bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14442: Tuberculosis-Specific Cell-Mediated Immune Responses Are Associated With Coronary Artery Atherosclerosis Among Persons With and Without HIV in Uganda
Authors: Huaman Moises A , Bittencourt Marcio S , Kityo Cissy M , Nalukwago Sophie , Nazzinda Rashidah , Fichtenbaum Carl J , Longenecker Chris T
Published: May 2021

Introduction:
Latent tuberculosis infection (LTBI) has been associated with increased odds of acute myocardial infarction. Here we assessed the relationship between subclinical coronary atherosclerosis, LTBI status, and
Mycobacterium tuberculosis
(
Mtb
)-specific cell-mediated responses.

Hypothesis:
LTBI and the magnitude of
Mtb
-specific cell-mediated responses are associated with increased rates of subclinical coronary artery disease (CAD).

Methods:
Cross-sectional study within a cohort of HIV-infected and -uninfected participants enrolled at the Joint Clinical Research Centre in Kampala, Uganda. Participants were ≥45 years with at least one risk factor for cardiovascular disease. Persons living with HIV (PLWH) were on stable antiretroviral therapy with HIV viral load ≤1,000 copies/mL within the 6 months prior to study entry. Participants underwent QuantiFERON®-TB Gold (QFT) testing to define LTBI status. Interferon-γ (IFN-γ) cell-mediated responses to
Mtb
antigens contained in the QFT TB tube were extracted. Participants underwent coronary computed tomography angiography (CCTA) utilizing a 128-slice Siemen’s scanner. Obstructive CAD was defined as having at least one coronary segment with plaque causing ≥ 50% luminal stenosis (CAD-RADS ≥3).

Results:
Of 138 participants, 66 (48%) had LTBI (17 PLWH and 49 HIV-uninfected), and 72 (52%) were non-LTBI (38 PLWH and 34 HIV-uninfected). Median age was 57 years; 91 (66%) were female; 120 (87%) had hypertension, 45 (33%) had diabetes mellitus, 24 (17%) had dyslipidemia, and 7 (5%) used tobacco. Median CD4 count was 569 cells/uL in PLWH. Prevalence of obstructive CAD was 9% in LTBI vs. 3% in non-LTBI;
p
=0.152.
Mtb
-specific responses were higher in persons with obstructive CAD compared to those without it (IFN-γ IU/mL median [IQR]; 5 [0.4 - 9.6] vs. 0.3 [0.1 - 2.9];
p
=0.04).
Mtb
-specific responses remained associated with obstructive CAD after adjusting for age, sex, HIV status, cholesterol, hypertension, tobacco use, and diabetes mellitus (adjusted OR, 1.33; 95% CI; 1.04 - 1.7).

Conclusions:
Higher
Mtb
-specific cell-mediated responses were associated with obstructive CAD. Our findings suggest that
Mtb
contributes to coronary plaque burden independently of HIV and cardiovascular risk factors.
Abstract 14447: 1-year Mortality After ICD Implantation in Ischemic Heart Disease
Authors: Ingelaere Sebastian , Hoffmann Ruben , Vandekerckhove Yves R , Vijgen Johan , le Polain de Waroux Jean-Benoît , Mairesse Georges , Blankoff Ivan , Willems Rik
Published: May 2021

Introduction:
According to guidelines ICD implantation should not be performed in patients with an expected survival less than 1 year. We investigated how useful validated risk scores are to predict 1-y mortality after ICD implantation in patients with ischemic heart disease (IHD).

Methods:
The QERMID-ICD registry, managed by the Belgian health authorities, contains data of all patients implanted with an ICD. Participation is mandatory for reimbursement. We analyzed all new implantations between 01/02/2010 and 31/01/2018 in Belgian IHD patients. Data is available about age, gender, ejection fraction (EF), NYHA class, type of prevention, type of device, QRS duration, center volume, comorbidities and socio-economic status based on the area of residency. We performed a Cox proportional hazard regression and applied a modified version of the MADIT- (Goldenberg et al., JACC 2008) risk score (reported renal failure instead of BUN > 26mg%) and AAACC (Nevzorov et al., JCE 2018) risk score (no data on anemia, so AACC score) to predict 1-y mortality.

Results:
On a total of 6320 IHD patients, the 1-y mortality was 5.7%. Patients who died within 1 year were significantly older (70.9 vs 65.9 years), had a worse EF (28.7 vs 31.5%) and differed in most comorbidities. In the Cox model age, worse EF, secondary prevention, VVI/DDD devices, atrial fibrillation, COPD, neurological antecedents and renal failure were independent predictors of 1-y mortality (table 1). Area under ROC was comparable for the modified Goldenberg and AACC score (0.647 vs 0.652). With a cut-off of 5 on the modified Goldenberg and 7 on the AACC-score a positive predictive value (PPV) of respectively 15.5% an 17.4% and negative predictive value of 94.2% and 94.7% were obtained.

Conclusion:
Despite significant differences in baseline characteristics, selection of patients not suitable for ICD implantation (because of high 1-y mortality risk) can only be slightly improved by using simple risk scores due to their low PPV.
Abstract 14468: Right Heart: Renal Venous Stasis Determinant in Acute Heart Failure
Authors: Vella Alessandro , Carenini Gianmarco , Bandera Francesco , Guazzi Marco
Published: May 2021

Introduction:
The heart-kidney interaction in heart failure (HF) is a matter of special interest, especially due to its strong prognostic significance. The search for a reliable, non-invasive parameter with high pathophysiological and prognostic impact to evaluate HF-related renal congestion remains attractive. Doppler evaluation of intra-renal venous flow (IRVF) has been recently employed in HF patients, with a spectrum of findings ranging from a normal continuous flow to a monophasic discontinuous one, indicative of low and high degrees of renal congestion, respectively.

