bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11111: In-Hospital Outcomes of Coronary Atherectomy in Teaching vs Non-Teaching Hospitals
Authors: Horoub Ali , Markson Favour , Sholi Tasnim , Farukhuddin FNU , Fatuyi Michael , Diabat Mohammad , Al-Khateeb Mohannad , Orji Richard , Al Jabiri Yazan , Kesiena Onoriode , Maqsood Muhammad H , Yusuf Mubarak , Kilani Yassine
Published: June 2023

INTRODUCTION:
Studies have analyzed contemporary data on outcomes at teaching vs non-teaching hospitals with the results found to be dissimilar in certain procedures in the United States. Coronary Atherectomy (CA) is a minimally invasive procedure that involves the opening of obstruction from heavily calcified blocked coronaries to improve blood flow to the heart. This study is set out to examine the differences in health care outcomes between teaching and non-teaching hospitals in patients who underwent CA using a nationally representative sample.

METHODS:
We reviewed data from the National Inpatient Sample (NIS) of patients admitted between 2016-2019. Using ICD-10 procedural codes, we identified patients who underwent CA (Rotational or Orbital) within the study period. We further categorized our study population into 2 groups based on teaching vs non-teaching status. Multivariate analysis was done to investigate the in-hospital outcomes between both groups and adjust for confounders.

RESULTS:
A total of 171,740 CA procedures were performed within the study period. 75% (129,585) vs 25% (42,155) of these procedures were performed in teaching vs non-teaching hospitals respectively. The mean age of patients who underwent the procedure was 65 years, with a higher preponderance in males (71.4%). There was no significant difference in in-hospital mortality in both groups (AOR 1.06, 95% CI 0.93 -1.21, p=0.372). There was also no observed difference in the odds of coronary perforation or cardiac tamponade (AOR 1.26, 95% CI 0.89-1.28 p=0.19) and (AOR 1.23, 95% CI 0.82-1.87, p=0.31) respectively. However, the teaching hospital groups had an increased odds of Coronary dissection (AOR 1.34, 95% CI 1.05 - 1.71, p=0.017) and heart Block (AOR 1.22, 95% CI 1.11-1.34, p< 0.001). We also noticed an increased odds of septic shock (AOR 1.24, 95% CI 1.05-1.80, p= 0.018), AKI (AOR 1.12, 95% CI 1.07-1.22, p=0.005) and a higher hospitalization duration (Adjusted coefficient 0.43, 95% CI 0.30-0.56, p< 0.001) in the teaching hospital group
.

CONCLUSION:
CA performed at teaching hospitals is found to be associated with an increased risk of cardiac (coronary dissection and heart block) and non-cardiac (septic shock and AKI) outcomes.
Abstract 11121: In-Hospital Outcomes of Aortic Dissection in Patients With Substance Use Disorder
Authors: Markson Favour , Horoub Ali , Sholi Tasnim , Farukhuddin FNU , Fatuyi Michael , Al Jabiri Yazan , Diabat Mohammad , Al-Khateeb Mohannad , Orji Richard , Kesiena Onoriode , Kilani Yassine , Yusuf Mubarak , Maqsood Muhammad H
Published: June 2023

Introduction:
Substance Use Disorder (SUD) is a chronic relapsing disease emanating from the uncontrolled use of drugs despite devastating physical, neurologic and psychological consequences. Studies have proven an association of SUD with a variety of life-threatening cardiac conditions. Aortic dissection (AD) is an acute condition caused by a tear in the inner layer of the aorta and requires immediate intervention. Our study aimed to ascertain the in-hospital outcomes of patients with substance use disorders presenting with Aortic dissection using a national representative sample.

Methods:
This was a retrospective study done using the 2016-2019 National inpatient sample, ICD 10 codes were used to identify individuals who were admitted for aortic dissection who were further categorized into two groups based on a history of SUD or not. Multivariate analysis was used to control for confounders and assess in-hospital mortality and other hospital outcomes.

Results:
A total of 63,380 patients were admitted for Aortic dissection during the study period. 26% (16,775) of the population sample had active abuse of at least 1 substance. AD was identified in a younger age group with SUD vs those without SUD with a mean age of 57. vs 65 years respectively. 68% of patients with SUD were found to be males with the predominant race being white (56%). A higher proportion of SUD patients had co-morbid Hypertension (60%) and smoked Cigarette (92%). Comparing both groups, there was no statistical difference in in-hospital mortality (AOR 1.06, 95% CI 0.88-1.26, p=0.50). However, there was a higher risk of acute coronary syndrome (AOR 1.77, 95% CI 1.20-2.40, p= 0.01), Cardiogenic shock (AOR 1.26, 95% CI 1.01-1.57, p< 0.001) and Embolic stroke (AOR 1.33, 95% CI 1.05-1.67, p=0.019) in the SUD group. We also observed no difference in the mean length of stay (adjusted coefficient 0.456, 95% CI 0.049- 0.96, p=0.077) or the mean of total hospital charges (adjusted coefficient 3882, 95% CI -10548.17- 18313.79, p= 0.60) in both groups.

Conclusions:
We observed that in hospitalized patients with AD, SUD is not associated with an increased risk of in-hospital mortality, however, there is a significantly increased risk of cardiogenic shock, coronary syndrome, and embolic stroke.
Abstract 11129: Left Atrial Proteomic Signature in Atrial Fibrillation and Advanced Heart Failure
Authors: Aleong Ryan G , Chang Shu , Tzou Wendy , Bristow Michael R
Published: June 2023

Introduction:
Atrial fibrillation has been shown to have a major impact on outcomes in Heart Failure with reduced Ejection Fraction (HFrEF). Identifying which proteins are differentially expressed may lead to a better understanding of how AF impacts the remodeling and outcomes in HFrEF.

Hypothesis:
To demonstrate a difference in proteomic analysis of left atrial (LA) tissue in patient with had atrial fibrillation compared to those with no history of atrial fibrillation from explanted hearts of patients with HFrEF.

