tbuckley/cabot-search huggingface dataset:
Abstract 18730: Correlates and Cut-points of the Triglyceride/HDL Cholesterol Ratio: The Very Large Database of Lipids 4 (VLDL-4)
Authors: Raoul Manalac, Seth S Martin, Michael J Blaha, Peter P Toth, Krishnaji R Kulkarni, Khurram Nasir, Salim S Virani, Roger S Blumenthal, Steven R Jones
Journal: Circulation (2013)

Background: An elevated TG/HDL-C is predictive of atherosclerotic cardiovascular disease; however, advanced lipoprotein correlates of the TG/HDL-C ratio and discrimination by standard cut-points are incompletely characterized. Hypothesis: Elevated TG/HDL-C correlates most strongly with triglyceride-rich remnant lipoprotein cholesterol (RLP-C) and also with LDL density, Lp(a)-C, and male gender. Methods: We examined 1,350,908 individuals from the Very Large Database of Lipids (Baltimore, MD; NCT01698489 ) who were clinically referred for lipoprotein cholesterol ultracentrifugation (Atherotech, Birmingham, AL). LDL density was assessed as a continuous LDL density parameter (LLDR) calculated as the natural log of the ratio of dense to buoyant LDL-C subfractions. RLP-C was defined as VLDL 3 -C plus IDL-C. Results: The strongest univariate correlates of the TG/HDL-C ratio were VLDL 3 -C (spearman rho= 0.824, p&lt;0.0001) and IDL-C (spearman rho=0.537, p&lt;0.0001). In a multivariable linear regression model including age, gender, LLDR, Lp(a)-C, VLDL 3 -C, and IDL-C, the overall adjusted R 2 was 0.764 (p&lt;0.0001). In this model, IDL-C was inversely correlated (partial R=-0.140, p&lt;0.0001) while VLDL 3 -C (partial R=0.697, p&lt;0.001) was more strongly and positively associated with TG/HDL-C. We compared demographic and lipid parameters across standard cut-points of TG/HDL-C (&lt;3, 3-5, &gt;5) ( Table ). Compared with the TG/HDL-C &lt;3 group, there was a 36% higher VLDL 3 -C level in those with a TG/HDL-C of 3-5, and 73% higher level in those with a TG/HDL-C &gt;5. There was a progressively higher LLDR across these groups characteristic of increasing LDL density. Conclusions: A higher TG/HDL ratio is correlated with an increasingly atherogenic lipid phenotype. Across increasing TG/HDL-C groups, VLDL 3 -C, IDL-C, and RLP-C increase. Non-HDL-C rises across these groups along with LDL density, despite similar LDL-C.
Abstract 12900: β-Adrenergic Receptor Kinase-1 is Strongly Associated With Physical Heart Failure Symptoms
Authors: Quin E Denfeld, James O Mudd, Wohaib Hasan, Kerri Winters-Stone, Shirin O Hiatt, Jill M Gelow, Christopher V Chien, Christopher S Lee
Journal: Circulation (2016)

Introduction: Heart failure (HF) is associated with significant physical symptom burden, but exactly how symptoms are related to pathophysiological mechanisms in HF is unclear. To date, no studies have examined the role of metabolic senescence in explaining HF symptoms. Hypothesis: There is a significant relationship between metabolic senescence and physical symptoms among adults with HF. Methods: This was a secondary analysis of data collected from a sample of adults with symptomatic HF. Metabolic senescence was measured with β-adrenergic receptor kinase-1 (βARK1; picograms/milliliter (pg/mL)). Physical symptoms were measured with the HF Somatic Perception Scale (HFSPS; range 0-90, higher = worse). The Seattle HF Model (SHFM) was used as a composite of traditional clinical variables (range roughly 0-4, higher = worse). Generalized linear modeling was used to quantify the relationship between βARK1 and HFSPS scores, adjusting for SHFM scores. Results: The average age of the sample ( n = 96) was 54.3±13.5 years, 77.1% were male, and a majority (83.3%) of the sample had Class III or IV HF. Median raw value of βARK1 was 10.7 (IQR [4.2-28.9]) pg/mL. βARK1 (β = 1.42 ± 0.31, p &lt;0.001) and SHFM scores (β = 12.40 ± 1.58, p &lt; 0.001) were significantly related to HFSPS scores, and there was a significant interaction effect of βARK1 and SHFM scores in predicting HFSPS scores (Figure; interaction effect: β = -0.42 ± 0.09, p &lt; 0.001; model: F (3,88) = 87.00, p &lt; 0.001). In stepwise modeling, βARK1 was significantly associated with HFSPS scores (β = 0.22±0.1, p = 0.038) after controlling for other predictors of physical symptoms (model R 2 = 0.250, F (7, 70) = 3.34, p = 0.004). Conclusions: Worse metabolic senescence is associated with worse physical symptoms in HF, providing preliminary evidence of alternative pathophysiologic mechanisms underlying physical symptoms in HF.
Abstract 18736: Relationship of PCSK9 With Measures of Vascular Disease and Global Risk in 1574 Individuals Enrolled in the FATE (Fireman And Their Endothelium) Study
Authors: Subodh Verma, Eva M Lonn, Marinda Fung, Todd J Anderson
Journal: Circulation (2013)

