bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10726: Cardiac Resynchronization Therapy Response in Cardiac Sarcoidosis
Authors: Shabtaie Samuel A , Lee Justin Z , Desimone Christopher V , Cha Yong-mei , Kapa Suraj , Bois John , Rosenbaum Andrew , Abouezzeddine Omar F , Siontis Konstantinos , Mulpuru Siva K , Deshmukh Abhishek
Published: March 2022

Introduction:
Cardiac Sarcoidosis (CS) is a non-ischemic cardiomyopathy (NICM) characterized by infiltration of non-caseating granulomas involving in the heart with highly variable clinical manifestations. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its effectiveness in patients with CS.

Hypothesis:
We sought to determine if CRT improved cardiac remodeling and reduced hospitalizations in patients with CS.

Methods:
We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at a Mayo Clinic site from 2000-2021. Baseline characteristics, echocardiographic parameters, heart failure hospitalization, and major adverse cardiac events (MACE) were assessed.

Results:
Our cohort was comprised of 55 patients with 61.8% male and a mean age of 58.7 ± 10.9 years. At baseline, 38 (69.1%) patients had isolated CS, while 17 (30.9%) had evidence of CS with extra-cardiac sarcoidosis. The overwhelming majority underwent CRT-D implantation (n=52, 94.5%) with 67.3% of implanted devices upgrades from prior pacemaker or implantable cardioverter defibrillator. At 6 months post-implantation there was no significant different in ejection fraction (34.8 ± 10.9 % vs. 37.7 ± 14.2 %, p = 0.237), left ventricular end systolic diameter (49.1 ± 9.9 mm vs. 45.7 ± 9.9 mm, p = 0.077) or left ventricular end-diastolic diameter (58.5 ± 10.2 mm vs. 57.5 ± 8.1 mm, p = 0.574). Within the first 6 months post-implantation, 5 (9.1%) patients sustained a heart failure hospitalization. At a mean follow up of 4.1 ± 3.7 years, 14 (25.5%) patients experienced a heart failure hospitalization, 11 (20.0%) underwent cardiac transplantation, 1 (1.8%) underwent LVAD implantation and 7 (12.7%) patients died.

Conclusions:
Our findings suggest a poor response to CRT in patients with CS with no significant evidence of reverse remodeling within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.
Abstract 10737: The Impact of Diabetes on Percutaneous Coronary Intervention Outcomes in STEMI Patients: The Asia-Pacific Evaluation of Cardiovascular Therapies (ASPECT) Collaboration
Authors: Wong Mark Y , Yap Jonathan J , Chih Hui Jun , Brennan Angela L , Yan Bryan P , Fong Alan , Beltrame John F , Wijaya Ika P , Nguyen Hoai , Reid Christopher , Yeo Khung Keong K
Published: March 2022

Introduction:
Diabetes is associated with poorer outcomes and increased complication rates in STEMI patients undergoing percutaneous coronary intervention (PCI). Regional variations have been described but data are notably lacking in the Asia-Pacific region.

Aims:
We report the associations of diabetes with clinical characteristics and outcomes in STEMI patients undergoing PCI across the Asia-Pacific.

Methods:
The Asia Pacific Evaluation of Cardiovascular Therapies (ASPECT) collaboration consists of data from the registries of contributing PCI centres across Australia, Hong Kong, Singapore, Malaysia, Indonesia and Vietnam. Clinical characteristics, lesion characteristics, and outcomes were provided for STEMI patients. Key outcomes included overall mortality at 30 days, and major adverse cardiovascular events (MACE; defined as peri-procedural myocardial infarctions, emergency CABG, stent thrombosis, target vessel revascularisation, cerebrovascular events, or death) at 30 days.

Results:
A total of 12,144 STEMI patients (mean(SD) age 59.3(12.3)) were included, of which 3912 (32.2%) had diabetes. Patients with diabetes were likely to be older, have a history of cardiovascular disease and previous acute coronary events (all p<0.05). They were also more likely to present with out-of-hospital cardiac arrest, require mechanical ventricular support and have lower estimated ejection fractions (all p<0.05). With regards to lesion characteristics, diabetic patients had a higher rate of multi-vessel disease, type C ACC-AHA lesions and diffuse lesions >20mm (all p<0.05). After adjustment for demographics, clinical presentation, lesion characteristics and procedural factors, diabetes was significantly associated with increased 30 day mortality (9.6%vs 5.5%, OR 1.70 (95% CI 1.33-2.18)) and 30-day MACE rates (13.3% vs 8.6%, OR 1.68 (95% CI 1.4-2.02)). Further analyses investigated inter-regional variations in this association.

Conclusions:
Diabetes portends poorer clinical outcomes in STEMI patients undergoing PCI in the Asia-Pacific. The development of effective preventative measures and interventional strategies targeted at this high-risk group is crucial.
Abstract 10738: Comparative Outcomes of Sacubitril/Valsartan Use Among Medicare Beneficiaries NaïVe to Renin-angiotensin System Inhibitors and Hospitalized with Heart Failure
Authors: Blumer Vanessa , Choi Sujung , Greene Stephen J , Hardy N. Chantelle , Greiner Melissa A , Carnicelli Anthony , Shen Xian , Lippmann Steven J , Peterson Pamela , Allen Larry A , Fonarow Gregg C , Mentz Robert J , OBrien Emily C
Published: March 2022

Introduction:
Sacubitril/valsartan improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF) compared to ACE inhibitors; however, comparative effectiveness data on post-discharge outcomes in renin-angiotensin system inhibitor (RASi)-naïve patients are limited.

