bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13085: Accelerated Aging is Associated With Cardiometabolic, Hematologic and Renal Abnormalities: A Project Baseline Health Substudy
Authors: Uchehara Best , Kwee Lydia , Regan Jessica A , Montgomery Ranee , Eckstrand Julie , Swope Susan , Gold Garry , Schaack Terry , Haddad Francois , Wu Joy , Shore Scarlet , Mega Jessica , Califf Robert , Hernandez Adrian F , Mahaffey Kenneth , Pagidipati Neha J , Shah Svati H
Published: April 2024

Background:
Genetic methylation patterns correlate with age, but some individuals demonstrate accelerated biologic aging as determined by higher methylation/epigenetic age compared with actual chronologic age.

Objective:
To determine characteristics of individuals who have accelerated aging (AA).

Methods:
The Project Baseline Health (PBH) study recruited 2501 participants who underwent multiple assessments (imaging, functional assessments, biospecimens) at enrollment and had annual visits. Methylation profiling (Illumina EPIC) was performed on enrollment blood samples (N=1661); repeat profiling was performed on year 1 blood (N=260). The Horvath method was used to calculate biologic age from methylation data. AA was calculated as the residual of the difference between methylation (i.e. biologic) and chronologic age. Characteristics were compared between low and high AA groups using linear and logistic regression.

Results:
Of 1661 individuals, 195 were low AA (-14.9 to -5.0 yrs difference in biologic vs chronologic age) and 188 were high AA (5.0 - 17.3 yrs). Discriminating characteristics between high and low AA were sex (60% vs 39% male), uric acid, BMI and waist circumference (all p<0.001, all higher in high AA), and hypertension (37% vs. 27%, p<0.05). Other laboratory variables that were significantly higher in the high AA group included: triglycerides, multiple complete blood count indices, creatinine and ALT (all p<0.05). Lab variables lower in high AA included: HDL cholesterol, 25-OH vitamin D, and glomerular filtration rate (all p<0.05). In a subset (N=260) with repeat methylation, individuals with biologic aging greater than chronologic aging had higher baseline glucose and diastolic blood pressure (p<0.05), and a trend for lower vitamin D (p=0.06).

Conclusions:
In this Project Baseline Health study, we used deep phenotyping to identify abnormalities associated with accelerated aging. Individuals with high AA had up to a 15 year higher biologic vs. chronologic age and were more often male with greater cardiometabolic, hematologic and renal abnormalities, and lower vitamin D levels. These results highlight factors that may mediate adverse effects of aging and identify targets for mitigation of these effects in future studies.
Abstract 13094: Pharmacokinetics and Therapeutic Efficacy of Drpitor1a, a Novel Dynamin-Related Protein 1 Inhibitor, in a Preclinical Model of Pulmonary Arterial Hypertension
Authors: Wu Danchen , Jansen-van Vuuren Ross D , Das Gupta Asish , Chen Kuang-Huieh , Al-qazazi Ruaa , Mewburn Jeffrey D , Lima Patricia D , Jones Oliver , Zhao Yuan Yuan , Sutendra Gopinath , Wells Michael , Archer Stephen L
Published: April 2024

Introduction:
Increased dynamin-related protein 1 (Drp1)-mediated mitochondrial fission contributes to the pathogenesis of pulmonary arterial hypertension (PAH). We investigated the pharmacokinetic characteristics of Drpitor1a, a novel, small molecule, ellipticine Drp1 inhibitor (prepared in-house), and tested its therapeutic efficacy in a pilot study using the rat monocrotaline (MCT)-PAH model.

Methods:
A single dose of Drpitor1a (5mg/kg) was administered IV or PO to male and female rats (n=3/sex). Blood was collected at 0, 5 and 30 minutes, and at 1, 2, 4, 6, 8 and 24 hours post drug administration. Plasma, lung and right ventricle (RV) were collected and tissue concentration of Drpitor1a was measured using HPLC coupled with mass spectrometry. The effects of Drpitor1a on mitochondrial fission and cell proliferation were assessed in human PAH pulmonary artery smooth muscle cells (PASMC). In an MCT-PAH model, a catheter was implanted in the left jugular vein on day 14 post-MCT injection. Drpitor1a (1mg/kg) was administered by IV every 48 hours from day 17 to day 27. On day 28, RV function and pulmonary hemodynamics were assessed.

Results:
Drpitor1a’s half-life varies by sex (9.9±5.3 hours and 24.3±21.4 hours in male and female rats respectively). Oral bioavailability of Drpitor1a was similar in males (21.1%) and females (19.7%). Lung concentration of Drpitor1a was similar between males and females (0.441±0.015 nM/mg and 0.444±0.581 nM/mg, respectively). In the RV, Drpitor1a level was higher in females (0.102±0.053

nM/mg) than males (0.055±0.015 nM/mg). Drpitor1a inhibited mitochondrial fission and cell proliferation in human PAH PASMC. In addition, Drpitor1a regressed pulmonary artery medial thickening (25.5% vs 34.9%), inhibited RV hypertrophy (Fulton index: 0.33 vs 0.39) and improved RV function (TAPSE: 2.2mm vs 1.8mm) in female MCT-PAH rats.

Conclusion:
Drpitor1a is a potential therapeutic agent for preclinical PAH and may be more effective in females.
Abstract 13113: Fragility of Functional/Symptomatic Endpoints to Assess the Efficacy of Drugs for Pulmonary Arterial Hypertension
Authors: Barca Luca , De Marzo Vincenzo , Toma Matteo , Guglielmi Giulia , Crimi Gabriele , Porto Italo , Ameri Pietro
Published: April 2024

Introduction:
Pulmonary arterial hypertension (PAH) drugs have historically been evaluated for the effects on functional capacity and symptoms. However, these assessments are approximate and the ensuing therapeutic choices may be aleatory.

