bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15774: Cu Uptake Transporter CTR1 Cys189 Oxidation Protects Against Atherosclerosis via Limiting Mitochondrial Dysfunction and Endothelial Senescence
Authors: Das Archita , Varadarajan Sudhahar , Yadav Shikha , Nagarkoti Sheela , McMenamin Malgorzata , Kaplan Jack H , Ushio-Fukai Masuko , Fukai Tohru
Published: December 2023

Background:
Copper (Cu) is an essential micronutrient, but excess Cu is toxic. Role of copper in atherosclerosis remains unclear. The major Cu-uptake transporter CTR1 provides Cu to Cu chaperone/transcription factor Atox1 to promote inflammation as well as mitochondrial cytochrome C oxidase (COX) to regulate mitochondrial (mito)function. We reported that growth factor VEGF induced CTR1 Cys189 oxidation promotes VEGFR2/CTR1 internalization and angiogenesis in endothelial cells (ECs) while excess Cu induces CTR1 internalization to prevent Cu toxicity. However, role of CTR1-Cys189 in ROS-dependent mito dysfunction and senescence in ECs involved in atherosclerosis remains unknown.

Results:
Here we showed that inducible EC-specific Ctr1
-/-
/ApoE
-/-
mice with high fat diet (HFD) reduced atherosclerosis (72%) and Mac3+ inflammatory cell (62%) vs. atherosclerotic ApoE
-/-
/HFD mice aorta which showed Ctr1-CysOH formation vs. control ApoE
-/-
mice. CRISPR-generated “redox-dead” Ctr1-Cys189A knock-in ApoE
-/-
/HFD mice aorta inhibited Ctr1-CysOH formation but enhanced atherosclerotic lesions and Cu accumulation (ICP-MS) vs. ApoE
-/-
/HFD mice. This in turn enhanced senescence (β-gal and markers), DNA oxidation, macrophage recruitment and mitochondrial hyperfusion (by TEM). In cultured human EC, proatherogenic cytokine TNFα stimulation rapidly induced CTR1-CysOH formation and CTR1 internalization, which were inhibited by CTR1-C189A or Nox4 shRNA. CTR1-C189A overexpression increased intracellular Cu and its downstream p-Drp1-S637 that promotes mitochondrial hyperfusion, mito dysfunction and mitoROS. This was associated with CTR1-C189A binding to mito Cu transporter SLC25A3, which might facilitate mito Cu overload and mito dysfunction. These CTR1-C189A-induced responses were inhibited by Cu chelator TTM and mito O
2
-
scavenger Mito-TEMPO.

Conclusions:
CTR1-Cys189 oxidation-induced internalization limits excess Cu entry to protect against pro-atherogenic phenotype of CTR1/Cu. Preventing CTR1-Cys189 oxidation increases mito dysfunction via enhancing novel Cu-pS637-Drp1 axis as well as CTR1-SLC25A3 axis, which promotes mitoROS and EC senescence, thereby accelerating atherosclerosis.
Abstract 15798: Clonal Hematopoiesis of Indeterminate Potential is Associated With Pro-Inflammatory Markers in Patients With Established Coronary Artery Disease
Authors: SINNADURAI SIAMALA , Vazquez Enrique , Diez-Diez Miriam , Quintas Ana , Barrera Martinez Jorge de la , Kondraciuk Marcin , Sawicka-Smiarowska Emilia , Chlabicz Malgorzata , Sharma Hari S. , van der Spek Peter , Sanchez-Cabo Fatima , Fuster Jose J , Dopazo Ana , Kaminski Karol
Published: December 2023

Introduction:
Progression of atherosclerosis is a result of systemic inflammation. Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to be associated with atherosclerosis, but pathways that lead to this are still not fully elucidated.

Hypothesis:
CHIP may contribute to atherosclerosis by facilitating low-grade inflammatory response.

Methods:
130 patients younger than 80 years, who were hospitalized for acute coronary syndrome or for myocardial revascularization were included in this study and followed for 18 months post-intervention. Targeted next-generation sequencing (NGS) was performed on peripheral blood mononuclear cells to detect CHIP mutations with a variant allelic fraction > 2% in 92 genes. Subsequently, multiplexed proteomic analysis with extension proximity assays (EPA) was used to quantify circulating pro-inflammatory biomarkers potentially related to CHIP.

Results:
Some 17.6 % (23) of 130 patients were detected with CHIP mutations. Patients with mutations in either DNA methyltransferase 3alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) showed significantly higher body mass index (BMI) (
p
=0.010), inflammatory markers (high sensitivity C-reactive protein
p
=0.015, interleukin- 6
p
=0.002, chemerin
p
=0.034) as well as higher markers of myocardial overload (troponin T
p
=0.022 and NT-proBNP). In multivariable model adjusted for BMI, age, and gender we found that the inflammatory markers HGF, IL10RB, IL5RA, IL18, OSM, PD-L1, TNFRSF9, and TNFSF14 presented statistically significant association with CHIP (p<0.01). Interestingly, these differently expressed proteins form an overlapping network between TET2 and DNMT3A mutations pointing to cytokine receptor activity, inflammatory response, and leucocyte activation pathways.

Conclusions:
There is a significant association between CHIP and enhanced inflammatory response in patients with coronary artery disease, even after adjustment for age and BMI.
Abstract 15806: An Age Index Derived From Heart Rate Metrics is Associated With Cardiovascular Risk Biomarkers
Authors: Valeriani Davide , Emir-Farinas Hulya , Faranesh Tony
Published: December 2023

Introduction:
Conventional cardiovascular (CV) risk scores depend on clinical and laboratory measurements, and therefore have limited accessibility in the general population. Consumer wearables provide heart rate measures which individually correlate with CV risk, but it is not known how well they align collectively with conventional clinical biomarkers.
Objective:
To demonstrate the alignment of a composite index based on heart rate metrics available from consumer wearables with clinical biomarkers and risk scores.