Methods:
We analyzed Medicare beneficiaries age ≥65 years who were hospitalized for HFrEF in the Get With The Guidelines Heart Failure registry between 10/2015 and 6/2019, had Part D prescription coverage, and were not on RASi therapy 6 months prior to hospital admission. We examined associations between sacubitril/valsartan prescription at hospital discharge and outcomes at 30 days and 1 year after discharge using overlap weighted Cox proportional hazards models. The primary endpoint was “home-time”, defined as days alive and out of any healthcare institution. Secondary endpoints included mortality and rehospitalization.

Results:
Among 3,572 patients with HFrEF and naïve to RASi therapy, 290 (8.1%) were prescribed sacubitril/valsartan at hospital discharge. After adjusting for baseline patient characteristics, patients prescribed sacubitril/valsartan had greater home-time (parameter estimate [PEs] 27.0, 95%CI 12.4-41.6, p<0.001) and lower all-cause mortality (HR 0.74, 95%CI 0.6-0.9, p=0.004) compared with patients not on sacubitril/valsartan. Prescription of sacubitril/valsartan was not significantly associated with all-cause (HR 0.87, 95%CI 0.7-1.0, p=0.10) or HF rehospitalization (HR 0.87, 95%CI 0.7-1.1, p=0.19)
(Figure)

Conclusions:
In this contemporary, real-world population of RASi-naïve patients with HFrEF, initiation of sacubitril/valsartan at discharge was associated with greater home-time and improvements in overall survival similar to that seen in randomized trials. These findings support recent expert consensus recommendations endorsing a direct-to-sacubitril/valsartan therapeutic approach among RASi-naïve patients.
Abstract 10740: Improving Diabetes Care Through a Hospital Award Program: Implementation Challenges, Strategies, and Opportunities
Authors: Halio Melody , Harpster Heather , Maynard Susan , Sednew Renee M , Niu Ray , Overton Katherine , Olson Liz , Thomas Kathie , Scharnott Michelle C
Published: March 2022

Background:
Guideline recognition programs are known to drive hospital performance improvement, yet rapid translation of guidelines into practice continues to be a challenge. This analysis identifies guideline implementation challenges and strategies following the introduction of a new guideline recognition program for diabetes care of patients with heart failure and/or stroke.

Methods:
Hospitals participating in American Heart Association’s (AHA) Get With The Guidelines (GWTG)-Stroke and/or GWTG-Heart Failure modules are asked to document adherence to guidelines for diabetes care. Representatives from 21 GWTG-Stroke and GWTG-Heart Failure hospitals were invited to take part in virtual focus groups. Four focus groups with 21 participants were conducted in March 2021. Participants shared their attitudes, strategies, and challenges related to the diabetes recognition program. Transcripts were coded and analyzed for common themes with NVivo 12.

Results:
Participants consistently reported positive attitudes towards national recognition and guideline recognition programs. Improved team-based care, care coordination, and antihyperglycemic medication education were consistently reported as diabetes-guideline implementation opportunities. Standard protocols following diabetes diagnosis varied, as did hospital practices for ensuring adherence to treatment guidelines and complete data documentation.

Conclusion:
These findings demonstrated consistency in both positive attitudes towards recognition and opportunities for improved guideline-implementation. Variability in established diabetes-treatment protocols and strategies for ensuring guideline adherence suggests the need for increased best practice sharing and guideline-implementation support. These results may be used to inform successful implementation of future guideline-based award programs to improve the care of those with diabetes and CVD.
Abstract 10744: Efficacy of Remote Pulmonary Artery Hemodynamic Monitoring in Reducing Heart Failure Readmissions Among Patients with Obstructive Sleep Apnea of Varying Severity
Authors: Oberoi Mansi , Rajpurohit Naveen , Petrasko Marian , Stys Adam , Stys Tom , Vicinsky Deborah , Jonsson Orvar
Published: March 2022

Introduction:
Obstructive sleep apnea (OSA) and heart failure (HF) often co-exist. Remote pulmonary artery (PA) hemodynamic monitoring has shown to decrease HF readmissions. However, there is limited data regarding its efficacy in patients with OSA of varying severity.

Hypothesis:
Outcomes of remote PA hemodynamic monitoring using CardioMEMS device in reducing HF hospitalization in patients with mild [apnea-hypopnea index (AHI)=5-14], moderate (AHI=15-30) and severe OSA (AHI>30).

Methods:
Retrospective data was collected for HF patients who had CardioMEMS device implanted based on FDA indications from April 2015 to August 2020. Number of hospitalizations, emergency department (ED) and HF clinic visits data was collected for 1-year pre and 1-year post-implantation. Mortality data was collected at 1-year post-implantation. Severity of OSA was based on AHI documented in the sleep study. Analysis was done using Kruskal-Wallis test for comparison between OSA groups. Mortality was compared with Pearson’s chi-squared test.

Results:
CardioMEMS device was implanted in 177 patients during the study period. Of this, 108(61%) patients had OSA diagnosed at the time of implantation. Among OSA patients, 52(48%) had severe OSA. There was a statistically significant decrease in overall mean HF admissions from 1.80(± 1.55) to 0.62(± 1.07), 65.6%, p<0.001 and mean HF ED visits from 1.37(± 1.50) to 0.5(± 0.95), 63.5%, p<0.001 in 1-year pre-and post-implantation among all OSA patients. When comparing different OSA groups, there was no statistically significant difference between them in all-cause admissions, HF admissions, ED visits, ED HF visits, and HF clinic visits 1-year pre and post-implantation. No statistically significant difference was observed in mortality.

Conclusions:
PA hemodynamic monitoring using CardioMEMS device had a net benefit in reducing HF admissions and HF ED visits in OSA patients and this benefit remained unchanged across different OSA groups.
Abstract 10746: Left Atrial Strain and the Risk of Arrhythmias on Extended Ambulatory Cardiac Monitoring: The Multi-Ethnic Study of Atherosclerosis
Authors: Huber Matthew , PANDIT Jay A , Jensen Paul , Wiggins Kerri , Patel Ravi B , Freed Benjamin , Bertoni Alain G , Shah Sanjiv J , Heckbert Susan , Floyd James S
Published: March 2022

Introduction:
Abnormalities in left atrial (LA) function can be identified before the development of overt LA structural changes. Little is known about the relationship between LA mechanics and the risk of subclinical atrial and ventricular arrhythmias.

