bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12039: Health Literacy Mediates the Relationship Between Perceived Control and Cardiac Event-free Survival in Patients With Heart Failure
Authors: Wu Jia-rong , Miller Jennifer L , Moser Debra K
Published: April 2024

Introduction:
Lower levels of perceived control and health literacy are independently associated with morbidity (higher levels of anxiety and depression or rehospitalizations) in individuals with heart failure (HF). However, little is known about the interrelationship of these two predictors. Low health literacy impairs engagement in the health care process and in doing so may play a role between perceived control and outcomes.

Objective:
The purpose of this study was to examine the relationships among perceived control, health literacy and cardiac event-free survival in patients with HF.

Methods:
This was a prospective study of 575 rural patients with HF (female 41%, age 66±13, married 57%). Perceived control was assessed using the Control Attitude Scale-Revised. Health literacy was measured by the Short Test of Functional Health Literacy in Adults. Cardiac events were followed for 24 months by patient/family interview and hospital database review. Linear/logistic regression and survival analyses were used to examine the associations among health literacy, perceived control, and cardiac event-free survival.

Results:
Patients with higher perceived control had higher health literacy. Higher perceived control and higher health literacy were associated with better cardiac event-free survival before and after adjusting for covariates (e.g. age, marital status, B-type Natriuretic Peptide) (
p
<.05). Perceived control was not a significant predictor of health outcomes (
p
=.10) after entering health literacy (
p
<.001) in the model demonstrating mediation (Figure).

Conclusions:
Lower perceived control was associated with worse outcomes and health literacy was a mediator between perceived control and health outcomes. Our results suggest that interventions intended to improve health outcomes in adults with HF need to increase their perceived control of HF care and also take into account patients’ level of health literacy.
Abstract 12079: Initial Report From an Emergency-Department-Based Registry of NSTEMI Patients Given Upstream Advanced Oral Antiplatelet Therapy
Authors: Pollack Charles V , Bhandary Durgesh D , Frost Alex , Peacock W. Frank , Diercks Deborah B , Silber Steven H , Rao Sunil V , Bangalore Sripal , Reicher Barry , Burke Lea M , DeRita Renato , Khan Naeem D
Published: April 2024

Introduction:
There are scant data on use of P2Y12 antagonist therapy upstream of diagnostic angiography (DA), especially when administered in the emergency department (ED) for NSTEMI. We are conducting a multicenter registry to describe patterns of upstream P2Y12 antagonist use and outcomes.

Methods:
UPSTREAM (NCT02271022) is an ongoing US multicenter, prospective, non-interventional registry of consecutive NSTEMI patients, evaluated in an ED, who are given a loading dose (LD) of ticagrelor, clopidogrel, or prasugrel ≥4h prior to DA, with DA performed ≤72h after ED arrival. All patients are followed to hospital discharge. Patients receiving ticagrelor throughout the index hospitalization and at discharge are also followed for vital status, rehospitalization, bleeding complications, and P2Y12 compliance at 30 days post-discharge.

Results:
We report in-hospital outcomes of the first 578 patients to have data entry completed at 24 US hospitals. Upstream P2Y12 LD was clopidogrel in 60%, ticagrelor in 39%, and prasugrel in 1%. Of these, 234 (40%) received at least one dose of ticagrelor; 116 (20.1%) were ticagrelor-consistent and had follow-up completed. One-fifth of patients were transferred to an UPSTREAM hospital. Mean age was of the poverall sample was 63 years with 19% older than 75. Approximately 23% of patients had a documented prior MI, 31% had at least one prior stent, and 16% had prior CABG. Chest pain was not part of presenting symptoms in 15%. The median (+/-IQR) time from first ED arrival to LD was 6.7h (+/- 6.8 h); time from LD to DA was 12h (+/- 9.6 h). DA was performed via femoral access in 66% of patients and radially in 34%. Post-DA management was 55% stent, 9% CABG, and 35% medical management. In-hospital CV events (0.7%), including mortality, were infrequent. Only 14 patients (6 [1.0%] CABG-related and 8 non-CABG patients [1.4%]) required RBC transfusion, while 8 (6 CABG-related) required a platelet transfusion. One stent thrombosis event was recorded.

Conclusions:
Upstream P2Y12 therapy in NSTEMI patients undergoing an invasive strategy is associated with good clinical outcomes and minimal risk of bleeding complications. The most commonly used upstream P2Y12 LD was clopidogrel, but in-hospital switching was common. Updated data will be shown.
Abstract 12082: Radiofrequency Ablation of the Atherosclerotic Plaque: A Safety and Feasibility Study in an Atherosclerotic Rabbit Model
Authors: Ellenbroek Guilielmus , van Hout Gerardus , de Jager Saskia , Timmers Leo , Vink Aryan , Goldschmeding Roel , van der Kraak Petra , Pasterkamp Gerard , Hoefer Imo , Doevendans Pieter , Appelman Yolande
Published: April 2024

Introduction:
Angiogenesis from the vasa vasorum plays a key role in atheroprogression and plaque vulnerability. Immature neovessels are prone to leakage, hence facilitating additional lipid and inflammatory cell accumulation and increasing intraplaque hemorrhage risk.

Hypothesis:
Heat-generating radiofrequency ablation (RFA) safely reduces vasa vasorum, decreases inflammatory cell influx and stabilizes the plaque.

Methods:
Thirteen New-Zealand White rabbits on a 0.5% cholesterol-enriched diet were subjected to balloon denudation of the infrarenal aorta. After 13 weeks, either the proximal or distal half of the infrarenal aorta was exposed to transluminal RFA, the untreated half served as an intra-individual control. Optical coherence tomography (OCT) was performed directly after RFA.

