bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15318: Longitudinal Changes in Pulmonary Pressure in Late Life: The Atherosclerosis Risk in Communities Study
Authors: Zierath Rani , Claggett Brian , Skali Hicham , Matsushita Kunihiro , Kitzman Dalane W , Konety Suma H , Mosley Thomas , Shah Amil M
Published: May 2021

Introduction:
While the prognostic implications of higher pulmonary artery systolic pressure (PASP) are well established, few data exist regarding longitudinal change in pulmonary pressure in the community. We characterized longitudinal changes in PASP over ~6.5 years in late life, and identified predictors of this change.

Methods:
We studied 1,426 elderly participants in the prospective, community-based Atherosclerosis Risk in Communities (ARIC) study who underwent protocol echocardiography and had assessable tricuspid regurgitation spectral Doppler at 5
th
(2011-2013) and 7
th
(2018-2019) study visits. We used multivariable linear regression to identify clinical, echocardiographic and biomarker predictors of change in PASP.

Results:
Mean age was 74±5 years at Visit 5, 32% were men, 24% black, and mean PASP was 27.5±5.0 mmHg. Over a median of 6.5±3.0 years, PASP increased by 5.2±7.7 mmHg on average, with no significant differences by race (white 5.0±7.6, black 5.8±7.9; p=0.40) or sex (women 5.2±7.7, men 5.1±7.8; p=0.95). In models adjusted for heart rate and blood pressure at both visits, and for PASP, clinical and echocardiographic measures at Visit 5, independent predictors of longitudinal increase in PASP at Visit 5 were higher NT-proBNP (p=0.005), larger left atrial volume index (p=0.045), and lower forced expiratory volume at 1 second (p=0.019). Longitudinal increase in PASP was associated with concomitant increases in LAVi, E/e’ ratio, and LV mass index (
Figure
; all p <0.003), but not with changes in LVEF or strain.

Conclusions:
PASP increased by 5±8 mmHg over 6.5±3.0 years in late life, with greater increases associated with higher filling pressure and worse pulmonary function. Increases in PASP are accompanied by longitudinal worsening in LV diastolic - but not systolic - measures.
Abstract 15328: Higher Non-exercise Estimated Cardiorespiratory Fitness in Midlife is Associated With Lower Risk of Incident Heart Failure: The Framingham Heart Study
Authors: Lee Joowon , Shrout Tara , Vasan Ramachandran S , Xanthakis Vanessa
Published: May 2021

Introduction:
Non-exercise estimated cardiorespiratory fitness (eCRF) algorithms have shown similar accuracy to CRF estimated from submaximal and maximal exercise tests in healthy adults. Using easily accessible health indicators, eCRF measurement does not involve in-person exercise testing, trained personnel, or specialized equipment for measuring CRF. Thus, eCRF may be a cost-effective alternative for heart disease risk stratification. The relation between eCRF and Heart failure (HF) remains unclear.

Hypothesis:
We hypothesized that higher midlife eCRF is associated with a lower risk of incident HF in later life.

Methods:
We evaluated 2,226 Framingham Offspring cohort participants attending examination cycles 2 and 7 (mean age of 42- 61years; 53% women). We used a validated longitudinal non-exercise algorithm for eCRF including age, sex, body mass index, waist circumference, resting heart rate, physical activity, and smoking status. Midlife eCRF was defined as a sex-specific standardized average of eCRF (z-score of the average eCRF with mean=0 and a standard deviation [SD]=1) between cycles 2 and 7. The sex-specific midlife eCRF were then categorized into three groups based on tertiles and was also analyzed as a continuous variable (per 1 SD increment). We used multivariable Cox proportional hazards regression models for pooled sexes to relate the midlife eCRF to incident HF after examination cycle 7.

Results:
Overall, 189 participants developed HF during a median of 17 years of follow-up. Participants in either moderate or high eCRF group experienced a 52% lower risk of HF compared to those in the low eCRF group, after adjustment for potential confounders. Additionally, each SD increment in midlife eCRF was associated with a 40% lower risk of HF in later life. The associations remained significant after excluding participants on antihypertensive treatment (Table).

Conclusions:
Lower eCRF during midlife may be a marker of higher HF risk in later life.
Abstract 15341: Multi-center Validation of a Novel Echocardiography Artificial Intelligence System to Predict Post-operative Right Ventricular Failure in LVAD Patients
Authors: Arora Rohan Shad , Quach Nicolas , Fong Robyn , Kong Sandra , Kasinpila Patpilai , Castro Miguel , Guha Ashrith , Suarez Erik E , Jovinge Stefan , Lee Sangjin , boeve theodore , Langlotz Curtis P , Amsallem Myriam , Haddad Francois , Shudo Yasuhiro , Woo Y Joseph Y , Teuteberg Jeffrey , Hiesinger William
Published: May 2021

Introduction:
Post-operative right ventricular failure (RV failure) is the single largest contributor to short-term mortality in patients with left ventricular assist devices (LVAD); yet predicting which patient is at risk of developing this complication in the pre-operative setting has remained beyond the abilities of experts in the field. We hypothesized that deep artificial intelligence (AI) driven characterization of subtle pre-operative myocardial motion features, could predict post-operative RV failure in LVAD patients.

Methods:
We developed a novel echocardiography AI system using an improved dense trajectory algorithm that tracks motion vectors in an unsupervised fashion, and a 3-dimensional convolutional neural network that tracks spatiotemporal features from videos. We used pre-operative ECHO videos from a 536 patient multicenter echocardiographic and clinical dataset, and via a standard 10-fold cross validation, trained and validated the AI system to predict severe or higher grades of post-operative RV failure at the time of index hospitalization. Finally, we independently benchmarked our AI system against clinicians equipped with contemporary clinical risk scores to predict post-operative RV failure (Penn and CRITT score) and manually derived echocardiographic metrics of RV function.

