bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13138: Antioxidant-1, a Copper Transport Protein, promotes Inflammatory Neovascularization via Chaperone and Transcription Factor Function
Authors: Varadarajan Sudhahar , Chen Gin-Fu , Das Archita , Youn Seock-Won , Surenkhuu Bayasgalan , Cho Jaehyung , Christman John W , Shantikumar Saran , Angelini Gianni D , Emanueli Costanza , Ushio-Fukai Masuko , Fukai Tohru
Published: April 2024

Copper (Cu), an essential micronutrient, has been implicated in inflammation and angiogenesis with unknown mechanism. Cu transport protein, antioxidant-1 (Atox1) functions not only as Cu chaperone to activate secretory Cu enzymes (including lysyl oxidase (LOX)) via Cu transporter ATP7A, but also as Cu-dependent transcription factor. However, role of Atox1 in inflammatory neovascularization has not been investigated. Here we show that Atox1 expression is markedly upregulated in patients and mice with critical limb ischemia. Together with immunohistochemistry, micro-CT analysis and sponge implant assay, Atox1 KO mice exhibit impaired ischemia induced perfusion recovery, arteriogenesis/angiogenesis and inflammatory cell infiltration (46%). Furthermore, bone marrow (BM) reconstitution and adenovirus mediated Atox1 gene transfer in Atox1 KO mice show that Atox1 in tissue resident endothelial cells (ECs), but not in BM cells, is essential for neovascularization and recruitment of inflammatory cells which release angiogenic cytokines TNFα and VEGF. Mechanistically, Atox1 depletion of mice or ECs shows inhibition of ischemia (3.4-fold) and VEGF (1.6 fold) induced extracellular matrix/secretory Cu enzyme LOX activity in Cu/ATP7A-dependent manner, resulting in impaired (42%) capillary tube formation. Moreover, Atox1 knockdown in ECs inhibits ROS production (2.5 fold) and its downstream NFκB-DNA binding, VCAM1/ICAM1 expression and monocyte adhesion in ECs activated by TNFα, in Cu-dependent and ATP7A-independent manner, which are further supported by in vivo DHE staining and Bioluminescence imaging of NFκB reporter mice. Of note, Atox1 translocates to the nucleus (90%) in response to TNFα, thereby increasing transcription of p47phox NADPH oxidase by binding to its promoter in Cu-dependent manner. p47phox re-expression rescued reduced TNFα -induced VCAM1 expression in Atox1 KO ECs. In summary, Atox1 plays an important role in inflammatory neovascularization via Cu chaperone for LOX to increase angiogenesis as well as transcription factor for p47phox to promote ROS and inflammatory responses. Thus, Atox1 is a potential therapeutic target for promoting tissue repair in ischemic cardiovascular disease.
Abstract 13179: Bare Metal vs Drug Eluting Stent Choice: The Impact of Atrial Fibrillation and Setting of Care Among Medicare Beneficiaries
Authors: Dadekian Gregory A , Smith Jeremy , Morden Nancy E , Kaplan Aaron V
Published: April 2024

Background:
In treating coronary artery disease, many factors influence the choice of bare metal (BMS) or drug eluting stents (DES), including bleeding risk and suitability for prolonged dual anti-platelet therapy (DAPT). Atrial fibrillation (AF) further complicates this choice. We examined stent selection among Medicare beneficiaries by AF status to explore how cardiologists are managing this complex choice overall and how this choice varies across academic medical centers (AMC).

Methods:
Using a 100% Medicare denominator file and associated inpatient claims (2008-2012), we identified patients over age 65 receiving inpatient coronary artery stents. We measured BMS and DES use in AF and non-AF patients overall and assessed variation in stent choice across 50 high volume AMCs.

Results:
Overall, 1,269,239 stent procedures were studied. BMS, as a percent of total inpatient stents, declined from 2008 to 2012 in AF (41% to 34%) and non-AF (30% to 21%) patients. Across high volume AMCs in 2012, the proportion of stent patients receiving BMS (5th to 95th percentile) ranged from 15% to 63% in AF patients and from 8% to 37% in non-AF patients. In 2012, the AMC-level difference in BMS stent use by AF status (proportion of BMS among AF patients minus proportion BMS in non-AF patients) ranged from 4% to 35% (5th to 95th percentile).

Conclusions:
Among stent recipients, AF patients are more likely to receive BMS than non-AF patients but treatment varies widely across AMCs, suggesting a lack of consensus. Studies of stent choice and outcomes among AF patients are needed to guide care decisions and optimize outcomes.
Abstract 13387: Effect of Ranolazine on the Incidence of Atrial Fibrillation Following Cardiac Surgery
Authors: Bekeith Soad , Meghani Mustafain , Shariff Masood A , Asti Deepak , Nalluri Nikhil , Agarwal Vratika , Shah Neeraj , Soomro Armaghan , Khan Muzaffar , Spagnola Johnathan , Chan Carmen , Quattrocchi Elaena , Youssef Elias , Nabagiez John P , McGinn Joseph T
Published: April 2024

Introduction:
Atrial fibrillation (AF) is common following cardiac surgery. Reduction of postoperative AF would decrease average length of stay and improve patient outcomes. Ranolazine has been shown to prevent AF by increasing postrepolarization refractoriness in atrial tissue. This study evaluates prophylactic ranolazine on postoperative AF in cardiac surgery.

Hypothesis:
To assess the effect of ranolazine as a selective atrial sodium channel blocker on prevention of AF following cardiac surgery.

Methods:
This double blinded, randomized trial assessed primary prevention of postoperative AF with ranolazine in patients undergoing coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) from 2012-13. Mitral valve surgery was an exclusion criterion. Fifty-four patients were randomly allocated to twice daily ranolazine 1000 mg (n=27) or placebo (n=27) 48 hours prior to surgical intervention and postoperatively for 14 days. Cardiac monitoring for arrhythmias was continued for 2 weeks post discharge using Holter monitor. The primary endpoint was AF up to postoperative day 14. Secondary endpoints included 30 day readmission, complications, and length of stay. (ClinicalTrials.gov: NCT01590979).

