bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14420: Outcomes in Women With Cardiogenic Shock: Data From the Critical Care Cardiology Trial Network (CCCTN)
Authors: Phreaner Nicholas , Aldiwani Haider , Berg David , Park Jeong-Gun , Katz Jason N , Van Diepen Sean , Morrow David A , Bohula Erin A , Daniels Lori B ,   on behalf of the CCCTN Investigators
Published: May 2021

Introduction:
Although sex-specific differences in treatment and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) have been described, little is known about sex-specific differences in acute decompensated heart failure-related CS (ADHF-CS).

Methods:
The CCCTN is an investigator-initiated multicenter network of cardiac intensive care units (CICUs) in North America. Consecutive admissions (n=8240) to the CICU during annual snapshots (mostly 2 months) were submitted to the coordinating center (TIMI Study Group, Boston, MA). Patients were stratified by sex and type of CS. Adjustments were made for age and SOFA score.

Results:
Between 2017 and 2019, 1487 admissions were for CS of which 879 (33% women) were for ADHF-CS. In this cohort, age (median 62 y), race, and BMI (median 28 kg/m
2
) did not differ by sex. Women and men also had similar SOFA and IABP-SHOCK II scores. Women were less likely to have CKD (28% vs 42%, p=<0.001) and CAD (28% vs 45%, p<0.001) but were significantly more likely to have underlying pulmonary disease (23% vs 15%, p<0.01). Although women and men had a similar burden of pre-existing HF (72% vs 75%, p=0.35), women were more likely to have HF with preserved ejection fraction (19% vs. 5%, p<0.001). Women had shorter CICU stays (4.0 vs 5.5 days, p<0.001), and numerically, though not significantly, lower use of pulmonary artery catheters (48% vs 53%, p=0.13) and mechanical circulatory support (28% vs 34%, p=0.11). In-hospital mortality in women with ADHF-CS was significantly higher than in men (39% vs 26%, p<0.001, adj-OR 2.05 (95% CI 1.47-2.86; p<0.001)). In contrast, in-hospital mortality for AMICS did not differ by sex (38% vs 40%, p=0.69).

Conclusions:
Compared to men, women admitted to the CICU with ADHF-CS had higher mortality despite similar indices of illness severity. The reason(s) behind this difference merit further study.
Abstract 14427: Differences in Molecular Phenotype in Mouse and Human Hypertrophic Cardiomyopathy Suggest Need for Precision Medicine Approach to Treatment Based on Human Studies
Authors: Vakrou Styliani , Liu Yamin , Zhu Li , Guan Yufan , Fukunaga Ryuya , Abraham M Roselle
Published: May 2021

Background:
Mouse studies at early stage of hypertrophic cardiomyopathy (HCM) indicate allele-specific differences in cardiac gene expression and mitochondrial function. But data at established disease stage in mouse and human HCM are lacking. We hypothesized that 1) allele-specific differences persist at established stage, and 2) mouse and human HCM have distinct molecular biosignatures.

Methods:
We analyzed the transcriptome (mRNA, miRNA) in 2 HCM
mouse
models (R92W-TnT, R403Q-MyHC)/littermate controls at 24weeks of age and in
human
myectomy samples/healthy-control hearts (
GSE36961, GSE36946
). We examined myocyte redox, mitochondrial DNA copy number (mtDNA-CN), respiration, ROSgeneration/scavenging and Ca
2+
handling in mutant/littermate-control
mice
.

Results:
Analysis of mRNA/miRNA expression and Ingenuity Pathway Analysis (IPA) revealed distinct allele-specific gene expression in mouse HCM and marked differences from human HCM. Only
CASQ1 and GPT1
were similarly regulated in both mouse HCM/human HCM. KEGG analysis revealed enrichment of several metabolic pathways, but only pyruvate metabolism was enriched in both mouse HCM/human HCM. IPA predicted upregulation of 2 pathways (inflammasome, type 2 diabetes signaling) in MyHC mutants, and upregulation of 18 pathways (including STAT3, ILK, Ca
2+
signaling) in TnT mutants; the anti-hypertrophic/anti-fibrotic LXR/RXR pathway was the most upregulated in human HCM. Losartan was a predicted therapy only in TnT mutants. Myocytes of both mutant mice exhibited an oxidized redox environment. Mitochondrial complex I respiration was lower in both mutants compared to controls. MyHC mutants had similar mtDNA-CN and mitochondrial Ca
2+
handling, but TnT mutants demonstrated lower mtDNA-CN and impaired mitochondrial Ca
2+
handling, compared to respective controls.

Conclusions:
Molecular profiling reveals allele-specific differences in mRNA/miRNA expression, intracellular signaling and mt-function/number in mouse HCM at established disease stage. Transcriptional differences between mouse and human HCM highlight the need for precision medicine approaches based on human studies.
Abstract 14463: A Novel Mouse Model of the Effect of Acute Kidney Injury on Neointima After Injury of an Artery
Authors: Diao Yanpeng , Lu Yuanqing , Segal Mark S
Published: May 2021

Introduction and Hypothesis:
Acute kidney injury (AKI), even if renal function returns to normal, is associated with an increased risk of cardiovascular disease. We have developed a novel, mouse model that allows investigation into the mechanism of this clinical scenario. We hypothesized that AKI, particular at a severe level, may result in a permanent change to the vasculature that would promote atherosclerotic lesions.

Methods and Results:
AKI was induced by clamping the bilateral renal vessels of male, C57/BL mice for 28-30 minutes. The creatinine (Cr) was measured two days later to determine the severity of the AKI. An increase in the Cr of at least three-fold, was defined as severe damage, corresponding to Kidney Disease Improving Global Outcomes (KDIGO) AKI Stage 3. If the Cr increased less than three times, this was defined as mild/moderate AKI. Ten weeks after AKI, the Cr was measured to determine if renal function returned to baseline and the femoral artery was injured by repeated introduction of a guidewire. After four weeks, the animals were sacrificed and the neointima lesions were analyzed. Immunohistochemistry for smooth muscle myosin heavy chain revealed that the neointima was mostly composed of smooth muscle cells. The re-endothelialization was almost complete, as determined by anti-CD31 staining. More interestingly, the narrowing rate of the injured artery in animals who suffered severe AKI was higher than in the mild/moderate AKI animals (53.2% vs 27.2%; P= 0.04). There is no difference between the sham-AKI animals and the mild/moderate AKI animals (34.9 % vs 27.2%, see picture).

