bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11028: Positive Airway Pressure Therapy for Obstructive Sleep Apnea in Heart Failure Patients With Preserved Ejection Fraction - Implications for Healthcare Resource Utilization
Authors: Malhotra Atul , Cole Kate , Malik Anita , Pépin Jean-Louis , Sert Kuniyoshi Fatima , Cistulli Peter , Benjafield Adam , Somers Virend K ,   on behalf of the medXcloud group
Published: June 2023

Introduction:
Heart failure patients with preserved ejection fraction (HFpEF) frequently have co-morbid obstructive sleep apnea (OSA), although the impact of OSA treatment remains unclear in this patient population. We assessed the association between adherence to positive airway pressure (PAP) therapy and healthcare resource utilization in patients with OSA and HFpEF.

Methods:
Administrative insurance claims data linked with objective PAP therapy usage data from patients with OSA and HFpEF were used to measure the association of PAP adherence and healthcare resource utilization, defined by hospitalizations and emergency room (ER) visits. US Medicare defines PAP compliance as use for at least 4 hours/night for 70% of nights in a consecutive 30-day period over 90 days. PAP adherent patients met this criteria for all 4 90-day periods, while PAP non-adherent patients did not meet this criteria for any 90-day period over one year. Propensity score methods were used to create well matched groups with differing PAP adherence levels.

Results:
The study cohort consisted of 4,237 eligible patients (54.0% female, mean age 64.1 years), of whom 40% were considered adherent to PAP therapy (30% intermediate-adherent, 30% non-adherent). After propensity score matching on prior year covariates, during the year after PAP prescription, PAP adherent patients had fewer hospital visits than non-adherent patients, with a 57% reduction in hospitalizations and a 36% reduction in ER visits for PAP adherent patients (Table 1a). These results remained consistent with inverse probability weighting, and furthermore showed a significant difference in hospitalizations between intermediate-adherent and non-adherent patients, but no significant difference in ER visits (Table 1b).

Conclusions:
Treating OSA with PAP therapy in patients with HFpEF is associated with a reduction in hospitalizations and ER visits. Adherence to PAP therapy is required to realize these clinical benefits.
Abstract 11032: Peptide Lv Promotes the Trafficking and Membrane Insertion of Endothelial K
Ca
31 Through the MEK1/ERK Pathway
Authors: Pham Dylan , Niemi Autumn , Blank Ria , Ko Gladys
Published: June 2023

Background:
Peptide Lv is an endogenous secretory peptide that is upregulated in the eyes of patients with diabetic retinopathy, an ocular disease with pathological angiogenesis. Peptide Lv promotes vascular endothelial cell proliferation, migration, and sprouting, and blocking peptide Lv with a specific antibody, anti-Lv, dampens neovascularization, so peptide Lv is an angiogenic factor. However, the molecular mechanism of how peptide Lv promotes angiogenesis is not clear. We found that peptide Lv causes endothelial cell membrane hyperpolarization, a step that is essential in endothelium-dependent angiogenesis. Peptide Lv augments the protein expression and current densities of K
Ca
3.1, an ion channel underlying the endothelial hyperpolarization. As ion channels require trafficking and insertion to the plasma membrane to be functional after they are expressed, we aimed to determine the downstream signaling of peptide Lv that is involved in the trafficking of K
Ca
3.1 in endothelial cells.

Hypothesis:
Peptide Lv activates the MEK1/ERK signaling pathway to promote the trafficking and membrane insertion of K
Ca
3.1 in endothelial cells. Blocking MEK1/ERK will prevent augmentation of K
Ca
3.1 by peptide Lv.

Methods:
Cultured human umbilical vein endothelial cells (HUVECs) were treated with peptide Lv (500 ng/ml) or PBS (vehicle control) in the presence/absence of FR180402 (10 μM; an ERK inhibitor) or PD98059 (10 μM, a MEK1 inhibitor) followed by the patch-clamp electrophysiological recordings and biotinylation assays.

Results:
Blocking ERK activation attenuated the peptide Lv-meditated membrane hyperpolarization and increase of K
Ca
3.1 currents in endothelial cells. Blocking ERK activation did not affect peptide Lv-elicited increases of K
Ca
3.1 protein expression, but it reduced the level of membrane-bound K
Ca
3.1

Conclusions:
The MEK1/ERK signaling pathway mediates peptide Lv-elicited trafficking and membrane insertion of K
Ca
3.1 but does not affect the increase of K
Ca
3.1 expression by peptide Lv.
Abstract 11038: Clinical Characteristics and Outcomes of High-Cost Pediatric Heart Transplant Hospitalizations in the United States
Authors: O'Connor Matthew J , Edelson Jonathan , Wittlieb-Weber Carol , Lin Kimberly Y , Edwards Jonathan , Rossano Joseph , Maeda Katsuhide , Gaynor James W , Burstein Danielle
Published: June 2023

Introduction:
Pediatric heart transplantation (HT) is resource-intensive, with the HT hospitalization being a major driver of costs. We sought to determine the characteristics and outcomes of patients whose HT hospital admissions incur high costs.

Methods:
The Pediatric Health Information System database was queried for pediatric (<18 y) hospital admissions between 1/1/2008 and 12/31/2021 in which HT was performed. High-cost HT admission was defined as ≥95
th
percentile of cost for all HT admissions during the study period. Costs were standardized across centers using a cost-to-charge ratio; all cost values (in US dollars) were indexed to the 2020 US Consumer Price Index. The primary outcome was mortality during the index HT admission. Clinical characteristics and outcomes were compared between high-cost HT admissions and lower-cost HT admissions (<95
th
cost percentile) using logistic regression.