Methods:
We reviewed the articles describing phase 3 PAH randomized controlled trials (RCTs) and calculated the fragility index (FI) for the outcomes exploring functional capacity and symptoms. For RCTs with a significantly different outcome rate between the investigational drug (ID) and placebo/comparator arms, the FI corresponded to the number of events that needed to be added to the arm with the smallest number of events to made the RCT result non-significant. For RCTs with non-significant results (neutral), the FI was the number of events that needed to be removed from the ID group to reach a p value <0.05. In general, the lower the FI, the fragile the RCT with respect to the endpoint examined. When possible, we also computed the FI for PAH hospitalization.

Results:
Data about the rate of functional/symptomatic improvement were available for 22 RCTs (Table). The ID was superior to placebo/comparator with p <0.05 in 10 (45%) of these studies. The median FI was 2 (IQR 6.5), with 4 RCTs having a FI = 1 and only 2 a FI >10. For the 12 RCTs in which the effect of the ID was neutral, the median FI was 6 (IQR 4.25). No correlation was found between FI and sample size or year of publication for either significant (R = 0.57, p = 0.08 and R = 0.23, p = 0.52, respectively) or neutral (R = 0.51, p = 0.09 and R = -0.18, p = 0.58) RCTs. The hospitalization FI was determined for 17 (77%) of the 22 RCTs and was overall higher than the one for functional/symptomatic outcomes (median 6, IQR 8) (Table).

Conclusions:
Very few events in one arm could have flipped the results of PAH RCTs from non-significant to significant or, more remarkably, from significant to non-significant. The evidence supporting the reduction of PAH hospitalizations as a treatment goal appears to be more robust.
Abstract 13127: Concordance in Nutrient Biomarker and Cardiometabolic Risk Factors Between Child-Parent Dyads Participating in a Family-Based Childhood Weight Management Intervention
Authors: Matthan Nirupa R , Barger Kathryn , Chia-Fang Tsai , Wylie-Rosett Judith , Groisman-Perelstein Adriana E , Diamantis Pamela M , Xue Xiaonan , Mossavar-Rahmani Yasmin , Ginsberg Mindy , Lichtenstein Alice H
Published: April 2024

Introduction:
Children are at elevated risk for developing obesity/cardiometabolic abnormalities when their parents have these conditions. Little is known about diet quality and subsequent impact on cardiometabolic risk factors (CMRFs) in child-parent dyads.

Objective:
To determine the concordance between nutrient biomarkers and CMRF changes in children (age 7-12 years; BMIz >85%tile) and their parents, who participated in a 1-year randomized controlled trial designed to evaluate the effects of adding an enhanced program to standard care.

Methods:
Pre-post intervention changes in nutrient biomarkers (plasma carotenoids; RBC fatty acid profiles) and CMRFs (BMI, blood pressure, and plasma glucose, insulin, lipid profile, inflammatory markers and adipokine concentrations) were evaluated in 226 child-parent dyads. Based on percent change in children’s BMIz score, they were grouped into high (
>
-8%), medium (0 to -8%) and low (
>
0%) responders. Spearman’s correlation coefficients were calculated to determine association between 1-year change in nutrient biomarkers and CMRFs within child-parent dyad groups.

Results:
There were positive associations in beta-carotene, and RBC SFA, MUFA, PUFA n-6, PUFA n-3 and trans fatty acid concentrations in child-parent dyads, regardless of group ( r= 0.25 to 0.83, p<0.05). Significant positive child-parent associations were observed for systemic (TNFa, IL-1, IL-6) and vascular (E- and P-selectin, thrombomodulin) inflammatory markers (r= 0.32 to 0.83, p<0.05), and adiponectin (r=0.47, p=0.001), but not other CMRFs. In the high responder group, there was a positive association between improvements in child’s BMIz scores and parental BMI (r=0.32, p=0.01). This dyad also had the most favorable improvements in nutrient biomarkers (increases in carotenoids, and decreases in SFA and trans fatty acids) and CMRFs (decreases in blood pressure, and LDL-C, TG and hsCRP concentrations).

Conclusions:
Our finding of concordance in child-parent dyad changes in nutrient biomarkers and selected CMRFs after a 1-year intervention, especially in the high responder group, suggests parallel dietary changes and highlights the importance of parental engagement in the effectiveness of childhood obesity interventions.
Abstract 13129: FXR1 Regulates Blood Pressure by Altering Vascular Contractility
Authors: St Paul Amanda , Preston Kyle , Corbett Cali , Leigh Tani , Kelemen Sheri E , Okune Rachael , Autieri Michael
Published: April 2024

Introduction:
Hypertension is a major risk factor for heart disease and stroke. Despite current medication, half a million deaths in the United States include hypertension as a primary contributing cause, presenting a need for additional targets. Vascular smooth muscle cells (VSMCs) play a central role in vascular contractility and the regulation of blood pressure (BP). Fragile X-related protein (FXR1) is a muscle-enhanced RNA binding protein. Knock down of FXR1 increases inflammatory mRNA stability, and overexpression of FXR1 decreases inflammatory mRNA stability in VSMC. FXR1 knock out mice have a muscle-specific phenotype. While little is known concerning FXR1 protein binding partners and its role in vascular disease, its muscle-enhanced expression suggests a specialized role in VSMC. The specific aim of this study is to test the hypothesis that FXR1 regulates vascular contractility by regulation of RNA stability and protein-protein interactions.