Methods:
As chronological age is a strong predictor of cardiovascular health, we trained a linear regression model on the UK Biobank (UKB) dataset to predict chronological age from sex, body mass index, resting heart rate (RHR), and mean HR, maximum HR, HR recovery and estimated VO2max during a cycle ergometry test. Data from 53,670 individuals aged 40-70 years were used: 30,247 for training and 23,423 for testing. A cardiovascular age (CVAge) index was obtained as the difference between chronological and predicted age of the individual: a positive/negative CVAge index indicates the CV health is better/worse than the age would suggest. Heart rate predictors and CVAge index were z-scored using age and sex data on the training set.

Results:
Individuals in the bottom quintile (“Poor CVAge index”) of the test set had higher systolic blood pressure (+5.0 mmHg), diastolic blood pressure (+3.0 mmHg), Framingham 10-year risk score (+1.8%) and ASCVD risk score (+0.8%), than those in the top quintile (“Very Good CVAge index”) - Figure 1.

Conclusions:
Continuous monitoring of heart rate metrics may help users track their heart health even in the absence of clinical and laboratory measurements.
Abstract 15825: County-Level Factors Explaining the Reversal of the Hispanic Mortality Paradox
Authors: Zuma Bongeka Z , Azizi Zahra , Sarraju Ashish , Ngo Summer , Scheinker David , Rodriguez Fatima
Published: December 2023

Introduction:
The Hispanic population in the United States (US) has lower-than-expected mortality rates when compared with the non-Hispanic White population; this is known as the “Hispanic Paradox.” After the coronavirus 2019 pandemic, many US counties had an unprecedented reversal in this Hispanic mortality advantage.

Methods:
With age-adjusted mortality rates (AAMRs) and county health rankings, we used univariable and multivariable linear regressions to measure the association between the decrease in Hispanic mortality advantage (between 2019 and 2020) and county-level factors, including demographic, socioeconomic, cardiovascular disease (CVD) risk, healthcare, and structural factors.

Results:
Five hundred sixteen counties had reliable all-cause mortality rates and 201 had reliable CVD-specific mortality rates for the Hispanic population. 76% of studied counties had a decrease in the Hispanic mortality advantage for all-cause deaths; the mean differences in AAMRs between non-Hispanic White and Hispanic populations were 236.7 (95% CI 219.4; 253.9) in 2019 and 89.0 (95% CI 68.3; 109.7) in 2020. 58% of studied counties had a decrease in the Hispanic mortality advantage for CVD-specific deaths; the mean differences in CVD-specific AAMRs between non-Hispanic White and Hispanic populations were 63.7 (95% CI 56.1; 71.3) in 2019 and 40.5 (95% CI 32.4; 48.6) in 2020. In adjusted analyses, all factors explained 34% of the all-cause and 33% of the CVD-specific variation in Hispanic mortality advantage. Demographic factors explained the greatest variation for both; followed by structural factors (16%) for all-cause, and CVD risk factors (7.4%) for the CVD-specific Hispanic mortality advantage (
Table
).

Conclusions:
Demographic factors played an important role in explaining the recent decline in the Hispanic mortality advantage for all-cause and CVD-specific deaths. Further research is needed to analyze which factors may contribute to reduced disparities.
Abstract 15836: Paraganglioma Presenting as Myocardial Infarction With Decompensated Heart Failure
Authors: Dusi Sashank M , Miller Alec , Kim Julie , Frye Jesse , Chen On
Published: December 2023

Description of Case: Paragangliomas are extra-adrenal catecholamine secreting tumors, classically presenting with paroxysmal hypertension, headache, and diaphoresis. However, presentations vary significantly, and can mimic cardiac pathologies including myocardial infarction and aortic dissection.

A 52-year-old male with history of hypertension and 1 year of palpitations presented for substernal chest pressure with associated dyspnea, nausea and diaphoresis. He reported two days of cough and nasal congestion, and recent addition of metoprolol for palpitations. His family history was notable for early ACS. On examination, he was tachycardic (140 bpm), hypertensive (220/140 mmHg), and hypoxic requiring non-rebreather mask. EKG revealed sinus tachycardia with 1mm J point elevations in V2 and V3. Chest X-Ray and bedside ultrasound indicated pulmonary edema and reduced systolic function. Nitroglycerin infusion was initiated and he was admitted to the Cardiac ICU. Laboratory testing showed a Troponin-T of 0.15 ng/L (normal <0.01 ng/L), ntPro-BNP 2764 pg/mL, lactic acid 3.2 mmol/L, and respiratory swab positive for Influenza A. A CT Aorta ruled out acute dissection but identified several large retroperitoneal masses. Urgent cardiac catheterization demonstrated non-obstructive CAD. Echocardiography noted severely reduced ejection fraction of 30-35%. With diuresis and alpha blockade, he clinically improved and was discharged. Plasma and urine studies revealed elevated metanephrines. He underwent open paraaortic mass resection and pathology later confirmed paraganglioma.

Discussion: With angina, elevated troponins, and acute decompensated heart failure, this presentation was initially concerning for ACS. However, the absence of obstructive CAD warranted further investigation. While concomitant Influenza A infection raised concern for viral myocarditis, abdominal imaging proved crucial in diagnosing paraganglioma.
Abstract 15838: To Tear Again: Recurrent and Complicated Spontaneous Coronary Artery Dissection
Authors: Sandhu Hasnoor , Desai Rahil , Sandhu Dalpinder
Published: December 2023

Background:
SCAD is as an infrequent cause of ACS with a predominance affecting a mean age of 42.6 years and 82% of patients being female. SCAD can be classified as primary or secondary, where primary dissections occur spontaneously, and secondary causes involve the aortic root and are a direct consequence of coronary interventions, surgery, or trauma.