Methods:
1,441 participants of the Multi-Ethnic Study of Atherosclerosis completed speckle-tracking echocardiography and Zio Patch monitoring from 2016-2018 (mean age 73 years, 52% female); participants in atrial fibrillation (AF) during echocardiography or cardiac monitoring were excluded. Absolute values of LA reservoir, booster pump, and conduit strain were measured. We evaluated associations of LA strain measures with atrial arrhythmias (presence of monitor-detected AF, AF burden, frequency of premature atrial contractions [PACs], frequency of supraventricular tachycardia [SVT] runs) and with ventricular arrhythmias (frequency of premature ventricular contractions, presence of non-sustained ventricular tachycardia [NSVT], frequency of NSVT runs). Primary analyses adjusted for demographic variables, blood pressure, smoking, diabetes, and clinical cardiovascular disease (4%).

Results:
Cardiac monitoring (median 14 days) detected AF in 3%. Each standard deviation (5.4%) lower (worse) LA reservoir strain was associated with a 64% higher risk of monitor-detected AF (95% CI 16-137%), 33% higher PAC frequency (95% CI 22-46%), and 15% higher SVT frequency (95% CI 7-24%). Adjustment for kidney function, NT-proBNP, LA volume, and LV ejection fraction and global longitudinal strain had little impact on associations. Findings were similar for LA booster pump strain and null for LA conduit strain (Figure). Associations of LA reservoir and booster pump strain with ventricular arrhythmias were completely attenuated after adjustment for LV function.

Conclusions:
In a multi-ethnic community-based cohort, abnormal LA mechanics may be an important risk factor for subclinical atrial arrhythmias.
Abstract 10747: Genetic Enhancement of Epicardial Paracrine Signalling for Cardiac Regeneration
Authors: Brito Liliana , Mylonaki Ioanna , Grigsby Christopher L , Seong Hyejeong , Higgins Stuart G , Smart Nicola , Noseda Michela , Rosenthal Nadia , Harding Sian , Stevens Molly
Published: March 2022

After myocardial infarction (MI), paracrine signalling has been shown to contribute to heart regeneration. The epicardium, as an important signalling centre, is crucial for heart development and it is re-activated after MI, indicating its involvement in the response to injury. This project aims to accomplish
in situ
transfection of the epicardium to stimulate the overexpression of growth factors that will enhance regenerative signalling pathways after MI, with cardiomyocyte proliferation as the primary target. Selective epicardial transfection can potentially be achieved via a surface-mediated delivery. Therefore, we developed a novel transfection approach consisting of the deposition of bioreducible cationic polymeric polyplexes onto flat and nanostructured silicon surfaces by freeze-drying. Recombinant growth factors (rGF) were used in single and combinatorial proliferation assays to select for genes to be delivered to the epicardium. The proliferative effects were assessed on cardiomyocytes, cardiac mesenchymal stromal cells, endothelial cells and cardiac fibroblasts via high-content image analysis. Neuregulin-1 led consistently to higher S-phase proliferation marker in IMR90- and H7-derived cardiomyocytes and higher cardiomyocyte cell numbers (fold increase 1.28 ± 0.12), quantified by flow cytometry. Hepatocyte Growth Factor induced proliferation of cardiac mesenchymal stromal cells (fold increase 2.75 ± 0.31) and angiogenesis (fold increase 1.47 ± 0.34). Follistatin-like 1, from animal and bacterial sources, was also tested but no proliferative effect was detected. The relevant rGF for each cell type maintained its positive effect in combination with other rGFs. Furthermore, preliminary results from
in vitro
transfection of epicardial cells with these GF genes indicate the proliferative advantage of enriched epicardial paracrine signalling over the incubation of cardiac cells with the rGF
.
This study remains to be a first-in-field potential material-based gene delivery strategy specific to the epicardium that explores a combinatorial treatment via the delivery of more than one gene for induction of cardiomyocyte proliferation and other regenerative mechanisms for MI treatment.
Abstract 10749: A Prospective Study of Health-Related Quality of Life Outcomes in Thoracic Aortopathy Patients
Authors: Zheng Wynne , Xu Samantha , Szpakowski Natalie M , Bittel Barbara , Ospina Susan , Kalahasti Vidyasagar , ROSELLI Eric E , Svensson Lars G , Frank Scott , Desai Milind Y
Published: March 2022

Introduction:
Health-related quality of life (QOL) outcomes in thoracic aortopathy (TA) patients who have not yet met the surgical threshold, but need significant lifestyle/weightlifting restrictions, are not well understood. We prospectively studied a newly developed QOL instrument to examine the associations between patient characteristics and self-reported QOL scores in TAA patients not anticipated to undergo aortic intervention for at least 6 months.

Methods:
All 128 adult TA patients (57±10 years, mean thoracic aortic diameter = 4.4±0.3cm, 77% male) were recruited prospectively as a single center and completed a baseline QOL instrument. The 70-item QOL instrument was adapted from validated QOL questionnaires. All patients signed informed consent.

Results:
Mean QOL scores for the eight scales of the instrument (range, 0 to 5, with 5 reflecting best function/QOL) were self-reported and as follows: physical function (4.2±0.8), depression (3.9±0.8), anxiety (3.8±0.9), post-traumatic stress disorder (PTSD) (4.1±0.9), social function (4.4±0.6), spiritual acceptance of diagnosis (3.6±0.7), self-efficacy (4.2±0.7), and resilience (4.1±0.6). Higher physical function score was associated with higher emotional (β=0.67, p<0.001) and social function (β=0.52, p<0.001) scores. Higher physical function (β=0.535), less depression (β=0.47), less anxiety (β=0.45), less PTSD (β =0.43), and higher social function (β=0.281) scores were all significant predictors of higher perceived overall health (all p<0.001). The degree of TA dilatations had no significant association with lower social function (β=-0.89, p=0.65), lower self-efficacy (β=-2.73, p=0.21), or lower resilience.

