bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16818: Frozen in Time: Endothelial Progenitor Cell-Derived Extracellular Vesicles Maintain Therapeutic Efficacy for Clinically Translatable Treatment of Acute Myocardial Infarction After Long Term Storage
Authors: Chung Jennifer J , Zaman Samir , Arisi Maria F , Li Elizabeth , Chen Minna H , Chen Carol W , Gaffey Ann C , Burdick Jason A , Atluri Pavan
Published: April 2024

Introduction:
Extracellular vesicles (EV) derived from progenitor cells are a novel therapy for ischemic cardiomyopathy, with promise for “off-the-shelf” delivery. Clinical translation and timely delivery post-myocardial infarction (MI) requires assurance of EV stability after storage. Bioactivity studies of EVs after freezing are currently lacking and are necessary to establish quality standards for widespread clinical use of EVs.

Hypothesis:
We hypothesize that endothelial progenitor cell-derived EVs (EPC-EVs) can be frozen at -80 °C for at least 2 months without decrement of therapeutic effect when delivered intramyocardially to ischemic tissue.

Methods:
EVs were isolated from male Wistar rat bone marrow EPCs. Fresh preparations of EVs isolated from 700,000 EPCs were compared to frozen EVs stored in dPBS for 2-4 months at -80 °C. Particle size of EVs was analyzed via nanoparticle tracking analysis. In vitro angiogenesis was measured with Matrigel assay. A rat model of MI via left anterior descending artery ligation was used to assess EPC-EV function. Hemodynamics, scar thickness and vasculogenesis were assessed 4 weeks post-intramyocardial injection of EPC-EV within a shear-thinning gel (STG).

Results:
After 4 months’ storage at -80 °C, frozen EVs had stable mean particle diameter. In vivo analysis demonstrated equivalent hemodynamic outcomes between fresh and 2-month frozen EVs (p=1.0), both of which had statistically significantly improved measures of contractility over PBS as measured by Ees (p=0.0001; p=0.0008) and dp/dt (p=0.01; p=0.03, respectively). Scar thickness was increased in fresh, but not frozen EVs vs PBS (0.68, 0.64 v 0.50; p=0.031, p=0.22). On IHC, fresh and frozen EVs had significantly increased vascular density vs PBS (Δ665.5, Δ907.5; p=0.05).

Conclusions:
EPC-EVs retain adequate functionality after 2 months of freezing to produce hemodynamic benefits equivalent to freshly prepared EPC-EVs when delivered in STG to ischemic myocardium.
Abstract 16820: Clinical Outcomes of Patients Presenting With Acute Heart Failure and Biopsy-Proven Myocarditis at a Major Academic Center
Authors: Nalbandian Ani , Topkara Veli K , Garan Arthur R
Published: April 2024

Introduction:
Myocarditis is an inflammatory disease of myocardium with heterogeneous clinical presentation. There is limited data on short and long term outcomes of patients with biopsy-proven myocarditis.

Methods:
We conducted a retrospective study of patients with biopsy-proven myocarditis treated at our institution from 2004-2015 and retrieved demographic, echocardiographic, and outcome data. The primary outcomes were need for mechanical circulatory support (MCS), transplant, or death at 1 year. The cohort was limited to viral or idiopathic myocarditis to exclude clinical variability resulting from other etiologies.

Results:
In total, 39 patients were identified with a clinical presentation of myocarditis who had a biopsy consistent with this diagnosis. Mean age was 40 ± 15 years and 15 (38.5%) were women. Mean LVEF was 32 ± 17%. Median INTERMACS score was 2 (IQR 1-4). Predominant histologic subtypes were 39% lymphocytic, 21% mixed infiltrate, 8% lymphohistiocytic, 8% mononuclear, 5% eosinophilic, 5% giant cell, 5% histiocytic/eosinophilic and 9% undesignated. Medical treatment included inotropes (64.1%), vasopressors (46.2%), intravenous immunoglobulin (2.6%), steroids (30.8%) or other immunosuppression (15.4%). Twenty (51.3%) patients were treated with MCS which included intra-aortic balloon pump (n=13, 33.3%), percutaneous ventricular assist device (n=2, 5.1%), short term ventricular assist device (n=11, 28.2%, average duration 18 ± 11 days), and veno-arterial extracorporeal membrane oxygenation (n=1, 2.6%); 1 (2.6%) patient required a durable ventricular assist device and was explanted for recovery after 38 days. No patients were transplanted; 6 (15.4%) died, all of whom were treated with MCS and died within 1 month of presentation. Histologic subtypes of those that died were: giant cell (2), lymphocytic (2), mononuclear (1), and mixed infiltrate (1). Cohort survival at 1 year was 84.6% (70% in MCS vs 100% in non-MCS subgroup,
p
= 0.009).

Conclusions:
Acute myocarditis is highly variable with regards to clinical presentation and infiltrate cell pattern. Early recognition and appropriate utilization of MCS could improve outcomes. The observed increased mortality with MCS likely reflects sicker substrates needing MCS.
Abstract 16829: Pericardium Improves Cardiac Scaffold Mechanics and Cell Retention
Authors: Xi Yutao T , Feng-Lee Po T , Hochman-Mendez Camila T , Chandler Anita T , Tang-Quan Karis R , Sampaio Luiz C , Taylor Doris A
Published: April 2024

Background:
Building a transplantable bioartificial heart from a decellularized extracellular matrix (dECM) scaffold is a promising option to solve the donor organ shortage. Yet, strategies are needed for cell retention, survival and function in recellularized dECM hearts. The objective of this work was to determine if the preservation of the pericardium during decellularization provides benefit to the resulting dECM mechanically and functionally when recellularized.