Case:
26-year-old female with no previous cardiac or significant family history presented with severe mid-sternal chest pain, radiating to both arms and back, and associated with nausea and cold sweats. Cardiovascular exam was unremarkable. Troponins were elevated at 0.18 and 0.59. Echo showed anteroseptal wall hypokinesis, consistent with Takotsubo cardiomyopathy. ECG showed anterolateral ST elevations. The patient went for cardiac catheterization and had spontaneous dissection of the left main into the LAD/diagonal with 100% occlusion of the LAD and 99% occlusion of the ramus/circumflex. Impella device was implanted due to persistent shock, V. fib., and cardiac arrest. Stents were placed in the proximal, mid, and distal LAD, ramus/circumflex, and LCA. The patient had an LVEF of 25%. Follow-up echo showed an LVEF of 30%, with subsequent Impella removal. Following week, LVEF increased to 45-50%. The patient began aspirin 81 mg, atorvastatin 10 mg, bisoprolol 5 mg, prasugrel 10 mg, and rivaroxaban 10 mg. Over the next few years, she had recurrent chest pain, syncope, palpitations, and a non-viable pregnancy at 12 weeks of gestation due to premature bleeding complications. 3 years after the initial SCAD, the patient presented with spiral dissection of the RCA, requiring three stents. LVEF was 30%. She is being managed with aspirin 81 mg, atorvastatin 20 mg, bisoprolol 10 mg, and prasugrel 10 mg.

Discussion:
The initial age of presentation of this patient makes this case unique. Risk of recurrent SCAD was present in 17% of patients at a median age of 2.8 years after the initial episode. Triggers for recurrent SCAD include extreme emotional/physical stress and pregnancy. Pregnancy it is not recommended in this patient population. Beta-blockade and adequate BP control are mainstay in medical management and reduce the reoccurrence of SCAD.
Abstract 15869: Antiarrhythmic Effects of Mesenchymal Stromal Cells in a Post-Infarct Swine Model of Ventricular Tachycardia
Authors: Mitrani Raul D , Velasquez Alex , Sundin Andrew , Ionescu Simona I , BAGNO LUIZA , Goldberger Jeffrey J , Balkan Wayne , Hare Joshua M
Published: December 2023

Introduction:
Mesenchymal Stromal Cells (MSC) reduce scar burden in models of ischemic cardiomyopathy. It is unknown whether MSCs exert antiarrhythmic effects.

Hypothesis:
MSCs reduce inducibility of monomorphic VT (mmVT) or prolong VT cycle length by ≥20 msec in a post-infarct swine model of VT.

Methods:
Two groups of 8 Yorkshire Swine underwent a 180-minute occlusion of the LAD. Group 1 (n=8) pigs underwent initial MRI scan, electrophysiology study (EPS), and 3D electroanatomic mapping (EAM) with injection of open-label MSCs (200M cells) around the borderzone of the infarct, using a NOGA Myostar catheter (J&J) guided by EAM. Group 1 pigs had repeat EAM, and final EPS 8 weeks later. Group 2 pigs (n=8) were randomized between placebo and MSC and underwent sequential MSC injections (100M cells/procedure), 7 weeks apart, followed by final EPS and MRI 7 weeks later. Scar% = total scar/myocardial mass (grams).

Results:
MmVT was induced in 5 of 8 (62.5%) at initial EPS (i-EPS) in Group 1 pigs and 3 of 8 (37.5%) at final EPS (f-EPS). In Group 2 all 4 MSC-treated swine had inducible mmVT during i-EPS but only 2 had mmVT at f-EPS. Overall, 9 of 12 MSC-treated pigs had mmVT initially and 5 of 12 pigs had mmVT at f-EPS (p=0.12). For MSC-treated pigs with persistently inducible mmVT (Groups 1 & 2), the baseline VT CL increased in all pigs by ≥20msec and increased from 216 ± 17 msec initially to 274 ± 35 msec at f-EPS (p = 0.001). In Group 1, Scar% was unchanged (22.2±1.6% to 20.5±2.1%) after single MSC treatment (p=0.17). In Group 2 MSC-treated pigs, Scar% decreased from 25.8±2.0% to 17.9±0.6% after 2 MSC treatments (p=0.014). In pigs with mmVT at i-EPS, the scar% was 24.4±1.2%, compared with 19.3±2.0% in pigs without i-EPS inducible mmVT (p=0.025). In pigs with mmVT at f-EPS, scar% was 22.5±1.8% compared with 18.1±1.6% in pigs without mmVT at f-EPS (p=0.048). Placebo-treated pigs showed no change in scar% (22.5±2.6% to 22.4±2.9%, p=0.44) and no change in VT inducibility (3 of 4 pigs at i-EPS and f-EPS).

Conclusions:
This study demonstrates that MSC injection reduced myocardial scar and either suppressed induction of VT or prolonged VT cycle length, consistent with an antiarrhythmic effect. Lower scar burden was associated with non-inducibility of VT, either at baseline or final EPS.
Abstract 15904: Hypertension Risk in Adolescent Females With Polycystic Ovary Syndrome
Authors: Zhang Sherry , Darbinian Jeanne A , Greenspan Louise C , naderi sahar , Lo Joan C
Published: December 2023

Background:
Polycystic ovary syndrome (PCOS) is associated with increased risk of hypertension (HTN) in adult women, but fewer studies have examined PCOS and HTN among adolescents. Characterizing blood pressure (BP) by PCOS status prior to adulthood may inform early cardiovascular risk surveillance efforts.
Aim:
To examine the prevalence of hypertension-range BP (HTN-BP) in adolescent females with and without PCOS and to characterize the association of PCOS and HTN-BP.