Methods:
We compared the protein expression from explanted left atria and left ventricles from HFrEF patients using t-tests to generate a heat map and volcano plots. Patients with any history of AF (paroxysmal or persistent) were compared to patients with no history of AF. We then compared patients in different AF subtypes using ANOVA analysis

Results:
The group comprised 11 patients with AF and 8 patients with no history of AF with mean age 56±4 yrs, and 68% were males. There were no differences in demographics between the groups. There was differential expression of three atrial proteins between the AF vs. no AF groups: CPA1 (P = 0.01, Panel A), CCL15 (P = 0.02), CPB1 (P = 0.04) [Volcano Plot, Panel B]. When AF subtypes were analyzed there a consistent differential pattern in the proteomic signature from the LA between the three groups in a total of 10 proteins (Panel C).

Conclusions:
This preliminary data is consistent with different proteomic signatures among HFrEF patients with AF and among different atrial fibrillation subtypes.
Abstract 11140: The Role of Cardiac Extracellular Vesicles in Tumor Growth
Authors: Caller Tal , Shaihov–Teper Olga , Schary Yeshai , Lendengolts Daria , Rotem Itai , Peled Racheli , Shai Ruty , Glick-Saar Efrat , Dominissini Dan , Boomgarden Alex , D'Souza-Schorey Crislyn , Naftali Shani Nili , Leor Jonathan
Published: June 2023

Background and aim:
Heart disease may promote tumor growth (reverse cardio-oncology). However, the cellular and molecular mechanisms that link heart disease to cancer remain elusive, and specific therapies are limited. We hypothesized that the diseased heart secret extracellular vesicles (cEVs) that carry and disseminate pro-tumorigenic factors.

Methods & Results:
We subjected female mice to myocardial infarction (MI) or sham-MI and 28 days of follow-up. Left ventricular remodeling was confirmed by echocardiography. To determine the role of cEVs in tumor growth, we focused on cardiac mesenchymal stromal cells (cMSCs), which play a central role in cardiac repair, remodeling, and fibrosis. Thus, we isolated cMSCs from mice hearts 10 or 28 days after MI or sham MI. cMSCs after MI secreted more small EVs than cMSCs from sham-MI. Proteomic analysis revealed a distinctive profile of cEVs after MI (
Fig A
). In addition, cMSC-EVs after MI encapsulated more pro-tumorigenic cytokines: periostin, osteopontin, IL-6 and TNFα and microRNA: mir-221, mir-21, mir-24 and mir-214 with tumorigenic potential (
Fig B
). cMSC-EV uptake by breast and lung cancer cells was demonstrated in vitro. Next, a scratch assay showed that MI-cEVs facilitated cancer cell proliferation and migration two times faster than sham-MI cEVs (
Fig C
, p=0.0002). Finally, lung or breast cancer cells were inoculated into the hind limb or mammary pad 10 days before or after MI. Serial ultrasound examinations monitored tumor growth. While MI stimulated tumor growth, EV inhibition by GW4869 markedly attenuated this effect (
Fig D
).

Conclusions:
We show, for the first time, that mesenchymal stromal cells from the infarcted heart secret extracellular vesicles that carry pro-tumorigenic factors, target cancer cells, and facilitate tumor growth. Thus, cardiac extracellular vesicles could be considered as therapeutic target in patients with concomitant heart disease and cancer.
Abstract 11150: The Effect of Eicosapentaenoic Acid and Docosahexaenoic Acid on Neutrophil/Lymphocyte Ratio, a Marker of Inflammation, in Subjects With Coronary Artery Disease: Results of a Randomized Trial
Authors: Asbeutah AbdulAziz A , Malik Abdulaziz , Welty Francine K
Published: June 2023

Background:
The neutrophil/lymphocyte (N/L) ratio increases with the systemic inflammatory response due to an increase in neutrophils and decrease in lymphocytes with systemic inflammation. An elevated N/L ratio has been associated with an increased risk of cardiovascular disease (CVD), cancer and mortality. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease levels of high sensitivity C-reactive protein (hs-CRP), the gold standard inflammatory marker, when levels of hs-CRP are elevated. Randomized trials have also reported a decrease in CVD events with EPA. The mechanism for this benefit is unclear.

Objective:
To examine the effect of high-dose EPA and DHA supplementation on inflammation as measured by the N/L ratio in the setting of low levels of hs-CRP.

Methods:
A total of 242 subjects with stable coronary artery disease on statin treatment were randomized to 3.36 g EPA+DHA daily or none. N/L ratio and the monocyte to lymphocyte (M/L) ratio were measured at baseline and 1 year.

Results:
Mean (SD) age was 63.1 years (7.7); mean (SD) LDL-C: 77.8 mg/dL (27.3); median [IQR] TG: 117.5 mg/dL [81.3,166.8] and median [IQR] hs-CRP: 0.75 mg/L [0.40,2.5]. Those on EPA+DHA had a 2.2% reduction in N/L ratio (P=0.014) at 1 year compared to those not on EPA+DHA who had a 12.2% increase (Figure) (between group P= 0.007). There was a trend toward benefit with the M/L ratio (P=0.078).

Conclusion:
High-dose EPA+DHA decreases systemic inflammation as reflected in the N/L ratio even with low hs-CRP levels. This is a new finding which suggests that under conditions of generally low levels of inflammation in terms of hs-CRP levels, the N/L ratio may be a more sensitive measure of underlying inflammation than hs-CRP and should be considered as an additional marker in future studies of omega-3 fatty acids. If a decrease in inflammation by N/L ratio were accompanied by a clinical decrease in CVD events, this would assist in determining a plausible mechanism of action.
Abstract 11177: Pulmonary Vein Reconnections Predict Good Clinical Outcomes After a Second Catheter Ablation of Persistent Atrial Fibrillation: Insight From the EARNEST-PVI Trial
Authors: Okada Masato , Tanaka Nobuaki , Oka Takafumi , Tanaka Koji , Hirao Yuko , OKAMURA ATSUNORI , Iwakura Katsuomi , masuda masaharu , Watanabe Tetsuya , Sunaga Akihiro , Hikoso Shungo , Inoue Koichi , Sakata Yasushi ,   the OCVC-Arrhythmia Investigators
Published: June 2023

Introduction:
The effect of an extensive ablation strategy in addition to pulmonary vein (PV) isolation is still controversial in persistent atrial fibrillation (AF) ablation. Electrical PV reconnection is an important confounder affecting the trial results.

