bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11071: Increased Circulating Raas Activity is Related to Functionally Significant Coronary Artery Disease as Defined by Ffr and [
15
O]h2o Pet Perfusion as Well as Vulnerable Plaque Characteristics on CT Angiography
Authors: Jukema Ruurt , de Winter Ruben , van Diemen Pepijn , Driessen Roel , Danser Jan H , Garrelds Ingrid , Raijmakers Pieter , van de Ven Peter , Knaapen Paul , Danad Ibrahim , De Waard Guus
Published: March 2022

Introduction:
Renin-angiotensin-aldosterone-system (RAAS) activity has been linked to coronary artery disease (CAD) and coronary microvascular dysfunction (CMD), opening potential frontiers for treatment. In this study we investigated if increased RAAS activation is related to CAD, high risk plaque (HRP), myocardial perfusion, and CMD in chest pain patients.

Methods:
Renin as a measure for RAAS activation, was quantified by immunoradiometric assay in 205 patients (64% men; age 58 ± 9 years) with suspected CAD. Patients underwent 256-slice coronary CT angiography for (quantitative) plaque analysis and coronary artery calcium (CAC) scoring, [
15
O]H2O PET perfusion imaging and invasive FFR measurements in all coronary arteries. A total of 585 vessels were stratified upon four categories based on [
15
O]H2O PET perfusion and invasive pressure measurements. Vessels with a FFR >0.80 but with an ischemic hyperemic MBF below 2.3 ml/min/g were defined as CMD.

Results:
In univariable analysis, renin associated positively with the CAC score, total plaque volume (TPV) and impaired perfusion (p<0.01 for all). Patients with HRP displayed higher levels of renin (p=0.04). As expected, renin (p<0.01) was elevated in males. After correction for baseline characteristics including sex, renin associated positively with CAC score and TPV (p<0.01 and p=0.03), but not with HRP and perfusion (p=0.14 and p=0.40). Figure 1 shows that vessels with a significant flow limiting stenosis (FFR+, PET+; p=0.04) occur in patient with elevated renin levels, while vessels defined as CMD (FFR-, PET+) do not, except for patient without RAAS inhibition.

Conclusion:
RAAS activation is associated with CAD defined by FFR and [
15
O]H2O PET and HRP. Future studies should clarify whether RAAS activation and CAD are causally related and represent modifiable targets.

Figure 1. Intergroup p values are depicted for significant p values only. The upper and lower whiskers represent the 10
th
and 90
th
percentile.
Abstract 11075: Unearthing the Gaps in Targeted Medical Therapy in Chronic Heart Failure
Authors: Galison Lotos , Pradhan Akshyaya , Sethi Rishi , Chandra Sharad , vishwakarma pravesh , Chaudhary Gaurav , Bhandari Monika , Kumar Sharma Akhil , sharma prachi , Singh Abhishek , Shukla Ayush , Dwivedi SK
Published: March 2022

Introduction:
Despite recent advancement in management of Heart failure (HF), the accessibility and affordability of this treatment is still an issue in developing countries.

Hypothesis:
We aimed to assess etiological and pharmacological profile of heart failure patients in our study.

Methods:
The study population consisted of 407 patients with chronic heart failure aged >18 years attending as outpatient. Acute Heart Failure and patients hospitalized for Acute Heart Failure within 4 weeks were excluded. The diagnosis of heart failure was made in accordance with 2016 ESC guidelines for the Heart failure. Patients were stratified into those with reduced ejection fraction(HFrEF: when EF < 40%), preserved ejection fraction (HFpEF: when EF > 50%), and those with mid-range ejection fraction (HFmrEF; when EF = 40-50%).

Results:
The mean age of the cohort was 58.8 years & 64.4% (n = 262) were males. The overall mean left ventricular ejection fraction (LVEF) of the cohort was 38.47±9.24%. Heart failure with reduced ejection fraction (HFrEF) was seen in 58.5% of patients. The two most prevalent etiologies of HF were ischemic heart disease (IHD) (53.6%; n = 218),) and idiopathic cardiomyopathy (34.2%; n = 133).The percentage of patients who received diuretics, angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), aldosterone antagonists, ARNI and Beta blockers as treatment were 93.12%, 71.99%, 8.11%, 82.31% , 6.63 % and 90.42 % respectively.The most commonly prescribed ACEI was ramipril (68.8%), Betablocker was carvedilol (45.7%) and MRA was Spironolactone (82.33%).Guideline directed medical therapy (beta-blocker,RAAS blocker and MRA-all 3) was prescribed in 63.88 % of patients. The median dose of ramipril was 2.86 mg (28% of target),carvedilol was 6.4 mg (12.8% of target), ARNI was 88.89mg (44.4% of target ) & spironolactone was 49.3mg (98.6% of target).

Conclusions:
Ischemic Heart Disease is the most common etiology of HF in the region.Despite the encouragement to follow the ESC Heart Failure Guidelines, only 63.88 % of patients were on prescribed guideline based therapy. Even among those getting drug, majority drugs failed to reach even 50% of the target doses with the exception of MRA.
Abstract 11078: Neighborhood Social Vulnerability is Associated with Major Adverse Cardiovascular Events and Deaths Among Patients Hospitalized with Covid-19: An Analysis of the Aha Covid-19 Cardiovascular Disease Registry
Authors: Islam Shabatun , Malla Gargya , Tian Wei , Song Yang , Kazi Dhruv S , Nayak Aditi , Mehta Anurag , Ko Yi-An , Quyyumi Arshed A , Yeh Robert W , Goyal Abhinav , Wadhera Rishi
Published: March 2022

Introduction:
The COVID-19 pandemic has disproportionately affected low-income and racial/ethnic minority populations in the US. However, it remains unclear whether hospitalized COVID-19 patients who live in socially vulnerable neighborhoods are more likely to experience major adverse cardiovascular events and/or death. We evaluated the association between neighborhood social vulnerability and in-hospital outcomes in a national cohort of hospitalized COVID-19 patients.

