bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15314: Gene Therapy With Pellino1 Improves Perfusion and Decreases Tissue Loss in an Flk-1 Heterozygous Murine Limb Ischemia Model But Fails in Mapkapkinase 2 Knockout Mice
Authors: Accorsi Diego , Thirunavukkarasu Mahesh , Ukani Gopi , Youssef Mark , Swaminathan Santosh , Palesty J. Alexander , Maulik Nilanjana
Published: May 2021

Introduction:
Peripheral vascular disease (PVD) is a major cause of morbidity in the US. Vascular endothelial growth factor (VEGF) induces angiogenesis through Fetal-Liver Kinase-1 (Flk-1 or VEGFR-2), an endothelial tyrosine kinase receptor which activates a downstream signaling cascade involving MAPKAPKinase2 (MK2). We have demonstrated poorer recovery in hind limb ischemia models using Flk-1
+/-
and MK2
-/-
knockout mice compared to wild type mice. We also demonstrated overespression of Pellino1 (Peli1), an E3 Ligase, can attenuate ischemic damage and increase neovascularization and survivability of ischemic myocardium and skin flaps. Therefore, in this study we aim to show if Peli1 gene therapy can help rescue function in Flk-1
+/-
and MK2
-/-
after femoral artery ligation.

Methods:
8-12 week-old Flk-1
+/-
and MK2
-/-
mice were subjected to femoral artery ligation of the right hind limb and treated with either adenovirus carrying Peli1 (Ad.Peli1) or LacZ (Ad.LacZ), for a total of 4 groups: Flk-1
+/-
Ad.LacZ, Flk-1
+/-
Ad.Peli1, MK2
-/-
Ad.LacZ and MK2
-/-
Ad.Peli1. Perfusion was assessed with laser Doppler imaging preop and on days 0, 3, 7, 14, 21 and 28. Extent of limb ischemia was also quantified using a standardized scoring scale (0 = no ischemia, to 8 = full limb amputation).

Results:
Perfusion was significantly higher in the Flk-1
+/-
Ad.Peli1 group compared to Flk-1
+/-
Ad.LacZ on days 7 (0.19±0.03 vs 0.08±0.02), 14 (0.41±0.07 vs 0.09±0.03), 21 (0.33±0.05 vs 0.14±0.05) and 28 (0.31±0.05 vs 0.15±0.02) (n=9-15, p<0.05). The level of ischemia (ischemic score) was significantly lower in the Flk-1
+/-
Ad.Peli1 group when compared to Flk-1
+/-
Ad.LacZ on days 3 (1.89±0.56 vs 4.88±0.85), 7 (2.11±0.54 vs 5.69±0.92), 14 (2.18±0.52 vs 6.31±1.02), 21 (1.83±0.58 vs 6.50±1.05) and 28 (1.67±0.62 vs 6.50±1.05) (n=8-9, p<0.05). There was no difference in perfusion or ischemic score between the MK2
-/-
Ad.Peli1 and MK2
-/-
Ad.LacZ groups. Values are mean +/- SEM.

Conclusions:
Treatment with Ad.Peli1 resulted in improved perfusion and decreased tissue ischemia in Flk-1
+/-
mice. These results were not paralleled in MK2
-/-
mice suggesting that Peli1 acts upstream to MK2 but downstream of VEGF/Flk-1. Overall, Peli1 gene therapy is a promising candidate in the management of PVD.
Abstract 15324: Mavacamten Favorably Impacts Key Pathophysiologic Processes in Obstructive Hypertrophic Cardiomyopathy: Results From the EXPLORER-HCM Study
Authors: Hegde Sheila M , Abraham Theodore P , Jacoby Daniel , Wang Andrew , Ho Carolyn , Li Wanying , Sehnert Amy J , Solomon Scott D , olivotto iacopo , Lester Steven J
Published: May 2021

Introduction:
Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by dynamic LV outflow tract (LVOT) obstruction resulting from ventricular hypertrophy and mitral valve systolic anterior motion (SAM), and by elevated left ventricular (LV) filling pressures, all of which result in a significant morbidity despite medical therapy. Mavacamten (Mava) is a novel inhibitor of cardiac myosin that significantly reduces LVOT gradients in oHCM, noted initially in the phase 2 PIONEER and more recently in the phase 3 EXPLORER-HCM studies. Additional echocardiographic analyses were performed to investigate the effect of Mava on focused measures of cardiac structure and function in oHCM.

Methods:
EXPLORER-HCM (NCT03470545) was a multicenter, double-blind, placebo-controlled, phase 3 study that randomized symptomatic oHCM patients (LV ejection fraction ≥55% and resting and/or provoked LVOT gradient ≥50 mmHg) 1:1 to Mava vs placebo for 30 weeks. Echocardiograms were performed serially every 2-4 weeks over 30 weeks.

Results:
In total, 251 patients with oHCM were enrolled and 244 patients completed the study (mean age 58.5; 40.6% female). Compared to placebo, 30-week treatment with Mava led to significant reductions in LA volume index (-7.5 ml/m
2
, p<0.0001), lateral E/e’ (-3.8, p<0.0001), septal E/e’ (-3.4, p<0.0001), and LV mass index (-15.5 g/m
2
, p<0.0001) (
Table
). Significantly more Mava-treated patients achieved resolution of mitral valve SAM compared to placebo (80.9% vs 34.0% of patients; difference of 46.8%; p<0.0001) and mitral regurgitation (MR) (9.0% vs 0.0% of patients; difference of 9.0%; p=0.0006).

