bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16860: Racial Disparity in COVID-19 Patients With Concomitant Myocardial Injury
Authors: Case Brian C , Yerasi Charan , Forrestal Brian , Chezar Azerrad Chava , Satler Lowell F , ben-dor itsik , Hashim Hayder , Bernardo Nelson L , Waksman Ron
Published: May 2021

Introduction:
Cardiac involvement in Coronavirus Disease 2019 (COVID-19) is common. Estimated that 30% of patients hospitalized with COVID-19 have an elevated troponin and these patients have worse prognosis when compared to patients without myocardial injury.

Hypothesis:
The purpose of this study is to investigate if there is any racial disparity in the in-hospital clinical outcomes of COVID-19 patients with myocardial injury.

Methods:
This study included all COVID-19 positive patients within the MedStar Health System (11 acute hospitals in the DC/Maryland/Virginia area) with an elevation of troponin and a diagnosis of either ST-Elevation Myocardial Infarction (STEMI) or Non-ST-Elevation Myocardial Infarction (NSTEMI) based on International Classification of Diseases-10.

Results:
There was 3,589 COVID-19 admissions between March to June 2020. Of these, a total of 75 COVID-19 patients had either a STEMI or NSTEMI. Overall mean age was 70.9 ± 14.6 and 54.7% were male. Of these patients, the majority were African American (51; 68%) followed by Caucasians (15; 20%). The overall in-hospital mortality rate was 24.3%, with African Americans having a higher rate (73.7%) as compared to Caucasians (15.8%) p 0.05. Furthermore, African Americans trended toward having higher rates of intensive care unit (ICU) admissions, intubation, and longer ICU stays; however, not statistically significant. Despite African Americans appearing to be a sicker cohort, inflammatory markers and myocardial involvement did not differ between the two groups (Table 1).

Conclusions:
Patients with COVID-19 and concomitant myocardial injury have a high in-hospital mortality rate. There is a racial disparity with African Americans having a higher rate of in-hospital mortality. However, inflammatory markers and myocardial injury does not differ between the two groups meaning other unidentified underlying issue may be the etiology for a sicker cohort in African Americans.
Abstract 16879: Utility of Transthoracic Echocardiography in Adult Patients With D-Transposition of the Great Arteries and Atrial Switch Operation
Authors: Xiao Ran , Broda Christopher R , Harrison Darren , Aggarwal Shivani R , Ermis Peter R , Opina Angeline , Franklin Wayne , Parekh Dhaval R , Lam Wilson W
Published: May 2021

Introduction:
Per 2018 ACC AHA adult congenital heart disease guidelines, routine transthoracic echocardiography (TTE) is recommended for follow-up in patients with d-transposition of the great arteries (dTGA) after atrial switch operation at least annually. Little data are available to suggest utility in clinical management with frequent surveillance, either with or without symptoms.

Hypothesis:
We hypothesized that frequent TTEs would not lead to significant clinical changes in management and that TTEs performed for symptoms would lead to more detection of pathology and clinically relevant management decisions.

Methods:
We conducted a retrospective review of all echocardiograms performed for dTGA patients corrected with the atrial switch procedure at Texas Children’s Hospital from 2000-2009 to obtain baseline TTEs and 2010-2019 to analyze for changes in clinical management, associated with TTE performance.

Results:
We identified 50 patients with dTGA and atrial switch operation with 54% Mustard operation. A total of 333 echocardiograms were performed (6.7/person), 30% (100) with symptoms. The average age at time of all TTEs was 35 +/- 11 years. Most frequent symptoms were palpitations (n=39), dyspnea (n=30), and fatigue (n=27). Changes in management occurred after 9% of studies (10/100 of symptomatic, 21/233 asymptomatic patients, p = NS). Most of these were medication changes (n=18, 11 asymptomatic) and advanced imaging (n=12, 9 asymptomatic). Invasive management after TTE was rare (1 baffle stenting in asymptomatic patient) but after advanced imaging included 4 baffle stent implantations (3 asymptomatic). The interval between TTEs was 1.2 +/- 0.9 years, regardless of symptoms.

Conclusions:
In dTGA patients after atrial switch operation, routine screening TTEs and symptomatic TTEs had similar yield in detecting pathology leading to a clinical change in management. TTE and subsequent advanced imaging preceded invasive intervention (baffle stenting) in 10% of patients, mostly asymptomatic. Less frequent surveillance TTEs in asymptomatic and advanced imaging in symptomatic dTGA patients with atrial switch operation is cost-effective and should be considered
.
Abstract 16887: Utilization of Cardiovascular Procedures in Cardiac Amyloidosis
Authors: Buck Benjamin , Kahwash Rami , Efebera Yvonne , bumma naresh , Vallakati Ajay
Published: May 2021

Background:
Cardiac amyloidosis (CA) is characterized by restrictive cardiomyopathy, atrial and ventricular arrhythmias, as well as atrioventricular block. However, it is unclear whether the use of procedures to treat these specific complications are utilized at different rates during admissions for heart failure (HF) patients with and without CA.

Hypothesis:
Patients with HF and CA undergo invasive and noninvasive cardiac procedures at a higher rate than those with HF alone.

Methods:
The National Inpatient Sample database was queried to identify hospitalizations from 2003 to 2014 for patients ≥18 years old admitted with a diagnosis of HF with or without CA. Admissions with CA were propensity-score matched 5:1 with admissions for HF without CA. Procedures, including cardioversion, pacemaker implantations and implantable cardioverter-defibrillator (ICD) implantations were identified by ICD-9 procedure codes; other comorbidities were identified by ICD-9 diagnosis codes. Rates of procedural utilization, length of stay, total charges cleared and discharge disposition were compared between matched groups.

