bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15562: Incidence and Risk Factors of Device-related Infection in
De Novo
Transvenous Implantable Cardiac Defibrillator Medicare Patients
Authors: El-Chami Mikhael F , Jacobsen Caroline M , Griffiths Robert I , Hansen Linda K , Wold Nicholas , Amorosi Stacey L , Stivland Timothy M , Knight Bradley P , Weiss Raul , Mark George E , Biffi Mauro , Probst Vincent , Lambiase Pier D , Miller Marc A , Baddour Larry M
Published: May 2021

Introduction:
Practice guidelines recommend use of subcutaneous implantable cardioverter-defibrillators (ICD) in patients (pts) at risk of sudden cardiac death and high risk for infection. This has prompted a need to better identify pts at high risk of infection to assist in
de novo
device selection. The objective of this study is to estimate infection incidence in
de novo
transvenous (TV) ICD implants and assess risk factors associated with infection in a large Medicare population.

Methods:
A retrospective cohort study was conducted using 100% Medicare administrative and claims data to identify pts who underwent
de novo
TV-ICD implantation between 7/2016 and 1/2018. Device-related infection within 2 years of implantation was identified using ICD-10 diagnosis and procedure codes. Baseline pt factors associated with infection were identified by univariable logistic regression analysis of all variables of interest, including factors in Charlson and Elixhauser comorbidity indices, followed by stepwise selection criteria with a p≤0.25 for inclusion in a multivariable model and a backwards, stepwise elimination process with p≤0.1 to remain in the model. A time-to-event analysis was also conducted.

Results:
Among 26,742 pts with
de novo
TV-ICD, 519 (1.9%) had a device-related infection over 2 years. The mean pt age with and without infection was 68 and 71 years, respectively. While more than half (54%) of infections occurred within 90 days post implant, infections continued to be diagnosed with 16% of infections occurring between years 1 and 2. Multivariable analysis revealed several significant predictors of infection (Figure) including age <70 years, end stage renal disease with chronic dialysis and diabetes with complications.

Conclusion:
The rate of
de novo
TV-ICD infection in a large real-world Medicare population is clinically significant. The factors associated with increased infection risk identified here can be used to help determine device selection.
Abstract 15567: Residual Cholesterol and Cardiovascular Events in Patients With Coronary Artery Disease Under Different Glucose Metabolism Status
Authors: Li Jian-jun , Cao Yexuan , Zhang Hui-Wen , Jin Jing-Lu , Zhang Yan , Xu Rui-Xia , Guo Yuan-Lin , Wu Na-Qiong , Zhu Cheng-Gang
Published: May 2021

Introduction:
The atherogenicity of residual cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM).

Hypothesis:
This study aimed to examine the prognostic value of plasma RC, clinically presented as triglyceride-rich lipoprotein-cholesterol (TRL-C) or remnant-like lipoprotein particles-cholesterol (RLP-C), in CAD patients with different glucose metabolism status.

Methods:
Fasting plasma TRL-C and RLP-C levels were directly calculated or measured in 4331 patients with CAD. Patients were followed for incident MACEs for up to 8.6 years and categorized according to both glucose metabolism status [DM, pre-DM, normal glycaemia regulation (NGR)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals.

Results:
During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NGR groups (p>0.05). When stratified by status of glucose metabolism and RC levels, highest levels of RLP-C, calculated and measured TRL-C were significant and independent predictors of developing MACEs in pre-DM (HR: 2.10, 1.98, 1.92, respectively; all p<0.05) and DM (HR: 2.25, 2.00, 2.16, respectively; all p<0.05).

Conclusions:
In this large cohort study with long-term follow-up, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting RC might be a target for patients with impaired glucose metabolism.
Abstract 15576: Cardiovascular Disease in Elderly Familial Hypercholesterolemia Individuals Attending a Cascade Screening Program
Authors: coutinho elaine , Miname Marcio H , Rocha Viviane Z , Bittencourt Marcio S , Jannes Cinthia , Pereira Alexandre , Krieger Jose E , Santos Raul D
Published: May 2021

Introduction:
Familial hypercholesterolemia (FH) is associated with early onset of cardiovascular disease (CVD) and mortality. Lipid lowering treatment (LLT) may change the natural history of FH, however there is scant information about elderly individuals (older than 60 years) with FH. This study describes characteristics of elderly FH individuals presenting or not CVD.

Hypothesis:
Monogenic defects are important markers of CVD risk and initiation and long-term use of lipid lowering therapy (LLT) is relevant to minimize this risk.

Methods:
Cross-sectional analysis of clinical and laboratory of molecularly proven elderly FH (FH+) and non-affected (FH-) individuals attending a cascade screening program. FH+ were divided in those presenting or not CVD (defined as previous myocardial infarction or ischemic stroke, carotid or coronary revascularization and angina with stenosis ≥50% on angiography).

Results:
From 4,111 genotyped individuals, 462 (11.2%) elders were included (198 FH+ and 264 FH-). There was predominance of females in either groups, however with more men in FH+ 37.4% vs. 24.2%, p=0.002. No differences were seen between FH+ and FH- regarding age, [median (%25;75%)] 66 (62;71) and 66 (63;71) years, p=0.68; use of LLT 88.5% vs. 91.5%, p=0.29 and high intensity LLT 61.7 % vs. 55.8%, p=0.20, respectively. Despite longer LLT duration in FH+ 11(7;20) vs. 7 (3;13) years, p<0.001, in either groups LLT was started late, at 54 (47;61) and 59 (52;64) years, p <0.001, respectively in FH+ and FH-. FH+ had higher LDL-C at diagnosis, 243 (179;302) vs. 228 (209;251) mg/dL, p=0.013, as well as greater frequencies of previous CVD 40.9% vs. 27.3%, p=0.002, and early CVD 22.2% vs. 9.0%, p<0.001. In FH+, male sex [OR (95%CI)] 5.29 (2.25-12.45), p<0.001, and use of high intensity LLT 2.51 (1.08-5.87), p=0.03, were independently associated with CVD.

