bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16647: Left Ventricular Electro-Mechanical Discoordination is Present in Patients With Tetralogy of Fallot Not Meeting Conventional Criteria for Pulmonary Valve Replacement
Authors: Gerk Alexis L , Schafer Michal , Frank Benjamin , von Alvensleben Johannes , IVY Dunbar D , Mitchell Max B
Published: May 2021

Introduction:
Pulmonary regurgitation (PR) and RV dilation influence timing of pulmonary valve replacement (PVR) in patients with repaired Tetralogy of Fallot (rTOF). LV function is an independent marker of TOF patient outcomes. New markers of electromechanical discoordination (EMD) have recently been described.
Systolic stretch fraction
(SSF) quantifies the ratio of ventricular myocardium inappropriately relaxing during systole.
Diastolic relaxation fraction
(DRF) quantifies inappropriate myocardial contraction during diastole. We analyzed LV EMD using SSF and DRF in rTOF patients with PR who do not meet commonly used criteria for PVR with mild to moderate RV dilation (<150 mL/m
2
).

Hypothesis:
Patients with rTOF will have abnormal LV EMD.

Methods:
Patients (n=18) and healthy controls (n=20) with rTOF and PR underwent cardiac MRI. LV EMD was analyzed using SSF and DRF (Figure) derived from strain and strain rate analysis considering individual LV myocardial segments. Rank-sum test was used to compare groups. SSF and DRF were assessed for linear correlations with RVEDVi by Pearson method.

Results:
There were 9 male and 9 female TOF patients (Mdn age 15, range 9-55). TOF patients had increased RVEDVi (118±23 ml/m
2
, p<0.001) and increased RVESVi (56±13 ml/m
2
, p<0.001) compared to controls. RV EF was lower in TOF patients but within normal physiologic range (53±6%, p=0.008). LV size indices and EF did not differ. TOF patients had increased SSF (Mdn 0.035, IQR 0.015-0.052, p=0.002) and significantly decreased DRF (Mdn 2.735, IQR 2.358-2.959, p<0.0001). RVEDVi correlated with increased SSF (R=0.51, p=0.011) and decreased DRF (R=0.62, p=0.007).

Conclusions:
TOF patients with PR and mild to moderate RV dilation have significant LV EMD during both systole and diastole. The degree of systolic and diastolic EMD correlate with RV dilation. SSF and DRF are unique and sensitive early markers of LV dysfunction compared to conventional MRI metrics.
Abstract 16650: Segmental and Global Longitudinal Strain Differences Between Children With Paediatric Inflammatory Multisystem Syndrome Temporally Associated With Sars-cov-2 Pandemic and Kawasaki Disease: Preliminary Data From an Ongoing Study
Authors: Piccinelli Enrico , herberg jethro , Kang Heechan , fraisse alain , Krupickova Sylvia , Bermejo Altamar Ivan , Sabatino Jolanda , Singh Yogen , Bautista-Rodriguez Carles , Di Salvo Giovanni
Published: May 2021

Introduction:
The paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and Kawasaki disease (KD) have overlapping features. This study aimed to describe the strain segmental analysis among both entities.

Methods:
Retrospective review of strain segmental analysis within 4 weeks of presentation of symptoms among children diagnosed with PIMS-TS between April and June 2020 and a historic cohort of typical KD from the Royal Brompton Hospital, London.

Results:
We included 33 PIMS-TS patients (23 males, 69.7%) at a mean age of 8 ± 4,9 years old and 45 KD patients (31 males, 68,9%) at a mean age of 5,8 ± 4,5 years old. PIMS-TS patients were older at presentation (p = 0.038). Left ventricle ejection fraction (LVEF) was normal in both groups (63,3% vs 63,5%; p= 0,89), 4/33 PIMS-TS children (12,1%) had coronary arteries abnormalities (CAA), whereas 100% of KD cohort had CAA. Both groups had a normal global longitudinal strain (GLS), but in PIMS-TS it was significantly reduced compared to the KD group (-20% vs -22%; p=0,008). Basal segments were the most affected in PIMS-TS with significant difference in the basal anterior and anterolateral strain compared to KD (respectively -18,2% vs -23,4%; p < 0,001 and - 16,7% vs -22,7%; p < 0,001). PIMS-TS had a greater anterior, anterolateral and posterior segments involvement with a significant reduction in the anterolateral mid-wall longitudinal strain (-18,3% vs -22%; p=0,002). Apical segments were less involved, with a significant difference only in the septal and inferior apical strain (respectively p=0.001 and p=0,032).

Conclusions:
These preliminary data showed that after 4 weeks from the onset of symptoms, all PIMS-TS patients had a normal LVEF but they had a significant reduction in GLS and different segmental involvement compared to KD cohort. We hypothesize that these findings may be related to direct myocardial damage in PIMS-TS rather than caused by coronaries perfusion abnormalities.
Abstract 16658: Serum Potassium and Risk of Death in Patients With HFpEF: An Analysis of PARAGON-HF
Authors: Ferreira Joao , ZANNAD Faiez , Desai Akshay S , Jering Karola , Pfeffer Marc A , Rouleau Jean L , Shah Sanjiv J , Rouleau Jean L , Van Veldhuisen Dirk J , Solomon Scott , McMurray John J
Published: May 2021

Introduction:
Hyper- and hypo-kalemia have each been associated with higher risk of death in in heart failure with reduced ejection fraction but the relationship between serum potassium and risk of death in heart failure with preserved ejection fraction (HFpEF) is not well established. We assessed the risk associated with high and low potassium in patients with HFpEF enrolled in the PARAGON-HF trial.

Aim:
To explore the association between serum potassium and mortality in patients with HFpEF and examine the interaction with renal function.

Methods:
Repeated events, Cox and mixed-effects models. The primary outcome in this analysis was death from any cause.

