bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9276: Subcutaneous and Transvenous Defibrillator in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Wang Weijia , Gasperetti Alessio , Sears Samuel , Tichnell Crystal , Murray Brittney , Tandri Harikrishna S , James Cynthia , Calkins Hugh G
Published: June 2023

Introduction:
There is limited evidence guiding the selection between subcutaneous and transvenous ICD in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) at risk for sudden death.Hypothesis: We aimed to compare clinical and quality of life outcomes between transvenous and subcutaneous implantable defibrillators (ICD) among patients with ARVC.

Methods:
Patients with subcutaneous ICD (n=57) were matched to patients with transvenous ICD (n=88) based on sex, proband status, primary prevention or secondary prevention, monomorphic ventricular tachycardia before implant, and year of implant. Appropriate therapy for ventricular arrhythmia, inappropriate shocks, and complications were compared. Quality of life surveys were conducted annually.

Results:
The matched cohort (median age of 35 years, 43% male, 78% proband, and 37% secondary prevention device) were prospectively followed for 5.1 (+/-2.5) years. No significant difference was observed in the rate of appropriate ICD shocks. The subcutaneous group had more inappropriate shocks (23% versus 10%) and fewer procedure related complications (4% versus 14%) than the transvenous group (p <0.05). The association between ICD type and the composite of inappropriate shock and complication was not statistically significant (adjusted hazard ratio 1.43 subcutaneous vs. transvenous, 95% confidence interval 0.72-2.84). Subcutaneous ICD was associated with more body image concerns and range of motion than transvenous ICD (p <0.05).

Conclusions:
In patients with ARVC receiving an ICD, the risk of inappropriate shocks from subcutaneous ICD should be balanced against the significant vascular complication risk from transvenous ICD. Patients with subcutaneous ICD had more concerns for body image and range of motion.
Abstract 9381: Lipoprotein(a), Oxidized Phospholipids, and Coronary Artery Disease Severity and Outcomes
Authors: Gilliland Thomas C , Liu Yuxi , Mohebi Reza , Miksenas Hannah , Haidermota Sara , Wong Megan , Hu Xingdi , Cristino Joaquim , Browne Auris , Plutzky Jorge , Tsimikas Sam , Januzzi James L , Natarajan Pradeep
Published: June 2023

Introduction:
Lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPLs) are independent risk factors for atherosclerotic cardiovascular disease. The extent to which Lp(a) and OxPLs together predict coronary artery disease (CAD) severity and outcomes is unclear. We measured Lp(a) isoform-independent particle number and OxPLs associated with apolipoprotein(a) [OxPL-apo(a)] and apolipoprotein-B (OxPL-apoB) among participants in CASABLANCA (ClinicalTrials.gov NCT00842868), a contemporary cath-based registry, and assessed angiographic CAD at baseline and CV events in follow-up.

Methods:
In 1098 participants undergoing baseline coronary angiography, logistic regression estimated odds of any CAD (≥1 severe coronary stenosis) or multi-vessel CAD (≥2 severe coronary stenoses). Cox proportional hazards regression estimated risk of major adverse cardiovascular events (MACE: non-fatal MI, non-fatal stroke, CV death, or coronary revascularization) over median 4.2 years. Models were adjusted for age, sex, medical history, cholesterol, smoking, and statin use.

Results:
Median [IQR] Lp(a) was 26.45 nmol/L [11.39-89.49]. Lp(a), OxPL-apoB, and OxPL-apo(a) were highly correlated (Spearman R≥0.91 for all pairwise combinations). Biomarkers were not associated with any CAD, but Lp(a) and OxPL-apoB were associated with multi-vessel CAD. All biomarkers were associated with CV events. Odds of multi-vessel CAD per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.10 (95% CI 1.03-1.18, P=0.006), 1.18 (95% CI 1.03-1.34, P=0.01), and 1.07 (95% CI 0.99-1.16, P=0.07), respectively (
Figure, A
). Hazard ratios for MACE per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.08 (95% CI 1.03-1.14, P=0.001), 1.15 (95% CI 1.05-1.26, P=0.004), and 1.07 (95% CI 1.01-1.14, P=0.02), respectively (
Figure, B
).

Conclusions:
Lp(a) and OxPL-apoB are associated with multi-vessel CAD. Lp(a), OxPL-apoB, and OxPL-apo(a) are associated with incident CV events.
Abstract 9385: Adipokines and Venous Thromboembolism: The Multi- Ethnic Study of Atherosclerosis (MESA)
Authors: Broni Eric K , Ogunmoroti Oluseye , Quispe Renato , Sweeney Ty , Varma Bhavya , Fashanu Oluwaseun E , Lutsey Pamela L , Allison Matthew A , Szklo Moyses , Ndumele Chiadi E , Michos Erin D
Published: June 2023

Introduction:
Obesity leads to adipocyte hypertrophy and adipokine dysregulation, with implications for cardiovascular disease. Prior studies have linked adipokines to many obesity-related pathologies, with higher adiponectin levels considered cardioprotective whereas higher leptin and resistin are generally considered deleterious to cardiovascular health. In this regard, obesity is an independent risk factor for incident venous thromboembolism [VTE (deep vein thrombosis or pulmonary embolus)]. However, the associations of adipokines with VTE are not well established.

Methods:
We studied 1,888 MESA participants who were initially free of VTE and had adipokine levels measured at either visit 2 or 3. VTE was ascertained through hospitalization records and death certificates using ICD-9 and 10 codes. We used multivariable Cox proportional hazards regression to assess the association between 1 standard deviation (SD) log-transformed increments in adipokines and incident VTE.