Conclusions:
The genetic diagnosis of FH was associated with higher rates of CVD and early CVD vs. FH- hypercholesterolemics. Elders with FH+ who survived despite late LLT initiation have a worse CVD history than FH- elders, emphasizing the relevance of a monogenic defect as cause of long-lasting hypercholesterolemia and CVD risk, particularly in men.
Abstract 15619: Personalized Assessment of Stroke Risk in AF Patients Undergoing Left Atrial Appendage Closure Using Blood-flow Analysis
Authors: Paliwal Nikhil , Ohara Ryan , Daimee Usama A , Aronis Konstantinos , Ali Rheeda , Akhtar Tauseef , Berger Ronald D , Spragg David D , Calkins Hugh G , Trayanova Natalia
Published: May 2021

Introduction:
Left atrial appendage (LAA) is the primary source of clot formation that can cause stroke or transient ischemic attack (TIA) in patients with atrial fibrillation (AF). LAA closure devices have emerged as alternatives to traditional anticoagulation therapy for reducing stroke risk in AF patients. However, ~1-2% of AF patients undergoing LAA closure have subsequent stroke/TIA event.

Hypothesis:
The presence of a persistent low-flow zone in LA, distinct from LAA, explains why some patients have stroke/TIA events after LAA closure.

Methods:
We developed a personalized stroke risk prediction tool that uses patient’s CT image to perform computational fluid dynamics simulation and determine presence of low blood-flow in the LA before and after LAA closure. Low flow is quantified by the establishment of low velocity fraction (LVF) in the LA volume, and low wall shear stress fraction (LWSSF) on the surface of the LA wall. The tool was applied retrospectively on 4 AF patients who had undergone LAA closure: 2 patients with TIA 4 months after LAA closure, and 2 controls matched for age, gender, CHA2DS2-VASc score and LAA dimensions with no complications at follow-up up to 2 years.

Results:
Before LAA closure, TIA and control groups had similar LVF (0.07 and 0.06, respectively) and LWSSF (0.12 and 0.16, respectively). However, after LAA closure, the TIA group had smaller reductions as compared to controls in both LVF (67% vs 79%) and LWSSF (17% vs 52%). This suggests that the LA low-flow region (especially at LA wall) was not substantially reduced after LAA closure, explaining why these patients might have experienced TIA.

Conclusion:
This proof-of-concept study demonstrates that LAA closure might not substantially reduce low-flow zones for all AF patients, as some retain low-flow zones in LA. Our stroke prediction tool has the potential to identify patients at risk of future stroke/TIA, thus enabling personalized patient selection to increase efficacy of LAA closure devices.
Abstract 15625: Social Determinants of Health and Non-cigarette Tobacco Products:results From the 2014-2017 National Health Interview Survey
Authors: Al Rifai Mahmoud , Valero-Elizondo Javier , Blaha Michael J , Osei Albert D , Virani Salim S , Satish Priyanka , Bhugra Priyanka , Bhugra Priyanka , Blankstein Ron , Hyder Adnan , Cainzos-Achirica Miguel , Nasir Khurram
Published: May 2021

Introduction:
The recent decline in use of cigarette products has been offset by an increase in non-cigarette tobacco products (NCP) among young individuals. In this study, we assess the prevalence and association of NCP use across the range of social determinants of health (SDOH) among a nationally representative population of young U.S. adults.

Hypothesis:
Lower SDOH is associated with higher likelihood of NCP use.

Methods:
We utilized cross-sectional data from the 2014-2017 National Health Interview Survey (NHIS). Current use of e-cigarettes, smokeless tobacco, and other NCP was self-reported. Relevant SDOH features were identified based on published literature and included 39 key items from 6 major domains. Each of these items was scored 1 if unfavorable and 0 if favorable and summed to derive a total SDOH risk score. Weighted multivariable logistic regression was used to assess the association between computed SDOH risk quartiles and NCP use.

Results:
The study population consisted of 53,023 participants (mean age 30 [SD 7] years, 50% men, 58% white), which translates to 113M US adults. Of them, 4.2%, 3.0% and 6.1% reported current use of e-cigarettes, smokeless tobacco and other NCP products, respectively with overall (any) NCP use at 11.6%. The respective prevalence in non-cigarette users was 2.3%, 2.4% and 4.4%. A graded increase in age-adjusted prevalence of specific and overall NCP was noted across increasing SDOH risk score quartiles (
Figure).
Accounting for demographics and comorbidities, those in the highest SDOH risk score quartile vs lowest had 1.86-fold higher odds of use of e-cigarettes (1.49-2.34), smokeless tobacco (1.33 [1.05-1.68]) and overall NCP (1.44 [1.26-1.65]).

Conclusions:
In a nationally representative sample, 1 in 14 young adults with the most unfavorable SDOH profile reported NCP use. Evaluation of SDOH may provide opportunities for targeted public health approaches to prevent NCP use and its ensuing complications.
Abstract 15658: Anatomical Characteristics of the Cavotricuspid Isthmus and Their Correlation With Obstructive Sleep Apnea
Authors: Gianni Carola , Gökoglan Yalçin , Sanchez Javier E , TRIVEDI CHINTAN , Mohanty Sanghamitra , Della Rocca Domenico G , Al-ahmad Amin , Bassiouny Mohamed A , Burkhardt J D , Gallinghouse G J , Horton Rodney P , Hranitzky Patrick M , Di Biase Luigi , Natale Andrea
Published: May 2021

Introduction:
Macro-reentrant arrhythmias involving the cavo-tricuspid isthmus (CTI) are common in patients with atrial fibrillation (AF). Bidirectional CTI block is the ablation strategy of choice, but it can be surprisingly difficult to obtain at times.

Objective:
Aim of this study was to systematically assess the characteristics of the CTI to determine its most common anatomical variants to be anticipated for ablation.

