bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12186: The Role of Extracellular Matrix Turnover in Early Diastolic Recoil Efficiency
Authors: Tayon Kevin G , MacNamara James P , Carrick-Ranson Graeme C , Francis Spinale G , Levine Ben D , Sarma Satyam
Published: April 2022

Introduction:
Diastolic recoil is an important component of cardiac relaxation and depends on the efficient recovery of energy stored in cardiac tissue during systolic deformation. Abnormalities in the cardiac extracellular matrix (ECM) have been implicated in cardiovascular remodeling and diastolic dysfunction. Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of MMPs (TIMPs) regulate protein deposition and degradation in the ECM. We compared MMP and TIMP profiles in healthy seniors to study the role of ECM turnover in diastolic recoil efficiency.

Hypothesis:
Increased levels of MMPs and TIMPs involved in ECM protein turnover will be associated with improved diastolic recoil efficiency.

Methods:
Healthy but sedentary seniors (13 men, 9 women; age 68 ± 8 yrs) underwent echocardiogram and plasma biomarker assay for human MMP 1, 2, 3, 7, 9 and TIMP 1, 2, 3, 4. Diastolic recoil efficiency was modeled as an elastic spring and measured as the ratio of systolic longitudinal excursion (Sexc) and early diastolic excursion (EDexc) obtained from tissue doppler velocity-time integrals.

Results:
Increasing EDexc/Sexc ratios were directly associated with TIMP-1 levels (R=0.45, p=0.035) and TIMP-4 levels (R=0.50, p=0.019). There was a trend towards an association with MMP-2 (R=0.76, p=0.076). There were no significant correlations between the EDexc/Sex ratio and MMPs 1, 3, 7 or 9, TIMPs 2 or 3, MMP2/TIMP1, MMP2/TIMP4, MMP9/TIMP1, or MMP9/TIMP4 ratios.

Conclusions:
Abnormalities in ECM deposition and degradation via MMPs and TIMPs may impact cardiac relaxation by altering the efficiency of energy recovery in the transition from systole to diastole. TIMP-1 and -4 may preserve diastolic efficiency by attenuating fibrillar collagen fragmentation and pathologic remodeling of the ECM. MMP-2 trended towards a positive association with diastolic recoil efficiency and likely mediates a beneficial effect outside of its proteolytic action.
Abstract 12213: Exercise Induced Pulmonary Hypertension in Long Term Survivors of Congenital Diaphragmatic Hernia
Authors: Critser Paul J , Chen Ming Hui , Gauvreau Kimberlee , Zalieckas Jill M , Sheils Catherine A , Visner Gary A , Shafer Keri M , Rhodes Jonathan , Buchmiller Terry L , Mullen Mary P
Published: April 2022

Introduction:
Survivors of congenital diaphragmatic hernia (CDH) are at risk of pulmonary hypertension (PH) due to pulmonary hypoplasia and other pulmonary vascular abnormalities.

Hypothesis:
Exercise stress echocardiography (ESE) may detect PH, not apparent on echocardiography at rest, in children and young adults with repaired CDH.

Methods:
Single center retrospective cohort study of all CDH survivors who underwent ESE at Boston Children’s Hospital (January 2006 – June 2020). Severity of PH was assessed at baseline and after exercise. Patients were assigned to one of two categories based on right ventricular pressure: group 1: no or mild PH after exercise; and group 2: moderate or severe PH after exercise (right ventricular pressure ≥ 60 mmHg or ≥ ½ systemic blood pressure).

Results:
During the study period 84 CDH patients (70% male) underwent 173 ESE with a median age 8.1 (4.8 – 19.1) years at first ESE. Sixty-four patients were classified as group 1, 11 as group 2, and 9 were unable to be classified due to inconclusive ESE. Moderate to severe PH after exercise was found in 8 (10%) patients with no or mild PH at rest. Risk factors for PH after exercise included larger CDH defect size, patch repair, use of extracorporeal membrane oxygenation, and supplemental oxygen at discharge in univariate analysis (Table 1). Exercise and pulmonary function test parameters associated with a group 2 test included higher VE/VCO2 slope, lower peak oxygen saturation, and lower percent predicted FEV1 and FEV1/FVC ratio. Nine of 11 group 2 patients had a change in management based on ESE. PH was found in all 5 group 2 patients with cardiac catheterization after ESE, including 3 patients with no or mild PH on baseline ESE.

Conclusions:
Among long term CDH survivors, ESE identified 10% with moderate-severe exercise induced PH indicating ongoing pulmonary vascular abnormalities. Further studies are needed to optimally define screening and treatment for patients with repaired CDH.
Abstract 12214: Characterization of Iatrogenic Left Bundle Branch Block After Septal Myectomy for Hypertrophic Cardiomyopathy
Authors: Gionfriddo William , Gionfriddo William , Burrows Austin , Narayanan Chockalingam , Shrestha Srijan , Rastegar Hassan , Garlitski Ann , Weinstock Jonathan , Homoud Munther , Rowin Ethan J , Maron Martin S , Maron Barry , Madias Christopher
Published: April 2022

Introduction:
LBBB results in impaired transseptal conduction and delayed posterolateral LV activation. Criteria for left bundle branch block (LBBB) vary across scientific organizations. Septal myectomy for hypertrophic cardiomyopathy (HCM) could serve as an iatrogenic anatomic model to characterize LBBB.

Objective:
To describe ECG features of LBBB after septal myectomy for HCM.

Methods:
ECG data were analyzed for 377 HCM patients (204 male) who developed post-operative LBBB after extended septal myectomy between 2004-2018.