Results:
The mean ± SD age was 64.7 ± 9.6 years; 50% women, 40% White, 20% Black, 26% Hispanic, and 13% Chinese - American participants. Median (IQR) of adiponectin, leptin and resistin were 17.3 (11.8 - 26.2) mcg/mL ,13.5 (5.6 - 28.2) ng/mL, and 15.0 (11.9 - 19.0) ng/mL respectively. There were 78 incident cases of VTE after a median of 9.7 (5.0 - 12.4) years of follow-up. The adjusted hazard ratio (95%) per 1 SD increment of adiponectin, leptin and resistin were 1.10 (0.86 - 1.42), 1.30 (0.97 - 1.74) and 1.39 (1.10 - 1.75), respectively
(Table 1,
Model 1
).
Associations for resistin persisted after adjustment for body mass index (Model 2) and computed tomography derived total visceral and subcutaneous adipose tissue area (Model 3).

Conclusions:
In this multi-ethnic cohort of adults free of cardiovascular disease at baseline, higher resistin levels were independently associated with greater risk of incident VTE. Larger prospective cohort studies are warranted to confirm this association.
Abstract 9399: Elevated MCU Expression by CaMKIIδB Limits Pathological Cardiac Remodeling
Authors: Wang Pei , Wang Wang
Published: June 2023

Introduction:
Calcium (Ca
2+
) is a key regulator of energy metabolism. Impaired Ca
2+
homeostasis damages mitochondria, causing cardiomyocyte death, pathological hypertrophy, and heart failure. This study investigates the regulation and the role of the mitochondrial Ca
2+
uniporter (MCU) in chronic stress-induced pathological cardiac remodeling.

Methods:
MCU knockout or transgenic mice were infused with isoproterenol (ISO; 10 mg/kg per day, 4 weeks). Cardiac hypertrophy and remodeling were evaluated by echocardiography and histology. Primary cultured rodent adult cardiomyocytes were treated with ISO (100 nmol/L, 48 hours). Intracellular Ca
2+
handling and cell death pathways were monitored. Adenovirus-mediated gene manipulations were used in vitro.

Results:
Chronic administration of the β-adrenergic receptor agonist ISO increased the levels of the MCU and the MCU complex in cardiac mitochondria, raising mitochondrial Ca
2+
concentrations, in vivo and in vitro. ISO also upregulated MCU without affecting its regulatory proteins in adult cardiomyocytes. It is interesting that ISO-induced cardiac hypertrophy, fibrosis, contractile dysfunction, and cardiomyocyte death were exacerbated in global MCU knockout mice. Cardiomyocytes from knockout mice or overexpressing a dominant negative MCU exhibited defective intracellular Ca
2+
handling and activation of multiple cell death pathways. Conversely, cardiac-specific overexpression of MCU maintained intracellular Ca
2+
homeostasis and contractility, suppressed cell death, and prevented ISO-induced heart hypertrophy. ISO upregulated MCU expression through activation of Ca
2+
/calmodulin kinase II δB (CaMKIIδB) and promotion of its nuclear translocation via calcineurin-mediated dephosphorylation at serine 332. Nuclear CaMKIIδB phosphorylated CREB (cAMP-response element binding protein), which bound the
Mcu
promoter to enhance
Mcu
gene transcription.

Conclusions:
The β-adrenergic receptor/CaMKIIδB/CREB pathway upregulates Mcu gene expression in the heart. MCU upregulation is a compensatory mechanism that counteracts stress-induced pathological cardiac remodeling by preserving Ca2+ homeostasis and cardiomyocyte viability.
Abstract 9409: Risk Factors and Outcomes Associated With Loss of Follow-Up in Children With Congenital Heart Disease
Authors: Rosamilia Michael B , Williams Jason , Bair Courtney A , Mulder Hillary , Chiswell Karen , DOttavio Alfred , Spears Tracy G , Hartman Robert J , Sang Charlie J , Welke Karl F , Walsh Michael J , Hoffman Timothy M , Landstrom Andrew P , Li Jennifer S , Sarno Lauren A
Published: June 2023

Introduction:
Adults with congenital heart disease (CHD) benefit from cardiology follow-up. However, benefit for children is less clear as studies of follow-up patterns in children with CHD are limited.

Hypothesis:
There are identifiable risks for loss to cardiology follow-up in children with CHD, and loss to follow-up changes healthcare utilization and outcomes.

Methods:
Our cohort included children <10 years old with CHD and a healthcare encounter from 2008 to 2013 at one of four North Carolina hospitals. Using a Cox proportional hazards model, we assessed associations between demographics, presence of a severe lesion (conotruncal, endocardial cushion, and single ventricle lesions, aortic arch interruption, and total anomalous pulmonary venous return), and healthcare access, including educational isolation (EI) via geo-coded neighborhood of residence, and at least one cardiology follow-up visit within two years of initial encounter. We analyzed healthcare utilization by follow-up using a negative binomial landmark analysis. We described incidence of death and cardiac transplantation.

Results:
Of the 6,969 children, 24.8% were non-Hispanic Black and 14.1% were Hispanic. Overall, 60.4% received follow-up within 2 years, including 53.1%, 58.1%, and 79.0% of those with valve, shunt, and severe lesions respectively. Factors associated with loss to follow-up were increased drive time to the nearest cardiology clinic (Hazard Ratio 0.92 per 15-minute increase), EI (HR 0.94 per 0.2-unit increase), lower lesion severity (HR 0.48 for shunt/valve vs severe), and older age at initial encounter (HR 0.95 per month if <1 year old and 0.94 per year if >1 year old;
p<0.05
). Children lost to follow-up had more emergency department (ED) visits (Rate Ratio 1.59) and fewer inpatient encounters and procedures (RR 0.51, 0.35;
p<0.05
). Only 0.8% of children died or received a cardiac transplant after the 2-year landmark with no significant difference between follow-up groups.