Objectives:
To evaluate the PV reconnection rate and association between the reconnection and AF recurrence after a re-do AF ablation in the EARNEST-PVI trial (NCT03514693).

Methods:
The analysis was performed using the extended data of the EARNEST-PVI trial (N=512), a randomized controlled trial to evaluate ablation strategies for persistent AF, which was conducted in the Osaka region of Japan. During a median follow-up of 47 months, a total of 126 (25%) patients underwent a re-do AF ablation. Among them, 120 (median age, 68 years; 36% female; 31% long-standing persistent AF, 95% contact force-sensing catheter use) whose follow-up data were available after the 2
nd
AF ablation were enrolled in this study.

Results:
PV reconnections were observed in 75 (63%) patients. Although there was no difference in age, gender, long-standing persistent AF, and CA strategy during the index procedure, AF recurrence within 1 year was more frequent in patients with PV reconnections (81.3% vs. 64.4%, p = 0.039). During a median follow-up of 31 months after the re-do AF ablation, patients with PV reconnections had a lower clinical recurrence rate than those without (38.7 vs. 44.4%, log-rank p = 0.047). However, additional linear ablation did not affect the recurrence rate. Even after adjustment for age, gender, long-standing persistent AF, and presence of non-PV triggers, Cox regression analysis revealed that a number of reconnected PVs of ≥2 was independently associated with a lower recurrence of AF after the 2
nd
AF ablation (hazard ratio, 0.36; 95% confidence interval, 0.19-0.67; p = 0.001).

Conclusions:
Among patients who underwent a redo-AF ablation in the EARNEST-PVI trial, about two-thirds exhibited PV reconnections. Patients with ≥2 PV reconnections had better clinical outcomes than those with ≤1 PV reconnections. A durable PV isolation is an important pre-requisite before exploring any additional ablation strategies for persistent AF.
Abstract 11182: The Morphological Feature of Left Atrial Appendage With Thrombus in Patients With Atrial Fibrillation
Authors: Sugitani Miho , Mine Takanao , Kogame Takehiro , Kitagaki Ryo , Fukuhara Eiji , Ishihara Masaharu
Published: June 2023

Background:
In atrial fibrillation (AF) patients, non-chicken wing type left atrial appendage (LAA) morphology is involved in thromboembolic events, and windsock and cauliﬂower LAA morphologies have been reported to be related to silent cerebral ischemia (CI). However, the morphology of the LAA in patients with left atrial appendage thrombus (LAAT) that is the main pathogenesis of cardiogenic CI due to AF remains unclear.

Methods:
We retrospectively studied the LAA morphology in 43 patients with LAAT detected by transesophageal echocardiography (TEE) prior to cardioversion or catheter ablation for AF and the LAA morphology of 144 patients without LAAT who undertook TEE on the same day, out of 1864 examined patients. Patients with significant valvular disease and cardiac surgery were excluded. LAA morphology constructed by computed tomography has been classiﬁed into 4 types: chicken wing, cauliﬂower, windsock, and cactus. We evaluated clinical data, blood samples, and transthoracic echocardiography at the time of TEE.

Results:
Non-paroxysmal AF (37% vs. 0%, P<0.0001), higher history of heart failure (40% vs. 15%, P=0.0004), elevated BNP level (454±436 vs. 119±133 pg/mL, <0.0001), reduced left ventricular ejection fraction (LVEF, 52.3±16.8% vs. 65.2±10.2%, P <0.0001), larger LA dimension (LAD, 48.6±6.0 vs. 41.9±6.1 mL/m
2
, P<0.0001), higher E/e` ratio (13.4±7.0 vs. 10.7±3.8, p=0.0017), and LAA morphology were associated with LAAT (Figure). On multivariate analysis, non-paroxysmal AF (P=0.0002), BNP level (P=0.0033), LVEF (P=0.0015), and LAA morphology (especially, cactus type LAA, P=0.0027) were significantly correlated to LAAT.

Conclusion:
The LAA morphology relates to the LAAT in AF patients. The characteristics of the LAA morphology in LAAT patients may be different from those in silent CI patients.
Abstract 11197: Gender Differences and Temporal Trends in Clinical Characteristics and Use of Myocardial Scintigraphy in Evaluation of Stable CAD
Authors: Lakshmanan Suvasini , Frumento Paolo , Giorgetti Assuero , Dalmiani Stefano , Gimelli Alessia
Published: June 2023

Introduction:
Data on temporal and gender differences in referral patterns and clinical characteristics of patients referred for myocardial scintigraphy for suspected coronary artery disease (CAD), is lacking. Furthermore, the differential impact of COVID-19 pandemic on gender differences in referrals and clinical risk profile of referred patients is not known.

Methods:
This is a cross-sectional observational single center study of patients evaluated across 3 yearly time intervals in 2000, 2010 and 2020. We evaluated 2,615 patients (68% women) with mean age 65.9 years, who were referred for stress/rest myocardial scintigraphy. Trends in clinical characteristics and test results were compared in women and men across these intervals.

Results:
Men were more likely to be referred for testing than women, however there was a consistent increase in proportion of women referred over time, including the time of COVID pandemic in 2020. Men were more likely to present with typical symptoms, compared to women. Among women, there is a significant increase in prevalence of active smoking and a decrease in age at presentation and hypertension, over time (p<0.05). Among men, there was a significant decrease in history of previous MI, with no change in other risk factors over time. Across time intervals, in both men and women, there was a significant increase in EF (Ejection Fraction) and decrease in presence of ischemic myocardium at risk, identified by semi-quantitative scores including summed rest score (SRS), summed stress score (SSS) at rest (p<0.05).