Conclusions:
Severe AKI induces a permanent change to the vasculature and/or the immune cells that hastens the development of neointima even after renal function recovers. This work has implications for the development of human atherosclerosis in the clinical setting after AKI. Potential mechanisms for this increased propensity will be discussed.
Abstract 14469: The Automatically Assessed P-wave Notch Associated With Not Only Left Atrial Enlargement but Also Cardio-ankle Vascular Index in Patients With Cardiovascular Risks: The Coupling Study
Authors: Kabutoya Tomoyuki , Hoshide Satoshi , Kario Kazuomi
Published: May 2021

Background:
The notched P-wave characteristics is associated with atrial remodeling. However, the relationship between notched P-wave characteristics and atherosclerosis remains unclear.

Hypothesis:
We hypothesized that notched P-wave would associated with measurements of atherosclerosis in patients with cardiovascular risk factors.

Methods:
We enrolled 4,877 subjects from the coupling Study who had ≥1 of cardiovascular risk factors. Twelve-lead electrocardiography was conducted, and the peak-to-peak distance in the M-shape was calculated automatically using a 12-lead ECG Analysis system (Fukuda Denshi, Tokyo). P waves were defined as "notched" if the peak-to-peak distance in the M-shape was ≥40 msec in lead II. We measured cardio-ankle vascular (CAVI), NT-proBNP, and Troponin T. We also assessed the left atrial diameter and left ventricular mass index (LVMI) by echocardiography in 501 patients.

Results:
The CAVI with notched P wave were significantly higher than those in the patients without notched P wave (9.75±1.56 vs. 8.86±1.37, p<0.001). The LA diameter, LVMI, and BNP in the patients with notched P wave were significantly higher than those in the patients without notched P wave (LA dia.: 40.2±7.0 vs. 37.0±5.0 mm, p=0.008; LVMI: 105.7±25.7 vs. 96.9±25.2 g/m
2
, p<0.001; median BNP: 41.6 vs. 16.5 pg/dL, p<0.001). A multivariate regression analysis including age, gender, smoking, history of hypertension, dyslipidemia, diabetes revealed that notched P wave was independently associated with an increase of CAVI (odds ratio 2.14, 95%CI 1.40-3.27, p<0.001).

Conclusions:
The automatically assessed P-wave notch associated with not only left atrial enlargement but also CAVI in patients with cardiovascular risks.
Abstract 14476: A Randomized, Double-blind Comparison Study of Royal Jelly to Improve Endothelial Function in Healthy Volunteers
Authors: Fujisue Koichiro , Tsujita Kenichi
Published: May 2021

Backgrounds:
Royal jelly is a creamy substance secreted by honeybees. It has been reported that royal jelly has benefits on dyslipidemia and metabolic syndrome. However, the effects of royal jelly on atherogenesis remains unknown. We prospectively evaluated the effects of royal jelly on endothelial function, which can reflect early atherogenesis, in healthy volunteers.

Methods:
This was a single center, double-blind, 1:1 randomized placebo-controlled study. One-hundred healthy volunteers were randomly assigned to receive royal jelly 690 mg daily (equivalent 2040 mg of fresh royal jelly) or placebo from October 2018 and December 2019. Royal jelly or placebo were administered for 28 days. Endothelial function assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) and blood chemistries were compared between baseline and 28 days after enrollment. Primary endpoint was the change of RH-PAT index. Secondary endpoint was the change of liver function and lipid profiles.

Results:
The mean (SD) age of the participants was 35.0 (9.3) and 36.1 (9.1) years, and male was 45% and 50% in the placebo and the royal jelly group, respectively. The relative change of RH-PAT index was significantly higher in the royal jelly group compared with placebo control (21.4 ± 53.1% vs. 0.05 ± 40.9%, P = 0.037). The relative change of alanine aminotransferase and γ-glutamyl transpeptidase were significantly lower in the royal jelly group than the placebo group (alanine aminotransferase: –6.06 ± 22.2% vs. 11.6 ± 46.5%, P = 0.02; γ-glutamyl transpeptidase: -3.45 ± 17.8% vs. 4.62 ± 19.4%, P = 0.045). Lipid profiles were not significantly different between two study groups.

Conclusions:
Royal jelly improved endothelial function assessed by RH-PAT and liver function in healthy volunteer. It can be expected that royal jelly has anti-atherogenic property through improving endothelial function.
Abstract 14479: Fontan Patients With Dominant Left Ventricular Morphology Have Severe Ventricular Electromechanical Discoordination Associated With Worse Exercise Capacity
Authors: Schafer Michal , Younoszai Nolan , Frank Benjamin , von Alvensleben Johannes , IVY Dunbar D , Barker Alexander , Mitchell Max B , Jaggers James , Jacobsen Roni , Younoszai Adel K , Di Maria Michael V
Published: May 2021

Introduction:
Fontan patients with a single left ventricle (SLV) develop late systolic and diastolic dysfunction. The development of SLV dysfunction has been associated with abnormal loading conditions, myocardial ischemia and fibrosis, and compromised ventricular-aortic coupling. However, electromechanical discoordination, a prime determinant of ventricular performance, has not been adequately evaluated in patients with SLV.

Hypothesis:
Patients with SLV and Fontan circulation will have abnormal electromechanical discoordination compared to controls, and this will be associated with their functional status.

Methods:
Patients with SLV (n=20) and healthy controls (n=20) underwent MRI-based tissue deformation analysis. Circumferential strain and strain rate data were used to calculate systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF) (Figure 1). SSF is the proportion of myocardial segments undergoing relaxation in systole, while the DRF is the proportion of myocardial segments undergoing contraction in diastole. SSF and DRF were correlated with standard MRI indices and standard exercise tests.

