bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15566: The Impact of Aspirin Use on Progression and Mortality of Abdominal Aortic Aneurysm
Authors: Hariri Essa H , Layoun Habib , Matta Milad , Iskandar Jean Pierre , Burton Robert , Cameron Scott J
Published: June 2023

Introduction:
Preclinical studies demonstrated a potential role for aspirin (ASA) to slow the progression of abdominal aortic aneurysms (AAA) to rupture. We aim to investigate the association of long-term ASA use with progression and mortality in AAA.

Methods:
We queried the vascular ultrasound database at Cleveland Clinic for patients who underwent consecutive abdominal vascular ultrasound 2010-2020 if at least two available ultrasounds were conducted, without prior history of aneurysm repair, dissection, or rupture. ASA use was defined as at least one prescription of ASA during the during the follow-up period. The primary outcome was all-cause mortality, assessed by survival analysis with multivariable-adjust Cox regression. The secondary outcome was the mean annualized change of aneurysm diameter, assessed by multivariable-adjusted linear regression.

Results:
A total of 3,803 patients were included, with an average age of 73, and of which 826 (22%) were female and 2,380 (62.5%) were prescribed ASA (median duration of use ~ 9 years). ASA use was not significantly associated with all-cause mortality irrespective of age, sex and smoking status, except among those with a baseline diameter > 3.5 cm (Figure 1). ASA use was negatively associated with the mean annualized AAA diameter change only in males (0.25 vs 0.38 cm/year, p = 0.002) and in nonsmokers (0.26 vs 0.37 cm/year, p = 0.003).

Conclusions:
ASA use reduces the expansion of abdominal aortic aneurysms with altering all-cause mortality except in certain high-risk individuals in men and non-smokers. Mechanistic and randomized studies are needed to ascertain the role of ASA in patients with abdominal aortic aneurysms.
Abstract 15569: Association of Volatile Organic Compound Levels With Pod-Based Electronic Cigarette-Induced Changes in Vascular Function of Young Adults
Authors: Majid Sana A , Fetterman Jessica L , Weisbrod Robert M , Stokes Andrew , Blaha Michael J , Srivastava Sanjay , Robertson Rose M , Bhatnagar Aruni , Keith Rachel J , Hamburg Naomi M
Published: June 2023

Introduction:
Pod-based electronic (e-) cigarettes including JUUL are the most frequently used product type in young adults. Here, we evaluated the acute and chronic impact of pod-based e-cigarettes on vascular health and their relation to volatile organic compound (VOC) exposure.

Methods:
We performed a short-term observational study of healthy young adults (N = 106) and recruited pod-based e-cigarette users (N = 48), combustible cigarette users (N = 21), and tobacco nonusers (N = 37). Vascular function via flow-mediated dilation and blood pressure (BP) was measured before and after 10-min structured product use of the participant's own product. Urinary VOCs were measured 1 hour after product use. In human aortic endothelial cells (HAECs) in culture exposed to select VOCs, nitric oxide production was measured with DAF-2 indicator.

Results:
Among pod-based e-cigarette users, 64% were exclusive users including 37% who had never used combustible cigarettes. Pod-based e-cigarette users and combustible cigarette users had higher systolic BP compared to non-users (121±11 mmHg, 121±13 mmHg, 112±10 mmHg, P=0.0004). Structured pod-based e-cigarette use acutely decreased flow-mediated dilation (-3.2±2.7%), raised systolic and diastolic BP (6±8mmHg, 4±5mmHg) and heart rate (5±7bpm), similar to combustible cigarette use (-2.6±2.6%, 9±8mmHg, 6±5mmHg, 6±6bpm P=0.83, 0.3, 0.4, 0.56 vs pod-based), and to a greater extent than nonuse (0.3±4.1%, 0.7±5mmHg, 0.3±3mmHg, -3±4bpm, P=1.0x10-7, 0.002, 0.003, 2.6x10
-7
). Differences remained in models adjusted for age, sex, and race. The effect of pod-based e-cigarette use was similar in adults who had never used combustible cigarettes. Levels of VOCs acrolein, acrylamide, acrylonitrile, and crotonaldehyde were associated with changes in vascular health measures. Exposure of HAECs in culture to acrolein and acrylamide reduced acetylcholine-stimulated nitric oxide production.

Conclusions:
Our findings demonstrated that pod-based e-cigarette use had acute and chronic vascular effects in healthy young adults including those who never used combustible cigarettes. Select VOC metabolites were associated with the vascular changes and altered nitric oxide production suggesting relevance to vascular health.
Abstract 15587: Combined Spontaneous Coronary Artery Dissection and Takotsubo Cardiomyopathy in a Patient With Chest Pain
Authors: Salam Mohammad Fahad , Al-abcha Abdullah , Radwan Yasser , Martinez Salazar Adolfo , Qutrio Baloch Zulfiqar , Wilcox Matthew
Published: June 2023

Introduction:
Spontaneous coronary artery dissection (SCAD) and Takotsubo cardiomyopathy (TCM) are uncommon non-atherosclerotic causes of acute myocardial infarction (MI). These patients have fewer cardiovascular risk factors than those who have atherosclerotic MI. Clinical presentation in both subsets of MI is identical due to which diagnosis requires echocardiography and coronary angiography. The incidence of TCM and SCAD in the same patient is scarce and only documented in a few case reports and a case series.