Results:
Average age of the cohort at myectomy was 53 ± 14 years. Baseline QRS duration (QRSd) was 94 ± 10ms. The post myectomy QRSd was 152 ± 15ms, consistent with an average ΔQRSd of 58 ± 13ms. There was positive correlation between pre and post myectomy QRSd (r = 0.485; p < 0.0001). The average LV end-diastolic diameter (LVEDd) pre and 2 months post myectomy was 40 ± 5.6mm and 46.2 ± 6.5mm, respectively. Positive correlation between post myectomy QRSd and post myectomy LVEDd was also observed (r = 0.340; p < 0.0001). Females and males had pre myectomy QRSd of 93 ± 10ms and 95 ± 10ms respectively (p = 0.007) and post myectomy QRSd of 147 ± 13ms (120-184ms) and 157 ± 14ms (126-209ms) respectively (p < 0.0001). ΔQRSd was less in females than males (54 ± 13ms vs. 62 ± 11ms; p<0.0001). Only 13 females and 3 males had post myectomy QRSd < 130ms. Only 23 males had QRSd < 140ms.

Conclusions:
Surgical myectomy serves as a model to characterize LBBB. Following myectomy, QRSd correlated with LVEDd as well as pre-myectomy QRSd, and was longer in males due to delayed depolarization of larger hearts in men. Notably only 3 males and a minority of females had QRSd < 130ms. These data provide important insights for the validation of electrocardiographic LBBB criteria.
Abstract 12247: Mitochondrial Metabolic Transcriptome Profiles During Cardiomyocyte Differentiation From Mouse and Human Pluripotent Stem Cells
Authors: Cho Sung Woo , Kim Hyoung Kyu , Sung Ji-Hee , Han Jin
Published: April 2022

Introduction:
Simultaneous increase of myofibrils and mitochondria is a key process of cardiomyocyte differentiation from pluripotent stem cells (PSCs). Specifically, development of mitochondrial oxidative energy metabolism in cardiomyocytes is essential to providing the beating function. Although previous studies reported that mitochondrial oxidative metabolism have some correlation with the differentiation of cardiomyocytes, the mechanism by which mitochondrial oxidative metabolism is regulated and the link between cardiomyogenesis and mitochondrial function are still poorly understood.

Methods:
We performed transcriptome analysis on cells at specific stages of cardiomyocyte differentiation from mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs). We selected highly upregulated mitochondrial metabolic genes at cardiac lineage commitment and time-dependent manner during cardiomyocyte differentiation and identified the protein-protein interaction network connecting between mitochondrial metabolic and cardiac developmental genes.

Results:
We found several mitochondrial metabolic regulatory genes at cardiac lineage commitment (Cck, Bdnf, Fabp4, Cebpa, Cdkn2a in mESC-derived cells and CCK, NOS3 in hiPSC-derived cells) and time-dependent manner during cardiomyocyte differentiation (Eno3, Pgam2, Cox6a2, Fabp3 in mESC-derived cells and PGAM2, SLC25A4 in hiPSC-derived cells). Notably, mitochondrial metabolic proteins are highly interacted with cardiac developmental proteins time-dependent manner during cardiomyocyte differentiation rather than cardiac lineage commitment. Furthermore, mitochondrial metabolic proteins are mainly interacted with cardiac muscle contractile proteins rather than cardiac transcription factors in cardiomyocyte.

Conclusions:
Mitochondrial metabolism is critical at cardiac maturation rather than cardiac lineage commitment.
Abstract 12257: The Utility of PREDICT-HF Score in High-Risk Asian Heart Failure Patients Receiving Sacubitril/Valsartan Treatment
Authors: Hsu Chien-Yi , Chang Hung-Yu , Lee Ying-Hsiang
Published: April 2022

Introduction:
Although the efficacy and safety of sacubitril/valsartan (Sac/val) for treating patients with heart failure and reduced ejection fraction (HFrEF) have been shown in global clinical trials, long-term tolerability and effectiveness data from Asian patients are limited.

Hypothesis:
The aim of this study was to investigate the effectiveness and tolerability of Sac/val in clinical practice and the utility of PREDICT-HF score for outcome prediction in Asian heart failure patients with difference risk profiles.

Methods:
The TAROT-HF study was a multicenter, single-arm, observational study. Totally 1,187 outpatients with HFrEF treated with Sac/val were enrolled and categorized by: (1) high-risk group with one or more of the following three risk factors: old age (≥80 years), low baseline systolic blood pressure (<100mmHg), and renal impairment (eGFR <30ml/min/1.73 m2), and (2) standard-risk group, those who did not have any risk factors. Clinical outcomes were assessed using the PREDICT-HF risk model.

Results:
A total of 305 (25.7%) patients matched the criteria for the high-risk group. The event rates of cardiovascular death or first unplanned heart failure hospitalization (HFH) among the overall population, high-risk, and standard-risk groups were 13.7, 24.9, and 10.8 events per 100 patient-years, respectively. The C statistics for the PREDICT-HF model in the overall cohort and high-risk group for cardiovascular death or first unplanned HFH at 2 years were 0.73 (95% CI 0.70-0.76) and 0.71 (95% CI 0.65-0.76), respectively.

Conclusions:
Real-world outcomes of the TAROT-HF study showed good tolerability of Sac/val. Although the current study enrolled high-risk patients not included in the PARADIGM-HF trial, the PREDICT-HF model performed well in real-world Asian HFrEF patients. Three easily detected clinical profiles of age, renal function, and systolic BP could help to identify patients at risk before initiating Sac/val therapy.
Abstract 12994: Invasive Left Atrial Pressure Monitoring and Survival on Veno-Arterial Extracorporeal Membrane Oxygenation for Cardiogenic Shock
Authors: Tonna Joseph E , Selzman Craig H , Billia Filio , Luk Adriana , Baran David , Batchelor Wayne B , Tehrani Behnam N , Marashly Qussay , Kyriakopoulos Christos P , Taleb Iosif , Jones Tara , Nunez Jose , Grandin E. Wilson , Kapur Navin K , Rycus Peter , Drakos Stavros G ,   for the Extracorporeal Life Support Organization (ELSO) Member Cntrs
Published: April 2022

Introduction:
Elevated left atrial pressures (LAP) are associated with worse outcomes among patients with cardiogenic shock (CS), yet there are limited data on the utility of continuous invasive monitoring of LAPs on outcomes for CS. This is additionally true among refractory CS patients on peripheral VA ECMO, which itself can increase arterial afterload.