Conclusions:
Treatment with Mava for 30 weeks led to improvement in LV hypertrophy and markers of left-sided filling pressures (LA volume and E/e’). Furthermore, Mava treatment was associated with reduction of SAM and MR. These findings suggest that Mava has beneficial effects on several adverse pathophysiologic processes that are hallmarks of oHCM.
Abstract 15356: Echocardiographic Features in Neuromuscular Diseases
Authors: Kim Byung-Jun , Nam Jong-Ho , Kim Hun-Tae , Park Jong-Il , Son Jang-Won
Published: May 2021

Introductions:
Cardiac involvement is a major cause of morbidity and mortality in neuromuscular disease patients. However, echocardiographic features in these patients have not been well evaluated. We aimed this study to analyze echocardiographic features of the patients with neuromuscular disease

Methods:
We retrospectively enrolled 112 adult patients with neuromuscular disease who performed echocardiography. Patients were divided into two groups according to the main involving site; diseases that invades the nervous system (Group 1, N=51) and diseases that invades muscular system (Group 2, N=62); and echocardiographic features were analyzed. Group 1 was consisted with amyotrophic lateral sclerosis (43 patients), Guillain-Barre’s syndrome (4 patients), and other diseases (4 patients). Group 2 was consisted with Duchenne muscular dystrophy (6 patients), myotonic muscular dystrophy (4 patients), spinal muscle atrophy (2 patients) and unclassified muscular dystrophy (49 patients)

Results:
Compared with the Group 1, the patients in Group 2 were younger (62.4±11.5 vs. 37.2±14.4, p<0.001), had significantly lower ejection fraction (EF : 52.1±13.7% vs. 62.2±7.7%, p<0.001), had larger left ventricular (LV) size (end systolic LV dimension: 32.7±8.6mm vs. 29.0±4.8mm, p<0.001) and thinner interventricular septum (IVSd: 7.42±1.61mm vs 8.88±1.57mm, p<0.001). Group 2 also showed lower A velocity, higher E/A ratio and shorter deceleration time (DT) compared with Group 1 (A velocity : 0.507±0.147cm/s vs. 0.781±0.219cm/s , p<0.001, E/A ratio : 1.398±0.657 vs. 0.801±0.242, p<0.001 and DT : 191.5±52.6 vs. 219.7±42.9, p=0.004)

Conclusions:
Patients with neuromuscular disease mainly involving muscular system had lower LV systolic function and impaired diastolic function compared with the patients mainly involving nervous system. More careful cardiac evaluation should be performed in these patients.
Abstract 15365: Natural History of Immune Checkpoint Inhibitor Associated Myocarditis With Preserved Ejection Fraction
Authors: Nowatzke Joseph , Power John R , Meijers Wouter C , Orimoloye Olusola , Fenioux Charlotte , Tamura Yuichi , Cautela Jennifer , Lehmann Lorenz H , Finke Daniel , Hayek Salim , Azam Tariq U , Asnani Aarti , Mehegan Tyler , Weppler Alison , Baik Alan H , Aras Mandar A , Narezkina Anna , Arangalage Dimitri , rocher fanny , Alexandre Gerard , Palaskas Nicolas L , Salem Joe-elie , Moslehi Javid
Published: May 2021

Introduction:
Immune Checkpoint Inhibitor (ICI)-associated myocarditis can be fatal, and is often characterized by arrhythmogenicity, although > 50% present with preserved ejection fraction (pEF). The natural history of ICI-myocarditis with pEF is unknown.

Methods:
We utilized a multicenter network of ICI-myocarditis cases spanning 12 countries to identify 83 cases of definite or probable myocarditis presenting with an EF above 50% on initial echocardiography. We further stratified patients based on continued pEF or worsening EF (rEF) during hospitalization. We compared independent variables, vital signs on presentation, and laboratory values between the two groups. Mortality was defined as those who died or were discharged to hospice within 90 days from admission. Fulminant myocarditis was defined as need for circulatory support, atrioventricular block requiring electrical pacing, ventricular tachycardia or fibrillation, or cardiac arrest while in the hospital.

Results:
Of the 83 patients, 15 developed a rEF; 68 maintained pEF during hospitalization. Although no significant change in heart rate was noted on presentation, systolic blood pressure was lower in the rEF group (111 vs 129, p=0.010). The rEF cohort were more prone to have a peak troponin elevation (432 vs 41, p=0.021), and to develop fulminant myocarditis (73% vs 26%, p=<0.001). Both in-hospital mortality (46% vs 17%, p=0.015) and 90-day all-cause mortality were significantly increased in those who develop a rEF (72% vs 29%, p=0.007). Overall, there was a 36.8% 90-day mortality rate for all those presenting with an initially normal EF.

Conclusions:
Patients with ICI-myocarditis can still have a fulminant course despite initial echocardiogram revealing EF>50%. In our database, 18% go on to develop new rEF and 73% die in the following 90 days. Decreased BP and troponin on presentation may identify patients at risk of subsequent rEF and fulminant course.
Abstract 15366: Cancer Diagnosis Following Bleeding in Patients With Atrial Fibrilation Undergoing Anticoagulation Therapy
Authors: Cespon-Fernandez Maria , Raposeiras-Roubin Sergio , Abu-Assi Emad , Barreiro-Pardal Cristina , Muñoz-Pousa Isabel , Cobas-Paz Rafael J. , Parada-Barcia Jose A. , Represa-Montenegro Marta , Melendo-Viu Maria , Íñiguez-Romo Andrés
Published: May 2021

Introduction:
Bleeding is frequent in patients with atrial fibrillation (AF) undergoing oral anticoagulation (OAC), and may be the first manifestation of underlying cancer. OAC could be usefull as a screening tool to unveil an occult cancer and enhance early diagnosis.

Hypothesis:
We aim to analyze whether bleeding represents an useful tool to unmasking an occult cancer in AF patients treated with OAC.

Methods:
We used a cohort including all patients ≥ 75 years-old from the health area of Vigo (Galicia, Spain) with AF between 2014 and 2017 (CardioCHUVI-AF_75 registry).

