bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10453: Fat, Fibre, Sodium Score -A Quick And Valid Tool to Measure Eating Behavior Change Patterns in Cardiac Prevention & Rehabilitation Programs
Authors: Firth Wanda , Pancura Bernice , Tilley Maureen , Giacomantonio Nicholas
Published: July 2021

Introduction:
The history of nutrition scoring tools and food frequency evaluations is plagued with errors and limitations. However, there remains a need to capture outcomes for eating patterns and nutrition behavior change. Our past work led to development of a valid eating stage scoring tool but it was labor intensive and not practical for many clinic or program settings so we developed a new scoring tool. Hypothesis: The new Fat, Fibre, Sodium score is a quickly applied tool to accurately represent eating behavior and effectively measure nutrition changes, during and post cardiac rehabilitation (CR) programs.

Methods:
Patients attending a community CR program, participated in an intensive nutrition behavior change intervention with a dietitian. Nutrition evaluation was conducted using three methods; a general Food Score, the new self evaluation tool called the Fat Fibre Sodium score (FFSS) and thirdly,the dietitian's nutrition assessment and evaluation. Patients also had biomedical measures, exercise stress testing and anthropometrics at baseline and 3 month program completion.

Results:
In the General Food Score,patients went from meeting 79% to 84% of healthy eating guidelines(p<0.0001). 390 patients completed the new FFSS and had improvements for each category; Fat, Fibre and Sodium (p<0.0001). Fibre intake increased from 19 g/day to 27g day. The FFSS for Fibre was validated, and every 8 out of 10 patients had self-scores with 100% accuracy when compared to the dietitian evaluation (p<0.001) The FFSS Fat scores went from 'moderate' to 'low' intake and while the dietitian's assessment validated the fat score at program completion, the baseline FFSS was underreported for fat intake. The sodium component of the FFSS was not valid. Impact of nutrition changes showed that a FFSS 'low fat' score at program completion led to statistically significant weight changes , and LDL lowering (p<0.001)even while changes in exercise were held constant.

Conclusions:
The FFSS tool is easy to use and is a valid measure of eating behavior changes with fibre intake and also accurately represents dietary fat intake at program completion. Although work needs to continue on the sodium component of the FFSS, the new Fat Fibre Scoring tool can be used with confidence in CR settings.
Abstract 10756: Chronic Kidney Disease in Long-term Survivors After Fontan Palliation
Authors: Sharma Sheena , Ruebner Rebecca L , Furth Susan L , Dodds Kathryn M , Rychik Jack , Goldberg David J
Published: July 2021

Background:
The Fontan operation is a palliative procedure for children with congenital single ventricle heart disease. With advances in prenatal diagnosis and surgical techniques, more children are surviving into adulthood with unique cardiovascular physiology. Little is currently known about long-term kidney function in these patients.

Hypothesis:
We hypothesize that long-term survivors after Fontan palliation will have a higher prevalence of chronic kidney disease (CKD) compared to healthy controls.

Methods:
We performed a retrospective cohort study of subjects evaluated through the Single Ventricle Survivorship Program (SVSP) at the Children’s Hospital of Philadelphia between July 1, 2010 and December 5, 2014 and healthy children similar in sex and age. The primary outcome was CKD, defined as eGFR <90 ml/min/1.73m2 calculated with age-appropriate estimating equations using creatinine and cystatin C. Secondary outcomes included proteinuria and hyperparathyroidism.

Results:
The Fontan cohort included 68 subjects with mean age of 13.9 years (SD 5.8) at SVSP visit who were 11.2 years (SD 5.7) from Fontan operation. The healthy cohort included 70 patients with mean age of 15.9 years (SD 3.9). Mean eGFR was 102.6 versus 101.9ml/min/1.73m2 (p=0.89) in pediatric Fontan versus healthy subjects using the complete CKiD equation, and 128.5 versus 129.7ml/min/1.73m2 (p=0.56) in adult Fontan versus healthy subjects using the CKD-EPI creatinine and cystatin formula. 10% of Fontan subjects had an eGFR<90 ml/min/1.73m2. Mean intact parathyroid hormone level was higher at 68.0pg/mL (SD 35.4) in the Fontan group compared to 26.0pg/mL (SD 13.6) in the healthy group. Proteinuria was found within 34% of the Fontan group compared to 4.6% within the control group.

Conclusion:
We found that 10% of subjects have eGFR <90ml/min/1.73m2 after Fontan palliation which would indicate CKD if this remained persistent over time. Although the majority of the cohort had normal kidney function by eGFR, we found a higher proportion with proteinuria and increased parathyroid hormone levels which may indicate early kidney disease. Future studies will focus on evaluating changes in kidney function over time in long-term survivors after Fontan palliation.
Abstract 10804: Incidence and Prognostic Significance of Silent Versus Clinically Manifest Myocardial Infarction in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Zhang Zhu-ming , Rautaharju Pentti M , Prineas Ronald J , Rodriguez Carlos J , Loehr Laura , Rosamond Wayne , Kitzman Dalane , Couper David , Soliman Elsayed Z
Published: July 2021

Background:
Differences in the incidence and prognostic significance of silent myocardial infarction (SMI) vs. MI with clinical manifestations (CMI) are not well-established in racially diverse populations.

Methods:
We compared the incidence of SMI and CMI and their associations with coronary heart disease (CHD) death and death from all causes in 9,498 participants (mean age 54 years, 56.9% women, 20.3% African-American) from the Atherosclerosis Risk in Communities (ARIC) study who were free of cardiovascular disease at baseline visit (1987-89). Incident SMI was defined as ECG evidence of MI without documented CMI occurring after the baseline visit until visit 4 (1996-98). CHD and all-cause deaths were ascertained starting from ARIC visit 4 until 2010 (median follow up 12 years).