Results:
Over the 12 years considered, we matched 10,519 admissions with HF and CA to 52,595 admissions for HF without CA. When compared to HF patients with CA, the rates of cardioversion and ICD implantation were higher and the rates of pacemaker implantation were lower in the HF patients without CA (p<0.001 all comparisons). Discharge disposition was more favorable in the cohort without CA (p<0.001); in particular the cohort with CA had a much higher in-hospital mortality rate (9.5% compared to 6.2%) as well as a longer length of stay (p<0.001). There was no difference in charges cleared between the two groups. Procedure use is depicted in the figure.

Conclusions:
Despite longer hospital stays and higher inpatient mortality, the rates of utilization of procedures, particularly cardioversion and ICD implantation, was lower among HF patients with CA.
Abstract 16898: Clinical Implementation of Pharmacogenomics Testing to Guide P2Y12 Inhibitor Use in Older Adults With Acute Coronary Syndrome: Insights From a Prospective Pilot Study
Authors: Sakya Sagune , Regan CHRISTOPHER J , Picot-Vierra Lionel , Riello Ralph J , Tran Lydia , Schulz Wade , Smolderen Kim G , Mena-Hurtado Carlos , Pulk Rebecca
Published: May 2021

Introduction:
CYP2C19
testing is a known pharmacogenomics application to identify patients who can activate clopidogrel. Evidence-based guidelines now support second generation P2Y12 inhibitors over clopidogrel for the management of acute coronary syndrome (ACS). However, continued broad use of clopidogrel within our health-system indicated the potential value of pharmacogenomic testing to guide P2Y12 inhibitor prescribing. This study aimed to evaluate the clinical application of pharmacogenomic testing within a cardiovascular population and identify optimizations to the implementation process.

Methods:
This was a prospective, descriptive cohort pilot study at a large academic health-system. A high-impact pilot population included patients 65 years and older admitted for ACS who underwent percutaneous coronary intervention (PCI). Pharmacists identified eligible patients and made genomic-guided P2Y12 inhibitor recommendations for each patient. Surrogate markers of clinical impact included clopidogrel prescribing rates and quantification of active medication-gene interactions. Process indicators included acceptance rate of recommendations.

Results:
A total of 151 patients were included. At the time of result return, 46% of patients were on clopidogrel. Of these patients, 27% were identified as poor or intermediate metabolizers and were indicated for a change in therapy. The acceptance rate of genomic-guided recommendations was 42%. Identified barriers to uptake included result turnaround time limiting application of findings and unclear responsibility of follow-up.

Conclusions:
Results from this real-world study support implementation of
CYP2C19
testing to guide P2Y12 inhibitor use. Identifying candidates for clopidogrel use through testing has potential clinical and cost benefits, but further studies are needed. Process optimizations are required to address implementation barriers and increase follow-up on actionable results.
Abstract 16904: Hypercoagulability in Pediatric Patients Infected With SARS-Coronavirus 2
Authors: Emani Sirisha , Torres Andrew , Diallo Fatoumata , Diallo Mamadou , Nathan Meena , Ibla Juan , Ghbeis Muhammad , Vanderpluym Christina J , Emani Sitaram
Published: May 2021

Introduction:
Thrombosis is a complication associated with Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), Corona Virus Disease 2019 (COVID-19). Although, abnormalities in coagulation markers have been reported in adults with COVID-19, coagulopathy in pediatric patients infected with coronavirus has not been elucidated.

Hypothesis:
In this study, we evaluated the coagulation profile in pediatric patients with COVID-19 using Thromboelastography (TEG).

Methods:
This is a retrospective study of pediatric (≤18yrs) patients with seropositive COVID-19 (N=35) regardless of symptom status. Coagulation markers including TEG were obtained from review of medical records under an IRB approved study. All TEG parameters were compared between patients with COVID-19 and age matched controls without COVID-19 (N=35).

Results:
Regardless of symptom status, COVID-19 patients had significantly lower R-time (5.3±2.7 min vs. 6.5±1.5 min;
p=0.03
), K-time (1.1±0.3 min vs. 1.8±1.1 min;
p<0.001
) and fibrinolysis (1.7±1.7% vs. 3.2±3.6%;
p=0.04
); and significantly elevated angle (73.6±4.8 deg vs.66.7±6.2 deg;
p<0.001
), maximum amplitude (68.9±6.1 mm vs. 59.5±8.7 mm;
p<0.001
) and overall clot strength G (11.7±3.3 Kdynes/cm
2
vs. 7.8±2.4 Kdynes/cm
2
;
p<0.001
). Whereas the standard coagulation tests such as PT/INR, PTT, Thrombin time and Heparin levels were within the normal pediatric reference ranges. D-dimer expression was also higher (0.94 μg/ml) in COVID-19 patients compared to the normal pediatric reference range (<0.4 μg/ml). In patients with COVID-19 undergoing aspirin therapy, all patients responded to the treatment and platelet function was significantly inhibited compared to patients not given aspirin (85% vs. 8% platelet inhibition;
p<0.001
).

Conclusions:
Abnormal expression of all TEG parameters and D-dimer is consistent with a hypercoagulable profile. TEG may be useful in reducing thrombosis-risk in patients with COVID-19 by guiding anticoagulation management.
Abstract 16910: High-Frequency In-Person Visits During Clinical Trial Enrollment is Associated With Relative Reduction in Event Rates in Heart Failure Patients Followed Longitudinally
Authors: Brooks Liana C , Bhat Rohan R , Farrell Robyn F , Schoenike Mark W , Sbarbaro John A , Cunningham Thomas F , Malhotra Rajeev , Nayor Matthew G , Ho Jennifer E , Ibrahim Nasrien E , Coglianese Erin , Cocca-Spofford Diane , Lewis Gregory D
Published: May 2021

Introduction:
The COVID-19 Pandemic has mandated limiting routine visit frequency for patients with chronic cardiovascular (CV) diseases. In patients with heart failure (HF) followed longitudinally, the period of clinical trial participation provides an opportunity to evaluate the influence of high-frequency per-protocol in-person visits compared to less frequent routine visits during longitudinal clinical care.

