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Cardiovascular Health in African Americans: A Scientific Statement From the American Heart Association [AHA Scientific Statements]

2017-11-20T10:40:37-08:00

Background and Purpose:Population-wide reductions in cardiovascular disease incidence and mortality have not been shared equally by African Americans. The burden of cardiovascular disease in the African American community remains high and is a primary cause of disparities in life expectancy between African Americans and whites. The objectives of the present scientific statement are to describe cardiovascular health in African Americans and to highlight unique considerations for disease prevention and management.Method:The primary sources of information were identified with PubMed/Medline and online sources from the Centers for Disease Control and Prevention.Results:The higher prevalence of traditional cardiovascular risk factors (eg, hypertension, diabetes mellitus, obesity, and atherosclerotic cardiovascular risk) underlies the relatively earlier age of onset of cardiovascular diseases among African Americans. Hypertension in particular is highly prevalent among African Americans and contributes directly to the notable disparities in stroke, heart failure, and peripheral artery disease among African Americans. Despite the availability of effective pharmacotherapies and indications for some tailored pharmacotherapies for African Americans (eg, heart failure medications), disease management is less effective among African Americans, yielding higher mortality. Explanations for these persistent disparities in cardiovascular disease are multifactorial and span from the individual level to the social environment.Conclusions:The strategies needed to promote equity in the cardiovascular health of African Americans require input from a broad set of stakeholders, including clinicians and researchers from across multiple disciplines.






Prognostic Value of Coronary Artery Calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) [Original Research Article]

2017-11-20T10:40:37-08:00

Background:Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However, limited data exist as to how CAC compares with functional testing (FT) in estimating prognosis in symptomatic patients.Methods:In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain (or dyspnea) and intermediate pretest probability for obstructive coronary artery disease were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4209) and compared that with results of FT (n=4602). We stratified CAC and FT results as normal or mildly, moderately, or severely abnormal (for CAC: 0, 1–99 Agatston score [AS], 100–400 AS, and >400 AS, respectively; for FT: normal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia, and severe=large ischemic region abnormality). The primary end point was all-cause death, myocardial infarction, or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios (HRs) and C statistics to determine predictive and discriminatory values.Results:Overall, the distribution of normal or mildly, moderately, or severely abnormal test results was significantly different between FT and CAC (FT: normal, n=3588 [78.0%]; mild, n=432 [9.4%]; moderate, n=217 [4.7%]; severe, n=365 [7.9%]; CAC: normal, n=1457 [34.6%]; mild, n=1340 [31.8%]; moderate, n=772 [18.3%]; severe, n=640 [15.2%]; P<0.0001). Moderate and severe abnormalities in both arms robustly predicted events (moderate: CAC: HR, 3.14; 95% confidence interval, 1.81–5.44; and FT: HR, 2.65; 95% confidence interval, 1.46–4.83; severe: CAC: HR, 3.56; 95% confidence interval, 1.99–6.36; and FT: HR, 3.88; 95% confidence interval, 2.58–5.85). In the CAC arm, the majority of events (n=112 of 133, 84%) occurred in patients with any positive CAC test (score >0), whereas fewer than half of events occurred in patients with mildly, moderately, or severely abnormal FT (n=57 of 132, 43%; P<0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6% for FT versus 35.2% for CAC; P<0.001). Overall discriminatory ability in predicting the primary end point of mortality, nonfatal myocardial infarction, and unstable angina hospitalization was similar and fair for both CAC and FT (C statistic, 0.67 versus 0.64). Coronary computed tomographic angiography provided significantly better prognostic information compared with FT and CAC testing (C index, 0.72).Conclusions:Among stable outpatients presenting with suspected coronary artery disease, most patients experiencing clinical events have measurable CAC at baseline, and fewer than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests.Clinical Trial Registration:URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.






Modeling Major Adverse Outcomes of Pediatric and Adult Patients With Congenital Heart Disease Undergoing Cardiac Catheterization [Original Research Article]

2017-11-20T10:40:37-08:00

Background:Risk standardization for adverse events after congenital cardiac catheterization is needed to equitably compare patient outcomes among different hospitals as a foundation for quality improvement. The goal of this project was to develop a risk-standardization methodology to adjust for patient characteristics when comparing major adverse outcomes in the NCDR’s (National Cardiovascular Data Registry) IMPACT Registry (Improving Pediatric and Adult Congenital Treatment).Methods:Between January 2011 and March 2014, 39 725 consecutive patients within IMPACT undergoing cardiac catheterization were identified. Given the heterogeneity of interventional procedures for congenital heart disease, new procedure-type risk categories were derived with empirical data and expert opinion, as were markers of hemodynamic vulnerability. A multivariable hierarchical logistic regression model to identify patient and procedural characteristics predictive of a major adverse event or death after cardiac catheterization was derived in 70% of the cohort and validated in the remaining 30%.Results:The rate of major adverse event or death was 7.1% and 7.2% in the derivation and validation cohorts, respectively. Six procedure-type risk categories and 6 independent indicators of hemodynamic vulnerability were identified. The final risk adjustment model included procedure-type risk category, number of hemodynamic vulnerability indicators, renal insufficiency, single-ventricle physiology, and coagulation disorder. The model had good discrimination, with a C-statistic of 0.76 and 0.75 in the derivation and validation cohorts, respectively. Model calibration in the validation cohort was excellent, with a slope of 0.97 (standard error, 0.04; P value [for difference from 1] =0.53) and an intercept of 0.007 (standard error, 0.12; P value [for difference from 0] =0.95).Conclusions:The creation of a validated risk-standardization model for adverse outcomes after congenital cardiac catheterization can support reporting of risk-adjusted outcomes in the IMPACT Registry as a foundation for quality improvement.






Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension [Original Research Article]

2017-11-20T10:40:37-08:00

Background:Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH.Methods:Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource–Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured.Results:Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%–35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23–38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival.Conclusions:Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation.






Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction [Original Research Article]

2017-11-20T10:40:37-08:00

Background:Heart failure with preserved ejection fraction (HFpEF) represents approximately half of heart failure, and its incidence continues to increase. The leading cause of mortality in HFpEF is sudden death, but little is known about the underlying mechanisms.Methods:Dahl salt-sensitive rats were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF (n=38). Rats fed a normal-salt diet (0.3% NaCl) served as controls (n=13). Echocardiograms were performed to assess systolic and diastolic function from 14 weeks of age. HFpEF-verified and control rats underwent programmed electrical stimulation. Corrected QT interval was measured by surface ECG. The mechanisms of ventricular arrhythmias (VA) were probed by optical mapping, whole-cell patch clamp to measure action potential duration and ionic currents, and quantitative polymerase chain reaction and Western blotting to investigate changes in ion channel expression.Results:After 7 weeks of a high-salt diet, 31 of 38 rats showed diastolic dysfunction and preserved ejection fraction along with signs of heart failure and hence were diagnosed with HFpEF. Programmed electric stimulation demonstrated increased susceptibility to VA in HFpEF rats (P<0.001 versus controls). The arrhythmogenicity index was increased (P<0.001) and the corrected QT interval on ECG was prolonged (P<0.001) in HFpEF rats. Optical mapping of HFpEF hearts demonstrated prolonged action potentials (P<0.05) and multiple reentry circuits during induced VA. Single-cell recordings of cardiomyocytes isolated from HFpEF rats confirmed a delay of repolarization (P=0.001) and revealed downregulation of transient outward potassium current (Ito; P<0.05). The rapid components of the delayed rectifier potassium current (IKr) and the inward rectifier potassium current (IK1) were also downregulated (P<0.05), but the current densities were much lower than for Ito. In accordance with the reduction of Ito, both Kcnd3 transcript and Kv4.3 protein levels were decreased in HFpEF rat hearts.Conclusions:Susceptibility to VA was markedly increased in rats with HFpEF. Underlying abnormalities include QT prolongation, delayed repolarization from downregulation of potassium currents, and multiple reentry circuits during VA. Our findings are consistent with the hypothesis that potassium current downregulation leads to abnormal repolarization in HFpEF, which in turn predisposes to VA and sudden cardiac death.



SIRT2 Acts as a Cardioprotective Deacetylase in Pathological Cardiac HypertrophyUniversity of Michigan [Original Research Article]

2017-11-20T10:40:37-08:00

Background:Pathological cardiac hypertrophy induced by stresses such as aging and neurohumoral activation is an independent risk factor for heart failure and is considered a target for the treatment of heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. We aimed to investigate the roles of SIRT2 in aging-related and angiotensin II (Ang II)–induced pathological cardiac hypertrophy.Methods:Male C57BL/6J wild-type and Sirt2 knockout mice were subjected to the investigation of aging-related cardiac hypertrophy. Cardiac hypertrophy was also induced by Ang II (1.3 mg/kg/d for 4 weeks) in male C57BL/6J Sirt2 knockout mice, cardiac-specific SIRT2 transgenic (SIRT2-Tg) mice, and their respective littermates (8 to ≈12 weeks old). Metformin (200 mg/kg/d) was used to treat wild-type and Sirt2 knockout mice infused with Ang II. Cardiac hypertrophy, fibrosis, and cardiac function were examined in these mice.Results:SIRT2 protein expression levels were downregulated in hypertrophic hearts from mice. Sirt2 knockout markedly exaggerated cardiac hypertrophy and fibrosis and decreased cardiac ejection fraction and fractional shortening in aged (24-month-old) mice and Ang II–infused mice. Conversely, cardiac-specific SIRT2 overexpression protected the hearts against Ang II–induced cardiac hypertrophy and fibrosis and rescued cardiac function. Mechanistically, SIRT2 maintained the activity of AMP-activated protein kinase (AMPK) in aged and Ang II–induced hypertrophic hearts in vivo as well as in cardiomyocytes in vitro. We identified the liver kinase B1 (LKB1), the major upstream kinase of AMPK, as the direct target of SIRT2. SIRT2 bound to LKB1 and deacetylated it at lysine 48, which promoted the phosphorylation of LKB1 and the subsequent activation of LKB1-AMPK signaling. Remarkably, the loss of SIRT2 blunted the response of AMPK to metformin treatment in mice infused with Ang II and repressed the metformin-mediated reduction of cardiac hypertrophy and protection of cardiac function.Conclusions:SIRT2 promotes AMPK activation by deacetylating the kinase LKB1. Loss of SIRT2 reduces AMPK activation, promotes aging-related and Ang II–induced cardiac hypertrophy, and blunts metformin-mediated cardioprotective effects. These findings indicate that SIRT2 will be a potential target for therapeutic interventions in aging- and stress-induced cardiac hypertrophy.



Risk Stratification in Arrhythmogenic Right Ventricular Cardiomyopathy [In Depth]

2017-11-20T10:40:37-08:00

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by ventricular arrhythmias and an increased risk of sudden cardiac death. Although structural abnormalities of the right ventricle predominate, it is well recognized that left ventricular involvement is common, particularly in advanced disease, and that left-dominant forms occur. The pathological characteristic of ARVC is myocyte loss with fibrofatty replacement. Since the first detailed clinical description of the disorder in 1982, significant advances have been made in understanding this disease. Once the diagnosis of ARVC is established, the single most important clinical decision is whether a particular patient’s sudden cardiac death risk is sufficient to justify placement of an implantable cardioverter-defibrillator. The importance of this decision reflects the fact that ARVC is a common cause of sudden death in young people and that sudden death may be the first manifestation of the disease. This decision is particularly important because these are often young patients who are expected to live for many years. Although an implantable cardioverter-defibrillator can save lives in individuals with this disease, it is also well recognized that implantable cardioverter-defibrillator therapy is associated with both short- and long-term complications. Decisions about the placement of an implantable cardioverter-defibrillator are based on an estimate of a patient’s risk of sudden cardiac death, as well as their preferences and values. The primary purpose of this article is to provide a review of the literature that concerns risk stratification in patients with ARVC and to place this literature in the framework of the 3 authors’ considerable lifetime experiences in caring for patients with ARVC. The most important parameters to consider when determining arrhythmic risk include electric instability, including the frequency of premature ventricular contractions and sustained ventricular arrhythmia; proband status; extent of structural disease; cardiac syncope; male sex; the presence of multiple mutations or a mutation in TMEM43; and the patient’s willingness to restrict exercise and to eliminate participation in competitive or endurance exercise.





















Abstract 11582: Skeletal Muscle Mass Determined by Bioelectrical Impedance Analysis is Associated With Exercise Capacity and Cardiac Events in Patients With Congenital Heart Disease [Session Title: Vascular Function in Congenital Heart Disease]

2017-11-11T04:35:56-08:00

Introduction: Exercise capacity of patients with heart failure (HF) was thought to entirely associate with oxygen supply as central hemodynamic factor. However, skeletal muscle disorders in patients with HF have been recently reported to contribute to exercise intolerance. Bioelectrical impedance analysis (BIA) is a rapid and non-invasive method that measures skeletal muscle mass (SMM) and has been widely used in clinical research. However, little has been reported regarding SMM values in patients with congenital heart disease (CHD).Hypothesis: We assessed the hypothesis that SMM determined by BIA is associated with exercise capacity and prevalence of cardiac events in patients with CHD.Methods: We performed a prospective single-center study of 222 consecutive patients (mean age, 33 [range 12-76] years; 48% males) with CHD, who were admitted to our institute between April 2013 and April 2016. We determined SMM of patients by BIA, and reviewed their medical records in order to evaluate the relationship between SMM and either exercise capacity or prevalence of cardiac events.Results: A significant correlation was found between 6-minute walking test distance and whole body SMM (r = 0.36, p = 0.002), arms (r = 0.35), trunk (r = 0.34), and legs (r = 0.39), as well as between peak oxygen uptake (peak VO2) and whole body SMM (r = 0.59, p < 0.001), arms (r = 0.54), trunk (r = 0.56), and legs (r = 0.54). During the median 36-month follow-up period, receiving operating characteristic (ROC) curve analysis showed that the cutoff point of SMM for predicting cardiac events was 24.4 for males (area under the curve [AUC], 0.75; sensitivity, 0.92; specificity, 0.54) and 19.1 for females (AUC, 0.73; sensitivity, 0.91; specificity, 0.63). Using the Cox hazard model, we determined that the hazard ratio of cardiac events in male patients with SMM < 24.4 compared to those with SMM ≥ 24.4 was 5.9 (95% confidence interval [CI] 1.6-38.4). The same analysis gave a hazard ratio of 3.2 in female patients with SMM < 19.1 compared to those with SMM ≥ 19.1 (95% CI 1.1-13.8).Conclusions: SMM determined by BIA correlates with exercise capacity and constitutes a useful tool for predicting cardiac events in patients with CHD.



Abstract 11584: Direct Oral Anti-coagulation Significantly Reduces Mortality in Atrial Fibrillation [Session Title: Treatment of Arrhythmias: Pharmacologic]

2017-11-11T04:35:56-08:00

Introduction: Direct anticoagulants (DOACs) have demonstrated significant reduction in stroke and all-cause mortality rates in non-valvular atrial fibrillation (NVAF) patients. However, utilization of DOACs is still limited, with many patients not receiving any anticoagulation therapy. Data on long-term mortality implications of DOAC underutilization in the general NVAF population is limited. Our objective was to explore the effect of DOACs on mortality of NVAF patients in a clinical practice setting with long-term follow-up.Hypothesis: We assessed the hypothesis that DOAC therapy significantly reduces mortality in eligible NVAF patients.Methods: We identified all NVAF patients eligible by Israel guidelines for DOAC therapy (CHADS2 ≥2) in Clalit Health Services from 2011 to 2016. Mean age of eligibility to DOAC therapy was 78 in both groups. Patients were followed to May 15, 2017, or death event. Drug adherence was assessed based on electronic records of DOAC prescription data. Patients were considered to be “on-therapy” up to 30 days of their last issued prescription.Results: All-cause mortality rates were calculated for 19,881 patients treated with DOAC and 24,871 patients with no anticoagulation therapy. Compared to patients with no anticoagulation, risk adjusted hazard ratio for death for DOAC treated patients was 0.646 (95% CI: 0.621-0.672). While “on-therapy”, the risk of death of DOAC patients was halved to 0.329 (95% CI: 0.312-0.346).Conclusions: In this cohort of general clinical practice NVAF patients, mortality rates were significantly lower with DOAC therapy. Our findings support further evidence for the importance of initiation and adherence of DOAC therapy in all eligible NVAF patients.



Abstract 11585: Long-term Therapy With a Chymase-1 Inhibitor (BAY 1142524) Improves Left Ventricular Systolic Function and Prevents Progressive Chamber Remodeling in Dogs With Heart Failure [Session Title: A CHF/Cardiomyopathy Potpourri]

2017-11-11T04:35:56-08:00

Introduction: Chymase-1 (CMA1) is a serine protease found in secretary granules of mast cells. When stimulated to de-granulate by an enhanced inflammatory state, as in heart failure (HF), mast cells release CMA1. CMA1 triggers angiotensin-II formation, induces cardiomyocyte apoptosis and promotes release of collagen-III and transforming growth factor-β1 (TGF-β1) leading to interstitial fibrosis.Objective: Examine the long-term effects of a CMA1 inhibitor (BAY 1142524) on LV function and chamber remodeling in dogs with chronic HF (LV ejection fraction, EF~30%).Methods: Studies were performed in 16 coronary microembolization-induced HF dogs randomized to 3 months oral therapy with low dose (LD) BAY 1142524 (0.5 mg/kg bid, n=4), medium dose (MD) BAY 1142524 (2.0 mg/kg bid, n=4), high dose (HD) BAY 1142524 (5.0 mg/kg bid, n=4) or to no therapy (Control, n=4). The treatment effect Δ, between pre- and post-treatment was calculated from ventriculograms for LV end-systolic volume (ESV) and EF. Plasma n-terminal-pro brain-natriuretic peptide (nt-proBNP), TGF-β1 and tumor necrosis factor-α (TNFα) were measured by ELISA. LV volume fraction of interstitial fibrosis (VFIF) and myocyte cross-sectional area (MCSA), a measure of myocyte hypertrophy, were measured histomorphometrically.Results: In Controls, ESV increased and EF decreased over the course of therapy whereas treatment with BAY 1142524 improved EF and tended to reduce ESV in a dose-dependent manner (Table). Compared to controls, BAY 1142524 decreased nt-proBNP, TGF-β1, TNF-α, VFIF and MCSA in a dose-dependent manner (Table).Conclusions: In ischemia-induced HF dogs, therapy with BAY 1142524 improved LV systolic function and attenuated LV remodeling. BAY 1142524 also normalized plasma biomarkers and reduced cardiac burden of fibrosis and hypertrophy. The findings support development of this CMA1 inhibitor for treating LV dysfunction following myocardial infarction and prevent progression toward HF.



Abstract 11589: Accelerated Atherosclerosis Development in C57BL6 Mice by Overexpressing Adeno-associated Virus-mediated Gain-of-function Mutant of Proprotein Convertase Subtilisin/kexin Type 9 Gene and Partial Carotid Ligation [Session Title: Atherosclerosis--From the Microbiome to Immune Responses]

2017-11-11T04:35:56-08:00

Introduction: Studying the role of a particular gene in atherosclerosis typically requires a time-consuming and often difficult process of generating double-knockouts or transgenics on ApoE-/- or LDL receptor-/- background. Recently, it was reported that adeno-associated-virus-8 (AAV8) mediated overexpression of PCSK9 (AAV8-PCSK9) rapidly induced hyperlipidemia. However, using this method in C57BL6 wild-type (C57) mice, it took approximately 3 months to develop atherosclerosis. Our partial carotid ligation model is used to rapidly develop atherosclerosis by inducing disturbed flow in the left common carotid artery within 2 weeks in ApoE-/- or LDLR-/- mice.Hypothesis: Combination of these two approaches (AAV-PCSK9 and partial carotid ligation) will accelerate atherosclerosis development in C57 mice.Methods and Results: C57 mice were injected with AAV9-PCSK9 or AAV9-Luciferase (control) and high-fat diet was initiated. A week later, partial ligation was performed. Compared to the control, AAV-PCSK9 led to elevated serum PCSK9, hypercholesterolemia, and rapid atherosclerosis development within 3 weeks as determined by gross plaque imaging, and staining with Oil-Red-O, Movat’s pentachrome and CD45 antibody. These plaque lesions were comparable to the atherosclerotic lesions that have been previously observed in ApoE-/- or LDLR-/- mice that were subjected to partial carotid ligation and high-fat diet. Next, we tested whether our method can be utilized to rapidly determine the role of a particular gene in atherosclerosis. Using eNOS-/- and NOX1-/y mice on C57 background, we found that the eNOS-/- mice developed more advanced lesions, while the NOX1-/y mice developed less atherosclerotic lesions as compared to the C57 controls (Figure). These results are consistent with the previous findings using double knockouts (eNOS-/-_ApoE-/- and NOX1-/y_ApoE-/-).Conclusion: AAV9-PCSK9 injection followed by partial carotid ligation is an effective and time-saving approach to rapidly induce atherosclerosis. This accelerated model is well-suited to quickly determine the role of gene(s) interest without generating double- or triple-knockouts.