Results:
A total of 4352 pediatric HTs were identified; for the entire cohort, median HT admission cost was $501,535 (IQR $270,291 - $902,302). Within the high-cost group (N = 217), HT admission costs ranged from $1,971,069 - $44,500,000; the majority (N = 195) had costs between $2 million and $5 million. High-cost admissions accounted for 23% of costs within the entire cohort. Median length of stay in the high-cost group was 247d (IQR 160d-342d) and 59d (IQR 24d-115d) in the lower-cost group (P<0.001). High-cost HT admissions increased over time (2.9% of admissions in 2008; 5.5% in 2021, P<0.001). Patients with high-cost HT admissions were younger (1y vs 6y, P<0.001), more likely to have single ventricle congenital heart disease (42.4% vs 28.9%, P<0.001), undergo ECMO (55.3% vs 19.3%) and/or VAD (37.3% vs 16.2%, P<0.001 for both), and receive dialysis (13.8% vs 3.6%, P<0.001). Hospital mortality was higher in high-cost HT patients (22.6% vs 4.2%, P<0.001); this relationship persisted after adjusting for clinical and center characteristics (OR 7.2, 95% CI 4.97 - 10.57, P<0.001).

Conclusions:
High-cost admissions for pediatric HT contribute disproportionately to overall hospital mortality and cost after HT, and are associated with high resource utilization. These findings highlight opportunities to improve outcomes in this growing and high-risk population.
Abstract 11109: Electrocardiogram-Based Deep Learning to Predict Peak Oxygen Consumption During Exercise
Authors: Khurshid Shaan , Churchill Timothy , Diamant Nathaniel , Di Achille Paolo , Reeder Christopher , Singh Pulkit , Wasfy Meagan M , Ho Jennifer E , Baggish Aaron L , Batra Puneet , Lubitz Steven A , Guseh James S
Published: June 2023

Introduction:
Peak oxygen consumption (V̇O2 Peak) is a robust marker of cardiovascular health. However, V̇O2 Peak assessment requires specialized exercise testing.

Methods:
We studied individuals who underwent cardiopulmonary exercise testing (CPET) with available resting 12-lead electrocardiogram (ECG) within 1 year. We developed a deep learning model to generate 320-dimensional representations of ECG waveforms. We trained and validated 3 penalized linear models to estimate V̇O2 Peak using 1) basic clinical factors (age, sex, and body mass index), 2) clinical factors plus routine ECG parameters (e.g., PR interval), and 3) clinical factors plus deep learning- ECG embeddings (“Deep ECG-V̇O2”). We assessed model performance by comparing Pearson correlation (r) and mean absolute error (MAE) against true V̇O2 Peak. Within a separate ambulatory sample, we assessed associations between Deep ECG-V̇O2-estimated V̇O2 Peak and incident outcomes using Cox proportional hazards models adjusted for age, sex, and body mass index.

Results:
The analysis set included 2,339 individuals (age 46±19 years, 37% female) who underwent CPET and was divided into development (n=1,891) and test (n=448) sets. Mean V̇O2 Peak was 33.6±14.4 mL/kg/min. In the test set, correlation and agreement with true V̇O2 Peak were favorable using Deep ECG-V̇O2 versus the comparison models (
Figure
). Within a separate set of 84,718 individuals, estimated V̇O2 Peak <14 mL/kg/min (a clinical threshold for substantially impaired fitness) was associated with higher risks of incident atrial fibrillation (hazard ratio [HR] 1.36, 95% CI 1.21-1.54), myocardial infarction (HR 1.21, 95% CI 1.02-1.45), heart failure (HR 1.67, 95% CI 1.49-1.88), and all-cause death (HR 1.84, 95% CI 1.68-2.03) (
Figure
).

Conclusions:
Information encoded within 12-lead ECGs can estimate V̇O2 Peak. Estimated V̇O2 Peak demonstrates strong inverse relationships with incident cardiovascular disease and all-cause mortality.
Abstract 11305: CSL112 (Apolipoprotein A-I (Human)) Infusion in Post Myocardial Infarction Patients Promotes Hepatocyte Cholesterol Uptake Ex Vivo
Authors: Velkoska Elena , Greene Brandon , Collins Heidi L , Adelman Steven , Mears Jenny , Duffy Danielle , Gibson C. Michael , Diditchenko Svetlana , Kingwell Bronwyn A
Published: June 2023

Background:
Cholesterol efflux capacity (CEC) is inversely related to incident cardiovascular events. CSL112 (apoA-I (human)) infusion rapidly and robustly increases CEC in AMI patients, but it is unknown whether this translates to increased hepatocyte cholesterol uptake, the subsequent step in reverse cholesterol transport.

Purpose:
To determine whether CSL112 increases cholesterol uptake by hepatocytes when administered post AMI.

Methods:
Patients from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study received either placebo, 2g or 6g CSL112 post AMI. Serum samples from a subset of subjects (n=15 per group) were studied
ex vivo
. Firstly, CEC was assessed using J774 macrophages loaded with labelled [
3
H]cholesterol tracer. Cholesterol uptake media (200μL) was then collected and applied to Fu5AH hepatocytes for assessment of labelled cholesterol uptake.

Results:
CSL112 infusion dose-dependently increased hepatocyte cholesterol uptake, with the 6g dose inducing a < 2-fold increase at the end of infusion (2 h), and sustained elevation above baseline at 24 - 48 h (Fig 1A). Hepatocyte cholesterol uptake across all dose groups and timepoints was strongly correlated with total CEC (r=0.949; p<0.001; Fig 1B) and plasma apoA-I (r=0.746; p<0.001).

Conclusion:
Infusion of CSL112 increased uptake of cholesterol into hepatocytes in direct proportion to increased CEC and apoA-I levels. This study demonstrates that the rapid, robust increase in CEC induced by CSL112 is also associated with substantial elevation in hepatocyte cholesterol uptake using an assay which models the final step in reverse cholesterol transport prior to cholesterol excretion in bile.