Case presentation:
We present the case of a 50-year-old female with a past medical history of hypertension, hypothyroidism, and median arcuate ligament syndrome. She presented to the emergency department with intermittent chest pain radiating to her upper back, both arms, and her left jaw and it was associated with nausea. On examination, she was tachycardic, tachypneic, and anxious. She had normal heart sounds with no chest tenderness. Her EKG demonstrated ST-elevations in leads II, III, aVF, V4, V5, and V6. Laboratory results showed elevated high sensitivity troponin of 11,949 (pg/ml) and 30,256 (pg/ml) four hours later. The patient underwent emergent coronary angiography, which revealed diffuse tubular stenosis suggestive of type 2 SCAD in the second obtuse marginal artery but otherwise normal coronary anatomy with minimal stenosis. Left ventriculogram showed antero-apical, apical, and infero-apical hypokinesis and basal hyperkinesis, suggestive of Takotsubo cardiomyopathy. Transthoracic echocardiogram (TTE) completed 48 hours later demonstrated improved contractility with lateral wall hypokinesis. The patient was managed conservatively with medical management, and she was discharged on aspirin, plavix, carvedilol, isosorbide mononitrate, and losartan.

Conclusions:
SCAD and TCM are uncommon diagnoses that can rarely co-exist. TTE can help diagnose TCM in patients with chest pain and elevated cardiac biomarkers. Non-occlusive coronary vasculature is a diagnostic criterion per the proposed Mayo Clinic criteria. This case highlights the importance of coronary angiography in patients with TCM for assessment of potential co-existent coronary vascular pathology; SCAD in our case.
Abstract 15594: Decreasing the High Risk of Ponatinib-Induced Cardiovascular Toxicity in Chronic Myeloid Leukemia
Authors: Hnatiuk Hnatiuk Anna P , Bruyneel Arne A , Taylor Dhanir , Pandrala Mallesh , Dheeraj Arpit , Li Wenqi , Serrano Ricardo , Feyen Dries , Vu Michelle , Amatya Prashila , Saloni Gupta , Nakauchi Yusuke , Morgado Isabel , Wiebking Volker , Liao Ronglih , Porteus Matthew , Majeti Ravindra , Malhotra Sanjay , Mercola Mark
Published: June 2023

Introduction:
Cardiovascular (CV) toxicity of cancer therapeutics is a growing problem. Ponatinib is one of the most cardiotoxic Tyrosine Kinase Inhibitors (TKIs) and is used as a highly effective TKI against ABL T315I mutation in Chronic Myeloid Leukemia (CML). Long-term exposure to ponatinib increases CV events including myocardial infarction, heart failure, stroke, peripheral vascular disease and venous thrombosis. There is need of novel therapeutics to provide treatment for CML while avoiding CV toxicity.

Hypothesis:
Using
in vitro
and
in vivo
models of CV toxicity can make possible to reengineer ponatinib to minimize its toxicity.

Methods:
We developed new safer analogues of ponatinib using fragment-based approach. Their anti-tumor efficacy was tested in 2 different CML cell lines and CML patient samples. We assayed for myocardial toxicity by measuring contractile function in human iPSC-cardiomyocytes (hiPSC-CMs) using high-throughput functional imaging, for vascular toxicity by measuring vasculogenesis in human microvascular endothelial cells (HMVECs), and for bone marrow toxicity by colony formation assay in human bone marrow cells (HBMCs). Finally, we confirmed the safer CV profile and adequate anti-tumor efficacy in an
in vivo
xenograft mouse model of CML.

Results:
The new analogues inhibited T315I BCR-ABL kinase activity similar to ponatinib and suppressed T315I mutant CML tumor growth
in vitro
and
in vivo
. Compared to ponatinib, the new compounds showed markedly decreased adverse effects on contractility of hiPSC-CMs, vasculogenesis in HMVECs and bone marrow toxicity in HBMCs
in vitro
. The therapeutic window was increased
in vivo
, leading to regression of human T315I mutant CML xenografts comparable to ponatinib but without increased levels of cardiac troponin. Additionally, we identified multiple kinases, including FGFR1, that were inhibited by ponatinib but not the analogues, suggesting that there is a specific set of kinases responsible for ponatinib toxicity.

Conclusions:
This study demonstrates that chemical reengineering can generate novel, CV-safe TKIs that retain effective therapeutic properties against CML carrying ABL T315I mutation, but that exhibit minimal CV toxicity compared to ponatinib.
Abstract 15599: Sex-Based Differences in Coronary Artery Morphology, Disease Distribution, and Lesion Outcomes
Authors: Jain Aditya , Unlu Ozan , Di Achille Paolo , Pomerantsev Eugene V , Garasic Joseph M , Ellinor Patrick T , Philippakis Anthony A , FAHED AKL C
Published: June 2023

Introduction:
Despite the unique pathophysiology, clinical presentation, and disparities in care of women with coronary artery disease, sex-based differences in coronary morphology and their relation to disease remain poorly understood.

Methods:
We constructed a retrospective cohort of adult patients who underwent a coronary angiogram between 2000 and 2021 at Massachusetts General Hospital and compared dominance, branching, and coronary lesion location and severity at baseline between males and females. We mapped lesions over time and studied differences in risk of receiving a future intervention by sex of the patient and location of the lesion in the coronary tree.

Results:
50,988 patients (age 65.7+12.8 years, 33.0% female) had a baseline coronary angiogram and 174,502 lesions were reported. Compared to males, females were less likely to have left or mixed dominance (15.7% vs. 17.4% p<0.001) and trifurcation of the left main (LM) (5.9% vs. 11.1%, p<0.001). Compared to males, females had more lesions reported in the left anterior descending (30.0% vs. 28.3%, p<0.001) and right coronary artery (26.5% vs. 24.4% p<0.001), and less lesions in branches - obtuse marginal, diagonal, posterior descending, and posterolateral (21.8% vs. 25.1%, p<0.001). Obstructive disease - defined as ≥50% stenosis in the LM or ≥70% stenosis in any other vessel - was less common in females (48.8% vs. 69.1% , p<0.001). 8,432 patients (age 65.8+11.0 years, 25.8% female) with 37,842 lesions were evaluated longitudinally over a median follow-up of 2.9 (IQR 0.9-6.7) years, excluding follow-up of ≤2 months. The adjusted hazard ratio for need for a future intervention was 1.16 (95% CI 1.08-1.25) in females as compared to males, but this varied significantly by location in the coronary tree and sex (Figure).