Methods:
Hearts ± pericardium (8.0 ± 1.3 g) from New Zealand White rabbits (2.9 ± 0.6 kg) were perfusion decellularized via Langendorff under constant pressure (60 mmHg). Perfusion solutions were: hypertonic NaCl (500mM), hypotonic NaCl (20mM), 1% sodium dodecyl sulfate (SDS), peracetic acid (0.01%) in 1% SDS, and PBS. After decellularization, dECM hearts (n=7 with pericardium, n=9 without pericardium) were sectioned into 2 mm thick rings. Force-elongation curves, DNA, SDS, glycosaminoglycan (GAG) content, and matrix fiber density were measured. Vasculature of dECM whole hearts (n=14) was recellularized by anterograde infusion of human endothelial cells (hECs, 86.09 ± 18.26 million) through the coronary vasculature (2 ml/min at 1.5 million cells/ml).

Results:
Hearts decellularized with pericardium contained more DNA (427± 26, n=6, vs. 217 ± 46 ng/mg, n=7, p<0.05) than those without, but remnant DNA content was less than 10% of cadaveric. The GAG content was comparable in hearts with or without pericardium. Matrix fiber densities were higher in hearts with pericardium (64.47% ± 1.55%, vs. 54.28% ± 2.45%, p<0.01, n=3). Force-elongation tests showed that rings of left ventricle with pericardium had better flexibility with a slope of 1.56% ± 0.65% mm/gram vs. 0.91% ± 0.28% mm/gram (p<0.01, n=3 hearts per group). In recellularized hearts, more hECs were retained (83.82% vs. 70.04%, p<0.05, n=7) in hearts with pericardium.

Conclusion:
Retaining the native pericardium preserves the mechanical flexibility and matrix fiber densities of dECM scaffold, which promotes cell retention during recellularization.
Abstract 16836: Incidence and In-Hospital Outcomes of Post-Operative Venous Thromboembolism in Patients Undergoing Coronary Artery Bypass Surgery - a National Analysis
Authors: Panhwar Muhammad S , Kalra Ankur , Gupta Tanush , Khera Sahil , Ginwalla Mahazarin
Published: April 2024

Introduction:
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is rare after coronary artery bypass grafting (CABG). Given the low incidence of VTE, post-operative anticoagulation in these patients is controversial. Given the low rate of VTE, prior studies on this topic may not have been adequately powered to detect adverse outcomes. We sought to investigate the post-operative incidence and outcomes of VTE in CABG patients using a large national in-patient database.

Methods:
We utilized the 2013-2014 National Inpatient Sample to identify all patients over 18 years of age who underwent CABG without concomitant valvular procedures (isolated CABG) and had VTE during the hospital stay. We then compared clinically relevant outcomes in patients with and without VTE.

Results:
Of 59,391,030 patients, we identified 401,075 (0.7%) hospitalizations with CABG listed as the primary or secondary procedure. We excluded 69,125 hospitalizations with concomitant valvular procedures, resulting in 331,950 procedures for isolated CABG. Of these, 4,205 (1.3%) had VTE. Patients with VTE were more likely to be older (mean 67.2 vs 65.2 years, p<0.0001), female (30.4% vs 25.2%, p<0.0001), have coagulopathy (32.0% vs 17.8%, p<0.0001), and prior VTE (4.5% vs 1.8%, p<0.0001). Patients with VTE also had higher hospital costs (median $74,639 vs $40,702, p<0.0001) and longer length of stay (median 16 vs 8 days, p<0.0001). In multivariate regression analysis adjusting for baseline patient characteristics, patients with VTE had higher odds of inpatient mortality (adjusted odds ratio(aOR) 2.10 [95% confidence interval: 1.53-2.90]; p<0.0001), acute kidney injury (aOR 2.50 [2.12-3.05]; p<0.0001), dialysis (aOR 1.81 [1.17-2.81]; p = 0.008), acute respiratory failure (aOR 2.98 [2.55-3.49]; p<0.0001), and stroke (aOR 2.78 [2.00-3.87]; p<0.0001).

Discussion:
Our analysis of over 330,000 CABG procedures suggests that while post-operative VTE after CABG is rare, it is a strong independent predictor of adverse in-patient outcomes. Clinicians taking care of such patients should consider prophylactic mechanical or pharmacologic measures to prevent VTE when safe to do so.
Abstract 16839: The Outer Mitochondrial Membrane Protein, mitoNEET, Sustains Structure of Mitochondrial Cristae
Authors: Furihata Takaaki , Kinugawa Shintaro , Takada Shingo , Maekawa Satoshi , Katayama Takashi , Shirakawa Ryosuke , Nambu Hideo , Obata Yoshikuni , Yamanashi Katsuma , Kakutani Naoya , Saito Akimichi , Fukushima Arata , Yokota Takashi , Anzai Toshihisa
Published: April 2024

Background:
Mitochondria are essential organelles with various functions, and change its network dynamically. The inner mitochondrial membrane (IMM) contains the cristae membrane (CM), which extends into mitochondrial matrix space. A loss of mitofilin, one of the main component of mitochondrial contact site and cristae organizing system (MICOS) complex in the IMM, has known to be unable to preserve CM structure, accompanied with lower membrane potential. And a disruption of mitoNEET, novel protein located in the outer mitochondrial membrane, has been shown to decrease mitochondrial membrane potential, however, the role of mitoNEET in structure of the CM has not been elucidated.

Methods and Results:
mitoNEET flox/flox mice were generated with lox-P and homologous recombination strategies. Cardiac-specific deletion of mitoNEET (mitoNEET-knockout) was achieved using αMHC-Cre. Transmission electron microscopy showed the mitochondria isolated from mitoNEET-knockout mice reduced number of cristae, loss of the cristae junctions, and accumulation of cristae stack. These mitochondria also exhibited a swollen morphology. ROS production from the mitochondria were higher in mitoNEET-knockout mice. Mitochondrial state 3 respirations were comparable between the groups, however, mitochondrial maximal capacity and reserve capacity in mitoNEET-knockout mice. Mitochondrial membrane potential measured by using cultured cells transfected with
CISD1
, encoding mitoNEET, siRNA was decreased in this condition compared to scramble. Mass spectrometry analysis revealed that endogenous mitoNEET coprecipitated with endogenous mitofilin, which is known to be localized in the IMM and involved in CM structure. Echocardiography showed cardiac dysfunction in mitoNEET-knockout mice.