Hypothesis:
We postulated a role for right atrial dynamics in the renal congestion pathophysiology. The impairment in atrial deformation and pump function may play a primary role increasing the pulsatile backward load in the venous system, especially in acute heart failure (AHF) patients.

Methods:
119 consecutive AHF patients were prospectively investigated within 48 hours from admission. Doppler-derived descriptors of renal hemodynamics included the renal arterial resistive index, IRVF pattern, venous impedance index and renal venous stasis index (RVSI).

Results:
Right atrial peak longitudinal strain (RAPLS) showed a strong correlation with IRVF pattern (Fig A) and various indices of RV function (TAPSE, S’, FAC) and RV coupling as represented by the TAPSE/PASP ratio (Fig B). At multivariate regression analysis, TAPSE/PASP ratio emerged as the main determinant of RVSI. On the other hand, considering only patients with a clearly impaired RV coupling (TAPSE/PASP <0.30), RAPLS emerged as the best determinant of RVSI (Fig C-D).

Conclusions:
Our data confirms the main role of the right heart in determining renal stasis in HF patients. When RV to pulmonary circulation uncoupling is severe, the right atrium becomes the key balancing factor in the venous renal flow response. Studies on the mechanistic contribution of the RA dysfunction and the recovery potential of interventions are warranted.
Abstract 14470: Type 2 Diabetes and Risk of Cardiovascular Events in Peripheral Artery Disease versus Coronary Artery Disease Patients
Authors: Sprenger Lukas , Vonbank Alexander , Larcher Barbara , Mader Arthur , Maechler Maximilian , Klement Margaretha , Zanolin-Purin Daniela , Leiherer Andreas , Muendlein Axel , Drexel Heinz , Saely Christoph H
Published: May 2021

Introduction:
The prevalence of type 2 diabetes (T2DM) is higher in peripheral artery disease (PAD) than in coronary artery disease (CAD) patients, and PAD overall confers higher cardiovascular risk than CAD.

Hypothesis:
We hypothesize that there is a difference in cardiovascular risk between PAD and CAD patients when analyses are stratified by the presence of T2DM.

Methods:
We prospectively recorded cardiovascular events over 7.6±5.0 years in 253 patients with PAD, of whom 41.9% had T2DM and in 923 patients with stable CAD, of whom 26.7% had T2DM. Four groups were analyzed: CAD patients without diabetes (CAD/T2DM-; n=677), CAD patients with T2DM (CAD/T2DM+; n=246), PAD patients without diabetes (PAD/T2DM-; n=147) and PAD patients with T2DM (PAD/T2DM+; n=106).

Results:
The cardiovascular event rate was lowest in CAD/T2DM- patients (40.5%). It was significantly higher in CAD/T2DM+ patients (50.2%; p=0.007), in PAD/T2DM- patients (55.2%; p<0.001), and in PAD/T2DM+ patients (67.6%; p<0,001), who in turn were at a higher risk than CAD/T2DM+ or PAD/T2DM- patients (p<0.001 and p=0.013, respectively). Further, cardiovascular risk was significantly higher in PAD/T2DM- than in CAD/T2DM+ patients (p<0.001). Cox regression analysis after multivariate adjustment confirmed that PAD versus CAD (HR=2.58 [2.12-3.15]; p<0.001) more strongly than the presence of T2DM (HR=1.55 [1.30- 1.85]; p<0.001) predicted cardiovascular events.

Conclusions:
We conclude that even when compared to CAD PAD confers a higher risk than T2DM. PAD patients without diabetes are at a higher risk than the extremely high risk patients with the combination of CAD and T2DM; risk is exceedingly high in PAD patients with T2DM.
Abstract 14474: Cdk9-activated Sgk3 Promotes Myocardial Repair and Regeneration After Myocardial Infarction via Gsk-3Å/Å-catenin Pathway
Authors: Li YaFei , Wei Tianwen , Yi Fan , Wang Hao , Wang Liansheng
Published: May 2021

Background:
Neonatal heart maintains entire regeneration capacity in a transient regeneration window, but the adult heart loses this function. This process involves numberous core hubs dysregulation of expression and activity that adversely affect the myocardium regeneration ability. Present study screened a functional kinase of serine/threonine-protein kinase 3 (SGK3) in cardiac regeneration after neonatal myocardial infarction (MI) using quantitative phosphoproteomics.

Methods:
We used quantitative phosphoproteomics data of infarct border zone in newborn heart after MI to identify regeneration related kinases. Gain- and loss-of-function experiments were performed to determine the effect of SGK3 in cardiomyocyte (CM) proliferation and cardiac repair after apical resection (AR) or MI. Pull-down assay and co-immunoprecipitation (Co-IP) experiments were conducted to investigate the direct binding target proteins of SGK3.

Results:
SGK3 protein expression was highly expressed at postnatal day 1 (P1), reduced at postnatal day 7 (P7) until adult.
In vitro,
CM proliferation ratio was elevated by SGK3 overexpression, while it was decreased by knockdown of SGK3.
In vivo,
inhibition of SGK3 shortened the time window of cardiac regeneration after AR in neonatal mice, and overexpression of SGK3 significantly promoted CM proliferation and cardiac repair after MI. Mechanistically, SGK3 could be directly combined with and activated by cyclindependent kinase 9 (CDK9). Inhibition of CDK9 partially abolished the effect of SGK3 on CM proliferation. Moreover, SGK3 could repress GSK-3β activity and increase β-catenin expression.