Results:
There were 386 (4.1%) incident CMIs and 317 (3.3%) SMIs. Both CMI and SMI were more common in men (6.8% and 4.3%, respectively) than in women (2.0% and 2.6%, respectively) p<0.001. Although SMI rates were comparable in blacks and whites (3.8% vs.3.2%, respectively), CMI was higher in whites (4.4% vs. 2.8%, respectively), p=0.003. In multivariable adjusted Cox Proportional models, both SMI and CMI (compared to no MI) were associated with increased risk of CHD and all-cause deaths, but the risk was higher in the CMI group (
Table
). A significant interaction by sex was observed; SMI and CMI were associated with higher risk of CHD and all-cause deaths in women compared to men (interaction p-value= 0.014). No significant interactions by age or race were detected.

Conclusions:
SMI is as common as CMI, and both are associated with increased risk of CHD and all-cause mortality. Racial and sex differences in the distribution of SMI and CMI, as well as sex differences in the prognostic significance of SMI and CMI exist. These findings suggest that an ECG finding of MI in persons without a history of MI may warrant consideration in personalized CHD prevention risk management efforts particularly in women.
Abstract 10889: Treating Heart Failure With Preserved Ejection Fraction Through Troponin I Phospho-mimicry
Authors: Moutsoglou Maria E , Kim Gi-Ho , Solis-Ocampo Christopher , Kumar Mohit , de Tombe Pieter , Robinson John M
Published: July 2021

Background
—Heart failure with preserved ejection fraction (HF-pEF), characterized by resistance to ventricular filling from impaired myofilament relaxation (lusitropy), is the most common variant of heart failure. In HF-pEF, blunting of the lusitropic effect of troponin I (TnI) Ser-23/24 phosphorylation through the β-receptor-cAMP- protein kinase A (PKA) pathway contributes to impaired diastolic relaxation.

Methods and Results
—To identify small molecule compounds capable of generating the lusitropic effect of PKA-dependent TnI phosphorylation, we developed a 2D
in vitro
screen, where dye-labeled thin filaments are titrated with Ca
2+
and myosin motors. Thin filament activation is monitored by a FRET assay with FRET donor on the mobile element of TnI and the FRET acceptor on the C-lobe of troponin C (TnC). We observed that full activation of the thin filament required myosin binding. The Ca
2+
-sensitizer bepridil acted as myosin, enhancing thin filament affinity for Ca
2+
and stabilizing the association of the mobile element of TnI with TnC. In the presence of saturating bepridil, adding myosin had no effect on activation, suggesting that bepridil and myosin activate the thin filament through a common mechanism. PKA-treatment decreased the sensitivity of the thin filament to Ca
2+
and to myosin motors, and it reduced the FRET efficiency in the absence of Ca
2+
, suggesting that TnI phosphorylation causes a structural transition in the C-lobe of TnC. Epigallocatechin-3-gallate, the most prevalent polyphenol in green tea, acted as Ser23/24 phospho-TnI, reducing thin filament affinity for Ca
2+
and reducing affinity of myosin for the thin filament under both relaxing and Ca
2+
-activated conditions, suggesting that epigallocatechin-3-gallate and Ser23/24 phospho-TnI relax the myofilament through a common mechanism.

Conclusions
—Our results suggest that bepridil and myosin activate the cardiac thin filament through a common mechanism while epigallocatechin-3-gallate and Ser23/24 phospho-TnI deactivate the thin filament through a common mechanism. “Myofilament relaxers,” small molecule compounds that mimic the effects of Ser23/24 phospho-TnI may be an effective strategy in correcting diastolic dysfunction in HF-pEF.
Abstract 10898: The Probiotic Bacterium
Lactobacillus Plantarum 299v
Improves Vascular Endothelial Function and Decreases Inflammatory Biomarkers in Men With Established Cardiovascular Disease
Authors: Malik Mobin , Widlansky Michael E , Suboc Tisha , Coulliard Allison , Su Jidong , Salzman Nita H , Baker John E
Published: July 2021

Introduction:
There is a significant unmet clinical need to identify novel therapies to prevent and treat the progression of cardiovascular disease. This requires identification of additional contributory processes to the pathogenesis of heart disease so that mechanism-based interventions may be developed.

Hypothesis:
Our objective was to translate the recently discovered mechanistic link in rats between changes in the intestinal microbiota and the pathogenesis of cardiovascular disease to humans.

Methods:
Twenty male adult patients with stable coronary heart disease on stable doses of vasoactive medications and HMG-CoA reductase inhibitors consumed a probiotic drink containing
Lactobacillus plantarum 299v
(3 oz. serving containing 20 billion colony forming units) once a day for 42 days. Vascular endothelial function was measured at the beginning and end of the study period by brachial flow-mediated dilation.

Results:
The probiotic improved brachial artery flow mediated dilation, a surrogate marker of cardiovascular risk, by 33% from 3.55
+
1.96% to 4.73
+
2.33% with a trend towards decreased LDL-cholesterol by 8% from 96
+
11 mg/dl to 88
+
10 mg/dl. Probiotic therapy decreased circulating levels of the inflammatory cytokines IL-8 by 24% (17±2 to 13±1 pg/ml) and IL-12 by 20% (56±7 to 45±6 pg/ml). Whole microbiome analysis based on abundance of 2,206 taxa using hierarchical clustering revealed no separation of the overall intestinal microbial population between pre- and post-probiotic treatment samples. Bacterial genus richness ranged from 334 to 530 and archaeal ranged from 8 to 25, with no significant differences between pre- and post-probiotic samples. Lactobacillus and Bacillus species were enriched in post-probiotic samples.
Lactobacillus plantarum 299v
levels were elevated in post-probiotic samples, confirming patient compliance.

