bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12981: Digital Health for the Management of Oral Anticoagulation Therapy: A Systematic Review and Meta-Analysis
Authors: Ferreira Letícia B , Marcolino Milena S , Lanna de Almeida Rodrigo , Pedroso Thais M , Rosa Ferreira Samuel , Ribeiro Antonio L , Boersma Eric
Published: December 2023

Background:
Direct oral anticoagulants (DOACs) have progressively replaced vitamin K antagonists (VKAs). However, in certain conditions, especially antiphospholipid syndrome, mechanical heart valves and rheumatic mitral stenosis, VKAs remain the only drugs with established safety and efficacy. In low-income contexts, they are frequently the preferred option due to the high costs of DOACs. Its management is often challenging, and different digital health strategies have been implemented to support it.

Aims:
To systematically review the evidence on the impact of digital health strategies to support anticoagulation management compared to usual care on thromboembolic and bleeding events.

Methods:
Randomized controlled trials were searched in 5 databases from inception to September 2021. Two independent reviewers performed study selection, data extraction, and quality assessment using the Cochrane risk of bias tool (RoB2). Total thromboembolic events, major bleeding, mortality, and time in therapeutic range were assessed. Results were pooled using random effect models.

Results:
In total, 25 randomized controlled trials were included (25,746 patients) and classified as moderate to high risk of bias. Telemedicine resulted in a trend of reduced risk of thromboembolic events (13 studies, relative risk [RR] 0.75, 95% CI 0.53-1.07; I2=42%), comparable rates of major bleeding (11 studies, RR 0.94, 95% CI 0.82-1.07; I2=0%) and mortality (12 studies, RR 0.96, 95% CI 0.78-1.20; I2=11%), and an improved time in therapeutic range (16 studies, mean difference 3.38, 95% CI 1.12-5.65; I2=90%). In the subgroup of multitasking intervention, telemedicine resulted in an important reduction of thromboembolic events (RR 0.20, 95% CI 0.08-0.48).

Conclusions:
Digital health strategies resulted in similar rates of major bleeding and mortality, a trend for fewer thromboembolic events and better anticoagulation quality compared to standard care. Given the potential benefits of digital health-based care, such as greater access to remote populations, these findings may encourage further implementation of these strategies for anticoagulation management, particularly as part of multifaceted interventions for integrated care of chronic diseases.
Abstract 12996: Association Between Blood Cadmium Level and Congestive Heart Failure: Analysis of the NHANES 2017 - 2020
Authors: Wattanachayakul Phuuwadith , rujirachun pongprueth , Polpichai Natchaya , Lopimpisuth Chawin , Lalitnithi Pakin , Kunupakan Sasithorn , Tantisattamo Ekamol
Published: December 2023

Introduction:
Cadmium toxicity affects various organs, including the heart and kidneys. Whether the relationship between a broad range of cadmium levels, from normal to highly toxic and congestive heart failure (CHF), remains unclear.

Hypothesis:
Blood cadmium (Cd) level is associated with a higher prevalence of CHF.

Methods:
A nationwide cross-sectional study involving participants (≥ 18 years old) in the 2017 - 2020 NHANES was examined by using multiple logistic regression to determine the association between Cd levels and history of CHF informed by a doctor or other health professional.

Results:
Of 12,102 participants with blood cadmium (Cd) results were identified, of which mean age was 37±24 years, and 50.6% were female. The majority were White (33%), followed by Black (25%), Mexican American (13%), and Asian (10%). Among 8,074 participants with Cd results, 304 participants (3.8%) had a history of CHF. The participants were stratified into quartiles (Q) based on their Cd levels, with mean Cd levels of 0.08, 0.16, 0.29, and 0.93 μg/L for each quartile, respectively. Individuals in Q2, Q3, and Q4 were 2.48, 3.20, and 4.29 times more likely to experience CHF than those in Q1. (Q2: 95% CI 1.22, 5.06; Q3: 95% CI 1.61, 6.37; Q4: 95% CI 2.18, 8.45).After adjusting for age, gender, race, BMI, smoking status, high systolic blood pressure (<130 vs. >130 mmHg), diabetic status, and urine albumin creatinine ratio, participants in Q3 and Q4 remained at a higher risk of CHF compared to an individual in Q1, with a risk increase of 2.18 and 3.04, respectively. (Q3: 95% CI 1.02, 4.68; Q4: 95% CI 1.41, 6.52; Figure 1). While CHF was 2.11 times as likely to occur among participants in Q2 but not statically significant (Q2: 95% CI 0.97, 4.59; Figure 1).

Conclusions:
A graded association exists between blood cadmium levels, even within the non-toxic range, and an increased prevalence of CHF. Further longitudinal cohort studies are required to elucidate this relationship.
Abstract 13013: Predictors of Mortality in Elderly Patients Admitted With Takotsubo Cardiomyopathy and a History of Depression
Authors: Ramphul Kamleshun , Aggarwal Shruti , Akkaramani Sudhamai , Dhaliwal Jasninder S , Memon Rahat A , Pekyi-Boateng Prince K , Sombans Shaheen , Kumar Nomesh , Bawna Fnu , Ravalani Abhimanyu , Sakthivel Hemamalini
Published: December 2023

Introduction:
Takotsubo cardiomyopathy(TC) (broken heart syndrome or stress-induced cardiomyopathy) is usually a catecholamine-driven weakening of the left ventricle wall motion due to severe emotional or physical stress. It presents as an acute onset of reversible symptoms resembling acute coronary syndrome without occluded coronary arteries. As emotional stressors often trigger the condition, we aim to evaluate factors that can cause hospital death following admission for TC among elderly patients with depression.

Methods:
Our study group assessed mortality risk factors in patients ages ≥60 years with a diagnosis of TC and depression from the 2016-2020 National Inpatient Sample.