Conclusions:
There are gender differences in proportion of men and women who are referred for stress testing, for evaluation of stable CAD. There was a substantial change in risk of inducible myocardial ischemia among male and female patients with known or suspected CAD. Our findings are relevant to understand the implications of gender differences on risk assessment and diagnostic accuracy in known or suspected CAD, over time.
Abstract 11209: The Distance From the Right Coronary Artery to the Cavotricuspid Isthmus is a Predictor of First-Pass Conductional Block of Cavotricuspid Isthmus by Cryoablation
Authors: Nodera Minoru , Nehashi Takeshi , Yamada Shinya , Kaneshiro Takashi , Takeishi Yasuchika
Published: June 2023

Background
: Several studies have reported that the blood flow in the right coronary artery (RCA), located beneath the anterior cavotricuspid isthmus (CTI), has cooling effect which might prevent CTI block from radiofrequency ablation and make this ablation procedure difficult. However, the details of this effect by RCA blood flow remain unclear in cryoablation of CTI.

Methods:
This study included 63 consecutive patients (46 men; 66±11 years) who underwent CTI cryoablation for common AFL. A computed tomography (CT) scan with contrast injection was performed before ablation in all patients. Patients were divided into 2 groups: one pass group who achieved first-pass conductional block of the CTI (n=47) and non-one pass group who did not (n=16). CTI ablation was performed with 2.5-min freezing cycles and 8-mm tip cryocatheter. We analyzed anatomical features of the CTI, the presence of Eustachian valves on CT, and the temperature changes at the catheter tip during first pass in CTI cryoablation.

Results:
The distance from the RCA to the CTI in the one pass group was significantly longer than that in the non-one pass group (2.9±0.7 vs. 2.2±0.6 mm,
P
<0.001). On the other hand, there was no significant difference in the variants of CTI anatomy or the CTI length or the presence of a Eustachian valve between the two groups. The time to reach the nadir freezing temperature in the anterior CTI, where the RCA was located beneath it, was significantly shorter in the one pass group than in the non-one pass group (31.3±6.5 vs. 34.7±6.1 sec,
P
=0.034). The time to reach the nadir freezing temperature in the anterior CTI correlated inversely with the distance from the RCA to the CTI (R=-0.404,
P
=0.001). Using multivariate analysis, the distance from the RCA to the CTI was an independent predictor of achievement of first-pass conductional block of the CTI (odds ratio 8.776, 95% confidence interval 2.358-32.662,
P
=0.001). The distance from the RCA to the CTI >2.2 mm had 83% sensitivity and 63% specificity to predict one pass conduction block (area under the curve, 0.813).

Conclusions:
The distance from the RCA to the CTI is a predictor of first-pass conductional block of CTI by cryoablation. The warming effect of the RCA blood flow might prevent CTI block during cryoablation.
Abstract 11212: Mirabegron Relaxes Arteries From Human Visceral Adipose Tissue Through Antagonism of Alpha
1
-Adrenoceptors
Authors: SCHINZARI Francesca , De Stefano Alessandro , Vizioli Giuseppina , Tesauro Manfredi , Cardillo Carmine
Published: June 2023

Introduction:
As adequate perfusion has turned out to be a key determinant of adipose tissue (AT) remodeling, interest has grown regarding possible pharmacological interventions to promote this process and hence prevent the metabolic abnormalities associated with obesity and aging. Clinical trials have shown that mirabegron improves insulin sensitivity and glucose homeostasis in obese humans via stimulation of β
3
-adrenoceptors. Ligands of these receptors have also emerged as endothelium-dependent vasodilators in disparate human vascular beds.

Hypothesis:
We hypothesized, therefore, that mirabegron might exert vasodilator effect in human AT arteries and tried to characterize the underlying mechanism(s).

Methods:
Small arteries (116-734 μm) isolated from visceral AT were studied ex vivo in a wire myograph. After vessels had been contracted, changes in vascular tone in response to mirabegron were determined under different experimental conditions.

Results:
Mirabegron elicited vasorelaxation in vessels contracted with endothelin-1 (P<0001), but not in those contracted with U46619 or high-K
+
(both P>0.05). Notably, mirabegron markedly blunted the contractile effect of the α
1
-adrenergic receptor agonist phenylephrine (P<0.001). Also, vessels with removed endothelium contracted with phenylephrine had preserved vasorelaxing response to mirabegron. The anti-contractile action of mirabegron on phenylephrine-induced vasoconstriction was not influenced by the presence of the selective β
3
-adrenoceptor blocker L-748,337 (P<0.05); lack of involvement of β
3
-adrenoceptors was further supported by absent vascular staining for them at immunohistochemistry. Similar to the observed effect of mirabegron, preincubation with the α
1
-adrenoceptor antagonist doxazosin abolished the contractile response to phenylephrine.

Conclusions:
Mirabegron induces endothelium-independent vasorelaxation in arteries from visceral adipose tissue, likely through antagonism of α
1
-adrenoceptors. This action suggests that mirabegron might effectively improve visceral AT perfusion, thereby favoring a healthy AT remodeling and preventing, in turn, some of the unwanted cardiometabolic consequences of obesity and aging.
Abstract 11237: Dose Response and Long QT Genotype During Exercise Stress Testing in Children
Authors: Webster Gregory , Coons Dana E , Carberry Thomas , Chandler Stephanie F , Cherny Sara , Jacobson Elli N , Onorato Angela C , Ward Kendra M , Laternser Christina
Published: June 2023

Introduction:
Beta-blockers (BB) are first-line therapy for long QT syndrome (LQTS). Many physicians rely on repeated exercise stress tests (ESTs) to establish the optimal dose in each patient.

Hypothesis:
Increased BB dose is associated with a decrease in maximum heart rate, influenced by precision-medicine factors including genotype.