Abstract 11593: The Impact of Impaired Pancreatic Beta Cell Function on Cardiovascular Prognosis in Heart Failure Patients Without Diabetes Mellitus [Session Title: Heart Failure]

2017-11-11T04:35:56-08:00

Introduction: Insulin resistance (homeostasis model assessment ratio; HOMA-R) is associated with latent myocardial damage in apparently healthy subjects in health check. Meanwhile, diabetes mellitus is a well-known unfavourable prognostic risk factor in patients with heart failure (HF). However, it is still unclear whether beta cell function is associated with HF. HOMA-beta is reported to estimate beta cell function based on fasting plasma glucose and insulin concentration. We examined the impact of beta cell dysfunction on clinical outcomes in HF patients without diabetes mellitus (DM).Methods and Results: This study enrolled 312 HF patients without DM. Beta cell dysfunction was defined as HOMA-beta less than 30%. There were 90 cardiovascular events (29%) including 25 cardiovascular deaths and 65 rehospitalizations. There were 108 patients (35%) who showed beta cell dysfunction. Serum heart type fatty acid-binding protein (H-FABP) levels were higher in patients with beta cell dysfunction compared with those without (14.1 vs. 7.1 ng/ml, P< 0.001), whereas there was no significant difference between patients with and without insulin resistance. Plasma brain natriuretic peptide (BNP) levels were higher in patients with beta cell dysfunction compared with those without (625.2 vs. 399.0 pg/ml, P<0.001). HOMA-beta (r = -0.26, P < 0.001) was negatively correlated with log-BNP levels, whereas there was no correlation between HOMA-R and log-BNP levels. Kaplan-Meier analysis revealed significantly higher cardiovascular events rate was observed in patients with beta cell dysfunction (log-rank test p=0.001). However, there was no significant difference in cardiovascular events rates between patients with and without insulin resistance. Cox hazard analysis showed that beta cell dysfunction was independently associated with cardiovascular events after adjustment for confounding factors (hazard ratio 1.58, 95% confidence interval 1.02-2.45), whereas insulin resistance was not associated with cardiovascular events.Conclusion: Beta cell dysfunction, but not insulin resistance, was associated with unfavorable outcomes in HF patients without DM. Our results provide an important insight into impairment of insulin secretion in patients with HF.



Abstract 11595: Characterization of Human Coronary Atherosclerosis Using Polarization-Sensitive Optical Frequency Domain Imaging [Session Title: Interventional Catheterization]

2017-11-11T04:35:56-08:00

Introduction: Characterizing the content of collagen and smooth muscle cells (SMC), the source of arterial collagen, is central to the understanding of the pathophysiology of coronary atherosclerosis. Plaques that rupture typically have a thin fibrous cap with diminished collagen content and few SMCs. Polarization sensitive (PS-) optical frequency domain imaging (OFDI) provides maps of birefringence (BF), a tissue property elevated in collagen and SMCs, and depolarization, which hints at the presence of lipid, in addition to the conventional image of plaque structure.Hypothesis: We hypothesized that PS-OFDI could elucidate the role of collagen and SMCs in coronary atherosclerosis, and especially in fibrous caps.Methods: We performed PS-OFDI in patients with coronary artery disease (CAD; n=30). Imaged coronary arteries were divided into 340 segments and a single cross-section was analyzed from each segment. Plaques were segmented and classified based on conventional OFDI. The median BF and depolarization of each plaque was measured and compared among plaque types. In fibrous caps, we further computed the fraction of low-BF area to total fibrous cap area.Results: Plaques were classified into normal (n=42), fibrous (n=97), fibro-fatty (lipid arc <90 degree: n=43), and fibro-calcified plaques (n=95), fibroatheromas (lipid-arc ≥90 degree, FA: n=61), and ruptured plaques (n=2). The median BF (p<0.001) and depolarization (p<0.0001) showed a statistically significant difference among plaque types (Figure). In fibrous caps, Thin-capped FA and ruptured plaques had higher fraction of low-BF area compared with thick-capped FA (72 ± 11% versus 55 ± 19%, p<0.01).Conclusions: Intravascular PS-OFDI provides unique information by quantifying the polarization properties of the coronary arterial wall, and may help to advance our understanding of plaque progression and destabilization in human coronary atherosclerosis.



Abstract 11598: Coronary Flow Reserve in Patients With Prior Spontaneous Coronary Artery Dissection and Recurrent Angina [Session Title: Novel Insights into the Pathogenesis of Hypertension]

2017-11-11T04:35:56-08:00

Background: Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI) in young women. A significant proportion of SCAD patients have ongoing chronic chest pain despite healing of their dissection, the etiology of which is poorly understood. We sought to determine whether coronary microvascular dysfunction (CMD) contributes to post-SCAD chronic chest pain by performing coronary reactivity testing (CRT).Methods: Vancouver General Hospital is a quaternary referral center for SCAD patients and we prospectively follow over 350 SCAD patients. Patients with persistent chronic chest pain at least 3 months post-SCAD were eligible for our study. Eleven patients consented to having coronary angiography with CMD assessment. CRT was performed with the PressureWire wire (St Jude Medical) using thermodilution technique. Fractional flow reserve (FFR), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR) were measured in two coronary arteries: a previously affected SCAD artery and one non-SCAD artery. CFR <2.5 was defined as diagnostic of CMD. Low CFR was defined as CFR <3.0; abnormal IMR was defined as >25 units.Results: The average age of these 11 women was 50.2±7.2yrs. Mean baseline Seattle angina questionnaire (frequency domain) was 33.0±12.5. All presented with MI, ST-elevation in 3 women and 2 were revascularized with stenting during the initial SCAD event. Fibromuscular dysplasia (FMD) was present in 82.7% upon screening renal, iliac and cerebrovascular arteries. All patients who did not have stenting had spontaneous angiographic healing of their SCAD arteries. Nine out of eleven patients (81.8%) had CFR <2.5 in at least 1 artery; 10 (90.9%) had CFR <3.0 in at least 1 artery and 8 (72.7%) had an IMR >25. There was no difference in the frequency of a low CFR between SCAD and non-SCAD arteries.Conclusion: Among patients with chronic chest pain after a SCAD event, over eighty percent had CMD as indicated by abnormal CFR in at least one coronary artery on invasive CRT. Presence of CMD in both SCAD and non-SCAD artery suggests that underlying microvascular abnormalities such as coronary FMD may be the underlying etiology. Future research should examine targeted therapies for these post-SCAD symptomatic patients.



Abstract 11601: Weight Change is Not Associated With Risk of Outcomes in Heart Failure: Secondary Analysis of the HF-ACTION Study [Session Title: Lifestyle Potpourri: Habits, Exposures, and Activity]

2017-11-11T04:35:56-08:00

Introduction: The obesity paradox, as observed in those with heart failure and a reduced ejection fraction (HFrEF), suggests that a higher body mass index values (≥25 kg/m2) is associated with an improved survival. It is unknown if healthy weight change in those with HFrEF affects survival. Data from the HF-ACTION trial provides a unique opportunity to assess the association between change in weight and outcome risk in patients with HFrEF.Hypothesis: Weight change will be associated with outcome.Methods: The HF-ACTION study randomized patients with HFrEF to 36 sessions of cardiac rehabilitation or usual care. Body weight was determined at baseline (BL) and 3 mo. We excluded patients with missing weight data or who were hospitalized or died prior to 3 mo. Weight change was assessed as both a continuous and 3 categories (i.e., > 3 kg gain, > 3 kg loss, or -3 to +3 kg change) variable. Cox proportional hazards regression analysis was used to evaluate the impact of weight change on a composite outcome of all-cause mortality or hospitalization.Results: 1,242 subjects (mean age: 59±12 y; BMI 31±7 kg/m2; 28% female) met the inclusion criteria, including complete covariate data. Follow-up was over 1.8+1.1 y. In unadjusted analysis, neither weight change as a continuous (HR=0.99; 95% CI, 0.94-1.04) or categorical (HR=1.08; 95% CI, 0.82-1.43) variable was significantly associated with the endpoint. Analyses with adjustment for 14 clinical co-variates (including randomization assignment) were also not significant (HR=0.99; 95% CI, 0.94-1.04; HR=1.08; 95% CI, 0.82-1.43) for continuous and categorical weight, respectively.Conclusions: In this cohort of patients with HFrEF, weight change during a supervised exercise program was not associated with time to the composite outcome of all-cause mortality and hospitalization. This data suggests that a weight change of 3 kg or greater (gain or loss) over 3 mo does not affect outcome up to 1.8 y. For those with HFrEF and weight-loss responsive comorbidities, weight loss through exercise and cardiac rehabilitation can be encouraged without concern for elevating mortality and hospitalization risk.



Abstract 11602: The Bystander Support Network: Building a Resource for the Forgotten Patient [Session Title: ReSS Poster Session Day 3, Section 02]

2017-11-11T04:35:56-08:00

Introduction: Bystander CPR is the most closely associated intervention to increased survival from out-of-hospital cardiac arrest (OHCA); a victim is almost 4 times more likely to survive when someone witnesses their arrest and performs CPR while emergency personnel are enroute - unfortunately, bystander CPR rates remain astoundingly low, rarely exceeding 35%. Various attempts have been made in the past to improve bystander response rates and many qualitative studies have attempted to understand the barriers to responding in various parts of the world. However, something which has never been addressed is the psychologic impacts and support needs of bystanders after such a traumatic event.Methods: Using an experience based design methodology, we designed and launched the first Sudden Cardiac Arrest Bystander Support Network - www.bystandernetwork.org - in April 2017. The Network has created a community of OHCA lay rescuers which connects those with similar experiences, builds a longitudinal community-based research network and enhances public engagement in resuscitation research design and priority setting.Results: As of the abstract submission date we have had 65 lay rescuers join the network and 32 people share their heroic stories on the website. We have had 517 visits to the site.Conclusions: Bystanders are a crucial part of prehospital resuscitation process and to date their experience and needs following this traumatic event have largely been ignored. The establishment of the Bystander Network has begun to provide support and empowerment for this group and provide opportunity for community led research which will lead to a better understanding of bystander response and potentially OHCA survival in the future.



Abstract 11604: The Relationship of Sudden Death and All-cause Mortality to Baseline Values of High-sensitivity Cardiac Troponin T and I in the EVOLVE Trial [Session Title: Novel Applications for Troponin]

2017-11-11T04:35:56-08:00

Introduction: High sensitivity cardiac troponin (hs-cTn) levels are strong predictors of adverse outcomes. There is uncertainty regarding their use in end-stage renal disease (ESRD) pts. We analyzed the association of hs-cTnI and hs-cTnT for outcomes of sudden death (SD) and all-cause mortality (ACM) in the EVOLVE (Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events) trial; 3883 hemodialysis pts with secondary hyperparathyroidism randomly assigned to receive cinacalcet or placebo, with follow-up for CV events and death.Methods: A random subset of baseline samples were measured for hs-cTnT (n = 2491) and hs-cTnI (n = 2520), with linkage to the EVOLVE dataset. Long-term event-free survival for SD and ACM associated with hs-cTns quintiles was estimated by Kaplan-Meier method. The risks of SD and ACM associated with hs-cTns levels were assessed in demographically and comorbidity-adjusted Cox models.Results: Demographics: 60% male, 57% white, 20% black, 34% US, 35% Europe, 20% Latin America, 7% Russia, 4% Canada, mean age 54y (+/- 14). ACM-free survivals are shown for hs-cTnT (Fig A) and SD-free survivals for hs-cTnI (Fig B), both p < 0.001 by log rank test. There were no differences between hs-cTnT and hs-cTnI in predictive value of for ACM or SD. By quintiles (Q)1-5 hazard ratio (HR) for ACM and SD were respectively Q1(1.0 ref), Q2 1.61 (1.17-2.23), Q3 1.85(1.35-2.54), Q4 2.55(1.88-3.45), Q5 3.48(2.57-4.70) and Q1(1.0 ref), Q2 1.00(0.54-1.86), Q3 1.67(0.95-2.92), Q4 1.87(1.08-3.24), Q5 3.14(1.85-5.35) for hs-cTnT and Q1(1.0 ref), Q2 1.12(0.83-1.52), Q3 1.48(1.11-1.97), Q4 1.94(1.46-2.57), Q5 2.90(2.20-3.81) and Q1(1.0 ref), Q2 1.11(0.62-2.10), Q3 1.37(0.77-2.46), Q4 2.19(1.26-3.82), Q5 3.99(2.34-6.78) for hs-cTnI.Conclusion: Both hs-cTnI and hs-cTnT are strong predictors of all-cause death and sudden death in hemodialysis pts. Our data support the role of these cardiac biomarkers for more precise identification of risk in ESRD pts.



Abstract 11606: Significance of Non-PV Triggers in Patients With Persistent Atrial Fibrillation: Results From 5 Years of Follow-up [Session Title: Electrophysiology and Arrhythmias: General Topics III]

2017-11-11T04:35:56-08:00

Introduction: Pulmonary vein antrum isolation (PVAI) alone is reported to have limited success rate in patients with persistent AF (PerAF).Hypothesis: This study evaluated the prevalence of triggers from left atrial appendage (LAA) in perAF patients and the impact of LAA isolation on long-term outcome.Methods: We prospectively analyzed 939 consecutive patients with perAF undergoing the first ablation at our institution (73% male, mean age 62±10 years). PVAI extended to the posterior wall between the pulmonary veins was performed in all patients. Non-PV vein triggers were disclosed with high-dose isoproterenol challenge. These were ectopic triggers originating from sites other than pulmonary veins such as interatrial septum, left atrial appendage (LAA), crista terminalis and coronary sinus (CS).Follow-up was performed every 3 months for the first year, and every 6-9 months for the next 4 years. Success was considered as freedom from any atrial arrhythmia off anti-arrhythmic drugs.Results: Non-PV triggers were seen and ablated during the first procedure; CS triggers in 678 (72.2%) and LAA triggers in 631 (67.2%) patients. At 5 years, single-procedure arrhythmia-free survival was achieved in 54.2% of patients. Of the 430 (45.8%) patients who failed the first procedure, distribution of recurrence was 290 (30.9%) 1st year, 59 (6.3%) 2nd year, 26 (2.8%) 3rd year, 21 (2.2%) 4th year and 34 (3.6%) patient at 5th year. A total of 281 out of the 430 with recurrence after first ablation went for redo; 226 received LAAI and LAA not isolated in 55 patients. The 149 patients who failed and did not undergo repeat procedure, LAA was not isolated at the first procedure in 107 (71.8%) patients. At 6 month follow-up of the 2nd ablation, recurrence rate was 40% (90/226) in those with LAAI and 56% (31/55) where LAA not isolated (log-rank p= 0.021).Conclusions: In persistent AF patients, non-PV triggers play a relevant role in the early and late recurrence of atrial arrhythmia and their ablation should be considered to increase the success rate.



Abstract 11608: The Effects of a Lifestyle-focused Text-message Program on Dietary Patterns in Patients With Coronary Heart Disease: An Analysis of the TEXT ME Study [Session Title: Dietary Components and Dietary Interventions for CV Health II]

2017-11-11T04:35:56-08:00

Introduction: A healthy diet is an important lifestyle factor in secondary prevention of coronary heart disease (CHD). TEXT ME was a randomised clinical trial of patients with CHD that were randomised into usual care or a text-message program. The intervention group received 4 text-messages per week for 6 months, including 1 message per week focussing on diet.Hypothesis: A lifestyle-focused text-message program improves dietary patterns in patients with CHD.Methods: Dietary data were collected using a self-report questionnaire to evaluate adherence to 8 recommendations of the Australian dietary guidelines as follows: 1) consumption of ≥ 35 serves of vegetables/week (≥ 5 serves/day for 7 days/week); 2) consumption of ≥ 14 serves of fruits/week (≥ 2 serves/day for 7 days/week); 3) use of unsaturated fat oils when cooking; 4) use of margarine and unsaturated fat oils on bread; 5) consumption of ≥ 300 grams of fish/week (300 grams/week ~ 2 serves/week); 6) consumption of takeaway food ≤ 1/week; 7) salt intake control on a regular basis; and 8) consumption of ≤ 14 standard alcohol drinks/week (≤ 2 standard drinks/day for 7 days/week). Proportion of patients achieving ≥ 4/8 recommendations and achieving each recommendation individually were analysed using chi-square tests.Results: Among 710 patients (mean age 57.6 ± 9.2 years, 82% male) at baseline, 54% were meeting ≥ 4/8 dietary recommendations (intervention 53% vs control 56%, p = 0.3762). At 6-months, 93% of intervention patients were achieving ≥ 4/8 recommendations compared to 76% of control patients (p < 0.0001). The results for each recommendation are presented in Table 1.Conclusion: A lifestyle-focused text-message program improved the proportion of patients meeting diet recommendations for consumption of vegetables, fruits, fish, takeaway foods and salt intake in patients with CHD. This simple and scalable text-messaging intervention could be used as a strategy to improve dietary patterns in patients with CHD.



Abstract 11623: Reduced ERK1/2 and AP-1 Activity Contribute to Aortic Dilatation in Patients With Bicuspid Aortic Valve Disease [Session Title: Vivien Thomas Young Investigator Award Competition]

2017-11-11T04:35:56-08:00

Background: Bicuspid aortic valve (BAV) disease is a congenital abnormality that often leads to ascending aortic aneurysms. Previous studies suggest that aneurysm progression may be caused by a combination of hemodynamic stress and genetics but many of the molecular mechanisms remain unknown.Objective: Identify novel molecular mechanisms of aneurysm formation in patients with BAV.Methods: Microarray analysis of the proximal (severely dilated) and distal (less dilated) regions of the ascending aorta from BAV patients (n=5) was performed. RT-qPCR and western blot analysis was completed in normal aorta (n=5) and aneurysmal aortic tissue from BAV (n=9), Marfan (n=5), tricuspid aortic valve (TAV) (n=5), BAV-Marfan (n=1), and TAV-Loeys-Dietz (n=1) tissue. Aortic smooth muscle cells (SMCs) from normal and BAV patients were cultured in vitro and treated with TGF-β to measure ERK1/2 activation.Results: Several members of the Activator Protein 1 (AP-1) transcription factor family were upregulated in the distal region of BAV aneurysmal tissue including Fos, Fosb and Jun. This trend was conserved in BAV-Marfan samples but not within paired Marfan or TAV aneurysmal tissue. Immunofluorescence showed that Jun expression is within the periphery of the aorta, near the intima and adventitia. AP-1 protein expression was similar in proximal and distal BAV tissue however Fos expression was higher in BAV aorta compared to normal aorta. ERK1/2 activity, which stabilizes AP-1 protein expression, was reduced in BAV aneurysmal tissue compared to normal aorta, Marfan and TAV samples. Expression of MAPK phosphatases, Dusp1 and Dusp6, was also reduced in BAV aorta compared to normal aortic tissue. TGF-β treatment induced ERK1/2 activity in normal aortic SMCs in a dose-dependent manner but this was not observed in SMCs isolated from the proximal BAV aorta.Conclusions: AP-1 and ERK1/2 activity are dysregulated in BAV aneurysm progression. These data also demonstrate that activation of the non-canonical TGF-β pathway is impaired in BAV aortic disease. Restoration of ERK1/2 signaling may be a novel therapeutic strategy to limit aortic dilatation in BAV disease.



Abstract 11653: The Dynamic Norwood Mortality Estimator: Characterizing Instantaneous, Personalized Risk Trajectories for Infants After the Norwood Operation [Session Title: CVDY Early Career Investigator Award Competition]

2017-11-11T04:35:56-08:00

Background: Post-Norwood, mortality is high and unpredictable. Adverse events and re-interventions are also common. Current risk scores only incorporate baseline data. We sought to create a novel statistical model, including post-operative events and measures that predicts individual patient instantaneous mortality risk between the Norwood and Stage 2.Methods: From the CHSS Critical LVOTO prospective inception cohort, 360 neonates underwent a Norwood. The risk of death post-Norwood was modeled using a novel application of parametric hazard analysis, incorporating baseline and operative characteristics, in addition to 26 types of time-related adverse events, procedures, and repeated measures of weight and SaO2, as time-varying covariates. Individual patient risk trajectories for mortality, which dynamically update (increase or decrease) with the occurrence of each time-related event or measure over time, were derived from the model.Results: Post-Norwood, 1,814 post-operative events occurred and 963 measures of both weight and SaO2 were obtained. Risk factors for death (n=60) included resuscitated cardiac arrest, moderate/severe AV valve regurgitation, intracranial hemorrhage/stroke, sepsis, lower SaO2, readmission, smaller baseline aortic diameter, smaller baseline mitral valve z-score, and lower weight. Post-operative events and measures displaced most baseline and operative characteristics in the model. Each patient’s risk of death varied over time, as risk factors varied or occurred over time (Panel A). Groups with qualitatively similar risk trajectories and outcomes were noted (Panel B).Conclusions: The risk of death post-Norwood is dynamic and primarily driven by time-related complications and measures, rather than on baseline or operative characteristics. Dynamic risk estimates for individual patients and their visualization may aid in surveillance and data-driven decision making during the high-risk post-Norwood period.



Abstract 11661: Novel Phytopeptide Osmotin Mimics Atheroprotective Effects of Adiponectin via AdipoR1 [Session Title: Novel Lipid Modifying Approaches]

2017-11-11T04:35:56-08:00

Introduction: A novel phytohormone osmotin has been recently reported to act like the mammalian adiponectin possibly through PHO36/AdipoR1 in various in vitro and in vivo models. However, there have been no reports regarding effects of osmotin on atherosclerosis.Methods: We assessed the atheroprotective effects of osmotin on inflammatory molecules in human umbilical vein endothelial cells (HUVECs), THP1-HUVEC adhesion, the inflammatory phenotype, cytokine secretion, and foam cell formation in THP1-derived macrophages, and the migration, proliferation, and extracellular matrix expression in human aortic smooth muscle cells (HASMCs). We examined whether osmotin administration could suppress the development of atherosclerotic lesions in ApoE-/- mice.Results: AdipoR1 was abundantly expressed in HUVECs, THP1, THP1-derived macrophages, and HASMCs. Osmotin suppressed lipopolysaccharide-induced up-regulation of monocyte chemotactic protein-1 and vascular adhesion molecule-1 in HUVECs, and tumor necrosis factor-α (TNF-α)-induced THP1-HUVEC adhesion. In THP1-derived macrophages, osmotin suppressed inflammatory M1 phenotype, lipopolysaccharide-induced secretion of interleukin-6 and TNF-α, and oxidized LDL-induced foam cell formation associated with CD36 and acyl-CoA:cholesterol acyltransferase-1 down-regulation and ATP-binding cassette transporter A1 up-regulation. In HASMCs, osmotin suppressed the migration, proliferation, and expression of collagen-1, fibronectin, and matrix metalloproteinases without inducing apoptosis via the down-regulation of Raf-1, phosphorylated ERK1/2, JNK, p38, and NF-κB and the up-regulation of phosphoinositide 3-kinase, phosphorylated Akt, AMPK, and Bcl-2. Four-week infusion of osmotin into ApoE-/- mice suppressed the development of aortic atherosclerotic lesions and stabilized atheromatous plaques.Conclusions: This study provide the first evidence to demonstrate that osmotin exerts atheroprotective effects via AdipoR1 in human vascular cells and ApoE-/- mice aorta, which may open up a new therapeutic window for combating atherosclerosis and related diseases.



