bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13462: Assessment of the Physiological and Pathological Structural Differences Along the Aorta in a Rat Model of Metabolic Syndrome
Authors: Ameer Omar Z , Salman Ibrahim M
Published: April 2022

Introduction:
Vascular geometry may vary along the aortic length in normal and chronic disease conditions such as metabolic syndrome.

Aim:
This study investigated regional structural changes in the aorta in a rodent model of metabolic syndrome, the high-fat diet streptozotocin-induced diabetes mellitus (HFD-D).

Methods:
Four-week-old male Wistar albino rats received a control diet (CD) or high fat diet (HFD) for 10 weeks. On week 6, 40 mg/kg streptozotocin and its buffer were injected intraperitoneally into the HFD and CD groups, respectively. Glucose and insulin tolerance tests (GTT and ITT) and tail-cuff systolic blood pressure (SBP) were measured. At the end of the study, rats were euthanized, and the thoracic and abdominal aortic segments collected for histomorphometric analysis of aortic media thickness, medial cross-sectional area (CSA), elastic lamellae number, interlamellar spacing, collagen density and lipid deposit density.

Results:
HFD-D rats showed elevated GTT, ITT and SBP. Abdominal aortic segments of both CD and HFD-D rats showed smaller media thickness and CSA, lower elastin lamellae number and higher collagen density compared with the thoracic segments, suggestive of physiological rather than pathological structural differences in both groups. Elastin interlamellar spacing and lipid plaque deposits were higher in the abdominal aorta of the HFD-D relative to controls, indicating that early vascular pathological changes favor the abdominal aorta in HFD-D rats.

Conclusions:
In this disease model of metabolic syndrome, vascular structural changes are differentially expressed along the aorta, with pathological features limited to the abdominal rather than the thoracic aorta. These structural abnormalities may underlie the elevated blood pressure seen in this model and potential progression to hypertensive cardiovascular disease.
Abstract 13554: High-Throughput Investigation of Human Genes and Variants Affecting LDL Cholesterol Uptake
Authors: Hamilton Marisa C , Fife James D , Cha Minsun , Cassa Christopher A , Sherwood Richard I
Published: April 2022

Introduction:
Genetic differences in cholesterol metabolism are major contributors to the risk of coronary artery disease (CAD), which is the leading cause of death in the USA. Genome-wide association screens have identified over 300 independent genomic loci where genetic variation is associated with serum LDL cholesterol (LDL-C) levels. While several of these loci are important drug targets, for the vast majority of loci, it is unknown which exact genetic variants, genes and cellular pathways are impacted by these variants.

Hypothesis:
We hypothesize that combining high-throughput CRISPR-Cas9 screening, gene clustering and network analysis, and human genetic biobank cohort analysis will increase our power to reveal the genetic basis behind human variation in cholesterol levels.

Methods:
We have devised sensitive high-throughput CRISPR-Cas9-based screens to gain insight into the genetic mechanisms that impact cellular cholesterol metabolism.

Results:
Through a combination of CRISPR-Cas9-nuclease and CRISPR base editing screens, we have identified hundreds of human genes and GWAS-associated variants that influence cellular LDL-C uptake in liver cells. We have developed experimental and computational methods to group these genes into biological pathways, uncovering previously unappreciated cellular mechanisms driving variation in LDL-C uptake. We have connected these novel LDL-C uptake-altering genes and pathways to serum LDL-C levels by analyzing rare coding variant burden from a UK Biobank exome sequencing cohort, identifying functional gene modules for which damaging coding variants in the population have significant effects LDL-C levels. Finally, we have identified GWAS-associated non-coding variants that alter LDL-C uptake through modulating expression of previously unappreciated cholesterol-related genes.

Conclusions:
Through high-throughput CRISPR screening followed by mechanistic follow-up, we have made progress in dissecting the non-coding loci, genes, and pathways that underlie variation in human cellular cholesterol uptake.
Abstract 13560: Household Income Less Than 150% of Federal Poverty Level is Associated With Heart Failure Mortality
Authors: Agboola Olayinka J , Okoroafor Chidi , Yanchou Njike Valentine , Herrin Jeph , Spatz Erica S
Published: April 2022

Introduction:
The per capita cost of managing heart failure (HF) is rising and so is the patient’s financial responsibility. This study examined the association between household income expressed as percentage of federal poverty level (FPL) and HF mortality.

Methods:
The United States Census National Longitudinal Mortality Study (NLMS), consisting of surveys administered between March 1973 and March 2011, was designed to study the effect of socioeconomic factors on mortality rates in the US. Matching the NLMS database to the National Death Index, we identified and retrospectively analyzed data of all cases of heart failure deaths in the NLMS. For this analysis, we included only records that could be prospectively followed for 11 years from time of survey. Study sample was categorized into three groups by baseline household income expressed as a percentage of FPL: Group 1 ≤ 150%FPL (n=1260); 2 >150% but ≤ 300% (n=1059) and 3 > 300% (n=907). We assessed the association between the 3 groups and risk of mortality using unadjusted and adjusted Cox regression. Kaplan Meir plots were computed and survival between the three groups was compared using log-rank statistics.

Result:
Among the 1,835,072 records that could be followed for 11 years, there were 3,226 HF deaths. Median (IQR) survival (in years) were 5.6 (2.9 – 8.3), 6.2 (3.4 – 8.6) and 6.3 (3.4 – 8.8) for groups 1, 2, and 3 respectively [p=0.002]. Having income less than 150% FPL was associated with 14% increased risk of mortality (hazards ratio [HR]= 1.14 (1.07 – 1.23; P=0.0002) compared with income >150%FPL. Adjusting for age, race, sex, and health insurance status, income less than 150% was independently associated with a 21% higher risk of mortality (HR=1.21 (1.11 – 1.32; p=<.0001)) compared with income >150%FPL.