Figure 1: (A)

Effect of CSL112 on hepatocyte cholesterol uptake (mean
±

SEM).
(B)
Intra-subject correlation using individual data points across all timepoints.
Abstract 11374: Aspirin for Primary Prevention of Cardiovascular Events in Patients With Elevated Lipoprotein(a): The Multi-Ethnic Study of Atherosclerosis
Authors: Bhatia Harpreet S , Trainor Patrick , Carlisle Samantha , Tsai Michael Y , Criqui Michael H , Defilippis Andrew P , Tsimikas Sotirios
Published: June 2023

Introduction:
There is a lack of effective therapies for reducing risk in people with elevated Lp(a), especially for primary prevention. We aimed to evaluate the association between aspirin use and cardiovascular events (CVD) in people with elevated Lp(a).

Methods:
We performed a prospective cohort study using data from participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of baseline cardiovascular disease. We matched aspirin users and non-users using a propensity score based on CVD risk factors. We then evaluated the association between aspirin use and coronary heart disease (CHD) events (CHD death, non-fatal myocardial infarction) stratified by baseline Lp(a) level (above and below 50 mg/dL) using Cox proportional hazards models with adjustment for CVD risk factors.

Results:
Our study cohort included 6,632 participants, including 1,138 (20%) with Lp(a) >50 mg/dL and 1,592 (24%) with baseline aspirin use. Participants with elevated Lp(a) had a higher burden of CVD risk factors, with a trend toward greater aspirin use (25.7% vs 23.6%, p=0.10) and significantly higher CHD events (9.0% vs 7.3%, p=0.03). After propensity matching, aspirin was associated with a significant reduction in CHD events among those with elevated Lp(a) (HR 0.54, 95% CI 0.32-0.94, p=0.03). Those with Lp(a) >50 mg/dL with aspirin use had similar freedom from CHD as those with Lp(a) ≤50 mg/dL regardless of aspirin use (
Figure
).

Conclusions:
Aspirin use was associated with a significant reduction in CHD events in participants with elevated Lp(a) without baseline CVD. These results are hypothesis generating and require confirmation in studies with randomization of aspirin use.
Abstract 11378: Spontaneous Esophageal Hematoma in Chronically Anticoagulated Atrial Fibrillation
Authors: Jasti Manasa , MD Ammu Thampi Susheela , Rana Custodio Alejandro , Srivastava Amit , Cusick David
Published: June 2023

Introduction:
Intramural esophageal hematoma is a rare condition presenting with dysphagia, nausea and mid epigastric or retrosternal chest pain. We present a unique case of spontaneous esophageal hematoma in a patient anticoagulated with apixaban for atrial fibrillation.

Case presentation:
An 88-year-old woman with history of hypertension, hypothyroidism, persistent atrial fibrillation on apixaban presented to emergency department with sudden onset epigastric pain, dysphagia and nausea without vomiting while having dinner. Physical examination was unremarkable except for mild tenderness in the epigastric region. Initial workup including complete blood count, complete metabolic panel, lipase, troponin was unremarkable. EKG showed atrial fibrillation with no ischemic changes. CT chest showed abnormal hyperdense mass-like thickening approximately 4 x 3 x 12 cm involving the mid/distal thoracic esophagus with possible differentials being food bolus, esophageal hematoma or mass. Prothrombin complex concentrate (Kcentra) was given as patient was on apixaban and gastroenterology was consulted for upper endoscopy which showed a large hematoma occupying most of the esophageal lumen at the entire length of esophagus. After family discussion on stroke-versus-bleeding risk with anticoagulation, cardiology recommended holding anticoagulation for at least a month and future evaluation for WATCHMAN device. With stable hemoglobin and gradual advancement to a soft diet, patient was discharged home with repeat endoscopy planned in two weeks.

Conclusion:
Spontaneous esophageal hematoma, although rare in incidence, should be identified as a differential diagnosis in a patient on anticoagulation presenting with chest pain. Literature shows a higher incidence of this complication in women. Timely diagnosis and management along with discontinuing anticoagulation can significantly lower morbidity and mortality and overall has favorable prognosis.
Abstract 11742: Regional Disparities in Major Adverse Cardiac and Cerebrovascular Events During Hospitalizations in Young (18-44 Years) Obese Patients, 2019 National Inpatient Sample Analysis
Authors: Mondal Avilash , Damarlapally Nanush , Singh Birgurman , Arote Dr. Vaishnavi , Vadiyala Mounika Reddy , Singh Pranjali , Rana Nishtha , Paidi Gokul , Tandra Rineetha , Patel Hardik , Desai Rupak
Published: June 2023

Background:
Inpatient outcomes in obese patients have been investigated, although regional inequalities in cardiac and cerebrovascular events in young obese patients have not been explored previously.

Methods:
The National Inpatient Sample 2019 was queried for young obese patients (18-44 years) in 4 regions (Northeast, Midwest, South, West) using ICD-10-CM codes. Baseline characteristics and comorbidities inpatient MACCE including all-cause mortality, AMI, cardiac arrest, and stroke were identified.

Results:
Young obese cohort (Total n: 1,285,775, median age: 33 years, females: 75.4%) often consisted of admissions in the South (41.1%), followed by the Midwest (22.3%), West (20.7%), and Northeast (20.7%). HTN and DM were more frequent in the Midwest (32.3% and 22.3%) and South (34.4% and 22.8%) respectively, with higher MACCE of South (3.3%) and Midwest (3%) as compared to Northeast (2.3%) and West (2.6%) regions. All regions had comparable median hospital stay (3 days); however, the admissions in the West and Northeast regions (USD 36861 and 31211) had a higher cost burden. After adjusting for sociodemographic and comorbidities, the odds of in-hospital MACCE were higher in the West (aOR 1.15 95%CI 1.02-1.29), and South (aOR 1.16 95%CI 1.04-1.29), (p<0.001) vs. Northeast admissions
(Fig. 1)
.