Results:
Within 24 hours after RFA, no plaque ruptures or adverse events were observed by OCT or histology. Treated regions showed widespread decellularization of intimal, medial and (to a lesser extent) adventitial layers, which were recellularized after 7 and 28 days. Vasa vasorum density was not different between both regions at short-term (24 hours; RFA 19.8±5.1 vs. control 29.2±8.3/mm
2
; p=0.15) or long-term follow-up (7 days; 39.1±11.5 vs. 41.7±8.6/mm
2
; p=0.81 and 28 days; 46.4±13.4 vs. 38.5±6.6/mm
2
; p=0.06). After 7 days, treated regions were comparable to control areas with respect to plaque size (5.6±1.7 vs. 5.5±1.5mm
2
; p=0.62), intimal collagen (34.6±11.9 vs. 32.7±13.0%; p=0.22) and macrophage content (14.3±2.8 vs. 18.5±5.8%; p=0.32). RFA-treated regions did show a major decrease in intimal smooth muscle cell (αSMA) content (1.8±0.4 vs. 18.0±5.9%; p=0.038), which remained decreased after 28 days (6.8±3.8 vs. 12.6±1.6%; p=0.020). Again, after 28 days no differences were observed in plaque area (4.6±0.9 vs. 4.4±1.1 mm
2
; p=0.46), intimal collagen (39.2±9.1 vs. 40.3±12.4%; p=0.85) or macrophage content (13.2±2.5 vs. 12.6±2.0%; p=0.73).

Conclusion:
Radiofrequency ablation of the rabbit atherosclerotic plaque is safe and leads to a major reduction in αSMA content, but does not affect other aspects of plaque stability over time. It may thus serve as a therapeutic option for major (re)stenosis in peripheral arterial disease.
Abstract 12085: In Vivo Performance of a Novel Permanently Implanted Left Atrial Pressure Monitoring System
Authors: Perl Leor , Meerkin David , Levi Yair , Erdheim Dedi , Goldstein Oren , Abraham William T
Published: April 2024

Introduction:
Heart failure (HF) is a prevalent and burdensome chronic disease, with a characteristic high rate of hospital admissions. Left ventricular filling pressure is the earliest, most objective sign of impending HF exacerbation. Previous implantable devices, positioned in the pulmonary artery, have shown good safety and clinical efficacy. The Vectorious Left Atrial Pressure (V-LAP) monitoring system is a robust, miniature, battery-less sensor. It uses advanced application-specific integrated circuit (ASIC)-based technologies, enabling left-sided daily pressure readings with a wirelessly connected external unit. Our aim was to examine the safety and the functionality of the device in animal subjects.

Methods:
Using a dedicated repositionable delivery system, through a standard transseptal approach, adult sheep were implanted with a V-LAP device. Aspirin (325mg) and clopidogrel (750mg) were given prior to the procedure, the latter continued (225mg daily) during follow-up. An external wearable belt was used to remotely power the implant, interrogate the bi-directional digital data from the sensor, and transmit detailed wireless left atrial pressure waveforms to a web-based database.

Results:
The device was implanted in 10 animals, and was able to communicate well with the external belt, at depths of up to 30 cm in the thorax, for periods of up to 100 days, generating accurate and precise waveforms, with high temporal resolution. No peri-implant thrombotic events were observed (figure). There were no device-related complications.

Conclusions:
Using an advanced, left sided, intracardiac monitoring system, safety and feasibility were demonstrated with good functionality in animals, as evidenced by high resolution pressure wave outputs. Data in human subjects will determine whether the V-LAP is a safe and an effective monitoring system of hemodynamic data in heart failure patients, thus reducing readmission, morbidity and mortality rates.
Abstract 12102: Use of Mean Platelet Volume to Predict Significant Coronary Artery Disease in Patients With Non-ST Elevation Acute Coronary Syndromes
Authors: Taskesen Tuncay , Sekhon Harsimran , Wroblewski Igor , Goldfarb Mikhail , Ahmad Muhammad B , Nyguen Quang , Gidron Adi , Shahriar Dadkhah
Published: April 2024

Background:
Acute coronary syndrome (ACS) is characterized by unstable plaque and thrombotic process involving central role of platelets (PLT). Significant number of patients undergoing cardiac catheterization with non-STE ACS have non-significant coronary artery disease (CAD). It is postulated that an increase in Mean platelet volume (MPV) signifies an increase in inflammation during ACS, and thus, a higher risk of significant CAD.

Method:
This retrospective study enrolled patients with non-STE ACS who underwent coronary angiography from two teaching hospitals from 2011 to 2016. Significant CAD was defined >70% stenosis in at least one coronary artery. Exclusion criteria included patients with known CAD, hematologic disease, and on anticoagulant medication. Hematologic and angiographic data were collected by independent observers.

Results:
A total of 213 patients were enrolled (male 53%, mean age 61± 12.3). Mean MPV level was 8.9 fl and 45% of patients had significant CAD. When comparing patients with high MPV (MPV>=9 fl) vs low MPV (MPV<9 fl), high MPV group had significantly more significant CAD (55% vs 35%
p
=0.005) and higher HbA1c (6.9 vs 6.4
p
=0.02). Both groups had similar DM, HTN, smoking, and obesity rates. Patients with significant CAD had high MPV level (9.2± 1.07 fl vs 8.6 ± 1.03 fl
p
=0.001), high MPV/PLT (0.46 vs 0.40
p
=0.01), older age (64.5±11 vs 59.2 ± 12
p
=0.02), low HDL level (42±12 vs 47 ±16
p
=0.01), and non-significantly low PLT count (219 vs 230
p
=0.2). Multivariate analysis showed that increased age (AOR 1.04 95% CI 1.01-1.07,
p
=0.002), high MPV (AOR 1.46, 95% CI 1.01-1.076,
p
=0.01), high troponin (AOR 3.01, 95% CI 1.40-6.46,
p
=0.005), and low HDL levels (AOR 0.96, 95% CI 0.94-0.99,
p
=0.005) were associated with significant CAD. High MPV along with high troponin level was associated with a 4.8-fold increased risk for significant CAD as compared with normal MPV with high troponin (OR 4.8, 95% CI 1.31-17.6,
p
=0.001).