Conclusion:
Low income is associated with increased risk of HF mortality. This finding may help guide planning for social interventions and resource allocation.
Abstract 13585: Red Flag Comorbid Conditions That Are Easily Extracted From the Electronic Health Record Often Precede Diagnosis of Cardiac Amyloidosis by Years
Authors: Cavalier Joanna S , Loungani Rahul , Khouri Michel G
Published: April 2022

Introduction:
With new and emerging disease-modifying therapies for cardiac amyloidosis (CA), there is a growing impetus for improved awareness and early diagnosis of this condition. Several groups have identified comorbid conditions, termed ‘red flag’ systemic symptoms and diagnostic findings, that occur commonly in patients with CA. To better understand the prevalence and temporal relationship of these ‘red flag’ comorbid conditions to a CA diagnosis, we used automated extraction of clinical data stored in the electronic health record (EHR) at a single institution.

Methods:
Patients with confirmed light-chain (AL) and transthyretin (ATTR) cardiac amyloidosis were identified at a single institution. The dates of diagnosis of ‘red flag’ comorbid conditions and for CA were extracted from the EHR via ICD-9 and ICD-10 codes, electrocardiogram intervals, and echocardiogram reports. Frequency and time between the diagnoses of red flags and CA were assessed.

Results:
Of 175 CA patients (85% ATTR), mean age was 72.7 years with majority (76.6%) male patients. Patients were most commonly black (52.6%) followed by Caucasian (42.3%). A diagnosis code for amyloidosis was found in 89.1% of patients, followed by heart failure in 84.6% of patients. ‘Red flag’ comorbid conditions were more likely to have been diagnosed before rather than after CA. When the ‘red flag’ was diagnosed prior to CA, the greatest average intervals between diagnoses were seen in carpal tunnel syndrome (8.3 years), spinal stenosis (5.9 years), and atrial fibrillation (2.8 years) (Table 1).

Conclusions:
EHR data from a single institution demonstrates that the diagnosis of CA is often delayed following the diagnosis of ‘red flag’ comorbid conditions. Our automated extraction of EHR data provides a foundational step in the ongoing development of an EHR-based warning score aimed at improving clinician awareness of the possibility of CA in appropriate patients.
Abstract 13587: Long-Term Outcomes of CT-Derived Fractional Flow Reserve in the Emergency Department
Authors: O'Connell Thomas F , Palomo Andres , Tariq Rehan , Safian Robert D , Gallagher Michael , Chinnaiyan Kavitha M
Published: April 2022

Introduction:
In acute chest pain (ACP) patients, CT-derived fraction flow reserve (FFRCT) is feasible and adjudicates need for immediate coronary revascularization. There are no long-term outcome studies of FFRCT in ACP.

Hypothesis:
In ACP patients, FFRCT is safe and associated with favorable outcomes when negative.

Methods:
ACP patients with no known coronary artery disease or definitive acute coronary syndrome undergoing coronary CTA with FFRCT were compared to those having CTA alone for the composite major adverse cardiac event (MACE) endpoint of death, nonfatal myocardial infarction, unplanned percutaneous (PCI) or surgical (CABG) revascularization over 2 years. FFRCT ≤ 0.80 was considered positive for hemodynamically significant stenosis.

Results:
From September 2015 to July 2018, 2,568 ACP patients (mean age 55 years, 52% female) underwent CTA of which 236 (10%) had FFRCT (156 negative, 80 positive). Of the total, 1629 (63.2%) had normal coronaries, and 43 (1.7%) were uninterpretable. FFRCT patients were older (p<0.001) with more diabetes mellitus (18.2% vs. 12.2%, p = 0.009), hypertension (50.8% vs. 38.2%, p<0.001), hyperlipidemia (43.6% vs. 25.4%, p<0.001), and >25% stenosis on CTA (93% vs. 13.6%, p<0.001). Positive FFRCT was associated with higher MACE (10% vs. 2.1%, p<0.001). With comparable stenosis on CTA, positive FFRCT had higher MACE compared to negative FFRCT or CTA alone (Table 1).

Conclusions:
In ACP patients, negative FFRCT and CTA alone are comparable for MACE. Positive FFRCT portends higher MACE at 2 years within similar stenosis categories. FFRCT can provide incremental value to ACP evaluation with coronary CTA.
Abstract 13606: Is Pulmonary Hypertension a Poor Prognostic Sign in Patients Hospitalized for Transcatheter Aortic Valve Replacement
Authors: Mughal Mohsin S , Ghani Ali , Kumar Sundeep , Nasir Ammar , Hafeez Hamza , Grewal Jagpreet , Ahmad Talha , Aslam Sara , Akbar Hafsa , Khakwani Muhammad , Alam Mahboob , wasty najam , Waxman Sergio
Published: April 2022

Introduction:
Pulmonary hypertension (PH) is common in patients with severe aortic stenosis (AS). The prevalence of PH in transcatheter aortic valve replacement (TAVR) patients is reported upto 78% and causes significant morbidity and mortality. We queried the National Inpatient Sample (NIS) database to explore the different outcomes of patients hospitalized for TAVR with and without the history of PH.

Hypothesis:
PH may increase mortality in hospitalized patients undergoing TAVR.

Methods:
This is a retrospective cohort study utilizing the 2016-2017 National Inpatient Sample. We identified patients hospitalized for TAVR with and without the history of PH using ICD10 codes. The primary outcome was inpatient mortality. The secondary outcomes were cost of hospitalization, and length of stay (LOS). Multivariate regression was used to adjust for potential confounders including age, gender, race, pulmonary embolism, acute coronary syndrome, heart block, left bundle branch block (LBBB), diabetes, heart failure, and chronic kidney disease. STATA 15.0 was utilized for data analysis.