Methods:
Retrospective chart review of treadmill ESTs with the outcome variable “% predicted heart rate (HR)” = (maximum HR achieved/(220-age))*100. Genotype positive patients had pathogenic or likely pathogenic variants, re-adjudicated in 2022. Doses of BB other than nadolol were converted to nadolol equivalents using an established methodology.

Results:
We evaluated 345 ESTs in 132 LQTS patients (58% genotype positive) from 2003-21. The mean age at first EST was 12.5 years (standard deviation 4.0 years). Most patients were prescribed nadolol (59%) or atenolol (28%). When controlled for person-level fixed effects, we observed an inverse relationship between BB dose and % predicted HR. The dose-response slope was steeper in genotype positive patients than genotype negative patients (-4.8 vs. -3.3,
Figure
, p<0.01). We observed mild decreases in blood pressure as BB dose increased, (mean 5 mmHg decrease in systolic blood pressure per 1 mg/kg increase in BB). However, neither maximum VO2 nor maximum respiratory exchange ratio were affected by increased BB dose (the slope of each was indistinguishable from 0 in person-level fixed effects models).

Conclusion:
In children with LQTS, genotype positive patients were more sensitive to BB than genotype negative patients. We developed a multivariate model to predict the dose of BB required to achieve therapeutic beta-blockade, conditional on individual patient demographics and genotype. The model may decrease the need for serial ESTs. BB dose did not affect maximum VO2 or respiratory exchange ratio, which is reassuring for children and adolescents with LQTS who exercise.
Abstract 11256: Endothelial-to-Mesenchymal Transition (endMT) is a Driver of Endothelial Cell Heterogeneity in Human
in vitro
and
ex vivo
Atherosclerotic Plaques
Authors: Adelus Maria L , Romanoski Casey E
Published: June 2023

Atherosclerosis begins with endothelial cell (EC) dysfunction. However, the relationship between single-cell (sc) EC profiles
in vitro
and in human atherosclerotic plaques is unexplored. Herein, we exploited sc EC transcriptomes from human plaques and related them to
in vitro
models of inflammation and angiogenesis, which we expected to be relevant. To curate a gene expression profile of ECs found in human atherosclerotic plaques, we performed a meta-analysis of three publicly available human scRNA-seq datasets comprised of 17 coronary and carotid specimens. In parallel, we generated a Multiome
in vitro
dataset composed of 6 primary human aortic ECs (HAECs), under three experimental conditions: (1) untreated control, and (2) IL-1B-treated (10ng/mL for 1 hour) HAECs on typical gelatin-coated plastic dishes; and (3) untreated HAECs grown on Matrigel to mimic angiogenesis. Five clusters represented the HAECs from all three
in vitro
conditions. Pathway enrichment analysis revealed that Matrigel-grown ECs (cluster 1) were largely distinguished by Signaling by Rho GTPases, Miro GTPases and RHOBTB3 (R-HSA-9716542; Log10(P) -45.96), while untreated and IL-1B-treated ECs (clusters 0 and 2) were distinguished by regulation of cell adhesion (GO:0030155; Log10(P) -39.92) and Cell Cycle (R-HSA-1640170; Log10(P) -32.2). Of note, clusters 3 and 4 were comprised of HAECs from all 3 conditions and appeared to represent partial and complete endMT, respectively. Cluster 3 and 4 were characterized by greater expression of mesenchymal markers (COL1A1, COL1A2, COL3A1, TAGLN, VIM, and CDH2), while cluster 4 was additionally characterized by a reduction in EC markers (ERG, CDH5, PECAM1). When
in vitro
HAEC and
ex vivo
plaque data were integrated, cells from
in vitro
cluster 4 clustered with vascular smooth muscle cells from human atherosclerotic plaques. Taken together, these results reveal that HAECs are heterogeneous both
in vitro
and
ex vivo
atherosclerotic conditions. Since endMT occurs spontaneously at some minor frequency
in vitro
(~5%) with expression signatures observed in vivo, these data establish a clinically relevant
in vitro
model to understand the molecular processes driving endMT.
Abstract 11266: Trend, Predictors and Outcomes of Transcatheter Aortic Valve Implantation in Patients With End-Stage Renal Disease: Insights From the Nationwide Readmissions Database
Authors: Sandhyavenu Harigopal , Badu Irisha , Patel Bhavin , Polam Aravind R , Taha Amro , Ullah Waqas
Published: June 2023

Background:
Evidence on the safety of transcatheter aortic valve implantation (TAVI) in End-stage renal disease (ESRD) patients is limited.

Methods:
The Nationwide Readmissions Database (NRD) from 2015-2019 was queried to identify patients undergoing TAVI in ESRD versus patients with no ESRD. The in-hospital, 30-day, and 180-day outcomes were assessed using a propensity-score matched (PSM) analysis to calculate adjusted odds ratios (aOR).

Results:
A total of 198,816 underwent TAVI, of which 34,546 patients (TAVI-ESRD:16,986 vs non-ESRD:17,560) were selected on PSM analysis. The adjusted odds of net adverse cardiovascular events (NACE) (aOR 1.65, 95% CI 1.49-1.82), in-hospital mortality (aOR 2.99, 95% CI 2.52-3.55), major bleeding (aOR 1.21, 95% CI 1.05-1.40), postprocedural cardiogenic shock (aOR 1.54, 95% CI 1.11-2.13), permanent pacemaker implantation (PPM) (aOR 1.24, 95% CI 1.15-1.38) were significantly higher in TAVI-ESRD patients compared with non-ESRD patients at index admission. There was no significant difference in the odds of stroke (aOR 1.09, 95% CI 0.86-1.34) and cardiac tamponade (aOR 1.06, 95% CI 0.78-1.45) between two groups. Table 1. At 30-day follow-up, TAVI-ESRD patients had higher odds of major bleeding while there was no significant difference in outcomes of stroke, cardiac tamponade and PPM implantation between the two groups up to 180-day follow-up, Table 2. On trend analysis, the rate of utilization of TAVI in ESRD has significantly increased to 30% by 2019.

