bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11041: Time Course of Recovery from Left Ventricular Systolic Dysfunction in Patients with Arrhythmia and Newly Diagnosed Heart Failure
Authors: Schach Christian , Koertl Thomas , Harler Bianca , Muehleck Franzisk , Baum Paul , Zeman Florian , Meindl Christine , Resch Markus , Maier Lars S , Wachter Rolf , Sossalla Samuel T
Published: March 2022

Background:
Newly diagnosed heart failure and concomitant persistent arrhythmia often is a challenging situation for clinicians, especially if left ventricular systolic dysfunction (LVSD) is otherwise not explainable. The time to recovery of arrhythmia-induced cardiomyopathy (AIC) is not well known and the prevalence of this disease is likely underestimated.

Purpose:
As AIC only can be diagnosed after rhythm control (RC) and thereafter recovery from LVSD (diagnosis ex juvantibus), we aimed to characterize the time course of recovery and describe the prevalence in such a specific cohort.

Method and Results:
We prospectively screened 95 patients hospitalized for newly diagnosed and otherwise unexplainable LVSD (left ventricular ejection fraction (LVEF) <50%) and coexisting tachyarrhythmia (atrial fibrillation/flutter + heart rate (HR) >100/min) in three cardiological centers. Coronary angiography and cardiac magnetic resonance imaging were performed to exclude other causes for LVSD. RC was achieved by electrocardioversion, ablation, pharmacologically or a combination of those. 50 of 68 included patients (age 69±11y, 63% male, LVEF 35.6±8%, mean±SD) were free from recurrent arrhythmia after 6 months and analyzed: AIC was diagnosed by any increase of ≥15% in absolute LVEF or an LVEF ≥50% with an improvement of ≥10% 6 months after RC; all others were diagnosed idiopathic DCM. LVEF was assessed by echocardiography at presentation and at follow-up visits 2, 4, and 6 months after RC. 9 patients did not meet the AIC-criteria, resulting in a prevalence of 82% for AIC. At presentation, AIC vs. DCM had smaller left ventricles (LVEDD 53.6±7.5 vs. 59.7±3.1mm, P<0.05; LVESD 44.4±6.6 vs. 51.6±5.1mm, P<0.01), biomarkers did not differ: NT-proBNP 4525±4535 vs. 4793±4076pg/mL, P=n.s., Troponin T-hs: 46.8±108.8 vs. 22.9±15.7ng/L, P=n.s.. 2 and 4 months after RC, 58% and 73% of patients fulfilled AIC criteria.

Conclusion:
The prevalence of AIC in patients in this specific collective with newly diagnosed and otherwise unexplainable LVSD with concomitant persistent tachycardia is surprisingly high and the time course of recovery suggests that the final diagnosis cannot be established before 6 months after rhythm restoration.
Abstract 11043: Clinical Safety Outcomes in Relation to Lipoprotein(a) Concentration: Insights from the FOURIER Trial
Authors: Gencer Baris , Giugliano Robert P , Tang Minao , Mach Francois , Stroes Erik S , Gouni-berthold Ioanna , Ceska Richard , Ezhov Marat , Jukema J Wouter W , Jensen Henrik , Tokgozoglu Lale S , Huber Kurt , Sabatine Marc S , Odonoghue Michelle L
Published: March 2022

Background:
Lipoprotein(a) is believed to play a causal role in atherogenesis. Drugs are in development that directly target Lp(a) and lower levels by >75%. Thus, the safety of low Lp(a) levels is of importance.

Methods:
FOURIER randomized 27,564 patients w/ stable ASCVD to evolocumab (EVO) vs placebo on background statin (median f/up 2.2 y); EVO lowered Lp(a) levels by 27%. The relationships between Lp(a) levels, change in Lp(a) and 5 safety outcomes of interest based on prior reports (diabetes [DM], serious bleeding, hemorrhagic stroke, neurocognitive events, malignancy) were examined. Analyses were conducted in the overall population and by treatment arm. Multivariable models included age, sex, race, region, clinical predictors, high-intensity statin, ezetimibe, baseline hs-CRP, “Lp(a)-corrected” LDL-C, and treatment arm.

Results:
Lp(a) was assessed in 25,083 participants at baseline (median 37nM, range 5-1451) and 25,686 at week 12. There was no association between baseline or achieved Lp(a) levels and risk of serious bleeding, hemorrhagic stroke, neurocognitive events, or malignancy, even in the 3271 patients with Lp(a) levels ≤6nM. There was an inverse association between baseline Lp(a) levels and prevalent or incident DM [OR 1.09, 95%CI 1.07-1.12, for every 50nM lower Lp(a) below 250nM]. However, absolute change in Lp(a) with EVO was not associated with subsequent DM risk (HR 1.03, 0.91-1.16, per 50nM) and EVO did not increase the risk of DM irrespective of baseline Lp(a) (P int=0.97), even in participants in the top decile of baseline Lp(a) (HR 0.91, 0.51-1.62) in whom EVO reduced Lp(a) by 63nM.

Conclusion:
Lp(a) concentration and changes in Lp(a) were not associated with serious bleeding, hemorrhagic stroke, neurocognitive events, or malignancy. Levels were inversely correlated with having DM, but Lp(a) lowering over a median of 2.2 years with EVO did not further increase the risk. These findings provide new insights for ongoing trials of Lp(a)-lowering drugs.
Abstract 11047: Racial Balance in Heart Failure Treatment, Use of Implantable Left Ventricular Assist Devices, and Cardiac Transplantation
Authors: Musfee Fadi I , hamden randa , Buddha Mrinalini , Naizer Hayden , Zingg Guzman Alexandra Q , Ganduglia Cazaban Cecilia M , Letsou George V
Published: March 2022

Introduction:
The incidence of left ventricular assist device (LVAD) implantation in heart failure (HF) patients across various racial groups has not been examined in large databases. We present an analysis of racial groups and LVAD implantation using a large US database.

