bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11860: Poly-2-Methyl-2-Oxazoline as a Novel Mitigation Strategy in Bioprosthetic Heart Valves Affected by Calcification and Structural Degeneration in Patients With Metabolic Syndrome
Authors: Abramov Alexey , Xue Yingfei , Zakharchenko Andrey , Soni Rajesh , Tom Jessica , Moreno Vivian , Shimada Yuichi J , LEVY Robert , Ferrari Giovanni
Published: June 2023

I:
Bioprosthetic heart valves (BHV) engineered from glutaraldehyde-fixed bovine pericardium (GBP) are widely used for surgical and transcatheter interventions and affected by structural valve degeneration (SVD), often associated with calcification. Risk factors for accelerated SVD are under study. Susceptibility to oxidation, glycation and protein infiltration are key mechanisms. Here we characterize mechanisms of accelerated SVD in patients with metabolic syndrome (MetS) and propose a novel mitigation strategy with poly-2-methyl-2-oxazoline (POZ) coating.

M:
Retrospective chart review assessed risk factors for accelerated SVD. BHVs affected by SVD were selected (N=24) with/without MetS and next-generation proteomics with enrichment analysis (STRING-Db) performed. Unmodified (U) GBP and POZ GBP were incubated in serum from patients (N=128) with/without MetS to mimic protein absorption. U-GBP and POZ-GBP were subcutaneously implanted in Zucker Diabetic Fatty rats and controls. GBPs were analyzed with immunohistochemistry (IHC), differential scanning calorimetry (DSC), second-harmonic generation (SHG) and scanning electron microscopy (SEM).

R:
Kaplan Meier log-rank test (N = 251 patients) revealed patients with MetS were at increased risk of accelerated SVD (p = 0.004). Proteomics revealed (N=452) permanently incorporated proteins were differentially expressed (log2FC >0.58, qvalue<0.05) between MetS and nonMetS. Proteins involved in ECM remodeling and immune activation pathways were overrepresented (Fig 1). IHC, DSC, SHG and SEM results from revealed that POZ-GBP reduced protein infiltration, reduced calcification, and preserved structural integrity when compared to U-GBP.

C:
Accelerated SVD associated with MetS with calcification and serum protein accumulation is risk factor dependent and can be mitigated with POZ. This opens a possibility to chemically modify biomaterials for patients with this highly prevalent comorbidity.
Abstract 11868: Design and Development of Automatic Extraction Transformation and Load (ETL) Process and Machine Learning for Echocardiography Data Extraction and Validation: Houston Methodist CVD Learning Health System Registry
Authors: BOSE BUDHADITYA , Butt Sara A , POURNAZARI PAYAM , Arshad Hassaan B , Nicolas Charlie C , Gullapelli Rakesh , Nwana Nwabunie , Javed Zulqarnain , Patel Kershaw , PASHA MOHAMMED A. C , Little Stephen H , FAZA NADEEN N , Jones Stephen L , CAINZOS MIGUEL A , SOSTMAN DIRK H , Zoghbi William A , Nagueh Sherif , KHURRAM NASIR
Published: June 2023

Introduction:
Echocardiogram is one of the most performed cardiac study usually stored in heterogenous non-standardized format and not readily available for analysis, resulting in barriers to improve phenotyping use in prospective electronic health medical record (EMR) based cardiovascular research initiatives.

Methods:
We extracted echocardiograms imaging report data for 73,986 patients in Houston Methodist Hospital between 1
st
January 2016 to 31
st
March 2021 to be merged with the ongoing prospective Houston Methodist CVD Learning Health System registry. Using Structured Query Language (SQL), we implemented Extraction, Transformation and Load (ETL) data pipeline to extract and label data for 7 commonly used echocardiogram parameters: diastolic function (DF), ejection fraction (EF), severities for mitral regurgitation (MR), mitral stenosis (MS), aortic regurgitation (AR), aortic stenosis (AS) and classification per gradient characteristics.

Results:
Successful ETL operations transformed & loaded data for identified echocardiogram parameters into Data warehouse. A total of 37 labels for MR, MS, AR, AS, DF, AS classification along with distribution for EF were generated. Using random sample draw of 2% (n=1,352) of comparing classification results of program to study files, the SQL program was debugged iteratively 7 times for data quality validation with accuracy of 100% for manual validation. For a total of 73,986 latest echo reports, 3 machine learning models i.e. support vector machines, XGBoost and random forest classifier, were trained on 67% data to test accuracy of data labels over 33% remaining data. All models generated 100% accuracy for of data labelling using rule-based SQL.

Conclusion:
A well-built locally developed ETL data pipeline removes barriers to semantically annotate, integrate and accurately curate large scale untapped echocardiographic data with significant potential to scale and support clinical and research registries.
Abstract 11874: Clinical Outcomes and Predictors of Long-Term Survival in Patients With and Without Extra-Cardiac Sarcoidosis Using Machine Learning: A Swedish Multicenter Study
Authors: Bobbio Emanuele , Eldhagen Per , Polte Christian L , Hjalmarsson Clara , Kullberg Susanna , Sorensson Peder , Bergh Niklas , Bollano Entela
Published: June 2023

Introduction:
Sarcoidosis is a systemic disease but cardiac involvement (CS) as first organ manifestation is not uncommon.