Conclusions:
Significant sex-based differences in coronary artery morphology, location, and disease distribution exist. Their interplay may inform future need for intervention.
Abstract 15646: The Need for Speed - Early Experience of Very High-Power Short Duration (QDOT
TM
) Ablation
Authors: Walsh Ronan , Kehoe Fiona , Frohlich Stephen , Murphy Noelle , Crinion Derek , Lyne Jonathan C
Published: June 2023

Introduction:
Ablation is a cornerstone of therapy for atrial fibrillation (AF), as well as one of the most common procedures in electrophysiology. Use of intermediate-power ablation has given way to high-power short duration radiofrequency ablation. However, more recently the emergence of very high-power very short duration (vHPvSD) ablation at 90W may prove to be more efficient and effective in the management of AF. The radius of the resistive heating zone is increased, while the conductive heating zone tapers off more quickly, potentially reducing collateral tissue damage.

Methods:
This was a single centre prospective study using the QDOT
TM
(Biosense Webster, Irvine, California) ablation catheter. Our workflow involves double trans-septal puncture via TOE guidance, use of a deflectable sheath, LASSO 10-pole mapping for first time AF ablations or PENTARAY
TM
for redo procedures, ablation while paced in sinus rhythm were possible, general anaesthetic, low tidal volumes, and an I:E ratio of 1:4. All pulmonary vein isolations (PVI) and posterior wall isolations (PWI) were performed at 90W for 4s, while cavo-tricuspid isthmus (CTI) lines were completed using QMode at 40W for 20s.

Results:
65 patients under went vHPvSD for treatment of atrial fibrillation. Of these 12 were re-do cases that had previously been treated with either radiofrequency or cryo-ablation. The average age was 58.9±9.7 (yrs) with 73% males. Paroxysmal atrial fibrillation was seen in 69%, 31% had persistent AF, and 7% had co-morbid atrial flutter. The average CHADSVASC score was 1.18±1.03. Pulmonary vein isolation was achieved in 100% of patients, 10% had posterior wall isolation, and 16% underwent cavo-tricuspid isthmus ablation. Average skin-to-skin and total ablation times were 58.2±13.1 (mins) and 23.4±6.5 (mins), respectively. Average RF time was 8.1±0.7 (mins). Mean follow up was 126±21 days, where 2 recurrences were seen. We saw no complications in our patient cohort.

Conclusions:
The method of vHPvSD is safe and durable in the treatment of atrial fibrillation. Total procedure time and RF time were significantly lower than previous RF ablation therapies. This relatively large study on the safety and early efficacy of vHPvSD adds to the emerging data on this promising technology.
Abstract 15660: Impaired Mitochondrial Quality Control Drives the Development of Cardiomyopathy in Anderson-Fabry Disease
Authors: Gambardella Jessica , Fiordelisi Antonella , Avvisato Roberta , Cerasuolo Federica A , Buonaiuto Antonietta , Prevete Nella , Perrino Cinzia , D'Argenio Valeria , Paolillo Roberta , D'Apice Stefania , Santulli Gaetano , Sorriento Daniela , IACCARINO GUIDO
Published: June 2023

Introduction:
Anderson-Fabry disease (AFD) is a systemic disorder caused by impaired alpha-galactosidase (GLA) activity, leading to a progressive cardiomyopathy, with hypertrophy and diastolic dysfunction. However, the molecular mechanisms underlying these features are unknown.

Aim:
To explore the role of mitochondria as a pathogenic mechanism of cardiac dysfunction in AFD.

Methods:
We tested a transgenic mouse that lacks endogenous GLA and expresses human R301Q-GLA [Tg/GLA knockout]. We performed serial ecochardiographic, histological, and biochemical analyses on cardiac tissue and single cell contractility on isolated adult cardiomyocytes (CM). Moreover, we assessed mitochondrial morphology/function in mouse embryonic fibroblasts (MEFs).

Results:
AFD-MEFs display an impaired mitochondrial respiration and reduced ATP synthesis. Increased mitochondrial levels of DRP1, LC3II, and MFN-ubiquitination along with accumulation of fragmented mitochondria and autophagosomes indicate the presence of mitophagy-targeted mitochondria that were not removed. Reduced PGC-1a and mitochondrial-DNA synthesis in AFD-MEFs indicate impaired mitochondrial biogenesis as well. Altogether, our data indicate impaired mitophagy and quality control of AFD-mitochondria. At echocardiography, AFD mice showed diastolic dysfunction and hypertrophy starting from 9 months. Isolated AFD-CMs exhibit reduced inotropic response to isoproterenol. Remarkably, alterations of cardiac mitochondrial function were observed starting from 3 months, including increased levels of MFN2-ubiquitination, DRP1 and LC3II, decreased levels of PGC-1a along with accumulation of disarranged mitochondria and autophagosomes. Frank impairment of mitochondrial respiration in AFD-CMs and reduced myocardial ATP-content was detected from 6 months, together with increased release of Cytochrome-C in the cytosol. Strikingly, mitochondrial dysfunction was also detected in fibroblasts isolated from AFD patients, which have a significantly reduced electron transport chain activity.

Conclusions:
In AFD, energetic alterations associated with impaired autophagy/mitophagy, are evident at 3 months and progressively lead to cardiac hypertrophy and dysfunction.
Abstract 15676: Sex Differences in Leg Microvascular Arteriolar Function in Patients With Limb Ischemia
Authors: Bronas Ulf G , Tintle Nathan , Luong Anna , Drab Yuliya , Naquiallah Dina , Borhani Martin , Phillips Shane A
Published: June 2023

Introduction:
There are known sex differences in peripheral artery disease (PAD) symptom presentation with women manifesting atypical symptoms and a higher vascular burden. Women are also more prone to periprocedural complications possibly due to sex-specific endothelial dysfunction and microvascular impairment. There is a critical need to understand sex specific differences in microvascular function to improve outcomes for women with PAD.