Hypothesis:
Among patients hospitalized with COVID-19, residence in socially vulnerable neighborhoods is associated with worse in-hospital outcomes.

Methods:
The American Heart Association COVID-19 Cardiovascular Disease Registry includes patients hospitalized with COVID-19 across 107 hospitals in the US between January 14, 2020 to November 30, 2020. The Social Vulnerability Index (SVI), a composite measure of community vulnerability developed by Center for Disease Control was used to classify the social vulnerability of patients’ place of residence defined by zip codes. We fit multivariable logistic regression models to evaluate the association between patient’s SVI and in-hospital death or major adverse cardiovascular events (MACE, defined as composite of all-cause death, MI, stroke, new onset heart failure, or cardiogenic shock).

Results:
Among 20,925 hospitalized COVID-19 patients in the registry, 6083 (29.1%) resided in the most vulnerable communities (highest national quartile of SVI). Compared with those in lowest quartile of SVI, patients in the highest quartile were younger (mean age 59.8±17.7 versus 62.0±17.9), more likely to be women (47.1% vs. 43.2%), Black patients (36.1% vs. 13.3%), and less likely to have private insurance (29.0% vs. 39.1%). After adjusting for demographics (age, sex, race/ethnicity), insurance status, and comorbidities, the highest quartile of SVI (compared to lowest) was associated with higher likelihood of in-hospital MACE (OR [95% CI] 1.28 [1.12, 1.46], p<0.001) as well as in-hospital death (OR 1.37 [1.21, 1.54], p<0.001).

Conclusion:
Hospitalized patients with COVID-19 who reside in more socially vulnerable neighborhoods experience higher rates of in-hospital MACE and death, independent of race and ethnicity.
Abstract 11090: Therapeutic Effect of VEGF- and SDF-Nanoparticles in the Rat Monocrotaline Model of Pulmonary Hypertension
Authors: Guarino Victoria A , Wertheim Bradley M , Loscalzo Joseph , Zhang Yingyi
Published: March 2022

Introduction:
Pulmonary vascular endothelial cell injury, dysfunction, and apoptosis are associated with the development of pulmonary arterial hypertension (PAH). Improving endothelial function may be therapeutically beneficial in this disorder. In the present study, we examined the effect of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α), proteins that support endothelial repair and tissue regeneration, in rats with monocrotaline-induced PAH. A polysaccharide nanoparticle was used as a carrier for VEGF and SDF-1α delivery, the formulation of which extends the retention time of the proteins in the lung by ~17-fold compared with free protein.

Method:
A crosslinked dextran sulfate-chitosan nanoparticle (XDSCS NP) was prepared as the carrier. Recombinant human VEGF and SDF-1α were incorporated in the XDSCS NP to generate VEGF-NP and SDF-NP, respectively. Athymic nude rats were injected with monocrotaline (50 mg/kg, IP) to induce PAH. Two weeks after the injection, VEGF-NP (8 μg/rat) and SDF-NP (4 μg/rat) were delivered to the lungs of rats via intratracheal aerosolization. At 4 weeks, catheterization of right and left heart was performed, and lung tissue collected for histological analysis.

Results:
Monocrotaline induced PAH in the nude rats, leading to right ventricular systolic pressure (RVSP) of 71±8 mmHg (mean±SD, n=8) vs. 29±2 mmHg in the untreated control rats. VEGF-NP and SDF-NP treatment reduced the RVSP to 48±13 mmHg. The Fulton indices of the three groups were 0.45±0.07, 0.22±0.01, and 0.25±0.06, respectively. The pulmonary vascular resistance indices of the groups were 3.2±0.7, 0.6±0.3, and 2.1±1.0 mmHg.min/ml/kg, respectively. Histological analysis showed monocrotaline-treated rats had prominent muscularization of precapillary vessels, which was markedly reduced by the VEGF-NP and SDF-NP treatment. Aerosolization of free VEGF and SDF-1α or of empty XDSCS NP carrier had no effect on monocrotaline-induce PAH.

Conclusion:
These data indicate that the delivery of VEGF and SDF to the lungs of rats in a NP-bound form had beneficial therapeutic effects in monocrotaline-induced PAH, and offer the potential for a novel therapeutic strategy for human pulmonary hypertensive disorders.
Abstract 11091: Failure of Right Ventricular Adaptation to Pressure Overload Due to a Profound Deficiency in Adenylate Kinase 1 and Impaired Ventricular Energetics
Authors: Zelt Jason , Cadete Virgilio , Deng Yupu , Godoy Rafael , Cuillerier Alexanne , Rowe Katelynn , Abdul-Ghani Mohammad , Megeney Lynn , Burelle Yan , Giulivi Antonio , STEWART Alexandre F , Provencher Steeve , Breuils-bonnet Sandra , bonnet sébastien , deKemp Robert , Beanlands Rob S , Mielniczuk Lisa , Stewart Duncan J
Published: March 2022

Introduction:
Interindividual heterogeneity in the ability of the right ventricular (RV) to adapt to pressure overload in pulmonary hypertension (PH) is likely influenced by genetic determinants. We took advantage of strain-dependent, maladaptive RV remodeling in Fischer compared to Sprague-Dawley (SD) rats to define the molecular and genetic mechanisms that predispose to development of RV failure in PH.