Conclusion:
Cardiovascular comorbidities and MACCE were higher in young obese admissions in the South. This disparity may be due to differences in behavioral risk factors, socioeconomic status and healthcare access/prices. Future prospective studies on regional differences can help identify high-risk young, obese populations for targeted screening.
Abstract 11856: Characterization of Endothelial Adipose Triglyceride Lipase in a Preclinical Model of Heart Failure With Preserved Ejection Fraction
Authors: Stahnke Max , Schwanbeck Juliane , Goeritzer Madeleine , Kolb Dagmar , Grabner Gernot F , Breinbauer Rolf , Zechner Rudolf , Foryst-Ludwig Anna , Kintscher Ulrich
Published: June 2023

Background:
Metabolic syndrome and endothelial dysfunction are identified as key drivers of Heart Failure with preserved Ejection Fraction. Endothelial cells have an important barrier function including the control of lipid transport from the coronary circulation to the myocardium. In order to determine the role of EC lipid metabolism in HFpEF, we generated mice with an EC-specific deletion of adipose triglyceride lipase and subjected these mice to a hypertensive-obese two-hit HFpEF model.

Methods and Results:
Cell culture experiments were performed in HUVECS with a pharmacological ATGL inhibitor NG-497.
In vitro
experiments showed significant reduction of lipolysis by NG-497 and marked endothelial lipid droplet accumulation. Inducible endothelial cell-specific ATGL knockout mice were generated by crossbreeding Atgl fl/fl mice with Cdh5(PAC)-CreERT2 mice. Animals were randomized in a HFpEF or control group. HFpEF mice received a high fat diet and L-NAME for 15 weeks, while animals in the control group were put on a low fat diet and water. To analyse cardiac function, conventional and speckle-tracking echocardiography were performed. After 15 weeks, cre
-
littermates (wt) with HFpEF developed obesity and hypertension (body weight: wt-Ctrl: 33.8±2.5g vs. wt-HFpEF: 45.1±4.4g, p=0.0001; systolic blood pressure: wt-Ctrl: 99.9±3.7mmHg vs. wt-HFpEF: 135.5±5.6mmHg, p=0.0001), which did not significantly differ in ecATGL-KO mice. In parallel, wt-HFpEF mice developed echocardiographic signs of HFpEF including diastolic dysfunction: E/é: (wt-Ctrl: -22.1±1.4 vs. wt-HFpEF: -45.5±3.8; p<0.0001), IVRT: (wt-Ctrl: 17.8±0.7ms vs. wt-HFpEF: 19.5±0.8ms; p= p<0.0001), and an impaired global longitudinal strain (GLS) (wt-Ctrl: -20.7±1.1% vs. wt-HFpEF 12.9±0.7%; p<0.0001). Parameters of diastolic dysfunction were significantly improved in ecATGLKO mice after 15weeks of HFD/ L-NAME: E/é:-29.3±2.8; p<0.0001 vs. wt-HFpEF; IVRT: 18.3±0.5; p<0.05 vs. wt-HFpEF; GLS: -19.1±1.7; p<0.0001 vs. wt-HFpEF).

Conclusion:
This study demonstrates that loss of ATGL in ECs may protect from HFpEF. We hypothesize that lipid droplet accumulation in coronary ATGL-deficient ECs may save the myocardium from lipid overload and lipotoxicity, as shown in Cre- HFpEF mice.
Abstract 11865: Statin Decreases Risk of Dementia in Patients With Osteoarthritis: A Population-Based Study Abstract
Authors: Man Chung Chun , Yiu Kai Hang , Ren Qingwen , Yu Shuk Yin , Wong Pui Fai ,   HKUSZH
Published: June 2023

Emerging evidence suggested osteoarthritis is associated with increasing risk of dementia possibly because of accumulative age-related comorbidity and physical inactivity. Our study investigated whether statin use could reduce risk of dementia in patients with osteoarthritis.

Methods
Using a territory-wide health care database, we identified all eligible patients with osteoarthritis (
n
= 146 933) from 2000 to 2010. Inverse probability of treatment weighting was used to adjust age, sex, comorbidities and concurrent medications between statin nonusers (n = 102 100) and statin users (n = 44 833). The adjusted hazard ratio was calculated using competing risk regression with Cox proportional-hazard model.

Results
Among all eligible patients, the mean age was 68.3 ± 13.4 years. The median follow-up was 5.6 years (interquartile range: 1.4-10.2 years), and 8247 (5.61%) patients developed dementia. Statin user (vs statin nonuser) was associated with a lower risk of dementia incidence [multivariable adjusted subdistribution hazard ratio (SHR) = 0.76 ; 95% confidence interval (CI), 0.72-0.80]. Among the subtypes of dementia, statin user (vs statin nonuser) was associated with a lower risk of Alzheimer disease [multivariable adjusted SHR = 0.67 ; 95% CI, 0.60-0.74] as well as vascular dementia [multivariable adjusted SHR = 0.88 ; 95% CI, 0.78-0.99]. This observation remains consistent in patients across all time-weighted LDL levels.

Conclusions
Our study suggested that statin use is associated with a lower risk of dementia in osteoarthritis patients, irrespective of time-weighted LDL level. In particular, statin user has a lower risk of Alzheimer disease and vascular dementia when compared with statin nonuser.
Abstract 11882: Exploring Abnormalities in Coronary Vascular Resistance Reserve as a Distinct Feature of The Hfpef Syndrome in Women
Authors: Crosier Rebecca , Mielniczuk Lisa , deKemp Robert , Beanlands Rob S , Liu Peter , Coutinho Thais
Published: June 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is more common in women than men, but mechanisms underlying this female predominance are incompletely understood. Impaired systemic vasodilatory reserve and coronary microvascular dysfunction have been separately described as key abnormalities of HFpEF. However, the coronary vascular resistance reserve (CVRR), defined as the drop in coronary vascular resistance (CVR) from rest to peak stress, and its sex-specific nuances have not been explored in HFpEF. We sought to: (1) determine whether stress CVR differs between HFpEF and controls, and (2) assess sex differences in CVRR in HFpEF.