Conclusions:
The protein-protein interaction between mitoNEET and mitofilin may regulate CM structure through the maintenance of MICOS complex including mitofilin. The lack of this interaction could induce mitochondrial dysfunction, suggesting that mitoNEET play an important role in the regulation of mitochondrial function via mitochondrial morphology.
Abstract 16869: Clinical Relevance of Troponin I in Advanced Chronic Kidney Disease for Suspected Coronary Artery Disease
Authors: Hanumanthu Balaram Krishna J , Chokshi Bhavin , Bizzocchi Lilian , Pervez Muhammad , Mahato Poonam , Batra Sachin , Jim Belinda
Published: April 2024

Background:
Troponin elevations are common in advanced chronic kidney disease (CKD) but its association with angiographically significant coronary artery disease (CAD) remains unclear. We wish to elucidate the test characteristics of troponin in chronic kidney disease population.

Methods:
We retrospectively reviewed the charts of all patients who underwent coronary angiograms performed at Jacobi Medical Center between April 2007 to May 2017. Significant CAD was defined as ≥70% on angiography. We divided patients into subgroups of mild CKD (I,II,III) and advanced CKD (IV,V) based on MDRD staging for CKD classification.

Results:
Baseline characteristics of cardiovascular risk factors were similar among patients with mild and advanced CKD except hypertension (81 vs 96, p < 0.001), diabetes (52 vs 66, p = 0.015), LDL (93 vs 78, p=0.004) and lower HDL (79 vs 91, p = 0.01), respectively. Of 795 patients, 371 had angiographically significant CAD. Accuracy of troponins in predicting significant CAD was greater in advanced CKD (AUC 0.76) as compared to mild CKD (AUC 0.62), p = 0.016). Troponin I > 0.254 was 62% sensitive and 60% specific in mild CKD and Troponin I > 0.47 was 73% sensitive and 73% specific in advanced CKD.

Conclusions:
We conclude that troponin retains its diagnostic value and infact has a higher accuracy in advanced CKD patients with angiographically significant CAD.
Abstract 16916: Shortening of Pressure Half Time During Exercise as a Predictor for Exercise Capacity in Patients With Bileaflet Mitral Valve Replacement
Authors: Choi Jah Yeon , Cho In-Jeong , Chang Byung-Chul , Lee Sak , Lee Seung Hyun , Shim Chi Young , Chang Hyuk-Jae , Hong Geu-Ru , Ha Jong-Won
Published: April 2024

Introduction:
In patients with mechanical mitral valve replacement (MVR), effective orifice area is fixed during dynamic exercise. Therefore, pressure half time (PHT) change during exercise might be mainly influence by exercise-induced left ventricular end-diastolic pressure raise.

Hypothesis:
We hypothesized that shortening of PHT during supine bicycle exercise would predict exercise capacity in patients with bileaflet mechanical MVR.

Methods:
Patients with isolated bileaflet MVR (n = 40) prospectively underwent symptom-limited supine bicycle exercise testing with Doppler echocardiography. Heart rate (HR), peak and mean transprosthetic gradient, PHT, and systolic pulmonary artery pressure (SPAP) were assessed at different stages of exercise. Changes in PHT during 25W and 50W exercise (ΔPHT-25W and ΔPHT-50W, respectively) were measured. Changes in HR during 25W and 50W exercise (ΔHR-25W and ΔHR-50W, respectively) were calculated.

Results:
There were significant negative correlations between exercise duration and ΔPHT-25W (r = -0.345, p = 0.032) or ΔPHT-50W (r = -0.369, p = 0.027) (
Figure A and B
). Exercise duration demonstrated independent significant correlation with both ΔPHT-25W (p = 0.018) and ΔPHT-50W (p = 0.006), even after adjusting for age, sex, and ΔHR-25W/50W, respectively.

Conclusion:
Degree of PHT shortening during 25W and 50W exercise predicted exercise capacity in patients with bileaflet mechanical MVR. More shortened PHT during exercise was associated with low exercise capacity, which might be associated with diastolic dysfunction resulted from exercise-induced left ventricular end-diastolic pressure raise.
Abstract 16938: Late Gadolinium Enhancement on Cardiac Magnetic Resonance as Predictor of Overall Mortality in Patients With Non-Ischemic Cardiomyopathy
Authors: Foroutan Farid , Gaztañaga Juan , White James , Merlo Marco , Alonso-Rodriguez David , Vallejo-García Victor , Vidal-Perez Rafael , Corros-Vicente Cecilia , Katz Stuart , Flewitt Jacqueline , Sinagra Gianfranco , Farkouh Michael , Alba Ana Carolina
Published: April 2024

Background:
Patients with heart failure due to non-ischemic cardiomyopathy (NICM) constitute a heterogenous group of patients with diverse prognosis. The presence of late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging represents a measure of myocardial damage and can provide prognostic information.

Objective:
This study aimed to evaluate the prognostic role of the presence and pattern of LGE in patients with NICM .

Methods:
Using the NICM registry, we conducted a retrospective cohort study of adult patients with NICM, undergoing CMRI between 1999–2016. Using multivariable Cox regression model and Fine and Gray’s competing risk regression model, we evaluated the association between LGE presence and patterns with all-cause mortality, heart transplant, and ventricular assist device (VAD). We adjusted the model for clinically important covariates.

Results:
Our cohort of 1842 patients showed a mean age of 56 ± 14, 73% male sex, 30% NYHA class III-IV, 15% diabetic and 89% had idiopathic dilated cardiomyopathy. During a median follow-up of 2.3 years, we observed 215 composite outcome of all-cause mortality, transplant, or VAD. LGE was present in 56% of our cohort: 18% subendocardial, 18% mid-wall, 17% diffuse pattern, and 3% subepicardial. LGE was significantly associated with a 2-fold increased risk of events (HR 2.0, 95%CI 1.4-3.0) (figure). Of all LGE patterns, subendocardial, midwall, and diffuse LGE patterns were associated with the worst prognosis. (table).