Methods:
We used data from an existing cohort of 171,855 females aged 13-17y in a US healthcare system with well-child visit (2012-2018) and measured systolic/diastolic BP. The 2017 American Academy of Pediatrics Practice Guideline was used to classify normal BP [<120/<80], elevated BP [120/<80-129/<80], stage 1 HTN [130/80-139/89] and stage 2 HTN [≥140/90 mmHg]. PCOS was based on clinical diagnosis (ICD-9 265.4, ICD-10 E28.2) within 1 year of the visit. Body mass index (BMI) was classified as healthy, overweight, moderate and severe obesity using BMI percentile data; 3062 underweight females were excluded from analyses. Differences by PCOS (N=1142) and no PCOS (N=167,651) status were compared. Multivariable logistic regression examined the association of PCOS and HTN-BP, with adjusted odds ratios (aOR) and 95% confidence intervals (CI).

Results:
The cohort included 168,793 females (33.6% non-Hispanic White, 9.7% Black, 30.5% Hispanic, 19.9% Asian/Pacific Islander, and 6.3% other/unknown race ethnicity), of whom 65.9% had healthy weight, 18.7% overweight, and 15.4% obesity. Based on visit BP data, 75.6% were normotensive, 17.5% had elevated BP, and 7.0% had HTN-BP (6.1% Stage 1, 0.9% Stage 2). HTN-BP prevalence was much higher for PCOS vs no PCOS (18.6% vs 6.9%, p<0.001). After accounting for age, race/ethnicity, and BMI level, PCOS was associated with 1.3-fold greater odds of HTN-BP (aOR 1.3, CI 1.1-1.5). Similar findings were seen among females with obesity (aOR 1.3, CI 1.1-1.6).

Conclusions:
Prevalence of HTN-BP was 30% higher for those with PCOS after adjusting for BMI, race/ethnicity, and age. Similar findings were evident among those with obesity. Future studies should examine persistent HTN and the independent association of PCOS and HTN severity in this high-risk population.
Abstract 15906: Cardiovascular Effects of CAR-T Cell Therapy: A Prospective Study
Authors: Lefebvre Benedicte , Kang Yu , Vakilpour Azin , Onoue Takeshi , Frey Noelle , Brahmbhatt Priya , Huang Brian , Oladuja Kemi , Koropeckyj-Cox Daniel , Wiredu Courteney , Smith Amanda M , Chittams Jesse , CARVER Joseph , Scherrer-Crosbie Marielle
Published: December 2023

Background:
Previous retrospective studies have shown that CAR-T cell therapy may be associated with major adverse cardiovascular events (MACE) especially in context of cytokine release syndrome (CRS) events.
Objectives.
The aim of this prospective observational study was to define the occurrence of MACE in adults undergoing treatment with CAR-T cell therapy and identify associated risk factors.

Methods:
Vital signs, blood samples and an echocardiogram were collected prior to, two days, one week, one month, and six months after CAR-T cell infusion, and chart consulted at 12 months. In the event of CRS, an echocardiogram was repeated within 72 hours. MACE were defined as cardiovascular death, symptomatic heart failure, acute coronary syndrome, ischemic stroke, and de novo cardiac arrhythmia.

Results:
A total of 44 patients were enrolled (58 ±11 years-old, 77 % male). The median follow-up was 487 days (258-622 days). There were 24 episodes of CRS in 23 patients (52%) (13 with grade 1, 10 with grade 2, and one with grade 3) with a median time to CRS of 4 days. Two patients had MACE (HFpEF and atrial fibrillation) within one year, six and seven days after CAR-T cell infusion respectively. There was no change in left ventricular ejection fraction (LVEF), however, a modest decrease in global longitudinal strain (GLS) was noted.

Conclusions:
There were few cardiac effects associated with contemporary CAR-T cell therapy. A small decline in LV mechanics was detected. As MACE occurred after CRS episodes, aggressive treatment and close follow-up during CRS events are essential.
Abstract 15914: Cardiac Troponin I versus T for Revascularization and Survival in Non-ST Elevation Acute Coronary Syndrome in Patients With Chronic Kidney Disease
Authors: Wu Bovey , Abramov Dmitry , Rangaswami Janani , Sidhu Mandeep S , Bangalore Sripal , Mathew Roy O
Published: December 2023

Introduction/Background
Cardiac troponins (cTn) underlie the diagnosis of non-ST elevation (NSTE)- acute coronary syndrome (ACS). Utility of specific cTn types is less delineated for patients with chronic kidney disease (CKD).
Goals/Aims
Determine the predictive value of two cardiac enzymes-cTnI and cTnT- for revascularization procedures (percutaneous coronary intervention [PCI]/coronary artery bypass grafting [CABG]) and mortality.

Methods/Approach
Patients with CKD (estimated glomerular filtration rate < 60mL/min/1.73m2) admitted with a diagnosis of NSTE-ACS within the Veterans Affair Healthcare System between 1999 and 2022 (n=56711). Proportional change of serial cTnI and cTnT was calculated. Outcomes included PCI and CABG, and inpatient and 12 months after hospitalization mortality. Classifier ability is quantified by comparison of area under receiver operating characteristic (AUROC) for proportional change in cTnI or cTnT; hypothesis testing is completed with empirical AUC, Mann-Whitney U testing.

Results/Data
Proportional change in serial cTnT was not found to be statistically different compared to cTnI in predicting revascularization (AUROC 0.524 vs 0.512; p = 0.423). Proportional cTnT change had statistically higher predictive ability compared to cTnI for inpatient mortality (AUROC 0.584 vs 0.500; p = 0.007) and 12-month mortality (AUROC 0.550 vs 0.515; p = 0.038) (Figure).