Results:
Fifty-one patients completed the study to 30 days postoperatively. Cohort mean age was 64.3±11.4 years, females were 10(19%), mean ejection fraction was 46.4±14.6%, hypertension 48(89%), dyslipidemia 32(59%) and diabetes 22 (41%), with no difference between the groups. Patients underwent isolated CABG (44, 81%), AVR (4, 7%) and combined AVR/CABG (3, 6%). The incidence of AF was 24%, control 8 (30%) and treated 5 (19%) groups, a 38% reduction, not statistically significant (p=0.530). QT duration was longer in the ranolazine group (p=0.014). The length of stay of patients who developed AF was significantly longer (8.3±5.0 vs. 5.4±2.7, p=0.009), with no drug related adverse events.

Conclusion:
This study illustrates the prevalence of AF following cardiac surgery. Ranolazine is an antianginal medication that can be used safely in patients to reduce postoperative AF. In conclusion, this study showed a reduction in the incidence of AF by 38%. Although not statistically significant, this indicates a trend towards our hypothesis.
Abstract 13402: Selection of Stent Types Among AMI patients With Atrial Fibrillation: National Patterns From NCDR ACTION Registry - GWTG 2008-2014
Authors: Vora Amit N , Wang Tracy Y , Li Shuang , Chiswell Karen , Hess Connie N , Rao Sunil V , Peterson Eric D
Published: April 2024

Background:
Patients receiving an oral anticoagulant on top of dual antiplatelet therapy are known to be at high risk for bleeding events; thus the selection of drug-eluting stents (DES) versus bare metal stents (BMS) can have important implications for acute MI patients with atrial fibrillation (AF).

Methods:
From the NCDR ACTION Registry - GWTG, we identified 14,427 AF patients presenting with acute MI undergoing PCI from 2008-2014. Temporal trends and hospital variation in DES use were examined as were patterns of use by stroke risk (CHA
2
DS
2
-VASc) and bleeding risk (ATRIA).

Results:
Overall, DES was used in 58.9% of MI patients with AF. This rate increased from 47.1% in 2008 to 67.9% in 2014 (p<0.001). Use of DES vs BMS varied widely among hospitals (median 60% DES implantation, interquartile range 50% - 74%) (Figure). Relative to BMS patients, those receiving DES were younger (median age 72 years vs. 75 years) but had more comorbidities such as diabetes, dyslipidemia, prior MI, and prior revascularization (all p<0.001). DES placement was more common than BMS placement among patients at high stroke risk (CHA
2
DS
2
-VASc ≥ 2) and high bleeding risk (ATRIA ≥ 4) (59% and 56%, respectively, p<0.01 for both) Although aspirin and a P2Y12 inhibitor were prescribed in >95% of all patients, warfarin was prescribed at discharge less frequently among patients receiving DES than BMS (31% vs. 39%, p<0.001)

Conclusions:
Use of DES among MI patients with AF has increased over time, yet substantial hospital-level variation is observed. Patients with AF meeting indication for anticoagulation are still more likely to receive DES than BMS, even among those at both high predicted stroke risk and bleeding risk. Those with AF receiving DES were however less likely to receive warfarin therapy.
Abstract 13425: Low Income Patients With Myocardial Infarction Are Less Likely to Receive a Drug Eluting Stent Than Patients From High Income Areas
Authors: Fiser Wesley , Mazhari Ramesh , Nagy Christian , Young Heather , Reiner Jonathan
Published: April 2024

Introduction:
Choosing a bare metal stent (BMS) vs a drug eluting stent (DES) during STEMI intervention is an important and complex decision that must be made quickly. The on-call physician who is often unfamiliar with the patient (pt) must incorporate both qualitative and quantitative medical factors, as well as estimate the pt's ability to adhere to a prolonged dual antiplatelet strategy. We examined disparities between device allocation (BMS vs DES) and pt socio-demographic factors in a diverse population treated at an urban hospital.

Hypothesis:
Patient socioeconomic status is an influential factor in stent selection during STEMI.

Methods:
Records from 332 consecutive pts undergoing percutaneous coronary intervention for STEMI were retrospectively reviewed. Demographic data included: age, gender, ZIP code, stent type, self-identified race, and health insurance status. Logistical regression models were used to identify significant co-variables.

Results:
The mean age was 55.5 yrs (42% African American (AA), 45% White (W), 13% other). Of the 332 pts, 176 (53%) received BMS and 140 (42%) received DES; and 49% of W pts received DES vs 33% AA (adj OR 0.74, CI 0.41-1.31). Using 2010 U.S. Census Bureau data, median household income (inc) was estimated using home ZIP code (range $21,633-$214,219), and pts were then stratified into inc quartiles. Compared to the highest inc quartile, pts in the lowest quartile were more likely to be AA (72% vs 20%,
p
<0.0001) and female (34% vs 16%,
p
=0.01). Nearly all patients were insured (93%), with no differences among inc groups. Strikingly, pts residing in the highest inc quartile were significantly more likely to receive a DES than those residing in the lowest inc quartile (57% vs 33%, adj. OR 2.67, 95% CI 1.27-5.63,
p
=0.004). The impact of inc on stent choice was strongest with AA (adj. OR 4.37, 95% CI 1.20-15.93,
p
=0.008), compared to W (adj. OR 1.15, 95% CI 0.34-3.92,
p
=0.32). Gender, age, and insurance status did not influence stent choice.

