bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13344: Do Heart Failure Patients’ Personal Priorities Influence Their Self-care Maintenance Behaviors?
Authors: Osei Baah Foster , Riegel Barbara J
Published: May 2021

Introduction:
The personal priorities of community dwelling patients with HF may influence their self-care behavior. However, clinicians are unsure of the personal priorities that influence self-care choices in patients with HF.

Objective:
To explore personal priorities ranked highest among HF patients with poor or excellent self-care behaviors.

Methods:
We conducted a cross sectional convergent mixed methods study of community dwelling patients with HF in the US, excluding those with significant cognitive impairment (MoCA score ≤22). All completed the Self-Care of HF Index v7.2 (scores standardized 0-100). Extreme case sampling was used to select people with poor self-care maintenance scores (≤60) or excellent self-care maintenance scores (≥80). In interviews, participants placed their personal and healthcare needs into the same imaginary bucket and then rank-order them from highest to lowest priority. Interview data was audio-recorded, transcribed verbatim and analysed using qualitative inductive analysis.

Results:
We enrolled 33 patients with HF (aged 42-82 years, 57% male, 45.5% black, 45.5% married, 54.6% unemployed). Sixteen patients were poor in self-care maintenance and 17 were excellent. Two themes representing HF patients’ personal priorities emerged: a) Healthcare (60.6%, N=20), and b) Family and Housing (36.4%, N=12). Patients who chose healthcare identified medications, insurance and living a longer life as important. As stated by one patient,
“without your health you have nothing.”
Patients who chose family and housing identified; 1) rent, mortgage, or real estate taxes and 2) food for their children and a roof over their head as most important. They explained by saying “
I have to have some place to live and the utilities
” and “
I can be in a card box, but I just wanna make sure they are fed
.” Of those who chose healthcare as their priority, 12 (60%) had excellent self-care maintenance. Only 4 patients (33.3%) who chose family and housing had excellent self-care.

Conclusion:
HF patients who identify healthcare needs as their highest priority may be better at self-care maintenance. Identifying the priorities of patients with HF will help clinicians tailor discharge instructions.
Abstract 13347: Effect of Severe Anemia (hemoglobin < 10g/dl) on Short- and Long-term Outcome in Acute Coronary Syndrome: Insights of a Terciary Centre
Authors: Campos Isabel , Oliveira Cátia , Medeiros Paulo , Marques Pires Carla , Flores Rui , Mané Fernando , Braga Carlos , Gaspar António , Pereira Regina , Vieira Catarina
Published: May 2021

Introduction:
Although invasive strategies are the generalized approach in the management of ACS pts, their benefits in pts with significant anemia are unclear, as anemia is strongly associated with increased risk of morbidity and mortality.

Aim:
To determine the incidence and the impact of severe anemia (hemoglobin<10g/dL) on short- and long-term outcome in pts hospitalized with ACS.

Methods:
We analyzed retrospectively 2905 ACSpts admitted for 6 years in our CCU. Pts were divided into two groups: group 1-pts with severe anemia(hemoglobin < 10g/dL) (n=257,8.8%); group 2-pts without severe anemia (hemoglobin >=10g/dL) (n=2648,91.2%). Primary endpoint was the occurrence of a composite of death and adverse cardiovascular events (stroke, reinfarction, and rehospitalization of cardiovascular etiology) at 6 months; FU was completed in 96%pts.

Results:
The sample consisted in 77.9% men and 22.1% women, with mean age of 64±13 years. The incidence of severe anemia was 8.8%. Group1 pts were older (p<0.001), had a higher proportion of women (p<0.001), diabetes (p<0.001), CKD (p<0.001) and AF (p<0.001). During hospitalization, group 1 had more HF (p<0.001), angor (p<0.001), refarction (p=0.006), bleeding (p<0.001) and transfusion (p<0.001). Group 1 had a higher proportion of NSTEMI (p=0.009) as opposed to group2 which had more STEMI (p=0.031). During hospitalization, group 2 pts were more likely to undergo revascularization (p<0.001). A multivariate analysis identified age [OR 1.06, 95%CI 1.04 to 1.07; p<0.001] and feminine sex [OR 2.61, 95%CI 1.89 to 3.61; p<0.001] as independent predictors of severe anemia during hospitalization. Pts with severe anemia had higher 6-month mortality (32.1%vs6.9%;p<0.001). In multivariate analysis and after adjusting for different baseline characteristics, pts with severe anemia had higher occurrence of a composite of death and MACE at 6months [OR5.04,95%CI 1.21 to 21.04;p=0.026].

Conclusion:
Severe anemia was strongly associated with increased risk of morbidity and mortality in ACS pts. However, pts with severe anemia who were double antiaggregated had no worse outcomes than those who had simple antiaggregation after 6months. Therefore, there was no significant difference regarding revascularization in these pts.
Abstract 13351: Association of Atrial Fibrillation With In-hospital Mortality Among Patients With Takotsubo Cardiomyopathy
Authors: Dai Qiying , Bose Abhishek , Li Pengyang , CAI PENG , Laidlaw Douglas
Published: May 2021

Introduction:
Takotsubo cardiomyopathy (TC), characterized by transient left ventricular dysfunction, is known to be precipitated by sudden physical or emotional stress. Atrial fibrillation (AF) is a common arrhythmia and its presence increases mortality in patients with chronic underlying diseases. Furthermore, multiple studies have suggested that in TC patients, underlying AF correlates with a higher in-hospital mortality. However, these studies were constrained by either a disproportionate percentage of AF patients or lack of risk factor matching. To systematically explore the association between TC and AF, we decided to perform a propensity score matching analysis.

Methods:
We performed a retrospective cohort analysis using the ICD-10 codes for a primary diagnosis of TC from the 2016 National Inpatient Sample. To adjust for underlying risk factors a multivariable logistic regression model was employed followed by a propensity score matching analysis for the AF group and the non-AF group. A similar analysis method was followed for the subset of patients with paroxysmal AF. In-hospital mortality rates were compared between the two groups.