Hypothesis:
Patients enrolled in clinical trials will have a lower CV and HF event rates during periods of trial enrollment than during non-trial periods.

Methods:
We examined clinical characteristics, CV and HF hospitalization rates, and outcomes in patients with HF receiving longitudinal HF care at a single center. We evaluated hospitalization rates during the 1-year preceding trial enrollment and hospitalization and death rates during enrollment in clinical trials and for up to 1 year following trial completion.

Results:
Among the 121 patients enrolled in HF clinical trials, 72% were HFrEF (age 62±11, 19% females, BMI 30.4±6.0, LVEF 25±7, NYHA 2.7±0.6, NT-proBNP 2336±2671) and 28% were HFpEF (age 69±9, BMI 32.1±5.5, 29% females, LVEF 60±10, NYHA 2.4±0.5, NT-proBNP 957±997). Average clinical trial exposure was 8±6.6 months. Per-protocol visit frequency was 16±7 per year during clinical trial enrollment. In the one-year pre-trial period, compared to the within-trial period, CV hospitalizations were 0.88/patient-year vs. 0.32/patient-year (p<0.001) and HF hospitalizations were 0.63/patient-year and 0.24/patient-year (p<0.001), with a mortality rate of 0.04/patient-year during trial participation. In the period of up-to 1 year following the end of trial enrollment CV and HF hospitalizations were intermediate at 0.51/patient-year and 0.27/patient-year with an annualized incremental mortality rate of 0.03/patient-year.

Conclusion:
In HF patients followed longitudinally at a single center, periods of clinical trial enrollment were associated with high visit frequency and lower CV and HF hospitalization rates. These findings highlight the potential benefits of trial enrollment and high-frequency visits for HF patients at a time when routine visit frequency is being carefully considered during the COVID-19 Pandemic.
Abstract 16915: Potential Role of Endothelial Cell WWOX in the Pulmonary Vascular Response to Hypoxia
Authors: Gomes Marta T , Chen Jiwang , Bai Yang , Li Haibin , Singla Sunit , MacHado Roberto F
Published: May 2021

Introduction:
Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation and dysfunction of pulmonary artery smooth muscle and endothelial cells (PASMC, PAEC). The WWOX/ Wwox gene encodes a tumor suppressor WW domain-containing oxidoreductase, known as WWOX. WWOX has been linked to several protein networks, highlighting its functions in cell homeostasis, survival and proliferation. Loss of WWOX gene expression is observed in human cancer cells, as lung cancer. We hypothesize that during hypoxia, WWOX expression is modulated in PAECs, regulating cell proliferation and selecting apoptosis-resistant cells, thus causing vascular remodeling.

Methods and Results:
Endothelial cell specific Wwox knockout mice were developed by a conditional ablation of
Wwox
gene expression using the
Cre
-Lox site-specific recombination system. We crossed Wwox
flox/flox
mice with CDH5 Cre+ mice, generating Wwox floxed, CDH-Cre+ specific mice that are tamoxifen-inducible (EC- WWOX KO). EC-WWOX KO mice were treated daily with tamoxifen or vehicle for 5 days and exposed to 10% hypoxia. After four weeks of hypoxia exposure, EC-WWOX KO mice showed increased right ventricular systolic pressure (RVSP) (P=0.0003) and Fulton index (RV (LV+S)) (
P=0.049),
when compared to controls, suggesting PH development.
In vitro
, PAECs exposure to 3% hypoxia for 6 hours showed an increase of WWOX mRNA (P=0.0154) and protein (P<0.05) expression levels, decreased of cell proliferation detected by CyQUANT assay and PCNA protein expression (P=0.0024). These effects did not extend to cells exposed to 3% hypoxia for 24h. Immunoblots showed activation of apoptotic markers, such as cleaved caspase 3, PARP and Bax, suggesting that in hypoxia there is a potential controlled balance between increased WWOX expression, decreased cell proliferation and stimulation of apoptosis in these cells.

Conclusion:
Loss of EC WWOX expression plays a significant role in the development of PH in mice exposed to chronic hypoxia. We speculate that increased WWOX expression with acute hypoxia exposure could contribute to the selection of proliferative and pro-apoptotic PAECs, characteristic of PAH. Studies seeking to understand the mechanisms surrounding WWOX expression in PAECs are ongoing.
Abstract 16951: Feasibility of IVUS-Derived FFR as a Novel Technique to Estimate Functional Severity of Coronary Stenosis: Systematic Evaluation of Optimal Major Side Branch Definition to Determine the Reference Site for Automated FFR Calculation
Authors: Kashiyama Kuninobu , Sonoda Shinjo , Okada Kozo , Matsushita Kensuke , Hibi Kiyoshi , Hollak M Brooke , Yock Paul G , Young Alan , Fitzgerald Peter , Honda Yasuhiro
Published: May 2021

Background:
IVUS-derived FFR (IVUS-FFR) is a novel technique to estimate functional severity of coronary stenosis. Using a fluid dynamics algorithm, pressure loss (ΔP) across a stenosis is calculated as ΔP = FV + SV
2
, where V is the flow velocity; F and S are the coefficients defined based on IVUS-determined minimum lumen area (MLA), stenosis length, and reference lumen area (RLA). While the first 2 variables are well defined by IVUS, the RLA can be affected by the presence of side branches near the target lesion due to blood flow distribution.

Methods:
To determine the threshold of side branch size that affects the RLA for IVUS-FFR calculation, 73 coronary lesions (41 LAD: 9 LCx: 23 RCA) underwent both IVUS and wire-derived FFR (W-FFR). RLA was defined as the largest lumen area proximal or distal to the target lesion with no intervening major side branches. In determining the reference site, 3 different definitions of the “major” side branch were used: >25%, >50%, and >75% of the main vessel in diameter. The diagnostic accuracy of calculated IVUS-FFR was then evaluated with each definition as referenced to W-FFR.