Conclusion
In CKD patients with NSTE-ACS, cTnT demonstrated higher predictive ability in the prognostication of short- and long-term outcomes. Prospective studies are needed to further characterize optimal cTn assay type in patients with kidney disease presenting with symptoms concerning for ACS.
Abstract 15954: The Impact of Lipid Rich Plaque on Microvascular Dysfunction Evaluated by Angiography-Derived Index of Microcirculatory Resistance After Percutaneous Coronary Intervention
Authors: Yamada Nobuhiro , Ueno Masafumi , kazuyoshi kakehi , Onishi Kyohei , Nakazawa Gaku
Published: December 2023

Introduction:
Microvascular damage due to distal embolization during percutaneous coronary intervention (PCI) is an important cause of periprocedural myocardial infarction (PMI). Microcirculatory resistance index using pressure wires (invasive IMR) has been used to assess microvascular dysfunction, but recently angiography-derived microcirculatory resistance index (IMRangio) as a noninvasive method has received increasing attention. There have been few reports examining the relationship between noninvasive IMR and LRP assessed by near-infrared spectroscopy (NIRS). The purpose of this study was to investigate the impact of LRP assessed by NIRS on noninvasive IMRangio before and after PCI.

Hypothesis:
The purpose of this study was to investigate the impact of LRP assessed by NIRS on noninvasive IMRangio before and after PCI.

Methods:
We retrospectively evaluated consecutive patients admitted for coronary artery disease without ST elevated myocardial infarction (STEMI) who underwent coronary angiography at our hospital from November 2021 to January 2023. We analyzed 50 patients who performed NIRS before and after PCI and IMRangio available. The maximum value of LCBI for any of the 4-mm segments at the culprit lesion (maxLCBI4mm) was calculated at the culprit lesion. We divided the patients into 2 groups using a cutoff of culprit maxLCBI4mm ≥600. On the other hand, the value of IMRangio in culprit vessels was evaluated before and after PCI. The IMRangio values were compared between those two groups.

Results:
Mean pre-maxLCBI4mm was 529±260 and mean pre and post-PCI IMRangio were 17.5±9.00 and 22.1±10.2, respectively. Mean ΔIMRangio (=IMRangio after PCI–IMRangio before PCI) was 4.63±9.34. ΔIMRangio values were significantly higher in patients with high maxLCBI4mm than in those with low maxLCBI4mm (7.46±1.74 vs 2.23±1.74, P=0.047).The incidence of microvascular dysfunction (IMR ≥25 U) was higher in the high maxLCBI4mm group (52.2% vs. 22.2%, p=0.027). Furthermore, patients with elevatedΔIMRangio were significantly more likely to have a maxLCBI4mm ≥ 600 (59.3% vs. 87.0%, P=0.025).

Conclusions:
IMRangio is a valid alternative to invasive IMR to detect microvascular dysfunction in patients with lipid rich plaque assessed by NIRS.
Abstract 15964: Ferroptosis Integrates Mitochondrial Dysfunction and Pathological Inflammation to Promote Pulmonary Hypertension
Authors: Vogel Neal T , Annis Jeffrey , Prisco Sasha Z , Barnes Jackson , Kazmirczak Felipe , Brittain Evan , Prins Kurt W
Published: December 2023

Introduction:
Ferroptosis is an iron-dependent, mitochondrial-mediated, non-apoptotic, highly inflammatory form of cell death. Ferroptosis plays important roles in numerous disease states via activation of complement and NLRP3 inflammasome, but its role in pulmonary hypertension (PH) is less well defined.

Methods:
Male Sprague Dawley rats were randomized into 3 groups: control, monocrotaline-vehicle (MCT-V), and MCT rats treated with ferrostatin-1 (MCT-FI). Pulmonary vascular disease severity and right ventricular function were assessed with histology, echocardiography, and pressure-volume loop analysis. Mitochondrial enrichments from lung tissue were subjected to quantitative proteomics. RNAseq evaluated global lung expression changes. KEGG analysis was performed on proteomics and RNAseq datasets to delineate which pathways were most associated with PH severity and modulated by ferrostatin-1 treatment. The hemodynamic effects of single-nucleotide polymorphisms in
GPX4
were evaluated in the BioVU dataset.

Results:
Ferroptosis inhibition reduced right ventricular systolic pressure and improved RV function in MCT rats. Proteomics analysis identified a link between ferroptosis and multiple metabolic pathways that were associated with PH severity. RNAseq demonstrated ferroptosis inhibition partially suppressed complement and inflammatory signaling. Finally, patients with SNP
rs1444732 in GPX4
had a higher pulmonary vascular resistance and mean pulmonary arterial pressure.

Conclusions:
Ferroptosis may integrate disrupted metabolism and inflammation to promote pulmonary vascular disease.
Abstract 15969: Temporal Trends and Cardiovascular Outcomes in Hospitalized Patients With Fabry Disease: Insights From the National Inpatient Sample
Authors: Kong Darren , Choi James , Diaz Saravia Sara , Adegbite Bejamin , Moras Errol C , Mahmood Kiran
Published: December 2023

Introduction:
Fabry disease, a lysosomal storage disease consisting of an alpha-galactosidase-A deficiency, is associated with multi-organ disease including the liver, kidneys, and heart. New enzyme replacement and gene therapies have emerged in recent years to treat Fabry disease.

Hypothesis:
We aim to study temporal trends and cardiovascular outcomes in hospitalized patients with Fabry disease.

Methods:
Using the National Inpatient Sample (NIS) database we collected major adverse cardiovascular events (MACE) including arrhythmias, acute myocardial injury, stroke, cardiac arrest, and heart failure that occurred each year from 2017-2019. Appropriate ICD-10 codes were used for data collection. Proportions were calculated and adjusted odds ratios OR were determined using the Charlson Comorbidity Index.

Results:
Overall, there was an increase in total hospitalizations in patients with Fabry disease from 2017 to 2019. Fabry disease was associated with increased risk of MACE (OR=2.88, CI 1.99-3.68, P<0.000) when compared with patients without Fabry disease. There was a significantly higher proportion of MACE in Fabry disease when compared to the general population from 2017-2019 (P-trend <0.000). Secondary outcomes showed a increased risk of arrhythmias (OR=4.89, CI 3.22-7.08, P<0.000) and heart failure (OR=4.34, CI 2.90-6.50, P<0.000), but no significantly increased risk of acute myocardial injury (OR=3.11, CI 0.96-4.62, P=0.07) or stroke (OR=1.79, CI 0.76-2.41, P=0.11).