Hypothesis:
Our objective was to determine whether invasive LAP monitoring impacts survival for patients with refractory CS after 24 hours of VA ECMO support.

Methods:
We performed a cohort analysis among 10,906 patients ≥18yrs of age from the Extracorporeal Life Support Organization (ELSO) Registry from 2015 - 2020, with refractory CS treated with VA ECMO. The presence of invasive LAP monitoring was defined as either pulmonary capillary wedge pressure (PCWP) or pulmonary arterial diastolic pressure (PAD) values at 24 hours on VA ECMO. The exposure was measurement of LAPs at 24 hours on VA ECMO support, and the primary outcome was 30 day survival. We performed Kaplan Meier survival analysis, adjusting for age, PaO2/FiO2, pH, SCAI classification stage prior to ECMO, presence of a pre-ECMO cardiac arrest, mean arterial blood pressure on ECMO and year.

Results:
Median age of patients was 57 [IQR,46; 65] years with 31% females. Thirty two percent (n=3,465) presented with acute myocardial infarction, 29% (n=3,112) with acute heart failure and 1% (n=965) with both etiologies. Invasive LAP monitoring at 24 hours was performed in 33% (n=3608) of patients. The use of invasive LAP was associated with lower mortality (adjusted Hazard Ratio 0.88 [95% CI 0.81 to 0.95]; p=0.002).

Conclusions:
Implementation of invasive LAP monitoring may be associated with higher adjusted hospital survival in patients with refractory CS requiring VA-ECMO support. These findings merit further investigation and prospective validation to assess the relationship between invasive hemodynamic monitoring and outcomes in this patient population.
Abstract 13203: Exercise Decreases Stress-Associated Neural Activity Predominantly by Upregulating Regulatory Medial Prefrontal Cortical Activity
Authors: Zureigat Hadil , Abohashem Shady , Gharios Charbel , Mezue Kenechukwu , Abbasi Taimur , Cardeiro Alexander , Shin Lisa , Baggish Aaron L , Fayad Zahi A , Osborne Michael , Tawakol Ahmed A
Published: April 2022

Introduction:
Exercise associates with dose-dependent decreases in stress-associated neural activity (SNA) which, in part, mediate exercise’s beneficial impact on major adverse cardiovascular event (MACE) risk. SNA can be assessed as a ratio of the resting metabolic activity of the brain’s fear centers (i.e., the amygdala [Amyg]), to that of regulatory centers (i.e., the medial prefrontal cortex [PFC]). However, it is unknown whether exercise reduces SNA by impacting the activity of Amyg, mPFC, or both.

Hypothesis:
We tested whether exercise reduces SNA primarily through enhancing the activity of the mPFC. We further hypothesize that it is the regulatory effect of the mPFC on SNA that contributes to MACE risk reduction.

Methods:
Self-reported physical activity data were obtained from Partners Biobank participants and total metabolic equivalents-minutes per week (MET-min/wk) were calculated. In a subset with clinical 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging, Amyg and mPFC activity were measured and corrected by whole cerebrum activity. SNA was calculated (Amyg/mPFC activity). MACE and cardiovascular risk factors were obtained using International Classification of Diseases codes.

Results:
Out of 684 subjects with both physical activity and imaging data (median age 68 years [IQR 60,75]), 275 (40.2%) developed MACE. Physical activity (as tertiles) associated with a dose-dependent increase in mPFC activity (Figure 1A; standardized β [95% CI]: 0.087 [0.002,0.036], p=0.025). Moreover, while SNA predicted MACE in adjusted analysis, the activities of the Amyg or PFC alone did not (Figure 1B).

Conclusions:
Exercise associates with dose dependent increases in mPFC activity. This effect does not directly reduce MACE risk; however, it may reduce MACE risk via its regulatory action on SNA. These observations may also have relevance in the impact of exercise on depression/anxiety disorders and cognitive function.
Abstract 13301: Microarray Reveals Differentially Expressed Long Non-coding Ribonucleic Acids In Dysferlinopathy
Authors: Lukose Rachel , Carr Gwenyth , Vajravelu Bathri
Published: April 2022

Introduction:
Dysferlinopathy is a type of muscular dystrophy, a group of inherited degenerative muscle disorders characterized by progressive muscle weakness. It is caused by the deficiency of dysferlin, a type II transmembrane protein highly expressed in the skeletal muscle and the heart. Dysferlin interacts with several proteins and plays a crucial role in calcium dependent membrane repair in skeletal muscles. Long non-coding RNAs (lncRNAs) are non-coding RNA transcripts greater than 200 nucleotides that participate in regulating gene expression through multiple mechanisms.

Hypothesis:
We hypothesized the disease process in dysferlinopathy is linked to an aberrant expression of lncRNAs.

Methods:
LncRNA and mRNA expression profiling between the normal and dysferlin deficient murine myoblasts (C2C12 cells) were performed using a microarray (n=3). Several differentially expressed lncRNAs were validated using qRT-PCR. Tissue expression analysis was performed for selected lncRNAs across ten mice tissues. Further bioinformatics analysis was used to explore the potential function, lncRNA-mRNA correlation and potential targets of the differentially expressed lncRNAs.

Results:
We found 3470 lncRNAs and 2335 mRNAs that are differentially expressed by more than two fold. A set of 13 lncRNAs were selected based on their fold change, and were validated using qRT-PCR. Six out of the 13 lncRNAs tested were predominantly expressed in either myoblasts or skeletal muscle tissue. Pathway analysis of the differentially expressed genes indicated the involvement of several signaling pathways including PI3K-Akt, FoxO, Wnt, cAMP and Hippo. The differentially expressed genes were also enriched for the GO terms, developmental process and muscle system process.