Hypothesis:
Patients with CS as the first manifestation of sarcoidosis has worse outcome compared to patients with known extra cardiac sarcoidosis (ECS)

Methods:
A retrospective cohort of 141 patients with CS enrolled at two Swedish university hospitals was studied. Presentation, treatment and outcomes of de novo CS and previous-known extra-CS group (ESC) were compared. Survival free time of primary composite outcome (ventricular tachycardia /ventricular fibrillation , heart transplantation , or death) was assessed. Using a data-driven approach with a machine learning (ML) algorithm, we studied the relative importance of several factors

Results:
62 de novo CS patients and 79 with known ECS at time of cardiac manifestation. No difference in the demographics was observed between the groups. De novo CS patients showed more advanced NYHA class (p=0.02) as well as higher circulating levels of natriuretic peptides (p<0.001), troponins (p<0.001). Imaging findings were similar between the two groups. During a median (IQR) follow-up time was 28 [16-80] months, the composite end-point occurred in 37% of patients with CS as first clinical manifestation and in 20% of patients with ECS. Kaplan-Meier analysis showed that event-free survival was significantly worse in patients with de novo CS (p<0.001) (
Fig. 1
). The top four factors to predict event-free survival in order of importance were: tricuspid annular plane systolic excursion (TAPSE), Cardiac Index (CI), Right Ventricular (RV) ejection fraction, previous known ECS

Conclusions:
Patients presenting with CS as their first recognized organ manifestation of disease display worse outcomes compared to patients with previous-known ECS. Using machine learning, we show that the most important predictor of survival in CS is TAPSE, following by CI, RV ejection fraction and previous known ECS
Abstract 11889: Effectiveness of sST2-Guided Therapy in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Muksinova Marina , Narusov Oleg , Masenko Valeriy , Sychev Alexey , Tereschenko Sergey , Skvortsov Andrey
Published: June 2023

Introduction:
Natriuretic peptide-guided therapy has not proven to be more sufficiently effective than usual care (UC) in patients with heart failure (HF). Soluble ST2 (sST2) has a number of advantages over natriuretic peptides.

Hypothesis:
sST2-guided therapy (sST2-GT) will be more effective than UC in patients with HFrEF.

Methods:
The prospective study included 76 patients (pts) with HFrEF, who were hospitalized due to acute decompensated HF. Pts with sST2 levels ≥ 37.8 ng/ml at the time of discharge constituted the high-risk cohort and were randomized into 2 groups: 19 pts in the sST2-GT and 18 patients in the UC. 39 pts with sST2 < 37.8 ng/ml and NT-proBNP < 1700 pg/ml were included in the low-risk cohort. The duration of the active treatment period was 6 months with monthly visits for therapy correction, the total follow-up period was up to 1 year. Therapy was carried out in accordance with clinical recommendations. In the sST2-GT group, therapy was also adjusted taking into account the concentration of sST2. The goal in this group was to reduce sST2 concentration by more than 30% or to less than 30 ng/ml. Measurement of sST2 (ASPECT-PLUS) concentration, echocardiography and registration combined endpoints (CEP) (HF decompensation (HFD) or cardiovascular mortality) were identified in all groups after 6 and 12 months.

Results:
Pts therapy in both high-risk groups was comparable, but pts in the sST2-GT group had a greater number of study clinic visits (7.1±2.3 vs 5.6±1.6 (p=0.024) compared with UC group. Pts sST2 concentration decreased in both high-risk groups, with the study goal achieved in 68,4% of pts in sST-GT group. Fewer CEP were registered In sST2-GT group pts compared to the UC group (for 6 months - 5 (0.26 / pt) vs 15 (0.83 / pt), p = 0.029 and 9 (0.47/pt) vs 22 (1.22/pt), p=0.035 over the entire follow-up) and it was practically similar low-risk cohort (0.46/patient). Fewer HFD were registered in the sST2-GT group compared to the UC group (for 6 months 4 (0.21 /pt) vs 13 (0.72 /pt), p < 0.001 and 8 (0.42/pt) vs 19 (1.06/pt), p<0.001 over entire follow-up), which was similar the low-risk group (0,31/pt). LV EF increased only in the sST2-GT group (from 29.2±6.2 up to 36.1±8.8, p=0.003 for 6 months).

Conclusions:
sST2-GT in high-risk pts with HFrEF is more effective than UC.
Abstract 11898: Bovine Milk-Derived Extracellular Vesicles as a Novel Injury-Targeting Drug Delivery System Following Cardiac Injury
Authors: Marsh Spencer R , Jourdan Jane , Gourdie Robert G
Published: June 2023

Introduction:
A novel protocol provides large amounts of highly purified small extracellular vesicles (also called exosomes) from bovine milk (Marsh et al, PMID: 34367882). We sought to examine the targeting potential of these pure, highly concentrated bovine milk-derived extracellular vesicles (mEVs) to injured cells and tissues, with the intent of identifying an effective drug delivery platform capable of targeting injured cardiac tissue.

Methods:
Targeting of mEVs to injured cells and tissues was tested
in vitro
using a scratch assay on human dermal fibroblast (hDFs) and MDCK cell monolayers, and
in vivo,
using mouse models of skin wounding and cardiac injury - methods we have previously reported (PMID:34246197; PMID:29351451). mEVs were isolated using our published approach (PMID: 34367882), then fluorescently tagged with Cell Tracker Deep Red (CTDR). Labelled mEVs were then applied to cell cultures at 20 ug/mL for 15 minutes post wound; cells were then rinsed, fixed and stained for cell nuclei with Hoechst. Mice were provided 2 ug/kg loaded mEV’s by oral gavage before skin surgery and induction of cardiac ischemic reperfusion injury. Mice were sacrificed 4 hours post-surgery, fixed by perfusion with 4% paraformaldehyde followed by PBS rinsing, then organs were explanted. Organs were then embedded in O.C.T, sectioned on a cryostat, and stained for nuclei and actin with FITC-Phalloidin. Imaging was performed on a Leica SP8 laser scanning confocal microscope and quantified using mEV uptake normalized to cell nuclei on ImageJ.

Results:
mEV uptake was significantly increased in scratch wounded cultures of both hDFs and MDCK cells (p<0.001), over uninjured control cells. Similarly, injured heart and skin tissues exhibited significantly increased exosomal uptake (p<0.001), relative to sham injury controls and skin tissues remote from the injury.