Methods/Results:
In the SU5416/hypoxia(SUHx) PH model, Fischer rats exhibited RV failure and 100% mortality by 5-weeks, whereas SD rats showed preserved RV function and 88% survival beyond 9 weeks (p<0.0001).
In vivo
oxidative metabolism, assessed by [
11
C]acetate PET, was increased in Fischer rats at 4 weeks (p<0.05), associated with impaired RV efficiency compared to SD (work metabolic index: 58±12 vs 102±20 mmHg·mL/cm
2
, respectively; p<0.001), but no differences were observed in mitochondrial complex activity in permeabilized RV cardiac fibers. Adenylate Kinase 1 (AK1) was among the top ten differentially expressed genes between Fischer and SD rats by unbiased transcriptomic analysis, with markedly lower expression in the RV of Fischer rats (FC:3.36, P<0.05). Profound AK1 deficiency was confirmed by proteomics and validated by Western blotting (>10-fold reduction, P<0.001). Fischer rats also exhibited evidence of hemolysis, recapitulating the hemolytic phenotype seen in patients with rare AK1 coding region mutations. While whole genome sequencing failed to reveal any coding region mutations in Fischer rats, there was a unique variant in a highly conserved upstream flanking region. AK1 levels were also reduced in the RV of PH patients with decompensated RV function and right heart failure.

Conclusion:
Fischer rats with AK1 deficiency have inefficient energetics likely related to reduced ATP shuttling from the mitochondria to the contractile fibers, which represents a novel mechanism for RV failure in response to chronic increases in afterload.
Abstract 11099:
Treml4
, Snps and Regulatory Mirnas in the Diagnosis of Subclinical Atherosclerosis
Authors: DUARTE VICTOR HUGO REZENDE R , COSTA DE SOUZA KARLA SIMONE C , Lopes Mariana , Freitas Renata C , Bertolami Adriana , Hirata Rosario , Hirata Mario , Luchessi Andre D , Silbiger Vivian N
Published: March 2022

Considering the multifactorial nature of the development of coronary artery calcificatioN (CAD), and the difficulty in making its early diagnosis, this study sought to investigate the role of the
TREML4
in the development of atherosclerotic lesions by genotyping of two main variants associated with this gene (rs2803495 and rs2803496), mRNA expression and identification of its regulatory miRNAs. 329 patients with Subclinical atherosclerosis (AS) were recruited. The results with AS patients stratified according to the Duke score demonstrated an association of the Duke score with increased expression of mRNA of the
TREML4
in peripheral blood leukocytes (OR. = 3.173, 95% CI = 1.29-7, 78, p = 0.012). Furthermore, genotyping revealed that the SNP genotype combination rs2803495 (AG + GG) (OR = 9,007, 95% CI = 4.1-19.8, p <0.001) and rs2803496 (CT + CC) ( OR = 11.1, 95% CI = 4.8-25.4, p = 0.011), favor the expression of TREML4 mRNA. Patients with AS and carriers of the SNP G alleles rs2803495 (AG + GG) (OR = 13.31, 95% CI = 5, 79-30.61, p <0.001) and C allele rs2803496 (CT + CC) (OR = 18.99, 95% CI = 7.60-47.44, p <0.001) are more likely to express
TREML4
. Once again, the C allele was associated with higher levels of mRNA expression (OR = 3.98, 95% CI = 1.67-9.48, p = 0.002). The rs2803495 (AG + GG) and rs2803496 (CT + CC) variants were not related to the development of type 2 Diabetes Mellitus (DM2; p> 0.05). However, patients who express
TREML4
and are DM2 have higher levels of expression of
TREML4
when compared to the control group (OR = 2.6, 95% CI = 1.19-5.72, p <0.001). Patients with DM2 and rs2803495 (AG + GG) genotypes are more likely to express
TREML4
(OR = 20.77, 95% CI = 2.29-188.41, p = 0.007). In silico analyzes showed that 8 miRNAs (hsa-miR-181a-5p, hsa-miR-200b-3p, hsa-miR-24-3p, hsa-miR-296-5p, hsa-miR-361-5p, hsa-miR- 423-5p, hsa-miR-486-3p and hsa-miR-708-5p) are expected to interact with
TREML4
mRNA.The results suggest that mRNA expression of the
TREML4
is associated with the presence of SNPs and increased in patients with AS with DM2 and that miRNAs may be involved in the regulation of the
TREML4
being directly or indirectly involved in the pathophysiology of CVD being potential circulating biomarkers for early detection and/or individualized treatment of AS and CAD.
Abstract 11100: Modified EDACS-ADP Score Using Derived 12-Lead Electrocardiogram and Cardiac Electrical Biomarker
Authors: Schreck David M , Fishberg Robert D , Bessette Noelle
Published: March 2022

Introduction:
The EDACS-ADP risk score includes 12-lead electrocardiogram (ECG) and troponin (cTn) to stratify patients presenting with chest pain. The ECG can be derived (dECG) from 3 measured leads with high correlation. A new cardiac electrical biomarker (CEB®) that correlates with cTn can be constructed in real-time from the dECG with reportedly high diagnostic accuracy for detection of acute myocardial infarction (AMI).

Objective:
Compare the EDACS-ADP to a modified risk score that includes substitution of dECG for ECG, and CEB® for cTn.

Methods:
This study included 138 consecutive patients presenting to an emergency facility with complaints of chest pain. The prevalence of AMI was 14.5% including 7 STEMI and 13 Non-STEMI. The dECG and CEB® were constructed from leads {I, II, V2} directly from an ECG device (VectraplexECG System, VectraCor Inc, Totowa, NJ). Each EDACS-ADP was calculated and compared to a modified score that utilized the dECG instead of the actual ECG, and CEB® instead of cTn. Sensitivities and specificities were calculated for the EDACS-ADP scores and respective modified scores. ROC curves were constructed to identify risk score cut-offs.

Results:
The CEB® showed high diagnostic accuracy for AMI with sensitivity 85%, specificity 95.8%, negative predictive value 97.4%, and positive predictive value 77.3%. The cTn showed sensitivity 100%, specificity 89.8%, negative predictive value 100%, and positive predictive value 62.5%. EDACS-ADP with ECG and cTn showed sensitivity 100%, specificity 88.1%, negative predictive value 100%, and positive predictive value 58.8% compared to the modified score with dECG and CEB that showed sensitivity 85%, specificity 94.9%, negative predictive value 97.4%, and positive predictive value 73.9%. The reported EDACS cut-off of 16 was validated by ROC curve analysis.

