%, P=0.011). The percentage of dilated phase HCM was significantly higher in the patients with MACEs than those without MACEs (21% vs 0%, p=0.003). LV-ECV was the only significant predictor of MACEs based on the multivariate analysis by Cox proportional hazard model (hazard ratio 1.13, 95% confidence interval 1.06-1.21). The optimal threshold of LV-ECV to predict MACEs was 37.59% based on the receiver operating characteristic analysis. The sensitivity and specificity of LV-ECV to predict MACEs were 79% and 75% at the best cut-off, and the area under the curve was 0.78 (Figure A). The patients with LV-ECV ≥ 37.59% (29 patients) had significantly higher MACEs than those with LV-ECV < 37.59% during the follow-up periods (P <0.001) (Figure B).

Conclusion:
ECV analysis on CT helped predict MACEs in HCM cases.
Abstract 16649: Clonal Hematopoiesis as a Predictor of Left Ventricular Reverse Remodeling in Non-Ischemic Dilated Cardiomyopathy
Authors: Inoue Shunsuke , Nomura Seitaro , Dai Zhehao , Jimba Takahiro , Ko Toshiyuki , Amiya Eisuke , Hatano Masaru , Morita Hiroyuki , Komuro Issei
Published: December 2023

Background:
Clonal hematopoiesis of indeterminate potential (CHIP) is an independent risk factor of major adverse cardiovascular events, including heart failure (HF) with reduced left ventricular ejection fraction (LVEF). Although genetic mutations are known to affect clinical prognosis and left ventricular reverse remodeling (LVRR) in non-ischemic dilated cardiomyopathy (DCM), the prevalence and clinical significance of CHIP in DCM remain elusive.

Objectives:
The principal aim of this study is to delineate the distribution and prognostic impact of CHIP in non-ischemic DCM.

Methods:
We included 198 cases of DCM with LVEF ≤ 40% and no identifiable cause for left ventricular systolic dysfunction from the Japanese multi-center cohort. Whole exome sequencing was performed for germline analysis, and deep target sequencing focusing on CHIP driver genes for somatic analysis was conducted. We detected cardiomyopathy-related pathogenic mutations and CHIP driver mutations using GATK best practices and Mutect2, respectively. The primary endpoint was LVRR, defined as an absolute increase in LVEF by ≥ 10% at a one-year follow-up echocardiogram.

Results:
Twenty-seven CHIP driver mutations were detected in 24 (12%) of the DCM patients. The mean read coverage for CHIP driver mutation was 2156.
DNMT3A
was the most frequent mutated gene in CHIP, followed by
TET2
. Ninety-two (46%) patients have cardiomyopathy-related pathogenic mutations.
TTN
was the most frequent mutated gene, followed by
LMNA
. Although the CHIP-positive group showed similar LVEF and prevalence of cardiomyopathy-related pathogenic mutations compared with the CHIP-negative group, the occurrence of LVRR was significantly lower in the CHIP-positive group (47.0% vs. 20.8%, P=0.018). Multivariate logistic regression analysis revealed that CHIP (odds ratio (OR): 0.23, P=0.022) and cardiomyopathy-related pathogenic mutations (OR: 0.28, P<0.001) were independent negative predictors of LVRR.

Conclusions:
Determining germline and somatic mutations in DCM significantly predict clinical prognosis.
Abstract 16652: Cardiovascular Outcomes of Renin-Angiotensin System Inhibition Amongst Non-Proteinuric Chronic Kidney Disease Patients in the Chronic Renal Insufficiency Cohort
Authors: Shulman Rachel , Cohen Jordana , Yang Wei , Cohen Debbie L , Reese Peter , Townsend Raymond R
Published: December 2023

Introduction:
Chronic kidney disease is a leading cause of CVD morbidity and mortality. The majority of CKD patients do not have proteinuria. Current therapies, including renin-angiotensin system (RAS) blockers, are only known to be beneficial in proteinuric CKD. Our goal was to evaluate the association of RAS blockade with long-term CVD outcomes and survival among those with non-proteinuric CKD.