Conclusions:
Our discovery of a relationship between
Lactobacillus plantarum 299v,
improved vascular endothelial function and decreased inflammation indicates intestinal microbiota may be developed as therapies to prevent and treat the progression of cardiovascular disease.
Abstract 10909: LDL and HDL Particle vs. Cholesterol Concentration in Metabolic Syndrome and Diabetes for the Prediction of Coronary Heart Disease: The Multiethnic Study of Atherosclerosis
Authors: Tehrani David M , Zhao Yanglu , Blaha Michael , Mora Samia , Mackey Rachel , Michos Erin , Budoff Matthew , Cromwell William , Otvos James , Rosenblit Paul , Wong Nathan
Published: July 2021

Background:
A more important role of both low and density lipoprotein (LDL-P and HDL-P) than cholesterol (LDL-C and HDL-C) concentration in predicting coronary heart disease (CHD) has been noted. However, the role of these factors and extent of particle-cholesterol discordance in metabolic syndrome (MetS) and diabetes (DM) for event prediction is unknown.

Methods:
In adults aged 45-84 from the Multi-Ethnic Study of Atherosclerosis, a prospective study of subjects without baseline cardiovascular disease, we defined percent discordance of LDL and HDL based on a subject’s difference between baseline particle and cholesterol percentiles. Separate Cox regressions adjusted for standard risk factors were performed to assess the relationship of the continuous lipoprotein discordance variables, as well as LDL-C, LDL-P, HDL-C, and HDL-P, to incident CHD events in those with DM, MetS (without DM), or neither condition.

Results:
Among 6,417 subjects (52.5% male, mean age 62.1) with 10 year follow-up, those with DM and MetS had significantly greater LDL and HDL discordance compared to those without these conditions (Figure). In discordance models, only LDL discordance [per standard deviation (SD)] within the MetS group was positively associated with CHD events [Hazard Ratio (HR) =1.25, p<0.01]. In models with individual particle/cholesterol variables (per SD), within the DM group, HDL-P was negatively (HR=0.71, p<0.05) and LDL-C positively (HR=1.47, p<0.05) associated with CHD. In those with MetS, only LDL-P was positively associated with CHD (HR=1.34, p<0.05). In those with neither disease, only LDL-C was positively associated with CHD (HR=1.27, p<0.05).

Conclusion:
LDL discordance (mainly through higher LDL-P) in those with MetS and higher LDL-C with lower HDL-P in those with DM predicts CHD risk. These results support a potential role for examining lipoprotein particles and discordances in persons with MetS and DM to better assess CHD risk.
Abstract 10923: Indoxyl Sulfate Predicts the Presence of Polyvascular Disease in Patients With Coronary Artery Disease
Authors: Watanabe Ippei
Published: July 2021

Introduction:
Progression of chronic kidney disease (CKD) is associated with extending multiple damaged vascular beds. Data to evaluate the relevance of accumulated uremic toxin for systemic atherosclerosis is limited. In the present study we assessed the clinical role of serum indoxyl sulfate (IS), a protein-bound uremic toxin for the presence of polyvascular disease (PVD) in patients with coronary artery disease (CAD).

Methods and Results:
We analyzed clinical data from 94 patients who underwent percutaneous coronary intervention for CAD and the prevalence of PVD, defined as 1-, 2- or 3-vessel disease was preoperatively screened. Serum IS levels were determined from blood sample by using high performance liquid chromatograph. Receiver operator characteristic (ROC) curve was used for discriminative ability between elevated IS levels and the presence of PVD. The prevalence of PVD among CAD patients was 38%. The median value of serum IS was 0.103 mg/dl and IS levels were negatively correlated with estimated glomerular filtration rate (e-GFR) (r=0.66 p <0.001). IS levels in PVD patients were significantly higher than in patients who had only CAD (1.171 ± 4.38 mg/dl vs 0.147 ± 0.144 mg/dl, p <0.001) and ROC analysis determined serum IS levels of 0.142 mg/dl as a cut-off value to predict the presence of PVD (sensitivity: 73.4 %, specificity: 79.6%, the area under curve: 0.778). Multivariate analysis found IS (odds ratio [OR]: 6.77, 95% confidence interval [CI] : 1.84-24.9, p=0.003), e-GFR <60 ml/min/1.73m
2
(OR: 5.74, 95% CI : 1.47-22.4, p=0.01) and diabetes mellitus (OR: 4.80, 95% CI: 1.40-16.4, p=0.01) were independently associated with the presence of PVD.

Conclusions:
IS is an independent predictor of PVD in patients with CAD. This result may contribute to understanding the mechanism of accelerated atherosclerosis in CKD.
Abstract 10941: Hepatic Overexpression of Endothelial Lipase Induces a Markedly Low HDL-Cholesterol but Maintains Macrophage Reverse Cholesterol Transport in Mice in an ABCA1-dependent Fashion
Authors: Takiguchi Shunichi , Ayaori Makoto , Uto-Kondo Harumi , Yakushiji Emi , Nakaya Kazuhiro , Sasaki Makoto , Komatsu Tomohiro , Kamiyama Masumi , Nishida Takafumi , Ikewaki Katsunori
Published: July 2021

We previously showed that hepatic overexpression of endothelial lipase (EL) by adenoviral vectors markedly reduced plasma HDL levels but maintained macrophage reverse cholesterol transport (RCT) in an SR-BI-dependent fashion in mice. In the present study, we further investigated roles of ABCA1 using probucol, an ABCA1 inhibitor, under EL overexpression. In vivo RCT assay demonstrated that hepatic EL overexpression reduced macrophages-derived 3H-cholesterol in plasma, especially HDL fractions but maintained fecal 3H-cholesterol excretion as compared with the control under normal chow. Probucol diet reduced both 3H- and non-radiolabeled-cholesterol levels in HDL fraction, which were further exacerbated by EL overexpression. Interestingly, probucol diet combined with EL overexpression clearly promoted fecal excretion of macrophages-derived 3H-cholesterol, indicating that EL overexpression and ABCA1 inhibition synergistically enhanced macrophage RCT despite of extremely low HDL levels.
Abstract 10958: Identification of Right Ventricular Myocardial Infarction With Late Gadolinium Enhancement in Chronic Ischemic Heart Disease: Comparison With Pathological Findings
Authors: Chaowu Yan , Li Li , Wei Fang , Hua Li , Yang Wang
Published: July 2021

Introduction:
Late gadolinium enhancement (LGE) has the potential to become an excellent technique in the diagnosis of right ventricular myocardial infarction (RVMI). However, the gold standard, pathological findings from patients, is still unavailable to validate the true value of LGE.