Results:
Out of the total 3139 patients with a primary diagnosis of TC, 433 (13.7%) had AF and 243 (7.7%) had paroxysmal AF. In the unmatched group, patients with AF appeared to be older (74.7 vs. 65.3 years, P<0.001) and more likely to have comorbidities like diabetes mellitus (24.0% vs 19.2%, P=0.024), chronic kidney disease (15.7% vs 7.6%, P<0.001) and obstructive sleep apnea (8.8% vs 4.9%, P=0.002). On multivariable logistic regression, in-hospital mortality was higher in the AF group (3.9% vs 1.3%, P< 0.001). However, after propensity score matching, there was no significant difference in the mortality rate between the two groups (3.7% vs 1.9%, P=0.082). Similarly, on logistic regression followed by propensity matching for patients with paroxysmal AF, no significant difference was noted for in-hospital mortality rates (3.3% vs 1.3%, P=0.112).

Conclusions:
In patients with TC, the presence of underlying AF had no effect on the in-hospital mortality rate.
Abstract 13356: Who Doesn't Respond to Motivational Interviewing for Heart Failure Self-care?
Authors: Stawnychy Michael A , Zeffiro Valentina , Iovino Paolo , Vellone Ercole , Riegel Barbara J
Published: May 2021

Background:
Motivational interviewing (MI) improves HF self-care yet fails to work for some patients. Lack of intervention response leaves clinicians and patients with fewer treatment options.

Aim:
Identify the characteristics of non-responders to MI in adults with HF.

Methods:
Secondary analysis of intervention group (
n
=230) from MOTIVATE-HF trial. Study conducted in Italy to evaluate effectiveness of MI in improving HF self-care. Self-care maintenance measured with the validated Self-care of Heart Failure Index (SCHFI) v6.2 at baseline and 3 months from enrollment. Standardized scores range 0-100; changes > 7 pts from baseline are clinically significant. Participants dichotomized: MI non-responder (change in SCHFI < 7 pts) vs MI responder (change in SCHFI ≥ 7 pts). Logistic regression, adjusted for group differences (employment, income, living alone, HF etiology, baseline self-care, cognitive impairment, mutuality, medications, sleep quality, and HF health status), was used to estimate odds ratio with 95% confidence interval (OR [95% CI]) to identify determinants of non-response.

Results:
Half of the intervention group were non-responders to MI (
n
=115) at 3 months. Non-responders were 72±13 years old and 53% male. Twice the number of non-responders were employed (
n
=36 vs
n
=18,
p
<.005) and many reported ‘more than enough’ income (23% vs 13%,
p
<.046). They had more non-ischemic HF (79% vs 54%,
p
<.001), higher baseline self-care maintenance (48.8±19.2 vs 43.5±12.0,
p
<.009), and took fewer medications (6.1±3.0 vs 7.6±2.5,
p
<.009). Patients who responded to MI had worse HF quality of life (
p
<.018), more sleep disturbances (
p
<.042), and worse sleep quality (
p
<.002). Significant risk factors for non-response were non-ischemic HF (2.606 [1.340-5.071],
p
<.005), fewer daily medications (0.829 [0.738-0.931],
p
<.002), and better baseline self-care maintenance (1.025 [1.001-1.050],
p
<.039). These variables explained 31% of HF self-care maintenance at 3 months (Nagelkerke R
2
=.309).

Conclusion:
MI may be less beneficial for patients with non-ischemic HF, lower medication burden, and relatively better self-care. Identifying characteristics of non-responders to MI in HF contributes to clinical decision making and personalized interventions.
Abstract 13357: Dhtkd1 Knock-out Alters Cellular Respiration by Preventing Electron Transport Chain Related Proteins From Entering Into Mitochondria
Authors: Wang Chuan , Smith Holly , Ferguson Jane
Published: May 2021

The metabolite α-aminoadipic acid (2-AAA) has been identified as a predictor of diabetes and atherosclerosis in large human prospective studies. However, the mechanisms linking this metabolite to disease pathophysiology remain unknown.
DHTKD1
is a central gene in the 2-AAA pathway, and has been linked to variation in 2-AAA levels in humans and animals. However, little is known about the role of
DHTKD1
in cellular metabolism. We hypothesized that
DHTKD1
is an important regulator of mitochondrial energy metabolism, with potential involvement in cardiometablic disease.

Methods and Results:
We investigated the consequences of loss of
DHTKD1
function in a human HAP-1 cell line. Treatment with 2-AAA increased mitochondrial respiration in wild-type (WT) cells, but had no effect in
DHTKD1
knock-out (KO) cells.
DHTKD1
KO cells had significantly lower mitochondrial respiration (Mito Stress Test, Seahorse Analyzer), with no differences in glycolytic function, supporting an important role for
DHTKD1
in mitochondrial metabolism. Membrane potential and mitochondrial content were up-regulated in KO compared to WT cells, suggesting a potential compensatory mechanism. We investigated the mechanisms underlying impaired mitochondrial function, and found TOM40 and TIM23, the pivotal proteins required for the movement of proteins into mitochondria, were decreased in
DHTKD1
KO cells. Further,
DHTKD1
KO resulted in reduced expression of electron transport chain related proteins (NDUF88, SDHB, MTCO1, UQCRC2, ATP5A) in mitochondria, but increased expression in the cytosol, suggesting impaired ability to cross the mitochondrial membrane.