Conclusions:
In patients with NICM, LGE in significantly associated with increased risk of death or need for advanced heart failure therapies. The use of CMR in patients with NICM provides both diagnostic and prognostic information.
Abstract 16940: Frailty Predicts Mortality Among Patients Referred for Cardiac Catheterization
Authors: Widmer Robert J , Kanwar Amrit , Al-Hijji Mohammed A , Gulati Rajiv , El Sabbagh Abdallah , Lennon Ryan J , Lerman Amir , Singh Mandeep
Published: April 2024

Introduction:
Survivorship needs to be comprehensively evaluated amongst older adults. We examined follow-up mortality in patients referred to cardiac catheterization laboratory by prospectively examining frailty.

Methods:
Frailty in 923 patients ≥55 years was determined using Rockwood’s deficit index. The frailty deficit was based on symptoms, signs, disabilities, diseases, and laboratory measurements. The number of deficits was expressed as a proportion of the total measured deficits. Frailty index was grouped into <0.10 (control), 0.10-<0.20, 0.20-<0.30, 0.30+ and age- and gender-adjusted follow-up mortality was determined using a Cox proportional hazards model.

Results:
There were 180 (20%) with frailty index <0.10, 348 (38%) in 0.10-<0.20, 215 (23%) in 0.20-<0.30 and 177 (19%) with an index of 0.30 or higher. Patients with a frailty index of 0.30+ were significantly older than those with an index <0.10 (75 ± 10 vs 67 ± 8 years; p<0.001) and more likely to be women (50% vs 20%; p<0.001). Patients with frailty index ≥0.20 and ≥0.30 had a significantly higher mortality risk (HR 3.95, 95% CI 1.51-10.3 and HR: 10.3, 95% CI 4.11-25.7, respectively) on follow-up which remained significant following adjustment for age and gender (HR 3.20, 95% CI 1.21-8.45 and HR: 7.99, 95% CI 3.13-20.4).

Conclusions:
Among older adults refereed to catheterization laboratory, frailty deficit index predicts follow-up mortality.
Abstract 16984: Oral Delivery of Angiotensin Converting Enzyme 2 and Angiotensin-(1-7) Bioencapsulated in Lettuce Cells Attenuates Experimental Pulmonary Hypertension (PH)
Authors: Lahm Tim , Yakubov Bakhtiyor , Mangu Venkata , Park Jiyoung , Daniell Henry
Published: April 2024

Introduction:
The renin-angiotensin system (RAS) plays a key role in the development of PH. Angiotensin converting enzyme 2 (ACE2) and its product, angiotensin-(1-7) [Ang-(1-7)] are RAS inhibitors, and their administration attenuates PH development in animal models. However, oral delivery systems for repetitive delivery of ACE2/Ang-(1-7) are not available, thus limiting their clinical applicability. Bioencapsulation of protein drugs within plant cells and their fusion with the transmucosal carrier CTB facilitates oral delivery of biopharmaceuticals.

Hypothesis:
Orally delivered, CTB-fused ACE2/Ang-(1-7) bioencapsulated in lettuce cells increases plasma Ang-(1-7) levels and attenuates experimental PH.

Methods:
CTB-ACE2 and CTB-Ang-(1-7) were expressed in lettuce chloroplasts. Proper folding, quantification and assembly of CTB-ACE2/Ang-(1-7) pentamers in lyophilized plant cells were confirmed by immunoblots or GM1 ganglioside receptor ELISA. PH was induced by monocrotaline (MCT) in male Sprague Dawley rats. Rats were gavaged with plant cells (5x/week for 4 weeks) expressing 250 μg, 500 μg or 750 μg of CTB-ACE2 and 400 μg, 800 μg or 1200 μg of CTB-Ang-(1-7). A control group of MCT rats received plant cells without ACE2 or Ang-(1-7). Ang-(1-7) in plasma was measured by ELISA. Functional/structural PH endpoints were assessed by echocardiography, right heart catheterization, Fulton index and analysis of pulmonary artery (PA) remodeling. Expression of PH-relevant genes was evaluated by real-time RT-PCR. p<0.05 by one-way ANOVA was considered significant.

Results:
Oral administration of CTB-ACE2 and CTB-Ang-(1-7) resulted in dose-dependent accumulation of Ang-(1-7) in plasma (p<0.05 vs control) and attenuation of PH development, evidenced by 30-50% decreases in right ventricular (RV) hypertrophy, RV systolic pressure, total pulmonary resistance and PA remodeling (p<0.05 vs control). Cardiac index increased in a dose-dependent manner (p<0.05 vs control). Bioencapsulated ACE2/Ang-(1-7) dose-dependently attenuated PH-induced alterations in mRNA expression of Ang-(1-7) receptor MAS and angiotensin II receptor AGTRI as well as IL-1β and TGF-β1 (p<0.05 vs control).

Conclusions:
Orally delivered CTB-ACE2/CTB-Ang-(1-7) bioencapsulated in plant cells dose-dependently increased Ang-(1-7) in the circulatory system, attenuated experimental PH and abrogated PH-induced gene alterations. Chloroplast-derived CTB-ACE2/CTB-Ang-(1-7) may be a novel oral treatment strategy for PH.
Abstract 16991: Relationship Between Restenosis After Percutaneous Transluminal Renal Angioplasty for Atherosclerotic Renal Artery Disease and the Preprocedural Renal Resistance Index in the Contralateral Kidney
Authors: Ito Nobuyasu , Zen Kan , Kawarada Osami , Yasuda Satoshi , Matoba Satoaki
Published: April 2024

Introduction:
Percutaneous transluminal renal angioplasty (PTRA) is an established treatment for atherosclerotic renal artery disease. Renal resistive index (RRI) is known as an indicator of renovascular atherosclerosis, and several studies reported that high preoperative RRI in the target kidney predicts poor response in hemodynamics and renal function after PTRA. However, RRI is elevated not as a sequence of proximal renal artery stenosis, and relationship between the patency after PTRA and RRI still has not been clarified.