Results:
Of 8,753 AF patients evaluated (mean age, 82.7 years; women, 61.7%), 2,171 (24.8%) experienced any (major or non-major) bleeding and 479 (5.5%) were diagnosed with cancer (mean follow-up of 3 years). Among 2,171 who experienced bleeding, 198 (9.1%) were diagnosed with cancer. Patients with bleeding have a 3-fold higher risk of new cancer diagnosis compared with those without bleeding (4.7 per 100 patient/year vs1.4 per 100/patients year; hazard ratio [HR]: 3,72 [95% CI 3.05-4.55]). Gastrointestinal bleeding was associated with a 13-fold higher hazard of new gastrointestinal cancer diagnosis (HR 13.44 [95% CI 9.11-19.85]). Genitourinary bleeding was associated with an 18-fold higher hazard of new genitourinary cancer diagnosis (HR 18.11 [95% CI 12.52-26.20]). And bronchopulmonary bleeding was associated with a 15-fold higher hazard of new bronchopulmonary cancer diagnosis (HR 15.78 [95% CI 6.03-41.28]). For those other bleeding (non-gastrointestinal, non-genitourinary, non-bronchopulmonary), the HR for cancer was 2.31 (95% CI 1.47-3.64).

Conclusions:
Any gastrointestinal, genitourinary, or bronchopulmonary bleeding was associated with higher rates of new cancer diagnosis in AF patients undergoing OAC. These bleeding events behave as an useful screening tool and should encourage prompt investigation for underlying cancers at those sites.
Abstract 15371: Risk of Early Recurrent Myocardial Infarction After Index Myocardial Infarction Stratified by Index Treatment Strategy
Authors: Nair Raunak , Johnson Michael , Kravitz Kathleen A , Rajeswaran Jeevanantham , Anabila Moses , Blackstone Eugene H , Menon Venu , Lincoff A Michael M , Kapadia Samir R , Khot Umesh N
Published: May 2021

Introduction:
Survivors of Myocardial Infarction (MI) remain at increased risk for another cardiovascular event. The purpose of our study was to assess the role of index treatment strategy in developing early recurrent MI after acute MI.

Methods:
We analyzed all cases of MI at a single quaternary care medical center from January 1
st
, 2010 to January 1
st
, 2017, and identified all cases of recurrent MI within 90 days of index MI. Early recurrent MI cases were further stratified depending on the treatment strategy for index MI. Reinfarctions were also stratified according to the time of readmission into early (0-30 days after discharge) and late (30-90 days after discharge) time periods.

Results:
We identified 6,626 patients admitted with an acute MI and 168 cases of recurrent MI within 90 days of discharge. Among the index MI patients, 4354 (66%) patients underwent revascularization whereas 2272 (34%) underwent medical management. An unadjusted comparison of the risk of readmission among the 3 different revascularization strategies showed that the CABG group appeared to have the lowest risk of readmission with a recurrent MI, and there was no significant difference in the late risk of readmission between PCI and CABG groups (P=0.8). The medically managed group had the highest late risk of readmission with a recurrent MI.

Conclusions:
The risk of readmission with a recurrent MI is higher in patients who undergo medical management for index MI. Aiming to improve the standard of care in these patients should be the focal point of interest to curb these reinfarctions.
Abstract 15375: Patients With Congenitally Corrected Transposition of the Great Arteries Following Anatomic Repair Are at Risk of Impaired Quality of Life
Authors: Lim Tiffany R , Watkins Kimberly , Hartog Rebecca R , Wilde Megan , Rodenbarger Andrew , Afton Katherine , Lowery Ray , Yu Sunkyung , Ohye Richard G , Dorfman Adam L , Goldberg Caren S
Published: May 2021

Introduction:
Children with complex congenital heart disease (CHD) are at increased risk for neurodevelopmental impairments and reduced quality of life (QOL). Patients (pts) with congenitally corrected transposition of the great arteries (ccTGA) often undergo anatomic repair to make the left ventricle the systemic ventricle, with the goal of long term cardiac benefits. Understanding long-term outcomes and QOL may inform preoperative counseling and treatment strategies for ccTGA.

Methods:
We measured QOL using PedsQL generic and cardiac modules for pts following anatomic repair of ccTGA with Senning/Arterial Switch or Senning/Rastelli operations. Impaired QOL by the PedsQL is defined by total scores <65.4 for parent report and <69.7 for pt report (possible score 0-100). Scores were compared to healthy controls and to pts with other forms of CHD, previously described in existing literature. Risk analysis for QOL impairment was performed using univariate logistic regression.

Results:
Of 88 eligible pts, 56 (64%) returned surveys (29% female, median age 11.8 years). Respondents were more likely to have pre-operative arrhythmias or pacemaker implantation compared to non-respondents. Mean total PedsQL score was 72
+
19 for pt report and 75
+
18 for parent report; 22 of 56 (39%) pts had impaired QOL scores, compared to 20% impaired scores in pts with any type of CHD, previously described. Mean physical functioning score was 72
+
22 for pt report and 76
+
21 for parent report. Mean psychosocial summary score was 73
+
18 and 75
+
18 for pt and parent report, respectively. Communication was the lowest scored subscale of the Cardiac module by pt (63
+
26) and parent (66
+
31) report. The treatment II subscale addressing medication compliance was the highest scored subscale with scores of 90
+
8 for pts and 91
+
15 for parent, respectively. Longer cardiopulmonary bypass time (p = 0.01), surgical or catheter-based reintervention following hospital discharge (p = 0.02) and heart failure symptoms (p = 0.04) were associated with impaired QOL.

Conclusions:
After anatomic repair of ccTGA, pts are at risk of impaired QOL compared to healthy controls and to pts with a broad range of CHD. Indicators of more complex surgical and post-operative courses were associated with impaired QOL.
Abstract 15380: Association of Change in Body Mass Index With Premature Atrial Contractions Frequency and Atrial Fibrillation in Older Age: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Decker Joseph , Wang Wendy , Norby Faye L , Parikh Romil , Reyes Jorge L , Alonso Alvaro , Lutsey Pamela L , Soliman Elsayed Z , Ndumele Chiadi E , Chen Lin Y
Published: May 2021

Introduction:
The proportions of obese and aging adults are rapidly growing. While obesity and advancing age are associated with atrial fibrillation (AF), data are limited on weight change in the elderly as a risk factor for premature atrial contractions (PACs)—which are known to precede AF—or AF.