Conclusions:
Our data suggest that the absence of
DHTKD1
leads to less TOM40 and TIM23 expression, preventing key proteins in the electron transport chain from entering into mitochondria, resulting in impaired mitochondrial respiration. These findings highlight the vital role of
DHTKD1
in cellular metabolism, and establish DHTKD1-mediated mitochondrial dysfunction as a potential novel pathway in cardiometabolic disease. Elevated 2-AAA observed in individuals prior to onset of diabetes and atherosclerosis may be an early biomarker of dysfunction in this pathway.
Abstract 13363: Renoprotective Effects of Empagliflozin in Patients With Acute Myocardial Infarction and Type 2 Diabetes Mellitus; Subgroup Analysis of the Embody Trial
Authors: Mozawa Kosuke , Kubota Yoshiaki , Hoshika Yu , Tara Shuhei , Tokita Yukichi , Yodogawa Kenji , Iwasaki Yu-ki , Yamamoto Takeshi , Takano Hitoshi , Tsukada Yayoi , Asai Kuniya , Miyamoto Masaaki , Miyauchi Yasushi , Kodani Eitaro , Maruyama Mitsunori , Tanabe Jun , Shimizu Wataru
Published: May 2021

Introduction:
Although renoprotective effect of sodium glucose co-transporter-2 (SGLT2) inhibitors has been recognized in the patients with heart failure or type 2 diabetes mellitus (T2DM), this protection has not been fully examined in patients with acute myocardial infarction (AMI). We therefore examined renoprotection of the SGLT2 inhibitor empagliflozin in patients with AMI and T2DM.

Methods:
The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of the SGLT inhibitor on cardiac sympathetic hyperactivity in patients with AMI and T2DM in Japan. One hundred and five patients were randomized (1:1) to receive once-daily 10-mg empagliflozin, or placebo 2 weeks after the onset of AMI. In this sub-analysis, we specifically focused on the time-course of renal function on baseline, weeks 4, 12 and 24.

Results:
Overall, 96 patients (64±11 y, 78 male) were included in the full analysis set (n = 46 and 50 in empagliflozin and placebo groups, respectively). In the placebo group, estimated glomerular filtration rate (eGFR) decreased from 66.1 at baseline to 62.8 mL/min/1.73m
2
on week 24, (P = 0.02). On the other hand, the empagliflozin group did not worsen it (from 64.6 to 64.4 mL/min/1.73m
2
, P = 0.84). The empagliflozin group exhibited the significant reduction in systolic blood pressure and uric acid level from baseline to week 24 (129.7 mmHg to 123.1 mmHg, P = 0.004, and 5.8 mg/dL to 4.9 mg/dL, P < 0.0001, respectively), whereas the reduction was not significant in the placebo group (123.1 mmHg to 126.2 mmHg, P = 0.19, and 5.7 mg/dL to 5.8 mg/dL, P = 0.82, respectively). The change in eGFR from baseline to 24 weeks was negatively correlated with the changes in uric acid in the placebo group (r=0.685, P<0.001), but not in the empagliflozin group. In stratified analysis among the patients with eGFR 60-90 mL/min/1.73m
2
, the empagliflozin group showed the significant increase in eGFR compared with the placebo group (+1.15 mL/min/1.73m
2
vs, - 6.43 mL/min/1.73m
2
, P=0.008), but not among the other population.

Conclusions:
Empagliflozin seemed to prevent the progression of renal dysfunction compared with placebo in the patients with AMI and T2DM. This tendency was remarkable when eGFR was 60-90 mL/min/1.73m
2
.
Abstract 13373: Exercise Improves Angiogenic Function of Circulating Exosomes in Type 2 Diabetes: Role of Extracellular SOD
Authors: Abdelsaid Kareem , Varadarajan Sudhahar , Das Archita , Liu Yutao , Fang Xuexiu , McMenamin Malgorzata , Tang Yaoliang , Fukai Tohru , Ushio-fukai Masuko
Published: May 2021

Background:
Exosomes, key mediators of cell-cell communication, derived from type 2 diabetes mellitus (T2DM) have detrimental effects. Exercise not only improves endothelial dysfunction and angiogenesis in T2DM but also induces secretion of exosomes into circulation. Extracellular superoxide dismutase (ecSOD) is a major secretory Cu containing antioxidant enzyme that catalyzes dismutation of O
2
•-
to H
2
O
2
and its full activity requires Cu transporter ATP7A. We reported that ecSOD-derived H
2
O
2
in endothelial cells (ECs) enhances angiogenesis while impaired ATP7A-ecSOD axis in diabetes induces endothelial dysfunction. Here we examined whether exercise-derived exosomes (Exe-Exo) may have pro-angiogenic effects via regulating ATP7A-ecSOD axis in T2DM.

Results:
Two weeks of voluntary wheel exercise of control C57Bl6 mice increased plasma exosome levels (6.2-fold) characterized by Nanosight, TEM and exosome markers (CD63, CD81, Tsg101). Treatment of HUVECs with equal number of exosomes revealed that angiogenic responses such as EC migration (1.8-fold) and tube formation (1.7-fold) were significantly enhanced by Exe-Exo compared to sedentary-derived exosomes (Sed-Exo). This was associated with increased ATP7A (2.9-fold) and ecSOD (1.4-fold) expression in Exe-Exo. Sed-Exo from high fat-induced T2DM mice significantly decreased EC migration (40%) and tube formation (10%) as well as ATP7A expression (28%) compared to Sed-Exo from control mice, which were restored by T2DM Exe-Exo, but not by T2DM/ecSOD KO Exe-Exo. Furthermore, exosomes overexpressing ecSOD (ecSOD-Exo) which mimic exercise increased angiogenesis and H2O2 levels in ECs, which were inhibited by overexpression of catalase. In vivo, skin wound healing model showed that direct application of T2DM Sed-Exo delayed while T2DM Exe-Exo enhanced wound healing of control mice. Furthermore, defective wound healing in T2DM mice or ecSOD KO mice were rescued by ecSOD-Exo application.