Results:
173 (32%) patients were adjudicated to have severe post-operative RV failure. The area under the receiver operator characteristic curve (AUC ROC) for the AI system was 0.86 (95% CI 0.824-0.896). The performance of our AI system exceeded that of both the best performing clinical risk score and manually derived echocardiographic metric by a significant margin (ΔAUC +0.30, 95% CI 0.27 - 0.33 and ΔAUC +0.24, 95% CI 0.21 - 0.27; both p < 0.0001).

Conclusions:
A novel ECHO AI system trained and validated on a multicenter dataset outperformed clinical experts equipped with both contemporary risk scores and manually calculated echocardiographic metrics.
Abstract 15343: Increasing Left Ventricular Mass is Associated With Greater Microvascular Obstruction During ST-elevation Myocardial Infarction
Authors: Bonfig Nicole L , Soukup Chase R , Garberich Ross F , Davidson Sarah J , Peterson Rose M , Schmidt Christian W , TRAVERSE Jay H
Published: May 2021

Introduction:
The development of microvascular obstruction (MVO) in the setting of ST-Elevation Myocardial Infarction (STEMI) is a powerful predictor of reduced left-ventricular (LV) function, adverse LV remodeling and increased mortality. Although MVO is associated with increasing infarct size and ischemic duration, additional causes of MVO have not been clearly identified. Although MVO may arise from intravascular obstruction from embolization of thrombus, it may also arise from compression of the microvasculature due to increased myocardial edema and extravascular compressive forces.

Hypothesis:
Because left-ventricular hypertrophy (LVH) is associated with increased extravascular compressive forces, we hypothesized that patients with greater LV mass may be more susceptible to the development of MVO during STEMI.

Methods:
We measured MVO in 385 patients (59.4
+
12.3 years; 77% male) admitted to our Institution with STEMI who underwent cardiac MRI for measurement of LV function and infarct size following successful primary PCI. A total of 219 patients (57%) had MVO on cardiac MRI measured 1-3 days following PCI of which 172 patients had paired measurements of LV mass.

Results:
Patients with MVO (13.7
+
13.9 grams) had significantly greater infarct size (54 vs. 31 g; p < 0.001) and LV mass (151 vs 140 g; p<0.01) but reduced LVEF (43.1 vs. 47.8%) despite having similar ischemic times. Among patients with MVO, there was a linear increase in MVO with increasing LV mass (Figure).

Conclusions:
MVO increases with increasing LV mass and may contribute to the known adverse effects of LVH in STEMI.
Abstract 15352: Age-associated Nuclear Remodeling May Contribute to Cardiac Dysfunction
Authors: Kirkland Natalie J , Hocker James D , Preissl Sebastian , Ren Bing , Bodmer Rolf , Engler Adam J
Published: May 2021

Introduction:
Cardiac performance depends on proper function of the extracellular matrix, cytoskeleton and nucleus to regulate systolic contraction and diastolic relaxation. As we age, the mechanical properties of these structures change, but their influence on tissue-level function is unclear. Nuclear Lamins (Lam), intermediate filaments that underly the nuclear envelope, change in expression and localization with age, leading to irregularly shaped nuclei. Mutations in LamA/C can cause premature aging and cardiomyopathy but whether Lamin changes with age contribute to cardiac dysfunction is unknown. Hence, we hypothesize that age-associated LamA/C reduction remodels nuclear shape, force propagation, and gene accessibility to reduce cardiac function.

Methods:
We profiled nuclear morphology and protein expression in hearts from two wildtype
Drosophila melanogaster
strains for up to 5 weeks, when median survival is less than 50%. We performed live imaging to assess heart performance in wildtype flies and flies with Lamin knock-down using the Gal4-UAS system. To profile chromatin accessibility changes we use an ATAC-seq protocol that we optimized for frozen heart nuclei.

Results:
Cardiomyocyte nuclei become smaller and more circular with age in contrast to skeletal nuclei across

w
1118

and
yw
wildtype fly strains. Expression of both LamB and LamC (
Drosophila
LamA/C) decrease with age and differentially regulate nucleus size and circularity. LamC knockdown, but not LamB, induces contractile dysfunction, measured by fractional shortening, at 1-week, and shortens lifespan. LamB and LamC knockdown also mimicked DNA decondensation observed in aged wildtype flies, suggesting that reduced DNA packaging could result from fewer contacts with the nuclear lamina. Thus, we developed a novel ATAC-seq pipeline that will identify how age-related nuclear architecture may influence the epigenome and contribute to pathogenic heart remodeling.

Conclusions:
Cardiomyocyte nuclei decrease in size and increase in circularity upon aging as a result of diminished Lamin expression. Loss of Lamin expression induces cardiac dysfunction. Our future work aims to elucidate the mechanism by which nuclear aging contributes to age-related cardiac dysfunction.
Abstract 15355: Interleukin-1beta Inhibition Attenuates Accelerated Atherosclerosis in Mice With
Tet2
Loss of Function in a Sex-dependent Fashion
Authors: Vromman Amelie , Vellarikkal Shamsudheen , Janini Gomes Mariana , Ruvkun Victoria , Shvartz Eugenia , Kritikou Eva , Carter Paul , Moscavitch Samuel , Nakao Tetsushi , Sellar Rob , McConkey Marie , Sausen Grasiele , Wong Waihay , Tesmenitsky Yevgenia , Kavi Shah , Lichtman Andrew H , Ebert Benjamin , Sukhova Galina K , Gupta Rajat , Libby Peter
Published: May 2021

Introduction:
Clonal hematopoiesis of indeterminate potential (CHIP) describes somatic mutations of bone marrow derived blood cells in the absence of overt hematological disease. CHIP correlates with aging and atherosclerotic cardiovascular diseases in humans.
Tet2
mutations, common in CHIP, augment atherosclerosis.
Tet2
-deficient macrophages over-express Interleukin-(IL)1β mRNA in response to LDL. IL-1β neutralization reduces recurrent events in patients post myocardial infarction with residual inflammatory risk.We previously showed that IL-1β neutralization reduces evolution of established mouse atherosclerosis.