Conclusion:
The rate of utilization of TAVI in ESRD has significantly increased in recent years despite the higher risk of NACE, in-hospital mortality, major bleeding and PPM implantation.
Abstract 11275: Comorbidity Score is Positively Associated With Hopelessness in Adults With Ischemic Heart Disease
Authors: Dunn Susan L , Tintle Nathan L , Gutierrez-Kapheim Melissa , Rivera Stephanie Eleanor , Alonso Windy W , KETEYIAN Steven J , Devon Holli A
Published: June 2023

Introduction:
Comorbidities are associated with increased risk of mortality in adults with ischemic heart disease (IHD). Hopelessness, a negative outlook and sense of helplessness towards the future, is identified in 27–52% of patients with IHD and associated with a 3.4 times increased risk of mortality or nonfatal myocardial infarction. The relationship between comorbidities and hopelessness in adults with IHD is unknown.

Hypothesis:
A higher comorbidity score is positively associated with state and trait hopelessness levels in adults hospitalized with an IHD event.

Methods:
Participants completed the State-Trait Hopelessness Scale and reported basic demographics. Continuous (range 0-14) and categorical scores for the Charlson Comorbidity Index (CCI) were generated based on patient medical records.

Results:
Participants (n=132) were typical of the U.S. IHD population except for race/ethnicity. Ninety-one were male (68.4%), mean age was 62.6 years (SD= 9.6), and 97% were non-Latinx White (3.0%). The mean CCI was 3.5 (SD=2.2), with 36.4% having a score of 1-2 (mild), 41.2% with a score of 3-4 (moderate) and 22.7% with a score of ≥5 (severe). The CCI was positively associated with both state and trait hopelessness in unadjusted and adjusted (demographics, medical history, and exercise history) analyses (unadjusted: r=0.26, p=0.002 (state); r=0.23, p=0.009 (trait) and adjusted: r=0.22, p=0.008 (state); r=0.18, p=0.052 (trait)). Components of the CCI showing the strongest relationships with higher levels of hopelessness were cerebrovascular accident (n=8), organ damage from diabetes (n=17), COPD (n=24), and renal failure (n=9). Interaction terms were evaluated and there was no evidence that the relationship between the CCI and hopelessness differed by age, gender, education level, or cardiac intervention type.

Conclusions:
Our hypothesis of a positive association between comorbidity score and state and trait hopelessness was confirmed. Knowledge of hopelessness in IHD patients with comorbidities is important for health care professionals in acute care and outpatient settings so at-risk patients can be identified and appropirate interventions employed. Future work should be conducted in larger, more heterogeneous samples.
Abstract 11293: Atrial Fibrillation Associated With Ivabradine: An Analysis of FDA Adverse Events Reporting System Database
Authors: Ahmad Javaria , Ahmad Hassaan Ali A , Dominic Paari
Published: June 2023

Introduction:
Ivabradine has been shown to be associated with atrial fibrillation (AF) in a metanalysis of 11 studies, however, AF has not been routinely reported as an adverse event of ivabradine in clinical trials. The FDA Adverse Event Reporting System (FAERS) is a publicly available database of adverse events (AE) of various drugs. We analyzed the database for real-world AF reporting with Ivabradine.

Methods:
FAERS was searched for the adverse events reported for ivabradine. All AF cases were individually analyzed.

Results:
A total of 3550 AE reports of Ivabradine were reported to FAERS from April 2011 to August 2021 out of which 1117 were cardiac adverse events. A total of 78 cases of AF were reported, accounting for 2.1% of the total AE reports and 31% of cardiac AE reports. Sex was reported in 83% of total AF cases, of which 50% were male, and the other 50% were female. 79% of the AF cases were reported by health care professionals, and 21% by consumers. 51% of cases were reported from the United States, 10% from France, and 9% from Germany. In 51% of the cases, no concomitant drug was given with ivabradine, and in 49% a concomitant drug was given; 10% of those was Digoxin/Digitalis that has been associated with AF. When searched using OpenVigilFDA (a web-based user interface to the FAERS for extraction and analysis of adverse events reports), the reporting odds ratio (ROR) of Ivabradine for AF was 3.18 (95% CI: 2.46 - 4.10) and the proportional reporting ratio was 3.15. The comparison of RORs of ivabradine with the drugs traditionally known to cause AF is shown in the figure.

Conclusions:
Disproportionate reporting of AF with ivabradine indicates that AF is associated with Ivabradine use. Further studies are required to confirm this association
Abstract 113: Protection Of Cardiomyocytes Against Hypoxia/reoxygenation Injury: Interaction Of Poloxamer 188 And Endothelial Cells
Authors: Li Zhu , Barajas Matthew B , Oyama Takuro , Walter Miriam J , Riess Matthias L
Published: June 2023

Administration of Poloxamer (P) 188, a copolymer-based cell membrane stabilizer, significantly improves myocardial ischemia/reperfusion (IR) injury through its ability to protect cell membranes. Cell-to-cell interactions between endothelial cells (ECs) and cardiomyocytes (CMs) further protect CM from IR injury. Thus, we established a co-culture model of ECs and CMs and could previously demonstrate that the mere presence of ECs potentiates cardioprotection as evidenced by dose-dependent attenuation of LDH release from CMs caused by hypoxia/reoxygenation (HR). Here, we sought to determine if P188 can further potentiate the attenuation of LDH release in the presence of different ECs densities.

Mouse CMs cultured in wells underwent 24 h hypoxia followed by 2 h reoxygenation. Mouse coronary artery ECs were plated in well-inserts at densities of 25,000, 50,000, or 100,000 per well which were placed into the CM wells. P188 at 0, 30, 100, 300, or 1,000 μM was administered upon reoxygenation. Statistics: ANOVA and SNK, alpha 0.05.