Results:
In this patient population, 42% of the lesions were physiologically significant (W-FFR <0.8). MLA and W-FFR were 2.1±0.9 mm
2
and 0.81±0.1, respectively. Overall, IVUS-FFR showed significant linear correlations with W-FFR (p<0.0001 for all definitions). Among the 3 definitions tested, the >50% definition showed the highest diagnostic accuracy (area under the curve [AUC]: 0.95) for physiologic ischemia (Figure).

Conclusion:
In defining the reference site for IVUS-FFR calculation, the optimal definition of the major side branch was >50% of main vessel in diameter. The current results help to develop objective and automated estimation of FFR using IVUS. Further investigation is warranted to evaluate clinical utility of combined anatomical and physiological information that IVUS may offer through this technology.
Abstract 16959: A Youthful Cardiomyocyte Phenotype Drives Enhanced Cardiac Recovery in Adult Spiny Mice
Authors: Peng Hsuan , Shindo Kazuhiro , Donahue Renee , Levitan Bryana , Satin Jonathan , Seifert Ashley W , Abdel-latif Ahmed
Published: May 2021

Introduction:
Adult mammals, including humans, experience limited recovery following myocardial infarction (MI). Recently, our group has uncovered a unique ability for enhanced cardiac recovery in adult spiny mice (
Acomys
).

Methods and Results:
Our preliminary studies have established appropriate similarities in heart structure and coronary anatomy between
Acomys
and
Mus
. Following the same permanent left artery descending (LAD) ligation surgery,
Acomys
and
Mus
showed a similar degree of early cardiac injury. Echocardiography and histological analyses showed more robust cardiac recovery and smaller scar area in
Acomys
. Moreover,
Acomys
exhibited a higher survival rate compared to
Mus
with no evidence of cardiac rupture or hypertrophy (measured by increasing heart/body weight) after MI. To investigate the mechanisms underlying this phenomenon, we isolated and quantified the size, nuclei number, and ploidy of adult cardiomyocytes (CMs) in both species (n=5 animals/group) using the Langendorff perfusion technique.
Acomys
CMs are significantly smaller in size compared to
Mus
and
Acomys
hearts have higher percentage of mononucleated cardiomyocytes. Using flow cytometry, we found that
Acomys
possess a higher percentage of diploid CMs compared to
Mus
. A closer examination of cardiomyocytes using electrophysiology revealed the presence of a T-type calcium current in adult
Acomys
CMs; a characteristic which is usually found in highly proliferative embryonic ventricular cardiomyocytes. Lastly,
Acomys
CMs demonstrated higher proliferative rates after injury compared to
Mus
.

Conclusion:
Taken together, our data provide strong evidence for enhanced cardiac repair in an adult mammalian model. Our results strongly suggest that
Acomys
maintain proliferative adult cardiomyocytes as adults and thus provide a cellular mechanism for their enhanced cardiac recovery after AMI.
Abstract 16966: A p53-Toll-Like Receptor 3-Bone Morphogenic Protein Interaction Regulates the Endothelial Phenotype and Function in Pulmonary Hypertension
Authors: Bhagwani Aneel Roy , Farkas Daniela , Mehboob Ali , Goncharova Elena , Farkas Laszlo
Published: May 2021

Introduction:
Pulmonary arterial hypertension (PAH) is characterized by complex remodeling of pulmonary arteries. In addition to impaired bone morphogenic protein (BMP) signaling, deficiency of the cell cycle regulator p53 has been implicated in PAH pathogenesis. Endothelial cells (ECs) from PAH patients have reduced levels of toll-like receptor 3 (TLR3), impairing EC function. This study investigated whether the p53, TLR3 and BMP pathways regulate endothelial phenotype and function in PAH.

Methods:
Human pulmonary artery ECs (PAECs) and rat CD117
+
ECs were used. Knockdown experiments were carried out by targeting p53 and TLR3. Cells were further treated with the MDM2 antagonist Nutlin 3a, reducing p53 degradation, and with the TLR3 agonist Poly(I:C). Rats received CD117
+
EC clones or SU5416 and were subjected to chronic hypoxia and then treated with Nutlin-3a, Poly(I:C) or vehicle.

Results:
We detected reduced p53 levels in PAECs from PAH patients. Clonal expansion of rat CD117
+
ECs resulted in hyperproliferative cells with reduced p53 and TLR3 levels and evidence for histone methylation. Then, knockdown of p53 or TLR3 increased tube formation in surviving human and rat ECs. In addition, knockdown or activation of p53 indicated regulation of TLR3 mRNA by p53. TLR3 knockdown reduced expression of BMP2, whereas the TLR3 agonist Poly(I:C) induced BMP receptor 2 expression. Upstream, reduced p53 degradation by Nutlin 3a not only increased TLR3, but also BMP2 expression and increased BMP signaling in rat ECs. Interestingly, clonal selection resulted in EC clones with high BMP2 expression. TLR3 knockdown caused partial endothelial mesenchymal transition with increased expression of Snail, which was ameliorated by Poly(I:C). In vivo, Nutlin-3a treatment reduced PH while increasing TLR3 expression in rats. Poly(I:C) reduced PH and Smad2 phosphorylation in rats, and the protective effects were abolished in TRIF KO mice.