Hypothesis:
Lower limb arteriolar flow induced dilation (FID) will be significantly reduced in women, compared to men.

Methods:
Combined muscle and fat tissue were obtained from the affected leg in patients undergoing revascularization due to PAD. Arterioles were dissected, cannulated, and suspended in a physiological chamber at a stable intraluminal pressure. FID was assessed at increasing intraluminal pressure gradients. A subsample of vessels underwent arteriolar dilation with ACh with and without L-NAME, and SNP.

Results:
We quantified arteriolar FID in 24 arterioles (7=not viable) from 18 patients undergoing revascularization due to PAD (age 60.2
+
7.4, 44%=F, 61%=Black). Heterogeneity was observed in FID with significantly reduced response observed in women. FID in women at 60 cmH
2
O was 24.7
+
20.5%, compared to 52.6
+
28.0% in men, p=.05, and AUC was 69.0
+
66.8 in women, compared to 147.6
+
82.0 in men (p=.07). Findings were similar in both muscle and adipose arterioles. Vessels treated with Ach responded similar to FID. Vessels treated with L-NAME and SNP showed variable blunted response.

Conclusions:
Women had more impairment in arteriolar function compared to men, providing insight into sex dimorphism in the PAD population. Findings indicated that FID in arterioles is mostly nitric oxide dependent, although patient and sex specific changes in vascular smooth muscle signaling/function are present. This study support the need to develop microvascular and sex specific interventions for patients with PAD.
Abstract 15689: Efficacy and Safety of Non-Fluoroscopic Radiofrequency Ablation of Ventricular Arrhythmias Originating in the Sinuses of Valsalva
Authors: Romero Jorge , Diaz Juan C , Cerna Luis , Alviz Isabella , Varrias Dimitrios , Krishnan Suraj , Rodriguez Daniel , Gabr Mohamed , Rodriguez-Taveras Joan , Matias Jose , Gamero Maria , DAVE KARTIKEYA P , Purkayastha Sutopa , Marin Jorge , Duque Mauricio , Lakkireddy Dhanunjaya , Natale Andrea , Della Rocca Domenico G , Di Biase Luigi
Published: June 2023

Introduction:
Catheter ablation (CA) for premature ventricular contractions (PVCs) coming from the sinus of Valsalva have been historically challenging due to complex anatomy and mobility of the valve cusps. More importantly, coronary angiography or aortogram was the standard or care during these procedures. Alternative imaging methods without the use of fluoroscopy have emerged as a new modality of radiofrequency ablation therapy. We sought to compare the safety and efficacy of fluoroscopy-based ablation vs. non-fluoroscopic ablation in patients who underwent CA of PVCs originating from the Sinuses of Valsalva.

Methods:
A retrospective analysis of 35 patients at Montefiore Medical Center who underwent CA of PVCs originating from the sinus of Valsalva was made. Considering “Use of fluoroscopy or not” as the primary grouping variable, multivariate linear and logistic regression models were created using STATA (version IC/16.1). The primary safety endpoint was absence of any procedure related complication; the primary efficacy endpoint was acute procedural success. The secondary endpoint was total procedural time.

Results:
Thirty-five patients underwent CA of PVCs from the right or left coronary cusps with a retrograde approach. The mean age was 62±13.6 years, with 48% being female. Eighteen (51.4 %) patients underwent a non-fluoroscopic approach. There were no differences in the primary safety and efficacy endpoints. There were no complications and all cases were successful. The mean procedural time in the non-fluoroscopic group was 138 minutes (SD=34.8) compared to 227 (SD=71) in the fluoroscopic approach (p= 0.001). When controlled for baseline characteristics in a linear regression model, fluoroscopy was the only independent association with procedural time, increasing it by 98 minutes (SE =20.4, p =0.001).

Conclusion:
Non-fluoroscopic CA is a feasible technique for PVCs originating from complex locations including the Sinuses of Valsalva, demonstrating similar safety and efficacy. Moreover, a fluoroless approach is associated with decreased procedural times and eliminates the risks associated with radiation exposure, thus improving lab efficiency and reducing the risks of lead associated orthopedic injuries.
Abstract 15694: Mitochondrial Dysfunction and Fatty Acid Metabolism Derangement in Pediatric Single Ventricle Congenital Heart Disease
Authors: Samad Tahmina , Galdos Francisco X , Paige Sharon , Lee Soah , Lee Daniel , Heinrich Paul , Wu Sean M
Published: June 2023

Introduction:
Cardiac dysfunction is a common complication in pediatric patients with single ventricle (SV) physiology. While many factors contribute to the development of SV heart failure (HF), metabolic switch from fatty acid utilization to carbohydrate metabolism has been shown to contribute to cardiac dysfunction in adult HF.

Hypothesis:
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from pediatric SV HF patients exhibit reduced fatty acid utilization and decreased contractility when compared with hiPSC-CMs from healthy control individuals.

Methods:
We differentiated iPSCs from pediatric patients with hypoplastic left heart syndrome (HLHS) who developed early onset HF and from healthy control individuals to generate hiPSC-CMs. We plated hiPSC-CMs on hydrogel micropattern for single-cell plating and measured their contractile phenotype using the Sony SI8000 cell motion imaging system. We used Seahorse XF assay to measure metabolism in hiPSC-CMs. Furthermore, we performed metabolomic profiling of day 20 and day 45 hiPSC-CMs.