Results:
Global circumferential strain was decreased in SLV compared to controls (16.4±2.7 vs 19.9±1.7, P<0.001). SLV had increased median SSF when compared to the LV of controls [(0.023 (IQR: 0.006-0.036) vs. 0.007 (IQR: 0.006-0.013), P=0.023] and increased median DRF [0.39 (IQR: 0.30-0.44) vs. 0.30 (IQR: 0.26-0.32), P=0.002]. SSF correlated with the peak VO
2
index (R=-0.56, P=0.027) and DRF correlated with ejection fraction (R=-0.56, P=0.010).

Conclusion:
Fontan patients with SLV exhibit systolic and diastolic electromechanical discoordination, which is associated with lower peak VO
2
and reduced ejection fraction, respectively. Electromechanical discoordination might contribute to global SLV dysfunction by limiting both effective contractility and preload generation.
Abstract 14484: The Association of Pre-operative Glycemic Control With Long-term Survival in Diabetic Patients After Coronary Artery Bypass Grafting
Authors: Sheikh Muhammad , Deo Salil V , Sundaram Varun , Wilson Brigid , Sahadevan Jayakumar , Rubelowsky Joseph , Mohan Srikrishna M , Josephson Richard A , Elgudin Yakov , cmolik Brian L
Published: May 2021

Introduction:
We analyzed the national Veteran Affairs (VA) data to evaluate the association of preoperative glycated Hemoglobin (HbA1c) and long-term outcome after isolated coronary artery bypass grafting (CABG).

Methods:
Between January 2007 - December 2014, Veterans with diabetes mellitus (DM) that underwent isolated CABG were divided on into three groups (I: HbA1c < 8%, II: HbA1c 8 - 10% and III: HbA1c > 10%). Demographic and clinical differences between groups were evaluated with the t-test or chi-square test. The relationship of preoperative HbA1c and long-term survival was evaluated with a multivariable proportional hazards model; restricted cubic splines were used to model non-linear effects. The cumulative incidence of secondary end-points (myocardial infarction, urgent revascularization) for each group was modeled as a competing-risk analysis.

Results:
Overall, 3,210 patients (mean age 64.6 years, male 98.8%; insulin dependent - 53%) with DM underwent isolated CABG. Group III patients were younger (61 vs 65 years in group I). Median HbA1c levels were similar between races (white - 7.3% and blacks - 7.35%). Insulin dependence was higher in group III (79.3%) vs groups I (43.5%) and II (69.9%). In groups I,II and III, 5 and 10 year survival was 76.2%, 74.4%, 75.4% and 38.9%, 36.9% and 30.2% respectively. HbA1c was observed to have a J-shaped association with mortality with values < 6% and > 9% at higher risk of death. Left ventricular systolic dysfunction [HR 1.5 (1.3 - 1.7)], prior myocardial infarction [HR 1.3 (1.2 - 1.5)] and insulin dependence [HR 1.4 (1.2 - 1.5)] were also associated with lower survival. Myocardial infarction was observed in 9.8% , 13.4% and 12.8% patients in groups I, II and III respectively.

Conclusions:
Pre-operative HbA1c impacts long-term survival among diabetic patients undergoing CABG. We observed a J-shaped relationship between HbA1c and survival with values < 6% and > 9% associated with increased mortality.
Abstract 14625: Clinical Outcomes of Autologous Stem Cell Patch Implantation for Heart Failure Patients With Non-ischemic Dilated Cardiomyopathy
Authors: Domae Keitaro , Miyagawa Shigeru , Toda Koichi , Yoshioka Daisuke , Kainuma Satoshi , Kawamura Takuji , Kawamura Ai , Kashiyama Noriyuki , Iseoka Hiroko , Ito Emiko , Harada Akima , Takeda Maki , Yamada Tomomi , Sawa Yoshiki
Published: May 2021

Background:
Although pre-clinical researches proved that cardiac regenerative therapy with autologous skeletal stem cell (SSC) patch implantation healed non-ischemic dilated cardiomyopathy (NIDCM) animal model by anti-fibrotic effect and preservation of cytoskeletal proteins in distressed myocytes, its clinical effectiveness for NIDCM has not been clearly elucidated. We hypotheses SSC patch implantation for NIDCM is feasible, safe and have therapeutic efficacy and we aim to identify the predictor of responder of this treatment in NIDCM patients

Methods:
Twenty-four NIDCM patients with ejection fraction less than 35% underwent SSC patch transplantation (average: 3.9±0.4х10
8
cells) via the left thoracotomy without concomitant procedures. We identified thirteen responders (Group RP) and eleven non-responders (Group NR) using the combined indicator of major cardiac adverse event and incidence of heart failure event.

Results:
In Group RP, symptoms, exercise capacity and cardiac performance were improved postoperatively (NYHA functional class; 2.5±0.5 to 1.9±0.3, p<0.05, six-minute walk test; 471(370-541) to 525(425-555)m, p<0.05, LVSWI; 31.1(22.7-35.5) to 32.8(28-38.5)g/m
2
/beat, p=0.21). However, such improvement was not observed in Group NR. Overall survival rate was 90.9±8.7% at 5 years, which was superior to estimated survival rate using Seattle heart failure model (SHFM) of 70.9±5.4% in Group RP. However overall and estimated survival rate using SHFM was similar in Group NR (47.7±21.6% and 56.3±8.1%). Preoperative histological analysis demonstrated significant low level of hypertrophy of myocyte and interstitial fibrosis and high expression of histone methylation-related molecules in Group RP compared with Group NR. Multivariate regression model with BNP, PCWP and expression of histone H3 lysine 4 trimethylation (H3K4me3) strongly predicted the responder (BNP: OR 0.96, PCWP: OR, 0.58, H3K4me3; OR, 1.35, AUC in ROC, 0.96, p<0.001).