ECs did not have a protective effect by themselves when a low number of ECs (25,000 per well) were present, but P188 could reduce LDH release in CMs after HR injury in a dose-dependent manner (lower panel). When a high number of ECs (100,000 per well) were co-cultured with CMs, ECs themselves exerted a protective effect while P188 did not further decrease LDH release significantly (upper panel). An intermediate number of ECs (50,000 per well) did not produce significant results in either direction (center panel). Our data suggests that the EC-mediated protection of CMs depends on EC density; furthermore, while at low density the role of ECs was limited and allowed P188 to promote additional protection against HR injury, at high density ECs appeared to saturate cardioprotection and blunt additional P188’s CM protection.

These findings suggest an important, yet not additive interaction between the protection conferred by ECs and that by P188.
Abstract 11307: Longer Outflow Tract Conduction Time by Magnetocardiography as a Novel Non-Invasive Maker for Predicting Lethal Events in Patients With Brugada Syndrome Without Ventricular Fibrillation
Authors: Aiba Takeshi , Nagase Satoshi , Inoue Yuko Y , Kamakura Tsukasa , Miyazaki Yuichiro , Wakamiya Akinori , Shimamoto Keiko , Ueda Nobuhiko , Nakajima Kenzaburo , Wada Mitsuru , ishibashi kohei , Miyamoto Koji , Takaki Hiroshi , Kamakura Shiro , Kusano Kengo
Published: June 2023

Introduction:
Many of the Brugada syndrome (BrS) patients have no symptom or only syncope without ventricular fibrillation (VF)/sudden cardiac death (SCD), thus to whom we should recommend implantable cardioverter defibrillator (ICD) for primary prevention of SCD is still the biggest concern in the BrS. Here we investigated whether a high spatial resolution magnetocardiography (MCG) could predict lethal events of the BrS without history of VF/SCD.

Methods:
This study retrospectively enrolled 157 BrS patients without VF or cardiopulmonary arrest (CPA) (150 male, 42±13 years old, 118 spontaneous and 39 drug-induced type-1 ECG). Outflow tract conduction time (OT-CT) from 2-D current map of MCG was measured in all patients as well as the standard 12-lead ECG and signal-averaged ECG (SAECG). Programmed electrical stimulation (PES) for VF induction was performed in 47 patients.

Results:
Patients with spontaneous type-1 ECG had longer OT-CT compared with type-2 BrS patients. Na channel blocker, pilsicainide (25-50mg) unmasked type-1 ECG as well as increased OT-CT (54±18 to 127±62 ms; p<0.05), whereas additional isoproterenol (1ug/kg/min) reversed the pilsicainide-induced delayed OT-CT, thus normalized the ST elevation of ECG. During follow-up (mean 72 [6-147] months), 10 (6%) patients suffered VF/CPA, and those had a higher incidence of previous syncope (50% vs. 14.4%, p=0.01) and longer baseline OT-CT (83±31ms vs. 55±24ms, p=0.01) compared with event-free patients. Receiver operating curve (ROC) revealed OT-CT=65ms was a cut-off value of VF/CPA (AUC=0.78), whereas, spontaneous type-1 ECG, late potential of SAECG, family history, and VF inducibility by PES were not associated with VF/CPA events during follow-up. Multivariate Cox proportional analysis revealed that previous syncope (HR=1.70, 95%CI:1.01-3.05, p=0.04) and OT-CT≥65ms (HR=1.72, 95%CI=1.16-2.62) were the independent predictor for lethal events in the BrS without VF/CPA. Among asymptomatic BrS patients (n=131), OT-CT≥65ms was also an independent predictor for VF/CPA (HR=1.69, 95%CI=1.04-2.79, p=0.03).

Conclusion:
Longer OT-CT in the MCG may noninvasively demonstrate substrate of VF in BrS and stratify the risk of lethal events in patients with BrS without history of VF or CPA.
Abstract 11314: Essential and Evidence-Based Cardiovascular Disease Medicine Availability in Low-Cost Generic Drug Plans
Authors: Ton Ivy , Rahman Towhid , Moon Jungyeon , Jackevicius Cynthia
Published: June 2023

Introduction:
Patients’ lack of access to affordable cardiovascular disease (CVD) medicines poses a crucial barrier to achieving desired cardiovascular outcomes. Many pharmacies have launched low-cost generic programs (LCGP) to expand medication accessibility. It is uncertain whether LCGPs include CVD drugs recommended by World Health Organization Essential Medicines List (WHO EML) and promote evidence-based prescribing. Our study aimed to estimate the availability of essential and guideline-recommended CVD medicines on LCGP in the United States (US).

Methods:
We selected 6 CVD conditions: atrial fibrillation (AF), heart failure (HF), hyperlipidemia (HLD), hypertension (HTN), stable angina (SA), and secondary prevention (SPX). LCGPs in the US with publicly available formularies were identified in February 2022. We used the 22
nd
WHO EML edition and Class 1A recommendations (1ARec) from current CVD guidelines as reference standards. Availability was estimated using the proportion of coverage for each LCGP overall, and by condition.

Results:
Nineteen LCGPs were included. There were 122 WHO EML and 155 1ARec CVD drugs. No LCGPs offered at least 50% of WHO EML and 1ARec. Both WHO EML and 1ARec analyses showed that 9 of 19 LCGPs covered at least 30% of listed medications. Out of the 19 LCGPs, the proportion of essential and evidence-based CVD medicine availability was highest at Kroger (46.3% and 47.9%) and lowest at Costco (5.0% and 6.1%), respectively. Higher availability was observed for HLD medications: only TOPS and the Mark Cuban Plan had at least 80% of WHO EML available, and only the Mark Cuban Plan had at least 80% of 1ARec medications covered. HTN drugs were least available for both.