Conclusion:
Non-STE ACS patients with high MPV had significantly more significant CAD. Adding high MPV level to troponin level increased the predictive value of significant CAD. This result may help determine who would benefit from cardiac catheterization. This finding needs to be further validated in larger, prospective studies.
Abstract 12103: Vascular Function Affects Aortic Root Dilatation in Patients After Fontan Procedure
Authors: Asagai Seiji , Inai Kei , Harada Gen , Shimizu Mikiko , Ishii Tetsuko , Shinohara Tokuko , Sugiyama Hisashi , Tomimatsu Hifofumi , Park In-Sam
Published: April 2024

Introduction:
It is well known that, in patients with congenital heart disease, such as Tetralogy of Fallot, aortic root dilatation may gradually progress. Similar phenomenon also occur in patients with single ventricle circulation. However, the factors associated with aortic dilatation in these patients are still unknown.

Hypothesis:
We assessed the hypothesis that vascular function associated with the aortic root dilatation after Fontan procedure.

Methods:
Between July 2013 and April 2016, sixty-one patients who underwent the Fontan procedure (age, 12.8–55.8 years; median age, 23.2 years; postoperative duration, 8.2-31.3 years; median postoperative duration, 16.8 years) were enrolled. These patients were divided into 2 groups according to the presence or absence of aortic root dilatation and analyzed the relation between aortic root size and clinical profile, vascular function, hemodynamics, and neurohormonal factors. Aortic root dilatation was defined as observed/expected aortic root diameter >1.5 (aortic root dilatation, n=15, aortic root non-dilatation, n=46).

Results and Conclusions:
Age at Fontan procedure was significantly higher in the dilatation group than in the non-dilatation group (10.5±7.3 vs 5.3±4.0, P<0.01). FMD was significantly lower in the dilatation group than in the non-dilatation group (5.9±1.4 vs 8.3±2.3, OR 0.49, 95%CI 0.28-0.74, P<0.0001). Pulse wave velocity (PWV) was significantly higher in the dilatation group than in the non-dilatation group (1081±277 vs 943±140, P<0.05). Although hemodynamic variables and neurohormonal factors was not associated with aortic root size, pulmonary atresia was associated with aortic root dilatation (OR 5.43, 95%CI 1.55-20.18, P<0.01). In the multivariate analysis, impaired FMD had a close association with aortic dilatation (OR 0.45, 95%CI 0.19-0.82, P<0.01). FMD showed a negative correlation between age at Fontan procedure, PWV and parameter β(age at Fontan procedure r: -0.56, p<0.0001, PWV r: -0.32, p<0.05, β r: -0.27, p<0.05). We concluded that, in patients after Fontan procedure, vascular dysfunction such as aortic stiffness occurred in the patients who underwent Fontan procedure at older age and may play a role in progressive aortic dilatation.
Abstract 12114: Effects of an Educational Intervention on Disease Knowledge and Self-care Behaviors of Patients With Heart Failure: A Randomized Controlled Trial
Authors: Hwang Boyoung , Moser Debra K , Dracup Kathleen
Published: April 2024

Introduction:
In this randomized clinical trial, we tested the effects of an educational intervention designed to improve disease knowledge and self-care behaviors of patients with heart failure (HF).

Methods:
Patients with HF (n=602; 41% female, age 66.1 ± 12.9 years) were randomized into control (usual care) or 1 of 2 intervention groups: Fluid Watchers LITE (LITE) or Fluid Watchers PLUS (PLUS). Patients in both intervention groups received face-to-face education on HF self-care led by a nurse, and then received either 2 follow-up phone calls (LITE group) or biweekly calls until they demonstrated content competency (PLUS group). The levels of HF knowledge and self-care behaviors were measured with self-report questionnaires at baseline and 3, 12, and 24 months. Data were analyzed using linear mixed-models.

Results:
The 3 groups were not significantly different in their HF knowledge and self-care at baseline. Significant group-by-time interactions were found in models for knowledge and self-care (Figure). Both intervention groups showed improvement in HF knowledge at 3 months, but the improvement lasted only in the PLUS group throughout 24 months. Both intervention groups exhibited significantly better self-care behaviors at 3 and 12 months compared with the control group. The intervention effects on self-care remained stable in both groups, but were not significant at 24 months. Results were similar when covariates (i.e., socioeconomic characteristics and baseline psychological status) were controlled in the models.

Conclusions:
The face-to-face educational intervention was effective in improving disease knowledge and self-care behaviors among patients with HF. Both intervention groups showed improvement in knowledge and self-care at 3 months, and their effects on self-care remained significant until 12 months. In addition, the intervention with more follow-up calls resulted in greater and more sustained improvement in knowledge about HF.
Abstract 12132: A Genetic Risk Score is Associated With Atrial Fibrillation in the Malmö Prevention Project
Authors: Shiffman Dov , Sjögren Marketa , Louie Judy Z , Bare Lance A , Juhlin Tord , Sarabi Latif , Kitlinski Mariusz , Devlin James J , Melander Olle
Published: April 2024

Introduction:
Atrial fibrillation is associated with increased morbidity and mortality. A genetic risk score (GRS) comprising 12 single nucleotide polymorphisms (SNPs) has been found to be associated with atrial fibrillation in population-based prospective studies of middle aged participants but this association has not been investigated in the elderly.

Hypothesis:
A pre-specified GRS for atrial fibrillation is associated with incident atrial fibrillation in the elderly.