Hypothesis:
Compared to a stable body mass index (BMI) over time, increasing BMI will be associated with a higher PAC frequency and AF in elderly participants in ARIC.

Methods:
We included N=2,070 ARIC participants [age mean ± SD 79 ± 4.5 years, 59% female] without known AF who attended visit 6 and wore an ambulatory ECG-monitoring device (Zio XT® Patch, iRhythm Technologies Inc.) for ≥48 hours. BMI change was defined as change between V5 (2011-13) and V6 (2016-17) and was categorized into 4 groups: >10% decrease, 2 to 10% decrease, -2 to 2% change (stable BMI) and > 2% increase. PAC frequency was defined as percent of beats that are PACs. Linear regression was used to evaluate the association between BMI change and % PAC. Incident AF was ascertained after V6 through 2018 from hospital discharge codes and death certificates. Logistic regression was used to evaluate the association between BMI change and incident AF.

Results:
Median PACs per hour were 8.84. Participants with >2% BMI increase had 0.35% (95% CI: 0.06%-0.64%) higher frequency of PACs compared to those with stable BMI after multivariable adjustment (Table). After a mean (SD) follow-up of 19 (7) months, there were 82 incident AF cases. Compared to stable BMI, both >2% BMI increase and 2 to 10% decrease were nonsignificantly associated with higher odds of AF compared with stable BMI after multivariable adjustment (Table).

Conclusion:
Increasing BMI in the elderly is associated with higher PAC frequency and is nonsignificantly associated with higher odds of AF compared to stable BMI. This finding suggests that weight management, which is currently emphasized in middle age, may also apply in late-life to prevent atrial arrhythmias.
Abstract 15501: Repeated Social Defeat Exaggerates Cacl2-induced Abdominal Aortic Aneurysm Expansion by Suppression of Periaortic Fibrosis in Tissue Repair Phase
Authors: Kubota Hiroshi , Yamada Hiroyuki , Sugimoto Takeshi , Miyawaki Daisuke , Wakana Noriyuki , MATOBA Satoaki
Published: May 2021

Background and Objective:
Depression is an independent risk factor of cardiovascular disease and significantly associated with the prevalence of abdominal aortic aneurysm (AAA). We investigated the impact of repeated social defeat (RSD) on AAA formation.

Methods and Results:
Eight-week-old male WT mice were exposed to RSD by housing with a larger CD-1 mouse in a shared cage. They were subjected to vigorous physical contact daily for 10 consecutive days. Control mice were housed in the same cage without physical contact. After social interaction test to confirm depressive-like behaviors, mice underwent application of 0.5M calcium chloride (CaCl
2
) on the infrarenal aorta. At one-week, maximum diameter and circumference of external elastic membrane were comparable between the two groups. The number of F-4/80 and MMP-9-positive cells in immunofluorescent images were also comparable. Consistently, fluorescent image taken by IVIS revealed no difference in MMP activity, suggesting that acute inflammatory response was comparable between the two groups. In contrast, at two weeks, maximum diameter and circumference of external elastic membrane were significantly increased in defeated mice (
p
< 0.01). Intriguingly, periaortic fibrotic area in aneurysmal portion was markedly decreased in defeated mice (12.5х10
3
μm
2
vs. 3.7х10
3
μm
2
, Control vs. Defeat,
p
< 0.01). Consistently, accumulation of α-SMA-positive cells in adventitia of aneurysmal portion was much lesser in defeated mice (876 cells/mm
2
vs. 319 cells/mm
2
, Control vs. Defeat,
p
< 0.05), whereas those in tunica media of non-aneurysmal portion did not show any difference between the two groups. LPS-induced iNOS gene and protein expressions in bone marrow-derived macrophages (BMDMs) were significantly decreased in defeated mice, whereas the TGF-β-induced phosphorylation of Smad2 and ERK1/2 in primary cultured aortic VSMCs were comparable between the two groups.

Conclusions:
Our findings demonstrate that RSD enhances AAA expansion by suppressing the periaortic fibrosis following inflammatory response, and suggest that decreased NO production from accumulated macrophages contributes to the reduced VSMCs proliferation and collagen deposition.
Abstract 15532: Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction and a Worsening Heart Failure Event
Authors: CARNICELLI Anthony P , Clare Robert M , Hofmann Paul , Chiswell Karen , Devore Adam D , Vemulapalli Sreekanth , Felker Michael , Sarocco Phil , Mentz Robert J
Published: May 2021

Background:
Several recent heart failure trials enrolled patients with heart failure with reduced ejection fraction (HFrEF) who had a worsening heart failure (WHF) event.

Aim:
To describe the characteristics and outcomes of patients with HFrEF and a WHF event at a large tertiary medical center.

Methods:
We identified patients 18-85 years of age with chronic symptomatic HFrEF (EF ≤35% and ≥2 HF encounters in the prior 18 months) treated at Duke University between Jan 2009-Dec 2018 through the Duke Echo Lab Database. A WHF event was defined as either a hospitalization or ED visit for HF in the prior 12 mos. A set of exclusion criteria [e.g., renal dysfunction, left ventricular assist device (LVAD), heart transplant] were applied to patients with a WHF event to generate a patient cohort similar to those enrolled in contemporary HF trials. We did not restrict the cohort based on BP or BNP levels since these vary over time. Baseline characteristics and outcomes including death and hospitalization were assessed.

Results:
Of 4846 unique patients with HFrEF, 3668 (76%) had a WHF event in the year prior to index echo. Sequentially, patients with GFR <20 mL/min/1.73 m
2
(n=458), LVAD (n=291), or heart transplant (n=95) were excluded; 2824/4846 (58%) remained in the WHF study population.