Conclusions:
Our experiments indicate that injured cells and tissues show increased uptake of milk derived exosomes, with in vitro data suggesting that this enhanced uptake occurs, at least in part, in a cell autonomous manner. The data also supports that our isolation protocol provides a novel mEV-based drug delivery system that may preferentially target injured tissues, including ischemic cardiac tissue.
Abstract 11899: Biomarker Profile Associated With Provider Assessed Frailty in Advanced Heart Failure Patients Undergoing Lvad: An Intermacs Analysis
Authors: Chauhan Keshvi , Kuchnia Adam , Hess Timothy , Lorden Heather , Macy Ashley , Raza Farhan , Dhingra Ravi
Published: June 2023

Introduction:
Frailty is a state of increased vulnerability and decline in multi-organ physiologic reserve. Among patients considered for left ventricular assist device (LVAD), frailty is associated with increased morbidity and mortality. However, a biomarker profile that is associated with the presence of frailty and reflects multiorgan dysfunction is unknown.

Methods:
We selected all patients from Interagency Registry for Mechanical Assisted Circulatory Support (INTERMACS) national database who underwent an LVAD between years 2006-2017 and had available data on provider-assessed frailty (n=21,977; 4,659 females). Then, using several pre-implant variables (n=32) such as vitals, right heart catheterization hemodynamics, echocardiographic and serum biomarkers we created a stepwise multivariable logistic regression model that allowed every variable to enter or leave the model at a significance of 0.05 to examine the odds of provider-assessed frailty prior to LVAD.

Results
Frailty was present in 968 patients (238 females; mean age 63.1yrs). Frail patients were more likely to be older, had higher levels of blood urea nitrogen (BUN), alanine transaminase, total bilirubin, lactate dehydrogenase, B-type natriuretic peptide (BNP), N-terminal proBNP, international normalized ratio (INR) and white blood cell counts but lower albumin, prealbumin, hemoglobin and platelet counts (p <0.05 for all comparisons). In stepwise logistic regression model, advancing age, higher bilirubin, BUN, INR and a lower albumin, hemoglobin, creatinine and platelets levels were the remaining variables associated with higher odds of frailty (see table).

Conclusion
In our study, 7 commonly obtained serum biomarkers and age were associated with presence of frailty. Future studies will examine if treatment that ensures modifying these biomarkers can reduce the risk of post-LVAD morbidity and mortality.

Table
Abstract 11909: Education of Children Improves Awareness of Hypertension Novel Method to Improve Health Equity
Authors: Wallace Margaret K , Ladd Amy C , Innes David , McKnight Kimberly , Olson Kristine C , Davis Unice , Ravindra Krishna , Raghavan Namita , Mills Carrie R , Dagostino Ralph , Hundley William G , Duncan Phillip , Shah Sangeeta B
Published: June 2023

Introduction:
Approximately 45% of the U.S. population has hypertension (HTN), with increased prevalence in Black adults in urban areas. HTN is a risk factor for heart disease, stroke, and renal failure. Increasing awareness of HTN during early education may improve health equity. We hypothesized a blood pressure (BP) educational program administered to primary school children would increase their awareness and knowledge of HTN.

Methods:
We engaged 31 4
th
& 5
th
graders from a predominantly Black, urban school in an innovative, experiential educational program administered across four, one-hour sessions as part of their curriculum. We taught and assessed students’ awareness of HTN across four topics: (1) knowledge of BP & HTN, (2) organ systems impacted by HTN, (3) habits to maintain a healthy BP, and (4) their competence to operate a BP monitor according to AHA recommendations. Using a 24-question survey, assessments of the first three categories were completed pre-program (baseline [BL]), one-day & 42-days (6 weeks) post-program.

Results:
Students’ knowledge of BP & the AHA HTN definition and organ systems impacted by HTN was low pre-program, but significantly improved at one- & 42-days post-program. Students’ knowledge of habits to maintain healthy BP was high at BL and did not change throughout the program (Table). Forty-two days post-program most students were able to perform BP measurements per AHA guidelines (>57.7%) and were able to correctly identify systole and diastole measurements (>69.2%).

Conclusion:
Implementing an educational program focused on knowledge and measurement of BP and HTN in 4
th
& 5
th
grade classrooms significantly raised awareness of HTN immediately and at 42-days post-instruction. The students retained the ability to measure BP and understand the components of BP. Raising awareness of BP and HTN in urban early education settings is feasible and may be the first step to decreasing the morbidity of a highly prevalent and modifiable disease.
Abstract 11915: Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide in Patients With Left Ventricular Noncompaction
Authors: xu wei , Yang Yan-min
Published: June 2023

Introduction:
Left ventricular noncompaction (LVNC) is a limited knowledge myocardial disease. Risk stratification in such patients remains a controversy. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable predictor for risk stratification in patients with heart failure. However, data on the effect of NT-proBNP on patients with LVNC is limited. This study aimed to evaluate the predicted effect of NT-proBNP on patients with LVNC.

Hypothesis:
NT-proBNP can be a predictor for adverse outcomes in patients with LVNC.
Methods:
This retrospective study enrolled 287 patients diagnosed with LVNC through imaging criteria (Jenni criteria or Petersen criteria). The primary endpoint was major adverse cardiovascular events (MACEs), which represented a composite event of all-cause death, heart transplantation, stroke/TIA, intracardiac thrombi, and venous thrombosis.

Results:
Patients were divided into 2 groups based on the median of NT-pro BNP: group 1(NT-pro BNP <1008.1 fmol/L, n=143) and group 2(NT-pro BNP ≥1008.1 fmol/L, n=144). During a median of 2.8 years follow-up, 64 patients (22.3%) occurred MACEs. Patients in group 2 (36.8%) had a higher incidence of MACEs than group 1 (7.69%). The Kaplan-Meier curves showed that patients in group 2 were associated with a higher risk of MACEs (Log rank test,
P
<0.001). Crude Cox regression model results revealed that log NT-proBNP levels were associated with increased risk of MACEs (Crude HR 4.49, 95% CI 2.84-7.09,
P
<0.001). After adjusting for risk factors including BMI, systolic blood pressure, NYHA functional class, hypertension, prior thromboembolism, atrial fibrillation, left atrial diameter, and LVEF, log NT-proBNP level was an independent risk factor for MACEs (Adjusted HR 2.72, 95% CI 1.53-4.82,
P
<0.001). The ROC curves showed that the AUC of NT-proBNP was 0.767.