Results:
To characterize an
in vivo
role of FXR1 in vascular disease, we generated a novel, VSMC-specific FXR1 conditional knock out mouse (FXR1
VSMC/VSMC
). Preliminary data indicates that these mice are hypotensive as they show decreased systolic (P < 0.001) and diastolic (P < 0.01) BP, and increased resting heart rate (P < 0.05) at baseline compared to controls. To identify mRNA binding targets, gene ontology of RNA immuno-precipitation sequencing analysis (RIPseq) in human VSMCs identified that FXR1 preferentially binds to mRNA that participate in VSMC contractility and regulation of BP. Although considered an RNA stability protein, mass-spectrometry identified that FXR1 interacts with proteins related to VSMC contractile processes such as cell migration, adhesion and stress fiber formation. At a functional level, siRNA knock down of FXR1 decreased VSMC migration and collagen gel contraction corroborating
in vivo
observations.

Conclusion:
These data show that deletion of FXR1 decrease BP and VSMC contractile processes. They are the first to suggest FXR1 regulates BP and vascular contractility potentially by two mechanisms: mRNA stability and functional activity by protein-protein interactions. The findings support FXR1 activity may represent a target for therapeutic invention to regulate BP.
Abstract 13135: Transfusion Requirements and Outcomes of Adult Patients With Congenital Heart Disease Undergoing Cardiovascular Surgery
Authors: Dutta Puja , Emani Sirisha , Nathan Meena , Emani Sitaram , Ibla Juan
Published: April 2024

The number of adults with congenital heart disease (CHD) requiring cardiovascular (CV) surgery is increasing rapidly in the current era. We hypothesized that exposure to perioperative blood products is associated with poorer outcomes in adults. All adults (≥18 years old) undergoing CV surgery between 2015 and 2020 were reviewed retrospectively. Associations between transfusion (no products vs. any products) and outcomes were studied by univariate logistic regression and Wilcoxon rank sum tests. Multivariate cox/logistic regression was used to assess (a) postoperative ventilation time and length of stay, and (b) major complications, respectively. Of 323 patients, 147 (45%) received blood products during and/or after surgery. The median age was 27 (interquartile range [IQR]: 22-36) years, there were 181 (46%) males, and 16 (5%) patients had single ventricle anatomy. In the entire cohort, 110 (34%) were on preoperative anticoagulants: 39 (22%) received no products and 71 (48%) received products (OR: 3.28, 95% CI: [2.03,5.31], p<0.0001), and 47 (15%) had prior sternotomies: 16 (9%) received no products and 31 (21%) received products (OR: 2.76, 95% CI: [1.44, 5.28], p=0.0022). Patients who received blood products had more complications overall (OR: 4.25, 95% CI: [2.10, 8.61], p<0.0001) specifically, postoperative bleeding (OR: 7.54, 95% CI: [2.16, 26.28], p=0.0015) and cardiac arrest (OR: 8.75, 95% CI: [1.06, 71.94], p=0.04). Transfusion was associated with greater frequency of thrombosis (OR: 6.55, 95% CI: [1.86, 23.11], p=0.0035), longer ventilation time (HR: 3.05, 95% CI: [2.38, 3.91], p<0.0001), and longer length of stay (HR: 2.65, 95% CI: [2.05, 3.42], p<0.0001). In conclusion, adults who received perioperative blood products experienced more complications and worse in-hospital outcomes. Future research on optimizing blood product transfusion based on risk prediction models is needed to improve outcomes in adults with CHD undergoing CV surgery.
Abstract 13155: Validation of a Decision Aid for Familial Hypercholesterolemia
Authors: Bangash Hana , Miller Alexandra , Hargraves Ian , Hartasanchez Sandra , Gundelach Justin , Montori Victor M , Kullo Iftikhar J
Published: April 2024

Introduction:
We validated the “Familial Hypercholesterolemia (FH) Decision Aid” to promote shared decision making (SDM) about lipid lowering therapy, based on patient-clinician encounters.

Methods:
Validation of the DA included an assessment of whether the content and design of the tool facilitated SDM and patient engagement and to determine how well the tool integrated with clinical workflow. Validation was conducted during patient-clinician encounters in the Mayo preventive cardiology clinic. As inclusion criteria we considered an upcoming appointment in the clinic, an LDL-C level ≥ ~160 mg/dL, and no prior diagnosis of FH. Prior to the encounters, each clinician viewed a demonstration of the online, interactive DA. During the encounters, the DA was shared with patients using the clinic room computer screen, either in-person or virtually. Patient-clinician encounters were video recorded for further analysis by two design researchers and experts in SDM.

Results:
Ten patients were enrolled in the study (7 male; average age 51 years). The average patient LDL-C level was 207 mg/dL, range 157 - 248 mg/dL. Review and qualitative analysis of the encounter recordings yielded 4 key findings: i) clinicians primarily used the cardiovascular risk estimate in the DA to guide conversation with patients; ii) highly trained specialists needed to change their usual approach to care and conversation to integrate the DA with their clinical workflows; iii) as clinicians became more familiar with the DA, they moved through the tool at a more efficient pace; and iv) each clinician developed his/her own style of navigating the DA, either moving through it one screen at a time or focusing on one specific section for the duration of the conversation. The DA effectively guided conversation and facilitated active patient engagement in 6 of 10 encounters. Social distancing and use of telemedicine encounters, due to the COVID-19 pandemic, limited patient engagement in 2 of 10 encounters. Overall, the DA promoted SDM regarding FH management in 9 of 10 encounters.