Results:
A total of 18221 patients underwent TAVR in 2016-2017. Of these, 18.3% had PH. There were more women in the PH group (51% vs 46%, P<0.001). Patients were relatively younger in the PH group (79 yrs vs 80 yrs; p<0.001). The mean cost of hospitalization was 23022 USD in the PH group versus 209867 USD in the group without PH (p< 0.001). The patients in the PH group had higher inpatient mortality compared to patients without PH (2.28 % versus 1.49 %; Odds Ratio 1.54; p< 0.001; CI 1.1-2.0). The mean LOS was 6.0 days in the PH group versus 4.3 days in those without the PH group ( p:< 0.001). The mortality didn’t differ by gender, location of the hospital, and teaching status of the hospital.

Conclusions:
Our study showed higher inpatient mortality, length of stay, and cost of hospitalization in patients undergoing TAVR with PH as compared to those without PH.
Abstract 13614: Pulmonary Artery Catheter Guided Therapy of Cardiogenic Shock is Associated With Lower Short-Term Mortality: A Systematic Review and Meta-Analysis
Authors: Vyas Rohit , Mhanna Mohammed , Nazir Salik , Holtzapple Zachary , Brohi Zafrullah , Khouri Samer , Eltahawy Ehab
Published: April 2022

The utility of pulmonary artery catheterization (PAC) in treatment of cardiogenic shock (CS) is questionable. In this meta-analysis we aimed to evaluate the impact of PAC guided treatment on survival in CS patients.

We performed a comprehensive literature search of multiple databases for studies that evaluated the clinical utility of PAC-guided management versus standard care for patients with CS. The primary outcome of interest was short-term mortality. The secondary outcomes were the use of mechanical circulatory support (MCS) and inotropes. Pooled relative risk (RR) and corresponding 95% confidence intervals (CIs) were calculated and combined using random effects model meta-analysis.

A total of 9 studies including 364,001 patients with CS (29609 managed with PAC guided therapy vs. 334392 managed with slandered of care) were included in the final analysis. There was a significant difference in short-term mortality favoring PAC guided management (RR:0.83; 95% CI:0.76-0.92;
P
<0.00001). Standard of care guided management was associated with higher use of MCS and inotropic agents (RR:1.30; 95% CI:1.15-1.46;
P
<0.0001) and (RR:1.18; 95% CI:1.09-1.29;
P
<0.001) respectively.

Our meta-analysis demonstrates that PAC-guided therapy for patients with CS was associated with lower short-term mortality and a lower likelihood to use MCS and inotropes with their potential associated complications. Further randomized clinical trials are needed to evaluate the utility of PAC as an adjunct tool in the management of CS.
Abstract 13620: Comparison of Endothelial Shear Stress (ESS) Computation Utilizing Non-Invasive Coronary Computed Tomography Angiography (CCTA) vs Invasive Intravascular Ultrasound (IVUS) Imaging
Authors: Hakim Diaa , Coskun Ahmet , Maynard Chuck , pu zhongyue , Rupert Deborah , Cefalo Nicholas , Cormier Michelle , Croce Kevin , min james K , Earls James , Jennings Rob , Andreini Daniele , Mushtaq Saima , Conte Edoardo , Stone Peter H
Published: April 2022

Introduction:
Risk-stratification of individual coronary plaques is an important goal to detect high-risk plaques likely to progress/destabilize, which could inform preemptive intervention to prevent adverse cardiac events. IVUS imaging, the current gold standard to assess plaque risk, has shown that biomechanical variables, particularly local ESS, contributes critical synergistic prognostic insight when combined with anatomic high-risk plaque features. Non-invasive risk assessment of coronary plaques with CCTA would be invaluable to enable broad population risk screening, but it is unknown whether CCTA, which has less spatial resolution than IVUS, can adequately measure the critical local biomechanical and anatomic variables.

Aim:
To compare the accuracy of ESS computation of local ESS metrics by non-invasive CCTA vs invasive IVUS imaging.

Methods:
We analyzed 30 arteries (22 LAD, 4 LCx,4 RCA) from 30 patients selected from a registry of patients who underwent both IVUS and CCTA of the same artery for suspected CAD. CCTA images were acquired using a CCTA with either 64 or 256 detector rows. We segmented lumen, vessel, and plaque areas with both IVUS (manual segmentation) and CCTA (AI based software; Cleerly Inc, NY). Co-registration of IVUS and CCTA Images was performed using fiduciary anatomic landmarks. Images from IVUS and CCTA were used to generate a 3-D arterial reconstruction, and local ESS distribution was assessed by computational fluid dynamics and reported in consecutive 3-mm segments.

Results:
Table

Conclusion:
Compared to IVUS values, 256-slice is more accurate than 64-slice CCTA to measure lumen and vessel areas, but computation of detailed local ESS (average, low and high) is similar by both CCTA methods. Local ESS evaluation using non-invasive CCTA is feasible and comparable to invasive gold standard IVUS and is suitable to characterize the local flow patterns that play an important role in plaque development, progression, and destabilization
Abstract 13635: Isolated Right Ventricular Stress Cardiomyopathy: A Systematic Review of Literature
Authors: Rana Yesha P , Rana Vishal P , Hanumanthu Balaram J , Theetha Kariyanna Pramod , Misra Deepika
Published: April 2022

Background:
Takotsubo Cardiomyopathy (TTC), also known as stress cardiomyopathy, is characterized by transient systolic and diastolic dysfunction without evidence of significant coronary artery stenosis. In 2012, TTC attributed to about 0.02% of hospitalizations in the United states, largely seen in the elderly female population. Although it primarily affects the left ventricle, there are different variant patterns documented mostly affecting younger individuals. Here we present a systematic review of right ventricle TTC.

Methods:
On January 7th, 20221, a systematic search without limitation in the time frame was conducted using Pubmed, Google Scholar, CINAHL, Cochrane CENTRAL, and Web of Science databases and a total of 9 cases were identified (1 case was excluded due to duplicity).