Results:
Patients: mean age 73 years, 52% female. Higher potassium was not associated with higher risk of death: adjusted time-updated HR (95%CI) for potassium >5.0 mmol/l =1.06 (0.85-1.32); p=0.61 (potassium 4-5 mmol/l referent HR=1.0). However, lower potassium was associated with higher risk of death: adjusted HR for potassium <4.0 mmol/l=1.51 (1.21-1.87); p<0.001. However, the risk related to potassium was modified by baseline renal function (p for interaction <0.05), whereby the excess mortality in patients with low potassium was most prominent in patients with an eGFR <60 ml/min/1.73m
2
(Figure).

Conclusion:
In adjusted analyses, low potassium was independently associated with mortality in patients with HFpEF, especially in the context of renal impairment.
Abstract 16663: Importance of Assessment for Diffuse Ventricular Fibrosis in Atrial Fibrillation Using Cardiac Ct-Derived Myocardial Extracellular Volume Fraction
Authors: Kanazawa Hisanori , Ito Miwa , Kawahara Yusei , Hoshiyama Tadashi , Tsujita Kenichi
Published: May 2021

Introduction:
Previous cardiac MRI studies reported that the baseline diffuse LV fibrosis status should be evaluated before performing catheter ablation (CA) to identify the responders early and triage them with appropriate treatment. However, no study has been conducted to evaluate diffuse LV fibrosis in conjunction with pre-ablation planning cardiac CT.

Objectives:
The purpose of this study was to quantify diffuse left ventricular (LV) fibrosis by the CT-derived extracellular volume fraction (CT-ECV%) in conjunction with cardiac CT performed for CA planning and evaluate its determinants in patients with atrial fibrillation (AF).

Methods:
Prior to AF ablation, 98 patients (50 patients with paroxysmal AF and 48 patients with persistent AF) underwent pre-ablation planning cardiac CT. Additionally, delayed cardiac CT was performed to measure CT-ECV% as an index of diffuse myocardial fibrosis.

Results:
Persistent AF patients more frequently had a history of heart failure. Left atrial (LA) volume index was greater in persistent AF patients compared with paroxysmal AF patients. CT-ECV% of persistent AF patients was significantly higher than that of paroxysmal AF patients (30 ± 5 % vs. 26 ± 5 %, p < 0.001). Univariate and multivariate analysis revealed that only persistent AF was independent associated with CT-ECV%. Furthermore, CT-ECV% in recurrence group after CA for AF was higher than that in non-recurrence group (29 ± 4 % vs. 26 ± 5 %, p = 0.013). Multivariate logistic regression analysis revealed that CT-ECV% was significantly correlated with AF recurrence after CA for AF. Receiver operating characteristic analysis showed that more than 28 % in the CT-ECV% was a significant predictor of AF recurrence (area under the curve 0.692, log-rank test: p < 0.001).

Conclusions:
The quantification of diffuse LV fibrosis by CT-ECV% in conjunction with pre-ablation planning cardiac CT is feasible in AF patients, and persistent AF is independently associated with increasing diffuse LV fibrosis. Furthermore, CT-ECV% was significantly associated with AF recurrence after CA for AF. These findings suggested that it was more important to evaluate cardiac remodeling using CT and intervene early in AF.
Abstract 16667: Computed Tomography-Based Pulmonary Vascular Tortuosity as a Marker in Resting and Exercise Pulmonary Arterial Hypertension
Authors: Harder Eileen M , Nardelli Pietro , Sanchez-Ferrero Gonzalo , Ross James , Ash Sam Y , Singh Inderjit , Hunsaker Andetta , Waxman Aaron B , San Jose Estepar Raul , Washko George , Rahaghi Farbod
Published: May 2021

Introduction:
Increased vascular tortuosity has been proposed as a marker of pulmonary arterial hypertension (PAH). In this analysis, we compared arterial and venous vascular tortuosity between controls and subjects with resting PAH. Furthermore, we examined if abnormalities could be detected in exercise PAH (EPAH), thought to be an early form of PAH.

Methods:
From an institutional registry, 388 patients with both right heart catheterization and computed tomography angiography (CTA) data were selected. Within this cohort, three distinct groups were identified: 1) controls, who had no cardiopulmonary disease and normal resting and exercise hemodynamics; 2) EPAH, with normal resting hemodynamics but age-adjusted pre-capillary pulmonary hypertension on exertion, and 3) PAH, defined as resting mPAP >20mmHg, pulmonary vascular resistance >3 Wood Units, and pulmonary capillary wedge pressure <15mmHg. Tortuosity was defined as the actual path length of a vessel divided by the linear distance between the two farthest endpoints of the vessel segment on CTA. AV>10% was defined as the number of arterial segments with tortuosity >10% divided by the same venous measure. Analysis was performed with Wilcoxon rank sum tests in R 3.5.

Results:
There were 99 patients in the final cohort, including 47 (47.4%) with PAH, 12 (12.1%) with EPAH, and 40 (40.4%) without disease. Compared to controls, median arterial tortuosity was increased in PAH (3.3 ± 0.1% vs. 3.4 ± 0.1%, p=0.0009; Figure 1) but not in EPAH (3.3 ± 0.1%, p=0.82). Median venous tortuosity did not differ between groups. AV>10% was increased in EPAH (vs. controls, 1.86 ± 0.38 vs. 1.56 ± 0.44, p=0.03) and resting PAH (2.0 ± 1.2 p=2e-6).

Conclusions:
Increased arterial tortuosity on CTA is a biomarker of resting PAH. When corrected for venous tortuosity, arterial tortuosity also appears to be abnormal in EPAH.

Figure 1
.
Arterial vessels in PAH, EPAH, and control subjects. Red segments have tortuosity > 10%.
Abstract 16678: Incidence and Timing of Post-Infarction Ventricular Arrhythmias in a Contemporary ST Elevation Myocardial Infarction Population Undergoing Primary PCI
Authors: Wegermann Zachary K , Li Shuang , Smilowitz Nathaniel , Jneid Hani , wilson bryan H , Wang Tracy Y , Tamis-holland Jacqueline E
Published: May 2021

Introduction:
Stable patients with STEMI and successful reperfusion may be considered for early discharge; however, little is known about the incidence of late ventricular tachycardia or fibrillation (VT/VF occurring at least 1 day after PCI) that may warrant further monitoring.