Conclusions:
Fabry disease is associated with worse inpatient cardiovascular outcomes when compared to patients without Fabry disease. Tissue injury from infiltrative deposits may cause subsequent myocardial fibrosis and conduction diseases, leading to heart failure and conduction diseases, respectively.
Abstract 15979:
En Bloc
Heart-Lung Transplantation and Vascular Reconstruction With Native Tissue in a Patient With Situs Inversus Totalis
Authors: Elde Stefan , Wang Hanjay , Paulsen Michael J , Woo Y Joe J , Macarthur John
Published: December 2023

Case:
A 62-year-old male with primary ciliary dyskinesia, bronchiectasis, dextrocardia, ccTGA, VSD, ASD, and severe ventricular dysfunction was listed for HLTx. Suitable organs became available from a 21-year-old male donor after brain death. The right sided aorta, persistent left superior vena cava (LSVC), RIJ, and LCFV were cannulated for CPB. The bloc was procured in the typical fashion along with the donor’s pericardium and intact innominate vein. During the recipient cardiectomy, the LSVC was transected proximally, and right atrial (RA) tissue preserved in continuity with the left inferior vena cava (LIVC). To achieve situs solitus positioning of the mediastinum, a pericardial sling was created by plicating the right pericardium to the diaphragmatic pericardium, and the left pericardium was augmented with excess donor pericardial tissue to create a neo-pericardium in the left chest. The recipient’s RA tissue was used to extend the LIVC by forming a cavoatrial conduit and anastomosed to the donor RA, which required a slightly counterclockwise rotation of the cardiac axis and facilitated positioning the left phrenic nerve posterior to the apex. The tracheal and aortic anastomoses were performed in the typical fashion. The donor innominate vein was of sufficient caliber and length to complete the anastomosis to the recipient LSVC and the donor RIJ was ligated.

Discussion:
HLTx remains the only definitive therapy for patients with combined end-stage cardiopulmonary disease. The leading indication for HLTx is congenital heart disease. Accordingly, centers performing HLTx must be experienced in complex vascular reconstructions and concomitant procedures to address a broad spectrum of anatomical variants. With thoughtful pre-operative planning, close communication with the procurement team, and surgical experience, these procedures may be performed without the use of synthetic materials that predispose to infectious and thromboembolic complications.
Abstract 15989: Gore Cardioform Device Complicated by Delayed Right Atrial Disk Expansion
Authors: Iskandar Jean Pierre , Kaviratne Summanther , Rao Nikhila , Rao Nilesh , Rao Krishna , Ling Frederick
Published: December 2023

This is a 31-year-old male with a recently discovered secundum atrial septal defect (ASD) with significant left-to-right shunt and associated right ventricular enlargement and dysfunction underwent an uncomplicated percutaneous ASD closure device placement earlier in 2023. Five weeks later, upon repeat transthoracic echocardiogram (TTE), the patient was found to have new onset atrial flutter and what was thought to be a large device-related thrombus abutting the right atrial disc. The patient was admitted to the hospital, started on systemic anticoagulation, and AV nodal blocker therapy. X-rays and a transesophageal echocardiogram (TEE) were performed and showed a Gore Cardioform ASD occluder device that was complicated with significant expansion of the right atrial disk and loosening of fabric likely in the setting of displacement of locking pin (Figure 1A-B). No clear thrombus was visualized. The patient underwent an uncomplicated ASD closure device removal, ASD repair with pericardial patch, right sided Maze, and left atrial appendage ligation in May of 2023 (Figure 1C). We report a case of extreme expansion of the right atrial disk of the Gore Cardioform septal occlusion device. Very few cases of right or left atrial disk expansion have been reported but only in the immediate post-implantation period. This is thought to be secondary to immediate post-operative increase in left atrial pressures. In our patient, intra-procedural TEE and immediate post-procedural TTE the day after showed a well-apposed device across the ASD with no residual shunt. Furthermore, the wedge pressure measured during the procedure was within normal limits. Extreme expansion of the right atrial disk five weeks after the implantation has not been reported. While we know that the pin unlocking caused the expansion of the atrial disk, it is currently unclear as to what initiated this series of events.
Abstract 16057: Utilization of Advanced Cardiac Imaging Prior to Structural Ventricular Tachycardia Ablation
Authors: Swain William H , Siontis Konstantinos
Published: December 2023

Introduction:
Advanced imaging with cardiac magnetic resonance (CMR) or computed tomography (CCT) can be helpful for planning of ventricular tachycardia (VT) ablation procedures by defining the arrhythmogenic substrate. The frequency with which these modalities are utilized in the pre-ablation setting and the associated outcomes remain poorly studied.

Objectives:
(1) Determine the utilization of advanced cardiac imaging prior to structural VT ablation; (2) establish factors associated with improved VT ablation outcomes

Methods:
We retrospectively evaluated all VT ablations performed in patients with structural heart disease at a tertiary referral institution during a 2.5 year period (1/2020 - 7/2022). We documented pre-ablation use of cardiac imaging modalities and investigated their association with acute and long-term ablation outcomes. The primary outcome was time to VT recurrence, cardiac transplant, or death.

Results:
Our dataset included n = 129 subjects. Median post-ablation follow-up was 17 months. Recent echocardiogram, CMR, or CCT (<3 months pre-ablation) had been performed in 113 (88%), 48 (37%), and 31 (24%) patients, respectively. CMR was not associated with procedural success, post-ablation VT recurrence (p = 1), or the composite primary outcome (p = 0.72). Similarly, recent CCT was not associated with procedural success (p = 0.5), VT recurrence (p = 0.3), or the composite primary outcome (p = 0.31). When adjusted for other variables, EF (p = 0.048), recent echo (p = 0.02), and procedural success (p = 0.013) were associated with the primary outcome, but recent CCT (p = 0.11) and CMR (p = 0.4) were not. These results did not differ significantly in patients with ischemic and non-ischemic cardiomyopathy.