Results:
The mean age of the patients listed was 65.2 ± 23.35 with majority (8/9) 88% of patients being women. Commonest presentation was dyspnea (67%), followed by chest pain (22%), nonspecific discomfort in 11%, and acute heart failure in 11%. Cardiogenic shock was reported in 56% of the cases. Management and treatment included inotropic or vasopressor support in 67% of the cases and 11% requiring venoarterial extracorporeal membrane oxygenation (V-A ECMO). Improvement of right ventricular function was reported in all but 1 patient who died.

Conclusion:
Isolated right ventricular stress cardiomyopathy is rare but possibly underreported. Though associated with a higher incidence of cardiogenic shock on presentation than traditional stress cardiomyopathy, they do seem to spontaneously recover once out of the acute phase of the syndrome as noted in our study. While the pathogenesis of stress cardiomyopathy is still not fully understood, genetic predispositions may be involved. Current recommendations for management include conventional heart failure medications including beta blockers, ACE inhibitors and diuretics despite limited evidence.
Abstract 13638: Protein Calorie Malnutrition is an Adverse Prognostic Marker in Atrial Fibrillation Patients: An Analysis of the National Inpatient Sample Registry
Authors: Atluri Ramtej , Kodali Mouna , Velagapudi Sujitha , Murthi Mukunthan , Velazquez Genaro
Published: April 2022

Introduction:
Protein Calorie Malnutrition (PCM) is not thought to be associated with atrial fibrillation (AF). Some research has stipulated that overweight AF patients may have a better prognosis than those with normal weight, however, the interaction between poor nutritional status and AF has not been well explored. Dyselectrolytemias secondary to malnutrition could confer a poor prognosis in AF patients. We aimed to assess the impact of PCM on outcomes in patients admitted with AF.

Methods:
A retrospective cohort study was conducted using the Nationwide Inpatient Sample from 2017. About 412,159 hospitalizations who had AF as their primary diagnosis were identified and stratified based on the presence of PCM using ICD-10 codes. Multivariate regression analysis was used to adjust for confounders and to analyze the variables. The selection of covariates was done with a univariate screen and literature review.

Results:
Out of the 412,159 hospitalized patients with AF, 11,590 individuals had PCM. In-hospital mortality in AF patients with PCM were significantly higher than those without (4.62% vs 0.77%); p<0.0001. When adjusted for patient demographics, comorbidities, and hospital characteristics, AF patients with PCM had a higher risk of mortality (aOR=3.45, p<0.0001), cardiac arrest (aOR=2.41, p<0.0001), PE (aOR=2.06, p<0.0001), sepsis (aOR=4.72, p<0.0001), pneumonia (aOR=2.25, p<0.0001), AKI (aOR=1.41, p<0.0001), acute respiratory failure (ARF) (aOR=1.81, p=0.011), and being intubated (aOR=1.45, p=0.019). When adjusted similarly, AF patients with PCM had longer length of stay (LOS) by 2.76 days (mean LOS: 6.61 vs 3.25 days) (p<0.0001) and an additional hospital cost (HC) of $18,373 (mean HC: $62,093 vs $39,934) (p<0.0001). However, there was no difference in the risk of developing stroke (aOR=1.23, p=0.26) in AF patients with PCM.

Conclusions:
AF patients with PCM had worse outcomes in terms of in-hospital mortality, LOS, HC, cardiac arrest, PE, sepsis, pneumonia, AKI, ARF, and being intubated compared to those without PCM. This suggests that PCM is an adverse prognostic marker in this population. Current limitations include the underrepresentation of metabolic derangements due to inadequate coding within this administrative database.
Abstract 13820: Trends in Preterm Delivery Among Multiple Gestation Births With Critical Congenital Heart Disease
Authors: Pelka Michelle , Lopez Keila N , Salemi Jason , Shamshirsaz Alireza , Castellanos Daniel , Morris Shaine A
Published: April 2022

Introduction:
Studies have demonstrated that preterm delivery (PTD) in infants with critical congenital heart disease (CCHD) is associated with worse outcomes compared to those delivered at term. PTD in singletons with CCHD is decreasing. However, little is known about PTD trends over time in multiple gestation deliveries (MGD) with CCHD.

Hypothesis:
We hypothesized that in a state population-based cohort over the last 20 years, PTD in MGD with CCHD initially increased compared to the general population, but more recently decreased coincident with advancements in prenatal detection of CCHD.

Methods:
The Texas Public Use Data File 1999-2018 was used to evaluate percent PTD (<37 weeks) in MGD with CCHD (diagnoses requiring intervention <1 year of age). Trends in PTD were compared with all Texas livebirths of MGD. We then compared trends by race/ethnicity and insurance.

Results:
Of 7,428,329 livebirths from 1999-2018, 211,931 (2.8%) were MGD and of those 129,253 (61%) were PTD. Overall, the rate of PTD increased from 1999 to 2003 (mean increase of 1%/y) then remained constant 2003-2018 (Figure). Of 308 MGD with CCHD, 229 (74%) were PTD. The rate of PTD in CCHD decreased from 1999 to 2003 (mean decrease of 2.2%/y) then remained relatively constant 2003-2018. When examining by race/ethnicity, there was an overall decrease in PTD with CCHD in Non-Hispanic White and Hispanic MGD, but an increase in Non-Hispanic Black MGD (Figure). There was a decrease in PTD with CCHD for those with private insurance however an increase for those with public insurance (Figure).