Conclusions:
We found novel factors associated with loss to cardiology follow-up in children with CHD and worse utilization with loss to follow-up. Our findings demonstrate a need to mitigate healthcare barriers and generate clear cardiology follow-up guidelines for children.
Abstract 9410: Cardiovascular Disease Associated Metabolites TMA and TMAO Bind to Cystathionine Gamma-Lyase and Repress Its Enzymatic Production of Hydrogen Sulfide
Authors: Sharew Betemariam , Kim Suzie , Enders Jacob , Bithi Nazmin , Hine Christopher
Published: June 2023

While the causative factors of smoking and hypertension leading to cardiovascular disease (CVD) are well understood, those involved with diet-induced CVD are not. One metabolite regulated by diet that is involved with cardio-protection and vasodilation is the gasotransmitter hydrogen sulfide (H
2
S). However, the molecular inhibition of H
2
S-generating enzymes via CVD-inducing diets is not fully understood, nor is it known if this is the causative event leading to CVD. Enzymatic H
2
S production in mammalian tissues and cells is primarily via the transsulfuration enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL). A high fat Western diet contributes to CVD through gut microbiome metabolic pathways and subsequent host enzymes converting choline and carnitine into the metabolites trimethylamine (TMA) and trimethylamine-N-oxide (TMAO).
We hypothesized
that TMA and TMAO lower H
2
S production by directly interacting with CGL to reduce enzymatic activity and that these gut-related metabolites’ inhibition account for some of the CVD risks.

Results:
Using a lead acetate assay, we discovered that these metabolites reduce enzymatic H
2
S production in a CGL-dependent manner from tissues
ex vivo
as well as from purified human CGL
in vitro
to a similar extent as propargylglycine (PAG), a known CGL suicide inhibitor that also happens to be a bacterial metabolite. We found that
in vivo
, hepatic and renal H
2
S production increased in antibiotic treated mice surface plasma resonance (SPR) and micro-scale thermophoresis (MST) assays revealed direct and specific physical interactions between TMA and TMAO with CGL. Additionally, pre-incubation with PAG blocked the binding of TMAO with CGL, indicating that the mechanism and location of inhibition are shared.

Conclusion:
Diet-induced gut metabolites TMA and TMAO bind CGL enzyme and suppress enzymatic production of cardioprotective H
2
S.
Abstract 9418: Inhibition of Cardiac Mitochondrial Fission as an Effective Intervention Against Trastuzumab-Induced Cardiotoxicity in Rats
Authors: Maneechote Chayodom , Khuanjing Thawatchai , Ongnok Benjamin , Arinno Apiwan , Prathumsap Nanthip , Chunchai Titikorn , Arunsak Busarin , Kerdphoo Sasiwan , Chattipakorn Siriporn , Chattipakorn Nipon
Published: June 2023

Introduction:
Trastuzumab (TRZ) has been broadly used as a chemotherapeutic agent for the treatment of advanced human epidermal growth factor receptor type 2-expressing malignancies. However, cardiotoxicity exacerbated by TRA has become an adverse clinical manifestation of oncologic treatment. Although cardioprotective outcomes of a mitochondrial division inhibitor (Mdivi-1) have been demonstrated for a wide range of cardiovascular pathologies, the anti-cardiotoxic effects of Mdivi-1 against TRZ are unknown.

Hypothesis:
Treatment with Mdivi-1 rescues cardiac mitochondrial dysfunction, resulting in improved left ventricular (LV) function in rats with TRZ-induced cardiotoxicity.

Methods:
Male Wistar rats (n=18) were divided into either TRZ group (4 mg/kg/day for 7 days, I.P., n=12) or control group (CON, n=6). In the TRZ group, rats also received one of the following co-treatments: 1) vehicle (VEH, n=6) or 2) Mdivi-1 (MDV, 1.2 mg/kg/day, n=6) via I.P. injection for 7 days. LV ejection fraction (LVEF) and cardiac mitochondrial function were determined.

Results:
TRZ-treated rats had impaired cardiac mitochondrial function as shown by increased reactive oxygen species (ROS) production, mitochondrial depolarization (reduced red/green fluorescence intensity), and mitochondrial swelling (reduced absorbance intensity), leading to LV dysfunction (75% LVEF for TRZ vs. 88% LVEF for CON) (Fig. 1A-D). Mdivi-1 co-treatment attenuated cardiac mitochondrial dysfunction and LV dysfunction as evidenced by a decrease in ROS, mitochondrial depolarization, mitochondrial swelling, and increased LVEF (83%, 11% improvement from VEH group) (Fig. 1A-D).

Conclusions:
Mdivi-1 effectively protected the heart against TRZ-induced cardiotoxicity by attenuating mitochondrial and LV dysfunction, thus indicating that pharmacological inhibition of mitochondrial fission could be a novel anti-cardiotoxicity in TRZ-induced cardiotoxicity.
Abstract 9419: Empagliflozin Modulates Cardiac Na Homeostasis via Late I
Na
and I
NCX
Authors: Mustroph Julian , Baier Maria , Trum Maximilian , Pabel Steffen , Stehle Thea , Provaznik Zdenek , Sossalla Samuel , Maier Lars S , Wagner Stefan
Published: June 2023

Introduction:
The effects of empagliflozin on excitation-contraction coupling (ECC) have not been fully elucidated. We previously showed that empagliflozin directly reduces Ca
2+
/calmodulin kinase II (CaMKII) activity in human and murine heart failure, thereby improving contraction. Upon acute exposure, however, only subsarcolemmal [Na
+
] is decreased, while [Na
+
]
cytosolic
and [Ca
2+
]
cytosolic
are only decreased after 24 h empagliflozin.

Hypothesis:
We hypothesize that empagliflozin reduces cardiac late Na current (late I
Na
) via a reduction in CaMKII activity. We further hypothesize that Na
+
/Ca
2+
-exchanger (NCX) is acutely masking effects on cardiac [Na
+
], thereby delaying downstream effects on cardiac ECC.

Methods:
Informed consent was obtained according to the Declaration of Helsinki. Human/murine cardiomyocytes (CM) were isolated and incubated with 1 μM empagliflozin for 30 min or 24 h. Some CM were treated with H
2
O
2
or ATX-II to induce late I
Na
. Whole-cell patch clamp was used to measure late I
Na
or I
NCX
. Epifluorescence with SBFI was used to obtain cardiac [Na
+
]. Some CM were treated with NCX inhibitor KB-R7943 (5 μM).