Conclusion:
In TA patients not requiring aortic surgery, higher physical, emotional, and social function scores were significantly associated with self-perceived overall health. However, the actual size had no significant association with these metrics. Further research is needed to elucidate trends of patient-reported QOL and their correlation to clinical/imaging changes.
Abstract 10752: Clinical Predictive Models for Cardiovascular Disease Should Adjust for Race, Ethnicity and Social Determinants of Health to Inform More Equitable Interventions: Findings from a Targeted Review
Authors: Snowdon Jane L , Scheufele Elisabeth L , Pritts Jill , Le Phuong-Tu , Zhang Xinzhi , Dankwa-Mullan Irene
Published: March 2022

Introduction:
Clinical models of cardiovascular disease (CVD) that incorporate relevant predictors can provide powerful insights into the complex, inter-related mechanisms of CVD pathophysiology, risk for adverse outcomes, and correlations with social determinants of health (SDoH) to inform practice guidelines and targeted interventions. Despite the growing body of evidence demonstrating the role of race, ethnicity and SDoH on CVD outcomes, limited evidence exists about incorporating these factors into models.

Hypothesis:
We assessed the hypotheses that clinical predictive studies on CVD risk, outcomes, prognosis and treatment interventions: (1) do not fully examine race, ethnicity and SDoH factors, and (2) may not leverage adequate data sources fully representative of a population of interest or may lack the decisional context to ensure robustness. These are critical limitations that could lead to inaccurate predictions, perpetuating bias and ultimately health and racial inequities.

Methods:
This targeted literature review yielded 533 potentially relevant PubMed articles (2018-2019) after duplicate removal. Article titles and abstracts were reviewed for eligibility where 375 met the exclusion criteria (age <18 years old, outside North America, no clinical outcomes, language non-English) and were removed. The remaining 158 potentially relevant articles were screened and 116 met the criteria for exclusion (e.g. stroke, heart transplant). After screening, 42 citations were identified for full-text screening, of which 35 articles met criteria for inclusion.

Results:
Studies employed advanced statistical and machine learning methods to predict CVD risk (10/29%), mortality (19/54%), survival (7/20%), complication (10/29%), disease progression (6/17%), functional outcomes (4/11%) and disposition (2/6%). Most studies incorporated sex (34/97%), co-morbid conditions (32/91%), and behavioral risk factor (28/80%) variables. Race/ethnicity (23/66%) and SDoH variables (e.g. education (3/9%)) were less frequently observed.

Conclusions:
In conclusion, clinical risk and predictive models often do not adjust for or consider race, ethnicity and SDoH to improve model accuracy to inform more equitable interventions and decision-making.
Abstract 10754: Disrupted N-Cadherin Expression Leads to Sarcomeric Disassembly and Cell Cycle Activation in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Lee Soah , Lee Daniel , Ryan Julia , Paige Sharon , Galdos Francisco X , Goodyer William R , Wu Sean M
Published: March 2022

Introduction:
Induction of cardiomyocyte proliferation holds great promise for cardiac regenerative therapy. We showed previously that in the presence of Wnt signaling agonist, the removal of cell-cell contact between cardiomyocytes is the key to drive massive expansion of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). However, the molecular mechanism regulating cell contact-mediated suppression of hiPSC-CM proliferation remains unknown.

Hypothesis:
We hypothesized that N-cadherin, the major adherens junction molecule expressed in cardiomyocytes, mediates contact inhibition of hiPSC-CM proliferation.

Methods/Results:
By qPCR and Western blotting, we showed comparable transcript and protein expression level of N-cadherin when hiPSC-CMs were cultured either densely (with cell contact) or sparsely (without cell contact), despite the observed N-cadherin localization at intercellular junction in densely cultured cells only. We disrupted N-cadherin expression with transient transfection of siRNA and found that the loss of N-cadherin expression resulted in 1.75-fold increase in Ki67 expression in densely but not sparsely cultured day 30 hiPSC-CM, suggesting that junction-localized N-cadherin may affect hiPSC-CM proliferation. Furthermore, we found that the loss of N-cadherin expression led to wide-spread sarcomeric disassembly. To examine whether sarcomeric disassembly alone is sufficient to stimulate cell cycle activity in densely cultured hiPSC-CMs, we knocked down α-actinin expression which led to sarcomere disruption and an increase in Ki67+ expression by 1.6-fold in day 30 hiPSC-CMs.

Conclusions:
Taken together, our results suggest that N-cadherin mediates the previously observed cell-cell contact inhibition of hiPSC-CM proliferation and the disruption of N-cadherin expression in densely cultured hiPSC-CMs leads to sarcomeric disassembly and hiPSC-CM proliferation. Furthermore, we showed that sarcomeric disassembly alone stimulates hiPSC-CM proliferation. These findings support the need for inducing cardiomyocyte dedifferentiation to achieve
in situ
cardiomyocyte proliferation for developing novel regenerative therapy to treat congenital and adult heart diseases in the future.
Abstract 10755: Network Meta-Analysis of Randomized Controlled Trials of Eicosapentaenoic Acid for Cardiovascular Events Reduction
Authors: Yokoyama Yujiro , Kuno Toshiki , Morita Sae , Takagi Hisato , Briasoulis Alexandros , Latib Azeem , Heffron Sean , Bangalore Sripal
Published: March 2022

Background:
Randomized clinical trials (RCTs) investigating the impact of omega-3-fatty acid supplementation on cardiovascular events have largely shown no benefit. A recent RCT suggested benefit from an eicosapentaenoic acid (EPA)-only supplement. However, there is debate about the benign nature of the placebo in this trial.

