bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13441: Which Indices of Heart Rate Variability are the Best Predictors of Mortality After Acute Myocardial Infarction? Meta-Analysis of Observational Studies
Authors: Rueda-ochoa Oscar L , Osorio-Romero Luisa F , Sanchez Mendez Lizeth Daniela D
Published: April 2022

Introduction:
Cardiovascular disease is the first cause of death globally with myocardial infarction as the main event. Heart rate variability (HRV) has been associated with an increased risk of mortality post-myocardial infarction. However, which indices of heart rate variability are the best predictors for total and cardiac mortality post-myocardial infarction remains unclear. Predict mortality risk by these indices, is important as HRV is a low-cost, low-invasive, and easy biomarker to interpret.

Hypothesis:
Indices evaluating heart rate variability are differentially associated with cardiac and total mortality, but to date, there is no evidence about which is the best for these outcomes

Methods:
PubMed, Google Scholar, Embase, Cochrane databases, and grey literature were searched for studies with HRV as a predictive mortality marker. Two authors independently selected papers and extracted data. Disagreements were solved with a third author. Clinical and statistical heterogeneity was assessed. Forest and funnel plot graphs were made. HRV indices included were SDNN, SDANN, HRV index, Total power, RMSSD, pNN50, LF, HF, ULF, VLF, and LF/HF. Sensitivity analysis, cumulative and regression meta-analysis were performed. Stata 16 was used for statistical analysis.

Results:
From 338 articles found, 29 were included. Low values of SDNN, HRV index, HF, ULF, and VLF showed statistically significant association with cardiac mortality, but HRV index had the highest association RR: 5.10 (CI95% 3.92 - 6.65, I
2
of 22%). For overall mortality, SDNN, HRV index, LF, VLF y ULF had statistically significant association, but HRV index was the best index, RR:3.60 (CI95% 2.52- 5.15, I
2
0%). Both associations had high consistency in subgroup analysis, with quality of articles, year of publication, and different cut-off points.

Conclusions:
the best index associated with cardiac and total mortality post-myocardial infarction is low values of HRV index.
Abstract 13445: Precise Score Validation in Buenos Aires 1 Registry
Authors: Munoz Florencia , Garmendia Cristian M , Viruel Marcos , Costabel Juan , Arbucci Rosina , Duronto Ernesto , Fernandez Horacio E
Published: April 2022

Introduction:
The PRECICE DAPT Score predicts the bleeding risk in patients treated with dual antiplatelet treatment after primary percutaneous coronary intervention (pPCI).

Hypothesis:
We sought to assess and compare the prediction power of the PRECISE-DAPT score with regards to bleeding events in patients suffering from non-ST elevation acute coronary syndromes (NSTEACS) and undergoing invasive management in a real- world scenario from Argentina.

Methods:
Our external validation cohort included 862 patients from Buenos Aires 1 registry. The PRECISE DAPT score was calculated upon admission and the characteristics and evolution of the patients were analyzed in a period of 15 months. The ability of PRECISE-DAPT to predict BARC type 2, 3 or 5 bleeding and BARC type 3 or 5 bleeding and ischemic events (MACE: myocardial infarction, stent thrombosis, or ischemic stroke) during follow up was evaluated.

Results:
PRECISE-DAPT score was low effective at predicting bleeding events type 2, 3 or 5 (c-statistics 0.58 [95% CI, 0.52-0.61]) moderate at BARC 3 or 5 (c-statistics 0.72 [95% CI, 0.64-0.78]), and poor for MACE (c-statistics 0.49 [95% CI, 0.,45-0.51]). Calibration was accurate (χ2 > 0.05) in all scenarios. High PRECISE-DAPT score (≥25, n= [%]) was associated with very high risk of bleeding (HR 2.1) and ischemic events (HR 1.9)

Conclusions:
In real-world study, PRECISE DAPT was moderately accurate in predicting bleeding and ischemic events. PRECISE DAPT score ≥25 was able to identify a subgroup of patients with high bleeding and thrombotic events.
Abstract 13449: Myocardial Infarction With Non-Obstructive vs Obstructive Coronary Arteries Among Patients With Acute Coronary Syndrome at a Large Safety-Net Hospital
Authors: Singh Shruti , Mauricio Rina , Das Sandeep R
Published: April 2022

Introduction:
Myocardial infarction with non-obstructive coronary arteries (MINOCA) has been increasingly recognized. The differences between MINOCA and obstructive coronary artery disease (OCAD) patients have not been studied in lower socioeconomic status populations.

Methods:
The records of all patients undergoing angiography for ACS at a large Dallas County safety-net hospital from January 2018 to January 2020 were reviewed and categorized as MINOCA or OCAD.

Results:
During the study period, 592 cases of acute coronary syndrome (ACS) were identified; 10.8% (n=64) were MINOCA. OCAD patients had higher peak pre-angiography troponin compared with MINOCA patients (2498 vs 335 ng/L, p<0.001). MINOCA patients were younger compared with OCAD patients (56 vs 60 y, p=0.01), while MINOCA men were younger than MINOCA women (53 vs 61 y, p=0.009). A higher proportion of MINOCA patients were Black, compared with OCAD (Figure 1). MINOCA patients had a lower prevalence of dyslipidemia and diabetes mellitus but there were no differences in the prevalence of smoking, hypertension, family history of premature CAD, current dialysis or heart failure between the groups. There were no differences in statin, aspirin, beta blocker or calcium channel blocker prescription at presentation between MINOCA and OCAD patients, regardless of sex. The majority of MINOCA patients (75%) did not have a definitive etiology of their ACS event by discharge.