Methods:
This is a prospective observational study in which intracardiac echocardiography (ICE) was used to visualize the CTI of patients undergoing AF ablation. The presence of anatomical variants was recorded, and length was measured along the central CTI in atrial systole. CTI systolic shortening measured in sinus rhythm and defined as: [(diastolic length - systolic length)/(diastolic length)]x100.

Results:
180 patients (65±9 years old, 31% female, 37% paroxysmal AF) are included in the study. Mean CTI length was 31±9 mm, with a systolic shortening of 25±13%. A prominent Eustachian ridge was present in 32%, a Chiari network in 11%, and at least one pouch-like recess in 35%, with a mean depth of 5.3±2.5 mm (Figure). A longer CTI was observed in patients with non-PAF compared with patients with PAF (33 vs. 27 mm, P<0.0001) and in patients with known obstructive sleep apnea (OSA; 37 vs. 32 mm, P=0.0077). Of note, after excluding patients with heart failure, ROC analysis showed that a CTI length ≥ 33 mm was predictive of the presence of OSA (67 % sensitivity and specificity, AUC = 0.71). Less CTI systolic shortening was observed in patients with non-PAF compared those with PAF (22 vs. 32%; P<0.0001).

Conclusion:
Anatomical variants of the CTI are common and should be anticipated in case of a challenging CTI ablation. A long CTI is associated with OSA and might warrant further clinical screening to identify this common AF comorbidity. CTI systolic shortening correlates with the type of AF and could represent a measure of right atrial contractility.
Abstract 15659: Dynamic Device Derived Heart Failure Risk Score as a Predictor of Heart Failure Hospitalisation
Authors: Debski Maciej , Howard Lesley , Black Paula , Goode Angelic , Cassidy Christopher , Seed Alison
Published: May 2021

Introduction:
The number of people being admitted to hospital in England due to heart failure (HF) has risen by a third in the last five years. Implantable cardiac devices with integrated heart failure diagnostics are capable of combining daily measurements of multiple device-derived parameters and provide a heart failure risk score (HFRS) which might help predict HF worsening.

Methods:
Between 2015 and 2019 231 consecutive HF device patients were co-managed (CM) by specialist HF nurses in a tertiary centre. Follow-up was truncated at last device transmission in 2019. HF nurses’ interventions to alerts were recorded prospectively. HF-related hospitalisations were collected from hospital records. We analysed the predictive value of baseline variables on the count of days in high HFRS in a negative binomial regression model. The device settings: Optivol CareAlert switched ON vs OFF were compared.

Results:
200 patients with CRT-D were followed up for 2.6 [1.0-2.8] years (Figure). Baseline characteristics and their effect on the incidence rate ratio (IRR) of days in high HFRS are presented in Table. A total of 3,486 transmissions were assessed, median 7.3 [5.9-10.0] per patient-year; 591 high HFRS episodes occurred in 115 (58%) pts. Optivol OFF increased the rate of high HFRS being transmitted >30 days after its end (45% vs 35%, P=0.018) and increased the time from episode start to transmission (36 [16-68] vs 24 [8-53] days, P<0.001). Of 21 hospitalisations for decompensated HF, 15 were predicted by high HFRS within 30 days whereas 6 were predated by medium HFRS.

Conclusion:
Patients who have not had a single high HFRS during follow-up did not need admission for decompensated HF.
Abstract 15665: Can Pulmonary Vasodilators Grow Pulmonary Vasculature in Cases With Bidirectional Glenn for Fontan Candidates?
Authors: Yonehara Kousuke
Published: May 2021

Background:
The condition of pulmonary vasculature is a key to determine the outcome of Fontan candidates. The previous reports described no significant growth of pulmonary arteries (PA) after having bi-directional Glenn shunt (BDG), which may influence peri- and post-operative management of Fontan procedure.

Aim:
We hypothesized the pulmonary vasodilators (PVDs) facilitate to grow small PA even after BDG in Fontan Candidates.

Method:
The twenty-one cases after BDG, whose PA index (Nakata index) were less than 140 mm
2
/m
2
, were enrolled. The enrolled cases were divided into two group: 15 with PVDs treatment ( PV+) and 6 without (PV-). PVDs used in this study were PDE5 inhibitor, Endothelin-receptor-blocker, oral prostacyclines , and their combination. In addition to measure the hemodynamic parameters ( mean PA pressure(mPAp), indexed pulmonary vascular resistance (Rp), Pulmonary flow (Qp) ), PA index and PA branch index ( a sum of cross-sectional area of first PA branches at both side indexed by body surface area) were measured and compared at the timing of after BDG and at after Fontan completion, respectively.

Result:
PA index and PA branch index after BDG of (PV+) and (PV-)were 104±33 vs 104±17 mm
2
/m
2
: 151±33 vs 194±45 mm
2
/m
2
. PA index in both groups after Fontan procedure was increased up to 153±42 vs 152±56 mm
2
/m
2
in same fashion, while PA branch index of (PV+) was significantly increased up to 199±60 than that of (PV-) 226±65 mm
2
/m
2
(% increase was 131% vs 116%). Rp and mPAp in both groups were not changed , while Qp in (PV+) was significantly more increased (140%) than that in (PV-)(107%). In conclusion, PVDs facilitates the growth of PA branches by increasing Qp, which brings a favor outcome of Fontan patients.
Abstract 15671: Adipocyte-derived Exosomal Lncrna Nbr2 Promotes Diabetic Myocardial Fibrosis Through Regulating the Ikba/nf-kb Pathway
Authors: Guo Yue , Xu Xingfeng , Wu Lingling , Zhuang Xiaodong , Liao Xinxue
Published: May 2021

Introduction:
The activation of NF-κB is the dominant process that correlates with the pathogenesis of diabetic cardiomyopathy (DCM). Recently, accumulating evidence shows that long noncoding RNAs (lncRNAs) play crucial roles in sustaining the NF-κB pathway. However, the underlying mechanisms remain unclear. In this study, we identified the upregulated expressed lncRNA NBR2 in adipocyte-derived exosomes (AdEXO) and investigated its regulatory role in diabetic myocardial fibrosis.