Results:
There were a total of 26375 elderly patients who had a diagnosis of TC. Amongst them, 25225 (95.6%) did not survive their hospitalization. After adjusting for variables, we found several factors that increased the odds of all-cause mortality in these patients, such as cirrhosis (aOR 2.093, p<0.01), peripheral vascular disease (PVD)(aOR 1.319, p=0.017), and events of Acute Kidney Injury (AKI)(aOR 3.072, p<0.01). Meanwhile, Females (vs. Males, aOR 0.597, p<0.01), the presence of hypertension(aOR 0.854, p=0.029), lipid disorder (aOR 0.696, p<0.01), smoking (aOR0.74, p<0.01), history of stroke (aOR 0.612, p<0.01) or history of myocardial infarction (aOR 0.536, p<0.01) showed lower odds of mortality among elderly patients admitted with TC. No disparities based on race or insurance forms were observed (Table 1).

Conclusions:
Our analysis found that patients ages ≥ 60 years with TC had poorer outcomes if they had cirrhosis, PVD, or AKI. While reduced odds of death were seen in females and patients with specific comorbidities such as smoking, hypertension, lipid disorder, history of stroke, or myocardial infarction, further studies, adjusting for the length of diagnosis and the medications being used, should be encouraged to expand and understand our results better.
Abstract 13050: Dysfunctional Endothelial-Subcutaneous Adipocyte Cross-Talk in Patients With Reduced Ejection Fraction Heart Failure and Type 2 Diabetes Mellitus
Authors: Brown Oliver I , Bridge Katherine I , Makava Natallia , Straw Sam , Luk Cheukyau , Wijayagoonawardana Pradeep , Tayebjee Muzahir , drozd michael , Gierula John , Witte Klaus K , Cubbon Richard , Wheatcroft Stephen B , Kearney Mark T
Published: December 2023

Introduction:
Normal subcutaneous adipose tissue (SAT) function is critical to metabolic homeostasis and is dependent on normal microvascular endothelial cell (MVEC) function. Heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (T2DM) have a synergistic deleterious relationship and of relevance to this metabolic dysregulation may drive HFrEF progression in T2DM. Detailed phenotyping of SAT microvasculature in this population is lacking.

Aims:
To examine SAT MVEC function and cross talk between SAT MVEC and adipocytes in patients with HFrEF and T2DM.

Methods:
Pectoral SAT biopsies were taken from HFrEF patients with and without T2DM undergoing pacemaker implant. SAT was examined for angiogenic potential, vascularity, adipocyte morphology and inflammatory markers. MVEC were isolated from SAT and characterised for metabolic, mitochondrial and proliferative capacity, angiogenic potential and senescence. The direct effect of altered SAT MVEC physiology in T2DM on healthy adipocytes was examined using indirect (conditioned media) and direct (co-culture) techniques.

Results:
We recruited 51 people with HFrEF of whom 21 (41%) had T2DM (HFDM). There was no difference in age, sex, or body mass index between groups. Macroscopically, SAT from patients with HFDM had impaired angiogenesis and increased fibrosis compared to SAT from HFrEF patients alone. SAT MVEC from patients with HFDM had lower metabolic activity, ATP production, proliferation; increased senescence and impaired angiogenesis. Healthy adipocytes co-cultured with SAT MVEC from HFDM patients had significantly increased expression of interleukin-6 and reduced uptake of 2-NBD-glucose compared to HFrEF alone.

Conclusions:
Cross talk between SAT MVEC from HFDM patients and healthy adipocytes leads to a deleterious alteration in adipocyte phenotype. Future work identifying the mechanism of SAT MVEC to adipocyte cross talk may identify novel therapeutic targets for patients with HFrEF and/or T2DM.
Abstract 13054: Predictive Utility of a CAD Polygenic Risk Score in a Low-Risk Primary Prevention Cohort
Authors: Bertot John H , Melloni Giorgio , Ellinor Patrick T , Sabatine Marc S , Ruff Christian , Marston Nicholas A
Published: December 2023

Background:
Statin initiation is not recommended for individuals at low clinical risk of ASCVD as defined by the Pooled Cohort Equations (PCE). We sought to evaluate whether CAD PRS can be used to reclassify low ASCVD risk to a range in which a statin should be considered.

Methods:
We performed a longitudinal cohort study of low-risk participants from the UK Biobank excluding those on lipid-lowering therapy. The PCE was used to identify participants with low risk for ASCVD. We evaluated the actual 10-year ASCVD event rate as a function of the PCE risk score and a previously validated 2.3 million-SNP CAD PRS. The top 10%, 5%, and 1% of CAD PRS were used to depict estimates across PCE predicted risk and the Net Reclassification Index (NRI) was calculated for risk thresholds ≥5% and ≥7.5%.

Results:
294,371 participants were included with mean age of 56 ± 8 years and 56% female. High CAD PRS elevated a subset of clinically low-risk individuals to higher risk categories (
Figure
). The top 10% of CAD PRS reclassified individuals with a PCE estimated risk of ≥3.7% to ≥5% risk (borderline risk). For the top 5% and top 1% of CAD PRS, the PCE estimated risk thresholds to be reclassified to ≥5% risk dropped to ≥2.9% and ≥1.3%, respectively (p<0.001). Patients in the top 5% and 1% CAD PRS cross into intermediate risk (≥7.5% risk) at PCE risk estimates of ≥4.2% and ≥2.7%. In these low-risk individuals, the addition of the CAD PRS resulted in a NRI of 0.12 (CI 0.11-0.14) with 14% (CI 0.13-0.16) correctly upclassified to risk ≥5% and 5% (CI 0.04-0.06) correctly upclassified to risk ≥7.5%. Based on the 2021 US census, this corresponds to ~10.4 and ~3.7 million people reclassified, respectively. Incorrect upclassification occurred in 2% (CI 0.02-0.02) and 0.6% (CI 0.005-0.006) at these risk thresholds.