Conclusions:
In this large tertiary care ablation center, CMR and CCT were utilized in only a fraction of patients prior to VT ablations. In multivariate analysis, CMR or CCT were not associated with improved acute or long-term ablation outcomes.
Abstract 16118: Vitamin D3 Significantly Decreases Vascular Stiffness, Improving Cognitive Impairment and Sarcopenia in a Frail, Elderly Population From Buenos Aires, Argentina
Authors: Duarte Mariano , Davolos Ignacio , Aquieri Analia , Coyle Javier , Allevato Adela , Litta Maria A. , Delucchi Maria Clara , Lecouna Marcela , Giacobone Ciantia , Savio Galimberti Eleonora
Published: December 2023

Introduction:
Aging is the leading risk factor for multiple chronic diseases especially cardio and cerebrovascular and for a decline in physical and mental function. Progressive stiffening arterial wall, cognitive impairment and sarcopenia are hallmarks of aging. Due to the pleiotropic actions that have been discovered in vitamin D (VD), which include vascular ,muscular and cognitive effects, we hypothesized that VD3 supplementation might decrease vascular stiffness and could have beneficial effect on mental status and sarcopenia in a frailty elderly population.

Methods:
We randomized 42 residents (78±6.5 yo; 24 females) from a public geriatric institution, to receive either 100,000 IU of VD3 or placebo (P) every 15 days for 6 months. Arterial stiffness (AS) was evaluated through central systolic pressure (cSYS), central pulse pressure (cPP), and the augmentation index (AIx) a measure of systemic AS derived from the ascending aortic pressure waveform; using Uscom® device. Cognitive function was evaluated using the Clock-Drawing Test (CDT), which is simple and effective for this population. Skeletal muscle strength/sarcopenia, were assess with the up and go test (UGT), muscle strength with hydraulic dynamometer, body mass index (BMI) and mini-nutritional assessment (MNA) test.

Results:
VD group showed a statistically significant decrease in AS vs P. VD Δ cSYS -12.3 mmHg, Δ cPP -6.7 mmHg mmHg and Δ AIx -17.8 %, for all three parameters: p<0.05. The CDT score improved in VD group (4.3 to 5.9, p <0.05) but there were no statistically significant differences in P group. Muscle strength in VD group improved significantly (from 15.1±9.4 to 18.7±3.8 Kg force/cm
2
, p<0.05) vs no difference in P group. UGT improved with statistical significance in both VD and P group. The BMI and the MNA test were also favorable for VD group although they did not reach statistical significance.

Conclusions:
Vitamin D3 6-months supplementation improved vascular compliance by decreasing arterial stiffness, improved cognitive performance and sarcopenia indicators in this frail elderly people. Although this was a preliminary study, a larger number of patients studies should be conducted to validated these findings and to consider VD3 supplementation in this population.
Abstract 16120: Efficacy of an Electronic Medical Record Alert System in Identifying Cardiac Implantable Electronic Device Infection
Authors: Horton Edward R , Saporito Richard L , Fleece David , Enevoldsen John T , Cooper Joshua M , Cronin Edmond M , Whitman Isaac R , Gangireddy Chethan
Published: December 2023

Introduction:
Cardiac Implantable Electronic Device infection (CIED-I) is common, morbid, and frequently under recognized. Electronic Medical Record (EMR) based alerts have been proposed as a solution to improve detection of CIED-I.

Hypothesis:
Development of a real-time EMR algorithm to identify CIED-I can improve recognition of patients with CIED-I.

Methods:
An EMR (Epic, Verona, WI) alert system to identify inpatients with CIED-I was developed based on the presence of CIED and positive blood cultures. The presence of CIED was determined using patient problem list, structured data elements describing device implantation, and prior device interrogation. Alerts were generated each time a patient with CIED had a positive blood culture. We examined patients admitted between January 2020 - March 2023. Identified patients were adjudicated manually to confirm: (1) the presence of CIED and (2) true bacteremia versus contaminant based on patient and microbiological characteristics.

Results:
The algorithm generated 255 alerts, corresponding to 100 unique patients over 142 hospitalizations. Of these alerts, 213 appropriately identified 88 unique patients with positive blood cultures and CIEDs, resulting in an alert specificity of 84% and patient specificity of 88%. The remaining 42 (16.6%) alerts occurred in 10 patients who no longer had CIED due to prior CIED extraction (6 at the time of heart transplant and 4 with extraction without reimplantation) as well as 2 patients with erroneous blood culture identification (one positive syphilis antibody test and one lab documentation error). In patients with appropriate alerts, 27 patients had 4/4 positive blood culture bottles, 5 patients had 3/4, 10 patients had 2/4, 41 patients had 1/4, 2 patients had 2/2, and 1 patient had 1/2. The positive predictive value of the algorithm to identify true bacteremia was 0.65 (138/213).

Conclusions:
The algorithm has high specificity to identify patients with possible CIED infection. Improving the accuracy of device detection, by incorporating radiology imaging or history of extraction, could further improve specificity. Positive predictive value and alert fatigue could be improved by stratifying alerts by blood culture species and total number of positive blood cultures.
Abstract 16146: A Scoping Review of Adverse Outcomes Associated With Cardiac Resynchronization Therapy Device Implantation: Implications for Informed Consent
Authors: Mancini John , Naik Aanand , Goyal Parag
Published: December 2023

Background/Objectives:
Cardiac Resynchronization Therapy (CRT) is a treatment option for many adults with heart failure with reduced ejection fraction (HFrEF). While the benefits of CRT are well-established, the downstream implications of adverse events are not well-characterized. We sought to better understand the ramifications of CRT-related adverse events on length of hospital stay (LOS) and mortality—information relevant for patients and clinicians to make informed decisions about pursuing CRT.