Conclusions:
This clinical trial demonstrated that SSC patch implantation might promise functional recovery and good clinical outcome in selected NIDCM patients with preoperatively preserved diastolic function and ability of protein synthesis in myocytes.
Abstract 14629: Rare Variants for Electrocardiographic Traits Identify Arrhythmia Susceptibility Genes
Authors: Jurgens Sean J , Choi Seung Hoan , Haggerty Christopher M , Hall Amelia W , Halford Jennifer , Morrill Valerie , Weng Lu Chen , Lagerman Braxton , Mirshahi Tooraj , Pettinger Mary , Guo Xiuqing , Kornej Jelena , Lin Honghuang , Moscati Arden , Nadkarni Girish , Brody Jennifer , Wiggins Kerri , Cade Brian E , Lee Jiwon , Austin-Tse Christina , Blackwell Tom , Chaffin Mark , Lee Christina J , Rehm Heidi , Redline Susan , Mitchell Braxton D , Sotoodehnia Nona , Psaty Bruce M , Heckbert Susan R , Loos Ruth J , Vasan Ramachandran S , Benjamin Emelia J , Correa Adolfo , Boerwinkle Eric , Arking Dan E , Rotter Jerome I , Rich Stephen , Whitsel Eric A , Perez Marco V , Kooperberg Charles , Fornwalt Brandon , Lunetta Kathryn , Ellinor Patrick T , Lubitz Steven A
Published: May 2021

Introduction:
Electrocardiogram (ECG) intervals are quantitative and heritable endophenotypes for arrhythmias and sudden cardiac death (SCD). Studying rare sequence variation related to ECG intervals may help identify the genetic underpinnings of cardiac conduction and SCD.

Methods:
Using a discovery sample of 29,000 individuals with whole-genome sequences from TOPMed and a replication sample of about 100,000 individuals with whole-exome sequence data from the UK Biobank and MyCode, we examined associations between low-frequency (MAF<1%) and rare (MAF<0.1%) coding variants with 5 routinely ascertained ECG intervals (RR, P-wave, PR, QRS, and QTc intervals). We further assessed pathogenic variants in identified genes using ClinVar.

Results:
In low-frequency single variant analysis, we observed associations for PR interval in
PAM
(
P
=2x10
-7
) and
MFGE8
(
P
=5x10
-8
). In gene-based tests, we identified rare coding variation associated with marked effects in established SCD genes
KCNQ1, KCNH2, SCN5A
and
KCNE1
. For example, loss-of-function or pathogenic variants in
KCNQ1
and
KCNH2
were carried in 0.2% of individuals, were associated with 29 ms longer QTc intervals (
P
=2x10
-82
) and conferred up to 23-fold increased odds of marked QTc prolongation (
P
=4x10
-25
). Nevertheless, over 75% of carriers had normal QTc intervals. Similarly, loss-of-function or pathogenic variants in
SCN5A
, carried by 0.1% of individuals, conferred marked PR prolongation (31 ms), yet less than 30% of carriers had first-degree atrioventricular block.

Discussion:
This study demonstrates the value of studying ECGs in large sequenced biobanks for identifying rare variants predisposing to cardiac arrhythmias. Results define the frequency of pathogenic variation in SCD genes in the population and document incomplete penetrance of such variation. Our findings may serve as a benchmark for future population-based analyses aimed at discovering clinically actionable variants and genes.
Abstract 14631: Assessment and Resolution of Complex Coronary Configurations by the Multi-artery Fractional Flow Reserve Method
Authors: Yaeger Ilan A
Published: May 2021

Introduction:
Statistical studies have shown that an FFR method is superior to the traditional coronary assessment method based on angiographic appearance. The current FFR-oriented methods (resting P
d
/
P
a
, wave-free iFR and hyperemic FFR) however, share a common downside: They do not consider inter arterial interactions and therefore cannot resolve multi-artery configurations, a vital capability provided by the novel multi-artery FFR method.

Methods:
An independent stand-alone stenotic coronary artery is characterized by its intrinsic FFR (denoted FFR
true
). In a multi-artery configuration however, it is influenced by interconnected arteries and the treatment decision criteria apply to the actual FFR (denoted FFR
real
) that reflects the arterial current condition. Seeking an optimal resolution of a stenotic configuration, outcomes (FFR
true
and FFR
real
) of optional revascularizations are predicted and evaluated by the multi-artery FFR method.

Results:
In this work the multi-artery FFR method is applied to the stenotic unprotected configuration LMCA-LCx-LAD-M
2
(second obtuse marginal). The initial characteristics of the configuration are: FFR
true
(LMCA)=0.87 FFR
true
(LCx)=0.76 FFR
true
(LAD)=0.92 FFR
true
(M
2
)=0.93 FFR
real
(LMCA)=0.75 FFR
real
(LCx)=0.67 FFR
real
(LAD)=0.82 FFR
real
(M
2
)=0.63 After optimal resolution (by hyperemic FFR criteria), the final characteristics are: FFR
true
(LMCA)=0.87 FFR
true
(LCx)=1.00 FFR
true
(LAD)=1.00 FFR
true
(M
2
)=0.93 FFR
real
(LMCA)=0.87 FFR
real
(LCx)=0.87 FFR
real
(LAD)=0.87 FFR
real
(M
2
)=0.80

Conclusions:
This work shows that a prerequisite for a successful resolution of a stenotic coronary configuration is a prior numerical simulation of the whole process in which the multi-artery FFR method is applied to the measured intracoronary pressures. This holds for each FFR-oriented method, preserving its specific experimental technique and treatment decision criteria. In conclusion, the multi-artery FFR method has the potential to introduce the PCI practice into an all new era in which the practitioner can devise a resolution strategy and test it by predicting outcomes (in terms of FFR
true
and FFR
real
of the arteries) of potential revascularizations, prior to actual implementation.
Abstract 14634: Hospital Teaching Status and Variation in Outcomes: Evidence From Patients Undergoing Multi-vessel Percutaneous Coronary Interventions
Authors: Ajibawo Temitope ,   Oluwatimilehin Okunowo,   Farla Jean-Louis,   Uvie Ajibawo-Aganbi
Published: May 2021

Background and Objectives:
Evidence suggests variations in medical services provided by hospital teaching status. However, there is limited data on how it affects hospital outcomes. The aim of this study is to examine differences in outcomes among patients who underwent multi-vessel percutaneous coronary intervention (MVPCI) stratified by hospital teaching status.