Conclusion:
The RNA receptor and p53 transcriptional target TLR3 regulates the BMP pathway in ECs and this interaction may explain some of the protective effects of TLR3 stimulation in PH. However as clonally selected ECs retain high BMP2 expression, differences between EC subpopulations can be suggested and are under investigation.
Abstract 16999: Utilization of Recommended Guidelines Across States for the Annual Preparticipation Physical Evaluation of Adolescent Athletes
Authors: Blank Zane , ROBINSON JEFFREY , Spicer Robert L
Published: May 2021

Introduction:
Annual preparticipation physical evaluation (PPE) is used to screen adolescents for potential causes of sudden cardiac death prior to competitive athletics. While screening varies by state, the AHA published 14 recommended screening criteria in 2014. This study sought to define utilization of the 14 screening elements for high school athletes in the 50 states.

Methods:
PPE forms were requested from the high school athletics governing body of each state. Forms were analyzed to identify which of the 14 elements were explicitly fulfilled. Comparisons were made to the prior 12-point screening criteria (2007). Additional forms from private organizations or other professional societies were excluded.

Results:
A total of 48 states (96%) had PPE forms posted online and publicly accessible. The remaining 2 states (4%) deferred the specific method of PPE documentation to individual school districts and provided no standardized form. Of the 48 states providing forms, 13 (27%) included all 14 AHA screening elements. The median criteria met by each state was 11 (range 3-14). The 2 elements added by the AHA in 2014 (“prior restriction from participation in sports” and “prior testing for the heart, ordered by a physician”) were included by 42 (88%) and 36 (75%) states, respectively, with 13 (27%) states missing at least 1 of these. The 3 criteria most commonly absent were 1) examination of femoral pulses to exclude coarctation (58%), 2) family history of “hypertrophic or dilated cardiomyopathy, long-QT syndrome, or other ion channelopathies, Marfan syndrome, or clinically significant arrhythmias, or specific knowledge of genetic cardiac conditions in family members” (31%), and 3) personal history of elevated systemic blood pressure (27%). There was no difference in the number of states fulfilling all current 14-point criteria (13, 27%) versus the prior 12-point criteria (13, 27%) (
p
=NS).

Conclusions:
Annual preparticipation forms are intended to improve the health and safety of athletes; however, a minority of states currently include all 14 screening criteria from the AHA. As athlete wellness and the prevention of sudden cardiac death remain national priorities, interventions are needed to increase inclusion of recommended criteria across all states.
Abstract 17000: Quantifying Mitral Annular Calcification Using Echocardiography: Comparison to MAC Calcium Score From Gated Computed Tomography
Authors: Harvey William , Litwin Sheldon
Published: May 2021

Introduction:
Mitral Annular Calcification (MAC) is present in 25-40% of people ≥ 60 years old and has associations with atrial fibrillation, stroke, endocarditis, mitral regurgitation, and mitral stenosis. MAC poses major challenges to surgical or transcatheter mitral valve interventions. Current echocardiographic methods for assessing MAC are limited.

Goals:
To assess transthoracic echocardiographic (TTE) approaches for quantifying MAC severity compared to a gold standard of MAC calcium score by gated computed tomography (CT).

Methods:
75 patients undergoing evaluation for TAVR had TTE and CT in close proximity. MAC area and circumference were measured in parasternal long-axis (PLAX), parasternal short-axis (PSAX), and apical 2, 3, and 4-chamber views on TTE. Mitral valve gradients and left atrial volume were recorded. The curvilinear length of MAC in the PSAX view on TTE and cardiac CT were also measured. Associations between various TTE measures and MAC calcium score were assessed using linear regression.

Results:
Median age was 75.3, 50.4% female, 85.3% Caucasian. MAC area and circumference in PSAX on TTE showed moderate correlations (R
2
=0.32-0.37) with MAC calcium score. Curvilinear MAC length measures on SAX TTE and CT had improved correlation with MAC score (R
2
=0.41 & 0.78, Figure). Combined circumference of MAC from PLAX+PSAX had the strongest association (R
2
= 0.48). Interobserver variability on CT and TTE had coefficients of variation ranging 17-37%. Left atrial volume and mitral valve gradients had weak associations with MAC severity (R
2
=0.03-0.12). Tertiles of MAC calcium scores were 2650, 5150 and 7750.

Conclusions:
MAC length in the PSAX view showed the strongest association with MAC severity. Dedicated PSAX views of the mitral annulus may improve the ability to reproducibly grade MAC severity by echo.
Abstract 17018: Left Ventricular Assist Device Failure With Total Artificial Heart Bridge to Heart Transplant
Authors: Tushak Zackary , Wood Taylor , Quader Mohammed , Shah Keyur B
Published: May 2021

Mechanical support devices are used in cardiogenic shock as a bridge to heart transplantation (OHT) or as a destination treatment. The two long term variants are left ventricular assist devices (LVADs) and total artificial hearts (TAHs). Developed in tandem, LVADs have gained favor, but are not without limitations. Adverse events include thrombosis, bleeding, mechanical failures, ventricular arrhythmias (VAs), and right ventricular failure (RVF). When LVADs fail, often the only options becomes OHT or TAH implantation. This case series retrospectively follows ten patients requiring TAH implantation due to LVAD failure between 12/2009-09/2018 at VCU Health. On admission, all were in multiorgan failure with four requiring hemodialysis and two requiring intubation. Eight patients required extra support including pressors, inotropes, and additional mechanical support. The causes of failure included refractory infection, outflow graft mechanical compromise, right ventricular failure, VAs, and pump thrombosis. The mean time from admission to TAH was 13.5 days. Major adverse events included mediastinal hematoma with tamponade in three patients requiring surgical intervention and one patient with an acute cerebral vascular attack who died. One patient died from ongoing respiratory failure. Another patient died from multiorgan failure and hemorrhage. Of the seven surviving patients, all underwent successful OHT and were alive at one year follow-up. The patients who experience LVAD failure are extremely sick and have limited options. TAH implantation, while not without risk, can be a useful tool to bridge patients to transplant with favorable outcomes.
Abstract 17026: Pericardial Effusion in Children After Bone Marrow Transplant
Authors: Dham Niti , Lyons Kelly , Davila Saldana Blachy
Published: May 2021

Background:
Bone marrow transplant (BMT) is necessary in varying diseases. However, it has known cardiac risks and complications, including pericardial effusions (PE). PE can be life threatening if not identified early, and its treatment can be invasive, ie pericardiocentesis. Our objective is to identify echocardiographic (echo) findings that could help identify high risk subsets for developing a PE post BMT.