Abstract 11662: Riskof Glucose Intolerance is Increased in Japanese Male Manager Working in Shanghai-The Rosai Karoshi Study [Session Title: Workplace Health for Cardiologists and Non-Cardiologists]

2017-11-11T04:35:56-08:00

Introduction: Japanese working in Shanghai demonstrates higher cardiac mortality compared with age-matched domestic workers. We have recently shown that glucose metabolism is worse in Japanese men working in Shanghai than Chinese men. This was explained in part by short sleeping hours associated with work stress. It is controversial, however, if being manager is less healthy than non-manager and no data exists for overseas workers of Japanese.Hypothesis: Job class is related to glucose metabolism regulation of Japanese men working in Shanghai.Methods: We studied 281 Japanese and 1418 Chinese male workers, who have been registered for Japan-China cooperative study for the prevention of work-related cardiovascular events. Demographic data, fasting blood, weekly working hours, job stress, lifestyle characteristics were studied in all subjects according to previous report. Job demand and job control were quantified using the NIOSH questionnaire. Then we created 269 pairs matched for age and job categories based on the propensity scores. We examined if manager class is related to the risk of glucose intolerance compared with non-manager in both Japanese and Chinese. Glucose intolerance was defined as fasting blood sugar level 6.1 mmol/L or over or use of antidiabetic medication.Results: Manager group was older than non-manager group in both Japanese (45.8±7.3 vs. 39.8±9.2 yrs, p<0.001) and Chinese (46.5±7.8 vs. 41.1±11.6 yrs, p<0.001). Body mass index did not differ between manager and non-manager in either ethnic group. Manager group demonstrated higher prevalence of glucose intolerance in Japanese (31.7 vs. 12.8 %, p=0.001) but not in Chinese (11.2 vs. 6.9 %, p=0.366). Weekly working hours and score of job demand did not differ between manager and non-manager groups either in Japanese or Chinese. Score of job control was significantly higher in manager than in non-manager both in Japanese (59.3±10.7 vs. 49.8±8.9, p<0.001) and Chinese (54.6±13.1 vs. 46.1±12.9, p<0.001). Hours of sleep was shorter (6.1±0.9 vs. 6.5±0.9 h, p<0.001) and frequency of heavy drinking was higher (25.4 vs. 12.3 %, p=0.028) in manager than non-manager only in Japanese. After adjustments for age, BMI, lifestyle factors and hours of sleep, manager class was associated with significantly higher odds ratio for glucose intolerance compared with non-manager group in Japanese (OR 2.63, 95%CI: 1.01-6.86) but not in Chinese.Conclusions: Japanese male manager working in Shanghai demonstrated higher risk of glucose intolerance, which was not compensated by higher job control.



Abstract 11670: Chest Compression During Sustained Inflation and Versus 3:1 Chest Compression: Ventilation Ratio During Neonatal Cardiopulmonary Resuscitation - A Randomized Feasibility Trial [Session Title: ReSS Poster Session Day 1, Section 09]

2017-11-11T04:35:56-08:00

Introduction: Current resuscitation guidelines recommend 3:1 Compression:Ventilation (C:V) ratio. Recently, animal studies reported that continuous chest compressions (CC) during a sustained inflation significantly improved return of spontaneous circulation (ROSC). The approach of CC during SI (CC+SI) has not been examined in the delivery room during neonatal resuscitation.Hypothesis: Feasibility study to study CC+SI vs. 3:1 C:V ratio during neonatal resuscitation in the delivery room. We hypothesized that during neonatal resuscitation CC+SI will reduce the time to ROSC. Our aim was to examine if CC+SI reduces ROSC compared to 3:1 C:V CPR in preterm infants <33 weeks gestation.Methods: Study design: Randomized feasibility trial. Once CC was indicated all eligible infants were immediately and randomly allocated to either CC+SI (“CC+SI group”) or 3:1 C:V (“3:1 C:V group”). A sequentially numbered, brown, sealed envelope contained a folded card box with the treatment allocation was opened by the clinical team immediately before delivery. Study interventions: Infants in the CC+SI group, received CC at a rate of 90/min during an SI with a duration of 20sec (CC+SI). After 20 sec the SI was interrupted for 1 sec and the next SI was started for another 20sec until ROSC. Infants into the “3:1 group”, received CC using 3:1 C:V ratio until ROSC.Results: Overall the mean (SD) time to ROSC was significantly shorter in the CC+SI group with 31 (9) sec compared to 138 (72) sec in the 3:1 C:V group (p=0.011).Conclusions: CC+SI is feasible in the delivery room.Trial registration: Ciinicaltrials.gov NCT02083705



Abstract 11676: High-sensitive C-reactive Protein Does Not Predict Early and 1-year Outcomes After Coronary Artery Bypass [Session Title: Clinical Aspects of Atherosclerosis]

2017-11-11T04:35:56-08:00

Introduction: High-sensitive C-reactive protein (hsCRP) is an inflammtory marker of patients with coronary heart disease but there is still conflicting data on its impact on early and midterm outcomes after isolated coronary artery bypass grafting (CABG).Hypothesis: Preoperative elevated hsCRP is not an independent predictor of cardiovascular events after CABG surgery.Methods: We prospectively analysed data of consecutive 400 patients that underwent elective, isolated CABG between 2012 to 2016 within the randomized-controlled StaRT-CABG trial. Patients were subdivided into a low (2.5mg/l) versus high hsCRP group (>2.5mg/l) as assessed at hospital admission. The primary endpoint was a composite including all-cause mortality, myocardial infarction and cerebrovascular events (MACCE) at 30 days and 1-year survival was assessed.Results: After CABG surgery through postoperative day 30, 5 patients (1.3%) died and 102 patients (25.5%) suffered major morbidity. One-year survival was 96.5% (14 deaths). Univariable and multivariable model revealed a statistically not significant predictive effect of elevated preoperative values of hsCRP for 30-day mortality (odds ratio = 2.31, p = 0.36 versus odds ratio = 2.36, p = 0.36), myocardial infarction (odds ratio = 1.16, p = 0.64 versus odds ratio = 1.22, p = 0.57), MACCE (odds ratio = 1.17, p = 0.60 versus odds ratio = 1.17, p = 0.61), and of 1-year all cause mortality (hazard ratio = 2.64, p = 0.08 versus hazard ratio = 2.82, p = 0.08). Multivariable model indicated that elevated hsCRP is not an independent predictor of CABG setting. Kaplan-Meier plot of 1-year survival stratified according to preoperative low and high levels of hsCRP was not significant (logrank = 3.27, p = 0.07). Receiver operating characteristic curves (ROC) could not identify a cut-off point for hsCRP with respect to all analyzed outcomes.Conclusions: Preoperative hsCRP does not predict early and one-year outcomes after CABG.



Abstract 11678: National Trends in Hospitalization of Patients With Diastolic Heart Failure and Concurrent Amyloidosis [Session Title: Population Trends in CVD]

2017-11-11T04:35:56-08:00

Introduction: Amyloidosis is a systemic disease with a high incidence of concurrent diastolic heart failure (DHF)/preserved ventricular function. Trends in hospitalization for patients with a diagnosis of DHF and concurrent amyloidosis have not been reported previously.Hypothesis: To determine the trends of hospitalization and characteristics of patients with a diagnosis of DHF and concurrent amyloidosis.Methods: Patients were identified by querying the National Inpatient Sample database between years 2007 and 2013. Patients included were greater than 18 years old with a diagnosis of amyloidosis or DHF based on ICD9 codes. We excluded patients who were coded for systolic or combined heart failure for the same admission. We estimated the weighted prevalence and incidence of DHF and amyloidosis among all unique hospitalizations. We also present the average relative risk (RR) and clinical characteristics of DHF in amyloidosis population compared to general population of patients.Results: Over the 6-year period of time, we found 117,162 hospitalizations in patients with amyloidosis with the prevalence and incidence of DHF at 11.7% and 3.2%, respectively: mean age 72 years, female 50% and 64% white. Over the 7 years combined, RR of DHF is 5.9 ± 0.95 in amyloidosis population compared to general population. The annual trend of DHF incidence/prevalence and clinical characteristics in patients with amyloidosis is presented in the figure and table respectively.Conclusions: 1) The incidence and prevalence of hospitalization for DHF with concurrent amyloidosis has increased over time. 2) The RR of DHF in amyloidosis is much higher than the general population. 3) There are multiple demographic and clinical characteristic differences in DHF patients with and without amyloidosis.



Abstract 11682: Meta-Analysis of Studies on Coffee Consumption and Atrial Fibrillation Risk [Session Title: Lifestyle Potpourri: Habits, Exposures, and Activity]

2017-11-11T04:35:56-08:00

Introduction: The etiology of atrial fibrillation (AF) is multifactorial, including comorbidities such as hypertension, diabetes, or advanced age. Coffee is increasingly consumed worldwide, particularly in the United States; thus, it is necessary to assess the impact of coffee on cardiovascular health. There have been discrepant findings on whether coffee consumption is associated with the rate of developing AF.Hypothesis: This study aimed to explore the association between coffee consumption and AF.Methods: We conducted a comprehensive search of MEDLINE, MEDLINE In-Process 95% CI: 0.88-1.09; p < 0.001; I2 = 59.21%), compared to the lowest category (1 cup/day).Conclusions: We found no evidence that coffee consumption is associated with increased risk of AF.



Abstract 11689: Liver Functional Test Abnormalities in Chronic Heart Failure [Session Title: Heart Failure and Cardiomyopathies: General Topics III]

2017-11-11T04:35:56-08:00

Background: Abnormal liver functional tests (LFTs) have been shown to reflect abnormal hemodynamic status and predict poor clinical outcomes in acute heart failure. However, the clinical significance of LFTs was not well elucidated in chronic heart failure (CHF).Aim: We aimed to investigate the clinical significance of abnormal liver function in CHF patients.Methods: We analyzed 1190 patients (969 males, mean age 61.0 years) with CHF who admitted to our hospital and underwent blood examination immediately before discharge. Patients with liver diseases or acute coronary syndrome were excluded. We investigated the prevalence of abnormal LFTs, evaluated independent predictors of clinical profiles (systemic congestion, pulmonary congestion, and hypoperfusion defined by physical examination and echocardiography) in CHF and determined which variables including the LFTs were associated with composite adverse cardiac events.Results: Abnormal LFTs were common in CHF patients: aspartate aminotransferase (17.3%), alanine aminotransferase (31.3%), total bilirubin (TB, 10.7%), alkaline phosphate (44.3%), gamma-glutamyl transferase (G-GT, 33.9%), cholinesterase (ChE, 19.9%), total protein (19.9%) and albumin (37.7%). In logistic regression multivariate analysis, abnormal TB, ChE and G-GT were independently associated with clinical signs of systemic congestion (odds ratio [OR] 1.72, 1.75 and 1.52, respectively). In addition, abnormal ChE was independently associated with pulmonary hypertension by echocardiography (OR 3.20). On the other hands, lower albumin was independently associated with systemic hypoperfusion defined by the “Cold Modified 2014” definition criteria (OR 1.43). In the follow-up period (mean 1155 days), 407 adverse cardiac events (377 rehospitalization due to worsening heart failure and 30 cardiac deaths) occurred. In the Cox proportional hazard analyses after adjusting for other confounding factors, the abnormal ChE and G-GT were the independent factors to predict cardiac events (hazard ratio 2.73 and 1.28, respectively).Conclusion: Abnormal LFTs are common, and ChE and G-GT among them are strongly associated with congestion and adverse clinical outcomes in CHF patients.



Abstract 11694: 6-minute Walk Test Distance After Bosentan to Macitentan Switch in Adult Outpatients With Group 1 Pulmonary Hypertension: A Multicenter Retrospective Cohort [Session Title: Vascular Disease and Thrombosis: General Topics]

2017-11-11T04:35:56-08:00

Introduction: Endothelin receptor antagonists (ERA) have shown to be beneficial in improving clinical, haemodynamic and echocardiographic variables in patients with group 1 pulmonary hypertension. However, studies evaluating the comparative effects among ERA drugs are lacking. We studied the impact of bosentan-to-macitentan switch on the 6-minute walk test distance in adult outpatients with group 1 pulmonary hypertension.Methods: We performed a multicenter retrospective cohort analysis in adult outpatients with group 1 pulmonary hypertension using data bases from public and private hospitals in Argentina between March 2015 and October 2016. Patients were required to be over 18 years-old, have a group 1 pulmonary hypertension confirmed by catetherism, be in WHO functional class II-III/IV and receiving bosentan as monotherapy or in combination over a period of 6 months. Patients with incomplete medical records in 6 months follow-up were excluded. Primary outcome was change in mean 6-minute walk test distance 6 months after bosentan-to-macitentan switch. Secondary outcomes was change over time in mean 6-minute walk test distance 12 months after bosentan-to-macitentan switch. The primary outcome was analyzed with a paired t-test test and a multivariate linear regression model. Statistical analysis was performed with software package RStudio IDE®. Statistical significance was considered at p < 0.05.Results: Between March 2015 and October 2016, 80 patients were screened for enrolment. Since there were 2 incomplete medical records, 78 patients were included in the final analysis. Patients were mostly middle-aged (48.5 [20-77] years-old) females (74%). All patients were receiving sildenafil and bosentan at the beginning of the study; 21% was receiving some form of prostanoids. 12 month follow-up was 55%. There was a statistically significant difference in mean 6-minute walk test distance 6 months after bosentan to macitentan switch (304.0 to 361.8 meters; 95%CI 41.1-74.6; p < 0.0001), that was maintained after adjusting for age and gender (difference 65.4 meters; 95%CI 14.5-116.3; p < 0.012). This difference persisted at 12 months (307.2 to 392.8 meters; 95%CI 107.4-63.7; p < 0.0001). No patients had elevated liver enzymes during this study; only one patient developed anemia after drug switch.Conclusions: Observational real-world data suggests that macitentan could have additional benefits to bosentan in improving 6-minute walk test in adult outpatients with group 1 pulmonary hypertension at 6 and 12 months.



Abstract 11695: An Anti-Interleukin-1{beta} Antibody Suppresses Both Angiotensin II-induced Renal Inflammation and Hypertension [Session Title: Novel Insights into the Pathogenesis of Hypertension]

2017-11-11T04:35:56-08:00

Aims: Angiotensin II (AngII) increases arterial pressure and activates components of inflammatory cascade, which promotes development of renal injury. Clinical hypertension is associated with renal inflammation and elevated circulating levels of proinflammatory cytokines. IL-1 receptor antagonist (IL-1Ra) is one of the most important anti-inflammatory cytokines and plays a crucial role in inflammation. Inhibition of IL-1 may contribute to modulation of the AngII-induced hypertension response. This study aimed to elucidate the effects of IL-1Ra and anti-IL-1beta antibody (01BSUR) on AngII-induced hypertension and renal inflammation.Methods and Results: To determine the contrition of IL-1Ra to AngII-induced renal inflammation, male wild-type (WT) (n=8) and IL-1Ra-deficient (IL-1Ra-/-) (n=8) mice were infused with AngII (1000ng/kg/min) using subcutaneous osmotic pumps for 14 days. 14 days after infusion, systolic blood pressure (149±2 vs 126±3 mmHg, p<0.001) in IL-1Ra-/- mice significantly increased compared with WT mice. Furthermore, on day 14 of AngII infusion, plasma IL-6 was 5.9-fold higher in IL-1Ra-/- versus WT mice (p<0.001); renal preproendothelin-1 mRNA expression was also significantly higher in IL-1Ra-/- mice (p<0.05). In addition, renal histology revealed greater damage in IL-1Ra-/- mice compared with WT mice 14 days after infusion. These findings suggest that deficiency of IL-1Ra promotes AngII induced hypertension and renal damage via increased expression of endothelin-1. Finally, we administrated 01BSUR to both IL-1Ra-/- and WT mice, and 01BSUR treatment decreased AngII-induced hypertension (Fig A) and renal damage (glomerular injury (Fig B, upper) and fibrosis of the tubulointerstitial area (Fig B, lower)) in both IL-1Ra-/- and WT mice compared with IgG2a treatment.Conclusions: The present study demonstrates that deficiency of endogenous IL-1Ra significantly increases blood pressure and promotes renal inflammation after AngII infusion. Furthermore, we shows treatment of 01BSUR decreased AngII-induced hypertension and renal damage in both IL-1Ra-/- and WT mice. These results suggest that suppression of IL-1 may provide an additional strategy to protect against renal damage in hypertensive patients.



Abstract 11698: Endothelial Function Measured by Enclosed Zone Flow-mediated Vasodilation Predicts Cardiovascular Events [Session Title: New Aspects of Endothelial Function]

2017-11-11T04:35:56-08:00

Introduction: We developed a new device for automatic measurement of flow-mediated vasodilation (FMD) using an oscillometric method to solve technical problems of conventional FMD measurement. The name of this device is enclosed zone flow-mediated vasodilation (ezFMD). The purpose of this study was to evaluate the prognostic value of endothelial function assessed by ezFMD for future cardiovascular events.Methods: We measured ezFMD in 272 subjects who underwent health examinations. First, we investigated cross-sectional associations between ezFMD and cardiovascular risk factors, and then we assessed the associations between ezFMD and first major cardiovascular events (death from cardiovascular causes, stroke, and coronary revascularization).Results: Univariate regression analysis revealed that ezFMD was significantly correlated with age, triglycerides, glucose, smoking pack-years, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and Framingham risk score. During a median follow-up period of 36.1 months (interquartile range, 18.8 to 40.1 months), 12 subjects died (6 from cardiovascular causes), 3 had stroke, 8 had coronary revascularization, and 10 were hospitalized for heart failure. There was no episode of acute coronary syndrome during the study period. Subjects were divided into tertiles based on ezFMD. Kaplan-Meier curves for first major cardiovascular events among the 3 groups were significantly different (P=0.004). After adjustment for cardiovascular risk factors, the low group was significantly associated with an increased risk of first major cardiovascular events compared with the high group (hazard ratio, 6.47; 95% confidence interval, 1.09 to 125.55; P=0.038).Conclusions: These findings suggest that endothelial function assessed by ezFMD may be useful as a surrogate marker of future cardiovascular events.



Abstract 11699: Presence of Inconsistently Graded Severe Aortic Valve Stenosis Despite Pressure Recovery Adjustment Predicts Impaired Outcome [Session Title: Valvular Heart Disease: Disease Severity and Clinical Prognosis]

2017-11-11T04:35:56-08:00

Introduction: Conflicting evidence exists on the prognostic impact of inconsistently graded aortic valve stenosis (AS) in asymptomatic patients. Pressure recovery adjustment of aortic valve area (energy loss, EL) is recommended for more accurate grading, but the outcome in asymptomatic patients with inconsistently graded severe AS defined from combined EL ≤1cm2 and mean aortic gradient ≤40mmHg has not been reported.Hypothesis: Inconsistently graded severe AS identified by EL and mean gradient is associated with impaired outcome.Methods: Data from 1497 patients with initially asymptomatic mild-moderate AS and normal ejection fraction enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study was used. Median follow-up was 4.3 years. 25 patients with consistently graded severe AS at baseline were excluded, and included patients were grouped according to presence of consistently graded non-severe AS or inconsistently graded severe AS. Outcome was assessed in Cox regression analysis and reported as hazard ratio (HR) and 95% confidence interval (CI).Results: Inconsistently graded severe AS by EL was found in 213 patients (14.2%) at baseline and associated with older age, female sex, smaller aortic annulus diameter, more extensive valve calcification and lower stroke volume independent of more severe AS in multivariable logistic regression analysis (all p<0.05). In Cox regression analysis, inconsistently graded severe AS by EL was associated with a 3-fold increase in HR (95% CI 1.56-4.66) for hospitalization for heart failure and a 2-fold increase in HR (95% CI 1.10-3.09) for cardiovascular death also after adjusting for confounders (both p<0.05).Conclusions: Presence of inconsistently graded severe AS despite adjustment for pressure recovery is associated with increased risk for heart failure and cardiovascular death in asymptomatic AS patients.



Abstract 11700: Change of Exhaled Acetone Concentration Levels in Patients With Acute Decompensated Heart Failure [Session Title: Heart Failure and Cardiomyopathies: General Topics III]

2017-11-11T04:35:56-08:00

Background: Although breath analysis has emerged as a noninvasive tool in several clinical conditions, it is not widely used in cardiovascular disease yet. Exhaled acetone is one of the compounds expected as biomarkers for heart failure. However, it is unknown how exhaled acetone concentration changes in clinical course of heart failure.Objective: To investigate time course of exhaled acetone concentration in acute decompensated heart failure.Methods: This study included 19 patients with acute decompensated heart failure (ADHF group), and 14 stable patients (control group). Exhaled acetone was collected from these patients and the concentration was measured with gas chromatography.Results: The ADHF group had higher heart rates (p = 0.020), higher levels of brain natriuretic peptide (p < 0.001), and blood total ketone bodies (p = 0.003), compared with the control group. In ADHF group, exhaled acetone concentration was significantly decreased after treatment (median: 2.40 ppm vs. 0.92 ppm, p < 0.001). On the other hand, in the control group, exhaled acetone concentration did not significantly change (median: 0.69 ppm vs. 0.62 ppm, p = 0.370, Table 1).Conclusions: Exhaled acetone concentration in patients with acute decompensated heart failure was drastically decreased by treatment, and therefore, could be a novel noninvasive biomarker to evaluate the course of acute decompensated heart failure.