Methods:
The Malmö Prevention Project (MPP) is a population-based prospective study of 18,240 participants who were enrolled in the study between 2002 and 2006.

After excluding those with prevalent atrial fibrillation or missing clinical information 4,678 participants (median age of 68.2 years (IQR 66.5 to 73.0)) were randomly selected from the cohort for the current analysis. Cox proportional hazards models were used to estimate the association between GRS and incident atrial fibrillation after adjustment for age, sex, body mass index, systolic and diastolic blood pressure, use of antihypertensive medication, smoking, diabetes, coronary events, and heart failure.

Results:
Among 4,678 participants, 524 had a first atrial fibrillation event during a median 8.2 years follow-up. Participants in the top quintile of the GRS had two-fold greater risk of atrial fibrillation (HR = 2.03; 95%CI 1.54 to 2.67, P=5.0х10
-7
) compared with those in the bottom quintile. The GRS was also associated in the elderly (those above median age, >68.2 years): HR=1.82 for those in the top quintile compared with those in the bottom quintile (95%CI 1.31 to 2.52, P=0.0003) as well as in those below median age (HR =2.68; 95%CI 1.58 to 4.55, P =0.0003).

Conclusion:
A pre-specified GRS for atrial fibrillation comprising 12 SNPs was associated with incident atrial fibrillation in the elderly. Patients with high genetic risk for atrial fibrillation may benefit from aggressive monitoring and control of blood pressure.
Abstract 12145: Remote Ischemic Preconditioning Regulates Post-resuscitation Microcirculation via A K
Atp
Channel-dependent Mechanism in a Rat Model of Cardiac Arrest
Authors: Zhao Shen , Tang Ziren , Wang Jiangang , Yang Zhengfei , Chen Feng , Peberdy Mary A , Ornato Joseph P , Tang Wanchun
Published: April 2024

Introduction:
Remote ischemic preconditioning (RIPC) provides potent protection to tissue microcirculation against ischemic-reperfusion injury. However, the underlying microvascular mechanism of RIPC is not fully understood. The present study investigated whether the protective effects of RIPC on microcirculation and myocardial function after cardiopulmonary resuscitation (CPR) are related to K
ATP
channel activation.

Hypothesis:
RIPC-induced activation of the K
ATP
channel would result in improved microcirculation and myocardial function following resuscitation.

Methods:
Twenty-four male Sprague-Dawley rats were randomized into three groups (n=8 for each group): RIPC, RIPC with K
ATP
channel blocker, and control. Remote ischemic preconditioning was induced by four cycles of 5 min of limb ischemia followed by 5 minutes of reperfusion. Ventricular fibrillation was induced and untreated for 8 min followed by 8 min of CPR. The animals were monitored for 6 h and observed for an additional 66 h. Sublingual microcirculation was assessed by a sidestream dark-field imaging device, and myocardial function was measured by echocardiography at baseline, 30 min, 1 h, 2 h, 4 h, and 6h post-resuscitation.

Results:
At 30 min and subsequent intervals post-resuscitation, both perfused vessel density and microcirculatory flow index were significantly greater in the RIPC group than in the control group (
P
< 0.05). Compared with the control group, a significantly higher ejection fraction, myocardial performance index, and greater duration of survival were observed in the RIPC group (
P
< 0.05). Pretreatment with the K
ATP
channel blocker (glibenclamide) significantly reversed the microvasucular and myocardial protective effects of RIPC (
P
< 0.05) (Figure 1, 2).

Conclusions:
In a rat model of CPR, the beneficial effect of RIPC on sublingual microcirculation and cardiac function with improved survival was related, at least in part, to the activation of K
ATP
channel.
Abstract 12170: Long-term Clinical Outcomes of Drug-eluting Stent vs Bare Metal Stent for Unprotected Left Main Disease: A Meta-analysis
Authors: Gongora Carlos A , Lemor Alejandro , Casso Dominguez Abel , Zulbaran y Rojas Alejandro , Pena Jacobo , Bavishi Chirag , Arora Shilpkumar , Ul Hassan Hafeez , Gholitabar Farid , Lee Shawn , Vallejo Franco , Hosseinidehkordi Seyedhamed , Argulian Edgar
Published: April 2024

Background:
The long-term benefits of drug-eluting stents (DES) compared to bare metal stents (BMS) for the unprotected left main (ULM) disease are unclear. We aimed at investigating the long-term clinical outcomes in patients treated with DES vs. BMS for ULM disease.

Methods:
We performed a meta-analysis of studies examining ULM stenting with a follow-up duration of at least 3 years. We included the following end-points: all cause-mortality, myocardial infarction (MI), and target-lesion revascularization (TLR). In addition, we examined the rates of major adverse cardiac events (MACE) as specified by each individual study. Pooled risk ratios (RR) and their 95% confidence intervals (CI) were calculated for all outcomes using a random-effect model.

Results:
Thirteen studies were included in the analysis: 12 observational and 1 randomized study, with a total of 4,574 patients. We analyzed separately adjusted and unadjusted data. The adjusted data included a randomized trial and propensity-matched analysis of observational studies. Both analyses showed the benefit of DES for TLR (A p=0.004, UA p<0.001) and MACE (A p=0.02, UA p=0.007). While the unadjusted analysis showed a significant difference for all-cause mortality, the difference was not significant for the adjusted data. Neither of the analyses showed a significant difference for MI (Figure 1a and 1b).

Conclusions:
The study confirms the benefits of DES for TVR and MACE but there was no significant difference in adjusted all-cause mortality.
Abstract 12172: Development and Preliminary Evaluation of an Avatar-based Educational Application for Improving Knowledge on Symptom Recognition and Management in Patients With Acute Coronary Syndromes
Authors: Tongpeth Jintana , Du Hui Y , Clark Robyn A
Published: April 2024

Background:
A poor understanding of what are the symptoms of a heart attack is recognized as a major obstacle to timely medical treatment and it is associated with potentially preventable death and complications. Numerous studies have demonstrated that information technology plays an important role in improving patients’ knowledge and self-management ability.