Results and Conclusions:
Late I
Na
induced by H
2
O
2
was acutely inhibited in human and murine CM by empagliflozin, similar to CaMKII inhibition with AIP (2 μM). In CM lacking CaMKII or the CaMKII phosphosite S571 on Na
V
1.5, no effect of empagliflozin on late I
Na
was present (also not under ATX-II stimulation). As shown before, subsarcolemmal [Na
+
] estimated via patch clamp (Nernst equation) was already reduced after 30min (T30
min
). However, empagliflozin did not acutely reduce cytosolic [Na
+
] at T30
min
, but potently did so after 24h exposure (SBFI measurement). Acute inhibition of NCX with KB-R7943 showed no effect on cardiac Na
+
, but when performed in addition to empagliflozin, potently reduced [Na
+
] already at T30
min
. Matching this, NCX forward mode (patch clamp) was acutely induced by empagliflozin at T30
min
, thus resulting in Na
+
influx that initially masks the reduction in [Na
+
] resulting from a reduction in late I
Na
. This may explain why Na
+
/Ca
2+
homeostasis is only affected after 24h empagliflozin exposure. Our results may explain discrepant results on ECC by different groups on acute vs. prolonged empagliflozin exposure.
Abstract 9436: Treatment Options for Left Atrial Septal Pouch: A Case Report
Authors: Yuvaraj Yaswanraj , Girard Michael , PEREZ VIANKA
Published: June 2023

Introduction:
Left Atrial Septal pouch (LASP) is defined as an incomplete closure between the septum primum and septum secundum with an elongated septum secundum. This produces a crevice in the left atrium that functions as a source for static blood and atrial dissociation. This in turn could progress to the formation of thrombi within the left atrium that has the potential to embolize causing ischemic infarcts.

Case Description:
Here we present a 63 year old Hispanic female with a past medical history of paroxysmal atrial fibrillation on apixaban, recurrent strokes, dyslipidemia, and hypertension who presented with expressive aphasia, and prosopagnosia. Previously, the patient was reported of having two cardioembolic cerebral vascular accidents (CVA). Computed tomography of the brain demonstrated an old infarct of the left posterior parietal lobe. Patient was treated with intra-arterial tissue plasminogen activator of the left posterior cerebral artery and right middle cerebral artery. MRI demonstrated four acute punctate infarcts in the left frontal lobe consistent with embolic infarcts. TEE demonstrated a large patent foramen ovale (PFO), a prominent eustachian valve, and LASP. It was determined that her PFO and LASP were the culprit for her recurrent CVA despite appropriate AC. The PFO/LASP were successfully closed with an Amplatzer PFO occluder device. Patient was discharged home.

Discussion:
The LASP can function as a source of thrombus formation and atrial disassociation, which can cause embolic CVA. No guidelines exist on how to properly address a LASP. One option would be to use a PFO closure device to close LASP. Other options may include AC despite the absence of atrial fibrillation.

Conclusions:
In conclusion, further studies are necessary in order to establish the most appropriate management in patients with LASP.
Abstract 9444: Differences in Hospital Outcomes Following Watchman's Procedure Based on CHA
2
DS
2
VASc Score: Insight From National Inpatient Sample Database, 2016-2019
Authors: Shrestha Biraj , Poudel Bidhya , Donato Anthony
Published: June 2023

Background:
Uncertainty exists whether a higher CHA
2
DS
2
VASc risk score is associated with poorer in-hospital outcomes than a lower risk score following Left Atrial Appendage Occlusion (LAAO) procedures.

Methods:
The National Inpatient Sample (NIS) was queried for all hospitalizations with primary atrial fibrillation or flutter from 2016 to 2019 with codes for percutaneous left atrial appendage occlusion device placement. Cohorts with high (CHA
2
DS
2
VASc ≥5) and low (CHA
2
DS
2
VASc <5) risk of stroke were compared. Weighted multivariable logistic regression was used to assess the association between CHA
2
DS
2
VASc score and in-hospital outcomes.

Results:
Out of 60,350 procedures performed, 50.61% had high CHA
2
DS
2
VASc score (
>
5) and 49.39% had low score (< 5) (table 1). All patients received the Watchman device. The primary outcome of in-hospital mortality was not statistically different between high and low risk (0.18% vs. 0.12%, OR: 1.53, 95% CI: 0.59-3.96, p=0.37), a finding that did not change when adjusted for comorbidities in multivariate analysis (adjusted OR: 1.44, 95% CI: 0.55-3.62, p=0.46). In the high-risk group, total complication rates were similar (adjusted OR: 1.16, 95% CI: 0.97-1.38, p=0.09) as was ischemic stroke (adjusted OR: 2.05, 95% CI: 0.82-5.13, p=0.13) while systemic embolism (adjusted OR: 5.09, 95% CI: 1.08-23.99, p=0.04) and major bleeding requiring transfusion (adjusted OR: 3.84, 95% CI: 1.41-10.42, p=0.08) were higher after adjusting for confounders in multivariable analysis (figure 1).

Conclusion:
This study demonstrates that the LAAO procedure had similar short-term outcomes between high and low-risk patients in a study of real-world patients.
Abstract 9448: Pre-Stroke Statin Use is Associated With Mild Neurological Symptoms at the Onset of Acute Ischemic Stroke
Authors: Mori Takahisa , Yoshioka Kazuhiro , Miyazaki Yuichi
Published: June 2023

Introduction:
Statins have protective effects against ischemic injury, and pre-stroke statin use augments cerebral blood flow, reduces infarct size, and improves neurological function in mice.

Hypothesis:
Pre-stroke statin is associated with mild neurological symptoms at the onset of acute ischemic stroke (AIS).