Conclusions:
In this analysis of ACS patients presenting to a large safety-net hospital, MINOCA was common and MINOCA patients had many traditional risk factors. Men presented with MINOCA more commonly than has been seen in other studies. More Black patients presenting with ACS had MINOCA vs OCAD, likely reflecting the higher rates of left ventricular hypertrophy and diabetes in these patients. Lack of a definitive diagnosis for most MINOCA patients may reflect unfamiliarity with the diagnostic workup of MINOCA patients.
Abstract 13450: Role of PKC in Metabolic Regulation of Endothelial SK Channels
Authors: Xing Hang , Shi Guangbin , Liu Yuhong , Sellke Frank W , Feng Jun
Published: April 2022

Introduction:
Diabetes is associated with increases in metabolites NADH, and PKC. NADH has been recently found to inactivate endothelial SK channels. Overexpressed and activated PKC has been shown to play an important role in diabetes-induced endothelial dysfunction. However, it is undefined if PKC is involved in the NADH dysregulation of endothelial SK channels.

Hypothesis:
We hypothesized that PKC in a signaling cascade whereby NADH dysregulates endothelial SK channels and coronary relaxation function.

Methods:
SK channel currents of human coronary artery endothelial cells were measured by whole-cell patch-clamp method in the presence or absence of NADH, and/or PKC activator PMA, or PKC inhibitors or endothelial PKC
α
/PKC
β
knock-down by using short interfering RNA. The in-vitro coronary arterioles (n = 5) from the harvested atrial tissue samples of patients undergoing cardiac surgery were perfused with NADH in the presence or absence of PKC
β
inhibitor LY333531. Vascular reactivity was measured by vessel myography in the presence of vasoconstrictor and vasodilators.

Results:
NADH (30-300μM, n=7-9) or PKC activator PMA (30-300μM, n=6-12) reduced endothelial SK current density (p<0.05 vs. control (n=15), Fig. A-D), whereas the selective PKC
β
inhibitor LY333531 (50nM, n=12) significantly reversed the NADH-induced SK channel inhibition (p>0.05 vs. control (n=15), Fig. E). PKC
α
knock-down failed to affect NADH (n=13) and PMA (n=10) inhibition of endothelial SK currents (Fig. F). In contrast, PKC
β
knock-down significantly prevented NADH (n=12) and PMA (n=6)-induced SK inhibition (p>0.05, vs. control, Fig. G). Incubation of vessels with NADH significantly reduced relaxation response to the SK activator NS309 and this effect was abolished in the presence of LY333531.

Conclusions:
The metabolite NADH dysregulation of endothelial SK channels and impairment of endothelium-dependent relaxation function was via the PKC
β
signaling pathway.
Abstract 13458: Obese Heart Failure With Preserved Ejection Fraction Demonstrates Impaired Myocardial Substrate Utilization
Authors: Hahn Virginia S , Arany Zoltan , Kim Min-Soo , Petucci Christopher , Bedi Kenneth , Margulies Kenneth B , Kelly Daniel P , Kass David A , Sharma Kavita
Published: April 2022

Introduction:
Myocardial fatty acid oxidation is impaired in heart failure with reduced ejection fraction (HFrEF) but increases with obesity with diabetes. HF with preserved EF (HFpEF) patients are often obese, but their myocardial metabolomic profiling compared to HFrEF is unknown. We hypothesized that HFpEF patients have distinctive metabolomics signatures from HFrEF.

Methods:
Plasma and endomyocardial biopsies were collected from HFpEF patients with clinical HF, LVEF≥50%, and consensus criteria for HFpEF (n=45). Most were obese (median BMI 39.8 kg/m
2
). Data were compared to end-stage HFrEF (n=30) and unused donor controls (n=20). Liquid chromatography-mass spectrometry measured 97 metabolites (8 organic acids, 30 amino acids [AA], 59 acylcarnitines [AC]). Metabolites undetectable in ≥25% patients were excluded. Statistical analyses used one-way ANOVA with post-hoc Tukey test, and false discovery rate of 5% (Benjamini-Hochberg).

Results:
Myocardial metabolomics revealed HFpEF patients had greater pyruvate levels vs controls and HFrEF (2-2.5x, p<0.0001). Krebs cycle intermediates were reduced in HFpEF tissue vs controls (succinate, p=0.002; fumarate, p=0.009; malate, p=0.008), while myocardial branched chain AAs (isoleucine, leucine, valine) were greater than both controls (all p<0.0001) and HFrEF (p=0.048, <0.0001, <0.0001, respectively). Short chain ACs downstream of branched chain AA catabolism were reduced in HFpEF tissue vs Controls, whereas long chain ACs that reflect fatty acid oxidation were reduced in both HFpEF and HFrEF tissue vs controls, yet increased in HFrEF plasma. HFrEF had reduced tissue long chain ACs vs HFpEF. Plasma metabolomics replicated myocardial changes in only 11% of metabolites.

Conclusions:
HFpEF myocardium in obese patients displays metabolic signatures consistent with impaired utilization of fatty acids, glucose, and amino acids in a pattern quite distinct from HFrEF. This is not discerned from plasma metabolomics. These findings identify a unique metabolic phenotype in HFpEF in which obesity and associated insulin desensitization are coupled with compromised fat metabolism and alternate substrate utilization. This likely contributes to metabolic insufficiency in the HFpEF syndrome.
Abstract 13465: UFM1 Binding Protein 1 (UFBP1) is Indispensable for Normal Heart Function and Endoplasmic Reticulum (ER) Homeostasis
Authors: Li Jie , Yue Guihua , Ma Wenxia , Zhang Aizhen , Ayala Juan , Li Honglin , Su Huabo
Published: April 2022