Methods:
MEDLINE and EMBASE were searched through May, 2021 to identify RCTs that investigated cardiovascular outcomes with omega-3-fatty acid formulations (EPA, decosahexanoic acid (DHA) or the combination) versus placebo or standard care of controls. Outcomes of interest were cardiovascular death, myocardial infarction, stroke, coronary revascularization, and all-cause death.

Results:
Our analysis included 17 RCTs that enrolled a total of 141,009 patients randomized to EPA (n =13,655), EPA+DHA (n =56,908), mineral oil placebo (n =5,338), corn oil placebo (n =8,876), olive oil placebo (n =41,009) and controls (no placebo oil; n =15,223). Rates of cardiovascular death, myocardial infarction and stroke were significantly lower in those receiving EPA compared to those receiving mineral oil, but were not different from rates in those receiving other oils or standard of care controls. Rates of coronary revascularization were significantly lower in those receiving EPA than in those receiving either EPA+DHA, mineral oil, corn oil, or olive oil placebo, but not standard of care controls. All-cause death was similar among all groups.

Conclusion:
Our analyses demonstrate that although EPA supplementation lowers risk of coronary revascularization more than other oils, there is no benefit relative to standard of care. Further, EPA reduces the risk of cardiovascular events only in comparison to mineral oil and not when compared with other placebo oils or to standard of care. Any benefit of EPA-only supplementation in improving cardiovascular outcomes is not currently generalizable outside of select studies incorporating mineral oil placebo.
Abstract 10757: Patient-Reported Quality of Life Outcomes in Hypertrophic Cardiomyopathy Patients
Authors: Xu Samantha , Zheng Wynne , Szpakowski Natalie M , Bittel Barbara , Ospina Susan , Smedira Nicholas G , Lever Harry M , Popovic Zoran B , Frank Scott , Desai Milind Y
Published: March 2022

Background:
Few studies have systematically assessed quality of life (QOL) in hypertrophic cardiomyopathy (HCM) patients not meeting the septal reduction therapy (SRT) threshold, but require avoiding isometric exertion and weightlifting. We prospectively studied a newly developed QOL instrument to examine the associations between patient characteristics and self-reported QOL scores in HCM patients not anticipated to undergo SRT for at least 6 months.

Methods:
A single-center, prospective sample of 51 adult HCM patients (54±14 years, mean interventricular septum thickness = 1.7±0.4cm, 65% with left ventricular outflow tract (LVOT) obstruction, mean provokable LVOT gradient 65±42 mmHg, 59% men) completed a baseline 70-item QOL instrument, adapted from validated QOL questionnaires. All patients signed informed consent.

Results:
Mean self-reported QOL scores (on a 5-point Likert scale with higher scores indicating higher QOL) were as follows: physical function (3.5±1), depression (3.7±1), anxiety (3.6±1), post-traumatic stress disorder (PTSD) (3.7±1), social function (4.1±1), spiritual acceptance of diagnosis (3.8±1), self-efficacy (4±1), and resilience (4±1). Men vs. women reported higher physical function (3.9±1 vs. 2.9±1), less depression (4±1 vs. 3.3±1), less anxiety (3.8±1 vs. 3.3±1), and higher social function (4.3±0.7 vs. 3.8±1) (all p<0.05). Patients with obstructive HCM reported lower physical function scores (3.3±0.8) vs. non-obstructive HCM (3.8±0.8), p=0.03. Symptomatic patients reported lower physical function (3.2±0.8 vs. 4.3±0.5), social function (3.8±0.8 vs. 4.5±0.6) and worse depression (3.5±0.7 vs. 4.3±0.6), anxiety (3.4±0.8 vs. 4.1±0.7) and PTSD (3.5±0.8 vs. 4.3±0.9) scores (all p<0.01). Presence of an implantable cardioverter defibrillator (ICD) was associated with lower vs. higher physical (2.9±0.4 vs. 3.5±1) and social function (3.6±1 vs. 4.1±1) (all p<0.05).

Conclusion:
In HCM patients not requiring SRT, higher physical function scores were significantly associated with a better self-perceived overall health. Being a woman, having LVOT obstruction, presence of a defibrillator and presence of symptoms was significantly associated with worse perceived physical and social function.
Abstract 10760: Prophylactic versus Therapeutic Anticoagulation for Survival of Patients with Covid-19 on Steroid and Remdesivir
Authors: Kuno Toshiki , So Matsuo , Takahashi Mai , Egorova Natalia
Published: March 2022

Introduction:
Previous observational and randomized studies suggested potential benefit of therapeutic anticoagulation during hospitalization, but this treatment remains controversial

Objective:
We aimed to investigate the association of prophylactic and therapeutic anticoagulation with mortality for patients with COVID-19 who were treated with steroids and Remdesivir, which is the current standard treatments.

Methods:
This retrospective study was conducted by review of the electronic medical records for 9,565 patients with laboratory confirmed COVID-19 hospitalized in the Mount Sinai Health system between March 1
st
2020 and March 30
th
2021. The primary outcome of interest was the in-hospital mortality. Acute kidney injury was defined as any increase of creatinine by more than 0.3mg/dL or to more than 1.5 times baseline. A propensity score analysis (matching and weighting by inverse probability treatment weights) and multiple imputation was performed.