Conclusions:
Our study revealed a key role of SGK3 in cardiac regeneration following AR or MI injury, which may reopen a novel therapeutic avenue for MI.
Abstract 14478: Left Ventricular (LV) Determinants of Left Atrial (LA) Remodeling in Ischemic Cardiomyopathy (iCM): From the Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration (ALLSTAR) Double Blind Placebo Controlled Trial
Authors: Kapoor Karan , Varadarajan Vinithra , Ostovaneh Mohammad R , Ambale-Venkatesh Bharath , Henry Timothy D , Makkar Raj , Marban Linda , Marban Eduardo , Ac Lima Joao
Published: May 2021

Introduction:
ALLSTAR, a trial of cardiosphere-derived cells in iCM, phenotyped the subjects by cardiac magnetic resonance (CMR) at baseline, and 6- and 12- months post-randomization. The overall CMR dataset provides an opportunity to study temporal remodeling of the LA in the context of iCM-related LV alterations.

Hypothesis:
We hypothesize that LA volumetric and functional remodeling in iCM are coupled to LV determinants.

Methods:
LA volumes (LAV; maximum and minimum) were obtained from 4- and 2-chamber cine CMR images. LA functional parameters included total, passive and active LA emptying fractions and global longitudinal strain (GLS). LV parameters included end-diastolic and end-systolic volumes (indexed to body surface area; LVEDVi and LVESVi), as well as LV ejection fraction (EF), infarct size, GLS and end-diastolic mass. Six- and 12-month differences from the baseline CMR study were calculated for LA and LV parameters. Linear regression models were used to evaluate univariate associations between LA and LV parameters (at baseline, 6-months, 12-months and their differences [Δ]), independent of treatment effect (which is the subject of ongoing analysis).

Results:
101 participants had 6-month follow up CMR studies; 57 had 12-month studies. Baseline means(SD): age 53.9(10.9) years; 87(86.1%) male; LVEF 39.7%(7.0%); infarct size 22.7%(5.4%). In univariate analyses at 6 months, ΔLVEDVi and ΔLVESVi were both significantly associated with ΔLAVimax and ΔLAVimin, but not with LA functional parameters (Table). At 12 months, ΔLVEDVi remained significantly associated with ΔLAVimax, and ΔLVESVi with ΔLAVimin. No association with LA functional parameters was seen. LVEF, infarct size, GLS and end-diastolic mass were not associated with any volumetric or functional LA parameters (not shown).

Conclusions:
In conclusion, in this cohort of iCM, pathologic dilatation of the LV appears coupled to volumetric LA remodeling, but not other functional LA parameters.
Abstract 14482: Apparent Resistant Hypertension is a Marker of Risk: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Wijkman Magnus O , Malachias Marcus , Claggett Brian , Cheng Susan , Matsushita Kunihiro , Shah Amil M , Jhund Pardeep S , Coresh Josef , Solomon Scott , Vardeny Orly
Published: May 2021

Introduction:
Apparent resistant hypertension (ARH) is a common marker of risk in patients with established cardiovascular disease. We ascertained the prevalence and prognostic significance of ARH in patients without prior cardiovascular disease.

Methods:
This prospective observational cohort study included 9669 community-based participants without a history of heart failure, myocardial infarction, or stroke, who completed the Atherosclerosis Risk in Communities (ARIC) study visit 4 between 1996-1998. The definition of ARH was blood pressure (BP) above goal (traditional goal <140/90mmHg, more stringent goal <130/80mmHg) despite use of ≥3 antihypertensive drug classes, or any BP with ≥4 antihypertensive drug classes. Participants with controlled hypertension (CH), defined as BP at goal with use of 1-3 antihypertensive drug classes, constituted the reference group. The outcome was a composite endpoint of heart failure, myocardial infarction, stroke, or death. Cox regression models were adjusted for age, sex, race, BMI, heart rate, smoking, eGFR, LDL, HDL, triglycerides, glucose, and diabetes.

Results:
Applying the traditional BP goal, 154/9669 participants (1.6%) had ARH, and there were 2311 participants with CH (23.9%). Using the more stringent BP goal, 218/9669 participants (2.3%) had ARH, and 1523 participants (15.8 %) had CH. The median follow-up time was 19 years. Apparent resistant hypertension was associated with an increased risk for the composite endpoint (adjusted hazard ratio 1.58 [95% CI 1.32-1.90] with the traditional BP goal, and adjusted hazard ratio 1.51 [95% CI 1.28-1.79] with the more stringent BP goal).

Conclusions:
Apparent resistant hypertension had a low prevalence but was independently associated with adverse outcome during long term follow-up, compared to controlled hypertension and even compared to uncontrolled hypertension. This was observed for both traditional and more stringent BP goals.
Abstract 14494: Once You 1c It, You Can’t Unsee It: A Case of Flecainide Toxicity
Authors: Laczay Balint , Menon Venu
Published: May 2021

Introduction:
Flecainide is a class 1c antiarrhythmic commonly used for the treatment of atrial and ventricular arrhythmias in the absence of underlying structural heart disease. The significant proarrhythmic effects of the drug warrant familiarity with the drug and its toxicity. Flecainide overdose, whether intentional or iatrogenic, is a life threatening emergency with mortality rates as high as 22.5%. We present a case of intentional flecainide overdose and its management.

Case:
A 78-year-old man with a history of heart failure, paroxysmal atrial fibrillation on flecainide, presented to a local ED after a suicide attempt. He was initially hemodynamically stable and a 12-lead EKG revealed a wide-QRS bradyarrhythmia (See figure 1). Electrolyte panel showed normal potassium and pH. During transport to our tertiary cardiac intensive care unit, the patient declined and was critically ill on arrival. The diagnosis of flecainide toxicity was suspected and therapy was initiated on arrival. Despite therapy with sodium bicarbonate and fat emulsion, the patient continued to decline. Renal replacement therapy was started and the patient was evaluated for mechanical circulatory support. Ultimately, the patient’s family elected for palliative extubation. The patient’s flecainide level returned more than four times above the therapeutic range.