Conclusion:
Exercise training improves pro-angiogenic function of circulating exosomes in T2DM via increasing ATP7A-ecSOD axis, which may provide an effective therapy for promoting angiogenesis and wound repair in metabolic and cardiovascular diseases.
Abstract 13385: Protective Effect of Beta3-Adrenergic Receptor Deficiency on Diabetic Cardiomyopathy: Reversal of Type 2 Diabetes-Induced Contrast Changes of Cardiac SERCA 2a and Inducible Nitric Oxide Synthase
Authors: Cheng Heng Jie , Sun Xiaoqiang , Cao Jing , Chen Zhe , Liu Yixi , Zhao David , Kitzman Dalane , Cheng Che
Published: May 2021

Background:
We have shown that diabetes (DM)-induced cardiac dysfunction and β-adrenergic desensitization were prevented in β
3
-adrenergic receptor (AR) knockout (β
3
KO) mice. However, the molecular mechanism is unclear. We hypothesize that reversal of type 2 (T2) DM-induced alterations of cardiac SR Ca
2+
-ATPase (SERCA2a) and inducible nitric oxide synthase (iNOS) by β
3
KO may play a key role for the protective effect.

Methods:
LV myocyte protein levels of β
1
- and β
3
-AR, SERCA2a and iNOS, myocyte contractile and [Ca
2+
]
i
transient ([Ca
2+
]
iT
) responses to isoproterenol (ISO, 10
-8
M) were compared in 4 groups (n=6) female mice: 2
Vehicle controls
wild-type (CWT) and Cβ
3
KO; and 2
T2DM
of T2WT and T2β
3
KO.T2 was induced by fed high-fat diet (HFD) for 14 weeks (W), but after HFD for 4 W receiving streptozotocin (STZ, 40 mg/kg/day, i.p. for 5 days).

Results:
Mice-treated with HFD plus STZ had high blood glucose (~350 to 380 mg/dl). Versus CWT, T2WT myocytes had significantly decreased protein levels of SERCA2a (0.18 vs 0.29), and β
1
-AR (0.35 vs 0.49), but increased iNOS (0.25 vs 0.15) and β
3
-AR (0.25 vs 0.14) with reduced cell contraction (dL/dt
max
) (72.7 vs 140.9 μm/s), relaxation (dR/dt
max
) (50.9 vs 117.3 μm/s) and [Ca
2+
]
iT
(0.16 vs 0.22). Moreover, in T2WT myocytes, ISO caused significantly less increases in dL/dt
max
(37% vs 59%), dR/dt
max
(30% vs 53%) and [Ca
2+
]
iT
(19% vs 30%). Versus CWT, T2β
3
KO did not alter basal myocyte contraction and relaxation and response to ISO stimulation, but had significantly increased protein levels of SERCA2a (0.38 vs 0.29). T2β
3
KO prevented DM-caused increase in iNOS (T2β
3
KO: 0.16 vs CWT: 0.15) and decrease in β
1
-AR (0.46 vs 0.49). Versus T2β
3
KO, Cβ
3
KO mice had similar alterations. Importantly, in contrast to T2WT, in T2β
3
KO myocytes, the increased SERCA2a and reduced iNOS correlated with normal basal cell contraction and relaxation with preserved ISO-stimulated inotropic response. ISO caused similar increases in dL/dt
max
(60% vs 59%), dR/dt
max
(51% vs 53%) and [Ca
2+
]
iT
(32% vs 30%).

Conclusions:
β
3
KO prevents T2DM-caused downregulation of cardiac β
1
-ARs and reverses increased iNOS and decreased SERCA2a, leading to the preservation of myocyte function, [Ca
2+
]
iT
, and β-adrenergic reserve. Thus, β
3
-AR may provide a new target for DCM.
Abstract 13393: The Genetic Architecture of Plasma Kynurenine Points to Mechanisms Underlying Its Association With Cardiovascular Diseases
Authors: Bagheri Naraghi Minoo Sadat , Shi Mingjian , Wang Chuan , Mosley Jonathan D. , Ferguson Jane F
Published: May 2021

Background:
The etiological mechanisms accounting for epidemiological associations between biomarkers and cardiovascular diseases (CVD) are often poorly defined. One example is the metabolite kynurenine, which has been associated with diverse inflammatory-related disease including CVD. We leveraged genetic approaches to elucidate the underlying mechanisms and possible causal relationships accounting for the kynurenine-CVD association.

Methods:
In this phenome-wide association study (PheWAS), we identified genetic predictors of plasma kynurenine from published genome-wide association studies. We explored associations between both the individual variants and a kynurenine polygenic risk score (PRS) and diseases including heart disease, atherosclerosis, and myocardial infarction in genotyped populations including UK Biobank (n= 456422), Vanderbilt BioVU (n=62,303) and Electronic Medical Records and Genetics (eMERGE) (n=32,324). We applied both single-variant and multi-variant approaches using multivariable logistic regression models.

Results:
There were no disease associations with a kynurenine PRS, indicating that plasma kynurenine is not a direct mediator of cardiovascular disorders. However, single-variant association analyses identified a robust signal with the kynurenine-associated missense variant in
SH2B3
(rs3184504) and myocardial infarction, atherosclerosis of the extremities, peripheral vascular disease , chronic ischemic heart disease , and congestive heart failure (CHF) (all with FDR q<0.05). These findings were replicated in the UK Biobank data. In mice, loss of
SH2B3
was associated with significant differences in plasma and tissue levels of kynurenine.

Conclusions:
Plasma kynurenine may not be causal mediator of cardiovascular disorders. However, the observed relationship between kynurenine and CVD phenotypes in epidemiological studies may be driven through
SH2B3
mechanisms, the gene implicated as a novel genetic regulator of kynurenine.
Abstract 13417: Impact of Sex on the Prognostic Value of Galectin-3 in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study
Authors: Wada Hiromichi , Kotani Kazuhiko , suzuki masahiro , Matsuda Morihiro , Ajiro Yoichi , Shinozaki Tsuyoshi , Sakagami Satoru , Yonezawa Kazuya , shimizu masatoshi , FUNADA JUNICHI , Takenaka Takashi , Morita Yukiko , Nakamura Toshihiro , Fujimoto Kazuteru , Matsubara Hiromi , Kato Toru , Unoki Takashi , Takagi Daisuke , Wada Kyohma , Wada Miyaka , Iguchi Moritake , Masunaga Nobutoyo , ISHII MITSURU , Abe Mitsuru , Akao Masaharu , Hasegawa Koji
Published: May 2021

Background:
High circulating levels of galectin-3 are associated with all-cause mortality, cardiovascular (CV) mortality, and/or major adverse CV events (MACE) in patients with CV diseases such as heart failure and coronary artery disease (CAD). However, the impact of sex on the prognostic value of galectin-3 in patients with suspected or known CAD remains unclear.