Methods:
We analyzed data from a commercial and a national Medicare database using OPTUM® Clinformatic® Data Mart and a Medicare National Sample that comprised 57,585,519 US patients. We identified 346,345 adults with HF from 2014 to 2016. Comorbidities were identified including diabetes, coronary artery disease, hypertension, and cardiomyopathy. Data were collected for LVAD implantation, stroke, cerebral injury, mechanical ventilation, heart transplantation, renal insufficiency, and death through 2019 or until they were no longer enrolled. Race, sex, and age were discerned from enrollment information.

Results:
The incidence of HF was similar across all 5 racial groups (Table). Age at the time of HF diagnosis and LVAD implantation was lower in Blacks than in other races. LVADs were implanted at a higher rate in Blacks than in other groups. Age at LVAD implantation was lower in black men than in men of other races. Whites had a lower incidence of stroke, intracranial bleed, and cerebral injury after LVAD implantation than did Blacks, Hispanics, and Native Americans. The rate of eventual transplantation was similar among all groups. Because of the large database population analyzed, differences between groups were highly significant, with p<0.0001.

Conclusions:
In the largest US database analysis to date, we found that US racial groups showed no significant differences in the incidence of HF, rate of LVAD implantation, survival after LVAD implantation, or progression to cardiac transplantation. However, Blacks were diagnosed with HF and underwent LVAD implantation at somewhat younger ages than other groups.
Abstract 11051: A Common Variant Near the Fibrinogen Gamma Chain Gene is an Independent Risk Factor for Thrombosis After Congenital Heart Surgery
Authors: Mercer Evan T , Weiner Jeffrey G , Van Driest Sara , Breeyear Joseph , Edwards Todd L , Kannankeril Prince J
Published: March 2022

Introduction:
Postoperative thrombosis is a common complication after congenital heart disease (CHD) surgery in children, and is associated with increased mortality and morbidity. Identification of risk factors may allow preventive therapy and improved outcomes.

Hypothesis:
We tested the hypothesis that genetic variants are associated with postoperative thrombosis after CHD surgery in children.

Methods:
Children with CHD were prospectively enrolled in an observational cohort study at the time of initial surgical repair/palliation. Clinically detected thrombosis within 30 days of surgery while in hospital was the primary outcome. Patients were genotyped on the Axiom Precision Medicine Research Array. Clinical and genetic (8 common variants in candidate genes) factors were assessed for association with the primary outcome with univariate and multivariate analysis. A two-tailed P-value of < 0.05 was considered statistically significant.

Results:
A total of 2,398 unique patients (median age 6 months, median weight 6.7 kg) had complete clinical and genetic data for analysis. Postoperative thrombosis occurred in 242 (10.1%). Patients with thrombosis were younger (P<0.001), with longer bypass time (P<0.001) and higher initial postoperative lactate (P<0.001). Thrombosis was also associated with longer hospital stay (50 ± 59 days vs 16 ± 31days, P<0.001) and mortality (15.3% vs 2.9%, P<0.001). One common variant near fibrinogen gamma (
FGG
, rs7659024, NC_000004.12:g.154599778G>A) was associated with postoperative thrombosis, with a gene-dose effect (thrombosis observed in 8.9% GG, n=1370, 11% AG, n=869, 15.1% AA, n=159, P=0.025). In multivariate analysis age (per year older OR 0.7, 95% CI 0.61-0.79), bypass time (per hour OR 1.24, 95% CI 1.09-1.39), lactate (per mmol/L OR 1.15, 95% CI 1.19-1.32) and
FGG
genotype (GG reference, AG OR 1.51, 95% CI 1.09-2.08; AA OR 2.35, 95% CI 1.39-3.97) were each independently associated with postoperative thrombosis.

Conclusions:
A common variant near
FGG
previously associated with fibrinogen γ′ levels is an independent risk factor for postoperative thrombosis after CHD surgery. Preoperative genotyping with thromboprophylaxis for patients at sufficient risk may be considered.
Abstract 11056: Thoracoscopic Left Atrial Appendage Occlusion with Atriclip
TM
: An Initial Experience
Authors: Wang Edward , Joshi Pragnesh , Sadleir Paul , Weerasooriya Rukshen , Playford David
Published: March 2022

Introduction:
Left atrial appendage (LAA) closure is an important tool in stroke prevention. Totally thoracoscopic LAA closure using the AtriClip™ device avoids intracardiac components, although early outcomes have not been systematically documented.

Methods and Results:
105 consecutive fully thoracoscopic AtriClip
TM
procedures were examined, involving 84(80%) males, 21(20%) females and mean (+/- SD) age 70.1+/-9.2 years. The most common indication was as part of an AF ablation procedure (n=38, 36.2%), or anticoagulation-related hemorrhage (n=27, 25.7%). Median (interquartile range, IQR) CHADS
2
VaSc = 3 (2-4) and HAS-BLED = 3 (1-3). Half the patients (n=51, 48.6%) underwent isolated AtriClip insertion, 90% had a size 40 or 45mm AtriClip device, and none experienced circumflex coronary artery or phrenic nerve compromise. Intraprocedural transesophageal echocardiography demonstrated complete occlusion in all patients. Follow-up at 6 weeks with CT or transesophageal echocardiography confirmed occlusion in all patients (79% follow-up). The length of stay for isolated thoracoscopic AtriClip
TM
was 3 days (IQR 2-4) with longer admissions due to unrelated conditions (e.g. heart failure, AF or chest infection). No cases of LAA perforation were recorded and no patients with isolated AtriClip required transfusion. Transient pericarditis occurred in 10 patients (9.5%, 5 requiring readmission within 30 days) with a pericardial effusion in 3 patients (2.9%, requiring pericardiocentesis in one patient). No strokes occurred and 93% of isolated Atriclip patients had ceased anticoagulation at 30 days.