Methods:
We retrospectively included patients with AIS admitted to our institution within 24 hours of onset between April 2011 and March 2019. We collected data on age, sex, pre-stroke use of stains, antiplatelets, anticoagulants, antihypertensive drugs, and diabetes drugs, the National Institutes of Health Stroke Scale (NIHSS) score, serum levels of albumin, glucose, glycated hemoglobin, lipids, and c-reactive protein, and stroke subtypes at admission. In addition, we defined mild neurological symptoms (mNS) as the NIHSS score of three or less. We compared variables between patients with and without pre-stroke statins and identified variables with significant differences between them. We conducted a logistic regression analysis using variables for pre-stroke statin use except for the NIHSS score, mNS, lipids, or stroke subtypes, calculated propensity scores for a pre-stroke statin and implemented a one-to-one propensity score matching (PSM). We evaluated differences between matched pairs and whether pre-stroke statin was significant for mNS at admission. We used the McNemar test to evaluate symmetry on a binary matched pairs contingency table of mNS.

Results:
Two thousand six hundred fifteen patients met our inclusion criteria during the study period. In 594 patients (22.7%) with pre-stroke statins and 2021 patients without them, 308 (51.9%) and 895 (44.3%) patients presented mNS (p=0.0012). After one-to-one PSM, 555 patients underwent pre-stroke statin treatment, and 555 patients did not undergo it. There were no differences in variables between matched pairs except for the NIHSS score, mNS, or cholesterol levels; 286 patients with pre-stroke stains and 252 patients without them presented mNS at admission (p=0.0411), and the binary matched pairs contingency table of mNS was not symmetrical (p=0.0385).

Conclusions:
Pre-stroke statin use is associated with mNS at the onset of AIS.
Abstract 9451: Association Between Hypertension and Incident Infective Endocarditis
Authors: Lee Gyu B , SHIN KOH EUN , Han Kyung-Do , Son Ho-Sung , Jung Jae Seung , Kim Yang-Hyun , KIM Hee Jung
Published: June 2023

Introduction:
This study aimed to evaluate the association of hypertension with incident infective endocarditis (IE) by investigating the incidence of IE according to blood pressure levels using the National Health Insurance Service database.

Hypothesis:
Considering the recent rise in the incidence of IE and the fact that little research has been conducted on the relationship between blood pressure levels and IE incidence, we hypothesized that hypertension may serve as a risk factor for incident IE.

Methods:
The data of 4080331 individuals linked to the health screening database in 2009 were retrieved (males, 55.08%; mean age 47.12 ± 14.13 years). From 2009 to 2018, the risk factors for the first episode of IE were investigated. Hypertension was categorized into normotension, prehypertension, hypertension, and hypertension with medication. The Cox proportional hazard model assessed the effect of blood pressure level during the health screening exam on incident IE.

Results:
During the 9-year follow-up, 812 (0.02%) participants were diagnosed with IE. The incidence rates of IE in the normotension, prehypertension, hypertension, and hypertension with medication groups were 0.9, 1.4, 2.6, and 6.0 per 100,000 person-years, respectively. Those with prehypertension, hypertension, and hypertension with medication were correlated with an increased risk of IE in a dose-response manner compared with the normotension group (hazard ratio, 1.33 [95% CI, 1.06-1.68]; hazard ratio, 1.98 [1.48-2.66]; hazard ratio, 2.56 [2.02-3.24], respectively, all P<0.001).

Conclusions:
In a large national cohort study with an average follow-up of 9-years, increased blood pressure was identified as a risk factor for incident IE in a dose-dependent manner. Hypertension increases the public health care burden by acting as a risk factor for rare infective heart diseases.
Abstract 9453: The Role of Repeated PET/MRI Hybrid Imaging in Pulmonary Arterial Hypertension Patients Receiving Specific Therapy, Four-Year Observation
Authors: Kazimierczyk Remigiusz , Szumowski Piotr , Nekolla Stephan , Malek Lukasz , Blaszczak Piotr , hladunski Marcin , Sobkowicz Bozena , Mysliwiec Janusz , Kaminski Karol
Published: June 2023

Introduction:
PET/MRI hybrid imaging in pulmonary arterial hypertension (PAH) provides new prognostic parameters, which identify the group of patients who potentially might benefit from early PAH therapy escalation. In previous study we confirmed that right ventricle (RV) metabolic alterations are linked with PAH hemodynamics and both precede clinical deterioration.

Hypothesis:
Repeating PET/MRI scans improves PAH patients’ management.

Methods:
Twenty stable patients (49.9±14.9 y.o.) had second simultaneous PET/MRI scans during follow up visit (FU) after 24 months from baseline scans. SUV
RV
/SUV
LV
ratio was used to estimate and compare cardiac glucose uptake before and after PAH therapy escalation. Next, observation was extended to 48 months in total.

Results:
Between baseline and FU visits, 16 patients needed therapy escalation (mostly to prostacyclin); median SUV
RV
/SUV
LV
(observed in PET) has lowered with improvement in both RV ejection fraction (MRI) and mean pulmonary artery pressure (catheterization). In long observation (48 months) mean time to clinical worsening was 25.2±17.1 months. Cut-off value of PET-derived SUV
RV
/SUV
LV
in ROC analysis was 0.54, suggesting that even subtle shift in cardiac glucose metabolism in PAH may result in worse prognosis. PAH patients with baseline SUV
RV
/SUV
LV
higher than 0.54 had significantly worse prognosis in the 48-months observation (log-rank test, p=0.003). Finally, patients with follow-up SUV
RV
/SUV
LV
ratio higher than 1.14 had still significantly worse prognosis despite of previously escalated treatment during FU visits (log-rank test, p=0.04, Figure).

Conclusions:
Repeated PET/MRI imaging provides non-invasive assessment of PAH patients’ hemodynamics, prognosis and helps to determine effectiveness of targeted therapy affecting subtle cardiac metabolic changes. Even single PET/MRI assessment in PAH patients may help to determine long-term prognosis and to plan appropriate PAH therapy.
Abstract 9454: Cardiovascular Risks of Chemo-Immunotherapy for Lung Cancer: A Population-Based Cohort Study
Authors: Chan Jeffrey S , Tang Hoi Kiu Pias , Ng Kenrick , Dee Edward Christopher , Lee Teddy , Chou Oscar Hou In , Lee Yan Hiu Athena , Lau Dawnie Ho Hei , Liu Tong , Tse Gary
Published: June 2023

Introduction:
Chemo-immunotherapy combinations have proven efficacious for treating advanced lung cancer. However, their cardiovascular risks are unclear. This study thus aimed to compare the cardiovascular risks between programmed cell death protein 1 (PD-1) inhibitors, and chemo-immunotherapy in Asian patients with lung cancer.