Discussion:
This case highlights the importance of a high index of suspicion when faced with a wide-QRS arrythmia in a patient with suspected antiarrhythmic overdose. The persistence of these rhythms after correction of acid-base abnormalities and electrolyte derangements should prompt aggressive, empiric treatment of potential overdose. The presence of electromechanical dyssynchrony in this context is an ominous sign and should prompt simultaneous evaluation for biventricular mechanical circulatory support concomitant with medical therapy for suspected overdose. Figure 1
Abstract 14496: Frailty is Associated With Increased Cardiovascular Mortality in 2,837,152 United States Veterans Aged 65 and Older
Authors: Shrauner William , Lord Emily , Nguyen Xuan-Mai T , Song Rebecca J , Galloway Ashley , Gagnon David , Driver Jane , Gaziano John M , Wilson Peter , Djousse Luc , Cho Kelly , Orkaby Ariela R
Published: May 2021

Introduction:
Frailty has been associated with an increased risk of all-cause mortality and CV events. There are limited data from the modern era of CV prevention to examine the relationship between frailty and CV mortality. We hypothesized that frailty would be associated with with increased risk of CV mortality.

Methods:
All Veterans ≥65 who were regular users of VA care from 2002–2014 were included. Index date was the last visit date in the year of cohort entry. Data were queried biennially, with frailty & outcomes queried each period. Frailty was defined using a 31-item previously validated frailty index, ranging from 0-1. Degrees of frailty were defined as: not frail (FI <0.1), pre-frail (FI >0.1-≤0.2), mild frailty (FI >0.2-≤0.3), moderate frailty (FI >0.3-≤0.4), and severe frailty (FI >0.4). Variables were extracted from national VA administrative data linked to Medicare and Medicaid. The primary outcome was CV mortality. Survival analysis was performed. Models were adjusted for age, sex, race/ethnicity, geographic region, smoking status, hyperlipidemia, statin use, and blood-pressure medication use.

Results:
There were 2,837,152 Veterans included in the analysis. In 2002 mean age was 74+/- 5.8 years and in 2012 was 76+/- 8.1 years, 98% were male, 88.8% were white. In 2002, the median frailty score was 0.16 (IQR= 0.13). This increased and then stabilized to 0.19 for 2006 to 2012 (IQR= ranging 0.19 to 0.23). Overall frailty became more prevalent over time (prevalence increased from 31.9% in 2002 to 46.5% in 2012). The presence of frailty was associated with increased risk of CVD mortality at every degree of frailty and year, as shown in the Table.

Discussion:
Frailty is highly prevalent in the VA population, and both the presence and severity of frailty are tightly correlated with CV death. This study is the largest and most contemporary evaluation of the relationship between frailty and CV mortality to date. Further work is needed to understand how this risk can be diminished.
Abstract 14644: Hemoglobin A1c Carries Independent Mortality Risk in U.s. Veterans With Vascular Risk Factors
Authors: Garg Swapnil , Soofi Muhammad , Markert Ronald , Agarwal Ajay
Published: May 2021

Background:
Large epidemiologic studies have established diabetes mellitus as an independent risk factor for all-cause mortality. There is also evidence to suggest a linear relationship between hemoglobin A1c (HbA1c) and mortality. We find that poorly controlled diabetes in high-risk US Veterans carries an independent mortality risk mediated through reduced ejection fraction (rEF) and obstructive coronary artery disease (ObCAD).

Methods:
1535 consecutive US Veterans presenting for left heart catheterization were retrospectively analyzed for presence of risk factors with long-term follow-up.

Results:
248 patients had HbA1c ≥8 with 76.2% mortality compared to 198 patients with HbA1c in the prediabetic range of 5.70-6.49 with 67.2% mortality (p = 0.03) with univariate hazard ratio (HR) 1.25 [1.002-1.56, p=0.048]. Multivariate adjustment for age, BMI, hypertension, hyperlipidemia, chronic kidney disease yielded HR 1.28 [1.02-1.60, p=0.034]. Multivariate adjustment for aforementioned variables with addition of rEF, ObCAD and prior revascularization yielded HR 1.17 [0.93-1.48, p=0.19].

Conclusion:
We conclude that poorly controlled diabetes with HbA1c 8 or greater carries independent mortality risk when controlled for traditional risk factors however loses significance after controlling for rEF, ObCAD and prior revascularization.
Abstract 14652: Systolic Blood Pressure Trajectories and Cardiovascular Outcomes in SPRINT
Authors: German Charles A , Elfassy Tali , Singleton Matthew J , Rodriguez Carlos J , Ambrosius Walter T , Yeboah Joseph
Published: May 2021

Introduction:
Blood pressure trajectories have been associated with cardiovascular disease (CVD) in observational studies. It is unclear whether these associations are independent of average blood pressure over time.

Methods:
We used data from SPRINT to identify systolic blood pressure (SBP) trajectories among a cohort of 8901 participants by incorporating SBP measures during the first 12 months of the trial post randomization. Trajectories were identified using latent class based modeling. Study outcomes included incident CVD, defined as myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death attributable to CVD, and all-cause mortality. Cox proportional hazards models were used to evaluate associations between SBP trajectories and our outcomes of interest.