Hypothesis:
This study tested the hypothesis that IL-1β neutralization will reduce early accelerated atherosclerosis caused by
Tet2
deficiency in hematopoietic cells.

Methods:
We transplanted lethally irradiated
LDL-R
-/-
atherosclerotic prone mice with either
Tet2
+/+
or

Tet2
-

/-
bone marrow cells. Chimeric mice consumed a western diet and received a selective anti-mouse IL-1β monoclonal antibody or isotype-matched control. After nine weeks of treatment, we analyzed atherosclerotic lesions morphologically and by single cell mRNA analysis.

Results:
IL-1β neutralization reduced accelerated atherosclerosis associated with
Tet2
deficiency in female but not in male mice (Table). Single cell RNA-sequencing analysis of the dissociated aortic arch revealed differences in macrophage expression of genes involved in innate immune response interleukin signaling pathways between male and female mice.

Conclusions:
This unexpected sex-dependence of accelerated atherogenesis in

Tet2
-

/-
bone-marrow mice on IL-1β signaling lays the ground for further mechanistic exploration.
Abstract 15361: Comparison of Cardiovascular Outcomes of Supravalvar Aortic Stenosis Patients With Williams Syndrome and Non-williams Supravalvular Aortic Stenosis
Authors: Shahbah Doaa , Weigand Justin , Jacob Benjamin , Essandro Icadal , Beecroft Taylor , Stephen Sara , Keyes Ashley , Spurzem Gabrielle , Webb Melissa , Morris Shaine A
Published: May 2021

Introduction:
Cardiovascular outcomes in Williams syndrome (WS) with supravalvar aortic stenosis (SVAS) compared to those with non-Williams SVAS (NW-SVAS) have not been well-described in literature.

Hypothesis:
Cardiovascular outcomes are similar in SVAS patients in WS and those with NW-SVAS as both are typically mediated by elastin (
ELN
) deficiency.

Methods:
We included all patients (pts) at our institution with 1) WS and SVAS or 2) SVAS with negative testing for WS (2003-2020), excluding pts with Alagille or Turner syndrome, isolated bicuspid aortic valve, postoperative acquired SVAS, or insufficient records. We compared cardiovascular lesions and freedom from intervention using Kaplan-Meier analysis with comparison by log rank.

Results:
Of 163 included SVAS pts (67 WS, 96 NW-SVAS), 75 (46%) were females. Median age at last follow up was 11.9 years (IQR 5.7, 17). Of
ELN
testing performed in 13 NW-SVAS patients, 8 had pathogenic variants. The rest of the NW-SVAS cohort included 22 familial and 61 non-familial cases. Branch pulmonary artery stenosis (BPAS), renal artery stenosis (RAS), and hypertension were more prevalent in WS than in NW-SVAS (p=0.001, Table). There was no difference in freedom from BPAS intervention between the groups, but the WS group was significantly more likely to undergo intervention for RAS or be treated for hypertension (Figure). No difference was noted for SVAS, coarctation or coronary outcomes.

Conclusion:
For most cardiovascular lesions, there was no difference in interventions between WS and NW-SVAS. The increased intervention rate for RAS and hypertension in WS may reflect lower screening rates in NW-SVAS
Abstract 15502: Clinical Outcomes in Patients Undergoing Non-cardiac Surgery Within 1 Year of Pci
Authors: Cao Davide , Levin Matthew A , Sartori Samantha , Roumeliotis Anastasios , Chandiramani Rishi , Nicolas Johny , Waseem Zaha , Bedekar Rashi , Claessen Bimmer E , Goel Ridhima , Chiarito Mauro , Lupo Bonnie , Jhang Jeffrey , Dangas George , Baber Usman , Bhatt Deepak L , Sharma Samin K , Kini Annapoorna , Mehran Roxana
Published: May 2021

Introduction:
Perioperative cardiovascular events are an important cause of morbidity and mortality associated with non-cardiac surgery (NCS), especially in patients with recent percutaneous coronary intervention (PCI) who require dual antiplatelet therapy.

Objective:
To illustrate the types and timing of different noncardiac surgeries occurring within 1 year of PCI, and to evaluate the risk of thrombotic and bleeding events according to perioperative antiplatelet management.

Methods:
All patients undergoing NCS within 1 year of PCI at a tertiary-care center between 2011 and 2018 were included. The primary outcome was major adverse cardiac events (MACE; composite of death, myocardial infarction, stent thrombosis or target vessel revascularization). The key secondary outcome was major bleeding, defined as ≥2 units of blood transfusion. All outcomes were evaluated at 30 days after NCS.

Results:
A total of 1092 NCS (corresponding to 747 patients) were included and classified by surgical risk (low: 50.9%, intermediate: 38.4%, high: 10.7%) and priority (elective: 88.5%, urgent/emergent: 11.5%). High-risk and urgent/emergent surgeries tended to occur earlier post-PCI compared to low-risk and elective ones (
Figure-A
). The incidence of MACE and bleeding was time-dependent, with an increased risk in surgeries occurring in the first 6 months post-PCI (
Figure-B
). Perioperative antiplatelet cessation occurred in 487 (44.6%) NCS and was more likely for intermediate-risk procedures and after 6 months of PCI. There was no significant association between antiplatelet cessation and cardiac events.