Conclusion:
The results thus far imply that dysferlinopathy is associated with an aberrant expression of multiple lncRNAs many of which may have a specific function in the disease process. Identification of lncRNAs that are predominantly expressed in the skeletal muscle lineage suggests a muscle specific role for these lncRNAs. We are currently working on overexpressing selected lncRNAs in the normal and dysferlin deficient cells to understand their role in regulating key cellular functions.
Abstract 13324: One-Year Outcomes in Patients With Cardiogenic Shock: Insights From the Inova-Shock Registry
Authors: Sinha Shashank , Rosner Carolyn , Tehrani Behnam N , Maini Aneel , Truesdell Alexander G , BAGCHI PRAMITA , Cameron James , Damluji Abdulla , desai mehul , Desai Shashank , Epps Kelly C , Defilippi Christopher , Genovese Leonard , Moukhachen Hala , Park James , Psotka Mitchell , Raja Anika , Sherwood Matthew W , Singh Ramesh , Tang Daniel , Young Karl , O'Connor Christopher M , Batchelor Wayne B
Published: April 2022

Introduction:
Historically, studies have focused on short-term morbidity and mortality associated with cardiogenic shock (CS). Little is known about post discharge outcomes following acute myocardial infarction (AMI-CS) as compared to acute decompensated heart failure (ADHF-CS).

Methods:
We examined 520 (219 AMI-CS, 301 ADHF-CS) consecutive patients with CS (1/3/2017-12/31/2019) in a single center registry.

Results:
Median duration of post discharge follow up was 433 days (IQR, 199-699). Mean age was 61.5±13.5 years, 71% were male, and 64% had chronic kidney disease. The AMI-CS cohort was older (65.6 vs. 58.5, p <0.001), had more cardiac arrest (35.2% vs. 16.0%, p < 0.001), higher baseline lactates (2.7 vs. 2.2, p < 0.01), and decreased pulmonary artery pulsatility indices (1.21 vs. 1.50, p < 0.01). AMI-CS patients had higher in-hospital mortality (38.8% vs. 24.6%, p< 0.001) and at 30 days (46.1% vs. 31.9%, p =0.01) as compared to ADHF-CS. However, this difference was no longer significant at 12 months (52.9% vs. 44.3%, p =0.07). Patients with low (0-3), intermediate (4-5), and high-risk (6-9) CardShock scores on admission had 12-month mortalities of 18.3%, 42.5%, and 82.0%, respectively. For the 361 (69.4%) patients who survived to discharged, 28.9% (n=98) experienced a Major Adverse Cardiovascular Events (MACE) at least once in the 12 months post discharge and 22.7% (n=82) were readmitted within 30 days. There was no significant difference in the occurrence of MACE between the two cohorts (AMI-CS= 27.2% vs ADHF-CS= 31.9%, p=0.57) but the 30-day readmission rate was lower in the AMI-CS cohort as compared to the ADHF-CS group (19.6% vs 24.8%, p< 0.01).

Conclusions:
There is substantial one-year morbidity and mortality in patients with AMI-CS and ADHF-CS. The AMI-CS cohort had higher in-hospital mortality, which persisted post discharge, as compared to ADHF-CS patients. CardShock risk stratification may be useful for longer term prognostication in CS patients.
Abstract 13325: Racial Heterogeneity in Mortality and Complications Among Adult Women Presenting With ST Elevation Myocardial Infarction
Authors: Senthil Kumaran Sriviji , Del Cid Fratti Juan , Desai Anjali R , Mungee Sudhir , MUKHOPADHYAY EKANKA , Kizhakekuttu Tinoy J
Published: April 2022

Introduction:
There is a sparsity of studies on the outcomes in women presenting with ST Elevation Myocardial Infarction (STEMI) among the different racial minorities.

Methods:
National inpatient sample database was used to retrospectively study primary mortality outcomes and secondary complications among the different races (Whites, Blacks, Hispanic, Asian and other races which includes native Americans) of adult female patients hospitalized from January 1 2016 to December 31 2018 with STEMI as their primary diagnosis. Adjusted odds ratio (AOR) was calculated by comparing the different races to white women.

Results:
In hospital mortality was highest among Asian women (17.1%) followed by African American women (14.4%). Cardiogenic shock occurred less frequently among African American (11.5%) women with no statistical difference between other subgroups. Use of mechanical circulatory support (MCS) was highest in other minority races (8.7%). All minority subgroups required longer periods of mechanical ventilation > 24 hours (African Americans 6.1%; Hispanics 4.9%; Asians 5.1% and other race 4.8%). Acute kidney injury was highest among Hispanics (2.3%).

Conclusions:
Despite overall improvement in mortality of STEMI patients, heterogeneity in outcomes based on race persist. Our findings showed increased mortality and morbidity in the outcomes among women belonging to racial minorities. The increased need for renal replacement therapy, MCS, mechanical ventilation and higher rates for blood transfusion contribute to overall prognosis. Understanding these key differences will aid in improving outcomes and help guide management of these minority populations.
Abstract 13428: Mid-Life and Late-Life Exposure to Traditional Cardiovascular Risk Factors and Zero Coronary Artery Calcium: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Wang Frances M , Ballew Shoshana , Folsom Aaron R , Wagenknecht Lynne E , Howard-Claudio Candace M , Coresh Josef , Budoff Matthew J , Blaha Michael J , Matsushita Kuni
Published: April 2022

Introduction:
Our understanding of traditional atherosclerotic risk factors is largely based on their contributions to adverse atherosclerotic events. However, the relative contributions of mid-life and late-life risk factor exposures to persistent zero coronary artery calcium (CAC=0) in older adulthood, a representative healthy vascular aging phenotype, have not been fully examined.

Hypothesis:
Both mid-life and late-life risk factors are associated with CAC=0, with stronger results for the former.

Methods:
Using data from 2,035 community-dwelling participants free of coronary heart disease in the ARIC study, we evaluated traditional modifiable risk factors (i.e., lipids, systolic blood pressure, obesity, smoking, and diabetes) at mid-life (median age 49, visit 1 from 1987-1989) and late-life (median age 73, visit 5 from 2011-2013) and their associations with CAC=0 at visit 7 (median age 80, from 2018-2019), using multivariable logistic regression models adjusted for within-visit factors.