Hypothesis:
We hypothesized that LGE might correspond with histological infarction in RVMI.

Methods:
36 transplant candidates (35 M /1F) with chronic ischemic heart disease were studied prospectively with LGE. According to the 12-segment-model, the pathological findings of RV were compared with the previous in vivo LGE after heart transplantation.

Results:
Histological RVMI was detected in 7 patients, and corresponded with all LGE segments (n=23) and 2 non-LGE segments. A generalize linear mix effect model showed non-significant difference (P=0.152) between the results of LGE and histological infraction. In identifying the RV segments with histological infarction, sensitivity and specificity of LGE was 92.0% (95%CI 74.0% to 99.0%) and 100% (95%CI 99.9% to 100.0%), respectively. Furthermore, RV segments without LGE mainly included two pathological patterns: histologically normal myocardium (n=372) or the admixture of viable myocardium and scattered replacement fibrosis (n=35). In the non-LGE RV segments, wall motion abnormality was associated with volume fraction of collagen (11.4±6.5% vs 4.3±2.2%, P<0.001) and the presence of ischemia (96.4% vs 1.7%, P<0.001).

Conclusions:
The RV segments with LGE corresponded closely with histological infarction in ischemic heart disease. However, RV segments without LGE might be histologically normal myocardium or intermixed with scattered replacement fibrosis. Further studies are required to evaluate the significance of scattered replacement fibrosis in the non-LGE segments.
Abstract 10972: Transthoracic Echocardiography-guided Percutaneous Patent Ductus Arteriosus Occlusion: A New Strategy For Interventional Treatment
Authors: Pan Xiang-Bin , Ouyang Wen-Bin , Wang Shou-Zheng , Liu Yao , Zhang Da-Wei , Zhang Feng-Wen , Pang Kun-Jing , Zhang Zhe , Ge Yi , Hu Sheng-Shou
Published: July 2021

Objectives:
This prospective single center study investigated the safety and efficacy of percutaneous patent ductus arteriosus (PDA) occlusion using the Amplatzer Duct Occluder II (ADO II) under only guidance of transthoracic echocardiography, which avoids the radiation and contrast agents of traditional PDA occlusion.

Methods:
From June 2013 to February 2015, 54 consecutive PDA patients (age, 4.6 ± 2.9 years; weight, 18.5 ± 7.5 kg; PDA narrowest diameter, 3.3 ± 1.1 mm) underwent transthoracic echocardiography guided PDA occlusion through the femoral artery. Outpatient follow-up was conducted at 1, 3, and 6 months, and yearly.

Results:
Echocardiography-guided percutaneous PDA occlusion was successfully performed in 53 patients. The procedure was converted to minimally invasive transthoracic occlusion in one patient due to failure of delivery catheter passage through tortuous PDA. Mean procedure duration was 25.5 ± 7.4 minutes; ADO II diameter averaged 4.7 ± 0.9 mm; 8 cases showed traces of residual shunt immediately after operation; and mean hospital stay was 3.4 ± 0.7 days. There was no occluder migration, hemolysis or pericardial effusion at mean 10.2±4.9 months follow-up.

Conclusions:
Percutaneous PDA occlusion under only guidance of transthoracic echocardiography appears safe and effective while avoiding radiation and contrast agent use.

Legends:
A) A suprasternal view showed the tip of pigtail catheter (arrow) faced the aortic end of the PDA. B) The left parasternal long axis view of the pulmonary artery showed that the guide wire (arrow) was located within the main pulmonary artery. C) The release of the occluder at the pulmonary side (arrow). D) The occluder was completely released (arrows point to each side of the occluder). PDA, patent ductus arteriosus; DAO, descending aorta; PA, pulmonary artery; AO, ascending aorta.
Abstract 10980: Myositis, Myocarditis, and Mitochondria: A Thread Connecting the Myofilaments
Authors: Houston Brian A , Hsu Steve , Halushka Marc , Gelber Allan , Judge Daniel
Published: July 2021

A 67 year old man presented in 2013 with new heart failure symptoms. A curious past medical history prompted pursuit of an etiologic diagnosis. In 2006, he developed weakness and elevated creatine kinase (CK). Muscle biopsy was consistent with a necrotizing myopathy, and a serologic panel of auto-antibodies was unrevealing. He was started on prednisone. In 2011, he presented with atypical chest pain, and ECG demonstrated frequent atrial and ventricular ectopy. Both troponin-I and CK were elevated. Cardiac CT angiography ruled out obstructive coronary disease, and he remained stable until the onset of heart failure symptoms prompted his current admission. On examination, the patient had evidence of proximal muscle weakness and atrophy. His jugular venous pulse was elevated, and auscultation revealed an S3 gallop. Troponin (0.35 ng/mL) and CK (776 U/L) were both elevated and remained consistently so. Echocardiography revealed severely reduced left ventricular function.

Search for a unifying diagnosis prompted review of his myositis panel whereupon immunoprecipitation bands characteristic for anti-mitochondrial antibodies were discovered. Serologies for anti-mitochondrial antibodies returned positive. His plasma lactate was elevated with a normal pyruvate level, mimicking the changes seen in inborn errors of mitochondrial function. Cardiac magnetic resonance imaging showed patchy gadolinium enhancement in the mid-myocardium of the septum and lateral wall in a non-coronary distribution and no perfusion abnormalities. Endomyocardial biopsy established the presence of myocarditis, confirming the diagnosis of anti-mitochondrial antibody-associated myocarditis and myositis.