Conclusions:
Among patients undergoing NCS within 1 year of PCI, the perioperative risk of MACE is inversely related to time from PCI. Preoperative interruption of antiplatelet therapy was observed in less than half of all cases and was not associated with an increased risk of cardiac events.
Abstract 15508: Random Forest Classifier-incoporated Intravascular Optical Coherence Tomography-fluorescence Lifetime Imaging (oct-flim) Provides Automated Characterization of Key Biochemical Components of Coronary Atherosclerotic Plaques
Authors: Kim Sunwon , Nam Hyeong Soo , Kang Woo Jae , Song Joon Woo , Kim Hyun Jung , Kang Dong Oh , Han Jeongmoo , Kim Ryeoung Hyeon , Oh Wang-Yuhl , Yoo Hongki , Kim Jin Won
Published: May 2021

Introduction:
Fluorescence lifetime imaging (FLIm) allows label-free biochemical characterization of atheroma, however, multispectral FLIm produces massive data throughput making image interpretation problematic. We investigated whether machine learning algorithm can be applied to intravascular OCT-FLIm for automated biochemical characterization of coronary plaques.

Methods and Results:
We built a fully-integrated, high-speed OCT-FLIm system and a low-profile, dual-modal imaging catheter that can provide high-resolution OCT images and correctly co-registered multispectral fluorescence lifetime (FL) readouts: ch.1 and ch.2 FL, and FL intensity ratio (ch.2/ch.1). Rapid intracoronary imaging (10-20 mm/s, 100 rps) was safely performed in atheromatous pigs. There were significant differences in FL measurements according to plaque types (high-risk vs. fibrotic: p<0.001). Multispectral FL measurements sampled selectively from histologically-proven plaque components (lipid, macrophage, lipid+macrophage, SMC) were analyzed. Each component was distinguishable from one another either by difference of FLs or intensity ratio. Random forest classifier (RFC), trained with component-labeled multispectral FL dataset, accurately classified key biochemical components of atherosclerotic plaques. RFC-determined biochemical characteristics of target plaque were consistent across two repeated imaging data (intraclass correlation, p<0.0001) and corroborated closely with those derived from quantitative immunohistochemistries.

Conclusions:
Our OCT-FLIm incorporating RFC-based systematic multispectral FL analysis could provide high-resolution plaque imaging with automated biochemical characterization in beating coronary environment. The present imaging strategy enabling comprehensive characterization of multiple components of atherosclerotic plaques will open a new avenue in the field of cardiovascular imaging.
Abstract 15511: A Negative Tachycardic-induced Stress Test Predicts Against Myocardial Infarction at 30 Days Post Renal Transplantation
Authors: Montarello Nicholas J , Salehi Tania , Bate Alex P , Coates Patrick T , Worthley Matthew I
Published: May 2021

Background:
Cardiovascular (CV) events remain a major cause of death in kidney transplant recipients and an accurate CV risk assessment is required prior to a patient being placed on an active transplant wait-list. Determining the optimal protocol and non-invasive test modality for CV work-up remains contentious. The aim of this study was to assess the CV assessment protocol used within a single centre.

Methods:
We conducted a retrospective analysis on the rates of myocardial infarction (MI) and CV death at 30 days post renal transplantation in patients who had been processed through the CV assessment pathway at the Central Northern Adelaide Renal and Transplantation Service over a 5-year period. This protocol does not require asymptomatic patients under the age of 45, who are non-smokers, have no history of diabetes mellitus, and have been dialysis dependent for less than 24 months, to undergo objective testing for coronary artery disease (CAD) prior to listing. For all other asymptomatic patients, a tachycardic-induced stress test is required. The primary endpoint was the composite of MI and CV death at 30 days post renal transplantation.

Results:
Between January 2015 and December 2019, 380 patients received kidney only transplants: 79 patients (20.8%) were deemed low-risk and placed on the active transplant list without further CV assessment; 270 patients (71.1%) underwent a tachycardic-induced stress test; 31 patients (8.1%) proceeded directly to ICA.

In the five-year study period, a total of three patients (0.8%) experienced a MI at 30 days post transplantation. None of these occurred in the ‘low-risk’ or ‘tachycardic-induced stress test’ cohorts. There were no CV deaths at 30 days post transplantation in the entire cohort.

Conclusions:
Our review has validated tachycardic-induced cardiac stress testing in predicting MI following kidney transplant surgery. Patients with a valid negative tachycardic-induced stress test went on to have transplantation with no 30-day MI or CV death, supporting the listing without the need for invasive coronary testing. Similarly, we demonstrated that no preliminary testing is required for asymptomatic patients under 45 if they do not smoke or have diabetes, and if they have been dialysis dependent for less than 24 months.
Abstract 15526: Glucagon-like Peptide-1 Receptor Agonists Reduce Adverse Cardiovascular Disease (CVD) Events in Patients With Type 2 Diabetes: An Assessment of Heterogeneity Among CVD Outcomes and a Meta-regression Analysis
Authors: Grewal Simran , Zaman Ninad , Borgatta Louis , Nudy Matthew , Peterson Brandon
Published: May 2021

Introduction:
Recent evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce adverse cardiovascular disease (CVD) events. The objective of this study is to analyze randomized controlled trials (RCTs) testing GLP-1 RA’s effects on CVD among participants with type 2 diabetes (T2DM).

Methods:
RCTs comparing GLP-1 RA versus placebo among participants with T2DM were identified using PubMed and Cochrane databases. The endpoints of this analysis included major adverse cardiovascular events (MACE; a composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke), and the individual components of MACE. The primary analysis calculated risk ratios (RR) and 95% confidence intervals (CI) for each endpoint. Heterogeneity for each endpoint was calculated using Chi
2
and I
2
tests. For any endpoint with significant heterogeneity, a meta-regression was performed using baseline hemoglobin A1C (A1C) in each RCT as the moderator and a R
2
value was calculated.