Methods:
Using data from a multicenter, prospective cohort of 2418 patients with suspected or known CAD, we assessed the impact of sex on the association between galectin-3 levels and the risks of all-cause death, CV death, and MACE defined as a composite of CV death, nonfetal myocardial infarction, and nonfetal stroke. Galectin-3 was measured in 1624 men and 794 women enrolled in the ANOX Study. Patients were followed up over 3 years.

Results:
The mean ages (standard deviations) were 69.8 (10.6) years in men and 72.2 (9.9) years in women (
P
<0.001). Men exhibited significantly lower levels of galectin-3 compared to women (median [interquartile range], 9.0 [6.9-11.9] versus 9.6 [7.3-12.4] ng/mL, respectively;
P
=0.004). In the entire patient cohort, the galectin-3 level was significantly associated with all-cause death (hazard ratio per 1 standard deviation increase [HR], 1.28; 95% confidence interval [CI], 1.16-1.42), CV death (HR, 1.24; 95% CI, 1.04-1.46), and MACE (HR, 1.24; 95% CI, 1.09-1.41) after adjusting for potential clinical confounders. These associations were still significant in women (HR for all-cause death, 1.59; 95% CI, 1.26-1.98; HR for CV death, 1.53; 95% CI, 1.06-2.21; HR for MACE, 1.61; 95% CI, 1.21-2.09), whereas in men, galectin-3 was significantly associated with all-cause death (HR, 1.23; 95% CI, 1.08-1.39), but not with CV death (HR, 1.14; 95% CI, 0.93-1.40) or MACE (HR, 1.15; 95% CI, 0.99-1.35). Furthermore, galectin-3 provided incremental prognostic information for all-cause death, but not for CV death or MACE, to the model with potential clinical confounders and the established CV biomarkers in the entire cohort and in women, but not in men.

Conclusions:
We identified a significantly stronger prognostic value of galectin-3 in women than in men among patients with suspected or known CAD.
Abstract 13422: Long Term Association of Low Density Lipoprotein Patterns With Coronary Artery Calcium and Atherosclerotic Cardiovascular Disease Events: Insights From HeartSCORE Study
Authors: Saeed Anum , Swanson Justin , Saeed Gul J , Kip Kevin , Reis Steven
Published: May 2021

Introduction:
Low-density lipoprotein (LDL) cholesterol, a factor in progression of atherosclerotic cardiovascular disease (CVD), consists of sub-fractions with different sizes and densities in three patterns (A (large buoyant), B (small dense), AB (intermediate pattern). We examined the associations of LDL patterns with subclinical ASCVD and future events.

Methods:
Participants from the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study were assessed for baseline lipid levels and LDL sub-fraction types by an ultracentrifugation method (vertical auto profile). Electron beam CT scans were obtained in a subset of individuals and coronary artery calcium (CAC) scores were calculated (Agatston method). Adjusted odds ratios and hazard ratios (95% CI) were calculated using logistic regression and Cox regression, respectively, to estimate the independent association between LDL sub-fractions and both; CAC and ASCVD events (MI, ischemic stroke, death), respectively.

Results:
Among 1884 eligible participants (mean [SD] age; 59[7.5]y, 65.8% women, 37.9% black), mean HDL-c, LDL-c and Triglycerides were 142.2[36.0]mg/dL, 58.2[14.9]mg/dL and 111.2[47.7]mmHg, respectively. Sub-fractions of LDL pattern A, B and AB were observed in 761(40%), 507(26.9%) and 616(32.7%) individuals. Over a follow up of ~16y, patterns B(1.98[1.22-3.21) and AB (1.54[1.00-2.38)] were independently associated with incident risk of CVD events (vs pattern A). When stratified by race and gender, pattern AB showed independent risk of incident CVD events and CAC presence among blacks and males
(Table)
.

Conclusions:
In this biracial cohort of middle-aged adults, LDL sub-fraction patterns B and AB showed a significantly higher risk of long-term CVD events. Pattern AB was also associated with positive CAC in blacks and males. Further studies are needed to investigate LDL patterns in CVD risk profiling based on race and gender.
Abstract 13424: Demographic and Echocardiographic Predictors of Later-onset Cardiac Variant of Fabry Disease Among Chinese Patients With Left Ventricular Hypertrophy
Authors: Chan Tsz Ngai , Chow Josie Tsz ying , Kam Kevin Ka Ho , Sheng Bun , FAN YITING , Wong Ka Tak , Mei Po Mabel Tong , Choi Paul CL , Fung Erik , Chan Joseph YS , Chi Wai Kin , Lee Alex Pui-Wai
Published: May 2021

Introduction:
The genetic mutation IVS4+919G>A commonly found among Chinese is associated with later-onset cardiac variant of Fabry disease (FD). Patients with left ventricular hypertrophy (LVH) may be screened for FD by measuring plasma α-galactosidase activity.

Objective:
The aim of our study is to determine the prevalence of FD among Chinese LVH patients and to define demographic and echocardiographic predictors of FD.

Methods:
We measured plasma α-galactosidase activity using dried blood spot test in 500 Hong Kong Chinese patients with LVH (defined as maximal left ventricular septal or posterior wall thickness ≥13 mm on transthoracic echocardiography). LVH and deficiency in α-galactosidase activity prompted genetic analysis of galactosidase alpha gene. Demographic and echocardiographic predictors of FD were analysed.