Purpose:
To develop and evaluate the acceptability of an avatar-based education application for teaching chest pain recognition and management, among people who are at risk of a heart attack

Methods:
In phase one, a participatory action research method was used to develop the application. The development phase involved working with clinical experts, IT experts and consumers through two cycles of development and critical reflection. In phase 2, a pre and post design was used to assess the acceptability and effect of application on a sample of patients with acute coronary syndrome (ACS). Patients’ knowledge, attitude, belief and satisfaction were measured using the ACS Response Index.

Results:
The avatar-based education application involves illustration, concepts and quizzes which were developed for teaching chest pain recognition and management, among people who are at risk of a heart attack. Consumers feedback focused on usability, ease of navigation and encourage both learning and enjoyment. The application was tested on ten patients (mean age 52.2±10.4 years) with acute coronary syndrome. A high level of user satisfaction (87.3%) was reported. The knowledge score of the ACS response index increased from 62.4 (±13.4%) to 78.1 (±9.3%), the belief scores increased by 25.7% (73.2±6.1% to 98.9±1.7%) and symptom recognition scores increased by 24.3 % (72.5±5.6% to 96.8±8.0%).

Conclusion:
This study suggested that a multidisciplinary collaboration was effective in developing patient education intervention. The positive outcomes of this study will lead to a randomised trial to test the effectiveness of this intervention.
Abstract 12197: Increased Angiotensin II Sensitivity Contributes to Microvascular Endothelial Dysfunction in Women Who Have Had Preeclampsia
Authors: Stanhewicz Anna E , Santhanam Lakshmi , Alexander Lacy M
Published: April 2024

Introduction:
Women with a history of preeclampsia have increased cardiovascular disease risk, however the mechanisms responsible for this association remain unclear. Microvascular damage sustained during a preeclamptic pregnancy may persist post-partum. The putative mechanisms mediating this dysfunction include a reduction in nitric oxide (NO)-dependent dilation, and an increased sensitivity to angiotensin II (ang II). In this study, we evaluated endothelium-dependent dilation, ang II sensitivity, and the therapeutic effect of ang II receptor blockade (losartan) on endothelium-dependent dilation
in
vivo
in the microvasculature of women with a history of preeclampsia (PrEC, n=7) and control women who had a healthy pregnancy (HC, n=9). We hypothesized that PrEC would have 1) reduced endothelium-dependent dilation, 2) reduced NO-mediated dilation, and 3) increased sensitivity to ang II. We further hypothesized that losartan would increase endothelium-dependent dilation in PrEC.

Methods:
We assessed microvascular function by measurement of cutaneous vascular conductance responses to graded infusion of acetylcholine (ACh; 10
-10
-10
-1
M) and ang II (10
-20
-10
-4
M); and during ACh co-infusion with 15mM L-NAME (NO-synthase inhibitor) or 43μM losartan.

Results:
ACh-induced vasodilation was attenuated in PrEC compared to HC (PrEC -3.3±0.2 vs. HC -4.7±0.1 logEC50; p<0.05). There was no difference between PrEC and HC during ACh co-infusion with L-NAME (PrEC -4.4±0.2 vs. HC -4.6±0.2 logEC50; NS). NO-mediated dilation was attenuated in PrEC compared to HC (PrEC 10±4 vs. HC 35±4%; p<0.01). PrEC had a greater vasoconstriction response to ang II (PrEC -11.8±0.2 vs. HC -9.7±0.2 logEC50; p<0.05. Losartan co-infusion improved the vasodilation response to ACh in PrEC (losartan -4.6±0.2 vs. ACh alone -3.3±0.2 logEC50; NS).

Conclusions:
These findings suggest that women who have had preeclampsia have impaired endothelium-dependent vasodilation which is mediated, in part, by reductions in NO signaling and increased sensitivity to ang II. Furthermore, losartan improved endothelium-dependent dilation, suggesting that ang II receptor blockade may have therapeutic potential to treat microvascular dysfunction in women who have had preeclampsia.
Abstract 12215: Objective Stratification of Six-Month Mortality Risk among Patients Referred to Hospice
Authors: Horne Benjamin D , Muhlestein Joseph B , May Heidi T , Ronnow Brianna S , Bair Tami L , Lappé Donald L
Published: April 2024

Introduction:
The Intermountain Mortality Risk Scores (IMRS) are a suite of sex-specific mortality risk stratification tools created from the complete blood count (CBC), basic metabolic profile (BMP), and age. Patients referred to hospice should have probable 6-month mortality, but this is currently estimated based on clinical gestalt.

Hypothesis:
Use of an objective clinical decision tool like IMRS may improve estimation of 6-month mortality risk for evaluation of patient referral to hospice.

Methods:
Subjects were Intermountain Healthcare patients who were referred to hospice (females: n=1,753, males: n=1,522) from 2009-2014. Baseline CBC and BMP laboratory data from the time of initial referral to hospice were used to compute the previously-derived IMRS scores. Cox regression and Kaplan-Meier survival curves were used for statistical analyses to evaluate six-month all-cause mortality risk.

Results:
Females averaged 77.2±14.2 years of age, and males were 74.4±14.6 years. Six-month survival was 37% in females and 33% in males; stratified into IMRS deciles, survival was 44.9% in decile 1 and 27.8% in decile 10 for females, while in males survival was 39.5% and 25.2%, respectively. Females had hazard ratio (HR)=1.72 (95% CI=1.34, 2.18; p<0.001) for decile 10 vs. 1, and males had HR=1.57 (95% CI=1.18, 2.09; p=0.002). Stratified by previously-established IMRS thresholds (Figure), 12%, 38%, and 50% of females were grouped into low-, intermediate-, and high-risk groups, respectively, and 10%, 31%, 59% of males were in those groups.