Results:
7 RCTs (N = 56,004) were identified with 174,163 patient years of follow-up. GLP-1 RA reduced MACE [RR 0.89, 95% CI 0.83-0.95], cardiovascular death [RR 0.88, 95% CI 0.81-0.95], and nonfatal stroke [RR 0.85, 95% CI 0.77-0.94]. There was no significant heterogeneity among these RCTs (Figure 1). GLP-1 RA did not reduce nonfatal MI [RR 0.91, 95% CI 0.82-1.02]. However, there was significant heterogeneity among these RCTS (Chi
2
=12.94, p=0.04, I
2
=54%). When accounting for A1C in the regression model, there was no longer significant heterogeneity for this endpoint (p=0.23, I
2
=27%). A relationship between A1C and GLP-1 RA’s effect on nonfatal MI (R
2
=0.64, Figure 1) was observed when performing the meta-regression.

Conclusion:
GLP-1 RA reduced MACE, cardiovascular death, and nonfatal stroke in patients with T2DM with minimal heterogeneity among RCTs. GLP-1 RA did not reduce nonfatal MI, however there may be an association between A1C and GLP-1 RA’s effect on nonfatal MI.
Abstract 15541: Novel Molecular Entity for Effective Cardiac Regeneration: 5’ppp Microrna Induces Reprogramming and Accelerates Cardiomyocyte Maturation
Authors: Hu Jiabiao , Hodgkinson Conrad , Baksh Syeda S , Pratt Richard E , Dzau Victor J
Published: May 2021

We have shown that miR combo directly reprograms fibroblasts into cardiomyocytes. However, both in vitro and in vivo, the generated cardiomyocytes are immature. Recently, we discovered that cardiomyocyte maturation is enhanced by NFkB activation. While miR combo

initiates

reprogramming, the effect on NFkB activity is modest. Therefore, miR combo only has a modest effect on maturation. We have now made an important discovery that 5’triphosphorylation (5’ppp) of RNA molecules markedly enhance NFkB activation; leading to increased and accelerated maturation of reprogramed cardiomyocytes. The addition of 5’ppp-RNA increased the number of mature cardiomyocytes by 4-fold (N=5, P<0.05). Moreover, 5’ppp-RNA also accelerated the appearance of mature cardiomyocyte mRNAs (1 day after transfection vs 4 days for unmodified RNA). Importantly, these effects were lost when the 5’ppp moiety was removed. Knockdown studies suggest that 5’ppp-RNA binds to the Pattern Recognition Receptor Rig1. MNase-seq and ChIP-seq analysis suggests that 5’ppp-RNA activates YY1 (N=4, P<0.001). We next asked if 5’ppp modification of the miRNAs within miR combo would also enhance cardiomyocyte maturation; thus, providing a single molecular entity that can

initiate reprogramming and accelerate maturation

of cardiomyocytes. Indeed, 5’ppp modification of the miR combo miR-1 increased the expression of the mature cardiomyocyte markers Actn2 (4-fold, N=3, P<0.05) and Myh6 (4-fold, N=3, P<0.05). In conclusion, 5’ppp-miR combo is a novel approach that has the advantage of both initiating reprogramming and accelerating cardiomyocyte maturation and should lead to more effective cardiac regeneration and restore cardiac function.
Abstract 15545: Exercise-stress Real-time Cardiac Magnetic Resonance Imaging for Non-invasive Characterisation of Heart Failure With Preserved Ejection Fraction: The Hfpef Stress Trial
Authors: Backhaus Soeren Jan , Lange Torben , George Elisabeth , Hellenkamp Kristian , Gertz Roman , Billing Marcus , Steinmetz Michael , Wachter Rolf , Raaz Uwe , Kutty Shelby , Lotz Joachim , Uecker Martin , Hasenfuss Gerd , Seidler Tim , Schuster Andreas
Published: May 2021

Introduction:
Invasive right heart catherization (RHC) using exercise-stress is the reference-standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF) but carries the risk of the procedure. Real-time cardiovascular magnetic resonance (RT-CMR) imaging allows bicycle exercise CMR with unprecedented temporal and spatial resolution and may represent a novel non-invasive alternative.

Methods:
The HFpEF stress trial (NCT03260621) prospectively included 75 patients with echocardiographic signs of diastolic dysfunction and dyspnoea on exertion (E/E’>8, NYHA≥II) who underwent echocardiography, RHC and RT-CMR at rest and exercise-stress. HFpEF was defined according to pulmonary capillary wedge pressure (PCWP ≥15mmHg at rest or ≥25mmHg during exercise stress). RT-CMR functional assessments included time-volume-curves for total and early (1/3) diastolic left ventricular (LV) filling or left atrial (LA) emptying and LV/LA long axis strain (LAS).

Results:
HFpEF patients (n=34, mean PCWP rest 13mmHg, stress 27mmHg) had higher E/e’ (12.5 vs 9.15), NT-proBNP (255 vs 75ng/l) and LA volume index (43.8 vs 36.2ml/m
2
) compared to non-HFpEF patients (n=34, rest 8mmHg, stress 18mmHg, p≤0.001 for all). There were no differences in RT-CMR LV total and early diastolic filling at rest and during exercise-stress (p≥0.164). In contrast, RT-CMR revealed impaired stress LA total (p=0.033) and early (p<0.001) diastolic emptying in HFpEF. LA LAS was the only impaired parameter at rest (p<0.001) and emerged as the best predictor for the presence of HFpEF during exercise-stress testing (AUC rest 0.82 vs stress 0.93, p=0.029).