Methods:
We identified 162,822 STEMI patients treated with primary PCI and without VT/VF on the day of PCI in the NCDR Chest Pain-MI Registry from January 2015-December 2018. A low risk subgroup (n=96,188) was identified by excluding patients with prior MI, heart failure, systolic BP<90 mmHg, cardiogenic shock, cardiac arrest, re-infarction on the day of PCI, or ejection fraction<40%. The incidence and timing of VT/VF (any VT≥7 beats or VF) was determined in the overall and low risk cohorts. The association between late VT/VF and in-hospital mortality was evaluated using multivariable logistic regression.

Results:
Late VT/VF occurred in 2.6% of patients overall and 1.8% in the low risk cohort. In patients with late VT/VF, cardiac arrest occurred in 20.3% and 7.7% of the overall and low risk cohorts, respectively. Many late VT/VF events (37.0% overall, 24.4% low risk cohort) occurred ≥2 days after PCI. Patients with late VT/VF were older, more likely to be men, and have prior cardiovascular disease or risk factors than patients without VT/VF; they also had higher rates of post-PCI heart failure, cardiogenic shock, cardiac arrest, and stroke (
Figure
). The risk of death was higher for patients with vs. without VT/VF in both the overall (15.4% vs. 2.4%, adjusted OR [aOR] 6.40, 95% CI 5.63-7.29) and low risk cohorts (3.7% vs. 0.5%, aOR 8.74, 95% CI 6.53-11.70).

Conclusions:
Late VT/VF after STEMI was infrequent but often occurred ≥2 days post-PCI and was associated with an increased risk of death, even in the low risk cohort. Novel ways to monitor and rapidly treat late VT/VF may avoid prolonged hospitalization after STEMI.
Abstract 16687: The Use of Evidence by Stakeholders in Developing Nutrition Policy: Preventing Heart Disease and Stroke Through Reducing Sodium and Trans Fat Intake
Authors: James Lesley
Published: May 2021

Introduction:
High intake of sodium and trans fat are leading risk factors for heart disease and stroke. Scientific bodies including AHA have recommend reductions in their intake to prevent poor health outcomes. The government of Canada developed sodium and trans fat reduction strategies in collaboration with a wide range of stakeholders. Both strategies resulted in a voluntary approach despite the efforts of the cardiovascular and public health communities to secure regulation.

Methods:
A mixed method research study was undertaken to assess and analyze the policy making process around trans fat and sodium reduction. A novel content analysis was conducted on the Government of Canada lobby registry which quantified the lobbying efforts of various stakeholders. Next, key informant interviews were conducted with stakeholders involved in the policy processes to better understand contextual dynamics that led to the adoption of voluntary measures.

Results:
The lobby registry assessment found that the during the policy negotiations, the food industry was significantly more likely to meet with government officials than public health and clinical associations. The food industry also met with higher profile and powerful government officials than health organizations which may have facilitated a greater influence. Based on thematic analysis, the use of scientific evidence and values played a key role in the decision-making processes and the overall effectiveness of the voluntary policy measures. Data and evidence were misused by stakeholders, and this could have contributed to a general confusion about the need for public health policy and regulation.

Conclusions:
The policy processes around trans fat and sodium reduction were influenced by competing commercial interests which overtook the objectives of public health and clinical associations. As health groups aim to create healthier food environments around the world, it is important to understand and be prepared for the various interpretations of evidence, policy objections and counter tactics of powerful multi-national food companies. Efforts should also be made to strategically align stakeholders who influence public health policy including media, the general public and health professionals.
Abstract 16688: Effects of Evolocumab in Patients With Prior Percutaneous Coronary Intervention: An Analysis From the Fourier Trial
Authors: Furtado Remo H , Fagundes Antonio A , Oyama Kazuma , Zelniker Thomas A , Tang Minao , Kuder Julia F , Murphy Sabina A , Wang Huei , Hammer Andrew , Keech Anthony C , Pedersen Terje R , Giugliano Robert , Sabatine Marc S , Bergmark Brian A
Published: May 2021

Introduction:
Among patients with atherosclerotic cardiovascular disease (ASCVD), those with history of PCI represent an important population for potential high risk for cardiovascular (CV) events. We examined the clinical efficacy of the PCSK9 inibitor evolocumab in patients with prior PCI.

Methods:
FOURIER randomized 27,564 patients with ASCVD on statin therapy to evolocumab or placebo with a median follow-up of 2.2 yrs. The primary end point (PEP) was the composite of CV death, MI, stroke, unstable angina, or coronary revascularization; major coronary events were the composite of coronary death, MI, or coronary revascularization. The risk of events in patients with and without a history of PCI were compared in the placebo arm. The clinical benefit of evolocumab vs. placebo was compared using a Cox proportional hazards model.

Results:
17,073 (62%) patients had prior PCI at baseline. Among patients in the placebo arm, those with prior PCI (N=8563) had a 1.6x higher rate of the PEP (16.8 vs 10.7%; adjusted HR 1.61; 95% CI 1.42-1.84 P<0.0001) and nearly double the rate of major coronary events (14.5 vs. 7.8%; P<0.0001; adjusted HR 1.72; 95% CI 1.49-1.99; Figure left). In patients with prior PCI, evolocumab reduced the risk of the PEP by 16% (HR 0.84; 95% CI 0.77-0.91; P<0.0001) and of major coronary events by 18% (HR 0.82; 95% CI 0.75-0.90, P<0.0001; Figure right), including a 30% reduction in fatal or non-fatal MI (P<0.001) and a 24% reduction in coronary revascularization (P<0.001). After the first year, there was a 25% reduction in major coronary events (HR 0.75, 95% CI 0.66-0.86, P<0.0001). The absolute risk reduction at 3 years with evolocumab for major coronary events was 2.8% in patients with prior PCI vs. 0.3% in those without.