Conclusions:
NT-proBNP was independently associated with MACEs and can be a robust predictor for the risk stratification in patients with LVNC.
Abstract 11919: Differences in the Documentation of Atrial Fibrillation Symptoms in Electronic Health Records Between Patients With and Without Comorbid Heart Failure
Authors: Hobensack Mollie , Reading Turchioe Meghan
Published: June 2023

Introduction:
Atrial fibrillation (AF) causes burdensome symptoms that impact quality of life. One in four AF patients have comorbid heart failure (HF). Understanding whether comorbid HF impacts AF symptom experiences can guide interventions for symptom management.

Objective:
We aimed to investigate whether patients with AF and comorbid HF will have different symptoms compared to those with AF only.

Methods:
We used structured and unstructured data (i.e., clinical notes) from electronic health records of patients in a large, urban health system between 2010-2010. We created two cohorts: (1) AF only, and (2) AF and HF. We extracted symptoms from notes written immediately before a catheter ablation to treat AF because of high symptom enrichment in ablation consultation notes compared to general progress notes. To extract symptoms, we applied a natural language processing algorithm with high performance on the corpus of notes (precision=0.73, recall=0.93, F-score=0.81). A team of cardiologists and nurses with cardiology expertise chose 10 symptoms to evaluate. We used Chi squared tests to compare differences in the prevalence of documented symptoms between cohorts. We further characterized each cohort using the structured demographics data.

Results:
Patients with AF only (n=504) had a mean age of 65.1 (SD 10.5) years, 33.3% were documented as female, and 14.3% documented as non-White. Patients with AF and HF (n=575) had a mean age of 69.4 (SD 12.0) years, 38.8% were documented as female, and 23.5% documented as non-White. The HF and AF cohort had a significantly higher prevalence of 6 symptoms (Table 1). The AF only cohort had a significantly higher prevalence of one symptom (palpitations).

Conclusions:
There are clear differences in the prevalence of symptoms between cohorts, with HF patients experiencing greater symptom burden overall. Future work exploring differences, such as through symptom clusters, will further illuminate differences in symptom experiences.
Abstract 11926: Selective Inhibition of Rho Kinase 2 Limits No Re-Flow in Rat Hearts Following Ischemia/Reperfusion
Authors: Pearce Lucie , He David , Davidson Sean M , Yellon Derek M
Published: June 2023

Introduction:
Myocardial infarction causes several types of injury to the myocardium including lethal cell injury and ‘no-reflow’ (NRF) /microvascular obstruction (MVO). Nonselective Rho Kinase (ROCK1/2) inhibitors such as Fasudil, ameliorate myocardial ischemia/reperfusion (I/R) injury but cause unwanted hypotension. Selective ROCK2 inhibitors (e.g.: KD025) are safe in clinical trials without causing haemodynamic compromise, however they have not been investigated in myocardial I/R. ROCK inhibitors prevent vascular smooth muscle cell (VSMC) contraction; such VSMC contraction/coronary spasm being features of ‘no-reflow’ (NRF) and microvascular obstruction (MVO). At present, there are limited therapies to improve ischemic MVO outcomes, and prognosis is poor.

Hypothesis:
Using a rat model, we hypothesised that, i) ROCK2 mRNA is expressed in myocardium and coronary vasculature and ii) The selective ROCK2 inhibitor KD025, would reduce infarct size (IS%) and NRF% (MVO) following I/R.

Methods:
RNA scope in-situ hybridisation was performed with a fluorescent, multiplex assay for ROCK1/2 & VSMC mRNA in myocardium and coronary vasculature. Male SD rats underwent in-vivo myocardial infarction with 30min ischemia, 180min reperfusion. 15min prior to reperfusion, the ROCK inhibitors Fasudil and KD025 or vehicle (DMSO) were administered i.p. For IS%, myocardium was stained with TTC, and regions not perfused with 1.5% Thioflavin S (NRF%), were visualised under UV light.

Results:
RNAscope confirmed the presence of ROCK2 mRNA within myocardium and VSMC of coronary arteries. Fasudil (
10mg/kg
) vs control significantly reduced regional IS% (
30.3
±
4.4 vs
52.9
±
3.8
,
p=0.02, n=15
) and area of NRF% (
12.4
±
2.8 vs
28.6
±
2.2
,
p=0.001, n=15
). However, there was significant hypotension;- Mean BP (mmHg) (72±3.9) vs control (84±2.3,
p=0.007
). KD025 (
100mg/kg)
did not reduce IS%, but significantly reduced the area of NRF% vs control
(
18.4
±
2.8 vs
28.6
±
2.2,
p=0.02, n=14
) without hypotensive effect.

Conclusions:
Our results suggest that ROCK2 may be a prospective target in the management of coronary circulation reperfusion injury and ischemic MVO.
Abstract 11928: Effect of Hospitalizations on Benefits From Exercise Interventions in Peripheral Artery Disease: Results From LITE Randomized Clinical Trial
Authors: Thangada Neela D , Xu Shujun , Tian Lu , Zhao Lihui , McDermott Mary M
Published: June 2023

Background:
Walking exercise is first line therapy for lower extremity peripheral artery disease (PAD); however, hospitalizations during therapy are common. In post-hoc analyses, we evaluated the effect of hospitalizations on benefits from the exercise interventions in the LITE trial.