Methods:
We queried the 2016 Nationwide Inpatient Sample database and identified patients who underwent MVPCI using ICD-10 procedure codes. Hospital teaching status was classified as urban teaching vs. non- teaching. Chi-square and Wilcoxon rank-sum tests were used to compare the following outcomes between hospitals: patient demographics, clinical outcomes, in-hospital mortality, length of stay (LOS), and total charges.

Results:
Among the 15,611 MVPCI procedures performed, 73.5% were done in teaching hospitals. 68.4% of the MVPCI in teaching hospitals were in males and 54.1% in patients aged ≥65 years. Teaching hospitals had a lower proportion of whites (74.1% vs 79.5%, p<0.001). Teaching and non-teaching hospitals did not differ significantly in impella use (1.7% vs 1.7%, p=0.9928), IABP use (2.2% vs. 2.3%, p=0.7156) and in-hospital mortality (2.0% vs 2.2% p=0.3399). The incidence of acute renal failure (14.0% vs 13.5%, p=0.3858), cardiogenic shock (4.5% vs 4.7%, p=0.5969), cardiac tamponade (0.2% vs 0.2% p=0.5769), and ventricular fibrillation (2.6% vs 2.9%, p=0.2570) did not differ significantly. However, the median length of stay (LOS) (3 vs 2 days, p=0.0075) and hemorrhage requiring transfusion (HRT) (5.6% vs 4.7%, p=0.0414) were significantly greater in teaching centers. In contrast, total hospital charges ($96,465 vs. $106,711, p<0.0001) was lower in teaching centers.

Conclusion:
Our analysis did not show any differences with regards to in-hospital deaths, IABP use, impella use and many of the hospital outcomes in MVPCI. In teaching centers, the occurrence of HRT and the mean LOS was increased, but there was no increased financial costs.
Abstract 14639: An Integrated Heart Center Model Improves Outcomes After Congenital Heart Surgery
Authors: Mery Carlos M , Well Andrew M , Beckerman Ziv , Gottlieb Erin , Holt Byron , Stromberg Daniel , Krauklis Kimberly , Morton Laura , Denison Blake , McCullum Elizabeth , Fraser Charles D
Published: May 2021

Introduction:
Contemporary experience suggests that congenital heart surgery (CHS) outcomes are optimized with an integrated, focused, and multidisciplinary program. In July 2018, our institution transitioned to an integrated Heart Center (IHC) model with new dedicated surgical, cardiac intensive care, anesthesiology, perfusion, and nursing teams. Multidisciplinary protocols and quality processes were implemented. This transition provides an unusual opportunity to evaluate the impact of an IHC model on outcomes after CHS.

Methods:
Patients who underwent index CHS 10/16-3/20 were included. The cohort was divided into 2 groups: historical (first 21 mo) and IHC (second 21 mo). Cases were evaluated using STAT category, mortality, and other outcomes as defined by Society of Thoracic Surgeons criteria. Descriptive statistics, univariate analyses, and multivariable regression models were used.

Results:
The cohort included 627 patients (historical: 230, IHC: 396, 72% increase). Numbers of STAT 4 and 5 cases increased 174% (31 to 85) and 900% (1 to 10), respectively. Neonatal cases increased 100%, infants 138%, and adults 622%. Despite an increase in complexity, perioperative mortality decreased from 3.5% to 0.5% (p=0.007) (Table). Median postoperative length of stay (LOS) increased from 5[4-10] to 7 [4-18] days (p<0.001). 30-day readmission rates increased from 8.6% to 14% (p=0.048). After adjusting for patient characteristics and STAT category, perioperative mortality remained significantly lower (OR 3.4, 95% CI 1.1-5.6, p=0.004), postoperative LOS was longer (RR 6.9, 95% CI 2.6-11.1, p=0.002), and 30-day readmission was not different (p=0.7).

Conclusions:
Implementation of an IHC model improves perioperative survival after CHS, coupled with an increase in volumes and complexity. CHS care should be delivered as part of a dedicated and multidisciplinary IHC model.
Abstract 14666: Association Between Right Ventricular Systolic Pressure and Health Status Following Transcatheter Aortic Valve Replacement
Authors: Myadam Rahul , Malik Ali O , Pflederer Matthew , Gosch Kensey , Arnold Suzanne V , Chhatriwalla Adnan
Published: May 2021

Introduction:
Pulmonary hypertension (PH) was shown in multiple studies to be associated with an increased risk of mortality after transcatheter aortic valve replacement (TAVR). However, it is unclear if echocardiogram derived right ventricular systolic pressure (RVSP) is associated with health status outcomes in surviving patients after TAVR. We explored for an association between baseline RVSP and quality of life in patients before and after undergoing TAVR.

Methods:
We estimated RVSP by echocardiography using the modified Bernoulli equation in a single-center cohort of patients undergoing TAVR from 2012-2017
.
Disease-specific health status was assessed at baseline and 1-month and 12-months after TAVR with the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (KCCQ-OS). We then explored the association between baseline RVSP and KCCQ-OS before and after TAVR using a linear mixed model with an interaction for time and baseline RVSP and adjusted for baseline mitral valve regurgitation and systolic blood pressure.

Results:
Among 485 patients who underwent TAVR (mean age 81.7±7.9 years, 54.8% men), baseline RVSP was 42±15 mmHg, and 73% had RVSP >34 mmHg. After TAVR, mean RVSP decreased to 37±13 mmHg at 1 month and 36±14 mmHg at 12 months. Baseline KCCQ-OS was 46±25 and improved to 66.9±23.6 at 1 month and 69.5± 22.6 at 12 months. In the linear mixed model, there was a significant cross-sectional association between baseline RVSP and baseline KCCQ-OS, with higher RVSP associated with worse health status. However, baseline RVSP was not significantly associated with KCCQ-OS at 1 month or 12 months (Figure).