Results:
Four distinct SBP trajectories were identified: ‘low decline’ (40%), ‘high decline’ (6%), ‘low stable’ (48%), and ‘high stable’ (5%) (Figure 1). Relative to the low decline group, the low stable group was associated with a 29% increased risk of CVD (HR: 1.29, 95%CI: 1.06-1.57) and the high stable group was associated with a 76% increased risk of all-cause mortality (HR: 1.76, 95%CI: 1.15-2.68) after baseline multivariable adjustment. Relative to the low stable group, the high stable group was associated with a 54% increased risk of all-cause mortality (HR: 1.54, 95%CI: 1.05-2.28). When adjusting for average blood pressure across the 12 month time period, there were no significant differences in outcomes.

Conclusion:
We identified 4 SBP trajectories using data from SPRINT and found differences in the risk of CVD and all-cause mortality after baseline adjustment. However, there were no differences in the risk of these outcomes after adjusting for average blood pressure over time. These results suggest that the pattern of blood pressure control may not be relevant as long as the target blood pressure is achieved.
Abstract 14655: Diffusion Neuroimaging of Adults With D-Transposition of the Great Arteries Reveal White Matter Alterations in the Connectomic Rich Club
Authors: Chung Ai Wern , Gagoski Borjan , Newburger Jane W , Grant P. Ellen , GURVITZ Michelle
Published: May 2021

Introduction:
The population of adults with d-transposition of the great arteries (TGA) continue to grow. As this group has underlying neurocognitive impairment and longer-term neurovascular damage, advanced neuroimaging to identify markers for treatment is required. Diffusion (d)MRI tractography quantifies the structural integrity of white matter (WM) pathways in the brain - where lower FA (fractional anisotropy) and higher ADC (apparent diffusion coefficient) typify WM damage. The brain’s structural backbone is its rich club (RC), a set of highly interconnected regions established before birth and vital for effective cognitive function. Moreover, there are Feeder and Seeder subnetworks peripheral to the RC, which are thought to form later and may be more adaptive.

Hypothesis:
We hypothesize that adults with TGA have alterations in both the brain’s structural RC and in peripheral connections.

Methods:
Subjects were TGA adults from the Boston Circulatory Arrest Study (n = 25, mean age 28.46 ± 1.14yr) and Controls (n = 13, 28.35 ± 1.70). Multi-shell, high-angular resolution dMRI data were acquired and fitted with a multi-fiber model (Fig). After tractography, a connectome of the number of tracts connecting pairwise cortical regions was computed. A priori RC regions were bilateral superior frontal and parietal frontal gyri, precuneus, posterior cingulate and insular regions. Connections were grouped into subnetworks and mean FA and ADC computed.

Results:
Cohorts were age-matched (p=0.801, unpaired t-test). Overall, patients had lower FA and greater ADC than controls in all subnetworks. Group differences (unpaired t-tests) were significant in the RC (ADC p=0.029), Feeder subnetwork (FA p=0.041; ADC p=0.042), with trends in Seeder subnetworks (FA p=0.061; ADC p=0.062).

Conclusions:
Widespread WM alterations exist in adults with TGA not only in the brain’s most central system, but also connections feeding into the RC suggesting prenatal and adaptive changes.
Abstract 14672: Differential Risk Factor Profiles and Management of Acute Coronary Syndrome in Us Women With or Without Active Breast Cancer
Authors: Weidling Robert , Acharya Prakash , Shah Zubair , Porter Charles
Published: May 2021

Introduction:
Acute Coronary Syndrome (ACS) and breast cancer are major contributors to United States mortality. Breast cancer is a known risk factor for coronary artery disease, yet questions remain regarding the clinical impact of the intersection of these two diseases. We evaluated the patient characteristics, interventions and outcomes during ACS hospitalizations of US women with active breast cancer.

Methods:
We retrospectively analyzed the US National Readmissions Database years 2016-2017 to identify adult women with or without active breast cancer admitted with ACS defined asUA, NSTEMI or STEMI. Differences in baseline characteristics, interventions, and in-hospital mortality of these two groups were determined and analyzed.

Results:
Among 544,698 ACS cases in adult women identified, 2,782 (0.52%) had active breast cancer. Those with breast cancer were 3 years younger (mean age 69 vs 72 years, p < .001), and had significantly lower prevalences of dyslipidemia, hypertension, obesity and tobacco use. Although incidence of STEMIs were equivalent in both groups, those with breast cancer were less likely to undergo PCI (28.8% vs 34.36%, P<0.001) or CABG (5.67% vs 8.89%, p<0.001). Complication rates were not significantly different between groups, but those with breast cancer were less likely to undergo CPR in case of cardiac arrest (0.96% vs 1.47%, p =0.027). No significant difference was found between inpatient mortality rates or readmission rates.

Conclusions:
Women admitted for ACS with active breast cancer were younger and had more favorable CV risk profiles compared to those without breast cancer. These findings suggest that the presence of breast cancer is associated with a risk of ACS that is inadequately recognized by conventional CV risk assessment tools. Despite the more favorable CV risk profiles, STEMI rates were equivalent between groups, but revascularization was less common in those with breast cancer. Comparable outcomes with less invasive therapies suggest a difference in ACS pathophysiology. More specific predictive tools for ACS in the breast cancer population may be needed especially in light of contemporary era hormonal and targeted therapies which are increasing the rate of survivorship.
Abstract 14683: Central Nervous System Mediated Cardiac Bradyarrhythmia With Asystole That Required Permanent Pacemaker in a Young Woman With Anti- NMDAR Encephalitis
Authors: Mantha Yogamaya , Anjum Azeen , Holtz Anita G , Tatiraju Uday , Rizvi Macym , Feldman Mark
Published: May 2021

Background:
We report a young woman who presented with acute psychosis and autonomic dysfunction who was diagnosed with Anti-N-Methyl-D-Aspartate Receptor Encephalitis (anti-NMDARE). Her life-threatening autonomic instability was controlled only after the placement of a permanent cardiac pacemaker.