Conclusions:
Total thoracoscopic LAA closure using the AtriClip device is safe and effective. The most common complication is transient pericarditis (9.5%) and major complications were not seen.
Abstract 11062: The δC Isoform of Ca
2+
/Calmodulin-Dependent Protein Kinase II (camk2) Regulates Cardiac Metabolic Substrate Switching in Mice
Authors: Saadatmand Alireza , Pepin Mark E , Dewenter Matthias , Haberkorn Uwe , Backs Johannes
Published: March 2022

Introduction:
Ca
2+
/calmodulin-dependent protein kinase II (CaMK2) is a recognized driver of pathological cardiac remodeling and heart failure, but its role in the metabolic reprogramming of heart failure remains unclear, as do the molecular processes that trigger this pathologic switch.

Hypothesis:
Myocardial CaMKIIδ drives the pathological remodeling of cardiac metabolic substrate preference.

Methods and Results:
Adeno-associated viral (ssAAV9) overexpression of constitutively-active cytosolic (CaMK2δC) and nuclear (CaMK2δB) CaMK2δ isoforms, as well as the catalytic PKA subunit (PKAca), were created under the control of the cardiac troponin-T promoter and introduced via tail-vein injection into 12-week old mice (1 x 10
12
v.g., n = 5).
In vivo
metabolic phenotyping via 18-fluorodeoxyglucose (
18
FDG)-based positron emission tomography (PET) revealed a 3.4-fold (P = 0.02) higher glucose uptake among mice receiving ssAAV9-TnnT-CaMK2δC commensurate with cardiac CaMK2δC expression. In contrast, no differences were seen in glucose uptake following AAV overexpression of cardiac CaMK2δB or PKAca relative to luciferase control vector. Echocardiography subsequently revealed a 14.6% decrease in left ventricular ejection fraction at 6 weeks following CaMK2δC overexpression (P = 0.047), whereas no changes were seen following CaMK2δB or PKAca overexpression in systolic or diastolic cardiac parameters. Conversely, transcriptomic analysis of hearts from mice lacking cardiac CaMK2δC expression revealed disproportionate up-regulation of fatty acid oxidative genes (P < 0.001).

Conclusion:
Taken together, these preliminary findings implicate CaMK2δC as a crucial regulator of the cardiac metabolic reprogramming that likely precedes the hemodynamic manifestations of cardiac dysfunction in heart failure.
Abstract 11063: Non-Ischemic Fibrosis on Cardiac Magnetic Resonance Impacts Adverse Left Ventricular Remodeling and Mortality Among Patients with Functional Mitral Regurgitation
Authors: Kanduri Jaya , Mitlak Hannah W , Park Christine , Nambiar Lakshmi , Tak Katherine , Tafreshi Romina , Devereux Richard B , Levine Robert A , Ratcliffe Mark B , Kim Jiwon , Weinsaft Jonathan W
Published: March 2022

Introduction:
Functional mitral regurgitation (FMR) alters left ventricular (LV) remodeling, providing a nidus for non-ischemic fibrosis (NIF). Cardiac magnetic resonance (CMR) can measure FMR and LV tissue properties. Prevalence, remodeling manifestations, and prognostic implications of NIF in patients with FMR are unknown.

Hypothesis:
Among post-myocardial infarction (MI) patients with FMR, NIF associates with advanced LV remodeling and predicts adverse prognosis.

Methods:
The population comprised post-MI patients with FMR undergoing CMR. CMR exams were retrieved from a single-center registry, reviewed for MR etiology (degenerative excluded) and analyzed for FMR severity, LV structure/function, and late gadolinium enhancement (LGE) including ischemic pattern MI and NIF, which was defined via established criteria (mid-myocardial or epicardial LGE). Follow-up was performed for all-cause mortality.

Results:
467 consecutive FMR patients (74% male, 63±16 years old) were studied, of whom 14% had NIF. Prevalence of NIF increased stepwise with FMR severity (12% mild, 16% moderate, 21% severe; p=0.33). Patients with NIF had higher LV end-diastolic (241±72ml vs 194±64ml) and end-systolic volumes (174±70ml vs 120±63ml), paralleled by lower EF (31±13% vs 41±15%) and stroke volumes (67±20ml vs 74±24ml); all p<0.001. LV infarct size was similar between patients with and without NIF (13±8.6 vs 15±10, p=0.17). During follow-up (mean 3.0±2.5 years), overall mortality was 14% and was increased in patients with advanced (≥ moderate) FMR (HR 1.65 [CI 1.13-2.42], p=0.01) and NIF (HR 2.35 [CI 1.32-4.19], p=0.004: Figure). In multivariate analysis, NIF conferred over a 2-fold increase in risk for death (HR 2.15 [CI 1.20-3.85], p=0.01) independent of age and FMR severity.

Conclusions:
Among post-MI patients with FMR, NIF identifies an aggressive phenotype as evidenced by associations with adverse LV remodeling on CMR and increased mortality.
Abstract 11068: Smad3-Deficiency in Murine Smooth Muscle Cells Causes Global Defects in Expression of Focal Adhesion Components, but Drives Subset-Specific Compensatory Mechanisms Promoting Matrix Degradation and Oxidative Stress
Authors: Bramel Emily E , Creamer Tyler J , Saqib Muzna , Camejo Nunez Wendy A , Goff Loyal A , Gallo MacFarlane Elena
Published: March 2022