Methods:
We retrospectively identified BMT patients from January 2011 - December 2019 in our institution that developed moderate to large PE requiring treatment. Our controls consisted of BMT patients that did not develop PE. Baseline demographics, BMT data, PE treatments, and echo data was obtained. Echo variables included markers of systolic function, diastolic function, and LV size prior to BMT in both sets of patients. We performed a t-test for comparison and Pearson correlation.

Results:
We performed over 180 BMTs in our institution during this time. Of these, 50 were noted to have any degree of pericardial effusion, but 15 patients developed symptomatic pericardial effusions requiring further interventions. Our study included 13 subjects and 12 controls. Our subjects ranged from 8 months to 17 years old, 3F/10M. Even though the left ventricle end diastolic diameter (LVIDd) z-scores were within normal, they were statistically larger (p 0.02) in the PE group. Both groups had the same average hemoglobin (9.2). There was no difference in the pre-BMT systolic function or diastolic function parameters between the two groups. The duration of the PE (after the BMT)correlated with LVIDd z-score (Figure 1; r 0.6, p 0.02) and MV septal E’ (r -0.6, p 0.03) and E/E’ (r 0.6, p 0.05) from the pre-BMT echo.

Conclusions:
Assessing LV size and LV diastolic markers pre-BMT could be simple yet important measurements to pay closer attention to, which can then help direct improved screening in pediatric post-BMT patients. These findings should be explored further in larger studies.
Abstract 17044: Effect of Sham Controlled Renal Denervation in Uncontrolled Hypertension. A Systematic Review and Meta-Analysis
Authors: Khan Mohammad Saud , Azhar Abdullah Zoheb , Moustafa Abdelmoniem
Published: May 2021

Introduction:
Catheter-based ablation of renal artery has been studied as one of the interventions for blood pressure control in patients with uncontrolled hypertension. Previous randomized control trials (RCTs) comparing renal denervation versus sham procedure for the same have shown equivocal results. This meta-analysis summarizes the current evidence on the effect of sham-controlled renal denervation on blood pressure reduction.

Methods:
Pubmed, Embase and Cochrane Central databases were searched from inception until April 30, 2020. RCTs comparing catheter-based renal denervation with a sham control were included. Outcomes assessed were changes in ambulatory systolic blood pressure, change in ambulatory diastolic blood pressure, change in office systolic blood pressure and change in office diastolic blood pressure. Weighted mean differences (WMD) were calculated and pooled using inverse variance method into a random effect model meta-analysis.

Results:
Six studies with 1118 participants were included in the analysis. Catheter based renal denervation was associated with significant decrease in ambulatory systolic blood pressure (WMD: -3.71; 95% CI: -2.32 to -5.11, p value <.00001) and ambulatory systolic blood pressure (WMD: -1.71; 95% CI: -0.59 to -2.82, p value=0.003) compared with sham. The reduction in office systolic and office diastolic blood pressure was also significantly greater with catheter renal denervation than sham control (WMD: -5.82; 95% CI: -3.67 to -7.92; p value<0.00001 and WMD: -3.51; 95% CI: -2.29 to -4.73; p value<0.00001 respectively)

Conclusion:
This meta-analysis showed significant benefit of catheter-based renal denervation for uncontrolled hypertension for all the studied outcomes. Based on this data patients with uncontrolled hypertension, on lifestyle and pharmacological management may benefit from catheter-based renal denervation
Abstract 17048: The Association of Neighborhood Deprivation With Racial Disparities in 30-day Heart Failure Readmissions in Middle Aged Adults
Authors: Patel Shivani A , Nayak Aditi , Shirey Theresa , Long Kaitlyn , Dickert Neal W , Morris Alanna A
Published: May 2021

Introduction:
Neighborhood socioeconomic status (N-SES) is associated with incident heart failure (HF) and HF readmissions. N-SES may have a greater impact on young and middle-aged adults with heart failure (HF) due to fewer resources.

Hypothesis:
N-SES modifies the disparity in 30-d HF readmissions between Blacks and Whites in the Southeastern US.

Methods:
We created a geo-coded retrospective cohort of patients aged <65 years (N=11,469, mean age 52.1 yrs, 48% female, 46.5% Black) with at least one HF hospitalization at any Emory Healthcare facility from 2010-2018. Quartiles of the Social Deprivation Index (SDI), derived from US Census data, characterized neighborhood deprivation at the census tract level. Linear probability models estimated the “excess 30-d HF readmissions” between Blacks and Whites (referent) within each quartile of neighborhood deprivation. A base model accounted for geographical clustering, age, gender, and insurance type; a fully adjusted multivariable model further adjusted for clinical variables (composite Charlson Comorbidity Index, HbA1c, BP, SaO2, and HR).

Results:
Compared with Whites, Blacks were more likely to reside in deprived census tracts, be female, have public insurance, and higher comorbidity scores (Table 1). Between 2010-2018, 20.5% of Black and 12.5% of White patients experienced a 30-d HF readmission (p<.001). Black excess in HF readmissions ranged from 6.7% (95%CI: 3.6%-9.7%) to 8.4% (95%CI: 4.9%-12.0%) within the 2
nd
and 4
th
deprivation quartiles, respectively (Figure 1), with no excess readmissions in the least deprived quartile. Accounting for comorbidities and clinical presentation eliminated the Black excess in 30-d HF readmissions in the 2
nd
quartile but not within higher levels of area deprivation.