Abstract 11702: Vascular Function is Impaired in Subjects With Decreased Circulating Level of Pigment Epithelium-derived Factor [Session Title: Endothelial Dysfunction and Oxidative Stress]

2017-11-11T04:35:56-08:00

Introduction: Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. It has been shown that PEDF plays a protective role against atherosclerosis. Several investigators have reported that serum levels of PEDF are increased in subjects with cardiovascular risk factors. However, the role of PEDF in cardiovascular disease is still controversial. The aim of this study was to evaluate the associations between serum levels of PEDF and vascular function and structure.Methods: We measured serum levels of PEDF, assessed vascular function by measurements of flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation in the brachial artery, and measured brachial artery intima-media thickness (IMT) in 150 subjects who underwent health examinations, including subjects with cardiovascular disease. We investigated cross-sectional associations between serum levels of PEDF and vascular function and structure.Results: Univariate regression analysis revealed that serum level of PEDF was significantly correlated with body mass index (r=0.195, P=0.02), high-density lipoprotein cholesterol (r=-0.381, P<0.001), glucose (r=0.235, P=0.006), FMD (r=-0.170, P=0.04), nitroglycerine-induced vasodilation (r=-0.243, P=0.005), and brachial artery IMT (r=0.221, P=0.009). Multivariate analysis revealed that serum levels of PEDF remained an independent predictor of nitroglycerine-induced vasodilation (β=-0.20, P=0.02) and brachial artery IMT (β=0.14, P=0.03) after adjustment of cardiovascular risk factors, while serum level of PEDF was not associated with FMD (β=-0.02, P=0.79).Conclusions: These findings suggest that PEDF may have an anti-atherosclerotic effect on a system that is activated for the development of atherosclerosis. The serum level of PEDF may be a new biochemical marker of atherosclerosis.



Abstract 11709: Klotho, Fibroblast Growth Factor-23, and the Renin-Angiotensin System - An Analysis From the PEACE Trial [Session Title: Biomarkers and Imaging in Heart Failure]

2017-11-11T04:35:56-08:00

Introduction: Klotho, an essential co-receptor for fibroblast growth factor (FGF)-23, has potentially beneficial inhibitory effects on the renin-angiotensin system.Hypotheses: Low Klotho concentration will be associated with increased risk of cardiovascular (CV) death or hospitalization for heart failure (HHF) and the combination of low Klotho and high FGF-23 will predict benefit with the ACE-inhibitor trandolapril.Methods: 3,555 patients with stable ischemic heart disease and LVEF >40% enrolled in the PEACE trial of trandolapril vs placebo had biomarkers drawn at randomization. Patients were characterized by quartiles of Klotho and FGF-23 concentrations. 6-year Kaplan-Meier rates and adjusted risk were calculated for the composite of CV death/HHF and its components based on Klotho/FGF-23 concentrations and randomized treatment assignment.Results: Klotho and FGF-23 showed a weak inverse correlation (r=-0.06; p<0.01). Low (Q1-3) Klotho concentration was associated with an increased rate of CV death/HHF as compared to Q4 (8.2 vs 4.2%; p=0.02). After multivariable adjustment for clinical variables and renal and CV biomarkers (eGRF, cystatin-C, UACR, FGF-23, hsTnT, NT-proBNP, and hsCRP), low Klotho concentration remained strongly associated with increased risk of CV death/HHF (HRadj 2.62 [1.35-5.08]; p<0.01). The combination of low Klotho and high (Q4) FGF-23 concentration identified patients at particularly elevated risk as compared to patients with high Klotho and low FGF-23 (HRadj 3.99 [1.67-9.56]; p<0.01). This high risk combination additionally predicted benefit from trandolapril (HR 0.39 [0.23-0.68]; pint<0.01; Figure).Conclusions: Low Klotho concentration is associated with an increased risk of CV death/HHF in patients with stable ischemic heart disease. The combination of low Klotho and high FGF-23 further identifies patients at distinctly elevated risk who derive clinical benefit from the ACE-inhibitor trandolapril.



Abstract 11711: Heart Failure Following the Norwood Procedure [Session Title: The Single Ventricle]

2017-11-11T04:35:56-08:00

Introduction: Some young children with hypoplastic left heart syndrome (HLHS) and its variants develop heart failure (HF) following the Norwood procedure (NP). We report the incidence of and risk factors for HF by age 6 years in children who were prospectively followed after randomization to the modified Blalock-Taussig shunt (MBTS) or right ventricle to pulmonary artery shunt (RVPAS) in the Single Ventricle Reconstruction (SVR) trial.Hypothesis: Following the NP, HF is relatively common, and factors other than shunt type impact its risk.Methods: Study subjects were enrolled in the SVR trial, survived to hospital discharge after the NP, and were followed up to age 6 years. HF was defined as heart transplant listing after NP hospitalization, death attributable to HF, or NYHA class IV HF. Cox regression methodology was used to identify variables associated with early and late HF.Results: Of the 461 subjects discharged home following NP, 66 (14%) met criteria for HF. Among these, 15 died from HF with no transplant listing, 39 were listed for transplant (22 had transplants, 12 died after listing without receiving a transplant and 5 were alive and not yet transplanted), and 12 had NYHA Class IV HF but were never listed. Risk factors for development of early HF (<1 year) included fractional area change <35% at NP post-operative study (p=.02), need for ECMO in operating room (p=.004), non-Hispanic ethnicity (p=.04), greater use of regional cerebral perfusion compared to circulatory arrest (P<.001) and shorter total bypass time (p<.001). The only predictor of late HF (≥1 yr) was not using α-blockade at NP. HF was not associated with shunt type (Figure).Conclusions: HF develops in ~ 1 in every 7 children discharged after NP. Whereas almost half are listed for transplant, many die from HF before receiving a transplant or without being listed. Several NP perioperative variables, including perfusion strategies, are associated with development of HF, whereas shunt type is not.



Abstract 11731: Oligogenic Familial Hypercholesterolemia, LDL Cholesterol, and Coronary Artery Disease [Session Title: Biomarkers and Risk Factors for Cardiometabolic Disease]

2017-11-11T04:35:56-08:00

Background: The concept of severe familial hypercholesterolemia (FH) was introduced with the aim of identifying individuals at an extremely high-risk for coronary artery disease (CAD) among those with high LDL cholesterol.Objectives: We tested if genetic variants known to cause lipid-altering autosomal recessive diseases influenced LDL cholesterol levels and the odds for CAD in patients with extremely high LDL cholesterol.Methods: We recruited 500 individuals with significantly elevated LDL cholesterol levels (LDL cholesterol level ≥180 mg/dL, or ≥140 mg/dL for subjects <15 years of age, mean age: 45 years, 41% were male). We sequenced the exons of three conventional FH genes (LDLR, APOB, and PCSK9) and four LDL-altering accessory genes (ABCG5, ABCG8, APOE, and LDLRAP1). Oligogenic FH patients were defined as those who harbored damaging variants of both conventional FH genes and LDL-altering accessory genes. We assessed the impact of the mutations on the LDL cholesterol levels of the subjects as well as on the prevalence of CAD.Results: We identified damaging variants of conventional FH genes in 248 participants (50%). We also detected damaging mutations in accessory genes in 57 patients (11%) and identified oligogenic FH in 27 of these patients (5%). Compared to the participants without damaging variants, those with oligogenic FH exhibited significantly higher LDL cholesterol (265 mg/dL, 95% confidence interval [CI] 216–312, and 210 mg/dL, 95% CI 189–243; P = 3.7 х 10–12) and increased odds for CAD (odds ratio [OR] 5.0; 95% CI 2.2–7.4; P = 1.1 х 10–4). The presence of damaging variants of LDL-altering accessory genes was independently associated with increased LDL cholesterol (18 mg/dL 95% CI 3–33; P = 0.016).Conclusions: Among patients with severely elevated LDL cholesterol, those with oligogenic FH had higher LDL cholesterol and highly increased odds for CAD.



Abstract 11733: Risk Prediction of Future Cardiac Arrest by Evaluation of Genetic Risk Score Alone and in Combination With Traditional Risk Factors [Session Title: Oral Abstracts - Clinical]

2017-11-11T04:35:56-08:00

Background: Coronary heart disease (CHD) is a leading cause of death globally, commonly through sudden cardiac death (SCD). Cardiac arrest of cardiac origin (CA) is associated with a poor prognosis and there is a great need for improved risk assessment and intensified preventive actions.Purpose: To assess if a genetic risk score for CHD, composed of 50 common CHD susceptibility variants (GRS-CHD), predicts CA and to evaluate a novel composite risk score including traditional risk factors as well as GRS-CHD.Methods: The GRS-CHD score alone and in combination with traditional CHD risk factors was related to incident CA among 23 000 middle aged subjects free from history of CHD during 18.9 years of follow-up using Cox Regression.Results: Two-hundred-fifty-two patients suffered a cardiac arrest during the follow up, of which 181 were CA. In a multivariate model with all traditional CHD risk factors, high versus low genetic risk (top vs bottom quintile of the GRS-CHD) predicted CA with a hazard ratio (HR) of 2.53 {(95% CI 1.52-4.19) (P<0.001)}, surpassed only by a higher estimate for male sex with HR=2.85 {(95% CI 2.05-3.96) (P<0.001)}. Smoking, dyslipidemia, hypertension and diabetes mellitus also predicted CA but with lower HRs than GRS-CHD. A novel composite risk score including traditional cardiovascular risk factors (1 point per risk factor present) as well as GRS-CHD (1 point for high and 0.5 points for intermediate genetic risk) predicted CA with a HR=82.19 {(95% CI 20.07-336.69) (P<0.001)} for the highest versus the lowest decile of the composite risk score.Conclusion: Genetic risk of CHD is strongly associated with incident CA and when combined with traditional CHD risk factors may identify individuals who benefit from intensified preventive pharmacological treatment and potentially even prophylactic Implantable Cardiac Defibrillator.



Abstract 11738: Targeting Endothelial Integrin Linked Kinase Induces Spontaneous Myocardial Infarction and Regulates Cardiac Remodeling [Session Title: Atherosclerosis--From the Microbiome to Immune Responses]

2017-11-11T04:35:56-08:00

Introduction: Integrin linked kinase is associated with coronary artery disease (CAD) and myocardial infarction (MI). ILK is important for regulation of vasomotor tone and cardiomyocyte function.Hypothesis: Endothelial directed ILK deletion in mice produces cardiac structural, functional and electrophysiological changes.Methods and Results: We created a mouse that harbored floxed ILK and VE-Cadherin-promoter driven CreERT2 expression (ILK EC cKO). 5 days tamoxifen treatment induce endothelial-restricted deletion of ILK. The resulting conditional knockout mice and littermate controls were studied for arterial and cardiac response to carotid artery ligation. Conditional endothelial ILK deletion exacerbated neointimal formation following endothelial injury as expected. EKG assessment every two days after carotid ligation showed that 50% mice develop MI as early as 4 days after tamoxifen treatment. Impressively, 87 ± 3 % mice survived at 8 weeks post deletion compared with their control littermates showing impaired post-MI cardiac remodeling and decreased ejection fraction by 21 d after carotid artery ligation. Histology analysis revealed myocardial fibrosis, coronary artery remodeling with stenosis and perivascular fibrosis, and increased cardiomyocyte size. Mechanistically, the exacerbated responses in vascular and cardiac remodeling are attributable to the key role of ILK in promoting endothelial survival, nitric oxide production and angiogenesis.Conclusions: ILK thus represents a novel regulator of vascular homeostasis that functions in the endothelial compartment, with sufficient capacity to impact cardiac function and remodeling following spontaneous MI. Therapeutic strategies leading to increase or maintain endothelial ILK expression may be useful to prevent clinical restenosis after percutaneous coronary intervention and heart remodeling after MI.



Abstract 11764: Body Mass Index is Associated With Risk of Critical Limb Ischemia in the General Population [Session Title: Body Fat, BMI, and CV Risk]

2017-11-11T04:35:56-08:00

Introduction: Body mass index (BMI) is higher in individuals with risk factors for peripheral arterial disease (PAD), but there is currently no quantitative assessment of the prospective association between BMI and critical limb ischemia (CLI) in the general population. We conducted an analysis of data from the Atherosclerosis Risk in Communities (ARIC) Study to assess the independent association of BMI with PAD and CLI.Methods: All black and white ARIC participants without prevalent PAD at baseline (1987-1989) were included. We used Cox proportional hazards models adjusting for predefined sociodemographic, lifestyle, and comorbidity covariates to quantify the association between obesity (per 1 standard deviation increment of BMI and according to BMI category) and incident PAD- and CLI-related hospitalizations over time. BMI was categorized as underweight (BMI<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obese (30.0-34.9 kg/m2), or severely obese (≥35.0 kg/m2).Results: Our analysis included 13,988 men and women followed for a median of 24 years. Incident PAD and CLI occurred in 536 and 201 participants, respectively. Higher BMI at baseline was associated with increased risk of incident PAD and CLI after adjusting for potential confounders regardless of whether it was modeled categorically or continuously (Model 1 in Table). The associations of BMI with PAD and CLI were attenuated after further accounting for potential mediators (i.e., diabetes, cholesterol levels, systolic blood pressure, antihypertensive medications, kidney function; Model 2 in Table), but remained significant for CLI when BMI was linearly modeled (HR 1.19 [95CI 1.04-1.36]). The association between higher BMI and CLI was stronger than the association between BMI and PAD for all models (P<0.001).Conclusions: Higher BMI is modestly associated with incident PAD and strongly associated with risk of CLI in the general population. Maintaining an optimal weight may be important to reduce risk of CLI in addition to controlling other cardiovascular risk factors.



Abstract 11770: Human Cord Stem Cells Decrease Heart Fibrosis and Increase LV Ejection Fraction by Activating AKt and Decreasing JNK and p38 Activation in Congenital Cardiomyopathy [Session Title: Adult Congenital Heart Disease]

2017-11-11T04:35:56-08:00

Introduction: In TO2 hamsters with congenital cardiomyopathy, LV fibrosis occurs between ages 1 and 8 months and results in congestive heart failure (CHF) and death. We hypothesized that human umbilical cord stem cells (hUCBC) would impede LV fibrosis and limit CHF.Methods: 45 TO2 hamsters age 1 month, were randomly divided into either 22 Controls treated with Isolyte or 23 hamsters treated with intramyocardial hUCBC (4X106). Echo cardiac measurements were made monthly for 6 months and randomly selected hamsters from each group were sacrificed monthly for measurements of LV fibrosis, LV growth factors by microarrays, LV myocyte death proteins JNK and p38, and LV survival protein Akt by Western blots.Results: In Controls, LV fibrosis at 6 months involved 33.0 ± 5.0% of LVs and 35.0 ± 5.0% of interventricular septums (p<0.01). LV myocyte JNK activation at 6 months increased by 237±3% and p38 activation increased by 122±2% while Akt activation decreased by 50±2% compared with 1 month values (all p<0.01). These changes decreased LV fractional shortening (FS) over 6 months from 56.2 ± 1.0% to 19.7 ± 3.2% and decreased LV ejection fraction (EF) from 89.5 ± 1.4% to 44.9 ± 5.9% (p<0.0001). In contrast, hUCBC resulted in LV fibrosis that involved 13.5 ± 2.3% of LVs and 14.3 ± 1.8% of septums at 6 months (p<0.001). hUCBC increased over 6 months myocardial Hepatocyte Growth Factor (GF) by 338%, Insulin GF by 200%, Vascular Endothelial GF by 192%, Placental GF by 150%, IL-10 by 150% and Tissue Inhibitors of Metalloproteinase by 100% compared with initial values and Controls (all p<0.001). In addition, JNK and p38 activation decreased at 6 months by 49±2% and 37±%, respectively compared with initial values (p <0.01) and by 60±2% compared with Controls (p<0.001). LV Akt also increased by >25% (p< 0.05) compared with initial values and by 330±3% (p<0.001) compared with Controls at 6 months. In these hamsters, FS and EFs were ≥30% of Controls (p<0.01). The Akt inhibitor API-1 prevented the hUCBC induced decreases in myocyte JNK and p38.Conclusion: Our data suggest that hUCBC secrete biologically active factors that activate myocyte Akt, which decreases JNK and p38 activation, decreases LV fibrosis and results in increases in LV fractional shortening and ejection fraction and decreases in CHF.



Abstract 11776: Lower Body Mass Index is a Risk Factor of Blunted Response to {beta}-Blocker Therapy Using Carvedilol: Insights From J-CHF Study [Session Title: Heart Failure and Cardiomyopathies: General Topics II]

2017-11-11T04:35:56-08:00

Introduction: Cardiac cachexia is a strong predictor of a poor clinical outcome in patients with heart failure (HF), whereas the prognosis of obese HF patients is more favorable compared with lean ones, often referred to as “obesity paradox”. However, their underlying mechanisms still remain unknown. The aim of this study was to explore the impact of body mass index (BMI) on patients with HF and reduced ejection fraction (HFrEF) who receive carvedilol therapy in J-CHF study.Methods and Results: J-CHF study was a multicenter, prospective, randomized, stratified trial in which 364 patients with HFrEF (LVEF≤40%) were enrolled and they were assigned to target dose of carvedilol 2.5mg, 5mg, or 20mg daily. In this post-hoc analysis, 360 patients were available for analysis. The study population was divided into L group (BMI<25, n=246) and H group (BMI≥25, n=114) according to the BMI at baseline. The dose allocation and achieved dose of carvedilol were comparable between L and H groups. The time course change of LVEF, plasma BNP level, and estimated glomerular filtration rate (eGFR) was more favorable in patients with H group compared with L group over 56 weeks during carvedilol therapy (LVEF, L, 30±7 to 42±13% vs. H, 31±6 to 45±14%, P=0.007; BNP, L, 424±475 to 188±359 pg/ml vs. H, 315±364 to 91±137 pg/ml, P=0.001 by ANOVA; eGFR, L, 64±20 to 62±20 ml/min vs. H, 67±18 to 69±21 ml/min, P=0.029 by ANOVA). BMI at baseline was positively correlated with eGFR at 56 weeks (ρ=0.17, P=0.003) and absolute change of eGFR over 56 weeks (ΔeGFR, ρ=0.20, P=0.0003), although it was not correlated with baseline eGFR. By multiple regression analysis BMI was an independent predictor of ΔeGFR even after adjusting for age, gender, ischemic etiology, LVEF, hemoglobin level, serum sodium level and allocated dose of carvedilol (β=0.12, P=0.03). Primary endpoint defined as the composite of all cause death and hospitalization for cardiovascular causes including HF was more common in L compared with H (P=0.013, log-rank test). Cox proportional hazard model revealed that BMI was an independent predictor of primary endpoint (HR 0.90, P=0.01).Conclusions: Lower BMI might be associated with poorer clinical outcome in HF patients through the blunted response to β-blocker therapy using carvedilol.



Abstract 11778: Risk of Ischemic Stroke, Myocardial Infarction, Atrial Fibrillation and Major Bleeding in Patients Without Atrial Fibrillation: Implication for Expanding Indication of Non-Vitamin K Antagonist Oral Anticoagulants [Session Title: Pharmacoepidemiology]

2017-11-11T04:35:56-08:00

Introduction: The results of the COMPASS trial will likely increase the use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients without atrial fibrillation (AF). We aimed to provide a comprehensive assessment of the untreated risks in contemporary routine practice among non-AF patients who could be future candidates for NOACs.Methods: Using a U.S. administrative database, we identified 6,495,875 non-AF patients ≥50 years between 1/1/2011-9/30/2016, who were not treated with oral anticoagulants or non-aspirin antiplatelet agents. The primary outcome was a composite endpoint of ischemic stroke and myocardial infarction (MI). The secondary outcomes included individual outcomes of ischemic stroke, MI, AF, major bleeding, intracranial bleeding and death. We assessed the risks by age, sex, and the combination of risk factors. We also calculated the number needed to treat (NNT) or harm (NNH) over five years based on hypothetical relative risks.Results: The event rates were 0.67%/year for ischemic stroke and MI, 0.96%/year for AF, 0.52%/year for major bleeding, 0.13%/year for intracranial bleeding and 0.70%/year for death. Patients with certain combination of risk factors were at particularly high risk (Figure). Only 5% of strokes during follow up were preceded by an AF diagnosis. The NNT for preventing a stroke or MI among patients ≥65 years with at least one risk factor and patients <65 years with at least two risk factors would be below 100 if a NOAC could achieve a relative risk reduction of at least 20%. However, these patients also had high untreated risk of bleeding, which could be further increased if a NOAC is used.Conclusions: The high risk of stroke or MI in certain non-AF populations underscores the need to consider new prevention approach. In addition to the ongoing trials in patients with previous stroke and heart failure, future NOAC trials in other high-risk populations, such as diabetes and chronic kidney disease, may be needed.