The pathogenesis of aortic aneurysms caused by mutations that impair TGF-β/Smad signaling without completely ablating it remains unclear. To investigate TGF-β’s role independently of its developmental functions, we used mouse models to inactivate
Smad3
specifically in smooth muscle cells (SMCs) at 6 weeks of age, when postnatal matrix deposition is largely completed. This intervention was sufficient to induce dilation in the aortic root, but not the ascending aorta. To identify factors underlying this regional vulnerability, we analyzed aortas from control and Smad3-deficient mice by single-cell transcriptomics 10 weeks and 18 weeks after deletion, when dilation is undetectable and moderate, respectively. Three major SMC clusters were identified regardless of genotype or time-point. In situ hybridization showed that the aortic root and proximal ascending aorta were enriched in SMCs expressing cluster-defining transcripts for Cluster 3 and 2, while distal ascending and aortic arch were for Cluster 1. At the early time-point, all SMC clusters showed defective expression of genes coding for components (
Fblim1
,
Svil
,
Tes
and
Tln1
) and regulators (
Abra
and
Rock1)
of focal adhesions in response to
Smad3
inactivation. These defects associated with Cluster 3-specific upregulation of positive effectors of the TGF-β pathway, such as
Tgfb2,
and down-regulation of negative regulators of Angiotensin II signaling, such as
Rgs2
and
Rgs4
. At the later time point, whereas Smad3-deficient SMCs in Cluster 3 retained a similar profile, those in Cluster 2 showed transcriptional alterations consistent with increased TGF-β/Smad2 activation, accompanied by upregulation of
Neat1
, a lnc-RNA critical for SMC phenotypic switching. These included potentially adaptive changes, such as upregulation of genes coding for collagen and its processing enzymes (
Col1a2
,
Col3a1, Lox
and
Loxl1),
and maladaptive ones such as upregulation of proteases (
Fap
and
Mmp9)
, and upregulation of enzymes promoting oxidative stress (
Nox4
). These data suggest that Smad3-deficiency causes defective expression of focal adhesion machinery in SMCs, initiating secondary subset-specific compensatory mechanisms driving localized pathogenic increases in proteolysis and oxidative stress.
Abstract 11079: Calcitonin Signaling Controls Disease-Induced Left Ventricular Remodeling
Authors: Takawale Abhijit R
Published: March 2022

Introduction:
We recently discovered that the well-known thyroid hormone calcitonin (CT) is produced by atrialcardiomyocytes (CMs) and regulates atrial fibrogenesis and arrhythmia susceptibility via CT receptors (CTRs) inatrial cardiofibroblasts (CFs). Whether the CT-CTR system regulates ventricular function and structure isunknown and was the object of this study.

Method and Results:
Human studies were performed on left ventricular (LV) samples from 27 patients who hadcardiac surgery (Oxford, UK; ethical approval 18/SC/0404). Animal studies used 8-10 week-old male control(CTR
flx/flx
; n=150) and CTR
-/-
(n=131) mice subjected to transverse aortic constriction (TAC) and myocardialinfarction (MI), with selected analyses in wild type mice (n=5). Cardiac function was assessed byechocardiography at baseline, 3 and 6 weeks post-TAC, and 1 and 4 weeks post-MI.Expression profiling detected CTR and CT mRNA (qPCR; Fig. A-B) and protein (immunoblotting) in human LVtissue and mouse LV CMs and CFs, with a higher CT abundance in CMs. CTR protein was decreased in LV tissue from patients with hypertension vs non-hypertensive controls (Fig. C).CTR deletion enhanced atrial and LV fibrosis (Masson’s Trichrome; Fig. D-E), significantly exacerbated post-TAC LV ejection fraction reduction by 15.2% (Fig. F), and atrial (by 23.7%, Fig. G) and LV dilation (by 19.9%),while increasing induced-AF duration by 6-fold (Fig. H) and inducibility by 15% vs post-TAC controls.In CTR
-/-
mice, acute MI produced greater fibrosis in the LV risk-region (by 18%; Fig. I), ejection fractionreduction (by 14%, Fig. J) vs CTR
flx/flx
controls. Mortality, atrial dilation and AF-inducibility were similar inCTR
-/-
and control MI-mice.

Conclusion:
CTR deletion in mice exacerbates adverse LV remodeling and dysfunction in clinically-relevantdisease models, pointing towards an important protective role of CT-CTR signaling in ventricular myocardium.
Abstract 11080: A Young Woman with Incessant Left Atrial Tachycardia
Authors: Khetarpal Banveet K , Chokshi Binna M , Fakhra Sadaf , Gururaj Arjun
Published: March 2022

Introduction:
Left atrial tachycardia (AT) is uncommon and usually does not occur in the absence of congenital heart disease, or prior catheter ablation (CA).

Case:
A 29-year-old woman with a 2-year history of SVT refractory to metoprolol and no prior CA presented to the emergency department with palpitations. Initial ECG showed a regular, narrow complex, short RP tachycardia, at 180 bpm, insensitive to adenosine and 2 electrical cardioversions. Echocardiogram showed LVEF of 40%. The patient underwent an entirely non-fluoroscopic electrophysiology study using intracardiac echocardiography and electroanatomic mapping (EAM). AT (cycle length 300 ms) was induced by programmed atrial stimulation with isoproterenol infusion. AT was confirmed with ventriculo-atrial dissociation after pacing maneuvers and adenosine administration. Right atrial (RA) activation map revealed early atrial activation in the mid coronary sinus (CS), raising suspicion of a left atrial (LA) origin. LA was accessed via transseptal puncture. The site of earliest atrial activation was in the LA wall inferior to the left inferior pulmonary vein (LIPV) ostium and was successfully terminated with radiofrequency ablation (40 W, 5 to 10 g) (Figure) with no further inducibility. The patient's symptoms resolved after the procedure.

Discussion:
Left AT usually originates from PVs or the atrial wall. The EAM in this patient showed centrifugal activation consistent with a focal mechanism. Adenosine is generally not helpful in terminating AT but is useful in diagnosis. Rapid conduction across the LA to CS may have given rise to early activation in the mid CS on RA mapping. However, LA mapping revealed that atrial activation was earliest in the LA wall inferior to the LIPV.