Conclusions:
For MGD with CCHD, while PTD rates initially decreased, they have remained somewhat constant over the last 15 years. The rate of PTD in non-Hispanic Black MGD and in those publicly insured, however, remains the highest. Mechanisms for persisting disparities in PTD for these populations requires further investigation, including determining associations with other social determinants of health and implicit bias.
Abstract 13832: Perioperative Physician Care Model in Cardiothoracic Surgery: A Pilot Study
Authors: Freer Rosie , Tanner Sophie , Hardwick Jo , Pitcher Alex
Published: April 2022

Background and Methods:
Perioperative Medicine is an emerging discipline which seeks to optimise the care of patients during the preoperative and postoperative stages. This is particularly pertinent for older patients who are at an increased risk of a poor postoperative outcome. Evidence from other surgical disciplines demonstrates that Comprehensive Geriatric Assessment (CGA) is a valuable tool for optimising perioperative care. We describe the deployment of a single perioperative physician fellow, supported by consultant perioperative geriatricians, cardiologists and surgeons for a pilot 3-month period. We estimate the upper bounds of the impact that such a deployment could have on capacity and length of stay.

Results:
The perioperative fellow working 60% whole time equivalent undertook 80 CGAs during the 3 month pilot phase. Mean patient age was 75 ± 10 years, the ratio of female to male was 39:41. We therefore estimate that a perioperative physician could review and follow up 240 new patients per year, representing approximately 10% of the patients treated in our unit per year. However, when the perioperative fellow is directed to those patients with the longest stay lengths, there is substantial amplification of the effect size, as the top decile of patients occupy 34% of all bed-days within the cardiothoracic ward (Figure). Bed occupancy as a function of length of stay is described by non-normal distribution, and this fat-tailed distribution explains the large benefit likely to be accrued from relatively modest input costs in perioperative physicians (Figure b, Shapiro-Wilks p < 0.05).

Conclusion:
Perioperative fellowship models are likely to be a cost-effective solution to the challenge of escalating demand for complex cardiac care in the setting of constrained supply. Future work will focus on the refinement of a neural network which will seek to allow identification of patient variables which best predict prolonged length of stay.
Abstract 13834: The Effect of Dapagliflozin on Serum Uric Acid in Heart Failure With Reduced Ejection Fraction: Insights From DAPA-HF
Authors: Docherty Kieran F , WELSH Paul , Morrow David , Jhund Pardeep S , Sattar Naveed , Hammarstedt Ann , Langkilde Anna Maria , Sabatine Marc S , McMurray John J
Published: April 2022

Introduction:
Elevated serum uric acid (sUA) levels are common in patients with heart failure and reduced ejection fraction (HFrEF). sUA, in part, reflects the use of diuretics, and higher sUA is associated with a higher risk of adverse outcomes in HFrEF. We examined the effect of dapagliflozin on sUA, and the efficacy of dapagliflozin according to baseline sUA, in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial.

Methods:
Patients in NYHA class II-IV with a LVEF ≤40%, and elevated plasma NT-proBNP were included in DAPA-HF. Key exclusions included hypotension, systolic BP <95 mmHg, and eGFR <30 ml/min/1.73m
2
. The primary outcome was a composite of worsening HF (hospitalization for HF or an urgent HF visit requiring iv therapy) or CV death. sUA was measured pre-randomization and at 52 weeks. The effect of dapagliflozin on sUA was assessed using a linear regression model adjusted for baseline value. The efficacy of dapagliflozin was assessed using baseline sUA as a continuous variable.

Results:
Of the 4744 randomized patients, 3119 (65.7%) had sUA measured at baseline, with a mean of 6.10±1.70 (median 5.9, IQR 4.9-7.1) mg/dL. The placebo-corrected change in sUA at 52 weeks was -0.83 mg/dL (95% CI -0.93, -0.74); p<0.001.In adjusted models including diuretic use/dose, higher sUA was associated with an elevated risk of the primary endpoint; hazard ratio 1.09 (1.03-1.14) per 1mg/dL sUA; p=0.0015
Figure, Panel A
.The benefit of dapagliflozin, compared with placebo, on the primary endpoint was consistent across the range of sUA studied (
Figure, Panel B
; P interaction=0.77).

Conclusions:
In DAPA-HF, higher sUA was associated with worse outcomes and dapagliflozin significantly reduced sUA. The efficacy of dapagliflozin on outcomes was consistent across the range of sUA studied.
Abstract 13836: Unbiased Deep Learning Approach Utilizing Longitudinal Data in Assessing All-Cause Mortality in Patients With a
De Novo
or Worsened Heart Failure
Authors: Herman Robert , Vanderheyden Marc , Vavrik Boris , Beles Monika , Palus Timotej , Kepesiova Zuzana , Goethals Marc , Verstreken Sofie , Dierckx Riet , Heggermont Ward , Bartunek Jozef
Published: April 2022

Introduction:
Heart failure (HF) is a heterogenous syndrome with complex pathophysiology. Biomarkers and clinical risk scores often fail to capture modifications in the treatment continuity and provide suboptimal patient-level precision in the prognostic stratification. Electronic patient records provide necessary granularity yielding opportunities to develop new artificial intelligence (AI) based strategies for comprehensive prognostic re-stratification.

Hypothesis:
We assessed the hypothesis that, utilizing longitudinal patient data in an AI approach, yields superior performance predicting all-cause mortality in a cohort of patients hospitalized with
a de novo
or worsened HF, compared to single observational time point predictions.

Methods:
In a cohort of 2449 HF patients hospitalized between 2011-2017, we utilized 151 451 patient exams from 422 parameters. Features included clinical phenotyping, medication, ECG, laboratory, echocardiography, catheterization data or percutaneous and surgical interventions gathered on a routine clinical basis reflecting standard of care as captured in individual electronic records. AI models were developed, and their performance on the validation set was compared to industry standard clinical scores.