UFM1 (ubiquitin-fold modifier 1) is a novel ubiquitin-like protein that modifies protein targets via UFM1-specific conjugation enzymes. Dysregulation of UFM1 modification, termed ufmylation, has been linked to multiple human diseases but its importance in the heart remain unclear. We have previously reported that ufmylation is dysregulated in failing human hearts. Through deletion of the E3 UFM1 ligase 1 (UFL1) in mouse hearts, we demonstrated that ufmylation is essential for normal cardiac function and protects against pathological cardiac remodeling. However, how ufmylation exerts its cardioprotective effect remains unclear. Here, we report that UFBP1 (UFM1 binding protein 1), an ER-resident ufmylation target, is an important downstream effector of ufmylation in the heart. While deletion of UFBP1 in mouse hearts has no impact on ufmylation, the knockout (KO) mice developed dilated cardiomyopathy at resting condition, as indicated by left ventricular wall thinning, chamber dilatation and significantly decreased cardiac contractility at 6 months of age. Moreover, loss of UFBP1 exacerbated pressure overload-induced cardiac remodeling and dysfunction, recapitulating multiple aspects of the phenotypes of UFL1-deficient hearts. Mechanistically, inhibition of ufmylation destabilized UFBP1, and depletion of UFBP1 promoted ER stress-induced cell injury in cultured cardiomyocytes. Furthermore, excess ER stress is implicated in UFBP1KO hearts and is aggravated with the progression of cardiomyopathy. Interestingly, ER stress inducers upregulated the expression of ufmylation pathway components at both transcript and protein levels in cultured cardiomyocytes and mouse hearts, indicating an intimate cross-talk between ufmylation and ER stress. Collectively, our data identify a novel UFM1-UFL1-UFBP1 axis in constraining pathological cardiac remodeling and maintaining ER homeostasis.
Abstract 13466: In Experimental Pad miR29a Modulates Perfusion Recovery and ADAM12 Expression Through Direct Interaction With ADAM12 mRNA
Authors: Lamin Victor , Wong Thomas , Verry Joseph , Eigner-Bybee Isaac , Dokun Ayotunde O
Published: April 2022

Peripheral artery disease (PAD) is caused by atherosclerotic occlusion of vessels outside the heart and most commonly affects vessels of the lower extremities. Angiogenesis is a part of the post ischemic adaption involved in restoring blood flow in PAD. Previously, in a murine hind limb ischemia (HLI) model of PAD, we identified ADAM12 as a key genetic modifier of post-ischemic perfusion recovery. However, less is known about ADAM12 regulation in ischemia. MiRNAs are a class of small, non-coding, single-stranded RNAs that regulate gene expression primarily through transcriptional repression of mRNA. We showed miR29a modulates ADAM12 expression in the setting of type 1 DM and ischemia. However, how miR29a modulates ADAM12 was not known. Moreover, the physiological effects of miR29a modulation in a non-diabetic setting was not known. Here, we demonstrate that AAV-mediated ectopic overexpression of miR29a in ischemic mouse hind limbs impairs post ischemic perfusion recovery and angiogenesis. We further demonstrate that miR29a regulates ADAM12 through direct interaction with ADAM12 mRNA. Treatment of ischemic mouse hind limbs with AAV9 particles containing miR29a (pAV-miR29a) increased miR29a expression (pAV-control vs pAV-miR29a: 3.22 ± 0.36, vs 1.0 ± 0.09, p<0.05, n=5-6,) and decreased ADAM12 mRNA expression (1.0 ± 0.31 vs 0.30 ± 0.08, p<0.05, n=7-10) resulting in decreased angiogenesis (1.0 ± 0.07 vs 0.66 ± 0.04, p<0.05, n=5), and impairment perfusion (week 3 post HLI perfusion, 101.9±5.55 vs 66.13±12.39, p<0.05, n=5-6,).AGO2 miRNA/RNA-immunoprecipitation studies showed levels of miR29a and ADAM12 mRNA in the complex decreased in samples treated with antagomiR29a (4, 40, 400nM) in a dose dependent manner (miR29a: 0.87, 0.68, 0.44, and ADAM12: 0.89, 0.78, 0.67, fold) but was unchanged by control antagomir (miR29a: 0.84, 0.84, 0.87, fold, and ADAM12: 1.11, 1.12, 1.10, fold). Taken together the data shows miR29a suppresses ADAM12 expression by directly binding to its mRNA resulting in impaired angiogenesis and poor perfusion. Hence, elevated levels of miR29a as seen in diabetes likely contributes to vascular pathology and lowering miR29a could be a therapeutic target.
Abstract 13499: Racial Disparities in Revascularization in Female Patients Admitted for STEMI
Authors: Del Cid Fratti Juan Daniel , KUMARAN SRIVIJI , Desai Anjali R , Mungee Sudhir , Mukhopadhyay Ekanka , Kizhakekuttu Tinoy J
Published: April 2022

Background:
Management of STEMI has improved in the last decade with early PCI. Prior data has shown that minorities have less access to medical services and have decrease rates of PCI and CABG when compared to Whites. We aim to evaluate the revascularization of female patients admitted with STEMI according to race in a contemporary era.

Methods:
A retrospective analysis of the National Inpatient Sample from 2016-2018 of female patients admitted with a primary diagnosis of STEMI. Patients were subdivided according to race. The primary outcome was in-hospital mortality. Secondary outcomes were health-care utilization, revascularization rates (PCI with BMS, DES, fibrinolytic, and CABG), and complication. A multivariate regression analysis was constructed to adjust for confounders.

Results:
642,665 STEMI admission were identified, of those 32.6% were female. Of those 76% were White, 11.3% Black, 7.4% Hispanic, 2.4% Asian, and 4.3% other races. African-American, Hispanic, and Asian had higher comorbidity index scores, lower incomes, and to use more Medicaid. Revascularization rates with PCI was 57.4% White, 51.2% in African-American, 53.7% in Hispanic, 50.5% in Asian, and 57.7% in other races (p=<0.01). CABG rates were 3.6% in White, 3% in African-American, 4.2% in Hispanic, 4.4% in Asian and 4.8% in other races. After adjusting for confounders African-Americans, Hispanic, and Asian were less likely to receive PCI in the index admission when compared to whites. Blacks were less likely to undergo CABG when compared to whites (Figure 1).