Conclusions:
About one third of hospice patients did not die within 6 months, suggesting that additional objective evidence is needed to guide referral. IMRS, an evidence-based clinical decision tool derived in a large healthcare population, significantly stratified mortality risk in hospice patients. An electronically-deliverable stratification tool, IMRS may be useful in evaluation of patient risk prior to hospice referral.
Abstract 12225: Effects of Obesity on Noninvasive Testing and Angiography Results in Patients With Suspected Cardiac Ischemia: Insights From the PROMISE Trial
Authors: Litwin Sheldon , Coles Adrian , Pagidipati Neha J , Lee Kerry L , Pellikka Patricia A , Mark Daniel B , Udelson James E , Hoffmann Udo , Douglas Pamela S
Published: April 2024

Background:
Evaluation of obese patients with suspected CAD is challenging because obesity is a CV risk factor, but adiposity itself may mimic symptoms of CAD and reduce the accuracy of diagnostic testing. Optimal testing strategies in obese patients are not known.

Methods:
Patients with stable symptoms suggestive of cardiac ischemia from the PROMISE trial (n=9230) were classified according to BMI. Providers specified a functional test modality prior to stratified randomization to functional (stress testing) or anatomical (CTA) testing. We assessed relationships between BMI, physician’s preference of functional test, test positivity and results of catheter angiography (cath) using logistic regression.

Results:
Providers were more likely to choose SPECT over other functional tests as BMI increased (OR 1.04 per unit increase in BMI above 27, p<0.001). In patients with BMI ≥ 35 vs. < 35, the rate of positivity with CTA was similar (10% vs. 12%; see Table). The same was true for stress echo and stress ECG (positivity 8-13%, p>0.8 for both). In contrast, SPECT was significantly more likely to be positive in those with BMI ≥ 35 vs. <35 (18% vs. 13%; p=0.001). The likelihood of finding obstructive CAD at cath did not differ with BMI ≥ 35 vs. <35 in patients having CTA (59% vs. 52%, p=0.22), but among SPECT patients, positivity was only 29% with BMI ≥ 35 compared to 52% with BMI < 35 (p=0.005; Table).

Conclusions:
Increasing levels of obesity were associated with stronger physician preference for SPECT over other noninvasive tests. In patients receiving SPECT, higher levels of obesity were associated with a higher rate of positive results, but a lower cath yield for obstructive CAD. In contrast, in patients receiving CTA, positivity rates and cath yield did not vary by BMI. Obesity appears to significantly influence provider decision-making with regard to noninvasive test choice, probability of abnormal test results and probability of finding obstructive disease at cath.
Abstract 12230: Increased Left Ventricular Myocardial Stiffness is Associated With Incident Heart Failure in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Kamimura Daisuke , Suzuki Takeki , Hall Michael E , Wang Wanmei , Winniford Michael D , Butler Kenneth R , Mosley Thomas H
Published: April 2024

Background:
Increased left ventricular (LV) myocardial stiffness may be associated with future deterioration of LV hemodynamics and incident heart failure (HF). Diastolic wall strain (DWS) is a recently developed echocardiographic indicator of LV myocardial stiffness. We hypothesized that increased LV myocardial stiffness evaluated by DWS is associated with incident HF in a community-based African American cohort in the ARIC.

Methods and Results:
We investigated the association between LV myocardial stiffness and incident HF among 1553 African American participants (mean age 58.5 years, 66% women) without a history of cardiovascular diseases or LV wall motion abnormalities in the ARIC Study. Echocardiography was performed at Visit 3 in the African American cohort in Jackson, MS. DWS was calculated as (posterior wall thickness at end-systole - posterior wall thickness at end-diastole) / posterior wall thickness at end-systole. DWS quartiles were generated and used to make the Kaplan-Meier survival curves for incident HF with log-rank test. Cox proportional hazards models were used to evaluate the association between baseline DWS and incident HF. Over a median follow-up of 15.6 years, there were 251 HF events (incidence rate: 10.9 per 1,000 person-years). Participants with lower DWS (increased LV diastolic stiffness) had a higher incidence of HF than those with higher DWS (unadjusted hazard ratio 1.86, 95%CI 1.28-2.71 in 1
st
quartile vs 4
th
quartile, p=0.001). After adjustment for traditional risk factors and incident coronary heart disease during the course, DWS was independently associated with incident HF (hazard ratio 1.62, 95%CI 1.10-2.38 in 1
st
quartile vs 4
th
quartile, p=0.015).

Conclusions:
Increased LV myocardial stiffness evaluated by DWS was associated with an increased risk of HF in a community-based African American cohort in the ARIC. Increased LV myocardial stiffness may lead to future deterioration of LV hemodynamics and incident HF.
Abstract 12438: Intraoperative Magnesium Reduces Postoperative Arrhythmias in Congenital Heart Surgery Is the Effect Arrhythmia-Specific and Dose-Dependent?
Authors: He Dingchao , Aggarwal Nimisha , Fan Xiangming , Cheng Yao I , Berul Charles I , McCarter Robert , Jonas Richard A , Moak Jeffrey P
Published: April 2024

Introduction:
Magnesium (MG) has been used to decrease the incidence of postoperative junctional ectopic tachycardia (PO JET); its efficacy on other arrhythmias (A) is less known. We tested the hypotheses that the effect of MG on PO A may be: 1) arrhythmia-specific and 2) dose-dependent.