Results:
AI models yielded performance ranging from 0.83 to 0.89 AUC on the outcome-balanced validation set in predicting all-cause mortality at 30-, 90-, 180-, 360- and 720-day time-limits. The primary endpoint, 1-year mortality prediction model, recorded 0.85 AUC on the validation set compared to 0.7 AUC (Seattle HF model) and 0.73 AUC (MAGGIC HF Score) respectively.

Conclusions:
Our findings present a novel, patient-level, AI-based risk prediction approach of all-cause mortality in heart failure utilizing all historical data available in electronic health records. This suggests the potential of AI based predictive models in a point-of-care approach to guide clinical risk stratification.
Abstract 13838: Life-Years Lost After Incident Atrial Fibrillation in Heart Failure
Authors: Vinter Nicklas , Cordsen Pia , Lip Gregory , Benjamin Emelia J , Johnsen Søren P , Frost Lars , Trinquart Ludovic
Published: April 2022

Aims:
To estimate the life-years lost after newly-diagnosed atrial fibrillation (AF) in heart failure (HF) patients.

Methods and Results:
Among patients diagnosed with HF in 2008-2018 in the nationwide Danish Heart Failure Registry, we compared patients with incident AF (n=4,463, mean age 73.7 years, 29% women) to AF-free referents matched on age, sex, and time since HF (n=17,792). By using G-computation, we estimated the marginal hazard ratio for death (HR) and difference in restricted mean survival times (RMST) at 10 years after AF diagnosis accounting for sex, age at AF diagnosis, lifestyle factors, clinical characteristics, comorbidities, and medications. The marginal HR was 1.41 (95%CI 1.38 to 1.44). The difference in marginal RMST between HF patients with and without AF was -18.2 months (95%CI -16.8 to -19.6) at 10 years after AF diagnosis. Subgroup analyses showed differences between patients diagnosed with AF >1 year and ≤1 year after HF (marginal difference in RMST at 10 years, -25.7 months, 95%CI -23.7 to -27.7, vs. -10.4 months, 95%CI -8.2 to -12.5), women and men (-20.3 months, 95%CI -17.7 to -21.9, vs. -17.2 months, 95%CI -15.5 to -19.0, p<0.001), patients ≥75 and <75 years old at AF diagnosis (-20.1 months, 95%CI -17.9 to -22.2, vs. -17.8 months, 95%CI -15.6 to -20.0, p<0.001).

Conclusion:
There is evidence of loss in life expectancy associated with AF in HF, with 1.5 life-years lost over 10 years after AF diagnosis. Life-years lost were significantly larger among patients diagnosed with AF >1 year after HF, women, and older patients.
Abstract 13873: Ischemic Time and Interleukin 6 Levels in Acute Myocardial Infarction
Authors: Groot Hilde E , van Blokland Irene V , Karper Jacco C , van der Harst Pim , Lipsic Erik
Published: April 2022

Introduction:
Increased levels of the inflammatory cytokine interleukin 6 (IL-6) after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) are associated with larger infarct size and decreased cardiac function. Early treatment with the IL-6 receptor inhibitor tocilizumab in STEMI patients resulted in less myocardial damage, especially in patients treated >3 hours after symptom onset. However, the specific window of opportunity for IL-6 inhibition in STEMI patients remains to be investigated. Therefore, we studied IL-6 levels in STEMI patients varying in ischemic time (i.e. time from symptom onset to PCI), and its association with infarct size.

Methods:
In 369 STEMI patients IL-6 levels were measured at 24 hours post-PCI. Patients were categorized according to ischemic time (<2 hours, 2-3 hours, 3-4 hours, 4-5 hours, >5 hours). At 4 months, infarct size was assessed by magnetic resonance imaging. IL-6 levels were log transformed for statistical analysis.

Results:
IL-6 levels at 24 hours post-PCI increased from 9.2 ng/ml (IQR 5.2-16.7 ng/ml) in patients with symptom onset <2 hours to 13.2 ng/ml (IQR 9.0-20.2 ng/ml) in patients with symptom onset between 4-5 hours (P
trend
=0.036), stabilizing in patients with symptom onset >5 hours (
Figure 1A
). Higher IL-6 levels at 24 hours post-PCI were associated with larger infarct size in patients with symptom onset <4 hours (<2 hours: β 1.9, 95% CI 0.6-3.1, P=0.004; 2-3 hours: β 1.9, 95% CI 0.3-3.4, P=0.019; 3-4 hours: β 3.0, 95% CI 1.6-4.5, P<0.001) (
Figure 1B
).

Conclusions:
IL-6 levels at 24 hours post-PCI are related to ischemic time. Moreover, higher IL-6 levels are associated with larger infarct size in patients with ischemic time shorter than 4 hours, suggesting a time dependent role of IL-6. This suggests that the window of opportunity for IL-6 inhibition in STEMI patients is within 4 hours of symptom onset. Randomized controlled trials are necessary to further establish this relationship.
Abstract 13876: Activation of Immune System May Cause Pathophysiological Changes in the Myocardium of SARS-CoV-2 Infected Macaque Model
Authors: Gupta Manish K , Rabbani Maryam , Rappaport Jay
Published: April 2022

Background:
Recent reports suggest the presence of the SARS-CoV-2 virus in the myocardium of patients who died from the COVID-19 disease. Cardiovascular injury in COVID-19 patients is an established extra-pulmonary manifestation of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection which may lead to induction of arrhythmia, acute heartfailure, thickening of ventricular wall, reduced ejection fraction and thromboembolism. Non-human primates (NHP) provide a useful model to study cardiovascular changes due to their homology to the ACE2 receptor in humans.

Aim:
The aim of this study is to characterize the pathological changes in the heart of SARS-CoV-2 infected NHPs.

Methods:
In the present study, SARS-CoV-2 infected primates via aerosol route (n=4), multi-routes (i.e., oral, nasal, intratracheal and conjunctival) (n=4), and a control group (n=5) were included. Heart tissue samples were collected and the left ventricular tissue was analyzed by hematoxylin and eosin, trichrome, and immunohistochemical staining specific to CD3, CD68 andSARS-CoV-2 nucleocapsid protein.