Methods:
The cohort included subjects in the prospective Chronic Renal Insufficiency Cohort Study without proteinuria at study entry. Non-proteinuric CKD was defined as urine protein <0.5g/day. We excluded subjects with heart failure or not on hypertension treatment. We used Cox proportional hazards regression to evaluate the association of RAS blockade vs. other antihypertensive therapy with CVD outcomes and death. The primary outcome was a composite of physician-adjudicated CVD events, including MI, stroke, heart failure hospitalization and death. Baseline covariates were adjusted through inverse probability of treatment weighting including: age, sex, race, education, smoking, BMI, diabetes, blood pressure, eGFR, and statin use.

Results:
A total of 2,825 of subjects met inclusion criteria. There were 2,068 subjects using vs 757 not using (73% vs 27%) RAS blockade at entry. Users had a similar age (61 vs 62 years) and eGFR (50 vs 51ml/min/1.73m
2
) to non-users. Users were more likely to be male (66% vs 46%), to have diabetes (59% vs 30%), and to be on a statin (61% vs 50%). No significant association was found between RAS blockade and CVD events (adjusted HR 0.90, 95% CI 0.76-1.07) or mortality (adjusted HR 0.84, 95% CI 0.68-1.04) compared to other antihypertensive therapy.

Conclusions:
Among adults with non-proteinuric CKD, baseline use of RAS blockade was not associated with a lower risk of long-term events or mortality. Further studies are needed to determine if RAS blockade may play a role in high-risk patients with non-proteinuric CKD.
Abstract 16672: Effects of Evinacumab on Atherogenic Lipoproteins in Children and Adolescents From Ages 5 to 17 Years With Homozygous Familial Hypercholesterolemia
Authors: Brinton Eliot A , Gaudet Daniel , Raal Frederick J , Wiegman Albert , Baker-Smith Carissa M , Moriarty Patrick M , Greber-Platzer Susanne , Rosenson Robert S , Waldron Alpana , ali shazia , Skiba Paul , George Richard T , Pordy Robert , Zhao Xue-Qiao
Published: December 2023

Background:
Homozygous familial hypercholesterolemia (HoFH) is characterized by severely elevated LDL-C levels from birth. Diagnosis and aggressive LDL-lowering treatment (LLT) before adulthood are essential for optimal ASCVD prevention in HoFH; however, it is often undiagnosed and undertreated in pediatric patients. Specifically, HoFH children and adolescents routinely require advanced LLT, since few achieve LDL-C goal on standard LLT. Evinacumab, a novel angiopoietin-like-3 inhibitor and advanced LLT, has an established safety profile in younger and older pediatric HoFH patients, 5-11 and 12-17 years, respectively. For the first time, we compare its lipid efficacy in these two groups.

Methods:
Fourteen patients ages 5-11 years (Study 17100 part B; NCT04233918) and 14 patients ages 12-17 years (Study 1719; NCT03409744), all with HoFH on stable LLT, were treated with IV evinacumab 15 mg/kg Q4W. Notably, in Study 17100 part B, no patients were taking PCSK9 inhibitors at study entry, while in Study 1719, 42.9% of patients were receiving a PCSK9 inhibitor at baseline. Apheresis use differed little, 50.0% in the younger study vs 64.3% in the older. LDL-C and other atherogenic lipoproteins were tested at baseline and 24 weeks.

Results:
In patients ages 5-11 years, mean (SD) baseline LDL-C was 263.7 (91.0) mg/dL and was lowered 48.3% (131.9 mg/dL) by evinacumab (
Table
). In patients ages 12-17 years, baseline LDL-C was 300.4 (100.5) mg/dL and was lowered 55.4% (180.5 mg/dL), with similar baseline and changes to those of the younger patients. In both groups, evinacumab markedly reduced ApoB, non-HDL-C, and Lp(a) (
Table
).

Conclusions:
Evinacumab strikingly and comparably reduces atherogenic lipids in younger and older pediatric HoFH patients. Since standard LLT rarely lowers LDL-C levels to treatment goals in pediatric HoFH, evinacumab should be strongly and urgently considered in these patients whenever further LDL-lowering is needed after optimizing standard LLT.
Abstract 167: Neutrophil Maturity Following Resuscitation From Cardiac Arrest
Authors: deKay Joanne T , Weatherbee Sorcher Mary , May Teresa , Gagnon David , Sawyer Douglas B , Riker Richard , Seder David B. , Ryzhov Sergey V
Published: December 2023

Introduction:
Immature neutrophils mobilized from bone marrow in response to injury do not express CD10 and are characterized as pro-inflammatory. Maturity status of neutrophils has not yet been described in patients after the global ischemic-reperfusion injury following cardiac arrest (CA).