Conclusion:
Rates of revascularization in female patients with PCI after STEMI are low and are even lower in minority groups. Minorities have less odds of having PCI when compared to Whites, and African-Americans are less likely to have CABG when compared to Whites after STEMI. Further data are needed to evaluate the low rate of revascularization in female patients and these racial disparities.
Abstract 13524: 3-mercaptopyruvate Sulfurtransferase Deficiency Attenuates Branched-Chain Amino Acids Catabolism to Exacerbate Pressure Overload Heart Failure
Authors: Li Zhen , Xia Huijing , Sharp Thomas E , Lapenna Kyle , Casin Kevin , Liu Ken , Calvert John W , Nagahara Noriyuki , Goodchild Traci T , Lefer David J
Published: April 2022

Introduction:
Hydrogen sulfide (H
2
S) exerts mitochondria-specific actions that include the preservation of mitochondrial respiration, biogenesis, and ATP synthesis, while inhibiting apoptosis. 3-mercaptopyruvate sulfurtransferase (3-MST) is a mitochondrial H
2
S producing enzyme whose functions in cardiovascular physiology and pathology are yet to be fully elucidated. In the present study, we investigated the effects of global 3-MST deficiency in the setting of pressure overload-induced heart failure.

Methods:
3-MST knockout mice and C57BL/6J wild-type mice were subjected to transverse aortic constriction (TAC) to induce pressure-overload HFrEF. Cardiac structure and function, vascular reactivity, exercise performance, mitochondrial function and ATP synthesis efficiency were assessed. Additionally, unbiased metabolomic approaches were utilized to identify key pathways altered by 3-MST deficiency.

Results:
3-MST KO mice exhibited increased accumulation of branched-chain amino acids (BCAAs) in the myocardium, resulting in reduced mitochondrial respiration and ATP synthesis, exacerbated cardiac and vascular dysfunction, and worsened exercise intolerance in HFrEF. Promoting BCAAs catabolism through 3,6-dichlorobenzo1[b]thiophene-2-carboxylaic acid (BT2) treatment mitigated the detrimental effects of 3-MST deficiency and ameliorates the severity of HFrEF.

Conclusions:
Our data demonstrate that deficiency of 3-MST significantly inhibits BCAAs catabolism and impairs mitochondrial respiration and ATP synthesis efficiency, resulting in worsened HFrEF. These data suggest that 3-MST is critical in the protective response to cardiovascular diseases such as heart failure. Future studies are underway to define the mechanism by which 3-MST regulates BCAAs catabolism.
Abstract 13528: Interventional Hepatic ApoC-III Knockdown Improves Atherosclerotic Plaque Stability and Remodeling via Lowering Remnant Lipoproteins
Authors: Gordts Philip , Ramms Bastian , Pessentheiner Ariane , Sun Xiaoli , Ducasa Gloria M , Tsimikas Sam , Witztum Joseph L
Published: April 2022

Introduction:
Apolipoprotein C-III (apoC-III) is a key regulator in triglyceride (TG) metabolism and correlates positively with hypertriglyceridemia and incidences of CVD. Recent studies also identified apoC-III as an inducer of sterile inflammation by activating the inflammasome, another CVD risk factor. It remains unclear if therapeutic apoC-III lowering can reduce CVD risk, nor is it clear if this is dependent on lipid-lowering or anti-inflammatory properties or both.

Hypothesis:
We set out to test the concept that interventional apoC-III lowering reduces atherosclerosis development only when TG-lowering is achieved.

Methods:
We determined the impact of interventional apoC-III lowering on atherogenesis using an apoC-III antisense oligonucleotides (ASOs) in hypertriglyceridemic mouse models where the intervention results in TG-lowering (
Apoe
-/-
Ndst1
f/f
Alb-Cre
+
,
Ldlr
-/-
Ndst1
f/f
Alb-Cre
+
) or not (
Ldlr
-/-
Lrp1
f/f
Alb-Cre
+
).

Results:
ApoC-III ASO treatment did not alter atherosclerotic lesion volume in the murine models mice simultaneously fed a Western diet. However, when TG-lowering was obtained, apoC-III ASO treatment significantly attenuated advanced and unstable plaque development. In contrast, no improvement in lesion composition and hyperlipidemia was observed in apoC-III ASO-treated
Ldlr
-/-
Lrp1
f/f
Alb-Cre
+
mice lacking hepatic receptors responsible for apoC-III inhibition of TRL clearance. To mimic an interventional setting, we tested the impact of therapeutic apoC-III lowering in combination with a switch to a lipid-poor chow diet intervention after 12-week Western diet feeding. We observed that apoC-III ASO treatment significantly reduced atherosclerotic lesion size progression when an additive TG-lowering was achieved. No differences in lesion development were observed in similarly treated
Ldlr
-/-
Lrp1
f/f
Alb-Cre
+
mice wherein no additive TG-lowering was achieved by apoC-III ASO intervention.

Conclusions:
Our data highlight that the impact of apoC-III on atherogenesis depends on its lipid-modifying properties and suggest that interventional apoC-III lowering in hypertriglyceridemia patients can prevent plaque rupture and reduce CVD-associated mortality.
Abstract 13537: Mortality and Social Vulnerability in the COVID 19 Pandemic
Authors: Valencia Rendon Andres Felipe , Volschan Isabela , Pereira Manoella , Lima Monteiro Wagner , Bragança Pereira Basilio , Matos do Nascimento Emilia , Moraes de Oliveira Glaucia
Published: April 2022

Introduction:
A disastrous disease, the COVID-19, continues its spread, this, coupled with its severity, led to a initial global lockdown. Early evidence identified Black counties where mortality risk was higher than in white counties, even more evident in Latin America. In Brazil, with multiple forms of social inequalities, where color/race takes high relevance in this debate, it is even more relevant in Rio de Janeiro. We aimed to analyze these socio economic factors and its correlation with COVID 19 mortality.