Results:
HLHS hiPSC-CMs demonstrated metabolic derangement with significant reduction in ATP production (p <0.001) and in basal and maximal respiration (p <.001). We also found that HLHS hiPSC-CMs have impaired contractility when compared to WT hiPSC-CMs. Contraction force and acceleration were decreased on HLHS hiPSC-CMs compared to WT hiPSC-CMs (p<0.01). Our metabolomic profiling identified a reduction of tricarboxylic acid (TCA) cycle metabolites such as succinyl carnitine (p = 0.002) and alpha-ketoglutarate (p = 0.056) in HLHS cells compared to healthy controls at day 20 and day 45 of differentiation. In addition, succinate, fumarate, malate, itaconate and citraconate/ glutaconate were also significantly reduced in day 20 media of HLHS hiPSC-CMs and trended lower in day 45 HLHS hiPSC-CMs.

Conclusions:
The disrupted fatty acid metabolism in hiPSC-CMs from patients with SV HF provides new insight into the pathogenesis of this disease and may help to develop novel metabolic biomarkers that may be useful for identifying pediatric patients at an earlier stage of SV HF.
Abstract 15719: Proteomic Analyses Reveal Mechanistic Links Between Clonal Hematopoiesis of Indeterminate Potential and Coronary Artery Disease
Authors: Yu Zhi , Yu Bing , Vromman Amelie , Nguyen Quynh H , Khetarpal Sumeet , Honigberg Michael , Lin Amy E , Katz Daniel H , Tahir Usman A , Weinstock Joshua S , Jaiswal Siddhartha , Austin Thomas , Ramachandran Vasan S , Peloso Gina , Manson Joann E , Haring Bernhard , Kooperberg Charles , Reiner Alex P , Bis Joshua , Psaty Bruce M , Correa Adolfo , Lange Leslie , Post Wendy S , Rotter Jerome I , Rich Stephen S , Wilson James , Ballantyne Christie M , Coresh Josef , Sankaran Vijay , Libby Peter , Bick Alexander G , Ebert Benjamin L , Gerszten Robert E , Natarajan Pradeep
Published: June 2023

Introduction:
Clonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon where hematopoietic stem cells acquire leukemogenic mutations without blood cancer. CHIP is a causal risk factor for coronary artery disease (CAD), yet underlying mechanisms remain unclear. The plasma proteome may provide novel mechanistic insights into the links between CHIP and CAD.

Methods:
We studied the associations of CHIP with the plasma proteins and CAD risk in four Trans-Omics for Precision Medicine (TOPMed) longitudinal cohorts: ARIC (N=9,084), CHS (N=1,727), JHS (N=1,858), and MESA (N=978). CHIP (variant allele fraction >2%) was identified from whole genome sequences of blood DNA and modeled both as a composite of the most common drivers (
DNMT3A
,
TET2
,
ASXL1
, and
JAK2
) and separately. Levels of ~1,300 serum proteins measured by SomaScan were log-transformed and residualized on study-specific covariates. The association between CHIP and protein levels was estimated across all participants within each study, as well as by sex, and meta-analyzed. For proteins significantly (FDR<0.05) associated with CHIP, pathway analysis and functional validation in
Tet2-/-
mice were conducted.

Results:
Across all studies (mean age: 59.8 y; 43.6% male), 720 (5.6%) individuals were identified with CHIP. There were 143 significant CHIP-protein pairs, with carbonic anhydrase 1, lysozyme C, and properdin being the most associated proteins.
TET2
had the largest number of, and strongest, associations among examined driver genes. In sex-stratified analysis, follicle-stimulating hormone was inversely associated in females. Pathway analysis implicated the inflammation-related STAT3 and IL-17 signaling pathways. We observed significantly greater expression of
Cfp
and
Lyz
(encoding properdin and lysosome C, respectively) in the monocytes of
Tet2
-/- female mice compared to wild-type female mice and
Tet2
-/- male mice. A number of proteins (including PCSK9) were significantly associated with both CHIP and CAD, suggesting both shared and nonshared mechanisms.

Conclusions:
CHIP, particularly
TET2
, is broadly associated with plasma proteins, as validated by evidence in Tet2-/- mice. Further studies are needed to understand the biological mechanisms linking CHIP to CAD.
Abstract 15733: Investigation of Cerebral Vessel Geometric Morphometrics for Prediction of Mechanical Thrombectomy First Pass Outcome
Authors: Santo Briana , M. J. Sarayi S. Mostafa M , Baig Ammad , Monteiro Andre , Waqas Muhammad , Siddiqui Adnan H , Tutino Vincent M
Published: June 2023

Introduction:
Vessel tortuosity is a major factor in successful first pass outcomes for mechanical thrombectomy (MT), but prior methods to quantify tortuosity are not accurate enough to predict outcome. We investigated a new method for vessel characterization and outcome prediction based on geometric morphometrics (GMM).

Hypothesis:
Our hypothesis was that morphometric analysis of engineered centerline landmarks would identify vessel characteristics that can better predict first pass MT outcome.

Methods:
Vessels and clots were manually segmented and reconstructed from pre-treatment CTA and nCCT images (
n
=5 cases) (Fig. 1A). The vasculature corresponding to the ICA and MCA from the affected hemisphere was isolated, and centerlines were engineered as curved landmarks. MorphoJ, a GMM software, was used to complete generalized Procrustes and principal component (PC) Analysis that included registration of patient geometries, calculation of average morphology and landmark variation, and identification of anatomical landmarks differentiating MT outcomes (Fig. 1B). Morphometrics were compared against local and overall tortuosity by measuring the separability of and cohesion within outcome classes.

Results:
GMM produced two PCs, which described local variation in M1 (PC1) and the ICA (PC2) (Fig. 1B). When compared against vessel tortuosity features, GMM PCs increased the distance between outcome classes (first pass effect vs. no first pass effect), improving separability by 23.6%. Further, GMM PCs increased the compactness/cohesion of outcome classes, reducing cumulative distance between failures by 50% and successes by 9.4% (Fig. 1C).