Along with a beta-blocker and diuretic (he experienced worsening renal insufficiency on low-dose ACE inhibitor), we initiated azathioprine at 50 mg up-titrating to a dose of 150 mg daily over several weeks. The patient reported no recrudescence of heart failure symptoms. Echocardiogram three months later revealed improved left ventricular function, and his CK and troponin-I levels normalized. In cases of idiopathic myositis and myocarditis, anti-mitochondrial antibodies may provide a unifying diagnosis and significantly alter management and prognosis.
Abstract 11103: Increase of Oxidative Stress Precipitated by Selenium Deficiency Plays a Role in Cardiac Hypofunction in Uremic Cardiomyopathy
Authors: Hiraoka Yuji , Tanabe Masato , Yamazaki Taketoshi , Fujita Masatoshi
Published: July 2021

Introduction:
Various trace elements are deficient in hemodialysis patients, but the relationship of such deficiencies with cardiac hypofunction is unclear. We examined the deficiencies of trace elements in the blood and hair of hemodialysis patients diagnosed with uremic cardiomyopathy and investigated cardiac hypofunction mechanism from myocardial tissue.

Methods:
Using blood samples, we measured 25 elements including Se, Mn, Cu, and Zn by high-resolution inductively coupled plasma (ICP) mass spectrometry and ICP emission spectral analysis. We also compared glutathione peroxidase (GSHPx) activation and radical formation potential between the uremic cardiomyopathy patient group (n = 22) and a control group with normal cardiac function (n = 30). Using myocardial tissue, we assessed the exacerbation of oxidative stress by 8-hydroxy-2-deoxyguanosine, 4-hydroxy-2-nonenal, and GSHPx staining and microcirculatory disorder by the perivascular fibrosis area ratio (PVFR). We also measured concentrations of elements in hair at the Super Photon ring-8 GeV (SPring-8) facility.

Results:
Compared with the control group patients, the uremic cardiomyopathy patients had lower selenium (99.7 ± 21.4 vs. 146 ± 23.3 ng/ml, p < 0.00001) and manganese concentrations (0.39 ± 0.15 vs. 0.60 ± 0.12 ng/ml, p < 0.001); they also showed decreased activation of GSHPx (121 ± 33 vs. 328 ± 44 μmol/min/L, p < 0.00001), an antioxidant enzyme involving selenium, with only selenium concentration correlating to left ventricular ejection fraction (p = 0.0009). Oxidative stress marker staining, radical formation potential in serum, and PVFR were all augmented in the uremic cardiomyopathic patients (p < 0.001).

Conclusions:
Selenium concentration decrease in the serum of hemodialysis patients may reflect a decrease in GSHPx activation, increasing oxidative stress, and precipitating a coronary microcirculatory disorder involved in the cardiac hypofunction seen in uremic cardiomyopathy.
Abstract 11106: The Incidence of Sudden Cardiac Arrest Continues to Rise, but Outcome is at a Standstill in South Korea: Analyzed From National Health Insurance Database Cohort From 2003 to 2013
Authors: Yang Pil-sung , Lee Hancheol , Kim Tae-Hoon , Uhm Jae-Sun , Pak Hui-Nam , Lee Moon-Hyoung , Joung Boyoung
Published: July 2021

Introduction:
Sudden cardiac arrest (SCA) is a major clinical and public health problem. South Korea is aging faster than any other country, and the disease spectrum has changed profoundly in the last few decades. The purpose of this study was to investigate the change of the incidence and outcome of SCA over the past ten years.

Methods:
With the use of the National Health Insurance Database Cohort (NHID-Cohort) consisting of one million patients from 2003 through 2013, we identified the patient with sudden cardiac arrest using Korean Standard Classification of Diseases, 6th Revision, code I46.

Results:
In all, 5,307 (0.52%) patients with SCA were identified between 2003 and 2013. SCA occurred more frequent in men (59.3%) than women (40.7%) (p<0.001). The annual incidence of SCA increased by 116.3% from 28.9 in 2003 to 62.5 in 2013 (per 100,000 person-year, p<0.001). The increase of SCA was particularly predominant in patients with ≥60 years of age (from 153.8 to 259.1 per 100,000 person-year, p<0.001) and those with low economic status (from 27.5 to 85.2 per 100,000 person-year, p<0.001). Health care cost per 100,000 person-year also increased from $65,866 in 2003 to $241,534 in 2013 (p<0.001). However, there was no significant improvement in one-month survival rate during the same period (11.9% in 2003, 13.4% in 2013, p=0.526).

Conclusions:
The incidence of SCA in South Korea continues to rise over the past ten years, especially in elderly people. Despite the tremendous advances in the field of cardiovascular medicine, outcome of SCA is at a standstill.
Abstract 11107: The ECG has a Low Diagnostic Yield in Active Individuals With Dilated Cardiomyopathy
Authors: Millar Lynne , Webb Jess , Dhutia Harshil , Magavern Emma , Narain Rajay , Malhotra Aneil , Merghani Ahmed , Sharma Rajan , Sharma Sanjay
Published: July 2021

Introduction/Objective:
Around 90% of patients with HCM have an abnormal ECG; however there is paucity of data on the ECG in DCM. Approximately 14% athletes show an LV cavity >60mm and 1-2% reveal a borderline low LVEF which overlaps with DCM. The role of ECG in facilitating the differentiation between physiologic LV enlargement and DCM has not been investigated. We sought to ascertain the utility of the various ECG screening criteria in differentiating physiology from pathology in a cohort of individuals with LV dilatation.

Methods:
89 individuals with a dilated LVEDD (43 asymptomatic athletes from cardiac screening (male=37, female=6) and 46 non-ischaemic DCM NYHA class I from a cardiomyopathy clinic (males=33, female=13) were included. Fourty (87%) of the DCM patients were on a beta-blocker. The 2010 ESC, ‘Seattle’ and the novel ‘Refined’ screening criteria were applied to the most recent ECG in both cohorts to assess whether ECG screening would have accurately raised suspicion of pathology.