Conclusions:
The modified EDACS-ADP risk score based on substitution of the dECG for ECG and CEB® for cTn is comparable to the customary risk score. The modified risk score is easy to calculate and is available immediately allowing a shorter time to decision for possible admission. Also, the modified risk scores may be applicable in facilities where cTn is not immediately available such as in outpatient urgent care and post-acute care centers.
Abstract 11102: Ginsenoside Rb2 Alleviated Atherosclerosis Progression by Inhibiting M1 Macrophages Polarization Induced by Microrna-216a
Authors: Wang Shuting , YANG Shujun , Chen Yutong , Chen Yu , Zhang Weili
Published: March 2022

Background:
It has been reported that microRNA-216a (miR-216a) advanced atherosclerosis progression by promoting macrophage polarization to M1 pro-inflammation phenotype. Ginsenoside Rb2 (Rb2) is the major pharmacologically active compound extracted from ginseng. Bioinformatics predicted that Rb2 had a high affinity with miR-216a. In the present study, we aimed to investigate the effect of Rb2 on macrophages in atherosclerosis progression induced by miR-216a.

Methods:
ApoE
-/-
mice with miR-216a adenovirus infection and Rb2 intraperitoneal injection were used to explore the effect of Rb2 on miR-216a-mediated atherosclerosis development in vivo. Oil red O, Hematoxylin-Eosin (HE) and Masson's trichrome staining were performed to assess the thoracic aortic plaque progression and stability. Immunohistochemical staining was used to detect the M1 macrophages in plaque. Furthermore, macrophages transfected with miR-216a and treatment with Rb2 were used to explore the mechanism of Rb2 on M1 polarization in vitro. Neutral red phagocytic experiment and cholesterol efflux assay were performed to assess the role of Rb2 in lipid accumulation of M1 macrophages.

Results:
The results in ApoE
-/-
mice showed that Rb2 alleviated miR-216a-mediated atherosclerosis lesion area by 33%, and promoted plaque stability with a lipid accumulation decrease by 55% and a collage content increase by 250%. We further observed that Rb2 inhibited M1 macrophages in plaque by 76%. Mechanistically, the data from macrophages revealed that Rb2 reserved miR-216a-mediated Smad3 and IκBα protein expression to inhibit NF-κB-responsive genes, including M1 maker monocyte chemotactic protein-1 (MCP1) and tumor necrosis factor alpha (TNFα), and Rb2 attenuated miR-216a-mediated lipid deposit in M1 macrophages by decreasing lipid uptake and promoting cholesterol efflux.

Conclusion:
Our results first time showed that Rb2 alleviated atherosclerosis progression and stability induced by miR-216a. By inhibiting M1 macrophage polarization through Smad3/IκBα, Rb2 decreases lipid accumulation and increases collage content increase in plaque. The Rb2 could serve as a potential small molecule drug for atherosclerosis associated M1 polarization.
Abstract 11106: Unanticipated Interstage Readmissions in Infants with Hypoplastic Left Heart Syndrome: Association of Home Monitoring and Identification of Patient Risk Factors
Authors: Shustak Rachel J , Mercer-rosa Laura , Faerber Jennifer , Stagg Alyson , Hehir David A , Natarajan Shobha S , Preminger Tamar J , Szwast Anita , Rome Jonathan J , Giglia Therese M , Ravishankar Chitra , Gardner Monique M
Published: March 2022

Introduction:
Home monitoring in the interstage (IS) period has resulted in a significant decline in mortality in infants with hypoplastic left heart syndrome (HLHS). We hypothesize that this may in part be attributed to an increase in IS readmissions preventing out-of-hospital adverse events. We sought to examine the impact of our Infant Single Ventricle Monitoring Program (ISVMP) on the frequency and severity of unanticipated IS readmissions and to identify risk factors for readmission.

Methods:
This retrospective single-center cohort study compared infants with HLHS enrolled in ISVMP to historical controls. Readmission rate was defined as the number of unanticipated readmissions per interstage days. Severe readmission was defined by mortality, extracorporeal support, cardiopulmonary resuscitation, mechanical ventilation, or initiation of vasoactive medication. The relationship between ISVMP and number of interstage readmissions was modeled using inverse probability weighted (IPW) Poisson regression. The effect of ISVMP on the probability of severe readmission was modeled using IPW logistic regression. Multivariable Poisson regression models were used to identify risk factors for readmission.

Results:
We compared 198 ISVMP infants from 12/2010 to 12/2019 to 128 historical controls from 1/2007 to 11/2010. Readmissions were more frequent in the ISVMP group vs. controls (median 1.09 vs. 0.68 readmissions/100 days, p < 0.0001) with more than double the rate of readmissions in ISVMP infants (adjusted IRR 2.13; 95% CI 1.61-2.82; p < 0.0001). Despite a greater readmission rate, ISVMP infants were less likely to have severe readmissions (adjusted OR 0.25; 95% CI 0.11-0.60; p = 0.018). Independent risk factors for readmission were residing closer to our center, younger gestational age, postnatal diagnosis, genetic syndrome, and discharge with exclusive enteral tube feeds.

Conclusions:
In this single-center study, ISVMP infants had more frequent but less severe unanticipated readmissions. These findings suggest that the prevention of IS morbidity and mortality may have resulted in greater resource utilization. Future efforts should focus on strategies to decrease unanticipated readmissions without increasing adverse events.
Abstract 11116: Relationship Between Skeletal Muscle Decline During Acute Care and Recovery of Physical Function in Patients with Aortic Disease
Authors: Yamashita Masashi , Kamiya Kentaro , Kitamura Tadashi , Hamazaki Nobuaki , Ichikawa Takafumi , Uchida Shota , Noda Takumi , Maekawa Emi , Matsunaga Atsuhiko , Yamaoka-tojo Minako , Ako Junya , Miyaji Kagami
Published: March 2022

Introduction:
Low skeletal muscle area or density identified on computed tomography (CT) is associated with poor prognosis in patients with cardiovascular disease. However, there is a lack of evidence regarding the clinical process of skeletal muscle decline as a longitudinal change in the acute care setting.

