bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14610: Thoracic Aortic Aneurysm-causing Mutation, R258C, in Smooth Muscle Alpha-actin Inhibits Functional Effects of Wild-type Alpha-actin in Patient-derived Fibroblasts
Authors: Liu Zhenan , Chang Audrey , Grinnell Frederick , Trybus Kathleen , Milewicz Dianna , Kamm Kristine
Published: April 2024

Familial thoracic aortic aneurysms and dissections (TAAD) are most commonly caused by missense mutations in smooth muscle α-actin (SMαA), encoded by ACTA2. Although TAAD is hypothesized to result in part from a compromised ability of aortic smooth muscle cells (SMCs) to sense their mechanical environment, the specifics of how ACTA2 mutations affect cellular mechanotransduction remain to be defined. We established hTERT-immortalized lines of dermal fibroblasts from volunteers (WT) and patients with ACTA2 mutations (MT). SMαA expression was induced with adenovirus encoding MRTF-A, a potent co-activator of SM contractile genes, including ACTA2. We focus here on the ACTA2 R258C mutation, a recurrent mutation associated with early onset of TAAD. Quantification of actin expression by 2D-PAGE and western blotting showed that induced WT fibroblasts expressed ~40% β-, 30% γ- and 30% SM-α-actin, while heterozygous MT cells expressed ~40% β-, 30% γ-, 15% WT-SM-α- and 15% MT-SM-α-actin, with un-induced cells expressing <5% SMαA. Cytoskeletal structure was studied by immunofluorescence and confocal microscopy, and by sedimentation for actin distribution in filamentous (F) and monomeric (G) fractions. Cell motile and contractile properties were investigated by scratch-induced cell migration, trans-well migration, and collagen matrix contraction assays. As described for other models of SMαA induction in fibroblasts, we found that MRTF-A induction of SMαA in WT cells significantly increased formation of stress fibers and focal adhesions, F/G ratio (p<0.01), and matrix contraction (p<0.05), and significantly decreased cell migration in scratch-induced (p<0.01) and trans-well (p<0.0001) migration assays. In contrast, expression of MT SMαA in heterozygous R258C MT fibroblasts abrogated the effects of SMαA on formation of stress fibers and focal adhesions, F/G ratio, matrix contraction and cell migration in comparison to induction of SMαA in WT cells. These results demonstrate that R258C MT SMαA disrupts cytoskeletal functions attributed to SMαA in WT fibroblasts and are consistent with defects in mechanotransduction, which may shed light on cellular defects due to ACTA2 mutations in both aortic SMCs and adventitial fibroblasts.
Abstract 14772: Routine Coronary Angiography Prior to Pulmonary Thromboendarterectomy in Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Lee Noel S , Knowlton Kirk U , McDivit Anna M , Blanchard Daniel G , Pretorius Victor , Madani Michael M , Fedullo Peter F , Kerr Kim M , Kim Nick H , Poch David S , Auger William R , Daniels Lori B
Published: April 2024

Introduction:
At UC San Diego Health System, routine coronary angiography has been performed in men >40 years and women >45 years (or earlier in those with significant cardiovascular risk factors) prior to pulmonary thromboendarterectomy (PTE) for chronic thromboembolic pulmonary hypertension (CTEPH). However, the prevalence of significant coronary artery disease (CAD) in this population has not been evaluated, and the optimal screening strategy has not been systematically established.

Hypothesis:
We hypothesized that the current approach of routine age-based coronary angiography in screening candidates for PTE may be better optimized based on cardiac risk factors.

Methods:
The study included 349 consecutive patients (51.3% male) with CTEPH undergoing preoperative coronary angiography for PTE between January 1, 2007 and November 7, 2014. Charts were reviewed for baseline demographic and medical information. Major cardiac risk factors included: diabetes, hypertension, hyperlipidemia, obesity (BMI ≥25 kg/m2), tobacco use, and family history of CAD. Coronary angiography reports and PTE operative reports were reviewed for significant CAD (≥50% obstruction) and revascularization.

Results:
Significant CAD was found in 43 (12.3%) of the 349 patients who underwent routine preoperative coronary angiography. The subset with significant CAD included 14 (8.2%) of 170 women and 29 (16.2%) of 179 men. Significant CAD was present in only 5.6% of patients ≤50 years of age, compared to 14.6% of patients >50 years of age. The absence of major cardiac risk factors was a key indicator in excluding significant CAD in patients ≤50 years: no patient ≤50 years without risk factors for CAD was found to have significant coronary artery obstruction. Furthermore, in patients ≤50 years, significant CAD was found only among those with ≥3 major risk factors.

Conclusions:
In patients ≤50 years with CTEPH, the prevalence of significant CAD was low, and omitting preoperative coronary angiography in this subset of men and women may be reasonable when no cardiac risk factors are present. Routine preoperative coronary angiography is reasonable in individuals >50 years, as well as those ≤50 years with significant risk factors or clinical suspicion of CAD.
Abstract 14952: Disruption of a Newly Identified Complex Between soluble Guanylyl Cyclase and Connexin 43 is Potentially Linked to Cardiac Contractile Dysfunction
Authors: Crassous Pierre-Antoine , Huang Can , Shu Ping , Brouckaert Peter , Xie Lai-Hua , Beuve Annie
Published: April 2024

Background:
The role of nitric oxide (NO) in regulation of excitation-contraction (EC) coupling remains controversial. NO activates soluble Guanylyl Cyclase (sGC), a heme-containing heterodimer (α/ß subunits), to increase cGMP production and regulate downstream targets such as Protein Kinase G (PKG) and phosphodiesterases (PDE). Intercalated discs (ID) are essential for electro-mechanical coupling between cardiomyocytes. Connexin 43 (Cx43) via formation of gap junctions at the ID mediate the electrical coupling. Cx43 targeting and assembly at the ID involved phosphorylation by many protein kinases, including cAMP-activated PKA. In various cardiomyopathies such as arrhythmia, Cx43 is relocated from ID to the lateral membrane of cardiomyocytes. Recently, we discovered that sGCβ is localized at the ID with Cx43 and PDE3A, using immunofluorescence (IF) and Triton/Urea heart fractionation. Importantly, we showed by co-immunoprecipitation (co-IP) that sGC physically interacts with Cx43 in the heart.