Methods:
This retrospective cohort study included patients aged at least 18 years old with lung cancer receiving any PD-1 inhibitor in Hong Kong during 2013-2021. Patients with non-concurrent use of PD-1 inhibitor and chemotherapy, use of tyrosine kinase inhibitor, other immunotherapy, or those with prior stroke, heart failure, or myocardial infarction were excluded. Treatment groups were defined as PD-1 inhibitor only, and concurrent use of PD-1 inhibitor and chemotherapy (chemo-immunotherapy). The endpoint was major adverse cardiovascular events (MACE), that was the first occurrence of cardiovascular death, heart failure, stroke, or myocardial infarction. Patients were followed up until the end of 2021. Inverse probability treatment weighting (IPTW) was used to minimise covariate imbalances.

Results:
Of the 1508 patients identified, 713 were analysed (538 male, mean age 66.2±10.6 years old, mean follow up 1.4±1.3 years); 333 received PD-1 inhibitors only, and 380 received chemo-immunotherapy. IPTW achieved good balance for all covariates. The observed incidence rate of MACE was 2.8 events per 100 person-year (95% confidence interval (CI) 1.6-4.8) for patients on PD-1 inhibitors, and 2.1 per 100 person-year (95% CI 1.2-3.8) for those on chemo-immunotherapy. The log-rank test showed no significant difference in cumulative incidence of MACE between treatment groups (p=0.641; Figure 1).

Conclusions:
MACE may be uncommon amongst patients with lung cancer receiving PD-1 inhibitors or chemo-immunotherapy. The associated risks of MACE may not be significantly different between PD-1 inhibitors and chemo-immunotherapy.
Abstract 9543: Cilostazol Improves Symptom Scores and Lowers NT-proBNP in HFpEF Preliminary Results From the CLIP-HFpEF N-of-1 Study
Authors: Aiad Norman N , Alexy Tamas , Zhang Michael J , Nijjar Prabhjot S , Chaikijurajai Thanat , Martin Cindy M , Meyer Markus
Published: June 2023

Introduction:
Although heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly common, targeted HFpEF therapies remain limited. Current evidence-based treatment options are modestly effective and provide limited symptom relief.

Hypothesis:
Cilostazol, a generic and oral phosphodiesterase type 3 (PDE-3) inhibitor, rapidly improves HF symptoms and serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels in HFpEF patients with an ejection fraction of 50% or higher.

Methods:
A prospective, double-blind, n-of-1 study with three crossovers with unblinding at the 1-month endpoint was designed. Stable outpatients with HFpEF received either placebo twice daily or Cilostazol 100mg twice daily for one week followed by three weekly crossovers. HF symptoms were assessed each week using the Kansas City Heart Failure Questionnaire (KCCQ-12) and NT-proBNP levels were measured at the end of weeks one and four.

Results:
Preliminary data from the initial 11 participants are presented (six men and five women, mean age 67±13 years). The mean KCCQ-12 score was eight points higher with Cilostazol than placebo (47±12 vs. 39±12; p<0.05) (Figure 1A). Median NT-proBNP levels were lowered by 22% with Cilostazol compared to placebo (412 [293-1066] pg/dL vs. 659 [323-897] pg/dL; p<0.05) (Figure 1B).

Conclusions:
In this preliminary analysis of CLIP-HFpEF, treatment with Cilostazol led to a rapid alleviation of HF symptoms and a decline in NT-proBNP levels when compared to placebo. The results of CLIP-HFpEF suggest a marked benefit of Cilostazol in HFpEF patients. Further studies are needed to elucidate the mechanism and long-term clinical benefits of Cilostazol in patients with HFpEF.
Abstract 9563: Intravenously Infused Extracellular Vesicles Preserve Function of Anthracycline-Treated Hearts
Authors: Desgres Manon , Petrusca Lorena , Autret Gwennhael , Pezzana Chloé , Marigny Celine , Peuffier Ashley , Bellamy Valerie , Croisille Pierre , Hagege Albert , Tavitian Bertrand , Silvestre Jean-Sebastien , Menasche Philippe
Published: June 2023

Introduction:
Current treatments of chemotherapy-induced cardiomyopathy (CCM) are of limited efficacy.

Hypothesis:
Extracellular vesicles (EV) might represent a new therapeutic option.

Methods:
Male immunocompetent mice were subjected to 3 intraperitoneal (IP) injections of doxorubicin (DOX, 4mg/kg) followed by 3 sequential intravenous injections of EV (10x10
9
/injection) collected from human induced pluripotent stem cell (hiPSC)-differentiated cardiovascular progenitor cells. Outcomes were assessed 8-11 weeks after the onset of DOX treatment on MRI and compared with those of mice injected with saline (controls) or DOX-untreated (sham). Explanted hearts were subjected to transcriptomics. Next, female rats received 5 IP injections of DOX (3mg/kg) followed by 3 IV injections of EV (33x10
9
/injection) similar to those of the mouse study except that they had been GMP-manufactured to be of clinical grade. Control rats were saline-injected or DOX-untreated (sham). Outcomes were assessed 1 month after the onset of DOX treatment on echocardiography. In additional
in vitro
experiments, hiPSC-derived cardiomyocytes were stressed by DOX w/wo EV and assessed for ATP content.