Conclusion:
In low-risk individuals, a CAD PRS can be used to identify individuals with a higher ASCVD risk than expected based on conventional clinical risk stratification who may merit consideration of statin initiation.
Abstract 13062: Association Between Blood Pressure Levels and Cognitive Decline in Community-Dwelling Older Adults: A Prospective Analysis of the China Health and Retirement Longitudinal Study
Authors: Wang Man , Li Haibin
Published: December 2023

Background:
The association between blood pressure (BP) and the risk of cognitive impairment in older adults is limited. It is unclear at which thresholds BP increases the risk of cognitive decline. We aimed to investigate the association between BP and hypertension treatment status with cognitive decline in older adults.

Methods:
This study used data from the China Health and Retirement Longitudinal Study (CHARLS). Participants were categorized into five groups according to their visit measures of BP: 1) BP <120/80 mm Hg; 2) systolic BP (SBP) 120-129 mm Hg and diastolic BP (DBP) <80 mmHg; 3) BP ≥130/80 and <140/90 mmHg; 4) BP ≥ 140/90 mmHg; 5) and participants with anti-hypertensive medication treatment regardless of their BP levels. The global cognitive Z score was calculated as the average score of episodic memory and mental intactness. Linear mixed models were used to assess the longitudinal association between the BP group, SBP, pulse pressure (PP), and cognitive decline.

Results:
A total of 11,671 participants from CHARLS were included (47.3% men and mean age 58.6 ± 9.0 years). After adjusting for potential confounders, participants with BP ≥ 140/90 mm Hg but no anti-hypertensive medication were independently associated with accelerated cognitive decline (
β
= -0.020, 95% CI -0.028 to -0.012;
P
<0.001). This trend was not significant for participants on anti-hypertensive treatment regardless of their BP levels. Elevated SBP and PP were found to be independently associated with accelerated cognitive decline (
P
< 0.001 for both). However, participants on anti-hypertensive treatment for pre-existing hypertension, but with controlled SBP < 140 mm Hg and PP < 70 mm Hg did not have a significantly increased risk of cognitive decline.

Conclusions:
Uncontrolled hypertension was associated with subsequent cognitive decline. Effectively controlling BP with anti-hypertensive treatment can preserve cognitive health in older adults.
Abstract 13065: Comparative Efficacy of Endovascular Mechanical Thrombectomy With and Without Intravenous Thrombolysis in Acute Ischemic Stroke: A Meta-Analysis of Randomized Trials
Authors: Agrawal Vibhor , Suresh Vinay , Jena Rahul , Ramana Dabbara V , Jaiswal Vikash
Published: December 2023

Background:
Current guidelines states that intravenous tissue plasminogen activator (tPA) should be administered to eligible acute ischemic stroke (AIS) patients even if endovascular mechanical thrombectomy (EMT) is being considered. However, there is still uncertainty regarding the superiority of EMT with tPA over direct EMT.

Aim:
This meta-analysis seeks to provide a comprehensive evaluation of the comparative effectiveness of EMT with and without tPA in treating AIS.

Methods:
We performed a systematic literature search using PubMed, EMBASE, Cochrane, Web of Science, and clincialtrials.gov. Relevant articles from inception until April 10th, 2023, were scrutinized. The primary outcome of interest was functional independence assessed by the modified Rankin Score between 0-2 at 90 days. Secondary outcomes included all-cause mortality within 90 days, successful recanalization defined as extended thrombolysis in cerebral infarction score of 2b to 3, and safety outcome, i.e., the occurrence of symptomatic intracranial hemorrhage (sICH).

Results:
Our analysis included 6 RCTs involving 2334 patients. The pooled analysis of the primary outcome revealed no significant difference between EMT with tPA and direct EMT [OR, 1.08 (95% CI, 0.87-1.34), p=0.41]. All-cause mortality [OR, 0.93 (95% CI, 0.74-1.16), p=0.42] and sICH [OR, 1.22 (95% CI, 0.91-1.62), p=0.14] also did not significantly differ between the two groups. However, the results for successful recanalization [OR, 1.35 (95% CI, 1.01-1.80), p=0.04] indicate that patients who underwent EMT with tPA had a 35% significantly higher likelihood of achieving successful recanalization.

Conclusion:
Our meta-analysis found no significant difference in functional outcome, all-cause mortality, or sICH between EMT with tPA and direct EMT. However, EMT with tPA was associated with a higher likelihood of successful recanalization, suggesting its potential benefit in improving recanalization rates in AIS.
Abstract 13076: Geriatric Nutritional Risk Index and Sarcopenia in Patients Undergoing Cardiac Transplantation
Authors: Chung Alice , Driggin Elissa , Harris Erin , Bordon Abraham , Rahman Salwa , Sayer Gabriel T , Takeda Koji , Uriel Nir , Maurer mathew S , Leb Jay , Clerkin Kevin
Published: December 2023

Background:
The Geriatric Nutrition Risk Index (GNRI) is a simple nutritional assessment tool used in elderly patients. Sarcopenia, defined as reduced muscle mass strength, is widely prevalent in patients with advanced heart failure, and has been associated with worse clinical outcomes including post-transplant infections and mortality but is not routinely assessed. The relationship between GNRI and sarcopenia in advanced heart failure patients undergoing cardiac transplantation has not been well-established.

Aims/Hypotheses:
The primary outcome was to determine if GNRI was associated with sarcopenia as diagnosed using pectoralis muscle area index. We hypothesize that patients with a higher nutritional risk (GNRI < 92) will have higher rates of sarcopenia.

Methods:
Patients who underwent cardiac transplantation from January 2018 to June 2022 and who underwent preoperative chest CT scans were included. GNRI was calculated using albumin, height and weight on the day of transplant. Previous literature has defined malnutrition status as a GNRI < 92. The primary outcome was sarcopenia which was diagnosed as pectoralis muscle area index in the lowest sex-specific tertile.