Results:
There were 204 participants (10.0%) with CAC=0. Compared with participants with any CAC, those with CAC=0 had more favorable values for most traditional risk factors (lower cholesterol, BMI, and systolic blood pressure, higher HDL-C, and not smoking) in both mid-life and late-life, with the exception of fasting glucose (
Table
). The results were similar when we modeled diabetes instead of fasting glucose. Lower total cholesterol in mid-life, but not late-life, was associated with CAC=0.

Conclusions:
Having favorable modifiable risk factors both at mid-life and late-life were independently associated with CAC=0 in older adults free of clinical coronary heart disease. These results highlight the importance of maintaining a healthy risk factor profile from mid-life, with implications on public health promotion and strategy.
Abstract 13436: Temporal Changes In Demographic Characteristics, Use Of Multimodal Imaging, And Treatments In Patients With Bicuspid Aortic Valves: Data From A Large Korean Registry
Authors: Kim Kyu , Kim Dae-Young , Seo Jiwon , Cho Iksung , Hong Geu-Ru , Ha Jong-Won , Shim CHI YOUNG
Published: April 2022

Introduction:
We aimed to investigate the temporal changes in demographic characteristics, use of multimodal imaging, and treatments in patients with bicuspid aortic valves from a large Korean registry.

Methods:
A total of 1,514 patients (mean 71.5%, 56 ±14 years old) who were first diagnosed with BAV from Jan 2003 through Dec 2020 in a single tertiary referral center in Korea were investigated. They were divided into 3 groups according to the year of diagnosis: group 1 (2003-2008, n=270), group 2 (2009-2014, n=590), and group 3 (2015-2020, n=654). Significant aortic stenosis (AS) was defined as at least moderate AS and significant aortic regurgitation (AR) was defined as at least moderate AR based on the current guideline. Non-dysfunctional BAV was defined as BAV without significant AR or AR. Presence of aortopathy was defined as any portions of ascending aorta ≥ 45 mm. Use of imaging for diagnosis and the treatment method were comprehensively investigated.

Results:
Both age at diagnosis [55 (interquartile range [IQR], 44 to 60) in Group 1, 59 (48 to 67) in Group 2, 60 (60 to 68) in Group 3, p for trend <0.001] and surgery [56 (46 to 64), 60 (52 to 69), 62 (56 to 69), p for trend <0.001] showed increasing trend. Non dysfunctional BAV had increased (25.2%, 36.3%, and 33.9%, p=0.005). The frequency of IE as an initial presentation significantly decreased as time passes (4.8%, 2.9%, and 1.7%, p<0.008). The incidences of aortopathy were not significantly different among three temporal groups. The use of multimodal imaging (concomitant use of computed tomography and transesophageal echocardiography) had significantly increased (1.5%, 6.8%, 19.3%), p<0.001]. There was also increasing trend in transcatheter aortic valve replacement (2.2% in group 2; 4.5% in group 3, p<0.001]

Conclusions:
In the past 18 years, there were remarkable temporal changes in patients’ demographic characteristics, use of multimodal imaging for diagnosis, complications and treatment in patients with BAV.
Abstract 13456: Characterizing Changes in Quality of Life and in Older Patients With Acute Decompensated Heart Failure Enrolled in a Rehab Intervention Clinical Trial
Authors: Whellan David J , Kitzman Dalane W , Chen Haiying , Nelson Michael B , Pastva Amy M , McCarey Melissa , Duncan Pamela W , Mentz Robert J , Reed Shelby D
Published: April 2022

Introduction:
Older patients with acute decompensated heart failure (ADHF) have severely impaired QOL. We recently reported that a novel physical rehab intervention improves QOL. Here we report trajectories of improvement and relationship to participation in a rehab intervention.

Methods:
Patients with ADHF, regardless of EF and ≥ 60 years old were randomized to either attention control (AC) or rehab intervention (RI). Participants completed the KCCQ, a disease-specific QOL instrument, and 12-Item Short-Form Health Survey (SF-12), a general QOL instrument composed of a mental and physical composite score, at baseline (inpatient), 1 month and 3 months. Effects of the intervention were assessed using linear mixed effects models including the main effect of intervention, follow-up visit, and interaction term with adjustment for EF category, age, and sex.

Results:
The REHAB-HF trial enrolled 349 patients with a mean age of 72.7±8.1 years, 52% women and 49% non-white. Baseline KCCQ scores were low for both arms (Figure 1). There was a substantial increase in KCCQ score at 1 month in both arms. However, in contrast to the AC participants who showed no further improvement, RI participants continued to experience an increase in QOL at 3 months creating a significant difference between arms (p< 0.01). Both SF-12 composite scores also increased in both arms at 1 month with continued improvement only in the RI arm; reaching significance for the mental composite at 1 month (50.8±1.1 vs. 46.9±1.1, p < 0.01) and at 3 months (52.7±1.1 vs. 48.2±1.1, p< 0.01).

Conclusions:
Older patients hospitalized with ADHF have severely impaired disease-specific and general QOL that improves soon after discharge. Patients receiving a novel physical rehabilitation intervention experienced an early benefit in terms of QOL that continued to improve throughout the 3 months trial period. Future studies will help determine if these benefits are sustained with longer term follow-up.
Abstract 13463: Tricuspid Regurgitation Referral Population Characteristics
Authors: Lawlor Matthew , Ng Vivian , Ahmed Shaan , Dershowitz Lyle , Boyle Claudia , Vahl Torsten , Nazif Tamim , Hamid Nadira , Khalique Omar , Leon Martin , George Isaac , Hahn Rebecca T , Kodali Susheel K
Published: April 2022

Introduction:
Advanced tricuspid regurgitation (TR) is associated with adverse cardiovascular outcomes. Herein, we report demographics of patients presenting to a tertiary valve center and characterize measures of TR severity and right ventricular (RV) function.