HFrEF patients with WHF were typically men (68%) with median age of 65 years (IQR 54, 73) and low EF (EF <25% in 57%). Coronary disease (71%), diabetes (44%), and elevated NT-proBNP (median 2405 pg/mL [698, 6841]) were common. Beta-blocker, ACEi/ARB, and MRA use were 88%, 79% and 44%, respectively. HFrEF patients with WHF had a high 30-day, 1-year, and 5-year cumulative incidence of all-cause mortality and HF hospitalization after index echo (FIGURE).

Conclusions:
In patients with chronic HFrEF at Duke University, 76% had a WHF event in the past year and 58% met several of the key eligibility criteria of contemporary HF trials. Patients with recent WHF had a high burden of comorbidities and very high event rates.
Abstract 15534: Fully Automated "Hands-off" Evaluation of Left Atrial Volume in Children
Authors: Kauffman Hunter , Whitehead Kevin K , Convery Michael , O’Connor Matthew J , Quartermain Michael , Banerjee Anirban
Published: May 2021

Introduction:
Three-dimensional echocardiography (3DE) has been shown to be superior to two-dimensional echocardiography (2DE) for the quantification of chamber volumes and dimensions. However, the utility of 3DE in routine clinical practice has been restricted by time-consuming analysis and the need for 3D-specific training. This study aims to assess the accuracy and clinical utility of Philips Dynamic Heart ModelA.I. (DHM), a “hands off” automated software program, that may be used to measure LA chamber dimensions. This is notable, as indexed LA volume has been used as a predictor of heart failure in adults.

Hypothesis:
We hypothesize that DHM will be able to quickly and accurately calculate left atrial chamber volume when compared to Cardiac MRI (CMRI) used as a gold standard.

Methods:
To date, 10 patients (Average Age 14.8±1.9) have undergone clinically indicated CMRI, immediately followed by 3DE, at the Children’s Hospital of Philadelphia. 3D images were analyzed via DHM without manual editing (hands-off approach). DHM automatically calculated maximum LA volume. LA volume was also calculated from CMRI images using the biplane method. LA volume measurements by DHM were correlated with CMRI.

Results:
DHM was able to calculate LA volume in an average time of 32±8 seconds, without additional human input. Furthermore, inter-technique correlations showed that LA volume measurements made via DHM correlated very well with LA volume measurements made via CMRI (R=0.85, p<0.005). (Figure 1)

Conclusions:
In children, fully automated evaluation of LA volume based on artificial intelligence is a viable alternative to time-consuming 3D analysis when compared to a CMRI gold standard. This method of “hands-off” analysis may prove to be useful in situations where trained 3D personnel are unavailable. Furthermore, the utilization of this method may result in a greater integration of 3D LA volume into routine clinical practice.
Abstract 15540: Prevalence and Sociodemographic Determinants of Food Insecurity Among Adults With Atherosclerotic Cardiovascular Disease in the United States
Authors: Mahajan Shiwani , Grandhi Gowtham R , Valero Elizondo Javier , Acquah Isaac , Yahya Tamer , Virani Salim S , Blankstein Ron , Blaha Michael J , Cainzos-Achirica Miguel , Nasir Khurram
Published: May 2021

Background:
High out-of-pocket healthcare expenditures among US adults with atherosclerotic cardiovascular disease (ASCVD) may expose them to food insecurity, which can lead to worse health outcomes. However, few studies have examined the prevalence and determinants of food insecurity in this population.

Methods:
Using data from the 2013-18 National Health Interview Survey, a nationally representative annual survey of the US, we assessed prevalence and sociodemographic determinants of food insecurity among adults (≥18 years) with ASCVD. Food insecurity was defined as 3+ affirmative responses on a validated 10-item questionnaire with a 30-day look-back period.

Results:
Among 190,113 adults included, 18,442 (8.2%; ~19.9 million US adults annually) had ASCVD (38.3% <65 years; 47.6% women). Overall, 14.6% adults with ASCVD (~2.9 million US adults annually) reported being food insecure compared with 9.1% among those without ASCVD. Among adults with ASCVD, those who were <65 years, women, Black or Hispanic, uninsured, and had low income had significantly higher odds of reporting food insecurity (Table). On assessment of the cumulative effect of these high-risk characteristics, 4.2% individuals were food insecure among those with ≤1 of these characteristics compared with 18.1%, 36.0%, and 43.7% among those with 2, 3, and ≥4 high-risk characteristics, respectively. Using multivariable analyses, individuals with 2, 3, and ≥4 high-risk characteristics had nearly 4-fold (OR 4.26, 95% CI 3.59-5.07), 10-fold (OR 9.73, 95% CI 8.15-11.62), and 15-fold (OR 15.34, 95% CI 12.07-19.49) higher odds of being food insecure compared with those with ≤1.

Conclusion:
Nearly 1 in 7 adults with ASCVD in the US reported food insecurity, with prevalence being as high as 50% among the most vulnerable sociodemographic subgroups. There is a critical need to address the hindrances relating to social determinants of health, including food insecurity, among adults with ASCVD in the US.
Abstract 15563: Association of Weight With Ablation Outcomes in Pediatric Wolff-Parkinson-White Syndrome: Analysis of the NCDR® IMPACT Registry
Authors: Janson Christopher M , Shah Maully J , kennedy kevin , Iyer Ramesh , Behere Shashank P , Sweeten Tammy , O’Byrne Michael L
Published: May 2021

Introduction:
Guidelines for electrophysiology study (EPS) and catheter ablation in Wolff-Parkinson-White syndrome (WPW) are based on age. Size is an established factor in ablation risk and may be the more appropriate factor to consider when deciding timing of EPS.

Hypothesis:
Weight <30 kg is associated with higher rates of major adverse events (MAE) and deferred ablation, and lower rates of success.

Methods:
A multicenter retrospective cohort study was performed on children age 1-21 years with WPW and first-time EPS data in IMPACT from 4/16-12/19, excluding those with congenital heart disease, cardiomyopathy, and > 1 ablation target. MAE were defined as cardiac arrest, stroke, tamponade, permanent pacemaker, or unplanned cardiac / vascular surgery. Ablation success was evaluated in those with attempts. Multivariable logistic regression models were used to adjust for measurable confounders - accessory pathway (AP) type, AP location, and use of cryoablation (cryo).