Hypothesis:
Cx43 assembly and function at the ID through PKA-dependent Cx43 phosphorylation depends on NO-sGC-cGMP microdomain inducing inhibition of PDE3A.

Methods and Results:
To assess the role and relevance of the sGC-Cx43 complex, we used Angiotensin II (AngII) to induce cardiac hypertrophy and arrhythmia in wild-type (WT) mice and sGCα-KO mice, which are depleted for sGC activity. Co-IP indicates that sGC-Cx43 complex is decreased in AngII-treated WT (n=5), independently of decreased Cx43 expression and IF showed Cx43 lateralization. NO-dependent cGMP in membrane fraction of AngII-hearts was decreased by 50%. Conversely, in sGCα-KO mice Cx43-sGC complex was reduced and even more so with AngII treatment. In addition to a significant increased cardiac hypertrophy in sGCα-KO mice (heart to body weight ratio KO: 5.16±0.19 vs WT: 4.45±0.04, n=4-8, P<0.05), preliminary EKG (n=4) indicates that sGCα-KO mice suffer from cardiac arrhythmia with, intriguingly, alteration in P waves.

Conclusion:
Altogether, our data suggest that sGC via modulation of Cx43 location at ID is potentially involved in EC regulation. We currently explore the mechanism underlying these observations with in vivo, biochemical approaches and imaging.
Abstract 14953: STAT3 in Vascular Smooth Muscle Cells Protects Aorta From Dissection by Reinforcing Aortic Wall
Authors: Hirakata Saki , Aoki Hiroki , Nishihara Michihide , Ohno Satoko , Furusho Aya , Nishida Norifumi , Ito Sohei , Hayashi Makiko , Fukumoto Yoshihiro
Published: April 2024

Aortic dissection (AD) is a common and fatal disease for which pathogenesis is largely unknown. Recently we and others reported that JAK/STAT3-activating cytokines are highly expressed in human and mouse models of AD. In this study, we used a mouse model of AD that was induced by continuous infusion of beta-aminopropionitrile, an inhibitor of lysyl oxidase that cross-links collagen and elastin, and angiotensin II (BAPN+AngII). Mouse AD tissue showed STAT3 activation (phosphorylation) both in inflammatory cells and in vascular smooth muscle cells (VSMCs). We used the smooth muscle-specific knockout mice for SOCS3, a negative feedback regulator of STAT3 (smSOCS3-KO), to activate STAT3 specifically in VSMCs. smSOCS3-KO mice developed less severe AD in the aortic arch (WT; 0.093±0.018 vs. smSOCS3-KO; 0.018±0.013 mm/g body weight, P=0.014), as determined by the lesion length. Immunofluorescence staining showed phospho-STAT3 in medial VSMCs by BAPN+AngII, which was more prominent in smSOCS3-KO as expected. Interestingly, smSOCS3-KO aorta showed more collagen fibers, suggesting that STAT3 activation in VSMCs may augment the tensile strength of aorta. Indeed, direct measurement of the tensile strength of the excised aortic rings indicated that smSOCS3-KO aorta had more tensile strength compared to wild type aorta (WT; 0.171±0.018 vs. smSOCS3-KO; 0.234±0.011 N/mm, P=0.004). Consistently, adventitia of smSOCS3-KO aorta showed more fibroblasts, as determined by ER-TR7 staining, compared to WT aorta. We also examined surgical specimens from AD patients for phospho-STAT3 and collagen deposition. Strong signal of phospho-STAT3 was detected at the site of dissection. However, phospho-STAT3 was reduced where strong collagen deposition was observed, suggesting that STAT3 activity is reduced after the completion of collagen deposition. From these results we concluded that activation of STAT3 in VSMCs reinforces aortic wall by enhancing collagen deposition, thus protecting aorta from dissection. Understanding of the protection mechanism of the aortic walls from dissection would lead to better understanding of the molecular pathogenesis, which is essential for developing novel therapeutic strategy for AD.
Abstract 14959: RNA-Seq Analysis of Peripheral Blood Monocyte Gene Expression Before and After Cardiac Resynchronization Therapy
Authors: Bilchick Kenneth C , Meng Lingjin , Garmey James , McNamara Coleen A
Published: April 2024

Introduction:
Cardiac resynchronization therapy (CRT) management could be improved with a better understanding of physiological pathways associated with improved responses, but routine myocardial tissue assessment is not feasible because of risks associated with cardiac biopsies. RNA analysis of peripheral blood monocytes (PBMCs) may be a promising alternative.

Hypothesis:
CRT responders have a unique gene expression profile in circulating PBMCs compared with nonresponders.

Methods:
RNA-Seq analysis of PBMCs was performed in n=14 patients before CRT and at a median 2.05 years after initial CRT implantation in responders and surviving nonresponders. Responders had at least a 15% reduction in left ventricular end-systolic volume and at least a 2 ml/kg/minute improvement in peak VO
2
after CRT. Polymerase chain reaction (PCR) was used to confirm changes in selected genes of interest.