Conclusions:
DES were less frequently implanted in STEMI pts residing in low inc areas, suggesting that quickly made, non-quantitative, socioeconomic assessments may have important ramifications in stent selection. The fact that this effect was primarily seen in AA pts warrants further evaluation.
Abstract 13539: Functional Evaluation in Aortic Stenosis: Determinant of Exercise Capacity
Authors: Bandera Francesco , Generati Greta , Pellegrino Marta , Labate Valentina , Carbone Francesco , Alfonzetti Eleonora , Guazzi Marco
Published: April 2024

Background:
Aortic stenosis (AS) is clinically characterized by dyspnea and intolerance to exercise. Clinical interpretation of such symptoms is often difficult due to the advanced age of AS patients. We aimed at identifying cardiac determinants of exercise intolerance in AS (Aortic Vmax >3 m/s). Methods and results: We performed cardiopulmonary exercise test (CPET) simultaneously combined with exercise echocardiography in 43 patients with AS referred for functional assessment. Severe AS were evaluated because of symptoms not certainly related to valvular disease. Patients underwent a symptoms-limited maximal exercise, considering the 75% of predicted VO2 consumption as a marker of preserved functional capacity. Twenty-three patients had preserved functional capacity (group A), showing higher work, maximal VO2, O2 pulse and better VE/VCO2 and heart rate recovery. No differences were found in terms of rest systolic function and AS severity, while group A had higher peak heart rate (HR), higher peak cardiac power output (cardiac output x systolic pressure) and higher peak-rest transaortic mean gradient difference (ΔMG). At multivariate analysis, only ΔMG resulted independently associated with impaired functional capacity (p =0.048; CI 1.001-1.323). Conclusions: AS patients can present functional impairment which is related to cardiac response to exercise rather than to stenosis severity. These results suggest the role of inotropic and contractile reserve supporting the routinely evaluation of cardiac reserve as a determinant of symptoms development.
Abstract 13582: Fetal Cardiac Intervention for Hypoplastic Left Heart Syndrome With Intact or Restrictive Atrial Septum: A Report From the International Fetal Cardiac Intervention Registry
Authors: Jantzen David , Moon-Grady Anita J , Armstrong Aimee , Berg Christoph , Dangel Joanna , Fifer Carlen , Frommelt Michele , Gembruch Ulrich , Herberg Ulrike , Jaeggi Edgar , Kontopoulos Eftichia , Miller Owen , Morris Shaine A , Oberhoffer Renate , Pedra Carlos , Pedra Simone , Quintero Ruben , Gelehrter Sarah
Published: April 2024

Background:
Fetal cardiac intervention (FCI) for fetuses with hypoplastic left heart syndrome with restrictive or intact atrial septum (HLHS/IAS) has been reported in single-institution series as a modality that may improve outcomes in a high-risk subset of HLHS patients who historically have very high neonatal mortality.

Methods:
The International Fetal Cardiac Intervention Registry was established in 2010. For this descriptive analysis, the database was queried for fetuses with HLHS/IAS. Maternal-fetal dyads from 2001 through March 2015 were included.

Results:
Data from 15 institutions were submitted by data harvest. Of 87 cases of HLHS/IAS entered, 46 cases from 8 sites underwent FCI: 27 with atrial septal perforation/ balloon dilation and 19 with atrial septal stent placement. There were 34 procedural successes with a similar success rate between stents and balloons dilations (12/19=63% stent, 22/27=81% balloon dilation, p=0.19). Fetal complications were common (64% of cases), most frequently a pericardial effusion requiring treatment (51%), but no maternal complications. Procedure-related fetal demise occurred in 6 (13%). Seventeen had a clinical success (atrial septum not requiring urgent intervention at delivery), which was more likely in fetuses with a successful stent (75% stent vs 36% balloon dilation, p=0.03). Delivery by scheduled Cesarean section to facilitate immediate post-natal intervention was less common in those who underwent successful FCI compared with those with unsuccessful FCI or no FCI (3/34=8% FCI vs 18/46=39%, p=0.002). There was a trend toward improved survival to discharge for liveborn infants with HLHS/IAS in those who underwent successful FCI compared with those with unsuccessful FCI or no FCI (16/34=47% FCI vs 13/46=28%, p=0.10). Survival to hospital discharge was greater in those with clinical success compared to a procedural success but no clinical success (71% vs 24%, p=0.01).

Conclusion:
The early multicenter experience of FCI for HLHS/IAS has good procedural success, with atrial septal stent placement more likely to result in clinical success at delivery. There was a trend toward better survival if FCI was successful, and significantly improved survival if FCI resulted in clinical success at delivery.
Abstract 13670: Vitamin D Deficiency is Associated With Increased Risk of Subclinical Myocardial Damage in Younger but not Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Michos Erin D , Selvin Elizabeth , Misialek Jeffrey R , McEvoy John W , Ndumele Chiadi E , Folsom Aaron R , Gross Myron D , Ballantyne Christie M , Lutsey Pamela L
Published: April 2024

Background:
Vitamin D deficiency has been associated with increased risk of coronary heart disease (CHD) and heart failure (HF) in epidemiologic studies. It is unknown whether low 25-hydroxyvitamin D [25(OH)D] is associated with subclinical myocardial damage as assessed by high-sensitivity cardiac troponin T (hs-cTnT), and whether this association varies by age or race.

Methods:
We studied 11,311 white and black ARIC participants (median age 56 yrs) free of prevalent CHD and HF who had 25(OH)D and cTnT measured at baseline (1990-1992). 8,990 participants had a repeat hs-cTnT measurement 6 years later (1996-1998). We used logistic and Poisson regression models to characterize the cross-sectional association of 25(OH)D categories with elevated hs-cTnT (≥14 ng/L) and the prospective association with incident elevated cTnT at followup (among those without elevated hs-cTnT at baseline, n=8733). We tested for interaction by age and race.