Methods:
We conducted a single center retrospective analysis of patients referred to a specialty valve clinic from January 2016 to September 2020 with a primary or secondary diagnosis of tricuspid regurgitation. Baseline clinical, echocardiographic, and hemodynamic variables were evaluated.

Results:
A total of 348 patients were included. Median age was 79 years (IQR 70, 84), and 54% were female. Torrential TR was present in 41% (n = 146), massive in 11% (n = 40), severe 34% (n = 120), and moderate or less in 9% (n = 31). Increase in TR severity was associated with RV, right atrial, and annular dilatation. There was no difference in RV function between groups assessed by TAPSE or S’. Right atrial pressure v-wave was higher with increase in TR severity. Pulmonary arterial (PA) pressures were significantly different between groups, as was pulmonary vascular resistance (PVR): lower PA pressures and PVR were seen with increase in TR severity. There were no differences in cardiac output across groups, though a numeric trend in decreasing cardiac output was noted with increase in TR severity from severe to torrential. There was increase in S’/PASP and decrease in pulmonary artery pulsatility index seen with increasing TR severity.

Conclusion:
Patients referred for TR are frequently advanced in age with massive or torrential tricuspid regurgitation and evidence of adverse right ventricular remodeling. Increasing severity of advanced TR was associated with RV hemodynamic decompensation. Preservation of two-dimensional measures of right ventricular function in the setting of progressive TR, as well as markers of right ventricular-vascular coupling, may suggest these are late markers of right ventricular compromise.
Abstract 13475: Epicardial Adiposity Measured by a Deep Learning Network, Predicts Mortality and Cardiovascular Events in Patients Undergoing Cardiac CT
Authors: West Henry W , Williams Michelle C , Siddique Muhammad , Volpe Lucrezia , Desai Ria , Lyasheva Maria , Dangas Katerina , Tomlins Pete , Oikonomou Evangelos K , Shirodaria Cheerag , Neubauer Stefan , Channon Keith M , Rodrigues Jonathan , Nicol Ed , Newby David E , Antoniades Charalambos
Published: April 2022

Introduction:
Epicardial adipose tissue (EAT) is a visceral fat deposit within the pericardial sac. The automated quantification of EAT volume is possible from routine CCTA scans via deep-learning. The use of automated EAT quantification for the assessment of cardiovascular disease (CVD) risk in addition to standard measures of obesity like BMI has not been fully explored.

Purpose:
To use deep-learning for automated segmentation of EAT from routine CCTA scans to assess the long-term CVD risk conveyed by EAT.

Methods:
A deep-learning automated EAT segmentation tool using a 3D Residual-U-Net neural network architecture for 3D volumetric segmentation of CCTA data was created and trained on over 2500 consecutive CCTAs from within the Oxford Risk Factors And Non Invasive Imaging (ORFAN) Study. External validation in 817 patients demonstrated excellent correlation between machine and human expert (CCC = 0.972). The prognostic value of deep-learning derived EAT volume was assessed against 5 years outcomes from the SCOTHEART trial (n=1588), with adjustment for CVD risk factors. An optimal cutoff was selected by identifying the EAT value that maximized the Youden’s J index (sum of sensitivity and specificity) for the three outcomes of interest - high risk was deemed to be EAT ≥ 170.5cm
3
.

Results:
There were 35 deaths (all-cause mortality), 35 non-fatal myocardial infarctions and 8 non-fatal strokes during the 5 years follow up period. By using multi-variable cox-regression, EAT volume was predictive of all-cause mortality (Figure 1A), non-fatal MI (Figure 1B), and non-fatal stroke (Figure 1C) independently from CVD risk factors.

Conclusions:
Automatically segmented EAT volume measured using a deep learning network, predicts 5-year all-cause mortality, heart attacks and stroke independently of BMI and clinical risk profile of the patients. This suggests that measures of visceral obesity will be of value in the interpretation of cardiovascular computed tomography.
Abstract 13552: Mortality Trends in the United States Due to Underlying Rheumatic Heart Disease From 1999-2018
Authors: Mughal Mohsin S , Ahmad Talha , Madjid Mohammad , Ghani Ali , Mirza Hasan , Khakwani Muhammad , Grewal Jagpreet , Ahmad Khansa , Alam Mahboob , wasty najam , Waxman Sergio
Published: April 2022

Introduction:
Rheumatic heart disease (RHD) is a preventable disease which affects almost 33 million people globally. RHD was estimated to be responsible for 305,000 deaths worldwide and 11.5 million disability-adjusted life years lost in 2015. We investigated the temporal trends of RHD related mortality in the U.S. by using nationwide data.

Methods:
Death certificate data were retrieved from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER) database for 1999-2018. WONDER database reports the underlying cause of death across the United States. Mortality for Rheumatic heart disease ICD-10 (I05-I09) which includes rheumatic mitral valve diseases I05; rheumatic aortic valve diseases I06; rheumatic tricuspid valve diseases I07; multiple valve diseases I08; or other rheumatic heart disease I09; as an underlying cause of death were queried from 1999-2018. This study duration was further stratified into five-year periods. Crude mortality rate and age-adjusted mortality rate per 100,000 were calculated with a 95% confidence interval in four U.S census regions.

Results:
Overall AAMR showed a downward trajectory and declined from 1.3 to 0.9 per 100,000 from 1999 to 2018. AAMR for Northeast (CR-1) declined by 33%; for Midwest (CR-2) declined by 23%; for South declined by 27%, and for West (CR-4) declined by 33%. Crude mortality rate, AAMR, and % deaths are shown in table 1.Temporal trends are illustrated in figure 1.