Hypothesis:
Skeletal muscle loss occurs after acute care, and a high degree of skeletal muscle loss is associated with an insufficient recovery of physical function.

Methods:
This study used routinely acquired CT images for aortic disease management and prospectively reviewed the data of 123 patients who underwent abdominal CT before and after acute care. The area and density of all abdominal muscles and each muscle (such as the rectus abdominis, psoas, and erector spinae) divided into eight parts were measured at the third lumbar vertebra level after patient blinding. The short physical performance battery (SPPB) was used as a physical function parameter at the start and end of in-hospital cardiac rehabilitation. A generalized linear model with patients as random effects was used to investigate skeletal muscle loss during acute care. Multivariate linear regression analysis was performed to assess the relationship between skeletal muscle decline during acute care and the change in SPPB results during inpatient cardiac rehabilitation.

Results:
The median patient age was 70 years, and 70% of patients were men. All and each abdominal muscle density declined consistently after acute care (interaction: P = 0.998). In contrast, the whole muscle area was found to have no significant change, and the changes were different for each skeletal muscle (interaction: P = 0.037). After adjusting for confounding factors, greater declines in muscle density were associated with lower recovery on the SPPB (β = 0.30, P = 0.007).

Conclusions:
Muscle density declines consistently after acute care, and a greater decline in muscle density is associated with a lower recovery of physical function during in-hospital cardiac rehabilitation in patients with aortic disease.
Abstract 11121: Outcomes in Left Ventricular Thrombi Treated with Direct Oral Anticoagulants at a Safety Net Hospital
Authors: Kerchberger Anne , Mauricio Rina , Mathew Chris , Das Sandeep R
Published: March 2022

Introduction:
Direct oral anticoagulants (DoACs) are increasingly used off-label for the treatment of left ventricular (LV) thrombus due to ease of use. Current efficacy and safety data are mixed. DoACs offer advantages in low resource populations and have not been studied in this context. This study aimed to assess the efficacy of DOACs for the treatment of LV thrombus in a medically underserved population.

Methods:
A retrospective chart review was performed of patients treated with DoACs for LV thrombus from January 2017 to February 2020 in a medically underserved, multi-ethnic population receiving care at a large county hospital. Baseline demographic, clinical, and echocardiographic data were collected. Adverse events were obtained via chart review. AE were categorized into fatal bleeding, intracerebral hemorrhage and non-hemorrhagic stroke documented on CT or MRI, bleeding event requiring transfusion, myocardial infarction, and death.

Results:
Forty patients were identified. Average age was 52 ± 11 years, 19 (48%) were African American and 12 (30%) were women. At thrombus diagnosis, 19 (48%) initiated rivaroxaban. 21 started warfarin then transitioned to rivaroxaban (17, 43%) or apixaban (4, 10%). Average LV ejection fraction at diagnosis was 23 ± 13 % and average treatment length was 16 ± 10 months. Twenty-two (76%) of 29 follow up echoes showed thrombus resolution. Four patients were lost to follow up. Adverse events included 2 non-hemorrhagic strokes and 3 deaths.

Conclusion:
This is the largest single center retrospective study of LV thrombi at a publicly funded, county hospital caring for a diverse, medically underserved patient population. For this patient population treated with DoACs, successful resolution of LV thrombi occurred in most patients with few adverse events. These results underscore the need for randomized trials to understand the efficacy and safety of DOACs for the treatment of LV thrombus, particularly in underserved communities.
Abstract 11123: Racial and Ethnic Disparities Exist in Economic Stability and Healthcare Access and Utilization Among U.S. Children with Heart Conditions, National Survey of Children’s Health 2016-2019
Authors: Judge Ashley , Downing Karrie F , Oster Matthew , Nembhard Wendy N , Farr Sherry
Published: March 2022

Racial disparities exist in mortality among children with heart conditions, but less is known about disparities in upstream determinants of health. Our objective was to assess differences in economic stability, access to care, and healthcare utilization by race/ethnicity among children with heart conditions. Using caregiver-reported data on 0- to 17-year-olds from the 2016-2019 National Survey of Children’s Health, we calculated prevalence estimates for family economic stability (caregiver educational attainment and work status), child’s healthcare access (insurance type, usual place of care, and problems paying for child’s care), and child’s healthcare utilization (receipt of preventive care, specialty care, and 1 and ≥2 emergency room (ER) visits in the past 12 months) by race/ethnicity (Hispanic, non-Hispanic (NH) Black, and NH White), accounting for complex sampling and weighted to produce national estimates. We used the predicted marginal approach to multivariable logistic regression to generate adjusted prevalence ratios (aPRs) controlling for child’s age and sex. Of 2,596 children with heart conditions, 65.5% were NH White and 52.2% were male. Compared to NH White children, Hispanic and NH Black children, respectively, were 0.9 to 0.8 times less likely to have caregivers who were employed or had more than a high school education. Hispanic and NH Black children were more likely to have public insurance (respective aPRs 1.8, 2.1) and less likely to have a usual place of care (aPRs 0.9, 0.8). Hispanic children were less likely than NH White children to have visited the ER once in the past 12 months, whereas NH Black children were more likely to have visited the ER once (aPR 1.4) and twice or more (aPR 2.5). Among U.S. children with heart conditions, racial/ethnic disparities were seen in indicators of economic stability, access to care, and healthcare utilization.
Abstract 11127: Clinical Heart Failure Events After Doxorubicin Treatment in High Grade Osteosarcoma Patients
Authors: Heemelaar Julius C , Polomski Elissa S , al Jaff Ahmed A , Evenhuis Richard E , van de Sande Michiel A , Gelderblom Hans J , Speetjens Frank M , Antoni Maria Louisa D
Published: March 2022

Introduction:
Osteosarcoma patients are at high risk of developing an anthracycline-induced cardiomyopathy (AC-CMP) due to their cancer treatment. The purpose of the study was to evaluate incidence of heart failure (HF) in this specific population and to identify predictors of HF.