Methods:
The CARMEL study (Cardiac Benefits of Renal Artery Stenting: A Prospective Multicenter Observational study) is a study of patients with de novo symptomatic ARAD who underwent PTRA between September 2012 and December 2015 at 14 institutions in Japan. Of the 76 patients who included in the final analysis of the CARMEL study, 46 patients (71.8±9.9 years) whose bilateral RRI were recorded before PTRA procedure were retrospectively analyzed. We evaluated renal ultrasonographic data collected before PTRA, and at 1-day, 1-month and 6-month follow-up.

Results:
55 lesions of the 46 patients were treated, and preprocedural RRI in the target kidney (tRRI) were higher than 0.8 in 16 lesions (High-tRRI group) and preprocedural RRI in the contralateral kidney (cRRI) were higher than 0.8 in 18 lesions (High-cRRI group). Preprocedural peak systolic velocity (PSV) and renal/aorta ratio (RAR) of the lesions were comparable between High-tRRI group and the rest, and also between High-cRRI group and the rest. However, in High-cRRI group, PSV of the target lesion is significantly higher than the rest at every follow up exam (at 6-month follow up: PSV 224.4±126.5 cm/s vs 113.7±53.7 cm/s, p<0.001; RAR 3.91±2.68 vs 1.99±1.07, p=0.009). (Table 1, Table 2)

Conclusion:
High preprocedural RRI in the contralateral kidney could be a predictor of restenosis after PTRA.
Abstract 12320: Long-Term Outcomes of Open and Endovascular Management of Adult Aortic Coarctation
Authors: Moonsamy Philicia , Bhatt Ami B , Sundt Thoralf M , Defaria Yeh Doreen , Sakhuja Rahul , Boltje Jan W , Pagliaro Jaclyn , Pomerantsev Eugene V , Bloom Jordan P , Li Selena , Cameron Duke E , Eagleton Matthew , Jassar Arminder
Published: April 2024

Objective:
To compare outcomes of endovascular vs. surgical management of adult aortic coarctation (CoA).

Methods:
We performed a retrospective study of patients who underwent surgical vs. endovascular intervention for CoA during adulthood (age>16 years) at a single institution.

Results:
We identified 137 adult patients with coarctation of the aorta seen between 1975 - 2019. 18/137 (13%) required no intervention for their coarctation. While 23/137 (40%) had surgical procedures and 34/137 (60%) had endovascular procedures. Surgical procedures included extra-anatomic bypass (13/23), resection of coarctation segment with interposition graft (4/23), distal hemi-arch replacement (1/23) and total arch replacement (1/23). Endovascular interventions included balloon angioplasty alone in 2/34 patients and stenting in 32/34 patients. Median age at intervention was 38 years (IQR: 30-47) in the surgical group and 36 (30-47) in the endovascular group. Patient follow up time ranged from 0-45 years with a mean follow-up of 12 years as calculated from the first intervention for CoA during adulthood. Overall survival was 96% in the surgical group and 100% in the endovascular group. There was one post-operative transient ischemic attack in the surgical group and no post-procedural complications in the endovascular group. In a Kaplan Meier analysis of freedom from re-intervention during an overall follow-up period of 45 years, surgical intervention for CoA during adulthood was superior to endovascular treatment (p=0.008).

Conclusions:
Although long-term survival is similar, surgical intervention for adult CoA offers superior freedom from re-intervention than endovascular treatment (p=0.008).
Abstract 12330: The Degree of Common Carotid Artery Stenosis and the Risk of Cardiovascular Disease Incidence in the Suita Study
Authors: Teramoto Masayuki , Kokubo Yoshihiro , Arafa Ahmed , Sheerah Haytham , Nakao Yoko , Sakai Yukie , Watanabe Emi , Li Jiaqi , Honda-Kohmo Kyoko , Kashima Rena , Kataoka Hiroharu
Published: April 2024

Introduction:
Little is known about whether common carotid artery (CCA) stenosis is associated with the risk of incident cardiovascular diseases (CVD) in a general population. We aimed to examine the impact of CCA stenosis degree on incident CVD in a general population.

Methods:
We studied 5,133 Japanese men and women (mean age 59.7 years) without CVD whose CCA was measured by carotid ultrasonography on both sides at baseline (April 1994 to March 2005). We confirmed stenosis by color Doppler and calculated the stenosis degree as a percentage of the stenotic area of the lumen in the cross-section perpendicular to the long axis. The Cox proportional hazard model was used to calculate the multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of CVD and its subtypes for people with CCA stenosis ≥50 % and 25-49 % compared to those with CCA stenosis <25 % after adjusting for cardiovascular risk factors.

Results:
During 63,687 person-years of follow-up, we observed 400 cases of incident CVD (237 strokes and 163 coronary heart diseases [CHDs]). The respective prevalence of 25-49 % and ≥50 % stenosis were 8.2 % and 5.3 % in men and 3.8 % and 1.1 % in women. The CCA stenosis degree was associated with increased risks of incident CVD and CHD, and marginally increased risks of stroke; the multivariable-adjusted HRs for 25-49 % and ≥50 % compared to <25 % stenosis were 1.29 (0.94-1.77) and 1.88 (1.28-2.75) for CVD, 1.88 (1.19-2.97) and 2.37 (1.35-4.13) for CHD, and 0.95 (0.61-1.49) and 1.69 (0.99-2.88) for stroke. The sex-specific HRs of incident CVD for 25-49 % and ≥50 % compared to <25 % stenosis were 1.60 (1.10-2.33) and 1.85 (1.19-2.88) for men, and 0.80 (0.43-1.50) and 2.40 (1.04-5.55) for women.

Conclusion:
The degree of CCA stenosis was associated with increased risks of incident CVD, CHD, and stroke in the general population. For the first time, CCA stenosis can be used as a predictive tool for the onset of CVD in a general urban population.
Abstract 12339: Robotic Assistance Improves Cardiovascular Function Compared To Conventional Cardiac Rehabilitation Programs
Authors: Irfan Bahar , Cespedes Gomez Nathalia , Casas Jonhatan A , Senft Emmanuel , Sanchez Daniel , RINCON-RONCANCIO MONICA , GUTIERREZ LUISA FERNANDA F , Cifuentes Carlos , Tony Belpaeme , Munera Marcela
Published: April 2024

Introduction:
This study investigates the impact of socially assistive robots and personalization in cardiac rehabilitation, in terms of physiological progress and perceptions of the patients and clinicians.