Abstract 11779: The Acceleration Sugar Score -a New Way to Track Changes in Sugar Intake [Session Title: Dietary Components and Dietary Interventions for CV Health II]

2017-11-11T04:35:56-08:00

Background: Evidence is building about the risks associated with excess sugar consumption, particularly in combination with highly processed foods. We hypothesized that a transition of eating behaviors into healthy options with an emphasis on fibre, fruit and vegetables would result in a shift from high sugar eating patterns to low sugar. A sugar scoring tool was developed to track changes with the behavior change intervention to determine if overall sugar scores were lowered as a result of the intervention.Methods: The ACCELERATION Program is 12-weeks of self-management and collaboration with a health team for behavior change with healthy eating, exercise, and reduction of smoking and alcohol. One eating evaluation was to use the Sugar Score, an 8 category self-scoring tool to assess sugar intake according to low,medium and high levels of consumption. Baseline, 12 weeks, and 6 month intervals were monitored.Results: 140 Acceleration participants completed the Sugar Score at baseline. Of this group 97% self identified as consuming sugary products on a daily basis with the following top 3 sugar food choices; 1. Cookies & Donuts, 2. Added Sugar, and 3. Candy & Chocolate. At 12 weeks, only 43% were still eating sugary food on a daily basis. At the 6 month follow-up, there was slight relapse, but overall an impressive maintenance of sugar reduction with 59% vs. 97% of participants consuming sugar foods on a daily basis. Cookies and Added sugar remained as the common sugar choices. Both the frequency of sugar intake and the score decreased significantly. At baseline one third of all participants had a High Sugar Score but by the 12 week program completion they cut their score in half, putting them in the Low Sugar category ( p<0.0001). At 6 month follow-up this Low Sugar change was sustained (p<0.0001). Concurrently the percentage of people consuming 5 or more fruit and vegetables daily increased from 21% at baseline to 62% at program end.Conclusion: The behavior change intervention of the ACCELERATION program led to an uptake of fruit & vegetables, which displaced high sugar choices. The Sugar Score was effective in capturing the change in sugar consumption as the participants transitioned from the High Sugar category to becoming a Low Sugar consumer.



Abstract 11790: Impact of Diabetes Control on Subclinical Atherosclerosis: Analysis From Coronary Computed Tomographic Angiography Registry [Session Title: Coronary CT: Atherosclerosis]

2017-11-11T04:35:56-08:00

Introduction: There are limited data regarding the relationship between diabetes control and the risk of subclinical coronary atherosclerosis assessed by coronary computed tomographic angiography (CCTA).Objectives: We sought to evaluate the impact of diabetes control on the risk of subclinical coronary atherosclerosis.Methods: We analyzed 6,434 consecutive asymptomatic individuals without previous history of coronary artery disease who underwent CCTA (mean age, 53.7±7.6 years and 4,694 men [73.0%]). The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Study participants were categorized as normal (n=5,409), controlled diabetes (hemoglobin A1C <7%, n=666), or uncontrolled diabetes (hemoglobin A1C ≥7%, n=359), respectively.Results: Compared with normal individuals, controlled diabetic individuals had a higher risk for any atherosclerotic plaque (odds ratio 1.23, 95% confidence interval [CI] 1.02-1.47, p=0.029), but there was no difference in significant coronary artery stenosis (odds ratio 1.24, 95% CI 0.93-1.66, p=0.145). In contrast, uncontrolled diabetic individuals had consistently higher risks of any atherosclerotic plaque (odds ratio 2.26, 95% CI 1.76-2.91, p<0.001) and significant coronary artery stenosis (odds ratio 3.46, 95% CI 2.57-4.68, p<0.001) than normal individuals. During a median follow-up of median 21.8 months, there was no significant difference in cardiac events between normal and controlled diabetic individuals (hazard ratio 1.12, 95% CI 0.60-2.11, p=0.726). However, uncontrolled diabetes was associated with increased risk of cardiac events compared with normal individuals (hazard ratio 2.71, 95% CI 1.50-4.91, p=0.001).Conclusions: Among asymptomatic individuals, uncontrolled diabetes was associated with significant subclinical coronary atherosclerosis with subsequent high risk for cardiac events. These findings suggest the importance of diabetes control in asymptomatic individuals.



Abstract 11797: A Systematic Review and Meta-Analysis to Test the 'Timing Hypothesis' of Hormone Replacement Therapy and Cardiovascular Disease [Session Title: Excitement, Paradoxes & Prediction in CVD]

2017-11-11T04:35:56-08:00

Introduction: The ‘Timing Hypothesis’ states that the benefits and harms of hormone replacement therapy (HRT) are related to the proximity with which it is begun following the onset of menopause. We sought to test this hypothesis by performing a systematic review and meta-analysis of randomized controlled trials (RCTs).Methods: Thirty-two RCTs were identified that compared HRT to nonusers (n=40,521) and evaluated at least one of the primary endpoints, which included all-cause mortality, cardiac mortality, coronary heart events (a composite of nonfatal myocardial infarction (MI) and cardiac mortality), and a composite of stroke, transient ischemic attack (TIA) and systemic embolism. The primary aim of this analysis was to test for heterogeneity using Chi2 and I2 tests for early versus late initiators of HRT. Early initiation trials were defined as those where the mean age of participants was less than 60 and late initiation trials were those where the mean age was greater than 60.Results: There was significant heterogeneity of treatment effect noted between early versus late HRT initiators for all-cause mortality (Chi2 =9.74, p=0.002, I2 = 89.7%), cardiac mortality (Chi2=4.04, p=0.04, I2 = 75.2%), and coronary heart events (Chi2=3.06, p=0.08, I2 = 67.3%). Early HRT initiators experienced both all-cause and cardiac mortality benefit but the trend in late initiators was toward harm, see Figure 1. Both groups experienced an increase in TIA, stroke and systemic embolism (odds ratio (OR), 1.52; 95% confidence interval (CI), 1.38-1.67).Conclusion: Early initiation of HRT may be effective for reducing death and cardiac events but late initiation is harmful. Younger menopausal women using HRT to treat vasomotor symptoms are not at increased risk of dying or experiencing an event related to coronary heart disease.



Abstract 11798: The Nitric Oxide-Donor MPC-1011 Stimulates Angiogenesis and Arteriogenesis and Improves Hindlimb Ischemia via a cGMP-dependent Pathway Involving VEGF and SDF-1 Alpha [Session Title: Angiogenesis and Arteriosclerosis II]

2017-11-11T04:35:56-08:00

Introduction: Peripheral arterial disease (PAD) is an important cause of morbidity and mortality with little effective treatment currently available. Occlusive atherosclerosis in lower limbs occurs as a last step of endothelial nitric oxide (NO) deficiency limiting signal transduction necessary for normal vascular function. Thus, delivery of NO appears to be an attractive therapeutic option in several cardiovascular conditions.Hypothesis: We hypothesized that the NO-donor MPC-1011 might elicit vasodilation, angiogenesis and arteriogenesis and in turn improve limb perfusion, in a hindlimb ischemia model.Methods: Hindlimb ischemia was induced by femoral artery ligation in rats which were randomized to receive placebo, MPC-1011, cilostazol or both, for up to 28 days. Blood flow was assessed by laser Doppler imaging, angiogenesis and arteriogenesis by immunohistochemistry post mortem, and tissue VEGF, SDF-1 and cGMP levels by ELISA.Results: After femoral artery occlusion, limb perfusion in rats receiving either MPC-1011 alone or in combination with cilostazol was increased throughout the treatment regimen (P<0.05). Capillary density and the number of arterioles was increased only with MPC-1011 (+24.6% and +28.7%, vs placebo and cilostazol, resp.; P<0.05). MPC-1011 improved vascular remodeling by increasing luminal diameter in the ischemic limb (+23.1% and +27.0%, vs placebo and cilostazol, resp.; P<0.05). Moreover, MPC-1011 stimulated the release of proangiogenic cytokines, including VEGF (+42.2% vs placebo; P<0.05), SDF-1 alpha (+30.7% vs placebo; P<0.05) and increased tissue cGMP levels (+60.2% vs placebo; P<0.05), potentiated proliferation and migration of endothelial cells, which was blunted in the presence of soluble guanylyl cyclase inhibitor LY83583. In MPC-1011-treated rats Lin-/CD31+/CXCR4+ cells were increased by 92% and Lin-/VEGFR2+/CXCR4+ cells by 76.8% vs placebo (P<0.05).Conclusions: Here we show for the first time that the NO donor, MPC-1011, is a potent and specific promoter of angiogenesis and arteriogenesis in a hindlimb ischemia model in a NO-cGMP-VEGF-dependent manner. This sets the basis to evaluate and confirm the efficacy of such therapy in a clinical setting in patients with PAD and impaired limb perfusion.



Abstract 12124: Vitamin D Replacement Ameliorates Serum Lipoprotein Functions, Adipokine Profile and Subclinical Atherosclerosis in Pre-menopausal Women [Session Title: Lifestyle & Behavioral Medicine: General Topics III]

2017-11-11T04:35:56-08:00

Introduction: Low vitamin D (vitD) status has been linked to increased cardiovascular (CV) risk, but the effects of vitD supplementation on CV disease and its determinants, such as lipid metabolism, are not entirely clarified.Hypothesis: We hypothesized that vitD may modulate lipoprotein functions, such as the HDL cholesterol efflux capacity (CEC), which is inversely correlated to CV risk, and the pro-atherogenic serum cholesterol loading capacity (CLC). We evaluated the impact of vitD status normalization on HDL CEC, serum CLC, adipokine profile and subclinical atherosclerosis in premenopausal women.Methods: Healthy premenopausal women with vitD deficiency (n=31) were scheduled for vitD replacement. HDL CEC was measured by a radioisotopic assay and serum CLC by cholesterol fluorimetric quantification in macrophages. Serum adipokines were measured by ELISA. Subclinical atherosclerosis was evaluated by flow-mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AI), measured with standard techniques.Results: VitD replacement restored normal levels of serum 25(OH) vitD [from 9.50 (5.70-13.60) to 24.50 (22.30-28.70) μg/L]. Total CEC from macrophages significantly improved (+ 19.5%; p<0.01) after vitD replacement, due to a specific increase in the ABCA1-mediated CEC (+ 70.8%; p<0.0001). No change was observed in aqueous diffusion nor in ABCG1-mediated CEC. Serum CLC was significantly reduced (-13.3%; p = 0.0026) after replacement. After vitD replacement, plasma levels of adiponectin were increased (+50.6%; p<0.0001) and plasma levels of resistin were decreased (-24.3%; p<0.0001). HDL CEC, serum CLC and adipokine modifications were accompanied with a significant improvement in FMD (+4%; p<0.0001), PWV (-4.1%: p<0.0001) and AI (-16.1%; p = 0.0015).Conclusions: VitD replacement ameliorates lipoprotein functions involved in macrophage cholesterol homeostasis along with adipokine profile and markers of subclinical atherosclerosis. These new data support a beneficial effect of vitD supplementation in CV disease prevention.



Abstract 12125: Human Factors Affect the Time to Initiation of CPR in Pediatric ICUs [Session Title: ReSS Poster Session Day 2, Section 03]

2017-11-11T04:35:56-08:00

Introduction: Recognition of cardiopulmonary arrest (CPA) is critical to the timely initiation of CPR. With electronic medical records and continuous patient monitoring in ICUs we can better study the time interval between CPA and CPR. Our aim is to study the influence of patient characteristics, physiological parameters and unit ergonomics on the time to initiation of CPR.Methods: Single center study of children 0 to 21 years admitted to an ICU who experienced a CPA requiring chest compressions for >1 minute. Patients with CPR in progress at the time of admission or on ECMO were excluded. Time of CPA, as defined in AHA’s Pediatric Advanced Life Support criteria was determined by analysis of continuous ECG, plethysmography, arterial blood pressure and end-tidal CO2 (EtCO2) waveforms. Initiation of CPR was onset of cyclic artifact in the ECG with corresponding changes on plethysmography or arterial waveform. Patient characteristics and ergonomics included CPA cause, identification on the High-Risk Checklist, existing monitoring, ICU type, time of day, and occurrence during nursing shift change. Wilcoxon rank sum test and Pearson’s Chi-square test were used.Results: Time from CPA to initiation of CPR was 48s (IQR 24.5-135) in 37 CPAs. There was no difference in ICU unit (p=0.26), time of day (p=0.84), nursing shift change (p=0.45) or CPA cause (p=0.37). Patients with EtCO2 monitoring compared to those without had a longer time to initiation of CPR, 115s vs 35s (p=0.02) and those identified on the High-Risk Checklist had a shorter time to initiation of CPR, 28s vs 65s (p=0.05). Patients with eCPR to ECMO compared those not placed on ECMO had a longer time to initiation of CPR of 430s vs 42s (p<0.01).Conclusion: Early recognition of CPA and initiation of CPR appears dependent on human factors, not patient characteristics or unit ergonomics. The High Risk Checklist, a situational awareness tool has potential to improve time to initiation of CPR. Both the presence of EtCO2 monitoring and ECMO cannulation can increase cognitive load due to data integration and task saturation respectively, leading to potential cognitive error and delayed recognition of CPA. Our data supports further investigation into how human factors contribute to recognition and initiation of CPR.



Abstract 12128: Frailty in Patients With Heart Failure May be Caused by Catabolic Anabolic Imbalance and Ventricular Vascular Stiffening [Session Title: Palliative Care in Heart Failure]

2017-11-11T04:35:56-08:00

Background: Frailty is common in older adults with heart failure (HF), with a recent study suggesting it may be present in ≥ 70% of patients with HF and ≥ 80 years of age. The aim of this study was to clarify the pathophysiology underlying these patients.Methods: We included 176 hospitalized HF patients ≥ 75 years old. They were divided into Non-frail, Pre-frail and Frail according to Fried frailty phenotype. Elastance index (EAI) and left ventricular (LV) end-systolic elastance index (ELVI) were derived as the ratio of end-systolic pressure to stroke volume index and end-systolic volume index, respectively. End-systolic pressure was estimated from the equation 0.9 х brachial systolic blood pressure. The ratio of LV end-diastolic volume index to E/e’ mean was used to evaluate LV diastolic compliance.Results: Compared to Non-frail, Pre-frail had higher prevalence of myocardial infarction (MI) and glucose intolerance and lower motor functional independence measure (FIM) score. Frail was older, more often female, had lower body weight, prevalence of dyslipidemia, plasma creatinine, albumin, geriatric nutritional risk index, and FIM score (both motor and cognitive), had longer length of hospital stay and higher in-hospital mortality. EAI and ELVI were increased and LV diastolic compliance was decreased in Frail compared to Non-frail.Conclusions: Pre-frailty in old patients with HF is caused by MI and glucose intolerance, whereas, Frailty in very old patients with HF may be caused by catabolic/anabolic imbalance and ventricular-vascular stiffening due to aging.



Abstract 12129: Public Reporting of PCI Outcomes and Provider Risk Aversion: The Results of a Survey of Interventional Cardiologists in Massachusetts and New York [Session Title: Cardiovascular Care and Outcomes]

2017-11-11T04:35:56-08:00

Background: Public reporting of PCI outcomes is associated with risk-averse use of PCI and inferior outcomes. Contemporary data about how public reporting impacts interventional cardiologists’ (IC) clinical decision making are lacking.Methods: From November, 2016—February, 2017, we surveyed 456 ICs in MA and NY about their knowledge and beliefs about PCI public reporting, and how public reporting influences their clinical decision-making. The survey instrument was developed in consultation with survey design and public reporting experts. Questions used Likert-scale responses. Surveys were administered electronically to all ICs identified using a comprehensive database of licensed US physicians from Doximity, an online physician networking site, 2014 Medicare claims for PCIs, and internet searches. Respondents’ and non-respondents’ personal and hospital characteristics were compared. Eligible ICs were emailed a $20 gift card to encourage survey completion.Results: Response rates were 33% (149/456) overall, 52% for MA (67/129), and 25% for NY (82/327). Respondents and non-respondents had a similar number of years of IC experience (17.0 vs. 18.7, p=0.11); respondents performed more PCIs among Medicare patients in 2014 (31 vs 17, p<0.001). Among respondents, 74 (37.6%) reported that, on 5 or more occasions, they did not perform PCI due, in part, to a concern that a bad outcome would negatively impact their own, or their facility’s, publicly reported outcomes (Table 1); 41 (27.5%) reported that this happened 2-5 times. Overall, 141 (95%) reported believing that other ICs in their state “often” or “sometimes” avoided PCI due to these concerns, and 110 (73.8%) reported trusting clinical risk adjustment methods “very little” or “not at all.”Conclusions: The majority of surveyed ICs reported that PCI public reporting is related to PCI avoidance. Whether this avoidance is due to the act of reporting itself or mistrust of clinical risk adjustment methods is not known.



Abstract 12130: Risk Stratification of Severe Hypercholesterolemia Using EHR and Sequencing for Familial Hypercholesterolemia Genes [Session Title: Lipids and Cardiovascular Risk]

2017-11-11T04:35:56-08:00

Background: Heterozygous familial hypercholesterolemia (FH) affects 1 in 200 individuals, however severe hypercholesterolemia (untreated low density lipoprotein (LDL) cholesterol ≥ 190mg/dl) affects 7% of the adult American population.Objective: The study assessed the use of different methods to risk-stratify a Geisinger cohort with data from electronic health records (EHR) and exome sequencing.Methods: We deployed five phenotyping methods to stratify severe hypercholesterolemia in our cohort (18-85 years of age). These included lipid levels, clinical and family history components as well as variant status. A priori associated confounders were used for multivariate analyses using binary logistic regression for our outcome measures of myocardial infarction (MI), coronary interventions and a composite ischemic heart disease (IHD).Results: 41,649 subjects were included in our study (57.61% female, median age 62 years). Baseline characteristics identified by all phenotyping definitions showed that each definition was associated with a high prevalence of the outcome measures (Table 1). When compared to mutation negative individuals with LDL ≤ 130mg/dl, there was a step-wise increase in the odds for outcomes, starting with a simple LDL based cut-off (≥ 190mg/dl) to addition of data elements from EHR and finally FH mutation positivity (Figure 1). Subjects with LDL ≥ 190 and FH mutation positive status identified the highest risk with an OR of 28.9 (95% CI 15.0-55.8, p-value: <0.0001), 26.8 (13.9-51.6, <0.0001) and 44.3 (23.7-82.9, <0.0001) for MI, coronary interventions and IHD burden respectively.Conclusion: Lipid levels and other EHR-derived clinical elements can identify individuals with adverse cardiovascular outcomes. However, presence of FH mutation positivity helps differentiate severe hypercholesterolemia from mutation-directed life-long cholesterol elevation seen in FH and identifies the highest risk cohort.



Abstract 12131: Chronotropic Incompetence is Not Associated With Prognosis in Heart Failure Patients With Preserved Ejection Fraction and Atrial Fibrillation [Session Title: Stress Testing Exercise and Pharmacologic]

2017-11-11T04:35:56-08:00

Introduction: Both resting heart rate (HR) and chronotropic incompetence (CI) are independent prognostic markers in individuals with sinus rhythm (SR) and reduced left ventricular ejection fraction (HFrEF). In contrast, resting HR is not associated with survival for patients with atrial fibrillation (AF) and HFrEF.Aim: We aimed to investigate the impact of CI on exercise capacity and prognosis, focusing on left ventricular ejection fraction (LVEF) and atrial fibrillation (AF).Methods: We analyzed 1190 patients with CHF from 2007 to 2015 who admitted to our hospital and underwent cardiopulmonary exercise testing. These patients were divided into 4 groups based on basic rhythm and LVEF: group 1 (LVEF ≥ 45% and sinus rhythm (SR), n=435), group 2 (LVEF<45% and SR, n=470), group 3 (LVEF ≥ 45% and AF, n=100) and group 4 (LVEF < 45% and AF, n=185). Heart rate reserve (HRR= (peak HR - resting HR) / (predicted max HR-resting HR)) was used as an index of CI. Median value of HRR was 0.51 in all subjects. We examined the relations between peak VO2 and HRR in each group.Results: Resting HR was highest in group 4, followed by group 2, group 3 and group 1. HRR was the highest in group 1, followed by group 3, group 2 and group 4. There was the strongest correlation between peak VO2 and HRR in group 1, followed by group 4, group 2 and group 3 (r2=0.341, 0.305, 0.213 and 0.061, P<0.001, in each). In the follow-up period (median 1155 days), 407 adverse cardiac events occurred. Univariate Cox proportional hazard model demonstrated that HRR less than the median value in each group was associated with adverse cardiac events in group 1, group 2 and group 4 (hazard ratio [95% confidence interval] 2.64 [21.4-3.25], 3.86 [2.24-6.65] and 2.24 [1.75-3.29], respectively, P < 0.05 in each), but not in group 3 (1.41 [0.81-2.46], P=0.227).Conclusions: CI is an important predictor of adverse clinical outcomes and exercise capacity in CHF patients with SR, and with AF and reduced LVEF. In contrast, CI is minimally correlated with exercise capacity, and not associated with prognosis in patients with AF and preserved LVEF.