Conclusion:
AT is unusual in young, healthy women. A high index of suspicion to perform transseptal puncture can lead to successful ablation of AT with LA origin. We surmise that the patient’s EF may improve with termination of the tachycardia.
Abstract 11081: Measures of Food Inadequacy and Cardiovascular Disease Risk in Black Americans: The Jackson Heart Study
Authors: Zierath Rani , Claggett Brian , Hall Michael E , Correa Adolfo , Barber Sharrelle , Gao Yan , Talegawkar Sameera , Ezekwe Edith , Tucker Katherine L , Diez-Roux Ana , Sims Mario , Shah Amil M
Published: March 2022

Introduction:
Food insecurity is common in the U.S. and disproportionately impacts Black Americans, but its association with risk of heart failure (HF) and coronary heart disease (CHD) is unclear. We evaluated the associations of economic food insecurity and proximity to unhealthy food options with risk of incident HF and CHD, and assessed the potential impact of diet quality and stress on these associations.

Methods:
Among 3,024 Black adult participants in the community-based Jackson Heart Study (JHS) without prevalent HF or CHD who attended visit 1 (2000-2004), the associations of economic food insecurity (receiving food stamps, self-reported ‘not enough money for groceries’) and proximity to unhealthy food stores (>2.5 unfavorable food stores [fast food restaurants, convenience stores] within 1 mile) with incident HF hospitalization and CHD were assessed using multivariable Cox proportional hazard models. Adjustment covariates included age, sex, BMI, hypertension, and diabetes in the initial model and diet quality (Healthy Eating Index) and perceived stress (total Global Perceived Stress score) in the extended model.

Results:
Mean age was 54±12 years, 34% were men, 630 (21%) were economically food insecure, and 1,512 (50%) had >2.5 unfavorable food stores within 1 mile. In multivariable models, economic food insecurity was associated with a heightened risk of incident HF and of incident CHD, which persisted with minimal attenuation after further adjustment for diet quality and perceived stress (Table). Limited physical food access was not associated with heightened risk of incident HF or CHD after accounting for demographics.

Conclusions:
Economic food insecurity, but not proximity to unhealthy food options, is associated with HF and CHD risk independent of traditional cardiovascular risk factors. Increased perceived stress and worse diet quality do not appear to account for these associations.
Abstract 11095: Three Year After Acute Coronary Syndrome, 6/10 of the Patients Are Treated in Accordance with International Guidelines in Middle East and North Africa: The Touraco Study
Authors: Shoby Mohamed , Arafah Mohammed , Alsayed Mohamed , Al suwaidi Jassim M , Baslaib Fahad , Rajadhyaksha Viraj , Nibouche Djamaleddine , Hany Ragy , Rhouati Adel , Bazargani Nooshin , Guindy Ramez
Published: March 2022

Introduction:
The TOURACO study aimed to describe the short- and long-term (i.e., up to 3 years following the index event) management in patients hospitalized for an ACS, and the compliance with ESC and AHA/ACC guidelines in a ‘real-life’ setting in the Middle East and North Africa (MENA) area.

Methods:
TOURACO is an observational prospective study on adults hospitalized within 24 hours of ACS onset between December 2015 and February 2017 and having given written informed consent, in Algeria, Bahrain, Egypt, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates. Initial care, hospitalization and follow-up (1, 6, 12, 24 and 36 months after hospital discharge) data were recorded. Patients were followed-up until April 2020.

Results:
1,131 eligible patients (mean age: 56 [49; 64] years; 927 (82.0%) males; median BMI: 28.1 [25.1; 31.6] kg/m2) were included; 602 (53.2%) patients had a STEMI, 306 (27.1%) patients a NSTEMI and 223 (19.7%) patients an UA. The most common risk factor was hypercholesterolemia, affecting more than half of the patients, and 43% of the patients were current smokers. However, during the 3 months preceding ACS, only 191 (17.1%) patients received an anti-thrombotic agent, 14 (1.3%) at least 2 anti-platelet agents, 151 (13.5%) patients a cholesterol lowering agent, 135 (12.1%) patients an anti-diabetic agent and 233 (20.9%) an anti-hypertensive agent. Compliance with guidelines 1 month after discharge was high (79.2%). At 1 year, compliance was available for 614 (55%) and remained high (77%). Compliance decreased overtime and reached 65% at 3 years. Cumulative mortality rate was relatively low with a rate of 1.7 ±0.4% at 1 month, 3.8±0.6% at 1 year, 5.1±0.7% at 2-year and 6.2±0.7% at 3-years.

Conclusions:
TOURACO is the first study assessing compliance of treatments with international guidelines in the MENA region. Compliance was good 1 month after the ACS episode and remained high for the next 3 years likely responsible for the low mortality. However, patient’s baseline characteristics at arrival were not optimum: a high proportion of patients were not treated for their diabetes and their hypertension , and smoking cessation. This study highlights the importance of preventive therapies.
Abstract 11097: Radiation Doses to Interventional Echocardiographers During Percutaneous Structural Heart Interventions
Authors: McNamara David A , Chopra Rajus , Decker Jeffrey , McNamara Michael , VanOosterhout Stacie , Berkompas Duane , Dahu Musa , Merhi William , Parker Jessica L , Madder Ryan D
Published: March 2022

Background:
The use of transesophageal echocardiography during percutaneous left atrial appendage closure (LAAO) and transcatheter edge-to-edge repair of the mitral valve (TEER) requires an interventional echocardiographer (IE) to stand near the radiation source. The occupational radiation exposure of IEs remains understudied.

Hypothesis:
IE experience higher radiation doses than interventional cardiologists and sonographers.