Conclusions:
In a contemporary cohort with ASCVD on statin therapy, patients with prior PCI were at heightened risk for coronary events. Evolocumab was highly effective in this group, reducing major coronary events by 18% with a NNT at 3 years of only 36.
Abstract 16699: The Mayo Cardiac Intensive Care Unit Admission Risk Score Predicts One-Year Mortality
Authors: Breen Thomas J , Padkins Mitchell , Bennett Courtney , Anavekar Nandan S , Murphy Joseph G , Bell Malcolm R , Barsness Gregory W , Jentzer Jacob C
Published: May 2021

Introduction:
The Mayo Clinic Cardiac Intensive Care Unit Admission Risk Score (M-CARS) has been shown to predict hospital mortality in the CICU population better than conventional critical care scoring models. We tested the hypothesis that M-CARS could similarly be used to predict one-year mortality.

Methods:
We retrospectively reviewed adult CICU patients admitted from 2007 to 2018. M-CARS was calculated using admission data. Groups were compared using Wilcoxon test for continuous variables and chi-squared test for categorical variables.

Results:
This study included 12428 unique patients with a mean age of 67 ± 15 years (37% females), of whom 11279 (90.8%) survived hospitalization and 2839 patients (22.8%) died within 1 year of admission. The 1-year survival decreased incrementally as a function of increasing M-CARS (
Figure 1A
, p<0.0001), and all components of M-CARS were significant predictors of 1-year mortality (p<0.001). 1690 hospital survivors (15.0%) died within 1 year. The 1-year survival decreased incrementally as a function of increasing M-CARS for scores <3 (all p<0.001); however, there was no further adverse 1-year survival for patients with M-CARS ≥3 (
Figure 1B,
p=0.99). M-CARS components associated with 1-year mortality among hospital survivors included blood urea nitrogen, red blood cell distribution width, Braden score, and respiratory failure (all p<0.001), while cardiac arrest, cardiogenic shock, and anion gap were not.

Conclusions:
M-CARS accurately predicts 1-year mortality among CICU admissions, with a plateau effects at high M-CARS scores ≥3. Significant predictors of 1-year mortality among CICU survivors include frailty markers rather than admission severity.
Abstract 16802: Economics and Outcomes of Sotalol and Dofetilide In-Patient Dosing Approaches in Patients With Atrial Fibrillation
Authors: Bunch Thomas J , May Heidi T , Bair Tami L , Steinberg Benjamin A , Ranjan Ravi , Muhlestein Joseph B , Anderson Jeffrey L , Knowlton Kirk U
Published: May 2021

Background:
Inpatient initiation of sotalol (STL) and dofetilide (DFL) for patients with symptomatic atrial fibrillation (AF) can be variable, more so for STL.

Objective:
Define the impact of inpatient initiation of STL and DFL approaches on patient in-hospital costs and outcomes.

Methods:
AF patients that were admitted for STL (n=133) or DFL (n=38) initiation at an Intermountain Healthcare Hospital in 2018 were included to provide contemporary insight. Patient and dosing characteristics were described descriptively, and the impact of dosing schedule was correlated with daily hospital costs and outcomes. The CMS reimbursement for 3-day initiation of STL or DFL is $9,263.51.

Results:
The average age of the complete population was 69.7±11.7 years and 64.3% were male. Baseline risk factors were similar between groups. Mean ejection fraction was 59.2±8.9% and median QTc was 455.7±38.5 ms before STL dosing and 453.7±37.6 before DFL dosing. The average length of stay was 3.7±4.2 days and was shorter for DFL (3.0±2.0) compared to the STL (3.9±4.6). Within the DFL group, most received 5-6 doses, whereas STL dosing frequency was variable (Figure A). DFL discharge dose in 22 (57%) was 500 mcg BID and 125 mcg BID in 8 (21%). STL dose was 80 mg BID in 96 (72.1%) and 40 mg BID in 29 (21.8%). Total costs per hospitalization and per day were higher for STL compared to DFL (Figure B). QTc prolongation >500 ms was more common with DFL versus STL and other long-term outcomes were similar (Figure C). A 24 load of IV sotalol result in a cost savings of $871.55 vs. a 2-day load and $3,803.10 vs. a 3-day oral load.

Conclusion:
Routine contemporary inpatient STL dosing is markedly variable and results in the potential of both cost gain and loss to a hospital. Under dosing of STL is also common and may negatively impact long-term outcomes.
Abstract 16807: The Association Between Dietary Factors and the Distribution of Monocyte Subsets: A Systematic Review
Authors: Oh Ester , Na Muzi , Rogers Connie
Published: May 2021

Introduction:
Three subsets of monocytes have been identified in humans (i.e. classical, intermediate and non-classical), which have been proposed to differently contribute to the pathogenesis of atherosclerosis, a major cause of cardiovascular disease (CVD). Previous studies implicate a shift in the distribution of monocyte subsets from classical (CM) to intermediate (IM) and non-classical monocytes (NCM) in individuals with cardiometabolic disorders, which is hypothesized to contribute to CVD development. The risk of cardiometabolic disease is strongly associated with dietary habits. Thus, the aim of the current systematic review was to evaluate the association between dietary factors and the distribution of monocyte subsets.

Methods:
Articles were systematically searched in CINAHL, Cochrane Central Register of Controlled Trials, and PubMed until May 2020. A total of 2496 articles were independently screened by 2 reviewers. Eligible study subjects were adults > 18 years old. Eligible studies were cross-sectional, cohort, within-subject design studies and randomized-controlled trials that examine the effect of dietary factors on monocyte subset distribution. A total of 12 studies were included in this review.