Results:
172 patients were included in the primary analysis and were stratified into high (GNRI<92) and low (GNRI>92) nutritional risk. Patients with high nutritional risk had a lower BMI than those with low nutritional risk. Patients with high nutritional risk were more likely to meet criteria for sarcopenia than those with low risk (56.5% vs 28.9%, p=0.02). Additionally, patients with high nutritional risk had a longer hospital length of stay at their index hospitalization than patients with low nutritional risk (29 vs 22 days, p=0.03). There were no significant differences by nutritional risk in outcomes of rehospitalizations, days alive and out of the hospital, or death.

Conclusions:
Lower GNRI (higher nutritional risk) was associated with a greater prevalence of sarcopenia in patients undergoing cardiac transplantation. This index may represent a simple screening tool utilizing readily available data to ascertain sarcopenia in patients with advanced heart failure.
Abstract 13085: Sociodemographic Predictors of NYHA Class Assignment: An Analysis From CHAMP-HF
Authors: Sherrod Charles F , Khan Mirza , Gosch Kensey L , Chan Paul S , Sauer Andrew J , Butler Javed , Greene Stephen J , Albert Nancy M , Fonarow Gregg C , Spertus John A
Published: December 2023

Background:
The New York Heart Association (NYHA) class is the cornerstone of health status assessment in heart failure with reduced ejection fraction (HFrEF). However, prior work has shown marked variability compared to patient-reported health status - measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). As clinicians determine NYHA, systemic biases may impact class selection. It is unknown if patients’ age, race, sex, BMI, or education influence NYHA class assignment.

Aims:
To determine whether patient factors (age, race, sex, education, and BMI) predict NYHA class when controlling for KCCQ.

Methods:
Participants in CHAMP-HF, a prospective registry of ambulatory HFrEF patients, were evaluated by a clinician with a simultaneously completed NYHA and KCCQ-12. Using hierarchical multinomial logistic regression models with site-level random effects to account for clustering by site, we modeled NYHA class on age, Hispanic and Black vs White patients, males vs females, education, and BMI separately while adjusting for baseline KCCQ-12 as a restricted cubic spline.

Results:
4,742 participants were included. The table shows model summaries. Of all predictor variables, only age was associated with differential NYHA class assignment. Compared with class I, 5-year increases in age increased the odds of being assigned class II (OR 1.11; 95% CI 1.07-1.16), III (OR 1.2; 95% CI 1.15-1.26) and IV (OR 1.18; 95% CI 1.07-1.31).

Conclusions:
These results suggest clinicians assign higher NYHA classes to older patients irrespective of patient-reported health status, but there were no differences identified by race, sex, education or BMI. Whether this leads to differential treatment in older patients merits investigation.
Abstract 13094: Eliciting Home Health Aides Perspectives Towards Achieving Cardiovascular Health
Authors: Kuo Elizabeth , Yanez Melissa , Henriquez Taveras Yefrenia , Lee Ann , Klahr Rebecca , Lau Jennifer D , Safford Monika M , Phillips Erica , Wiggins Faith , Dell Nicola , Avgar Ariel , Moise Nathalie , Sterling Madeline R
Published: December 2023

Introduction:
Home Health Aides (HHAs) provide essential care to adults with cardiovascular (CV) disease in the home. Yet, HHAs themselves are a vulnerable workforce with a high burden of cardiovascular (CV) disease risk factors, which poses challenges to their own health, and potentially their patients’. We elicited the perspectives of HHAs towards achieving CV health within the context of their job.

Methods:
We conducted focus groups and interviews with HHAs from January to May 2023 in partnership with the 1199SEIU Training and Employment Fund, a benefit fund of the 1199SEIU United Healthcare Workers East, the largest US healthcare union. We included English and Spanish speaking HHAs with poor CV health, defined as having: 1) hypertension, 2) obesity, and 3) ≥1 other CV disease risk factor (self-reported hyperlipidemia, diabetes, smoking, and physical inactivity). Interviews were audio-recorded, professionally transcribed, and translated. Data were analyzed thematically using the Social-Ecological Model.

Results:
Nineteen HHAs from 12 home care agencies participated. They had a mean age of 57 years (SD 9.3), 18 (94.7 %) were female, 9 (47.4 %) were Black, and 7 (36.8 %) were of Hispanic ethnicity. In line with the Social-Ecological Model, 5 themes emerged. At the individual level, despite having several CV disease risk factors, HHAs’ perceptions of their health ranged from poor to excellent. Many were motivated to eat healthier and be more active but faced challenges including insufficient time and their own physical limitations. At the interpersonal level, the HHA-patient relationship influenced both aides’ and patients’ health (e.g., food in patients’ home). At the community level, HHAs wanted to connect with peers to improve their CV health together. At the organizational level, shift work, long commutes, and agency culture influenced their CV health. At the policy level, structural inequities (e.g., access to health insurance, citizenship) were barriers to CV health.

Conclusion:
HHAs’ ability to achieve CV health was influenced by personal, interpersonal, organizational, and societal-level factors. The findings can inform future, multi-level interventions, aiming to improve the CV health of HHAs and potentially their patients.
Abstract 13109: Empagliflozin Reverses Oxidized LDL-Induced RECK Suppression, MMP Activation, and Human Aortic Smooth Muscle Cell Proliferation and Migration
Authors: Bysani Chandrasekar , Mummidi Srinivas , DeMarco Vincent G. , Delafontaine Patrice , Higashi Yusuke
Published: December 2023