Background: Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that is transcriptionally regulated by cholesterol status. Elevated PCSK9 levels lead to an increase in circulating LDL-C by inhibiting hepatic LDL-receptor recycling by targeting LDL-receptors for lysosomal degradataion. Since loss-of-function PCSK9 variants are associated with marked cardiovascular protection, we hypothesized that plasma PCSK9 levels may serve as a biomarker of structural and functional atherosclerosis, and would add prognostic value beyond conventional global risk scores. Methods: The FATE cohort consisted of 1574 men (mean age, 49.4 years) free of vascular disease. Measurements included flow-mediated dilation (FMD) and its microvascular stimulus, hyperemic velocity (VTI), carotid intima-media thickness (CIMT), and high-sensitivity C-reactive protein (hs-CRP). Plasma PCSK9 was measured using a quantitative sandwich immunoassay technique, using a monoclonal antibody specific to PCSK9. Cox proportional hazard models evaluated the relationship between PCSK9, vascular markers, and Framingham risk score (FRS). Results: Subjects had low-medium Framingham risk score (7.9%), with mean LDL-C (3.3±0.8 mM), HDL-C (1.2±0.3 mM), and hs-CRP mg/L 1.27 (0.67-2.27). Mean brachial artery FMD was 8.6±4.1%, nitroglycerin-mediated dilatation was 15.6±5.8% and CIMT 0.70 (0.6-0.77) mm. Plasma PCSK9 was normally distributed (median 286 ng/ml [231-355 ng/ml]). In univariate analysis, both PCSK9 and logPCSK9 were related to CIMT (pearson coefficient 0.073, p&lt;0.005), but not to VTI (pearson coefficient -0.041, p=NS) or hs-CRP(pearson coefficient 0.003, p=NS). In multiple linear regression analysis, FRS was independently associated with both CIMT and VTI (both p&lt;0.001). However, PCSK9 was not associated with either CIMT or VTI beyond FRS. Conclusion: In a large cohort of 1574 otherwise healthy individuals, plasma PCSK9 levels were not related to measures of either microvascular or macrovascular dysfunction beyond the FRS score. Whether PCSK9 predicts cardiovascular events remains to be determined.
Abstract 12874: E/e’ SV is a Better Predictor of Outcome Than E/e’ in Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction
Authors: Takashi Kanda, Masashi Fujita, Osamu Iida, Masaharu Masuda, Shin Okamoto, Takayuki Ishihara, Kiyonori Nanto, Akihiro Sunaga, Takuya Tsujimura, Shota Okuno, Yasuhiro Matsuda, Koji Yanaka, Takuya Ohashi, Hiroyuki Kawai, Aki Tsuji, Yosuke Hata, Masaaki Uematsu
Journal: Circulation (2016)

Introduction: Predictors of outcome in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) remain unclear. The ratio of early diastolic transmitral flow velocity to early diastolic myocardial velocity (E/e’) has been proposed as one of them, but the predictive accuracy remains insufficient. Hypothesis: We hypothesized E/e’ SV, E/e’ normalized by the stroke volume (SV), may be a better predictor of outcome in patients with HFpEF than E/e’, by reflecting the terminal slope of the end-diastolic pressure-volume relation, i.e., stiffness of the left ventricle. The aims of this study were to propose a novel echocardiographic index, E/e’ SV, and investigate the feasibility and accuracy of this method in HFpEF patients. Methods: Echocardiography including E/e’ SV measurement was performed in consecutive 43 patients with HFpEF at discharge in index hospitalization (female 22 patients (51%), age 78±9 years old). Patients were followed for a median of 6.5 months. The end points included the admission for heart failure and cardiovascular death. Results: During the follow-up, 9 patients (21%) encountered the end points. In ROC analysis, E/e’ SV was a better predictive factor than E/e’ (E/e’ SV: AUC=0.820; E/e’: AUC=0.768). Kaplan-Meier analysis showed patients with E/e’ SV&gt;0.420 had a poorer prognosis than those with E/e’ SV&lt;0.420 (P&lt;0.01). In Cox regression multivariate analysis, high E/e’ SV was an independent predictor of event-free survival (Adjusted Hazard ratio [95% CI] = 17.2 [3.1, 94.8] (p=0.001)). Conclusion: E/e’ SV is a better predictor of outcome in patients with HFpEF than E/e’.
Abstract 18735: Worsening Right Ventricular Structural Mechanics in Constrictive Pericarditis; Pericardiectomy Didn’t Fix the Problem!
Authors: Muhammad U Tariq, M C Alraies, Kenya Kusunose, Allan Klein
Journal: Circulation (2013)