Methods:
We conducted a retrospective cohort study at a tertiary sarcoma center (timeframe: 1982-2017) among 400 high grade osteosarcoma patients whom underwent surgery and received chemotherapy. Relevant data on demographics, cardiovascular risk profile, medications, osteosarcoma diagnosis and treatment was acquired from the electronic healthcare records and local oncology clinical registry. The primary endpoint was the composite of initiation of HF medication, hospitalization for HF and ICD implantation as primary prevention of sudden cardiac death in reduced left ventricular function.

Results:
The median age at sarcoma diagnosis in our cohort was 19 [p25-p75: 15-32] years with a median follow up time of 6 [2-14] years. At baseline, few patients used any medication or had cardiovascular risk factors: resp. 5 (1.3%) and 15 (3.8%). The endpoint occurred in 5.8% (23 patients). In 10 patients (2.5%) an admission for decompensated HF was the first presentation of AC-CMP, and ICD-implantation due to a reduced left ventricular ejection fraction occurred in 4 patients (1%). When sarcoma was diagnosed after 30 years of age, patients had near 5-fold increased risk of reaching the primary endpoint within 10 years after diagnosis (competing risk regression with competing risk of death due to malignancy: SHR 5.8 [2.0-16.9],
p
=0.001) and the time to a first HF event was shorter than younger patients: 3.4 [0.8-7.9] vs. 11.7 [5.2-16.0] years,
p
=0.027.

Conclusions:
The risk of developing HF in sarcoma patients is substantial, which warrants close monitoring during treatment and long term follow-up. Older age at diagnosis is associated with higher risk of developing HF and a shorter duration to events.
Abstract 11130: Impact of the Covid-19 Pandemic on the Epidemiology of Out-of-hospital Cardiac Arrest: A Systematic Review and Meta-Analysis
Authors: Teoh Seth E , Masuda Yoshio , Tan Darren J , Liu Nan , Morrison Laurie , Ong Marcus E , Blewer Audrey L , Ho Andrew
Published: March 2022

Introduction:
The coronavirus disease 2019 (COVID-19) pandemic has influenced epidemiology through direct and indirect effects, yet the impact on out-of-hospital cardiac arrest (OHCA) is unclear. We aimed to evaluate the impact of the pandemic on the incidence, characteristics, and clinical outcomes of OHCA.

Hypothesis:
We hypothesized that compared to the pre-pandemic period, the COVID-19 pandemic period was associated with increased incidence and case fatality rate (CFR) of OHCA, as well as decreased rates of intermediate clinical outcomes (termination of resuscitation [TOR], return of spontaneous circulation [ROSC], survival to hospital admission, and survival to hospital discharge). We further postulated that there was a change in the etiologies of OHCA during the pandemic as well as a decline in the rate of shockable rhythm as the initial presenting rhythm.

Methods:
In this systematic review and meta-analysis, five scientific databases were searched from inception to May 3, 2021. Meta-analyses were performed for the primary outcomes, secondary outcomes, and clinical characteristics. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021253879).

Results:
The search yielded 966 articles. 20 articles were included for analysis. The COVID-19 pandemic was associated with a 39.5% increase in pooled annual OHCA incidence (p<0.001). Pooled CFR was increased by 2.65% (p<0.001), with an odds ratio (OR) of 1.95 for mortality (95% confidence interval [95%CI] 1.51-2.51). There was increased field TOR (OR=2.46, 95%CI 1.62-3.74). There were decreased ROSC (OR=0.65, 95%CI 0.55-0.77), survival to hospital admission (OR=0.65, 95%CI 0.48-0.89), and survival to discharge (OR=0.52, 95%CI 0.40-0.69). There was decreased shockable rhythm (OR=0.73, 95%CI 0.60-0.88) and increased asphyxial etiology of OHCA (OR=1.17, 95%CI 1.02-1.33). There was moderate-to-high statistical heterogeneity. Findings were robust to sensitivity analyses, with no publication bias detected.

Conclusions:
The COVID-19 pandemic was associated with significant changes in OHCA epidemiology. Compared to the pre-pandemic period, the pandemic period was associated with increased OHCA incidence and worse outcomes.
Abstract 11132: Impact of Obesity and Underweight Status by Body Mass Index on Mortality Among Hospitalized Patients with Hypertrophic Cardiomyopathy
Authors: Sreenivasan Jayakumar , Lloji Amanda , Kaul Risheek , Khan Mohammad S , Malik Aaqib H , Aronow Wilbert S , Michos Erin D , Naidu Srihari S
Published: March 2022

Introduction:
Even though obesity is associated with increased phenotypic expression in patients with hypertrophic cardiomyopathy (HCM), the effect of body mass index (BMI) on in-hospital mortality among hospitalized patients with HCM has not been established.

Hypothesis:
We hypothesized that among hospitalized patients with HCM, obesity and underweight status are associated with increased mortality

Methods:
We evaluated the National Inpatient Sample database to identify all adults (age ≥18 years) with HCM hospitalized for any cardiac illness between 2008 and 2017. Using ICD codes for BMI, the study cohort was stratified into underweight (BMI ≤19.9 kg/m
2
), non-obese (BMI 20.0-29.9 kg/m
2
), class I obesity (BMI 30.0-34.9 kg/m
2
), class II obesity (BMI 35.0-39.9 kg/m
2
) and class III (BMI ≥40.0 kg/m
2
). Multiple logistic regression analysis was used to analyze the independent association of various BMI categories and in-hospital mortality adjusted for age, sex and medical comorbidities.