Abstract 12133: Prehospital Advanced Life Support and Survival After Traumatic Out-of-Hospital Cardiac Arrest: A Cohort Study From the Japanese National Registry [Session Title: Best Oral Abstract Presentations and Presentation of the Best Abstract Awards for Cardiac and Trauma Resuscitation Science]

2017-11-11T04:35:56-08:00

Introduction: There has been controversy as to which is superior, advanced life support (ALS) or basic life support (BLS), for traumatic out-of-hospital cardiac arrest (OHCA), although many studies have indicated that prehospital ALS might be associated with poor outcomes in traumatic OHCA.Hypothesis: The effect of prehospital ALS for traumatic OHCA may differ depending on the type of healthcare provider. We sought to assess whether prehospital ALS by physicians would be associated with an increased chance of survival after traumatic OHCA.Methods: This was a nationwide population-based study of traumatic OHCA patients based on data from the All-Japan Utstein Registry. We included patients who experienced traumatic OHCA following traffic accidents in Japan from 2013 to 2014. The primary outcome was one-month overall survival.Results: A total of 4,382 patients were included; 828 received prehospital ALS by physicians, 1,591 received prehospital ALS by emergency medical service (EMS) personnel, and 1,963 received BLS only. Among these patients, 96 (2.2%) survived one month after OHCA, including 26/828 (3.1%) for ALS by physicians, 25/1,591 (1.6%) for ALS by EMS personnel, and 45/1,963 (2.3%) for BLS. After adjustment for potential confounders using multivariable logistic regression model, ALS by physicians was significantly associated with higher odds for one-month overall survival compared with both ALS by EMS personnel and BLS (adjusted OR 2.13, 95%CI 1.20 to 3.78; and adjusted OR 1.94, 95%CI 1.14 to 3.25, respectively), whereas there was no significant difference in one-month overall survival between ALS by EMS personnel and BLS (adjusted OR 0.91, 95%CI 0.54 to 1.51). In Propensity score (PS) analysis, ALS by physicians was significantly associated with increased chance of one-month overall survival compared with ALS by EMS personnel: PS-matching, OR 2.03 (95%CI 1.16 to 3.55); PS-adjustment (linear), OR 1.96 (95%CI 1.26 to 3.89); and PS-adjustment (quintiles), OR 2.01 (95%CI 1.15 to 3.54). Similar findings were observed for one-month neurologically favorable survival.Conclusions: Among traumatic OHCA patients, ALS by physicians was associated with favorable outcomes compared with both ALS by EMS personnel and BLS in the prehospital setting.



Abstract 12134: Gut Microbiota Play a Role in Calcific Aortic Valve Stenosis [Session Title: Samuel A. Levine Young Clinical Investigator Award Competition]

2017-11-11T04:35:56-08:00

Introduction: Degenerative aortic valve disease is the most prevalent valvular heart disease. Its pathogenesis has not been elucidated clearly.Hypothesis: In this study, we aimed to investigate the role of gut microbiota in the pathogenesis of CAVD.Methods: We recruited eligible subjects with calcific aortic stenosis(CAS), aortic sclerosis(ASc) and age- and gender- matched control subjects. Levels of plasma gut microbiota metabolites, namely choline, betaine and trimethylamine N- oxide(TMAO) and serum levels of biomarkers related to calcification and tissue remodeling were measured. Histopathological examinations were performed in aortic valves excised during aortic valve surgery.Results: We included patients with ASc(n=49), moderate- severe CAS(n=60) and 48 controls. These groups were age- and gender- matched. None of the baseline comorbidities or medications differed. Patients with moderate- severe CAS had significantly higher plasma levels of choline when compared to both control(p<0.001) and ASc(p=0.006). Betaine/ choline ratio was significantly lower in patients with moderate- severe CAS compared to both control(p= 0.002) and ASc(p= 0.009). Plasma TMAO levels did not statistically differ between groups. Patients with highest quartile plasma choline levels and lowest quartile betaine/ choline ratios had significantly higher peak aortic velocity in echocardiography(p= 0.002, p<0.001); higher aortic valvular(p<0.001, p=0.005) and mitral annular(p= 0.013, p= 0.123) calcification scores on CT; and greater absolute LV- GLS (p= 0.012, p= 0.005). Plasma choline levels were significantly elevated in aortic valves with denser lymphocyte infiltration(p< 0.001), more severe tissue remodeling(p= 0.002), neovascularization(p= 0.011), more severe calcification(p= 0.002), and osteoid metaplasia(p=0.004). These valves also demonstrated significantly higher CD11c+ dendritic cell and plasma cell infiltration, reflecting the chronic inflammatory nature of the disease.Conclusions: We found a significant association between gut microbiota metabolites and CAVD presence and severity evaluated with echocardiography, CT and histopathological examinations for the first time in the literature.



Abstract 12136: Decreased Mortality With Direct Oral Anticoagulants in Patients With Heart Failure and Atrial Fibrillation [Session Title: Heart Failure and Cardiomyopathies: General Topics II]

2017-11-11T04:35:56-08:00

Background: Atrial fibrillation (AF) is common in patients with heart failure (HF) and is associated with higher mortality. Although previous studies have reported that direct oral anticoagulants (DOACs) reduce the risk of cardiovascular events in patients with AF, it still remains unclear whether DOACs reduce mortality in HF patients with AF. Therefore, we examined the impact of DOACs on mortality in HF patients with AF.Methods and Results: Consecutive 497 HF patients with AF were divided into three groups on the basis of the presence of anticoagulant therapy: no anticoagulants group (Non, n=90), vitamin K antagonist (VKA) group (n=257) and DOACs group (n=150). In the Kaplan-Meier analysis (mean 1093 days), all-cause mortality was significantly lower in the VKA and DOACs groups than in the Non group (Figure 1). In the multivariable Cox proportional hazard analysis after adjusting for other potential confounding factors, including CHA2DS2-VASC score and HAS-BLED score, co-morbidities and pharmacotherapies, the usage of DOACs and VKA was independent suppressor of mortality in patients with HF and AF (DOACs, HR 0.356, P=0.001; VKA, HR 0.472, P=0.002). Furthermore, the propensity-matched 1:1 cohort was assessed based on propensity score (DOACs, n=114 and VKA, n=114). All-cause mortality was significantly lower in the DOACs group than in the VKA group in the post-matched cohort (Figure 2). In the Cox proportional hazard analysis, the use of DOACs was a suppressor of mortality in the post-matched cohort (HR 0.526, P=0.041).Conclusion: Appropriate use of anticoagulants in HF patients with AF is important, and DOACs potentially improve all-cause mortality in HF patients with AF.



Abstract 12137: Statin Use and the Risk of CIED Infection: A Cohort Study in a Veteran Population [Session Title: CIED Complications and Lead Extraction]

2017-11-11T04:35:56-08:00

Introduction: The rate of cardiovascular implantable electronic device infection (CIEDI) has increased, despite the use of perioperative antibiotics at the time of device placement. This may be due, in part, to the escalation in the prevalence of methicillin-resistant Staphylcoccus aureus. Statins may have an antibacterial effect, although there is currently no evidence that the number of CIEDI has been impacted by statin use.Hypothesis: Statins are associated with a reduced risk of CIEDI.Methods: A retrospective cohort study was performed to assess whether statins are associated with a reduced risk of CIEDI. The VA Informatics and Computing Infrastructure (VINCI) database, which includes all veterans who underwent CIED placement between 2008 and 2015, was used. A logistic regression model was constructed to estimate the adjusted risk of CIEDI among patients who were receiving statins after adjusting for other confounding factors. The effect of statins was also confirmed by propensity score analysis.Results: Overall, 18970 CIED procedures were included and 98% of them were performed in men with a mean age of 71 ± 11 years. The rate of diabetes mellitus (DM), heart failure (HF), advanced chronic kidney diseases (CKD), CIEDI, positive MRSA nasal colonization, and statin use were 23%, 15.7%, 3.3%, 1.14%, 12.6%, and 56%, respectively. The logistic regression analysis showed that statins were significantly associated with a reduced risk of CIEDI; after controlling for other effects, the reduction was 66% (OR 0.34 [0.2-0.59], P-value <0.0001). Propensity score analysis also confirmed that statins were associated with a reduce risk of CIEDI.Conclusions: Our study showed that among patients receiving statins who had undergone CIED, there was a 66% reduction in device infection. The mechanisms responsible for this association remain to be elucidated. Prospective clinical trials are needed to confirm these findings.



Abstract 12143: A Validation Study of Phenotype-guided Genetic Testing Using the Mayo HCM Genotype Predictor Score for Japanese Patients With Hypertrophic Cardiomyopathy [Session Title: Heart Failure and Cardiomyopathies: General Topics V]

2017-11-11T04:35:56-08:00

Background: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal-dominant disorder mainly caused by mutations in sarcomere genes. Clinical course of HCM patients with sarcomere gene mutation is reported to be significantly worse compared to those without mutation. Recently, a phenotype-based genetic test prediction score for patients with HCM was introduced by Mayo Clinic. They determined the predictive impact of five clinical markers that independently predicted a positive genetic test result as well as the negative predictor. However, it has not been assessed if this prediction model is useful in Japanese HCM cohort because some clinical features, such as apical HCM, in Japanese patients differ from those in Western patients.Methods and Results: We assessed the utility of the Mayo HCM genotype predictor score in 209 Japanese patients with the clinical diagnosis of HCM (age at diagnosis: 59 ± 16 years, gender: 146 men, family history of HCM: 48 patients) who had genetic testing for the six sarcomere genes (MYH7, MYBPC3, TNNT2, TNNI3, TPM1, ACTC). Overall, 62 patients (30%) were genotype positive for a putative HCM-associated mutation (67% was genotype positive in familial cases). The figure shows the yield of genetic testing for each of the scored subgroups predicting a positive genetic test result from 11% to 100%.Conclusions: In our Japanese HCM cohort, the Mayo HCM genotype predictor scoreis useful to predict a positive genetic test result.



Abstract 12144: Left Ventricular End-Diastolic Volume Predicts Exercise Capacity in Patients With a Normal Ejection Fraction [Session Title: Stress Testing Exercise and Pharmacologic]

2017-11-11T04:35:56-08:00

Background: Exercise capacity is a powerful predictor of all-cause mortality. The duration of exercise with treadmill stress testing is an important prognostic marker in both healthy subjects and patients with cardiovascular disease. Left ventricular (LV) dimensions are known to adapt to sustained changes in the level of physical activity. We therefore hypothesized that poor exercise capacity in patients with a preserved ejection fraction (EF) should be reflected in smaller LV dimensions, and a normal exercise capacity should be associated with larger LV dimensions, irrespective of comorbidities.Methods: This hypothesis was tested first in a cross-sectional analysis of 201 patients with normal chamber dimensions and preserved ejection fraction who underwent a clinically indicated treadmill stress echocardiogram using the Bruce protocol (derivation cohort). The major principle association of LV dimensions and exercise capacity was then tested in 1,285 patients who had a Bruce-protocol treadmill exercise stress test and a separate transthoracic echocardiogram (validation cohort).Results: In the derivation cohort, there was a strong positive relationship between exercise duration and LV end-diastolic volume (r2= 0.85, p < 0.001). Multiple regression analyses of several LV dimensional parameters revealed that the end-diastolic LV volume index was best suited to predict exercise capacity (p < 0.0001). In a large validation cohort of 1,285 patients, the end-diastolic LV volume index was confirmed to predict exercise capacity (p < 0.0001). Also, a predictive algorithm derived from the derivation cohort suggests that consideration of LV volume index improved the predictive capacity of age in the validation cohort.Conclusion: This is the first study to demonstrate a principal relationship between LV volume and exercise capacity in unselected patients with a normal ejection fraction. Patients with small LV volumes on echocardiography are likely to have a low exercise capacity and should be encouraged to increase their level of physical activity.



Abstract 12146: Cystatin C and Left Ventricle Function in Black Patients With Atrial Fibrillation and Acute Coronary Syndrome [Session Title: Heart Failure and Cardiomyopathies: General Topics IV]

2017-11-11T04:35:56-08:00

Introduction: Renal dysfunction, an independent risk factor for cardiovascular [CV] morbidity and mortality, has a higher prevalence in black patients. Along the spectrum of cardiovascular diseases [CVD], heart failure [HF] has amongst the highest mortality and this is further amplified in the presence of renal insufficiency.Hypothesis: There is a relationship between Cystatin- C [Cys-C] an endogenous marker of kidney function, and left ventricular function.Method: Eighty patients with a history of atrial fibrillation [AF] admitted with acute coronary syndrome [ACS], 88% black, 54% women, and 75% with clinical or echocardiographic evidence of HF. History significant for HTN, 95%; Diabetes, 46%; Hyperlipidemia, 79%; smoker or h/o smoking 49%; h/o myocardial infarction, 31%. Cys-C and NGAL levels along with standard laboratory data were measured.Results: B-type natriuretic peptide (BNP), as expected, was negatively associated with EF, p=0.02, r= -.27. On univariate analysis no association was found between creatinine (CR), p= 0.41, glomerular filtration rate (GFR), p=0.44, neutrophil gelatinase-associated lipocalin (NGAL), p= 0.75, and left ventricular ejection fraction (LVEF). However, a significant directional relationship was observed between Cys-C and LVEF, p= 0.016, r= .28 (Fig). Further, when risk factors known to be associated with LVEF were accounted for, the significance remained, p= 0.027. Using an EF cut point of 45%, a divide often utilized in clinical practice to delineate “systolic vs. diastolic” HF, Cys-C was more closely linked to an EF> 45%, p=0.016. No similar findings seen with the other markers of renal status.Conclusions: We found a significant relationship between serum Cys-C and LVEF. This relationship was not observed with other markers of renal dysfunction such as creatinine or GFR. The elevation of Cys-C was marked in EF > 45% suggesting the abnormal elevation is related to the diastolic function of the LV. In patients with renal insufficiency and CVD who experience increase morbidity and mortality isolating a marker that may provide preclinical identification of structural and functional abnormality of ventricular function would be of utmost ut[...]



Abstract 12147: P2y12 Antagonism Enhances the Release of Anti-apoptotic Exosomes From Human Cardiac Progenitor Cells in vitro [Session Title: Molecular and Stem-Cell Therapies for Heart Diseases]

2017-11-11T04:35:56-08:00

Introduction: Recent experimental evidences suggest that long-term antagonism of P2Y12, a G protein-coupled (GPCR) purinergic receptor, protect the heart against ischemic injury. However, the mechanisms remain unknown. Smallest membrane-surrounded nanovesicles, termed exosomes, from human cardiac progenitor cells (hCPCs) prevent cardiomyocyte apoptosis and may improve cardiac function after myocardial infarction.Hypothesis: We tested whether the long-term antagonism of P2Y12 receptor, expressed on hCPCs, induces the release of exosomes protecting cultured cardiomyocytes against hypoxia-induced apoptosis.Methods: hCPCs were derived from atrial appendage explants from patients who underwent heart valve surgery. hCPCs were treated for 72h with ticagrelor (T; 1uM), a potent antagonist of P2Y12 receptor, and/or with exogenous adenosine (A;10uM) and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; 10uM), a potent inhibitor of serum adenosine deaminase. Exosomes, isolated from conditioned medium by serial ultracentrifugation, were quantified by immunoblotting for the exosomal marker CD63, a tetraspanin. In order to assess the anti-apoptotic effects of T-induced exosomes, HL-1 cardiomyocytes were incubated for 48h with hCPCs-exosomes (100ug) and then exposed to severe hypoxia (1-2%O2 for 24h). The exosomal content of heat shock protein (HSP) 70, an anti-apoptotic protein, and the levels of activated caspase-3, a well-known effector of apoptosis, were measured by immunoblotting. TUNEL staining was used to detect apoptotic cardiomyocytes.Results: Ticagrelor significantly induced 7-fold increase in the levels of hCPCs-derived exosomes enriched with HSP-70. Conversely, the levels of exosomes HSP70+ were increased 2.5-fold after treatment with A+EHNA (P[...]



Abstract 12153: Urinary N-terminal Fragment of Titin Distinguishes Muscular Dystrophy From Other Types of Cardiomyopathy [Session Title: Biomarkers In Heart Failure and Cardiomyopathies]

2017-11-11T04:35:56-08:00

Background: Titin, a giant sarcomeric protein, is involved in myocardial passive tension and viscoelasticity, and associated with myocardial stiffness and hypertrophy. Mutations in titin gene have been identified in cardiac myopathies such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), as well as in muscular dystrophies (MD). It has been recently reported that in damaged muscle, the N-terminal fragment of titin (Titin-N), is cleaved by calpain-3, and the resulting fragments are excreted into the urine via glomerular filtration. Therefore, we examined whether Titin-N is a biomarker for muscular damage in cardiomyopathies.Methods and Results: We measured and compared urinary levels of Titin-N/creatinine (U-TN/Cr; pmol/mg/dl) in 44 control subjects and 232 patients with several types of cardiomyopathies (DCM, n=102; sarcoidosis, n=18; HCM, n=85; amyloidosis, n=14; Fabry disease, n=6; MD, n=7). U-TN/Cr was significantly higher in MD than in other cardiomyopathies and control subjects (Figure 1). In the multiple regression analysis to determine U-TN/Cr, the presence of MD was found to be an independent predictor of U-TN/Cr (ß=0.401, P<0.001). There was no significant correlations between U-TN/Cr and plasma levels of creatinine kinase, troponin I, or B-type natriuretic peptide. From the ROC analysis (Figure 2), TN/Cr (a cut off value of 8.7) identified MD with sensitivity 100%, specificity 82% and area under the curve (AUC) 0.92 (95% CI 0.867-0.974, P<0.001). The AUC of U-TN/Cr to predict MD was superior to those of U-TN, creatinine kinase or troponin I.Conclusion: Urinary titin-N is a novel marker to distinguish MD from other types of cardiomyopathies.



Abstract 12154: Change in Maximal Exercise Capacity is Inversely Related to Incident Diabetes Mellitus Among Men and Women: Data From the Henry Ford Exercise Testing (FIT) Project [Session Title: Physical Activity and Diet in CVD]

2017-11-11T04:35:56-08:00

Introduction: Maximal exercise capacity (fitness) is inversely related to incident diabetes mellitus (DM). While change in fitness is inversely associated with all-cause mortality, there are no data describing the relationship between change in fitness and incident DM.Hypothesis: Change in fitness between two clinical exercise stress tests is related to risk for incident DM.Methods: In this retrospective, observational study, we identified 8,995 patients (age = 55 ± 11 y; 38% women; 27% non-white) who completed two clinically-indicated exercise tests that were at least 12 mo apart between 1991 and 2009 within the Henry Ford Health System and were free of DM at the time of the second test. Fitness was quantified in metabolic equivalents of task (METs) estimated from peak treadmill speed and grade, then adjusted to the equivalent for a 50-year-old male. Incident DM was identified through May 2010 from administrative databases based on ≥3 encounters with ICD9 code = 250.xx. Cox regression analysis was used to evaluate the risk of incident DM associated with change in fitness between the two tests. Based on data at baseline, covariates included age, sex, race, METs, body mass, cardiovascular risk factors, medications for hypertension and dyslipidemia, reason for test, history of atrial fibrillation, and test year; as well years and delta body mass between the two tests.Results: The median time between the two exercise tests was 3.5 y (IQR 2.0-5.8 y). During a median follow-up of 4.9 y (IQR 2.5-7.8 y) after the second test, there were 1,582 (17%) new DM diagnoses. Adjusted Cox regression results are shown in the Table. Among all patients, each 1 MET increase in fitness at the second test was associated with a 5% lower risk of DM. There was a significant interaction by baseline fitness category, but not for sex or baseline body mass index category (p=0.18). Based on stratified analyses, change in METs was inversely associated with incident DM among patients with baseline fitness ≥8 METs, but not [...]



Abstract 12156: Contemporary Assessment of Fontan Fenestration: Overall Utilization and Impact on Post-operative Outcomes [Session Title: Early Outcomes After Congenital Heart Surgery]

2017-11-11T04:35:56-08:00

Introduction: Fontan fenestration reduces chest tube duration and shortens post-operative length of stay but is not universally performed. Using a large national database, we sought to describe current use of the Fontan fenestration, including factors associated with placement, and compare post-operative outcomes of fenestrated versus non-fenestrated Fontan procedures.Methods: The Virtual Pediatric System database was queried to identify patients with the Society of Thoracic Surgery code for a Fontan procedure during their admission from January 2009 until June 2016. Those undergoing a fenestrated Fontan were compared to those undergoing a non-fenestrated Fontan.Results: Of the 1695 patients, 1084 (64%) had a fenestration placed. There was variation between centers with the range of fenestration placement being 8 to 100% (Figure 1). Those with a fenestration placed had lower weight, despite similar age, and were more likely to have a single right ventricle. Those with a fenestration had lower systolic blood pressure and greater need for mechanical ventilation within the first hour of admission to the intensive care unit after Fontan. The fenestrated group had longer duration of chest tubes (103.6±82.1 vs 79.5±83.3 hours, p<0.0001) and intensive care stay (6.1±8.3 vs 5.1±7.3 days, p<0.0001). These differences remained significant in stratified analysis for both left and right ventricles.Conclusions: Most patients still have a fenestration placed at the time of Fontan but this varies markedly by center. Presence of a fenestration is not associated with improved early post-operative outcomes in the current surgical era. Further study is needed to delineate pre-operative risk factors and advances in surgical approach which may mitigate the benefits of fenestration on post-operative outcomes.



Abstract 12157: Decreased Post-Transplant Survival in Patients With Diabetes Bridged to Transplantation With Left Ventricular Assist Devices in the US [Session Title: The Rise of the Machines: VADs are Here]

2017-11-11T04:35:56-08:00

Introduction: Diabetes Mellitus (DM) is associated with increased mortality in advanced heart failure and in patients undergoing cardiac surgery. However, its impact on outcomes in patients supported with left ventricular assist devices (LVAD) is not well established.Hypothesis: We hypothesized that diabetes is associated with worse outcomes after LVAD implantation.Methods: We queried the United Network for Organ Sharing (UNOS) for all adults listed for heart transplantation and bridged with continuous flow LVAD in the US from 2000 to 2015. We compared the pre- and post- transplant mortality of patients with and without DM. Unadjusted and adjusted time-event analyses were performed.Results: A total of 4978 patients were included in this analysis, of whom 33% had diabetes. Mean age was 53 ± 12 years, 79% were male, and 65% were Caucasian. Compared with those without, patients with DM were older (age 52 vs 57 years, P<.001), more likely to be male (78% vs 82%, P=0.007), smokers (52% vs 57%, P=0.011), obese (mean BMI 28 vs 30, P <.00) and have ischemic cardiomyopathy (37% vs 53%, P<.001). DM was not associated with increased wait-list mortality (adjusted HR 1.16 [0.88-1.53], P=0.30), or wait-List mortality/delisting (HR 1.17 [0.97-1.41], P=0.11). Among patients who underwent transplantation, DM was associated with increased adjusted overall mortality (HR 1.25 [1.03-1.52], P=0.026) and graft failure (HR 1.23 [1.01-1.50], P=0.037).Conclusions: One third of patients bridged to transplantation with LVAD in the US have DM. While it does not increase wait-list mortality or delisting, DM is associated with decreased post-transplantation survival. Figure 1: Unadjusted crude patient survival (A) and graft survival (B) in patients who underwent transplantation.