Introduction: Constrictive pericarditis (CP) is the result of scarring and consequent loss of the normal elasticity of the pericardial sac. Pericardiectomy is the definitive treatment for most cases of constriction. However it is believed structural changes in the right ventricle (RV) may result in tricuspid regurgitation (TR) after total pericardiectomy in patients with CP. Case report This is the case of a 55-year-old man who had a history of viral pericarditis, HTN and heart failure. He was evaluated for progressive pedal edema and ascites, found to have CP with equalization of RV and LV diastolic pressures and respiratory discordance of systolic pressures, consistent with CP on right heart catheterization. He underwent pericardiectomy and was found to have extensive pericardial adhesions and severe calcifications. Seven weeks later, he presented with complaints of fluid overload and was noted to have newly decreased RV systolic function accompanied by increase in RV volume with tricuspid annular dilation and 2-3+TR (Table and Figure). Diuretics were reinitiated and he is followed for potential tricuspid valve surgery. Discussion TR may develop post pericardiectomy in patients with CP. This is commonly noted with persistent RV failure symptoms post operatively. It may be caused by RV dilation and worsening TR, which results in increased RV strain, signifying poor status of longitudinal RV function. Tricuspid regurgitation is explained by RV and tricuspid annular dilatation. It is important to have a detailed evaluation perioperatively in patients with CP undergoing pericardiectomy.
Abstract 18731: Prevention of Protease 2a-Mediated Cleavage of Dystrophin Inhibits Disruption of the Sarcolemma and Enteroviral-Mediated Cardiomyopathy
Authors: Angela K Peter, Byung-Kwan Lim, Dingding Xiong, Anya Narezkina, Aaron Yung, Kyung-Kuk Hwang, Toshitaka Yajima, Ju Chen, Kirk U Knowlton
Journal: Circulation (2013)

Introduction: Coxsackievirus (CV) is a member of the enteroviral genus of the picornavirus family and is known to be an important cause of myocarditis and heart failure in children and adults. Enteroviral protease 2A cleaves the viral polyprotein and a small number of host cell proteins such as the cytoskeletal protein, dystrophin, and the eukaryotic translation initiation factor (eIF4G)-1 and -2. Genetic deficiency of dystrophin causes cardiomyopathy in Duchenne muscular dystrophy and increases susceptibility to enteroviral myocarditis. However, the importance of protease 2A-mediated cleavage of dystrophin and disruption of the sarcolemma is not known. We hypothesized that cleavage of dystrophin by protease 2A is important in viral propagation, enteroviral-mediated cytopathic effects, and the development of cardiomyopathy following enteroviral infection. Methods and Results: The current studies were designed to test whether inhibition of dystrophin cleavage alters CVB3-mediated myocarditis. In order to address this hypothesis, we knocked-in a mutation at the protease 2A-cleavage site of the dystrophin gene, thus inhibiting only the cleavage of dystrophin following CVB3 infection. Mice expressing cleavage-resistant dystrophin were less susceptible to CVB3 infection as indicated by a significant decrease in the cardiac virus titer eight days post-CVB3 infection. Sarcolemmal integrity, as measured by Evan’s blue dye uptake and Von Kossa staining, was also significantly improved in cleavage -resistant mice. In addition, myocarditis was decreased in infected knock-in mice compared to wild-type infected littermate controls. Also, prevention of dystrophin cleavage in protease 2A expressing transgenic mice markedly inhibited the protease 2A-induced myocytopathic effect. Conclusions: These findings indicate that disruption of the sarcolemma by protease 2A-mediated cleavage of dystrophin can have a critical role in viral propagation, enteroviral-mediated cytopathic effects, and the development of cardiomyopathy in control mice. These findings demonstrate that alterations in the dystrophin-glycoprotein complex which alter sarcolemmal integrity could contribute to susceptibility to virus infection.
Abstract 12869: Uncontrolled Blood Pressure is a Predictor of Left Atrial Remodeling and Adverse Clinical Outcome After Pulmonary Vein Isolation in Patients With Paroxysmal Atrial Fibrillation
Authors: Masashi Kamioka, Hitoshi Suzuki, Yoshiyuki Matsumoto, Minoru Nodera, Takashi Kaneshiro, Yoshiyuki Kamiyama, Yasuchika Takeishi
Journal: Circulation (2016)