Results:
Responders exhibited many changes not seen in nonresponders, particularly in key pathways including immune system and cytokine signaling; apoptosis and the cell cycle; phospholipid metabolism; glucose metabolism including glycolysis; gluconeogenesis and pyruvate metabolism including the tricarboxylic acid (TCA) cycle; NF kappa beta signaling; tubular function; transforming growth factor-beta signaling; and the response to oxidative stress. 2,365 genes had significant changes in responders (p<0.05 after adjustment for multiple comparisons) but not nonresponders. Of these genes, 413 had at least a 2-fold change post-CRT, 322 had fold changes between 2 and 4, 88 had fold changes between 4 and 8, and 3 had fold changes greater than 8. PCR of a selected set of these genes linked to improved cardiac function confirmed RNA-Seq results.

Conclusions:
RNA-Seq analysis of PBMCs after CRT demonstrates many genes in key pathways with significant changes in responders but not nonresponders. These methods may be particularly useful in assessing prognosis after CRT.
Abstract 15011: Intravenous Immunoglobulin for Acute Myocarditis is Associated With Increased Resource Utilization but Equivalent Survival: An Outcome Analysis Amongst U.S. Children’s Hospitals
Authors: Shamszad Pirouz , Nandi Deipanjan , O'Connor Matthew J , Lin Kimberly Y , Costarino Andrew T , Shaddy Robert E , Rossano Joseph W
Published: April 2024

Introduction:
Intravenous immunoglobulin (IVIg) is frequently utilized in the treatment of pediatric acute myocarditis (AM) though the data surrounding the efficacy of intravenous immunoglobulin (IVIg) are equivocal.

Hypothesis:
IVIg utilization does not improve survival in pediatric AM but is associated with increased resource utilization.

Methods:
A retrospective review of the Pediatric Health Information System database was performed for children <18 years hospitalized with AM between 2004 and 2014. A 1:1 propensity matched case control design was used to compare children who received IVIg (IVIg-group) to those who did not receive IVIg (no IVIg-group). The propensity score was based on a model including treatment with mechanical ventilation (MV), inotropes, or mechanical circulatory support (MCS). High- and low-use hospitals were defined by quartiles of percent usage of IVIg.

Results:
A total of 1802 children with AM were identified (median age 8y [IQR 1 - 15]; 60% male, 60% IVIg given, 65% inotrope use, 46% MV use, 16% MCS use). After matching, 552 children were included in both the IVIg-group and no IVIg-group. Overall median follow-up of the matched cohort was 1.4y [IQR 0.4-3.4]. Unadjusted in-patient mortality was similar between groups (6% vs. 9%, p=0.09). On multivariable Cox regression, there was no association between IVIg and follow-up mortality (OR 1.0, 95%CI 0.3- 2.9). Although in-patient cardiac transplantation occurred more frequently in the IVIg-group (2% vs. 0%, p<0.001), there was no association between IVIg and cardiac transplantation during the follow up period (OR 0.5, 95%CI 0.2-1.1). Mortality was similar between high- and low-use centers (6% vs. 8%, p=0.316) as was length of stay (7d [IQR 8-18] vs. 7d [4-18], p=0.771). Total charges, as well as pharmacy charges, were significantly higher in the IVIg-group ($125k vs. $77k, $32k vs. $2.8k; p<0.001 for both) and high-use centers ($125k vs. $112k, p=0.025; $27k vs. $5.1k, p<0.001).

Conclusions:
IVIg is frequently utilized in children for the treatment of AM. Overall survival was similar in patients treated and not treated with IVIg, though resource utilization was significantly increased. Further study is needed to assess the most optimal, cost-effective treatment for AM in children.
Abstract 15033: Utilization of Cardiac Resynchronization Therapy Among Eligible Patients Receiving an Implantable Cardioverter-Defibrillator: Insights From the NCDR ICD Registry
Authors: Marzec Lucas N , Peterson Pamela N , Bao Haikun , Curtis Jeptha P , Masoudi Frederick A , Varosy Paul D , Bradley Steven M
Published: April 2024

Introduction:
Although ICDs are used inconsistently among eligible patients, it is unknown if similar variation exists in the use of cardiac resynchronization therapy (CRT) devices.

Methods:
Within the National Cardiovascular Data Registry (NCDR) ICD Registry, we identified 72,115 patients with a class I or IIa indication for CRT according to 2008 guidelines who underwent ICD or CRTD implantation at 1521 hospitals between April 1, 2010 and June 30, 2014. A hierarchical model including hospital specific random-effects was used to identify patient, provider, and hospital factors associated with CRTD use. We then determined risk-standardized rates of CRTD use across hospitals for the overall population and by strength of guideline indication. We applied 2012 CRT guidelines in secondary analyses.

Results:
A total of 62,900 (87.2%) eligible patients by 2008 guidelines received CRTD, with 60,730 (84.2%) having a class I indication and 11,385 (15.8%) a class IIa indication for CRTD. Patient factors associated with higher use included increasing age (OR 1.07, 95% CI 1.04-1.1) and NYHA class IV symptoms (OR 1.13, 95% CI 1.02-1.25) while black race was associated with lower use of CRTD (OR 0.81, 95% CI 0.75-0.88). Non-electrophysiology providers were less likely to implant CRTD (OR 0.35, 95% CI 0.28-0.43). After accounting for patient, provider, and hospital factors, the median hospital risk standardized rate of CRTD use was 77.3% (range 24.3-100%) (Figure). The hospital median risk standardized rate of CRTD for class I indication was 79% (range 32.5-100%) and for class IIa was 83.9% (range 79.8-100%). Similar findings were seen with the application of 2012 CRTD guidelines.