Hypothesis:
We hypothesized that AdEXO-NBR2 promotes diabetic myocardial fibrosis through regulating the IκBα/NF-κB pathway.

Methods:
We examined the effect of exosomes from diabetic (db/db) mice-derived adipocytes on ANG-II-induced cardiac fibrosis and function in non-diabetic (C57BL/6J mice). In the invitro study, HG (33mmol/L)-stimulated AdEXO were cultured with adult human cardiac fibroblasts (aHCFs). Differentially expressed lncRNAs in AdEXO were screened using lncRNA sequencing.

Results:
Intramyocardial injection of diabetic AdEXO in the non-diabetic heart significantly exacerbated myocardial fibrosis, as evidenced by poorer cardiac function and enhancer collagen deposition. Whereas administration of a exosomes biogenesis inhibitor mitigated cardiac fibrosis in diabetic mice. We found lncRNA-NBR2 is a common molecule significantly increased in diabetic AdEXO and HG-stimulated non-diabetic AdEXO. After four weeks of ANG II infusion, EXO-db/dbWT-injected mice displayed fibrosis in the heart. However, interestingly, mice receiving NBR2-deficient db/db-EXO showed a decrease in cardiac fibrosis. Similarly, AdEXO-NBR2 promoted aHCFs proliferation and transformation capabilities in vitro. Mechanistically, NBR2 was loaded to AdEXO by directly interacting with heterogeneous nuclear ribonucleoprotein K (hnRNPK). Subsequently, AdEXO-NBR2 was internalized by aHCFs and epigenetically downregulated IκBα expression by recruitment of hnRNPK/SETDB1 and increasing the H3K9 trimethylation level in the IκBα promoter, ultimately activating the NF-κB pathway.

Conclusions:
Our findings highlight a novel epigenetic mechanism of AdEXO lncRNA-mediated diabetic cardiac fibrosis and identify NBR2 as a therapeutic target of DCM.
Abstract 15685: Multicenter Analysis of Advanced Heart Failure Referral Outcomes by Race
Authors: Herr Jared J , Sheikh Farooq , Patel Parin , Lala Anuradha , Chien Christopher , Srivastava Ajay , Forest Stephen J , Tong Michael , DSouza Benjamin , Ravichandran Ashwin
Published: May 2021

Background:
Advanced heart failure (AHF) therapies can improve survival in Stage D HF patients. We sought to evaluate racial differences in AHF therapy referrals and decision-making across a multicenter survey.

Methods/Results:
We performed a retrospective analysis of patients referred for evaluation for AHF therapies at 9 centers (N=515) across the country. Data included: demographics, clinical/referring physician characteristics and evaluation outcomes. By identified racial/ethnic groups, referrals comprised of 55.7% Caucasian, 29.9% African American, 9.1% Hispanic, and 4.7% Asian. Univariate analysis was performed between Caucasian and a combined non-Caucasian group. Most patients were advanced in their disease state, with 47.7% of Caucasian and 55.7% of non-Caucasian patients having EF<20% with a high risk INTERMACS profiles (1-3), 77% and 71.1% respectively. Non-ischemic etiology was more common in non-Caucasians (66.6% vs. 47.4% p=0.001), ischemic etiology more common in Caucasians (41.1% vs. 23.2% p=0.001). The primary reasons for Caucasians to be referred were ventricular arrhythmias (7.6% vs. 3%, p=0.024) and pulmonary hypertension (3.4% vs 0.4% p=0.018), while non-Caucasians were referred most for worsening heart failure (35.9% vs. 25.4% p=0.009). Non-Caucasians were more likely to be declined/deferred for LVAD (45.9% vs. 39.7% p=0.014) or transplantation (48.2% vs. 66.9% p=0.002). Patient preference to not pursue LVAD therapy differed significantly between the groups (Non-Caucasians 17.6% vs. Caucasians 9.6% p=0.022).

Conclusions:
In this multicenter analysis of referrals for AHF therapies, significant differences exist in referral characteristics and evaluation outcomes between Caucasian and non-Caucasians. The driving factor for not offering LVAD therapy in non-Caucasians was patient preference, raising concerns for potential differences in patient education surrounding AHF therapies between racial groups. Further investigation is needed to explore these differences and why non-Caucasians were more likely to be declined or deferred for LVAD and transplantation.
Abstract 15691: The Novel High Mobility Group Protein Hmgxb4 Promotes Neointimal Formation in Response to Arterial Injury
Authors: he xiangqin , Dong Kunzhe , Shen Jian , Osman Islam , Hu Guoqing , Zhou Jiliang
Published: May 2021

Introduction:
Restenosis after percutaneous intervention is predominantly attributed to proliferation and migration of vascular smooth muscle cells (VSMCs). However, the key regulators responsible for VSMC proliferation and migration remain to be identified.

Hypothesis:
We previously reported that the novel high mobility group (HMG) nuclear protein HMGXB4 (HMG-Box containing 4) plays a critical role in the de-differentiation of vascular smooth muscle cells in vitro and in acute inflammatory response to septic shock. We hypothesize that HMGXB4 is critical for neointimal hyperplasia in response to inflammatory stimuli.

Methods and Results:
We found that the expression of HMGXB4 is dramatically induced in ligation or wire injury-induced neointimal hyperplasia and correlated with the activation of inflammatory signaling in mice. Using an inducible smooth muscle-specific
Hmgxb4
KO (knockout) mice model, we found specific KO of
Hmgxb4
in VSMCs ameliorates ligation- or wire- injury induced neointimal formation. Among an array of growth factors and inflammation cytokines, we found that TNFα and INFγ effectively induces the expression of HMGXB4 in VSMCs and correlates with the VSMC proliferation in vitro. Furthermore, we found deletion of HMGXB4 attenuates while over-expression of HMGXB4 promotes inflammation cytokines-induced VSMC proliferation in vitro. These results suggest injury-induced inflammatory signal triggers HMGXB4 induction, which, in turn, promotes the VSMC proliferation and neointimal formation.