Methods:
Prospective, blinded radiation doses were collected by dosimeters worn by IEs, interventional cardiologists, and sonographers during 30 consecutive LAAO and 30 TEER structural heart cases at a tertiary care center. Measured personal dose equivalents per case were compared among the three groups.

Results:
Over the 60 procedures, the median radiation dose per case was 5-fold higher for IEs than interventional cardiologists (10.6 [4.2, 22.4] μSv versus 2.1 [0.2, 8.3] μSv, p<0.0005). During TEER, IEs received a median radiation dose of 10.5 [2.3, 20.9] μSv, which was 11-fold higher than interventional cardiologists (0.8 [0.0, 12.1] μSv, p = 0.0005). During LAAO procedures, the median radiation dose was 10.8 [5.9, 24.6] μSv among IEs and 3.6 [1.4, 6.5] μSv among interventional cardiologists, representing a 3.0-fold greater radiation dose to echocardiographers (p<0.0001). Compared to IEs, sonographers exhibited low radiation doses during both LAAO (0.2 [0.0, 1.6] μSv, p<0.001) and TEER (0.03 [0.00, 0.15] μSv, p<0.0001).

Conclusions:
During LAAO and TEER procedures, IEs were exposed to 3-fold and 11-fold higher radiation doses than interventional cardiologists, respectively. These comparatively higher radiation doses indicate an important occupational risk faced by IEs, which has implications for the rapidly expanding structural heart team.
Abstract 11104: Association of Cigarette Smoking and Coronary Artery and Extra-Coronary Calcification in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Ding Ning , Wang Frances , Obisesan Olufunmilayo H , Wagenknecht Lynne , Folsom Aaron R , Howard-Claudio Candace M , Coresh Josef , Budoff Matthew J , Blaha Michael J , Matsushita Kuni
Published: March 2022

Introduction:
Smoking is a major risk factor for atherosclerosis, but its impact is heterogeneous across different vascular beds (e.g., stronger association with peripheral artery disease than coronary disease). However, whether the association of cigarette smoking with vascular calcification is (dis)similar across vascular beds is uncertain.

Methods:
In 1,961 ARIC participants without a history of coronary heart disease at visit 7 (2018-19), we quantified the associations of pack-years of smoking and years since cessation with coronary artery calcium (CAC) and extra-coronary calcification (ECC) using multivariable logistic regression models. High CAC and ECC (aortic valve, aortic valve ring, mitral valve, ascending aorta, and descending aorta calcification) were defined as Agatston score >75th percentile and were analyzed separately as dependent variables.

Results:
Pack-years of smoking demonstrated an independent and robust dose-response relationship with CAC, ascending and descending aorta calcification, and aortic valve ring calcification (Table). The association was particularly evident for descending aorta calcification (e.g., adjusted odds ratio [aOR] 3.57 [95%CI 2.46-5.19] for ≥40 pack-years). The results were similar for the duration since smoking cessation, with the most prolonged risk seen for the descending aorta (i.e., even ≥30 years of smoking cessation had OR of 1.34 [1.03-1.47]). Aortic valve and mitral valve calcification demonstrated modest associations with smoking.

Conclusions:
Cigarette smoking showed a robust association with coronary and extra-coronary calcification, and its association was particularly strong with descending aorta calcification. Our findings further emphasize the harm of smoking on broad ranges of vascular beds and simultaneously highlight unique pathophysiologic mechanisms across different vascular beds and cardiac valves.
Abstract 11108: Association of a Virtual Career Development Forum with Confidence and Presentation Performance in Early-Career Academic Cardiologists During Covid-19
Authors: Taylor Bryan C , Fowler Joan B , Weaver Rebecca , Bonow Robert O , Lloyd-jones Don , Khan Sadiya
Published: March 2022

Introduction:
Academic cardiology continues to face significant challenges in retaining physician-scientists with attrition occurring at key steps in career development progression, particularly in the transition from fellow to faculty. Available data demonstrate that factors that may promote retention and support success for early-stage investigators (ESIs) include structured mentorship, networking and peer collaboration, and didactics on scientific writing. However, the impact of the COVID-19 pandemic on career development activities, such as the Northwestern Cardiovascular Young Investigators’ Forum (NCYIF), is not known.

Hypothesis:
An adaptive, virtual NCYIF format, delivered on a remote basis, can still achieve important educational and career development outcomes metrics, including confidence and performance by ESIs.

Methods:
In 2020, the NCYIF pivoted its in-person content to an online, virtual delivery using the following elements: pre-meeting technical skills and Zoom trainings, virtual presentation coaching sessions, interactive Zoom breakouts for mentoring (including near-peer alumni mentoring), and a downloadable mobile app. We conducted a pre- and post-meeting survey-based analysis to examine outcomes for ESIs who attended the virtual NCYIF meeting, including confidence in presentation skills and responding to questions by meeting judges (5-point Likert scale). All participants had an opportunity to meet 1:1 with a pre-meeting public speaking coach.

Results:
Of 31 attendees, 44% were fellows, 20% were women, and 61% were non-White. From pre- to post-meeting assessment, change in confidence increased significantly for presentation skills (3.07 vs. 3.46, p=0.009) and for ability to respond to questions and comments during the judging session (2.76 vs. 3.17, p=0.025). 68% of individuals completed pre-meeting coaching. Performance improvements were significant regardless of use of pre-meeting coaching support.