Hypothesis:
Patients hospitalized with COVID 19 with a high social vulnerable background would had greater in-hospital mortality

Methods:
Prospective study of 274 confirmed adult COVID 19 hospitalized patients in the UHCFF. Clinical features/blood chemistry information were obtained from the clinical record. Using the individual address, we correlated it with the Census Code Area (CCA), using a novel methodology, we geoprocessed each home on the Division map. Giving a high relevance to the socio-economic variables for inequity and vulnerability markers, also analyzing the fact to be transferred from another primary care institution, for its delay potential of advanced medical care. We performed a logistic regression, with in-hospital mortality as our primary outcome.

Results:
Patients living in low adequacy households(p=0.030) with high in-house individual agglomeration markers (p=0.017), and the fact to have been transferred from another primary care institution (p=0.047) presented high in-hospital mortality, with high ICU admission and Mechanical Ventilation rates.

Conclusions:
In hospital mortality due to COVID 19 was influenced by social individual background characteristics of vulnerability. Among other clinical parameters, these markers should be taken into account to predict the individual likelihood of complications related to the pandemic, prioritizing the attention and vaccination for those at higher risk should be paramount.
Abstract 13544: Inflammasome Activation In Kawasaki Disease And Multisystem Inflammatory Syndrome In Children
Authors: Wang Wei-ting , He Ming , Shimizu Chisato , Croker Ben A , Hoffman Hal , Tremoulet Adriana H , Shyy John , Burns Jane
Published: April 2022

Introduction:
Multisystem Inflammatory Syndrome in Children (MIS-C) is a newly identified syndrome elicited by infection of acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although MIS-C shares several clinical features with Kawasaki disease (KD), a greater magnitude of systemic inflammation is usually associated with MIS-C. Inflammasome activation induces the secretion of pro-inflammatory cytokines, IL-1β and IL-18 and the inflammatory form of cell death, pyroptosis. To provide mechanistic insights into MIS-C and KD, we compared the expression and activation of the inflammasome in blood samples from MIS-C and KD patients.

Methods:
Expression levels of canonical and non-canonical inflammasome components, including
NLRP3
,
CASP1
,
CASP4
,
CASP5
,
IL1B
, and the inflammatory mediator,
TIFA
in whole blood from KD and convalescent patients were analyzed from microarray datasets. The expression of these inflammasome-related genes was further examined in whole blood samples from MIS-C, KD, KD shock syndrome (KDSS) and convalescent patients using RT-qPCR. Inflammasome activation and TIFA expression were validated in granulocytes of febrile control, KD and MIS-C patients by Western blotting.

Results:
TIFA
,
NLRP3
,
CASP1
,
CASP4
,
CASP5
,
IL1B
were upregulated in whole blood from MIS-C, KD, and KDSS patients as compared to convalescent patients. However, the differences were not significant among diseases. Although gene expression profiles were similar in KD, KDSS and MIS-C whole blood RNA, the processing of canonical and non-canonical inflammasome caspases, caspase-1, and caspase-4 were only observed in granulocytes isolated from MIS-C patients, but not KD and febrile controls. Moreover, TIFA was upregulated along with the activation of the inflammasome in granulocytes of MIS-C patients.

Conclusions:
Our results suggest that activation of inflammasomes, especially non-canonical inflammasome induction in granulocytes, is a hallmark of MIS-C, and differentiates it from KD.
Abstract 13545: Patient-Specific Computational Flow Simulation Reveals Differences in Aortic Hemodynamics Between Two versus Four Vessel Fenestrated Endovascular Aneurysm Repair
Authors: Tran Ken , Kaladji Adrien , Yang Weiguang , Marsden Alison L , Lee Jason
Published: April 2022

Objectives:
Fenestrated endovascular aneurysm repair (fEVAR) endografts with additional proximal fenestrations are the subject of upcoming pivotal trials in the United States. This study sought to use patient-specific flow simulation (CFS) to assess differences in hemodynamics associated with two (2v) versus four-vessel (4v) fEVAR after repair of complex aortic aneurysms.

Methods:
Patients from two institutions who underwent 2v fEVAR for juxatrenal, and 4v fEVAR for pararenal aortic aneurysms with the Cook Zenith Fenestrated platform were retrospectively selected. Device diameters were matched between 2v and 4v groups. Finite element volume meshes were created from pre- and post-operative imaging. Pulsatile flow simulations were performed using a non-compressible Navier-Stokes solver with equivalent patient-specific boundary conditions between pre- and post-operative states.

Results:
Patient-specific CFS was performed on 20 patients (10 2v, 10 4v fEVAR) with a total of 70 target vessels (40 renal, 10 celiac, 10 superior mesenteric (SMA) stents, and 10 SMA scallops). 4v fEVAR was associated with a decrease in SMA peak flow rate (-7.1 vs +1.1%, p=.042) compared to 2v fEVAR. 4v fEVAR was associated with decreased paravisceral aortic wall shear stress (WSS) (-31.3 vs +0.6%, p=.008), whereas SMA WSS was increased (+36.9 vs +15.5%, p=.049) compared to 2v fEVAR. No differences in celiac or renal perfusion or WSS was observed between groups (p=.14-.93). Streamline visualization revealed flow disturbances surrounding flared branch graft protrusions into the aortic lumen which may be associated with changes in SMA perfusion after 4v fEVAR (
Figure
). In conclusion, structural changes in paravisceral aortic geometry following 4v fEVAR may be associated with a decrease in SMA perfusion and large reduction in aortic wall shear stress compared to 2v fEVAR. Patient-specific CFS is useful for studying the unique hemodynamic effects of additional fenestrations.
Abstract 13550: Genotype-Phenotype Mismatch of Val122Ile Transthyretin Mutation in Dilated Cardiomyopathy
Authors: Bigham Thomas E , Brown Matthew T , Johns Eric , Bhatt Kunal N
Published: April 2022

Introduction:
An estimated 3.4% of African Americans carry the Valine 122 Isoleucine (Val122Ile) mutation associated with hereditary transthyretin (TTR) amyloidosis cardiomyopathy (hATTR-CM). Val122Ile is inherited in an autosomal dominant pattern, but penetrance of the clinical disease is variable and incompletely understood. Asymptomatic carriers therefore require screening for phenotypic manifestations of hATTR-CM before initiation of TTR-targeted therapies.