Methods:
We conducted a longitudinal study for 2.5 years with 43 patients. The intervention was classified into 3 conditions: control group (without a robot), a social robot and a personalized robot. Throughout the rehabilitation program (36 sessions), the initial heart rate, average heart rate during training, and heart rate recovery in the first minute. Heart rate recovery in the first minute was normalized with initial heart rate to homogenize the data: Heart rate recovery in the first minute normalized = heart rate recovery in the first minute/ initial heart rate. We apply Johansen's general formulation of the Welch-James statistic with approximate degrees of freedom on Heart rate recovery in the first minute normalized in 6 stages. Perceptions of the patients and clinicians are evaluated through surveys and interviews.

Results:
26 patients completed the rehabilitation program. Heart rate recovery in the first minute normalized changed significantly in each stage of the program (TWJ (5, 305) = 14.36, p < .001). Patients assisted by social and personalized robots achieved a higher improvement in cardiovascular functioning than the control group. Both robots improved motivation and trust due to continuous monitoring and immediate feedback, facilitated prompt detection of critical conditions, and were recommended for future use by clinicians and patients.

Conclusions:
Our results suggest that robots improve cardiovascular functioning compared to the conventional cardiac rehabilitation program. In addition, robots have motivational benefits for patients, and increase awareness of clinicians to detect complications, as a result, they were recommended for future use by patients and clinicians.
Abstract 12433: Distinct Immune and Mesenchymal Populations Identified by Single Cell RNA Sequencing Contribute to Chronic Thromboembolic Pulmonary Hypertension
Authors: Viswanathan Gayathri , Kirshner Helene , Nazo Nour , Ganapathi Asvin M , Cumming Ian , Haney John , Almeida Peters Susana , Corcoran David , Yu Yen-Rei , Rajagopal Sudarshan
Published: April 2024

Chronic thromboembolic pulmonary hypertension (CTEPH) is a sequelae of acute pulmonary embolism (PE) in which the PE remodels into a chronic scar in the pulmonary arterial system. This results in vascular obstruction, small vessel arteriopathy and pulmonary hypertension. Previous studies have attempted to identify cells that contribute to CTEPH thrombus but have been limited by the use of specific cell markers or phenotypic modulation after cell growth in culture. Here we have used single cell RNA sequencing (scRNAseq) of samples of CTEPH thrombus removed at the time of pulmonary thromboendarterectomy (PTE) surgery to identify clusters of macrophages, T cells, smooth muscle cells and endothelial cells in CTEPH thrombus. We identified that multiple macrophage subclusters, many of which have an inflammatory phenotype. T cells were a heterogeneous population consisting of CD4+ and CD8+ T cells that are predicted to be inflammatory and also promote vascular remodeling. In the smooth muscle cell cluster, a subcluster of myofibroblasts are predicted to arise from smooth muscle cells based on pseudotime analysis. Notably, cultured endothelial, smooth muscle and myofibroblast cells isolated from CTEPH thrombus have distinct phenotypes from control cells. For example, endothelial cells had reduced angiogenic potential, were proliferative and anti-apoptotic. Lastly, gene expression data identified protease-activated receptor 1 (PAR1) as a potential therapeutic target that links thrombosis to chronic PE in CTEPH. Together, these studies suggest a model in which chronic inflammation drives vascular remodeling and mesenchymal senescence in CTEPH pathogenesis and suggest new approaches for targeting this disease.
Abstract 12439: Sex-Specific Associations Between Adipose Depots With Subclinical Coronary Atherosclerosis and Cardiovascular Risk
Authors: Khawaja Tasveer , Rajagopalan Sanjay , Neeland Ian J , Al-Kindi Sadeer
Published: April 2024

Introduction:
Ectopic fat deposition (dysfunctional adipose tissue) is associated with atherosclerotic cardiovascular disease (ASCVD) risk. The value of adding fat distribution information to coronary artery calcium (CAC) score to predict ASCVD risk is unknown. Additionally, whether the association between fat distribution and CVD risk differs by sex is not well understood.

Hypothesis:
There are sex-specific relationships between adipose depots and CVD risk.

Methods:
We identified all participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study who underwent computed tomography of the chest and abdomen. We used machine learning models (logistic regression) to evaluate associations in men and women separately between 14 fat depot measurements encompassing visceral, subcutaneous, and ectopic fat (mean liver attenuation, total visceral, epicardial, intermuscular, intramuscular [paraspinous, rectus, psoas] and subcutaneous) and sex, non-zero CAC, and CVD risk using 10-fold cross-validation.

Results:
A total of 3163 individuals were included (1790 women and 1373 men). A model incorporating all fat depot variables had excellent discrimination of sex (AUROC = 0.88). In the entire cohort, our fat depot model had modest discrimination of non-zero CAC (0.69) and CVD events (0.58). The performance of CAC to predict CVD improved with the addition of fat depots (0.65 to 0.71). Women had higher AUROC for fat depots to predict non-zero CAC (0.63 vs 0.58) and CVD events (0.58 vs 0.52), which remained consistent in a model that includes CAC and fat (0.69 vs 0.66). Fat improved discrimination of CAC to predict CVD events more in women vs men (0.06 vs 0.03). The strength of association between various fat depots and sex differed between men and women (Figure).

Conclusions:
Visceral ectopic fat depots are associated with CAC and CV risk more strongly in women vs men. Future studies should focus on the sex-specific pathophysiology of cardiometabolic disease.
Abstract 12449: Clinical Impact of Reducing Bedrest After Pulmonary Vein Isolation
Authors: Freedman Benjamin L , Yang Shu , Shim David , Waks Jonathan W , Tung Patricia
Published: April 2024

Background:
Following pulmonary vein isolation (PVI), patients are typically prescribed 6 hours of bedrest to minimize bleeding. To streamline post-procedural care, our institution recently switched to a reduced bedrest period of 3 hours.

Objective:
To determine if reduced bedrest after PVI results in increased bleeding.