Results:
Using the ESC criteria 11 DCM patients had a normal ECG and 6 had group 1 changes; therefore 40.0% of DCM patients would have been considered to have an ECG compatible with athletic training. Excluding sinus bradycardia, the most common group 1 change was early repolarisation. The sensitivity and specificity of the ESC criteria for detecting pathology in our cohort was 63.0% and 69.0% respectively. The sensitivity and specificity of the ‘Seattle’ criteria is 50% and 76.7%. The ‘Refined’ criteria was less sensitive at 41.3% but had a higher specificity of 79.2%.

Conclusions:
It is often assumed the ECG is abnormal in patients with a dilated cardiomyopathy. In our cohort 40% of the ECGs in our DCM patients would have not prompted further investigation if seen at pre-participation screening. This study demonstrates the ECG is not a particularly useful investigation in distinguishing physiological from pathological LV dilatation.
Abstract 11139: Prevalence, Characteristics and Prognostic Associations of Carotid Plaque Among HIV-infected Subjects Free of Known Cerebrovascular Disease
Authors: Janjua Sumbal A , Staziaki Pedro V , Takx Richard A , Emami Hamed , Park Jakob , Ivanov Alexander V , Hallett Travis R , Ghoshhajra Brian B , Romero Javier M , Lu Michael T , Zanni Markella , Grinspoon Steven K , Hoffmann Udo , Neilan Tomas G
Published: July 2021

Introduction:
The risk of cerebrovascular events is increased among HIV-infected subjects; this risk is independent of conventional cardiovascular (CV) risk factors and may be related to persistent inflammation leading to accelerated carotid atherosclerosis. However, there are no data characterizing the prevalence, characteristics and prognostic associations of carotid plaque among subjects with HIV.

Methods:
From a clinical registry, we identified all HIV-infected subjects with a CT neck from 2005-2014. Data collection and CT analysis were performed by blinded independent teams and included CV and HIV specific risk factors. CT variables included presence of carotid plaque, plaque composition (calcified/non-calcified/mixed), degree of stenosis [≥ 50%] and high-risk plaque (HRP) features [low attenuation, spotty calcification]. The outcome was a cerebrovascular event (stroke, transient ischemic event) defined by ICD codes and independently adjudicated by a board certified physician. Association between plaque presence, characteristics and HRP with events was tested by Cox proportional hazard models.

Results:
Of 231 HIV-infected subjects, 32 had prior cerebrovascular disease,15 had poor image quality leaving an n=184 (46±10 yrs, 21% female,12% diabetics, 19% HTN, smoking in 31%, 14% on statins, average LDL of 90±39mg/dl). On CT, 36% had any carotid plaque and 23% had bilateral plaque. Of those with plaque,15% had a stenosis of ≥50% and 70% had any HRP feature. Both plaque and HRP were increased with age, duration of HIV and anti-retroviral therapy. Over a median of 4 yrs,13 (7%) cerebrovascular events occurred. After adjusting for the number of CV risk factors, a carotid plaque [HR: 3.5 (1.1-11)
P
=0.03, Fig 1A] and any HRP feature [HR: 3.2 (1.0-10)
P
=0.04, Fig 1B] were associated with incident cerebrovascular events.

Conclusions:
Among HIV-infected subjects, free of known cerebrovascular disease, carotid plaque and/or HRP predict cerebrovascular events.
Abstract 11144: Demographics of Study Participants in Clinical Trials for Cardiovascular Drugs Approved at FDA CDER From 2013 to 2014
Authors: Fadiran Emmanuel O , Itana Hawi , Elahi Merina , Igun Ayomide , Soon Greg , Chen Alice , Pariser Anne
Published: July 2021

Introduction:
Cardiovascular disease (CVD) is the leading cause of death for women in the United States. To assess the safety and efficacy of CVD drugs in the diverse population of patients who will use them post-approval, the US FDA has implemented guidance and regulation to encourage the inclusion of women and racial/ethnic minorities in drug clinical trials (CTs). This study assessed the participation of women and minorities in CTs for CVD indications for New Drug Applications (NDAs) approved at FDA CDER from 2013-2014.

Methods:
The sex, race/ethnicity, and age of subjects who participated in CVD drug CTs were assessed from final clinical study reports accessed via internal FDA databases, and were evaluated for the presence of data analysis by sex. The ratio of the percent of women in the CT population was also compared to those in the disease population.

Results:
Four novel CVD drugs were approved in this time frame, including 2 drugs indicated for pulmonary hypertension (PH) (riociguat, total CT population n=2691; macitentan, n=1884), and 1 drug each for prevention of thrombotic acute CV events (vorapaxar, n=41972) and treatment of neurogenic orthostatic hypotension (NOH) (droxidopa, n=1125). Demographic subgroup analysis indicated that percent female participation was 26% for thrombotic CV events, 40% for NOH, and 47% for PH. Female participation in pivotal trials only (in which benefit-risk was demonstrated) was 24% for thrombotic CV events, 33% for NOH, and 75% for PH.

The majority of the trial participants were White (85%), and mean ages were 48 years (PH), 61 years (thrombotic CV events), and 64 years (NOH). Sex-based analysis for both efficacy and safety was presented for all drugs. Three of the NDAs with available disease prevalence data had a ratio of percent female participation to disease prevalence that was between 0.80 and 1.2.

Conclusions:
Percent female participation varied substantially by disease indication, with PH (a female predominant disease) having the highest female participation. Female participation in the prevention of thrombotic CV events was lower than anticipated based upon disease prevalence in the population. Further exploration of demographic subgroup participation in CTs for CVD drugs in a larger sample size is ongoing.
Abstract 11473: Dabigatran Treatment Simulation in Patients Undergoing Maintenance Hemodialysis
Authors: Liesenfeld Karl-Heinz , Clemens Andreas , Kreuzer Joerg , Brueckmann Martina , Ahmad Azhar , Schulze Friedrich
Published: July 2021

Background:
Patients undergoing maintenance hemodialysis (HD) with atrial fibrillation (AF) are at increased risk of ischemic stroke and bleeds. At present, vitamin K antagonists, e.g. warfarin, are predominantly used for anticoagulation in this patient population. In such patients, limited data are available on the use of non-vitamin K oral anticoagulants. Dabigatran etexilate (DE) is mainly (85%) renally eliminated, thus its half-life is prolonged in renal impairment. It has been established that 4-hour HD can remove up to 60% of dabigatran from the plasma. The aim of the presented study is to evaluate the dose-exposure relationship for DE in HD patients considering different dosages and HD modalities by pharmacokinetic modeling. The resulting data could inform DE dose selection in future clinical trials.