Conclusions:
Regional AAMRs for U.S census regions showed a downward trajectory from 1999-2018. These trends suggest the efficacy of of primary and secondary prevention of rheumatic heart disease.
Abstract 13644: Depict Analysis Suggests Enrichment of Heart Valve Tissue Expression in African Rheumatic Heart Disease Patients From the RHDGen GWAS Study Cohort
Authors: Machipisa Tafadzwa , Chong Michael , Pare Guillaume , Engel Mark E ,   The RHDGen Network
Published: April 2022

Introduction:
Rheumatic heart disease (RHD) is a sequela of rheumatic fever that results in permanent heart valve damage. While it remains the primary cause of cardiac surgery in Africa, its pathophysiology is poorly understood.Genome-wide association studies (GWASs) are ‘hypothesis-free’, genetic discovery tools for common complex diseases. Recently, our African GWAS of RHD susceptibility uncovered a novel locus (11q24.1; OR=1.63; 95% CI, 1.38-1.94; P=4.36x10
-8
) which may explain the disproportionate burden in Africans.Here we further report secondary analyses investigating tissue type expression enrichment among suggestively associated loci, to elucidate the underlying biological processes involved in RHD susceptibility.

Aims and Objectives:
This study sought to identify tissue types enriched in gene-set analyses associated with RHD GWAS susceptibility data in Africans.

Methods:
A multicenter, ethnically matched case-control GWAS was performed in 2,548 RHD cases and 2,261 controls, from eight African countries. All 4,809 participants were assessed according to the 2012 World Heart Federation (WHF) criteria for echocardiographic diagnosis of RHD. After cleaning, the GWAS data were stratified by ethnicity and an association test was run via mixed linear models in GCTA that adjusted for gender, chip type and the first ten principal components. Using the resulting GWAS summary statistics suggestive loci (P<1x10
-5
), we conducted secondary analyses in DEPICT (Data-driven Expression Prioritized Integration for Complex Traits) to test for association with RHD and its related traits and tissues, to validate the GWAS findings.

Results:
DEPICT indicated promising and biologically relevant results; the most enriched tissues were heart valves (p=2.47x10
-3
; False Discovery Rate (FDR)=<0.20).

Discussion and Conclusion:
Our results indicate that genetic susceptibility to RHD may involve perturbed gene expression signatures characteristic of heart valves, known for their pathogenic involvement in RHD development. Future larger studies are warranted to identify the specific genes involved.
Abstract 14009: Longitudinal Analysis Supports Reproducibility Of Treatment With Sildenafil In The Semaxanib/Hypoxia Rat Model Of Pulmonary Arterial Hypertension
Authors: Doherty Kimberly R , Stephen Cayman A , Siegel Kyle R , Johnson Michelle M , Zammit Melissa D , Senese Peter B , Gralinski Michael R
Published: April 2022

Rats develop translatable pulmonary arterial hypertension (PAH) after exposure to the VEGF antagonist semaxanib (SU5416) concurrent with hypoxia. Sildenafil is used clinically for PAH and as a positive control in this preclinical model. A longitudinal analysis was constructed by pooling data from discrete rat PAH studies conducted over an 8-year period to evaluate the stability and reproducibility of the SU5416/Hypoxia rodent model as well as the response to sildenafil. Sprague-Dawley rats were administered SU5416 on Day 1 and subsequently maintained in a low oxygen environment for 28 days. Sildenafil was given as a positive control in either prevention or treatment mode. Pulmonary hemodynamics were obtained on the final day as appropriate by design; hearts were also assessed for right ventricular hypertrophy. Prevention studies (≥17) were terminated following 28 days of hypoxia while most treatment studies (≥17) had a protocol-defined period of normoxia following hypoxia. In prevention studies, the mean of both systolic pulmonary arterial pressure (sPAP) and the right ventricular hypertrophy Fulton’s Index (FI) remained consistent across studies over the 7-year period: sPAP: PAH vehicle control (PAH-VC) 70 ± 19 mmHg (n = 190), sildenafil 51 ± 15 mmHg (n = 165), p<.05; FI: PAH-VC 0.5573 ± 0.1048 (n = 210), sildenafil 0.4984 ± 0.1007 (n = 172), p<.05. Sildenafil elicited mean reductions in sPAP of 28% and FI of 11% over the 7-year period. Mean survival rate was comparable for PAH-VC (96%) and sildenafil groups (99%).In treatment studies, the mean of both sPAP and FI remained consistent across studies over the 8-year period: sPAP: PAH-VC 89 ± 24 mmHg (n = 148) vs. sildenafil 67 ± 22 mmHg (n = 168), p<.05 vs PAH-VC; FI: PAH-VC 0.5938 ± 0.0944 (n = 168) vs. sildenafil 0.5336 ± 0.1077 (n = 173), p<.05 vs PAH-VC. Sildenafil elicited mean reductions in sPAP of 25% and FI of 10% over the 8-year period. Mean survival rate was comparable for PAH-VC (91%) and sildenafil groups (95%).The effects of sildenafil on reduction of PAH were stable and of similar magnitude in both prevention and treatment studies over an 8-year period. Thus, this longitudinal analysis indicates a reproducible and consistent effect of both the SU5416/Hypoxia PAH model and the use of sildenafil as a positive control.
Abstract 14038: Deficiency of Arachidonate 5-Lipoxygenase Intensifies Sepsis-Induced Cardiac Dysfunction in Aging
Authors: Halade Ganesh V , Grilo Gabriel A , Tourki Bochra , Kain Vasundhara
Published: April 2022

Introduction:
Age-related cardiac dysfunction is a prime component of sepsis-induced multi-organ failure in the clinical setting. Arachidonate 5-lipoxygenase (5LOX) pathway and 5LOX-derived lipid mediators are critical in early inflammation and immune response signaling. In addition, 5LOX derived mediators activate macrophages and other cells to counter infection via surface receptors. However, the role of 5LOX in sepsis-induced cardiac dysfunction superimposed on aging is still under-investigated.

Hypothesis:
Given that the inflammatory role of 5LOX, we tested the hypothesis that deletion of 5LOX in aging would be deleterious to cardiac function in sepsis.