Conclusions:
Our study not only demonstrates a critical role of HMGXB4 in promoting neointimal hyperplasia in response the arterial injury, but also suggests HMGXB4 is a potential novel target for the management of restenosis in human.
Abstract 15715: Dna Methylation of Genes Involved in Inflammation Correlates With Cardiometabolic Function in Morbidly Obese Adults
Authors: Ali Mohamed M , Hassan Chandra , Masrur Mario , Bianco Francesco , Frederick Patrice , Cristoforo Giulianotti P , Gangemi Antonio , Phillips Shane A , Mahmoud Abeer M
Published: May 2021

Obesity is a major risk factor for cardiovascular disease. We previously demonstrated impaired vascular function that correlated with global DNA hypomethylation in adipose tissue (AT) isolated from obese adults (OB). Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers and stand as an unexploited precision medicine reserve.

Hypothesis:
We hypothesized a contributing role of DNA methylation to systemic inflammation in OB subjects compared to lean controls (CON). We also explored the correlation between these methylation profiles and cardiometabolic measurements.

Methods:
We obtained blood and AT samples from bariatric patients (n=24; age: 36±7 yrs; BMI: 50.7±8.7 kg/m2) and CON adults (n=24; age: 36±2 yrs; BMI: 25.8±1 kg/m2). AT-isolated arterioles were tested for flow-induced dilation (FID), nitric oxide (NO) and reactive oxygen species (ROS) production. Brachial artery flow-mediated dilation (FMD) was measured via Doppler ultrasound. Promoter methylation of 94 genes involved in inflammation and autoimmunity (EpiTect Methyl II PCR Arrays) were analyzed in whole-blood DNA in relation to vascular function and cardiometabolic risk factors.

Results:
70% of genes had a higher methylated fraction in CON compare to only 28% in OB subjects. After correction for multiple testing, 28 genes were significantly hypermethylated in CON compared to OB; on top of these genes are CXCL1, CXCL12, CXCL6, EGR1, HDAC4, IGF2BP2, IL12A, IL12B, and IL17RA. Ten of these genes had significantly higher mRNA in OB compared to CON indicating the functional impact of such signals on gene transcription; on top of these genes are CXCL6, TLR5, IL6ST, IL15RA, and HDAC4. Methylation % of differentially methylated genes inversely correlated with BMI, total fat %, visceral fat%, blood pressure, fasting plasma insulin, serum IL6 and CRP (C-reactive protein), arteriolar ROS, and alcohol consumption and positive correlations with lean %, HDL, plasma folate and vitamin B12, arteriolar FID and NO production, and brachial FMD.

Conclusions:
Our results suggest that vascular dysfunction in OB adults may be attributed to aberrant DNA methylation. A downstream target for this pathway could reside in endothelial cells resulting in vascular dysfunction
Abstract 15723: Risk Factors of Fluoropyrimidine Induced Cardiotoxicity Among Cancer Patients: A Systematic Review and Meta-analysis
Authors: Li Chao , Tanni Kaniz A , Ngorsuraches Surachat , Chou Chiahung , Chen Li , Qian Jingjing
Published: May 2021

Introduction:
Cancer patients are at increased risk of experiencing cardiotoxicity during their fluoropyrimidine-based chemotherapy. However, risk factors for fluoropyrimidine-induced cardiotoxicity (FIC) are not entirely understood.

Methods:
We searched PubMed, PsycINFO, IPA, CINAHL, Web of Science and ClinicalTrials.gov for studies published between January 1, 1990 and December 31, 2019, examining risk factors for cardiotoxicity induced by 5-fluorouracil, capecitabine or floxuridine. Two reviewers independently assessed publication quality and extracted study-level data into standardized evidence tables. Review Manager 5 software was used to convert data to risk ratios (RRs) and calculate pooled RRs for meta-analyses using a random-effects method. We conducted a Cochran’s Q test and obtained I
2
index to quantify study heterogeneity in each meta-analysis, with prediction interval (PI) to show the expected range of true effects in future similar studies.

Results:
Of 690 publications identified for abstract and title screening, 22 unique studies were included in the final review, and 20 of them had sufficient data for meta-analyses. Results indicated that patients undergoing capecitabine-based combination therapy had a higher risk of FIC than those with capecitabine monotherapy (pooled RR=1.61, 95% CI=1.01-2.55, I
2
=0%, 95% PI=0.08-31.71). Also, patients with pre-existing cardiac disease (pooled RR=3.01, 95% CI=2.02-4.49, I
2
=42%, 95% PI=1.03-8.78), hypertension (pooled RR=1.52, 95% CI=1.20-1.93, I
2
=0%, 95% PI=1.08-2.13) or smoking habit (pooled RR=2.22, 95% CI=1.03-4.78, I
2
=39%, 95% PI=0.15-32.46) had a significantly higher risk of FIC than their counterparts, while gender and comorbidities including diabetes, hyperlipidemia, and obesity were not significant risk factors of FIC.

Conclusions:
Cancer patients with pre-existing cardiac disease, hypertension, and smoking behavior had a higher risk of FIC when they are undergoing fluoropyrimidine-based treatments. Further research is needed to develop risk assessment tools for a risk prediction of FIC among cancer patients, which could advance risk stratification strategies and improve patient outcomes during the application of fluoropyrimidine-based treatments.
Abstract 15731: Sildenafil Improves Mitochondrial Function in Failing Single Ventricles
Authors: Garcia Anastacia M , Miyano Carissa A , Joschner Raleigh , Stone Matthew , Stauffer Brian L , SUCHAROV Carmen C , Miyamoto Shelley D
Published: May 2021

Introduction:
Heart failure (HF) remains a leading cause of death and indication for transplant in single ventricle congenital heart disease (SV). However, little is known regarding the molecular mechanisms leading to HF in SV. The purpose of this study was to characterize mitochondrial function in the myocardium of failing (SVHF) and non-failing (SVNF) SV patients compared to biventricular NF controls (BVNF). Furthermore, we investigated the effect of ex vivo treatment with the phosphodiesterase-5 inhibitor (PDE5i) sildenafil on mitochondrial function.