Conclusions:
Among patients receiving device therapy who have guideline based indications for CRTD, the use of this therapy varies widely by hospital even after accounting for patient, provider, and hospital factors. Strategies to address this variation may improve patient outcomes through optimal use of CRTD.
Abstract 15199: L-Citrulline Supplementation Reduces Plasma Arginase Activity in Type 2 Diabetes Patients
Authors: Shatanawi Alia , Momani Munther S , Aqtash Ruaa , Hamdan Mohammad H , Caldwell Ruth B , Caldwell R. William
Published: April 2024

Vascular dysfunction is a major cause of morbidity and mortality in diabetic patients. Diabetes has been linked to elevated arginase and associated with vascular endothelial dysfunction. The pathological process is characterized by impaired endothelial cell production of nitric oxide (NO) and/or decreased NO bioavailability. NO is produced by activity of endothelial NO synthase (eNOS) on its substrate L-arginine. Reduced availability of L-arginine to eNOS has been implicated in vascular dysfunction in diabetes. Arginase, which metabolizes L-arginine to urea and ornithine, competes directly with NOS for L-arginine. Hence increases in arginase activity can decrease arginine levels, reducing its availability to eNOS and decreasing NO production. We aimed to determine levels of plasma arginase activity in type 2 diabetic (T2DM) patients and the effects of L-citrulline, a natural arginase inhibitor, on inhibiting arginase activity in T2DM patients. We determined arginase activity levels in 62 T2DM patients and compared it to age matched healthy volunteers (ages 45-65). Our results show that arginase activity is 1.7 fold higher in T2DM patient’s plasma than healthy controls. Levels of arginase correlated with H1AC levels in diabetic patients r=0.81. Twenty five patients received L-citrulline supplements (2000 mg/day) for 1 month. Arginase activity was decreased 30% in T2DM patients after taking L- citrulline supplements. There was a modest improvement on H1Ac levels in these patients. The effect on L-citrulline on arginase activity was also measure in bovine aortic endothelial cells (BAECs) grown in high glucose (HG) conditions. HG (25mM, 72 hrs) caused a 2 fold increase in arginase activity in BAECs and decreased NO production by 40%. L-citrulline 100μM completely prevented the increase in arginase activity and restored NO production levels. These data indicate that inhibiting arginase activity can have therapeutic benefits in diabetic patients by preventing vascular dysfunction and maintaining NO levels.
Abstract 15262: Antiplatelet Activity and Clinical Outcomes on CYP3A4-metabolized Statin in Percutaneous Coronary Intervention
Authors: Park Jin sup , Cha Kwang Soo , Choi Jong Hyun , Kim Bowon , Lee Hye Won , Oh Jun-Hyok , Lee Han Cheol , Hong Taek Jong , Kim Hyo-Soo
Published: April 2024

Introduction:
Statins primarily metabolized by cytochrome P450 3A4 (CYP3A4) reportedly reduce clopidogrel metabolism to active metabolite. Recent studies suggest that CYP 3A4-metabolized statins attenuate the anti-aggregatory effect of clopidogrel.

Hypothesis:
We sought to assess the antiplatelet activity of a CYP 3A4 metabolized statin and its association with clinical outcomes during dual antiplatelet therapy following percutaneous coronary intervention (PCI).

Methods:
Among 3,755 patients enrolled the HOST-ASSURE trial, 1,187 patients with both baseline and 1-month platelet reactivity unit (PRU) values assessed by VerifyNow P2Y12 assay were assigned to the CYP 3A4-metabolized statin group (n=725) or non-CYP 3A4-metabolized statin group (n=462) according to type of statins used. The co-primary outcome were the differences between baseline and 1-month follow-up of PRU value and the composite of cardiovascular death, recurrent MI, including stent thrombosis, any revascularization and cerebrovascular accident (CVA) during the follow-up period. We compared the outcomes between groups both in the propensity adjusted and matched cohorts.

Results:
Mean difference of PRU values was not significant in the CYP 3A4-metabolized statin group (mean difference: -4±84, p=0.367) and was significant in the non-CYP 3A4-metabolized statin group (mean difference: -12±69, p=0.006) both in the propensity score adjusted and matched cohorts. Patients with high PRU value at baseline, irrespective of the type of used statins, were associated with a significant reduction in mean difference of PRU values both in the propensity score adjusted (mean difference: -53.35, p<0.001) and matched cohort (mean difference: -41.57, p<0.001). The composite of clinical events did not differ between groups both in the propensity score adjusted (hazard ratio [HR] 0.962, 95% confidence interval [CI] 0.621-1.489, p=0.861) and matched (HR 0.902, 95% CI 0.554-1.468, p=0.678) cohorts.

Conclusions:
This study showed that a CYP 3A4-metabolized statin slightly reduces antiplatelet activity of clopidogrel during dual antiplatelet therapy but did not increase clinical events in patients following PCI.
Abstract 15297: Active Rheumatoid Arthritis is Associated With Subclinical Left Ventricular Systolic Myocardial Dysfunction
Authors: Midtbø Helga , Semb Anne Grete , Matre Knut , Kvien Tore K , Gerdts Eva
Published: April 2024

Introduction:
Patients with rheumatoid arthritis (RA) have comparable cardiovascular risk to patients with diabetes mellitus. Lately, disease activity has emerged as a new, independent risk factor for cardiovascular disease in RA patients.

Hypothesis:
We tested if RA disease activity was associated with subclinical systolic left ventricular (LV) dysfunction independent of traditional cardiovascular risk factors.

Methods:
Echocardiography was performed in 78 patients with active RA (Simplified Disease Activity Index [SDAI] >3.3), 41 patients in remission (SDAI ≤3.3), and 46 controls, all without known cardiac disease. LV endocardial systolic function was determined by biplane Simpson ejection fraction and LV myocardial function by stress-corrected midwall shortening (scMWS) and global longitudinal strain (GLS).