Methods:
We performed a cross-sectional study of 32 HFpEF participants and 26 controls, all without obstructive epicardial coronary artery disease. HFpEF was defined according to ESC Guidelines. Dipyridamole stress
82
Rb positron emission tomography was performed, and rest and stress CVR was calculated by dividing mean arterial pressure by coronary flow at rest and stress. Multivariable linear regression assessed (1) the association of HFpEF with stress CVR; and (2) the association of female sex with CVRR in patients with and without HFpEF.

Results:
Mean age was 74±7 years, 67% were women and mean LVEF was 62±5%: no difference between HFpEF and controls (P>0.05 for each). Results of the multivariable models are summarized in the Image. HFpEF was independently associated with higher global left ventricular CVR at peak vasodilatory stress. In addition, women had lower global left ventricular CVRR as compared to men, and this was unique to women with HFpEF. Results were the same for coronary-specific CVR and CVRR (analyses not shown).

Conclusions:
To our knowledge, this is the first study to non-invasively explore CVR and CVRR in HFpEF. Our findings suggest increased stress CVR in HFpEF, with a distinct abnormality in CVRR in women with HFpEF. Abnormal CVRR in women may contribute to the female predominance of HFpEF.
Abstract 11891: Adverse Childhood Experiences are Associated With Elevated Blood Pressure and Disturbed Sleep in the First Trimester of Pregnancy in Apparently Healthy, Young Adult Women
Authors: Jenkins Nathaniel D , Kline Christopher E , Barone Gibbs Bethany , Catov Janet M , Feghali Maisa , Santillan Mark K , Thomas Emily B , Jones Melissa A , Whitaker Kara M
Published: June 2023

Introduction:
Adverse childhood experiences (ACEs) are potentially traumatic psychosocial stressors that occur in early life, such as abuse, neglect, and household dysfunction. We hypothesize that ACEs are an underlying risk factor for disturbed sleep and hypertension in pregnancy, which is a major cause of maternal-fetal morbidity and mortality.

Hypothesis:
In young adult women, ACE exposure will be positively associated with first trimester systolic (SBP), diastolic blood pressure (DBP), and wakefulness after sleep onset (WASO), and inversely associated with sleep efficiency (SE). Further, ACE exposure will be associated with greater odds of first trimester elevated or stage 1 hypertension (ES1H).

Methods:
Data were obtained at 10-12 weeks of gestation from 142 pregnant women who were enrolled in an ongoing, clinical cohort study in Iowa City and Pittsburgh. Participants were 18-45 y of age, had a BMI <40 kg/m
2
, and could not be taking medications or receiving treatment for sleep or cardiometabolic disorders such as chronic hypertension or diabetes. BP was assessed in accordance with AHA recommendations. Actigraphy was used to assess WASO and SE over ≥5 nights. ACE scores were log transformed and correlations were used to examine associations between ACE exposure and SBP, DBP, WASO and SE. Logistic regression was used to examine the association of ACE exposure with the probability of ES1H in an unadjusted model (model 1) and a model adjusted for age, race, ethnicity, BMI, and depressive symptoms (model 2).

Results:
56% reported exposure to ≥1 ACE, and 28% reported exposure to ≥3. ACE exposure was positively related to SBP (r = 0.17,
p
= 0.04), DBP (r = 0.21,
p
= 0.01), and WASO (ρ = 0.21,
p
= 0.01), and negatively associated with SE (ρ = -0.22,
p
= 0.009). ACE exposure was associated with greater odds of first trimester ES1H in model 1 (OR = 2.73, 95% CI = 1.36 - 5.50;
p
= 0.005) and model 2 (OR = 2.44, 95% CI = 1.07 - 5.56;
p
= 0.03).

Conclusions:
ACEs represent an important risk factor for elevated BP and disturbed sleep in pregnancy. Large cohort studies are needed to understand the links among ACE exposure, sleep, resilience factors and hypertensive risk in pregnancy to provide information for developing targeted interventions to improve maternal-fetal cardiovascular health.
Abstract 11896: Spontaneous Heparin-Induced Thrombocytopenia Presenting as Acute Stent Thromboses Following an Acute St-Segment Elevation Myocardial Infarction
Authors: Gier Chad , Jacobs Mark , Verma Gagan , Lawson William E , Chen On , Parikh Puja
Published: June 2023

Introduction:
Spontaneous heparin-induced thrombocytopenia (HIT) is a rare clinical variant that develops without prior exposure to heparin. We present a 40-year-old man who was diagnosed with spontaneous HIT after an acute ST-segment elevation myocardial infarction complicated by multiple acute stent thromboses and left ventricular (LV) thrombus.

Case:
A 40-year-old previously healthy man with no known history of heparin exposure presented to our emergency department with an acute ST-segment elevation myocardial infarction. Emergent coronary angiography revealed a severely thrombotic 100% occlusion of his distal left anterior descending artery for which thrombectomy and percutaneous coronary intervention (PCI) were performed with placement of a drug eluting stent. Prior to angiography, the patient received 4000 units of unfractionated heparin and an additional 2000 units intra-arterially during the case. Labs prior to PCI revealed thrombocytopenia and HIT enzyme-linked immunoassay testing was sent. He underwent repeat angiography two additional times during his course for recurrent chest pain which both revealed acute stent thrombosis. HIT testing eventually returned positive for the presence of platelet factor 4 antibodies. A subsequent serotonin release assay returned positive, confirming the diagnosis of HIT. A transthoracic echocardiogram during his hospitalization also revealed an LV thrombus.