Methods:
Freshly explanted ventricular tissue was saponin permeabilized and mitochondrial oxygen consumption was measured sequentially throughout the electron transport system using SUbstrate-Inhibitor-Titration (“SUIT”) protocols and an Oroboros O2k high resolution respirometer. Permeabilized ventricular tissue was treated for 40 min with sildenafil [1μM] prior to measurement of oxygen consumption. A Western blot for PDE5 was performed in isolated mitochondrial proteins from SVHF subjects ± PDE5i.

Results:
Compared to BVNF (n=15) and SVNF (n=6), SVHF (n=8) hearts have decreased function of Complex I and Complex I and II (A, B), and decreased maximal respiration (C), all of which improve with acute ex vivo treatment with sildenafil in SVHF (SVHF+PDE5i, n=6). Importantly, mitochondrial function is impaired in BVNF+PDE5i (n=5) and SVNF+PDE5i hearts (n=5) (A-C, one-way Anova p<0.05). PDE5 protein is expressed in SVHF mitochondria, but expression is not affected by ex vivo PDE5i treatment (D).

Conclusions:
Our results indicate that mitochondrial function is impaired in SVHF, PDE5 protein is expressed in SVHF mitochondria, and PDE5i improves mitochondrial function in SVHF, but may be detrimental to mitochondrial function in SVNF and BVNF. Together these data suggest that mitochondrial PDE5 is a potential therapeutic target, but that indiscriminate use of PDE5i in SV patients may not be advisable.
Abstract 15733: CD34
+
Cell Therapy is Associated With Improved Right Ventricular Function in Heart Failure With Preserved Ejection Fraction
Authors: Frljak Sabina , Poglajen Gregor , Zemljic Gregor , Cerar Andraz , Haddad Francois , VRTOVEC Bojan
Published: May 2021

Introduction:
Right ventricular (RV) dysfunction is an important predictor of adverse prognosis in patients with heart failure with preserved ejection fraction (HFpEF).

Hypothesis:
We sought to investigate the effects of transendocardial CD34
+
cell therapy on RV function in HFpEF patients.

Methods:
We enrolled 30 patients with HFpEF who underwent transendocardial CD34
+
cell transplantation. At baseline, all patients received granulocyte-colony stimulating factor; cells were collected by apheresis and immunomagnetic selection and injected transendocardialy in the left ventricle targeting the areas of local diastolic dysfunction. Patients were followed for 6 months and changes in RV function were assessed by tricuspid annular plane systolic excursion (TAPSE), peak systolic velocity of tricuspid annulus (St), and fractional area change (FAC). Impaired RV function was defined as TAPSE<1.8 cm.

Results:
At baseline, RV function was impaired in 11 (37%, Group A), and preserved in 19 (63%, Group B) of patients. The groups did not differ in age (64±6 years in Group A vs. 61±11 years in Group B, P=0.37), gender (male: 82% vs. 74%, P=0.61), or left ventricular E/e' (17.7±2.3 vs. 17.3±3.4, P=0.74). Patients in Group A had lower LVEF (55.6±5.1% vs. 61.3±6.5% in Group B, P=0.02), and higher NTproBNP levels (1750±1139 pg/ml vs. 1038±658 pg/ml, P=0.05). At 6 months after cell transplantation we found an overall improvement in all parameters of RV function (TAPSE: +0.21±0.37 cm, P=0.01; St: +0.7±2.1 cm/s, P=0.03; FAC: +8.5±1.9%, P=0.02). However, RV function improvement was significant in Group A (TAPSE: +0.43±0.37 cm, P=0.004; St: +1.4±2.3 cm/s; P=0.01; FAC: +9.8±2.0%, P=0.01), but not in Group B (TAPSE: +0.04±0.27 cm, P=0.65; St: +0.4±1.3 cm/s, P=0.32; FAC: +7.1±3.7%, P=0.08). In both groups we found comparable changes in E/e' (-5.1±3.0 in Group A vs. -5.9±3.2 in Group B, P=0.53), LVEF (1.2±5.7% vs. 1.9±6.5%, P=0.45) and NTproBNP (-462±410 pg/ml vs. -390±398 pg/ml, P=0.64) at 6 months after cell transplantation.

Conclusions:
Transendocardial CD34
+
cell therapy appears to be associated with improvement of right ventricular dysfunction in patients with HFpEF.
Abstract 15734: Left Atrial Reservoir Strain as a Novel Prognostic Marker in Biopsy-proven Light-chain Amyloidosis
Authors: Huntjens Peter , Zhang Kathleen , Soyama Yuko , Karmpalioti Maria , Lenihan Daniel , Gorcsan John
Published: May 2021

Introduction:
Light chain cardiac amyloidosis (AL) has a variable but usually poor prognosis. Left ventricular (LV) function measures including LV strain imaging for global longitudinal strain (GLS) have shown clinically prognostic value in AL. However, the utility of novel left atrial (LA) strain imaging and its associations with LV disease remains unclear.

Hypothesis:
LA strain is of additive prognostic value to GLS in AL.

Methods:
We included 99 consecutive patients with AL. Cardiac amyloidosis either confirmed by endocardial biopsy (25%) or by non-cardiac tissue biopsy and imaging data supportive of cardiac amyloidosis. Peak LA reservoir strain was calculated as an average of peak longitudinal strain from apical 2- and 4-chamber views. GLS and apical sparing ratio were assessed using the 3 standard apical views. All-cause mortality was tracked over a median of 5 years.