Results:
Of the 1,443 patients, 420 (29.1%) had therapeutic anticoagulation therapy. The 1,023 (70.9%) patients with prophylactic anticoagulation were older and had more comorbidities. After matching by propensity score (N=334 in each group), in-hospital mortality was not significantly different between patients with therapeutic anticoagulation and those with prophylactic anticoagulation (26.9% vs. 22.8%, P=0.24). Furthermore, IPTW and multiple imputation for missing data did not change the result (therapeutic versus prophylactic; odds ratio [95% confidential interval]: 1.14 [0.83-1.59], P=0.40]; 1.20 [0.84-1.73], P=0.31, respectively). Interestingly, patients with therapeutic anticoagulation had higher rate of acute kidney injury as compared to patients with prophylactic anticoagulation (26.6% vs. 16.8%, P=0.003).

Conclusions:
In conclusion, prophylactic versus therapeutic anticoagulation showed similar in-hospital mortality of COVID-19 patients treated with steroids and remdesivir, but therapeutic anticoagulation increased the risk of acute kidney injury compared to prophylactic anticoagulation.
Abstract 10766: Sovateltide Induces Neuroprotection in a Neonatal Rat Model of Hypoxic Ischemic Encephalopathy
Authors: Briyal Seema , Davis Ramos Michelle , Hurrell Sarah , Prazad Preetha , Gulati Anil
Published: March 2022

Introduction:
Hypoxic-ischemic encephalopathy(HIE) is a major cause of morbidity, mortality, and severe neurodevelopmental disability in term neonates. The development of a treatment strategy that could provide neuroprotection is still required. We have shown that agonism of endothelin B(ETB) receptors mediated through sovateltide provides neuroprotection and enhances neurovascular remodeling in several neuropathological conditions.

Hypothesis:
We hypothesize that administering sovateltide alone or as an adjuvant therapy with hypothermia could provide neuroprotection by reducing oxidative stress and promoting cell survival post-HIE brain injury.

Methods:
Sprague-Dawley male and female rat pups were grouped separately and were divided into 5 different subgroups (1) Control; (2) HIE+Vehicle; (3) HIE+Hypothermia; (4) HIE+sovateltide; and (5) HIE+sovateltide+hypothermia. HIE was induced by ligating the right carotid artery on a postnatal day (PND) 7, followed by hypoxia for 120 min and hypothermia (32-34°C) for 5 h. On PND 7, sovateltide (5 μg/kg, ICV) was injected after hypoxic-ischemic injury. Pups were euthanized on PND 10. Brains were isolated, and ETB receptors, VEGF, NGF, cell death and oxidative stress makers - malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were assessed.

Results:
Animals receiving sovateltide showed a significant (p<0.0001) upregulation of ETB receptor (135%), VEGF (110%), and NGF (183%) expression in the brain compared to vehicle. Vehicle-treated animals had high oxidative stress levels, as indicated by increased lipid peroxidation, MDA, and decreased antioxidants, SOD, and GSH compared to control. These effects were reversed (p<0.001) in sovateltide alone or in combination with the hypothermia, indicating reduced oxidative stress in these animals. Additionally, sovateltide alone or in combination with hypothermia reduced (p<0.001) cell death compared to vehicle or hypothermia alone. Similar findings were obtained in both male and female rats.

Conclusion:
Sovateltide alone or as an adjunct to hypothermia exerts neuroprotective effects in HIE-induced brain injury in rat pups, suggesting sovateltide could be a potential therapeutic agent for neonatal HIE.
Abstract 10770: Trans-Ancestry Multivariate Genome-Wide Analysis Highlights the Role of Common Genetic Variation in Cardiac Structure, Function, and Heart Failure-Related Traits
Authors: Levin Michael , Tsao Noah , Bellomo Tiffany , Bone William P , Judy Renae , Burke Megan , Morley Michael , Yang Yifan , Day Sharlene , Arany Zoltan , Ellinor Patrick T , Cappola Thomas P , Margulies Kenneth B , Voight Benjamin F , Damrauer Scott
Published: March 2022

Introduction:
The contribution of common genetic variation to heart failure (HF) risk has not been fully elucidated. Here, we applied multi-ancestry and multivariate methods to summary genetic data from >1 million individuals to improve power to identify common genetic variants, genes, cells, tissues, and circulating proteins/metabolites associated with HF and related cardiac imaging traits.

Methods:
Trans-ancestry meta-analysis of HF (56,722 cases and 1,133,054 controls) was performed using METAL. Multivariate analysis including GWAS of HF and imaging traits (MRI and echocardiogram) was performed using N-GWAMA. Downstream transcriptome-wide association studies (TWAS; S-PrediXcan), tissue/cell enrichment (LDSC-SEG using RNAseq and snRNAseq of human left ventricle samples from the MAGnet consortium), and Mendelian randomization (MR) analyses were performed.

Results:
The multi-ancestry HF GWAS identified 15 loci associated with all-cause HF (p < 5 x 10
-8
). Multivariate analysis identified 48 (16 novel) loci (p < 5 x 10
-8
), with enrichment for loci near Mendelian cardiomyopathy genes (p < 1 x 10
-4
). Genetic associations were enriched (FDR < 0.05) for cardiac and musculoskeletal gene expression and chromatin marks. Gene expression (p = 0.007) and splicing events (p = 0.01) were enriched for established cardiomyopathy genes. Branch chain amino acid dehydrogenase (
BCKDHA
) expression was prioritized in TWAS, and MR identified causal associations between circulating branch chain amino acids and cardiac imaging traits: LVEDV
MRI
(leucine β = -0.137, 95% CI -0.25 to -0.022, p = 0.02; isoleucine β = -0.276, 95% CI -0.38 to -0.17, p = 3 x 10
-7
) and LVSEV
MRI
(leucine β = -.131, 95% CI -0.24 to -0.026, p = 0.01; isoleucine β = -0.217, 95% CI -0.33 to -0.11, p = 1 x 10
-4
). Unbiased proteome-wide MR of 725 circulating proteins identified 18 significant (FDR < 0.05) causal protein-trait associations, including between lipoprotein(a) and HF (OR 1.09 per 1-SD increase in lipoprotein(a), 95% CI 1.06 to 1.11, p = 1.6 x 10
-11
).