Discussion:
Heparin-induced thrombocytopenia (HIT) is traditionally diagnosed after thrombocytopenia develops 5 to 10 days after exposure to heparin. However, there have been rare reports of a spontaneous form of HIT that can occur without prior exposure to heparin. This case highlights a rare presentation of spontaneous HIT. Although infrequent, cardiologists should be aware of atypical presentations of HIT, since almost all patients will receive heparin prior to or during coronary angiography and coronary interventions. Spontaneous HIT should be considered in all patients who present with unexplained thrombocytopenia with arterial and/or venous thrombi. Failure to recognize this clinical entity could lead to potentially life-threatening thrombotic complications from further administration of heparin.
Abstract 11902: Hypertension Severity Impacts Declines in Left Ventricular Ejection Fraction Among Women Receiving Adjuvant Chemotherapy for Breast Cancer (UPBEAT WF-97415)
Authors: Garg Riya , O'Connell Nathaniel S , Lesser Glenn J , Jordan Jennifer H , Sutton Arnethea L , Bottinor Wendy , Ladd Amy C , Dagostino Ralph , Hundley William G ,   The UPBEAT Study Team
Published: June 2023

Introduction:
AHA/ACC hypertension guidelines do not clearly address pharmacological treatment of increases in blood pressure (BP) in women receiving potentially cardiotoxic chemotherapy for treatment of breast cancer.

Methods and Results:
Magnetic resonance measures of left ventricular ejection fraction (LVEF) were performed in women with stage I-III breast cancer prior to and three months after initiating potentially cardiotoxic chemotherapy. Measurements of brachial BP were collected according to AHA recommendations. Using multivariable analysis, we assessed the association between change in LVEF and pre-existing ACC/AHA stages of hypertension (HTN) after accounting for pre-treatment LVEF, diabetes status, age, and body mass index (BMI). All analyses were performed by those blinded to all participant identifiers.

Participants (n=259, female) were aged 56±11 (Mn
+
SD) years and were 76% white & 19% black (NCT02791581 and NCT01719562). Cancer therapies included combinations of anthracyclines (23%), trastuzumab (10%), paclitaxel (22%) and cyclophosphamide (30%). After accounting for pre-treatment LVEF, diabetes status, age, and BMI, participants with stage 2 HTN experienced a significant decline (p=0.037, Figure) in LVEF relative to individuals with normal blood pressure.

Conclusion:
Relative to women with normal blood pressure, women with stage 2 HTN experienced a larger decline in LVEF (p=0.037) three months after initiating potentially cardiotoxic chemotherapy for breast cancer. This finding raises the possibility that lower blood pressure targets among women receiving adjuvant treatment for breast cancer may be associated with improved preservation of LVEF.
Abstract 11964: Implementation of a Near Peer ECG Didactic Curriculum in an Internal Medicine Residency Program
Authors: Kaye Matthew G , Khan Hassan A , Yatsynovich Yan , Gudleski Gregory D , Graham Susan P , Kwiatkowski Alysia
Published: June 2023

Introduction:
Electrocardiogram (ECG) interpretation is a fundamental skill. Near-peer teaching improves knowledge acquisition and learner satisfaction. We previously demonstrated an improvement in resident comfort level in interpreting ECGs following structured didactics. Here, we aim to establish whether a longitudinal didactic curriculum objectively increases resident performance in ECG interpretation.

Methods:
This prospective cohort study surveyed Internal Medicine residents at University at Buffalo who participated in monthly ECG didactics over a 7-month period. Pre- and post-curriculum surveys were administered. Responses were anonymous and participation voluntary. Data collected included demographics, attendance, exposure to clinical cardiology, interest in cardiology, and number of sessions attended. Residents were asked to interpret sixteen unique ECGs, divided evenly among eight common rhythms into both surveys. Fall 2021 and Spring 2022 cohorts were compared using t-tests and chi-square analyses. Associations between attendance, comfort level in interpretation, and number of correct interpretations were analyzed using Pearson correlations. Multivariate linear regression determined the strongest predictor of the number of correct ECG interpretations.

Results:
Spring cohort correctly interpreted a significantly greater percentage of ECGs than Fall cohort (74.5% vs. 60.9% , p < 0.001). Didactic attendance was significantly associated with comfort level in interpreting ECGs (r = .328, p = .018) and a showed trend towards increased number of correct interpretations (r = .248, p = .077). Attending three or more sessions resulted in a greater percentage of correct ECG interpretations compared to those who attended two or fewer sessions (80.0% vs. 71.1%, p = 0.48). Number of clinical cardiology blocks taken was significantly associated with correct interpretations (r = .310, p < .001) and was the strongest predictor of accurately interpreting ECGs (β = 0.29, p = .037).

Conclusions:
Dedicated ECG didactics improve residents’ ability to interpret ECGs. A longitudinal curriculum which contains both didactic sessions and clinical exposure appears to offer the greatest benefit in improving ECG interpretation skills.
Abstract 11976: Functional Characterization of Calcium Handling Kinetics in Patient-Derived Ipsc-Cm Models of Pkp2-Mediated Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Hamrick Samantha K , Kim CS John , Gluscevic Martina , Tester David J , Ackerman Michael J
Published: June 2023

Introduction:
Pathogenic variants in
PKP2
-encoded plakophilin 2 cause arrhythmogenic right ventricular cardiomyopathy (ARVC). Electrocardiographically,
PKP2
-mediated ARVC may mimic
RYR2
-mediated catecholaminergic polymorphic ventricular tachycardia (CPVT). We compare the underlying mechanism of arrhythmia in ARVC and CPVT using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs).

Methods:
iPSC-CMs were generated from 2 ARVC patients with different
PKP2
variants [E149X (PKP2-1) and c.2146-1G>C (PKP2-2)], 1 patient with a CPVT variant [RyR2-R176Q (CPVT1)], and a wild-type (WT) control. Fluo-4 AM calcium dye was used to assess calcium kinetics in iPSC-CMs before and during treatment with 100 nM isoproterenol (ISO) at 8-10 min.