Results:
The prevalence of elevated hs-cTnT at baseline was 4% (n=433). After adjustment for age/sex/race, 25(OH)D deficiency (<20 ng/ml) was cross-sectionally associated with elevated hs-cTnT [OR 1.35, 95% CI 1.01-1.81]; however findings were no longer significant after adjustment for behavioral/lifestyle factors [OR 1.17, 0.87-1.59]. At followup, there were 517 cases of incident elevated hs-cTnT. 25(OH)D was not associated with incident troponin elevation in the overall cohort, but significant interactions were present by age (p-interaction 0.01). Low 25(OH)D was associated with incident elevated hs-cTnT in younger but not older adults (
Table
). There were no interactions by race.

Conclusions:
The association of low 25(OH)D with incident elevated hs-cTnT varies by age. If these associations are causal, further research is needed to understand mechanisms by which low 25(OH)D confers subclinical myocardial damage among younger but not older adults and whether vitamin D supplementation can prevent myocardial damage.
Abstract 13674: Feedback Regulation of Cholesterol Metabolism by Lexis, a Lipid-responsive Non-coding RNA
Authors: Sallam Tamer , Jones Marius , Gilliland Thomas , Li Zhang , Wu Xiaohui , Eskin Ascia , Sandhu Jaspreet , Casero David , Vallim Thomas , Cynthia Hong , Tontonoz Peter
Published: April 2024

The LXR and SREBP transcription factors are key regulators of cellular and systemic cholesterol homeostasis in animals. The molecular mechanisms that integrate these pathways are incompletely understood. Here we show that ligand activation of LXR in liver not only promotes cholesterol efflux, but also simultaneously inhibits the cholesterol biosynthesis pathway. We further identify the long non-coding RNA LeXis as an unexpected mediator of this effect. LeXis is the most robustly induced transcript in mouse liver in response to western diet feeding or pharmacologic LXR activation. Tissue-specific overexpression of LeXis inhibits liver cholesterol biosynthesis and lowers plasma cholesterol levels. Reciprocally, knockdown of LeXis increases hepatic cholesterol content and raises plasma cholesterol levels. These studies outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms by which LXRs orchestrate systemic sterol homeostasis.
Abstract 13679: Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography is Associated With Impaired Coronary Flow Reserve From Diffuse versus Obstructive Coronary Artery Disease
Authors: Taqueti Viviany R , Shaw Leslee J , Murthy Venkatesh L , Shah Nishant R , Foster Courtney R , Hainer Jon , Blankstein Ron , Dorbala Sharmila , Di Carli Marcelo F
Published: April 2024

Introduction:
Case fatality rates for cardiovascular disease (CVD) are higher for women of all ages as compared with men, yet obstructive coronary artery disease (CAD) is less prevalent in women. Coronary flow reserve (CFR) is an integrated measure of large and small vessel CAD and myocardial ischemia, and identifies patients at risk for CVD death, independently of angiographic disease severity.

Methods:
Consecutive patients (N=329, 43% women) referred for invasive coronary angiography after stress testing with myocardial perfusion PET and with LV ejection fraction >40% were followed (median 3.0 years) for CVD death, nonfatal MI, or heart failure admission. The extent/severity of angiographic CAD was estimated using the CAD prognostic index (CADPI), and CFR quantified using PET.

Results:
Although women relative to men had lower pretest clinical scores, rates of prior MI, and burden of angiographic CAD (p<0.001), they demonstrated greater risk of CVD events (adjusted HR 2.05, 95%CI 1.05-4.02, p=0.03), even after adjustment for clinical risk factors, LV ejection fraction and ischemia, angiographic disease and time-dependent early revascularization. Impaired CFR was similarly present among women and men, but in patients with low CFR (<1.6, n=163), women showed higher frequency of nonobstructive CAD, while men showed higher frequency of severely obstructive CAD (p=0.002). After also adjusting for CFR (adjusted HR for unit decrease in CFR, 1.69; 95%CI 1.04-2.76, p=0.03), the effect of sex on outcomes was no longer significant (p=0.10). When stratified by sex and CFR (Figure), only women with impaired CFR demonstrated significantly increased adjusted risk of CVD events (p<0.0001, model p for interaction=0.04).

Conclusions:
Although women referred for coronary angiography had significantly lower burden of obstructive epicardial CAD relative to men, they were not protected from CVD events. Impaired CFR from diffuse CAD may represent a target for CVD risk reduction.
Abstract 13694: Hsf1 Attenuates Pressure Overload Induced-cardiac Fibrosis via Inhibiting Smad3 Phosphorylation and Nuclear Translocation
Authors: Zhou Ning , Ye Yong , Wang Xingxu , Wu Jian , Li Lei , Wang Dao Wen , Zou Yunzeng
Published: April 2024

Introduction:
Heat shock transcription factor 1 (HSF1) is an intrinsic cardioprotective factor against cardiac hypertrophy. However, little is known about the role of HSF1 in cardiac fibrosis. Here we hypothesize that HSF1 reverses pressure overload induced-cardiac fibrosis via inhibiting Smad3 phosphorylation and nuclear translocation.

Methods:
Human tissue samples were collected from the left ventricles of dilated cardiomyopathy patients undergoing heart transplant and normal heart donors for control and were interrogated via western blot and realtime-PCR. A HSF1 transgenic (TG) mouse was generated. Transverse aortic constriction (TAC) was performed with wild type (WT) mice as control and cardiac structure and function were measured by echocardiography and pathological test. Cardiomyocytes (CMs) isolated from neonatal mice were imposed with mechanical stretch (MS) in vitro.