Results:
Patients with active RA had higher frequencies of hypertension, diabetes and use of disease modifying antirheumatic drugs (all p<0.05) compared to patients in remission, while age and sex did not differ from RA patients in remission (Table). LV ejection fraction was normal in all groups, while mean GLS and scMWS were reduced in RA patients with active disease compared to RA in remission (p<0.05) (Table). In multivariate analyses, having active RA was associated with lower GLS (β=0.21) and scMWS (β=-0.22, both p<0.05) independent of cardiovascular risk factors and LV ejection fraction. Assessment of RA disease activity by other composite scores yielded similar results.

Conclusions:
Active RA is associated with subclinical reduced LV systolic myocardial function despite normal ejection fraction, and independent of presence of hypertension and diabetes.
Abstract 15307: Dairy Intake and Risk of Cardiovascular Mortality in Singapore Chinese Adults
Authors: Talaei Pashiri Mohammad , Koh Woon-Puay , Pan An
Published: April 2024

Introduction:
Studies have suggested that dairy foods may be associated with lower risk of metabolic syndrome, HTN, and T2D. However, the relation of dairy products with CVD risk has been less clear, with mixed findings from various epidemiological studies. So far, few reports are from Chinese populations where the consumption levels are generally low.

Methods:
The Singapore Chinese Health Study is a population-based cohort that recruited 63,257 Chinese adults aged 45-74 years from 1993 to 1998 in Singapore. A validated 165-item semi-quantitative food-frequency questionnaire was used to assess usual diet at recruitment, and mortality information was identified via registry linkage up to December 31, 2013. Cox proportional hazard models were used to calculate HRs (95% CI) with adjustment for potential confounders.

Results:
The median total dairy intake was 20.1 g/d (ranged 0-1084 g/d). During 981,480 person-years of follow-up, we identified 5,484 CVD deaths. After controlling for socio-demographic, lifestyle and other dietary factors, marginally inverse association was observed, and the HRs (95% CI) for CVD mortality were 1.00, 0.95 (0.88-1.02), 0.96 (0.89-1.04), and 0.91 (0.84-0.99) for increasing quartiles of total dairy intake (P-trend=0.08). No significant association was observed for CHD deaths (n=3,033), and the HR comparing extreme quartiles was 0.93 (95% CI: 0.84-1.04; P-trend=0.27). Although the trend was not significant (P-trend=0.15) for stroke mortality (n=1544), the HRs were 1.00, 0.88 (0.77-1.02), 0.88 (0.76-1.01), and 0.84 (0.72-0.98) for increasing quartiles of total dairy intake. In men, higher total dairy intake was inversely associated with risk of CVD mortality [HR comparing extreme quartiles 0.89 (0.80-0.99); P-trend=0.02] and stroke mortality [0.72 (0.58-0.89); P-trend=0.005], but no significant association was observed in women [CVD mortality 0.99 (0.88-1.12); P-trend=0.41; and stroke mortality 0.93 (0.75-1.15); P-trend=0.97].

Conclusions:
In this large cohort study of Chinese adults with generally low dairy consumption, high intake of total dairy products was associated with a modestly decreased risk of total CVD mortality, and this association was mainly observed for stroke mortality and only evident in men.
Abstract 15674: Can Heart Rate Turbulence and T-Wave Alternans on Holter Electrocardiograms Predict Serious Cardiac Events in Patients After Myocardial Infarction?
Authors: Nam Jong-Ho , Lee Chan-Hee , Park Kyu-Hwan , Son Jang-Won , Kim Ung , Park Jong-Seon , Shin Dong-Gu , Kim Young-Jo
Published: April 2024

Backgrounds:
Patients who survive a myocardial infarction (MI) are at risk of serious events such as sudden cardiac death (SCD). Although the implantable cardioverter-defibrillator (ICD) reduces mortality after MI, there is no reliable method to predict SCD. Because of the relatively low accuracy of Left ventricular ejection fraction (LVEF), noninvasive measures of autonomic tone and cardiac electrical substrate have been developed to identify patients at risk of SCD. Recent studies have reported that heart rate turbulence (HRT) and T-wave alternans (TWA), which can be assessed simply using 24-hr Holter electrocardiogram is a significant index for cardiac events.

Material and Methods:
A total of 464 patients who was first diagnosed with myocardial infarction and treated with percutaneous coronary intervention (age 63 ± 12, 70.9% male) were analyzed. All patients performed 24-h Holter ECG monitoring during hospitalization (mean duration after MI 2.7 ± 1.8 days) to measure HRT, modified moving average method (MMA)-TWA and other conventional parameters. HRT was determined positive when both turbulence onset and turbulence slope were abnormal and MMA-TWA was determined positive when the maximal voltage was > 64 μV. The cardiac mortality and sudden cardiac death were analyzed for 2 years.

Results:
HRT was positive in 48 patients (10.3%) and MMA-TWA was positive in 250 patients (53.9%). During 2 years follow-up, 23 patients (4.9%) were died from cardiac disease, including 19 patients (4.1%) with SCD. On univariative analysis, HRT was a significant predictor for cardiac death (Hazard ratio, 4.29; 95% C.I. 1.66-10.98; P = 0.003) and SCD (Hazard ratio, 5.75; 95% C.I. 2.14-15.41; P = 0.001). On multivariative analysis, HRT had the significant value, with a hazard ratio of 3.25 (95% C.I. 1.09-9.74, P = 0.035) for SCD. Older age, lower LVEF, non-use of beta-blocker, presence of non-sustained ventricular tachycardia were another predictor of cardiac events. However, MMA-TWA can not predict cardiac events in this study.