Conclusions:
RVSP is not associated with worse health status after TAVR. This suggests that while patients with high RVSP are at an increased risk for mortality after TAVR, surviving patients appear to have similar health status as those with normal RVSP.
Abstract 14673: Cardiomyocyte Specific Overexpression of Pellino 1 Reverses Sepsis Induced Cardiac Dysfunction in a Murine Model by Reducing Inflammatory Response and Cardiac Cell Death
Authors: Swaminathan Santosh , Pradeep Seetur R. , Wilson Rickesha I , Campbell Jacob , Thirunavukkarasu Mahesh , Accorsi Diego , Palesty J. Alexander , Maulik Nilanjana
Published: May 2021

Introduction:
Sepsis remains a significant cause of mortality in the intensive care unit till today. Recent research suggests nearly one in four deaths in people with heart failure is caused by sepsis. Overexpression of mammalian Pellino-1 (Peli1), a E3 ubiquitin ligase, causes inhibition of apoptosis, oxidative stress, and preservation of cardiac function in a myocardial infarction model. Therefore, in the present study, we explored the possibility to overcome sepsis mediated heart failure by overexpressing Peli1 (AMPEL1Tg/+) in a mouse model of severe sepsis.

Methods:
C57BL/6J (WT) and AMPEL1
Tg/+
mice were divided into Wild-type sham (WTS), Wild-type Cecal Ligation and Puncture (WTCLP), AMPEL1
Tg/+
sham (AMPEL1
Tg/+
S) and AMPEL1
Tg/+
CLP. Cardiac function (LVEF, FS) by two-dimensional echocardiography was assessed pre-procedure, at 6, and 24 hours post-surgery. Serum IL-6 and TNF-alpha (ELISA) at 6 hours and cardiac apoptosis (TUNEL assay) at 24 hours were measured. Results are expressed as mean ± SEM.

Results:
Analysis of echocardiographic parameters (EF, FS) preoperatively and among the sham groups were similar however there was significant preservation of post-procedure LVEF (%) in the AMPEL1
Tg/+
CLP at the 6 hour (AMPEL1
Tg/+
:52.7 ± 3.71 vs WT:40.7 ±2.46, p=0.013, n=10-11) and 24-hour time point (AMPEL1
Tg/+
:63.1 ± 1.63 vs WT:49.3 ± 4.41, p=0.002, n=9-11) compared to WT. Similar trend was observed in estimation of FS (%) at 6 hours (AMPEL1
Tg/+
:26.3 ± 2.22 vs WT:19.3 ±1.37, p=0.014, n=10-11) and 24 hours (AMPEL1
Tg/+
:32.4 ± 1.89 vs WT:24.4 ± 2.67, p=0.031, n=9-11). A marked decrease in serum IL-6 (AMPEL1
Tg/+
:259.7 ± 18.70 vs WT:483.2 ± 24.01, p<0.0001, n=6, pg/mL) and TNF-alpha (AMPEL1
Tg/+
:86.89 ± 14.36 vs WT:161.8 ± 20, p=0.012, n=6, pg/mL) was observed in the AMPEL1
Tg/+
CLP at 6 hours. The preserved cardiac function in CLP was further supported by a noticeable decrease in cardiac apoptosis (% TUNEL positive cells) at 24 hours in the AMPEL1
Tg/+
CLP group (4.7 ± 0.94 vs 11.7 ± 2.82, p=0.040, n=6,) compared to WTCLP.

Conclusions:
Thus, Peli1 overexpression is a novel approach that preserved cardiac function, reduced inflammatory markers, and apoptosis following severe sepsis in a murine genetic model.
Abstract 14688: Relative Blood Volume Change After Single Doses of a Loop Diuretic to Assess Volume Status: A Patient Level Meta-analysis
Authors: Misra Shantum , lucas brian P
Published: May 2021

Background:
In patients with congestive heart failure administration of an intravenous diuretic results in increased urine production and, depending on the volume status, an immediate change in relative blood volume (RBV). Changes in RBV are already applied clinically to monitor fluid removal and better guide diuresis in patients who undergo peripheral ultrafiltration. Using individual level patient data, we explored whether it is possible to measure changes in RBV after a single intravenous dose of loop diuretic through the measurement of serial hematocrit values. Based on normally occurring variation in volume-stable patients, the smallest change in RBV that would be detectable by routine serial hematocrits ranges from 6.4% to 8.6%.

Methods and Results:
Electronic databases were queried for articles that contained predefined MeSH terms in order to identify all studies in which patients received intravenous diuretics. The 764 studies that met our entry criteria were systematically reviewed and manually screened. We then conducted a meta-analysis from 14 studies that provided individual, patient-level data from at least 2 time points: just before and within 3 hours of administration of an intravenous loop diuretic. We found that among a total of 240 patients, RBV decreased by 11% (95% CI 10 to 12%) at 2 hours after an intravenous loop diuretic was given (Figure); there was no significant difference in this finding based on whether or not patients had heart failure.

Conclusion:
We found that anticipated RBV change with single doses of intravenous loop diuretics exceeds the smallest detectable change in RBV that can be obtained by serial hematocrits. This implies that routine hematocrits can be used to track RBV change across serial doses of intravenous loop diuretics, potentially providing a target for a dry interstitium in acute heart failure.
Abstract 14691: Heart Rate Trajectories and Clinical Correlates in Patients Recovering From Acute Myocardial Infarction: A Longitudinal Analysis of Apple Watch Heart Rate Recordings
Authors: Weng Daniel , Ding Jie , Sharma Apurva , Yanek Lisa R , Xun Helen , Osuji Ngozi , Huynh Pauline , Ogunmoroti Oluseye , Spaulding Erin , Knowles Kellen , Gao Yumin , Yang William , Lee Matthias , Demo Ryan , Marvel Francoise A , Martin Seth S
Published: May 2021

Introduction:
Vital signs can provide critical details regarding a patient’s health status for clinical decision making, and confirm feedback on treatments. Using mobile health technology, vital signs such as heart rate can be collected in larger quantities without requiring frequent clinic visits. In this study, we characterized HR trends of patients recovering from acute myocardial infarction (AMI) in the subacute period, with the goals of identifying higher risk patient subgroups.