Empagliflozin, an FDA-approved anti-hyperglycemic agent, is a potent and highly selective inhibitor of sodium glucose co-transporter-2 (SGLT-2) in renal proximal tubule epithelial cells. It blocks glucose reabsorption and promotes glucose excretion via urine. Intriguingly, several clinical trials have reported the pleiotropic beneficial effects of SGLT-2 inhibitors in cardiovascular diseases, including antioxidant and anti-inflammatory effects. Here we investigated whether empagliflozin reverses oxidatively modified LDL (OxLDL)-induced matrix metalloproteinase activation and smooth muscle cell (SMC) migration and proliferation. Quiesced human aortic SMCs (Lonza) were treated with empagliflozin (1 uM) followed by human medium OxLDL (40 ug/mL; Kalen Biomedical). OxLDL stimulated SMC migration (1.8-fold, P<0.05, n=4) and proliferation (1.5-fold, P<0.05, n=4), and empagliflozin attenuated both by 67% (P<0.05, n=4) and 61% (P<0.05, n=4), respectively. Increased migration and proliferation by OxLDL were accompanied by elevated MMP-2 (3.2-fold, P<0.05, n=5) and 9 (3.1-fold, P<0.05, n=5) activities, which were also suppressed by empagliflozin by 65% and 67%, respectively (both P<0.05, n=5). RECK (reversion inducing cysteine rich protein with Kazal motifs) is a membrane anchored MMP inhibitor, and we found that OxLDL dose-dependently downregulated RECK in SMCs (by 60%, P<0.05, n=3) via NF-kB-dependent miR-30b induction. Intriguingly, empagliflozin restored the OxLDL downregulation of RECK to 88% of the control (n=3), as it inhibited miR-30b induction (by 49%, P<0.05, n=5). Consistent with RECK-mediated effects of empagliflozin, adenoviral overexpression of RECK inhibited OxLDL-induced SMC migration (by 67%, P<0.05, n=5) and proliferation (by 50%, P<0.05, n=5). Together, these results suggest that the vasculoprotective effects of empagliflozin are at least in part mediated by restoring RECK, thereby attenuating SMC migration and proliferation under elevated oxidative stress condition. Our results also suggest therapeutic potential of empagliflozin or RECK overexpression in vascular proliferative diseases.
Abstract 13112: Cardiovascular Complications During Delivery Hospitalizations in Patients With Pulmonary Hypertension: A Nationwide Analysis
Authors: Agrawal Ankit , Bajaj Suryansh , Bhagat Umesh , Chandna Sanya , Jamil Yasser , Majid Muhammad , Arockiam Aro Daniela , El Mahmoud , Michos Erin D
Published: December 2023

Introduction:
Pregnancy in patients with pulmonary hypertension (PH) is associated with a high risk of medical complications. We aimed to study the patient characteristics and association between PH and delivery complications.

Hypothesis:
PH is associated with poor outcomes in pregnant patients.

Methods:
We utilized the National Inpatient Sample (NIS) database 2011-2020 to identify adult patients (≥18 years) with PH undergoing delivery hospitalizations. The primary outcomes were in-hospital medical and obstetric complications. Multivariate regression was performed to study the association of PH with these complications.

Results:
A total of 37,482,207 delivery hospitalizations were identified out of which 9,593 patients had PH. Pregnant patients with PH had a higher incidence of complications at delivery like preeclampsia/eclampsia, cardiac arrhythmias, pulmonary edema amongst others as well as a higher incidence of in-hospital mortality compared to those without PH (0.51% vs 0.007%). In adjusted analyses, PH was independently associated with a higher risk of pulmonary edema (Odds ratio (OR) 18.65 (95% confidence interval (CI) 13.71-25.38), p<0.001), peripartum cardiomyopathy (PPCM) (OR 14.06 (9.15-21.60), p<0.001), venous thromboembolism (VTE) (OR 12.25 (7.80-19.24), p<0.001), cardiac arrhythmias (OR 11.75 (10.11-13.67), p<0.001), acute kidney injury (AKI) (OR 7.53 (5.36-10.58), p<0.001), preeclampsia/eclampsia (OR 4.61 (4.04-5.25), p<0.001), and acute coronary syndrome (ACS) (OR 2.83 (1.17-6.85), p=0.02), compared with pregnant patients without PH. Further, stroke (OR 127.33 (78.49-206.57), p<0.001), AKI (OR 51.25 (34.40-76.36), p<0.001), cardiac arrhythmias (OR 24.80 (19.43-31.65), p<0.001), PPCM (OR 6.47 (3.23-12.97), p<0.001), pulmonary edema (OR 4.27 (2.18-8.37), p<0.001), VTE (OR 2.75 (1.07-7.10), p=0.036), and preeclampsia/eclampsia (OR 1.87 (1.35-2.60), p<0.001) were associated with a high risk of in-hospital mortality in pregnant patients with PH as compared to those without PH.

Conclusions:
Delivery hospitalizations in patients with PH are associated with worse outcomes. Prenatal counseling and multidisciplinary care are essential to help mitigate unfavorable outcomes in this cohort.
Abstract 13121: Incidence, Predictors, and Outcomes of Venous and Arterial Thrombosis in COVID-19: A Nationwide Analysis
Authors: Agrawal Ankit , Bajaj Suryansh , Bhagat Umesh , Chandna Sanya , Arockiam Aro Daniela , El Dahdah Joseph , Gupta Rahul , Shekhar Shashank , Raj Kavin , Nayar Divya , Bajaj Divyansh , Chaudhury Pulkit , Griffin Brian P , Wang Tom Kai Ming K
Published: December 2023

Introduction:
Coronavirus disease 2019 (COVID-19) is known to increase the risk of venous (VTE) and arterial (ATE) thromboembolism. However, the incidence, predictors, and outcomes of clinical thrombosis for inpatients with COVID-19 are not well known. We evaluated the incidence, associated factors, and mortality outcomes of VTE and ATE in COVID-19 infection.

Hypothesis:
COVID-19 is associated with a higher risk of thrombosis and mortality.

Methods:
Hospitalized patients with COVID-19 during 2020 were identified from the National Inpatient Sample database and data was retrieved regarding clinical characteristics, incident VTE and ATE and mortality outcomes. Multivariate regression was performed to identify clinical factors associated with thrombosis and in-hospital mortality in COVID-19 inpatients.