Results:
There are 9 (1.8%) of 500 LVH patients (all men, age 53–74 years) had low α-galactosidase activity (0.64±0.32 μmol/L wb/hr) and all were confirmed to have the FD genotype IVS4+919G>A. Among these 9 FD patients, 6 (66.7%) could be traced to the ancestral home Chaozhou (southern part of China), 4 had hypertension, but none exhibited extracardiac manifestations of FD. The left ventricular mass of FD patients ranged from 64.91–811.81 g. Ancestral home Chaozhou (odds ratio, 10.28; 95% confidence Interval, 2.52–41.94; p=0.001) and LVM ≥290 g (odds ratio, 7.39; 95% confidence Interval, 1.94–28.20; p=0.003) were predictors of FD. On receiver operating characteristic curve analysis, sensitivity and specificity of LVM ≥290 g to diagnose FD vs non-FD LVH are 67% and 86.4% respectively (area under curve, 0.8; p=0.002).

Conclusion:
There is a high prevalence of later-onset cardiac variant FD among Hong Kong Chinese LVH patients that is associated with IVS4+919G>A genotype. Male patients with ancestral home Chaozhou and LVM ≥290 g are at an increased risk of FD among Chinese LVH patients and should be screened with dried blood spot test.
Abstract 13435: Characterization of Open Chromatin in Human Mitral Valves to Identify Regulatory Mechanisms at Mitral Valve Prolapse Genetic Loci
Authors: Kyryachenko Sergiy , Georges Adrien , Yu Mengyao , Berrandou Takiy , Rubio Tony , Gronwald Judith , Baraki Hassina , Kutschka Ingo , Norris Russel , Voigt Niels , Bouatia-Naji Nabila
Published: May 2021

Introduction:
Mitral valve prolapse (MVP) is a common valve disease that leads to mitral insufficiency, heart failure, and sudden death. The identification of genetic risk loci provided insight into its genetic architecture, although the causal variants and target genes need to be fully characterized.

Hypothesis:
Functional genomic annotation, including chromatin accessibility profiles of human mitral valves, allows the characterization of variants and target genes at MVP loci.

Methods:
We determined open chromatin regions using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-Seq) from surgically removed human valves and primary cultures of fibroblasts. We analyzed the spatial conformation of MVP-associated loci using circular chromatin conformation capture (4C-Seq) with candidate causal variants as viewpoints. Candidate causal variants were followed-up using reporter assays and
in silico
analyses.

Results:
We mapped the open chromatin from 11 human mitral valves and 3 primary cell cultures. We found that mitral valve-specific ATAC-Seq peaks were enriched near genes involved in extracellular matrix organization, chondrocyte differentiation, and connective tissue development. We also found that MVP-associated variants (p<10
-5
) observed in the MVP GWAS were significantly enriched (p<0.05) in mitral valve open chromatin regions, but not in heart tissue from ENCODE. We found that rs6723013 on Chr2 belongs to a valve-specific enhancer at the
IGFBP5/TNS1
locus and is the most likely causal variant at this locus. We also identified several plausible causal SNPs and, by using 4C-Seq, potential target genes (
HIC1
and
DPH1
) at the
SMG6/SRR
locus.

Conclusions:
Here we describe unprecedented genome-wide open chromatin profiles from human mitral valves that indicate specific gene regulation profiles, compared to the heart. We also report
in vitro
functional evidence for potential causal variants and target genes at MVP risk loci involving established and new biological mechanisms relevant to mitral valve disease.
Abstract 13456: Association of Chronic Inflammatory Diseases With Incident Atrial Fibrillation
Authors: Tanaka Yoshihiro , Rivera Adovich , Sinha Arjun , Patel Ravi B , Passman Rod S , Feinstein Matthew J
Published: May 2021

Introduction:
Inflammation plays a vital role on the pathophysiology of atrial fibrillation (AF). Although it is hypothesized that chronic inflammatory diseases (CIDs) may increase the risk for incident AF, data are scarce regarding whether CIDs are associated with incidence of AF.

Objectives:
To determine associations of CIDs with incident AF in a large cohort comprised of patients with multiple different CIDs.

Methods:
Patients who visited outpatient clinic regularly due to CIDs (human immunodeficiency virus infection, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic sclerosis [SSc], and systemic lupus erythematosus [SLE]) and frequency-matched controls (in regular primary care/general medicine clinic) were extracted from the Northwestern electronic health records between 1/1/2000-1/1/2019. Multiple imputation was used for imputing missing values and all following statistical analyses. Cumulative incidence of AF was estimated by the Kaplan Meier Curve, and adjusted Cox proportional hazard models were used to compute hazard ratio (HR) for each CID.

Results:
We analyzed a total number of 37,601 patients (18,847 CIDs and 19,871 controls without CIDs, median age 48.4 years, male 43%). During a median follow-up period of 3.6 years, 1076 cases (2.9%) of incident AF were observed. After adjusting for covariates included in CHARGE-AF risk score, baseline year, insurance type, baseline hypertension, and estimated glomerular filtration rate, both SSc (HR, 2.29: 95% confidence interval [CI], 1.72 - 3.06; p < 0.01) and SLE (HR, 2.18; 95% CI, 1.65 - 2.90; p < 0.01) were associated with a significantly elevated incidence of AF (Table).

Conclusions:
Patients with SSc or SLE had a significantly elevated incidence of AF after multivariable adjustment. Future studies should investigate mechanisms underlying these findings to generate both disease-specific knowledge and more generalizable knowledge regarding inflammatory contributors to AF.
Abstract 13471: Additional Prognostic Value of Vasodilator Stress Cardiovascular Magnetic Resonance in Patients With Inconclusive Stress Test to Detect Coronary Artery Disease
Authors: Pezel Theo , Bonnet Guillaume , Sanguineti Francesca , Kinnel Marine , Asselin Anouk , Hovasse Thomas , Garot Philippe , Toupin Solenn , Morice Marie Claude , Champagne Stephane , Unterseeh Thierry , Louvard Yves , Garot Jerome
Published: May 2021

Introduction:
Non-invasive testing for ischemia to diagnose coronary artery disease(CAD) are frequently inconclusive(25%).