Method:
We compared modeled DE exposure at once- and twice-daily doses of 75 mg, 110 mg, 150 mg in HD patients from pre- and post-dialysis dosing, with values simulated from AF patients in the RE-LY
®
trial, based on a previously characterized pharmacometric model. Furthermore, variations in non-renal clearance, and several dialysis settings were simulated. Exposure (area under the curve, AUC) was compared to those from typical clinical HD settings.

Results:
Twice-daily DE doses showed a 1.5- to 3.3-fold increase in AUC of dabigatran compared with a typical RE-LY
®
patient. A once-daily dose of 75 mg given after dialysis or 110 mg given before dialysis achieved an AUC comparable (-13.3 and +4.4%, respectively) to typical RE-LY
®
patients. Of the patient and dialysis variables, non-renal clearance had the highest impact on exposure (≤ 31% change). Duration of dialysis, dialysate and blood flow rate changed exposure by ≤14%.

Conclusion:
Twice-daily dosing of all DE doses tested in this simulation resulted in exposures clearly above what can be seen in typical RE-LY
®
patients and thus might not be recommendable, although this is based on modeling only and the clinical impact is unknown. In patients undergoing maintenance HD, DE 75 mg once daily (given after dialysis) or 110 mg once daily (given before dialysis), resulted in exposure comparable to that simulated in typical RE-LY
®
patients.
Abstract 11505: Increased Mitochondrial Fission Plays a Critical Role in Low Glucose-Induced Endothelial Dysfunction
Authors: Tanner Michael J , Wang Jingli , Ying Rong , Malik Mobin , Branum Amberly , Suboc Tisha B , Coulliard Allison , Widlansky Michael E
Published: July 2021

Introduction:
Intensive glucose control in patients with Type 2 Diabetes Mellitus has resulted in increased incidence of hypoglycemia, often with elevated risk of adverse cardiovascular events. Studies of endothelial cells (ECs) and human arterioles exposed to a low glucose (LG) environment suggest the risk is mediated through a dysfunctional endothelium, characterized by greater reactive oxygen species (ROS) production and decreased nitric oxide (NO).

Hypothesis:
We propose that LG-induced endothelial dysfunction is driven by an imbalance in the fission/fusion process of mitochondrial networks within ECs.

Methods:
Human ECs were used to quantify mitochondrial fission and evaluate Mdivi-1, a fission inhibitor, following incubation in either LG (40 mg/dL) or normal glucose (NG, 90 mg/dL) physiologic environments for 2 hours. Similarly, human subcutaneous adipose arterioles subjected to either LG or NG, were used to detect ROS with MitoSOX and NO with DAF-2DA, ±Mdivi-1. Arteriole vasoactivity was measured ±Mdivi-1 in a dose-response manner to acetylcholine (Ach). This experiment was repeated employing siRNA to knockdown expression of the primary fission protein, Drp1.

Results:
More mitochondrial fragmentation was observed in ECs exposed to LG (LG vs NG: 3.2±0.6 vs 2.4 ±0.5, P<0.05) and was attenuated by Mdivi-1 (P<0.05). Vessels displayed increased ROS when exposed to LG (LG vs NG: 119.8±24.5 vs 80.1±21.8, P<0.02) and levels decreased with Mdivi-1 (P=0.005). Available NO decreased in LG treated vessels (LG vs NG: 19.3±2.7 vs 31.7±3.2, P<0.001) and improved with LG+Mdivi-1 (P<0.05). LG exposed vessels displayed impaired endothelial dependent vasodilation and co-incubation with Mdivi-1 rescued the dilation response (LG vs LG+Mdivi-1 at [Ach] x10
-7
to 10
-5
M, P<0.02). Likewise, knockdown of Drp1 also improved vasoactive response in the LG group (LG+scramble vs LG+siDrp1 at [Ach] x10
-7
to 10
-5
M, P<0.003).

Conclusion:
Human arterioles exposed to LG conditions exhibit a decrease in NO, increased ROS and an impaired vasodilatory response correlating with dynamic mitochondrial changes. The role of the mitochondria in LG-induced endothelial dysfunction appears to be rooted in an increased mitochondrial fission response.
Abstract 11509: QT Rate Dependence is Reduced in Brugada Syndrome Independent of Genotypic Status
Authors: Robyns Tomas , Willems Rik , Ector Joris , Garweg Christophe , Kuiperi Cuno , Corveleyn Anniek , Nuyens Dieter
Published: July 2021

Introduction:
Sudden cardiac death in Brugada syndrome (BrS) is most frequent in rest or during sleep suggesting an influence of the autonomic nervous system. Some limited data indicate reduced QT rate dependence and loss of its diurnal variation in BrS.

Hypothesis:
We evaluated the hypothesis that QT rate dependence and its diurnal variation is reduced in BrS and assessed whether presence of an SCN5A mutation influences this relationship.

Methods:
In this retrospective single center study we included 4 different groups: patients demonstrating a spontaneous or ajmaline-induced type 1 ECG with (N=17) and without (N=19) SCN5A mutation, carriers of an SCN5A mutation without phenotypic evidence of BrS based on serial ECG’s and provocation with ajmaline (N=22) and finally genotype negative family members of SCN5A mutation carriers as controls (N=25). All patients underwent 24 hour holter recordings. QT/RR analysis of 24 hour, daytime (8AM-9PM) and nighttime (11PM-6AM) data was performed along with manual review.