Results:
Echocardiographic GLS and peak longitudinal LA strain were feasible in 96 (97%) and 86 (87%) of patients, respectively. There were 48 AL patients who died during follow-up. Patients with low GLS (GLS < median; 10.3% absolute values) had worse prognosis than patients with high GLS group (p<0.001). Although peak longitudinal LA strain was correlated with GLS (R=0.65 p<0.001), peak longitudinal LA strain had additive prognostic value. AL patients with low GLS and low Peak LA strain (<13.4%) had a 8.3-fold increase in mortality risk in comparison to patients with high GLS (95% confidence interval: 3.84-18.03; p<0.001). Multivariable analysis showed peak longitudinal LA strain was significantly and independently associated with survival after adjusting for clinical and echocardiographic covariates (p<0.01).

Conclusions:
Peak longitudinal LA strain was additive to LV GLS in predicting prognosis in patients with biopsy confirmed AL amyloidosis. LA strain imaging has potential clinical utility in patients with AL cardiac amyloidosis.
Abstract 15772: Cardiovascular Hospitalizations and Procedures Plummet Nationwide During Covid-19 - an Analysis of US Medical Claims
Authors: Shah Monica R , Partridge Tanya F , Xue Xiaoqing , Gregg Justin L
Published: May 2021

Introduction:
Regional studies have reported a decline in cardiovascular (CV) hospitalizations and procedures with the onset of the coronavirus disease-2019 (COVID-19) pandemic. Factors may include patient reluctance to seek care and de-prioritization of approvals for CV admissions by hospitals. We wanted to assess these observations at a national level.

Hypothesis:
To examine national trends in CV hospitalizations for acute myocardial infarction (AMI), unstable angina (USA), and heart failure (HF), as well as left heart catheterizations (LHC), using US medical claims data.

Methods:
We interrogated IQVIA US Claims data, a verified source, from Jan 2019 to May 2020 (214 million patients; 76% private insurance claims, 19% Medicare claims, 5% Medicaid claims). Since confirmed COVID-19 cases in the US began rising in Mar 2020, this was used as reference point to identify cohorts for comparison. Trends in volumes of hospitalizations for key CV events (AMI, USA, and HF) and LHC were compared from Mar 1 to May 8, 2020 to the equivalent time period in 2019. We used a Bayesian hierarchical model to assess trends.

Results:
From Mar to May 2020, compared to 2019, there were significantly fewer hospitalizations for: key CV events (1,110,492 vs. 1,487,558; p=0.0016); AMI (277,615 vs. 412,235; p=0.0002); USA (1,007 vs. 1,688, p=0.1245); and, HF (831,870 vs. 1,073,635; p=0.0036). There were significantly fewer LHC (118,393 vs. 221,701; p=0.0002). As shown in the Figure, there was a significant decline in CV hospitalizations in 2020 compared to 2019.

Conclusions:
During the COVID-19 pandemic, CV hospitalizations have declined significantly in the US. We observed an ~25% drop in CV hospitalizations and an ~50% drop in LHC. To the best of our knowledge, this is the first national evaluation of trends in CV care during COVID-19 and validate concerns that acute CV care in the US has been delayed or deferred, potentially foreshadowing a surge of CV complications in the future.
Abstract 15783: A Simplified Machine Learning Algorithm for Identification of Patients At-risk for Wild-type Transthyretin Amyloid Cardiomyopathy
Authors: Heitner Stephen B , Masri Ahmad , Elman Miriam R. , Emir Birol , Nolen Kim D. , Schumacher Jennifer , Calambur Veena , Huda Ahsan , Bruno Marianna , Castano Adam
Published: May 2021

Introduction:
Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is a progressive, life-threatening, increasingly recognized but underdiagnosed cause of heart failure (HF). A previously validated machine learning (ML) model trained on medical claims data from 300 million US patients predicted wtATTR-CM among individuals diagnosed with HF with high sensitivity and specificity. Here, we simplified the ML model by reducing the number of predictive variables and tested it in a cohort of patients with confirmed wtATTR-CM at a large academic amyloid referral center.

Methods:
A retrospective, case-control study was conducted using electronic health records (EHR) from a random 1:1 sample of patients diagnosed with wtATTR-CM (cases) and non-amyloid HF (controls) at OHSU (Jul 2005-Nov 2019). Inclusion criteria were age ≥50 years; HF diagnosis (based on ICD-10 codes/SNOMED CT); and ≥1 of the following: ≥12 months of medical history, ≥5 clinical visits, or ≥10 documented diagnosis codes. The original 1,871 variables were systematically reduced to 15 based on recursive feature elimination and clinical relevance to ATTR-CM. After confirmation of the full ML model algorithm performance, the simplified model, validated against Optum EHR, was applied to the OHSU cohort of patients with wtATTR-CM.

Results:
Of 25,233 patients who met study criteria, 38 (0.2%) had wtATTR-CM and were evaluated along with 38 patients with non-amyloid HF. Performance of the simplified ML model was consistent with the previously validated model, with an ROC AUC of 0.812 and 0.804, respectively, and improved at lower thresholds (Table).

Conclusions:
A simplified ML algorithm to estimate the empirical probability of wtATTR-CM in patients with HF performed well at an academic amyloid referral center. This may serve as a practical approach to aid physicians in identifying HF patients who may be at-risk for wtATTR-CM. Additional studies are needed to confirm these findings in larger cohorts.
Abstract 15787: Ventricular Assist Devices May Cause Changes in Implantable Cardioverter Defibrillator Lead Parameters
Authors: Issa Tariq Z , Charron Jessica , Wasserlauf Jeremiah , Howell Soo , Harap Rebecca , Knight Bradley P , Rich Jonathan D , Chicos Alexandru B
Published: May 2021

Introduction:
Ventricular assist devices (VAD) are a primary method of treatment for patients with advanced heart failure. Previous studies have provided some evidence for alterations in ICD lead parameters following VAD implants, but all have had a very small sample size.

Hypothesis:
VAD implantation causes alterations in ICD lead parameters.