Conclusion:
Using patient-clinician encounters, we found the FH DA to facilitate SDM regarding lipid-lowering therapy. The tool has potential to improve care of FH patients and increase patient engagement and knowledge.
Abstract 13185: Emergency Department Total and Out-of-Pocket Costs for Adults With Congenital Heart Disease in the United States
Authors: Hong Jessica M , Sabanayagam Aarthi , Harris Ian S , Kouretas Peter , Mahadevan Vaikom S , Sano Shunji
Published: April 2024

Introduction:
Despite a growing emergency department (ED) burden in the aging adult congenital heart disease (ACHD) population, data regarding the cost of ED visits remains unknown. This information could help inform appropriate resource allocation to reduce costs and improve outcomes for ACHD patients.

Methods:
We used a national commercial insurance database (IBM MarketScan) to characterize total and out-of-pocket (OOP) ED costs for ACHD patients with one or more ED visits in the year 2016. Multivariate linear regression analysis after adjusting for age <40 years, gender, primary beneficiary status, employment, ACHD severity, cardiovascular (CV) and non-CV comorbidities was performed to determine variables associated with ED costs.

Results:
Of 3,579 ACHD patients with at least one ED visit, 53.4% were female, mean age was 35.5±14.4 years, and 33.2% had severe ACHD. Total (median; 25th, 75th) and OOP costs per visit were $2,004.79; $992.71, $4,034.63 and $232.32; $70, $695.30, respectively. Conditions with the highest per-visit total and OOP costs were neoplasm (total $6,186.89; $4,334, $13,005.19, OOP $329.20; $120, $1799.70), endocrine (total $3,467.51; $1,620.73, $9,878.38, OOP $428.99; $154.50, $1350.25), genitourinary (total $3,433.59; $1,739.97, $7,361.57, OOP $330.16; $120, $868.04), unclassified (total $3,370.04; $1,610, $7,793.22, OOP $347.50; $114.83, $1226.74), and symptoms, signs, and ill-defined (total $3,171.34; $1,740.55, $6,404.77, OOP $340.29; $100, $862.33). Factors independently associated with ED costs included comorbidities, primary beneficiary status, and employment (Figure).

Conclusions:
Non-CV comorbidities and noncardiac conditions during ED visits contribute substantially to ED costs among ACHD patients. Future studies to identify a collaborative, multidisciplinary care model to manage these noncardiac problems among ACHD patients might help reduce the overall burden of ACHD-related ED costs.
Abstract 13188: Invasive versus Conservative Strategy for Stable Coronary Artery Disease in Patients With Low Ejection Fraction
Authors: Dai Qiying , Bose Abhishek , Sharma Nitish , shah neeta , Ramsaran Eddison
Published: April 2024

Introduction:
Patient with stable coronary artery disease (CAD) are asymptomatic or symptom-controlled despite the presence of an underlying supply-demand mismatch. Studies have revealed no significant differences in all-cause mortality between medical therapy and invasive strategy. However, a recent study with subgroup analysis showed high risk patients with an ejection fraction (EF) of 35%-45% faring better with an invasive approach. Since the initial treatment strategy for stable CAD patients with reduced EF remains unclear, we performed a retrospective analysis.

Methods:
A total of 302 patients were enrolled between 2014-2019 and followed for a period of at least 16 months. All patients were classified as intermediate risk or high risk based on their nuclear stress test with an EF less than 40%. Patients were divided based on whether they underwent an initial invasive strategy versus medical management. A multivariable Cox regression analysis was performed to compare the primary outcome of all-cause mortality between the two groups.

Results:
Patients undergoing an initial invasive strategy were younger (68.3 ± 11.4 vs 71.1 ± 12.1 years, P = 0.04) compared to the medical therapy group. During follow up, 26 (18.3%) versus 48 (30.0%) patients died in the invasive versus medical therapy group, respectively. After adjusting for baseline demographics and comorbidities, we found no significant difference in mortality between the two groups (P=0.24) (
Figure
). Older age (HR = 1.08, P <0.001) and the presence of chronic lung disease (HR = 1.87, P = 0.014) were factors associated with higher mortality among stable CAD patients with low EF.

Conclusions:
In patients with stable CAD and low EF, an initial invasive approach has no significant mortality benefit when compared to medical therapy. An older age and a history of chronic lung disease predicted higher mortality in this patient population.
Abstract 13685: Combined Genetic Defects of Sitosterolemia and Familial Hypercholesterolemia
Authors: Takase Satoru , Ishiura Hiroyuki , Tanaka Masaki , Okazaki Sachiko , Takanashi Mikio , Li Chengcheng , Shi Jingxuan , Iizuka Yoko , Mitsui Jun , Tsuji Shoji , Kadowaki Takashi , Yamauchi Toshimasa , Okazaki Hiroaki
Published: April 2024

Background:
Familial hypercholesterolemia (FH) is an inherited disorder caused by mutations in the genes in the LDL receptor pathway, including
LDLR
,
PCSK9
,
APOB, and ARH
. Defective uptake of LDL by the liver increases plasma LDL-cholesterol (LDL-C) levels, leading to an increased risk of coronary heart disease. The differential diagnosis of FH includes sitosterolemia which is a rare autosomal recessive disorder caused by mutations in
ABCG5
or
ABCG8
.

Case presentation:
Here we present a rare case of sitosterolemia with a genetic diagnosis of FH. A 64-years-old woman, clinically diagnosed as FH with Achilles tendon thickness (>18 mm on X-ray imaging), had been taking statins only intermittently due to muscle pains. The combinatorial therapy with ezetimibe decreased her plasma LDL-C levels to around 90-250 mg/dL with variable adherence to statins and dietary management. Further addition of a PCSK9 inhibitor (evolocumab) was largely ineffective with plasma LDL-C levels of 90-190 mg/dL. A systemic medical evaluation revealed persistent joint pains of unknown etiology and slightly decreased platelet count. These clinical features led us to suspect sitosterolemia.