Case Description:
A 57-year-old African American male with non-ischemic dilated cardiomyopathy (DCM) presented in cardiogenic shock for advanced therapy evaluation. DCM was diagnosed 20 years prior, and family history was pertinent for cardiomyopathy in both parents. Echocardiography on admission revealed severely reduced left ventricular systolic function (EF 10%) with moderate cavitary dilation but no evidence of concentric or septal hypertrophy (LVeDd 6.1 cm, IVSd 0.9 cm, LVPWd 1.0 cm & LVMI 103 g/m
2
). His family history prompted genetic testing to evaluate hereditary etiologies of DCM. However, his genetic test only revealed a heterozygous Val122Ile mutation. He underwent left ventricular assist device (LVAD) implantation, after which LV apical core biopsy was negative for Congo red staining.

Discussion:
This case illustrates a clear genotype (Val122Ile) - phenotype (DCM) mismatch. Although positive for the Val122Ile mutation, the lack of Congo red staining on his LV core biopsy rules out cardiac infiltration of mutated TTR amyloid fibrils and instead suggests an entirely independent, idiopathic DCM. The increasing ease and availability of genetic testing, combined with the known high prevalence of the Val122Ile mutation in the African American population will inevitably lead to more cases of genotype-phenotype mismatch. The variable penetrance of this pathogenic mutation (Val122Ile) may lead to inappropriate treatment with TTR-targeted therapies in patients without clear disease, potentially increasing patient and healthcare costs unnecessarily. Further research is needed to understand the variable penetrance of Val122Ile and factors that may predict development of clinical disease in the future.
Abstract 13581: Heart Rhythm versus Heart Rate Control Strategy in Patients With Pre-Capillary Pulmonary Hypertension and Atrial Arrhythmias
Authors: Sammut Mark Anthony , Condliffe Robin , Hameed Abdul , Rothman Alex M , Kyriacou Andreas , Lewis Robert A , Durrington Charlotte , Elliot Charlie A , Thompson Alfred A , Sabroe Ian , Kiely David G , Charalampopoulos Athanasios
Published: April 2022

Introduction:
Atrial tachyarrhythmias in patients with pre-capillary pulmonary hypertension are often poorly tolerated leading to increased morbidity and mortality. Sinus rhythm restoration seems to improve outcomes but a direct comparison between rate and rhythm control has not been investigated. We sought to determine any difference in effectiveness between the two strategies.

Methods:
We performed a retrospective study in 88 patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) and new-onset atrial flutter or fibrillation seen in our centre from 2005-2020. Patients were divided into 3 groups based on management strategy: rate control (n=20), rhythm control with medication only (n=24) and rhythm control with DC cardioversion (DCCV) and medication (n=44) (Table 1). Differences in WHO functional class and incremental shuttle walk test distance (ISWTD) at arrhythmia onset and after treatment were measured.

Results:
Sinus rhythm was successfully restored in 42/44 (95%) of patients treated with DCCV and medication compared to 13/24 (54%) treated with amiodarone only (p<0.001). Cardioverted patients reported a significant improvement in functional class compared to patients treated with rate control (p<0.001). A similar improvement in ISWTD (≥15%) was also reported (p=0.004) (Table 2). No serious complications were reported with either strategy.

Conclusions:
A rhythm control strategy including DCCV and medication is a safe and effective way to restore sinus rhythm in patients with PAH/CTEPH and atrial tachyarrhythmias. Restoration and maintenance of sinus rhythm led to an improvement in their functional status.
Abstract 13586: Association Between Subclinical Atherosclerosis and Midlife Cognitive Function:
The Bogalusa Heart Study
Authors: De Anda-duran Ileana , Fernandez Camilo , Libon David J , Carmichael Owen T , Suglia Shakira F , Kolachalama Vijaya B , Au Rhoda , Bazzano Lydia A
Published: April 2022

Introduction:
Alzheimer’s disease and related dementias (ADRD) are increasing in prevalence. While overt atherosclerosis is recognizable from childhood and has been linked to cognitive impairment and dementia in late life, information is scant on the association between subclinical atherosclerosis and cognitive impairment in midlife. We examined this observation in a cohort of middle-aged noninstitutionalized participants living in a semirural community.

Hypothesis:
Increased cIMT is associated with worse cognitive performance in midlife.

Methods:
The analysis included 1,217 participants (age 48 ± 5.28 years; 66% white, 58% women) of the Bogalusa Heart Study. Multivariable-adjusted regression models were used to determine the association between composite cIMT, dichotomized at the 50thpercentile, and a standardized global cognitive z-score (GCS), as well as individual cognitive domains z-scores.

Results:
The composite cIMT (>0.87mm) was inversely associated with GCS (B= -0.39, SE= 0.18, p = 0.03), independent of cardiovascular risk factors (CVRF’s) and education.
(Table1)
The cIMT-composite was independently associated with poorer episodic memory (B= -0.23, SE=0.10, p = 0.015). The effect remained significant in Black and White participants after adjustment for CVRF’s (Blacks:B= -0.45, SE: 0.17, p = 0.008; Whites: B= -0.29, SE= 0.13, p = 0.028), but not for education.

Conclusions:
Subclinical atherosclerosis, as assessed via cIMT, is associated with worse cognitive function in midlife, independent of major CVRFs. The association is buffered by education, and this effect may be stronger among black participants than white. These findings reinforce the importance of establishing preventive measures in midlife and suggest subclinical atherosclerosis as a potential target to prevent cognitive decline.
Abstract 13602: Detection of Thermal Myocardial Injury Using the Microwave Return Loss Spectrum
Authors: Yang Edward , Tran Vu Toan , Barry Anthony , McEwan Alistair , Qian Pierre
Published: April 2022

Introduction:
Thermocouples located inside conventional ablation catheters do not measure tissue temperature nor determine thermal lesion size during cardiac catheter ablation.