Results:
A single high fat meal challenge increased the number and percentage of NCM (n=1) and increased the number and percentage of CM (n=1) in healthy subjects. Consuming a high-salt diet for a week increased the number and percentage of IM in healthy subjects, whereas these changes were reversed after switching to a low-salt diet (n=2). EPA+DHA supplementation (4 g/day) for 2 weeks decreased the number and percentage of IM in patients with hypertriglyceridemia (n=2). Lastly, one cross-sectional study showed that the number and percentage of IM was lower in patients with CVD who consumed a high quality diet compared to low quality diet.

Conclusions:
Dietary factors may influence the distribution of monocyte subsets. However, the role of diet-induced changes in the distribution of monocytes on atherosclerosis risk remains unknown. Additional mechanistic studies are needed to understand the relationship between dietary factors, changes in the distribution of monocyte subsets and atherosclerotic risk.
Abstract 16808: Divergent Mature Vascular Smooth Muscle Cell Fates Are Directed by Platelet-Derived Transcriptomic Codes in Aortic Aneurysms
Authors: HADI Tarik , Silvestro Michele , Rivera Martinez Cristobal , Sleiman Tellaoui Rayan , zias ariadne , Ramkhelawon Bhama
Published: May 2021

Introduction:
Loss of vascular smooth-muscle cells (vSMC) and subsequent defective replenishment of functional vSMC
de novo
are pathological hallmarks of abdominal aortic aneurysm (AAA). Evidence suggests that clusters of progenitors can be reprogrammed into vSMC lineage following vascular injury. However, the landscape of vSMC precursors and reprograming signatures that determine their fate in AAA is undefined.

Hypothesis:
We hypothesize that quiescent progenitor pools reside in aorta and undergo spatiotemporal fate decision into mature vSMC in AAA. We speculate that distinct ligand-receptor and transcriptional signals gear their pathogenic trajectories into dysfunctional vSMC in AAA.

Methods & Results:
Single-cell RNA-sequencing (scRNA-seq) identified vascular progenitor cells (Cd34
+
Pdgfrα+) in murine (angiotensin II-induced) and human AAA. Pseudotime analysis tracked two differentiation fates of progenitors into divergent mature vSMC pools characterized by enrichment in contractile cytoskeleton machinery (Acta2
+
Myh11
+
) or abnormally supplemented with matrix remodeling genes (Mmp2
+
Col8a1
+
). Mmp2
+
Col8a1
+
clusters were dominant in AAA suggesting pathological reprograming in AAA. Gene regulatory network analysis mapped distinct libraries of upstream transcription factors in each mature vSMC states in AAA. Acta2
+
Myh11
+
and Mmp2
+
Col8a1
+
transcriptomes were driven by opposing actions of Pparγ and its repressor Runx1 respectively. Interestingly, cellular interaction analysis revealed that platelet-derived Pdgfβ fueled the phenotypic switch into Mmp2
+
Col8a1
+
vSMC via its receptor Pdgfrα. Dampening Pdgfrα signaling by systemic platelet depletion repressed Runx1 activation thereby increasing Pparγ transcriptomic activity in progenitors in the aortic wall. This rescued functional regeneration of vSMC (Acta2
+
Myh11
+
) with contractile properties consistent with reduced aortic damage and diminished AAA incidence.

Conclusions:
Our data demonstrate that platelets are novel actors capable of awakening progenitor pools by coding their fate into pathogenic vSMC lineage in AAA. We provide evidence suggesting that strategies aimed at sustaining vSMC contractile destiny could encourage repair of vascular damage in AAA.
Abstract 16812: ETV2-
Rhoj
Cascade Regulates Endothelial Progenitor Cell Migration During Embryogenesis
Authors: Sierra-Pagan Javier , SINGH BHAIRAB N , Gong Wuming , Das Satyabrata , Skie Erik , Garry Mary G , Garry Daniel J
Published: May 2021

Background:
Endothelial progenitors migrate early during embryogenesis to form the primary vascular plexus. ETV2, an Ets-transcription factor, governs the specification of the earliest hemato-endothelial progenitors during embryogenesis. The regulatory mechanisms that govern their migration are undefined. In the present study, we describe a novel role for ETV2 in cell migration and provide evidence for an ETV2
-Rhoj
network as a mechanism responsible for this process.

Approach and Results:
We analyzed our RNAseq datasets, which revealed robust enrichment of migratory/motility pathways following overexpression of ETV2 during mesodermal differentiation. We then analyzed ETV2 ChIPseq and ATACseq datasets, which showed enrichment of ChIPseq peaks with increased chromatin accessibility in migratory genes following overexpression of ETV2. Additionally, scratch and sprouting assays showed that overexpression of ETV2 enhanced cell migration in mouse embryonic stem cells (ESCs), embryoid bodies (EBs) and mouse embryonic fibroblasts (MEFs). Knockout of
Etv2
led to migratory defects of

Etv2-EYFP
+

angioblasts to their pre-defined regions of developing embryos relative to wildtype controls at embryonic day (E) 8.5, supporting its role during migration. Mechanistically, we showed that ETV2 binds to the promoter region of
Rhoj
serving as an upstream regulator of cell migration. Single cell RNAseq analysis of

Etv2-EYFP
+

sorted cells revealed co-expression of
Etv2
and
Rhoj
in endothelial progenitors at E7.75 and E8.25. Overexpression of ETV2 led to a robust increase in
Rhoj
in both EBs and MEFs, whereas, its expression was abolished in the
Etv2
knockout EBs. Finally, shRNA-mediated knockdown of
Rhoj
resulted in migratory defects which were rescued by overexpression of ETV2.