Results:
HSF1 phosphorylation at Ser230 was significantly decreased in failing hearts (55% vs normal hearts) characterized with significant cardiac fibrosis manifested with increased expression of collagen III and connective tissue growth factor (CTGF) . WT mice and TG mice were subjected to TAC. After 4 weeks of TAC, WT mice developed a remarkable maladaptive hypertrophy and cardiac fibrosis in comparison to WT mice. TG mice exhibited a smaller LV end-diastolic diameter (LVEDD), higher ejection fraction (EF), decreased LV weight/tibial length (LW/TL) and CMs cross sectional area (CSA), less interstitial and perivascular fibrosis, as well as preserved expression of collagen III and CTGF compared to WT mice. TG mouse hearts also showed reduced phosphorylation and nuclear translocation of Smad3 than WT mice. MS was found to significantly inhibit HSF1 phosphorylation, but promoted the Smad3 phosphorylation and nuclear translocation in CMs. Co-Immunoprecipitation showed that HSF1 directly binds Smad3 in CMs in vitro, which was decrease by MS or treatment with KNK437 (HSF1 inhibitor). TG mice demonstrate more of HSF1 and Smad3 binding and less phosphorylation and nuclear translocation of Smad3 compared to WT mice after TAC.

Conclusion:
HSF1 attenuates pressure overload induced-cardiac fibrosis by inhibiting Smad3 phosphorylation and nuclear translocation.
Abstract 13739: Progression of Mitral Stenosis in Patients With Severe Mitral Annular Calcification and Chronic Kidney Disease
Authors: Tsutsui Rayji S , Popovic Zoran B
Published: April 2024

Background:
Severe mitral annular calcification (MAC) is recognized as a rare cause of mitral stenosis. However, little is known regarding its relationship with chronic kidney’s disease (CKD). We evaluated progression of mean mitral valve (MV) gradients and the right ventricular systolic pressures (RVSP) over time in patients with CKD.

Methods:
Database for the years 1996 through 2013 was searched for patients with severe MAC. MAC was graded in a semi-quantitative manner. Patients were included if they had severe MAC at their index study, had ≥ 2 studies in the period of ≥ 2 years, and had glomerular filtration rate estimated ≤ 3 months from the index study. Patients with prior MV surgery, rheumatic heart disease, or other MV disease were excluded. CKD was classified by 5 conventional stages. The slope of regression line using all studies of a given patient was used to determine the progression rate.

Results:
924 patients (7002 studies) were included. Data are expressed as mean ± standard deviation. Study population age was 72 ± 11 years. Follow up time was 4.8 ± 2.8 years. Number of echocardiograms performed per patient was 8 ± 5. Index MV gradient was 3.9 ± 3.2 mmHg with progression rate 0.13 ± 0.86 mmHg / year (p = 0.0001). Index RVSP was 39 ± 15 mmHg with progression rate 0.97 ± 4.49 mmHg / year (p = 0.0001). Progression appeared slower in younger (<65, n=189) than older (≥65, n = 735) patients (MV gradient p=0.07, RVSP p= 0.10). 66 patients had MV surgery with MV gradient at the time of surgery being 13.76 ± 4.15 mmHg. There were no significant differences in the progression rate among CKD stages (MV gradient p = 0.11, RVSP p = 0.87) or with dialysis status (n=41, MV gradient p= 0.50, RVSP p= 0.13).

Conclusion:
While there tended to be faster rate of progression of mitral stenosis in older patients with severe MAC, CKD class was not a differentiating factor. It appears that mitral stenosis in patients with severe MAC progress more in older patients but not necessarily in patients with poor kidney function.
Abstract 13892: Incidence and Risk Factors of Restenosis, and Its Impact on Blood Pressure Control After Percutaneous Transluminal Renal Angioplasty in Patients With Renovascular Hypertension
Authors: Iwashima Yoshio , Fukuda Tetsuya , Yoshihara Fumiki , Kusunoki Hiroshi , Kishida Masatsugu , Hayashi Shin-ichirou , Nakamura Satoko , Kamide Kei , Horio Takeshi , Kawano Yuhei
Published: April 2024

Background:
Percutaneous transluminal renal angioplasty (PTRA) is one of the standard treatments for renal artery stenosis (RAS). Restenosis after PTRA may influence disease prognosis, but little is known about its frequency, risk factors, or impact on blood pressure control.

Methods:
This study included 175 renovascular hypertensive patients (mean age= 59.6 years; 33.7% women; 30.3% fibromuscular dysplasia [FMD]) with 207 treated renal arteries and were followed more than 12 months after PTRA. Data including blood pressure (BP), antihypertensive medication, and duplex ultrasonography (DUS) was collected before and 12 months, and then yearly after PTRA. Cure of hypertension was defines as a BP below 140/90mmHg without antihypertensive medication. Diagnosis of restenosis was based on DUS, by applying a renal aortic ratio >3.5 in conjunction with a renal artery peak systolic velocity > 250cm/s.

Results:
At 12 months after PTRA, the cumulative incidence of restenosis was 35 (20.0%). We divided the total patients into four groups on the basis of cause of RAS; FMD or atherosclerotic RAS (ARAS), and the absence/presence of restenosis, and found that the decrease in systolic BP (F=3.10, p<0.05) as well as cure of hypertension (F=6.96, p<0.01) were significantly different among the subgroups. Decrease in systolic BP (-31±19 vs -12±25mmHg, p<0.05) as well as cure of hypertension (36.4 vs 5.0%, p<0.01) were significantly greater in FMD patients without restenosis than those with restenosis; whereas no significant difference was found in patients with ARAS. During a median follow-up of 4.0 (IQR, 1.2-8.0) years, 56 patients (32.0%) developed restenosis. In multivariate Cox regression analysis, FMD was an independent predictor of restenosis (hazard ratio [HR] 2.65, p=0.02). We then divided total patients into two groups according to the cause of RAS, and found that statin use (HR 0.50) in FMD, and the presence of previous cardiovascular disease (HR 2.88) as well as severe RAS (≥90%) (HR 3.30) in ARAS were significant predictors of restenosis (p<0.05, respectively).