Conclusions:
GMM analysis of pre-treatment vessel characteristic highlights regional variation in M1 as a strong indicator of MT failure and suggests that GMM has the potential to better predict MT outcome than ICA tortuosity alone. Investigation of more complex vessel morphometry through feature engineering is needed.
Abstract 15741: Is Home Blood Pressure Monitoring Useful in Diagnosing Hypertension in Young Adults in Primary Care?
Authors: Mello Tomas d , Campos Flora R , Alves Calvão Diego , Boghossian Rodney , Felipe Falcão Michelle , Zagni Jardim Gabriela , Ferrão Raphaella , Brandão Luisa , Maselli Giovanna , Costa Joana , Muguet Clara , Marinho Beatriz D , Fernandes Ana Cristina , Monteiro Daniela , MUXFELDT ELIZABETH B
Published: June 2023

Introduction:
Recent guidelines have recommended out-of-office blood pressure (BP) measurement to improve the accuracy of the diagnosis of hypertension (HTN) but there are few studies evaluating its use in the younger population and in the scope of primary care.

Objective:
To assess the degree of agreement between office BP and Home Blood Pressure Monitoring (HBPM), evaluating their use in a young population assisted in primary care.

Methods:
This is a cross-sectional population study with adults between 20-50 years old registered in the Family Health Strategy. Sociodemographic, anthropometric data and cardiovascular risk factors were recorded. Office BP was the mean of 2 measurements and HBPM followed the 7-day protocol. HBPM < 135 x 85 mmHg and office BP < 140 x 90 mmHg were considered normal while dentifying the 4 phenotypes: Normotension (controlled office BP and HBPM); white-coat HTN (uncontrolled office BP and controlled HBPM); masked HTN (controlled office BP and uncontrolled HBPM) and sustained HTN (uncontrolled office BP and HBPM).

Results:
475 individuals were included (male sex: 38%; mean age: 37.6 years ± 8.8 years) of which 93 (20%) had their diagnosis modified after HBPM (43 with white-coat and 47 with masked HTN). Through multiple logistics regression, male gender (OR 3.87: 95%CI 1.70-8.82) was independently correlated with white-coat HTN, while obesity and prehypertension increased the risk of masked HTN by 2 and 5.5 times respectively. Uncontrolled office BP had high specificity (89%) and low sensitivity (49%) for detecting sustained HTN, with a low concordance in the diagnosis of HTN (kappa=0.388). Among men with uncontrolled office BP, 55.6% had a diagnosis of white-coat HTN and among women, 37.1%.

Conclusion:
HBPM was a useful tool in the diagnosis of hypertension in a young and apparently healthy population in primary care, especially in those with uncontrolled office BP to identify white-coat HTN, and in those with high normal office BP, especially if they were male or obese, for early diagnosis of masked HTN.
Abstract 15809: Ascending Late Onset Bacteremia Causing ICD Pocket Infection via a Lead-Associated Veno-Pocket Fistulous Tract
Authors: Horton Edward R , Zaidi Syed M , Perucki William , Basil Anuj , Cronin Edmond , Cooper Joshua M , Whitman Isaac R
Published: June 2023

Case Presentation:
A 51-year-old man with a history of non-ischemic cardiomyopathy, resolved line-associated Staph aureus bacteremia (SAB), and subsequent defibrillator (ICD) implant presented with sepsis. He was covered empirically with antibiotics and 4/4 blood cultures from admission grew MSSA. On exam, the patient’s pocket was non-tender, non-erythematous, and non-fluctuant, with a well-healed incision. A chest CT revealed multiple septic pulmonary emboli. ICD extraction was performed, exactly 580 days after last pocket entry. In the OR, the pocket drained copious pus and a distinct fistulous tract was noted along the lead, tracking to the pocket from the axillary vein (
Figure
). Full pocket debridement was performed, the entire system was extracted, and a drain was placed. The ICD lead tip culture grew MSSA; however, the pocket culture was negative. A source for the SAB was not determined. After completion of antibiotics and confirmatory negative blood cultures, a contralateral ICD was implanted.

Discussion:
A significant subset of CIED pocket infections present late (≥1 year from last pocket entry) and presume either indolent pocket infection descending to the bloodstream or, more likely, in the case of virulent bacteria like Staph aureus, ascending hematogenous spread to the device pocket. However, macroscopic evidence of this mechanism has not yet been demonstrated. The
Figure
grossly illustrates a
presumed
phenomenon - bacteria from the bloodstream forming a lead-associated fistulous tract to a previously sterile pocket, demonstrating proof-of-concept of a
continuous environment
between the pocket and bloodstream. This pathophysiology is central to established CIED guidelines on bacteremia, which emphasize the importance of early extraction and alternate-site re-implantation.
Abstract 15856: Relationship Between Aortic Valve Area Assessment From Transthoracic Echocardiogram and Cardiac Computed Tomographic Angiogram
Authors: Sankaramangalam Kesavan P , Sulaiman Samian , Ludhwani Dipesh , Uqaily Muhammad , Zeb Irfan
Published: June 2023

Introduction:
AVA can be estimated by either TTE or CTA however there is only limited literature assessing the concordance between these two modalities. AVA of 1.2 has been proposed as an indicator for severe AS by cardiac CTA in previous literature.

Hypothesis:
In our single center experience, we are hypothesizing that if use CTA AVA cut off of 1.2 cm^2, it will have high sensitivity in identifying all severe AS patients rather than using 1 cm^2 in CTA.

Methods:
We retrospectively studied 255 patients with severe AS who underwent both CTA and TTE at our institute from 11/2018 to 08/2021. Aortic valve area was obtained by CTA planimetry and categorized the subjects into three groups (AVA < 1 cm^2; AVA 1-1.2 cm^2; AVA > 1.2cm^2). Aortic valve area from TTE was calculated by continuity equation. The subjects were further categorized into patients with high gradient severe AS (mean gradient >40 mmhg) and low gradient severe AS.