Conclusions:
These results define an ETV2
-Rhoj
cascade, which is important for the regulation of endothelial progenitor cell migration during embryogenesis.
Abstract 16824: Circulating Microvesicles in Heart Failure Patients Prior to, and Following LVAD Implantation
Authors: Cornwell William K , Stockelman Kelly A , DeSouza Noah , Greiner Jared , desouza chris
Published: May 2021

Introduction:
Elevated levels of circulating endothelial and platelet (EMV and PMV) microvesicles are associated with endothelial dysfunction and thrombosis/inflammation, respectively. EMVs and PMVs are elevated in patients with heart failure with reduced ejection fraction (HFrEF) and are associated with clinical outcomes. We sought to characterize longitudinal changes in EMV and PMV following LVAD implantation in these patients.

Methods:
Blood samples were obtained from patients with advanced HFrEF (59±9years, N=9 males) during an invasive hemodynamic assessment with Swan-Ganz catheterization 2.7±4.1 and 4.3±1.3 months prior to, and following CF-LVAD implantation, respectively. Circulating concentrations of total MV, EMVs (CD31+) and PMVs (CD42b+) were determined by flow cytometry.

Results:
Demographics and hemodynamics pre- and post-LVAD implantation are displayed in the
table
. Prior to LVAD, four patients were on inotropes. Six patients received a Heartware VAD, and four patients received a Heartmate 3 VAD. As demonstrated in the
figure
, there was a significant reduction in total MV concentration, as well as EMVs and PMVs following LVAD implantation.

Conclusion:
Circulating concentrations EMVs and PMVs decline significantly in HFrEF patients following LVAD implantation. These findings are indicative of improvements in both endothelial function and thrombotic/inflammatory state associated with the heart-failure syndrome.
Abstract 16833: Trends in Primary Payer Status and Association With Outcomes in Pediatric Heart Transplantation
Authors: Restaino Kathryn , Zhang Xuemei , Lin Kimberly Y , Rossano Joseph , Burstein Danielle , Wittlieb-Weber Carol , Mascio Christopher , O'Connor Matthew J
Published: May 2021

Background:
Pediatric heart transplantation (HT) is resource-intensive. Adult studies have shown an increase in the proportion of adult HT funded by public insurance with outcomes inferior to those with private coverage. Trends in the funding of pediatric HT and associations with outcomes in children have not been described.

Methods:
We queried the United Network for Organ Sharing (UNOS) database for patients less than 18 years of age, listed for and undergoing HT from 1994 to 2018. We identified primary payer at listing (TCR), transplant (TRR), 1 year follow up, and between 1-5 years following HT. Trends in primary payer were analyzed using generalized logit regression. Cox regression was used to evaluate the impact of insurance on survival.

Results:
An increase in the proportion of patients with public insurance at the time of HT was observed. Forty eight percent of HT patients in 1994 and 59% in 2018 were publicly insured (P<0.0001). Eight percent of patients changed from private to public insurance between TCR and TRR, and 15% transitioned from private to public from TRR to 1 year post-HT. Of those who changed insurance at one year follow up, 57% transitioned from private to public insurance. For patients undergoing HT, unadjusted long-term survival was worse for patients with public insurance (P <0.0001). When adjusted for age and region, black race (HR 1.57, P <0.001) and age 13-17y (HR 1.44, P<0.0001) were independently associated with mortality. When evaluating outcomes based on change of insurance and adjusting for age and region, age 13-17y (ref <1y, HR 2.3 P <0.0001), white race (ref. black race, HR 0.54, P <0.0001), continuous public insurance (ref continuous private insurance, HR 1.49, P <0.0001), and transition to public insurance (ref continuous private insurance, HR 1.37, P<0.007) were associated with increased mortality.

Conclusion:
There has been a statistically significant trend towards increasing public insurance for patients awaiting, at the time of, and after HT. Patients that maintain or transition to public insurance following transplant have worse long term outcomes. As the number of patients undergoing HT with public insurance funding continues to increase, understanding of how insurance status impacts long-term outcomes is important.
Abstract 16839: Maternal Placental Vascular Malperfusion Lesions Associated With Increased Cardiometabolic Risk and Reduced Microvascular Density in Women a Decade After Delivery: Which Placental Features Matter?
Authors: Gandley Robin E , Brands Judith , Hubel Carl A , Hauspurg Alisse , Parks William Tony , Catov Janet M
Published: May 2021

Introduction:
Maternal vascular malperfusion (MVM) lesions in the placenta are commonly found in women with adverse pregnancy outcomes associated with increased CVD in later life. Minimal criteria for MVM include vasculopathy, accelerated villous maturation and increased syncytial knots, and villous infarction upon pathologic examination; expanded definitions have included presence of fibrin deposition (intervillous or perivillous) or low placental weight (<10
th
%).

Hypothesis:
Women with a history of MVM lesions would have evidence of cardiometabolic risk factors and peripheral microvascular changes a decade after delivery independent of pregnancy outcome.

Methods:
A total of 469 women with placental pathology data available were evaluated at 8-10 years postpartum. Placental specimens were reviewed by a perinatal pathologist. Cardiometabolic variables were measured at the time of the study visit. Sidestream dark field imaging was used to assess the sublingual microcirculation. We compared the median size (diameter) of microvessels, density (total length of perfused microvessels/mm
2
) and penetration of red cells into the glycocalyx of vessels 5-25μm diameter (perfused boundary region, PBR) in women 8-10 years after pregnancy, using the minimal MVM criteria (compared to none). Expanded criteria were examined alone. Significance =*p<0.05 vs no MVM lesions.

Results:
Women with minimally defined MVM lesions in their placentas had higher diastolic blood pressure (79mmHg MVM vs. 75 mmHg No MVM*), LDL (111mg/dL MVM vs. 101 mg/dL No MVM*), Cholesterol (185 mg/dL MVM vs. 175mg/dL No MVM*) and insulin (14mg/dL MVM vs. 12mg/dL No MVM*), along with smaller-sized microvessels (median 8.75±1.1 μM vs. 9.06±0.7 μM*), and a lower density of perfused microvessels compared to women without MVM lesions (3590±1260mm/mm
2
MVM vs. 3970±820 mm/mm
2
No MVM*) a decade after delivery. Glycocalyx PBR was smaller in women with prior MVM vs. women without lesions (2.01±0.23μm vs. 2.09±0.15μm, P=0.02). Similar results were not seen in subjects with either presence of fibrin or small placenta in the absence of other MVM criteria.