Hypothesis:
Progressive, thermally mediated changes in tissue composition can be detected by the return loss spectrum of a microwave antenna coupling to tissue in the microwave band.

Results:
Return loss (RL) exhibited characteristic changes in the 1.6 to 1.7 GHz band during heating (Panel A). Heating to a temperature lethal to the myocardium (50°C) reduced the RL amplitude of the sample from baseline by 346.7% (-10.80 ± 4.430 dB, p = 0.0055). Further temperature rise restituted RL amplitude back to approximately baseline values at 64°C to 70°C (Panel B).

Conclusion:
The pattern of RL amplitude change in the 1.6 - 1.7 GHz microwave band may be useful for detecting lethal thermal myocardial injury and prevent overheating. This observation may have applications for monitoring cardiac catheter ablation.
Abstract 13609: Impact of Frailty on Hospital-Related Outcomes of Elective Left Atrial Appendage Closure
Authors: Li Weijia , Rios Saul , Wu Lingling , Jin Chengyue
Published: April 2022

Introduction:
Atrial fibrillation as the most common arrhythmia worldwide results in a significantly elevated risk of cardioembolic stroke. Left atrial appendage (LAA) closure has been advocated and supported by randomized clinical trials as an alternative treatment in patients with atrial fibrillation who have contraindications for anticoagulation. The safety of this procedure in patients who are considered frail remains unknown since they have been underrepresented in most clinical studies. Our study aims to investigate the impact of frailty on hospital-related outcomes in patients undergoing elective LAA closure.

Methods:
We reviewed the National Inpatient Sample database from January 2016 to December 2017 to identify patients that underwent elective percutaneous LAA closure using the ICD-10 code 02L73DK for the procedure. Frailty was defined using the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnoses indicator. An individual is considered frail if they present >=1 diagnosis within the indicator. The outcomes include in-hospital mortality, hemorrhage requiring blood transfusion, respiratory failure, sepsis, length of stay, and total hospitalization cost. Multivariate logistic or linear regression was adopted to determine the impact of frailty on the outcomes while reducing the effect of possible confounding baseline characteristics.

Results:
From the period of January 2016 to December 2017, a total of 14795 patients underwent elective LAA closure. Of those patients, 830 were determined to meet the criteria for frailty, while 13965 were considered non-frail. The frail group is older than the non-frail group with a mean age of 78.77 years old than 75.53 years old. Frailty was associated with an increased risk of hemorrhage requiring transfusion (odds ratio 2.82, p=0.030) and a longer length of stay (2.10 vs 1.30 days, p=0.003). The frail group appears to have higher hospitalization costs, but the result was not statistically significant ($122668.2 vs $114295.3, p=0.091).

Conclusions:
The presence of frailty was associated with an increased risk of hemorrhage requiring transfusion and a longer length of hospital stay after elective left atrial appendage closure.
Abstract 13616: Dismantling Structural Racism Starts With Understanding the Type of Hospitals That Provide Segregated Cardiovascular Care
Authors: Breathett Khadijah , Hollingsworth John , Shay Addison , Murali Sitara , Yan Phyllis , Yu Xianshi , Zhu Ji , Nallamothu Brahmajee K
Published: April 2022

Background:
Black patients receiving coronary artery bypass grafting (CABG) have higher likelihood of mortality if care is received in a highly segregated care settings, where healthcare professional care (HCP) teams predominantly treat either White or Black patients. It is unclear what factors are associated with being a hospital that provides segregated healthcare.

Methods:
Using the 100% Medicare Provider Analysis and Review file, we identified Fee-for-Service beneficiaries who underwent CABG from 2012 to 2018. We fit a multivariable logistic regression model to assess factors associated with higher odds of receiving high versus low segregated care for CABG. We accounted for the nested data structure (patients within hospitals) using a robust variance estimator and included in our model factors like patient sociodemographics, level of comorbidity, and hospital and hospital service area characteristics. Analogous to the dissimilarity index, care segregation equated to differences between relative frequency of Black and White patients summed over all billing HCP.

Results:
Among 312,503 patients (69.9% male, 84.5% White race) from 563 U.S. hospitals, a higher number of Black patients undergoing CABG at a hospital center [OR: 0.93 (95%CI 0.90-0.96)] and higher number of billing HCP [OR: 0.68 (95%CI 0.59-0.78)] were both associated with significantly lower odds of delivering high segregated care than low segregated care in fully adjusted analyses (Table). No other factors were associated with care segregation, including geographic region of hospital.

Conclusions:
Hospitals which routinely provide CABG to higher numbers of Black patients and employ a larger number of HCP were less likely to deliver segregated care. Dismantling structural racism in healthcare requires investigation of how to replicate cultural and business models of the low segregation hospitals that promote care of diverse patient populations.
Abstract 13625: Association of Antiphospholipid Antibodies With Venous Thromboembolism in COVID-19
Authors: Sharma Prerna , Popoola Victor , Sharma Aditya , Albon Dana
Published: April 2022

Introduction:
Coagulation abnormalities leading to arterial and venous thrombotic events have been described in patients with COVID-19 and studies have reported an overall pooled incidence of venous thromboembolism (VTE) of 17%, however little is known regarding VTE association with antiphospholipid antibodies in patients with COVID-19.

Hypothesis:
Antiphospholipid antibodies are associated with VTE events in COVID-19.