Hypothesis:
Immature neutrophils predominate the systemic cellular response after CA and are associated with mortality.

Goal:
To characterize neutrophils and their associations with clinical parameters in patients following resuscitation from CA.

Methods:
After informed consent, 100 subjects were enrolled. Blood samples were collected at 6, 12, 24, 48, 72, and 168 hours after return of spontaneous circulation (ROSC). White blood cells (WBC) were isolated and stained for flow cytometry. Data analysis was performed with FlowJo and GraphPad Prism; a P-value of <0.05 was deemed statistically significant.

Results:
In our cohort of 51 non-survivors and 49 survivors, there were no significant differences in WBC count at any time point. At 72 hours after ROSC, we found a higher absolute number (6.8 vs. 5.0; p=0.018) and percentage
(
87.1 vs. 80.3; p=0.030) of neutrophils in the WBC population in non-survivors compared to survivors. Analysis of neutrophil CD10 subpopulations revealed a higher number of immature CD10
-
neutrophils in non-survivors at 72 hours after ROSC (6.1 vs. 4.4; p=0.007) compared to survivors. There was no significant difference between non-survivors and survivors in mature CD10
+
neutrophil count or temporal changes. The CD10
-
/CD10
+
neutrophil ratio was significantly higher in non-survivors at 24 hours (4.7 vs. 3.1; p=0.036) and 48 hours (11.5 vs. 6.6; p=0.040) after ROSC.

Conclusions:
Neutrophils are important to inflammation resolution after injury; however certain subpopulations of immune cells may be involved in and perpetuate tissue damage after CA. The levels and temporal changes of pro-inflammatory, immature (CD10
-
) neutrophils in non-survivors point to the need for further research including functional studies. The identification of neutrophil marker targets that may impact the balance of pro- and anti-inflammatory immune cells and their related signaling pathways could offer opportunities to improve outcomes after cardiac arrest.
Abstract 16703: ST Elevation Myocardial Infarction and Chronic Total Occlusion: Trends and In-Hospital Outcomes in the United States
Authors: Bandaru Revanth Reddy , Mondal Avilash , Aggarwal Sanjana , Nathani Pratiksha Shankarlal , Sankaramangalam Kesavan , Desai Rupak
Published: December 2023

Introduction:
Acute ST-segment elevation myocardial infarction (STEMI) occurs due to sudden thrombotic complete occlusion of one or more coronary arteries resulting in transmural ischemia and eventually necrosis. Chronic total occlusions (CTO) are incidentally found in a minority of patients and have been implicated in poor outcomes in STEMI patients. There is a paucity of data analyzing the trends and outcomes of STEMI patients with a CTO (STEMI-CTO).

Methods:
We used the National Inpatient Sample to identify elderly (>65 years) STEMI patients with vs. without CTO. We compared the prevalence trends of STEMI, baseline characteristics, in-hospital mortality, and complications, including cardiogenic shock, in these two groups from 2016 to 2019. Chi-square test was used to determine the statistical significance of these variables.

Results:
Of 317,105 STEMI hospitalizations, 21,115 had concomitant CTO. Patients with CTO were more likely to be young (median age 73 vs. 74, p <0.001), obese (13.8% vs. 12.8%), males (67.5% vs. 60.5%), with peripheral vascular disease (13.4% vs. 10.8%), hyperlipidemia (67.5% vs. 65.5%), and prior history of MI (15.2% vs. 12.3%), PCI (14.1% vs. 13.0%) and CABG (9.4% vs. 6.1%) (p<0.001). In-hospital mortality was more frequent in CTO-STEMI compared to non-CTO-STEMI patients (12.5% vs. 11.8%, p=0.003). From 2016-2019, the prevalence of CTO kept decreasing (10.7% vs. 6.5%, P<0.001); however, increasing mortality trends in CTO patients (14.4% vs. 12.2%) compared to decreasing mortality trends in non-CTO patients (11.2% vs. 12.5%) was concerning. [Fig. 1]. Also, the frequency of in-hospital deaths was on a uptrend and peaked in 2019 amongst all CTO patients.