Aims: Little is known about the relation of blood pressure (BP) control with left atrial (LA) remodeling and clinical outcome after atrial fibrillation (AF) ablation. Methods: A 101 symptomatic paroxysmal AF patients (85 males, 62.2±8.4 years) undergoing successful pulmonary vein isolation (PVI) were enrolled. Uncontrolled hypertension (HT) was defined as BP more than 140/90 mmHg calculated as mean value being recorded at least 5 different days before PVI. LA wall thickness along ablation line was measured using computed tomography before PVI. LA dimension was measured by echocardiography before and 6 months after PVI. The recurrence was determined by the documentation of AF or atrial tachycardia lasting more than 30 sec. In case of the recurrence, the second procedure was performed based on the patient’s consent. At the second procedure, if AF sustained or was induced after the pulmonary vein (PV) re-isolation or when PV was still isolated, substrate modification such as linear ablation or complex fractionated atrial electrogram ablation was performed. Patients were classified into 3 groups: group 1 (no HT, n = 48), group 2 (controlled HT, n = 34) and group 3 (uncontrolled HT, n = 19). The comparisons of the data among the groups were performed by using ANOVA and the recurrence rate of each group was analyzed by the Kaplan-Meier method. Results: LA wall thickness in groups 2 and 3 were greater than that of group 1. However, LA wall thickness between groups 2 and 3 did not differ. During the follow up periods of 9±4 months, LA dimension of only group 3 increased after the procedure (38.2±5.6 mm to 41.3±6.2 mm, P=0.02). Thirty-one patients showed the recurrence. The recurrence rate was significantly higher in group 3 than in groups 1 and 2 (48% vs. 26% and 22%, P&lt;0.05, respectively). Out of 31 recurrence patients, 18 underwent the second procedure. The patients in group 3 needed substrate modification more frequently than those in group 1 (100% vs. 25%, P &lt; 0.05). Conclusion: The existence of HT causes LA hypertrophy, regardless of whether HT is controlled or not. On the other hand, the uncontrolled BP induced the anatomical and electrical remodeling of LA, resulting in adverse long-term outcome after PVI.
Abstract 13337: Heart-type Fatty Acid Binding Protein and High-Sensitivity Troponin T Are Myocardial Damage Markers That Could Predict Adverse Clinical Outcomes in Patients With Peripheral Artery Disease
Authors: Otaki Yoichiro, Tetsu Watanabe, Hiroki Takahashi, Akira Funayama, Gensai Yamaura, Takanori Arimoto, Tetsuro Shishido, Takuya Miyamoto, Isao Kubota
Journal: Circulation (2015)

Background: Despite many recent advances in endovascular therapy (EVT), peripheral artery disease (PAD) is an increasing health problem with high mortality. Heart-type fatty acid-binding protein (H-FABP) and high-sensitivity troponin T (hsTnT) are markers of ongoing myocardial damage and have been reported to be useful indicators for future cardiovascular events. However, it remains to be determined whether H-FABP and hsTnT can predict adverse clinical outcomes in patients with PAD. Methods and Results: We enrolled 208 de novo PAD patients who underwent EVT. Serum H-FABP and hsTnT were measured in all patients before EVT. During the median follow up period of 694 days, there were 40 major adverse cardiovascular and cerebrovascular events (MACCEs) including all-cause deaths, and re-hospitalizations due to cardiovascular and cerebrovascular diseases and amputations. H-FABP and hsTnT were found to be higher in patients with critical limb ischemia (CLI) compared to those without this condition. Multivariate Cox proportional hazard regression analysis revealed that both H-FABP and hsTnT were independent predictors of MACCEs after adjustment for confounding factors. Kaplan-Meier analysis demonstrated that patients in the highest tertile according to H-FABP levels, as well as those in the highest hsTnT tertile, were at greatest risk for MACCEs. The net reclassification index was significantly improved by the addition of H-FABP as well as the addition of hsTnT to traditional risk factors. Conclusion: The myocardial damage markers H-FABP and hsTnT were increased in PAD patients with CLI and could predict MACCEs in PAD patients.
Abstract 18715: Pituitary Apoplexy Following a Nuclear Stress Test
Authors: Suchith Shetty, Seema D’souza, David Moll, Liquin Song, Nithya Kumaradhas, Joseph Gnanaraj
Journal: Circulation (2013)