Results:
In mice, DOX+saline-injected hearts (n=14) incurred a significant decline in basal (global, epi- and endocardial) circumferential strain compared with the 14 sham mice (p=0.04 for each) while EV (n=11) preserved these indices which did not significantly differ from those of sham mice. Global longitudinal strain followed a similar pattern. EV also upregulated genes involved in the limitation of cardiac remodeling and preservation of contractile function. In rats, LV endsystolic volumes were significantly increased in saline-injected hearts (n=11) compared with the 6 sham (p=0.03) but were preserved after EV injections (n=12). Likewise, the percentages of "responder" rats which did not increase their enddiastolic LV volumes by more than 5% from their post-DOX pre-treatment values were 58%
vs
. 28% in EV- and saline-injected hearts, respectively.
In vitro
, EV increased ATP levels of DOX-stressed cardiomyocytes by 30% compared to placebo.

Conclusions:
The cardioprotective effects of IV-injected EV make them an attractive user-friendly option for the treatment of CCM.
Abstract 9578: Chronic Phosphodiesterase Type 5 Inhibition by Sildenafil Causes Regression of Heart Failure: Insights into Molecular and Cellular Mechanisms
Authors: Li Tiankai , Cheng Heng-Jie , Zhang Xiaowei , Zhang Zhi , Zhao David X , Herrington David M , Kitzman Dalane W , Cheng Che Ping
Published: June 2023

Background:
Sildenafil (SIL), a selective inhibitor of PDE5 has been shown to exert profound beneficial effects in heart failure (HF). However, whether and by what mechanisms SIL can stop the progression of HF, or maybe even reverse the clinical route remain unknown. We tested the hypothesis that chronic SIL would improve intrinsic myocyte function and [Ca
2+
]
i
regulation and reverse HF-induced detrimental alterations on cardiac SERCA2a, β-adrenergic receptors (AR) and nitric oxide synthase (NOS) isoforms, thus playing a salutary role in HF.

Methods:
We evaluated LV and myocyte function and the protein levels of myocyte β
1
- and β
3
- AR, SR Ca
2+
-ATPase (SERCA2a), phospholamban (PLB), and 3 NOS in 3 groups of male rats (8/group) for a period of 3 months (M): 1)
HF
, 3 M after receiving isoproterenol (ISO) (170 mg/kg sq for 2 days); 2)
HF/SIL
, 2 M after ISO, then SIL (70 μg/kg/day sq via mini pump) was initiated and given for 1 M; and 3)
Controls
.

Results:
Versus C, ISO-treated rats progressed to severe HF at 3 M with significantly reduced LV contractility (E
ES
, 0.7 vs 1.1 mmHg/μl), and slowed LV relaxation. LV myocyte contraction (dL/dt
max
, 77 vs 136 μm/sec), relaxation (dR/dt
max
, 62 vs 104 μm/sec) and [Ca
2+
]
iT
(0.15 vs 0.24) were significantly decreased accompanied by a diminished myocyte inotropic response to ISO (10
-8
M) superfusion. These abnormalities were associated with concomitant significant decreases in myocyte protein levels of β
1
-AR (0.23 vs 0.64), SERCA2a (0.46 vs 0.80), PLB
Ser16
/PLB ratio, and eNOS (0.28 vs 0.46), but increased protein levels of β
3
-AR (0.23 vs 0.10) and iNOS (0.18 vs 0.08). Chronic SIL treatment prevented HF-caused reduced E
ES
(1.3 mmHg/μl) and EF (62%) and retained normal dL/dt
max
(131μm/s), dR/dt
max
(106 μm/s), and [Ca
2+
]
iT
(0.24), and restored normal myocyte contractile response to ISO stimulation. With SIL, protein levels of myocyte β
1
- and β
3
-AR, SERCA2a were normalized to control values, but eNOS was significantly elevated (0.77).

Conclusions:
Chronic SIL prevents HF-caused downregulation of cardiac β
1
-AR and reverses contrast changes between iNOS and β
3
-AR with SERCA2a and eNOS expression, restores normal myocyte function, [Ca
2+
]
iT
, and β-adrenergic reserve, and leads to regression of LV dysfunction in a rat model of progressive HF.
Abstract 9584: Preoperative Characteristics Predict Death and Pump Replacement in Patients With HeartMate 3 Left-Ventricular Assist Devices
Authors: Pinsker Bret L , Jimenez Contreras Fabian , Schroder Jacob , Bryner Benjamin , Katz Jason N , Russell Stuart D , Milano Carmelo A
Published: June 2023

Introduction:
There is limited data examining predictors of outcome in patients with HeartMate 3 (HM3) LVAD. We sought to examine factors that predict pump replacement and death in patients with HM3 LVAD.

Hypothesis:
Traditional risk factors in older LVAD models may be unassociated with pump replacement and death in patients with HM3 LVAD.

Methods:
Patients that underwent HM3 LVAD implantation from 2015 to 2020 were identified from a single tertiary care center. Records were reviewed for demographic/clinical characteristics at LVAD implantation and a primary outcome of LVAD replacement or death. Predictors of outcome were identified using univariable Cox regression. Kaplan Meier (KM) analysis and log-rank test were used to assess outcome-free survival based on pre-operative BMI and albumin.

Results:
A total of 298 patients that met inclusion criteria were identified. Over a median follow-up of 2.3 years, 97 patients (33%) experienced a primary outcome. Predictors of outcome included age, peripheral vascular disease, ECMO prior to LVAD implantation, and pre-operative creatinine and albumin levels. BMI was not predictive of the primary outcome (Table 1). Outcome-free survival was different among patients with and without pre-operative hypoalbuminemia, but unassociated with differences in BMI (Figure 1).