Results:
Overall, 1,583,135 COVID-19 inpatients were identified out of which patients with thrombosis were 41% females with a mean age 65.4 (65.1-65.6) years. The incidence of thrombosis was 6.1%, including VTE 4.8%, ATE 3.0%, and in-hospital mortality rate was 13.4%. The main factors associated with overall thrombosis, VTE and ATE were paralysis, ventilation, solid tumors without metastasis, and metastatic cancer. Patients with thrombosis were more likely to have respiratory symptoms of COVID-19 (76.7% vs 75%, p<0.001) compared to patients without thrombosis, along with comorbidities like complicated diabetes mellitus and congestive heart failure, and acute presentations like septic shock, acute respiratory distress syndrome and acute kidney injury. Symptomatic and severe COVID-19 disease were associated with a higher risk of thrombosis (OR 1.37 (1.31-1.43) and OR 1.62 (1.49-1.76), respectively, p<0.001) and VTE (OR 1.40 (1.33-1.46) and OR 1.66 (1.52-1.80) respectively, p<0.001). Although all thrombosis categories were associated with higher in-hospital mortality for COVID-19 inpatients in univariable analyses (p<0.001), they were not significant in multivariate analyses.

Conclusions:
Overall, thrombosis, especially VTE was found in approximately 5% of COVID-19 inpatients, while ATE was rare, with important associated factors identified, however they were not independently associated with higher in-hospital mortality.
Abstract 13142: Prediction of Embolic Stroke in People Without Atrial Fibrillation and Prior Stroke Using Measures of Atrial Myopathy: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Maheshwari Ankit , Norby Faye L , Inciardi Riccardo M , Soliman Elsayed Z , Alonso Alvaro , Johansen Michelle C , Gottesman Rebecca , Solomon Scott , Shah Amil M , Chen Lin Y
Published: December 2023

Introduction:
There is no effective way to predict embolic stroke (ES) in people without atrial fibrillation (AF). Atrial myopathy—characterized by left atrial (LA) remodeling—is associated with ES independent of AF.

Hypothesis:
An ES prediction model for people without AF or stroke can be developed with measures of atrial myopathy.

Methods:
ARIC study participants without AF, stroke, or anticoagulation at visit 5 (2011-13) were followed for 5 years. Covariates included CHA
2
DS
2
VASc variables, P-wave indices, echocardiographic measures of LA function and size, and N-terminal B-type Natriuretic Peptide (NTproBNP). The primary outcome was ischemic stroke. A secondary outcome of possible embolic stroke (PES) was defined as non-lacunar strokes and strokes with new AF within 1 year of stroke. Cox proportional hazards models were created for 5-year ischemic stroke (model A) and PES (model B) risk. Stepwise backwards selection (inclusion threshold P<0.20) generated parsimonious models. Model discrimination and calibration were evaluated by the c-statistic and Hosmer-Lemeshow χ
2
statistic, respectively.

Results:
91 ischemic strokes (53 PES) were identified in 4154 participants (59.9% female, mean age 75.1(5.0) years). Age, sex, peripheral arterial disease, hypertension, abnormal P-wave axis, and left atrial reservoir strain were included in model A. Model B added NTproBNP. The C-statistics for models A and B were 0.653 (0.596-0.709) and 0.744 (0.680-0.808), respectively. Both models were well calibrated.

Conclusions:
Prediction of ES may be achieved using measures of atrial myopathy in people without AF and prior stroke. Validation of our model is needed.
Abstract 13154: Impact of Age for Right Atrial Strain in Patients With Submassive Pulmonary Embolism
Authors: Orihara Yoshiyuki , Eguchi Shunsuke , Eguchi Ayumi , Pfeiffer Michael , Peterson Brandon , Ruzieh Mohammed , Gao Zhaohui , Boehmer John , Gorcsan John , Wilson Ryan
Published: December 2023

Background:
Submassive pulmonary embolisms (sPE) are common and carry significant mortality. Strain imaging presents a novel method of assessing right atrial (RA) function. However, there are less reports focused on the feature of RA strain in patients with sPE. This study examines whether RA strain has different cutoff values according to aging in patients with sPE.

Method:
We performed a retrospective cohort study of 221 patients with sPE. The primary outcome was 30-day all-cause mortality. RA strain was analyzed retrospectively using TOMTEC ®. All patients were divided into three age groups according to tertiles. Receiver operating characteristic (ROC) curves were performed for evaluation.

Result:
Median age was 65 years and 31 patients died within 30 days. Of 221 patients, 84 patients (38%) were elder group (70 ≤ age), 66 patients (30%) were middle-aged group (58 ≤ age ≤ 69), and 71 patients (32%) were young group (age < 58). In all patients, statistical difference was observed in RA strain among the three groups (p = 0.042). ROC curve to predict 30-day mortality depicted area under the curve (AUC) and best cutoff value (BCV) were 0.688 and 27.7, respectively. (sensitivity [SE] 0.704, specificity [SP] 0.642) In elder group, ROC demonstrated AUC of 0.656 and BCV of 28.9 (SE 0.480, SP 0.889). In middle-aged group, ROC showed AUC of 0.647 and BCV of 27.7 (SE 0.636, SP 0.694). Interestingly, in young group, ROC demonstrated the lowest BCV of 17.4 with AUC of 0.75 (SE 0.571, SP 0.984) (Figure).

Conclusion:
RA strain as best cutoff shows different values among different age groups, especially low value in young groups. Further validation is needed to determine the role and utility of strain in patients with submassive PE.
Abstract 13159: Inverse Relationship Between Genetic Predisposition to Hyper- and Hypo- Cholesterolemia and Incident Type 2 Diabetes
Authors: Ravi Akshaya , Koyama Satoshi , Cho So Mi J , Haidermota Sara , Hornsby Whitney , Ellinor Patrick T , Natarajan Pradeep
Published: December 2023

Introduction:
High cholesterol and type 2 diabetes mellitus (T2DM) share metabolic and environmental risk factors. Nevertheless, previous literature suggests an inverse association between monogenic/polygenic hypercholesterolemia and T2DM prevalence. We investigated the extent to which polygenic and monogenic hyper- and hypo-cholesterolemia contributes to incident T2DM in a large prospective cohort.