Biochemical and genetic analyses:
Plasma concentration of sitosterol was elevated (16.8 mg/dL). Genetic testing was performed after obtaining informed consent. All procedures were subjected to approval by the human genome, gene analysis research ethics committee of the University of Tokyo. In addition to a heterozygous missense mutation in
LDLR
(p.Arg115His), a homozygous nonsense mutation in
ABCG5
(p.Tyr188Ter) was identified. No rare variants were found in
PCSK9
nor
ABCG8
.

Conclusions:
To our knowledge, this is the first case of a combined genetic defect of sitosterolemia and FH. Atypical clinical manifestations such as large fluctuations of LDL-C levels, unresponsiveness to a PCSK9 inhibitor, arthralgia, and a reduced platelet count led to the genetic diagnosis. Our case is informative in the perspective of precision medicine, highlighting the importance of systemic medical evaluation to select patients who will be benefited more from genetic testing as well as the necessity of future drug development for this rare and intractable disease.
Abstract 13691: High Burden of Sensing Changes in Periprocedural TAVR Patients With Pre-Existing CIEDs Presents A Unique Challenge
Authors: Madanat Luai , Shah Kuldeep , Haines David , Mehta Nishaki
Published: April 2024

Introduction:
The data on the management of patients undergoing transcatheter aortic valve replacement (TAVR) with pre-existing cardiac implantable electronic devices (CIED) is scarce.

Objective:
We describe the R wave sensing changes following TAVR in a patient with CIED and describe CIED behavior peri procedurally in a high volume center over 8 years.

Results:
A 64 year old male patient with a history of non-ischemic cardiomyopathy and a secondary prevention dual-chamber ICD presented for generator change. Six months prior, he underwent TAVR (29mm ES S3). Post TAVR, he developed a new RBBB. Device interrogation revealed a significant drop in sensed R waves from 9mV to 1.5mV which temporally correlated with TAVR (Figure 1). Pacing thresholds and impedance were stable. Chest x-rays showed stable lead position. Given drop in R wave sensing, successful defibrillation threshold testing was performed with generator change. Of the 115 patients with pre-existing CIEDs undergoing TAVR between 2012-2020, 23.5% (27 patients) showed changes in sensing (mean 3.0±2.5mV) peri procedurally with minimal change in impedance or threshold with no correlation with QRS changes.

Conclusions:
To our knowledge, this is the 1st reported case of a change in sensed R waves due to conduction disturbance following TAVR. We hypothesize this occurred due to a change in the activation wavefront sensed by the right ventricular lead following the development of new RBBB. Up to a quarter of patients have sensing fluctuations in our experience. Consideration of pre and post device interrogation with TAVR could be of value.
Abstract 13704: Early Trends in Cardiac Allograft Vasculopathy After Implementation of the New 2018 Donor Heart Allocation Protocol in the United States
Authors: Tehrani David M , Kim Soohyang S , Hsu Jeffrey J , Nsair Ali , Fearon William F , Parikh Rushi
Published: April 2024

Introduction:
The new donor heart allocation policy implemented in October 2018 prioritizes hemodynamically unstable patients with the greatest need for urgent transplantion. The impact of this policy change on the incidence of cardiac allograft vasculopathy (CAV) has not been described.

Methods:
We performed a retrospective analysis of adult (≥ 18 years) heart transplant recipients registered in the UNOS database between 10/18/2015 - 11/25/2019 to evaluate the effect of the new allocation system on angiographic CAV at 1 year. Recipients undergoing first-time single organ heart transplant with 1 year follow-up were stratified based on the old (10/18/2015 - 10/17/2018) or new (10/18/2018 - 11/25/2019) allocation system. Recipient and donor demographic and cardiovascular risk factors, wait-list factors, and transplant factors with a p-value < 0.10 in univariable analysis were included in multivariable logistic regression models to identify independent predictors of accelerated CAV.

Results:
Of 8,724 transplant recipients (mean age 54 ± 13 years, 73% male), 6,661 (76%) and 2,063 (24%) were listed in the old and new allocation systems, respectively. The old cohort consisted of 4,409 (66%) classified as Status 1A, while the new cohort consisted of 168 (8%) classified as Status 1 and 944 (46%) as Status 2. The incidence of accelerated CAV was 520 (7.8%) in the old allocation cohort compared with 130 (6.3%) in the new allocation cohort (p=0.02). In adjusted analyses, the new allocation system was significantly associated with a reduction in CAV (OR=0.72, 95% CI: 0.59-0.89, p=0.002; Table). This association persisted even after restricting the cohort to the highest acuity patients—Status 1A (old) and Status 1 or 2 (new) (OR=0.75, 95% CI: 0.57-0.99, p=0.04).

Conclusions:
The new donor heart allocation system is significantly associated with lower rates of accelerated angiographic CAV at 1 year, including among recipients requiring the most urgent transplants.
Abstract 13721: Impact of COVID-19 Pandemic on Door-to-Balloon Time and Mortality Within a High Reliability STEMI System of Care
Authors: Zheng Weili , Reed Grant W , Huded Chetan , Kumar Anirudh , Kravitz Kathleen A , Krishnaswamy Amar , Lincoff A M , Meldon Stephen , Kralovic Damon M , Kapadia Samir R , Khot Umesh N
Published: April 2024

Background:
The COVID-19 pandemic is associated with delayed revascularization and worse clinical outcomes for patients with ST-Elevation MI (STEMI). The purpose of this study was to evaluate whether a comprehensive STEMI protocol (CSP), which improved door-to-balloon times (D2BT) and mortality prior to the pandemic, mitigated the pandemic’s negative effect on STEMI care and outcomes.