Conclusions:
This is one of the largest single-institution cohorts that has examined predictors of adverse outcomes in patients with HM3 LVAD. Optimizing pre-operative nutrition (as reflected by albumin) may help prevent adverse outcomes in this population. Lastly, HM3 LVAD may be a safe option in obese patients who would otherwise not be candidates for transplantation.
Abstract 9616: A Cardiac Mass in the Postpartum: A Diagnostic and Therapeutic Dilemma
Authors: Dudorova Elena , Ravalli Stefano
Published: June 2023

Introduction:
Precise diagnosis of a cardiac mass has crucial prognostic and therapeutic implications. Case Presentation: A 23-year-old woman presented to an outside hospital 6 days after delivery with headaches, chest pain and very high BP. A CT angiogram found no pulmonary emboli but identified a mass in the right atrium. Surgical removal was attempted but had to be aborted because of inability to get clear margins. Frozen section showed atypical spindle cells, suggestive of sarcoma. Patient was transferred to our hospital for further management. TTE (Figure) revealed a large solid mass almost entirely filling the right atrium and a small pericardial effusion. CMR showed a 7.2 cm hypervascular mass in the right atrium with possible invasion of the superior vena cava, suggestive of angiosarcoma. Additional tissue sections showed vascular spaces lined by benign endothelial cells positive for the endothelial markers ERG, CD31 and CD34 and infiltrating the underlying myocardium; proliferation rate was <1%. Based on these findings a diagnosis of primary cardiac hemangioma was made. Subsequent PET CT showed mildly FDG-avid cardiac mass and no metastases.

Discussion:
Cardiac masses are a diagnostic challenge. Identification hinges on clinical history, location and multimodality imaging but histopathology and immunohistochemistry remain the gold standard for a definitive diagnosis. Primary cardiac tumors are rare, found only in <0.05% of autopsies; 80% are benign and 20% malignant. Hemangiomas are extremely rare, representing <3% of primary cardiac tumors. They are often misdiagnosed as other neoplasms, as was the case in our patient, possibly leading to unnecessary invasive procedures. Although benign, hemangiomas can infiltrate surrounding structures and cause serious complications, such as syncope, emboli, arrhythmias, heart block and stroke. Complete surgical excision remains the treatment of choice and, if successful, confers a positive prognosis.
Abstract 9691: Incidence of Atrial Fibrillation in Patients Hospitalized for COVID Compared to Non-COVID Pneumonia/ARDS
Authors: Bernstein Hannah , Paciotti Brian , Srivatsa Uma N
Published: June 2023

Introduction:
Though atrial fibrillation (AF) has been reported with COVID, it is unclear if it is related to myocarditis or lung injury. The aim of this study was to compare incident AF in pneumonia/ARDS with and without COVID.

Methods:
In this retrospective multicenter cohort study from 17 hospitals (3/2020 to 12/2021) utilizing the University of California COVID Research Data Set (CORDS), we included patients >18 years with primary diagnosis of pneumonia or ARDS during hospitalization by ICD-10. We excluded those with prior AF. Subjects were determined to have COVID based on positive PCR test within 10 days prior or during inpatient admission and compared to a control group with negative PCR test. Clinical data was extracted from electronic medical records. The cohorts were compared using χ2 test for categorical variables and Wilcoxon rank tests for continuous variables. Multivariable logistic regression models were used to investigate the association between COVID and development of new atrial fibrillation.

Results:
Of the 39,415 subjects, 12.2% had COVID. The COVID+ cohort was younger, had more males, and more co-morbidities. They required more mechanical ventilation, but less ICU care and hemodynamic support (Table 1). Incident AF occurred in 523 (10.85%) of COVID vs 4,899 (14.16%) in the non-COVID group (OR 0.74, p < 0.001), which remained significant after adjustment of demographics and co-morbidities (p < 0.001). AF was associated with higher mortality (26.2% vs. 10.21%, p <0.001) and longer hospitalization (22.5 vs. 15.1 days, p <0.001) in COVID group compared to the controls (Table 2).

Conclusions:
Incident AF is less in COVID compared to non-COVID pneumonia/ARDS despite requiring more mechanical ventilation, however had higher mortality and prolonged hospitalization.
Abstract 9695: Characteristics, Treatment, and Mortality of Patients Hospitalized for ST-Elevation Myocardial Infarction Without Standard Modifiable Cardiovascular Risk Factors in China
Authors: Guo Weihong , Wang Yunfeng , Tian AoXi , Liu Jiamin , Zhang Haibo , Li Jing , Hu Shengshou , Li Xi , zheng xin
Published: June 2023

Introduction:
Previous studies found that a substantial proportion of ST-elevation myocardial infarction (STEMI) patients with no standard modifiable cardiovascular risk factors (SMuRFs: hypertension, diabetes mellitus, hypercholesterolemia, smoking) at admission, had unexpected higher mortality compared with those with SMuRFs. However, little is known about what contributed to the excess risk of SMuRF-less patients.

Methods:
This study used a two-stage random sampling design to create a nationally representative sample of patients admitted with STEMI in China, from 2001 to 2015. We compared patient characteristics, treatments, and in-hospital mortality rates between SMuRF-less patients and those with SMuRFs, and established stepped mixed effect models on in-hospital mortality, to explore the potential contributors to different mortality risks (if exist).

Results:
Among 16541 patients included (aged 65±13 years, 30.0% women), 3288 (19.9%) were SMuRF-less. Compared with patients with SMuRFs, SMuRF-less patients were older (69 vs 65 years, p<0.001), and presented with more severe clinical conditions (mini-Global Registry of Acute Coronary Events risk score; 151 vs 138, p<0.001). SMuRF-less patients were less likely to receive primary percutaneous coronary intervention (17.3% vs 28.8%, p<0.001), as well as dual antiplatelet therapy (59.4% vs 77.0%, p<0.001), β-blocker (78.3% vs 85.7%, p<0.001), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (49.9% vs 68.1%, p<0.001), statin (69.9% vs 85.1%, p<0.001). Meanwhile, SMuRF-less patients had higher in-hospital mortality (18.5% vs 10.5%, p<0.001). Such difference was largely attenuated after adjusting for baseline characteristics (OR 1.45; 95%CI 1.29-1.64), while disappeared after additionally adjusting for in-hospital treatments (OR 1.04; 95%CI 0.91-1.19), particularly angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and statin.

Conclusion:
For the one-fifth patients with STEMI who had no SMuRFs the excess in-hospital mortality was associated with their relatively suboptimal treatments, highlighting the need for evidence-based therapy in SMuRF-less patients during hospitalization.