Results:
The survey-weighted sample included a total of 2,392,325 hospitalizations with a mean age of 66.1±12.2 years and 42.0% were females. The patients with class III obesity [adjusted mortality rate (AMR) 3.3%, adjusted odds ratio (AOR) 1.53, 95% confidence interval (CI)-1.29-1.82,
p
<0.001] and underweight patients (AMR 4.4%, AOR 2.07, 95% CI-1.74-2.46,
p
<0.001) had higher in-hospital mortality whereas patients with class I obesity (AMR-0.8%, AOR 0.35, 95% CI-0.27-0.45,
p
<0.001) and patients with class II obesity (AMR-0.8%, AOR 0.34, 95% CI-0.26-0.45,
p
<0.001) had lower mortality compared to non-obese patients (AMR-2.2%)

Conclusions:
Among patients with HCM, BMI has a non-linear U-shaped relationship with in-hospital mortality. The patients who were underweight and morbidly obese had significantly higher mortality, whereas those patients with class I and class II obesity had lower mortality compared to non-obese patients.
Abstract 11133: Endogenous Ketone Bodies Have Cardioprotective Effects in Obesity Related Heart Failure with Preserved Ejection Fraction
Authors: Yamada Toshihiro , Ishida Toshifumi , Yuquing Xu , Takashio Seiji , Hanatani Shinsuke , Araki Satoshi , Yamamoto Eiichiro , Nakamura Taishi , Matsushita Kenichi , Nishiyama Koichi , Arima Yuichiro , Tsujita Kenichi
Published: March 2022

We recently developed a murine model of insufficient ketogenesis by disrupting the rate-limiting enzyme of ketogenesis, HMG-CoA synthase 2 (
Hmgcs2
-/-
;
Keto-less
mice), and reported a mitochondrial protection by ketone body metabolism (Arima. et. al., Nature Metabolism 2021). While new evidence has suggested a cardiovascular-protective role by ketone bodies, the precise impact of ketone bodies on heart failure remains unknown. Using our new model in this study, we aimed to elucidate the role of ketone bodies in heart failure. We first generated a pressure-overload model using transverse aortic constriction and compared
keto-less
mice with wild-type mice. While
Keto-less
mice showed a tendency for increased cardiomyocytes size, there was no significant difference in mortality and heart weight. Our previous report revealed that fatty acid overload enhances ketogenesis. Therefore, we employed a dietary heart failure mouse model with preserved ejection fraction (HFpEF) using a high-fat diet and Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME). The HFpEF model confirmed increased ketogenesis and hyperacetylation of mitochondrial protein. We then tested the impact of ketone bodies by using hepatic-specific
keto-less
mice. Hepatic
keto-less
mice showed significantly decreased ketone body concentration, but did not show significant changes in body weight and blood pressure. However, cardiomyocyte hypertrophy was exacerbated in the HFpEF model with hepatic specific
keto-less
mice compared to wild-type mice (WT 325±90um2; hKL 402±110um2, p<0.0001). We examined the multifaceted effects of the ketone body, and addressed a significant reduction in sequential enzymatic reactions in the TCA cycle.These data suggested that ketone bodies have a protective role against heart failure by modulating cardiomyocyte energetics.
Abstract 11137: Caveolin 1 Ameliorated Coronary Flow Responsible for Cardiac Function Improvement After Cardiac Ischemia Reperfusion
Authors: Tsukuda Jumpei , Koa Jonathan , Meng Zhijun , Zhang Zhen , Wang Yajing , Ma Xinliang
Published: March 2022

Introduction:
Caveolin-1 (Cav-1) is the main structural protein of caveolae, which is dominantly expressed in vascular tissue. It associates with vascular homeostasis by regulating vascular signals. However, Cav-1 KO aggravated the cardiac dysfunction of systolic and diastolic function after cardiac ischemia reperfusion. Injection of Cav-1 peptides successfully preserved left ventricular function post-ischemic reperfusion through the increase in nitric oxide (NO).

Hypothesis and Methods:
To evaluate the role of Cav-1 in cardiac function, we assessed cardiac function, heart rate and coronary artery blood flow through global ischemia and reperfusion using Langendorff-perfused mouse heart model.

Results:
In the final analysis of 15 mice, 7 were wild type (WT) and 8 were Cav-1 KO at the age of 12-23 weeks. There are significantly differences in baseline of Left ventricular pressure (LVP), heart rate (HR), max and minimum dp/dp before and after ischemia in each mouse group. We further concluded that the markedly decrease of Coronary artery flow (CF) is the reason for the inhibition of cardiac diastolic function, while heart rate (HR) did not show obvious difference in WT and Cav-1 KO mice. Cav-1 deficiency inhibited the coronary artery flow after ischemia reperfusion and led to aggravation of cardiac dysfunction.

Conclusions:
As further experiments are needed, both cardiac functions and coronary flow in Cav-1 KO could be impaired. More experiments will be performed and results will be updated.
Abstract 11138: Impact of Heart Rate Reduction on Recurrence After Catheter Ablation of Persistent Atrial Fibrillation
Authors: Okada Masato , Inoue Koichi , Tanaka Nobuaki , Tanaka Koji , Hirao Yuko , Oka Takafumi , Masuda Masaharu , Furukawa Yoshio , Hirata Akio , Egami Yasuyuki , Watanabe Tetsuya , Minamiguchi Hitoshi , Miyoshi Miwa , Sunaga Akihiro , Sotomi Yohei , Dohi Tomoharu , Hikoso Shungo , Sakata Yasushi ,   the OCVC-Arrhythmia Investigators
Published: March 2022

Introduction:
Predicting heart rate (HR) after restoration of sinus rhythm (SR) remains one of the challenges when performing catheter ablation (CA) of persistent atrial fibrillation (AF).