Results:
Age and sex were comparable between groups, as was the use of a beta-blocker (9 in the total group). 24 hour QT/RR slope was reduced both in the SCN5A positive (0.141±0.045; p=0.04) and negative BrS group (0.141±0.047; p=0.03) as in the phenotype negative genotype positive group (0.128±0.046; p=0.001) compared to controls (0.183±0.054). Daytime QT rate dependence remained significantly reduced in the 3 pathological states, however nighttime QT rate dependence was not. In controls there was a trend towards a diurnal variation of QT rate dependence (QT/RR slope day 0.152±0.063; night 0.129±0.05; p=0.13), however this was not the case in any of the other groups. There was a clear trend towards lower values in 10 symptomatic BrS patients (0.118±0.045) compared to 26 asymptomatic BrS patients (0.15±0.043; p=0.06).

Conclusions:
In this large cohort of BrS patients, QT rate dependence was reduced during 24 hour and daytime periods without evidence of diurnal variation and independent of the presence of an SCN5A mutation. This attenuation of QT rate dependency further underscores the role of a pathological response to autonomic nervous system modulation in BrS arrhythmogenesis, irrespective of SCN5A genotypic status.
Abstract 11513: Eplerenone Treatment Mitigates Atrial Structural Remodeling but Does Not Modify the Transition From Paroxysmal to Persistent Atrial Fibrillation in an Ovine Model
Authors: Takemoto Yoshio , Ramirez Rafael J , Kaur Kuljeet , Ponce-Balbuena Daniela , Ramos-Mondragon Roberto , Willis Byrd C , Ennis Steven R , Guerrero-Serna Guadalupe , Pandit Sandeep V , Berenfeld Omer , Jalife José
Published: July 2021

Introduction:
Recently we demonstrated that inhibition of the pro-fibrotic protein Galectin-3 reduces atrial dilatation, fibrosis and electrical remodeling as well as atrial fibrillation (AF) burden in a clinically relevant sheep model of lone persistent AF (Takemoto Y, et al. Heart Rhythm 12:S4; 2015). The mineralocorticoid blocker eplerenone (EPL) has been shown to reduce fibrosis and the incidence of AF in patients with systolic heart failure and mild symptoms, but the mechanism is poorly understood. We tested the hypothesis that by reducing atrial dilatation and fibrosis alone in the absence of heart failure EPL treatment also reduces atrial fibrosis and prevents AF perpetuation.

Methods:
We conducted a placebo-controlled drug study in 17 atrially tachypaced sheep for 14±2 weeks (maximum 23 weeks). We compared effects of EPL treatment (100 mg/day, N=10) with sugar pill (SP, N=7) orally administered daily from the start of tachypacing. The terminal point of the study was a continuous 7-day stretch of persistent AF (N=14) or the completion of 23-weeks tachypacing (N=3).

Results:
In vivo, EPL significantly reduced the rate of left atrial (LA) dilatation, mitral regurgitation, cellular hypertrophy, interstitial fibrosis (picrosirius red staining), and serum procollagen III N-terminal peptide (P3NP) levels during AF progression. However EPL did not affect the rate of dominant frequency (DF) increase or the maximum DF (DFmax). Ex-vivo optical mapping of the explanted hearts showed that EPL did not affect action potential duration or conduction velocity during pacing, or the DFmax during AF compared with hearts from SP-treated animals. However, EPL treatment significantly reduced the number of rotors and the trajectory areas of wavebreaks in LA during AF. Most important, unlike Gal-3 inhibition, EPL treatment did not change AF inducibility or AF burden at any time of weekly evaluation during AF progression.

Conclusions:
Mineralocorticoid inhibition during AF progression mitigates fibrosis and structural remodeling, which reduces complexity of AF and possibly contributes to delay the AF substrate somewhat. However, while reduction of fibrosis might be necessary, it is not sufficient to prevent AF perpetuation when electrical remodeling endures.
Abstract 11518: Diastolic Left Ventricular Dysfunction is a Common and Early Cardiac Abnormality in Hutchinson-Gilford Progeria Syndrome
Authors: Prakash Ashwin , Gordon Leslie B , Kleinman Monica E , D'Agostino Ralph , Massaro Joe , Kieran Mark W , Gerhard-Herman Marie , Smoot Leslie B
Published: July 2021

Introduction:
Hutchinson-Gilford progeria syndrome (HGPS) is associated with premature death due to cardiovascular events. However, little is known about the natural history of cardiac disease in this population. We prospectively evaluated children with HGPS to identify echocardiographic abnormalities in ventricular and valve function and to assess the effect of treatment on these abnormalities.

Methods and Results:
Transthoracic echocardiography was used to evaluate 51 children with HGPS (45 with classic type, 6 with non-classic type; 55% males) at a median age of 10.7 (2.4-19.8) years. Among the study population, 19 were evaluated prior to entry into an open label drug trial of the farnesyltransferase inhibitor lonafarnib while the other 32 were receiving combination therapy with lonafarnib, pravastatin and zoledronic acid (triple therapy) at the time of evaluation. As seen in the Table, diastolic dysfunction diagnosed using pulsed wave tissue Doppler was the most common cardiac abnormality at all ages, developing early and present universally beyond 12.1 years of age. Other cardiac abnormalities including left ventricular hypertrophy (LVH), LV systolic dysfunction, and mitral or aortic valve disease were less common and appeared later. Using multiple linear regression to control for age and gender, patients receiving triple therapy demonstrated less severe LV diastolic dysfunction evidenced by higher lateral E’ velocities (p=0.01) and lower mitral inflow E velocity/lateral E’ velocity ratio (p=0.006). Other cardiac abnormalities were not associated with triple therapy.

Conclusions:
In patients with Hutchinson-Gilford progeria syndrome, LV diastolic dysfunction is common and appears early. Other cardiac abnormalities are less common and appear at a later age. Triple therapy is associated with less severe diastolic dysfunction. Echocardiographic parameters of LV diastolic dysfunction may be useful endpoints in future clinical trials.