Conclusion:
These analyses implicate novel common genetic variation in the pathogenesis of HF, highlight Mendelian cardiomyopathy genes in common HF, and identify circulating metabolites and proteins that may represent new treatment targets.
Abstract 10771: Avoidance of Lethal Isotherm Formation in Esophageal Tissue with an Active Cooling Device Under High-Power, Short-Duration Ablation
Authors: Mercado Montoya Marcela , Berjano Enrique , Mickelsen Steven R , Daniels James D , Gomez-Bustamante Tatiana , Hernandez-Arango Pablo , Kulstad Erik
Published: March 2022

Introduction:
Atrioesophageal fistula (AEF) is a severe complication of left atrial ablation for the treatment of atrial fibrillation. Thermal injury is the proposed mechanism, and a potential pathway occurs through exceeding the lethal isotherm of esophageal tissue in contact with the left atrial posterior wall. Active cooling with a novel cooling device has been shown to significantly reduce thermal injury, with no AEFs encountered after more than 4200 treatments worldwide. We aimed to evaluate the effects of active cooling when specifically using newer high-power short-duration (HPSD) ablation settings to further estimate the protective mechanisms of this novel approach to reduce serious injury.

Hypothesis:
Active cooling may preclude attainment of a lethal isotherm in esophageal tissue under HPSD ablation.

Methods:
We developed a model of the left atrium and esophagus, and simulated radiofrequency (RF) ablation of the left atrium under HPSD settings. Tissue thickness was set to typical posterior-wall parameters (Figure). Power settings were evaluated at 50 W for 10 seconds, and 90 W for 4 seconds. Active cooling was set to a typical 4 °C coolant temperature. Lethal isotherm temperature was taken as 50 °C.

Results:
In both scenarios of HPSD ablation, the peak esophageal mucosal temperature reached 39° C in control conditions, using no active cooling. With active cooling in place, peak temperatures remained below 11 °C (Figure). Peak temperatures at the epi-esophageal region of esophageal tissue exceeded the lethal isotherm of 50 °C in control conditions, but remained at or below the lethal isotherm with active cooling in place.

Conclusions:
Based on our mathematical modeling, esophageal cooling significantly reduced temperature rise and prevented the achievement of temperatures thought to be lethal to esophageal tissue. This finding may offer a mechanistic rationale for the absence of serious esophageal injury encountered to date using this approach.
Abstract 10776: Market-Level Variation in Utilization of Percutaneous Ventricular Assist Devices Utilization in the United States
Authors: Bjarnason Thorarinn Arni A , Sarrazin Mary , Gao Yubo , Girotra Saket
Published: March 2022

Introduction:
Percutaneous ventricular assist devices (PVAD) have begun to replace intra-aortic balloon pumps (IABP) for hemodynamic support during high-risk percutaneous coronary intervention (PCI) procedures even though data on effectiveness of PVAD compared to IABP for hard clinical endpoints remains limited. We examined variation in utilization of PVADs during PCI across U.S. markets and identify factors associated with PVAD utilization.

Methods:
Using 2013-2017 MEDPAR data, we identified all patients aged 65 years or older who underwent PCI with placement of either a PVAD or an IABP on the same date as the PCI procedure. The primary outcome was 30-day mortality. We used hospital referral region (HRR) to define regional healthcare markets with geographic contiguity. We examined variation in utilization of PVADs across HRRs and examined patient- and market-level characteristics across HRR quartiles of PVAD utilization. Using multilevel models, we examined the association of market-level factors with utilization of PVADs and whether higher utilization of PVADs was associated with lower risk of 30-day mortality at a market-level.

Results:
A total of 52,755 patients underwent inpatient PCI with either an IABP (36,260 [68.7%]) or PVAD (16,495 [31.3%]). There was a significant increase in the proportion of PCI procedures with PVAD (17% in 2013 to 46% in 2017), with a corresponding decrease in IABP (83% to 54%; P<.0001 for both). There was large variation in PVAD utilization across markets (0% to 84%), which persisted even after adjustment for differences in patient characteristics (adjusted median OR of 2.19; 95% CI: 2.03-2.35). Markets in the highest quartile of PVAD utilization were larger with a higher number of hospitals and had more market-level competition compared to markets in the lowest quartile of PVAD utilization. Greater utilization of PVAD at the market-level was not associated with lower risk-adjusted 30-day mortality.

Conclusions:
Utilization of PVADs for PCI in the U.S. continues to increase with marked variation in PVAD use across U.S. healthcare markets. Although patient- and market-level factors were associated with use of PVADs at the market-level, greater market utilization of PVADs was not associated with lower 30-day mortality.
Abstract 10780: Uptake of Direct Oral Anticoagulants in Older Adults with Atrial Fibrillation in 2010-2018
Authors: Ko Darae , Lin Joshua K , Najafzadeh Mehdi , Cheng Susan , Kim Erin , Bessette Lily G , Walkey Allan J , Kim Dae Hyun
Published: March 2022

Introduction:
Under-treatment with oral anticoagulants (OAC) in atrial fibrilliation (AF) is a persistent management gap, particularly in older adults. Understanding patterns of OAC adoption may enable design of implementation strategies to improve evidence-based care.

Objectives:
Determine changes in OAC use and overall uptake of direct oral anticoagulants (DOACs) in older adults.

Methods:
We analyzed administrative claims data (years 2010 to 2018) from Optum Clinformatics Data Mart to identify Medicare Advance Plan beneficiaries (aged ≥65) with AF and CHA
2
DS
2
-VASc score ≥2. We excluded patients with history of intracranial hemorrhage and end-stage renal disease. We calculated the proportion of patients prescribed a DOAC, warfarin, or no OAC each year. We examined uptake by patient subgroups, including those with dementia diagnoses and those with frailty, defined by a claims-based frailty index.