Conclusions:
Excess 30-d HF readmissions in middle aged Blacks increases with neighborhood deprivation and was not explained by patient sociodemographics or comorbidities in the most deprived Census tracts.
Abstract 17049: Outcomes of Bioprosthetic and Mechanical Aortic Valve Replacement in Patients With Congenital Heart Disease
Authors: Hobbs Reilly D , Schultz Megan , Wagner Catherine , Ohye Richard G , Bove Edward , Si Ming-Sing
Published: May 2021

Introduction:
Aortic valve replacement (AVR) is required in patients with congenital heart disease who are not candidates for Ross procedure or valve repair. The long-term outcomes of prosthetic AVR in patients with congenital heart disease are unknown.

Methods:
A single-institution, retrospective review of all patients treated with mechanical (M) and bioprosthetic (BP) AVR between 12/1985 to 2/2020 was undertaken.

Results:
One-hundred and ninety-three patients underwent BP (n=134) or M (n=59) AVR. Indications for AVR were insufficiency (91/193), stenosis (61/194), mixed (38/193), aneurysm (2/193), and unknown (1/193). Patients receiving M valves were more likely to be younger (18.5 years versus 29.0 years, p < 0.01) and less likely to require subsequent valve reintervention (p < 0.01). Average time to first reintervention was 76 and 71 months in the BP and M groups respectively (p = 0.785). Survival between the M and BP groups was similar (p = 0.120). Twenty-four patients who received a M valve and thirteen patients who received a BP valve died during the study period. Causes of death were cardiac (16/37), stroke (3/37), non-cardiac (4/37), and unknown (14/37).

Conclusions:
Long-term freedom from death or valve reintervention is poor in congenital heart disease patients requiring AVR. Survival is similar between patients treated with M and BP valves, however, BP valves more frequently required reintervention during the study period. Both BP and M valves are associated with significant long-term mortality. These results highlight the need for the development of robust aortic valve repair techniques so that AVR can be avoided.
Abstract 17052: Cardiothoracic Surgeons With a PhD Degree Exhibit Greater Research Productivity
Authors: Bajaj Simar , Wang Hanjay , Williams Kiah M , Heiler Joseph , Pickering Joshua , Manjunatha Keerthi , Sanchez Mark , O'Donnell Christian , Boyd Jack
Published: May 2021

Introduction:
A PhD degree can offer significant research experience for academic surgeons. Here, we evaluated the impact of a PhD on research productivity and career advancement in cardiothoracic (CT) surgeons.

Methods:
All CT surgeons practicing at an accredited United States CT surgery training program in 2018 who earned a PhD or completed a research fellowship during training (RF) were included (n=583). To ensure a more consistent training pathway, we performed a sub-analysis of U.S. medical school graduates (n=456). Surgeon-specific data were obtained from publicly available sources (eg. institutional webpages, Scopus).

Results:
92 (15.8%) surgeons obtained a PhD while 491 (84.2%) did not but did a RF (Table 1A). Importantly, attending start year was similar (2005 vs 2005, p=0.5202). As of 2018, PhD surgeons published greater first-author (17.0 vs 12.0, p=0.0079), last-author (12.0 vs 6.0, p=0.0462), and total papers (68.5 vs 52.0, p=0.0148), as well as total papers per year as an attending (4.6 vs 3.0, p=0.0148). However, PhD surgeons took a similar amount of time as non-PhD surgeons who did a RF to become a full professor from the start of their first job (12.0 vs 11.0, p=0.6620). No difference was observed in current academic rank neither (p=0.8047). For U.S. medical school graduates, there were 40 PhD surgeons and 416 non-PhD surgeons who did a RF (Table 1B). Both groups published a similar number of first-author (13.0 vs 13.0, p=0.5379), last-author (12.5 vs 6.0, p=0.0981), total papers (64.5 vs 54.0, p=0.3453), and total papers per year as an attending (3.2 vs 3.0, p=0.7546). Years to full professor were also similar between these two groups (12.0 vs 11.0, p=0.6007) as was current academic rank (p=0.3114).

Conclusions:
A PhD degree is not associated with faster career advancement but may be associated with enhanced research productivity for some surgeons due to the impact of their medical school training environment.
Abstract 17053: Cardiac AKAP12 Signalosome Overexpression Exacerbation of Heart Failure and Cardiac Calcium Handling
Authors: Qasim Hanan , McConnell Bradley K
Published: May 2021

Introduction:
Heart failure (HF) is responsible for 1 out of 8 deaths per year in the U.S.A. and is the major cause of death globally. Calcium cycling is crucial for proper signaling processes and efficient cardiac contraction. In failing hearts, remodeled calcium handling contributes to cardiac dysfunction. Previously we reported enhanced cardiac function in mice lacking a functional A-Kinase Anchoring Protein 12 (AKAP12). In this study, we aim to investigate the role of AKAP12 overexpression (oxAKAP12) on heart failure progression through assessing Sarco/Endoplasmic Reticulum Ca2+-ATPase (SERCA2) and its regulatory protein Phospholamban (PLN).

Hypothesis:
Cardiac AKAP12 overexpression potentiates HF development through its action on SERCA2.

Methods:
HF was developed in WT and oxAKAP12-Tg mice of 8-10 weeks old males and females, through chronic Isoproterenol (ISO) administration (60 mg/kg/day for 14-days). Left ventricular homogenates were used for gene expression analysis. Furthermore, AKAP12 was transiently overexpressed in AC16 cells (human cardiomyocytes cell line), to assess protein expression levels upon treatment with 100 nM of ISO for 12-hrs.