Conclusions:
RT-CMR allows highly accurate identification of HFpEF during physiological exercise and may establish itself as a novel non-invasive diagnostic alternative for routine clinical use.
Abstract 15550: Fully Automated "Hands-off" Validation of Left Ventricular Ejection Fraction in Children
Authors: Kauffman Hunter , Whitehead Kevin K , O’Connor Matthew J , Quartermain Michael D , Convery Michael , Banerjee Anirban N
Published: May 2021

Introduction:
Three-dimensional echocardiography (3DE) has been shown to be superior to 2DE when quantifying chamber dimensions. However, the clinical utility of 3DE has been limited by time-consuming analysis and need for 3D-specific training. This study aims to assess the clinical utility of a “hands-off,” artificial intelligence-driven software program, Philips Dynamic HeartModelA.I. (DHM), in a pediatric population.

Hypothesis:
We hypothesize that this program will be able to accurately calculate LVEF in children when compared to Cardiac MRI (CMRI) used as a gold standard.

Methods:
To date, 10 patients (Average Age 14.8±1.9) have undergone CMRI immediately followed by echocardiography at the Children’s Hospital of Philadelphia. Echocardiographic images were analyzed via DHM without manual editing and from full-volume 3D border tracing (3DEF). We excluded 3D imaging of 2 patients due to poor image quality. 2D LVEF was also evaluated visually in all patients by three experts, and by 2D Simpson’s Biplane method. All analyses were timed with a stopwatch. Each technique was correlated with CMRI.

Results:
Our results showed that LVEF measured via DHM was rapid and correlated very well with CMRI (R=0.85). DHM had a stronger correlation with CMRI than Biplane, 3DEF, and visual EF (R=0.56; R=0.68; R=0.57). Moreover, DHM analysis was faster than both Biplane and 3DEF (32±8 seconds vs 100±19 seconds, p<0.005; 32±8 seconds vs 98±16 seconds, p<0.005) (Figure 1). Notably, 3DEF correlated very well with visual estimation by expert observers (R=0.83).

Conclusions:
Based on our pilot data, DHM analysis in children was faster than both 3DEF and biplane method likely due to its hands-off nature. Furthermore, its correlation with CMRI was superior to both 3DEF and Biplane. Based on further patient enrollment by us and others, this completely automated method will likely be clinically useful as it has potential to become a standard application in large volume, busy echo labs.
Abstract 15571: Echocardiographic Characteristics and Their Association With Outcome in Hospitalized Covid-19 Patients With Cardiovascular Disease
Authors: Li Yuman , Fang Lingyun , Zhu Shuangshuang , Xie Yuji , Wang Bin , Lin He , Zhang Danqing , Zhang Yongxing , Yuan Hongliang , Wu Chun , Sun Wei , zhang yanting , Li Meng , Cai Yu , Cui Li , Wang Jing , Yang Yali , Qing Lv , Zhang Li , XIE Mingxing
Published: May 2021

Background:
Echocardiographic characteristics and the prognostic value of echocardiographic parameters in COVID-19 patients with cardiovascular disease (CVD) remain unclear.

Objectives:
We aimedto describe and compare echocardiographic characteristics of hospitalized COVID-19 patients with and without CVD, and explore the prognostic value of echocardiographic parameters in COVID-19 patients with CVD.

Methods:
157 consecutive hospitalized COVID-19 patients were enrolled in our study. Left ventricular (LV) and right ventricular (RV) structure and function were assessed using bedside echocardiography.

Results:
89 (56.7 %) patients had underlying CVD.Compared with patients without CVD, those with CVD were more likely to havehigher levels of high-sensitivity troponin I (hs-TNI) and B-type natriuretic peptide, and higher incidence of ARDS, acute heart injury and deep vein thrombosis. During hospitalization, 23(14.6%) patients died. Mortality was significantly higher in CVD compared with non-CVD patients (22.5% vs. 4.4%, p =0.002). CVD patients had increased mitral E/e’, lower tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change (RVFAC), and higher pulmonary artery systolic pressure. TAPSE, RVFAC and elevated hs-TNI level were independent predictors of higher mortality.Furthermore, we found the incremental prognostic value of TAPSE over RVFAC and clinical parameters in COVID-19 patients with CVD using a likelihood ratio test, Akaike information criterion and C-index.

Conclusions:
COVID-19 patients with CVD displayed impaired cardiac function, which is associated with higher mortality. The additional prognostic value of TAPSE over the other clinical and echocardiographic parameters indicate that TAPSE measurement may be important for risk stratification in COVID-19 patients with CVD.
Abstract 15577: Mst 4, a Novel Stripak Associated Kinase is Upregulated in Human Cardiomyopathy and Regulates Cardiomyocyte Hypertrophy, Contractility and Apoptosis
Authors: Eden Matthias , Leye Marius , Tannert Christin , Frey Norbert
Published: May 2021

Heart failure is one of the major causes of death worldwide. Its pathophysiology is complex and involves alterations in calcium cycling and hypertrophic signaling, as well as subsequent loss of cardiomyocytes due to apoptosis, cardiac fibrosis and progressive contractile dysfunction. The Striatin-interacting phosphatase and kinase (STRIPAK) complex is a mammalian multiprotein complex that consists of phosphatases, kinases and various adaptor proteins. Yet, the STRIPAK complex has so far not been studied in cardiomyocytes. Now we show in cardiomyocytes that the STRIPAK associated kinase MST4 directly interacts with a recently described novel cardiac STRIPAK protein, Myoscape/STRIP2. Multi tissue immunoblot experiments showed that Mst4 abundance is also highly enriched in heart and skeletal muscle. Immunoblot analyses in human biopsy samples form patients with dilated (DCM n=10) or ischemic cardiomyopathy (ICM n=10) revealed that MST4 is strongly upregulated in DCM (12-fold p<0.001) and ICM (9.6 fold p<0.05) vs. controls. Conversely, upon biomechanical stretch we observed a significant downregulation of MST4
in vitro
by 30% (p<0.05) as well as
in vivo
(-45%, n=6; P<0.001) in a murine model for pressure overload (experimental aortic constriction, (TAC) vs. Sham) under Moreover, we also observed downregulation of MST4 in a porcine myocardial infarction model (-48% vs. porcine controls; n=5 p<0.05). Adenoviral overexpression of MST4 in NRVCM results in significant cellular hypertrophy (485μm2 vs 421μm2; p<0.001) compared to LacZ. Overexpression of MST4 also increases cellular and sarcomeric fractional shortening in adult rat cardiac myocytes vs. LacZ (p<0.05). Finally, MST4 overexpression also protects from cardiac apoptosis as shown by 90% reduced PARP cleavage as well as significantly reduced expression of Caspase 3 and 7 (n=3; p<0.05). Taken together we show that MST 4 is a cardiac enriched Kinase that regulates cardiomyocyte hypertrophy, contractility and apoptosis and may thus be a target for future therapeutic intervention
Abstract 15578:
Propionibacterium Acnes
-associated Cardiac Sarcoidosis Presenting as Constrictive Pericarditis
Authors: Leya Marysa , Okwuosa Ike , Lomasney Jon W , Rigolin Vera H , Pawale Amit , Bazavan Mugurel V , Sporn Peter , Tibrewala Anjan
Published: May 2021