Conclusions:
Online-based delivery of a multi-day professional skills and career development forum for ESIs in academic cardiology resulted in significant improvements in confidence and presentation performance and supports the scalability of future content through a virtual platform.
Abstract 11110: Triomic Approach Reveals the Metabolic, Genomic and Proteomic Influences of the Endogenous Histidyl Dipeptides on Heart
Authors: Yan Keqiang , Mei Zhanlong , Zhao Jingjing , Obal Detlef , Katragadda Kartik , Hoetker David , Posa Dheeraj Kumar , Shah Jasmit , Lorkiewicz Pawel , Bhatnagar Aruni , Baba Shahid P
Published: March 2022

Background:
Histidyl dipeptides, such as carnosine (β-alanine-histidine) are synthesized in the heart
via
enzyme carnosine synthase (CARNS1). These dipeptides are present in the myocardium in micro-millimolar concentration, where they facilitate glycolysis and glucose oxidation by proton buffering and attenuate ischemia reperfusion injury. However, a composite understanding of their roles in myocardium is lacking.

Objective:
To understand the role of endogenous histidyl dipeptides in regulating the metabolic, genomic and proteomic profiles of heart under basal and ischemic conditions.

Methods and Results:
We found that mice with cardio specific overexpression of CARNS1, had higher myocardial levels of carnosine, anserine and homocarnosine. Under aerobic conditions, the transgenic hearts had lower levels of short- (dodecanal) and long-chain (propionic) fatty acids and TCA intermediate -succinic acid, and an increase in pyroglutamic acid-an intermediate of glutathione metabolism. When subjected to 5 and 15 min of ischemia, WT hearts showed progressive accumulation of fatty acids and depletion of amino acids, such as aspartate that were significantly attenuated in transgenic hearts. Further, the ischemic transgenic hearts had increased accumulation of citric acid cycle (TCA) intermediate - fumaric acid. Parallel with the increase in β-fatty acid oxidation and TCA cycle, transgenic hearts were enriched in enzymes of β-fatty acid oxidation and TCA cycle. Expression of enzyme glutathione synthetase that regulates pyroglutamic acid synthesis was decreased in the transgenic hearts. Overexpression of CARNS1 also led to a decrease in several micro RNAs, such as miR-6989 and miR-3100 which are paralleled to increased expression of succinate dehydrogenase and 2,3 enoyl-CoA hydratase. Further miR-142 levels in transgenic hearts were decreased that parallels with decreased glutathione synthetase.

Conclusion:
Our integrated analysis of metabolomics, transcriptomics and proteomics shows histidyl dipeptides are critical regulators of myocardial function and energetics. Importantly these dipeptides promote β-fatty acid oxidation and glycolytic activity under the basal and ischemic conditions.
Abstract 11114: Cardiovascular Disease Burden is Associated with Worsened Clinical Depression
Authors: Dhingra Radha , He Fan , Al-Shaar Laila , Saunders Erika F , Chinchilli Vernon M , Yanosky Jeff D , Liao Duanping
Published: March 2022

Objective:
To examine the association between prevalent cardiovascular diseases (CVDs) and CVD risk factors and depression symptoms in a US general population sample.

Methods:
US adults in the 2013-14 and 2015-16 National Health and Nutrition Examination Survey were included. CVDs (coronary heart disease [CHD], congestive heart failure [CHF], stroke) and CVD risk factors: current smoking; hypertension [HTN]; diabetes mellitus [DM]; and dyslipidemia; systolic BP (SBP), HbA1C, fasting plasma glucose (FPG), serum cholesterol (C), triglycerides (TG), HDL-C, and LDL-C were based on patient-report or lab tests, or medication prescriptions. The sum of HTN, DM, dyslipidemia, and current smoking represented a CVD risk score variable (range: 0-4). Depression symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9): 0-9 (none-mild); 10-27 (moderate-to-severe). Logistic regression models were used to assess the association between CVDs and moderate-to-severe depression.

Results:
A total of 12,105 participants (52% females, 64% Caucasians) of mean (SE) age of 46.8 (0.3) years and BMI of 29.2 (0.1) kg/m
2
were included. Moderate-to-severe depression was prevalent among 8.1% of participants. The proportions (%) of CVD risk score categories of 0-4 were: 20.5; 31.4; 32.1; 14.6; 1.5. After adjusting for age, race, sex, BMI, marital and educational status, participants with risk scores of 1; 2; 3; and 4 had 1.3 (95% CI: 0.8-2.1); 2.4 (1.5-3.7); 5.0 (3.2-7.8); and 5.5 (2.9-10.4) times higher odds of having moderate-to-severe depression, compared to those without CVD risk. One percent higher HbA1C and a five mg/dl decrease in HDL-C were associated with 1.1 (95% CI: 1.1-1.2) and 1.0 (95% CI: 1.0-1.1) times higher odds of having moderate-to-severe depression, respectively. Self-reported CHD; stroke; CHF; and any CVD were associated with 3.5 (1.8-6.7); 1.7 (0.7-3.9); 2.1 (1.3-3.4); and 2.1 (1.2-3.6) times higher odds of having moderate-to-severe depression, after additional adjustment for current smoking, LDL-C, SBP, and FPG.

Conclusions:
Prevalent CVDs and CVD risk factors are significantly associated with depression symptoms in the US general population, underscoring the need to integrate mental and physical healthcare services.
Abstract 11117: Metabolomic Signature of Ideal Cardiovascular Health in Black Adults: Results from the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity
Authors: Islam Shabatun , Liu Chang , Mohandas Appesh , Rooney Kimberly , Nayak Aditi , Mehta Anurag , Ko Yi-An , Kim Jeong Hwan , Olorundare Elizabeth I , Lewis Tene , Taylor Herman A , uppal karan , Jones Dean , Quyyumi Arshed A , Searles Charles D
Published: March 2022

Introduction:
Black Americans suffer from disparate levels of CVD and CVD risk factors, but metabolic pathways that underlie cardiometabolic risk in Blacks remain largely unknown.

Objective:
We defined metabolomic profiles and associated metabolic pathways underlying CVH in a Black community that is richly diverse in ethnic origin and socioeconomic status.