Results:
Compared to WT,
PKP2
and
RYR2
iPSC-CMs had a greater amplitude before (WT: 0.331±0.031, PKP2-1: 1.048±0.074, PKP2-2: 1.076±0.095, CPVT1: 0.966±0.061; P<0.0001) and during ISO (WT: 0.277±0.022, PKP2-1: 0.971±0.069, PKP2-2: 0.622±0.041, CPVT1: 0.756±0.051; P<0.0001). The Ca
2+
transient duration (CTD100) was longer in
PKP2
and
RYR2
iPSC-CMs compared to WT before (WT: 1.01±0.05 s, PKP2-1: 1.84±0.01 s, PKP2-2: 1.76±0.02 s, CPVT1: 1.81±0.02 s; P<0.0001) and during ISO (WT: 1.38±0.05 s, PKP2-1: 1.65±0.03 s, PKP2-2: 1.71±0.03 s, CPVT1: 1.61±0.05 s; P<0.001). Before (WT: 259±13 ms, PKP2-1: 538±23 ms, PKP2-2: 493±28 ms, CPVT1: 586±24 ms; P<0.0001) and during ISO (WT: 311±19 ms, PKP2-1: 406±21 ms, P=0.0172, PKP2-2: 487±28 ms, P<0.0001, CPVT1: 453±21 ms, P=0.0001), peak to 50% decay time was slower in
PKP2
and
RYR2
iPSC-CMs compared with WT. Upstroke time was longer in
PKP2
and
RYR2
iPSC-CMs compared to WT before (WT: 205±5 ms, PKP2-1: 539±13 ms, PKP2-2: 429±19 ms, CPVT1: 455±12 ms; P<0.0001) and during ISO (WT: 213±7 ms, PKP2-1: 375±16 ms, PKP2-2: 416±20 ms, CPVT1: 389±10 ms; P<0.0001).

Conclusion:
Here, iPSC-CMs, derived from patients with either
PKP2
-mediated ARVC or
RYR2
-mediated CPVT, display similar abnormal calcium handling properties such as greater amplitude, longer CTD100, and slower peak to 50% decay time and upstroke time compared to WT iPSC-CMs before and during ISO treatment. This may explain why patients with
PKP2
-mediated ARVC often mimic the treadmill stress test seen in patients with CPVT1.
Abstract 12010: Efficacy and Safety of Dofetilide and Sotalol in Patients With Hypertrophic Cardiomyopathy
Authors: Chen Christopher R , Lal Mallika , Burton Yunwoo , Chen Hongya , Stecker Eric , Masri Ahmad , Nazer Babak
Published: June 2023

Introduction:
Patients with hypertrophic cardiomyopathy (HCM) often have atrial fibrillation (AF) and ventricular arrhythmias (VA) requiring rhythm control. In the 2014 AF Guidelines, class III anti-arrhythmic drugs are not recommended in patients with left ventricular hypertrophy, but in the 2020 HCM Guidelines, sotalol (STL) and dofetilide (DOF) are deemed “reasonable” for rhythm control, both based on limited data.

Methods:
We conducted an observational study (2001-2021) of patients with HCM who were treated with DOF or STL for AF and/or VA. Baseline characteristics and drug-related adverse events were analyzed from the electronic medical record, and rates of discontinuation and arrhythmia recurrence at 1 year and by time of chart review were compared using Kaplan Meier curves and log rank test.

Results:
There were 21 DOF and 52 STL HCM patients with AF, and 18 STL patients with VA. At 1 year, AF patients on DOF or STL had no significant difference in rates of AF recurrence (42.9% vs 44.2%, p=0.664) or drug discontinuation (38.1% vs 29.4%, p=0.582). Recurrence and discontinuation rates of VA on STL were comparable (Figure). Over a median follow up of 1603 days (IQR 994, 4131), there was a trend toward greater efficacy for STL with respect to less AF recurrence (p=0.085) and less frequent discontinuation (p=0.153; Figure). On univariate analysis, only NYHA class predicted AF recurrence. Reasons for discontinuation were most often for inefficacy or mild side-effects. One patient with prior alcohol septal ablation who was on STL for AF developed complete heart block followed by non-sustained torsades de pointes in the setting of a severe influenza infection and later underwent defibrillator implantation. There were no other cases of pro-arrhythmia or sudden death related to DOF.

Conclusions:
DOF and STL are modestly effective for the treatment of AF and VA in HCM patients, with a low rate of serious adverse events.
Abstract 12046: Patient Characteristics and Use of Oral Anticoagulation Therapy in New-Onset Atrial Fibrillation: Results From a Nationwide Registry Study in Finland
Authors: Luojus Alex , Lehtonen Ossi , Halminen Olli , Haukka Jari , Niemi Mikko , Kuoppala Jaana , Mustonen Pirjo , Putaala Jukka , Linna Miika , Hartikainen Juha , Airaksinen Juhani , Lehto Mika
Published: June 2023

Background and Aims:
The risk of ischemic stroke associated with atrial fibrillation (AF) can be reduced with oral anticoagulation therapy (OAC). We examined the patient characteristics and nationwide use of OACs in primary and secondary care AF patients.

Methods:
The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) -study is a nationwide study of AF patients that combines data from several Finnish health care registers. In this study all new-onset AF patients in Finland from January 2011 to December 2018 with laboratory data were analyzed. Comorbidities and CHA
2
DS
2
-VASc -score were recorded until date of AF diagnosis. First OAC therapies from diagnosis of AF to the end of study were analyzed. For warfarin users with sufficient laboratory data, time in therapeutic range (TTR) was calculated and patient quartiles by TTR were assigned.

Results:
Of the 130 533 (50.7 % male) new-onset AF patients studied, 96 051 (73.6%) used any OAC medication after AF diagnosis. The used OACs were warfarin (n= 56 857; 43.6%), apixaban (n=16 377; 12.5%) rivaroxaban (n=14 821; 11.4%), dabigatran (n=7 224; 5.5%), and edoxaban (n=723; 0.6%). The mean TTR values in warfarin TTR-quartiles were 32% (0-52%) in the 1
st
quartile, 65% (56-72%) in the 2
nd
quartile, 77% (72-83%) in the 3
rd
quartile and 90% (83-100%) in the highest quartile. Among patients with standard dose of direct oral anticoagulants, the mean CHA
2
DS
2
VASc -score was 2.78 for dabigatran and 3.47 for apixaban. For patients with warfarin the mean CHA
2
DS
2-
VASc -score was 3.50 in the highest quartile. The mean CHA
2
DS
2-
VASc for patients without any OAC was 3.19.