Methods:
Between Nov. 2017 and Apr. 2019, type 1 AMI patients were enrolled in the Myocardial infarction, Combined device, Recovery Enhancement (MiCORE) study (NCT03760796). Patient information was collected via Research Electronic Data Capture (REDCap), and HRs were recorded using the Apple Watch and Corrie smartphone app between the time of admission to 30 days post-discharge. Associations with clinical covariates were assessed with multivariable linear mixed regression models (Figure 1).

Results:
We recruited 91 patients (mean age: 57 +/- 10.9, 74% male) who provided 4,447 HR recordings, with an overall mean daily HR of 74.5 bpm. Patients had a 0.168 bpm decrease in mean daily HR for each consecutive day post-discharge; the exception were patients who had a prior CABG before admission, hypertension, or type 2 diabetes, who had an associated elevation in HR across each day (Figure 1). Six of 11 AMI patients who were readmitted within 30 days exhibited at least 1 HR recording greater than 90 bpm within 3 days of readmission.

Conclusions:
While most AMI patients had a decrease in HR over the subacute period, we identified high-risk subgroups with increasing HRs (patients with prior CABG, HTN, and T2DM), and elevated HRs in patients three days prior to readmissions. This study highlights the potential of using longitudinal, biometric data sets in discerning higher risk patient populations post-AMI that require more targeted therapy.
Abstract 14724: Sex Differences in the Associations of Visceral Adipose Tissue and Cardiometabolic and Cardiovascular Disease Risk: The Framingham Heart Study
Authors: Kammerlander Andreas , Lyass Asya , Mahoney Taylor , Massaro Joseph , Long Michelle T , Ramachandran Vasan S , Hoffmann Udo
Published: May 2021

Background:
The current clinical practice of defining obesity based on body mass index (BMI) does not capture differences in fat distribution between men and women. Visceral adipose tissue (VAT) as measured by computed tomography (CT), is an advanced measure of obesity that closely correlates with cardiometabolic risk independent of BMI. However, it remains unknown whether VAT adds additional prognostic significance over BMI in men or women.

Methods:
In participants of the Framingham Heart Study, we tested the associations of BMI and VAT with incident cardiometabolic events (diabetes, hypertension, low HDL, hypertriglyceridemia), and incident cardiovascular events and death. Mean follow-up was 12.7±2.1 years. Logistic and Cox-regression models were adjusted for age and smoking and adjusted odds and hazard ratios (adj. OR, adj. HR), are presented per 1-SD increase of each measure of body fat.

Results:
The study cohort comprised 3,482 participants (48.1% women, 50.8±10.3 years old). In men, VAT, as compared to BMI, had a similar strength of association with all cardiometabolic outcomes and incident cardiovascular disease (Figure). In women, however, VAT conferred a markedly greater association with incident cardiometabolic and cardiovascular disease compared to BMI (Figure).

Conclusion and Relevance:
BMI adequately captures VAT-associated cardiometabolic and cardiovascular risk in men but not in women. In women, abdominal CT-based VAT measures permit more precise assessment of obesity-associated cardiometabolic and cardiovascular risk.
Abstract 14734: Characterisation and Prognostic Relevance of Left Ventricular Global Longitudinal Strain in Patients With Systemic Lupus Erythematosus
Authors: Khanna Shaun , Newman James M , Bhat Aditya , Chen Henry H , Gan Gary , Tan Timothy C
Published: May 2021

Introduction:
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease modulated by pro-inflammatory cytokines, which may result in myocardial dysfunction. Mean global longitudinal strain (GLS) is proposed to be a more sensitive measure of cardiac function in comparison to standard two-dimensional measures of left ventricular (LV) systolic function. Quantification of subclinical cardiac function, with impairment of LV-GLS, right ventricular free wall strain (RV-FWS), left atrial strain (LAs), and its prognostic relevance in patients with SLE is undefined.

Hypothesis:
SLE patients have evidence of subclinical cardiac dysfunction and the presence of impaired LV-GLS in this population portends a poor prognosis.

Methods:
Consecutive patients admitted to our institution with known history of SLE (> 1-year disease activity) were examined. Patients with pre-existing cardiac disease, LV ejection fraction (EF) <50% and those without comprehensive transthoracic echocardiograms were excluded. Mean GLS was performed offline using vendor-independent software (TomTec v4.6) and compared to age-, gender- and risk factor- matched controls. SLE patients were followed for up for the composite outcome of all-cause death and major adverse cardiovascular events.

Results:
A total of 51 patients with SLE were compared to 51 matched controls. No significant differences in baseline demographics, medications and laboratory investigations was observed. Patients with SLE showed evidence of subclinical cardiac dysfunction with significantly lower LV-GLS (%) (-16.7±2.8 vs -21.3±2, p<0.01), lower RV FWS (%) (-21.2±4.8 vs -28.8±4.7, p<0.01) and LAs (%) (31.9±6.7 vs 35.5±6.1, p<0.01) when compared to controls, despite normal LVEF, RV FAC and LAEF. On analysis of outcomes of SLE patients, a total of 11 (21.6%) patients suffered the composite end-point during a mean follow-up of 48 months. Of interest, LV-GLS was a predictor of the composite outcome on log-rank test and cox regression analysis (p<0.01).

Conclusions:
Our results suggest that SLE patients display evidence of subclinical cardiac dysfunction via a reduction in LV GLS, RV-FWS and LAs. Impairment in LV-GLS is associated with adverse cardiovascular outcomes in this population.
Abstract 14735: Volatile Organic Compounds Are Associated With Lower Ankle-Brachial Indexes in African Americans of the Jackson Heart Study
Authors: Kipchumba Rodney K , Musani Solomon K , Benjamin Emelia J , Oshunbade Adebamike A , Hamid Arsalan , Fetterman Jessica L , Fox Ervin R , White Wendy B , Keith Rachel J , CLARK Donald , Bhatnagar Aruni , Hamburg Naomi M , Hall Michael E
Published: May 2021

Introduction:
Cigarette smoking is associated with peripheral artery disease (PAD) in African Americans (AA), but the association between cigarette constituents and PAD remain inadequately studied. We evaluated the effect of volatile organic compounds (VOC) acrolein and crotonaldehyde on ankle-brachial index (ABI) as well as related biomarkers in AA participants of the Jackson Heart Study.