Objectives:
To evaluate the association between pre-ablation HR during AF and post-ablation HR during SR, and whether the HR reduction is associated with AF recurrence.

Methods:
The analysis was performed from the EARNEST-PVI trial, a randomized controlled trial designed to assess a CA strategy for persistent AF, which was conducted in the Osaka region of Japan. After excluding patients with beta-blocker prescription, a total of 216 patients (median age, 67 years; 20% female; 23% long-standing persistent AF) with AF rhythm at baseline and SR at discharge were enrolled in this study. Baseline HR during AF and post-ablation HR during SR was measured on admission and at discharge using the 12-lead electrocardiograms, respectively.

Results:
There was a mild correlation between baseline HR (median 82 [interquartile range 72-95] bpm) and post-ablation HR (78 [48-117] bpm) (r = 0.27, p <0.001). Reduction in HR was positively associated with baseline HR (r = 0.79, p <0.001) and was negatively associated with post-ablation HR (r = - 0.37, p <0.001). During the follow-up of 1 year, 56 patients (25.9%) experienced AF recurrence. HR reduction had the higher diagnostic accuracy in predicting AF recurrence than HR at baseline and HR after CA (area under the curve, 0.625; 95% confidence interval, 0.557-0.690; p = 0.003). AF recurrence rate was significantly higher in 141 patients with smaller HR reduction (cut-off, <14bpm) than those with larger HR reduction (31.9% vs. 14.7%, p = 0.009). After adjustment of age, gender, long-standing persistent AF, and CA strategy, HR reduction of <14 bpm was a significant predictor of AF recurrence (hazard ratio, 2.32; 95% confidence interval, 1.20-4.51; p = 0.013).

Conclusions:
There was a mild correlation between HR during AF and HR after restoration of SR in patients underwent CA of persistent AF. HR reduction after restoration of SR predicted AF recurrence.
Abstract 11140: Mitral Valve Repair with the Mitraclip System in Patients with Cardiogenic Shock
Authors: Chiang Caleb , Voudris Konstantinos , Kavinsky Clifford J , Suradi Hussam
Published: March 2022

Introduction:
The presence of significant mitral regurgitation (MR) in patients with cardiogenic shock (CS) patients is associated with worse prognoses. Limited data exists on the effect of percutaneous mitral valve repair (PMVR) with MitraClip in this population.

Hypothesis:
We examined short term outcomes of MitraClip PMVR in patients with CS and MR at 30 days and six months.

Methods:
Single-center, retrospective study of patients with CS and MR undergoing PMVR between January 2015 and December 2020. All patients were followed up for 6 months. Baseline and procedural characteristics as well as 30-day and six-months outcomes of all-cause mortality, heart failure hospitalizations, stroke, new atrial fibrillation, new pacemaker placement, and improvement in MR severity ≥2 grades were assessed.

Results:
A total of 20 patient were included for analysis. The mean age was 72.8 ± 11.1 years; 9 patients (45%) were men. MR was due to primary pathology in 9 patients (45%), functional in 2 (10%) and mixed in 9 (45%). Characteristics of the population are shown in Table 1. At 30 days all-cause mortality was 20% (n=4), while 2 patients (10%) required HF hospitalization. MR severity improved by at least 2 grades in 10 patients (50%). At six months, all-cause mortality was 40% (n=8), while 4 patients (20%) required heart failure readmission. 10 patients (50%) maintained the improvement in MR severity. There was no incidence of stroke, new atrial fibrillation, or new pacemaker placement at 30 days or 6 months.

Conclusions:
PMVR with the MitraClip system is a feasible and a safe option for MR in patients with CS. Improved MR severity is maintained at 30 days and 6 months.
Abstract 11143: Efficacy and Safety of Inclisiran by Baseline Body Mass Index: A Post Hoc Pooled Analysis of the ORION-9, ORION-10 and ORION-11 Phase III Randomized Controlled Trials
Authors: Leiter Lawrence A , Kallend David G , Koenig Wolfgang , Landmesser Ulf , Ray Kausik K , Schwartz Gregory G , Wright R S , chiang yanntong , Garcia Conde Orozco Lorena , Raal Frederick J
Published: March 2022

Introduction:
Excessive bodyweight, often associated with dyslipidemia, may affect the pharmacology of drugs. Inclisiran, a small interfering RNA targeting PCSK9 hepatic mRNA, is an effective LDL-C lowering agent with twice-yearly subcutaneous dosing (after the initial and 3-month doses).

Aim:
To analyze the efficacy and safety of inclisiran in patients with heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalent across body mass index (BMI) strata.

Methods:
In this post hoc analysis from ORION-9 (NCT03397121), ORION-10 (NCT03399370) and ORION-11 (NCT03400800), eligible patients were randomized 1:1 to receive 300 mg inclisiran sodium (equivalent to 284 mg inclisiran) or placebo at baseline, Day 90 and 6-monthly thereafter. Analyses were stratified by baseline BMI: <25, 25-<30, 30-<35 or ≥35 kg/m
2
. Percentage change in atherogenic lipids from baseline at Day 510 was evaluated. Safety was assessed over 540 days.

Results:
Baseline demographic and clinical characteristics including atherogenic lipid levels were mostly balanced between the treatment arms and across the BMI strata (
Table
). Percentage change in atherogenic lipids from baseline at Day 510 was significantly greater with inclisiran vs placebo within each BMI stratum (
Table
). Treatment-emergent adverse events (TEAE) and treatment-emergent serious adverse events were generally similar between the treatment arms and were reported more frequently with increasing BMI strata (data not shown). Clinically relevant TEAEs at the injection site were reported more frequently with inclisiran vs placebo similarly across strata, but all were mild or moderate.

Conclusions:
Twice-yearly dosing with inclisiran (after the initial and 3-month doses) provided effective and sustained lipid lowering in patients, irrespective of their baseline BMI, and was generally well tolerated.