Sarcoidosis is an antigen-mediated chronic multisystem inflammatory disease characterized by the formation of non-caseating epithelioid granulomas that disrupt tissue architecture, trigger fibrosis, and precipitate organ dysfunction. Cardiac involvement portends a poorer prognosis, presenting with conduction disease, heart failure, pulmonary hypertension, valvular disease, pericardial effusions, tamponade, ventricular arrhythmias, and sudden death. A 75-year-old man with a history of heart failure with mildly reduced ejection fraction, suspected ocular sarcoidosis, monoclonal gammopathy of uncertain significance and 6 months of exertional dyspnea and lower extremity edema presented with acute-on-chronic volume overload. His labs were notable for elevated inflammatory markers. Cardiac MRI showed pericardial thickening, complex pericardial fluid. The differential diagnosis included tamponade, restrictive cardiomyopathy or constrictive pericarditis secondary to paraproteinemia, viral/idiopathic, vasculitis, tuberculosis, lupus, or sarcoidosis. Simultaneous right and left heart catheterization was consistent with constriction. The patient underwent surgical pericardiectomy. The pathology was consistent with sarcoidosis and intraoperative cultures grew
Propionibacterium acnes.
This case reviews the mechanism and diagnosis of sarcoidosis, the diagnosis of constrictive pericarditis, and a possible role for
P. acnes
in the development of sarcoidosis. Constrictive pericarditis is a rare presentation of cardiac sarcoidosis, particularly when the only other suspected involvement of sarcoidosis is uveitis.
P. acnes
has been associated with granuloma formation in sarcoid, although the mechanism is still unknown.
P. acnes
may represent a potential therapeutic target once a mechanism is further elucidated.
Abstract 15588: Prediction of Mortality Using Standard 12-lead Electrocardiogram With Deep Neural Network
Authors: Huang Yu Chang , Kuo Chang-Fu , Hsu Yu Chun , Chen Yueh Peng , Chen Jung-Sheng , Wen Ming Shien
Published: May 2021

Background:
Electrocardiogram (ECG) is a low-cost, inexpensive, non-invasive, and ubiquitous test to detect structural or electrical cardiac abnormalities. The ECG interpretation is a visual task to correlate specific patterns with diseases. Subtle ECG patterns that are invisible to the human eyes may be useful for patient risk stratification. We aimed to develop a deep neural network to predict mortality using standard 12-lead ECG.

Methods:
We obtained the entire clinical MUSE database of Chang Gung Memorial Hospital for standard resting 12-lead 10-sec ECG voltage-time traces, which were linked to the National Death Registry for all-cause and cause-specific mortality. Ten thousand patients remained alive at one year from the ECG examination date, and 10000 patients died within one year were randomly selected to train a one-dimensional deep neural network to predict mortality risk. Data was split into 16,000 patients for the training and 4,000 patients for the validation sets. We prepared a separate held-out dataset of 19,737 randomly selected patients whose ECG traces were fed to the model to predict their mortality risk.

Results:
The mean age of the held-out dataset was 60.0±16.7 years, and 50.0% were female. Among them, 3,807 died during a mean follow-up period of 6.0 years (maximum period, 14 years). The model achieved an area under the receiver operator curve of 0.85 on the held-out dataset. The age- and sex-weighted Kaplan-Meier curve for the mortality was shown in figure 1, which stratified by the model prediction for survival status (log-rank test,
p
< 0.001). Using a Cox proportional hazards model, the ECG algorithm predicted death is associated with an age- and sex-adjusted hazard ratio of 3.2 (95% confidence interval, 3.0-3.4) for all-cause mortality and 2.9 (95% CI, 2.4-3.5) for cardiovascular mortality.

Conclusion:
The deep learning model could extract prognostic information from standard 12-lead ECG and predict mortality with reasonable precision.
Abstract 15598: Population Characteristics and Outcomes of Patients With Constrictive Pericarditis Undergoing Pericardiectomy in the Contemporary Era: A Systematic Review and Metaanalysis
Authors: Tzani Aspasia , Doulamis Ilias P , Tzoumas Andreas , Avgerinos Dimitrios V , Kampaktsis Polydoros
Published: May 2021

Introduction:
Studies have described the changing landscape of patients with constrictive pericarditis (CP) in the modern era, however no systematic review or meta-analysis has been performed.

Methods:
We systematically searched the MEDLINE, Embase and Cochrane databases from their inception to April 1, 2020 for studies assessing the characteristics and outcomes patients with CP undergoing pericardiectomy. A meta-analysis was performed to assess the impact of CP etiology on outcomes.