Conclusion:
The present study revealed that HRT was a significant predictor of SCD. However, MMA-TWA can not predict cardiac events in acute phase of myocardial infarction.
Abstract 15692: Resting Heart Rate and Chronotropic Response to Exercise: Prognostic Implications in Heart Failure
Authors: Santos Mario , West Erin , Skali Hicham , Junior Wilson N , Forman Daniel E , Shah Amil M
Published: April 2024

Background:
Higher resting heart rate (HR) and impaired chronotropic response to exercise are both prognostic of adverse outcomes in heart failure (HF). We aimed to study how resting HR and chronotropic response to exercise relate to each other, and to examine their prognostic value in HF patients across the LVEF spectrum.

Methods:
We studied 892 HF outpatients (mean age 55 years, 68% male, 33% with atrial fibrillation) who underwent maximal cardiopulmonary exercise testing. Chronotropic index (CIx) was calculated as (peak HR – resting HR)/(age-predicted maximal HR – resting HR). Cox proportional hazards models were fit to study the relationship between CIx and resting HR with the composite outcome of LVAD implantation, transplantation, or death (243 events during 4.2±1.9 yr of follow-up). Multivariate models adjusted for age, sex, symptomatic status, cardiomyopathy etiology, COPD, diabetes, atrial fibrillation, LVEF, eGFR, beta-blocker use, and peak VO
2
.

Results:
Resting HR was 72±14 bpm and CIx was 0.55±0.28. The average LVEF was 33±15%, with 28% with an LVEF ≥45%. 85% of patients were on beta-blockers. Both higher resting HR and lower CIx were associated with higher NYHA class and lower peak VO
2
, but resting HR poorly correlated with CIx (r=0.07; p=0.04). Both higher resting HR (per SD change: adjusted HR 1.26; 95%CI: 1.09-1.46; p=0.002) and CIx (per SD change: adjusted HR 0.63; 95%CI: 0.63-0.89; p=0.001) were independent prognostic markers in adjusted analyses including both measures. Similar findings were noted in analyses restricted to patients with an LVEF ≥45% or with atrial fibrillation.

Conclusion:
Higher resting HR and lower CIx are both associated with more severe HF, but correlate poorly with each other. Both are predictive of adverse outcomes suggesting that these two HR-related measures provide independent prognostic information.
Abstract 11153: Association of β1-Adrenergic,M2-Muscarinic Receptor Autoantibody With Occurrence of Nonvalvular Atrial Fibrillation
Authors: Hu Bing , Sun Yanxiang , Li Sha , Sun Jie , Liu Tong , Wu Zidi , Feng Li
Published: April 2024

Introduction:
Atrial fibrillation (AF) is the most common sustained arrhythmia and confers an independent increased risk of stroke and death. Although the exact mechanisms behind AF are not completely elucidated, A large number of evidence demonstrates that autoimmunity may play an important role in the initiation, the progression and the maintenance of AF.

Hypothesis:
In this study, we aimed to compare anti-β
1
-R and anti-M
2
-R levels between non-valvular AF patients and healthy control subjects

Methods:
Seventy-one patients with non-valve atrial fibrillation(age: 62.69±11.23 years, 54% male),along with 71healthy control subjects(age: 61.86±11.90 years, 52% male) were included . Enzyme-linked immunosorbent assay tests to measure serum anti-β
1
-R and anti-M
2
-R levels were performed in both groups. Hs-CRP concentration was measured by immunoturbidimetry.IL-6 concentration was measured by chemiluminescence.

Results:
Anti-β
1
-R and anti-M
2
-R levels were significantly higher in patients with non-valvular AF compared to healthy controls[anti-β
1
-R 221.11(132.38-291.69) vs. 198.14(125.70-278.40) ng/ml, P<0.01; anti-M
2
-R 271.81(144.99-378.20) vs. 235.01(121.53-358.99) ng/ml, P<0.01]. Compared with the control group, the serum level of IL-6,hs-CRP were higher in the non-valvular AF group(IL-6 19.65±5.6pg/mL vs 6.79±1.09pg/mL,hs-CRP 6.03±1.35mg/Lvs 2.73±0.63mg/L P<0.05).After multivariable analyses , the baseline value of serum anti-β
1
-R (OR: 13.176, p<0.001),anti-M
2
-R (OR:4.41, p<0.001),IL-6(OR:6.126, p<0.05) levels and LA diameter(OR:5.781, p<0.05) were independently predictors of non-valvular AF.

Conclusions:
We found a significant association between circulating serum anti-β1-R,anti-M2-R,IL-6 levels and non-valvular AF. The possible mechanism is that the autoimmunity and inflammation might take part in electrical remodeling and structural remodeling of left atrium. Larger studies are warranted to further investigate their role in these settings.
Abstract 11329: Risk Factors of Thromboembolism in Patients With Left Ventricular Noncompaction
Authors: Eguchi Ayumi , Eguchi Shunsuke , Kamiya Hiroki , Nanasato Mamoru , Yoshida Yukihiko
Published: April 2024

Introduction:
Left ventricular noncompaction (LVNC) is a newly recognized cardiomyopathy characterized by a pattern of prominent trabeculation and deep recesses. LVNC can lead to progressive left ventricular (LV) dysfunction and thromboembolism. However, there are few reports that the factors develop thromboembolism in patients with LVNC.

Purpose:
This study was sought to investigate a difference of characteristics in patients with LVNC developing thromboembolism.

Methods:
We retrospectively studied 43 patients (age 61 ± 17 years, 32 male) fulfilling the diagnostic criteria of LVNC out of 7842 adults patients (ejection fraction (EF)≦60%) undergoing echocardiography in our hospital between 2012 and 2015. A thickness of the noncompacted endocardial and the compacted epicardial layers was measured at the site of maximal thickness to calculate the ratio of noncompacted to compacted layer (NC/C). The LV wall was divided into five segments (apical, inferior, lateral, anterior and septal) to describe the location of the noncompacted segments. We defined the diagnostic criteria of LVNC as a presence of prominent trabeculation and deep recesses of LV on more than one segment and a maximal end systolic ratio of NC/C≧2.0.