Results:
Several pathological findings were observed in the heart, including cardiomyocyte disarray, mononuclear infiltrates of inflammatory cells as well as hypertrophy. Collagen specific staining showed development of cardiac fibrosis in the interstitial as well as in the perivascularregion in the hearts of infected primates. Moreover, the myocardial tissue samples displayed multiple foci of inflammatory cells positive for T lymphocytes and macrophages within the myocardium. Additionally, SARS-CoV-2 nucleocapsid protein staining detected the presence of virus particles in the myocardium.

Conclusion:
COVID19 infection is characterized by exaggerated inflammatory immune response in the heart which possibly contributes to myocardial remodeling and subsequent fibrosis. These findings suggest progression of disease which could lead to development of severe complications including heart failure.
Abstract 13880: Autoimmune Connective Tissue Diseases and Cardiac Surgery
Authors: Sponga Sandro , Ferrara Veronica , Dagenais Francois , de MANNA Nunzio Davide , Dralov Andriy , Lechiancole Andrea , Vendramin Igor , Livi Ugolino , Voisine Pierre
Published: April 2022

Introduction:
The results of cardiac surgery in patients affected by autoimmune connective tissue diseases (ACTD) have not been extensively reported. Accordingly, we sought to assess the outcomes of ACTD patients after cardiac surgery, focusing on postoperative complications and survival at short and long term.

Methods:
Since 2008, 1002 cardiac surgical patients affected by ACTD (rheumatoid arthritis (RA) 59%, autoimmune vasculitis 14%, autoimmune inflammatory disease 12%, psoriatic arthritis 9%, and systemic lupus erythematosus (SLE) 6%), were retrospectively analysed in two centres. Demographics, clinical characteristics and specific treatment were recorded. Type of surgery, postoperative complications, early and late mortality were analysed.

Results:
Median age was 71 (22-92) years, and 48% were female. Most patients presented severe comorbidities (shown in the table) and required urgent surgery in 17% of cases, most frequently CABG (56%). Perioperative mortality was 2% but 60% of patients developed postoperative complications (mainly acute renal failure 15%). Patients affected by systemic inflammatory autoimmune diseases needed longer time of mechanical ventilation (p<0.01), while those with vasculitis more frequently had pneumonia (p=0.05). SLE patients had higher 30-day mortality (7%, p=0.04). Survival at 1, 5 and 10 years was 97±1%, 82±1% and 59±2%, respectively, and most common causes of death were not cardiac related (75%). By multivariate analysis, RA (HR 1.30, 1.00-1.70) was a risk factor for late mortality while both SLE and vasculitis were risk factors for re-operation (p=0.04 and p<0.01, respectively), at a median follow up of 59 months (1-184).

Conclusions:
Cardiac surgery in ACTD patients can achieve satisfactory short- and long-term results despite higher rate of postoperative complications, mainly renal failure and infections.
Abstract 13881: Nogo-B Receptor is Essential for Preserving Histone Acetylation-Mediated CCM1/2 Expression in Endothelial Cells and Preventing Cerebrovascular Hemorrhage
Authors: Fang Zhi , hu wenquan , Sun Xiaoran , Wang Xiang , Ma Ji , Palaia Thomas , Ragolia Louis , Miao Qing R
Published: April 2022

Cerebral cavernous malformations (CCMs) are enlarged leaking vascular lesions in the brain caused by loss-of-function mutations in CCM1/2/3 genes or loss of expression. Although we previously showed that Nogo-B receptor (NgBR) knockout in endothelial cells (ECs) results in CCMs-like cerebrovascular lesions in the mouse embryo, the molecular mechanism by which NgBR regulates CCM1/2 expression has not been elucidated. Here, we show that temporal genetic depletion of NgBR in ECs at both the postnatal and adult stages results in CCM1/2 expression deficiency and consequently CCMs-like lesions such as enlarged vessels, blood-brain barrier (BBB) hyperpermeability, and cerebral hemorrhage. These cerebrovascular defects in the brain of NgBR endothelial-specific knockout (ecKO) mice can be rescued by adeno-associated virus (AAV)-mediated overexpression of CCM1 and CCM2 genes. To reveal the molecular mechanism, we used RNA-seq analysis to examine changes in the transcriptome. Surprisingly, we found that acetyltransferase HBO1 was downregulated in NgBR deficient ECs. The mechanistic study elucidated that NgBR is required for maintaining the expression of CCM1/2 in ECs via HBO1-mediated histone acetylation. ChIP-qPCR data further demonstrated that loss of NgBR impairs the binding of both the HBO1 and acetylated H4K5/K12 at the promoter of CCM1 and CCM2 genes. Similarly, AAV-mediated overexpression of HBO1 restores the acetylation of H4K5/K12 and rescues the CCMs-like cerebrovascular defects in the brain of NgBR ecKO mice. Our findings on epigenetic regulation of CCM1 and CCM2 provide a perspective that NgBR and HBO1-mediated histone H4 acetylation may be targeted for preventing the onset of CCMs-like cerebrovascular disease.
Abstract 13888: Impact of Atrial Fibrillation Ablation on Recurrent Cardiovascular Hospitalizations
Authors: Barakat Amr F , Canterbury Ann , Mulukutla Suresh , Thoma Floyd W , sezer ahmet , Bhonsale Aditya , Kancharla Krishna , Voigt Andrew , Estes N A , Saba Samir , Jain Sandeep
Published: April 2022

Introduction:
Atrial fibrillation (AF) ablation has been shown to improve quality of life in AF patients, however, its impact on healthcare resource utilization is not well established. We sought to evaluate the impact of AF ablation on cardiovascular hospitalizations as a surrogate for resource utilization.