Methods:
This is a retrospective cohort study of COVID-19 patients hospitalized at the University of Virginia Medical Center (UVA). Serum samples were collected and stored in the UVA COVID-19 biorepository. Anti-cardiolipin (aCL) and anti-b2glycoprotein1(ab2GLP1), IgM/IgG titres, were measured from stored samples, using the enzyme-linked immunosorbent assay (ELISA). Specimens were analysed at two distinct time-points/days during the patient’s hospitalization for COVID-19. VTE incidence was collected retrospectively by chart review. The study was approved by the Institutional Review Board at UVA. Two-tailed Mann-Whitney two-sample rank-sum tests were conducted to examine whether there were significant differences in APS antibody levels, and mean change in APS levels between the two time points analysed, and VTE events. Additionally, logistic regression models were constructed to examine whether APS antibody levels and mean change in APS levels had a significant effect on the odds of observing a case of VTE.

Results:
There were 53 patients included in the study. The mean age of participants was 57.2 years (SD 13.9). VTE did not corelate with the levels of APS at studied time points, or the mean change in APS levels during the disease course. aCL IgM (p = 0.24), aCL IgG (p = 0.92), ab2GLP1 IgM (p = 0.79), and ab2GLP1 IgG (p = 0.79). Changes in the APS antibody levels during the course of the disease were not predictive of the odds of having VTE. Similarly, these changes did not predict the need for ICU care.

Conclusions:
This study shows that neither the presence of antiphospholipid antibodies nor the change in APS levels during the course of COVID-19 correlated with VTE events.
Abstract 13645: Contemporary Propensity-Matched Analysis Reveals Alarmingly High Risk Of Mortality, Arrhythmia And Cardiac Arrest In Nationwide Hospitalizations Of Patients With Heart Failure With Preserved Ejection Fraction And Cannabis Use Disorder
Authors: Sachdeva Sonali , Chhina Arashpreet , Gawde Rashmi , Rahim Naima A , Jnaneswaran Geethu , Raju Athul Raj , Neha , , Gandhi Zainab , Desai Rupak
Published: April 2022

Background:
Preliminary reports have suggested a link between cannabis use and heart failure (HF); however, with inconclusive literature on the subject, there exists an unmet need for contemporary data on outcomes of HF patients with cannabis use. The rising prevalence of Heart Failure with Preserved Ejection Fraction (HFpEF) incited us to assess the impact of cannabis use disorder (CUD) on in-hospital outcomes of HFpEF using nationwide multicenter data.

Methods:
Adult admissions related to HFpEF with vs. without CUD were identified using the National Inpatient Sample (Oct 2015-Dec 2017). Demographically matched cohorts, HFpEF-CUD+ vs. HFpEF-CUD-, were obtained and compared for comorbidities and in-hospital outcomes. Multivariable regression analyses were performed after controlling for confounders (demographic/hospital characteristics, comorbidities and substance abuse) to assess the risk of adverse outcomes including all-cause mortality, arrhythmia (atrial fibrillation/flutter, ventricular arrhythmia & cardiac arrest) and stroke.

Results:
Of 3,835,473 HFpEF-related admissions, 10980 (0.3%) patients were cannabis users. Matched cohorts, CUD+ and CUD- were comparable for demographics (median age 55 vs. 54 years, >60% male, >80% white/black). The CUD+ cohort had a lower rate of comorbidities including hypertension (87.5% vs 88.5%), diabetes (33.7% vs 43.7%), hyperlipidemia (38.4% vs 42.1%), obesity (26.7% vs 36.2%), and renal failure (32.8% vs 39.8%) (Table 1). Despite a lower comorbidity burden, the CUD+ cohort was often admitted non-electively (95.2% vs. 92.8%) and had considerably higher odds of all-cause mortality (aOR 2.24, 95%CI:1.81-2.78), arrhythmia (aOR 1.15, 95%CI:1.05-1.25) and cardiac arrest (aOR 3.87, 95%CI: 2.88-5.21) (p<0.05) (Fig. 1).

Conclusions:
This nationwide multicenter analysis revealed HFpEF admissions in patients with CUD had a significantly higher risk of adverse in-hospital outcomes despite a lower CVD risk.
Abstract 13647: Genetic Deletion of Interleukin-22 Prevents Angiotensin II-Induced Cardiac Diastolic Dysfunction in Mouse
Authors: Yamamoto Mai , Yasukawa Hideo , Takahashi Jinya , Nohara Shoichiro , Minami Tomoko , Shibata Tatsuhiro , Yanai Toshiyuki , Okabe Kota , Akagaki Daiki , Fukumoto Yoshihiro
Published: April 2022

Introduction:
Interleukin-22 (IL-22) is a member of the IL-10 cytokine family, which promotes STAT3 activation in targets cells. Although it has been shown that persistent activation of STAT3 causes myocardial hypertrophy and fibrosis, little is known about the effect of IL-22 in the pathogenesis of cardiac diastolic dysfunction.

Hypothesis:
We hypothesized that IL-22 would be a factor that cardiac diastolic dysfunction.

Methods and Results:
We used angiotensin II (AngII) infusion mouse model, which has been reported to increase serum IL-22 levels, to cause cardiac diastolic dysfunction. We first investigated the effect of IL-22 deletion to cardiac function. Wild-type (WT) mice and IL-22 deficient (IL-22 KO) mice were compared cardiac function after 2 weeks AngII infusion. Echocardiographic analysis showed no decrease in systolic function as indicated by EF in both groups. However, In WT mice, E/e' was significantly increased compared to before AngII infusion. In contrast to WT mice, E/e' was not increased in IL-22KO mice by AngII infusion. These results suggested that AngII- induced cardiac diastolic dysfunction was prevented in IL-22KO mice. Next, we analyzed the effect of IL-22 deletion to histological changes. Compared to WT mice, ventricular weight to body weight ratio was significantly smaller in IL-22KO mice after 2 weeks AngII infusion. Echocardiographic analysis also showed that ventricular wall thickness was suppressed in IL-22KO mice. Sirius red staining revealed no difference in myocardial fibrosis between WT mice and IL-22KO mice after 2weeks AngII infusion.

Conclusions:
These results suggest that IL-22 plays an important role in the pathogenesis of AngII- induced cardiac diastolic dysfunction and cardiac hypertrophy.