Discussion:
Using minimal criteria MVM was associated most strongly with maternal cardiometabolic and microvascular differences a decade later.
Abstract 16841: Coaxial Anti-Inflammatory Scaffold Preserves the Phenotype of MSCs Under Stress
Authors: Nagiah Naveen , Franchi Federico , Olthoff Michaela , Peterson Karen , Rodriguez-Porcel Martin
Published: May 2021

Introduction:
Myocardial infarction is an inflammatory condition that leads to scar deposition and cardiac remodeling. Stem cells (SC) are an alternative to prevent cardiac remodeling, but have poor survival after transplanted to an pro-inflammatory ischemic myocardium. Polymeric biocompatible scaffolds are biomaterials that can improve SC retention and survival, with the goal to improve regional cardiac function.

Methods:
We electrospun fibers of a) uniaxial polycaprolactone (PCL) and b) coaxial PCL (core) and gelatin methacrylate (sheath), an anti-inflammatory substance. We first tested the SC retention of each scaffold. Then, adipose derived mesenchymal SCs (MSCs) were co-cultured with M1 macrophages (pro-inflammatory) with and without scaffold and we measure the expression of inflammatory-related genes (RT-PCR). Lastly, PCL+GelMA scaffolds with and without MSCs (3.5x10
3
MSCs) were implanted after myocardial ischemia/reperfusion (IR) and followed for 2 weeks.

Results:
The average diameter of PCL and PCL+GelMA fibers were 730±40nm and 1110±50nm, respectively. PCL+GelMA scaffolds increased MSCs adhesion compared to PCL (absorbance: 0.09±.03 for PCL and 0.24±0.02 for coaxial, p<0.05). Figure A shows that MSCs in presence of M1 macrophages had a significant increase in inflammatory genes, which was significantly ameliorated in the presence of GelMA. In preliminary animal studies (n=1-4), MSCs delivered in a PCL+GelMA scaffold had partial preservation of regional function parameteres compared to IR only or IR+PCL+GelMA (no MSCs) (Figure B).

Conclusion:
Coaxially PCL+gelMA scaffolds attenuate the pro-inflammatory milieu of MSCs under ischemic-like conditions, and may improve regional cardiac remodeling.
Abstract 16856: Mathematical Modeling of Blood Flow to Evaluate the Hemodynamic Significance of Peripheral Vascular Lesions
Authors: Mirramezani Seyed Mehran , Cimadomo Paul , Ahsan Ernie , Shavelle David , Clavijo Leonardo , Shadden Shawn C
Published: May 2021

Introduction:
Evaluating the severity of lesions in peripheral arteries is challenging. Image-based blood flow modeling from peripheral computed tomographic angiography (pCTA) may provide a non-invasive method to determine the hemodynamic significance of lesions. The objective of this study was to evaluate the diagnostic performance of a trans-lesion pressure drop computed from pCTA-based blood flow modeling in the peripheral arteries.

Methods:
Ten patients undergoing digital subtraction angiography (DSA) and pCTA were included. The peripheral arteries were divided into 8 segments per extremity and stenosis severity was visually graded by DSA as non-stenosed (grade 0), mild (grade I), moderate (grade II), severe (grade III), occluded (grade IV) or non-evaluable. A functionally significant lesion was defined as grade III or IV by DSA. Independent from the DSA review, a resting pressure gradient (rPG) and exercise PG (ExPG) for each segment was calculated from pCTA-based blood flow modeling (Figure), and a functionally significant lesion was defined as having an rPG > 5 mm Hg or an ExPG > 20 mm Hg.

Results:
Mean age was 52±16 years, 4 patients (40%) were male, 8 patients (80%) presented with critical limb ischemia, mean ankle brachial index was 0.60±0.29 and 66 arterial segments were available for both assessment methods. Twenty-two segments had functionally significant lesions by DSA. For rPG, sensitivity was 80%, specificity was 85% and accuracy was 79% with DSA as the standard; for ExPG, sensitivity was 84%, specificity was 89% and accuracy was 88%.

Conclusions:
Use of a resting pressure gradient > 5 mm Hg and an exercise pressure gradient > 20 mm Hg measured by peripheral computed tomography-based blood flow modeling accurately identifies functionally significant stenosis in patients with advanced peripheral vascular disease. These results support a prospective imaging trial to further validate this novel approach.
Abstract 16857: Acute Pericarditis With Concomitant Stemi Associated With Delayed Presentation in the Setting of SARS-COV-2 Pandemic
Authors: Galo Jason , Celli Diego , Khandaker Mariam , Drescher Murry , Alfonso Carlos
Published: May 2021

Background:
The classic ST-segment elevations seen in a STEMI can similarly be found during an episode of acute pericarditis, making the two entities difficult to distinguish. The incidence of post-myocardial infarction injury syndromes presenting with findings such as acute pericarditis is estimated to be around 3%. Prompt seek of medical care is pivotal in successful outcomes, which has been affected during the pandemic.

Case:
A 30-year-old female with a past medical history of uncontrolled type 1 diabetes, chronic kidney disease, obesity presented with a 24-hour long history of non-radiating chest pain. Upon interrogation she endorsed that initially she delayed her coming presentation to the hospital because of fears of contracting coronavirus. Physical examination showed tachycardia and tachypnea. EKG demonstrated diffuse ST elevations in the anterolateral leads concerning for a STEMI, PR-segment depressions on most leads and troponin elevation to 0.09 ng/ml. Point of care ultrasound (POCUS) echocardiogram showed significant anterolateral wall hypokinesis.