Abstract 12159: Red Cell Width is Associated With All-cause and Cardiovascular Mortality in Patients With Diabetes [Session Title: Novel Biomarkers for Integration with CVD Prevention]

2017-11-11T04:35:56-08:00

Introduction: Red cell distribution width (RDW), a measure of variability in red blood cell size, is routinely measured in complete blood counts. RDW has emerged as a prognostic marker in patients with cardiovascular diseases. Whether RDW predicts mortality in diabetes is not known.Hypothesis: We hypothesized that RDW is associated with increased risk of mortality in patients with diabetes.Methods: Using the National Health and Nutrition Examination Survey (1999-2010), we identified all adults with diabetes linked to mortality data up to 2011. We investigated the unadjusted and adjusted mortality by baseline RDW. RDW was divided into 4 quartiles (Q1: ≤ 12.4%, Q2: 12.5%-12.9%, Q3: 13.0%-13.7%, Q4: >13.7%).Results: A total of 3,061 patients were included: mean age 61 ± 14 years, 50% male, 39% White. Mean RDW was 13.2% ± 1.4%. Compared with first quartile (Q1) of RDW, patients in Q4 were more likely to be older (Q1 vs Q4, age 58 vs 65 years, P<.001), female (48% vs 57%, P<.001), African-Americans (13% vs 42%, P<.001), have had history of stroke (6% vs 15%, P<.001), myocardial infarction (6% vs 20%, P<.001), heart failure (3.8% vs 21%, P<.001) and have chronic kidney disease (13% vs 35%, P<.001). After a median follow-up of 6 years, 628 patient died (29% of cardiovascular disease). After adjusting for 17 covariates, RDW in Q4 remained significantly associated with all-cause mortality (HR 2.39 [1.30-4.38], P=0.005) and cardiovascular mortality (HR 1.99 [1.17-3.37], P=0.011).Conclusions: Red cell distribution width is a powerful and an independent prognostic marker for prediction of all-cause mortality and cardiovascular mortality in patients with diabetes. Further studies should focus on incorporating RDW in risk prediction models in diabetes. Figure 1: Kaplan-Meier curves of all-cause (A) and cardiovascular (B) mortality by quartile of RDW.



Abstract 12161: Mortality and Clinical Endpoints After 3-6 Months, 12 Months, and 18-48 Months of Dual Antiplatelet Therapy: A Bayesian Network Meta-Analysis of Drug-Eluting Stents [Session Title: Imaging and Nuclear Medicine: General Topics III]

2017-11-11T04:35:56-08:00

Introduction: Meta-analyses of randomized controlled trials (RCTs) of dual antiplatelet therapy (DAPT) have produced varying conclusions about the relation between outcomes and prolonged DAPT after drug-eluting stent (DES) implantation, but reasons for disagreement are uncertain.Hypothesis: Traditional meta-analyses define DAPT duration as either “short” or “long,” which unintentionally compares outcomes at 12 months with outcomes at 12 months, because this duration has been defined as “short” DAPT in 4 RCTs and as “long” DAPT in 7 RCTs.Methods: We created a Bayesian network meta-analysis to compare outcomes after 3-6 months with the common comparator of 12 months and with 18-48 months of DAPT in 14 RCTs of DAPT duration after DES implantation.Results and Conclusions: As shown in the Figure, mortality was not increased when DAPT was increased from 3-6 to 12 months (posterior odds ratio [OR], 0.97; 95% Bayesian credible interval [BCI], 0.66–1.30), from 12 to 18-48 months (OR, 1.07; 95% BCI, 0.76–1.48), or from 3-6 to 18-48 months (OR, 1.10; 95% BCI, 0.82–1.51), thus reducing the credibility that prolonged DAPT increases mortality. Secondly, no difference was seen between 3-6 months and 12 months of DAPT for any endpoint, supporting a shortening of the minimal mandatory DAPT duration to 6 months for patients with stable ischemic heart disease. Lastly, prolonged DAPT of 18-48 months resulted in a tradeoff between increased bleeding and reduced myocardial infarction and stent thrombosis, supporting the use of prolonged DAPT on an individual basis defined by bleeding and ischemic risk.



Abstract 12215: Comparison of Clinical Outcome Between DES Implantation and DCB Angioplasty in Patients With LMB-ISR Lesions [Session Title: Interventional Potpourri]

2017-11-11T04:35:56-08:00

Introduction: The current guideline recommended both repeat stenting (within drug-eluting stent (DES) or bare metal stent) and drug-coated balloon (DCB) for in-stent restenosis (ISR) lesions, if technically feasible. The previous small retrospective study suggested a potential benefit of DCB angioplasty for bifurcation lesions, but real-world clinical data on PCI strategies in patients with left main bifurcation (LMB)-ISR has been unrevealed.Hypothesis: To compare the clinical outcomes between DES implantation and DCB angioplasty in patients with LMB-ISR lesions.Methods: Seventy-five patients with LMB-ISR who underwent percutaneous coronary intervention (PCI) between January 2009 and July 2015 were enrolled in the study (repeated DES implantation [n=51], DCB angioplasty [n=24]).Results: Analysis of the baseline characteristics showed that the patients in the DCB group had a lesser incidence of NSTEMI/STEMI at the index PCI (8.3% vs. 25.5%; p=0.12), higher LDL-cholesterol level (92.9 mg/dL vs. 81.7 mg/dL; p=0.09), and more “stent-in-stent” lesions than those in the DES group (25% vs. 7.8%; p=0.07). Follow-up angiographic imaging outcomes indicated that patients in the DCB group had smaller minimal lumen diameter of target lesion (1.68 ± 0.96 mm vs. 2.34 ± 1.04 mm; p=0.06), bigger late lumen loss (1.06 ± 1.10 mm vs. 0.60 ± 0.85 mm; p=0.16), and higher binary restenosis rate (46.2% vs. 20%; p=0.14), compared with those in the DES group. The cumulative incidence rates of major adverse cardiac events (MACEs) were similar between both groups (median follow-up duration, 868 days; MACE rate, 25% in the DCB group vs. 25.5% in the DES group; log-rank test, p=0.34; Figure). The multivariate Cox regression analysis indicated that the true bifurcation of ISR was an independent risk predictor of MACEs (hazard ratio, 4.62; 95% confidence interval, 1.572-13.561; p[...]



Abstract 12219: Acyl CoA Lysocardiolipin Acyltransferase 1 Knockout Protects Against Hypoxia Induced Pulmonary Artery Hypertension and Cardiac Bioenergetic Dysfunction [Session Title: Vascular Disease and Thrombosis: General Topics II]

2017-11-11T04:35:56-08:00

Introduction: Cardiovascular disease remains one of the leading causes of death worldwide. Pulmonary artery hypertension (PAH) affects the lungs, pulmonary artery, and heart by histological modifications, increased arterial pressure, and reduced ventricular function respectively. We recently showed that Acyl CoA Lysocardiolipin Acyltransferase 1 (ALCAT1) mediates pathological remodeling of mitochondrial cardiolipin with aberrant fatty acyl chains that are highly sensitive to reactive oxygen and nitrogen species.Hypothesis: We hypothesize that ALCAT1 knockout (KO) may attenuate hypoxia induced pulmonary artery hypertension (PAH) and cardiac dysfunction.Methods: Adult C57BL/6 mice were divided into four groups (n = 5 per group), wild-type (WT), wild type exposed to hypoxia (WT-HP), ALCAT1 KO (AL), ALCAT1 KO exposed to Hypoxia (AL-HP). PAH was induced by a standard 3 to 4 weeks exposure, at an interval of 6 hours per day for six days per week, to 10% oxygen level in a hypoxia chamber. Cardiac function was assessed by echocardiography. Sirus red was used to detect fibrosis by histological analysis. Cellular bioenergetics were assessed using a seahorse XF24. Western blot analysis was used to determine expression levels of hypoxia induced proteins.Results: WT-HP demonstrated a significant increase (p[...]



Abstract 12221: Low Nasal Nitric Oxide as a Biomarker for Increased Pulmonary Vascular Resistance in Congenital Heart Disease [Session Title: Vascular Function in Congenital Heart Disease]

2017-11-11T04:35:56-08:00

Introduction: Pulmonary arterial hypertension (PAH) reflected by increased pulmonary vascular resistance (PVR) is an important cause of mortality and morbidity in congenital heart disease (CHD). In CHD patients, injury by shear stress from shunting lesions is associated with impaired production of endothelial derived nitric oxide (NO), which plays an essential role in regulating pulmonary vascular tone. We hypothesized CHD patients with increased PVR will have low NO. Given difficulty in measuring NO systemically, we used nasal NO (nNO) as a proxy for systemic NO.Methods: This study is a single center retrospective chart review of 207 patients with CHD (2010-2016). Patients were subdivided into biventricular (BV) and single ventricular (SV) physiology. Hemodynamic data was obtained from cardiac catheterization records. We measured nNO using ATS/ERS guidelines and classified them as low or normal based on published, age-specific cutoff values. PAH was defined per AHA/ATS guidelines (Table 1).Results: Mean age was 15 years (range: 1 day to 56 years). Compared to CHD patients with normal nNO, those with low nNO have significantly elevated PVR, mPAP, and PVR/SVR (Table 1). No difference was seen in pulmonary blood flow index (Qpi) (Table 1), suggesting increased pulmonary vascular tone rather than increased blood flow underlie the changes. These findings were more marked for BV physiology, while SV patients with low nNO showed only increased PVR/SVR (Table 1). Although mPAP was also elevated, it did not meet PAH criterion.Conclusions: We showed CHD patients with low nNO have elevated PVR, a finding more pronounced with BV physiology. These findings suggest nNO, which can be measured easily and noninvasively, may be a valuable marker for assessing long-term morbidity and mortality and risk for PAH in patients with CHD. Other variables including stage of palliation and other surgical parameters are being analyz[...]



Abstract 12223: Cardiac Arrest During Pediatric Cardiac Catheterization: A Report From the American Heart Association's Get With the Guidelines-Resuscitation Registry (GWTG-R) [Session Title: ReSS Poster Session Day 2, Section 07]

2017-11-11T04:35:56-08:00

Introduction: Pediatric in-hospital cardiac arrest (IHCA) occurs most commonly in intensive care units with overall survival to discharge rates of approximately 35% - 44%. Outcomes for children experiencing cardiac arrest in the cardiac catheterization laboratory (CCL-CA) remain under-reported with few studies reporting outcomes beyond the catheterization laboratory.Hypothesis: Children experiencing CCL-CA will have higher survival to discharge rates than children experiencing cardiac arrest in other hospital locations.Methods: Consecutive patients < 19 years of age experiencing CCL-CA reported to the AHA’s Get With the Guidelines-Resuscitation® registry between 2005 to 2015 were identified. CCL-CA was defined as the need for chest compressions, defibrillation, or both in the cardiac catheterization laboratory. All other event locations were excluded. rimary outcome was survival to discharge. Variables analyzed via multivariable logistic regression for association with survival included age, illness category (surgical cardiac, medical cardiac), pre-existing conditions, pharmacological interventions, and event duration.Results: A total 195 patients met definition of CA-CCL and were primarily composed of surgical and medical cardiac patients (52% and 43% respectively). Children < 1 year of age comprised the majority of patients 64% (124). Overall survival to discharge was 67% (131/195). Patients < 1 year of age comprised 73% (47/64) of patient deaths. Survival to discharge was 44% (16/36) for patients receiving E-CPR. Use of sodium bicarbonate and cumulative epinephrine dosing were significantly associated with poorer survival (p 35 minutes of CPR (81% vs. 38% respectively, p[...]



Abstract 12227: Long-Term Prognostic Value of Combined Free Triiodothyronine and Late Gadolinium Enhancement in Nonischemic Dilated Cardiomyopathy [Session Title: Novel Prognostic Markers in Heart Failure]

2017-11-11T04:35:56-08:00

Thyroid dysfunction and myocardial fibrosis are both associated with cardiovascular events in patients with dilated cardiomyopathy (DCM). The present study aims to determine whether the combination of thyroid hormone (TH) and myocardial fibrosis (detected by late gadolinium enhancement [LGE]) is an independent and incremental predictor of adverse events in DCM. LGE and thyroid function testing in 220 consecutive patients with idiopathic DCM were examined at Fuwai Hospital (China) from January 2010 to October 2011 and followed up through December 2015. Patients were divided into four groups according to the presence or absence of LGE and the FT3 (median level of 2.79 pg/ml): LGE-positive + FT3 <2.79 pg/ml, LGE-positive + FT3≥2.79 pg/ml, LGE-negative + FT3<2.79 pg/ml and LGE-negative + FT3≥2.79 pg/ml. After a median follow-up of 61 months, 56 patients (25.5%) died in total, with rates of 27/56 (48.2%), 8/45 (17.8%), 12/54 (22.2%) and 9/65 (13.8%) among four groups (p=0.009), respectively. Multivariable Cox regression analysis identified LGE-positive and FT3<2.79 pg/ml as a significant independent predictor of all-cause mortality (HR 2.893, 95% CI: 1.323, 6.326, p=0.008). Combining the predictive value of FT3 and LGE status significantly improved risk reclassification for all-cause mortality, as indicated by the net reclassification improvement (NRI=0.28, p=0.005) and integrated discrimination improvement (IDI=0.058, p=0.001). The combination of FT3 and LGE yielded a more accurate predictive value for long-term prognosis in patients with DCM.



Abstract 12230: Impact of Hyperuricemia on Clinical Outcomes After Percutaneous Coronary Intervention for In-stent Restenosis [Session Title: Interventional Potpourri]

2017-11-11T04:35:56-08:00

Introduction: Pathophysiologically, in-stent restenosis (ISR) is considered to be an intrinsic cellular and biologic response after stent implantation. Inflammation has been thought to be involved in this process. Hyperuricemic state could inhibit endothelial nitric oxide synthesis, promote vascular smooth muscle cell proliferation, induce microvascular injury. Previously, it was reported as an independent risk predictor of ISR after bare metal stent implantation. There have been limited data on the impact of hyperuricemia on long-term clinical outcomes after percutaneous coronary intervention (PCI) for ISR in drug-eluting stent era.Methods: From January 2009 to July 2015, 317 patients who underwent repeat PCI for ISR were divided into two groups: patients with normal serum uric acid (UA) levels (normal UA group) and patients with higher serum UA levels (higher UA group). The higher UA group included patients with serum UA levels more than 6.8 mg/dL or patients who took anti-hyperuricemic medication.Results: Hyperuricemia was present in 20.8% of patients with ISR lesions. Diffuse type of ISR was more frequent in patients with hyperuricemia (higher UA, 53.5% vs. normal UA 37.0%, p = 0.017). During a median follow-up period of 1088 days, the cumulative incidence rates of major adverse event (MAE), including a composite of all-cause death, non-fatal myocardial infarction, and any revascularization, were similar between the two groups (higher UA, 36.4% vs. normal UA, 29.9%, p = 0.389; log-rank p = 0.367; Figure). Follow-up angiographic data showed similar outcomes of late lumen loss (0.8 ± 0.9 mm vs. 0.8 ± 1.1 mm, p = 0.895) and binary restenosis rate (28.1% vs. 34.7%, p=0.622). Multivariate Cox regression analysis indicated higher levels of low-density lipoprotein cholesterol (hazard ratio (HR) 1.011, 95% CI 1.003- 1.019, p =[...]



Abstract 12231: Impact of Changes in the International Resuscitation Guidelines for Out-of-Hospital Cardiac Arrest Stratified by Initial Cardiac Arrest Rhythm [Session Title: ReSS Poster Session Day 1, Section 14]

2017-11-11T04:35:56-08:00

Background: The AHA and ILCOR published the Guidelines 2000 for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC). Since 2000, the ILCOR has reported the International Consensus on CPR and ECC Science with Treatment Recommendations (CoSTR) in 5-year cycles. However, few nationwide studies have investigated the efficacy of changes in those guidelines for out-of-hospital cardiac arrest (OHCA) stratified by initial cardiac arrest rhythm.Methods: A total of 1,136,283 adult OHCA patients receiving CPR based on each guidelines were enrolled from the All-Japan Utstein Registry between 2005 and 2014. The study patients were divided into 9 groups according to three guidelines eras (the G 2000 era in 2005, the CoSTR 2005 era from 2006 to 2010 and the CoSTR 2010 era from 2011 to 2014) and three initial cardiac arrest rhythms (ventricular fibrillation including pulseless ventricular tachycardia [VF], pulseless electrical activity [PEA] and asystole). The primary endpoint was 30-day favorable neurological outcome after OHCA.Results: Of the 89,376 VF cases, 7,610 (8.8%) were in the G 2000 era, 43,059 (48.2%) in the CoSTR 2005 era, and 38,707 (43.3%) in the CoSTR 2010 era. After adjustment for resuscitation, the CoSTR 2005 group and the CoSTR 2010 group (reference, the G 2000 group) were independent predictors of favorable neurological outcome (the CoSTR 2005 group: adjusted odds ratio [OR], 1.998; 95% confidence interval [CI], 1.833-2.179, the CoSTR 2010 group: adjusted OR, 3.273; 95% CI, 2.998-3.574, respectively). These findings remained significant for the 241,453 PEA cases (the CoSTR 2005 group: adjusted OR, 1.462; 95% CI, 1.833-2.179, the CoSTR 2010 group: adjusted OR, 2.183; 95% CI, 1.934-2.465, respectively). However, in the 759,797 asystole cases, both CoSTR groups were equivale[...]



Abstract 12233: UPR Effectors PERK and IRE1 Can Contribute to Electrical Remodeling in hiPSC-CMs [Session Title: Cardiac Ion Channel Modulation]

2017-11-11T04:35:56-08:00

Background: Heart failure (HF) is associated with endoplasmic reticulum stress and activation of the unfolded protein response (UPR). UPR inhibits protein translation. Ion channel downregulation is associated with arrhythmic risk. We have reported that the PERK branch of the UPR contributes to electrical remodeling in human HF by downregulating Nav1.5 and Kv4.3.Objective: The UPR has been found to be activated in ischemia/reperfusion, hypertrophy, and HF. In this study, we investigated whether the UPR regulates cardiac ion channels in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).Methods: hiPSC-CMs were utilized for channel currents and action potential (AP) measurements with patch clamp recording. Tunicamycin (TM, 5 μg/ml) was used to activate the UPR. GSK2606414 (GSK, 300 nM) and 4μ8C (5 μM) was used to inhibit PERK and IRE1, respectively. All treatment was 24 h at 37 °C in 95%CO2/5%O2 incubator.Results: TM induction of UPR activation was confirmed by elevated protein levels of Grp78, phospho-PERK, phosphor-IRE1, and ATF6. TM caused significant prolongation of the AP duration (APD90: 1575±154 vs. 477±23 ms of untreated, P[...]



Abstract 12234: Obesity and Stress Testing: Insights From a 25-year Registry [Session Title: Cardiometabolic Health and Diabetes II]

2017-11-11T04:35:56-08:00

Introduction: Obesity is a major public health problem and cardiovascular risk factor. Its influence on the choice of the modality of stress testing and impact on exercise (ex.) time have not been explored.Hypothesis: Higher body mass index (BMI) would translate into more referrals for pharmacologic (pharm.) testing and lower ex. time in those referred for ex. testing, the magnitude of which is uncertain.Methods: All patients referred for stress testing (ex. ECG, stress echo and nuclear) at our institution, between 1990 and 2015, were included. The modality of the stress test and the ex. time [in seconds (sec)], in case of ex. testing, were documented. Patients’ BMI and comorbidities [Diabets (DM), Hypertension (HTN) and hyperlipidemia (HL)] were determined at time of testing. Overweight was defined as BMI of 25-29.9 and obesity as BMI ≥ 30. Logistic regressions models were used to generate age adjusted odds ratios (OR) and their 95% confidence intervals (CIs) for the associations of BMI with stress testing modality and comorbidities, and linear models were used to estimate beta coefficients (β) and their 95% CI for the association of BMI with ex. time.Results: A total of 196,996 patients were included. The % of patients referred for pharm. testing and the prevalence of comorbidities in each BMI category are presented in table 1. Figure 1 shows the forest plot of the age adjusted OR (for pharm. testing and comorbidities) and the box plots of the ex. time. Compared to normal BMI ([...]