Conclusions:
Incidence of restenosis after PTRA was higher in FMD than in ARAS among renovascular hypertensive patients. Assessment of restenosis is important for treatment success, especially for FMD.
Abstract 14041: Caring for Infants With Complex Single Ventricle: Impact on Families
Authors: Uzark Karen , Sagi Janaki , Yu Sunkyung , Donohue Janet , Valentini Alicia , Zitterman Veronica , Gelehrter Sarah
Published: April 2024

Objective:
Outcomes for infants with single ventricle (SV) heart defects have steadily improved in recent decades, but there is still significant mortality and morbidity during the interstage period between stage 1 Norwood hospitalization discharge and stage 2 palliation at 4-6 months of age. The impact on families during this period of infant home surveillance is unknown. The aim of this study was to evaluate parental quality of life (QOL) and family functioning among parents of infants with SV during the interstage period.

Methods:
Parents (n= 32) completed the PedsQL Family Impact Module (FIM) via a web link or by telephone at 6 weeks post Norwood discharge and again prior to Stage 2 surgery. Higher scores indicate less negative impact. Data were compared to published norms for a Midwestern community sample of parents.

Results:
Median age at Norwood was 5 days (range 1-50) with a median hospital length of stay (LOS) of 28.5 days (range 14-102). Total FIM, family functioning, and parental QOL scores were not significantly lower than community norms. Across scales however, the SV parents had significantly worse scores related to worry (64.4 ± 20.6 vs 78.1 ± 20.1, p<.001), communication (74.0 ± 23.5 vs 81.9 ± 17.7, p=0.01) and daily activities (53.6 ± 30.2 vs 63.2 ± 22.5, p=0.02) at 6 wks. Interestingly, the mean scale score for family relationships was significantly higher in the SV parents than community norms at 6 wks (82.7 ± 14.4 vs 67.0 ± 19.4, p<.001) and pre-Stage 2 (76.3 ± 21.6 vs 67.0 ± 19.4, p=0.01). There was no significant change in any FIM scale scores between 6 wk and pre-Stage 2 assessments except parental physical functioning scores declined (p=0.004).Total FIM, including parental QOL and family functioning scores, were not significantly associated with Norwood hospital LOS. Most parents (97%) reported daily monitoring of their infant’s oxygen saturation at home was helpful and 22% felt monitoring decreased their stress.

Conclusion:
Care of an infant with SV has a significant impact on families throughout the interstage period with improved outcomes related to supportive family relationships. Home monitoring by parents with ongoing assessment of family concerns by healthcare providers may further support families caring for infants with single ventricle.
Abstract 14183: Adult Outcomes in Tetralogy of Fallot Repair With Pulmonary Annular Preserving Technique
Authors: Ducas Robin A , Harris Louise , Wald Rachel , Kayedpour Camilla , Krishna Kumar Nair Govind , Hickey Edward , Silversides Candice
Published: April 2024

Background:
Tetralogy of Fallot (ToF) is the most common cyanotic congenital lesion. The original ToF repair involved patching the pulmonic annulus (TAP); resulting in chronic severe pulmonic regurgitation. To prevent pulmonary regurgitation and its late sequelae, the pulmonary annulus preserving technique (ToF-AP) was developed. Outcomes in the adult population with ToF-AP have yet to be characterized.

Methods:
This was a retrospective study of all adults (birthdate 1982-1996) with childhood repair of ToF followed at our center. We excluded patients with ToF pulmonary atresia, atrioventricular canal defect, absent pulmonary valves, or conduit repair. The primary (composite) cardiac events of interest included death, ventricular arrhythmia, congestive heart failure or cerebrovascular accident. Secondary outcomes included atrial arrhythmia, pulmonary valve replacement (PVR), ventricular function, and exercise capacity. A log rank test was used to determine differences in the primary endpoint between adults with ToF-AP and TAP.

Results:
A total of 206 adults were included; 94 with ToF-AP [25± 4years] and 112 with TAP [25±5 years]. The average age at primary repair was 30 months, and approximately 30% of patients in both groups had a previous palliative shunt. There was a trend toward less adverse cardiac events in ToF-AP vs TAP group (1% vs. 6%, p=0.075). There was 1 death in the ToF-AP and 2 in the TAP group. Atrial arrhythmias occurred in 4% ToF-AP vs. 7% of the TAP group (p=0.55). At last follow up, preserved right ventricular systolic function by echocardiography was more common in the ToF-AP vs. TAP group (50% vs 32%, p=0.008). There was no difference in maximal predicted VO2 between groups (69% ToF-AP vs. 65% TAP). Fewer patients with ToF-AP underwent PVR in adulthood compared to TAP. (11% vs. 39%, p<0.001). Similarly, over a lifetime, PVR was less common in patients with ToF-AP vs TAP (17% vs. 64%, p<0.001).

Conclusion:
While most young adults with TOF do well, there is a subset of patients with complications. Cardiac complications in adults with ToF-AP are less frequent compared to those with TAP. Adults with ToF-AP are almost 4 times less likely to undergo PVR in childhood or early adulthood compared to patients with TAP.
Abstract 14242: Clinical Impact of Previous Ischemic or Hemorrhagic Stroke on the Intracranial Event in Japanese Patients With Atrial Fibrillation: The Fushimi AF Registry
Authors: An Yoshimori , Ishii Mitsuru , Unoki Takashi , Iguchi Moritake , Masunaga Nobutoyo , Ogawa Hisashi , Wada Hiromichi , Hasegawa Koji , Esato Masahiro , Chun Yeong-Hwa , Abe Mitsuru , Akao Masaharu ,   Fushimi AF Registry Investigators
Published: April 2024

Introduction:
Little is known about the risk factors for each of ischemic and hemorrhagic stroke in patients with atrial fibrillation (AF).

Methods:
The Fushimi AF Registry, a community-based survey, was designed to enroll all of the AF patients who visited the participating institutions in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,499 patients by April 2015 (median follow-up period: 849 days). We explored the predictors for each of ischemic and hemorrhagic stroke, especially focusing on previous ischemic or hemorrhagic stroke.