Results:
4456 subjects from 84 centers were evaluated, with 14% <30 kg. Subjects <30 kg were more likely to have pre-operative SVT (45% vs. 29%, p<0.001) and inducible SVT (71% vs. 61%, p<0.001), more likely to have left non-septal APs (46% vs. 37%, p<0.001), and less likely to have right septal APs (25% vs. 33%, p<0.001, Table). No difference was seen in the likelihood of deferred ablation based on weight (9.5% vs. 12%, p=0.07). Ablation success was higher in <30 kg: 95% vs. 92% (p=0.009). This effect persisted after adjusting for measurable covariates (OR 1.7, 95% CI 1.03-2.7, p = 0.04). Left non-septal AP location was also associated with success (OR 2.9, CI 1.9-4.2, p <0.0001), and cryo was negatively associated (OR 0.4, CI 0.3-0.5, p<0.0001). MAE were rare, though with higher incidence in <30 kg (0.3% vs. 0.05%, p=0.04).

Conclusions:
In this analysis of WPW patients with ablation data in IMPACT, weight <30 kg was associated with increased ablation success; a higher incidence of MAE (which were rare) was observed.
Abstract 15566: Autonomic Modulation by Cardiopulmonary Rehabilitation in Heart Failure With Reduced Ejection Fraction: Who Benefits?
Authors: Notarius Catherine F , Keir Daniel A , Badrov Mark B , Millar Philip J , Oh Paul , Floras John S
Published: May 2021

Introduction:
Elevated muscle sympathetic nerve activity (MSNA) both at rest and during dynamic cycling relates inversely to peak oxygen uptake (VO
2peak
) in patients with heart failure due to a reduced ejection fraction (HFrEF). We observed a drop in MSNA both rest (-6±2 bursts/min) and mild exercise (-4±2) in HFrEF patients after 6 months of cardiac rehabilitation.

Hypothesis:
We hypothesized that after training those HFrEF patients with LOW VO2peak (less than median 74% of age predicted) would have a larger decrease in MSNA during dynamic exercise than those with HIGH VO2peak (over 74%).

Methods:
In 21 optimally treated HFrEF patients (5 Female) (13 HIGH: mean VO
2peak
=26 ml·kg/min; 98% of predicted; 8 LOW VO
2peak
=12; 50%) we assessed VO
2peak
(open-circuit spirometry), heart rate variability (HRV) and fibular MSNA (microneurography) at rest, during 1-leg cycling (2 min each of mild and moderate intensity upright 1-leg cycling, n=19) and recovery before and after 6 months of exercise training (45 min aerobic exercise, 5 days/ wk at 60-70 % of VO
2peak;
and resistance training 2 days/wk).

Results:
HIGH and LOW groups had similar age (63±3 vs 63±4 years) , LVEF (30±2 vs 28±3%), BMI, resting heart rate (HR), blood pressure and MSNA (52±3 vs 50±3 bursts/min). Training increased VO
2peak
in both groups (main effect P=0.009), with no group difference in HR response or ratings of perceived exertion. MSNA at rest tended to decrease after training in the HIGH but not LOW group (interaction P=0.08). MSNA during cycling increased in both HIGH (P=0.04) and LOW (P<0.001) groups but was blunted post-training in the HIGH group only (P=0.04 vs. 0.90 in LOW). Training-induced sympatho-inhibition during exercise recovery occurred in the HIGH but not LOW group (interaction P=0.01). In contrast, HRV was not improved by training in either group.

Conclusions:
Contrary to our hypothesis, the sympatho-inhibitory effect of 6 months of exercise-based cardiac rehabilitation favours HFrEF patients with an already normal VO
2peak
. This suggests that increasing initially low VO
2peak
may be insufficient to trigger beneficial exercise and recovery autonomic modulation and altered training paradigms may be required in such patients.
Funded by Canadian Institutes for Health Research (CIHR)
Abstract 15580: The Impact of Sex and Gender-related Factors on Length-of-stay Following NSTEMI: A Multicountry Analysis
Authors: Bender Uri , Norris Colleen M , Raparelli Valeria , Christina Tadiri , Pilote Louise
Published: May 2021

Introduction:
Gender refers to psycho-socio-cultural characteristics typically ascribed to men, women and gender-diverse individuals and has been shown to be associated with adverse clinical outcomes in AMI independent of sex. Substantial heterogeneity in hospital length of stay exists among patients admitted with NSTEMI. Whether sex and gender-based differences contribute to length-of-stay (LOS) among patients with NSTEMI remains unknown.

Methods:
To examine the relationship between sex, gender-related factors and LOS in adults hospitalized for NSTEMI, data from the GENESIS-PRAXY (n=1,210, Canada, U.S. and Switzerland), EVA (n=430, Italy) and VIRGO (n=3,572, U.S., Spain and Australia) studies of adults hospitalized for AMI were combined and analyzed. A best-fit linear regression model was selected through incremental analysis by stepwise addition of gender-related variables thought to be different in either impact or distribution between men and women.

Results:
Among the overall cohort (n=5,212), 2,218 participants with a diagnosis of NSTEMI were included in the final cohort (66% women, mean age 48.5 years, 67.8% U.S.). Half of the patients had a LOS of longer than 4 days (n=1,124) and were more likely to be white and have a clustering of cardiac risk factors in comparison to those with shorter LOS. No association between sex and LOS was observed in the bivariate analysis (p=0.87). In the multivariable model adjusted for sex, age, country of hospitalization, level of education, marital status, employment status, income, and social support, age (0.062 days/year, p=0.0002), being employed (-0.63 days in workers, p=0.01) and the treatment country relative to Canada (Italy=4.1 days; Spain=1.7 days; and the U.S.=-1.0 days, all p-value<0.001) were significant predictors of LOS.