Methods:
In the LITE randomized clinical trial, participants with PAD were randomized to one of three groups for 12 months: home-based high intensity exercise (walking exercise inducing ischemic leg symptoms), home-based low intensity exercise (walking exercise without ischemic leg symptoms) or a control group (no exercise). The primary outcome was 12-month change in six-minute walk test (6MWT) distance. Hospitalizations were ascertained by monthly telephone calls to participants.

Results:
Of the 305 PAD participants randomized, 291 (95%) participants (mean age: 69, Black race: 59%) were alive at trial ending. Overall, high intensity exercise improved 6MWT compared to low intensity exercise (mean diff: +38.5 m [95% CI: 19.0, 58.1], P < 0.001) and compared to control (mean diff: +43.7 m [95% CI: 23.2, 64.2], P < 0.001). 95 participants had one or more hospitalization during the study period, including 37 (32%) in the high intensity group, 39 (36%) in the low intensity group, and 19 (29%) in the control group (P = 0.64). In the high intensity group, participants hospitalized during the trial had lower baseline 6MWT compared to those not hospitalized [294 meters vs. 349 meters (P = 0.005)]. Among high intensity participants, hospitalization during the trial was associated with less 6MWT improvement at 12-month follow-up (Table).

Conclusion:
Among people with PAD, hospitalization during an exercise intervention was associated with significantly less improvement in walking performance. Future studies should identify therapies to increase gains in walking performance in patients with PAD hospitalized during exercise interventions.
Abstract 11931: Plasma Volume Status at Cardiovascular Intensive Care Unit Discharge and Hospital Discharge is Associated With Overall Survival in Patients With Acute Decompensated Heart Failure
Authors: Hoshika Yu , Kubota Yoshiaki , Nishino Takuya , Nakata Jun , Miyachi Hideki , Iwasaki Yu-ki , Shimizu Wataru , Yamamoto Takeshi
Published: June 2023

Background:
Plasma volume status (PVS), a measure of plasma volume, has been evaluated as a prognostic marker for chronic heart failure. However, the significance of PVS in patients with acute decompensated heart failure (ADHF) admitted to the cardiovascular intensive care unit (CICU) remains unclear. Therefore, we examined the relationship between PVS and the long-term mortality.

Method:
Of 389 consecutive patients admitted to our CICU for ADHF from January 2018 to December 2020, a total of 206 patients (74.9 ± 12.9 years, 64.6% male) were enrolled, excluding those who received red blood cell transfusion, underwent dialysis, were discharged directly from the CICU, or died in the hospital. We measured PVS during the CICU stay and at discharge using the Kaplan-Hakim formula, and examined the association with all-cause mortality during the observation period (1037 days).

Result:
The group with decreasing PVS at 3 points, at admission to the CICU, at transfer to the GW, and at discharge, had a 3-year mortality rate of 0%. Cut-off values to predict long-term mortality were 10% and 9% for PVS at transfer to the GW and discharge according to ROC curve, respectively. All patients were divided into 2 groups by cut-off values, respectively, and the high PVS group had a significantly higher mortality rate (Figure 1, 2). In COX regression analysis, significant poor prognostic factors were PVS at transfer to the GW (HR=1.086 [1.04-1.13], P<0.001), PVS at discharge (HR=1.073 [1.03-1.12], P<0.001), and age (HR=1.052 [1.00-1.10], P=0.04). In multivariate analysis, PVS at discharge (HR=1.058 [1.00-1.12], P=0.048) was independent poor prognostic factor.

Conclusions:
In patients with ADHF who were admitted to the CICU, PVS at discharge may be useful in predicting prognosis. It is necessary to consider whether the treatment of heart failure that lowers PVS contributes to improved prognosis.
Abstract 11933: Cardiac and Fibrosis-Related Biomarker Levels Do Not Predict Disease Development in Presymptomatic Phospholamban Cardiomyopathy
Authors: de Brouwer Remco , te Rijdt Wouter P , Sillje Herman H , Cox Moniek G , De Boer Rudolf A , van den Berg Maarten P
Published: June 2023

Introduction:
Phospholamban (PLN) cardiomyopathy is an inherited cardiomyopathy with malignant arrhythmias and/or heart failure due to fibrosis. There is no proven treatment against disease progression. The i-PHORECAST trial investigated whether the antifibrotic properties of eplerenone prevent disease development in presymptomatic mutation carriers using late gadolinium enhancement (LGE) as a measure of cardiac fibrosis. As part of this study, several biomarkers linked to cardiac damage and fibrosis were measured to investigate their prognostic use.

Hypothesis:
We assessed if biomarkers linked to cardiac damage and fibrosis enable early detection of overt PLN cardiomyopathy.

Methods:
Presymptomatic PLN mutation carriers (N=84, age 39 [27-50] years, 44% male) were randomized to receive eplerenone or no treatment. Biomarkers (NT-pro-BNP, troponin, TP1NP, GDF-15, and IL-6) were measured from blood samples at baseline (N=84) and after a three year follow up (N=57, age 37 [26-46] years, 49% male). Composite endpoints included changes in LVEDV/RVEDV/LVEF/RVEF, new LGE, QRS voltage, symptoms requiring treatment, ventricular ectopy, and cardiovascular death.

Results:
No clinically relevant and statistically significant differences between treatment groups,
Table 1
. No significant association between baseline biomarker measurements and LVEF decrease or the development of new LGE,
Figure 1
.

Conclusions:
Levels of NT-pro-BNP, troponin, TP1NP, GDF-15, and IL-6 are not associated with development of cardiac fibrosis or left ventricular dysfunction in presymptomatic PLN mutation carriers, thus do not enable early detection of overt PLN cardiomyopathy.
Abstract 11938: Novel Approach for Optimal Assessment of Cardiovascular Risk of Blood Pressure in Asymptomatic Subjects Utilizing Mild Exercise Stress Test Protocol
Authors: El Shahawy Mahfouz , Sabatini Antonella , Izadi Lillee
Published: June 2023

Background:
BP risk class assessment has been relying on resting BP (rBP) measurements by healthcare providers. Often, this measurement does not correlate with 24-hour ambulatory BP monitoring nor with at-home measurements.
Purpose:
To assess whether abnormal rise in BP post-mild exercise protocol (PMEP), which resembles most of the activities subjects are under all day, will be more physiologic and informative for risk stratification, beyond the rBP measurements.