Conclusion:
The accessibility of CVD medicines is low in LCGP formularies with variation in availability by pharmacy and condition. To optimize the accessibility of CVD medicines and health outcomes, pharmacies with LCGPs should offer more essential and evidence-based CVD medicines.
Abstract 11324: Association of Patient Reported Outcomes With NYHA Class and Functional Capacity in Symptomatic Obstructive Hypertrophic Cardiomyopathy: An Analysis of Spirit-HCM Study
Authors: Tower Rader Albree , Szpakowski Natalie , Popovic Zoran B , Bittel Barbara , Fava Agostina , Xu Bo , Thamilarasan Maran , Mentias Amgad , Smedira Nicholas G , Desai Milind Y
Published: June 2023

Introduction:
Patient reported outcomes (PRO) are used to assess quality of life (QOL) in obstructive hypertrophic cardiomyopathy (oHCM).

Hypothesis:
In symptomatic oHCM patients, we sought to prospectively study the association between various PROs & their association with physician reported New York Heart Association (NYHA) class.

Methods:
This was a prospective study (ClinicalTrials.gov: NCT03092843) of symptomatic oHCM patients undergoing myectomy (n=173, mean 51 years, 62% men) between 3/2017 & 6/2020. At baseline, we recorded: a) Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score b) Patient-Reported Outcomes Measurement Information System [PROMIS] score c) Duke Activity Status Index [DASI] & d) European QOL score [EQ-5D], in addition to NYHA class, 6-minute walk test (6MWT) distance & peak left ventricular outflow tract gradient (PLVOTG).

Results:
The median baseline KCCQ summary, PROMIS physical, PROMIS mental, DASI, EQ-5D scores were 50, 37, 44, 25 & 0.61, respectively; 6MWT distance was 366 m. Figure 1 demonstrates highly significant correlations between various PROs, only modest correlations of PROs with 6MWT & PLVOTG. Figure 2 shows that ~1/3rd patients with NYHA class II had worse than median PROs, while ~1/3
rd
in NYHA III/IV had PROs better than median.

Conclusions:
In symptomatic oHCM patients, there is a high internal correlation between various prospectively recorded PROs but a modest correlation with 6MWT & LVOTG. Also, in symptomatic oHCM, NYHA class incompletely characterizes disease severity, and using a more sensitive metric like PROs may help to better identify patients with impaired QOL who will potentially benefit from myectomy.
Abstract 11339: Rates of Hospital Admissions for Syncope in the United States Using a National Database
Authors: Edwards Emily S , Bai Chen , Smoot Madeline , Dasa Osama , Petersen John W , Kimmel Stephen , Mardini Mamoun , Ruzieh Mohammed
Published: June 2023

Introduction:
Syncope accounts for 1% of emergency department (ED) visits, and a significant proportion of patients become hospitalized. Most causes of syncope are benign and can be evaluated in the outpatient setting. The yield for hospitalization and inpatient workup of syncope is low. In this study, we sought to characterize trends of syncope ED visits resulting in hospitalizations.

Methods:
We used data from the IBM MarketScan Research Database, which captures de-identified individual-level health data from approximately 100 commercial payers and self-insured corporations in the United States, not including Medicaid claims. We identified patients presenting to the ED for syncope from 2010-2020 using ICD-9 and ICD-10 codes. Subsequently, the number of hospital ED admissions (both observation and inpatient admissions) was calculated.

Results:
We identified 1,737,382 ED visits from 2010-2020. There was a significant reduction in hospital admissions for syncope (11.5% to 1.4%, p<0.001). In contrast, observation rates increased (5.4% to 8.5%, p<0.001), figure 1A. The rate of discharge home from the ED increased (83.1% to 90.1%, p<0.001). The same trends were seen for patients younger or older than 65 years, figures 1B and 1C, respectively. Nonetheless, the admission or observation rate was significantly higher for older patients (15.5% vs. 8.6%, p<0.001).

Conclusions:
Hospital admissions for syncope declined over the past decade. There is a need to assess if this has affected mortality or recurrent ED visits for syncope.
Abstract 11340: Characteristics of Patients Admitted to a Contemporary Cardiac Intensive Care Unit With Valvular Cardiogenic Shock
Authors: Nair Raunak M , Chawla Sanchit , Alkhalaileh Feras , Abdelghaffar Bahaa , Khot Umesh N , Higgins Andrew , Lee Ran , Jaber Wael A , Cremer Paul C , Rampersad Penelope , Menon Venu
Published: June 2023

Background:
Cardiogenic shock (CS) is a heterogeneous clinical entity associated with poor outcomes. Patients with CS primarily due to an acute valvular dysfunction (valvular cardiogenic shock; VCS) constitute a unique cohort who remain poorly defined. We sought to define the prevalence and underlying patient characteristics of patients with VCS.

Methods:
All patients admitted to Cleveland Clinic Cardiac Intensive Care Unit (CICU) between Jan 1
st
, 2010, to Dec 31
st
, 2021, with a diagnosis of CS were retrospectively identified through electronic medical records and confirmed via physician directed chart review. Patients with CS were subsequently categorized into those with VCS and non-VCS depending on the primary etiology responsible for CS. Characteristics of patients with VCS were analyzed to descriptively define this entity. Patients with mixed shock and those with incomplete variables were excluded.

Results:
Overall, 2754 patients were admitted to our CICU with CS of which 511 (18.6%) were determined to have VCS. The median age of patients with VCS was higher than those with non-VCS (70 yrs vs 64yrs, P<0.001). Patients with VCS were also more likely to be females (40.5% vs 31.8%, P<0.001), have higher prevalence of atrial fibrillation (56.9% vs 48.5%, p=0.001), chronic obstructive pulmonary disease (26.4% vs 20%, p=0.002), and prior history of valve replacement or repair (29.7% vs 7.9%, p<0.001) (Table 1). Patients with VCS were also significantly less likely to have prior MI (19.4% vs 46.6%, p<0.001). The aortic valve was most commonly implicated; with more native valve dysfunction as compared to prosthetic valve dysfunction (73% vs 27%, p<0.001). (Figure 1).

Conclusion:
One in 5 patients admitted with CS has VCS with native valves and the aortic position being the common culprit. The availability and impact of emergent percutaneous structural-interventions on clinical outcomes in this population warrants investigation.