Conclusion:
In unadjusted analyses patients with dabigatran had the lowest and patients with apixaban the highest mean CHA
2
DS
2-
VASc score. In patients with warfarin, the highest TTR quartile had the lowest mean CHA
2
DS
2-
VASc -score and mean TTR of 77%. Contrary to the guidelines, a remarkable number of patients with high CHA
2
DS
2-
VASc score remained without any OAC treatment.
Abstract 12057: Absence of Pericarditis Recurrence in Rilonacept-Treated Patients With COVID-19 and mRNA Vaccinations: Experience From Phase 3 Rhapsody Long-Term Extension
Authors: brucato antonio , Trotta Lucia , Arad Michael , Cremer Paul C , Gaddam Eliyazar , Insalaco Antonella , Klutstein Marc W , Lewinter Martin M , Lin David , Luis Sushil A , Wasserstrum Yishay , Plummer Emily , Samant Manoj , Zou Liangxing , Klein Allan L , Imazio Massimo , Paolini John F
Published: June 2023

Introduction:
Rare cardiac complications of COVID-19 and COVID-19 mRNA vaccination include pericarditis and myocarditis. Patients with recurrent pericarditis may be at increased risk of triggered recurrence. The known efficacy of the interleukin (IL)-1 antagonist rilonacept in treating and preventing recurrence could inform COVID-19 disease and vaccination management.

Methods:
The Phase 3 trial RHAPSODY was a global, double-blind, placebo-controlled, randomized-withdrawal study. A long-term extension (LTE) enabled up to 24 months further open-label treatment from May 2020 until June 2022. Concomitant vaccination data and adverse events, including COVID-19, were collected.

Results:
No COVID-19 cases were reported during the run-in and randomized withdrawal periods (n=86). As of the 6 May 2022 data cutoff, a COVID-19 AE was reported in 19% (14/74) of LTE subjects, of whom 12 were on rilonacept: 5 of 44 fully-vaccinated (≥14 days beyond second serial dose) subjects (11.4%) and 9 of 30 unvaccinated or partially-vaccinated subjects (30.0%). Of the fully-vaccinated subjects, 1 case occurred ~11 months post primary vaccination cycle (no booster). COVID-19 severity was mild (n= 11), moderate (n=2), or severe (n=1). All cases resolved except the severe AE complicated by comorbidities; the subject discontinued. Of 12 subjects receiving rilonacept at the time of COVID-19 diagnosis, 10 maintained dosing with rilonacept, 1 interrupted rilonacept for ~4 weeks, and 1 discontinued rilonacept permanently; none experienced a pericarditis recurrence (PR) after the AE. The remaining 2 subjects had previously interrupted rilonacept for off-treatment observation: one had a PR >4.5 months after suspending rilonacept and 18 days after COVID-19 resolution; no PR in the other (>6 months). There were no PR AEs associated with COVID-19 vaccination (all subjects were receiving rilonacept).

Conclusions:
In patients on rilonacept in this study, although numbers are small, vaccination reduced COVID-19 events, pericarditis recurrence was not increased by vaccination or disease, and no pericarditis recurrences occurred during rilonacept treatment. One pericarditis recurrence occurred remotely after rilonacept suspension in the peri-COVID-19 period.
Abstract 12070: Post-Cardiac Arrest Sedation Modulates Electroencephalographic Slow-Wave Activity and Promotes Neurological Recovery in a Mouse Model of Cardiac Arrest
Authors: Ikeda Takamitsu , Amorim Edilberto , Miyazaki Yusuke , Kato Risako , Marutani Eizo , Silverman Michael G , Malhotra Rajeev , Solt Ken , Ichinose Fumito
Published: June 2023

Introduction:
The majority of patients resuscitated from cardiac arrest (CA) present in coma or with an altered level of consciousness. Although CA survivors are routinely sedated during targeted temperature management, the effects of sedation on CA outcomes remain to be determined.

Hypothesis:
Post-CA sedation would modulate cerebral physiology and improve neurological outcomes in mice.

Methods:
Adult C57BL/6J mice of both sexes were subjected to potassium chloride-induced CA and thereafter resuscitated with manual chest compression. Starting at return of spontaneous circulation (ROSC) or at 60 minutes after ROSC, mice received intravenous infusion of propofol at 40 mg · kg
-1
· h
-1
, dexmedetomidine at 1 μg · kg
-1
· h
-1
, or normal saline for 2 hours. Body temperature was lowered and maintained at 33°C during sedation. Cerebral blood flow was measured for 4 hours after ROSC. Telemetric electroencephalogram (EEG) was recorded in freely moving mice from 3 days before up to 7 days after CA.

Results:
Sedation with propofol or dexmedetomidine starting at ROSC attenuated brain injury and improved survival in hypothermia-treated post-CA mice (propofol [13/16] vs. no sedation [4/16],
P
= 0.008; dexmedetomidine [14/16] vs. no sedation [4/16],
P
= 0.002). Mice that were not sedated after ROSC exhibited cerebral hyperemia immediately after resuscitation and EEG power in all frequency bands remained less than 20% of the baseline in the first 4 hours after ROSC. Administration of propofol or dexmedetomidine starting at ROSC attenuated cerebral hyperemia and induced slow-wave (0.5-4 Hz) EEG activity that reached near baseline levels during and early after sedation. Increased EEG activity within 6 hours after ROSC was associated with improvement in neurological outcomes at 24 hours post-CA. In contrast, delayed sedation starting at 60 minutes after ROSC failed to improve outcomes, without attenuating cerebral hyperemia and inducing slow-wave EEG activity.

Conclusions:
Post-CA sedation with propofol or dexmedetomidine improved neurological outcomes and survival in mice resuscitated from CA and treated with hypothermia. The beneficial effects of sedation were accompanied by attenuation of the cerebral hyperemic response and induction of EEG slow-wave activity.