Results:
Our sample size ranged from 123,700 in 2010 to 398,385 in 2018. The mean age ranged 76-79 years and the proportion of women ranged 50-53%. The proportion of eligible patients receiving OAC increased from 50.9% to 53.8% for the total sample (+2.9%) (Figure A). This increase was greater for younger patients (65-79 years: 53.7% to 58.1% vs ≥80 years: 48.9 to 49.5%) (Figures B & C), those with dementia (dementia: 39.6% to 44.8% vs no dementia: 52.5% to 55.3%) (Figures D & E), and those with frailty (frailty: 48.1% to 52.1% vs no frailty: 53.4% to 55.3%) (Figures F & G). There was a consistent decreasing trend in warfarin use in all subgroups from 2010 to 2018 (51 to 19 % in the total population, Figures A-G).

Conclusion:
Following the advent of DOACs, overall OAC use modestly increased in older adults, including for those with dementia and frailty. A large proportion of patients with guidelines-based eligibility for OAC remain untreated. Implementation strategies for improving OAC use are needed, particularly for high-risk older patients who stand to benefit the most.
Abstract 10784: Circulating Obesity Associated Pro-Fibrotic Protein Promotes Fibrosis in Liver and Heart
Authors: Hsiao Yung-ting , Shimizu Ippei , Yoshida Yohko , Katsuumi Goro , Minamino Tohru
Published: March 2022

Introduction:
Non-alcoholic steatohepatitis (NASH), driven by the obesity epidemic, has become the most common form of liver disease. Obesity contributes inflamed visceral adipose tissue secretes pro-inflammatory adipokines that is causal for systemic metabolic disorders. Despite its importance, the mechanism of NASH in the presence of morbid obesity related adipokines from BAT remains unclear.

Hypothesis:
Various kinds of white adipokines are known in obesity. However, brown adipokines still remain to be explored.

Methods:
To identify the function of obesity associated pro-fibrotic protein (OAFP), we generated a murine obese NASH model by imposing a high fat diet in C57BL6/NCr mice, and murine systemic OAFP knockout (KO) model. We also conducted functional
in vitro
studies with differentiated brown adipocytes.

Results:
Analyzing two sets of DNA microarray data with bioinformatics, we identified a secreted form OAFP expressed in dysfunctional brown adipose tissue (BAT) in mice. Testing our biobank samples, we found this protein increased in plasma of NASH patients or aged individuals. We generated a murine obese NASH model by imposing a high fat diet in C57BL6/NCr mice, and found that OAFP is produced predominantly by BAT. In this model, we also found that OAFP increased in plasma. For this reason, we generated a murine systemic OAFP knockout (KO) model and found that liver fibrosis ameliorated in OAFP-KO model. In addition, vaccination therapy also inhibited liver fibrosis. In contrast, liver fibrosis augmented in OAFP gain of function (GOF) model, and these results suggested that OAFP has causal role for the progression of fibrotic response in liver. In the obese NASH model, we found that cardiac fibrosis also developed and this ameliorated in OAFP-KO model, indicating that OAFP may have pathological roles for heart failure with preserved ejection fraction (HFpEF) related with age-related disorders. In vitro studies with differentiated brown adipocytes showed that OAFP was upregulated through by PERK/JNK/c-fos/AP1 pathways.

Conclusions:
Our results suggest that OAFP contributes for the progression of fibrotic responses in obese or aged models. Inhibition of OAFP may become a therapy for NASH or HFpEF.
Abstract 10785: Cardiac Magnetic Resonance Imaging and Optical Coherence Tomography in Patients with a Clinical Diagnosis of Myocardial Infarction with Non-Obstructive Coronary Arteries - A Systematic Review and Meta-Analysis
Authors: Machanahalli Balakrishna Akshay , Ismayl Mahmoud , Thandra Abhishek , Ganesan Vaishnavi , Walters Ryan , Aboeata Ahmed S
Published: March 2022

Background:
Myocardial Infarction with Non-Obstructive Coronary arteries (MINOCA) is defined as acute Myocardial Infarction (MI) despite the absence of severe coronary artery stenosis on angiography (i.e., stenosis severity <50%) and no specific alternative diagnosis (e.g., sepsis, pulmonary embolism). MINOCA remains a serious diagnostic and therapeutic challenge given the various possible underlying etiologies. Cardiac Magnetic Resonance Imaging (CMR) can distinguish between acute myocarditis (AM), MI, and Takotsubo cardiomyopathy (TCM) which are some of the commonest causes of MINOCA. Hence, The European Society of Cardiology (ESC) recommend CMR in all MINOCA patients with an unclear etiology. Intracoronary Optical coherence tomography (OCT) is a high-resolution imaging modality that allows for assessment of the integrity of the atheroma. We aimed to study the efficacy of CMR and OCT in detecting the etiology in MINOCA patients, which has the potential to guide medical therapy.

Methods:
A systematic search was made in PubMed, Medline and Cochrane database. Search terms used: Myocardial infarction, Coronary angiography, Normal coronary arteries, CMR, and OCT. Inclusion criteria was fulfilled by 18 studies. Meta-analysis and meta-regression was performed with 14 studies due to increased heterogeneity.

Results:
A total of 2474 patients were included in the meta-analysis. The mean age of all the patients was 51.5 and 56.4% were men. CMR was able to establish diagnosis in 74% of the patients; 30.4% had AM, 21.3% had true MI and 12% had TCM. Upon meta-regression the demographic variables, cardiovascular risk factors, troponin levels and C-reactive protein levels did not have any association with AM or MI. Incorporation of OCT with CMR was better at finding the etiology than either modalities individually.

Conclusion:
CMR is integral in finding the cause of MINOCA. Coupling coronary OCT and CMR is better than either techniques alone at identifying the etiology.