Results:
Among 116 patients with low gradient severe AS (TTE AVA <1cm^2), 45 patients had CTA AVA <1 cm^2 and 39 patients had CTA AVA 1-1.2 cm^2 and 32 patients had CTA AVA >1.2 cm^2. And among 129 patients with high gradient severe AS (TTE AVA <1cm^22), 55 patients had CTA AVA <1 cm^2, 42 patients had CTA AVA 1-1.2 cm^2 and 32 patients had CTA AVA >1.2 cm^2. Overall when we use CTA AVA <1.2 cm^2 in low gradient severe AS cohort, we were able to identify 72% of severe AS patients and in high gradient severe AS cohort, we were able to identify 75.2% of severe AS patients.

Conclusions:
From our single center retrospective study, we are observing that for both high gradient and low gradient AS, there is high level of correlation between CTA and TTE when the AVA is either less than 1 cm^2 or when it is between 1-1.2 cm^2. However, for the AVA greater than 1.2 cm^2 there is lesser degree of correlation between the modalities especially in low gradient cohort. Overall, we suggest that using the cut off AVA 1.2 cm^2 by Cardiac CTA would achieve higher sensitivity for identifying the severe AS patients.
Abstract 15868: Prevalence and Effects of Acute Myocardial Infarction on Hospital Outcomes Among COVID-19 Patients
Authors: Appunni Sandeep , Ramamoorthy Venkataraghavan , Zhang Zhenwei , Ahmed Md Ashfaq , McGranaghan Peter , Salami Joseph , Morcos Ramez , Rubens Muni , Saxena Anshul , Veledar Emir , Jimenez Javier , Chaparro Sandra
Published: June 2023

Introduction:
In the US, there are approximately 84 million cases of COVID-19 accounting for 1 million deaths. Though there are not many studies, acute myocardial infarction (AMI) is one of the most lethal complications of COVID-19. In this study, we looked for occurrence of AMI and its effects on hospital outcomes among COVID-19 patients.

Hypothesis:
AMI among COVID-19 hospitalizations could worsen the levels of adverse in-hospital outcomes.

Methods:
Data from the 2020 California State Inpatient Database was used retrospectively. All COVID-19 hospitalizations with age ≥18 years were included in the analyses. Adverse hospital outcomes included in-hospital mortality, prolonged length of stay, vasopressor use, mechanical ventilation, and ICU admission. Prolonged length of stay included any hospital length of stay ≥75th percentile. We explored for differences in adverse hospital outcomes between those with and without AMI. Multivariate logistic regression analyses were used to understand the strength of these associations after adjusting for cofactors.

Results:
Our analysis had a total of 94,114 COVID-19 hospitalizations and 1548 (1.6%) had AMI. Adverse hospital outcomes such as mortality (43.2% versus 10.8%, P<0.001), prolonged length of stay (39.9% versus 28.2%, P<0.001), vasopressor use (7.8% versus 2.1%, P<0.001), mechanical ventilation (35.0% versus 9.7%, P<0.001), and ICU admission (33.0% versus 9.4%, P<0.001) were significantly higher among COVID-19 hospitalizations with AMI. The odds of adverse outcomes such as mortality (aOR, 3.90, 95% CI: 3.48-4.36), prolonged length of stay (aOR, 1.23, 95% CI: 1.10-1.37), vasopressor use (aOR, 3.71, 95% CI: 3.30-4.17), mechanical ventilation (aOR, 2.71, 95% CI: 2.21-3.32), and ICU admission (aOR, 3.51, 95% CI: 3.12-3.96) were significantly more prevalent among COVID-19 hospitalizations with AMI.

Conclusions:
In spite of very low prevalence of AMI among COVID-19 hospitalizations, we observed a substantially greater risk of adverse hospital outcomes and mortality. The hyperinflammatory response of COVID-19 could additionally worsen the factors precipitating mortality among AMI. COVID-19 patients with AMI should be aggressively treated to improve hospital outcomes.
Abstract 15869: Blood Pressure Trajectories Across the Life Course and Midlife Ventricular Systolic Function: The Bogalusa Heart Study
Authors: De Anda-Duran Ileana , Duran Antonio , Alonso Camilo , Bazzano Lydia A
Published: June 2023

Introduction:
Markers of adverse cardiac remodeling such as left ventricular (LV) hypertrophy and diastolic dysfunction have been associated with higher blood pressure (BP) during early and mid-life. Mid to late life hypertension is a well-known risk factor for left LV systolic dysfunction and progression to clinical heart failure (HF). We explore the association between BP in early to mid-life and LV systolic dysfunction measured by left ventricular ejection fraction (LVEF) in mid-life.

Hypothesis:
Higher BP in early to mid-life is associated with LV dysfunction as measured by LVEF.

Methods:
This complete-case analysis considered 1,140 participants of the Bogalusa Heart Study (57.5% female, 34.4% Black) with at least 3 traditional cardiometabolic risk factor (CMRF) observations since childhood (mean age 9.6±3.2 years) and transthoracic echocardiography-based LVEF estimations in midlife (48.9±5). Mean follow-up time was 38.6±3.8 years. A latent class trajectory modeling framework was employed to define trajectories of SBP. LVEF was divided into quartiles, and multivariable logistic regression models were utilized to estimate the association between life-course SBP trajectories and the lower quartile (Q1) of LVEF, controlling for traditional CMRF. Race, sex, and SBP trajectories interactions were tested to explore effect modification.