Conclusions:
Employed individuals are more likely to experience a shorter LOS following NSTEMI. Variation in LOS exists across different countries and is likely due to institutional policy, resource allocation, and differences in cultural and psychosocial influences.
Abstract 15582: Hospitalized COVID-19 Patients With Elevated Cardiac Troponin I Have Increased Overall Mortality and Ventilation Requirements
Authors: Hanna George , Johnson Andre , Napatkamon Ayutyanont , Kubomoto Scott , Biswas Mimi S
Published: May 2021

Introduction:
Coronavirus disease 2019 (COVID-19) causes increased mortality and morbidity in patients with underlying cardiovascular disease. Elevated cardiac troponin I (cTnI) can suggest either a co-concurrent myocarditis or acute primary or secondary myocardial injury. Understanding how laboratory values predict disease severity is important for clinicians to guide therapy and triage patients.

Hypothesis:
cTnI may help identify the subsets of COVID-19 patients that progress to worse clinical outcomes.

Methods:
A cross sectional study was performed utilizing the 184 hospital United States database of HCA. Patients were selected based on inpatient visits to HCA facilities from February 2020 to May 2020 with a COVID-19 diagnosis and at least one cTnI lab test. Patients were divided according to an elevated or normal cTnI value based on the 99th percentile reference range of the test. Outcomes, such as mortality and need for mechanical ventilation, were compared.

Results:
3968 patients hospitalized with COVID-19 were identified. Of those, 3158 patients had at least one cTnI test during their hospitalization. 829 (26%) had at least one positive cTnI during their hospitalization. 328 patients with at least one positive cTnI during their hospitalization died and 174 patients without a positive cTnI died (OR: 14.4 CI: 11.39 -18.30 p<0.0001). 333 patients with positive cTnI required mechanical ventilation, but only 314 with negative cTnI required mechanical ventilation (p<0.001).

Conclusions:
Patients with at least one positive cTnI during their hospitalization had increased mortality. Using a large nationwide database we confirmed previously published findings in smaller patient populations associating cardiovascular disease with COVID-19 severity. Patients with elevated cTnI were also more likely to require mechanical ventilation, suggesting the COVID-19 acute respiratory distress syndrome has a more complicated relationship to troponin levels. These findings suggest that patients with an increased cTnI should be triaged to receive aggressive management. Future steps would be to evaluate effects of aging and other risk factors on the outcome.
Abstract 15602: Sex-differences in Extreme Exercise-induced Adverse Cardiovascular Remodeling
Authors: Sanguesa Gemma , Meza Aline , Alcarraz Anna , Rubies Cira , Mont Lluis , Batlle Montserrat , Guasch Eduard
Published: May 2021

Introduction:
There is emerging evidence in men that sustained high-intensity training promotes an adverse cardiovascular remodeling, thereby increasing the risk of atrial fibrillation, ventricular arrhythmias and coronary calcification. Whether men and women are similarly affected by high intensity exercise-induced harm is unclear. Our aim was to study sex differences in a long-term endurance training rat model.

Methods:
Male and female Wistar rats were subjected to high intensity training for 16 weeks (INT, 60min 60cm/s, male n=20, female n=15). Sedentary rats (SED, male n=20, female n=18) were used as controls. At the end of the training period, rats had an electrocardiogram and echocardiography performed. Vascular fibrosis was assessed in descending aorta, left carotid, and intramyocardial arteries (IMA), right and left atria, and left ventricle (LV) histological samples. mRNA levels of cardiac hypertrophy, fibrosis, oxidative stress and inflammation genes were assessed in LV samples by Real-Time PCR.

Results:
INT male rats presented lower heart rate (382±9, 340±10, SED vs INT, p<0.01) and a longer QRS duration (18.8±0.6, 22.4±1.1, SED vs INT, p<0.01), while these were not modified in the INT female group. Echocardiography showed eccentric LV hypertrophy in both trained male and female rats. High intensity exercise induced fibrosis in the descending aorta and carotid in both males and females, but IMA were only affected in trained male rats. In the heart, exercise-induced atrial fibrosis similarly occurred in both trained male and female rats. No training-induced fibrosis was evident in the LV of both INT male and female rats. Regarding LV mRNA analysis, INT males showed a reduction of desmin, TTN and N2BA/N2B ratio, whereas INT females exhibited higher desmin mRNA levels and lower αMHC/βMHC ratio. Intense exercise did not increase LV mRNA levels of fibrosis, oxidative stress and inflammation markers neither in males nor in females. In comparison to males, females had lower LV myocardial fibrosis as well as lower fibrosis markers.

Conclusions:
Male and female rats exhibit qualitatively different cardiovascular remodeling after extreme exercise. Nevertheless, both sexes might develop exercise-induced adverse vascular and cardiac effects.
Abstract 15624: The Anti-lung Cancer Drug (R)-crizotinib Predisposes and Exacerbates Pulmonary Hypertension
Authors: awada Charifa , Potus Francois , Tremblay Eve , Paulin Roxane , Provencher Steeve , Bonnet Sebastien , BOUCHERAT Olivier
Published: May 2021

Introduction:
Pulmonary arterial hypertension (PAH) is a vascular disease characterized by persistent elevation of pulmonary vascular resistance leading to right heart failure and death. In 10% of cases, PAH is induced by drugs including chemotherapeutic agents such as RTK inhibitors (e.g. dasatinib). (R)-Crizotinib is an ALK/ROS1/MET inhibitor increasingly used for the treatment of non-small cell lung cancer (NSCLC). Interestingly, (R)-Crizotinib has been shown to induce endothelial cells (EC) dysfunction and is associated with dyspnea and peripheral oedema, which are central symptoms of PAH. We thus hypothesized that chronic administration of (R)-Crizotinib exacerbates and predisposes PAH.