Abstract 12236: Differential Roles of GRK2 and GRK5 in Cardiac Aldosterone Signaling Suggest GRK5-Mediated Cardio-protection Against Mineralocorticoids [Session Title: Mechanisms and Heart Failure Therapy]

2017-11-11T04:35:56-08:00

Introduction: Aldosterone (Aldo) contributes significantly to the morbidity & mortality of heart failure (HF). In the heart, Aldo binds the mineralocorticoid receptor (MR) to exert damaging effects, e.g. fibrosis, apoptosis, oxidative stress, etc. Additionally, Aldo can activate the G protein-coupled estrogen receptor (GPER), which may have beneficial, anti-apoptotic effects for cardiomyocytes, e.g. in ischemia/reperfusion injury. GRK2 and GRK5 are the most abundant G protein-coupled receptor (GPCR)-kinases (GRKs) in the heart and both phosphorylate GPCRs but also non-GPCR substrates. The human MR is known to undergo inhibitory phosphorylation at Ser-843, inside its ligand binding domain, which blocks its transcriptional activity.Hypothesis: In the heart, GRK5 phosphorylates and inhibits the MR, whereas GRK2 phosphorylates and desensitizes GPER.Methods: We used the cardiomyocyte cell line H9c2 and isolated adult rat ventricular myocytes (ARVMs). We performed co-immunoprecipitation experiments for GRK interactions with MR or GPER. We measured MR phosphorylation via immunoblotting and MR transcriptional activity via the luciferase reporter assay. We also measured apoptosis and oxidative stress in ARVMs.Results: GRK5, but not GRK2, phosphorylates the MR in H9c2 cardiomyocytes. Beta2-adrenoceptor activation stimulates this non-canonical effect of GRK5. In contrast, GRK2, but not GRK5, phosphorylates and desensitizes agonist-activated GPER. The GRK5-phosphorylated MR is incapable of activating gene transcription, since MR transcriptional activity is markedly suppressed upon GRK5 overexpression. Conversely, CRISPR-mediated GRK5 gene deletion augments cardiac MR transcriptional activity. Importantly, GRK5 is necessary for th[...]



Abstract 12241: Delayed Time to Intrinsicoid Deflection on the 12-Lead ECG and Myocardial Scarring From the Multi-Ethnic Study of Atherosclerosis [Session Title: MRI: T1 Mapping; Myocardial Infarction]

2017-11-11T04:35:56-08:00

Background: Delayed time to intrinsicoid deflection (DID) is an ECG finding associated heart failure (HF) independent of left ventricular hypertrophy (LVH). Myocardial scarring has been postulated as an additional cause for the development DID and may influence the adverse findings associated with this ECG marker beyond left ventricular mass (LVM). In this study, we further characterized the relationship of DID with the presence of myocardial scarring as detected on cardiac MRI (CMRI).Methods: 1708 individuals without clinical cardiovascular disease or ventricular conduction delays (QRS >120 ms) from the Multi-Ethnic Study of Atherosclerosis were studied over an average of 9.5 years. An adjudication committee determined incident HF and the time to the development of HF during the follow up period. CMRI studies were performed using gadolinium contrast to assess for the presence and percentage of myocardial scar. Intrinsicoid deflection was automatically measured in leads V5and V6 from 12-lead ECGs, and DID was classified as ≥ 45 ms in either lead. To determine if DID predicts incident HF independent of myocardial scarring, we examined the association between DID and HF with presence of scar in the model.Results: 229 individuals had DID (age 66.8 ± 8.2, 63.8% male, 49.8% Caucasian) and 1479 individuals did not (age 67.7 ± 8.8, 49.1% male, 43.9% Caucasian). Individuals with DID were more likely to have scar present on CMRI (12.7% vs. 6.5%, p=0.001) and increased scar percentage (0.99 ± 3.91% vs. 0.31 ± 1.91%, p=0.010). Only scarring of the apical lateral wall was associated with increased time to intrinsicoid deflection (43.2 ± 7.3 ms vs 40.4 ± 5.8 ms, p=0.042). In a logistic regression[...]



Abstract 12243: A Contemporary Analysis of Predictors of Mortality in Patients With Heart Failure and Preserved Ejection Fraction From the National Inpatient Sample 2014 Database [Session Title: The Hospitalized Heart Failure Patient]

2017-11-11T04:35:56-08:00

Introduction: There are limited data regarding the predictors of mortality in patients with heart failure and preserved ejection fraction (HFpEF).Hypothesis: We aim to study the impact of predictors of mortality in patients admitted for HFpEF.Methods: Data for this retrospective cohort study were extracted from the Nationwide Inpatient Sample for 2014 using the 9th revision of the International Classification of Diseases (ICD). Demographics, in-hospital mortality, conventional risk factors (diabetes, hypertension, hyperlipidemia, and tobacco abuse), acute critical illnesses (SIRS, sepsis, septic shock), acute coronary syndrome, stroke, acute respiratory insufficiencyResults: 294,990 patients with HFpEF were identified. The mean age was 75 years and 62% were females. There was an inpatient mortality rate of 2.4%. Ethnicity and gender did not predict mortality. On multivariable analysis, significant predictors of mortality in HFpEF patients were advanced age (adjusted odd ratio [OR] 2.06; 95% CI 1.32-3.41, p[...]



Abstract 12246: Combination of Oral Anti-coagulation With Single Versus Dual Anti-platelet Agents Post Percutaneous Coronary Intervention and Atrial Fibrillation-Challenging the Conventional Approach: A Meta Analysis [Session Title: Pharmacology for ACS and PCI]

2017-11-11T04:35:56-08:00

Introduction: Current American Heart Association guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and P2Y receptor antagonists after percutaneous coronary intervention (PCI) with stent implantation or acute coronary syndrome (ACS). Up to 10 % of these patients have atrial fibrillation (AF) requiring prolonged oral anticoagulation (OAC).Hypothesis: The Superiority of triple therapy [(TT): OAC + DAPT] compared to combination OAC and single antiplatelet agent (OAC+SAP) in patients with coronary stenting or ACS and AF stems from non- randomized studies (NRS); and contradict the results of randomized controlled trials (RCTs).Methods: Eight studies including three RCTs and 5 NRS were extracted using MEDLINE, EMBASE and Cochrane Library(Inception-December 2016). Outcomes are stratified based on study designs and estimates are reported as random effects odds ratio (OR) with 95% confidence interval (CI).Results: In RCTs restricted analysis, the risk of major bleeding was significantly lower in OAC+SAP arm compared to TT (OR, 0.73; 95%CI, 0.58-0.91. P=0.01; I2=0). This significance was lost in NRS based analysis (OR, 0.92; 95%CI, 0.63-1.33; P=0.65; I2=0). NRS restricted analysis suggested that OAC+SAP increased the risk of MI (OR, 1.82; 95%CI, 1.21-2.74; P[...]



Abstract 12255: Differential Expression of miRNAs in BAG3-mutation Carriers With Dilated Cardiomyopathy [Session Title: Genetic Mechanisms of Cardiomyopathies and Arrhythmias]

2017-11-11T04:35:56-08:00

Introduction: A new familial dilated cardiomyopathy (DCM) was found related to mutations in the antiapoptotic BAG3 gene. MicroRNAs (miRNAs) are short non-coding RNAs playing significant roles in cardiac disease, including DCM, representing new targets of treatment.Hypothesis: No previous studies have evaluated the clinical association between BAG3-related DCM and circulating miRNAs. We aimed to study whether a clinical association between BAG3-related DCM and circulating miRNAs may represent a new tool for the diagnosis and progression assessment of the disease.Methods: Detailed clinical and echocardiographic information was obtained from 21 patients with familial DCM carrying a BAG3 mutation and 20 age-matched healthy subjects, analyzing 1759 circulating miRNAs in symptomatic and asymptomatic BAG3 mutation carriers, and compared to healthy age-matched subjects.Results: The expression profiles showed significant differences between controls and BAG3 mutation carriers for miRNAs 3191-3p, 6769b-3p, 1249-ep, 154-5p, 6855-5p, and 182-5p, when compared to healthy subjects. Comparisons between phenotypically symptomatic vs asymptomatic BAG-3-mutation carriers, restricted the differences to miRNAs 154-5p, 6885-5p, and 182-5p, finding a statistical correlation between miRNAs 6855-5p and 182-5p with different parameters tested in the subjects of the study, including systolic and diastolic blood pressure, A wave, and of particular interest statistical correlations between miRNA-6855-5p with left atrium length (r=-0.73897 p[...]



Abstract 12273: High Prevalence of Brugada Syndrome Among Thai Migrant Workers in Israel [Session Title: ReSS Poster Session Day 2, Section 05]

2017-11-11T04:35:56-08:00

Background: According to the report of Thailand-Israel cooperation on the placement of workers, an incidence of unclear etiology sudden unexpected death (SUD) in Thai migrant workers in Israel between 2012-2014 was as high as 153 per 100,000 person-year and 90.4% of the victims were originally from northeastern region of Thailand. Brugada syndrome was previously reported as the most common cause of SUD in northeastern Thai population. This study aims to identify the prevalence of Brugada syndrome among this workers.Method: Records of 12-lead ECG from Thai migrant workers between January to June 2016 were retrospectively analyzed by 2 cardiac-electrophysiologists. Any inconsistencies were reviewed by third expert cardiac-electrophysiologists. Brugada syndrome and Type-2 Brugada pattern were diagnosed according to the recent criteria published by European Society of Cardiology. Provocative drug test was not done in our study. Basics characteristics were recorded. To compare the prevalence of Brugada syndrome among difference regions in Thailand, previous recorded ECG conducted in central region of Thailand from occupational workforce population-based cohort study in 2009 were analyzed by same cardiac-electrophysiologists.Result: Screened ECGs of Thai migrant workers (n=2,936, 97% males, mean age 31.6±5.0 years) were analyzed. Majority, 86.20% of the workers was originally from northeastern region of Thailand. Overall, there were 38 (1.3%) Brugada syndrome and 158 (5.4%) Type-2 Brugada pattern were identified. Particularly in northeastern Thai workers population, there were 38 (1.4%) Br[...]



Abstract 12277: Iatrogenic Atrial Septal Defect After Percutaneous Mitral Valve Repair With the MitraClip System [Session Title: Percutaneous Non-Coronary Cardiac Intervention II]

2017-11-11T04:35:56-08:00

Introduction: Persistent iatrogenic atrial septal defect (iASD) has been reported in patients with a trans-septal puncture performed for access to the left atrium. The data on the characteristics of iASD after the MitraClip procedure is limited.Hypothesis: The aim of this study was to examine the incidence of iASD after the MitraClip procedure and its influence on echocardiographic and clinical outcomes.Methods: We retrospectively examined 96 patients who underwent a successful MitraClip procedure and who also had baseline and 1-year post-procedure transthoracic echocardiograms.Results: At one year follow-up, iASD were observed in 24% of cases. Compared to the patients without iASD, the patients with iASD had a larger right atrium and greater severity of tricuspid regurgitation (TR) at baseline. After the MitraClip procedure, MR improved significantly in both groups. Although right atrial area and right ventricular diameters increased significantly in patients with iASD (25.3±8.0 to 28.3±9.5 cm2, 39.7±7.1 to 42.2±8.1 mm, p< 0.05 for both comparisons), these variables did not change in patients without iASD. In addition, patients with iASD had worse TR at follow-up. The incidence of stroke was comparable between the 2 groups during 1-year follow-up (4.3% versus 4.1%). However, patients with iASD had a markedly higher re-hospitalization rate for heart failure (HF) (26% versus 2.7%, p < 0.05).Conclusions: IASD occurred in 24% of patients who underwent the MitraClip therapy. The presence of iASD was associated with right heart enlargement, worse TR, and a h[...]



Abstract 12278: Mitochondrial Ca2+ Influx Contributes to Arrhythmic Risk in Nonischemic Cardiomyopathy [Session Title: Molecular Mechanisms of Cardiac Arrhythmias]

2017-11-11T04:35:56-08:00

Introduction: Heart failure (HF) is associated with increased arrhythmic risk and triggered activity. Abnormal Ca2+ handling is thought to underlie triggered activity, and mitochondria participate in Ca2+ homeostasis.Hypothesis: We assumed mitochondrial Ca2+ flux contributed to early afterdepolarizations (EADs) in HF.Methods: A model of nonischemic HF (NI-HF) was induced in C57BL/6 and CD1 mice by hypertension. Tail-cuff plethysmography, transthoracic echocardiography, telemetry were used to record blood pressure, ejection fraction and ECG. Cytoplasmic Ca2+ transients, mitochondrial Ca2+ transients, mitochondrial membrane potential and mitochondria labeling were using Fluo-4, Rhod-2, TMRM and Mitochondria-GFP respectively. Mitochondrial Ca2+ uniporter (MCU) expression was detected by Real-time PCR, Western blotting and IP. Patch-clamp was employed to record action potentials and channel currents.Results: Isoproterenol-induced premature ventricular contractions and ventricular fibrillation were more prevalent in NI-HF mice than sham controls. Isolated myopathic myocytes showed decreased cytoplasmic Ca2+ transients, increased mitochondrial Ca2+ transients, and increased action potential duration at 90% repolarization (APD90). The alteration of APD90 was consistent with in vivo QTc prolongation and could be explained by augmented L-type Ca2+ currents, increased Na+-Ca2+ exchange currents (NCX) and decreased total K+ currents. Sixty-six percent of myopathic ventricular myocytes showed EADs compared with 17% of sham myocytes (p[...]



Abstract 12287: Circulating MicroRNAs and Myocardial Damage in Paediatric Cancer Patients Receiving Anthracycline Therapy [Session Title: Integrative Aspects of Cardiac Failure and Function]

2017-11-11T04:35:56-08:00

Introduction: We investigated whether circulating heart-associated microRNAs (miRNAs) and the conventional cardiac biomarker, cardiac troponin T as detected by a highly senstive assay (hs-cTnT), are increased in paediatric cancer patients receiving anthracycline therapy and whether the increased levels reflect myocardial damage.Methods: The in vitro study utilized a human embryonic stem cell-derived cardiomyocyte cell model of anthracycline cardiotoxicity. A prospective patient cohort study was completed in 20 children diagnosed to have acute leukaemia with serial echocardiographic speckle tracking assessment of left ventricular (LV) myocardial deformation and quantification of circulating heart-associated microRNAs and plasma hs-cTnT at five time points during and after completion of anthracycline-based chemotherapy.Results: In vitro study showed that heart-associated miRNAs including miR-1, miR-133a, miR-208a, miR-208b, and miR-499 are released from the cells into the culture medium in a time- and dose-dependent manner on exposure to doxorubicin. In patients, significant reduction of LV global longitudinal systolic strain, systolic strain rate, and early and late diastolic strain rate (all p10% reduction of global systolic strain) of LV myocardial deformation.Conclusions: Circulating miR-1 and hs-cTnT showed significant increase during anthracycline-based therapy in children with leukaemias. Plasma hs-cTnT level may, however, be better than circulating miR-1 as a biomarker of early subclinical myocardi[...]



Abstract 12288: Circulating Arterial Microrna Profiles Identify Variant Angina Among Patients Presenting Chest Pain [Session Title: Molecular and Stem-Cell Therapies for Heart Diseases]

2017-11-11T04:35:56-08:00

Introduction: Variant angina is difficult to be identified with patients presenting chest pain in real-world clinics.Hypothesis: With microRNA (miR), we aimed to classify the patients presenting typical chest pain into variant angina (VA), atherothrombotic angina (AA), and patients with no/insignificant coronary lesion (NCL).Methods: Patients underwent coronary angiography (CAG) due to typical chest pain were screened. Patients with previously known coronary artery disease, elevated cardiac marker, finally diagnosed with myocardial infarction, and vasospasm combined with significant fixed lesion were excluded. Blood samples were obtained during CAG from aorta and microRNAs subsequently assessed after extraction from serum; they were miR-17, miR-92, miR-126, miR-145, miR-221, and miR-222.Results: Among 121 included patients, patients were diagnosed as VA (n=46), AA (n=49), and NCL (n=26). VA patients showed different level of miRNA in miR-17 (P=0.036), miR-92 (P=0.002), and miR-126 (P=0.013) compared to NCL patients. Between VA and AA, there were significantly different level of miRNA-145 (P=0.038) and miRNA-222 (P=0.032). By receiver operating characteristic curve analysis, miR-145 [area under the curve (AUC) 0.625, P=0.036], miR-221 (AUC 0.622, P=0.041), miR-222 (AUC 0.620, P=0.043) discerned VA and AP patients. miR-145 [Odds ratio (OR) 1.122; 95% Confidence interval (CI) 1.004-1.252; P=0.042] and miR-222 (OR 1.107; 95% CI 1.006-1.218; P=0.037) proved their association with V[...]



Abstract 12292: Hypokalemia in Patients Undergoing Targeted Temperature Management Following Cardiac Arrest: Temporal Pattern and Prognostic Significance [Session Title: ReSS Poster Session Day 3, Section 14]

2017-11-11T04:35:56-08:00

Introduction: Hypokalemia has been consistently reported as a common occurrence during targeted temperature management (TTM) in comatose survivors of cardiac arrest.Hypothesis: Serum potassium likely fluctuates within the different stages of TTM and excess deviation may be associated with neurological outcomes, death, or recurrent ventricular arrhythmia.Methods: The study included 240 patients treated with TTM following cardiac arrest at a tertiary care hospital between 2007 and 2014. Designated outcomes were poor neurological outcome, death, and recurrent ventricular arrhythmia prior to hospital discharge. Multivariable logistic regression was used to assess for association of hypokalemia and hyperkalemia with the designated outcomes.Results: Two-hundred forty subjects were included in the study. Hypokalemia occurred in 203 (85%) patients at target temperature and 25 (10%) patients were hyperkalemic following normothermia, Figure 1. In multivariable logistic regression, neither hypokalemia nor hyperkalemia was not associated with poor neurological outcomes or recurrent ventricular arrhythmia. Hypokalemia was associated with reduced odds of death prior to hospital discharge (OR=0.36, 95% CI 0.13-0.97, p=0.044), Table 1.Conclusions: Hypokalemia during TTM is very common and may be associated with reduced odds of death prior to hospital discharge.Figure 1. Variation in serum potassium during different stages of TTM.Table 1. Odds ratios of poor neurolog[...]



Abstract 12296: Identification of Five Genetic Variants as Novel Determinants of Type 2 Diabetes Mellitus in Japanese by Exome-wide Association Studies [Session Title: Genomic Applications To Heart Disease]

2017-11-11T04:35:56-08:00

Introduction: Genome-wide association studies (GWASs) have identified >80 susceptibility loci for type 2 diabetes mellitus (DM) in individuals of European ancestry. Genetic variants identified in these previous studies typically have a minor allele frequency of ≥5% and a small individual effect size. Genetic variants that contribute to predisposition to type 2 DM in Japanese remain to be identified definitively.Hypothesis: Low-frequency or rare genetic variants with larger effect sizes might contribute to the genetic architecture of type 2 DM in Japanese. We have performed exome-wide association studies (EWASs) to identify single nucleotide polymorphisms (SNPs) that either influence fasting plasma glucose (FPG) level or blood hemoglobin A1c (HbA1c) content or confer susceptibility to type 2 DM in Japanese.Methods: EWASs were performed with the use of Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays and with 11,729 or 8635 subjects for FPG level or blood HbA1c content, respectively, or with 14,023 subjects for type 2 DM (3573 individuals with type 2 DM, 10,450 controls). Based on Bonferroni’s correction, a P value of < 1.21 х 10-6 was considered statistically significant for the EWAS.Results: The relation of genotypes of 41,265 SNPs to FPG level or blood HbA1c content was examined by linear regression analysis. After Bonferroni’s correction, 41 and 17 SNPs were significantly (P < 1.21 [...]



Abstract 12297: Effect of Study Design and Follow-up Protocol on Success Rates of Catheter Ablation for Paroxysmal Atrial Fibrillation: Findings From the SMASH-AF Meta-Analysis Study Cohort [Session Title: Treatment of Arrhythmias: Ablation]

2017-11-11T04:35:56-08:00

Introduction: Reported success rates for paroxysmal atrial fibrillation (PAF) ablation are highly variable with limited investigation into drivers of heterogeneity. Study design and follow-up may have a significant effect on reported ablation success rate.Methods: We performed a systematic review and meta-analysis of PAF ablation from 1/1/1990 to 8/1/2016. The full protocol is registered with PROSPERO. Major exclusion criteria were insufficient outcome reporting and ablation strategies that were not prespecified and uniform. We included studies with 100% PAF patients. To estimate impact of study parameters on single procedure success rate, we performed multivariate meta-regressions, with all lesions sets and PVI-only models, controlling for study design, recurrence definition, follow-up protocol, patient characteristics, and ablation equipment, and lesion set.Results: A total of 191 treatment arms from 138 studies (23,514 patients) met inclusion criteria. There was substantial variation in reported success rates (29.2% - 94.0%). In the all lesion sets analysis, compared to randomized clinical trials, case-control study type was associated with an 18.0% absolute increase in success rate (95% CI: 0.7% - 35.4%; p 0.04) while prospective and retrospective study types were not associated with success rate. Longer duration of follow up was strongly associated with decreased success rates (-4.6% per yea[...]



Abstract 12300: Differential Impact of Plasma Brain Natriuretic Peptide Level on Long-term Clinical Outcomes in Acute Heart Failure Patients With Reduced, Mid-range and Preserved Ejection Fraction [Session Title: Biomarkers and Imaging in Heart Failure]

2017-11-11T04:35:56-08:00

Introduction: Plasma brain natriuretic peptide (BNP) is an important prognostic marker in acute heart failure (AHF) patients. Measurement of BNP level is recommended for estimating the risk of adverse outcomes in AHF patients during indexed hospitalization. However, it is unclear which BNP parameter, on admission, at discharge, or change during hospitalization, has the highest predictive performance for long-term adverse outcomes, and whether its prognostic impact differs according to the new HF phenotype classification by left ventricular ejection fraction (LVEF); reduced EF (HFrEF), mid-range EF (HFmrEF), and preserved EF (HFpEF).Methods and Results: We firstly examined 3026 consecutive AHF patients from our prospective registries. Prognostic performance of each BNP parameter was assessed by Harrell’s C-index. During a median follow-up of 677 days, 619 (20%) patients died and 1208 (40%) patients had all-cause death or HF rehospitalization. Discharge BNP had the highest C-index, 0.684 for mortality and 0.639 for mortality or HF rehospitalization, amongst all BNP parameters (P [...]