Case Presentation:
A 29-year-old woman presented with abnormal movements and depersonalization. Vital signs showed BP 132/94 mmHg, HR 110 beats/min, RR 26 cycles/min, temperature of 101 F and spO2 of 80 % on RA. She was emergently intubated. Laboratory evaluation showed elevated CRP 6.98 mg/dL and CK 3329 U/L. Brain MRI revealed an abnormality in the right amygdala and hippocampus. Infectious workup was negative; however, a high titer of CSF NMDAR antibody was present. CT abdomen and pelvis revealed a 1.1 cm cyst within the left ovary. With a diagnosis of anti-NMDARE, she was treated with plasmapheresis, methylprednisolone, and immunoglobulin G therapy and underwent bilateral salpingo-oophorectomy with pathology confirming a teratoma. Despite these treatments, she continued to display autonomic dysfunction. Telemetry showed tachycardia-bradycardia with asystole that remained refractory to treatment and required placement of a permanent pacemaker (PPM). She showed clinical improvement after PPM and treatment (
Figure
).

Conclusion:
This is a rare case of severe bradyarrhythmia in anti NMDARE that necessitated placement of a permanent cardiac pacemaker. Neural-mapping studies show that the amygdala and hippocampus strongly modulate autonomic control. Disruption of cortical circuitry related to autonomic tone likely lead to arrhythmias in our case. Class I indications for pacemakers in the ICU include asystole, symptomatic bradycardia with hypotension and/or unresponsive to atropine. Early recognition, cardiorespiratory support, multistep pharmacological care and sometimes early electrophysiological support in anti-NMDARE are paramount.
Abstract 14705: Clinical Profile and Health Disparities in Patients With Hypertrophic Cardiomyopathy in a Multi-ethnic Cohort
Authors: Butters Alexandra
Published: May 2021

Background:
The clinical characteristics and management of hypertrophic cardiomyopathy (HCM) are well-described in European cohorts. However, less is known about other ethnic groups. We compared demographic, clinical, genetic and service use characteristics of patients with HCM across major ethnic groups represented in our cohort.

Methods:
Retrospective cohort study of 812 HCM probands attending a specialised clinic between 2002 and 2020. The ethnic groups were European n=611, East Asian n=75, South Asian n=58 and Middle Eastern and North African n=68. Analysis included one-way ANOVA with Dunnett's post-hoc comparison or Bonferroni adjustment.

Results:
The mean age was 55 ± 17 years and 527 (65%) were male. Using the European group as the control, East Asians had a lower body mass index (29 versus 25 kg/m
2
, p<0.05) and South Asians had a lower prevalence of atrial fibrillation (10% versus 31%, p<0.02). Differences also existed in echocardiographic characteristics with East Asians more likely to have apical hypertrophy (23% versus 6%, p<0.02 and Middle Eastern and North African patients more likely to present with left ventricular outflow tract obstruction (46% versus 34%, p<0.02). East Asians were less likely to undergo genetic testing (55% versus 85%, p<0.02) or have an implantable cardioverter defibrillator (19% versus 36%, p<0.02) despite similar HCM-Risk score. Middle Eastern and North Africans and South Asians had the highest rates of variants of unknown significance (27% and 21%, p<0.02; Fig A), while East Asians were more likely to have a causative sarcomere gene variant other than
MYBPC3
or
MYH7
(58% versus 11%, p<0.02 (Fig B).

Conclusion:
We demonstrate variability in the phenotype expression and management of HCM by ethnic group, representing differences in pathophysiology, sociocultural contexts, and access to healthcare. This may indicate a role of ethnicity in understanding the clinical course of HCM, and highlight disparities faced by some groups.
Abstract 14727: Meteorin-like Glial Cell Differentiation Regulator is a Novel Protein Biomarker of Cardiovascular Outcomes in Patients With Diabetes and Vascular Disease: A TECOS Substudy
Authors: Truby Lauren K , Regan Jessica A , Nguyen Maggie , Giamberardino Stephani , Mentz Robert J , McGarrah Robert W , Zheng Yinggan , McGuire Darren K , Buse John B , Armstrong Paul W , Green Jennifer , standl eberhard , Peterson Eric D , Shah Svati H , Holman Rury
Published: May 2021

Introduction:
To date, there are limited data on the potential role of proteomic biomarkers to predict future cardiovascular (CV) events among patients with type 2 diabetes mellitus (DM).

Hypothesis:
Specific protein biomarkers will be predictive of major adverse CV events (MACE) and incident heart failure hospitalization (HFH) among patients with DM.

Methods:
Using the Olink aptamer-based platform, we performed proteomic profiling (>700 proteins) on 440 paired cases and matched controls from placebo-assigned participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Cases were defined as having met the primary composite outcome of MACE or incident HFH and matched to controls on baseline prevalent heart failure, coronary artery disease, BMI, hemoglobin A1C, creatinine, low-density lipoprotein cholesterol, fasting status and ejection fraction. Conditional logistic regression was used to determine the association between log-transformed relative protein expression and incident MACE or HFH. False-discovery-rate (FDR) was used to adjust for multiple comparisons.

Results:
We identified three specific proteins that were significantly associated with prevalent MACE or HFH: METRNL, Notch 3, and ROR1 (OR 2.1, 1.6, 1.7 and q-value 0.01, 0.02, and 0.05 respectively) (Figure 1). METRNL, in particular, performed similarly to the established biomarker NT-proBNP (Figure 1). When MACE and HFH were analyzed separately, METRNL, in particular, remained strongly associated with both outcomes (OR 2.0, p<0.001 and OR 2.7, p=0.05).