Results:
We analyzed 27 eligible studies and 2114 patients. Etiology was most commonly idiopathic (50.2%), post-cardiac surgery (26.2%) and radiation (6.9%)(Figure 1A-B). Patients were mostly men (76%), with a mean age of 58 years and with advanced symptoms (NYHA III/IV 70.1%). Total pericardiectomy was preferred (85.8%) (Figure 1C-D) and concomitant cardiac surgery was relatively common (23.8%). Operative mortality was 6.9% and 5-year mortality was 32.7% (Table 1). Radiation and post-cardiac surgery patients had higher long-term risk for mortality respectively compared to idiopathic pericarditis (HR: 2.15; 95% CI: 1.21-1.36, p=.01 and HR: 3.21; 95% CI: 1.56-6.50, p<.01, respectively). Thirty percent of included studies had more than low bias. A sensitivity analysis did not result in changes in the results.

Conclusions:
Pericardiectomy is performed mostly in middle-aged men with advanced symptoms and low comorbidity burden and still carries a significant operative mortality. Radiation and post-cardiac surgery patients have a significantly higher risk compared to idiopathic. Several methodological issues and significant heterogeneity limit the generalization of these data.
Abstract 15601: On the Mechanisms of Accelerated Calcification of Bioprosthetic Heart Valve Biomaterials in Juvenile Animal Models
Authors: Xue Yingfei , Kossar Alexander , THIENE Gaetano , LEVY Robert , Ferrari Giovanni
Published: May 2021

Objective:
Bioprosthetic heart valves (BHV) are subject to accelerated structural valve degeneration (SVD) in pediatric patients. Prior literature has reported differences in circulating markers of mineralization in pediatric patients compared to adults. Here we test the hypothesis that calcification-related circulating markers are differentially expressed in juvenile vs adult animals, and these markers functionally drive the accelerated SVD in juvenile animals
in vitro
and
in vivo
.

Methods:
Serum calcium (Ca
2+
), phosphate (PO
4
-
), alkaline phosphatase (ALP), and osteopontin (OPN) levels of juvenile (3 week-old; n=5) and adult (8 month-old; n=5) Sprague-Dawley rats were measured by commercially-available assay kits. Glutaraldehyde-fixed bovine pericardial discs (BP) were incubated in juvenile or adult rat serum
in vitro
for 4 or 8 weeks. BP were subcutaneously implanted in juvenile or adult rats for 7 or 30 days (4-6 discs/rat). Pericardial transcatheter valves were implanted in juvenile Dorset sheep for 150 days (n=3). Alizarin Red staining, Von Kossa staining, and a quantitative assay were used for calcium analyses. Second harmonic generation imaging visualized collagen structure.

Results:
Serum Ca
2+
(p<0.05), PO
4
-
(p<0.05), ALP (p<0.01), and OPN (p<0.01) were all increased in juvenile rats compared to adult rats. BP incubated in juvenile rat serum resulted in higher calcium deposition (p<0.05) and more disruption to collagen structure as evidenced by reduced alignment coefficient (p<0.01) as compared to those incubated in adult rat serum. Similarly, BP explanted from juvenile rats had higher calcium deposition (p<0.01) and more disrupted collagen structure in terms of collagen alignment and crimp period (p<0.01). Results in progress in juvenile sheep implantation model further confirmed the
in vitro
and
in vivo
findings that BHV explants had substantial calcium deposition and collagen disalignment.

Conclusion:
Calcium accumulates within BHV biomaterials more prominently in juvenile rats; increased serum markers of mineralization may explain the increased susceptibility to SVD in pediatric patients. Future studies will investigate novel strategies for the prevention and mitigation of accelerated SVD in pediatric patients.
Abstract 15603: Discovery of Plasminogen Activator Inhibitor-1 Platelet-derived Extracellular Vesicles to Predict Major Adverse Cardiac Events
Authors: Jung Richard , Simard Trevor , Di Santo Pietro , Duchez Anne-Claire , Labinaz Alisha , Parlow Simon , Yang Jiayue , Dhaliwal Shan , Ramirez F Daniel , Xiao Fengxia , Lordkipanidze Marie , Burger Dylan E , Hibbert Benjamin M
Published: May 2021

Objective:
To evaluate the utility of plasminogen activator inhibitor-1 positive platelet-derived extracellular vesicles (PAI-1
+
PEV) as a biomarker for major adverse cardiac events (MACE) following angiography.

Background:
The stented coronary artery is at high-risk for complications, predominantly in the form of stent thrombosis and in-stent restenosis. Clinical risk scores have been attempted but no current models nor biomarkers yet accurately identifies the high-risk cohort following revascularization.

Methods:
PAI-1
+
PEV was measured by flow cytometry in 172 patients undergoing coronary angiography. Biological characteristics and utility of PAI-1
+
PEV as a biomarker were evaluated. The primary outcome was the incidence of MACE (composite of death, myocardial infarction, cerebrovascular accident, and unplanned revascularization) at 12 months.

Results:
During a median follow-up period of 377 days (IQR, 269.5 to 442.5 days), 38 patients (20.9%) experienced MACE. In this study, the existence of PAI-1
+
PEV complex was validated by flow cytometry (Figure 1A). Furthermore, low log-transformed PAI-1
+
PEV levels were associated with MACE (4.17 0.40 vs. 4.33 0.59 logPAI-1
+
PEV, p=0.02). After adjustment for known clinical risk factors, low PAI-1
+
PEV levels were independently associated with MACE with a hazard ratio of 7.79 (95% CI, 1.87 to 32.4, p=0.005). Finally, low plasma PAI-1
+
PEV levels was predictive of MACE in both the discovery and validation cohort (Figure 1B-C).

Conclusion:
Our results demonstrate the existence of a PAI-1
+
PEV and its potential utility as a biomarker to predict MACE. Low plasma PAI-1
+
PEV levels was predictive of MACE in both the discovery and validation cohort.