Methods:
We retrospectively included consecutive patients undergoing AF ablation at our multi-hospital healthcare system (2013 - 2020). Hospital admissions were assessed in the 12-month period preceding the ablation procedure (or from the time of AF diagnosis, if AF was diagnosed <12 months before ablation), and up to 24 months post-ablation. In each patient, pre- and post-ablation hospitalization rates were compared using paired t-test.

Results:
We included 4,310 patients who underwent AF ablation in our hospital system. Mean age was 63 ± 10 years, 65.5% were males, and mean CHA2DS2-VASc was 2.1 ± 1.5. AF ablation was associated with a statistically significant reduction in the total number of hospitalizations (0.7 ± 1.9 admission per person-year pre-ablation vs. 0.3 ± 0.7 post-ablation, P<0.001), total number of cardiovascular hospitalizations (0.7 ± 1.2 admission per person-year pre-ablation vs. 0.2 ± 0.6 post-ablation, P<0.001), total number of AF-related hospitalizations (0.6 ± 1.1 admission per person-year pre-ablation vs. 0.1 ± 0.4 post-ablation, P<0.001), and total number of hospital admission days (2.2 ± 4.8 days per person-year pre-ablation vs. 1.3 ± 4.9 post-ablation, P<0.001). The percentage of patients who had a cardiovascular hospitalization during each quarter (3-month period) of the pre- and post-ablation study period are shown in the Figure.

Conclusions:
In a large multi-hospital US healthcare system, AF ablation was associated with a significant reduction in the rates of hospitalization, including total, cardiovascular and AF-related hospitalizations, which may have significant implications for healthcare resource utilization.
Abstract 14006: Cardiovascular Health Benefits of Theobromine in Cacao and Chocolate
Authors: Hahn Joshua , Virk Hafeez Ul Hassan , Wang Zhen , Tang Wai Hong W , Krittanawong Chayakrit
Published: April 2022

Introduction:
Theobromine is a naturally occurring substance found in cocoa products. Theobromine may have beneficial cardiovascular effects through various mechanisms. We used the NHANES database to analyze associations between theobromine consumption and cardiovascular health outcomes.

Methods:
The NHANES database represents a nationally representative population which was used to construct the study population from 1996-2016. We assessed multiple demographic factors and compared differences amongst those who consumed various amounts of theobromine to those who did not. The primary outcome measures were hypertension and lipid profiles.

Results:
Among 42,038 NHANES survey participants, 37569 and 4469 of the participants reported never consuming theobromine and consuming theobromine, respectively. Table 1 demonstrates baseline characteristics of those reporting no theobromine consumption in comparison to the theobromine consuming participants (100-400md/g and 400-850mg/d). Moderate to high amounts of theobromine consumption was observed in participants who were older with higher BMI and more education and were more likely to be tobacco users in comparison to those with no theobromine consumption (all p-values <0.05). Moderate to high theobromine consumption was also observed to be associated with a higher hemoglobin level, higher LDL cholesterol, lower HDL cholesterol, and prevalence of hypertension (all p-values <0.05).

Conclusions:
We observed that individuals who consumed moderate to high amounts of theobromine had associated improvements in lipid profile parameters as well as reduced blood pressure. Theobromine may represent a complementary non-pharmacologic supplementation to typical lifestyle modifications to improve cardiovascular outcomes. Further prospective studies are needed to better clarify this potential association.
Abstract 14007: Transcatheter Mitral Valve Replacement Among Patients With Chronic Kidney Disease: Insights From The National Readmissions Database
Authors: Elbadawi Ayman , ABDELGHANY MAHMOUD , Dang Alexander , Javaid Awad , Eid Mennaallah , PANIAGUA DAVID , Jneid Hani
Published: April 2022

Introduction:
There is a paucity of data regarding the outcomes of trans-septal transcatheter mitral valve replacement (TS-TMVR) among patients with chronic kidney disease (CKD).

Methods:
We queried the Nationwide Readmissions Database (2015-2018) for patients undergoing TS-TMVR. We identified patients with CKD (stages III or more). We conducted propensity score matching analysis to compare the outcomes of patients with versus without CKD. The main outcomes were in-hospital mortality and 30-day non-elective readmissions.

Results:
From 2015 to 2018, there were 2,017 discharge records for patients receiving TS-TMVR, of whom 733 (36.34%) had CKD. Among the CKD group, 76 (10.4%) required chronic dialysis. During the study time period, there was an increase in the uptake of TS-TMVR among patients with CKD (p<0.001). Patients with CKD were older (73.311.1 vs. 71.213.2 years, p<0.001), less likely to be women and more likely to have chronic heart failure, CAD and prior CABG. There was no difference in in-hospital mortality after TS-TMVR among those with versus without CKD in the matched cohorts (7.8% vs. 7.3%; OR 1.09; 95% CI: 0.64-1.80, p=0.78). Subgroup analysis showed no interaction between chronic dialysis status and in-hospital mortality after TS-TMVR. In the matched cohort, TS-TMVR among those with CKD was associated with higher rates of cardiogenic shock (12.3% vs. 7.6%, p=0.03), AKI (35.7% vs. 16.7%, p<0.001), and new requirement for hemodialysis (5.4% vs. 1.5%, p=0.01) and longer median length of stay, (7[12] vs. 5 [8] days, p<0.001). Patients with CKD were more likely to have 30-day non-elective readmissions (25.8% vs. 16.5%, p = 0.01), driven by more readmissions for bleeding/ anemia.

Conclusions:
TS-TMVR among patients with CKD is associated with increased risk for cardiogenic shock, worsening renal function requiring hemodialysis, but no increase in mortality when compared with non-CKD patients. A higher length of stay and 30-day readmission rate was observed in CKD patients versus non-CKD patients.