Hypothesis:
We hypothesized that genetic predisposition to blood cholesterol would associate with incident T2DM risk.

Methods:
UK Biobank participants who underwent whole-exome sequencing and genome-wide genotyping were included. Based on the Cox proportional hazards model, the associations of familial hypercholesterolemia (FH), polygenic risk scores (PRS) for low-density lipoprotein cholesterol (LDLC), and APOB and PCSK9 predicted loss of function (pLOF) variants with incident T2DM after adjusting for age, sex, genotyping array, lipid-lowering medication use, and the first ten genetic principal components.

Results:
Among the 443,428 participants, 2,357 (0.56%) had FH and 1,280 (0.30%) had APOB or PCSK9 pLOF variants; the remaining 425,710 (99.13%) were categorized based on LDLC-PRS percentile. Individuals with FH or higher LDLC-PRS had lower risk of incident T2DM. In contrast, individuals with lower LDLC-PRS and APOB and PCSK9 pLOF had an increased risk of T2DM.

Conclusions:
Monogenic and polygenic risks for increasing and decreasing LDLC were inversely associated with T2DM risk.
Abstract 13173: Loss of ACE2 in a Diabetic Obese Setting Exacerbates Cardiovascular Dysfunction in the Setting of Gut Dysbiosis
Authors: Gheblawi Mahmoud , Wang Faqi , Basu Ratnadeep , Prasad Ram , Grant Maria B , Oudit Gavin Y
Published: December 2023

Introduction:
COVID-19 disproportionately affects older, male obese patients leading to a high prevalence of adverse outcomes. SARS-CoV-2 mediated ACE2 loss may further increase the susceptibility of these patients to adverse outcomes. Loss of ACE2 may be a causative factor in cardiovascular (CV) injury independent of primary viral-mediated injury.

Methods:
Male, 6-month-old, diabetic, obese

db/db Ace2
-/y

(double mutant, DM) mice and respective WT,

Ace2
-/y

, and
db/db
controls (n=12) were assessed for injury across the gut-heart axis. Cardiovascular parameters were evaluated by echocardiography, pressure-volume loops, and histology. Alterations in gut permeability were determined by measuring plasma peptidoglycan (PGN) levels and immunological staining of microvilli structure. Metagenomics and metatranscriptomics determined the functional and phyla alterations of the gut microbiota.

Results:
Loss of ACE2 in diabetic obese mice led to increased left atrium diameter (P<0.001) and elevated left ventricular end-diastolic pressures (P<0.05) compared to
db/db
mice. Cardiac remodeling was prevalent in DM hearts with increased cardiomyocyte hypertrophy (P<0.001), cardiac fibrosis (P<0.05), lipid accumulation (P<0.01), and reactive oxygen species (ROS; P<0.01) compared to
db/db
mice. This was associated with elevated aortic ROS (P<0.001), and impaired femoral artery vasodilation (P<0.001). DM mice had increased gut-blood barrier permeability, with elevated plasmalemma vesicle-associated protein-1 staining (P<0.05) and plasma PGN levels (P<0.01). Principal coordinates analysis of gut microbial β diversity showed distinct populations across the experimental groups (P<0.05). Loss of ACE2 in
db/db
mice resulted in the divergence of metatranscriptomics profiles with increased expression of neutral amino acid metabolism, PGN and toxin production pathways.

Conclusions:
Loss of ACE2 in diabetic obese mice worsened cardiovascular dysfunction and adverse remodeling and was associated with an altered gut-cardiovascular axis characterized by elevated gut permeability and dysbiosis. Our results support worsening CV injury arising from the loss of ACE2 and may indicate a pathway of SARS-CoV-2 infection mediated CV injury.
Abstract 13183: The Burden of Uncontrolled Hypertension (HTN) in Chronic Kidney Disease (CKD). Impact of the Revised KDIGO Guidelines
Authors: McGregor Richard , Yang Y Fred F , McCabe James , Cacheris Bill
Published: December 2023

Introduction:
The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease for patients not receiving dialysis highlights the increasing awareness of controlling HTN in CKD patients.

Goals/Aims:
To identify the number of persons in the US with HTN and advanced CKD.

Research Question:
Determine the current number of persons with advanced CKD and HTN based on various blood pressure thresholds and to project the increase in the number of patients over the next 10 years.

Methods:
The analysis is based on multiple years of the US National Health and Nutrition Examination Survey (NHANES).

Results:
We examined and projected the prevalence, awareness and treated number of HTN patients as well as the number of patients with uncontrolled HTN. Uncontrolled HTN was defined as taking at least 2 or more anti-hypertensive medications and the analysis focused on advanced CKD patients not requiring dialysis (stage 3b/4). Lowering the systolic/diastolic blood pressure threshold (mm Hg) from >140/90 to >130/80 or > 120/70 shows significant current numbers of patients with uncontrolled HTN and advanced kidney disease of 1.5 MM, 2.0 MM, and 2.7 MM, respectively. The number of patients is expected to increase 20% in the next 10 years highlighting the need for effective management of HTN in CKD.
Abstract 13192: Anti-Factor Xa Activity in Patients With Chronic Thromboembolic Pulmonary Disease With or Without Pulmonary Hypertension Treated With Factor Xa Inhibitors
Authors: NAKANO YOSHIHISA , Adachi Shiro , Kondo Hiroki , Hirose Miku , Adachi Takeshi , Nishiyama Itsumure , Yasuda Kenichiro , Yoshida Masahiro , Yatsuya Hiroshi , Murohara Toyoaki
Published: December 2023

Introduction and Hypothesis:
Data on the efficacy and safety of factor Xa (FXa) inhibitors in chronic thromboembolic pulmonary disease (CTEPD) patients, especially in chronic thromboembolic pulmonary hypertension (CTEPH) patients, remain limited. Here, we aimed to evaluate the effect of FXa inhibitors by measuring anti-factor Xa activity (AXA) in both patients with CTEPD without pulmonary hypertension (PH) and CTEPH.