Methods:
1871 out of a total of 2208 congenital heart surgeries (CHS), performed from 2005 to 2013, were reviewed based on selection criteria. 750 cases did not receive MG, 338 cases received 25 mg/kg MG (25 Mg) and 783 cases received 50 mg/kg MG (50 Mg) after aortic cross clamp release. All procedures were classified according to Aristotle Score (1 to 4). The incidence of 5 PO A categories was recorded: JET, accelerated junctional rhythm (AJR), atrial tachycardia (AT), ventricular tachycardia (VT) and 2°and 3° heart block (HB). Pearson chi-square test and logistic model analyses were used to evaluate the effect of MG on arrhythmia. BSA, Aristotle score, cardiopulmonary bypass, aortic cross-clamp and surgery times were controlled in logistic models.

Results:
1) PO JET was reduced with MG use (0 Mg 15.3%; Mg 7.2%; p<0.001), but without evidence of a difference by dose (25 Mg 7.1%: 50 Mg 7.3%). 2) AJR was reduced with MG use (0 Mg 4.3%: 25 Mg 2.4%: 50 Mg 2.2%, NS between doses). 3) AT was reduced with MG use (0 Mg 9.1%: 25 Mg 3.6 %: 50 Mg 4.0%, NS between doses). 4) VT was reduced in low dose (0 Mg 5.1%: 25 Mg 2.7%; p =0.02), but not at the higher dose (50 Mg 5.5%). 5) PO HB did not differ by Mg use (0 Mg 4.8 %: 25 Mg 3.3 %: 50 Mg 2.6 %). The reduction of PO JET was significantly greater with increasing surgical complexity. Effect of MG was independent of Aristotle score in other A- categories.

Conclusion:
In agreement with prior clinical trial results, MG use was preventive of PO arrhythmia; however its effect appeared to be arrhythmia-specific. The occurrence of PO JET, AJR, and AT was reduced with Mg use. The effect of MG on PO VT appeared inversely dose dependent with no effect at higher dose and MG appeared to have no impact on PO HB. In general, higher doses of MG did not enhance PO arrhythmia suppression, but might be proarrhythmic (VT) in patients undergoing CHS. Our results suggest that an intraoperative MG dosage of 25 mg/kg may be optimal.
Abstract 12443: Incident Heart Failure Risk After Acute Myocardial Infarction is Stratified by the Intermountain Major Adverse Cardiovascular Events (IMACE) Risk Scores
Authors: Horne Benjamin D , Muhlestein Joseph B , Bhandary Durgesh , Kfoury Abdallah G , Hoetzer Greta L , Bair Tami L , Khan Naeem D , Lappé Donald L
Published: April 2024

Introduction:
Previously, the Intermountain Mortality Risk Scores (IMRS) were created to predict all-cause mortality, but also predicted incident heart failure (HF) in unselected catheterization laboratory patients. The Intermountain Major Adverse Cardiovascular Events (IMACE) risk scores were created using IMRS principles to predict MACE (CV mortality, recurrent myocardial infarction [MI], stroke) for acute MI patients.

Hypothesis:
IMACE stratifies the risk of HF in acute MI patients free of HF at baseline.

Methods:
Acute MI patients (females: 1,846; males: 4,720) hospitalized at the Intermountain Heart Institute (9/1993-4/2015) were included if they were free from a clinical HF diagnosis and (if available) had LVEF >40%. Incident HF was monitored electronically in Intermountain’s 22 hospitals. A composite of HF and all-cause mortality was also examined. IMACE was computed from previously-derived weightings for age, complete blood count and comprehensive metabolic panel factors, and B-type natriuretic peptide.

Results:
Mean age at MI was 65.1±13.6 years in females and 59.8±12.3 in males. Cumulative HF-free survival was 90.2% during follow-up of 8.8±5.9 years (max: 21.6 years). Median time to HF diagnosis was 6.0 years, with a stable annual hazard (median 0.4%/year; interquartile range: 0.4%-0.6%). IMACE risk scores (high- vs. low-risk) predicted HF (Figure) in females (HR=3.72, CI=1.68, 8.27) and males (HR=6.90, CI=3.82, 12.48). IMACE predicted mortality/HF for females (HR=6.39, CI=4.83, 8.42) and males (HR=6.34, CI=5.12, 7.85). Other HF predictors were 16 of 53 clinical and treatment variables.

Conclusions:
IMACE effectively stratified HF incidence after acute MI in patients initially free from HF. Data suggested high-risk females died prior to HF diagnosis. IMACE is a clinically feasible tool for efficiently identifying MI patients for whom additional evaluation and more aggressive therapeutic management may improve long-term prognosis.
Abstract 12448: AMPKα1 Knockout Mice Have Dysfunctional Perivascular Adipose Tissue (PVAT) and Impaired Vascular Function
Authors: Almabrouk Tarek A , Riddell Alex , Ugusman Aziza B , Salt Ian P , Kennedy Simon
Published: April 2024

Introduction:
Perivascular adipose tissue (PVAT) surrounds blood vessels and releases many mediators which regulate vascular tone. AMP-activated protein kinase (AMPK) is a critical regulator of cellular metabolism and although expressed throughout the vessel wall, its function in PVAT is unknown. Although aortic PVAT from mice with global AMPKα1 knockout releases significantly less adiponectin and does not augment vasodilator responses in isolated vessels, these mice remain normotensive.

Hypothesis:
Mice with global AMPKα1 deficiency will have inflamed PVAT and that high fat feeding will increase PVAT inflammation further and raise blood pressure.

Methods:
Unfixed samples of wild-type (WT) and KO aortic PVAT (n>3 for each) were incubated with dihydroethidium (DHE) or 4,5 diaminofluorescein diacetate (DAF-2DA) to detect superoxide and NO respectively. Images were captured using a fluorescence microscope. Nitrotyrosine expression and macrophages in the PVAT were examined using immunohistochemistry and FACS respectively. Matched KO and WT littermates were fed either chow diet or hfd (21% lard, 0.15% chol.) for up to 12 weeks and BP measured by tail-cuff plethysmography every 4 weeks. Measurement of vascular function in aortic rings was via wire myography and adiponectin release was measured using ELISA assay.