Methods:
To induce sepsis, lipopolysaccharide (LPS; E. coli O55:B5) was injected into aging male C57BL/6J (WT) and 5LOX
-/-
mice (18-20 months). To study heart function, molecular, and cellular mechanisms, mice were challenged with a single subcutaneous dose of LPS (20mg/kg) for 4 hours. Survival was monitored for 7 days post-LPS challenge to testify therapeutic application of outcome.

Results:
Lack of 5LOX increased mortality (~70%) in aging mice with severe depression in cardiac function post-LPS compared with age-matched WT controls. LPS challenge in 5LOX
-/-
aging mice decreased resolution mediators (RvD1) and inflammation mediators (LTB
4
) in the spleen with robust recruitment of leukocytes in a spleno-cardiac manner indicative of non-resolving inflammation. The spleen monocytes (CD11b
+
), macrophages (F4/80
+
), and neutrophils (Ly6G
+
) were significantly decreased in 5LOX
-/-
mice post-LPS with the consistent increase in the heart. The absence of 5LOX blunted physiological inflammatory response in aging by attenuating TLR4 and CD169 in both the heart and spleen as a sign of immunosuppression.

Conclusion:
Our results suggest that 5LOX
-/-
aging mice fail to initiate physiological inflammation-resolution signaling in response to LPS-induced septic shock, leading to cardiac dysfunction and immunosuppression. Our study highlights the role of 5LOX and 5LOX-derived mediators as targets for the inflammation-resolution response and therapeutics potential in aging-related sepsis.
Abstract 8963: Mitochondrial Dysfunction in Peripheral Blood Mononuclear Cells is Associated With Heart Failure in Patients With Single Ventricle Congenital Heart Disease
Authors: Zegelbone Phillip M , BAYBAYON-GRANDGEORGE ANGELA , Stauffer Brian , Sucharov Carmen , Miyamoto Shelley , Garcia Anastacia M
Published: April 2022

Introduction:
Heart failure (HF) remains a leading cause of death and indication for heart transplant in children with single ventricle congenital heart disease (SV). The purpose of this study was to evaluate mitochondrial function in circulating peripheral blood mononuclear cells (PBMCs) from failing pediatric SV patients compared to age-matched nonfailing controls (NF). Prior data obtained at the time of cardiac transplant shows associations between SV PBMC mitochondrial function and ex-vivo high-resolution respirometry analysis conducted on permeabilized myocardial fibers, suggesting that PBMCs may be surrogates for myocardial mitochondrial function.

Hypothesis:
SV patients will have impaired mitochondrial respiratory capacity in circulating PBMCs.

Methods:
Subjects were recruited from Children’s Hospital Colorado. SV patients ages 0-18 years were included. Healthy children 0-18 years of age with normal biventricular cardiac function were included as a control group. PBMCs were isolated from whole blood (EDTA) using density gradient centrifugation in Histopaque Accuspin tubes. Oxygen consumption rates (OCR) of intact PBMCs were measured using the Seahorse XFe Bioanalyzer (Agilent). OCR is measured under 4 different conditions (Figure 1): baseline, after addition of oligomycin, after addition of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, and after addition of antimycin A and rotenone.

Results:
Baseline respiratory capacity, coupling efficiency, and mitochondrial oxygen flux were decreased in failing SV PBMCs relative to NF controls (Figure 2).

Conclusions:
Our results demonstrate impaired mitochondrial respiratory capacity in circulating PBMCs of pediatric SV patients relative to healthy age-matched controls. Combined with our ex vivo data showing decreased mitochondrial function in failing SV myocardium, our findings suggests PBMCs may serve as a viable non-invasive biomarker of myocardial respiratory capacity.
Abstract 9414: Utilization of Antithrombotic Therapies in Patients With Atrial Fibrillation Across the Spectrum of Stroke Risk
Authors: Yao Xiaoxi , Cohen Ken , Latif Omar , Siontis Konstantinos , Van Houten Holly , Gersh Bernard J , Abraham Neena , FRIEDMAN Paul A , Noseworthy Peter A
Published: April 2022

Introduction:
OAC are recommended for AF patients with CHA
2
DS
2
-VASc ≥2 in men or ≥3 in women (high-risk group), may be considered in patients with CHA
2
DS
2
-VASc 1 in men or 2 in women (medium-risk group), and are reasonable to omit in patients with CHA
2
DS
2
-VASc 0 in men or 1 in women (low-risk group). Furthermore, NOACs are recommended over warfarin in most AF patients. This study aimed to investigate AF stroke prevention treatment patterns in patients managed in routine practice, in particular, the under-use of OAC in the high-risk group and over-use in the low-risk group.

Methods:
Adult patients with AF were identified using de-identified claims for commercial and Medicare Advantage enrollees in the OptumLabs Data Warehouse. Prescription fills were assessed within 90 days of a patient’s AF encounter between 1/1/2016-12/31/2020. Patients with other indications for OAC, such as VTE, recent joint replacement, prior mechanical or bioprosthetic valve replacement, rheumatic mitral stenosis, and patients who underwent LAAO were excluded.

Results:
Among the 339,197 AF patients, 4.4%, 8.0%, and 87.6% were in the low-, medium-, and high-risk groups, respectively. The mean age was 51.2 ±10.5 yr, 59.9 ±9.4 yr, and 75.1 ±8.8 yr. In the low-risk group, 29.6% were treated with OAC, whereas in the high-risk group, 40.3% were not treated with any antithrombotic therapy and 7.5% used thienopyridine only. Although 71% of patients on OAC were on a NOAC, the proportion of patients on NOAC decreased from 91% in the low-risk group to 69% in the high-risk group.

Conclusions:
There are potentially both under-use of guideline-recommended stroke prevention therapies in the high-risk patients and over-use in the low-risk group. Because patients at a high risk of stroke are also at a high risk of major and intracranial bleeding who might benefit from NOACs, the decreased use of NOAC in high-risk patients might highlight the need for future quality improvement efforts.