Hypothesis:
To assess the prognostic value of stress CMR in patients with a first inconclusive stress test.

Methods:
Between 2008 and 2018, consecutive patients with inconclusive stress test, defined by stress echocardiography or nuclear testing with uncertain conclusion, prospectively referred for stress CMR with dipyridamole were followed for major adverse cardiovascular events(MACE): cardiac death or myocardial infarction. An unsupervised clustering analysis was performed.

Results:
Of 1502 patients (62±12yrs, 59%men), 1397 completed the follow-up (median 5.5±2.3yrs). Three clusters were identified: Cluster 1 (n=524) had the highest prevalence of previous PCI, the highest presence of a myocardial scar defined, the lowest LVEF (35±7%) and the highest LV dilatation. Cluster 2 (n=406) had the highest previous CABG prevalence, preserved LVEF, absence of LV dilatation, and presence of myocardial scar. This cluster comprised predominantly male patients, with the highest rate of hypertension. Cluster 3 (n=572) had the lowest rate of previous PCI/CABG, the lowest rate of myocardial scar, predominantly female, the highest atrial fibrillation rate and body mass index. Survival analysis found significant differences across clusters for the occurrence of MACE (p=0.02). Inducible ischemia was associated with MACE occurrence in each cluster (C1, HR 2.28; 95%CI[1.31-3.99]; p=0.0028; C2, HR 3.37; 95%CI[1.97-5.75]; p<0.0001; C3, HR 2.73; 95%CI[1.67-4.46]; p<0.0001). In multivariable analysis, inducible ischemia predicted MACE in each cluster (p<0.001 for all).

Conclusions:
Cluster analysis identified 3 different phenotypes with distinct clinical and prognostic profiles. Within these clusters, stress CMR has an additional prognostic value to predict MACE..
Abstract 13478: Pulmonary Embolism in Covid-19 Patients:A French Multicentre Cohort Study
Authors: Fauvel Charles , Weizman Orianne , Trimaille Antonin , Mika Delphine , Pace Nathalie , Douair Amine , Barbin Eva , Fraix Antoine ,   Critical Covid-19 France Investigators, Duceau Baptiste , Sutter Willy , Waldmann Victore , Bonnet Guillaume , COHEN Ariel , Pezel Theo
Published: May 2021

Introduction:
While pulmonary embolism(PE) appears to be a major issue in Covid-19, data remain sparse.

Hypothesis:
We aimed to describe the risk factors and baseline characteristics of patients with PE in a cohort of Covid-19 patients.

Methods:
In a retrospective multicentric observational study, we included consecutive hospitalised patients for Covid-19. Patients without computed tomography pulmonary angiography (CTPA)-proven PE diagnosis and those who were directly admitted to an intensive care unit(ICU) were excluded.

Results:
Among 1,240 patients (58.1% men, mean age 64±17 years), 103 (8.3%) patients had PE confirmed by CTPA. The ICU transfer and mechanical ventilation were significantly higher in the PE group (for both p<0.001). In an univariable analysis, traditional venous thromboembolic risk factors were not associated with PE (p>0.05), while patients under therapeutic-dose anticoagulation before hospitalisation or prophylaxis-dose anticoagulation introduced during hospitalisation had lower PE occurrence (OR 0.40, 95%CI(0.14-0.91); p=0.04 and OR 0.11, 95%CI(0.06-0.18); p<0.001, respectively). In a multivariable analysis, the following variables, also statistically significant in univariable analysis, were associated with PE: male gender (OR 1.03, 95%CI(1.003-1.069); p=0.04), anticoagulation with prophylaxis-dose (OR 0.83, 95%CI(0.79-0.85), p<0.001) or therapeutic-dose (OR 0.87, 95%CI(0.82-0.92), p<0.001), C-reactive protein (OR 1.03, 95%CI(1.01-1.04), p=0.001) and time from symptom onset to hospitalisation (OR 1.02, 95%CI(1.006-1.038), p=0.002).

Conclusions:
Pulmonary embolism risk factors in Covid-19 context do not include traditional thromboembolic risk factors but rather independent clinical and biological findings at admission, including a major contribution to inflammation.
Abstract 13484: Acute Coronary Syndrome: A Unique Presentation of Libman Sacks Endocarditis
Authors: Hussain Sheraz , Afshar Ambar A , Joshi Anjali , Khan Muhammad A , Tatooles Antone , Pappas Patroklos
Published: May 2021

Introduction:
Systemic Lupus Erythematosus (SLE) is a chronic inflammatory disease with multiorgan involvement. Cardiac involvement can range from endocarditis to cardiomyopathy. We present a case of SLE complicated by Libman Sacks Endocarditis (LSE) presenting as an acute coronary syndrome (ACS).

Case Presentation:
A 34 year old male with a history of SLE, DVT/PE, RCA thrombus status post thrombectomy, noncompliance and drug abuse presented to the hospital with complaints of central chest pain associated with right neck, jaw, mouth and arm pain. Vitals were stable. Troponin increased from 0.8 to 13. EKG demonstrated inferior Q waves and ST elevation. CT angiogram was negative for pulmonary embolism but revealed a mobile aortic mass involving the right coronary cusp at the origin of right coronary artery. Transthoracic echocardiogram confirmed this finding. He was started on an infusion of heparin. Surgical evaluation was obtained for emergent thrombectomy and coronary artery bypass grafting. Due to the aortic root thrombus, coronary angiogram was not performed. Lower extremity venous and arterial doppler revealed chronic bilateral DVTs as well as a thrombus in the right common femoral artery. A right heart catheterization demonstrated normal cardiac output and intracardiac filling pressures.Rheumatology was consulted and the patient’s presentation was deemed secondary to Libman sacks endocarditis in the setting of untreated SLE. The pro-coagulant state was chronic and exacerbated secondary to medical noncompliance. Patient was started on hydroxychloroquine with plans for long term anti-coagulation with warfarin in addition to daily aspirin. His symptoms subsided and was discharged home with plans for outpatient follow up.