Results:
LVEF was 38.0 ± 13.0%, LV end-diastolic diameter was 60.0 ± 9.5mm and left atrial diameter (LAD) was 43.8 ± 8.8 mm, respectively. Eight patients (18.6%) were complicated with thromboembolism. There were no significant difference between the patients with thromboembolism and without them on atrial fibrillation, EF and the dilation LAD. The multivariate analysis showed that the patients with thromboembolism had a significantly larger prevalence of patients with a pattern of prominent trabeculation and deep recesses of LV on more than two segments (Odds ratio 6.964, P=0.050) and the height of noncompacted layer ≧ 15 mm (Odds ratio 4.879, P=0.049).

Conclusions:
The findings such as more than two segments with a pattern of prominent trabeculation and deep recesses of LV and the height of noncompacted layer ≧ 15mm on echocardiography were associated with thromboembolism in patients with LVNC. Anticoagulants should be considered to prevent the patients from thromboembolism regardless of LV function and arrhythmia.
Abstract 11402: Mindfulness Based Stress Reduction and Group Support Decrease Stress, Anxiety and Depression in Adolescents With Cardiac Diagnoses: A Randomized Two-Group Study
Authors: Freedenberg Vicki A , Hinds Pamela S , Berul Charles I , Friedmann Erika
Published: April 2024

Introduction:
Adolescents with cardiac diagnoses face unique challenges that can cause psychosocial distress. Psychosocial interventions are effective for adults with cardiac diagnoses and may also impact adolescents’ adjustment. This study compares a Mindfulness Based Stress Reduction (MBSR) program to a video online support group (VG) for adolescents with cardiac diagnoses. MBSR is a structured psycho-educational program which includes yoga, meditation, cognitive restructuring and group support. A published feasibility study by our group showed significant reduction in anxiety following MBSR intervention.

Methods:
This study was a prospective, randomized, two-group design. Participants were randomized to MBSR or VG and completed measures of anxiety and depression (A/D) (Hospital Anxiety and Depression Scale), stress and coping (Responses to Stress Questionnaire) pre-and post their 6-session intervention. Qualitative data were obtained from post-intervention interviews.

Results:
Mean age of the sample (N=46) was 14.8 yrs; 63% were female. Eleven participants (24%) had an ICD, 7 (15%) had a pacemaker, 24 (52%) had congenital heart disease, 22 (48%) had POTS. There were 26 (56%) participants in the MBSR group and 20 (43%) in the VG. Study completion rate was 95% (44/46). Stress significantly decreased in both groups [t(44)=3.7, p=.001]. Greater use of coping skills predicted lower levels of post-intervention depression (r=-.30, p=.04). Higher baseline A/D scores predicted improved A/D scores post-intervention (A: r=.43, p=.01, D: r=.36, p=.02). Qualitatively, both groups reported the benefits of social support, with MBSR participants reporting using learned coping skills to help manage stress and heart symptoms.

Conclusion:
Both interventions were effective in reducing distress in this adolescent sample. Qualitative data elucidated the added benefits of using MBSR techniques to manage stress. The video group format is useful for teens who are unable to meet in person but can benefit from group support. Both groups spontaneously exchanged contact information, wanting to continue as a group. Psychosocial interventions with stress management techniques and/or group support can reduce distress in adolescents with cardiac diagnoses.
Abstract 11544: Rosuvastatin Dose-dependently Improves Flow-mediated Dilation, but Reduces Adiponectin Levels and Insulin Sensitivity in Hypercholesterolemic Patients
Authors: Koh Kwang K , Han Seung H , Oh Pyung C
Published: April 2024

Background:
Genetic analysis from patients participated in the randomized trials reported that the increased risk of type 2 diabetes noted with statins is at least partially explained by HMG-coenzyme A reductase inhibition. We investigated vascular and metabolic phenotypes of different dosages of rosuvastatin in hypercholesterolemic patients.

Methods:
This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. Forty-eight patients were given placebo, and 47, 48, and 47 patients given rosuvastatin 5,10, and 20 mg, respectively daily during a 2 month treatment period.

Results:
Placebo therapy did not significantly change insulin, adiponectin, glycated hemoglobin, and insulin sensitivity relative to baseline measurements. Rosuvastatin 5,10, and 20 mg dose-dependently and significantly improved flow-mediated dilation (34, 40, and 46%) after 2 months therapy when compared with baseline (
P
<0.001 by paired
t
-test) or when compared with placebo (
P
<0.001 by ANOVA). Rosuvastatin 5,10, and 20 mg dose-dependently and significantly increased insulin (median % changes; 16, 20, and 20%, respectively) and glycated hemoglobin levels (mean % changes; 2, 2, and 3%, respectively), and decreased adiponectin levels (mean % changes; 3, 9, and 14%, respectively) and insulin sensitivity (mean % changes; 2, 3, and 4%, respectively) after 2 months therapy when compared with either baseline (all
P
<0.05 by paired
t
-test). These effects with rosuvastatin 5,10, and 20 mg were significant when compared with placebo (
P
=0.006 for insulin,
P
=0.012 for glycated hemoglobin,
P
=0.007 for adiponectin, and
P
=0.002 for insulin sensitivity by ANOVA).