Material and results:
We found that daily administration of (R)-Crizotinib (100mg/kg for 2 weeks) in Sugen/Hypoxia (Su/Hx) PAH rat model significantly increased mortality rates. Compared to vehicle-treated rats, (R)-Crizotinib was associated with worsening of hemodynamic parameters (RVSP, mPAP, SV, CO and TPR measured by right heart catheterization; p<0.05; n=4-6). Histologically, (R)-Crizotinib enhanced pulmonary arteries (PA) wall thickness (EVG stain; p<0.05) and increased fibrosis and macrophages accumulation in the lungs and right ventricle. In addition, we showed that pretreatment of rats with (R)-Crizotinib exaggerates the response to monocrotaline (MCT, 40mg/kg), as revealed by histological (increase in vascular remodeling) and hemodynamic measurements (mPAP; TPR; CO) (p<0.01; n=7-10). In vitro, (R)-Crizotinib reduced MET and AKT activation (WB) in human PA endothelial cells promoting endothelial dysfunction via decreased proliferation (Ki67) and increased apoptosis (Annexin V) rates. In addition, (R)-Crizotinib interferes with autophagy flux (increase in LC3-II and p62 accumulation) and was accompanied by the appearance of atypical morphological phenotypes in PA endothelial cells (multinucleated cells).

Conclusion:
We showed for the first time that (R)-Crizotinib treatment predisposes and exacerbates PAH in animal models (Sugen/Hypoxia and monocrotaline). Understanding the mechanism will provide promising perspectives for a better management of patients treated with (R)-Crizotinib or ALK/ROS1/MET inhibitors.
Abstract 15630: Gender-related Differences in the Management of Chronic Coronary Syndrome: Registry Data of a Tertiary Center in Brazil
Authors: Serrano Carlos V , Moreira Eduardo M , Garzillo Cibele L , Montenegro Luiz M , Tabuse Cindy L , Kormann-Moreira Mylena C , segre alexandre W , Bolta Paula M , Favarato Desiderio , Pitta Fabio G , Lima Eduardo G , Rezende Paulo H , Hueb Whady A
Published: May 2021

Introduction:
There is scarce data on sex-related differences in chronic coronary syndrome (CCS) management in low-and-middle-income countries. We aimed to describe those in CCS patients in a tertiary center in Brazil.

Hypothesis:
Multiple gender-related differences may affect management of CCS and, subsequently, influence outcome in developing countries - improvement in tertiary care is justified.

Methods:
Patients from an outpatient clinic with known history of myocardial infarction (MI), coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI), or stable angina with documented coronary artery lesions > 50% were evaluated for differences regarding prescription, laboratory data, symptoms and other clinical variables. Patients were deemed to have optimal goal-directed therapy if blood pressure (BP) was < 140/90 mmHg, LDL-cholesterol < 70 mg/dL and were in use of antithrombotics. We also assessed incidence of MI, stroke or death.

Results:
625 patients, 208 (33.3%) women and 417 men, were included. We found no sex-related differences in mean age (65 years, SD 9.6 for the cohort) or in prevalence of previous MI, CABG or PCI. Women had higher systolic BP (134 vs 128 mmHg, p < 0.001), higher left ventricular ejection fraction (56 vs 51%, p < 0.001), lower creatinine clearance (69 vs 73 mL/min, p= 0.04), and higher LDL (103 vs 87 mg/dL, p < 0.001). We found no differences regarding glucose levels, BMI or symptoms. Women were less likely to be prescribed calcium-channel blockers (p = 0.04), but equally likely to be prescribed statins. Gender-related differences in LDL and BP were present even after adjustments. Women were less likely to have optimized goal-directed therapy (14.9% vs 28.3%, p < 0.001), even after adjustments. Gender was not associated with event-free survival on one-year follow-up (97% vs 98%).

Conclusions:
In this setting, women had higher LDL-cholesterol, higher SBP, and lower proportion of optimized goal-directed therapy than men, but gender was not related to worse one-year prognosis.
Abstract 15634: High-fat Diet Consumption Accelerates Cardiometabolic Impairment via Deteriorating Mitochondrial Function in Non-obese Spontaneously Type 2 Diabetic Rats
Authors: Pongkan Wanpitak , JINAWONG KEWARIN , Chattipakorn Siriporn , CHATTIPAKORN Nipon
Published: May 2021

Introduction:
Type 2 Diabetes Mellitus (T2DM) is a complex disease which is related to genetic, environmental, and lifestyle factors. In genetically-induced T2DM rats, normal diet could induce spontaneous diabetes, and induce left ventricular (LV) dysfunction over time. However, the effect of high-fat diet (HFD) in these genetically-induced T2DM rats on the cardiometabolic changes, including LV function and cardiac mitochondrial function has rarely been investigated.

Hypothesis:
High-fat diet (HFD) consumption accelerates the development of T2DM and LV dysfunction by inducing mitochondrial dysfunction in genetically-induced non-obese T2DM-Spontaneously Diabetic Torii (SDT) rats.

Methods:
Male SDT rats (n=18/group) were divided into 2 groups to receive either normal diet (ND, 19.77% fat) or HFD (57.60% fat) for 4, 8 or 12 weeks. At each time course, cardiac function determined by echocardiography and the pressure-volume loop determined by invasive intracardiac catheterization were assessed. The heart was removed to study cardiac mitochondrial function at each time-course.

Results:
The body weight, food intake, and visceral fat were not different between ND and HFD rats at any times. Increased blood glucose was seen earlier at week 4 in HFD rats, but later at week 12 in ND rats. The development of LV contractile dysfunction and decreased stroke volume was observed earlier at week 8 in HFD rats, compared to ND rats and HFD rats at the baseline. Increased cardiac mitochondrial ROS production and decreased mitochondrial membrane potential (i.e. mitochondrial depolarization) was observed earlier at week 8 in HFD rats, compared to ND rats (Fig).

Conclusions:
High-fat diet accelerates cardiometabolic impairments via impaired cardiac mitochondrial function in genetically-induced non-obese T2DM rats.