Decision making:
Given her high cardiovascular risk factors the patient was urgently taken to the catheterization laboratory which found a 100% ostial left anterior descending artery and a large left main coronary artery thrombus. The thrombus was initially treated with mechanical thrombectomy and the plaque with a percutaneous coronary intervention (PCI) with a drug-eluding stent to the proximal LAD. In the days following her PCI, the patient continued to endorse sporadic sharp chest pain with the same characteristics as on presentation. Post-PCI transthoracic echocardiogram demonstrated ejection fraction of 20-25% and a small pericardial effusion. She was started on colchicine for pericarditis. She was discharged home on dual antiplatelet therapy with close follow up.

Conclusion:
Given that our patient had clinical pericarditis before her presentation to the hospital with a STEMI, it is unlikely that her pericarditis was due to a post myocardial infarction syndrome. Delayed presentation to the hospital associated with fear of contracting or spreading COVID-19 is a silent collateral culprit that adds up to increased cardiovascular morbidity and mortality during this pandemic.
Abstract 16862: Culture of Cardiac Mesenchymal Cells (CMCs) at Physiologic Oxygen Tension Greatly Enhances Cell Retention
In Vivo
After Myocardial Infarction
Authors: Dasari Chandrashekhar , Bolli Robi , Arshia Asma , Alkasir Amr , Guo Yiru , Ashraf Usman , Li Qianhong
Published: May 2021

A major obstacle to using cell therapy for heart failure is the poor survival of transplanted cells. We have found that CMCs (a promising type of reparative cells) grown at 5% O
2
(the physiologic O
2
tension in the heart) are more resistant to severe hypoxia
in vitro
than CMCs grown at 21% O
2
, but the survival of these cells
in vivo
is unknown. Thus, female mice subjected to a 60-min coronary occlusion and 30 days of reperfusion received 1x10
6
male CMCs cultured at 21% O
2
or 5% O
2
(21%O
2
CMCs or 5%O
2
CMCs) via echo-guided injection into the LV cavity. Quantitative real-time PCR for single copy of a Y-chromosome-specific
Sry
gene sequence was performed using genomic DNA isolated from heart (right ventricle [RV], risk region [RR] and non-risk region [NR] of LV), lung, liver, spleen and kidney 24 h or 7 days after cell administration (Figure). Compared with 21% O
2
CMCs, culture at 5% O
2
markedly increased cell retention in RR > NR > RV at 24 h and up to 7 days after CMC administration (Figs. C-D). At 24 h, although 25% of all transplanted cells were present in the liver (Fig. E), the number of
Sry
+ cells per mg of tissue was strikingly greater in RR (2131±248) > NR (1447±250) > RV (1047±156) compared with liver (274±131,
P
<0.01) and kidney (619±140,
P
<0.05) (n=6/group). These differences persisted up to 7 days (820±156 in RR, 667±156 in NR, 327±33 in RV vs. 103±45 in liver,
P
<0.01; 179±50 in kidney,
P
<0.05) (n=4-5/group). In summary, we provide a systematic, time-dependent, and highly quantitative analysis of cell retention and distribution after infusion of CMCs into the LV cavity of failing hearts. The results demonstrate that, compared with 21% O
2
, physiologic 5% O
2
tension greatly enhances the retention of CMCs in the heart at 24 h and 7 days after cell transplantation, especially in the scarred regions where O
2
is very low (1-2%). Thus, culture at 5% O
2
may improve the reparative properties of CMCs (and possibly other cell types) used for cell therapy, providing an approach that may be applicable in the clinic.
Abstract 16886: Wall Stress Profiles in Tricuspid Aortic Valve Associated Ascending Thoracic Aortic Aneurysms: The Effect of Surgical Threshold Diameter ≥5.5cm
Authors: Gomez Axel , Wang Zhongjie , XUAN Yue , Ge Liang , Tseng Elaine E
Published: May 2021

Introduction:
Ascending thoracic aortic aneurysms (aTAAs) carry a risk of dissection. Elective repair guidelines are designed around size thresholds, but the one-dimensional parameter is insufficient to predict acute events in small aneurysms. Biomechanically, aortic events can occur when wall stress exceeds wall strength. Patient-specific aTAA wall stresses may be a better predictor of complications. Our aim was to compare wall stresses in aTAAs associated with a tricuspid aortic valve (TAV) based on diameter.

Methods:
Patients with TAV-aTAA and diameter >4.0cm (n=448) were divided into groups by 0.5 cm diameter increments. Pre-stress three-dimensional aneurysm geometries were reconstructed from ECG-gated computer tomography images. A fiber-embedded hyperelastic material model was applied to obtain longitudinal and circumferential wall stress distributions under systolic pressure. Medians with interquartile ranges are reported. The Kruskal-Wallis test is used for comparisons between size groups.

Results:
Peak longitudinal wall stresses for TAV-aTAA were 308[282-338] kPa for size 4.0-4.4cm vs 341[309-362] kPa for 4.5-4.9cm vs 339[289-370] kPa for 5.0-5.4cm vs 319[297-355] kPa for 5.5-5.9cm vs 373[364-449] for 6.0cm (p=0.003). Peak circumferential wall stresses were 487[448-579] kPa for size 4.0-4.4cm vs 516[473-619] kPa for 4.5-4.9cm vs 506[422-580] kPa for 5.0-5.4cm vs 540[468-591] kPa for 5.5-5.9cm vs 565[506-634] for >6.0cm (p=0.19) (figure). 95th-percentile longitudinal peak stress for TAV-aTAA <5.5cm vs ≥5.5cm is 408 vs 465 kPa.

Conclusions:
Longitudinal wall stresses are higher as diameter increases. The 95% percentile longitudinal peak stress for diameter ≥5.5cm is ~450 kPa, which correlates with established ~5% dissection risk for size ≥5.5cm. Wall stress thresholds may be a better predictor of patient-specific risk of dissection than diameter and require testing in clinical trials.