Conclusions:
Three novel protein biomarkers, in particular METRNL (a circulating adipokine that regulates insulin-sensitivity), may identify diabetic patients at high risk for subsequent HF and MACE. Additional studies are needed to replicate these findings and uncover the biologic mechanism linking adipokine signaling and heart failure.
Abstract 14738: Classification of Atrial Fibrillation by Deep Learning of Electrogram Shapes versus Rate and Regularity
Authors: Rodrigo Miguel , Rogers Albert J , Ganesan Prasanth , Alhusseini Mahmood , XU JUSTIN , Narayan Sanjiv M
Published: May 2021

Introduction:
It is unclear whether atrial fibrillation (AF) is best identified on intracardiac recordings by varying shape, rapid rate or extent of irregularity. Prioritizing these features may improve device diagnosis of AF.

Hypothesis:
AF can be separated from organized atrial flutter (AFL) by electrogram shape, independent of the contributions of rate or regularity.

Methods:
In 86 patients (25 female, age 65±11 years) we trained a convolutional neural network (CNN) to classify AF or AFL from 64 unipolar electrograms of persistent AF recorded for 60 seconds. In cases labelled as AF, we modified inputs by progressively regularizing (a) electrogram shape; (b) rate or (c) regularity in timing, to define which switched the classification to AFL.

Results:
The CNN provided a c-statistic of 0.95 ± 0.05 to identify AF or AFL in independent test cohorts not used for training, using 10-fold cross validation. Fig A shows AF in which progressive regularization of shape and timing from #1 to #4 flipped CNN classification into AFL in 45%. EGMs with 100% consistent shape and timing were classified by their cycle length (CL=1/rate): ~90% AF for CL < 175 ms, ~80% AFL for CL from 200-280 ms. Fig. B shows sequences simulated from patient-specific EGMs of AF that were classified as AF in 91 ± 12% of cases even if regular with CL of 200-280 ms, showing AF classification based on EGM shape alone. Figure B illustrates some ‘AF pathognomic’ electrogram shapes in red.

Conclusions:
AF may be identified by specific EGM shape patterns independent of regularity or rate. Regularity in shape and timing contribute ~45% to AFL classification, and adding CL explains up to 80%. Studies are required to study the mechanistic basis and clinical implications of specific AF-electrogram shapes.
Abstract 14739: Temporal Trends, Predictors and Outcomes of Acute Ischemic Stroke in Acute Myocardial Infarction in the United States
Authors: Patlolla Sri Harsha , Aggarwal Gaurav , Aggarwal Saurabh , Vallabhajosyula Saraschandra
Published: May 2021

Introduction:
There are limited contemporary data on prevalence and outcomes of acute ischemic stroke (AIS) complicating acute myocardial infarction (AMI).

Methods:
Adult (>18 years) AMI admissions using the National Inpatient Sample database (2000-2017) were evaluated for in-hospital AIS. Outcomes of interest included in-hospital mortality, hospitalization costs, length of stay, and use of tracheostomy and percutaneous endoscopic gastrostomy (PEG). The discharge destination was used to classify AIS survivors into good and poor functional outcomes with poor (moderate to severe disability) defined as discharge to extended care facility including short-term hospital/rehabilitation facility, intermediate care or long-term care facilities.

Results:
Of a total 11,622,528 AMI admissions, 183,896 (1.6%) had concomitant AIS. Over the 18-year period, AIS rates were stable in STEMI admissions and decreased in NSTEMI (p<0.001). Compared to those without, the AIS cohort was on average older, female, of non-White race, with greater comorbidities, and higher rates of arrhythmias. The AMI-AIS admissions received less frequent coronary angiography (46.9% vs. 63.8%) and percutaneous coronary angiography (22.7% vs 41.8%) (p<0.001). Female sex, non-White race, higher comorbidity, ST-segment-elevation AMI presentation, atrial fibrillation/flutter, use of mechanical circulatory support and invasive mechanical ventilation were identified as individual predictors of AIS after AMI. The AIS cohort had higher in-hospital mortality (16.4% vs. 6.0%; adjusted OR 1.75 [95% CI 1.72-1.78]; p<0.001) with a steady decrease in the adjusted in-hospital mortality in over the 18-year period (21% in 2000 vs 17% in 2017). The AIS cohort had longer hospital length of stay, higher hospitalization costs, greater use of tracheostomy and PEG, and less frequent discharges to home (all p<0.001). In AMI-AIS survivors (N=153,318), 57.3% had a poor functional outcome with temporal trends showing a slight increase in recent years (57% in 2000 vs 62% in 2017).

Conclusions:
AIS is associated with significantly higher in-hospital mortality and poor functional outcomes in AMI admissions. Despite improvement in in-hospital mortality, poor functional outcomes remain high.
Abstract 14750: Characteristics Associated With Postpartum Physical Activity Levels Among Women With Hypertensive Disorders of Pregnancy
Authors: Lewey Jennifer , Murphy Samantha , Elovitz Michal , Levine Lisa
Published: May 2021

Background:
Hypertensive disorders of pregnancy (HDP), such as preeclampsia, are associated with increased risk of CV disease. Postpartum interventions may mitigate this risk but have not been well studied in women with HDP. STEP UP Mom is a randomized clinical trial to increase physical activity (PA) in postpartum women with HDP using remote monitoring and social incentives (NCT04119232). We analyzed patient characteristics associated with daily step count prior to study randomization to understand factors associated with postpartum PA.

Methods:
Between October 2019 and May 2020, 168 women were enrolled. Participant characteristics were collected from surveys and chart abstraction. We used univariate and multivariable linear regression to identify characteristics associated with step count, as measured by wearable devices. We also compared women with low step count (defined as ≤ 4800 steps/day, the lowest step count quartile) vs. > 4800 steps per day using chi-square test. This analysis includes 137 participants with complete baseline data available at end of enrollment.