Methods:
Electronic medical records of a large patient cohort receiving VAD implants at Northwestern Hospital from 2012-2018 were manually reviewed. When available, high-voltage (HV) impedance, right ventricular (RV) lead pacing impedance, pacing threshold, and sensing amplitude were compared both immediately (I) and late (L), at 6-12 months follow-up after VAD implant, to baseline (B) pre-implant values.

Results:
A total of 271 VAD patient records were reviewed. Long-term, HV impedance changed from 51 ± 16 Ω to 49 ± 15 Ω (N=63, p=0.04), and 29% of patients had a long-term absolute change of at least 10 Ω. RV pacing impedance decreased slightly acutely from 405± 84 to 427 ±78 (N=96, p=.006), but there was no significant change long-term: 443 ± 201 Ω vs 449 ± 94 Ω (N=85, p=0.77). Yet, 19% of patients had a long-term change ≥ 100 Ω. Long-term RV pacing threshold was not significantly changed 1 ± 0.8 V to 1.1 ± 0.7 V (N=47, p=0.5), and all leads were still functional for pacing. RV sensing amplitude decreased acutely from 10.8 ± mV to 8.6 ± 4.3 mV (N=81, p<0.001). Additionally, 17% of patients had a change that was more than 50%, and new R waves below 5 mV were noted in only 13 patients (16%). Long-term RV sensing amplitude decreased from 11.3 ± 5 mV to 8.2 ± 4.3 mV (N=73, P<0.001), and 18 patients had a decrease in R wave of at least 50%.

Conclusions:
In conclusion, our data suggest that VAD implantation in patients with an ICD may result in immediate and long-term ICD parameter changes. For many patients, these changes may be clinically insignificant, but careful monitoring is warranted. The clinical impact of those changes merits further investigation.
Abstract 15792: Etiology, Treatment and Outcomes in Patients With Left Ventricular Thrombus - Experiences From an African Center
Authors: Varwani Mohamed Hasham , Jeilan Mohamed , Shah Jasmit , Ngunga Leonard
Published: May 2021

Introduction:
Left ventricular thrombus (LVT) may lead to thromboembolism and has been associated with increased morbidity and mortality. Little is known about the incidence, etiology and outcomes in patients with LVT in Africa.

Objectives:
To determine the etiology, treatment practices, rate of resolution and outcomes in patients with LVT in the region.

Methods:
A review of all echocardiograms performed in 2017 and 2018 at the Aga Khan University Hospital, Nairobi was carried out and patients with LVT identified. Physician review of charts was performed to document clinical characteristics and outcomes.

Results:
During the study period 100 patients with LVT were identified (1.3% of adult echoes). The mean LVEF was 28.5% (±11.0%) and 88% of the patients had an LVEF of less than 40%. Underlying etiology of LV dysfunction was post MI in 28%, chronic ischemic cardiomyopathy in 42% and non ischemic cardiomyopathy in 30%. In 15% of the patients a stroke or TIA predated the diagnosis of LVT. Long term anticoagulation was given to 92 patients. Among these, 37% received warfarin while 63% were treated with a DOAC (rivaroxaban (50%), dabigatran(7.6%) and apixaban(5.4%)). In 60% of the patients, anticoagulation was continued beyond a year. In patients with reassessment imaging (64%, median time 177 days), complete thrombus resolution was noted in 59.4%. One year follow-up data was available for 85 patients: 13 (15.3%) patients had died, 4 (4.7%) had suffered a stroke, and 8(9.4%) had a bleeding episode. Rates of thrombus resolution, stroke and bleeding were not significantly different among patients treated with warfarin and DOAC (Figure 1).

Conclusions:
We noted a high incidence of LVT compared to contemporary Western series. The majority of our patients were treated with DOACs. There were no significant differences in outcomes between patients treated with a DOAC and those receiving warfarin. Prospective evaluation on the efficacy and safety of DOACs for this indication is needed.
Abstract 15953: Impact of Citizenship on Heart Transplantation Outcomes in the United States
Authors: Levin Allison P , Hanff Thomas C , Zhang Robert S , McLean Rhondalyn C , Wald Joyce W , Atluri Pavan , Acker Michael A , Goldberg Lee R , Birati Edo Y
Published: May 2021

Background:
Non-citizens of the United States face complex social and economic issues, which may impact their post-transplant outcomes compared to US citizens. To this end, we utilized the United Network for Organ Sharing (UNOS) database to examine post-heart transplant (OHT) outcomes, stratified by citizenship status.

Methods:
UNOS was queried to identify OHT recipients from 03/01/12 (start of new schema for citizenship categorization) through 10/18/18 (start of new heart allocation algorithm). Groups for analysis, were as follows: US Citizen, Non-US Citizen/Resident (NC-R) and Non-US Citizen/Non-US Resident (NC-NR). Post-transplant survival and rate of post-transplant rejection were assessed via Kaplan-Meier analysis and tests of proportions.

Results:
Of the 16,211 OHT recipients identified, 15,677 (96.7%) were US citizens and 534 (3.3%) were Non-Citizens. Among Non-Citizens, 430 were NC-R and 104 were NC-NR, representing 2.7% and 0.6% of the total transplants. Notably, NC-NR were younger than either Citizens or NC-R, and had the shortest median time from listing to transplant (NC-R 80 days vs. Citizens 107 days vs. NC-NR 76 days, p=0.001). The proportion of transplants received by non-citizens varied widely by region, ranging from 0.59% in region 8 (6/1018) to 8.31% (84/1011) in region 9. There was no significant difference in post-transplant survival estimates in citizens vs. non-citizens (logrank p = 0.542), nor in the proportion of patients treated for rejection by one year (15.0% vs. 16.1%, p= 0.504)

Conclusion:
Non-US Citizens receive three percent of heart transplants performed in the US each year. Post-heart transplant survival and rate of rejection are similar in US citizens and non-citizens. These data may be relevant in the context of evolving UNOS policies. Additional studies are needed are to further inform organ allocation policy.