Methods:
We performed a prospective, single-center, registry-based study of 433 patients who received PCI for STEMI though an established CSP. We compared D2BT and in-hospital mortality of the period immediately prior to the pandemic (control period; 1/1/19 -3/14/20, N=291) with the period from 3/15/20 to 12/31/20 (study period, N=142), in-line with the declaration of a state of emergency by the state of Ohio.

Results:
Between control and study period, patients were similar in regards to age (61.2 +/- 12.0 yrs vs. 61.7 +/-13.2 yrs), female sex (32.3% vs 30.3%), nonwhite race (30% vs 26%), smoking status, BMI (30.4 +/- 8.9 vs 29.9 +/- 6.3), and other comorbidities. There was no significant difference in % meeting D2BT goals for STEMI (<=90 minutes for ED and in-hospital, <=120 minutes for hospital transfer patients) during control and study periods (79.0% v 78.9%, p = 0.97). When stratified by STEMI presenting location, there was no significant difference between control and study period D2BT for patients presenting in primary ED (48 min [IQR 36-66] vs 60 min [IQR 42-73], p = 0.09), as hospital transfers (96 min [IQR 79-119] vs 95 min [IQR 80-112], p = 0.86), or from in-hospital locations (95 min [IQR 80-112] vs 95.8 min [IQR 52-120], p = 0.50). There was no significant difference in in-hospital mortality between the control and study periods (4.5% and 2.1%, p = 0.22).

Conclusions:
Despite the profound effect of pandemic on overall health care operations, there was little overall change in STEMI process and outcome metrics within a high reliability CSP.
Abstract 13723: Gender, Racial, and Socioeconomic Disparities in Patients With Heart Failure and Psychiatric Disorders
Authors: Ramadan Salma , Sammour Yasser , kennedy kevin , Sperry Brett
Published: April 2024

Background:
Psychiatric diseases are common in patients with heart failure (HF) resulting in higher morbidity and mortality. Disparities in healthcare are well-described in cardiovascular medicine. Minorities often suffer from more frequent mental illnesses. Whether disparities related to gender, racial and socioeconomic status affect outcomes in patients with HF and mental illnesses remains unknown.

Methods:
We queried ICD-10 codes in the national inpatient sample (2016-2018) for patients with HF and psychiatric disorders including psychotic (F20-29), mood (F30-39), and/or anxiety (F40-43) disorders. Multivariable analysis, adjusting for age and 29 HCUP comorbidities, assessed outcomes of in-hospital mortality, length of stay, and hospital charges based upon gender, race, and household income.

Results:
Among 685,912 admissions for patients with HF and psychiatric disorders, 63.5% had mood disorders, 55.2% anxiety disorders, and 6.8% psychotic disorders. Mean age was 68.7±14.2 years, 59.8% were females, 75.8% Caucasians, 14.2% African Americans, and 6.6% Hispanics. In multivariable analysis, females, African Americans, Hispanics, and lower median household income were associated with lower in-hospital mortality (Table, p<0.001 for all). There were minimal absolute differences in length of stay and hospital cost (Table).

Conclusion:
In patients with both HF and psychiatric illness, disparities related to gender, race, and income exist and may modify outcomes. Further data are necessary to determine the impact of these disparities on care delivery among this patient population.
Abstract 13755: A Systematic Review and Meta-Analysis of Interventions to Support Caregivers of Patients With Heart Disease
Authors: Knowles Kellen , Xun Helen , Jang Sun Y , Pang Sharon , Ng Charles , Sharma Apurva , Spaulding Erin , Singh Rohanit , Diab Alaa , Osuji Ngozi , Materi Joshua , Amundsen Danielle , Wongvibulsin Shannon , Weng Daniel , Huynh Pauline , Nanavati Julie , Wolff Jennifer , Marvel Francoise A , Martin Seth S
Published: April 2024

Background:
Family caregivers play an important role in the support of patients with heart disease, yet little is known about how the clinical team can best support them. We recently published the CARE model (Caregiver-centered, Active engagement, Reflection & reinforcement, Education) as a guide for the clinical team to better engage caregivers. In this current study, we aimed to determine if psychoeducational interventions designed to support caregivers of patients with heart disease led to improvements in caregiver anxiety, depression, burden, and quality of life.

Methods and Results:
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) written in English that evaluated outcomes of interventions to support caregivers of patients with heart disease. In our review of six databases, we identified 20 unique RCTs, representing a total of 1,570 patients and 1,776 caregivers, with 17/20 RCTs using a psychoeducational approach. The meta-analysis suggested small increases in physical QoL (Hedges’ g = 0.178, 95% CI: -0.09 to 0.45) and mental QoL (Hedges’ g = 0.22, 95% CI: -0.04 to 0.48) and small reductions in anxiety (Hedges’ g = -0.48, 95% CI: -1.08 to 0.12), as well as moderate reductions in caregiver depression (Hedges’ g = -0.64, 95% CI: -1.34 to 0.06) and caregiver burden (Hedges’ g = -0.51, 95% CI: -2.71 to 1.70); however, none of these improvements were statistically significant. Study results were limited by use of various outcome measures, variable intervention designs, and may have been insufficiently powered.