Results:
The prevalence of Q1 LVEF was higher among Black (32.1%, p<0.01) and male (31.3%, p<0.01) participants, compared to their counterparts. Four distinct trajectories were identified: stable-increasing (SI, 82.3%), moderate-increasing (MI, 5.2%), high-increasing (HI, 3.2%), and increasing-decreasing (D, 9.3%). Using SI as a reference, the following independent associations with the lower quartile of LEVF were identified: MI (OR: 1.4, 95%CI: 0.8 - 2.6, p=0.18), HI (OR: 0.72, 95%CI: 0.23-1.9, p=0.18), D (OR: 1.68, 95%CI: 1.1-2.6, p=0.02)

Conclusion:
Elevated systolic BP during early to mid-life (particularly 15-40 years of age) is associated with lower LEVF in midlife. These findings suggest the possibility of cardiac remodeling starting early in life. Increased awareness of elevated BP in childhood might be an avenue to prevent the progression to systolic dysfunction in late life.
Abstract 166:

Lung Parenchymal And Pleural Findings On Computed Tomography After Out-of-Hospital Cardiac Arrest
Authors: Newton Maranda , Counts Catherine , Sarikaya Basar , Srinivasan Vasisht , Branch Kelley R , Johnson Nicholas J
Published: June 2023

Introduction:
Lung injury and the acute respiratory distress syndrome (ARDS) are common after out-of-hospital cardiac arrest (OHCA), but the imaging characteristics of lung parenchymal and pleural abnormalities in these patients have not been well-characterized. We aimed to describe the incidence of lung parenchymal and pleural findings among patients who had return of spontaneous circulation (ROSC) after OHCA who underwent computed tomography (CT) of the chest.

Methods:
This was a retrospective cohort study conducted at two academic hospitals from 2014 to 2019. We included adults with OHCA who received a head-to-pelvis or dedicated chest CT scan. The primary outcome was the incidence of lung parenchymal and pleural abnormalities. CT scans were overread by attending radiologists and lung parenchymal and pleural findings were categorized based on predefined criteria. Data are presented as absolute numbers and percentages.

Results:
We evaluated 243 eligible patients. Median age was 56 years, 32% were women, and 59% were Caucasian. An initial shockable rhythm was found in 29% and in 71 patients (30%) the etiology of arrest was cardiac. A total of 162 patients underwent head-to-pelvis CT and 81 patients had dedicated chest imaging. The median time from OHCA to CT scan was 2.7 (IQR 2.1-3.8) hours. A total of 190 (78%) of patients had abnormal lung parenchymal or pleural findings. The most common findings are depicted in Table 1.

Conclusion:
Over three-quarters of patients who survive to the hospital post OHCA have lung parenchymal or pleural abnormalities on CT, the most common of which are aspiration, pulmonary edema, and consolidation/pneumonia. Future planned research will characterize the clinical impact of these findings and whether early chest CT could identify patients at risk for ARDS.
Abstract 175: Prognostic Value Of Serum Phosphate Level In Elderly Post-cardiac Arrest Patients
Authors: Kim Hee Eun , Park Seung Min
Published: June 2023

A recent study has shown that serum phosphate (SP) may be a prognostic indicator for poor neurological outcomes in cardiac arrest patients. We aimed to confirm the hypothesis that a higher SP level predicts a poor neurological outcome of cardiac arrest, even in elderly patients. This retrospective observational study included post-cardiac arrest patients aged ≥65 years who were admitted to three hospitals in urban areas in South Korea from December 2013 to February 2020. Patient characteristics, laboratory values, and neurological outcomes at 28 days were collected from patients’ medical records. The primary outcome was poor neurological outcome (CPC scores 3-5) at 28 days. Of the 389 eligible patients, 334 had poor neurological outcomes. SP levels were higher in those with poor neurological outcomes (7.31
vs
. 5.01, p<0.001). Multivariate logistic regression analysis showed that SP levels were independently associated with neurological outcomes. Higher SP levels are associated with poor neurological outcomes after cardiac arrest in the elderly population.
Abstract 183: Prioritizing Interventions To Reduce The Caregiver Burden Among Racially And Ethnically Diverse Co-survivors Of Cardiac Arrest Survivors: A Cross-sectional National Survey Study
Authors: Chap Jennifer F , Newman Mary M , Abukhadra Sabine L , Rojas Danielle , Deforge Christine L , Tincher Isabella , Wylie Jasmine , LOPEZ-ANDERSON MARTHA E , Marchionda Cindy , Agarwal Sachin
Published: June 2023

Introduction:
Cardiac arrest (CA) co-survivors i.e., close family members of CA survivors, have high levels of caregiver burden and poor quality of life. We aim to prioritize potential patient-, and co-survivor-centric interventions that may alleviate caregiver burden.

Methods:
We distributed an online survey to adult, co-survivor members of the Sudden Cardiac Arrest Foundation and Parent Heart Watch national databases and CA-specific Facebook groups. Participants provided demographics, details on their loved ones’ CA, and their caregiving role. They then ranked their top choice among 8 unique interventions focusing on either patient-centric education-based needs (n=4) or co-survivor-centric resources for self-care and enhanced psychological support (n=4). The survey was developed by a multidisciplinary research team and patient and co-survivor stakeholders.

Results:
Of 657 responses received, 550 co-survivors (57% were between the age of 18-40 years, 65% were women, 51% of minority race/ethnicity, 53% partners or spouse, an average of 8 hours of caregiving, for an average of 5 months) with the complete ranking data, were analyzed. A total of 347 (63%) co-survivors ranked patient-centric education-based interventions as their top choice (
Figure 1 shows distributions
). A multivariate model estimating the drivers of preferences for education-based interventions over co-survivors resource-based interventions showed age>40 years, direct discharge to home after CA vs inpatient rehabilitation, co-survivor witnessing the CA, or assuming the caregiver role during hospitalization or within 1-month of CA, were significant predisposing factors.

Conclusions:
Education-based interventions, particularly information related to their loved ones’ recovery, are the top priorities for co-survivors during the early phase of CA survivorship. Future studies should focus on developing and testing these interventions for alleviation of caregiver burden.