Methods:
We screened 2,924 subjects, ages 20-79, for CVD risk using the Early Cardiovascular Disease Risk Scoring System, also known as the Rasmussen Risk Score, which consists of 10 tests: 7 vascular and 3 cardiac (published previously). The vascular tests include rBP, BP PMEP (2.4 mi/hr and 7% elevation for 3 minutes), small (C2) artery stiffness, and CIMT. Out of the total subjects, 1094 (37%) were asymptomatic and on no medications. These were divided into four BP classes according to the current ACC/AHA guidelines.

Results:
In the table, normotension with an abnormal rise in BP PMEP has significant cardiovascular structural and functional abnormalities (CVSFA) than those without. Also noted, the higher the BP class, the higher the CVSFA with and without an abnormal rise in BP PMEP.

Conclusions:
Abnormal rise in BP PMEP in normotensive subjects is associated with significant CVSFA. This may represent a “masked hypertension” cohort. These findings mandate early diagnosis, follow-up, and optimal treatment. Additionally, an abnormal rise in BP PMEP in other classes is more pronounced with stepwise increases in BP class. Hence, we advocate for PMEP for BP classification and treatment. Early detect to protect.
Abstract 11940: Does Mixing Matter? Is This the Final Device Hurdle for Mri Patients?
Authors: Biederman Robert W , Gevenosky Loretta , Doyle Mark
Published: June 2023

Introduction:
Over the last decade substantial efforts have been aimed at improving acceptability of pacemakers and ICDs in the MRI. Many labs have evaluated the construction, safety, efficacy, reproducibility and more recently, clinical impact value in such legacy devices. In parallel, there has been extensive effort by major vendors to develop safe MRI compatible devices. To date, there remains few reasons for hesitation in universal use of any PM/ICD in the MRI bore. However, mixing vendor leads and generators remains a major hurdle limiting MRI usage.

Hypothesis:
Mixed leads and generators has no distinct safety signal from common devices; whether CIED or non-CIED.

Methods:
We undertook a retrospective DB analysis to determine safety signals in those pts possessing mixed vendor leads and devices. Comparisons of impedance, amplitude, threshold and battery voltage and patient safety etc. were performed.

Results:
Pts from 5/2010 to 5/2022, representing 1739 pts with CIED (81%) and non-CIED (19%) underwent an MRI in a dedicated CMR Lab. The majority of the mixed cohort were obtained from the non-CIED population (>98%), not having need for generator replacement. Accordingly, 11% of these underwent an MRI to include: 73% neurologic, 8% orthopedic and 19% cardiac indications. In comparison of safety signals between standard and mixed lead/generator implants, there were no differences in any implant parameters either pre-MRI study or post-interrogation (p=NS). Similarly, there were no peri-MRI pt events or reported in the 30d and 180d post-MRI scan (p=NS). Importantly, especially for EP considerations, there were no added complications to interrogations. Moreover, utilizing a similar approach to manipulation of MRI parameters for maximum safety intrinsic to dependent/non-dependent PM status was employed regardless of lead/generator configuration yielding no complications.

Conclusions:
Employing a similar approach to MRI scanning in those pts with mixed vendor lead/generator configurations yielded no difference in a multitude of safety, interrogation, devices and efficacy parameters. This reassurance suggests, despite inherent incompatibility concerns between vendors while in the magnetic field, no such fears are truly warranted.
Abstract 11963: Blood Level of Coffee-Eelated DNA Methylation and Long-Term Changes in Blood Pressure in Response to Weight-Loss Diet Interventions: The Pounds Lost Trial
Authors: Li Xiang , Shao Xiaojian , Champagne Catherine M , Xue Qiaochu , Grundberg Elin , Bazzano Lydia A , Bray George , Sacks Frank M , Qi Lu
Published: June 2023

Introduction:
Coffee intake has been associated with a lower risk of hypertension. Recent epigenome-wide association studies linked DNA methylation (DNAm) at
PHGDH
(cg14476101) with coffee consumption and blood pressure, which may explain the mechanism underlying coffee intake and blood pressure. However, little is known about whether the coffee-related DNAm is associated with long-term changes in blood pressure in response to dietary weight-loss interventions.

Hypothesis:
We hypothesized that participants with varying coffee-related DNAm levels may respond differently to dietary weight-loss interventions on long-term changes in blood pressure.

Methods:
The current study included 669 participants with overweight/obesity, who were randomly assigned to 1 of 4 diets varying in macronutrient components. Blood DNAm levels were profiled by a high-resolution methylC-capture sequencing at baseline. The regional DNAm at
PHGDH
was defined as the average methylation level over CpGs within ±250 bp of cg14476101. Two-year changes in blood pressure were calculated. Linear regression models were used to examine the associations between DNAm at
PHDGH
and 2-year changes in blood pressure in response to dietary weight-loss interventions, adjusting for age, race, sex, body mass index, anti-hypertensive medications, and concurrent weight loss.

Results:
Regional DNAm at
PHDGH
was not associated with 2-year changes in blood pressure in the total population. We found significant interactions between regional DNAm at
PHDGH
and dietary protein intake on 2-year changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (p-interaction=0.018 and 0.005, respectively). Among participants assigned to an average-protein diet (15% of energy intake), higher baseline regional DNAm at
PHDGH
was associated with greater reductions in SBP (beta [SE]: -9.7 [3.4], p=0.005) and DBP (beta [SE]: -6.5 [2.4], p=0.007); while no association was observed among those assigned to a high-protein diet (25% of energy intake; p=0.40 for SBP, p=0.15 for BP).