Conclusions:
The prevalence of CTO in STEMI patients is decreasing, while in-hospital mortality, cardiogenic shock and hospital expenses continue to rise. Future prospective studies are necessary to understand the trends among CTO-STEMI patients to avoid poor outcomes.
Abstract 16712: Cardio-Ankle Vascular Index as an Independent Predictor of Cardiovascular Events in Patients With and Without Previous Cardiovascular Disease: A Systematic Review and Meta-Analysis
Authors: Tavolinejad Hamed , Chirinos Julio A
Published: December 2023

Background:
Large artery stiffness predicts the risk of major adverse cardiovascular events (MACE). However, most data to date are related to carotid-femoral pulse wave velocity. Data about the prognostic value of cardio-ankle vascular index (CAVI), a less blood pressure-dependent marker, are limited, especially among individuals without prior cardiovascular disease (primary prevention).

Hypothesis:
Higher baseline CAVI is associated with incident MACE and all-cause death.

Methods:
PubMed, Scopus, and Web of Science were searched up to 29 April 2023 for longitudinal studies reporting the association of CAVI with incident fatal and nonfatal cardiovascular events. Risk of bias was assessed using the MINORS tool. Pooled hazard ratios were calculated separately based on use of CAVI as a categorical or continuous variable. Subgroup analysis focused on studies of patients without prior cardiovascular disease.

Results:
We included 21 studies (37,658 participants; mean age range 52-75 years; 53.9% males). Median study follow-up duration was 5 years (IQR 4.4-6; range 2-12.4). Despite variations in multivariable models, studies reported adjustments for conventional risk factors. Higher CAVI was associated with risk of MACE among all studies (categorical HR=1.45 [1.23-1.70], I
2
=51%; continuous HR=1.24 [1.15-1.33], I
2
=18%) and in primary prevention studies (categorical HR=1.48 [1.12-1.96], I
2
=67%; continuous HR=1.22 [1.12-.33], I
2
=25%). While CAVI was associated with all-cause mortality in the overall analysis (HR=1.34; 95% CI: 1.09-1.63, I
2
=41%), primary prevention studies did not show a significant association (HR=1.09; 95% CI: 0.9-1.32 I
2
=15%).

Conclusion:
CAVI holds promise as an independent predictor for MACE, including individuals without established cardiovascular disease. Further epidemiological studies are needed to better understand its prognostic role, normative values in different groups, and its role in primary prevention strategies.
Abstract 16714: An Injectable Thermo-Responsive Hydrogel as a Tool for Cardiac Tissue Engineering Efforts: In vitro and in vivo Biocompatibility Assessment
Authors: Kumar Maydha , Cavasin Maria , Vagnozzi Ronald J , Park Dae Won , McKinsey Timothy A , Song Kunhua , Taylor Matthew , Mestroni Luisa , Pena Brisa
Published: December 2023

Background:
Heart failure (HF) is a major contributor to the global burden of cardiovascular disease. Current treatments for HF do not regenerate muscle nor function and so cardiac transplantation remains the only definitive treatment for HF. Thus, novel therapies for HF are still needed. To overcome this limitation, we engineered an injectable thermo-responsive hydrogel that transitions from a liquid-solution to a gel-based matrix upon reaching body temperature allowing for a liquid injection rapidly followed by gel localization. Previously, we demonstrated the potential of our hydrogel for cardiac tissue applications using primary cardiomyocytes.

Goal:
The goal of this project is to assess the biocompatibility of the thermo-responsive hydrogel with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and its effect on mice heart tissue.

Methods:
3D cell culture: 9x104 hiPSC-CM were encapsulated for 21 days using 150μl of hydrogel solution (1.5% w/w) and cell function was assessed afterwards. Mouse intracardial injection: a left thoracotomy was performed via the fourth intercostal space in an adult C57BL/6 mouse model. Then, three injections of 10 μl of either (i) lipofectamine, (ii) hydrogel (1% w/w) or (ii) saline were injected into the left ventricle anterior wall. After injections, the thoracotomy site was closed, and the animals recovered. Four weeks post inject the tissues were harvested and prepared for studies.

Results:
We found that our hydrogel promotes hiPSC-CMs alignment, elongation with increased Cx43 localization and improved contraction function when compared with traditional 2D fibronectin controls. Furthermore, the in-vivo biocompatibility in mice (intracardial injection) proved that our hydrogel is well tolerated by cardiac tissue.

Conclusion:
Our results indicated that the injectable thermos-responsive hydrogel is a biocompatible material with potential to be used in cardiac tissue engineering efforts.