Results:
In aortic PVAT, superoxide and NO production was unchanged in KO mice but nitrotyrosine expression and macrophage content was significantly higher. In WT mice, 12 weeks of hfd attenuated vasodilator responses of aortic rings containing PVAT (n=6; p<0.05) and reduced adiponectin production by PVAT. In KO rings containing PVAT the vasodilator response was already suppressed and hfd did not lower it further or alter production of adiponectin. High fat diet increased PVAT macrophage content of both WT and KO but did not alter mean arterial BP after 8 weeks in either strain.

Conclusions:
AMPK in aortic PVAT regulates production of adiponectin and suppresses inflammation. Mice lacking AMPKα1 lose the beneficial effects of PVAT on vascular relaxation and while fat feeding increases inflammation of the PVAT, BP did not rise, perhaps through compensation effects in smooth muscle or endothelial function.
Abstract 12450: Trpv1 Responses to Heat and Induces Il-6 Production in Skeletal Muscle Cells
Authors: Obi Syotaro , Nakajima Toshiaki , Inoue Teruo
Published: April 2024

Introduction:
Interluekin-6 (IL-6) is released from skeletal muscle cells and induced by exercise, heat, catecholamine, glucose, lipopolysaccharide, reactive oxygen species, and inflammation. However, the mechanism, which induces release of IL-6 from skeletal muscle cells, remains unknown. Thermo-sensitive transient receptor potential subfamily V member 1 (TRPV1) plays vital roles in cellular functions.

Hypothesis:
We hypothesized thatTRPV1 senses heat, transmits a signal into the nucleus, and produces IL-6. We investigated the underlying mechanisms, where skeletal muscle cells sense heat and respond to it.

Methods:
Mouse C2C12 myoblast cells were cultured at 37°C under 5% CO
2
atmosphere. When cells were exposed to heat, culture dishes were placed in another incubator which was preset to an environment temperature of 39°C, 40°C, 41°C, and 42°C. The calcium influx concentration was measured by a fura-2 fluorescence dual-wavelength excitation method. The IL-6 mRNA expression level of IL-6 was analyzed by using real-time PCR. The protein density level of IL-6 released from myoblast cells was analyzed by using an ELISA. The phosphorylation level of TRPV1 was analyzed by using western blotting.

Results:
When myoblast cells were exposed to temperatures ranging from 37 degrees C to 42 degrees C for two hours, the mRNA expression of IL-6 increased in a temperature-dependent manner. Heat also increased IL-6 secretion. Heat increased the intracellular calcium flux temperature-dependently. TRPV1 agonists, capsaicin and NADA, increased the intracellular calcium flux and the IL-6 mRNA expression, while TRPV1 antagonists, AMG9810 and SB366791, and the siRNA mediated knockdown of TRPV1 decreased them. Western blotting with inhibitors demonstrated that heat increased the phosphorylation levels of TRPV1 followed by PKC and CREB. PKC inhibitors, Go6983 and staurosporine, CREB inhibitors, curcumin and naphthol AS-E, and the knockdown of CREB suppressed the heat induced increases of IL-6 mRNA.

Conclusions:
TRPV1 senses heat and increases IL-6 production in skeletal muscle cells through the PKC and CREB pathway. Moreover it suggests that hyperthermic conditioning is effective for the exercise therapy or rehabilitation.
Abstract 12497: Diminished Cavolin-1 Expression and Augmented Nitrative Stress Secondary to Prolyl-4 Hydroxylase 2 Deficiency Contribute to Obliterative Vascular Remodeling and Severe Pulmonary Arterial Hypertension
Authors: Dai Zhiyu , Zhu Maggie M. , Zhao You-Yang
Published: April 2024

Background:
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary vascular resistance and vascular remodeling. Our recent study for the first time demonstrated that loss of prolyl-4 hydroxylase 2 (PHD2) in endothelial cells and bone marrow cells in mice induces severe PAH with obliterative pulmonary vascular remodeling and plexiform-like lesions recapitulating clinical PAH. However, it is unclear whether nitrative stress is involved in the pathogenesis of PAH in this mouse model.

Methods:
Endothelial-specific
Egln1
(encoding PHD2) disruption (

Egln1
Tie2

),
Egln1
and
Hif2a
double knockout (
EH2
) mice were generated. Western blotting and immunostaining were performed to quantify nitration stress and caveolin-1 expression in WT,
Egln1
Tie2
and
EH2
mice. MnTMPyP (a superoxide scavenger) were administrated to

Egln1
Tie2

mice. Right ventricular systolic pressure (RVSP) and RV/(LV+S) ratio, indicator of RV hypertrophy, were measured. Medial thickness and muscularization of distal pulmonary arteries were assessed by histological examination. Human lung microvascular endothelial cells (HLMECs) was cultured.

Results:
Nitrotyrosine was increased in

Egln1
Tie2

mice and normalized in EH2 mice. MnTMPyP treatment inhibited RVSP increase and RV hypertrophy, and decreased medial thickness and muscularization of distal pulmonary arterials in

Egln1
Tie2

mice. Mechanistically, endothelial Caveolin-1 expression was decreased in

Egln1
Tie2

mice and normalized in EH2 mice. Consistently, PHD inhibitor DMOG decreased Caveolin-1 expression in HLMECs.

Conclusion:
These data show that loss of endothelial PHD2 suppresses Caveolin-1 expression in a HIF-2α dependent manner. Decrease of Caveolin-1 expression and resultant activation of nitration stress contribute to the severe vascular remodeling and PAH in

Egln1
Tie2

mice. Thus, targeting nitrative stress is a novel therapeutic strategy for the treatment of PAH.