Results:
Mean daily baseline step count was 7444 (SD 3453). The associations between participant characteristics and baseline daily step count are presented in the Table. In multivariable regression, characteristics associated with higher baseline step count were self-reported health as good or better (2789 steps, p<0.001), tobacco use (2622 steps, p=0.03) high school education or less (1676 steps, p=0.019) and weeks since delivery (293 steps per week, p=0.011). Participants with low baseline step count (≤ 4800 steps/day) were more likely to enroll after the COVID-19 pandemic (34% vs. 18%, p=0.04) and be married (71% vs. 49%, p=0.029) compared to those with normal/high step count.

Conclusion:
Multiple patient characteristics impact postpartum PA levels, which may be helpful in planning lifestyle interventions in high-risk postpartum women.
Abstract 14757: Impact of Including Smoking Duration Data in Atherosclerotic Cardiovascular Disease Risk Estimation
Authors: Duncan Meredith S , Greevy Robert , Tindle Hilary A , Ramachandran Vasan S , Lipworth Loren , Aldrich Melinda C , Kundu Suman , Coady Sean , Lloyd-jones Donald M , Freiberg Matthew S
Published: May 2021

Recent results from 5 decades of Framingham Heart Study (FHS) data suggest former heavy smokers (≥20 pack-years) have higher ASCVD risk than never smokers up to 16 years after quitting. However, the ASCVD Risk Estimator Plus, which is based on the 2013 Pooled Cohort Equations (PCE) does not account for pack-years smoked and considers former smokers to have ASCVD risk equal to never smokers after 5 years quit. Using data from 18,400 person-exams (exams 1-8) on 3,908 white FHS Offspring cohort participants, and follow-up through 12/31/2016, we built 5 sex-specific ASCVD risk prediction models to assess the added value of smoking history data. Models used pooled repeated Cox proportional hazards regression with 10-year follow-up blocks and age, SBP, antihypertensive medications, diabetes, total and HDL cholesterol, lipid-lowering medications, smoking status, pack-years smoked, and years since quitting smoking as predictors. We refit the 2013 PCE in the FHS person-exam sample (model 1) for fair model comparison. Subsequent models refit model 1 with continuous predictors on their natural scale (i.e., not logarithmically transformed) with polynomials to account for nonlinearity (model 2), and cumulatively adjusted for: former smoking (model 3), pack-years smoked (model 4), and years since quitting (model 5). We compared models by change in c-index, continuous net reclassification improvement (NRI(>0)), and relative integrated discrimination improvement (rIDI).We included 1,895 men (358 events) and 2,013 women (197 events) with a mean age of 55 years and similar risk factor profiles. Over pooled examinations, ever smoking prevalence was high in men (77%) and women (78%), as was median pack-years smoked (M:39; W:32). Utilizing former smoking status, pack-years, and years quit (model 5) had significant but modest NRI(>0) and rIDI values compared to the 2013 PCE on the natural scale in both sexes {Men: NRI(>0)=0.23, rIDI=0.19; Women: NRI(>0)=0.34, rIDI=0.11); the change in c-index (0.01) was significant only in men}. Pack-years smoked and years since quitting improved ASCVD risk prediction significantly but modestly in our sample. If validated in other race/ethnicity groups, these variables should be considered for improving ASCVD risk prediction tools.
Abstract 14760: Myocardial Scarring by Magnetic Resonance Predicts Sudden Cardiac Death in Pediatric Patients With Hypertrophic Cardiomyopathy
Authors: Grosse-Wortmann Lars , van der Wal Laurine , Vaikom House Aswathy , Benson Lee , Chan Raymond
Published: May 2021

Introduction:
Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) has been shown to be an independent predictor of sudden cardiac death (SCD) in adults with hypertrophic cardiomyopathy (HCM). The clinical significance of LGE in pediatric HCM patients is unknown.

Hypothesis:
LGE improves the SCD risk prediction in children with HCM.

Methods:
We retrospectively analyzed the CMR images and reviewed the outcomes pediatric HCM patients.

Results:
Amongst the 720 patients from 30 centers, 73% were male, with a mean age of 14.2±4.8 years. During a mean follow up of 2.6±2.7 years (range 0-14.8 years), 34 experienced an episode of SCD or equivalent. LGE (Figure 1A) was present in 34%, with a mean burden of 14±21g, or 2.5±8.2g/m2 (6.2±7.7% of LV myocardium). The presence of ≥1 adult traditional risk factor (family history of SCD, syncope, LV thickness >30mm, non-sustained ventricular tachycardia on Holter) was associated with an increased risk of SCD (HR=4.6, p<0.0001). The HCM Risk-Kids score predicted SCD (p=0.002). The presence of LGE was strongly associated with an increased risk (HR=3.8, p=0.0003), even after adjusting for traditional risk factors (HR
adj
=3.2, p=0.003) or the HCM Risk-Kids score (HR
adj
=3.5, p=0.003). Furthermore, the burden of LGE was associated with increased risk (HR=2.1/10% LGE, p<0.0001). LGE burden remained independently associated with an increased risk for SCD after adjusting for traditional risk factors (HRadj=1.5/10% LGE, p=0.04) or HCM Risk-Kids (HRadj=1.9/10% LGE, p=0.0018, Figure 1B). The addition of LGE burden improved the predictive model using traditional risk markers (C statistic 0.67 vs 0.77, p=0.003) and HCM Risk-Kids (C statistic 0.68 vs 0.74, p=0.045).

Conclusions:
Quantitative LGE is an independent risk factor for SCD in pediatric patients with HCM and improves the performance of traditional risk markers and the HCM Risk-Kids Score for SCD risk stratification in this population.