Conclusion:
Our data indicate that participants with a higher regional DNAm level at
PHDGH
benefited more in long-term improvement in blood pressure when consuming an average-protein weight-loss diet.
Abstract 11981: Neutrophil-To-Lymphocyte Ratio and Ventricular Arrhythmia in Mitral Valve Prolapse
Authors: Gupta Suhani , Cesmat Andrew , Chaudry Abdul , Weickert Thelsa , Simpson Ross J , Syed Faisal
Published: June 2023

Introduction:
Inflammation may mediate the association of mitral valve prolapse (MVP) with ventricular scarring and arrhythmia. The purpose of this study is to investigate the association of neutrophil- and platelet-to-lymphocyte ratios (NLR, PLR) with ventricular arrhythmia in MVP.

Hypothesis:
We hypothesized that hematological markers of inflammation predict ventricular arrhythmia in MVP.

Methods:
Clinical and demographic data were extracted from electronic medical records for all patients aged 18-90 years with MVP on echocardiography between 2016-19 at our institution. We studied 65 patients who had a differential blood count within six months prior to an ambulatory ECG (A- ECG) monitor (median age [IQR] 69.6 [60.5-77.1] years; 61.5% female; 12.3% African American). Patients with surgery or infection within six months prior to CBC were excluded. PVC burden and complex ventricular ectopy (cVE) on A-ECG were compared with NLR and PLR. Logistic and bivariate regression was used to analyze clinical, ECG, and echocardiographic factors associated with NLR and PLR.

Results:
Factors associated with NLR were congestive heart failure (p=0.005), male sex (p=0.015), age (p=0.033), and bileaflet MVP (p=0.036). NLR was associated with absolute PVC burden (R2 0.08, p=0.023) and cVE (median [IQR] 3.1 [1.6 - 5.8]), versus without cVE (1.7 [1.6-3.1], p=0.044). An NLR of 5.6 yielded 50% sensitivity and 90% specificity for PVC burden >1% (AUC 0.69). No significant association was found between PLR and PVC burden or cVE.

Conclusions:
NLR is associated with PVC burden and complex ventricular ectopy in MVP, suggesting that inflammation is a significant factor in the pathogenesis of ventricular arrhythmia in this condition.
Abstract 11989: PiRNA Mined From Therapeutic Cell Extracellular Vesicles, Protects Cardiac Tissue Post-Injury Through Epigenetic Silencing of Pick1 in Circulating Macrophages
Authors: Ciullo Alessandra , Li Liang , Li Chang , Marban Eduardo , Ibrahim Ahmed G
Published: June 2023

Introduction:
Small non-coding RNAs (snRNAs) comprise the majority of extracellular vesicle (EV) cargo. Therapeutic cells secrete EVs replete with snRNAs that repair damaged tissue through gene regulation in target cells. Piwi RNAs (piRNAs) are the most diverse class of snRNAs and a major component of EVs (called IMEX) secreted by engineered cardiosphere-derived cells. While much is known about the role of piRNAs in germline cells, little is known about their mechanism in tissue repair. Here we investigate the role of an enriched piRNA (piR-33044, we dub TEP3.4) in cardioprotection.

Methods:
W
e used ischemia/reperfusion (I/R) injury in rats to evaluate the cardioprotective effect of TEP3.4. To identify a target cell type, we exposed bone-marrow-derived macrophages (BMDMs), cardiac fibroblasts, and cardiomyocytes to TEP3.4 to assess transcriptomic changes. To identify the gene target of TEP3.4, we performed whole-genome bisulfite sequencing (WGBS) and methylation-specific sequencing. Finally, to evaluate the role of macrophages in TEP3.4 cardioprotection, we adoptively transferred BMDMs exposed to TEP3.4 in I/R injury.

Results:
In vivo
, TEP3.4 reduced infarct size (TEP3.4: 3.45±0.43g vs vehicle: 11.41±1.32g or scramble: 11.88±2.44g) and circulating cardiac troponin I (TEP3.4: 5.79±0.83ng/ml vs vehicle: 19.16±2.81ng/ml or scramble: 17.42±2.07ng/ml). BMDMs showed more transcriptomic changes compared to cardiac fibroblasts or cardiomyocytes (5435 genes vs 4114 and 2653, respectively). Methylation analysis identified pick1 as a target of TEP3.4. Pick1 downregulation enhanced Smad3 phosphorylation and phagocytic capacity in BMDMs.
In vivo,
Adoptive transfer of BMDMs exposed to TEP3.4 or pick1 silencing reduced infarct size (TEP3.4: 6.55± 0.85g vs vehicle: 16.73±2.13 or scramble: 16.15±3.43g in scramble) and cardiac troponin I (TEP3.4: 7.62 ±0.83ng/ml vs vehicle: 13.27 ±3.09ng/ml or scramble:15.24 ±4.04ng/ml).

Conclusions:
TEP3.4 exerts cardioprotection through methylation of pick1 and enhances phagocytosis in infiltrating macrophages. Pick1 downregulation in macrophages enhances phagocytosis and potentiates tissue healing and repair.
Abstract 11998: ADAR1 Mediates Macrophage Activation by Its Non-Editing Activity-Mediated Pri-miRNA Processing in Abdominal Aortic Aneurysm
Authors: Cai Dunpeng , Chenming Sun , Murashita Takashi , Que Xingyi , Chen Shiyou
Published: June 2023

Introduction:
Macrophage activation plays a critical role in abdominal aortic aneurysm (AAA) development. However, molecular mechanisms controlling macrophage activation in AAA remain largely unknown. The objective of the study was to identify novel mechanisms underlying adenosine deaminase acting on RNA (ADAR1) function in macrophage activation and AAA formation.