Methods:
Twenty-five CTEPD patients without PH and 52 CTEPH patients, treated with either of the FXa inhibitors were enrolled. AXA was measured by using HemosIL heparin calibrator. Blood samples were collected two times at the same day: immediately before the drug administration (trough) and 2-3 h after drug administration (peak).

Results:
In all 77 patients, median age was 66 (Interquartile range [IQR] 51–73) years, and 43% were male. In addition, 47% of the patients received rivaroxaban of 15 mg/day, 27% received apixaban of 10 mg/day, 14% received edoxaban of 60mg/day, and 12% received edoxaban of 30 mg/day. The median peak AXA of all 77 patients was 1.92 IU/mL and was comparable between CTEPD without PH and CTEPH patients. Significant difference of trough and peak AXA was shown among four different prescribed drugs (P < .001 and P = .006, respectively). During the observational period of median 519 (IQR 364–1118) days, major and clinically relevant non-major bleeding occurred in six patients. ROC analysis to predict bleeding events revealed that the sensitivity and specificity of the cutoff point of a peak AXA of 2.1 IU/mL were 67% and 66%, respectively (AUC 0.66). The cumulative rate of major and clinically relevant non-major bleeding tended to be higher in patients with peak AXA ≥ 2.1 IU/mL than in patients with values below this point (p = .092, Figure).

Conclusion:
Measuring AXA could be a useful method to evaluate the effect of FXa inhibitors in CTEPD with or without PH patients.
Abstract 13198: Assessment of the Clot Real-Time Risk Prediction Model of Hospital-Associated Venous Thrombosis in Children After Congenital Heart Surgery
Authors: Sunthankar Sudeep D , Moore Ryan P , Byrne Daniel W , Domenico Henry J , Wheeler Allison P , Walker Shannon C , Kannankeril Prince J
Published: December 2023

Introduction:
Children with congenital heart disease (CHD) are at high risk for hospital-associated venous thromboembolism (HA-VTE) after cardiac surgery. The Children's Likelihood Of Thrombosis (CLOT) trial validated a real-time predictive model for HA-VTE using data extracted from the EHR for pediatric inpatients with an available online application (https://cqs.app.vumc.org/shiny/PediatricVTEPrediction/).

Hypothesis:
We tested the hypothesis that addition of CHD surgical specific data would improve the CLOT model for HA-VTE prediction in the CHD surgical population.

Methods:
The performance of the model in CHD patients from 2010-2022, was assessed using three iterations of the CLOT model: 1) the original CLOT model, 2) the original model refit using only data from the CHD cohort, and 3) the model updated with the addition of cardiopulmonary bypass time, surgical severity (STAT category), and BMI as covariates. The discrimination of the three models was quantified and compared using AUROC.

Results:
Our cohort included 1457 patients (median 2.0 IQR[0.5-5.2] y/o) following cardiac surgery. HA-VTE was present in 5% of our CHD cohort compared to 1% in the general pediatric population. The AUROC for the original (0.80 [95% CI: 0.74-0.85]), refit (0.85 [0.80-0.88]), and updated (0.86 [0.81-0.90]) models demonstrated excellent discriminatory ability within the CHD cohort (Figure 1).

Conclusions:
The addition of cardiac specific features improved model performance for discrimination of HA-VTE; however, this benefit was marginal compared to refitting the original model to the CHD cohort. This suggests strong predictive models, such as CLOT, can be optimized for cohort subsets without additional data extraction, thus reducing cost of model development and deployment. Identification of high-risk individuals using real-time predictive models deployed in the EHR may allow for prophylactic therapy and reduction of thrombosis in CHD surgical patients.
Abstract 13204: Single-Nucleus Multiomic Analyses Identifies Gene Regulatory Dynamics of Phenotypic Modulation in Human Aneurysmal Aortic Root
Authors: Zeng Qingyi , Liu Xuanyu , Zhou Zhou
Published: December 2023

Introduction:
Aortic root aneurysm is a potentially life-threatening condition because it may lead to aortic rupture. However, a single-nucleus transcriptomic and epigenomic landscape in the aortic root tissue of humans is lacking, and the regulatory mechanism of pathogenesis in aneurysmal aortic root remains elusive. We sought to identify molecular triggers for aortic root aneurysm in Marfan syndrome patients.

Methods:
Aneurysmal aortic root tissues from MFS patients (n=6) and normal aortic root tissues from age-matched, heart transplantation recipients (n=6) were collected. Samples from four subjects of each group were individually subjected to single-nucleus multiomic sequencing (gene expression and chromatin accessibility). Spatial transcriptomic assays were applied to aortic root tissue sections from two subjects of each group.

Results:
The single-nucleus dataset revealed three subclusters for the vascular smooth muscle cells (VSMCs) lineage including contractile VSMC1 (expressed a high level of
RYR2
), modulated VSMC2 and VSMC3(expressed a high level of
CFH
). Statistically significant expansion of the modulated VSMCs was observed in MFS patients. In addition, the modulated VSMCs are not only associated with the diseased states but also associated with the spatial location. The modulated VSMCs are preferentially located in the inner layer of the tunica media close to the intima in both healthy and diseased conditions. Based on the evidence from comparative analyses, we obtained 11 candidate key regulators (such as FOXN3, TEAD1, and BACH1) that potentially drive the phenotypic modulation of VSMCs and the pathogenesis of aortic root aneurysms. The experimental evidence supporting that the forkhead transcription factor FOXN3 may function as a key regulator for maintaining the contractile phenotype of human aortic VSMCs, whose expression decreased during phenotypic modulation and was downregulated in MFS VSMCs.

Conclusions:
We present the first atlas of gene expression and chromatin accessibility in human aortic root tissue at single-nucleus and spatial resolution. FOXN3 was identified as a novel key regulator for maintaining the contractile phenotype of human aortic VSMCs, which may serve as a potential therapeutic target.