Results:
The mean age was 73.6±10.9 years. The mean CHADS2, CHA2DS2-VASc and HAS-BLED scores were 2.01, 3.35 and 1.49, respectively. 53.5% of patients received oral anticoagulation (OAC) at baseline. Ischemic stroke occurred in 132 patients (3.8%) and hemorrhagic stroke in 42 (1.2%). On multivariate analysis, the independent predictors for ischemic stroke were as follows: advanced age (≥75 years) (hazard ratio [HR]: 2.37, 95% confidence interval [CI]: 1.63-3.53), sustained (persistent or permanent) AF (HR: 1.51, 95% CI: 1.05-2.23) and previous ischemic stroke (HR: 2.23, 95% CI: 1.54-3.19). As for hemorrhagic stroke, the independent predictor was previous hemorrhagic stroke (HR: 4.96, 95% CI: 1.19-13.8), whereas either of hypertension, previous ischemic stroke or OAC prescription was not.

In patients with versus without previous ischemic stroke, the annual incidence of ischemic stroke was higher (3.55% vs. 1.35%; p<0.01), but that of hemorrhagic stroke was similar (0.58% vs. 0.53%; p=0.81). This was also the case with patients with versus without previous hemorrhagic stroke; the incidence of hemorrhagic stroke was higher (2.67% vs. 0.51%; p<0.01), and that of ischemic stroke was similar (1.78% vs. 1.73%; p=0.99)
(Figure)
.

Conclusions:
The risk of stroke in patients with AF was dependent on the type of stroke. The history of ischemic or hemorrhagic stroke was a risk of the same type of stroke, but not of the other one.
Abstract 14267: Clinical Characteristics of Patients With Out-of-hospital Cardiac Arrest Caused by Ventricular Fibrillation due to Acute Coronary Syndromes Who Responded to Extracorporeal Cardiopulmonary Resuscitation
Authors: Hosoda Hayato , Tahara Yoshio , Nakashima Takahiro , Noguchi Teruo , Yasuda Satoshi , Ogawa Hisao , Morimura Naoto , Nagao Ken , Asai Yasufumi , Yokota Hiroyuki , Hase Mamoru , Atsumi Takahiro , Sakamoto Tetsuya ,   SAVE-J Study Group
Published: April 2024

Background:
Extracorporeal cardiopulmonary resuscitation (ECRP) have been reported to be effective in patients with out-of-hospital cardiac arrest (OHCA) associated with an initial rhythm of ventricular fibrillation (VF) caused by acute coronary syndromes (ACS) refractory to conventional cardiopulmonary resuscitation (CPR). However, the clinical characteristics of patients who best respond to ECRP remain unclear.

Methods:
Between 2008 and 2012, we prospectively collected Utstein-style data at 46 institutions on 454 consecutive patients with OHCA aged 20 to 74 years had an initial rhythm of VF and arrived at the hospital within 45 minutes after the onset of cardiac arrest. They did not respond to conventional CPR given for more than 15 minutes after hospital arrival and received combination therapy with ECPR, percutaneous coronary intervention (PCI), intra-aortic balloon pumping (IABP), and therapeutic hypothermia (TH). ACS was diagnosed on emergency coronary angiography or clinical course in 133 patients. These patients were classified according to whether neurologic outcomes at 6 months, i.e., good outcome group (cerebral performance category [CPC] = 1 to 2) or poor outcome group (CPC = 3 to 5). Demographic characteristics were compared between two groups.

Results:
Among the 133 ACS patients given ECPR, good neurologic outcomes at 6 months in 14 (11%) patients, but not in 119 (89%) patients. There were no significant differences of age, the rate of witnessed arrest, bystander CPR, TH and time from hospital arrival to PCPS start between the 2 groups. Good outcome group had a shorter time from cardiac arrest to hospital arrival (24.9± 8.6 vs. 29.5± 10.1 min, p=0.03) and time from cardiac arrest to PCPS start (44 ± 8.8 vs. 53.7 ± 15.9 min, p=0.01) than poor outcome group.

Conclusions:
Our results suggest that shortening the interval from cardiac arrest until PCPS start, especially until hospital arrival, may improve neurologic outcomes in patients with refractory VF caused by ACS.
Abstract 14296: Site-targeting Nitroglycerin Nanotherapeutic for Local Immunosuppression Without Induction of Tolerance
Authors: Ardekani Soroush , Eum Shane , Scott Harry A , Gupta Sharad , Yang Xiao , Brunelle Alex R , Wilson Sean M , Mohideen Umar , Ghosh Kaustabh
Published: April 2024

Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration.

Our findings reveal that NTG significantly inhibits human monocyte adhesion to NO-deficient human microvascular ECs in vitro (EC50 = 0.64 uM) through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamelar lipid nanoparticles that were ~150 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced an approximately two orders of magnitude greater anti-inflammatory effect than free NTG while preventing excessive mitochondrial superoxide production and loss of arterial vasorelaxation associated with high NTG doses. Finally, to facilitate targeting of NTG-NL to inflamed ICAM-1-expressing vessels, we have tethered a non-immunogenic fragment of ICAM-1 antibody to the surface of NTG-NL. Our preliminary in vitro studies show that NTG-NL modified with anti-ICAM-1 fragment exhibits 6-fold greater binding to inflamed (ICAM-1-expressing) ECs than to normal ECs. Thus, by identifying the superior therapeutic effects of NTG nanoformulation and conferring potent site-targeting capability to it, this study provides the rationale for detailed investigation of NTG nanotherapeutic as a potentially superior anti-inflammatory therapy.
Abstract 14630: Elevated CETP Activity is Associated With Low, Dysfunctional HDL in High Cardiovascular Risk South Asians
Authors: Melone Michelle , Rashid Shirya
Published: April 2024

Background and Rationale:
Low HDL in South Asians (SA) contribute greatly to their high coronary heart disease (CHD) risk relative to European Caucasians (EC), however, the cause of low HDL in SA is unknown. Here we investigated whether cholesteryl-ester transfer protein (CETP) plays a role in mediating low HDL in SA.