Methods:
Aortic transplantation was conducted to determine the importance of non-vascular ADAR1 in AAA development. Angiotensin II (Ang II) infusion of ApoE–/– mouse combined with macrophage-specific knockout of ADAR1 was used to study ADAR1 macrophage-specific role in AAA formation. Primary cultured bone-marrow derived and peritoneal macrophages were used to study how ADAR1 regulates macrophage activation. Moreover, a novel humanized AAA model was established by transplanting human artery to immunodeficient mouse aorta followed by immunity reconstitution with ADAR1-deficient human monocytes to test the role of human macrophages in aneurysm formation in human arteries.

Results:
Allograft transplantation of wild type abdominal aortas to ADAR1+/- recipient mice significantly attenuated AAA formation, suggesting that non-vascular ADAR1 is essential for AAA development. ADAR1 deficiency in hematopoietic cells decreased the prevalence of AAA while inhibited macrophage infiltration and aorta wall inflammation. ADAR1 deletion blocked the classic macrophage activation, diminished NF-κB signaling, and enhanced the expression of many anti-inflammatory miRNAs. Mechanistically, ADAR1 interacted with Drosha to promote its degradation, which attenuated Drosha-DGCR8 interaction, and consequently inhibited pri- to pre-miRNA processing of miRNAs targeting IKKβ, resulting in an increased IKKβ expression and enhanced NF-κB signaling. Reconstitution of ADAR1-deficient, but not the wild type, human monocytes to immunodeficient mice blocked the aneurysm formation in transplanted human arteries.

Conclusions:
Macrophage ADAR1 promotes AAA formation in both mouse and human arteries through a novel mechanism, i.e., Drosha protein degradation, which inhibits the processing of miRNAs targeting NF-kB signaling and thus elicits macrophage-mediated vascular inflammation.
Abstract 12005: Association of Prehospital Hypotension Depth and Dose With Survival Following Out-of-Hospital Cardiac Arrest
Authors: Smida Tanner , Menegazzi James J , WEISS LEONARD , Crowe Remle , Salcido David D
Published: June 2023

Introduction:
Hypotension following resuscitation from out-of-hospital cardiac arrest (OHCA) may cause harm by exacerbating secondary brain injury; however, limited research has explored this relationship. Our objective was to examine the association between duration and depth of prehospital post return of spontaneous circulation (ROSC) hypotension and survival.

Hypothesis:
We hypothesized that increased severity and duration of post-ROSC hypotension in the prehospital setting would be associated with unfavorable patient outcomes.

Methods:
We utilized the 2019 and 2020 ESO Data Collaborative public use research data sets for this study (ESO, Austin, TX). Hypotension dose (mmHg*min.), average prehospital systolic blood pressure (SBP), and lowest recorded prehospital SBP were calculated. The association of these measures with survival to home (STH) and rearrest were explored using multivariable logistic regression. Time to hypotension resolution analyses were conducted using Cox proportional hazards models adjusted for known prognostic factors according to the Utstein template. We also assessed the association of hypotension management strategy (push dose vasopressors, vasopressor infusion, or fluid only) with survival, rearrest, and time to hypotension resolution.

Results:
17,280 OHCA patients met inclusion criteria, of which 3,345 had associated hospital outcome data. Over one-third (37.8%; 6,526/17,280) of all patients had at least one recorded SBP below 90 mmHg. When modeled continuously, average prehospital SBP (1.19 [1.15, 1.23] per 10 mmHg), lowest prehospital SBP (1.20 [1.17, 1.24] per 10 mmHg), and hypotension dose (0.995 [0.993, 0.996] per mmHg*min.) were independently correlated with STH. Differences in hypotension management were not associated with differences in survival, rearrest, or time to hypotension resolution.

Conclusion:
Severity and duration of hypotension were significantly associated with poorer outcomes in this dataset. The incidence of hypotension was significantly associated with known unfavorable prognostic factors. Defining a threshold for hypotension requiring treatment above the classical SBP threshold of 90 mmHg may be warranted in the setting of prehospital post-resuscitation care.
Abstract 12021: Investigation of the Role of Long Non-Coding RNA H19 on Endothelial to Mesenchymal Transition in Aortic Valve Stenosis
Authors: Maus Katharina , Hosen M. Rabiul , Jansen Felix
Published: June 2023

Background:
Endothelial to mesenchymal transition (EndMT) is a transdifferentiation process of cells that is associated with the development of aortic valve stenosis (AVS) in adulthood. It was shown that long non-coding RNAs are dysregulated in this process and might play a crucial role in EndMT-mediated AVS. Here we aim to elucidate the role of long non-coding RNA H19 (LncRNA H19) in the pathogenesis of EndMT-related AVS.

Methods and Results:
RNA sequencing of aortic valve tissue explanted from AVS-patients with coronary artery disease (CAD) revealed that H19 was significantly dysregulated. EndMT was induced
in vitro
in vascular and valvular endothelial cells (VECs) via TNFα and TGFß+IL1ß stimulation and expression of endothelial marker genes
vWF
and
eNOS
and mesenchymal marker genes
αSMA
,
SM22
,
Vimentin
and
SNAI2
was confirmed by RT-qPCR. Loss of function of H19 followed by EndMT induction demonstrated distinct changes in gene expression profile and protein levels which were detected by qRT-PCR, immunoblotting, and immunofluorescence. Further experiments indicate that loss of H19 may promote EndMT. Functional assays in vascular and valvular endothelial cells suggested that H19 is a critical regulator of angiogenic sprouting and migration. To unveil the specific molecular signature in angiogenesis a RT
2
profiler array was performed to identify the regulation of angiogenesis with 84 angiogenesis-related genes. Our assay revealed JAG1 as a potential dysregulated candidate with a 4.43-fold regulation. Further molecular mechanism will be investigated via identification of binding partners and downstream targets of H19 in EndMT by using primary cells and VECs.

Conclusion:
Our data suggests that H19 might play a role in EndMT in context of AVS. Further investigation by using a murine model of AVS should confirm the H19-mediated of EndMT in the development of AVS.