Conclusion:
Our study highlights the need for greater understanding of the challenges faced by caregivers of heart disease patients. Future work should focus on consistent intervention design, use established outcome measures, and be conducted in larger populations.
Abstract 13758: Right Ventricular Dysfunction Contributes to Left Ventricular Thrombus Formation After Myocardial Infarction
Authors: Nordbeck Peter , Chen Mengjia , Liu Dan , hu kai , Lengenfelder Björn , Ertl Georg , Frantz Stefan
Published: April 2024

Introduction:
Thromboembolic events such as stroke due to left ventricular thrombus (LVT) formation accompany acute myocardial infarction (MI). Risk factors for the development of LVT after MI have been identified based on limited data, including MI location, severe ventricular wall motion abnormalities or aneurysm, and reduced left ventricular ejection fraction (LVEF).

Hypothesis:
The purpose of this study was to define additional determinants of LVT formation following acute anterior MI through comparing clinical and echocardiographic characteristics between patients with and without LVT formation during the first 3 months after MI.

Methods:
This case-control-study comprised acute anterior MI patients with and without LVT, who were selected from a cohort of 1327 consecutive patients with ischemic heart failure in our hospital. The cases and controls were matched for age, sex, and LVEF. LVT was detected by routine/contrast echocardiography or cardiac magnetic resonance imaging during the first 3 months following MI.

Results:
Formation of apical aneurysm after MI was independently associated with LVT formation (72.0% vs. 43.5%, odds ratio [OR]=5.06, P=0.005). Echocardiographic risk factors associated with LVT formation included reduced mitral annular plane systolic excursion (MAPSE<7mm, OR=4.69), moderate-severe diastolic dysfunction (OR=2.71), and right ventricular (RV) dysfunction [reduced tricuspid annular plane systolic excursion (TAPSE)<17mm (OR=5.48), reduced RV factional area change (RV_FAC)<0.35 (OR=3.32), and enlarged RV diameters (OR=1.62)]. Subgroup analysis showed reduced TAPSE (OR=5.12, P=0.010) associated with increased risk of LVT formation in anterior MI patients without apical aneurysm, independent of clinical and other echocardiographic covariates.

Conclusions:
RV dysfunction as determined by reduced TAPSE and RV_FAC is independently associated with LVT formation in acute anterior MI patients, especially in the setting of MI patients without the formation of an apical aneurysm. This suggests that besides assessment of left ventricular abnormalities, assessment of concomitant RV dysfunction is of importance in risk stratification of LVT formation in patients with acute anterior MI.
Abstract 13787: Use of a Novel Cardiac Implantable Electronic Device Digital Care Pathway (TriageHF-Plus) is Associated With a Reduction in All-Cause Unplanned Hospitalizations
Authors: Ahmed Fozia Z , Sammut-Powell Camilla , Callan Paul , Cunnington Colin , Kahn Matthew , Kale Mita , Gerritse Bart E , Khalidi Hakam , Lanctin David , Leonard Catherine , Laager Verla L , Soken Nelson , Martin Glen P , Campbell Niall G , Taylor Joanne K
Published: April 2024

Introduction:
Heart failure hospitalization (HFH) is common, but it is also potentially preventable. The TriageHF risk score is an implantable cardiac device feature that uses data from up to 9 physiological parameters to classify patients as low, medium, or high risk of HFH in the next 30-days.

Aim:
To evaluate a remote management heart failure (HF) care pathway (“TriageHF-Plus”) that combines the TriageHF risk score with a structured telephone-based remote clinical patient assessment, by comparing rates of non-elective hospitalizations experienced by patients receiving TriageHF-Plus in a real-world clinical setting to those observed in patients receiving Standard of Care (SoC).

Methods:
Between Sept 2019 - Sept 2020, 415 patients with TriageHF compatible ICD or CRT devices were prospectively recruited from 3 UK hospitals. Once enrolled, all high risk TriageHF episodes were managed via the TriageHF-Plus pathway; these patients received a structured telephone assessment to assess for both HF and non-HF-related acute issues. Rates of non-elective hospitalizations observed following enrollment in the TriageHF-Plus cohort were compared with those observed in an unselected control cohort of HF patients with CIEDs receiving SoC (n=435) between Jan 2017 - Dec 2018.

Results:
Patient demographics and hospitalization data are presented in the Table. Nearly all patients in the TriageHF-Plus cohort had HF (91.9%) and the majority (77.8%) had a CRT device. In TriageHF-Plus, there were 135 unplanned all-cause hospitalizations, compared with 358 in SoC; and rates per patient year for all-cause (0.41 vs 0.57, p=0.001), cardiovascular (0.14 vs 0.29, p=0.037) and heart failure (0.02 vs 0.07, p=0.003) hospitalizations were all significantly lower in the TriageHF-Plus cohort.

Conclusions:
In a population of predominantly HF patients with CIEDs, the TriageHF-Plus pathway reduced rates of unplanned hospitalizations compared with SoC, with the greatest reduction observed in HFH.
Abstract 13791: Trends in the Use of Oral Anticoagulation for Nonvalvular Atrial Fibrillation in a Large Integrated Health Care System 2011-2020
Authors: Chronowski Joseph , Grassi Stacey , Roman Patrick , Voyce Stephen J
Published: April 2024

Introduction:
Direct Oral anticoagulants (DOACs) have demonstrated superiority or noninferiority to vitamin K antagonists (VKAs) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). The uptake of DOACs into clinical medicine has been variable and may be influenced by many factors.

Objective:
To determine how the prescription (Rx) pattern for DOACs has evolved since their introduction and to evaluate the temporal effects of factors which may impact DOAC Rx.

Methods:
We performed a retrospective review of patients with NVAF within the Geisinger Health System from 2011-2020. We evaluated longitudinal yearly trends in anticoagulant use and new/initial Rx of DOAC vs VKA in NVAF. We examined subgroups based on clinical and demographic indices. Key points in the timeline regarding DOAC availability and medical society or institutional guidelines were incorporated to determine whether changes DOAC Rx were temporally associated with these events.