Methods:
Serum was obtained from metabolically well characterized individuals of SA and EC descent (N=244 and 238, respectively) and measured for CETP activity. HDL lipid and protein contents were quantified and HDL size and particle number were measured via NMR. The capacity of HDL to mediate cholesterol efflux was assessed in J774 macrophages with apoB-depleted patient serum.

Results:
CETP activity was elevated in SA compared with EC (26.5±0.45 vs. 18.5±0.45 pmol/uL/hr, P< 0.0001). HDL from SA was pro-atherogenic - that is, triglyceride-enriched, cholesteryl ester-depleted, reduced in apoAI and smaller in size than in EC (P< 0.05 for all). SA HDL, moreover, showed a reduced capacity to mediate macrophage cholesterol efflux (by 20%, P< 0.0001), even in a subset of younger SA (<40 years, P<0.01). Composition and size changes in HDL were independent predictors of carotid artery intima-media thickness (IMT) in SA (P< 0.05).

Conclusions:
We have identified for the first time a mechanism to account for low HDL in SA. Elevated CETP in SA was associated with triglyceride-enriched, cholesteryl ester-depleted HDL, smaller in size and reduced in apoA-I content, producing HDL that is less stable in the circulation and less atheroprotective. This was confirmed with the lower relative capacity of HDL from SA to mediate cellular cholesterol efflux and independent correlation of their HDL compositional changes with carotid IMT.
Abstract 14709: Right Sternal Lead Placement Increases Eligibility for Subcutaneous Defibrillator Implantation in Adults With Congenital Heart Disease
Authors: Okamura Hideo , McLeod Christopher J , Bashir Mohammad U , Webster Tracy L , Bonnichsen Crystal R , Grogan Martha , Phillips Sabrina D , Warnes Carole A , Ammash Naser M , Connolly Heidi M , Friedman Paul A
Published: April 2024

Introduction:
The subcutaneous implantable cardioverter defibrillator (S-ICD) is an attractive option for patients with congenital heart disease (CHD) in whom a transvenous system is contraindicated. However, more than 10% of adult patients with CHD fail S-ICD screening due to a large T- to R-wave ratio. We hypothesized right-sternal electrodes may permit S-ICD placement in patients who fail left-sternal screen.

Methods:
We prospectively screened 40 patients with CHD for S-ICD using the standard proprietary approach. We also screened with right sternal electrodes (with left can electrode position).

Results:
The mean age of the cohort was 46+/-15 years; 24 males were enrolled. CHD anomalies consisted of tetralogy of Fallot (n=11), Ebstein’s anomaly (n=7), atrial septal defect (n=6), dextro-looped transposition of the great artery (n=5) and other (n=11). Left side screening ECG failed in 9 patients (23%), five of whom passed with right sternal electrodes, increasing the pass rate from 77% to 90%. Figure shows the screening ECG and chest x-ray of a patient who failed in all three vectors on the left side but passed in the alternative vector on the right side and underwent right sided implantation.

Conclusions:
The addition of right sternal electrodes during screening increases S-ICD eligibility and may avoid thoracotomy for high risk patients with CHD.
Abstract 14745: Acute Post-ischemic GPER1 Activation Protects the Myocardium Against Ischemia/Reperfusion Injury by Reducing Mitochondrial Protein Ubiquitination, Histone Acetylation and Calpain10 levels and Inhibition of the mPTP Opening
Authors: Feng Yansheng , Kabir Mohammad E. , Hernandez Cesar Humberto , Olde Bjorn , Leeb-Lundberg Fredrik , Bopassa Jean C.
Published: April 2024

Introduction:
We recently found that acute pre-ischemic estrogen-induced cardioprotection against ischemia/reperfusion injury was mainly mediated via G protein-coupled estrogen receptor1 (GPER1) activation but not through classical estrogen receptors: alpha (ERα) and beta (ERβ).

Hypothesis:
We investigated whether acute post-ischemic estrogen (PI-E2) treatment can also induce cardioprotective effect via GPER1 activation in the intact animal subjected to ischemia/reperfusion injury.

Methods:
Male and ovarectomized female Sprague-Dawley rats were anesthetized with ketamine (80 mg/kg i.p.) and xylazine (8 mg/kg i.p.). Hearts were subjected to 35 min of the left anterior descending (LAD) artery occlusion, followed by 180 min reperfusion. An E2 bolus (50 mg/kg body weight) or PBS (same volume) was applied via the femoral vein 5 min before reperfusion and a GPER1 antagonist, G15, was given 10 min before E2. Area at risk (AAR) was identified using Evans Blue dye and myocardial infarct size assessed by TTC staining method. Mitochondria calcium retention capacity (CRC) required to induce mitochondrial permeability transition pore (mPTP) opening was assessed after 10 min reperfusion. Expression levels of ubiquitinated; histone acetylated; calpains 1 and 10 proteins were measured by Western Blot in mitochondrial and cytosolic fractions.

Results:
We found that PI-E2 treatment reduced myocardial infarct size normalized to the AAR or the whole LV and improved mitochondrial CRC. PI-E2 treatment reduced protein histone acetylation in mitochondrial but not in cytosolic fractions, decreased mitochondrial proteins ubiquitination and also decreased calpain1 and calpain10 levels in cytosolic and mitochondrial fractions as compared to control, respectively. Interestingly, all these of E2 effects were abolished by addition of G15.

Conclusion:
Acute post-ischemic GPER1 activation by estrogen induces cardioprotection against ischemia/reperfusion injury. PI-E2 effects through GPER1 involve the reduction of the level of mitochondrial protein histone acetylation, ubiquitination, calpain1 and calpain10. This PI-E2-GPER1 effect is associated with the inhibition of the mPTP opening.