Discussion:
Libman sacks endocarditis is a form of noninfectious endocarditis in SLE patients with deposition of thrombi on heart valves. In literature it has been reported to cause valvular dysfunction and cerebrovascular thromboembolism. Our case was unique as it represents a rare manifestation of LSE with an embolic event to a coronary vessel causing ACS. The patient was known to have had prior LSE and due to the complexity of his case and history of medical noncompliance, he was deemed a poor surgical candidate.
Abstract 13493: Mechanism and Prognostic Significance of Cardiothoracic Ratio in Patients With Heart Failure With Preserved Ejection Fraction - Insights From Pursuit-hfpef Registry -
Authors: Okada Masato , INOUE KOICHI , Iwakura Katsuomi , Onishi Toshinari , Hikoso Shungo , Nakatani Daisaku D , Tamaki Shunsuke , Yano Masamichi , Hayashi Takaharu , Nakagawa Akito , Nakagawa Yusuke , Yasumura Yoshio , Yamada Takahisa , Sakata Yasushi
Published: May 2021

Introduction:
The cardiothoracic ratio (CTR) is a widely accepted method of quantifying cardiac size, and carries prognostic information in acquired heart disease. However, little is described in the underlying mechanism and prognostic value in heart failure with preserved ejection fraction (HFpEF).

Methods:
Analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 871 patients hospitalized for acute HF (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction (LVEF) ≥50% and brain natriuretic peptide (BNP) ≥100 pg/ml. We included 629 patients (age, 81±9 years; men, 46%; atrial fibrillation, 37%) whose follow-up data after survival discharge were available and whose CTR were measured from posterior-anterior chest X-ray. The endpoint was defined as the composite of death, re-hospitalization for HF, and cerebrovascular accident.

Results:
Median CTR at discharge was 56% (interquartile range: 51-61%). Comparison with echocardiographic data revealed that CTR significantly correlated with increased left atrial size (left atrial volume; r = 0.39, p <0.001) and LV filling pressure (E/e’ ratio; r = 0.13, p = 0.002), but not with LV size (LV end-diastolic volume; r = -0.014; LV end-systolic volume: r = -0.002) and LVEF (r = -0.035). Age (r = 0.16, p <0.001) and log-transformed N-terminal-pro-BNP value (r = 0.21, p <0.001) were also correlated with CTR. Female patients exhibited more higher CTR than male patients (54±7 vs. 58±7%, p <0.001). During a median follow-up of 15 months, 257 patients experienced the endpoint. When patients were classified into the CTR quartile groups, there was a positive correlation between the incidence rate and the quartiles (Q1, 31.0%; Q2, 39.5%; Q3, 35.7%; Q4 55.8%, p <0.001). After adjustment for age and gender, Cox regression analysis revealed that CTR at discharge was a significant predictor of the composite endpoint (hazard ratio per quartile increase; 1.23; 95% confidence interval, 1.10-1.39; p = 0.006).

Conclusions:
CTR was not associated with LV size but left atrial size in patients with HFpEF. Increased CTR at discharge predicted unfavorable prognosis in patients with HFpEF.
Abstract 13499: Percutaneous Coronary Intervention for Bifurcation Lesions in Patients With Acute Coronary Syndrome
Authors: CHOUDHARY RAHUL , Deora Surender , Kaushik Atul , Sharma Jai B
Published: May 2021

Introduction:
Percutaneous coronary intervention (PCI) for the treatment of bifurcation lesions in acute coronary syndrome (ACS) setting is a high-risk procedure and is associated with higher periprocedural complications and a lower procedural success rate.

Hypothesis:
We assessed the hypothesis that PCI for bifurcation stenting in ACS is safe and effective as in non ACS condition.

Methods:
Out of 986 patients who underwent PCI for ACS, 144 (14.6%) patients having bifurcation lesion were included in study. Provisional stenting was favored whenever feasible (86.8%), elective bifurcation stenting (2 stent strategy) was reserved for significant long segment side branch involvement (13.2%). Occurrence of major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction, target lesion revascularization, and stent thrombosis, was observed during follow up.

Results:
LAD bifurcation was the most common lesion (49.3%), most common Medina class was 1, 1, 1 (52.1%), 70.8% of the procedures were done transradially, angiographic success rate for main vessel was 97.9% and there was no periprocedural mortality or stroke. There was no significant difference regarding risk factors (age, hypertension, diabetes mellitus, dyslipidemia and smoking history;
p
> 0.05) between 1 stent and 2-stent groups. Median Syntax score was 14(IQR 10-20) in 1 stent group and 22(IQR 17-25) in 2 stent group. The 2-stent group had higher proportion of left main coronary involvement as compared to 1 stent group (47.4 vs 24.8%). Crush was preferred elective 2-stent strategy as compared to TAP in provisional approach (used in 73.7 and 62.5%). Final kissing balloon inflation was used in 38.4% patients in 1- stent group, while it was utilised in all patients with 2- stent approach. Post procedural side branch diameter stenosis (by QCA) differed significantly between the 2 groups (1-stent vs 2-stent, 34.9 vs 6.4%).The rate of MACE was similar in both groups ( total 7 MACE events; median follow-up of 18 months) but radiation dose and contrast volume utilization were significantly more in 2-stent group.

Conclusions:
PCI for bifurcation lesions had acceptable success and MACE rate even during ACS settings and whenever feasible, provisional stenting should be preferred approach.