Conclusions:
Despite beneficial reductions in LDL cholesterol and improvement of flow-mediated dilation, rosuvastatin treatment dose-dependently and significantly resulted in decreasing insulin sensitivity and increasing ambient glycemia by reducing adiponectin levels and increasing insulin levels in hypercholesterolemic patients.
Abstract 11855: Coronary Computed Tomography Angiography Increases Invasive Procedures Without Improving Clinical Outcomes in Patients With Suspected Acute Coronary Syndrome - A Meta-analysis of Randomized Controlled Trials
Authors: Foy Andrew J , Dhruva Sanket , Mandrola John M , Morgan Daniel J , Redberg Rita F
Published: April 2024

Introduction:
Coronary computed tomography angiography (CCTA) is considered equal to other forms of noninvasive cardiac testing for low-to-intermediate risk patients with suspected ACS. Clinical trials comparing CCTA to standard care (SC) suggest that CCTA increases invasive coronary angiography (ICA) and revascularization procedures without reducing major adverse cardiac events (MACE), ED revisits, or follow up hospitalizations but were underpowered to detect differences in these endpoints. Given technological advances in CCTA and new trials comparing it to SC, we sought to ascertain the impact of CCTA on clinical outcomes in patients with suspected ACS and a nonischemic workup.

Methods:
We performed a systematic search of PubMed and EMBASE for randomized controlled trials of CCTA compared to SC from January 2006 through April 2016 with a minimum of 100 patients and 28 days follow up. Studies were restricted to those which included patients with suspected ACS, who were either ED or inpatient status, and whose initial workup was negative for ischemia.

Results:
Six randomized, controlled trials met our inclusion criteria and involved 2,397 patients undergoing CCTA and 1,834 undergoing SC. Patients who underwent CCTA were significantly more likely to undergo ICA (7.7% vs 5.3%; RR 1.6, p<0.001) and revascularization (4.3% vs 2.1%; RR 2.3, p<0.001). There was no difference in the incidence of death or MI following the index visit, post-discharge ED visits, or rehospitalizations (table).

Conclusions:
CCTA compared to SC increases rates of ICA and revascularization in patients with suspected ACS and a negative workup but does not improve clinically relevant patient outcomes. CCTA may increase harm compared to SC by exposing patients to unnecessary downstream invasive procedures.
Abstract 11878: Physiologic Changes Induced by Cardiac Rehabilitation in Post Myocardial Infarction Patients: A Systematic Review and Meta-analysis
Authors: Kirolos Irene , Pendola Fiorella , Picado-Roque Omar , Andrade-Bucknor Sharon , Chaparro Sandra , Alfonso Carlos E , Cohen Mauricio G
Published: April 2024

Introduction:
A meta-analysis to evaluate the physiologic changes associated with Cardiac Rehabilitation (CR) in post myocardial infarction (MI) patients was conducted.

Hypothesis:
CR is a non-pharmacological intervention associated with improved outcomes after MI

Methods:
We performed an online database search of PubMed, MEDLINE, EMBASE, SCOPUS, COCHRANE, and GOOGLE SCHOLAR (1988 - Present); and reviewed key bibliographies. Studies comparing post MI patients according to CR referral were included. Relative risks with the corresponding 95% confidence intervals (CI) by random effects models of pooled data were calculated. Study quality was assessed using STROBE criteria. Outcomes of interest measured after conclusion of CR, these included resting and maximum heart rate (HR), Peak VO2, ejection fraction (EF), wall motion score index (WMSI), left ventricular end diastolic diameter (LVEDD)

Results:
Of 147 studies searched, 23 studies met our selection criteria, 19 of which were randomized clinical trials, including 1683 patients (827 referred to CR vs 855 not enrolled in CR). Median age was 58 years. There were no significant difference between the two groups in terms of age, comorbidities, severity, baseline EF or HR. CR patients had significantly lower post-exercise resting HR (RR:-0.72, CI:-0.87 to -0.56; p<0.05), higher EF (RR:0.14, CI:0.04-0.25, p<0.05), lower LVEDD (RR: -0.31, CI:-059,-0.02;p <0.05), lower WMSI (RR:-0.33, CI:-0.62, -0.05; p<0.05), and higher peak VO2 (RR:1.00, CI:0.56 - 1.45; p<0.05)

Conclusions:
This meta-analysis demonstrates that CR is associated with positive physiologic changes post MI. This may explain the reported improvement of functional status and decreased mortality among patients referred to CR. Further randomized trials may help evaluate the long term benefits of CR
Abstract 11891: Nitroglycerin Improves Microcirculation During and After Cardiopulmonary Resuscitation in a Porcine Model of Cardiac Arrest
Authors: Miao Changqing , Yang Zhengfei , Wen Cai , Zhai Xiaozhu , Yu Tao , Peberdy Mary A , Ornato Joseph P , Tang Wanchun
Published: April 2024

Introduction:
We have previously demonstrated that vasopressors administered during cardiopulmonary resuscitation (CPR) significantly decrease microcirculatory flow. In the present study, we investigated the effects of nitroglycerin on the macrocirculation macro and microcirculation and microcirculation during and after CPR in a porcine model of cardiac arrest (CA).

Hypothesis:
Nitroglycerin improves microcirculation but without undesirable effects on the macrocirculation during and after resuscitation.

Methods:
Ten male domestic pigs weighing 40±2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 5 min. The animals were then randomized to receive NTG (N group) or saline (C group). Coincident with the start of CPR, NTG (5 μg/kg) or saline was administrated into the right atrium. Defibrillation was attempted by a single 150 J shock after 5 min of CPR. Hemodynamics were recorded continuously and sublingual microcirculation was assessed with the orthogonal polarisation spectral (OPS) at baseline (BL), 1, 5 min of CPR and 1, 5 min after resuscitation.

Results:
All animals were resuscitated successfully resuscitated. There were no differences in coronary perfusion pressure (CPP), end-tidal carbon dioxide (ETCO
2
) between the two groups (Figure 1). Sublingual perfused vessel density (PVD) and microcirculatory flow index (MFI) were significantly better in NTG treated animals than those of control animals during and after CPR.

Conclusion:
Administration of nitroglycerin at the onset of CPR improves microcirculation without undesirable effects on macrocirculation during and after resuscitation.