Results:
We identified 34, 936 patients with NVAF. The average age of the was 74.3 years, 48% were female and 98% white. The average CHA
2
DS
2
Vasc score was 2.5. There was a linear increase in overall and new Rx for DOACs with 77.7% of all new Rx for DOAC in 2020. The greatest increase in new DOAC Rx coincide with timepoints of DOAC incorporation into ACC/AHA Guidelines, approval of Xa reversal agent and institutional formulary change. Apixaban was the most common DOAC Rx since 2015 and now accounts for 70.9% of all new anticoagulation Rx and 91.3% of new DOAC Rx at our institution.

Conclusions:
There was a linear increase in DOACs use for NVAF over time and apixaban has become the most prescribed DOAC at our institution. Society guidelines, approval of reversal agents and institutional formulary changes appear to be temporally associated with increased Rx of DOACs for NVAF.
Abstract 13804: True Anemia in Heart Failure Patients: Peripheral Hematocrits Lack Sensitivity and Specificity as a Predictor of Measured Red Blood Cell Volumes in a Mixed-LVEF Cohort
Authors: Silver Marc A , Strobeck John E , Feldschuh Jonathan A
Published: April 2024

Introduction:
Anemia is a common and serious co-morbidity of heart failure (HF) that is undertreated, impacting outcomes for HF patients and the overall economics of HF. Studies have shown that anemia is associated with worse outcomes in HF, but to date interventional studies aimed at treating anemia in HF have failed to demonstrate conclusive outcome improvements. A common feature of past studies is that they generally defined anemia via a threshold of peripheral Hct (or via Hemoglobin, which has a direct linear relationship to Hct).

Methods:
In a recently published study of a mixed-LVEF cohort of 245 HF patients, red cell volume status relative to patient norms was quantified using direct blood volume analysis (BVA, Daxor, Oak Ridge, TN). We evaluated the suitability of a Hct for detecting true anemia (as measured by BVA) in this group. Although Hct was somewhat correlated (R
2
=0.43) with red cell volume (RCV) deviation from ideal (as measured directly by BVA), actual RCV status was heterogeneous. We performed an analysis of the specificity and sensitivity of Hct as an indicator of true anemia, defined as RCV < 90% of normal value.

Results:
The distribution of true anemia is shown in Figure 1. Visual inspection shows mixed anemia status across a broad range of Hct values. We examined three Hct thresholds for determining true anemia. Two thresholds were defined based on deviations from normal Hct (M=45, F=40); a third threshold was chosen at 24 for both genders, corresponding to a common transfusion trigger. Using a moderate 10% deviation threshold yielded a sensitivity of 96%, but a specificity of only 50%, due to a False Positive (dilutional anemia) rate of 19%. Using a more extreme 25% deviation threshold yielded a specificity of 90%, but a sensitivity of only 62%, due to a False Negative (FN) rate of 23%. The transfusion trigger had a FN rate of 61%.

Conclusions:
Hct lacks sensitivity and specificity for detecting true anemia. Interventions for anemia in HF would benefit from BVA.
Abstract 13898: Redo Catheter Ablation for Atrial Fibrillation: Assessment of Quality of Life and Clinical Outcomes Using Patient Reported Outcomes
Authors: Farwati Medhat , Wazni Oussama , Tarakji Khaldoun , Diab Mohamed , Scandinaro Anna , Amin Mustapha , Zmaili Mohammad , Nakagawa Hiroshi , Kuroda Shunsuke , Kanj Mohamed H , Dresing Thomas J , Callahan Thomas D , Bhargava Mandeep , Baranowski Bryan , Rickard John , Cantillon Daniel J , Tchou Patrick , Saliba Walid I , Hussein Ayman
Published: April 2024

Background:
Catheter ablation for symptomatic atrial fibrillation (AF) is frequently used for sustained rhythm control and improved quality of life (QoL). Although success rates are high, a significant proportion of patients require redo ablation. Data is scarce on patient-centered outcomes in patients undergoing redo AF ablation.

Objective:
To investigate QoL and clinical outcomes using a large prospectively maintained automated patient reported outcomes (PRO) database.

Methods:
All patients undergoing redo AF ablation (2013-2016) at our center were enrolled and assessed for QoL effect using automated PRO surveys (baseline, 3 and 6 months after ablation, every 6 months thereafter). This analysis included data over 3 years of follow-up. The atrial fibrillation severity scale (AFSS) was used as the main measure for QoL assessment. Additional variables collected included patient-reported clinical improvement, AF burden, as well as AF related healthcare utilization including ER visits and hospitalizations.

Results:
A total of 848 patients were included (28% females, mean age 63.8, 51% persistent AF). By automated PRO, significant improvement in QoL was noted (baseline median AFSSS of 12 [5-18] and ranged between 2 and 4 on subsequent assessments; P<0.0001), with ≥70%of patients reported marked improvement in their overall AF-related symptoms. The proportion of patients in AF at the time of completion of the baseline survey was 36%, and this decreased to <8% across all time points during follow-up (P<0.0001). Further, AF burden was significantly reduced (including frequency and duration of episodes; P<0.0001), with associated decrease in healthcare utilization after 6 months from the time of ablation (including ER visits and hospitalizations; P<0.0001). The proportion of patients on anticoagulants, antiarrhythmics, or rate control medications decreased on follow-up across all time points (P<0.0001 for all variables).

Conclusions:
Most patients derive significant QoL benefit from redo AF ablation. A fully automated PRO system enhanced collection of AF-specific outcomes and showed improvement in QoL, AF burden, and healthcare utilization after redo ablation procedures.