Results:
Cardiac oxAKAP12 in both males and females reduced left ventricular ejection fraction (EF) by 14.5±2.5% and fractional shortening (FS) by 22.7±2.0% after 14-days of chronic ISO treatment when compared to control groups. Both RNA sequencing and RTqPCR analysis showed a significant reduction of SERCA2 and PLN mRNA levels, respectively, in left ventricular homogenates of male (53.5±2.0%, 39.0±2.5%) and female (50.0±2.5%, 45.0±2.0%) groups overexpressing AKAP12 treated with ISO (14-days) compared to control groups (p<0.005). In AC16 cells overexpressing AKAP12 and treated with ISO, SERCA2 protein expression was reduced by 37% (p=0.0413) while PLN protein expression was not significantly reduced compared to control groups.

Conclusions:
Cardiac oxAKAP12 negatively influences systolic function in both male and female mice, potentially through affecting calcium handling, which will be assessed in future experiments by evaluating calcium transients and sarcomere shortening in isolated primary cardiomyocytes from oxAKAP12 and control mice.
Abstract 17069: NAD+Redox Imbalance in the Heart Exacerbates Diabetic Cardiomyopathy
Authors: Chakraborty Akash Deep D , Chiao Ying Ann , Light Christine M , Tian Rong , Sadoshima Junichi , Shi Xiaojian , Gu Haiwei , Lee Chi Fung
Published: May 2021

Diabetes is a risk factor of heart failure and leads to cardiac dysfunction, a condition named diabetic cardiomyopathy (DCM). NAD redox imbalance is observed in diabetic tissues. However, whether NAD redox imbalance promotes cardiac dysfunction in DCM remains unknown. The objective of this study is to determine the causal role of NAD redox imbalance in DCM.Type 1 diabetes was induced in C57BL6 mice by streptozotocin (STZ) injections, and DCM was allowed to develop for 16 weeks. Diabetes-induced chronic stress led to systolic and diastolic cardiac dysfunction along with a lowered NAD/NADH ratio. The diabetogenic protocol was applied to control and cardiac-specific Ndufs4-KO mice (cKO), a mouse model with lowered cardiac NAD/NADH without baseline cardiac dysfunction. Analyses of blood glucose and >200 metabolites in plasma showed no significant change in diabetic control and diabetic cKO mice, suggesting that their hearts experienced similar diabetic stress. Diabetic cKO hearts showed lowered NAD/NADH, aggravated contractile and relaxation dysfunction compared to the diabetic control hearts in both sexes. The data suggest that NAD redox imbalance exacerbated DCM. Collagen staining and transcript analyses of fibrosis-related genes showed no change in diabetic cKO hearts, signifying that the exacerbated dysfunction was due to cardiomyocyte dysfunction. A global protein acetylation was promoted in the diabetic cKO hearts with an increase in SOD2 acetylation levels at lysine-68 (SOD2-K68Ac) and enhanced protein oxidation. Diabetic cKO mice displayed enhanced levels of TnI S150 phosphorylation (TnI-S150Pi), but not phosphorylation of TnI-S23/24 or MyBPc-S282. These data suggest that enhanced oxidative stress and altered myofilament Ca
2+
sensitivity via TnI-S150Pi are responsible for the NAD redox imbalance-exacerbated DCM.To confirm the role of NAD redox imbalance in DCM, we elevated cardiac NAD levels in diabetic cKO mice by cardiac-specific expression of NAMPT. Expression of NAMPT in the heart improved cardiac systolic and diastolic function in diabetic cKO hearts. This was due to increased NAD/NADH ratio and reversed pathogenic mechanisms (lowered SOD2-K68Ac and TnI-S150Pi). This study supports the causal role of NAD redox imbalance in DCM.
Abstract 17073: In Hospital Outcomes in Patients With Infective Endocarditis With and Without Liver Cirrhosis - Insight From National Inpatient Sample
Authors: Jamal Shakeel , shah zaib muhammad , Kichloo Asim , Riaz Iqra , Bailey Beth , Aljadah Michael , Amjad Waseem , Khan Muhammad Zatmar , Vipparla Navya Sree , Soni Ronak , SINGH Jagmeet P , Sudhakar Rajeev
Published: May 2021

Introduction:
Chronic liver disease is known to be an important prognostic factor in determining morbidity and mortality in preoperative risk assessment and mortality in general. Data are limited on outcomes in patients with infective endocarditis (IE) and comorbid concurrent liver cirrhosis. Objective of our study is to evaluate the clinical outcomes of patient with IE with and without underlying liver cirrhosis and determining in-hospital mortality and outcomes of interest i.e. renal failure, cardiogenic shock, hematologic (coagulopathy/thrombocytopenia) and hepatic complications (hepatic encephalopathy/hepatitis).

Hypothesis:
Liver Cirrhosis worsen clinical outcomes in patients with IE.

Methods:
Patients with principle diagnosis of IE with and without liver cirrhosis were identified by querying the Healthcare Cost and Utilization (HCUP) database, specifically, National Inpatient Sample for year 2013 and 2014 based on ICD9 codes.

Results:
During 2013 and 2014, a total of 17, 952 patients were admitted with diagnosis of IE, out of whom 780 had concurrent liver cirrhosis. There was an increased in-hospital mortality [15.6% vs 10.2%, aOR 1.57(1.27-1.93)], acute kidney injury [41.4% vs 32.6%, aOR 1.45(1.24-1.69)], coagulopathy/thrombocytopenia [32.1 vs 14.7%, aOR 2.87(2.44-3.37)] in patients with IE with liver cirrhosis when compared to patients with IE without liver cirrhosis. IE without liver cirrhosis underwent increased number of interventions i.e. aortic (7.2 vs 3.7%, 0.51(0.34-0.76)] and mitral (4.9% vs 3.4%, aOR 0.39(0.23-0.69)] valvular replacements as compared to without liver cirrhosis.

Conclusions:
Liver cirrhosis is an important prognostic marker of in-hospital mortality in patients with concurrent IE. High risk surgical state with coagulopathy, bleeding complications, worsening hepatic complications and renal dysfunction lead to higher mortality.