Methods:
We prospectively examined rates of bleeding, length of hospital stay, and urinary catheterization among patients undergoing PVI at our institution from April-May 2021. We compared these metrics to patients who underwent PVI with 6-hour bedrest in April-May 2019, predating our institutional protocol change. Figure-of-8 (FO8) sutures were used to achieve hemostasis in all patients. Continuous and categorical variables were compared using Student’s t-test and Fisher’s exact test, respectively.

Results:
Bilateral access was more common and procedure times were slightly longer in the 6-hour cohort; other baseline characteristics were similar between groups (Table 1). There was 1 major vascular access site complication (a retroperitoneal bleed) in the 6-hour and none in the 3-hour cohort. Minor bleeding occurred in 11% of each group. Same-day discharge was achieved in 42/45 (93%) of the 3-hour and 4/55 (7%) of the 6-hour group (p<0.001). Nine of 45 patients (20%) in the 3-hour group required urinary catheterization compared with 33/55 (60%) in the 6-hour group (p<0.001). Catheter-associated urinary tract infections (2% vs. 4%) and opioid analgesia use (22% vs. 36%) were lower in the 3- vs. 6-hour cohort, but these differences were not statistically significant.

Conclusion:
These data suggest that reducing post-PVI bedrest from 6 to 3 hours decreases length of hospital stay and urinary catheterization rates without increasing the risk of bleeding or vascular access site complications. Use of FO8 sutures, enhanced procedural efficiency and a shift toward unilateral femoral access may have contributed to the safety of this protocol change.
Abstract 12521: Atherosclerotic Cardiovascular Disease Risk and Small Dense Low-Density Lipoprotein Cholesterol in Men, Women, African Americans and Non-African Americans
Authors: Schaefer Ernst J , Ikezaki Hiroaki J , Diffenderfer Margaret R , Lim Elise , Cupples L. Adrienne , Liu Ching-Ti , Hoogeveen Ron H , Guan Weihua , Tsai Michael Y , Ballantyne Christie H
Published: April 2024

Introduction:
Increased small dense low-density lipoprotein cholesterol (sdLDL-C) has been reported to be a significant atherosclerotic cardiovascular disease (ASCVD) risk factor

Hypothesis:
SdLDL-C is an independent ASCVD risk factor in men, women, African Americans, and non-African Americans.

Methods:
A total of 15,933 participants (median age 62 years, 56.7% female, 19.7% African-American, free of inclusive ASCVD at baseline) pooled from three studies (Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and Multi-Ethnic Study of Atherosclerosis) were followed for 10 years for incident hard ASCVD and inclusive ASCVD (includes angioplasty and/or coronary artery bypass). These endpoints occurred in 6.1% and 9.7% of subjects, respectively. Information on all standard risk factors was obtained, and serum sdLDL-C levels were measured at baseline using automated analysis. The utility of traditional cardiovascular risk factors and sdLDL-C in 10-year hard and inclusive ASCVD risk was assessed-using univariate and multivariable regression analyses.

Results:
All standard risk factors were significant for hard and inclusive ASCVD in men, women, African-Americans and non-African-Americans on univariate statistical analysis. SdLDL-C was a significant risk factor when added to the pooled cohort equation for hard and inclusive ASCVD in all subjects, and for inclusive ASCVD in all subgroups, and significantly improved the C-Statistic and affected the net reclassification index for all subjects (p<0.0001). When subjects with elevated sdLDL-C levels of
>
50 mg/dL were compared to those with optimal levels of <25 mg/dL after adjustment for all standard risk factors, the hazard ratios (HR) and confidence intervals (CI) for incident inclusive ASCVD were all significant at p<0.01: all subjects (HR 1.54, CI 1.30-1.83), men (HR 1.59, CI 1.27-1.99), women (HR 1.51, CI 1.05-1.27), non-African-Americans (HR 1.49, CI 1.24-1.80[CLA3] ), and African-Americans (HR 1.88, CI 1.23-2.89).

Conclusions:
An elevated sdLDL-C value
>
50 mg/dL was independently associated with a 50% increased 10-year inclusive ASCVD risk in all subjects regardless of sex or race[MD1] , and therefore is an important ASCVD risk enhancer.
Abstract 12642: Heart Failure Prognosis in Diabetic Patients on SGLT2 (Sodium-Glucose Cotransporter-2) Inhibitors: A Systematic Review and Meta-Analysis
Authors: Nso Nso , EMMANUEL KELECHI , Nassar Mahmoud , Ayinde Hakeem
Published: April 2024

Introduction:
Cardiovascular disease complications predominantly increase the incidence of mortality and hospitalizations in the setting of type-2 diabetes. This systematic review and meta-analysis aimed to evaluate the therapeutic impact of SGLT-2 (sodium-glucose cotransporter-2) inhibitors on heart failure prognosis in patients with type-2 diabetes.

Methods:
We systematically explored PubMed/Medline, JSTOR, Google Scholar, and Cochrane Library for relevant randomized controlled trials published between January 2015 and April 2020, evaluating the effect of SGLT-2 inhibitors on cardiovascular outcomes. The main outcomes included (1) overall MACEs (MI, stroke, cardiovascular death), (2) overall CV death, (3) overall hospitalization for heart failure, (4) overall kidney outcomes (worsening kidney disease, need for dialysis or transplant, and death due to kidney disease), (5) adverse outcomes (each of genital infections, hypoglycemia, and amputation risk).

Results:
We extracted nine studies that included a total of 1,33,276 adult patients with type-2 diabetes and a predisposition for heart failure complications. Compared to placebo, patients receiving SGLT2 inhibitors had a lower incidence of MACE (OR: 0.80 [95% CI 0.71, 0.90]), cardiovascular deaths (OR: 0.85 [95% CI 0.77, 0.94]), worsening kidney disease, need for dialysis/transplant, death due to kidney disease (OR 0.65 [95% CI 0.48, 0.87]), and all-cause mortality (OR: 0.86 [95% CI 0.80, 0.94] p=0.0007). The patients on SGLT2 inhibitors did not experience a reportable reduction in genital infections, hypoglycemia, and amputation risk compared to placebo. The moderate heterogeneity of most studies was determined by their (31%-80%) I-square values.