Methods:
Urinary VOC concentrations were measured in a subset of participants at baseline including 345 self-reported current smokers and 718 never smokers. Multivariable linear regression assessed the association between ABI and VOC concentrations after adjustment for acute (cotinine) and chronic (pack-years) smoking measures in models 1 and 2, respectively. The degree of association was assessed after adjusting for possible mediation (Baron & Kenny procedure) by C-reactive protein (CRP), fibrinogen, and homocysteine (HCY) concentrations. VOC concentrations were natural log transformed for normal distribution and all models adjusted for relevant covariates.

Results:
The mean age of included participants was 52 years and 49% women. Individuals who smoked were more likely to be men, less educated, have prevalent cardiovascular disease, and lower mean ABI. In model 1, ABI was inversely associated with urinary acrolein and crotonaldehyde concentrations. Model 2 retained the inverse ABI association for both VOC. Crotonaldehyde was directly associated with CRP and HCY in models 1 and 2. In model 1, acrolein was associated with HCY (Table). Biomarker mediation of the VOC-ABI relationship was insignificant.

Conclusions:
Acrolein and crotonaldehyde concentrations are associated with lower ABI and higher measures of inflammation and thrombosis in a community-based sample of AA. These findings suggest reduction in VOC exposure may reduce the risk of PAD in AA who smoke cigarettes.
Abstract 14740: Sympathetic Down-regulation With Zamicastat Reduces Arrhythmogenicity in Isolated Hearts From Rats With Pulmonary Hypertension
Authors: Pires Nuno , Igreja Bruno , Magalhaes Luis , Bonifacio Maria-Joao , chevalier eric , Soares-da-Silva Patricio
Published: May 2021

Introduction:
Pulmonary arterial hypertension (PAH) is a disease often causing right ventricular failure and death. During disease progression, structural and electrical remodeling of the right ventricle creates proarrhythmic substrates and triggers for arrhythmias. Studies of PAH patients show a hyperstimulation of the sympathetic nervous system (SNS) indicating that PAH may be mediated by SNS hyperactivation. Zamicastat (ZAM) is a reversible dopamine β-hydroxylase inhibitor that modulates SNS by reducing the biosynthesis of norepinephrine in peripheral sympathetic nerves. ZAM improves survival in the monocrotaline (MCT) rat model of PAH.

Hypothesis:
To evaluate the effect of ZAM on electrophysiological parameters in isolated hearts from MCT-treated rats.

Methods:
Male Wistar Han rats were randomized in 3 groups, Sham (n=6), MCT (n=15) and MCT+ZAM (n=17). On day zero, MCT and MCT+ZAM groups received MCT (60 mg/kg, SC) and Sham group received saline. Starting on day 12, MCT+ZAM rats were daily administered ZAM (30 mg/kg, PO) while all other animals were given vehicle. On day 28, hearts were excised and mounted on a Langendorff system. A bipolar circuit of two electrodes was placed on the epicardium for ECG recording. Provoked arrhythmias were induced with a burst pacing protocol (50Hz, 1 second) and the recovery time was measured as the time needed to reach 3 consecutive stable R-R intervals.

Results:
MCT increased the proportion of hearts exhibiting bundle branch blocks, 3
rd
degree atrioventricular (AV) blocks, atrial fibrillation (AF), ventricular fibrillation (VF) and premature ventricular contractions (PVCs) when compared to Sham group. ZAM treatment suppressed 3
rd
degree AV blocks, AF and VF. In addition, PVCs were less frequent in hearts from MCT+ZAM animals as compared to MCT group. Isolated hearts naturally entered a pause following overpacing-induced VF. MCT hearts showed a non-significant 1.7-fold increase in recovery time compared to Sham group. Hearts from MCT+ZAM animals had a significant ≈50% reduction in post-fibrillation pause.

Conclusions:
These data suggest that treatment with Zamicastat yields a lower proarrhythmic cardiac tissue decreasing the incidence of cardiac arrhythmias.
Abstract 14741: Autologous Cd34+ Cells (clbs119) for Repair of Covid-19 Induced Microvascular Lung Damage: Rationale and Study Design
Authors: Losordo Douglas W , Kotynski Christine , Bartel Ronnda , Takagi Hiroshi , Wang Jian , Lewis Michelle , Sietsema William K , Sterman Daniel , Harris Alan
Published: May 2021

Early evidence from COVID-19 patients and autopsy series indicates that moderate to severe cases are accompanied by damage to the pulmonary endothelium and microcirculation. These data indicate that SARS-CoV-2 infection is particularly avid for lung microvascular endothelium, reflecting endothelial cell infection, inflammation, and focal thrombi occluding the pulmonary circulation leading to progressive fibrosis reminiscent of endothelial-mesenchymal transition. This appears to be a potential mechanism by which COVID-19 causes progressive fibrotic changes, impairment in the pulmonary vasculature, and loss of lung function that persists after acute recovery. Early data from the SARS-CoV-1 epidemic indicated that CD34+ cells in the lung could also be a target of infection and that destruction of lung CD34+ progenitors could account for persistence of pulmonary manifestations. Preclinical studies reveal that restoration of microvasculature in the lung can trigger and sustain regeneration of lung tissue. The microvascular repair function of CD34+ has been documented in preclinical models and multiple human trials in ischemic tissue repair. Accordingly, we designed a clinical trial to evaluate autologous CD34+ cells (CLBS119) for amelioration/repair of COVID-19 lung damage. Subjects must be hospitalized for COVID-19 and have ongoing pulmonary involvement based on room air hypoxia. The study will include approximately 50% of subjects who cannot be liberated from ventilatory support. CD34+ cells will be mobilized with plerixafor and selected from the mononuclear fraction following apheresis. Doses up to 500 x 10
6
cells will be administered IV. Subjects will receive a single administration of cells. Key measures will include assessment of oxygenation, need for supplemental oxygen, pulmonary function assessments, radiographic assessments, and biomarkers. Subjects will be followed for 6 months following administration. Interim findings will be presented.