Design:
Scoping Review

Methods:
We conducted an initial PubMed search using terms including “Congestive Heart Failure” or “Heart Failure” and "Cardiac resynchronization" or "Cardiac re-synchronization" or "Biventricular pacing.” We reviewed resulting articles that were written in English, studied CRT devices, and outlined adverse events related to CRT device placement. We separately searched PubMed for additional articles outlining individual adverse events identified using search terms “event name,” “mortality,” and “hospital stay.” We read articles and summarized data regarding the impact of reported adverse events on hospital LOS and mortality.

Results:
Our search identified 18 full length articles with relevant data. The most common adverse events included device implant failure/non-response, lead dislodgment, coronary sinus dissection, and pocket hematoma. The LOS and mortality rates of each event are shown in Table 1. Of note, LOS for implantation in the ambulatory setting is up to 1 day; LOS for uncomplicated implantation during hospitalization is 4.6 days. Implantation during hospitalization with complication is mean 13.6 days.

Conclusion:
While absolute risks for adverse events associated with CRT implantation are low, several have important implications on hospital LOS and mortality. These findings warrant inclusion in discussion regarding the risks of CRT when clinicians and patients engage in informed decision making related to CRT.
Abstract 16149: Recruitment Strategies for a Remote Implementation Study in Diabetes Management - Insights Into Optimizing Enrollment
Authors: Hassan Shahzad , Chang Lee-Shing , Colling Caitlin , Stern Gretchen , Chasse Jacqueline , Gabovitch Dan , Zelle David , Aronson Samuel , Figueroa Christian , Collins Emma , Ruggiero Ryan , Zacherle Emily , Noone Josh , Robar Carey , Gaziano Thomas , Plutzky Jorge , Matta Lina , Cannon Christopher P , Wexler Deborah , Scirica Benjamin , Blood Alexander J
Published: December 2023

Background/Objectives:
Remote clinical studies offer new outreach opportunities, but recruitment remains challenging. We report our experience in identifying potential participants from diverse sources and adopting various outreach and recruitment methods.

Methods:
We utilized multiple screening and recruitment methods to identify and enroll patients into an implementation study for guideline-directed care in patients with T2D at high risk of cardio-renal complications within the Mass General Brigham health network. Patients were identified by querying the EHR and invited by emails, individualized, or bulk EHR-portal messages. Traditional outreach included reviewing upcoming clinic visits, accepting provider referrals, and mailing invite letters. All screened-in patients received phone calls following the initial invitation (
Figure
).

Results:
Of 200 enrolled participants, 190/200 (95%) were identified from the EHR, 2/200 (1%) from upcoming clinic visits, and 8/200 (4%) from provider referrals. Of patients identified through the EHR, 49/3317 (1%) of the total enrolled were invited by an individualized EHR message, 61/3317 (2%) by e-mail, 80/588 (14%) by mailed letter, and 0/3666 (0%) by bulk EHR message. From clinic, 2/102 (2%) of upcoming visits and 8/36 (22%) of provider referrals were enrolled. Overall, 90/200 (45%) of enrolled patients came from letters or clinic while 110/200 (55%) came from electronic outreach.

Conclusion:
Conducting remote clinical research is feasible, however, enrollment remains labor-intensive. Traditional methods of patient engagement are difficult to scale, although they led to high enrollment rates. While the EHR was the primary method for identification of our enrolled participants, traditional approaches including manual screening, mailed letters, and provider referrals continue to play a role in patient enrollment. Innovative approaches are necessary to improve the process.
Abstract 16153: Electrocardiographic Correlations With Cardiac Magnetic Resonance in Left Bundle Branch Area Pacing
Authors: Bilchick Kenneth C , Bivona Derek , Mareddy Chinmaya , Wang Yu , Dennis Spencer , Malhotra Rohit , Mason Pamela K , Hundley Greg G , Epstein Frederick H , Ellenbogen Kenneth A
Published: December 2023

Introduction:
As the use of left bundle branch area pacing (LBBAP) continues to increase, there remains uncertainty about the mechanical effects of achieving selective LBB capture.

Hypothesis:
The hypothesis was that cardiac magnetic resonance (CMR) strain and functional parameters would be similar with and without LBBAP, and mechanical function would be more favorable with surface ECG parameters indicative of LBB capture.

Methods:
CMR was performed at 3T in two centers in the first year after implantation of dual-chamber pacemakers with LBBAP. Imaging sets were obtained with dual-chamber LBBAP (DOO mode) and, in patients with intact atrioventricular (A-V) conduction, atrial-only pacing (AOO mode), including strain imaging with displacement encoding with stimulated echoes (DENSE).

Results:
In 17 patients, the median LVEF with LBBAP was 50% (IQR 48-52%). The median LVEF and RVEF were similar with LBBAP on (DOO mode) and off (AOO mode) (p=0.27 and p=0.37, respectively); however, there were differences in synchrony (CURE-SVD) (p=0.0081), mean septal Ecc (p=0.011), and mean LV free wall Ecc (p=0.011) that favored atrial-only pacing with A-V conduction vs. sequential LBBAP (Figure 1). A shorter interval between R wave peaks in ECG leads V6 and V1 (V6-V1 interpeak interval), shown to be associated with selective LBB capture, was the best predictor of a greater LVEF with LBBAP (p=0.0016). A shorter paced QRS duration predicted greater global Ecc (p=0.044) and more synchrony by the CURE-SVD (p=0.027) (Figure 2).

Conclusions:
LBBAP reproduces biventricular function by CMR with some differences noted in CMR strain, and selective LBB capture was associated with a greater LVEF by CMR.