Conclusions and Relevance:
This meta-analysis revealed moderately heterogeneous but statistically significant outcomes confirmed the role of SGLT-2 inhibitors in reducing the incidence of worsening kidney disease, all-cause mortality, overall kidney outcomes, hospitalization for heart failure, cardiovascular deaths, and overall MACEs in the setting of diabetes mellitus.
Abstract 12651: Non-Pharmacological Interventions to Improve Electrical Cardioversion Success in Patients With Atrial Fibrillation: A Scoping Review
Authors: Nguyen Stephanie T , Belley-cote Emilie P , Ibrahim Omar , Um Kevin J , Lengyel Alexandra , Qiu Yuan , Adli Taranah , Sibilio Serena , Wong Michael , Benz Alexander P , Wolf Alex , Nicola Whitlock , Acosta J. Gabriel , Healey Jeff S , Baranchuk Adrian , McIntyre William F
Published: April 2024

Introduction:
Electrical cardioversion is used commonly in patients with atrial fibrillation (AF). However, success rates vary and practical guidance is limited.

Methods:
We searched CENTRAL, Medline and EMBASE from inception to present and the grey literature. We included randomized controlled trials (RCTs) comparing any two interventions. Outcomes were initial and cumulative cardioversion success. We pooled data using random effects models.

Results:
From 13481 citations, we included 52 RCTs. Biphasic as compared to monophasic waveforms resulted in a higher rate of cardioversion for initial (18 studies, risk ratio [RR] 1.45, 95% confidence interval [CI] 1.10-1.90, I
2
=89%) and cumulative success (21 studies, RR 1.07, 95% CI 1.02-1.13, I
2
=75%). Fixed, maximum-energy shocks as compared to low-dose escalating energy protocols had a higher likelihood of initial (4 studies, RR 1.62, 95% CI 1.33-1.98, I
2
=72%) but not cumulative success (3 studies, RR 1.13, 95% CI 0.97-1.32, I
2
=86%). Initial or cumulative cardioversion success did not differ significantly for several other interventions. This included: antero-apical/lateral vs. anteroposterior positioned pads (initial: 10 studies, RR 1.06, 95% CI 0.89-1.27; cumulative: 13 studies, RR 0.99, 95% CI 0.95-1.04); rectilinear/pulsed biphasic vs. biphasic truncated exponential waveform (initial: 3 studies, RR 1.07, 95% CI 0.76-1.50; cumulative: 3 studies, RR 0.95, 95% CI 0.80-1.12); cathodal vs. anodal configuration (cumulative: 2 studies, RR 1.03, 95% CI 0.97-1.09); magnesium pre-treatment vs. none (initial: 2 studies, RR 1.36, 95% CI 0.82-2.24; cumulative: 2 studies, RR 1.05, 95% CI 0.96-1.14); and patches vs. manual pressure/paddles (initial: 2 studies, RR 1.04, 95% CI 0.26-4.12; cumulative: 2 studies, RR 0.87, 95% CI 0.61-1.25).

Conclusions:
Biphasic shock waveforms and high-energy shocks increase the efficacy of cardioversion of AF. Other interventions, including pad placement, biphasic waveform properties, electrode polarity, electrolyte pre-treatment, and manual pressure require further study.
Abstract 12755: Effects of Intravenously Delivered Extracellular Vesicles on Cardiac Function in Chemotherapy-Induced Cardiomyopathy
Authors: Desgres Manon , Autret Gwennhael , Petrusca Lorena , Lima Correa Bruna , Marigny Céline , Le Gac Line , Guillas Chloé , Tavitian Bertrand , Croisille Pierre , Silvestre Jean-Sébastien , Menasche Philippe
Published: April 2024

Introduction:
Extracellular Vesicles (EV) are increasingly recognized as key mediators of the effects of cellular therapy but repeated dosing is likely required for optimizing their therapeutic benefits. This, in turn, requires a noninvasive delivery route.

Hypothesis:
Repeated intravenous (IV) EV infusions might improve cardiac function in chemotherapy-induced cardiomyopathy.

Methods:
All EV were collected from human iPSC-derived cardiovascular progenitor cells.
In vitro experiments
: iPSC-derived cardiomyocytes were stressed 3 times by doxorubicin (Dox, 0.2 μM), once every 48 hours (D0, D2, D4), and then exposed to EV once (D6) or twice (D6 and D8). Outcomes were assessed on D8 and D10 on mitochondrial function and intracellular ATP levels assessed by the Seahorse XF Cell Mito Stress Test and ATPlite Luminescence Assay System, respectively.
In vivo experiments
: Male BALB/c mice were subjected to 3 weekly injections of Dox (total cumulated dose: 12 mg/kg) followed by 3 IV infusions of EV (10
9
per dose, n=11) or an equivalent volume of saline (n=14) over 1-2 weeks. The main outcome measure was Global Longitudinal Strain (GLS), a robust and early marker of LV dysfunction, blindly assessed by MRI at baseline and 8-11 weeks following the onset of Dox treatment. Explanted hearts were then processed for histology and transcriptomics.

Results:
Compared with Dox-stressed controls, EV increased ATP levels by 30%±8% (n=7, each in triplicate, p=0.047; m±SEM) and enhanced both mitochondrial respiration and anaerobic glycolysis.
In vivo
, GLS at baseline averaged -14.98±0.24. It was well preserved after EV treatment with a decrease at end-study of only 2.96%±7.18% from baseline while it fell by 11.90%±3.51% in PBS-injected controls. Similar patterns of changes were seen for longitudinal endocardial strain which declined by 0.22%±7.29% and 8.39%±3.42% from baseline in EV- and PBS-injected hearts, respectively, while the corresponding declines for epicardial strains were 3.92%±7.20% and 13.44%±3.28%. Basal global circumferential strain was also better preserved in EV-treated hearts.

Conclusions:
Repeated IV infusions of EV decrease chemo-triggered cardiomyocyte toxicities and help preserving cardiac function in chemotherapy-induced cardiomyopathy.