Methods:
The MECA study cohort consisted of 375 Black adults (age 53
+
10, 39% male) without known CVD. CVH was determined by the AHA Life’s Simple 7 (LS7) score, calculated from measured blood pressure, body mass index (BMI), fasting blood glucose, total cholesterol, and self-reported physical activity, diet, and smoking. Plasma metabolites were assessed by high-resolution metabolomics. Metabolome wide association study (MWAS) was used to identify metabolites associated with LS7 after adjusting for age and sex. Metabolic pathways significantly enriched in metabolites associated with LS7 were identified using Mummichog software. Concentrations of metabolites representative of these pathways were compared across clinical domains of LS7 score (ANOVA) and then a multivariable model was developed into a metabolomics risk score for prediction of CVH.

Results:
MWAS and pathway analysis identified 301 metabolites significantly associated with LS7 score (FDR<0.2) and enriched in pathways responsible for glutathione, alanine, tyrosine and glutamate metabolism. Plasma concentrations of six metabolites (glutamine, glutamate, serine, alanine, tyrosine and urate) were associated with blood pressure, fasting glucose, BMI, and physical activity (p<0.05). Assessed in conjunction, these metabolites were independent predictors of CVH - 1 SD increase in metabolomics risk score was associated with 0.93 increase in LS7 or 12.1% decrease in incident CVD.

Conclusions:
We identified a novel metabolomic signature of ideal CVH in Blacks without known CVD. This includes five non-essential amino acids and urate, which are known to be central elements of key metabolic processes (i.e. TCA cycle, urea cycle, nucleotide synthesis, one carbon metabolism). These data provide insight into metabolic pathways underlying cardiometabolic risk in Blacks and potential avenues for addressing health disparities.
Abstract 11120: Congenitally Corrected Transposition of the Great Arteries - Fetal Diagnosis, Associations and Natural History: A Fetal Heart Society Research Collaborative Study
Authors: Cohen Jennifer , Arya Bhawna , Donofrio Mary T , Harrington Jamie K , Ho Deborah Y , Hogan Whitnee J , Hornberger Lisa K , Killen Stacy A , Michelfelder Erik , Moon-Grady Anita J , Patel Sheetal R , Quezada Emilio , ronai christina , Sanchez Mejia Aura A , Schidlow David N , Srivastava Shubhika
Published: March 2022

Introduction:
Congenitally corrected transposition of the great arteries (ccTGA) is rare with varied associated cardiac defects and rhythm abnormalities. We aimed to describe the natural history, associated anomalies and prenatal outcome in a cohort of prenatally diagnosed patients in which biventricular repair is anticipated.

Methods:
A retrospective cohort study was conducted via the Fetal Heart Society Research Collaborative. All fetuses with ccTGA encountered at 15 North American cardiac centers between 1/2004-7/2020 were identified. Fetuses with a hypoplastic ventricle precluding biventricular repair were excluded. Data is presented as median (interquartile range).

Results:
Inclusion criteria were met in 139 fetuses who were diagnosed with ccTGA at 24 (21-29) weeks. There was a family history of congenital heart disease in 12%. Maternal diabetes was present in 10%. Prenatal genetic testing in 50 pregnancies was normal. Excluding 14 fetuses with heterotaxy, extracardiac anomalies were observed in 9/125 (7.1%). Associated cardiac/extracardiac defects are detailed in table 1. Fetal atrioventricular block (AVB) was present in 17 fetuses (12%), diagnosed at a median of 26 (23-28), range 20-36 weeks. Two fetuses had SVT; 1 self-resolved and 1 during labor. Change occurred during follow-up in 34 fetuses, most commonly in severity of tricuspid regurgitation (6 improved, 4 worsened) and worsening of pulmonary stenosis (n=5). There were 112 live births, 17 terminations, 2 fetal deaths (FD) and 8 lost to follow-up. Both fetuses with FD had AVB, making the intrauterine mortality associated with fetal AVB 11.8% (2/17).

Conclusions:
This study represents the largest cohort to date of fetuses with ccTGA. Fetal ccTGA is associated with a spectrum of cardiac defects that may evolve, with extracardiac pathology occurring in 7.1%. AVB is found in 12% of fetuses and is a risk factor for FD. This data informs fetal counseling and can aid in delivery planning and perinatal care.
Abstract 11122: Understanding Patients’ Experience in an Outpatient IV Diuretic Clinic
Authors: Emmons Margaret , D'Anna Susan , Cantlin Deborah , DeMark Carolyn , Ambrose Kim , Gilstrap Lauren
Published: March 2022

Introduction:
Nurse led, outpatient IV diuretic clinics are being established with the goal of improving heart failure (HF) care and reducing hospitalizations. To date, limited data exists regarding what is most important to the patients who receive care in this novel setting. In order to better understand patients’ priorities and to improve the quality of care delivered in the multidisciplinary, IV diuretic clinic, a qualitative study was undertaken.

Methods:
We conducted semi-structured interviews with 19 patients within 24-72 hours after they received care in the IV diuretic clinic to explore their expectations and experience in clinic as well as their care goals. The interview was recorded and transcribed. The recording was listened to while reviewing the transcript. The interviews were then analyzed and coded for thematic analysis. Based on the results of these qualitative interviews, changes to clinic operations were made and the patients’ clinic experience evolved over time (
Figure 1
).

Results:
In terms of care goals, almost all patients stated they wanted the clinic visit to “improve” or “relieve” their HF symptoms. Specifically, patients expressed wanting “fluid off” and a desire to be able to “breathe better.” Many expressed a desire to return to a “normal life.” In terms of expectations, patients expected the staff to be competent and were appreciative that the staff was available to them to answer questions. In terms of their experiences, patients were very satisfied with their clinic experience and appreciated that they did not have to be admitted to the hospital to receive care.

Conclusions:
An ongoing understanding of patients’ goals, expectations and experiences will enable us to continually refine the clinic processes and enhance the clinic experience to provide competent out of hospital care to HF patients.