Background: Regadenoson is an A2A adenosine receptor agonist with weak affinity for A1, A2B and A3 adenosine receptors. Regadenoson(RAD) is used in MPI in patients who are unable to undergo exercise stress test. It acts primarily by activating A2A receptors causing coronary vasodilatation and increase blood flow. RAD has gained popularity since its approval in 2008 for its longer half life, ease of administration and obviating the need to stop beta blockers prior to testing. The common side-effects are dyspnea, headache and flushing. Here we describe the first documented case of pituitary apoplexy following regadenoson stress test. Case: Our patient is a 49 year-old female who underwent RAD stress test for evaluation of CAD. Within hours of testing she developed excruciating pressure like headache in peri-orbital and frontal regions. BP was moderately elevated and physical examination, including fundoscopy was normal. CT head showed a 1.3 x 1.4 cm pituitary mass. MRI with gadolinium confirmed a sellar and suprasellar 22 x 16 x 18 mm mass with small element of acute hemorrhage and necrosis suggesting pituitary apoplexy. Patient subsequently underwent resection of pituitary mass. Pathology revealed pituitary early infarction and hemorrhage. Conclusion: RAD induced coronary and possible peripheral vasodilatation is mediated primarily by the A2A adenosine receptor (A2A-AdoR) present in the vascular wall. The A2A-AdoR is widely distributed including the cerebral circulation. The effects of RAD such as arterial vasodilatation, sympathomimetic excitation, inhibition of platelet aggregation, reduced airway hyper-responsiveness, are known to mediate through this receptor. The vasodilatory effect on the cerebral arteries is postulated as the mechanism of headaches in patients receiving RAD. Based on our case findings and mechanism of action of RAD we hypothesize that reduced blood flow in the pituitary gland from vasodilatation and rapid fluctuations in blood pressure from RAD might have precipitated pituitary apoplexy in our patient. This case illustrates that although rare, pituitary apoplexy should be included in the differential diagnosis of patients with persistent headache of more than 30 minute duration after completion of ragedenoson stress test.
Abstract 12882: Provider Rather Than Patient Misperceptions Appear to be the Most Common Barriers to Oral Anticoagulation Use for Stroke Prevention in Atrial Fibrillation
Authors: Sean D Pokorney, Christopher B Granger, Diane Bloom, Kevin L Thomas, Sana M Al-Khatib, John Anderson, Mitchell T Heflin, Bradi B Granger
Journal: Circulation (2016)

Introduction: Atrial fibrillation (AF) is associated with increased risk of stroke, yet 50% of patients at high risk are not treated with guideline recommended oral anticoagulants (OACs). This qualitative analysis explored the barriers to OAC use from both physician and patient perspectives. Methods: Patients (n=25) from academic and community care settings with AF and CHA 2 DS 2 -VASc score ≥ 2 were included with a maximum variation sampling strategy for patients on OAC (n=13) and not on OAC (n=12). Provider sampling (n=25) included community primary care providers (n=15), academic geriatricians (n=5), and cardiologists (n=5) caring for the patient cohort. Semi-structured qualitative interviews were conducted with both groups focusing on perceptions of stroke risk and OAC use. Provider interviews used 3 standard AF cases to ascertain how stroke and bleeding risks affected OAC recommendation. Interviews continued until saturation of themes was achieved. Content analysis identified and coded dominant themes. Results: A major theme was missing evidence of shared decision-making for OAC use. A majority of patients “took what was prescribed.” Nearly all physicians reported fall and bleeding risks as the primary reasons for not recommending OACs, but patients reported no communication with their physicians about falls or bleeding risk, other than in the setting of prior bleeding (Table). A second major theme was the knowledge gap in the lack of efficacy of aspirin for stroke prevention and the need for OAC in patients with infrequent or mildly symptomatic AF. Physicians (92%) understood that infrequent AF episodes required OAC, but in 33% of cases, patients with infrequent AF episodes were told that OACs were not warranted (Table). Conclusions: These findings suggest that provider rather than patient concerns prevent appropriate OAC. Opportunities exist, particularly among non-cardiology providers, to increase the appropriate OAC use for AF patients at risk of stroke.